Ozanimod is an oral sphingosine 1-phosphate receptor modulator. It is indicated for the treatment of relapsing forms of multiple sclerosis (MS) in adults, to include clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease and the drug is additionally indicated for moderately to severely active ulcerative colitis (UC) in adult patients. Oral sphingosine 1-phosphate receptor modulators reduce the frequency of clinical exacerbations and delay the accumulation of physical disability in patients with MS. The efficacy of ozanimod for the treatment of relapsing forms of MS was demonstrated in 2, randomized, double-blind, active comparator trials, in which ozanimod was compared to interferon beta-1a. Across both trials, ozanimod significantly reduced annualized relapse rates compared to interferon beta-1a (relative reductions of 38% to 48%) and the drug reduced 3-month confirmed disability progression defined as a 1-point increase in the Expanded Disability Status Scale (7.6% ozanimod vs. 7.8% interferon beta-1a; not statistically significant). The efficacy of ozanimod for the treatment of moderately to severely active UC in adults was studied in 2, randomized, double-blind, placebo-controlled trials. Significantly more patients with UC treated with ozanimod achieved clinical remission (12% treatment difference), clinical response (22% treatment difference), endoscopic improvement (16% treatment difference), and endoscopic-histologic mucosal improvement (9% treatment difference) vs. placebo at week 10. Patients with certain cardiac conditions or with hepatic impairment should not receive ozanimod; clinicians should also review the potential for drug interactions before prescribing this drug.
General Administration Information
For storage information, see the specific product information within the How Supplied section.
Route-Specific Administration
Oral Administration
Oral Solid Formulations
-Ozanimod capsules should be swallowed whole.
-May be administered with or without food.
-Missed dose: If a dose is missed during the first 2 weeks of treatment, reinitiate treatment using the titration regimen.
Hypersensitivity reactions may occur with ozanimod. Rash and urticaria have been reported with ozanimod use during active, controlled clinical trials.
Initiation of ozanimod results in a transient decrease in heart rate and atrioventricular (AV) conduction delays. An up-titration of the dose is necessary to minimize decreases in heart rate. Bradycardia was reported on the day of treatment initiation in 0.2% to 0.6% of multiple sclerosis (MS) patients who received ozanimod compared to no patients who received interferon beta-1a or placebo. After day 1, the incidence of bradycardia was 0.8% or less. After an initial dose of ozanimod 0.23 mg, the greatest mean decrease from baseline in heart rate (0.7 to 1.2 bpm) occurred at hour 5 on day 1. Near return to baseline occurred at hour 6. With continued dose titration, the maximal heart rate effect of ozanimod occurred on day 8. Heart rates below 40 bpm were not observed. In the UC studies, bradycardia was reported on the day of treatment initiation in 1 ozanimod-treated patient (0.2%) vs. 0% with placebo. After Day 1, bradycardia was reported in 1 UC patient (0.2%) treated with ozanimod. Second or third-degree AV block was not observed in MS or UC patients treated with ozanimod with dose titration during clinical trials; however, first and second degree AV block was observed in healthy volunteers who received ozanimod at exposures higher than the recommended dosage without dose titration. Hypertension was reported in 4% or less of patients who received ozanimod during clinical trials. Patients treated with ozanimod had an average increase of approximately 1 to 3.5 mmHg in systolic blood pressure (SBP) over patients who received interferon beta-1a or placebo, and no effect on diastolic pressure. The increase in SBP was first detected after approximately 3 months of treatment and persisted throughout treatment. In MS trials, 2 patients treated with ozanimod experienced a hypertensive crisis that was not clearly influenced by the use of a concomitant medication. In UC trials, hypertensive crisis was reported in 2 actively-treated patients and 1 placebo-treated patient. Blood pressure should be monitored during treatment managed appropriately. During clinical trials, orthostatic hypotension was reported in 4% of MS patients who received ozanimod compared to 3% of patients who received interferon beta-1a.
One patient in an MS study discontinued ozanimod because of dyspnea. Dose-dependent reductions in absolute forced expiratory volume over 1 second (FEV1) and forced vital capacity (FVC) were seen in MS patients as early as 3 months after ozanimod initiation. In pooled analyses of MS clinical trials, the decline in absolute FEV1 from baseline in patients treated with ozanimod compared to patients who received interferon beta-1a was 60 mL (95% CI: -100, -20) at 12 months. The mean difference in percent predicted FEV1 at 12 months between patients treated with ozanimod and patients who received interferon beta-1a was 1.9% (95% CI: -2.9, -0.8). Dose-dependent reductions in forced vital capacity (FVC) (absolute value and percent predicted) were seen at month 3 in pooled analyses that compared patients treated with ozanimod to patients who received interferon beta-1a [60 mL, 95% CI (-110, -10); 1.4%, 95% CI: (-2.6, -0.2)]. In one of the UC trials, the mean difference in decline in FEV1 from baseline in those treated with ozanimod compared to those treated with placebo was 22 mL (95% CI: -84, 39) at 10 weeks. The mean difference in percent predicted normal FEV1 at 10 weeks was 0.8% (95% CI: -2.6, 1). The difference in reductions in forced vital capacity (FVC) (absolute value and percent predicted) was 44 mL (95% CI: -114, 26); 0.5% 95% CI (-2.3, 1.2), respectively. There is insufficient information to determine the reversibility of the decrease in FEV1 or FVC after drug discontinuation or whether changes are progressive with continued use.
Upper respiratory infection was reported in 26% of ozanimod-treated patients and 23% of interferon beta-1a-treated patients during MS clinical trials. In UC trials, upper respiratory tract infections occurred in 5% of actively treated patients compared to 4% of those given placebo. Infections included nasopharyngitis, pharyngitis, pharyngotonsillitis, upper respiratory tract infection, upper respiratory tract inflammation, bronchitis, rhinitis, rhinorrhea, tracheitis, laryngitis, sinusitis, catarrh, labrinthitis, laryngeal or pharyngeal inflammation. Urinary tract infections (cystitis) occurred in 4% of patients who received ozanimod and 3% of patients who received interferon beta-1a during MS trials. The overall rate of infections and rate of serious infections in patients treated with ozanimod was similar to that in patients who received interferon beta-1a in MS study 1 and 2 (35% vs. 34% and 1% vs. 0.8%, respectively) and to those who received placebo in UC study 1 and 3 (9.9% vs. 10.7% and 0.8% vs. 0.4%, respectively). In UC study 2, the overall rate of infection was 23% in ozanimod-treated patients and 12% in placebo-treated patients; rate of serious infections was similar (0.9% vs. 1.8%). Ozanimod causes a mean reduction in peripheral blood lymphocyte count to approximately 45% of baseline values because of reversible sequestration of lymphocytes in lymphoid tissues. The proportion of patients who experienced lymphocyte counts less than 0.2 x 109/L was 2% to 3.3%. These values generally returned to greater than 0.2 x 109/L while patients remained on treatment with ozanimod. After discontinuing ozanimod 0.92 mg, the median time for lymphopenia resolution was 30 days, with approximately 80% to 90% of patients in the normal range within 3 months. Herpes zoster was reported in 0.4% to 2.2% of ozanimod-treated patients compared to 0% to 0.5% of patients receiving interferon beta-1a (MS) or placebo (UC). Herpes simplex encephalitis and varicella zoster meningitis have been reported with another sphingosine 1-phosphate receptor modulator. Patients without a healthcare professional-confirmed history of varicella (chickenpox), or without documentation of a full course of vaccination against varicella zoster virus, should be tested for antibodies to varicella zoster before initiating ozanimod. Cases of fatal cryptococcal meningitis and disseminated cryptococcal infections have been reported with another sphingosine 1-phosphate receptor modulator. Patients with symptoms or signs consistent with a cryptococcal infection should undergo prompt diagnostic evaluation and treatment. Discontinue ozanimod until cryptococcal infection is ruled out. A complete blood count within the past 6 months is needed for all patients before ozanimod initiation. Do not start ozanimod in a patient with active acute or chronic infections; the infection needs to be resolved before fingolimod initiation. If a patient develops a serious infection, consider ozanimod discontinuation; reassess the benefits and risks before reinitiation of ozanimod. Ozanimod may persist in the body for up to 3 months after discontinuation, so continue to monitor patients for infection. Instruct patients to report any signs or symptoms of infection.
In controlled clinical trials of ozanimod, 1 case of posterior reversible encephalopathy syndrome (PRES) was reported. Symptoms include sudden onset of severe headache, altered mental status, visual disturbance, and seizure. Symptoms of PRES are usually reversible but may progress into ischemic stroke or cerebral hemorrhage. If PRES is suspected, discontinue ozanimod. Delay in diagnosis and treatment may lead to permanent neurologic sequelae. A case of progressive multifocal leukoencephalopathy (PML), an opportunistic viral infection of the brain caused by the JC virus (JCV), has been reported with ozanimod during postmarketing experience. PML has been associated with some risk factors, including immunocompromised patients and the use of multiple immunosuppressants. PML has been reported in patients treated with another sphingosine 1-phosphate (S1P) receptor modulator, fingolimod. The majority of cases occurred in patients treated for at least 2 years; however, the relationship between the risk of PML and the duration of treatment is unknown. Withhold ozanimod and perform an appropriate diagnostic evaluation at the first sign or symptom of PML. Typical symptoms of PML are diverse, progress over days to weeks, and include progressive weakness on one side or clumsiness of the limbs; vision disturbance; and changes in thinking, memory, and orientation leading to confusion and personality changes. MRI findings may be visible before clinical signs and symptoms. Hence, MRI monitoring for signs that may be consistent with PML may be useful, and any suspicious findings should spark further investigation to allow for an early diagnosis of PML, if present. Cases of immune reconstitution inflammatory syndrome (IRIS) or immune reconstitution syndrome have been reported in patients treated with other S1P receptor modulators who developed PML and subsequently discontinued treatment. PML-associated IRIS may lead to rapid onset of serious neurological complications or death, and is often associated with characteristic changes on MRI. PML-associated IRIS onset occurred within a few months following S1P receptor modulator discontinuation. Monitor patients and appropriately treat any inflammation associated with IRIS.
Macular edema occurred in 0.2% to 0.4% of MS or UC patients who received ozanimod, 0.3% of MS patients who received interferon beta-1a, and 0% of UC patients who received placebo during clinical trials. Perform an examination of the fundus including the macula in all patients at any time after a patient reports visual disturbance while on ozanimod therapy. Patients with a history of uveitis and patients with diabetes mellitus are at increased risk of macular edema or visual impairment during ozanimod receipt, and these patients should have regular follow-up ophthalmologic examinations. Continuation of ozanimod in patients with macular edema has not been evaluated. The decision to continue treatment in patients with macular edema should be based on the benefits and risks to the patient.
Elevated hepatic enzymes was reported in 5% to 11% of ozanimod-treated patients during clinical trials. Elevations of ALT to 5-fold the upper limit of normal (ULN) or more occurred in 0.9% to 1.6% of patients treated with ozanimod, 1.3% of patients who received interferon beta-1a (MS), and 0.5% or less of patients who received placebo (UC). Elevations of 3-fold the ULN or greater occurred in 2.3% to 5.5% of patients treated with ozanimod, 3.1% of MS patients who received interferon beta-1a, and 0.5% or less of UC patients who received placebo. The median time to hepatic enzyme elevation (3 times the ULN) during clinical trials was 6 months. The majority of patients continued treatment with values returning to less than 3 times the ULN in approximately 2 to 4 weeks. Ozanimod was discontinued for a confirmed elevation greater than 5-fold the ULN during clinical trials. Overall, the discontinuation rate because of elevations in hepatic enzymes was 0.4% to 1.1% of patients treated with ozanimod. Ozanimod is not recommended for use in patients with hepatic impairment. Obtain serum transaminases (ALT and AST) and total bilirubin prior to treatment initiation (within 6 months). Monitor patients for signs of hepatotoxicity; those with preexisting severe hepatic disease may be at greater risk of adverse reactions. Promptly obtain liver transaminase and bilirubin concentrations in any patients who report symptoms that may indicate liver injury, such as new or worsening fatigue, anorexia, righter upper abdominal discomfort, dark urine, or jaundice. Discontinue ozanimod if significant hepatic injury is suspected.
Upper abdominal pain (2%), back pain (4%), headache (4% to 5%), fever (3%), nausea (3%), arthralgia (2%), and peripheral edema (3%) were reported during the various clinical trials for ozanimod.
Ozanimod receipt may increase the risk for a new primary malignancy. Skin cancer including melanoma and basal cell carcinoma were reported during clinical trials in patients receiving ozanimod. Periodic skin examination is recommended for all patients, particularly those with risk factors for skin cancer, and patients are advised to follow skin protection practices, such as using protective clothing and appropriate sunscreens. Breast cancer and seminoma were also reported with ozanimod.
In patients with multiple sclerosis (MS), monitor for severe multiple sclerosis exacerbation after ozanimod discontinuation. Rare cases of severely increased MS disability with multiple new lesions on MRI have been observed after discontinuation of another sphingosine 1-phosphate receptor modulator, fingolimod. Cases typically within 12 weeks, although cases up to 24 weeks after treatment have been reported. Most MS patients did not return to the functional status they had before fingolimod discontinuation, and permanent disease worsening occurred in some cases. Over 8 years, 35 cases of severe increases in disability with new MRI lesions occurred. Following drug discontinuation, disability began in less than 12 weeks in 29 cases, and between 12 and 24 weeks in 6 cases. Time on fingolimod before discontinuation ranged from 7 to 96 months. The disability was more severe than typical MS relapses, as several patients who were able to walk without assistance while taking fingolimod progressed to needing wheelchairs or became bed-bound. Eight patients experienced permanent disability, 17 patients had a partial recovery, and 6 patients had a full recovery (reported as either a return in Expanded Disability Status Scale score reported while on fingolimod or complete recovery as recognized by clinical judgment). Optimal methods for the treatment of severe disability have not been defined; however, all 35 patients received corticosteroids as the initial treatment. Of those who fully recovered, 3 received only IV methylprednisolone, and the other 3 received plasma exchange, intrathecal triamcinolone, or re-started the drug. Advise patients of the potential risk of an exacerbation of their MS when ozanimod is discontinued, and to seek immediate medical attention if they experience new or worsened symptoms of MS. If an increase in disability occurs, test for new or enhancing lesions on MRI and begin appropriate treatment if clinically indicated.
In general, avoid use of ozanimod in patients with a severe hypersensitivity to the drug. Hypersensitivity reactions, such as rash and urticaria, were reported in some patients during clinical trials.
Ozanimod is contraindicated in patients with a history or presence of Mobitz type II second- or third-degree AV block, sick sinus syndrome, or sinoatrial block unless the patient has a functioning pacemaker; and by patients who in the last 6 months experienced myocardial infarction, unstable angina, stroke, transient ischemic attack (TIA), decompensated heart failure requiring hospitalization, or Class III/IV heart failure. Because ozanimod initiation may result in decreased heart rate and transient atrioventricular conduction delays, the dosage should be titrated upward to reach the maintenance dosage. Obtain an electrocardiogram (ECG) to determine whether preexisting conduction abnormalities are present prior to treatment initiation. Patients with ischemic cardiac disease, history of myocardial infarction, congestive heart failure, history of cardiac arrest, cerebrovascular disease, uncontrolled high blood pressure; significant QT prolongation (QTcF more than 450 msec in males or more than 470 msec in females); cardiac arrhythmias requiring treatment with Class Ia or class III anti-arrhythmic drugs; or a history of second-degree Mobitz type II or higher AV block, sick sinus syndrome, or sinoatrial heart block need a cardiac evaluation by an appropriately trained physician prior to ozanimod initiation. These patients may poorly tolerate ozanimod-induced bradycardia or may experience serious rhythm disturbances. Because of potential additive effects on heart rate, ozanimod should generally not be initiated in patients who are concurrently treated with QT-prolonging drugs; if treatment is considered, a cardiac evaluation should be performed prior to treatment.
If treatment with ozanimod is considered, advice from a cardiologist and a cardiac evaluation should be sought for those individuals with uncontrolled hypertension. These patients may poorly tolerate ozanimod-induced bradycardia or may experience serious rhythm disturbances after the first dose. Cautious use of ozanimod is warranted in all patients who have hypertension. Blood pressure elevation may occur with ozanimod use in any patient. Regularly monitor the blood pressure of any patient during ozanimod receipt. Dietary counseling is needed for all patients. Because patients taking ozanimod have an increased sensitivity to tyramine, advise patients to avoid food containing a very large amount of tyramine while taking ozanimod. Certain foods that may contain very high amounts (i.e., more than 150 mg) of tyramine could cause severe hypertension because of a potential tyramine interaction in patients taking ozanimod, even at the recommended doses.
Ozanimod is contraindicated in patients taking monoamine oxidase inhibitor therapy (MAOI therapy). The metabolites of ozanimod may inhibit MAO. An increased risk of nonselective MAO inhibition could lead to a hypertensive crisis.
Ozanimod is contraindicated for use in patients with severe untreated sleep apnea. Cautious use of ozanimod may be warranted for patients with respiratory insufficiency or pulmonary disease, including asthma or chronic obstructive pulmonary disease (COPD). Spirometric evaluation of respiratory function should be performed during therapy with ozanimod if clinically indicated. Dose-dependent reductions in absolute forced expiratory volume over 1 second (FEV1) and forced vital capacity (FVC) were seen as early as 3 months after treatment initiation during clinical trials. There is insufficient information to determine the reversibility of the decrease in FEV1 or FVC after drug discontinuation or whether changes are progressive with continued use.
Ozanimod increases the risk of macular edema. Perform an examination of the fundus including the macula in all patients at any time after a patient reports visual disturbance while on ozanimod therapy. Patients with a history of uveitis and patients with diabetes mellitus are at increased risk of macular edema during ozanimod receipt, and these patients should have regular follow-up ophthalmologic examinations. Continuation of ozanimod in patients with macular edema has not been evaluated. The decision to continue treatment in patients with macular edema should be based on the benefits and risks to the patient.
Ozanimod may increase the risk for infection. Delay initiation of ozanimod in patients with an active infection until the infection is resolved. Life-threatening and rare fatal infections have occurred in patients receiving ozanimod. Serious infections with opportunistic pathogens including viral infection (e.g., John Cunningham virus [JCV], herpes infection, varicella-zoster, human papillomavirus [HPV]), fungal infection (e.g., cryptococcal infection), and bacterial infection (e.g., atypical mycobacterial infection) have been reported with ozanimod use or the use of other sphingosine 1-phosphate receptor modulators. Prior to treatment initiation, obtain a recent (i.e., within 6 months or after discontinuation of prior MS or ulcerative colitis therapy) complete blood count (CBC) including lymphocyte count. Patients with signs and symptoms consistent with serious infections should undergo a prompt diagnostic evaluation and appropriate treatment. Consider interruption of treatment with ozanimod if any patient develops a serious infection. Because the elimination of ozanimod after discontinuation may take up to 3 months, continue monitoring after treatment discontinuation infections throughout this period. Ozanimod may be inappropriate for use in patients with leukemia, lymphoma, human immunodeficiency virus (HIV) infection, or acquired immunodeficiency syndrome (AIDS). Concomitant use of ozanimod with chemotherapy or corticosteroid therapy may increase the risk of immunosuppression. When switching from immune-modulating or immunosuppressive medications to ozanimod, consider the mode of action and duration of effect of these therapies to avoid unintended additive immunosuppressive effects, particularly when initiating other drugs within 4 weeks after the last dose of ozanimod. Test patients without a confirmed history of chickenpox or without documentation of a full course of vaccination against varicella-zoster virus (VZV) for antibodies to VZV prior to treatment initiation. Vaccinate antibody-negative patients prior to treatment initiation. Postpone ozanimod initiation for 1 month after vaccination to allow the full effect of vaccination to occur. Consider HPV vaccination prior to ozanimod treatment initiation, taking into account vaccination recommendations. Cancer screening, including a Papanicolaou (Pap) test in females, is recommended as per standard of care for patients using an immunosuppressive therapy. Administer live attenuated vaccines at least 1 month prior to ozanimod initiation. Avoid vaccination with live vaccines during treatment and for 3 months after ozanimod discontinuation due to potential immunosuppression and increased risk of infection during ozanimod therapy. A diminished vaccine response may occur if vaccinations are administered during ozanimod treatment.
Progressive multifocal leukoencephalopathy (PML) has occurred with other sphingosine 1-phosphate (S1P) receptor modulators, and may occur with ozanimod. As PML can be fatal, instruct patients to notify their healthcare provider immediately if they notice new or worsening neurological signs or symptoms such as ataxia, visual changes, or confusion. Similarly, suspect PML in any patient presenting with neurological symptoms; discontinue ozanimod at the first sign or symptom of PML and perform a clinical evaluation. Consider MRI monitoring for signs that may be consistent with PML. MRI findings suggestive of PML and detection of JC virus (JCV) DNA in the CSF in the absence of clinical signs and symptoms of PML have been reported in patients treated with other multiple sclerosis medications; many cases progressed to symptomatic PML. Promptly investigate any suspicious findings to allow for early diagnosis. Monitor for the development of immune reconstitution inflammatory syndrome (IRIS) (also known as immune reconstitution syndrome), in patients treated with a S1P modulator who develop PML and subsequently discontinue treatment. Cases of IRIS typically occurred within a few months after S1P modulator discontinuation. PML-associated IRIS may lead to rapid onset of serious neurological complications or death, and is often associated with characteristic changes on MRI. Appropriately treat any inflammation associated with IRIS. A case of posterior reversible encephalopathy syndrome (PRES) has been reported in patients receiving ozanimod. Symptoms reported included sudden onset of severe headache, altered mental status, visual disturbances, and seizure. Symptoms of PRES are usually reversible but may evolve into ischemic stroke or cerebral hemorrhage. A delay in diagnosis and treatment may lead to permanent neurological sequelae. If PRES is suspected, discontinue ozanimod and perform a clinical evaluation.
Ozanimod is not recommended for use in patients with severe hepatic impairment (Child-Pugh class C). Reduce the ozanimod dose in patients with mild hepatic impairment (Child-Pugh class A) or moderate hepatic impairment (Child-Pugh class B). Elevations of aminotransferases (ALT and AST) may occur in patients receiving ozanimod. Obtain serum transaminases (ALT and AST) and total bilirubin prior to treatment initiation (within 6 months). Monitor patients for signs of hepatotoxicity; those with preexisting severe hepatic disease may be at greater risk of adverse reactions. Promptly obtain liver transaminase and bilirubin concentrations in any patients who report symptoms that may indicate liver injury, such as new or worsening fatigue, anorexia, righter upper abdominal discomfort, dark urine, or jaundice. Discontinue ozanimod if significant hepatic injury is suspected. The median time to hepatic enzyme elevation, defined as 3 times the upper limit of normal (ULN) during clinical trials was 6 months. The majority of patients continued treatment with values returning to less than 3 times the ULN in approximately 2 to 4 weeks.
Limit sunlight (UV) exposure during ozanimod therapy due to an increased risk for skin cancer. Wear protective clothing and use a sunscreen with high protection factor. Basal cell carcinoma (BCC) and melanoma were reported during clinical trials for ozanimod, and an increased risk of cutaneous malignancies has been reported with another sphingosine 1-phosphate receptor modulator. Periodic skin examination is recommended for all patients, particularly those with risk factors for skin cancer. Providers and patients are advised to monitor for suspicious skin lesions. If a suspicious skin lesion is observed, it should be promptly evaluated.
There are no adequate and well-controlled studies of ozanimod use during human pregnancy. In animal studies, administration of ozanimod during pregnancy produced adverse effects on development, including embryolethality, an increase in fetal malformations, and neurobehavioral changes. In rabbits, fetal blood vessel malformations occurred at clinically relevant maternal ozanimod and metabolite exposures. Counsel women of childbearing age on the potential serious reproductive risk to the fetus. Discuss contraception requirements with the patient. Women should use effective contraception during treatment with ozanimod and for 3 months after discontinuation because of the time necessary for drug elimination from the body. The receptor affected by ozanimod (sphingosine-1-phosphate) has been demonstrated to have an important role in embryogenesis, including vascular and neural development. Increases in embryofetal mortality, increased fetal malformations and skeletal variations (abnormal/delayed ossification), and reduced fetal body weight occurred with oral administration of ozanimod (5 mg/kg/day) to female rats during organogenesis. The no-effect dose (1 mg/kg/day) for adverse effects on embryofetal development was approximately 60 times that in humans at the maximum recommended human dose (MRHD) of 0.92 mg/day based on plasma ozanimod exposure (AUC). Plasma AUCs for major active human metabolites, CC112273 and CC1084037, were similar to and less than, respectively, those in humans at the MRHD. Oral administration of ozanimod (0, 0.2, 0.6, or 2 mg/kg/day) to female rabbits during organogenesis resulted in a marked increase in embryofetal mortality at the highest dose tested and increased fetal malformations (malformed blood vessels) and skeletal variations at the mid and high doses. At the no-effect dose (0.2 mg/kg/day) for adverse effects on embryofetal development was approximately 2 times the MRHD based on plasma exposure. Plasma exposures for major active metabolites CC112273 and CC1084037 were less than those in humans at the MRHD. Bodyweight reductions, prolonged estrus cycle, and increased motor activity occurred in the offspring of rats given a dose of oral ozanimod 2 mg/kg/day throughout pregnancy and lactation. The no-effect dose (0.7 mg/kg/day) for adverse effects on embryofetal development was 30 times the MRHD based on plasma exposure. Plasma exposures for metabolites CC112273 and CC1084037 were less than those in humans at the MRHD. There is a pregnancy exposure registry that monitors outcomes in pregnant patients exposed to ozanimod; information about the registry can be obtained at www.zeposiapregnancyregistry.com or by calling 1-877-301-9314. This registry is only enrolling patients with multiple sclerosis and not patients with ulcerative colitis.
There are no data on the presence of ozanimod in human milk, the effects on the breastfed infant, or the effects on milk production. Following oral administration, ozanimod and/or metabolites were detected in the milk of lactating rat at levels higher than those in maternal plasma. It may be prudent to avoid this drug during breast-feeding until more data are available regarding infant safety. Glatiramer, interferon beta-1a, interferon beta-1b, may be potential alternatives to consider for the patient with multiple sclerosis who is breast-feeding. Consider the developmental and health benefits of breast-feeding along with the mother's clinical need for ozanimod and any potential adverse effects on the breastfed infant from ozanimod or the underlying maternal condition.
In patients with multiple sclerosis (MS), monitor for severe multiple sclerosis exacerbation after ozanimod discontinuation. Rare cases of severe disability increases with multiple new lesions on MRI have been observed after discontinuation of another sphingosine 1-phosphate receptor modulator, fingolimod. Exacerbations typically occurred within 12 weeks, although cases up to 24 weeks after treatment have been reported. The disability was more severe than typical MS relapses, as several patients who were able to walk without assistance while taking fingolimod progressed to needing wheelchairs or became bed-bound. Most patients did not return to the functional status they had before treatment discontinuation, and permanent disease worsening occurred in some cases. Advise patients of the potential risk of an exacerbation of their MS when ozanimod is discontinued, and to seek immediate medical attention if they experience new or worsened symptoms of MS. If an increase in disability occurs, test for new or enhancing lesions on MRI and begin appropriate treatment if clinically indicated.
Prior to ozanimod administration
-Obtain a recent (within the last 6 months or after discontinuation of prior MS or UC therapy) complete blood count, including lymphocyte count.
-Obtain an electrocardiogram (ECG) in all patients prior to ozanimod initiation. Certain patients with preexisting conditions also require a cardiac evaluation by an appropriately trained physician prior to treatment initiation.
-Determine whether patients are taking drugs that could slow heart rate or atrioventricular (AV) conduction prior to treatment initiation.
-Additionally, the history of use of immunosuppressive medications and their additive effects should be evaluated.
-Test patients without a confirmed history of chickenpox or without documentation of a full course of vaccination against varicella zoster virus (VZV) for antibodies to VZV prior to treatment initiation. Vaccinate antibody-negative patients prior to treatment initiation. Postpone ozanimod initiation for 1 month after vaccination to allow the full effect of vaccination to occur.
-Obtain serum transaminase (ALT and AST) and total bilirubin concentrations if they have not been acquired in the last 6 months.
-An ophthalmologic evaluation is also needed in patients with a history of uveitis or macular edema.
For the treatment of relapsing forms of multiple sclerosis, including clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease:
Oral dosage:
Adults: 0.23 mg PO once daily on days 1 to 4, then 0.46 mg PO once daily on days 5 to 7, and then 0.92 mg PO once daily.
For the treatment of moderately to severely active ulcerative colitis:
Oral dosage:
Adults: Initiate with a 7-day titration as follows: Days 1 to 4: Give 0.23 mg PO once daily. Days 5 to 7: Give 0.46 mg PO once daily. On day 8 and after that, give 0.92 mg PO once daily. If a dose is missed during the first 2 weeks of treatment, reinitiate treatment using the titration regimen.
Maximum Dosage Limits:
-Adults
0.92 mg/day PO.
-Geriatric
0.92 mg/day PO.
-Adolescents
Safety and efficacy have not been established.
-Children
Safety and efficacy have not been established.
-Infants
Safety and efficacy have not been established.
-Neonates
Safety and efficacy have not been established.
Patients with Hepatic Impairment Dosing
Mild hepatic impairment (Child-Pugh class A) or moderate hepatic impairment (Child-Pugh class B): Initiate with a 7-day titration as follows: Days 1 to 4: Give 0.23 mg PO once daily. Days 5 to 7: Give 0.46 mg PO once daily. On day 8 and after, the dose is 0.92 mg PO once every other day.
Severe hepatic impairment (Child-Pugh class C): Use not recommended.
Patients with Renal Impairment Dosing
No dosage adjustments are needed.
*non-FDA-approved indication
Acebutolol: (Moderate) Ozanimod may cause bradycardia and AV-conduction delays, which may be enhanced with the concomitant use of beta-blockers. If a calcium channel blocker that slows heart rate/cardiac conduction is also prescribed with ozanimod and a beta-blocker, a cardiologist should be consulted due to the likelyhood of additive effects.
Acetaminophen; Caffeine; Dihydrocodeine: (Major) If possible, do not use dihydrocodeine in patients taking MAO inhibitors or within 14 days of stopping them. Dihydrocodeine, like all opioid analgesics, interacts with MAO inhibitors causing central nervous system excitation, and an increased risk for serotonin syndrom and hypertension. An active metabolite of ozanimod inhibits MAO-B. MAO inhibitor interactions with dihydrocodeine may manifest as serotonin syndrome, hypertensive crisis, or opioid toxicity (e.g., respiratory depression, coma). Although a small number of patients treated with ozanimod were concomitantly exposed to opioids, this exposure was not adequate to rule out the possibility of an adverse reaction from coadministration.
Acetaminophen; Chlorpheniramine; Dextromethorphan: (Contraindicated) Coadministration of ozanimod with dextromethorphan is contraindicated. Allow at least 14 days between discontinuation of ozanimod and initiation of dextromethorphan. Consider if an alternative to dextromethorphan would be appropriate. An active metabolite of ozanimod inhibits MAO-B, which may increase the potential for serious and possibly fatal drug interactions with dextromethorphan, including serotonin syndrome.
Acetaminophen; Chlorpheniramine; Dextromethorphan; Phenylephrine: (Contraindicated) Coadministration of ozanimod with dextromethorphan is contraindicated. Allow at least 14 days between discontinuation of ozanimod and initiation of dextromethorphan. Consider if an alternative to dextromethorphan would be appropriate. An active metabolite of ozanimod inhibits MAO-B, which may increase the potential for serious and possibly fatal drug interactions with dextromethorphan, including serotonin syndrome. (Major) Coadministration of ozanimod with sympathomimetics such as phenylephrine is not routinely recommended due to the potential for hypertensive crisis. If coadministration is medically necessary, closely monitor the patient for hypertension. An active metabolite of ozanimod inhibits MAO-B, which may increase the potential for hypertensive crisis. Sympathomimetics may increase blood pressure by increasing norepinephrine concentrations and monoamine oxidase inhibitors (MAOIs) are known to potentiate these effects. Concomitant use of ozanimod with pseudoephedrine did not potentiate the effects on blood pressure. However, hypertensive crisis has occurred with administration of ozanimod alone and also during coadministration of sympathomimetic medications and other selective or nonselective MAO inhibitors.
Acetaminophen; Chlorpheniramine; Dextromethorphan; Pseudoephedrine: (Contraindicated) Coadministration of ozanimod with dextromethorphan is contraindicated. Allow at least 14 days between discontinuation of ozanimod and initiation of dextromethorphan. Consider if an alternative to dextromethorphan would be appropriate. An active metabolite of ozanimod inhibits MAO-B, which may increase the potential for serious and possibly fatal drug interactions with dextromethorphan, including serotonin syndrome. (Major) Coadministration of ozanimod with sympathomimetics such as pseudoephedrine is not routinely recommended due to the potential for hypertensive crisis. If coadministration is medically necessary, closely monitor the patient for hypertension. An active metabolite of ozanimod inhibits MAO-B, which may increase the potential for hypertensive crisis. Sympathomimetics may increase blood pressure by increasing norepinephrine concentrations and monoamine oxidase inhibitors (MAOIs) are known to potentiate these effects. Concomitant use of ozanimod with pseudoephedrine did not potentiate the effects on blood pressure. However, hypertensive crisis has occurred with administration of ozanimod alone and also during coadministration of sympathomimetic medications and other selective or nonselective MAO inhibitors.
Acetaminophen; Chlorpheniramine; Phenylephrine : (Major) Coadministration of ozanimod with sympathomimetics such as phenylephrine is not routinely recommended due to the potential for hypertensive crisis. If coadministration is medically necessary, closely monitor the patient for hypertension. An active metabolite of ozanimod inhibits MAO-B, which may increase the potential for hypertensive crisis. Sympathomimetics may increase blood pressure by increasing norepinephrine concentrations and monoamine oxidase inhibitors (MAOIs) are known to potentiate these effects. Concomitant use of ozanimod with pseudoephedrine did not potentiate the effects on blood pressure. However, hypertensive crisis has occurred with administration of ozanimod alone and also during coadministration of sympathomimetic medications and other selective or nonselective MAO inhibitors.
Acetaminophen; Codeine: (Contraindicated) Do not use codeine in patients taking MAOIs or within 14 days of stopping them. An active metabolite of ozanimod inhibits MAO-B. MAO inhibitor interactions with codeine may manifest as serotonin syndrome, hypertensive crisis, or opioid toxicity (e.g., respiratory depression, coma). Although a small number of patients treated with ozanimod were concomitantly exposed to opioids, this exposure was not adequate to rule out the possibility of an adverse reaction from coadministration.
Acetaminophen; Dextromethorphan: (Contraindicated) Coadministration of ozanimod with dextromethorphan is contraindicated. Allow at least 14 days between discontinuation of ozanimod and initiation of dextromethorphan. Consider if an alternative to dextromethorphan would be appropriate. An active metabolite of ozanimod inhibits MAO-B, which may increase the potential for serious and possibly fatal drug interactions with dextromethorphan, including serotonin syndrome.
Acetaminophen; Dextromethorphan; Doxylamine: (Contraindicated) Coadministration of ozanimod with dextromethorphan is contraindicated. Allow at least 14 days between discontinuation of ozanimod and initiation of dextromethorphan. Consider if an alternative to dextromethorphan would be appropriate. An active metabolite of ozanimod inhibits MAO-B, which may increase the potential for serious and possibly fatal drug interactions with dextromethorphan, including serotonin syndrome.
Acetaminophen; Dextromethorphan; Guaifenesin; Phenylephrine: (Contraindicated) Coadministration of ozanimod with dextromethorphan is contraindicated. Allow at least 14 days between discontinuation of ozanimod and initiation of dextromethorphan. Consider if an alternative to dextromethorphan would be appropriate. An active metabolite of ozanimod inhibits MAO-B, which may increase the potential for serious and possibly fatal drug interactions with dextromethorphan, including serotonin syndrome. (Major) Coadministration of ozanimod with sympathomimetics such as phenylephrine is not routinely recommended due to the potential for hypertensive crisis. If coadministration is medically necessary, closely monitor the patient for hypertension. An active metabolite of ozanimod inhibits MAO-B, which may increase the potential for hypertensive crisis. Sympathomimetics may increase blood pressure by increasing norepinephrine concentrations and monoamine oxidase inhibitors (MAOIs) are known to potentiate these effects. Concomitant use of ozanimod with pseudoephedrine did not potentiate the effects on blood pressure. However, hypertensive crisis has occurred with administration of ozanimod alone and also during coadministration of sympathomimetic medications and other selective or nonselective MAO inhibitors.
Acetaminophen; Dextromethorphan; Guaifenesin; Pseudoephedrine: (Contraindicated) Coadministration of ozanimod with dextromethorphan is contraindicated. Allow at least 14 days between discontinuation of ozanimod and initiation of dextromethorphan. Consider if an alternative to dextromethorphan would be appropriate. An active metabolite of ozanimod inhibits MAO-B, which may increase the potential for serious and possibly fatal drug interactions with dextromethorphan, including serotonin syndrome. (Major) Coadministration of ozanimod with sympathomimetics such as pseudoephedrine is not routinely recommended due to the potential for hypertensive crisis. If coadministration is medically necessary, closely monitor the patient for hypertension. An active metabolite of ozanimod inhibits MAO-B, which may increase the potential for hypertensive crisis. Sympathomimetics may increase blood pressure by increasing norepinephrine concentrations and monoamine oxidase inhibitors (MAOIs) are known to potentiate these effects. Concomitant use of ozanimod with pseudoephedrine did not potentiate the effects on blood pressure. However, hypertensive crisis has occurred with administration of ozanimod alone and also during coadministration of sympathomimetic medications and other selective or nonselective MAO inhibitors.
Acetaminophen; Dextromethorphan; Phenylephrine: (Contraindicated) Coadministration of ozanimod with dextromethorphan is contraindicated. Allow at least 14 days between discontinuation of ozanimod and initiation of dextromethorphan. Consider if an alternative to dextromethorphan would be appropriate. An active metabolite of ozanimod inhibits MAO-B, which may increase the potential for serious and possibly fatal drug interactions with dextromethorphan, including serotonin syndrome. (Major) Coadministration of ozanimod with sympathomimetics such as phenylephrine is not routinely recommended due to the potential for hypertensive crisis. If coadministration is medically necessary, closely monitor the patient for hypertension. An active metabolite of ozanimod inhibits MAO-B, which may increase the potential for hypertensive crisis. Sympathomimetics may increase blood pressure by increasing norepinephrine concentrations and monoamine oxidase inhibitors (MAOIs) are known to potentiate these effects. Concomitant use of ozanimod with pseudoephedrine did not potentiate the effects on blood pressure. However, hypertensive crisis has occurred with administration of ozanimod alone and also during coadministration of sympathomimetic medications and other selective or nonselective MAO inhibitors.
Acetaminophen; Dextromethorphan; Pseudoephedrine: (Contraindicated) Coadministration of ozanimod with dextromethorphan is contraindicated. Allow at least 14 days between discontinuation of ozanimod and initiation of dextromethorphan. Consider if an alternative to dextromethorphan would be appropriate. An active metabolite of ozanimod inhibits MAO-B, which may increase the potential for serious and possibly fatal drug interactions with dextromethorphan, including serotonin syndrome. (Major) Coadministration of ozanimod with sympathomimetics such as pseudoephedrine is not routinely recommended due to the potential for hypertensive crisis. If coadministration is medically necessary, closely monitor the patient for hypertension. An active metabolite of ozanimod inhibits MAO-B, which may increase the potential for hypertensive crisis. Sympathomimetics may increase blood pressure by increasing norepinephrine concentrations and monoamine oxidase inhibitors (MAOIs) are known to potentiate these effects. Concomitant use of ozanimod with pseudoephedrine did not potentiate the effects on blood pressure. However, hypertensive crisis has occurred with administration of ozanimod alone and also during coadministration of sympathomimetic medications and other selective or nonselective MAO inhibitors.
Acetaminophen; Guaifenesin; Phenylephrine: (Major) Coadministration of ozanimod with sympathomimetics such as phenylephrine is not routinely recommended due to the potential for hypertensive crisis. If coadministration is medically necessary, closely monitor the patient for hypertension. An active metabolite of ozanimod inhibits MAO-B, which may increase the potential for hypertensive crisis. Sympathomimetics may increase blood pressure by increasing norepinephrine concentrations and monoamine oxidase inhibitors (MAOIs) are known to potentiate these effects. Concomitant use of ozanimod with pseudoephedrine did not potentiate the effects on blood pressure. However, hypertensive crisis has occurred with administration of ozanimod alone and also during coadministration of sympathomimetic medications and other selective or nonselective MAO inhibitors.
Acetaminophen; Hydrocodone: (Major) When possible, hydrocodone should not be used in patients taking MAOIs or within 14 days of stopping such treatment. An active metabolite of ozanimod inhibits MAO-B. MAO inhibitor interactions with hydrocodone may manifest as serotonin syndrome, hypertensive crisis, or opioid toxicity (e.g., respiratory depression, coma). If concurrent use is absolutely necessary, use the lowest possible doses of hydrocodone, and monitor blood pressure and for serotonergic symptoms closely. Although a small number of patients treated with ozanimod were concomitantly exposed to opioids, this exposure was not adequate to rule out the possibility of an adverse reaction from coadministration.
Acetaminophen; Oxycodone: (Major) When possible, oxycodone should not be used in patients taking MAOIs or within 14 days of stopping such treatment. An active metabolite of ozanimod inhibits MAO-B. MAO inhibitor interactions with oxycodone may manifest as serotonin syndrome, hypertensive crisis, or opioid toxicity (e.g., respiratory depression, coma). If concurrent use is absolutely necessary, use the lowest possible doses of oxycodone, and monitor blood pressure and for serotonergic symptoms closely. Although a small number of patients treated with ozanimod were concomitantly exposed to opioids, this exposure was not adequate to rule out the possibility of an adverse reaction from coadministration.
Acetaminophen; Phenylephrine: (Major) Coadministration of ozanimod with sympathomimetics such as phenylephrine is not routinely recommended due to the potential for hypertensive crisis. If coadministration is medically necessary, closely monitor the patient for hypertension. An active metabolite of ozanimod inhibits MAO-B, which may increase the potential for hypertensive crisis. Sympathomimetics may increase blood pressure by increasing norepinephrine concentrations and monoamine oxidase inhibitors (MAOIs) are known to potentiate these effects. Concomitant use of ozanimod with pseudoephedrine did not potentiate the effects on blood pressure. However, hypertensive crisis has occurred with administration of ozanimod alone and also during coadministration of sympathomimetic medications and other selective or nonselective MAO inhibitors.
Acetaminophen; Pseudoephedrine: (Major) Coadministration of ozanimod with sympathomimetics such as pseudoephedrine is not routinely recommended due to the potential for hypertensive crisis. If coadministration is medically necessary, closely monitor the patient for hypertension. An active metabolite of ozanimod inhibits MAO-B, which may increase the potential for hypertensive crisis. Sympathomimetics may increase blood pressure by increasing norepinephrine concentrations and monoamine oxidase inhibitors (MAOIs) are known to potentiate these effects. Concomitant use of ozanimod with pseudoephedrine did not potentiate the effects on blood pressure. However, hypertensive crisis has occurred with administration of ozanimod alone and also during coadministration of sympathomimetic medications and other selective or nonselective MAO inhibitors.
Acrivastine; Pseudoephedrine: (Major) Coadministration of ozanimod with sympathomimetics such as pseudoephedrine is not routinely recommended due to the potential for hypertensive crisis. If coadministration is medically necessary, closely monitor the patient for hypertension. An active metabolite of ozanimod inhibits MAO-B, which may increase the potential for hypertensive crisis. Sympathomimetics may increase blood pressure by increasing norepinephrine concentrations and monoamine oxidase inhibitors (MAOIs) are known to potentiate these effects. Concomitant use of ozanimod with pseudoephedrine did not potentiate the effects on blood pressure. However, hypertensive crisis has occurred with administration of ozanimod alone and also during coadministration of sympathomimetic medications and other selective or nonselective MAO inhibitors.
Adagrasib: (Major) Concomitant use of adagrasib and ozanimod increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. Ozanimod has a limited effect on the QT/QTc interval at therapeutic doses but may cause bradycardia and atrioventricular conduction delays which may increase the risk for TdP in patients with a prolonged QT/QTc interval.
Alemtuzumab: (Major) Initiating treatment with ozanimod after alemtuzumab treatment is not recommended due to the characteristics and duration of the immunosuppressive effects of alemtuzumab.
Alfentanil: (Major) When alfentanil is administered to patients who have received ozanimod within 14 days, monitor patients for hypertension and ensure ready availability of vasodilators and beta-blockers for the treatment of hypertension as needed. Severe and unpredictable potentiation of monoamine oxidase (MAO) inhibitors has been reported rarely with alfentanil. An active metabolite of ozanimod inhibits MAO-B. The MAOI interactions with opioids may also manifest as serotonin syndrome or opioid toxicity (e.g., respiratory depression, coma).
Alfuzosin: (Major) In general, do not initiate ozanimod in patients taking alfuzosin due to the risk of additive bradycardia, QT prolongation, and torsade de pointes (TdP). If treatment initiation is considered, seek advice from a cardiologist. Ozanimod initiation may result in a transient decrease in heart rate and atrioventricular conduction delays. Ozanimod has not been studied in patients taking concurrent QT prolonging drugs; however, QT prolonging drugs have been associated with TdP in patients with bradycardia. Alfuzosin may prolong the QT interval in a dose-dependent manner.
Almotriptan: (Major) Coadministration of ozanimod with serotonin receptor agonists "triptans" is not recommended due to the potential for hypertensive crisis or serotonin syndrome. If coadministration is necessary, closely monitor patients for hypertension and serotonergic effects. An active metabolite of ozanimod inhibits MAO-B, which may increase the potential for hypertensive crisis or serotonin syndrome. Serotonin receptor agonists may increase blood pressure by increasing serotonin concentrations.
Amiodarone: (Major) Concomitant use of amiodarone and ozanimod increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. Ozanimod has a limited effect on the QT/QTc interval at therapeutic doses but may cause bradycardia and atrioventricular conduction delays which may increase the risk for TdP in patients with a prolonged QT/QTc interval. Due to the extremely long half-life of amiodarone, a drug interaction is possible for days to weeks after drug discontinuation.
Amisulpride: (Major) In general, do not initiate ozanimod in patients taking amisulpride due to the risk of additive bradycardia, QT prolongation, and torsade de pointes (TdP). If treatment initiation is considered, monitor ECGs. Ozanimod initiation may result in a transient decrease in heart rate and atrioventricular conduction delays. Ozanimod has not been studied in patients taking concurrent QT prolonging drugs; however, QT prolonging drugs have been associated with TdP in patients with bradycardia. Amisulpride causes dose- and concentration-dependent QT prolongation.
Amitriptyline: (Contraindicated) Do not use tricyclic antidepressants (TCAs) in patients taking MAOIs or within 14 days of stopping them. An active metabolite of ozanimod inhibits MAO-B, and interactions with TCAs may manifest as serotonin syndrome, hypertensive crisis, QT prolongation or other serious side effects. Hyperpyretic crises, severe convulsions, and deaths have occurred in patients receiving TCAs and MAO inhibiting drugs simultaneously. Consider an alternative to the TCA. Ozanimod is a monoamine oxidase inhibitor that may result in a transient decrease in heart rate and atrioventricular conduction delays. Ozanimod has not been studied in patients taking concurrent QT prolonging drugs; however, QT prolonging drugs have been associated with TdP in patients with bradycardia. TCAs are serotonergic drugs that share pharmacologic properties similar to the Class IA antiarrhythmic agents and may prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations).
Amoxapine: (Contraindicated) Do not use amoxapine in patients taking MAOIs or within 14 days of stopping them. An active metabolite of ozanimod inhibits MAO-B, and interactions with amoxapine may manifest as serotonin syndrome, hypertensive crisis, QT prolongation or other serious side effects. Hyperpyretic crises, severe convulsions, and deaths have occurred in patients receiving cyclic antidepressants and MAO inhibiting drugs simultaneously. Consider an alternative to amoxapine. Ozanimod is a monoamine oxidase inhibitor that may result in a transient decrease in heart rate and atrioventricular conduction delays. Ozanimod has not been studied in patients taking concurrent QT prolonging drugs and there are limited data for the use of amoxapine in combination with other QT-prolonging drugs.
Amoxicillin; Clarithromycin; Omeprazole: (Major) In general, do not initiate ozanimod in patients taking clarithromycin due to the risk of additive bradycardia, QT prolongation, and torsade de pointes (TdP). If treatment initiation is considered, seek advice from a cardiologist. Ozanimod initiation may result in a transient decrease in heart rate and atrioventricular conduction delays. Ozanimod has not been studied in patients taking concurrent QT prolonging drugs; however, QT prolonging drugs have been associated with TdP in patients with bradycardia. Clarithromycin is associated with an established risk for QT prolongation and TdP.
Amphetamine: (Major) Avoid concurrent use of ozanimod and amphetamines when possible as this combination may increase the risk for serious adverse reactions such as hypertensive crisis. If use is necessary, monitor for hypertension. Amphetamines may increase blood pressure by increasing norepinephrine and serotonin concentrations and monoamine oxidase inhibitors (MAOIs) are known to potentiate these effects. An active metabolite of ozanimod inhibits MAO-B in vitro. Sympathomimetics are contraindicated for use with non-selective MAOIs, however the risk for hypertensive reactions may be lower with selective MAO-B inhibitors.
Amphetamine; Dextroamphetamine: (Major) Avoid concurrent use of ozanimod and amphetamines when possible as this combination may increase the risk for serious adverse reactions such as hypertensive crisis. If use is necessary, monitor for hypertension. Amphetamines may increase blood pressure by increasing norepinephrine and serotonin concentrations and monoamine oxidase inhibitors (MAOIs) are known to potentiate these effects. An active metabolite of ozanimod inhibits MAO-B in vitro. Sympathomimetics are contraindicated for use with non-selective MAOIs, however the risk for hypertensive reactions may be lower with selective MAO-B inhibitors.
Amphetamines: (Major) Avoid concurrent use of ozanimod and amphetamines when possible as this combination may increase the risk for serious adverse reactions such as hypertensive crisis. If use is necessary, monitor for hypertension. Amphetamines may increase blood pressure by increasing norepinephrine and serotonin concentrations and monoamine oxidase inhibitors (MAOIs) are known to potentiate these effects. An active metabolite of ozanimod inhibits MAO-B in vitro. Sympathomimetics are contraindicated for use with non-selective MAOIs, however the risk for hypertensive reactions may be lower with selective MAO-B inhibitors.
Anagrelide: (Major) In general, do not initiate ozanimod in patients taking anagrelide due to the risk of additive bradycardia, QT prolongation, and torsade de pointes (TdP). If treatment initiation is considered, seek advice from a cardiologist. Ozanimod initiation may result in a transient decrease in heart rate and atrioventricular conduction delays. Ozanimod has not been studied in patients taking concurrent QT prolonging drugs; however, QT prolonging drugs have been associated with TdP in patients with bradycardia. TdP and ventricular tachycardia have been reported with anagrelide. In addition, dose-related increases in mean QTc and heart rate were observed in healthy subjects.
Apomorphine: (Major) In general, do not initiate ozanimod in patients taking apomorphine due to the risk of additive bradycardia, QT prolongation, and torsade de pointes (TdP). If treatment initiation is considered, seek advice from a cardiologist. Ozanimod initiation may result in a transient decrease in heart rate and atrioventricular conduction delays. Ozanimod has not been studied in patients taking concurrent QT prolonging drugs; however, QT prolonging drugs have been associated with TdP in patients with bradycardia. Dose-related QTc prolongation is associated with therapeutic apomorphine exposure.
Aripiprazole: (Major) In general, do not initiate ozanimod in patients taking aripiprazole due to the risk of additive bradycardia, QT prolongation, and torsade de pointes (TdP). If treatment initiation is considered, seek advice from a cardiologist. Ozanimod initiation may result in a transient decrease in heart rate and atrioventricular conduction delays. Ozanimod has not been studied in patients taking concurrent QT prolonging drugs; however, QT prolonging drugs have been associated with TdP in patients with bradycardia. QT prolongation has occurred during therapeutic use of aripiprazole and following overdose.
Arsenic Trioxide: (Major) Avoid concomitant use of arsenic trioxide and ozanimod due to the potential for additive QT prolongation; discontinue or select an alternative drug that does not prolong the QT interval prior to starting arsenic trioxide therapy. If concomitant drug use is unavoidable, consult cardiology and frequently monitor ECGs. Torsade de pointes (TdP), QT interval prolongation, and complete atrioventricular block have been reported with arsenic trioxide use. Ozanimod initiation may result in a transient decrease in heart rate and atrioventricular conduction delays. Ozanimod has not been studied in patients taking concurrent QT prolonging drugs; however, QT prolonging drugs have been associated with TdP in patients with bradycardia.
Artemether; Lumefantrine: (Major) Avoid coadministration of artemether; lumefantrine with ozanimod due to the potential for additive QT prolongation. Consider ECG monitoring and consultation with cardiology if ozanimod must be used with or after artemether; lumefantrine treatment. Artemether; lumefantrine is associated with prolongation of the QT interval. Ozanimod initiation may result in a transient decrease in heart rate and atrioventricular conduction delays. Ozanimod has not been studied in patients taking concurrent QT prolonging drugs; however, QT prolonging drugs have been associated with TdP in patients with bradycardia. (Major) Avoid coadministration of artemether; lumefantrine with ozanimod due to the potential for additive QT prolongation. Consider ECG monitoring if ozanimod must be used with or after artemether; lumefantrine treatment. Artemether; lumefantrine is associated with prolongation of the QT interval. Ozanimod initiation may result in a transient decrease in heart rate and atrioventricular conduction delays. Ozanimod has not been studied in patients taking concurrent QT prolonging drugs; however, QT prolonging drugs have been associated with TdP in patients with bradycardia.
Articaine; Epinephrine: (Major) Coadministration of ozanimod with sympathomimetics such as epinephrine is not routinely recommended due to the potential for hypertensive crisis. If coadministration is medically necessary, closely monitor the patient for hypertension. An active metabolite of ozanimod inhibits MAO-B, which may increase the potential for hypertensive crisis. Sympathomimetics may increase blood pressure by increasing norepinephrine concentrations and monoamine oxidase inhibitors (MAOIs) are known to potentiate these effects. Concomitant use of ozanimod with pseudoephedrine did not potentiate the effects on blood pressure. However, hypertensive crisis has occurred with administration of ozanimod alone and also during coadministration of sympathomimetic medications and other selective or nonselective MAO inhibitors.
Asenapine: (Major) In general, do not initiate ozanimod in patients taking asenapine due to the risk of additive bradycardia, QT prolongation, and torsade de pointes (TdP). If treatment initiation is considered, seek advice from a cardiologist. Ozanimod initiation may result in a transient decrease in heart rate and atrioventricular conduction delays. Ozanimod has not been studied in patients taking concurrent QT prolonging drugs; however, QT prolonging drugs have been associated with TdP in patients with bradycardia. Asenapine has been associated with QT prolongation.
Aspirin, ASA; Carisoprodol; Codeine: (Contraindicated) Do not use codeine in patients taking MAOIs or within 14 days of stopping them. An active metabolite of ozanimod inhibits MAO-B. MAO inhibitor interactions with codeine may manifest as serotonin syndrome, hypertensive crisis, or opioid toxicity (e.g., respiratory depression, coma). Although a small number of patients treated with ozanimod were concomitantly exposed to opioids, this exposure was not adequate to rule out the possibility of an adverse reaction from coadministration.
Aspirin, ASA; Oxycodone: (Major) When possible, oxycodone should not be used in patients taking MAOIs or within 14 days of stopping such treatment. An active metabolite of ozanimod inhibits MAO-B. MAO inhibitor interactions with oxycodone may manifest as serotonin syndrome, hypertensive crisis, or opioid toxicity (e.g., respiratory depression, coma). If concurrent use is absolutely necessary, use the lowest possible doses of oxycodone, and monitor blood pressure and for serotonergic symptoms closely. Although a small number of patients treated with ozanimod were concomitantly exposed to opioids, this exposure was not adequate to rule out the possibility of an adverse reaction from coadministration.
Atenolol: (Moderate) Ozanimod may cause bradycardia and AV-conduction delays, which may be enhanced with the concomitant use of beta-blockers. If a calcium channel blocker that slows heart rate/cardiac conduction is also prescribed with ozanimod and a beta-blocker, a cardiologist should be consulted due to the likelyhood of additive effects.
Atenolol; Chlorthalidone: (Moderate) Ozanimod may cause bradycardia and AV-conduction delays, which may be enhanced with the concomitant use of beta-blockers. If a calcium channel blocker that slows heart rate/cardiac conduction is also prescribed with ozanimod and a beta-blocker, a cardiologist should be consulted due to the likelyhood of additive effects.
Atomoxetine: (Major) In general, do not initiate ozanimod in patients taking atomoxetine due to the risk of additive bradycardia, QT prolongation, and torsade de pointes (TdP). Increased blood pressure or hypertensive crisis may also be possible, as atomoxetine may increase heart rate and blood pressure. If treatment initiation is considered, seek advice from a cardiologist. Ozanimod initiation may result in a transient decrease in heart rate and atrioventricular conduction delays. Ozanimod has not been studied in patients taking concurrent QT prolonging drugs; however, QT prolonging drugs have been associated with TdP in patients with bradycardia. QT prolongation has occurred during therapeutic use of atomoxetine and following overdose.
Azithromycin: (Major) Avoid coadministration of azithromycin with ozanimod due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. QT prolongation and torsade de pointes (TdP) have been spontaneously reported during azithromycin postmarketing surveillance. Ozanimod initiation may result in a transient decrease in heart rate and atrioventricular conduction delays. Ozanimod has not been studied in patients taking concurrent QT prolonging drugs; however, QT prolonging drugs have been associated with TdP in patients with bradycardia.
Bacillus Calmette-Guerin Vaccine, BCG: (Major) Avoid the use of live vaccines and live attenuated vaccines during ozanimod treatment and for up to 3 months after discontinuation of ozanimod treatment. Live vaccinations may be less effective during ozanimod treatment and also may carry the risk of infection.
Bedaquiline: (Major) In general, do not initiate ozanimod in patients taking bedaquiline due to the risk of additive bradycardia, QT prolongation, and torsade de pointes (TdP). If concomitant use is unavoidable, monitor ECGs and consult cardiology. Discontinue bedaquiline if evidence of serious ventricular arrhythmia or QTcF interval greater than 500 ms. Bedaquiline prolongs the QT interval. Ozanimod initiation may result in a transient decrease in heart rate and atrioventricular conduction delays. Ozanimod has not been studied in patients taking concurrent QT prolonging drugs; however, QT prolonging drugs have been associated with TdP in patients with bradycardia.
Belladonna; Opium: (Contraindicated) Do not use opium in patients taking MAOIs or within 14 days of stopping them. An active metabolite of ozanimod inhibits MAO-B. MAO inhibitor interactions with opium may manifest as serotonin syndrome, hypertensive crisis, or opioid toxicity (e.g., respiratory depression, coma). Although a small number of patients treated with ozanimod were concomitantly exposed to opioids, this exposure was not adequate to rule out the possibility of an adverse reaction from coadministration.
Benzhydrocodone; Acetaminophen: (Major) Do not use benzhydrocodone in patients taking MAOIs or within 14 days of stopping them. An active metabolite of ozanimod inhibits MAO-B. MAO inhibitor interactions with benzhydrocodone may manifest as serotonin syndrome, hypertensive crisis, or opioid toxicity (e.g., respiratory depression, coma). Although a small number of patients treated with ozanimod were concomitantly exposed to opioids, this exposure was not adequate to rule out the possibility of an adverse reaction from coadministration.
Benzoic Acid; Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate: (Major) Concurrent use of intravenous (IV) methylene blue and drugs with selective MAOI activity, such as ozanimod, should generally be avoided due to the potential for serotonin syndrome. If emergent treatment with methylene blue is required in a patient receiving an MAOI it is advisable to discontinue the MAOI and monitor the patient for symptoms of CNS toxicity for two weeks or until 24 hours after the last dose of methylene blue, whichever comes first. During non-emergent use of methylene blue, it is advisable to discontinue ozanimod at least 2 weeks prior to methylene blue treatment, taking into consideration the half-life of ozanimod. Because the metabolites of ozanimod inhibit primarily monoamine oxidase-B (MAO-B), an interaction may be less likely to occur than with other traditional MAOIs. Methylene blue is a thiazine dye that is also a potent, reversible inhibitor of the enzyme responsible for the catabolism of serotonin in the brain (MAO-A). Cases of serotonin syndrome have been reported, primarily following administration of IV methylene blue (1 to 8 mg/kg) as a visualizing agent in patients receiving serotonergic agents.
Benzphetamine: (Major) Avoid concurrent use of ozanimod and amphetamines when possible as this combination may increase the risk for serious adverse reactions such as hypertensive crisis. If use is necessary, monitor for hypertension. Amphetamines may increase blood pressure by increasing norepinephrine and serotonin concentrations and monoamine oxidase inhibitors (MAOIs) are known to potentiate these effects. An active metabolite of ozanimod inhibits MAO-B in vitro. Sympathomimetics are contraindicated for use with non-selective MAOIs, however the risk for hypertensive reactions may be lower with selective MAO-B inhibitors.
Beta-blockers (without QT/QTc prolongation): (Moderate) Ozanimod may cause bradycardia and AV-conduction delays, which may be enhanced with the concomitant use of beta-blockers. If a calcium channel blocker that slows heart rate/cardiac conduction is also prescribed with ozanimod and a beta-blocker, a cardiologist should be consulted due to the likelyhood of additive effects.
Betamethasone: (Moderate) Concomitant use of ozanimod with systemic betamethasone may increase the risk of immunosuppression. Monitor patients carefully for signs and symptoms of infection. In clinical studies for ulcerative colitis, the use of systemic corticosteroids did not appear to influence safety or efficacy of ozanimod.
Betaxolol: (Moderate) Ozanimod may cause bradycardia and AV-conduction delays, which may be enhanced with the concomitant use of beta-blockers. If a calcium channel blocker that slows heart rate/cardiac conduction is also prescribed with ozanimod and a beta-blocker, a cardiologist should be consulted due to the likelyhood of additive effects.
Bismuth Subcitrate Potassium; Metronidazole; Tetracycline: (Major) Concomitant use of metronidazole and ozanimod increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. Ozanimod has a limited effect on the QT/QTc interval at therapeutic doses but may cause bradycardia and atrioventricular conduction delays which may increase the risk for TdP in patients with a prolonged QT/QTc interval.
Bismuth Subsalicylate; Metronidazole; Tetracycline: (Major) Concomitant use of metronidazole and ozanimod increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. Ozanimod has a limited effect on the QT/QTc interval at therapeutic doses but may cause bradycardia and atrioventricular conduction delays which may increase the risk for TdP in patients with a prolonged QT/QTc interval.
Bisoprolol: (Moderate) Ozanimod may cause bradycardia and AV-conduction delays, which may be enhanced with the concomitant use of beta-blockers. If a calcium channel blocker that slows heart rate/cardiac conduction is also prescribed with ozanimod and a beta-blocker, a cardiologist should be consulted due to the likelyhood of additive effects.
Bisoprolol; Hydrochlorothiazide, HCTZ: (Moderate) Ozanimod may cause bradycardia and AV-conduction delays, which may be enhanced with the concomitant use of beta-blockers. If a calcium channel blocker that slows heart rate/cardiac conduction is also prescribed with ozanimod and a beta-blocker, a cardiologist should be consulted due to the likelyhood of additive effects.
Brimonidine; Timolol: (Moderate) Ozanimod may cause bradycardia and AV-conduction delays, which may be enhanced with the concomitant use of beta-blockers. If a calcium channel blocker that slows heart rate/cardiac conduction is also prescribed with ozanimod and a beta-blocker, a cardiologist should be consulted due to the likelyhood of additive effects.
Brompheniramine; Dextromethorphan; Phenylephrine: (Contraindicated) Coadministration of ozanimod with dextromethorphan is contraindicated. Allow at least 14 days between discontinuation of ozanimod and initiation of dextromethorphan. Consider if an alternative to dextromethorphan would be appropriate. An active metabolite of ozanimod inhibits MAO-B, which may increase the potential for serious and possibly fatal drug interactions with dextromethorphan, including serotonin syndrome. (Major) Coadministration of ozanimod with sympathomimetics such as phenylephrine is not routinely recommended due to the potential for hypertensive crisis. If coadministration is medically necessary, closely monitor the patient for hypertension. An active metabolite of ozanimod inhibits MAO-B, which may increase the potential for hypertensive crisis. Sympathomimetics may increase blood pressure by increasing norepinephrine concentrations and monoamine oxidase inhibitors (MAOIs) are known to potentiate these effects. Concomitant use of ozanimod with pseudoephedrine did not potentiate the effects on blood pressure. However, hypertensive crisis has occurred with administration of ozanimod alone and also during coadministration of sympathomimetic medications and other selective or nonselective MAO inhibitors.
Brompheniramine; Phenylephrine: (Major) Coadministration of ozanimod with sympathomimetics such as phenylephrine is not routinely recommended due to the potential for hypertensive crisis. If coadministration is medically necessary, closely monitor the patient for hypertension. An active metabolite of ozanimod inhibits MAO-B, which may increase the potential for hypertensive crisis. Sympathomimetics may increase blood pressure by increasing norepinephrine concentrations and monoamine oxidase inhibitors (MAOIs) are known to potentiate these effects. Concomitant use of ozanimod with pseudoephedrine did not potentiate the effects on blood pressure. However, hypertensive crisis has occurred with administration of ozanimod alone and also during coadministration of sympathomimetic medications and other selective or nonselective MAO inhibitors.
Brompheniramine; Pseudoephedrine: (Major) Coadministration of ozanimod with sympathomimetics such as pseudoephedrine is not routinely recommended due to the potential for hypertensive crisis. If coadministration is medically necessary, closely monitor the patient for hypertension. An active metabolite of ozanimod inhibits MAO-B, which may increase the potential for hypertensive crisis. Sympathomimetics may increase blood pressure by increasing norepinephrine concentrations and monoamine oxidase inhibitors (MAOIs) are known to potentiate these effects. Concomitant use of ozanimod with pseudoephedrine did not potentiate the effects on blood pressure. However, hypertensive crisis has occurred with administration of ozanimod alone and also during coadministration of sympathomimetic medications and other selective or nonselective MAO inhibitors.
Brompheniramine; Pseudoephedrine; Dextromethorphan: (Contraindicated) Coadministration of ozanimod with dextromethorphan is contraindicated. Allow at least 14 days between discontinuation of ozanimod and initiation of dextromethorphan. Consider if an alternative to dextromethorphan would be appropriate. An active metabolite of ozanimod inhibits MAO-B, which may increase the potential for serious and possibly fatal drug interactions with dextromethorphan, including serotonin syndrome. (Major) Coadministration of ozanimod with sympathomimetics such as pseudoephedrine is not routinely recommended due to the potential for hypertensive crisis. If coadministration is medically necessary, closely monitor the patient for hypertension. An active metabolite of ozanimod inhibits MAO-B, which may increase the potential for hypertensive crisis. Sympathomimetics may increase blood pressure by increasing norepinephrine concentrations and monoamine oxidase inhibitors (MAOIs) are known to potentiate these effects. Concomitant use of ozanimod with pseudoephedrine did not potentiate the effects on blood pressure. However, hypertensive crisis has occurred with administration of ozanimod alone and also during coadministration of sympathomimetic medications and other selective or nonselective MAO inhibitors.
Bupivacaine; Epinephrine: (Major) Coadministration of ozanimod with sympathomimetics such as epinephrine is not routinely recommended due to the potential for hypertensive crisis. If coadministration is medically necessary, closely monitor the patient for hypertension. An active metabolite of ozanimod inhibits MAO-B, which may increase the potential for hypertensive crisis. Sympathomimetics may increase blood pressure by increasing norepinephrine concentrations and monoamine oxidase inhibitors (MAOIs) are known to potentiate these effects. Concomitant use of ozanimod with pseudoephedrine did not potentiate the effects on blood pressure. However, hypertensive crisis has occurred with administration of ozanimod alone and also during coadministration of sympathomimetic medications and other selective or nonselective MAO inhibitors.
Buprenorphine: (Major) In general, do not initiate buprenorphine in patients taking ozanimod or vice-versa due to the risk of additive serotonergic effects, bradycardia, QT prolongation, and torsade de pointes (TdP). There is also a potential for increased blood pressure. If treatment initiation is considered, seek advice from a cardiologist and monitor for hypertension. Some buprenorphine dosage forms should not be used in patients taking MAOIs or within 14 days of stopping them. An active metabolite of ozanimod inhibits MAO-B. MAO inhibitor interactions with meperidine may manifest as serotonin syndrome, hypertensive crisis, or opioid toxicity (e.g., respiratory depression, coma). Although a small number of patients treated with ozanimod were concomitantly exposed to opioids, this exposure was not adequate to rule out the possibility of an adverse reaction from coadministration. Ozanimod may also result in a transient decrease in heart rate and atrioventricular conduction delays. Ozanimod has not been studied in patients taking concurrent QT prolonging drugs; however, QT prolonging drugs have been associated with TdP in patients with bradycardia. Buprenorphine is associated with QT prolongation and has a possible risk of TdP.
Buprenorphine; Naloxone: (Major) In general, do not initiate buprenorphine in patients taking ozanimod or vice-versa due to the risk of additive serotonergic effects, bradycardia, QT prolongation, and torsade de pointes (TdP). There is also a potential for increased blood pressure. If treatment initiation is considered, seek advice from a cardiologist and monitor for hypertension. Some buprenorphine dosage forms should not be used in patients taking MAOIs or within 14 days of stopping them. An active metabolite of ozanimod inhibits MAO-B. MAO inhibitor interactions with meperidine may manifest as serotonin syndrome, hypertensive crisis, or opioid toxicity (e.g., respiratory depression, coma). Although a small number of patients treated with ozanimod were concomitantly exposed to opioids, this exposure was not adequate to rule out the possibility of an adverse reaction from coadministration. Ozanimod may also result in a transient decrease in heart rate and atrioventricular conduction delays. Ozanimod has not been studied in patients taking concurrent QT prolonging drugs; however, QT prolonging drugs have been associated with TdP in patients with bradycardia. Buprenorphine is associated with QT prolongation and has a possible risk of TdP.
Buspirone: (Major) Coadministration of ozanimod with buspirone is not recommended due to the potential for hypertensive crisis. If coadministration is necessary, closely monitor patients for hypertension. An active metabolite of ozanimod inhibits MAO-B, which may increase the potential for hypertensive crisis. Buspirone may increase blood pressure by increasing serotonin concentrations.
Butalbital; Acetaminophen; Caffeine; Codeine: (Contraindicated) Do not use codeine in patients taking MAOIs or within 14 days of stopping them. An active metabolite of ozanimod inhibits MAO-B. MAO inhibitor interactions with codeine may manifest as serotonin syndrome, hypertensive crisis, or opioid toxicity (e.g., respiratory depression, coma). Although a small number of patients treated with ozanimod were concomitantly exposed to opioids, this exposure was not adequate to rule out the possibility of an adverse reaction from coadministration.
Butalbital; Aspirin; Caffeine; Codeine: (Contraindicated) Do not use codeine in patients taking MAOIs or within 14 days of stopping them. An active metabolite of ozanimod inhibits MAO-B. MAO inhibitor interactions with codeine may manifest as serotonin syndrome, hypertensive crisis, or opioid toxicity (e.g., respiratory depression, coma). Although a small number of patients treated with ozanimod were concomitantly exposed to opioids, this exposure was not adequate to rule out the possibility of an adverse reaction from coadministration.
Butorphanol: (Moderate) Coadministration of butorphanol, an opioid agonist/antagonist, with ozanimod is not recommended due to the potential for serotonergic effects. An active metabolite of ozanimod inhibits MAO-B, which may increase the potential for serotonin syndrome or increased blood pressure. If concomitant use of butorphanol is warranted in a patient taking an MAO inhibitor, carefully observe the patient and monitor blood pressure, particularly during treatment initiation and dose adjustment. Discontinue serotonergic agents if serotonin syndrome is suspected. Although a small number of patients treated with ozanimod were concomitantly exposed to opioids, this exposure was not adequate to rule out the possibility of an adverse reaction from coadministration.
Cabotegravir; Rilpivirine: (Major) In general, do not initiate ozanimod in patients taking rilpivirine due to the risk of additive bradycardia, QT prolongation, and torsade de pointes (TdP). If treatment initiation is considered, seek advice from a cardiologist. Ozanimod initiation may result in a transient decrease in heart rate and atrioventricular conduction delays. Ozanimod has not been studied in patients taking concurrent QT prolonging drugs; however, QT prolonging drugs have been associated with TdP in patients with bradycardia. Supratherapeutic doses of rilpivirine (75 to 300 mg/day) have caused QT prolongation.
Calcium, Magnesium, Potassium, Sodium Oxybates: (Major) Coadministration of ozanimod with sodium oxybate is not recommended due to the potential for hypertensive crisis. If coadministration is necessary, closely monitor patients for hypertension. An active metabolite of ozanimod inhibits MAO-B, which may increase the potential for hypertensive crisis. Sodium oxybate has been associated with cases of serotonin syndrome. Excess serotonin may contribute to the development of hypertensive crisis.
Capsaicin; Metaxalone: (Major) Coadministration of ozanimod with metaxalone is not recommended due to the potential for hypertensive crisis. If coadministration is necessary, closely monitor patients for hypertension. An active metabolite of ozanimod inhibits MAO-B, which may increase the potential for hypertensive crisis. Metaxalone may increase blood pressure by increasing serotonin concentrations.
Carteolol: (Moderate) Ozanimod may cause bradycardia and AV-conduction delays, which may be enhanced with the concomitant use of beta-blockers. If a calcium channel blocker that slows heart rate/cardiac conduction is also prescribed with ozanimod and a beta-blocker, a cardiologist should be consulted due to the likelyhood of additive effects.
Carvedilol: (Moderate) Ozanimod may cause bradycardia and AV-conduction delays, which may be enhanced with the concomitant use of beta-blockers. If a calcium channel blocker that slows heart rate/cardiac conduction is also prescribed with ozanimod and a beta-blocker, a cardiologist should be consulted due to the likelyhood of additive effects.
Celecoxib; Tramadol: (Contraindicated) Do not use tramadol in patients taking MAOIs or within 14 days of stopping them. An active metabolite of ozanimod inhibits MAO-B. MAO inhibitor interactions with tramadol may manifest as serotonin syndrome, hypertensive crisis, or opioid toxicity (e.g., respiratory depression, coma). An active metabolite of ozanimod inhibits MAO-B. Although a small number of patients treated with ozanimod were concomitantly exposed to opioids, this exposure was not adequate to rule out the possibility of an adverse reaction from coadministration.
Ceritinib: (Major) Avoid coadministration of ceritinib with ozanimod if possible due to the risk of QT prolongation. If concomitant use is unavoidable, consult cardiology, periodically monitor ECGs and electrolytes; an interruption of ceritinib therapy, dose reduction, or discontinuation of therapy may be necessary if QT prolongation occurs. Ceritinib causes concentration-dependent QT prolongation. Ozanimod initiation may result in a transient decrease in heart rate and atrioventricular conduction delays. Ozanimod has not been studied in patients taking concurrent QT prolonging drugs; however, QT prolonging drugs have been associated with torsade de pointes in patients with bradycardia.
Cetirizine; Pseudoephedrine: (Major) Coadministration of ozanimod with sympathomimetics such as pseudoephedrine is not routinely recommended due to the potential for hypertensive crisis. If coadministration is medically necessary, closely monitor the patient for hypertension. An active metabolite of ozanimod inhibits MAO-B, which may increase the potential for hypertensive crisis. Sympathomimetics may increase blood pressure by increasing norepinephrine concentrations and monoamine oxidase inhibitors (MAOIs) are known to potentiate these effects. Concomitant use of ozanimod with pseudoephedrine did not potentiate the effects on blood pressure. However, hypertensive crisis has occurred with administration of ozanimod alone and also during coadministration of sympathomimetic medications and other selective or nonselective MAO inhibitors.
Chikungunya Vaccine, Live: (Major) Avoid the use of live vaccines and live attenuated vaccines during ozanimod treatment and for up to 3 months after discontinuation of ozanimod treatment. Live vaccinations may be less effective during ozanimod treatment and also may carry the risk of infection.
Chlophedianol; Dexchlorpheniramine; Pseudoephedrine: (Major) Coadministration of ozanimod with sympathomimetics such as pseudoephedrine is not routinely recommended due to the potential for hypertensive crisis. If coadministration is medically necessary, closely monitor the patient for hypertension. An active metabolite of ozanimod inhibits MAO-B, which may increase the potential for hypertensive crisis. Sympathomimetics may increase blood pressure by increasing norepinephrine concentrations and monoamine oxidase inhibitors (MAOIs) are known to potentiate these effects. Concomitant use of ozanimod with pseudoephedrine did not potentiate the effects on blood pressure. However, hypertensive crisis has occurred with administration of ozanimod alone and also during coadministration of sympathomimetic medications and other selective or nonselective MAO inhibitors.
Chlordiazepoxide; Amitriptyline: (Contraindicated) Do not use tricyclic antidepressants (TCAs) in patients taking MAOIs or within 14 days of stopping them. An active metabolite of ozanimod inhibits MAO-B, and interactions with TCAs may manifest as serotonin syndrome, hypertensive crisis, QT prolongation or other serious side effects. Hyperpyretic crises, severe convulsions, and deaths have occurred in patients receiving TCAs and MAO inhibiting drugs simultaneously. Consider an alternative to the TCA. Ozanimod is a monoamine oxidase inhibitor that may result in a transient decrease in heart rate and atrioventricular conduction delays. Ozanimod has not been studied in patients taking concurrent QT prolonging drugs; however, QT prolonging drugs have been associated with TdP in patients with bradycardia. TCAs are serotonergic drugs that share pharmacologic properties similar to the Class IA antiarrhythmic agents and may prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations).
Chloroquine: (Major) Avoid coadministration of chloroquine with ozanimod due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. Chloroquine is associated with an increased risk of QT prolongation and torsade de pointes (TdP); the risk of QT prolongation is increased with higher chloroquine doses. Ozanimod initiation may result in a transient decrease in heart rate and atrioventricular conduction delays. Ozanimod has not been studied in patients taking concurrent QT prolonging drugs; however, QT prolonging drugs have been associated with TdP in patients with bradycardia.
Chlorpheniramine; Codeine: (Contraindicated) Do not use codeine in patients taking MAOIs or within 14 days of stopping them. An active metabolite of ozanimod inhibits MAO-B. MAO inhibitor interactions with codeine may manifest as serotonin syndrome, hypertensive crisis, or opioid toxicity (e.g., respiratory depression, coma). Although a small number of patients treated with ozanimod were concomitantly exposed to opioids, this exposure was not adequate to rule out the possibility of an adverse reaction from coadministration.
Chlorpheniramine; Dextromethorphan: (Contraindicated) Coadministration of ozanimod with dextromethorphan is contraindicated. Allow at least 14 days between discontinuation of ozanimod and initiation of dextromethorphan. Consider if an alternative to dextromethorphan would be appropriate. An active metabolite of ozanimod inhibits MAO-B, which may increase the potential for serious and possibly fatal drug interactions with dextromethorphan, including serotonin syndrome.
Chlorpheniramine; Dextromethorphan; Phenylephrine: (Contraindicated) Coadministration of ozanimod with dextromethorphan is contraindicated. Allow at least 14 days between discontinuation of ozanimod and initiation of dextromethorphan. Consider if an alternative to dextromethorphan would be appropriate. An active metabolite of ozanimod inhibits MAO-B, which may increase the potential for serious and possibly fatal drug interactions with dextromethorphan, including serotonin syndrome. (Major) Coadministration of ozanimod with sympathomimetics such as phenylephrine is not routinely recommended due to the potential for hypertensive crisis. If coadministration is medically necessary, closely monitor the patient for hypertension. An active metabolite of ozanimod inhibits MAO-B, which may increase the potential for hypertensive crisis. Sympathomimetics may increase blood pressure by increasing norepinephrine concentrations and monoamine oxidase inhibitors (MAOIs) are known to potentiate these effects. Concomitant use of ozanimod with pseudoephedrine did not potentiate the effects on blood pressure. However, hypertensive crisis has occurred with administration of ozanimod alone and also during coadministration of sympathomimetic medications and other selective or nonselective MAO inhibitors.
Chlorpheniramine; Dextromethorphan; Pseudoephedrine: (Contraindicated) Coadministration of ozanimod with dextromethorphan is contraindicated. Allow at least 14 days between discontinuation of ozanimod and initiation of dextromethorphan. Consider if an alternative to dextromethorphan would be appropriate. An active metabolite of ozanimod inhibits MAO-B, which may increase the potential for serious and possibly fatal drug interactions with dextromethorphan, including serotonin syndrome. (Major) Coadministration of ozanimod with sympathomimetics such as pseudoephedrine is not routinely recommended due to the potential for hypertensive crisis. If coadministration is medically necessary, closely monitor the patient for hypertension. An active metabolite of ozanimod inhibits MAO-B, which may increase the potential for hypertensive crisis. Sympathomimetics may increase blood pressure by increasing norepinephrine concentrations and monoamine oxidase inhibitors (MAOIs) are known to potentiate these effects. Concomitant use of ozanimod with pseudoephedrine did not potentiate the effects on blood pressure. However, hypertensive crisis has occurred with administration of ozanimod alone and also during coadministration of sympathomimetic medications and other selective or nonselective MAO inhibitors.
Chlorpheniramine; Hydrocodone: (Major) When possible, hydrocodone should not be used in patients taking MAOIs or within 14 days of stopping such treatment. An active metabolite of ozanimod inhibits MAO-B. MAO inhibitor interactions with hydrocodone may manifest as serotonin syndrome, hypertensive crisis, or opioid toxicity (e.g., respiratory depression, coma). If concurrent use is absolutely necessary, use the lowest possible doses of hydrocodone, and monitor blood pressure and for serotonergic symptoms closely. Although a small number of patients treated with ozanimod were concomitantly exposed to opioids, this exposure was not adequate to rule out the possibility of an adverse reaction from coadministration.
Chlorpheniramine; Ibuprofen; Pseudoephedrine: (Major) Coadministration of ozanimod with sympathomimetics such as pseudoephedrine is not routinely recommended due to the potential for hypertensive crisis. If coadministration is medically necessary, closely monitor the patient for hypertension. An active metabolite of ozanimod inhibits MAO-B, which may increase the potential for hypertensive crisis. Sympathomimetics may increase blood pressure by increasing norepinephrine concentrations and monoamine oxidase inhibitors (MAOIs) are known to potentiate these effects. Concomitant use of ozanimod with pseudoephedrine did not potentiate the effects on blood pressure. However, hypertensive crisis has occurred with administration of ozanimod alone and also during coadministration of sympathomimetic medications and other selective or nonselective MAO inhibitors.
Chlorpheniramine; Phenylephrine: (Major) Coadministration of ozanimod with sympathomimetics such as phenylephrine is not routinely recommended due to the potential for hypertensive crisis. If coadministration is medically necessary, closely monitor the patient for hypertension. An active metabolite of ozanimod inhibits MAO-B, which may increase the potential for hypertensive crisis. Sympathomimetics may increase blood pressure by increasing norepinephrine concentrations and monoamine oxidase inhibitors (MAOIs) are known to potentiate these effects. Concomitant use of ozanimod with pseudoephedrine did not potentiate the effects on blood pressure. However, hypertensive crisis has occurred with administration of ozanimod alone and also during coadministration of sympathomimetic medications and other selective or nonselective MAO inhibitors.
Chlorpheniramine; Pseudoephedrine: (Major) Coadministration of ozanimod with sympathomimetics such as pseudoephedrine is not routinely recommended due to the potential for hypertensive crisis. If coadministration is medically necessary, closely monitor the patient for hypertension. An active metabolite of ozanimod inhibits MAO-B, which may increase the potential for hypertensive crisis. Sympathomimetics may increase blood pressure by increasing norepinephrine concentrations and monoamine oxidase inhibitors (MAOIs) are known to potentiate these effects. Concomitant use of ozanimod with pseudoephedrine did not potentiate the effects on blood pressure. However, hypertensive crisis has occurred with administration of ozanimod alone and also during coadministration of sympathomimetic medications and other selective or nonselective MAO inhibitors.
Chlorpromazine: (Major) In general, do not initiate ozanimod in patients taking chlorpromazine due to the risk of additive bradycardia, QT prolongation, and torsade de pointes (TdP). If treatment initiation is considered, seek advice from a cardiologist. Ozanimod initiation may result in a transient decrease in heart rate and atrioventricular conduction delays. Ozanimod has not been studied in patients taking concurrent QT prolonging drugs; however, QT prolonging drugs have been associated with TdP in patients with bradycardia. Chlorpromazine is associated with an established risk of QT prolongation and TdP.
Cholera Vaccine: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the live cholera vaccine. When feasible, administer indicated vaccines prior to initiating immunosuppressant medications. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure to cholera bacteria after receiving the vaccine.
Ciprofloxacin: (Major) Concomitant use of ciprofloxacin and ozanimod increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. Ozanimod has a limited effect on the QT/QTc interval at therapeutic doses but may cause bradycardia and atrioventricular conduction delays which may increase the risk for TdP in patients with a prolonged QT/QTc interval.
Cisapride: (Contraindicated) Coadministration of cisapride with ozanimod is contraindicated due to the risk for additive QT prolongation and torsade de pointes (TdP). QT prolongation and ventricular arrhythmias, including TdP and death, have been reported with cisapride. Ozanimod initiation may result in a transient decrease in heart rate and atrioventricular conduction delays. Ozanimod has not been studied in patients taking concurrent QT prolonging drugs; however, QT prolonging drugs have been associated with TdP in patients with bradycardia.
Citalopram: (Major) In general, do not initiate ozanimod in patients taking citalopram due to the risk of additive bradycardia, QT prolongation, and torsade de pointes (TdP). Additionally, there is a potential for hypertensive crisis and serotonin syndrome. If treatment initiation is considered, seek advice from a cardiologist and monitor for hypertension and serotonergic effects. Ozanimod is a monoamine oxidase inhibitor that may result in a transient decrease in heart rate and atrioventricular conduction delays. Ozanimod has not been studied in patients taking concurrent QT prolonging drugs; however, QT prolonging drugs have been associated with TdP in patients with bradycardia. Citalopram is a serotonergic drug that is associated with QT prolongation.
Cladribine: (Moderate) Concomitant use of ozanimod with cladribine may increase the risk of immunosuppression. Ozanimod has not been studied in combination with other immunosuppressive or immune modulating therapies used for the treatment of multiple sclerosis.
Clarithromycin: (Major) In general, do not initiate ozanimod in patients taking clarithromycin due to the risk of additive bradycardia, QT prolongation, and torsade de pointes (TdP). If treatment initiation is considered, seek advice from a cardiologist. Ozanimod initiation may result in a transient decrease in heart rate and atrioventricular conduction delays. Ozanimod has not been studied in patients taking concurrent QT prolonging drugs; however, QT prolonging drugs have been associated with TdP in patients with bradycardia. Clarithromycin is associated with an established risk for QT prolongation and TdP.
Clofazimine: (Major) Concomitant use of clofazimine and ozanimod increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. Ozanimod has a limited effect on the QT/QTc interval at therapeutic doses but may cause bradycardia and atrioventricular conduction delays which may increase the risk for TdP in patients with a prolonged QT/QTc interval.
Clomipramine: (Contraindicated) Do not use tricyclic antidepressants (TCAs) in patients taking MAOIs or within 14 days of stopping them. An active metabolite of ozanimod inhibits MAO-B, and interactions with TCAs may manifest as serotonin syndrome, hypertensive crisis, QT prolongation or other serious side effects. Hyperpyretic crises, severe convulsions, and deaths have occurred in patients receiving TCAs and MAO inhibiting drugs simultaneously. Consider an alternative to the TCA. Ozanimod is a monoamine oxidase inhibitor that may result in a transient decrease in heart rate and atrioventricular conduction delays. Ozanimod has not been studied in patients taking concurrent QT prolonging drugs; however, QT prolonging drugs have been associated with TdP in patients with bradycardia. TCAs are serotonergic drugs that share pharmacologic properties similar to the Class IA antiarrhythmic agents and may prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations).
Clozapine: (Major) In general, do not initiate ozanimod in patients taking clozapine due to the risk of additive bradycardia, QT prolongation, and torsade de pointes (TdP). If treatment initiation is considered, seek advice from a cardiologist. Ozanimod initiation may result in a transient decrease in heart rate and atrioventricular conduction delays. Ozanimod has not been studied in patients taking concurrent QT prolonging drugs; however, QT prolonging drugs have been associated with TdP in patients with bradycardia. Treatment with clozapine has been associated with QT prolongation, TdP, cardiac arrest, and sudden death.
Codeine: (Contraindicated) Do not use codeine in patients taking MAOIs or within 14 days of stopping them. An active metabolite of ozanimod inhibits MAO-B. MAO inhibitor interactions with codeine may manifest as serotonin syndrome, hypertensive crisis, or opioid toxicity (e.g., respiratory depression, coma). Although a small number of patients treated with ozanimod were concomitantly exposed to opioids, this exposure was not adequate to rule out the possibility of an adverse reaction from coadministration.
Codeine; Guaifenesin: (Contraindicated) Do not use codeine in patients taking MAOIs or within 14 days of stopping them. An active metabolite of ozanimod inhibits MAO-B. MAO inhibitor interactions with codeine may manifest as serotonin syndrome, hypertensive crisis, or opioid toxicity (e.g., respiratory depression, coma). Although a small number of patients treated with ozanimod were concomitantly exposed to opioids, this exposure was not adequate to rule out the possibility of an adverse reaction from coadministration.
Codeine; Guaifenesin; Pseudoephedrine: (Contraindicated) Do not use codeine in patients taking MAOIs or within 14 days of stopping them. An active metabolite of ozanimod inhibits MAO-B. MAO inhibitor interactions with codeine may manifest as serotonin syndrome, hypertensive crisis, or opioid toxicity (e.g., respiratory depression, coma). Although a small number of patients treated with ozanimod were concomitantly exposed to opioids, this exposure was not adequate to rule out the possibility of an adverse reaction from coadministration. (Major) Coadministration of ozanimod with sympathomimetics such as pseudoephedrine is not routinely recommended due to the potential for hypertensive crisis. If coadministration is medically necessary, closely monitor the patient for hypertension. An active metabolite of ozanimod inhibits MAO-B, which may increase the potential for hypertensive crisis. Sympathomimetics may increase blood pressure by increasing norepinephrine concentrations and monoamine oxidase inhibitors (MAOIs) are known to potentiate these effects. Concomitant use of ozanimod with pseudoephedrine did not potentiate the effects on blood pressure. However, hypertensive crisis has occurred with administration of ozanimod alone and also during coadministration of sympathomimetic medications and other selective or nonselective MAO inhibitors.
Codeine; Phenylephrine; Promethazine: (Contraindicated) Do not use codeine in patients taking MAOIs or within 14 days of stopping them. An active metabolite of ozanimod inhibits MAO-B. MAO inhibitor interactions with codeine may manifest as serotonin syndrome, hypertensive crisis, or opioid toxicity (e.g., respiratory depression, coma). Although a small number of patients treated with ozanimod were concomitantly exposed to opioids, this exposure was not adequate to rule out the possibility of an adverse reaction from coadministration. (Major) Coadministration of ozanimod with sympathomimetics such as phenylephrine is not routinely recommended due to the potential for hypertensive crisis. If coadministration is medically necessary, closely monitor the patient for hypertension. An active metabolite of ozanimod inhibits MAO-B, which may increase the potential for hypertensive crisis. Sympathomimetics may increase blood pressure by increasing norepinephrine concentrations and monoamine oxidase inhibitors (MAOIs) are known to potentiate these effects. Concomitant use of ozanimod with pseudoephedrine did not potentiate the effects on blood pressure. However, hypertensive crisis has occurred with administration of ozanimod alone and also during coadministration of sympathomimetic medications and other selective or nonselective MAO inhibitors. (Major) In general, do not initiate ozanimod in patients taking promethazine due to the risk of additive bradycardia, QT prolongation, and torsade de pointes (TdP). If treatment initiation is considered, seek advice from a cardiologist. Ozanimod initiation may result in a transient decrease in heart rate and atrioventricular conduction delays. Ozanimod has not been studied in patients taking concurrent QT prolonging drugs; however, QT prolonging drugs have been associated with TdP in patients with bradycardia. Promethazine is associated with a possible risk for QT prolongation.
Codeine; Promethazine: (Contraindicated) Do not use codeine in patients taking MAOIs or within 14 days of stopping them. An active metabolite of ozanimod inhibits MAO-B. MAO inhibitor interactions with codeine may manifest as serotonin syndrome, hypertensive crisis, or opioid toxicity (e.g., respiratory depression, coma). Although a small number of patients treated with ozanimod were concomitantly exposed to opioids, this exposure was not adequate to rule out the possibility of an adverse reaction from coadministration. (Major) In general, do not initiate ozanimod in patients taking promethazine due to the risk of additive bradycardia, QT prolongation, and torsade de pointes (TdP). If treatment initiation is considered, seek advice from a cardiologist. Ozanimod initiation may result in a transient decrease in heart rate and atrioventricular conduction delays. Ozanimod has not been studied in patients taking concurrent QT prolonging drugs; however, QT prolonging drugs have been associated with TdP in patients with bradycardia. Promethazine is associated with a possible risk for QT prolongation.
Cortisone: (Moderate) Concomitant use of ozanimod with systemic cortisone may increase the risk of immunosuppression. Monitor patients carefully for signs and symptoms of infection. In clinical studies for ulcerative colitis, the use of systemic corticosteroids did not appear to influence safety or efficacy of ozanimod.
Crizotinib: (Major) Avoid coadministration of crizotinib with ozanimod due to the risk of QT prolongation. If concomitant use is unavoidable, monitor ECGs for QT prolongation and monitor electrolytes. An interruption of therapy, dose reduction, or discontinuation of therapy may be necessary for crizotinib if QT prolongation occurs. Crizotinib can cause concentration-dependent QT prolongation. Ozanimod initiation may result in a transient decrease in heart rate and atrioventricular conduction delays. Ozanimod has not been studied in patients taking concurrent QT prolonging drugs; however, QT prolonging drugs have been associated with torsade de pointes in patients with bradycardia.
Cyclobenzaprine: (Contraindicated) Coadministration of ozanimod with cyclobenzaprine is contraindicated. Allow at least 14 days between discontinuation of ozanimod and initiation of cyclobenzaprine. An active metabolite of ozanimod inhibits MAO-B, which may increase the potential for hypertensive crisis. Cyclobenzaprine may increase blood pressure and serotonergic side effects by increasing norepinephrine and serotonin concentrations.
Dasatinib: (Major) In general, do not initiate ozanimod in patients taking dasatinib due to the risk of additive bradycardia, QT prolongation, and torsade de pointes (TdP). If treatment initiation is considered, seek advice from a cardiologist. Ozanimod initiation may result in a transient decrease in heart rate and atrioventricular conduction delays. Ozanimod has not been studied in patients taking concurrent QT prolonging drugs; however, QT prolonging drugs have been associated with TdP in patients with bradycardia. In vitro studies have shown that dasatinib has the potential to prolong the QT interval.
Degarelix: (Major) In general, do not initiate ozanimod in patients taking degarelix due to the risk of additive bradycardia, QT prolongation, and torsade de pointes (TdP). If treatment initiation is considered, seek advice from a cardiologist. Ozanimod initiation may result in a transient decrease in heart rate and atrioventricular conduction delays. Ozanimod has not been studied in patients taking concurrent QT prolonging drugs; however, QT prolonging drugs have been associated with TdP in patients with bradycardia. Androgen deprivation therapy (i.e., degarelix) may prolong the QT/QTc interval.
Dengue Tetravalent Vaccine, Live: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the dengue virus vaccine. When feasible, administer indicated vaccines at least 2 weeks prior to initiating immunosuppressant medications. If vaccine administration is necessary, consider revaccination following restoration of immune competence. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure after receiving the vaccine.
Desflurane: (Major) In general, do not initiate ozanimod in patients taking halogenated anesthetics due to the risk of additive bradycardia, QT prolongation, and torsade de pointes (TdP). If treatment initiation is considered, seek advice from a cardiologist. Ozanimod initiation may result in a transient decrease in heart rate and atrioventricular conduction delays. Ozanimod has not been studied in patients taking concurrent QT prolonging drugs; however, QT prolonging drugs have been associated with TdP in patients with bradycardia. Halogenated anesthetics can prolong the QT interval.
Desipramine: (Contraindicated) Do not use tricyclic antidepressants (TCAs) in patients taking MAOIs or within 14 days of stopping them. An active metabolite of ozanimod inhibits MAO-B, and interactions with TCAs may manifest as serotonin syndrome, hypertensive crisis, QT prolongation or other serious side effects. Hyperpyretic crises, severe convulsions, and deaths have occurred in patients receiving TCAs and MAO inhibiting drugs simultaneously. Consider an alternative to the TCA. Ozanimod is a monoamine oxidase inhibitor that may result in a transient decrease in heart rate and atrioventricular conduction delays. Ozanimod has not been studied in patients taking concurrent QT prolonging drugs; however, QT prolonging drugs have been associated with TdP in patients with bradycardia. TCAs are serotonergic drugs that share pharmacologic properties similar to the Class IA antiarrhythmic agents and may prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations).
Desloratadine; Pseudoephedrine: (Major) Coadministration of ozanimod with sympathomimetics such as pseudoephedrine is not routinely recommended due to the potential for hypertensive crisis. If coadministration is medically necessary, closely monitor the patient for hypertension. An active metabolite of ozanimod inhibits MAO-B, which may increase the potential for hypertensive crisis. Sympathomimetics may increase blood pressure by increasing norepinephrine concentrations and monoamine oxidase inhibitors (MAOIs) are known to potentiate these effects. Concomitant use of ozanimod with pseudoephedrine did not potentiate the effects on blood pressure. However, hypertensive crisis has occurred with administration of ozanimod alone and also during coadministration of sympathomimetic medications and other selective or nonselective MAO inhibitors.
Desvenlafaxine: (Major) Coadministration of ozanimod with desvenlafaxine is not recommended due to the potential for hypertensive crisis. If coadministration is necessary, closely monitor patients for hypertension and serotonergic effects. An active metabolite of ozanimod inhibits MAO-B, which may increase the potential for hypertensive crisis. Desvenlafaxine may increase blood pressure by increasing serotonin and norepinephrine concentrations.
Deutetrabenazine: (Major) In general, do not initiate ozanimod in patients taking deutetrabenazine due to the risk of additive bradycardia, QT prolongation, and torsade de pointes (TdP). If treatment initiation is considered, seek advice from a cardiologist. Ozanimod initiation may result in a transient decrease in heart rate and atrioventricular conduction delays. Ozanimod has not been studied in patients taking concurrent QT prolonging drugs; however, QT prolonging drugs have been associated with TdP in patients with bradycardia. Deutetrabenazine may prolong the QT interval, but the degree of QT prolongation is not clinically significant when deutetrabenazine is administered within the recommended dosage range.
Dexbrompheniramine; Pseudoephedrine: (Major) Coadministration of ozanimod with sympathomimetics such as pseudoephedrine is not routinely recommended due to the potential for hypertensive crisis. If coadministration is medically necessary, closely monitor the patient for hypertension. An active metabolite of ozanimod inhibits MAO-B, which may increase the potential for hypertensive crisis. Sympathomimetics may increase blood pressure by increasing norepinephrine concentrations and monoamine oxidase inhibitors (MAOIs) are known to potentiate these effects. Concomitant use of ozanimod with pseudoephedrine did not potentiate the effects on blood pressure. However, hypertensive crisis has occurred with administration of ozanimod alone and also during coadministration of sympathomimetic medications and other selective or nonselective MAO inhibitors.
Dexchlorpheniramine; Dextromethorphan; Pseudoephedrine: (Contraindicated) Coadministration of ozanimod with dextromethorphan is contraindicated. Allow at least 14 days between discontinuation of ozanimod and initiation of dextromethorphan. Consider if an alternative to dextromethorphan would be appropriate. An active metabolite of ozanimod inhibits MAO-B, which may increase the potential for serious and possibly fatal drug interactions with dextromethorphan, including serotonin syndrome. (Major) Coadministration of ozanimod with sympathomimetics such as pseudoephedrine is not routinely recommended due to the potential for hypertensive crisis. If coadministration is medically necessary, closely monitor the patient for hypertension. An active metabolite of ozanimod inhibits MAO-B, which may increase the potential for hypertensive crisis. Sympathomimetics may increase blood pressure by increasing norepinephrine concentrations and monoamine oxidase inhibitors (MAOIs) are known to potentiate these effects. Concomitant use of ozanimod with pseudoephedrine did not potentiate the effects on blood pressure. However, hypertensive crisis has occurred with administration of ozanimod alone and also during coadministration of sympathomimetic medications and other selective or nonselective MAO inhibitors.
Dexmedetomidine: (Major) Concomitant use of dexmedetomidine and ozanimod increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. Ozanimod has a limited effect on the QT/QTc interval at therapeutic doses but may cause bradycardia and atrioventricular conduction delays which may increase the risk for TdP in patients with a prolonged QT/QTc interval.
Dexmethylphenidate: (Contraindicated) Coadministration of ozanimod with methylphenidate derivatives is contraindicated. Allow at least 14 days between discontinuation of ozanimod and initiation of methylphenidate. An active metabolite of ozanimod inhibits MAO-B, which may increase the potential for hypertensive crisis. Sympathomimetics such as methylphenidate may increase blood pressure by increasing norepinephrine concentrations and monoamine oxidase inhibitors (MAOIs) are known to potentiate these effects. Methylphenidate derivatives may also have serotonergic effects that may increase blood pressure. Concomitant use of ozanimod with pseudoephedrine did not potentiate the effects on blood pressure. However, hypertensive crisis has occurred with administration of ozanimod alone and during coadministration of sympathomimetic medications and other selective or nonselective MAO inhibitors.
Dextroamphetamine: (Major) Avoid concurrent use of ozanimod and amphetamines when possible as this combination may increase the risk for serious adverse reactions such as hypertensive crisis. If use is necessary, monitor for hypertension. Amphetamines may increase blood pressure by increasing norepinephrine and serotonin concentrations and monoamine oxidase inhibitors (MAOIs) are known to potentiate these effects. An active metabolite of ozanimod inhibits MAO-B in vitro. Sympathomimetics are contraindicated for use with non-selective MAOIs, however the risk for hypertensive reactions may be lower with selective MAO-B inhibitors.
Dextromethorphan: (Contraindicated) Coadministration of ozanimod with dextromethorphan is contraindicated. Allow at least 14 days between discontinuation of ozanimod and initiation of dextromethorphan. Consider if an alternative to dextromethorphan would be appropriate. An active metabolite of ozanimod inhibits MAO-B, which may increase the potential for serious and possibly fatal drug interactions with dextromethorphan, including serotonin syndrome.
Dextromethorphan; Bupropion: (Contraindicated) Coadministration of ozanimod with dextromethorphan is contraindicated. Allow at least 14 days between discontinuation of ozanimod and initiation of dextromethorphan. Consider if an alternative to dextromethorphan would be appropriate. An active metabolite of ozanimod inhibits MAO-B, which may increase the potential for serious and possibly fatal drug interactions with dextromethorphan, including serotonin syndrome.
Dextromethorphan; Diphenhydramine; Phenylephrine: (Contraindicated) Coadministration of ozanimod with dextromethorphan is contraindicated. Allow at least 14 days between discontinuation of ozanimod and initiation of dextromethorphan. Consider if an alternative to dextromethorphan would be appropriate. An active metabolite of ozanimod inhibits MAO-B, which may increase the potential for serious and possibly fatal drug interactions with dextromethorphan, including serotonin syndrome. (Major) Coadministration of ozanimod with sympathomimetics such as phenylephrine is not routinely recommended due to the potential for hypertensive crisis. If coadministration is medically necessary, closely monitor the patient for hypertension. An active metabolite of ozanimod inhibits MAO-B, which may increase the potential for hypertensive crisis. Sympathomimetics may increase blood pressure by increasing norepinephrine concentrations and monoamine oxidase inhibitors (MAOIs) are known to potentiate these effects. Concomitant use of ozanimod with pseudoephedrine did not potentiate the effects on blood pressure. However, hypertensive crisis has occurred with administration of ozanimod alone and also during coadministration of sympathomimetic medications and other selective or nonselective MAO inhibitors.
Dextromethorphan; Guaifenesin: (Contraindicated) Coadministration of ozanimod with dextromethorphan is contraindicated. Allow at least 14 days between discontinuation of ozanimod and initiation of dextromethorphan. Consider if an alternative to dextromethorphan would be appropriate. An active metabolite of ozanimod inhibits MAO-B, which may increase the potential for serious and possibly fatal drug interactions with dextromethorphan, including serotonin syndrome.
Dextromethorphan; Guaifenesin; Phenylephrine: (Contraindicated) Coadministration of ozanimod with dextromethorphan is contraindicated. Allow at least 14 days between discontinuation of ozanimod and initiation of dextromethorphan. Consider if an alternative to dextromethorphan would be appropriate. An active metabolite of ozanimod inhibits MAO-B, which may increase the potential for serious and possibly fatal drug interactions with dextromethorphan, including serotonin syndrome. (Major) Coadministration of ozanimod with sympathomimetics such as phenylephrine is not routinely recommended due to the potential for hypertensive crisis. If coadministration is medically necessary, closely monitor the patient for hypertension. An active metabolite of ozanimod inhibits MAO-B, which may increase the potential for hypertensive crisis. Sympathomimetics may increase blood pressure by increasing norepinephrine concentrations and monoamine oxidase inhibitors (MAOIs) are known to potentiate these effects. Concomitant use of ozanimod with pseudoephedrine did not potentiate the effects on blood pressure. However, hypertensive crisis has occurred with administration of ozanimod alone and also during coadministration of sympathomimetic medications and other selective or nonselective MAO inhibitors.
Dextromethorphan; Guaifenesin; Pseudoephedrine: (Contraindicated) Coadministration of ozanimod with dextromethorphan is contraindicated. Allow at least 14 days between discontinuation of ozanimod and initiation of dextromethorphan. Consider if an alternative to dextromethorphan would be appropriate. An active metabolite of ozanimod inhibits MAO-B, which may increase the potential for serious and possibly fatal drug interactions with dextromethorphan, including serotonin syndrome. (Major) Coadministration of ozanimod with sympathomimetics such as pseudoephedrine is not routinely recommended due to the potential for hypertensive crisis. If coadministration is medically necessary, closely monitor the patient for hypertension. An active metabolite of ozanimod inhibits MAO-B, which may increase the potential for hypertensive crisis. Sympathomimetics may increase blood pressure by increasing norepinephrine concentrations and monoamine oxidase inhibitors (MAOIs) are known to potentiate these effects. Concomitant use of ozanimod with pseudoephedrine did not potentiate the effects on blood pressure. However, hypertensive crisis has occurred with administration of ozanimod alone and also during coadministration of sympathomimetic medications and other selective or nonselective MAO inhibitors.
Dextromethorphan; Quinidine: (Contraindicated) Coadministration of ozanimod with dextromethorphan is contraindicated. Allow at least 14 days between discontinuation of ozanimod and initiation of dextromethorphan. Consider if an alternative to dextromethorphan would be appropriate. An active metabolite of ozanimod inhibits MAO-B, which may increase the potential for serious and possibly fatal drug interactions with dextromethorphan, including serotonin syndrome. (Major) In general, do not initiate ozanimod in patients taking quinidine due to the risk of additive bradycardia, QT prolongation, and torsade de pointes (TdP). If treatment initiation is considered, seek advice from a cardiologist. Ozanimod initiation may result in a transient decrease in heart rate and atrioventricular conduction delays. Ozanimod has not been studied in patients taking concurrent QT prolonging drugs; however, QT prolonging drugs have been associated with TdP in patients with bradycardia. Quinidine administration is associated with QT prolongation and TdP.
Diethylpropion: (Contraindicated) Coadministration of ozanimod with diethylpropion is contraindicated. Allow at least 14 days between discontinuation of ozanimod and initiation of diethylpropion. An active metabolite of ozanimod inhibits MAO-B, which may increase the potential for hypertensive crisis. Sympathomimetics such as diethylpropion may increase blood pressure by increasing norepinephrine concentrations and monoamine oxidase inhibitors (MAOIs) are known to potentiate these effects. Concomitant use of ozanimod with pseudoephedrine did not potentiate the effects on blood pressure. However, hypertensive crisis has occurred with administration of ozanimod alone and during coadministration of sympathomimetic medications and other selective or nonselective MAO inhibitors.
Diltiazem: (Major) Treatment with ozanimod should generally not be initiated in patients who are concurrently treated with both a heart rate lowering calcium channel blocker (e.g., diltiazem) and a beta blocker. If treatment initiation with ozanimod is considered in patients on both a heart rate lowering calcium channel blocker and beta blocker, advice from a cardiologist should be sought.
Dimethyl Fumarate: (Moderate) Concomitant use of ozanimod with dimethyl fumarate may increase the risk of immunosuppression. Ozanimod has not been studied in combination with other immunosuppressive or immune modulating therapies used for the treatment of multiple sclerosis.
Diphenhydramine; Phenylephrine: (Major) Coadministration of ozanimod with sympathomimetics such as phenylephrine is not routinely recommended due to the potential for hypertensive crisis. If coadministration is medically necessary, closely monitor the patient for hypertension. An active metabolite of ozanimod inhibits MAO-B, which may increase the potential for hypertensive crisis. Sympathomimetics may increase blood pressure by increasing norepinephrine concentrations and monoamine oxidase inhibitors (MAOIs) are known to potentiate these effects. Concomitant use of ozanimod with pseudoephedrine did not potentiate the effects on blood pressure. However, hypertensive crisis has occurred with administration of ozanimod alone and also during coadministration of sympathomimetic medications and other selective or nonselective MAO inhibitors.
Diroximel Fumarate: (Moderate) Concomitant use of ozanimod with diroximel fumarate may increase the risk of immunosuppression. Ozanimod has not been studied in combination with other immunosuppressive or immune modulating therapies used for the treatment of multiple sclerosis.
Disopyramide: (Major) In general, do not initiate ozanimod in patients taking disopyramide due to the risk of additive bradycardia, QT prolongation, and torsade de pointes (TdP). If treatment initiation is considered, seek advice from a cardiologist. Ozanimod initiation may result in a transient decrease in heart rate and atrioventricular conduction delays. Ozanimod has not been studied in patients taking concurrent QT prolonging drugs; however, QT prolonging drugs have been associated with TdP in patients with bradycardia. Disopyramide administration is associated with QT prolongation and TdP.
Dobutamine: (Major) Coadministration of ozanimod with sympathomimetics such as dobutamine is not routinely recommended due to the potential for hypertensive crisis. If coadministration is medically necessary, closely monitor the patient for hypertension. An active metabolite of ozanimod inhibits MAO-B, which may increase the potential for hypertensive crisis. Sympathomimetics may increase blood pressure by increasing norepinephrine concentrations and monoamine oxidase inhibitors (MAOIs) are known to potentiate these effects. Concomitant use of ozanimod with pseudoephedrine did not potentiate the effects on blood pressure. However, hypertensive crisis has occurred with administration of ozanimod alone and also during coadministration of sympathomimetic medications and other selective or nonselective MAO inhibitors.
Dofetilide: (Major) In general, do not initiate ozanimod in patients taking dofetilide due to the risk of additive bradycardia, QT prolongation, and torsade de pointes (TdP). If treatment initiation is considered, seek advice from a cardiologist. Ozanimod initiation may result in a transient decrease in heart rate and atrioventricular conduction delays. Ozanimod has not been studied in patients taking concurrent QT prolonging drugs; however, QT prolonging drugs have been associated with TdP in patients with bradycardia. Dofetilide, a Class III antiarrhythmic agent, is associated with a well-established risk of QT prolongation and TdP.
Dolasetron: (Major) In general, do not initiate ozanimod in patients taking dolasetron due to the risk of additive bradycardia, QT prolongation, and torsade de pointes (TdP). Additionally, there is a potential for hypertensive crisis. If treatment initiation is considered, seek advice from a cardiologist and monitor for hypertension. An active metabolite of ozanimod inhibits MAO-B, which may increase the potential for hypertensive crisis. Ozanimod may also result in a transient decrease in heart rate and atrioventricular conduction delays. Ozanimod has not been studied in patients taking concurrent QT prolonging drugs; however, QT prolonging drugs have been associated with TdP in patients with bradycardia. Dolasetron is a serotonergic drug that has been associated with a dose-dependent prolongation in the QT, PR, and QRS intervals on an electrocardiogram.
Dolutegravir; Rilpivirine: (Major) In general, do not initiate ozanimod in patients taking rilpivirine due to the risk of additive bradycardia, QT prolongation, and torsade de pointes (TdP). If treatment initiation is considered, seek advice from a cardiologist. Ozanimod initiation may result in a transient decrease in heart rate and atrioventricular conduction delays. Ozanimod has not been studied in patients taking concurrent QT prolonging drugs; however, QT prolonging drugs have been associated with TdP in patients with bradycardia. Supratherapeutic doses of rilpivirine (75 to 300 mg/day) have caused QT prolongation.
Donepezil: (Major) In general, do not initiate ozanimod in patients taking donepezil due to the risk of additive bradycardia, QT prolongation, and torsade de pointes (TdP). If treatment initiation is considered, seek advice from a cardiologist. Ozanimod initiation may result in a transient decrease in heart rate and atrioventricular conduction delays. Ozanimod has not been studied in patients taking concurrent QT prolonging drugs; however, QT prolonging drugs have been associated with TdP in patients with bradycardia. Case reports indicate that QT prolongation and TdP can occur during donepezil therapy.
Donepezil; Memantine: (Major) In general, do not initiate ozanimod in patients taking donepezil due to the risk of additive bradycardia, QT prolongation, and torsade de pointes (TdP). If treatment initiation is considered, seek advice from a cardiologist. Ozanimod initiation may result in a transient decrease in heart rate and atrioventricular conduction delays. Ozanimod has not been studied in patients taking concurrent QT prolonging drugs; however, QT prolonging drugs have been associated with TdP in patients with bradycardia. Case reports indicate that QT prolongation and TdP can occur during donepezil therapy.
Dopamine: (Major) Coadministration of ozanimod with sympathomimetics such as dopamine is not routinely recommended due to the potential for hypertensive crisis. If coadministration is medically necessary, it is recommended that patients who have been treated with MAO inhibitors, such as ozanimod, within 2 to 3 weeks prior to the administration of dopamine should receive initial doses of dopamine no greater than one-tenth of the usual dose. Closely monitor the patient for hypertension. An active metabolite of ozanimod inhibits MAO-B, which may increase the potential for hypertensive crisis. Dopamine is metabolized by monoamine oxidase (MAO), inhibition of this enzyme prolongs and potentiates the effect of dopamine. Sympathomimetics may increase blood pressure by increasing norepinephrine concentrations and monoamine oxidase inhibitors (MAOIs) are known to potentiate these effects. Concomitant use of ozanimod with pseudoephedrine did not potentiate the effects on blood pressure. However, hypertensive crisis has occurred with administration of ozanimod alone and during coadministration of sympathomimetic medications and other selective or nonselective MAO inhibitors.
Dorzolamide; Timolol: (Moderate) Ozanimod may cause bradycardia and AV-conduction delays, which may be enhanced with the concomitant use of beta-blockers. If a calcium channel blocker that slows heart rate/cardiac conduction is also prescribed with ozanimod and a beta-blocker, a cardiologist should be consulted due to the likelyhood of additive effects.
Doxapram: (Major) Coadministration of ozanimod with sympathomimetics such as doxapram is not routinely recommended due to the potential for hypertensive crisis. If coadministration is medically necessary, closely monitor the patient for hypertension. An active metabolite of ozanimod inhibits MAO-B, which may increase the potential for hypertensive crisis. Sympathomimetics may increase blood pressure by increasing norepinephrine concentrations and monoamine oxidase inhibitors (MAOIs) are known to potentiate these effects. Concomitant use of ozanimod with pseudoephedrine did not potentiate the effects on blood pressure. However, hypertensive crisis has occurred with administration of ozanimod alone and also during coadministration of sympathomimetic medications and other selective or nonselective MAO inhibitors.
Doxepin: (Contraindicated) Do not use tricyclic antidepressants (TCAs) in patients taking MAOIs or within 14 days of stopping them. An active metabolite of ozanimod inhibits MAO-B, and interactions with TCAs may manifest as serotonin syndrome, hypertensive crisis, QT prolongation or other serious side effects. Hyperpyretic crises, severe convulsions, and deaths have occurred in patients receiving TCAs and MAO inhibiting drugs simultaneously. Consider an alternative to the TCA. Ozanimod is a monoamine oxidase inhibitor that may result in a transient decrease in heart rate and atrioventricular conduction delays. Ozanimod has not been studied in patients taking concurrent QT prolonging drugs; however, QT prolonging drugs have been associated with TdP in patients with bradycardia. TCAs are serotonergic drugs that share pharmacologic properties similar to the Class IA antiarrhythmic agents and may prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations).
Dronedarone: (Contraindicated) Coadministration of dronedarone with ozanimod is contraindicated due to the risk for additive QT prolongation and torsade de pointes (TdP). Dronedarone administration is associated with a dose-related increase in the QTc interval. The increase in QTc is approximately 10 milliseconds at doses of 400 mg twice daily (the FDA-approved dose) and up to 25 milliseconds at doses of 1,600 mg twice daily. Although there are no studies examining the effects of dronedarone in patients receiving other QT prolonging drugs, coadministration of such drugs may result in additive QT prolongation. Ozanimod initiation may result in a transient decrease in heart rate and atrioventricular conduction delays. Ozanimod has not been studied in patients taking concurrent QT prolonging drugs; however, QT prolonging drugs have been associated with TdP in patients with bradycardia.
Droperidol: (Major) Avoid coadministration of droperidol with ozanimod due to the risk of additive bradycardia, QT prolongation, and torsade de pointes (TdP). If coadministration cannot be avoided, use extreme caution; initiate droperidol at a low dose and increase the dose as needed to achieve the desired effect. Droperidol administration is associated with an established risk for QT prolongation and TdP. Some cases have occurred in patients with no known risk factors for QT prolongation and some cases have been fatal. Ozanimod initiation may result in a transient decrease in heart rate and atrioventricular conduction delays. Ozanimod has not been studied in patients taking concurrent QT prolonging drugs; however, QT prolonging drugs have been associated with TdP in patients with bradycardia.
Duloxetine: (Major) Coadministration of ozanimod with duloxetine is not recommended due to the potential for hypertensive crisis. If coadministration is necessary, closely monitor patients for hypertension and serotonergic effects. An active metabolite of ozanimod inhibits MAO-B, which may increase the potential for hypertensive crisis. Duloxetine may increase blood pressure by increasing serotonin and norepinephrine concentrations.
Efavirenz: (Major) In general, do not initiate ozanimod in patients taking efavirenz due to the risk of additive bradycardia, QT prolongation, and torsade de pointes (TdP). If treatment initiation is considered, seek advice from a cardiologist. Ozanimod initiation may result in a transient decrease in heart rate and atrioventricular conduction delays. Ozanimod has not been studied in patients taking concurrent QT prolonging drugs; however, QT prolonging drugs have been associated with TdP in patients with bradycardia. QTc prolongation has been observed with the use of efavirenz.
Efavirenz; Emtricitabine; Tenofovir Disoproxil Fumarate: (Major) In general, do not initiate ozanimod in patients taking efavirenz due to the risk of additive bradycardia, QT prolongation, and torsade de pointes (TdP). If treatment initiation is considered, seek advice from a cardiologist. Ozanimod initiation may result in a transient decrease in heart rate and atrioventricular conduction delays. Ozanimod has not been studied in patients taking concurrent QT prolonging drugs; however, QT prolonging drugs have been associated with TdP in patients with bradycardia. QTc prolongation has been observed with the use of efavirenz.
Efavirenz; Lamivudine; Tenofovir Disoproxil Fumarate: (Major) In general, do not initiate ozanimod in patients taking efavirenz due to the risk of additive bradycardia, QT prolongation, and torsade de pointes (TdP). If treatment initiation is considered, seek advice from a cardiologist. Ozanimod initiation may result in a transient decrease in heart rate and atrioventricular conduction delays. Ozanimod has not been studied in patients taking concurrent QT prolonging drugs; however, QT prolonging drugs have been associated with TdP in patients with bradycardia. QTc prolongation has been observed with the use of efavirenz.
Eletriptan: (Major) Coadministration of ozanimod with serotonin receptor agonists "triptans" is not recommended due to the potential for hypertensive crisis or serotonin syndrome. If coadministration is necessary, closely monitor patients for hypertension and serotonergic effects. An active metabolite of ozanimod inhibits MAO-B, which may increase the potential for hypertensive crisis or serotonin syndrome. Serotonin receptor agonists may increase blood pressure by increasing serotonin concentrations.
Eliglustat: (Major) In general, do not initiate ozanimod in patients taking eliglustat due to the risk of additive bradycardia, QT prolongation, and torsade de pointes (TdP). If treatment initiation is considered, seek advice from a cardiologist. Ozanimod initiation may result in a transient decrease in heart rate and atrioventricular conduction delays. Ozanimod has not been studied in patients taking concurrent QT prolonging drugs; however, QT prolonging drugs have been associated with TdP in patients with bradycardia. Eliglustat is predicted to cause PR, QRS, and/or QT prolongation at significantly elevated plasma concentrations.
Emtricitabine; Rilpivirine; Tenofovir alafenamide: (Major) In general, do not initiate ozanimod in patients taking rilpivirine due to the risk of additive bradycardia, QT prolongation, and torsade de pointes (TdP). If treatment initiation is considered, seek advice from a cardiologist. Ozanimod initiation may result in a transient decrease in heart rate and atrioventricular conduction delays. Ozanimod has not been studied in patients taking concurrent QT prolonging drugs; however, QT prolonging drugs have been associated with TdP in patients with bradycardia. Supratherapeutic doses of rilpivirine (75 to 300 mg/day) have caused QT prolongation.
Emtricitabine; Rilpivirine; Tenofovir Disoproxil Fumarate: (Major) In general, do not initiate ozanimod in patients taking rilpivirine due to the risk of additive bradycardia, QT prolongation, and torsade de pointes (TdP). If treatment initiation is considered, seek advice from a cardiologist. Ozanimod initiation may result in a transient decrease in heart rate and atrioventricular conduction delays. Ozanimod has not been studied in patients taking concurrent QT prolonging drugs; however, QT prolonging drugs have been associated with TdP in patients with bradycardia. Supratherapeutic doses of rilpivirine (75 to 300 mg/day) have caused QT prolongation.
Encorafenib: (Major) Avoid coadministration of encorafenib and ozanimod due to QT prolongation. If concurrent use cannot be avoided, monitor ECGs for QT prolongation and monitor electrolytes; correct hypokalemia and hypomagnesemia prior to treatment. Encorafenib has been associated with dose-dependent QT prolongation. Ozanimod initiation may result in a transient decrease in heart rate and atrioventricular conduction delays. Ozanimod has not been studied in patients taking concurrent QT prolonging drugs; however, QT prolonging drugs have been associated with torsade de pointes in patients with bradycardia.
Entrectinib: (Major) In general, do not initiate ozanimod in patients taking entrectinib due to the risk of additive bradycardia, QT prolongation, and torsade de pointes (TdP). If treatment initiation is considered, seek advice from a cardiologist. Ozanimod initiation may result in a transient decrease in heart rate and atrioventricular conduction delays. Ozanimod has not been studied in patients taking concurrent QT prolonging drugs; however, QT prolonging drugs have been associated with TdP in patients with bradycardia. Entrectinib has been associated with QT prolongation.
Ephedrine: (Major) Coadministration of ozanimod with sympathomimetics such as ephedrine is not routinely recommended due to the potential for hypertensive crisis. If coadministration is medically necessary, closely monitor the patient for hypertension. An active metabolite of ozanimod inhibits MAO-B, which may increase the potential for hypertensive crisis. Sympathomimetics may increase blood pressure by increasing norepinephrine concentrations and monoamine oxidase inhibitors (MAOIs) are known to potentiate these effects. Concomitant use of ozanimod with pseudoephedrine did not potentiate the effects on blood pressure. However, hypertensive crisis has occurred with administration of ozanimod alone and also during coadministration of sympathomimetic medications and other selective or nonselective MAO inhibitors.
Ephedrine; Guaifenesin: (Major) Coadministration of ozanimod with sympathomimetics such as ephedrine is not routinely recommended due to the potential for hypertensive crisis. If coadministration is medically necessary, closely monitor the patient for hypertension. An active metabolite of ozanimod inhibits MAO-B, which may increase the potential for hypertensive crisis. Sympathomimetics may increase blood pressure by increasing norepinephrine concentrations and monoamine oxidase inhibitors (MAOIs) are known to potentiate these effects. Concomitant use of ozanimod with pseudoephedrine did not potentiate the effects on blood pressure. However, hypertensive crisis has occurred with administration of ozanimod alone and also during coadministration of sympathomimetic medications and other selective or nonselective MAO inhibitors.
Epinephrine: (Major) Coadministration of ozanimod with sympathomimetics such as epinephrine is not routinely recommended due to the potential for hypertensive crisis. If coadministration is medically necessary, closely monitor the patient for hypertension. An active metabolite of ozanimod inhibits MAO-B, which may increase the potential for hypertensive crisis. Sympathomimetics may increase blood pressure by increasing norepinephrine concentrations and monoamine oxidase inhibitors (MAOIs) are known to potentiate these effects. Concomitant use of ozanimod with pseudoephedrine did not potentiate the effects on blood pressure. However, hypertensive crisis has occurred with administration of ozanimod alone and also during coadministration of sympathomimetic medications and other selective or nonselective MAO inhibitors.
Eribulin: (Major) In general, do not initiate ozanimod in patients taking eribulin due to the risk of additive bradycardia, QT prolongation, and torsade de pointes (TdP). If concomitant use is necessary, monitor ECGs. Ozanimod initiation may result in a transient decrease in heart rate and atrioventricular conduction delays. Ozanimod has not been studied in patients taking concurrent QT prolonging drugs; however, QT prolonging drugs have been associated with TdP in patients with bradycardia. Eribulin has been associated with QT prolongation.
Erythromycin: (Major) In general, do not initiate ozanimod in patients taking erythromycin due to the risk of additive bradycardia, QT prolongation, and torsade de pointes (TdP). If treatment initiation is considered, seek advice from a cardiologist. Ozanimod initiation may result in a transient decrease in heart rate and atrioventricular conduction delays. Ozanimod has not been studied in patients taking concurrent QT prolonging drugs; however, QT prolonging drugs have been associated with TdP in patients with bradycardia. Erythromycin is associated with QT prolongation and TdP.
Escitalopram: (Major) In general, do not initiate ozanimod in patients taking escitalopram due to the risk of additive bradycardia, QT prolongation, and torsade de pointes (TdP). Additionally, there is a potential for hypertensive crisis and serotonin syndrome. If treatment initiation is considered, seek advice from a cardiologist and monitor for hypertension and serotonergic effects. Ozanimod is a monoamine oxidase inhibitor that may result in a transient decrease in heart rate and atrioventricular conduction delays. Ozanimod has not been studied in patients taking concurrent QT prolonging drugs; however, QT prolonging drugs have been associated with TdP in patients with bradycardia. Escitalopram is a serotonergic drug that is associated with QT prolongation and TdP.
Esmolol: (Moderate) Ozanimod may cause bradycardia and AV-conduction delays, which may be enhanced with the concomitant use of beta-blockers. If a calcium channel blocker that slows heart rate/cardiac conduction is also prescribed with ozanimod and a beta-blocker, a cardiologist should be consulted due to the likelyhood of additive effects.
Etrasimod: (Major) Concomitant use of etrasimod and ozanimod increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. Ozanimod and etrasimod have a limited effect on the QT/QTc interval at therapeutic doses but may cause bradycardia and atrioventricular conduction delays which may increase the risk for TdP in patients with a prolonged QT/QTc interval.
Fentanyl: (Major) When possible, fentanyl should not be used in patients taking MAOIs or within 14 days of stopping such treatment. An active metabolite of ozanimod inhibits MAO-B. MAO inhibitor interactions with fentanyl may manifest as serotonin syndrome, hypertensive crisis, or opioid toxicity (e.g., respiratory depression, coma). If concurrent use is absolutely necessary, use the lowest possible doses of fentanyl, and monitor blood pressure and for serotonergic symptoms closely. Although a small number of patients treated with ozanimod were concomitantly exposed to opioids, this exposure was not adequate to rule out the possibility of an adverse reaction from coadministration.
Fexinidazole: (Major) Concomitant use of fexinidazole and ozanimod increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. Ozanimod has a limited effect on the QT/QTc interval at therapeutic doses but may cause bradycardia and atrioventricular conduction delays which may increase the risk for TdP in patients with a prolonged QT/QTc interval.
Fexofenadine; Pseudoephedrine: (Major) Coadministration of ozanimod with sympathomimetics such as pseudoephedrine is not routinely recommended due to the potential for hypertensive crisis. If coadministration is medically necessary, closely monitor the patient for hypertension. An active metabolite of ozanimod inhibits MAO-B, which may increase the potential for hypertensive crisis. Sympathomimetics may increase blood pressure by increasing norepinephrine concentrations and monoamine oxidase inhibitors (MAOIs) are known to potentiate these effects. Concomitant use of ozanimod with pseudoephedrine did not potentiate the effects on blood pressure. However, hypertensive crisis has occurred with administration of ozanimod alone and also during coadministration of sympathomimetic medications and other selective or nonselective MAO inhibitors.
Flecainide: (Major) In general, do not initiate ozanimod in patients taking flecainide due to the risk of additive bradycardia, QT prolongation, and torsade de pointes (TdP). If treatment initiation is considered, seek advice from a cardiologist. Ozanimod initiation may result in a transient decrease in heart rate and atrioventricular conduction delays. Ozanimod has not been studied in patients taking concurrent QT prolonging drugs; however, QT prolonging drugs have been associated with TdP in patients with bradycardia. Flecainide is a Class IC antiarrhythmic associated with a possible risk for QT prolongation and/or TdP; flecainide increases the QT interval, but largely due to prolongation of the QRS interval. Although causality for TdP has not been established for flecainide, patients receiving concurrent drugs that have the potential for QT prolongation may have an increased risk of developing proarrhythmias.
Fluconazole: (Major) In general, do not initiate ozanimod in patients taking fluconazole due to the risk of additive bradycardia, QT prolongation, and torsade de pointes (TdP). If treatment initiation is considered, seek advice from a cardiologist. Ozanimod initiation may result in a transient decrease in heart rate and atrioventricular conduction delays. Ozanimod has not been studied in patients taking concurrent QT prolonging drugs; however, QT prolonging drugs have been associated with TdP in patients with bradycardia. Fluconazole has been associated with QT prolongation and rare cases of TdP.
Fluoxetine: (Major) In general, do not initiate ozanimod in patients taking fluoxetine due to the risk of additive bradycardia, QT prolongation, and torsade de pointes (TdP). Additionally, there is a potential for hypertensive crisis and serotonin syndrome. If treatment initiation is considered, seek advice from a cardiologist and monitor for hypertension and serotonergic effects. Ozanimod is a monoamine oxidase inhibitor that may result in a transient decrease in heart rate and atrioventricular conduction delays. Ozanimod has not been studied in patients taking concurrent QT prolonging drugs; however, QT prolonging drugs have been associated with TdP in patients with bradycardia. Fluoxetine is a serotonergic drug that is associated with QT prolongation and TdP.
Fluphenazine: (Minor) Coadministration of ozanimod with fluphenazine may increase the potential for additive QT prolongation. Ozanimod initiation may result in a transient decrease in heart rate and atrioventricular conduction delays. Ozanimod has not been studied in patients taking concurrent QT prolonging drugs; however, QT prolonging drugs have been associated with torsade de pointes in patients with bradycardia. Fluphenazine is associated with a possible risk for QT prolongation. Theoretically, fluphenazine may increase the risk of QT prolongation if coadministered with other drugs that have a risk of QT prolongation.
Fluvoxamine: (Major) In general, do not initiate ozanimod in patients taking fluvoxamine due to the risk of additive bradycardia, QT prolongation, and torsade de pointes (TdP). Additionally, there is a potential for hypertensive crisis and serotonin syndrome. If treatment initiation is considered, seek advice from a cardiologist and monitor for hypertension and serotonergic effects. Ozanimod is a monoamine oxidase inhibitor that may result in a transient decrease in heart rate and atrioventricular conduction delays. Ozanimod has not been studied in patients taking concurrent QT prolonging drugs; however, QT prolonging drugs have been associated with TdP in patients with bradycardia. Fluvoxamine is a serotonergic drug that is associated with QT prolongation and TdP.
Food: (Major) Patients should be advised to avoid foods containing a large amount of tyramine while taking recommended doses of ozanimod. Certain foods that may contain very high amounts (i.e., more than 150 mg) of tyramine could cause severe hypertension because of a potential tyramine interaction in patients taking ozanimod, even at the recommended doses. Ozanimod metabolites inhibit MAO in vitro. MAO in the gastrointestinal tract and liver (primarily type A) provides protection from exogenous amines (e.g., tyramine). If tyramine were absorbed intact, it could lead to severe hypertension, including hypertensive crisis. Aged, fermented, cured, smoked, and pickled foods containing large amounts of exogenous amines (e.g., aged cheese, pickled herring) may cause release of norepinephrine resulting in a rise in blood pressure (tyramine reaction).
Foscarnet: (Major) In general, do not initiate ozanimod in patients taking foscarnet due to the risk of additive bradycardia, QT prolongation, and torsade de pointes (TdP). If treatment initiation is considered, seek advice from a cardiologist. Ozanimod initiation may result in a transient decrease in heart rate and atrioventricular conduction delays. Ozanimod has not been studied in patients taking concurrent QT prolonging drugs; however, QT prolonging drugs have been associated with TdP in patients with bradycardia. Both QT prolongation and TdP have been reported during postmarketing use of foscarnet.
Fostemsavir: (Major) Concomitant use of ozanimod and fostemsavir increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. Ozanimod has a limited effect on the QT/QTc interval at therapeutic doses but may cause bradycardia and atrioventricular conduction delays which may increase the risk for TdP in patients with a prolonged QT/QTc interval. The degree of QT prolongation associated with fostemsavir is not clinically significant when administered within the recommended dosage range; QT prolongation has been described at 4 times the recommended daily dose.
Frovatriptan: (Major) Coadministration of ozanimod with serotonin receptor agonists "triptans" is not recommended due to the potential for hypertensive crisis or serotonin syndrome. If coadministration is necessary, closely monitor patients for hypertension and serotonergic effects. An active metabolite of ozanimod inhibits MAO-B, which may increase the potential for hypertensive crisis or serotonin syndrome. Serotonin receptor agonists may increase blood pressure by increasing serotonin concentrations.
Gemfibrozil: (Major) Coadministration of ozanimod with gemfibrozil is not recommended. Coadministration may increase the exposure of the active metabolites of ozanimod, which may increase the risk of adverse reactions. Ozanimod is a CYP2C8 substrate and gemfibrozil is a strong CYP2C8 inhibitor. Coadministration with gemfibrozil increased the exposure of active metabolites CC112273 and CC1084037 by approximately 47% and 69%, respectively. No clinically significant differences in the exposure of ozanimod were observed when coadministered with gemfibrozil.
Gemifloxacin: (Major) In general, do not initiate ozanimod in patients taking gemifloxacin due to the risk of additive bradycardia, QT prolongation, and torsade de pointes (TdP). If treatment initiation is considered, seek advice from a cardiologist. Ozanimod initiation may result in a transient decrease in heart rate and atrioventricular conduction delays. Ozanimod has not been studied in patients taking concurrent QT prolonging drugs; however, QT prolonging drugs have been associated with TdP in patients with bradycardia. Gemifloxacin may prolong the QT interval in some patients. The maximal change in the QTc interval occurs approximately 5 to 10 hours following oral administration of gemifloxacin. The likelihood of QTc prolongation may increase with increasing dose of the drug; therefore, the recommended dose should not be exceeded especially in patients with renal or hepatic impairment where the Cmax and AUC are slightly higher.
Gemtuzumab Ozogamicin: (Major) In general, do not initiate ozanimod in patients taking gemtuzumab due to the risk of additive bradycardia, QT prolongation, and torsade de pointes (TdP). If these agents are used together, obtain an ECG and serum electrolytes prior to the start of gemtuzumab and as needed during treatment. Although QT interval prolongation has not been reported with gemtuzumab, it has been reported with other drugs that contain calicheamicin. Ozanimod initiation may result in a transient decrease in heart rate and atrioventricular conduction delays. Ozanimod has not been studied in patients taking concurrent QT prolonging drugs; however, QT prolonging drugs have been associated with TdP in patients with bradycardia.
Gilteritinib: (Major) In general, do not initiate ozanimod in patients taking gilteritinib due to the risk of additive bradycardia, QT prolongation, and torsade de pointes (TdP). If treatment initiation is considered, seek advice from a cardiologist. Ozanimod initiation may result in a transient decrease in heart rate and atrioventricular conduction delays. Ozanimod has not been studied in patients taking concurrent QT prolonging drugs; however, QT prolonging drugs have been associated with TdP in patients with bradycardia. Gilteritinib has been associated with QT prolongation.
Glasdegib: (Major) Avoid coadministration of glasdegib with ozanimod due to the potential for additive QT prolongation. If coadministration cannot be avoided, monitor patients for increased risk of QT prolongation with increased frequency of ECG monitoring. Glasdegib therapy may result in QT prolongation and ventricular arrhythmias including ventricular fibrillation and ventricular tachycardia. Ozanimod initiation may result in a transient decrease in heart rate and atrioventricular conduction delays. Ozanimod has not been studied in patients taking concurrent QT prolonging drugs; however, QT prolonging drugs have been associated with torsade de pointes in patients with bradycardia.
Glatiramer: (Moderate) Concomitant use of ozanimod with glatiramer may increase the risk of immunosuppression. Ozanimod has not been studied in combination with other immunosuppressive or immune modulating therapies used for the treatment of multiple sclerosis. Ozanimod can generally be started immediately after discontinuation of glatiramer.
Goserelin: (Major) In general, do not initiate ozanimod in patients taking goserelin due to the risk of additive bradycardia, QT prolongation, and torsade de pointes (TdP). If treatment initiation is considered, seek advice from a cardiologist. Ozanimod initiation may result in a transient decrease in heart rate and atrioventricular conduction delays. Ozanimod has not been studied in patients taking concurrent QT prolonging drugs; however, QT prolonging drugs have been associated with TdP in patients with bradycardia. Androgen deprivation therapy (i.e., goserelin) may prolong the QT/QTc interval.
Granisetron: (Major) In general, do not initiate ozanimod in patients taking granisetron due to the risk of additive bradycardia, QT prolongation, and torsade de pointes (TdP). Additionally, there is a potential for hypertensive crisis. If treatment initiation is considered, seek advice from a cardiologist and monitor for hypertension. An active metabolite of ozanimod inhibits MAO-B, which may increase the potential for hypertensive crisis. Ozanimod may also result in a transient decrease in heart rate and atrioventricular conduction delays. Ozanimod has not been studied in patients taking concurrent QT prolonging drugs; however, QT prolonging drugs have been associated with TdP in patients with bradycardia. Granisetron is a serotonergic drug that has been associated with QT prolongation.
Guaifenesin; Phenylephrine: (Major) Coadministration of ozanimod with sympathomimetics such as phenylephrine is not routinely recommended due to the potential for hypertensive crisis. If coadministration is medically necessary, closely monitor the patient for hypertension. An active metabolite of ozanimod inhibits MAO-B, which may increase the potential for hypertensive crisis. Sympathomimetics may increase blood pressure by increasing norepinephrine concentrations and monoamine oxidase inhibitors (MAOIs) are known to potentiate these effects. Concomitant use of ozanimod with pseudoephedrine did not potentiate the effects on blood pressure. However, hypertensive crisis has occurred with administration of ozanimod alone and also during coadministration of sympathomimetic medications and other selective or nonselective MAO inhibitors.
Guaifenesin; Pseudoephedrine: (Major) Coadministration of ozanimod with sympathomimetics such as pseudoephedrine is not routinely recommended due to the potential for hypertensive crisis. If coadministration is medically necessary, closely monitor the patient for hypertension. An active metabolite of ozanimod inhibits MAO-B, which may increase the potential for hypertensive crisis. Sympathomimetics may increase blood pressure by increasing norepinephrine concentrations and monoamine oxidase inhibitors (MAOIs) are known to potentiate these effects. Concomitant use of ozanimod with pseudoephedrine did not potentiate the effects on blood pressure. However, hypertensive crisis has occurred with administration of ozanimod alone and also during coadministration of sympathomimetic medications and other selective or nonselective MAO inhibitors.
Halogenated Anesthetics: (Major) In general, do not initiate ozanimod in patients taking halogenated anesthetics due to the risk of additive bradycardia, QT prolongation, and torsade de pointes (TdP). If treatment initiation is considered, seek advice from a cardiologist. Ozanimod initiation may result in a transient decrease in heart rate and atrioventricular conduction delays. Ozanimod has not been studied in patients taking concurrent QT prolonging drugs; however, QT prolonging drugs have been associated with TdP in patients with bradycardia. Halogenated anesthetics can prolong the QT interval.
Haloperidol: (Major) In general, do not initiate ozanimod in patients taking haloperidol due to the risk of additive bradycardia, QT prolongation, and torsade de pointes (TdP). If treatment initiation is considered, seek advice from a cardiologist. Ozanimod initiation may result in a transient decrease in heart rate and atrioventricular conduction delays. Ozanimod has not been studied in patients taking concurrent QT prolonging drugs; however, QT prolonging drugs have been associated with TdP in patients with bradycardia. QT prolongation and TdP have been observed during haloperidol treatment. Excessive doses (particularly in the overdose setting) or IV administration of haloperidol may be associated with a higher risk of QT prolongation.
Histrelin: (Major) In general, do not initiate ozanimod in patients taking histrelin due to the risk of additive bradycardia, QT prolongation, and torsade de pointes (TdP). If treatment initiation is considered, seek advice from a cardiologist. Ozanimod initiation may result in a transient decrease in heart rate and atrioventricular conduction delays. Ozanimod has not been studied in patients taking concurrent QT prolonging drugs; however, QT prolonging drugs have been associated with TdP in patients with bradycardia. Androgen deprivation therapy (i.e., histrelin) may prolong the QT/QTc interval.
Homatropine; Hydrocodone: (Major) When possible, hydrocodone should not be used in patients taking MAOIs or within 14 days of stopping such treatment. An active metabolite of ozanimod inhibits MAO-B. MAO inhibitor interactions with hydrocodone may manifest as serotonin syndrome, hypertensive crisis, or opioid toxicity (e.g., respiratory depression, coma). If concurrent use is absolutely necessary, use the lowest possible doses of hydrocodone, and monitor blood pressure and for serotonergic symptoms closely. Although a small number of patients treated with ozanimod were concomitantly exposed to opioids, this exposure was not adequate to rule out the possibility of an adverse reaction from coadministration.
Hydrocodone: (Major) When possible, hydrocodone should not be used in patients taking MAOIs or within 14 days of stopping such treatment. An active metabolite of ozanimod inhibits MAO-B. MAO inhibitor interactions with hydrocodone may manifest as serotonin syndrome, hypertensive crisis, or opioid toxicity (e.g., respiratory depression, coma). If concurrent use is absolutely necessary, use the lowest possible doses of hydrocodone, and monitor blood pressure and for serotonergic symptoms closely. Although a small number of patients treated with ozanimod were concomitantly exposed to opioids, this exposure was not adequate to rule out the possibility of an adverse reaction from coadministration.
Hydrocodone; Ibuprofen: (Major) When possible, hydrocodone should not be used in patients taking MAOIs or within 14 days of stopping such treatment. An active metabolite of ozanimod inhibits MAO-B. MAO inhibitor interactions with hydrocodone may manifest as serotonin syndrome, hypertensive crisis, or opioid toxicity (e.g., respiratory depression, coma). If concurrent use is absolutely necessary, use the lowest possible doses of hydrocodone, and monitor blood pressure and for serotonergic symptoms closely. Although a small number of patients treated with ozanimod were concomitantly exposed to opioids, this exposure was not adequate to rule out the possibility of an adverse reaction from coadministration.
Hydrocortisone: (Moderate) Concomitant use of ozanimod with systemic hydrocortisone may increase the risk of immunosuppression. Monitor patients carefully for signs and symptoms of infection. In clinical studies for ulcerative colitis, the use of systemic corticosteroids did not appear to influence safety or efficacy of ozanimod.
Hydromorphone: (Major) When possible, hydromorphone should not be used in patients taking MAOIs or within 14 days of stopping such treatment. An active metabolite of ozanimod inhibits MAO-B. MAO inhibitor interactions with hydromorphone may manifest as serotonin syndrome, hypertensive crisis, or opioid toxicity (e.g., respiratory depression, coma). If concurrent use is absolutely necessary, use the lowest possible doses of hydromorphone, and monitor blood pressure and for serotonergic symptoms closely. Although a small number of patients treated with ozanimod were concomitantly exposed to opioids, this exposure was not adequate to rule out the possibility of an adverse reaction from coadministration.
Hydroxychloroquine: (Major) Avoid coadministration of hydroxychloroquine and ozanimod due to the risk of increased QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. Hydroxychloroquine prolongs the QT interval. Ozanimod initiation may result in a transient decrease in heart rate and atrioventricular conduction delays. Ozanimod has not been studied in patients taking concurrent QT prolonging drugs; however, QT prolonging drugs have been associated with torsade de pointes in patients with bradycardia.
Hydroxyzine: (Major) In general, do not initiate ozanimod in patients taking hydroxyzine due to the risk of additive bradycardia, QT prolongation, and torsade de pointes (TdP). If treatment initiation is considered, seek advice from a cardiologist. Ozanimod initiation may result in a transient decrease in heart rate and atrioventricular conduction delays. Ozanimod has not been studied in patients taking concurrent QT prolonging drugs; however, QT prolonging drugs have been associated with TdP in patients with bradycardia. Postmarketing data indicate that hydroxyzine causes QT prolongation and TdP.
Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate; Sodium Biphosphate: (Major) Concurrent use of intravenous (IV) methylene blue and drugs with selective MAOI activity, such as ozanimod, should generally be avoided due to the potential for serotonin syndrome. If emergent treatment with methylene blue is required in a patient receiving an MAOI it is advisable to discontinue the MAOI and monitor the patient for symptoms of CNS toxicity for two weeks or until 24 hours after the last dose of methylene blue, whichever comes first. During non-emergent use of methylene blue, it is advisable to discontinue ozanimod at least 2 weeks prior to methylene blue treatment, taking into consideration the half-life of ozanimod. Because the metabolites of ozanimod inhibit primarily monoamine oxidase-B (MAO-B), an interaction may be less likely to occur than with other traditional MAOIs. Methylene blue is a thiazine dye that is also a potent, reversible inhibitor of the enzyme responsible for the catabolism of serotonin in the brain (MAO-A). Cases of serotonin syndrome have been reported, primarily following administration of IV methylene blue (1 to 8 mg/kg) as a visualizing agent in patients receiving serotonergic agents.
Ibuprofen; Oxycodone: (Major) When possible, oxycodone should not be used in patients taking MAOIs or within 14 days of stopping such treatment. An active metabolite of ozanimod inhibits MAO-B. MAO inhibitor interactions with oxycodone may manifest as serotonin syndrome, hypertensive crisis, or opioid toxicity (e.g., respiratory depression, coma). If concurrent use is absolutely necessary, use the lowest possible doses of oxycodone, and monitor blood pressure and for serotonergic symptoms closely. Although a small number of patients treated with ozanimod were concomitantly exposed to opioids, this exposure was not adequate to rule out the possibility of an adverse reaction from coadministration.
Ibuprofen; Pseudoephedrine: (Major) Coadministration of ozanimod with sympathomimetics such as pseudoephedrine is not routinely recommended due to the potential for hypertensive crisis. If coadministration is medically necessary, closely monitor the patient for hypertension. An active metabolite of ozanimod inhibits MAO-B, which may increase the potential for hypertensive crisis. Sympathomimetics may increase blood pressure by increasing norepinephrine concentrations and monoamine oxidase inhibitors (MAOIs) are known to potentiate these effects. Concomitant use of ozanimod with pseudoephedrine did not potentiate the effects on blood pressure. However, hypertensive crisis has occurred with administration of ozanimod alone and also during coadministration of sympathomimetic medications and other selective or nonselective MAO inhibitors.
Ibutilide: (Major) In general, do not initiate ozanimod in patients taking ibutilide due to the risk of additive bradycardia, QT prolongation, and torsade de pointes (TdP). If treatment initiation is considered, seek advice from a cardiologist. Ozanimod initiation may result in a transient decrease in heart rate and atrioventricular conduction delays. Ozanimod has not been studied in patients taking concurrent QT prolonging drugs; however, QT prolonging drugs have been associated with TdP in patients with bradycardia. Ibutilide administration can cause QT prolongation and TdP; proarrhythmic events should be anticipated. The potential for proarrhythmic events with ibutilide increases with the coadministration of other drugs that prolong the QT interval.
Iloperidone: (Major) In general, do not initiate ozanimod in patients taking iloperidone due to the risk of additive bradycardia, QT prolongation, and torsade de pointes (TdP). If treatment initiation is considered, seek advice from a cardiologist. Ozanimod initiation may result in a transient decrease in heart rate and atrioventricular conduction delays. Ozanimod has not been studied in patients taking concurrent QT prolonging drugs; however, QT prolonging drugs have been associated with TdP in patients with bradycardia. Iloperidone has been associated with QT prolongation.
Imipramine: (Contraindicated) Do not use tricyclic antidepressants (TCAs) in patients taking MAOIs or within 14 days of stopping them. An active metabolite of ozanimod inhibits MAO-B, and interactions with TCAs may manifest as serotonin syndrome, hypertensive crisis, QT prolongation or other serious side effects. Hyperpyretic crises, severe convulsions, and deaths have occurred in patients receiving TCAs and MAO inhibiting drugs simultaneously. Consider an alternative to the TCA. Ozanimod is a monoamine oxidase inhibitor that may result in a transient decrease in heart rate and atrioventricular conduction delays. Ozanimod has not been studied in patients taking concurrent QT prolonging drugs; however, QT prolonging drugs have been associated with TdP in patients with bradycardia. TCAs are serotonergic drugs that share pharmacologic properties similar to the Class IA antiarrhythmic agents and may prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations).
Inotuzumab Ozogamicin: (Major) Avoid coadministration of inotuzumab with ozanimod due to the potential for additive QT prolongation and torsade de pointes (TdP). If coadministration is unavoidable, obtain ECGs and electrolytes prior to the start of treatment and periodically during treatment. Inotuzumab has been associated with QT interval prolongation. Ozanimod initiation may result in a transient decrease in heart rate and atrioventricular conduction delays. Ozanimod has not been studied in patients taking concurrent QT prolonging drugs; however, QT prolonging drugs have been associated with TdP in patients with bradycardia.
Interferon Beta-1a: (Moderate) Concomitant use of ozanimod with interferon beta may increase the risk of immunosuppression. Ozanimod has not been studied in combination with other immunosuppressive or immune modulating therapies. Ozanimod can generally be started immediately after discontinuation of interferon beta.
Interferon Beta-1b: (Moderate) Concomitant use of ozanimod with interferon beta may increase the risk of immunosuppression. Ozanimod has not been studied in combination with other immunosuppressive or immune modulating therapies. Ozanimod can generally be started immediately after discontinuation of interferon beta.
Intranasal Influenza Vaccine: (Major) Avoid the use of live vaccines and live attenuated vaccines during ozanimod treatment and for up to 3 months after discontinuation of ozanimod treatment. Live vaccinations may be less effective during ozanimod treatment and also may carry the risk of infection.
Isocarboxazid: (Contraindicated) Coadministration of ozanimod with monoamine oxidase (MAO) inhibitors is contraindicated. Allow at least 14 days between discontinuation of ozanimod and initiation of treatment with MAO inhibitors. Metabolites of ozanimod may inhibit MAO. The potential for a clinical interaction with MAO inhibitors has not been studied; however, the increased risk of nonselective MAO inhibition may lead to a hypertensive crisis.
Isoflurane: (Major) In general, do not initiate ozanimod in patients taking halogenated anesthetics due to the risk of additive bradycardia, QT prolongation, and torsade de pointes (TdP). If treatment initiation is considered, seek advice from a cardiologist. Ozanimod initiation may result in a transient decrease in heart rate and atrioventricular conduction delays. Ozanimod has not been studied in patients taking concurrent QT prolonging drugs; however, QT prolonging drugs have been associated with TdP in patients with bradycardia. Halogenated anesthetics can prolong the QT interval.
Isoniazid, INH; Pyrazinamide, PZA; Rifampin: (Major) Coadministration of ozanimod with rifampin is not recommended. Coadministration may decrease the exposure of the active metabolites of ozanimod, which may reduce its efficacy. Ozanimod is a CYP2C8 substrate. Coadministration with rifampin (a strong inducer of CYP3A and P-gp, and a moderate inducer of CYP2C8) reduced the exposure for ozanimod, CC112273, and CC1084037 by approximately 24%, 60%, and 55%, respectively. The effect on CC112273 and CC1084037 is primarily caused by induction of CYP2C8.
Isoniazid, INH; Rifampin: (Major) Coadministration of ozanimod with rifampin is not recommended. Coadministration may decrease the exposure of the active metabolites of ozanimod, which may reduce its efficacy. Ozanimod is a CYP2C8 substrate. Coadministration with rifampin (a strong inducer of CYP3A and P-gp, and a moderate inducer of CYP2C8) reduced the exposure for ozanimod, CC112273, and CC1084037 by approximately 24%, 60%, and 55%, respectively. The effect on CC112273 and CC1084037 is primarily caused by induction of CYP2C8.
Isoproterenol: (Major) Coadministration of ozanimod with sympathomimetics such as isoproterenol is not routinely recommended due to the potential for hypertensive crisis. If coadministration is medically necessary, closely monitor the patient for hypertension. An active metabolite of ozanimod inhibits MAO-B, which may increase the potential for hypertensive crisis. Sympathomimetics may increase blood pressure by increasing norepinephrine concentrations and monoamine oxidase inhibitors (MAOIs) are known to potentiate these effects. Concomitant use of ozanimod with pseudoephedrine did not potentiate the effects on blood pressure. However, hypertensive crisis has occurred with administration of ozanimod alone and also during coadministration of sympathomimetic medications and other selective or nonselective MAO inhibitors.
Itraconazole: (Major) Concomitant use of ozanimod and itraconazole increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. Ozanimod has a limited effect on the QT/QTc interval at therapeutic doses but may cause bradycardia and atrioventricular conduction delays which may increase the risk for TdP in patients with a prolonged QT/QTc interval.
Ivosidenib: (Major) Avoid coadministration of ivosidenib with ozanimod if possible due to an increased risk of QT prolongation. If concomitant use is unavoidable, monitor ECGs for QTc prolongation and monitor electrolytes; correct any electrolyte abnormalities as clinically appropriate. An interruption of therapy and dose reduction of ivosidenib may be necessary if QT prolongation occurs. Prolongation of the QTc interval and ventricular arrhythmias have been reported in patients treated with ivosidenib. Ozanimod initiation may result in a transient decrease in heart rate and atrioventricular conduction delays. Ozanimod has not been studied in patients taking concurrent QT prolonging drugs; however, QT prolonging drugs have been associated with torsade de pointes in patients with bradycardia.
Ketoconazole: (Contraindicated) Avoid concomitant use of ketoconazole and ozanimod due to an increased risk for torsade de pointes (TdP) and QT/QTc prolongation. Ozanimod has a limited effect on the QT/QTc interval at therapeutic doses but may cause bradycardia and atrioventricular conduction delays which may increase the risk for TdP in patients with a prolonged QT/QTc interval.
Labetalol: (Moderate) Ozanimod may cause bradycardia and AV-conduction delays, which may be enhanced with the concomitant use of beta-blockers. If a calcium channel blocker that slows heart rate/cardiac conduction is also prescribed with ozanimod and a beta-blocker, a cardiologist should be consulted due to the likelyhood of additive effects.
Lansoprazole; Amoxicillin; Clarithromycin: (Major) In general, do not initiate ozanimod in patients taking clarithromycin due to the risk of additive bradycardia, QT prolongation, and torsade de pointes (TdP). If treatment initiation is considered, seek advice from a cardiologist. Ozanimod initiation may result in a transient decrease in heart rate and atrioventricular conduction delays. Ozanimod has not been studied in patients taking concurrent QT prolonging drugs; however, QT prolonging drugs have been associated with TdP in patients with bradycardia. Clarithromycin is associated with an established risk for QT prolongation and TdP.
Lapatinib: (Major) In general, do not initiate ozanimod in patients taking lapatinib due to the risk of additive bradycardia, QT prolongation, and torsade de pointes (TdP). If treatment initiation is considered, seek advice from a cardiologist. Ozanimod initiation may result in a transient decrease in heart rate and atrioventricular conduction delays. Ozanimod has not been studied in patients taking concurrent QT prolonging drugs; however, QT prolonging drugs have been associated with TdP in patients with bradycardia. Lapatinib has been associated with concentration-dependent QT prolongation; ventricular arrhythmias and TdP have been reported in postmarketing experience with lapatinib.
Lasmiditan: (Major) Coadministration of ozanimod with lasmiditan is not recommended; monitor patients for hypertension if used together. An active metabolite of ozanimod inhibits MAO-B, creating potential for hypertensive crisis when give with medications that increase serotonin, such as lasmiditan.
Lefamulin: (Major) Avoid coadministration of lefamulin with ozanimod as concurrent use may increase the risk of QT prolongation. If coadministration cannot be avoided, ECG monitoring is recommended during treatment. Lefamulin has a concentration dependent QTc prolongation effect. The pharmacodynamic interaction potential to prolong the QT interval of the electrocardiogram between lefamulin and other drugs that effect cardiac conduction is unknown. Ozanimod initiation may result in a transient decrease in heart rate and atrioventricular conduction delays. Ozanimod has not been studied in patients taking concurrent QT prolonging drugs; however, QT prolonging drugs have been associated with torsade de pointes in patients with bradycardia.
Lenvatinib: (Major) In general, do not initiate ozanimod in patients taking lenvatinib due to the risk of additive bradycardia, QT prolongation, and torsade de pointes (TdP). If treatment initiation is considered, seek advice from a cardiologist. Ozanimod initiation may result in a transient decrease in heart rate and atrioventricular conduction delays. Ozanimod has not been studied in patients taking concurrent QT prolonging drugs; however, QT prolonging drugs have been associated with TdP in patients with bradycardia. Prolongation of the QT interval has been reported with lenvatinib therapy.
Leuprolide: (Major) In general, do not initiate ozanimod in patients taking leuprolide due to the risk of additive bradycardia, QT prolongation, and torsade de pointes (TdP). If treatment initiation is considered, seek advice from a cardiologist. Ozanimod initiation may result in a transient decrease in heart rate and atrioventricular conduction delays. Ozanimod has not been studied in patients taking concurrent QT prolonging drugs; however, QT prolonging drugs have been associated with TdP in patients with bradycardia. Androgen deprivation therapy (i.e., leuprolide) may prolong the QT/QTc interval.
Leuprolide; Norethindrone: (Major) In general, do not initiate ozanimod in patients taking leuprolide due to the risk of additive bradycardia, QT prolongation, and torsade de pointes (TdP). If treatment initiation is considered, seek advice from a cardiologist. Ozanimod initiation may result in a transient decrease in heart rate and atrioventricular conduction delays. Ozanimod has not been studied in patients taking concurrent QT prolonging drugs; however, QT prolonging drugs have been associated with TdP in patients with bradycardia. Androgen deprivation therapy (i.e., leuprolide) may prolong the QT/QTc interval.
Levobunolol: (Moderate) Ozanimod may cause bradycardia and AV-conduction delays, which may be enhanced with the concomitant use of beta-blockers. If a calcium channel blocker that slows heart rate/cardiac conduction is also prescribed with ozanimod and a beta-blocker, a cardiologist should be consulted due to the likelyhood of additive effects.
Levofloxacin: (Major) Concomitant use of levofloxacin and ozanimod increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. Ozanimod has a limited effect on the QT/QTc interval at therapeutic doses but may cause bradycardia and atrioventricular conduction delays which may increase the risk for TdP in patients with a prolonged QT/QTc interval.
Levoketoconazole: (Contraindicated) Avoid concomitant use of ketoconazole and ozanimod due to an increased risk for torsade de pointes (TdP) and QT/QTc prolongation. Ozanimod has a limited effect on the QT/QTc interval at therapeutic doses but may cause bradycardia and atrioventricular conduction delays which may increase the risk for TdP in patients with a prolonged QT/QTc interval.
Levomilnacipran: (Major) Coadministration of ozanimod with levomilnacipran is not recommended due to the potential for hypertensive crisis. If coadministration is necessary, closely monitor patients for hypertension and serotonergic effects. An active metabolite of ozanimod inhibits MAO-B, which may increase the potential for hypertensive crisis. Levomilnacipran may increase blood pressure by increasing serotonin and norepinephrine concentrations.
Levorphanol: (Moderate) Coadministration of levorphanol with ozanimod is not recommended due to the potential for serotonergic effects. An active metabolite of ozanimod inhibits MAO-B, which may increase the potential for serotonin syndrome or increased blood pressure. If concomitant use of levorphanol is warranted in a patient taking an MAO inhibitor, carefully observe the patient and monitor blood pressure, particularly during treatment initiation and dose adjustment. Discontinue serotonergic agents if serotonin syndrome is suspected. Although a small number of patients treated with ozanimod were concomitantly exposed to opioids, this exposure was not adequate to rule out the possibility of an adverse reaction from coadministration.
Lidocaine; Epinephrine: (Major) Coadministration of ozanimod with sympathomimetics such as epinephrine is not routinely recommended due to the potential for hypertensive crisis. If coadministration is medically necessary, closely monitor the patient for hypertension. An active metabolite of ozanimod inhibits MAO-B, which may increase the potential for hypertensive crisis. Sympathomimetics may increase blood pressure by increasing norepinephrine concentrations and monoamine oxidase inhibitors (MAOIs) are known to potentiate these effects. Concomitant use of ozanimod with pseudoephedrine did not potentiate the effects on blood pressure. However, hypertensive crisis has occurred with administration of ozanimod alone and also during coadministration of sympathomimetic medications and other selective or nonselective MAO inhibitors.
Linezolid: (Contraindicated) Coadministration of ozanimod with monoamine oxidase (MAO) inhibitors, like linezolid, is contraindicated. Allow at least 14 days between discontinuation of ozanimod and initiation of treatment with linezolid. Metabolites of ozanimod may inhibit MAO. The potential for a clinical interaction with MAO inhibitors has not been studied; however, the increased risk of nonselective MAO inhibition may lead to a hypertensive crisis.
Lisdexamfetamine: (Major) Avoid concurrent use of ozanimod and amphetamines when possible as this combination may increase the risk for serious adverse reactions such as hypertensive crisis. If use is necessary, monitor for hypertension. Amphetamines may increase blood pressure by increasing norepinephrine and serotonin concentrations and monoamine oxidase inhibitors (MAOIs) are known to potentiate these effects. An active metabolite of ozanimod inhibits MAO-B in vitro. Sympathomimetics are contraindicated for use with non-selective MAOIs, however the risk for hypertensive reactions may be lower with selective MAO-B inhibitors.
Lithium: (Major) In general, do not initiate ozanimod in patients taking lithium due to the risk of additive bradycardia, QT prolongation, and torsade de pointes (TdP). Additionally, there is a potential for hypertensive crisis and serotonin syndrome. If treatment initiation is considered, seek advice from a cardiologist and monitor for hypertension and serotonergic effects. An active metabolite of ozanimod inhibits MAO-B, which may increase the potential for hypertensive crisis and serotonin syndome. There is an increased risk of serotonin syndrome during concurrent use of drugs with central serotonergic properties such as lithium and MAO inhibitors. Ozanimod may also result in a transient decrease in heart rate and atrioventricular conduction delays. Ozanimod has not been studied in patients taking concurrent QT prolonging drugs; however, QT prolonging drugs have been associated with TdP in patients with bradycardia. Lithium is a serotonergic drug that has been associated with QT prolongation.
Live Vaccines: (Major) Avoid the use of live vaccines and live attenuated vaccines during ozanimod treatment and for up to 3 months after discontinuation of ozanimod treatment. Live vaccinations may be less effective during ozanimod treatment and also may carry the risk of infection.
Lofexidine: (Major) In general, do not initiate ozanimod in patients taking lofexidine due to the risk of additive bradycardia, QT prolongation, and torsade de pointes (TdP). If concomitant use is necessary, monitor ECGs. Ozanimod initiation may result in a transient decrease in heart rate and atrioventricular conduction delays. Ozanimod has not been studied in patients taking concurrent QT prolonging drugs; however, QT prolonging drugs have been associated with TdP in patients with bradycardia. Lofexidine has been associated with QT prolongation.
Loperamide: (Major) In general, do not initiate ozanimod in patients taking loperamide due to the risk of additive bradycardia, QT prolongation, and torsade de pointes (TdP). If treatment initiation is considered, seek advice from a cardiologist. Ozanimod initiation may result in a transient decrease in heart rate and atrioventricular conduction delays. Ozanimod has not been studied in patients taking concurrent QT prolonging drugs; however, QT prolonging drugs have been associated with TdP in patients with bradycardia. At high doses, loperamide has been associated with serious cardiac toxicities, including syncope, ventricular tachycardia, QT prolongation, TdP, and cardiac arrest.
Loperamide; Simethicone: (Major) In general, do not initiate ozanimod in patients taking loperamide due to the risk of additive bradycardia, QT prolongation, and torsade de pointes (TdP). If treatment initiation is considered, seek advice from a cardiologist. Ozanimod initiation may result in a transient decrease in heart rate and atrioventricular conduction delays. Ozanimod has not been studied in patients taking concurrent QT prolonging drugs; however, QT prolonging drugs have been associated with TdP in patients with bradycardia. At high doses, loperamide has been associated with serious cardiac toxicities, including syncope, ventricular tachycardia, QT prolongation, TdP, and cardiac arrest.
Lopinavir; Ritonavir: (Major) Avoid coadministration of lopinavir with ozanimod due to the potential for additive QT prolongation. If use together is necessary, obtain a baseline ECG to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. Lopinavir is associated with QT prolongation. Ozanimod initiation may result in a transient decrease in heart rate and atrioventricular conduction delays. Ozanimod has not been studied in patients taking concurrent QT prolonging drugs; however, QT prolonging drugs have been associated with torsade de pointes in patients with bradycardia.
Loratadine; Pseudoephedrine: (Major) Coadministration of ozanimod with sympathomimetics such as pseudoephedrine is not routinely recommended due to the potential for hypertensive crisis. If coadministration is medically necessary, closely monitor the patient for hypertension. An active metabolite of ozanimod inhibits MAO-B, which may increase the potential for hypertensive crisis. Sympathomimetics may increase blood pressure by increasing norepinephrine concentrations and monoamine oxidase inhibitors (MAOIs) are known to potentiate these effects. Concomitant use of ozanimod with pseudoephedrine did not potentiate the effects on blood pressure. However, hypertensive crisis has occurred with administration of ozanimod alone and also during coadministration of sympathomimetic medications and other selective or nonselective MAO inhibitors.
Lorcaserin: (Major) Coadministration of ozanimod with lorcaserin is not recommended due to the potential for hypertensive crisis. If coadministration is necessary, closely monitor patients for hypertension. An active metabolite of ozanimod inhibits MAO-B, which may increase the potential for hypertensive crisis. Lorcaserin may increase blood pressure by increasing serotonin concentrations.
Macimorelin: (Major) Avoid concurrent administration of macimorelin with drugs that prolong the QT interval, such as ozanimod. Use of these drugs together may increase the risk of developing torsade de pointes-type ventricular tachycardia. Sufficient washout time of drugs that are known to prolong the QT interval prior to administration of macimorelin is recommended. Treatment with macimorelin has been associated with an increase in the corrected QT (QTc) interval. Ozanimod initiation may result in a transient decrease in heart rate and atrioventricular conduction delays. Ozanimod has not been studied in patients taking concurrent QT prolonging drugs; however, QT prolonging drugs have been associated with torsade de pointes in patients with bradycardia.
Maprotiline: (Contraindicated) Do not use maprotiline in patients taking MAOIs or within 14 days of stopping them. An active metabolite of ozanimod inhibits MAO-B, and interactions with maprotiline may manifest as serotonin syndrome, hypertensive crisis, QT prolongation or other serious side effects. Hyperpyretic crises, severe convulsions, and deaths have occurred in patients receiving cyclic antidepressants and MAO inhibiting drugs simultaneously. Consider an alternative to maprotiline. Ozanimod is a monoamine oxidase inhibitor that may result in a transient decrease in heart rate and atrioventricular conduction delays. Ozanimod has not been studied in patients taking concurrent QT prolonging drugs; however, QT prolonging drugs have been associated with TdP in patients with bradycardia. Maprotiline has been reported to prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations). Cases of long QT syndrome and TdP tachycardia have been described with maprotiline use, but rarely occur when the drug is used alone in normal prescribed doses and in the absence of other known risk factors for QT prolongation. Limited data are available regarding the safety of maprotiline in combination with other QT-prolonging drugs.
Measles Virus; Mumps Virus; Rubella Virus; Varicella Virus Vaccine, Live: (Major) Avoid the use of live vaccines and live attenuated vaccines during ozanimod treatment and for up to 3 months after discontinuation of ozanimod treatment. Live vaccinations may be less effective during ozanimod treatment and also may carry the risk of infection.
Measles/Mumps/Rubella Vaccines, MMR: (Major) Avoid the use of live vaccines and live attenuated vaccines during ozanimod treatment and for up to 3 months after discontinuation of ozanimod treatment. Live vaccinations may be less effective during ozanimod treatment and also may carry the risk of infection.
Mefloquine: (Major) In general, do not initiate ozanimod in patients taking mefloquine due to the risk of additive bradycardia, QT prolongation, and torsade de pointes (TdP). If treatment initiation is considered, seek advice from a cardiologist. Ozanimod initiation may result in a transient decrease in heart rate and atrioventricular conduction delays. Ozanimod has not been studied in patients taking concurrent QT prolonging drugs; however, QT prolonging drugs have been associated with TdP in patients with bradycardia. There is evidence that the use of halofantrine after mefloquine causes a significant lengthening of the QTc interval. Mefloquine alone has not been reported to cause QT prolongation.
Meperidine: (Contraindicated) Do not use meperidine in patients taking MAOIs or within 14 days of stopping them. An active metabolite of ozanimod inhibits MAO-B. MAO inhibitor interactions with meperidine may manifest as serotonin syndrome, hypertensive crisis, or opioid toxicity (e.g., respiratory depression, coma). Although a small number of patients treated with ozanimod were concomitantly exposed to opioids, this exposure was not adequate to rule out the possibility of an adverse reaction from coadministration.
Metaxalone: (Major) Coadministration of ozanimod with metaxalone is not recommended due to the potential for hypertensive crisis. If coadministration is necessary, closely monitor patients for hypertension. An active metabolite of ozanimod inhibits MAO-B, which may increase the potential for hypertensive crisis. Metaxalone may increase blood pressure by increasing serotonin concentrations.
Methadone: (Major) In general, do not initiate ozanimod in patients taking methadone due to the risk of bradycardia, QT prolongation, and torsade de pointes (TdP). Additionally, there is a potential for increased blood pressure and serotonin syndrome. If treatment initiation is considered, seek advice from a cardiologist and monitor for hypertension. Ozanimod may result in a transient decrease in heart rate and atrioventricular conduction delays. An active metabolite of ozanimod inhibits monoamine oxidase B (MAO-B). The concomitant use of opioids with MAO inhibitors has resulted in serotonin syndrome. Ozanimod has not been studied in patients taking concurrent QT prolonging drugs; however, QT prolonging drugs have been associated with TdP in patients with bradycardia. Methadone is a serotonergic drug that is associated with QT prolongation and TdP, especially at higher doses (more than 200 mg/day but averaging approximately 400 mg/day in adult patients). Most cases involve patients being treated for pain with large, multiple daily doses of methadone, although cases have been reported in patients receiving doses commonly used for maintenance treatment of opioid addiction. Although a small number of patients treated with ozanimod were concomitantly exposed to opioids, this exposure was not adequate to rule out the possibility of an adverse reaction from co-administration.
Methamphetamine: (Major) Avoid concurrent use of ozanimod and amphetamines when possible as this combination may increase the risk for serious adverse reactions such as hypertensive crisis. If use is necessary, monitor for hypertension. Amphetamines may increase blood pressure by increasing norepinephrine and serotonin concentrations and monoamine oxidase inhibitors (MAOIs) are known to potentiate these effects. An active metabolite of ozanimod inhibits MAO-B in vitro. Sympathomimetics are contraindicated for use with non-selective MAOIs, however the risk for hypertensive reactions may be lower with selective MAO-B inhibitors.
Methenamine; Sodium Acid Phosphate; Methylene Blue; Hyoscyamine: (Major) Concurrent use of intravenous (IV) methylene blue and drugs with selective MAOI activity, such as ozanimod, should generally be avoided due to the potential for serotonin syndrome. If emergent treatment with methylene blue is required in a patient receiving an MAOI it is advisable to discontinue the MAOI and monitor the patient for symptoms of CNS toxicity for two weeks or until 24 hours after the last dose of methylene blue, whichever comes first. During non-emergent use of methylene blue, it is advisable to discontinue ozanimod at least 2 weeks prior to methylene blue treatment, taking into consideration the half-life of ozanimod. Because the metabolites of ozanimod inhibit primarily monoamine oxidase-B (MAO-B), an interaction may be less likely to occur than with other traditional MAOIs. Methylene blue is a thiazine dye that is also a potent, reversible inhibitor of the enzyme responsible for the catabolism of serotonin in the brain (MAO-A). Cases of serotonin syndrome have been reported, primarily following administration of IV methylene blue (1 to 8 mg/kg) as a visualizing agent in patients receiving serotonergic agents.
Methylene Blue: (Major) Concurrent use of intravenous (IV) methylene blue and drugs with selective MAOI activity, such as ozanimod, should generally be avoided due to the potential for serotonin syndrome. If emergent treatment with methylene blue is required in a patient receiving an MAOI it is advisable to discontinue the MAOI and monitor the patient for symptoms of CNS toxicity for two weeks or until 24 hours after the last dose of methylene blue, whichever comes first. During non-emergent use of methylene blue, it is advisable to discontinue ozanimod at least 2 weeks prior to methylene blue treatment, taking into consideration the half-life of ozanimod. Because the metabolites of ozanimod inhibit primarily monoamine oxidase-B (MAO-B), an interaction may be less likely to occur than with other traditional MAOIs. Methylene blue is a thiazine dye that is also a potent, reversible inhibitor of the enzyme responsible for the catabolism of serotonin in the brain (MAO-A). Cases of serotonin syndrome have been reported, primarily following administration of IV methylene blue (1 to 8 mg/kg) as a visualizing agent in patients receiving serotonergic agents.
Methylphenidate Derivatives: (Contraindicated) Coadministration of ozanimod with methylphenidate derivatives is contraindicated. Allow at least 14 days between discontinuation of ozanimod and initiation of methylphenidate. An active metabolite of ozanimod inhibits MAO-B, which may increase the potential for hypertensive crisis. Sympathomimetics such as methylphenidate may increase blood pressure by increasing norepinephrine concentrations and monoamine oxidase inhibitors (MAOIs) are known to potentiate these effects. Methylphenidate derivatives may also have serotonergic effects that may increase blood pressure. Concomitant use of ozanimod with pseudoephedrine did not potentiate the effects on blood pressure. However, hypertensive crisis has occurred with administration of ozanimod alone and during coadministration of sympathomimetic medications and other selective or nonselective MAO inhibitors.
Methylphenidate: (Contraindicated) Coadministration of ozanimod with methylphenidate derivatives is contraindicated. Allow at least 14 days between discontinuation of ozanimod and initiation of methylphenidate. An active metabolite of ozanimod inhibits MAO-B, which may increase the potential for hypertensive crisis. Sympathomimetics such as methylphenidate may increase blood pressure by increasing norepinephrine concentrations and monoamine oxidase inhibitors (MAOIs) are known to potentiate these effects. Methylphenidate derivatives may also have serotonergic effects that may increase blood pressure. Concomitant use of ozanimod with pseudoephedrine did not potentiate the effects on blood pressure. However, hypertensive crisis has occurred with administration of ozanimod alone and during coadministration of sympathomimetic medications and other selective or nonselective MAO inhibitors.
Methylprednisolone: (Moderate) Concomitant use of ozanimod with methylprednisolone may increase the risk of immunosuppression. Monitor patients carefully for signs and symptoms of infection. In clinical studies for ulcerative colitis, the use of systemic corticosteroids did not appear to influence safety or efficacy of ozanimod.
Metoprolol: (Moderate) Ozanimod may cause bradycardia and AV-conduction delays, which may be enhanced with the concomitant use of beta-blockers. If a calcium channel blocker that slows heart rate/cardiac conduction is also prescribed with ozanimod and a beta-blocker, a cardiologist should be consulted due to the likelyhood of additive effects.
Metoprolol; Hydrochlorothiazide, HCTZ: (Moderate) Ozanimod may cause bradycardia and AV-conduction delays, which may be enhanced with the concomitant use of beta-blockers. If a calcium channel blocker that slows heart rate/cardiac conduction is also prescribed with ozanimod and a beta-blocker, a cardiologist should be consulted due to the likelyhood of additive effects.
Metronidazole: (Major) Concomitant use of metronidazole and ozanimod increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. Ozanimod has a limited effect on the QT/QTc interval at therapeutic doses but may cause bradycardia and atrioventricular conduction delays which may increase the risk for TdP in patients with a prolonged QT/QTc interval.
Midodrine: (Major) Avoid coadministration of ozanimod with midodrine due to the potential for hypertensive crisis. If coadministration is medically necessary, closely monitor the patient for hypertension. An active metabolite of ozanimod inhibits MAO-B, which may increase the potential for hypertensive crisis. Midodrine may increase blood pressure through alpha agonist activity. Hypertensive crisis has occurred with administration of ozanimod alone and also during coadministration of sympathomimetic medications.
Midostaurin: (Major) In general, do not initiate ozanimod in patients taking midostaurin due to the risk of additive bradycardia, QT prolongation, and torsade de pointes (TdP). If concomitant use is necessary, consider ECG monitoring. Ozanimod initiation may result in a transient decrease in heart rate and atrioventricular conduction delays. Ozanimod has not been studied in patients taking concurrent QT prolonging drugs; however, QT prolonging drugs have been associated with TdP in patients with bradycardia. QT prolongation was reported in patients who received midostaurin in clinical trials.
Mifepristone: (Major) In general, do not initiate ozanimod in patients taking mifepristone due to the risk of additive bradycardia, QT prolongation, and torsade de pointes (TdP). If treatment initiation is considered, seek advice from a cardiologist. Ozanimod initiation may result in a transient decrease in heart rate and atrioventricular conduction delays. Ozanimod has not been studied in patients taking concurrent QT prolonging drugs; however, QT prolonging drugs have been associated with TdP in patients with bradycardia. Mifepristone is associated with dose-related prolongation of the QT interval.
Milnacipran: (Major) Coadministration of ozanimod with milnacipran is not recommended due to the potential for hypertensive crisis. If coadministration is necessary, closely monitor patients for hypertension and serotonergic effects. An active metabolite of ozanimod inhibits MAO-B, which may increase the potential for hypertensive crisis. Milnacipran may increase blood pressure by increasing serotonin and norepinephrine concentrations.
Mirtazapine: (Major) In general, do not initiate ozanimod in patients taking mirtazapine due to the risk of additive bradycardia, QT prolongation, and torsade de pointes (TdP). Additionally, there is a potential for hypertensive crisis. If treatment initiation is considered, seek advice from a cardiologist and monitor for hypertension. An active metabolite of ozanimod inhibits MAO-B, which may increase the potential for hypertensive crisis. Ozanimod may also result in a transient decrease in heart rate and atrioventricular conduction delays. Ozanimod has not been studied in patients taking concurrent QT prolonging drugs; however, QT prolonging drugs have been associated with TdP in patients with bradycardia. Mirtazapine is a serotonergic drug that has been associated with dose-dependent prolongation of the QT interval. TdP has been reported postmarketing, primarily in overdose or in patients with other risk factors for QT prolongation.
Mitoxantrone: (Moderate) Concomitant use of ozanimod with mitoxantrone may increase the risk of immunosuppression. Ozanimod has not been studied in combination with other immunosuppressive or immune modulating therapies used for the treatment of multiple sclerosis. Use caution when switching patients from long-acting therapies with immune effects such as mitoxantrone. The median elimination half-life of mitoxantrone is 75 hours (range 23 to 215 hours).
Mobocertinib: (Major) Concomitant use of mobocertinib and ozanimod increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. Ozanimod has a limited effect on the QT/QTc interval at therapeutic doses but may cause bradycardia and atrioventricular conduction delays which may increase the risk for TdP in patients with a prolonged QT/QTc interval.
Monoamine oxidase inhibitors: (Contraindicated) Coadministration of ozanimod with monoamine oxidase (MAO) inhibitors is contraindicated. Allow at least 14 days between discontinuation of ozanimod and initiation of treatment with MAO inhibitors. Metabolites of ozanimod may inhibit MAO. The potential for a clinical interaction with MAO inhibitors has not been studied; however, the increased risk of nonselective MAO inhibition may lead to a hypertensive crisis.
Monomethyl Fumarate: (Moderate) Concomitant use of ozanimod with monomethyl fumarate may increase the risk of immunosuppression. Ozanimod has not been studied in combination with other immunosuppressive or immune modulating therapies used for the treatment of multiple sclerosis.
Morphine: (Major) When possible, morphine should not be used in patients taking MAOIs or within 14 days of stopping such treatment. An active metabolite of ozanimod inhibits MAO-B. MAO inhibitor interactions with morphine may manifest as serotonin syndrome, hypertensive crisis, or opioid toxicity (e.g., respiratory depression, coma). If concurrent use is absolutely necessary, use the lowest possible doses of morphine, and monitor blood pressure and for serotonergic symptoms closely. Although a small number of patients treated with ozanimod were concomitantly exposed to opioids, this exposure was not adequate to rule out the possibility of an adverse reaction from coadministration.
Morphine; Naltrexone: (Major) When possible, morphine should not be used in patients taking MAOIs or within 14 days of stopping such treatment. An active metabolite of ozanimod inhibits MAO-B. MAO inhibitor interactions with morphine may manifest as serotonin syndrome, hypertensive crisis, or opioid toxicity (e.g., respiratory depression, coma). If concurrent use is absolutely necessary, use the lowest possible doses of morphine, and monitor blood pressure and for serotonergic symptoms closely. Although a small number of patients treated with ozanimod were concomitantly exposed to opioids, this exposure was not adequate to rule out the possibility of an adverse reaction from coadministration.
Moxifloxacin: (Major) In general, do not initiate ozanimod in patients taking moxifloxacin due to the risk of additive bradycardia, QT prolongation, and torsade de pointes (TdP). If treatment initiation is considered, seek advice from a cardiologist. Ozanimod initiation may result in a transient decrease in heart rate and atrioventricular conduction delays. Ozanimod has not been studied in patients taking concurrent QT prolonging drugs; however, QT prolonging drugs have been associated with TdP in patients with bradycardia. Quinolones have been associated with a risk of QT prolongation. Although extremely rare, TdP has been reported during postmarketing surveillance of moxifloxacin. These reports generally involved patients with concurrent medical conditions or concomitant medications that may have been contributory.
Nadolol: (Moderate) Ozanimod may cause bradycardia and AV-conduction delays, which may be enhanced with the concomitant use of beta-blockers. If a calcium channel blocker that slows heart rate/cardiac conduction is also prescribed with ozanimod and a beta-blocker, a cardiologist should be consulted due to the likelyhood of additive effects.
Nalbuphine: (Moderate) Nalbuphine should not be used in patients taking MAOIs or within 14 days of stopping such treatment due to the potential for serotonergic effects. An active metabolite of ozanimod inhibits MAO-B, which may increase the potential for serotonin syndrome or increased blood pressure. If concomitant use of nalbuphine is warranted in a patient taking an MAO inhibitor, carefully observe the patient and monitor blood pressure, particularly during treatment initiation and dose adjustment. Discontinue serotonergic agents if serotonin syndrome is suspected. Although a small number of patients treated with ozanimod were concomitantly exposed to opioids, this exposure was not adequate to rule out the possibility of an adverse reaction from coadministration.
Naproxen; Pseudoephedrine: (Major) Coadministration of ozanimod with sympathomimetics such as pseudoephedrine is not routinely recommended due to the potential for hypertensive crisis. If coadministration is medically necessary, closely monitor the patient for hypertension. An active metabolite of ozanimod inhibits MAO-B, which may increase the potential for hypertensive crisis. Sympathomimetics may increase blood pressure by increasing norepinephrine concentrations and monoamine oxidase inhibitors (MAOIs) are known to potentiate these effects. Concomitant use of ozanimod with pseudoephedrine did not potentiate the effects on blood pressure. However, hypertensive crisis has occurred with administration of ozanimod alone and also during coadministration of sympathomimetic medications and other selective or nonselective MAO inhibitors.
Naratriptan: (Major) Coadministration of ozanimod with serotonin receptor agonists "triptans" is not recommended due to the potential for hypertensive crisis or serotonin syndrome. If coadministration is necessary, closely monitor patients for hypertension and serotonergic effects. An active metabolite of ozanimod inhibits MAO-B, which may increase the potential for hypertensive crisis or serotonin syndrome. Serotonin receptor agonists may increase blood pressure by increasing serotonin concentrations.
Natalizumab: (Major) Avoid coadministration of ozanimod and natalizumab. Natalizumab should not be used in combination with ozanimod because of the potential for increased risk of progressive multifocal leukoencephalopathy and other serious infections. Ordinarily, multiple sclerosis patients receiving chronic immunomodulatory therapy should not be treated with natalizumab.
Nebivolol: (Moderate) Ozanimod may cause bradycardia and AV-conduction delays, which may be enhanced with the concomitant use of beta-blockers. If a calcium channel blocker that slows heart rate/cardiac conduction is also prescribed with ozanimod and a beta-blocker, a cardiologist should be consulted due to the likelyhood of additive effects.
Nebivolol; Valsartan: (Moderate) Ozanimod may cause bradycardia and AV-conduction delays, which may be enhanced with the concomitant use of beta-blockers. If a calcium channel blocker that slows heart rate/cardiac conduction is also prescribed with ozanimod and a beta-blocker, a cardiologist should be consulted due to the likelyhood of additive effects.
Nefazodone: (Major) Coadministration of ozanimod with nefazodone is not recommended due to the potential for hypertensive crisis. If coadministration is necessary, closely monitor patients for hypertension. An active metabolite of ozanimod inhibits MAO-B, which may increase the potential for hypertensive crisis. Nefazodone may increase blood pressure by increasing serotonin concentrations.
Netupitant, Fosnetupitant; Palonosetron: (Major) Coadministration of ozanimod with palonosetron is not recommended due to the potential for hypertensive crisis. If coadministration is necessary, closely monitor patients for hypertension. An active metabolite of ozanimod inhibits MAO-B, which may increase the potential for hypertensive crisis. Palonosetron may increase blood pressure by increasing serotonin concentrations.
Nilotinib: (Major) In general, do not initiate ozanimod in patients taking nilotinib due to the risk of additive bradycardia, QT prolongation, and torsade de pointes (TdP). If treatment initiation is considered, seek advice from a cardiologist. Ozanimod initiation may result in a transient decrease in heart rate and atrioventricular conduction delays. Ozanimod has not been studied in patients taking concurrent QT prolonging drugs; however, QT prolonging drugs have been associated with TdP in patients with bradycardia. Sudden death and QT interval prolongation have occurred in patients who received nilotinib therapy.
Norepinephrine: (Major) Coadministration of ozanimod with sympathomimetics such as norepinephrine is not routinely recommended due to the potential for hypertensive crisis. If coadministration is medically necessary, closely monitor the patient for hypertension. An active metabolite of ozanimod inhibits MAO-B, which may increase the potential for hypertensive crisis. Sympathomimetics may increase blood pressure by increasing norepinephrine concentrations and monoamine oxidase inhibitors (MAOIs) are known to potentiate these effects. Concomitant use of ozanimod with pseudoephedrine did not potentiate the effects on blood pressure. However, hypertensive crisis has occurred with administration of ozanimod alone and also during coadministration of sympathomimetic medications and other selective or nonselective MAO inhibitors.
Nortriptyline: (Contraindicated) Do not use tricyclic antidepressants (TCAs) in patients taking MAOIs or within 14 days of stopping them. An active metabolite of ozanimod inhibits MAO-B, and interactions with TCAs may manifest as serotonin syndrome, hypertensive crisis, QT prolongation or other serious side effects. Hyperpyretic crises, severe convulsions, and deaths have occurred in patients receiving TCAs and MAO inhibiting drugs simultaneously. Consider an alternative to the TCA. Ozanimod is a monoamine oxidase inhibitor that may result in a transient decrease in heart rate and atrioventricular conduction delays. Ozanimod has not been studied in patients taking concurrent QT prolonging drugs; however, QT prolonging drugs have been associated with TdP in patients with bradycardia. TCAs are serotonergic drugs that share pharmacologic properties similar to the Class IA antiarrhythmic agents and may prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations).
Ocrelizumab: (Moderate) Concomitant use of ozanimod with ocrelizumab may increase the risk of immunosuppression. Ozanimod has not been studied in combination with other immunosuppressive or immune modulating therapies used for the treatment of multiple sclerosis.
Ofatumumab: (Moderate) Concomitant use of ofatumumab with ozanimod may increase the risk of immunosuppression. Ofatumumab has not been studied in combination with other immunosuppressive or immune modulating therapies used for the treatment of multiple sclerosis, such as ozanimod. Consider the duration and mechanism of action of drugs with immunosuppressive effects when switching therapies for multiple sclerosis patients.
Ofloxacin: (Major) Concomitant use of ofloxacin and ozanimod increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. Ozanimod has a limited effect on the QT/QTc interval at therapeutic doses but may cause bradycardia and atrioventricular conduction delays which may increase the risk for TdP in patients with a prolonged QT/QTc interval.
Olanzapine: (Major) In general, do not initiate ozanimod in patients taking olanzapine due to the risk of additive bradycardia, QT prolongation, and torsade de pointes (TdP). Additionally, there is a potential for hypertensive crisis or serotonin syndrome. If treatment initiation is considered, seek advice from a cardiologist and monitor for hypertension and serotonergic effects. An active metabolite of ozanimod inhibits MAO-B, which may increase the potential for hypertensive crisis or serotonergic effects. Olanzapine has also been associated with serotonin syndrome reports postmarketing, but the mechanism is not clear. Ozanimod may also result in a transient decrease in heart rate and atrioventricular conduction delays. Ozanimod has not been studied in patients taking concurrent QT prolonging drugs; however, QT prolonging drugs have been associated with TdP in patients with bradycardia. Olanzapine has been associated with a significant prolongation of the QTc interval.
Olanzapine; Fluoxetine: (Major) In general, do not initiate ozanimod in patients taking fluoxetine due to the risk of additive bradycardia, QT prolongation, and torsade de pointes (TdP). Additionally, there is a potential for hypertensive crisis and serotonin syndrome. If treatment initiation is considered, seek advice from a cardiologist and monitor for hypertension and serotonergic effects. Ozanimod is a monoamine oxidase inhibitor that may result in a transient decrease in heart rate and atrioventricular conduction delays. Ozanimod has not been studied in patients taking concurrent QT prolonging drugs; however, QT prolonging drugs have been associated with TdP in patients with bradycardia. Fluoxetine is a serotonergic drug that is associated with QT prolongation and TdP. (Major) In general, do not initiate ozanimod in patients taking olanzapine due to the risk of additive bradycardia, QT prolongation, and torsade de pointes (TdP). Additionally, there is a potential for hypertensive crisis or serotonin syndrome. If treatment initiation is considered, seek advice from a cardiologist and monitor for hypertension and serotonergic effects. An active metabolite of ozanimod inhibits MAO-B, which may increase the potential for hypertensive crisis or serotonergic effects. Olanzapine has also been associated with serotonin syndrome reports postmarketing, but the mechanism is not clear. Ozanimod may also result in a transient decrease in heart rate and atrioventricular conduction delays. Ozanimod has not been studied in patients taking concurrent QT prolonging drugs; however, QT prolonging drugs have been associated with TdP in patients with bradycardia. Olanzapine has been associated with a significant prolongation of the QTc interval.
Olanzapine; Samidorphan: (Major) In general, do not initiate ozanimod in patients taking olanzapine due to the risk of additive bradycardia, QT prolongation, and torsade de pointes (TdP). Additionally, there is a potential for hypertensive crisis or serotonin syndrome. If treatment initiation is considered, seek advice from a cardiologist and monitor for hypertension and serotonergic effects. An active metabolite of ozanimod inhibits MAO-B, which may increase the potential for hypertensive crisis or serotonergic effects. Olanzapine has also been associated with serotonin syndrome reports postmarketing, but the mechanism is not clear. Ozanimod may also result in a transient decrease in heart rate and atrioventricular conduction delays. Ozanimod has not been studied in patients taking concurrent QT prolonging drugs; however, QT prolonging drugs have been associated with TdP in patients with bradycardia. Olanzapine has been associated with a significant prolongation of the QTc interval.
Ondansetron: (Major) In general, do not initiate ozanimod in patients taking ondansetron due to the risk of additive bradycardia, QT prolongation, and torsade de pointes (TdP). Additionally, there is a potential for hypertensive crisis. If concomitant use is necessary, monitor ECGs and for hypertension. An active metabolite of ozanimod inhibits MAO-B, which may increase the potential for hypertensive crisis. Ozanimod may also result in a transient decrease in heart rate and atrioventricular conduction delays. Ozanimod has not been studied in patients taking concurrent QT prolonging drugs; however, QT prolonging drugs have been associated with TdP in patients with bradycardia. Ondansetron is a serotonergic drug that has been associated with a dose-related increase in the QT interval and postmarketing reports of TdP.
Osilodrostat: (Major) In general, do not initiate ozanimod in patients taking osilodrostat due to the risk of additive bradycardia, QT prolongation, and torsade de pointes (TdP). If treatment initiation is considered, seek advice from a cardiologist. Ozanimod initiation may result in a transient decrease in heart rate and atrioventricular conduction delays. Ozanimod has not been studied in patients taking concurrent QT prolonging drugs; however, QT prolonging drugs have been associated with TdP in patients with bradycardia. Osilodrostat is associated with dose-dependent QT prolongation.
Osimertinib: (Major) Concomitant use of ozanimod and osimertinib increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. Ozanimod has a limited effect on the QT/QTc interval at therapeutic doses but may cause bradycardia and atrioventricular conduction delays which may increase the risk for TdP in patients with a prolonged QT/QTc interval.
Oxaliplatin: (Major) In general, do not initiate ozanimod in patients taking oxaliplatin due to the risk of additive bradycardia, QT prolongation, and torsade de pointes (TdP). If concomitant use is necessary, monitor ECGs and electrolytes; correct electrolyte abnormalities prior to administration of oxaliplatin. Ozanimod initiation may result in a transient decrease in heart rate and atrioventricular conduction delays. Ozanimod has not been studied in patients taking concurrent QT prolonging drugs; however, QT prolonging drugs have been associated with TdP in patients with bradycardia. QT prolongation and ventricular arrhythmias, including fatal TdP, have been reported with oxaliplatin use in postmarketing experience.
Oxycodone: (Major) When possible, oxycodone should not be used in patients taking MAOIs or within 14 days of stopping such treatment. An active metabolite of ozanimod inhibits MAO-B. MAO inhibitor interactions with oxycodone may manifest as serotonin syndrome, hypertensive crisis, or opioid toxicity (e.g., respiratory depression, coma). If concurrent use is absolutely necessary, use the lowest possible doses of oxycodone, and monitor blood pressure and for serotonergic symptoms closely. Although a small number of patients treated with ozanimod were concomitantly exposed to opioids, this exposure was not adequate to rule out the possibility of an adverse reaction from coadministration.
Oxymorphone: (Major) When possible, oxymorphone should not be used in patients taking MAOIs or within 14 days of stopping such treatment. An active metabolite of ozanimod inhibits MAO-B. MAO inhibitor interactions with oxymorphone may manifest as serotonin syndrome, hypertensive crisis, or opioid toxicity (e.g., respiratory depression, coma). If concurrent use is absolutely necessary, use the lowest possible doses of oxymorphone, and monitor blood pressure and for serotonergic symptoms closely. No specific interaction between oxymorphone and MAOIs has been observed, but caution is warranted. Although a small number of patients treated with ozanimod were concomitantly exposed to opioids, this exposure was not adequate to rule out the possibility of an adverse reaction from coadministration.
Pacritinib: (Major) Concomitant use of pacritinib and ozanimod increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. Ozanimod has a limited effect on the QT/QTc interval at therapeutic doses but may cause bradycardia and atrioventricular conduction delays which may increase the risk for TdP in patients with a prolonged QT/QTc interval.
Paliperidone: (Major) In general, do not initiate ozanimod in patients taking paliperidone due to the risk of additive bradycardia, QT prolongation, and torsade de pointes (TdP). If treatment initiation is considered, seek advice from a cardiologist. Ozanimod initiation may result in a transient decrease in heart rate and atrioventricular conduction delays. Ozanimod has not been studied in patients taking concurrent QT prolonging drugs; however, QT prolonging drugs have been associated with TdP in patients with bradycardia. Paliperidone has been associated with QT prolongation; torsade de pointes and ventricular fibrillation have been reported in the setting of overdose.
Palonosetron: (Major) Coadministration of ozanimod with palonosetron is not recommended due to the potential for hypertensive crisis. If coadministration is necessary, closely monitor patients for hypertension. An active metabolite of ozanimod inhibits MAO-B, which may increase the potential for hypertensive crisis. Palonosetron may increase blood pressure by increasing serotonin concentrations.
Panobinostat: (Major) In general, do not initiate ozanimod in patients taking panobinostat due to the risk of additive bradycardia, QT prolongation, and torsade de pointes (TdP). If treatment initiation is considered, seek advice from a cardiologist. Ozanimod initiation may result in a transient decrease in heart rate and atrioventricular conduction delays. Ozanimod has not been studied in patients taking concurrent QT prolonging drugs; however, QT prolonging drugs have been associated with TdP in patients with bradycardia. QT prolongation has been reported with panobinostat.
Paroxetine: (Major) Coadministration of ozanimod with paroxetine is not recommended due to the potential for hypertensive crisis and serotonin syndrome. If coadministration is necessary, closely monitor patients for hypertension and serotonergic effects. An active metabolite of ozanimod inhibits MAO-B, which may increase the potential for hypertensive crisis or serotonin syndrome. Paroxetine may increase blood pressure or sertonergic side effects by increasing serotonin concentrations.
Pasireotide: (Major) In general, do not initiate ozanimod in patients taking pasireotide due to the risk of additive bradycardia, QT prolongation, and torsade de pointes (TdP). If treatment initiation is considered, seek advice from a cardiologist. Ozanimod initiation may result in a transient decrease in heart rate and atrioventricular conduction delays. Ozanimod has not been studied in patients taking concurrent QT prolonging drugs; however, QT prolonging drugs have been associated with TdP in patients with bradycardia. QT prolongation has occurred with pasireotide at therapeutic and supra-therapeutic doses.
Pazopanib: (Major) In general, do not initiate ozanimod in patients taking pazopanib due to the risk of additive bradycardia, QT prolongation, and torsade de pointes (TdP). If concomitant use is necessary, closely monitor the patient for QT interval prolongation. Ozanimod initiation may result in a transient decrease in heart rate and atrioventricular conduction delays. Ozanimod has not been studied in patients taking concurrent QT prolonging drugs; however, QT prolonging drugs have been associated with TdP in patients with bradycardia. Pazopanib has been reported to prolong the QT interval.
Peginterferon beta-1a: (Moderate) Concomitant use of ozanimod with peginterferon beta-1 may increase the risk of immunosuppression. Ozanimod has not been studied in combination with other immunosuppressive or immune modulating therapies used for the treatment of multiple sclerosis.
Pentamidine: (Major) In general, do not initiate ozanimod in patients taking pentamidine due to the risk of additive bradycardia, QT prolongation, and torsade de pointes (TdP). If treatment initiation is considered, seek advice from a cardiologist. Ozanimod initiation may result in a transient decrease in heart rate and atrioventricular conduction delays. Ozanimod has not been studied in patients taking concurrent QT prolonging drugs; however, QT prolonging drugs have been associated with TdP in patients with bradycardia. Systemic pentamidine has been associated with QT prolongation.
Pentazocine; Naloxone: (Moderate) Coadministration of pentazocine, an opioid agonist/antagonist, with ozanimod is not recommended due to the potential for serotonergic effects. An active metabolite of ozanimod inhibits MAO-B, which may increase the potential for serotonin syndrome or increased blood pressure. If concomitant use of pentazocine is warranted in a patient taking an MAO inhibitor, carefully observe the patient and monitor blood pressure, particularly during treatment initiation and dose adjustment. Discontinue serotonergic agents if serotonin syndrome is suspected. Although a small number of patients treated with ozanimod were concomitantly exposed to opioids, this exposure was not adequate to rule out the possibility of an adverse reaction from coadministration.
Perphenazine: (Minor) Coadministration of ozanimod with perphenazine may increase the potential for additive QT prolongation. Ozanimod initiation may result in a transient decrease in heart rate and atrioventricular conduction delays. Ozanimod has not been studied in patients taking concurrent QT prolonging drugs; however, QT prolonging drugs have been associated with torsade de pointes in patients with bradycardia. Perphenazine is associated with a possible risk for QT prolongation. Theoretically, perphenazine may increase the risk of QT prolongation if coadministered with other drugs that have a risk of QT prolongation.
Perphenazine; Amitriptyline: (Contraindicated) Do not use tricyclic antidepressants (TCAs) in patients taking MAOIs or within 14 days of stopping them. An active metabolite of ozanimod inhibits MAO-B, and interactions with TCAs may manifest as serotonin syndrome, hypertensive crisis, QT prolongation or other serious side effects. Hyperpyretic crises, severe convulsions, and deaths have occurred in patients receiving TCAs and MAO inhibiting drugs simultaneously. Consider an alternative to the TCA. Ozanimod is a monoamine oxidase inhibitor that may result in a transient decrease in heart rate and atrioventricular conduction delays. Ozanimod has not been studied in patients taking concurrent QT prolonging drugs; however, QT prolonging drugs have been associated with TdP in patients with bradycardia. TCAs are serotonergic drugs that share pharmacologic properties similar to the Class IA antiarrhythmic agents and may prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations). (Minor) Coadministration of ozanimod with perphenazine may increase the potential for additive QT prolongation. Ozanimod initiation may result in a transient decrease in heart rate and atrioventricular conduction delays. Ozanimod has not been studied in patients taking concurrent QT prolonging drugs; however, QT prolonging drugs have been associated with torsade de pointes in patients with bradycardia. Perphenazine is associated with a possible risk for QT prolongation. Theoretically, perphenazine may increase the risk of QT prolongation if coadministered with other drugs that have a risk of QT prolongation.
Phendimetrazine: (Contraindicated) Coadministration of ozanimod with phendimetrazine is contraindicated. Allow at least 14 days between discontinuation of ozanimod and initiation of phendimetrazine. An active metabolite of ozanimod inhibits MAO-B, which may increase the potential for hypertensive crisis. Sympathomimetics such as phendimetrazine may increase blood pressure by increasing norepinephrine concentrations and monoamine oxidase inhibitors (MAOIs) are known to potentiate these effects. Concomitant use of ozanimod with pseudoephedrine did not potentiate the effects on blood pressure. However, hypertensive crisis has occurred with administration of ozanimod alone and during coadministration of sympathomimetic medications and other selective or nonselective MAO inhibitors.
Phenelzine: (Contraindicated) Coadministration of ozanimod with monoamine oxidase (MAO) inhibitors is contraindicated. Allow at least 14 days between discontinuation of ozanimod and initiation of treatment with MAO inhibitors. Metabolites of ozanimod may inhibit MAO. The potential for a clinical interaction with MAO inhibitors has not been studied; however, the increased risk of nonselective MAO inhibition may lead to a hypertensive crisis.
Phentermine: (Contraindicated) Coadministration of ozanimod with phentermine is contraindicated. Allow at least 14 days between discontinuation of ozanimod and initiation of phentermine. An active metabolite of ozanimod inhibits MAO-B, which may increase the potential for hypertensive crisis. Sympathomimetics such as phentermine may increase blood pressure by increasing norepinephrine concentrations and monoamine oxidase inhibitors (MAOIs) are known to potentiate these effects. Concomitant use of ozanimod with pseudoephedrine did not potentiate the effects on blood pressure. However, hypertensive crisis has occurred with administration of ozanimod alone and during coadministration of sympathomimetic medications and other selective or nonselective MAO inhibitors.
Phentermine; Topiramate: (Contraindicated) Coadministration of ozanimod with phentermine is contraindicated. Allow at least 14 days between discontinuation of ozanimod and initiation of phentermine. An active metabolite of ozanimod inhibits MAO-B, which may increase the potential for hypertensive crisis. Sympathomimetics such as phentermine may increase blood pressure by increasing norepinephrine concentrations and monoamine oxidase inhibitors (MAOIs) are known to potentiate these effects. Concomitant use of ozanimod with pseudoephedrine did not potentiate the effects on blood pressure. However, hypertensive crisis has occurred with administration of ozanimod alone and during coadministration of sympathomimetic medications and other selective or nonselective MAO inhibitors.
Phenylephrine: (Major) Coadministration of ozanimod with sympathomimetics such as phenylephrine is not routinely recommended due to the potential for hypertensive crisis. If coadministration is medically necessary, closely monitor the patient for hypertension. An active metabolite of ozanimod inhibits MAO-B, which may increase the potential for hypertensive crisis. Sympathomimetics may increase blood pressure by increasing norepinephrine concentrations and monoamine oxidase inhibitors (MAOIs) are known to potentiate these effects. Concomitant use of ozanimod with pseudoephedrine did not potentiate the effects on blood pressure. However, hypertensive crisis has occurred with administration of ozanimod alone and also during coadministration of sympathomimetic medications and other selective or nonselective MAO inhibitors.
Pimavanserin: (Major) In general, do not initiate ozanimod in patients taking pimavanserin due to the risk of additive bradycardia, QT prolongation, and torsade de pointes (TdP). If treatment initiation is considered, seek advice from a cardiologist. Ozanimod initiation may result in a transient decrease in heart rate and atrioventricular conduction delays. Ozanimod has not been studied in patients taking concurrent QT prolonging drugs; however, QT prolonging drugs have been associated with TdP in patients with bradycardia. Pimavanserin prolongs the QT interval.
Pimozide: (Contraindicated) Coadministration of pimozide with ozanimod is contraindicated due to the risk for additive QT prolongation and torsade de pointes (TdP). Pimozide is associated with a well-established risk of QT prolongation and TdP. Ozanimod initiation may result in a transient decrease in heart rate and atrioventricular conduction delays. Ozanimod has not been studied in patients taking concurrent QT prolonging drugs; however, QT prolonging drugs have been associated with TdP in patients with bradycardia.
Pindolol: (Moderate) Ozanimod may cause bradycardia and AV-conduction delays, which may be enhanced with the concomitant use of beta-blockers. If a calcium channel blocker that slows heart rate/cardiac conduction is also prescribed with ozanimod and a beta-blocker, a cardiologist should be consulted due to the likelyhood of additive effects.
Pitolisant: (Major) In general, do not initiate ozanimod in patients taking pitolisant due to the risk of additive bradycardia, QT prolongation, and torsade de pointes (TdP). If treatment initiation is considered, seek advice from a cardiologist. Ozanimod initiation may result in a transient decrease in heart rate and atrioventricular conduction delays. Ozanimod has not been studied in patients taking concurrent QT prolonging drugs; however, QT prolonging drugs have been associated with TdP in patients with bradycardia. Pitolisant prolongs the QT interval.
Posaconazole: (Major) In general, do not initiate ozanimod in patients taking posaconazole due to the risk of additive bradycardia, QT prolongation, and torsade de pointes (TdP). If treatment initiation is considered, seek advice from a cardiologist. Ozanimod initiation may result in a transient decrease in heart rate and atrioventricular conduction delays. Ozanimod has not been studied in patients taking concurrent QT prolonging drugs; however, QT prolonging drugs have been associated with TdP in patients with bradycardia. Posaconazole has been associated with prolongation of the QT interval as well as rare cases of TdP.
Prednisolone: (Moderate) Concomitant use of ozanimod with prednisolone may increase the risk of immunosuppression. Monitor patients carefully for signs and symptoms of infection. In clinical studies for ulcerative colitis, the use of systemic corticosteroids did not appear to influence safety or efficacy of ozanimod.
Prednisone: (Moderate) Concomitant use of ozanimod with prednisone may increase the risk of immunosuppression. Monitor patients carefully for signs and symptoms of infection. In clinical studies for ulcerative colitis, the use of systemic corticosteroids did not appear to influence safety or efficacy of ozanimod.
Prilocaine; Epinephrine: (Major) Coadministration of ozanimod with sympathomimetics such as epinephrine is not routinely recommended due to the potential for hypertensive crisis. If coadministration is medically necessary, closely monitor the patient for hypertension. An active metabolite of ozanimod inhibits MAO-B, which may increase the potential for hypertensive crisis. Sympathomimetics may increase blood pressure by increasing norepinephrine concentrations and monoamine oxidase inhibitors (MAOIs) are known to potentiate these effects. Concomitant use of ozanimod with pseudoephedrine did not potentiate the effects on blood pressure. However, hypertensive crisis has occurred with administration of ozanimod alone and also during coadministration of sympathomimetic medications and other selective or nonselective MAO inhibitors.
Primaquine: (Major) In general, do not initiate ozanimod in patients taking primaquine due to the risk of additive bradycardia, QT prolongation, and torsade de pointes (TdP). If treatment initiation is considered, seek advice from a cardiologist. Ozanimod initiation may result in a transient decrease in heart rate and atrioventricular conduction delays. Ozanimod has not been studied in patients taking concurrent QT prolonging drugs; however, QT prolonging drugs have been associated with TdP in patients with bradycardia. Primaquine has been associated with QT interval prolongation.
Procainamide: (Major) In general, do not initiate ozanimod in patients taking procainamide due to the risk of additive bradycardia, QT prolongation, and torsade de pointes (TdP). If treatment initiation is considered, seek advice from a cardiologist. Ozanimod initiation may result in a transient decrease in heart rate and atrioventricular conduction delays. Ozanimod has not been studied in patients taking concurrent QT prolonging drugs; however, QT prolonging drugs have been associated with TdP in patients with bradycardia. Procainamide is associated with a well-established risk of QT prolongation and TdP.
Prochlorperazine: (Minor) Coadministration of ozanimod with prochlorperazine may increase the potential for additive QT prolongation. Ozanimod initiation may result in a transient decrease in heart rate and atrioventricular conduction delays. Ozanimod has not been studied in patients taking concurrent QT prolonging drugs; however, QT prolonging drugs have been associated with torsade de pointes in patients with bradycardia. Prochlorperazine is associated with a possible risk for QT prolongation. Theoretically, prochlorperazine may increase the risk of QT prolongation if coadministered with other drugs that have a risk of QT prolongation.
Promethazine: (Major) In general, do not initiate ozanimod in patients taking promethazine due to the risk of additive bradycardia, QT prolongation, and torsade de pointes (TdP). If treatment initiation is considered, seek advice from a cardiologist. Ozanimod initiation may result in a transient decrease in heart rate and atrioventricular conduction delays. Ozanimod has not been studied in patients taking concurrent QT prolonging drugs; however, QT prolonging drugs have been associated with TdP in patients with bradycardia. Promethazine is associated with a possible risk for QT prolongation.
Promethazine; Dextromethorphan: (Contraindicated) Coadministration of ozanimod with dextromethorphan is contraindicated. Allow at least 14 days between discontinuation of ozanimod and initiation of dextromethorphan. Consider if an alternative to dextromethorphan would be appropriate. An active metabolite of ozanimod inhibits MAO-B, which may increase the potential for serious and possibly fatal drug interactions with dextromethorphan, including serotonin syndrome. (Major) In general, do not initiate ozanimod in patients taking promethazine due to the risk of additive bradycardia, QT prolongation, and torsade de pointes (TdP). If treatment initiation is considered, seek advice from a cardiologist. Ozanimod initiation may result in a transient decrease in heart rate and atrioventricular conduction delays. Ozanimod has not been studied in patients taking concurrent QT prolonging drugs; however, QT prolonging drugs have been associated with TdP in patients with bradycardia. Promethazine is associated with a possible risk for QT prolongation.
Promethazine; Phenylephrine: (Major) Coadministration of ozanimod with sympathomimetics such as phenylephrine is not routinely recommended due to the potential for hypertensive crisis. If coadministration is medically necessary, closely monitor the patient for hypertension. An active metabolite of ozanimod inhibits MAO-B, which may increase the potential for hypertensive crisis. Sympathomimetics may increase blood pressure by increasing norepinephrine concentrations and monoamine oxidase inhibitors (MAOIs) are known to potentiate these effects. Concomitant use of ozanimod with pseudoephedrine did not potentiate the effects on blood pressure. However, hypertensive crisis has occurred with administration of ozanimod alone and also during coadministration of sympathomimetic medications and other selective or nonselective MAO inhibitors. (Major) In general, do not initiate ozanimod in patients taking promethazine due to the risk of additive bradycardia, QT prolongation, and torsade de pointes (TdP). If treatment initiation is considered, seek advice from a cardiologist. Ozanimod initiation may result in a transient decrease in heart rate and atrioventricular conduction delays. Ozanimod has not been studied in patients taking concurrent QT prolonging drugs; however, QT prolonging drugs have been associated with TdP in patients with bradycardia. Promethazine is associated with a possible risk for QT prolongation.
Propafenone: (Major) In general, do not initiate ozanimod in patients taking propafenone due to the risk of additive bradycardia, QT prolongation, and torsade de pointes (TdP). If treatment initiation is considered, seek advice from a cardiologist. Ozanimod initiation may result in a transient decrease in heart rate and atrioventricular conduction delays. Ozanimod has not been studied in patients taking concurrent QT prolonging drugs; however, QT prolonging drugs have been associated with TdP in patients with bradycardia. Propafenone is a Class IC antiarrhythmic which increases the QT interval, but largely due to prolongation of the QRS interval.
Propranolol: (Moderate) Ozanimod may cause bradycardia and AV-conduction delays, which may be enhanced with the concomitant use of beta-blockers. If a calcium channel blocker that slows heart rate/cardiac conduction is also prescribed with ozanimod and a beta-blocker, a cardiologist should be consulted due to the likelyhood of additive effects.
Protriptyline: (Contraindicated) Do not use tricyclic antidepressants (TCAs) in patients taking MAOIs or within 14 days of stopping them. An active metabolite of ozanimod inhibits MAO-B, and interactions with TCAs may manifest as serotonin syndrome, hypertensive crisis, QT prolongation or other serious side effects. Hyperpyretic crises, severe convulsions, and deaths have occurred in patients receiving TCAs and MAO inhibiting drugs simultaneously. Consider an alternative to the TCA. Ozanimod is a monoamine oxidase inhibitor that may result in a transient decrease in heart rate and atrioventricular conduction delays. Ozanimod has not been studied in patients taking concurrent QT prolonging drugs; however, QT prolonging drugs have been associated with TdP in patients with bradycardia. TCAs are serotonergic drugs that share pharmacologic properties similar to the Class IA antiarrhythmic agents and may prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations).
Pseudoephedrine: (Major) Coadministration of ozanimod with sympathomimetics such as pseudoephedrine is not routinely recommended due to the potential for hypertensive crisis. If coadministration is medically necessary, closely monitor the patient for hypertension. An active metabolite of ozanimod inhibits MAO-B, which may increase the potential for hypertensive crisis. Sympathomimetics may increase blood pressure by increasing norepinephrine concentrations and monoamine oxidase inhibitors (MAOIs) are known to potentiate these effects. Concomitant use of ozanimod with pseudoephedrine did not potentiate the effects on blood pressure. However, hypertensive crisis has occurred with administration of ozanimod alone and also during coadministration of sympathomimetic medications and other selective or nonselective MAO inhibitors.
Pseudoephedrine; Triprolidine: (Major) Coadministration of ozanimod with sympathomimetics such as pseudoephedrine is not routinely recommended due to the potential for hypertensive crisis. If coadministration is medically necessary, closely monitor the patient for hypertension. An active metabolite of ozanimod inhibits MAO-B, which may increase the potential for hypertensive crisis. Sympathomimetics may increase blood pressure by increasing norepinephrine concentrations and monoamine oxidase inhibitors (MAOIs) are known to potentiate these effects. Concomitant use of ozanimod with pseudoephedrine did not potentiate the effects on blood pressure. However, hypertensive crisis has occurred with administration of ozanimod alone and also during coadministration of sympathomimetic medications and other selective or nonselective MAO inhibitors.
Quetiapine: (Major) In general, do not initiate ozanimod in patients taking quetiapine due to the risk of additive bradycardia, QT prolongation, and torsade de pointes (TdP). Additionally, there is a potential for hypertensive crisis. If treatment initiation is considered, seek advice from a cardiologist and monitor for hypertension. An active metabolite of ozanimod inhibits MAO-B, which may increase the potential for hypertensive crisis. Ozanimod may also result in a transient decrease in heart rate and atrioventricular conduction delays. Ozanimod has not been studied in patients taking concurrent QT prolonging drugs; however, QT prolonging drugs have been associated with TdP in patients with bradycardia. Quetiapine is a serotonergic drug that has been associated with a significant prolongation of the QTc interval in rare instances.
Quinidine: (Major) In general, do not initiate ozanimod in patients taking quinidine due to the risk of additive bradycardia, QT prolongation, and torsade de pointes (TdP). If treatment initiation is considered, seek advice from a cardiologist. Ozanimod initiation may result in a transient decrease in heart rate and atrioventricular conduction delays. Ozanimod has not been studied in patients taking concurrent QT prolonging drugs; however, QT prolonging drugs have been associated with TdP in patients with bradycardia. Quinidine administration is associated with QT prolongation and TdP.
Quinine: (Major) In general, do not initiate ozanimod in patients taking quinine due to the risk of additive bradycardia, QT prolongation, and torsade de pointes (TdP). If treatment initiation is considered, seek advice from a cardiologist. Ozanimod initiation may result in a transient decrease in heart rate and atrioventricular conduction delays. Ozanimod has not been studied in patients taking concurrent QT prolonging drugs; however, QT prolonging drugs have been associated with TdP in patients with bradycardia. Quinine has been associated with QT prolongation and rare cases of TdP.
Quizartinib: (Major) Concomitant use of quizartinib and ozanimod increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. Ozanimod has a limited effect on the QT/QTc interval at therapeutic doses but may cause bradycardia and atrioventricular conduction delays which may increase the risk for TdP in patients with a prolonged QT/QTc interval.
Racepinephrine: (Contraindicated) Coadministration of ozanimod with racepinephrine is contraindicated. Allow at least 14 days between discontinuation of ozanimod and initiation of racepinephrine. An active metabolite of ozanimod inhibits MAO-B, which may increase the potential for hypertensive crisis. Sympathomimetics such as racepinephrine may increase blood pressure by increasing norepinephrine concentrations and monoamine oxidase inhibitors (MAOIs) are known to potentiate these effects. Concomitant use of ozanimod with pseudoephedrine did not potentiate the effects on blood pressure. However, hypertensive crisis has occurred with administration of ozanimod alone and during coadministration of sympathomimetic medications and other selective or nonselective MAO inhibitors.
Ranolazine: (Major) In general, do not initiate ozanimod in patients taking ranolazine due to the risk of additive bradycardia, QT prolongation, and torsade de pointes (TdP). If treatment initiation is considered, seek advice from a cardiologist. Ozanimod initiation may result in a transient decrease in heart rate and atrioventricular conduction delays. Ozanimod has not been studied in patients taking concurrent QT prolonging drugs; however, QT prolonging drugs have been associated with TdP in patients with bradycardia. Ranolazine is associated with dose- and plasma concentration-related increases in the QTc interval.
Rasagiline: (Contraindicated) Coadministration of ozanimod with monoamine oxidase (MAO) inhibitors, like rasagiline, is contraindicated. Allow at least 14 days between discontinuation of ozanimod and initiation of treatment with rasagiline. Metabolites of ozanimod may inhibit MAO. The potential for a clinical interaction with MAO inhibitors has not been studied; however, the increased risk of nonselective MAO inhibition may lead to a hypertensive crisis. In addition, MAOB inhibitors, such as rasagiline, may decrease exposure of the active metabolites of ozanimod.
Relugolix: (Major) In general, do not initiate ozanimod in patients taking relugolix due to the risk of additive bradycardia, QT prolongation, and torsade de pointes (TdP). If treatment initiation is considered, seek advice from a cardiologist. Ozanimod initiation may result in a transient decrease in heart rate and atrioventricular conduction delays. Ozanimod has not been studied in patients taking concurrent QT prolonging drugs; however, QT prolonging drugs have been associated with TdP in patients with bradycardia. Androgen deprivation therapy (i.e., relugolix) may prolong the QT/QTc interval.
Relugolix; Estradiol; Norethindrone acetate: (Major) In general, do not initiate ozanimod in patients taking relugolix due to the risk of additive bradycardia, QT prolongation, and torsade de pointes (TdP). If treatment initiation is considered, seek advice from a cardiologist. Ozanimod initiation may result in a transient decrease in heart rate and atrioventricular conduction delays. Ozanimod has not been studied in patients taking concurrent QT prolonging drugs; however, QT prolonging drugs have been associated with TdP in patients with bradycardia. Androgen deprivation therapy (i.e., relugolix) may prolong the QT/QTc interval.
Remifentanil: (Major) When remifentanil is administered to patients who have received ozanimod within 14 days, monitor patients for hypertension and ensure ready availability of vasodilators and beta-blockers for the treatment of hypertension as needed. Severe and unpredictable potentiation of monoamine oxidase (MAO) inhibitors has been reported rarely with remifentanil. An active metabolite of ozanimod inhibits MAO-B. The MAOI interactions with opioids may also manifest as serotonin syndrome or opioid toxicity (e.g., respiratory depression, coma).
Ribociclib: (Major) In general, do not initiate ozanimod in patients taking ribociclib due to the risk of additive bradycardia, QT prolongation, and torsade de pointes (TdP). If treatment initiation is considered, seek advice from a cardiologist. Ozanimod initiation may result in a transient decrease in heart rate and atrioventricular conduction delays. Ozanimod has not been studied in patients taking concurrent QT prolonging drugs; however, QT prolonging drugs have been associated with TdP in patients with bradycardia. Ribociclib has been shown to prolong the QT interval in a concentration-dependent manner. The ribociclib ECG changes occurred within the first four weeks of treatment and were reversible with dose interruption.
Ribociclib; Letrozole: (Major) In general, do not initiate ozanimod in patients taking ribociclib due to the risk of additive bradycardia, QT prolongation, and torsade de pointes (TdP). If treatment initiation is considered, seek advice from a cardiologist. Ozanimod initiation may result in a transient decrease in heart rate and atrioventricular conduction delays. Ozanimod has not been studied in patients taking concurrent QT prolonging drugs; however, QT prolonging drugs have been associated with TdP in patients with bradycardia. Ribociclib has been shown to prolong the QT interval in a concentration-dependent manner. The ribociclib ECG changes occurred within the first four weeks of treatment and were reversible with dose interruption.
Rifampin: (Major) Coadministration of ozanimod with rifampin is not recommended. Coadministration may decrease the exposure of the active metabolites of ozanimod, which may reduce its efficacy. Ozanimod is a CYP2C8 substrate. Coadministration with rifampin (a strong inducer of CYP3A and P-gp, and a moderate inducer of CYP2C8) reduced the exposure for ozanimod, CC112273, and CC1084037 by approximately 24%, 60%, and 55%, respectively. The effect on CC112273 and CC1084037 is primarily caused by induction of CYP2C8.
Rifapentine: (Major) Coadministration of ozanimod with rifapentine is not recommended. Coadministration may decrease the exposure of the active metabolites of ozanimod, which may reduce its efficacy. Ozanimod is a CYP2C8 substrate and rifapentine is a moderate CYP2C8 inducer. Coadministration with a strong inducer of CYP3A and P-gp, and a moderate inducer of CYP2C8 reduced the exposure for ozanimod, CC112273, and CC1084037 by approximately 24%, 60%, and 55%, respectively. The effect on CC112273 and CC1084037 is primarily caused by induction of CYP2C8.
Rilpivirine: (Major) In general, do not initiate ozanimod in patients taking rilpivirine due to the risk of additive bradycardia, QT prolongation, and torsade de pointes (TdP). If treatment initiation is considered, seek advice from a cardiologist. Ozanimod initiation may result in a transient decrease in heart rate and atrioventricular conduction delays. Ozanimod has not been studied in patients taking concurrent QT prolonging drugs; however, QT prolonging drugs have been associated with TdP in patients with bradycardia. Supratherapeutic doses of rilpivirine (75 to 300 mg/day) have caused QT prolongation.
Risperidone: (Major) In general, do not initiate ozanimod in patients taking risperidone due to the risk of additive bradycardia, QT prolongation, and torsade de pointes (TdP). If treatment initiation is considered, seek advice from a cardiologist. Ozanimod initiation may result in a transient decrease in heart rate and atrioventricular conduction delays. Ozanimod has not been studied in patients taking concurrent QT prolonging drugs; however, QT prolonging drugs have been associated with TdP in patients with bradycardia. Risperidone has been associated with a possible risk for QT prolongation and/or TdP, primarily in the overdose setting.
Rizatriptan: (Major) Coadministration of ozanimod with serotonin receptor agonists "triptans" is not recommended due to the potential for hypertensive crisis or serotonin syndrome. If coadministration is necessary, closely monitor patients for hypertension and serotonergic effects. An active metabolite of ozanimod inhibits MAO-B, which may increase the potential for hypertensive crisis or serotonin syndrome. Serotonin receptor agonists may increase blood pressure by increasing serotonin concentrations.
Romidepsin: (Major) In general, do not initiate ozanimod in patients taking romidepsin due to the risk of additive bradycardia, QT prolongation, and torsade de pointes (TdP). If concomitant use is necessary, consider monitoring electrolytes and ECGs at baseline and periodically during treatment. Ozanimod initiation may result in a transient decrease in heart rate and atrioventricular conduction delays. Ozanimod has not been studied in patients taking concurrent QT prolonging drugs; however, QT prolonging drugs have been associated with TdP in patients with bradycardia. Romidepsin has been reported to prolong the QT interval.
Rotavirus Vaccine: (Major) Avoid the use of live vaccines and live attenuated vaccines during ozanimod treatment and for up to 3 months after discontinuation of ozanimod treatment. Live vaccinations may be less effective during ozanimod treatment and also may carry the risk of infection.
Safinamide: (Contraindicated) Coadministration of ozanimod with monoamine oxidase (MAO) inhibitors, like safinamide, is contraindicated. Allow at least 14 days between discontinuation of ozanimod and initiation of treatment with safinamide. Metabolites of ozanimod may inhibit MAO. The potential for a clinical interaction with MAO inhibitors has not been studied; however, the increased risk of nonselective MAO inhibition may lead to a hypertensive crisis. In addition, MAOB inhibitors, such as safinamide, may decrease exposure of the active metabolites of ozanimod.
Saquinavir: (Major) Avoid coadministration of saquinavir boosted with ritonavir with ozanimod due to the risk of additive QT prolongation. If no acceptable alternative therapy is available, perform a baseline ECG prior to initiation of concomitant therapy and carefully follow monitoring recommendations. Saquinavir boosted with ritonavir increases the QT interval in a dose-dependent fashion, which may increase the risk for serious arrhythmias such as torsade de pointes (TdP). Ozanimod initiation may result in a transient decrease in heart rate and atrioventricular conduction delays. Ozanimod has not been studied in patients taking concurrent QT prolonging drugs; however, QT prolonging drugs have been associated with TdP in patients with bradycardia.
SARS-CoV-2 (COVID-19) vaccines: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the SARS-CoV-2 virus vaccine. When feasible, administer indicated vaccines prior to initiating immunosuppressant medications. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure to SARS-CoV-2 virus after receiving the vaccine.
SARS-CoV-2 Virus (COVID-19) Adenovirus Vector Vaccine: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the SARS-CoV-2 virus vaccine. When feasible, administer indicated vaccines prior to initiating immunosuppressant medications. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure to SARS-CoV-2 virus after receiving the vaccine.
SARS-CoV-2 Virus (COVID-19) mRNA Vaccine: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the SARS-CoV-2 virus vaccine. When feasible, administer indicated vaccines prior to initiating immunosuppressant medications. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure to SARS-CoV-2 virus after receiving the vaccine.
SARS-CoV-2 Virus (COVID-19) Recombinant Spike Protein Nanoparticle Vaccine: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the SARS-CoV-2 virus vaccine. When feasible, administer indicated vaccines prior to initiating immunosuppressant medications. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure to SARS-CoV-2 virus after receiving the vaccine.
Selegiline: (Contraindicated) Coadministration of ozanimod with monoamine oxidase (MAO) inhibitors, like selegiline, is contraindicated. Allow at least 14 days between discontinuation of ozanimod and initiation of treatment with selegiline. Metabolites of ozanimod may inhibit MAO. The potential for a clinical interaction with MAO inhibitors selegiline has not been studied; however, there may be an increased risk of hypertensive crisis.
Selpercatinib: (Major) In general, do not initiate ozanimod in patients taking selpercatinib due to the risk of additive bradycardia, QT prolongation, and torsade de pointes (TdP). If concomitant use is necessary, monitor ECGs more frequently for QT prolongation. Ozanimod initiation may result in a transient decrease in heart rate and atrioventricular conduction delays. Ozanimod has not been studied in patients taking concurrent QT prolonging drugs; however, QT prolonging drugs have been associated with TdP in patients with bradycardia. Concentration-dependent QT prolongation has been observed with selpercatinib therapy.
Serdexmethylphenidate; Dexmethylphenidate: (Contraindicated) Coadministration of ozanimod with methylphenidate derivatives is contraindicated. Allow at least 14 days between discontinuation of ozanimod and initiation of methylphenidate. An active metabolite of ozanimod inhibits MAO-B, which may increase the potential for hypertensive crisis. Sympathomimetics such as methylphenidate may increase blood pressure by increasing norepinephrine concentrations and monoamine oxidase inhibitors (MAOIs) are known to potentiate these effects. Methylphenidate derivatives may also have serotonergic effects that may increase blood pressure. Concomitant use of ozanimod with pseudoephedrine did not potentiate the effects on blood pressure. However, hypertensive crisis has occurred with administration of ozanimod alone and during coadministration of sympathomimetic medications and other selective or nonselective MAO inhibitors.
Serotonin-Receptor Agonists: (Major) Coadministration of ozanimod with serotonin receptor agonists "triptans" is not recommended due to the potential for hypertensive crisis or serotonin syndrome. If coadministration is necessary, closely monitor patients for hypertension and serotonergic effects. An active metabolite of ozanimod inhibits MAO-B, which may increase the potential for hypertensive crisis or serotonin syndrome. Serotonin receptor agonists may increase blood pressure by increasing serotonin concentrations.
Sertraline: (Major) In general, do not initiate ozanimod in patients taking sertraline due to the risk of additive bradycardia, QT prolongation, and torsade de pointes (TdP). Additionally, there is a potential for hypertensive crisis and serotonin syndrome. If treatment initiation is considered, seek advice from a cardiologist and monitor for hypertension and serotonergic effects. Ozanimod is a monoamine oxidase inhibitor that may result in a transient decrease in heart rate and atrioventricular conduction delays. Sertraline may increase blood pressure or cause serotonergic side effects by increasing serotonin concentrations. Ozanimod has not been studied in patients taking concurrent QT prolonging drugs; however, QT prolonging drugs have been associated with TdP in patients with bradycardia. Sertraline is a serotonergic drug that is associated with a possible risk of QT prolongation. The risk of sertraline-induced QT prolongation is generally considered to be low in clinical practice. Its effect on QTc interval is minimal (typically less than 5 msec), and the drug has been used safely in patients with cardiac disease (e.g., recent myocardial infarction, unstable angina, chronic heart failure.
Sevoflurane: (Major) In general, do not initiate ozanimod in patients taking halogenated anesthetics due to the risk of additive bradycardia, QT prolongation, and torsade de pointes (TdP). If treatment initiation is considered, seek advice from a cardiologist. Ozanimod initiation may result in a transient decrease in heart rate and atrioventricular conduction delays. Ozanimod has not been studied in patients taking concurrent QT prolonging drugs; however, QT prolonging drugs have been associated with TdP in patients with bradycardia. Halogenated anesthetics can prolong the QT interval.
Smallpox and Monkeypox Vaccine, Live, Nonreplicating: (Major) Avoid the use of live vaccines and live attenuated vaccines during ozanimod treatment and for up to 3 months after discontinuation of ozanimod treatment. Live vaccinations may be less effective during ozanimod treatment and also may carry the risk of infection.
Smallpox Vaccine, Vaccinia Vaccine: (Major) Avoid the use of live vaccines and live attenuated vaccines during ozanimod treatment and for up to 3 months after discontinuation of ozanimod treatment. Live vaccinations may be less effective during ozanimod treatment and also may carry the risk of infection.
Sodium Oxybate: (Major) Coadministration of ozanimod with sodium oxybate is not recommended due to the potential for hypertensive crisis. If coadministration is necessary, closely monitor patients for hypertension. An active metabolite of ozanimod inhibits MAO-B, which may increase the potential for hypertensive crisis. Sodium oxybate has been associated with cases of serotonin syndrome. Excess serotonin may contribute to the development of hypertensive crisis.
Sodium Stibogluconate: (Major) Concomitant use of sodium stibogluconate and ozanimod increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. Ozanimod has a limited effect on the QT/QTc interval at therapeutic doses but may cause bradycardia and atrioventricular conduction delays which may increase the risk for TdP in patients with a prolonged QT/QTc interval.
Solifenacin: (Major) In general, do not initiate ozanimod in patients taking solifenacin due to the risk of additive bradycardia, QT prolongation, and torsade de pointes (TdP). If treatment initiation is considered, seek advice from a cardiologist. Ozanimod initiation may result in a transient decrease in heart rate and atrioventricular conduction delays. Ozanimod has not been studied in patients taking concurrent QT prolonging drugs; however, QT prolonging drugs have been associated with TdP in patients with bradycardia. Solifenacin has been associated with dose-dependent prolongation of the QT interval. TdP has been reported with postmarketing use, although causality was not determined.
Sorafenib: (Major) In general, do not initiate ozanimod in patients taking sorafenib due to the risk of additive bradycardia, QT prolongation, and torsade de pointes (TdP). If treatment initiation is considered, seek advice from a cardiologist. Monitor electrocardiograms and correct electrolyte abnormalities. An interruption or discontinuation of sorafenib therapy may be necessary if QT prolongation occurs. Ozanimod initiation may result in a transient decrease in heart rate and atrioventricular conduction delays. Sorafenib is associated with QTc prolongation. Ozanimod has not been studied in patients taking concurrent QT prolonging drugs; however, QT prolonging drugs have been associated with TdP in patients with bradycardia.
Sotalol: (Major) In general, do not initiate ozanimod in patients taking sotalol due to the risk of additive bradycardia, QT prolongation, and torsade de pointes (TdP). If treatment initiation is considered, seek advice from a cardiologist. Ozanimod initiation may result in a transient decrease in heart rate and atrioventricular conduction delays. Ozanimod has not been studied in patients taking concurrent QT prolonging drugs; however, QT prolonging drugs have been associated with TdP in patients with bradycardia. Sotalol administration is associated with QT prolongation and TdP. Proarrhythmic events should be anticipated after initiation of therapy and after each upward dosage adjustment.
St. John's Wort, Hypericum perforatum: (Major) Coadministration of ozanimod with St. John's Wort is not recommended due to the potential for hypertensive crisis. If coadministration is necessary, closely monitor patients for hypertension. An active metabolite of ozanimod inhibits MAO-B, which may increase the potential for hypertensive crisis. St. John's Wort may increase blood pressure by increasing serotonin concentrations.
Stiripentol: (Major) Coadministration of ozanimod with stiripentol is not recommended. Coadministration may increase the exposure of the active metabolites of ozanimod, which may increase the risk of adverse reactions. Ozanimod is a BCRP substrate and stiripentol is a BCRP inhibitor. Coadministration with another BCRP inhibitor had no effect on ozanimod exposure, but doubled the exposure of the minor active metabolites, RP101988 and RP101075 (the direct precursor of the major active metabolite CC112273). Coadministration of ozanimod with BCRP inhibitors may also increase exposure of CC112273 and CC1084037.
Sufentanil: (Major) When sufentanil is administered to patients who have received ozanimod within 14 days, monitor patients for hypertension and ensure ready availability of vasodilators and beta-blockers for the treatment of hypertension as needed. Severe and unpredictable potentiation of monoamine oxidase (MAO) inhibitors has been reported rarely with sufentanil. An active metabolite of ozanimod inhibits MAO-B. The MAOI interactions with opioids may also manifest as serotonin syndrome or opioid toxicity (e.g., respiratory depression, coma).
Sumatriptan: (Major) Coadministration of ozanimod with serotonin receptor agonists "triptans" is not recommended due to the potential for hypertensive crisis or serotonin syndrome. If coadministration is necessary, closely monitor patients for hypertension and serotonergic effects. An active metabolite of ozanimod inhibits MAO-B, which may increase the potential for hypertensive crisis or serotonin syndrome. Serotonin receptor agonists may increase blood pressure by increasing serotonin concentrations.
Sumatriptan; Naproxen: (Major) Coadministration of ozanimod with serotonin receptor agonists "triptans" is not recommended due to the potential for hypertensive crisis or serotonin syndrome. If coadministration is necessary, closely monitor patients for hypertension and serotonergic effects. An active metabolite of ozanimod inhibits MAO-B, which may increase the potential for hypertensive crisis or serotonin syndrome. Serotonin receptor agonists may increase blood pressure by increasing serotonin concentrations.
Sunitinib: (Major) In general, do not initiate ozanimod in patients taking sunitinib due to the risk of additive bradycardia, QT prolongation, and torsade de pointes (TdP). If treatment initiation is considered, seek advice from a cardiologist. Ozanimod initiation may result in a transient decrease in heart rate and atrioventricular conduction delays. Ozanimod has not been studied in patients taking concurrent QT prolonging drugs; however, QT prolonging drugs have been associated with TdP in patients with bradycardia. Sunitinib can prolong the QT interval.
Tacrolimus: (Major) Concomitant use of ozanimod and tacrolimus increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. Ozanimod has a limited effect on the QT/QTc interval at therapeutic doses but may cause bradycardia and atrioventricular conduction delays which may increase the risk for TdP in patients with a prolonged QT/QTc interval.
Tamoxifen: (Major) In general, do not initiate ozanimod in patients taking tamoxifen due to the risk of additive bradycardia, QT prolongation, and torsade de pointes (TdP). If treatment initiation is considered, seek advice from a cardiologist. Ozanimod initiation may result in a transient decrease in heart rate and atrioventricular conduction delays. Ozanimod has not been studied in patients taking concurrent QT prolonging drugs; however, QT prolonging drugs have been associated with TdP in patients with bradycardia. Tamoxifen has been reported to prolong the QT interval, usually in overdose or when used in high doses. Rare case reports of QT prolongation have also been described when tamoxifen is used at lower doses.
Tapentadol: (Contraindicated) Do not use tapentadol in patients taking MAOIs or within 14 days of stopping them. An active metabolite of ozanimod inhibits MAO-B. MAO inhibitor interactions with tapentadol may manifest as serotonin syndrome, hypertensive crisis, or opioid toxicity (e.g., respiratory depression, coma). An active metabolite of ozanimod inhibits MAO-B. Although a small number of patients treated with ozanimod were concomitantly exposed to opioids, this exposure was not adequate to rule out the possibility of an adverse reaction from coadministration.
Tedizolid: (Major) Coadministration of ozanimod with tedizolid is not recommended; monitor patients for hypertension if used together. An active metabolite of ozanimod inhibits MAO-B, creating potential for hypertensive crisis when give with medications that increase serotonin, such as tedizolid.
Telavancin: (Major) In general, do not initiate ozanimod in patients taking telavancin due to the risk of additive bradycardia, QT prolongation, and torsade de pointes (TdP). If treatment initiation is considered, seek advice from a cardiologist. Ozanimod initiation may result in a transient decrease in heart rate and atrioventricular conduction delays. Ozanimod has not been studied in patients taking concurrent QT prolonging drugs; however, QT prolonging drugs have been associated with TdP in patients with bradycardia. Telavancin has been associated with QT prolongation.
Tetrabenazine: (Major) In general, do not initiate ozanimod in patients taking tetrabenazine due to the risk of additive bradycardia, QT prolongation, and torsade de pointes (TdP). If treatment initiation is considered, seek advice from a cardiologist. Ozanimod initiation may result in a transient decrease in heart rate and atrioventricular conduction delays. Ozanimod has not been studied in patients taking concurrent QT prolonging drugs; however, QT prolonging drugs have been associated with TdP in patients with bradycardia. Tetrabenazine causes a small increase in the corrected QT interval (QTc).
Thioridazine: (Contraindicated) Coadministration of thioridazine with ozanimod is contraindicated due to the risk for additive QT prolongation and torsade de pointes (TdP). Thioridazine is associated with a well-established risk of QT prolongation and TdP. Ozanimod initiation may result in a transient decrease in heart rate and atrioventricular conduction delays. Ozanimod has not been studied in patients taking concurrent QT prolonging drugs; however, QT prolonging drugs have been associated with TdP in patients with bradycardia.
Timolol: (Moderate) Ozanimod may cause bradycardia and AV-conduction delays, which may be enhanced with the concomitant use of beta-blockers. If a calcium channel blocker that slows heart rate/cardiac conduction is also prescribed with ozanimod and a beta-blocker, a cardiologist should be consulted due to the likelyhood of additive effects.
Tobacco: (Major) Advise patients to avoid smoking tobacco while taking ozanimod. During pharmacokinetic studies, the steady-state exposure (AUC) of one of the major active metabolites of ozanimod, CC112273, was approximately 50% lower in tobacco smokers than in nonsmokers. The clinical impact of smoking on ozanimod treatment is not known.
Tolterodine: (Major) In general, do not initiate ozanimod in patients taking tolterodine due to the risk of additive bradycardia, QT prolongation, and torsade de pointes (TdP). If treatment initiation is considered, seek advice from a cardiologist. Ozanimod initiation may result in a transient decrease in heart rate and atrioventricular conduction delays. Ozanimod has not been studied in patients taking concurrent QT prolonging drugs; however, QT prolonging drugs have been associated with TdP in patients with bradycardia. Tolterodine has been associated with dose-dependent prolongation of the QT interval, especially in poor CYP2D6 metabolizers.
Toremifene: (Major) Avoid coadministration of ozanimod with toremifene due to the risk of additive QT prolongation. If concomitant use is unavoidable, closely monitor ECGs for QT prolongation and monitor electrolytes. Toremifene has been shown to prolong the QTc interval in a dose- and concentration-related manner. Ozanimod initiation may result in a transient decrease in heart rate and atrioventricular conduction delays. Ozanimod has not been studied in patients taking concurrent QT prolonging drugs; however, QT prolonging drugs have been associated with torsade de pointes in patients with bradycardia.
Tramadol: (Contraindicated) Do not use tramadol in patients taking MAOIs or within 14 days of stopping them. An active metabolite of ozanimod inhibits MAO-B. MAO inhibitor interactions with tramadol may manifest as serotonin syndrome, hypertensive crisis, or opioid toxicity (e.g., respiratory depression, coma). An active metabolite of ozanimod inhibits MAO-B. Although a small number of patients treated with ozanimod were concomitantly exposed to opioids, this exposure was not adequate to rule out the possibility of an adverse reaction from coadministration.
Tramadol; Acetaminophen: (Contraindicated) Do not use tramadol in patients taking MAOIs or within 14 days of stopping them. An active metabolite of ozanimod inhibits MAO-B. MAO inhibitor interactions with tramadol may manifest as serotonin syndrome, hypertensive crisis, or opioid toxicity (e.g., respiratory depression, coma). An active metabolite of ozanimod inhibits MAO-B. Although a small number of patients treated with ozanimod were concomitantly exposed to opioids, this exposure was not adequate to rule out the possibility of an adverse reaction from coadministration.
Trandolapril; Verapamil: (Major) Treatment with ozanimod should generally not be initiated in patients who are concurrently treated with both a heart rate lowering calcium channel blocker (e.g., verapamil) and a beta blocker. If treatment initiation with ozanimod is considered in patients on both a heart rate lowering calcium channel blocker and beta blocker, advice from a cardiologist should be sought.
Tranylcypromine: (Contraindicated) Coadministration of ozanimod with monoamine oxidase (MAO) inhibitors is contraindicated. Allow at least 14 days between discontinuation of ozanimod and initiation of treatment with MAO inhibitors. Metabolites of ozanimod may inhibit MAO. The potential for a clinical interaction with MAO inhibitors has not been studied; however, the increased risk of nonselective MAO inhibition may lead to a hypertensive crisis.
Trazodone: (Major) In general, do not initiate ozanimod in patients taking trazodone due to the risk of additive bradycardia, QT prolongation, and torsade de pointes (TdP). Additionally, there is a potential for hypertensive crisis or serotonin syndrome. If treatment initiation is considered, seek advice from a cardiologist and monitor for hypertension and serotonergic effects. An active metabolite of ozanimod inhibits MAO-B, which may increase the potential for hypertensive crisis. Ozanimod may also result in a transient decrease in heart rate and atrioventricular conduction delays. Ozanimod has not been studied in patients taking concurrent QT prolonging drugs; however, QT prolonging drugs have been associated with TdP in patients with bradycardia. Trazodone can prolong the QT/QTc interval at therapeutic doses. In addition, there are postmarketing reports of TdP. Trazodone may increase blood pressure or cause serotonergic side effects by increasing serotonin concentrations.
Triclabendazole: (Major) Concomitant use of triclabendazole and ozanimod increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. Ozanimod has a limited effect on the QT/QTc interval at therapeutic doses but may cause bradycardia and atrioventricular conduction delays which may increase the risk for TdP in patients with a prolonged QT/QTc interval.
Tricyclic antidepressants: (Contraindicated) Do not use tricyclic antidepressants (TCAs) in patients taking MAOIs or within 14 days of stopping them. An active metabolite of ozanimod inhibits MAO-B, and interactions with TCAs may manifest as serotonin syndrome, hypertensive crisis, QT prolongation or other serious side effects. Hyperpyretic crises, severe convulsions, and deaths have occurred in patients receiving TCAs and MAO inhibiting drugs simultaneously. Consider an alternative to the TCA. Ozanimod is a monoamine oxidase inhibitor that may result in a transient decrease in heart rate and atrioventricular conduction delays. Ozanimod has not been studied in patients taking concurrent QT prolonging drugs; however, QT prolonging drugs have been associated with TdP in patients with bradycardia. TCAs are serotonergic drugs that share pharmacologic properties similar to the Class IA antiarrhythmic agents and may prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations).
Trifluoperazine: (Minor) Coadministration of ozanimod with trifluoperazine may increase the potential for additive QT prolongation. Ozanimod initiation may result in a transient decrease in heart rate and atrioventricular conduction delays. Ozanimod has not been studied in patients taking concurrent QT prolonging drugs; however, QT prolonging drugs have been associated with torsade de pointes in patients with bradycardia. Trifluoperazine is associated with a possible risk for QT prolongation. Theoretically, trifluoperazine may increase the risk of QT prolongation if coadministered with other drugs that have a risk of QT prolongation.
Trimipramine: (Contraindicated) Do not use tricyclic antidepressants (TCAs) in patients taking MAOIs or within 14 days of stopping them. An active metabolite of ozanimod inhibits MAO-B, and interactions with TCAs may manifest as serotonin syndrome, hypertensive crisis, QT prolongation or other serious side effects. Hyperpyretic crises, severe convulsions, and deaths have occurred in patients receiving TCAs and MAO inhibiting drugs simultaneously. Consider an alternative to the TCA. Ozanimod is a monoamine oxidase inhibitor that may result in a transient decrease in heart rate and atrioventricular conduction delays. Ozanimod has not been studied in patients taking concurrent QT prolonging drugs; however, QT prolonging drugs have been associated with TdP in patients with bradycardia. TCAs are serotonergic drugs that share pharmacologic properties similar to the Class IA antiarrhythmic agents and may prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations).
Triptorelin: (Major) In general, do not initiate ozanimod in patients taking triptorelin due to the risk of additive bradycardia, QT prolongation, and torsade de pointes (TdP). If treatment initiation is considered, seek advice from a cardiologist. Ozanimod initiation may result in a transient decrease in heart rate and atrioventricular conduction delays. Ozanimod has not been studied in patients taking concurrent QT prolonging drugs; however, QT prolonging drugs have been associated with TdP in patients with bradycardia. Androgen deprivation therapy (i.e., triptorelin) may prolong the QT/QTc interval.
Typhoid Vaccine: (Major) Avoid the use of live vaccines and live attenuated vaccines during ozanimod treatment and for up to 3 months after discontinuation of ozanimod treatment. Live vaccinations may be less effective during ozanimod treatment and also may carry the risk of infection.
Vandetanib: (Major) Avoid coadministration of vandetanib with ozanimod due to an increased risk of QT prolongation and torsade de pointes (TdP). If concomitant use is unavoidable, monitor ECGs for QT prolongation and monitor electrolytes; correct hypocalcemia, hypomagnesemia, and/or hypomagnesemia prior to vandetanib administration. An interruption of vandetanib therapy or dose reduction may be necessary for QT prolongation. Vandetanib can prolong the QT interval in a concentration-dependent manner; TdP and sudden death have been reported in patients receiving vandetanib. Ozanimod initiation may result in a transient decrease in heart rate and atrioventricular conduction delays. Ozanimod has not been studied in patients taking concurrent QT prolonging drugs; however, QT prolonging drugs have been associated with TdP in patients with bradycardia.
Vardenafil: (Major) In general, do not initiate ozanimod in patients taking vardenafil due to the risk of additive bradycardia, QT prolongation, and torsade de pointes (TdP). If treatment initiation is considered, seek advice from a cardiologist. Ozanimod initiation may result in a transient decrease in heart rate and atrioventricular conduction delays. Ozanimod has not been studied in patients taking concurrent QT prolonging drugs; however, QT prolonging drugs have been associated with TdP in patients with bradycardia. Vardenafil is associated with QT prolongation. Both therapeutic and supratherapeutic doses of vardenafil produce an increase in QTc interval.
Varicella-Zoster Virus Vaccine, Live: (Major) Avoid the use of live vaccines and live attenuated vaccines during ozanimod treatment and for up to 3 months after discontinuation of ozanimod treatment. Live vaccinations may be less effective during ozanimod treatment and also may carry the risk of infection.
Vemurafenib: (Major) Concomitant use of ozanimod and vemurafenib increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. Ozanimod has a limited effect on the QT/QTc interval at therapeutic doses but may cause bradycardia and atrioventricular conduction delays which may increase the risk for TdP in patients with a prolonged QT/QTc interval.
Venlafaxine: (Major) In general, do not initiate ozanimod in patients taking venlafaxine due to the risk of additive bradycardia, QT prolongation, and torsade de pointes (TdP). Additionally, there is a potential for hypertensive crisis and serotonergic effects. If treatment initiation is considered, seek advice from a cardiologist and monitor for hypertension and serotonin-related adverse effects. An active metabolite of ozanimod inhibits MAO-B, which may increase the potential for hypertensive crisis. Ozanimod may also result in a transient decrease in heart rate and atrioventricular conduction delays. Ozanimod has not been studied in patients taking concurrent QT prolonging drugs; however, QT prolonging drugs have been associated with TdP in patients with bradycardia. Venlafaxine increases serotonin and norepinephrine concentrations and is associated with a possible risk of QT prolongation; torsade de pointes (TdP) has reported with postmarketing use.
Verapamil: (Major) Treatment with ozanimod should generally not be initiated in patients who are concurrently treated with both a heart rate lowering calcium channel blocker (e.g., verapamil) and a beta blocker. If treatment initiation with ozanimod is considered in patients on both a heart rate lowering calcium channel blocker and beta blocker, advice from a cardiologist should be sought.
Vilazodone: (Major) Coadministration of ozanimod with vilazodone is not recommended due to the potential for hypertensive crisis and serotonin syndrome. If coadministration is necessary, closely monitor patients for hypertension and serotonergic effects. An active metabolite of ozanimod inhibits MAO-B, which may increase the potential for hypertensive crisis and serotonin syndrome. Vilazodone may increase blood pressure or cause serotonergic side effects by increasing serotonin concentrations.
Viloxazine: (Moderate) Monitor blood pressure if concomitant use of ozanimod and viloxazine is necessary. Hypertensive crisis has occurred with ozanimod alone and this risk may increase with concomitant use of viloxazine. Some ozanimod metabolites inhibit MAO-B which may potentiate the hypertensive effects of viloxazine.
Voclosporin: (Major) In general, do not initiate ozanimod in patients taking voclosporin due to the risk of additive bradycardia, QT prolongation, and torsade de pointes (TdP). If treatment initiation is considered, seek advice from a cardiologist. Ozanimod initiation may result in a transient decrease in heart rate and atrioventricular conduction delays. Ozanimod has not been studied in patients taking concurrent QT prolonging drugs; however, QT prolonging drugs have been associated with TdP in patients with bradycardia. Voclosporin has been associated with QT prolongation at supratherapeutic doses.
Vonoprazan; Amoxicillin; Clarithromycin: (Major) In general, do not initiate ozanimod in patients taking clarithromycin due to the risk of additive bradycardia, QT prolongation, and torsade de pointes (TdP). If treatment initiation is considered, seek advice from a cardiologist. Ozanimod initiation may result in a transient decrease in heart rate and atrioventricular conduction delays. Ozanimod has not been studied in patients taking concurrent QT prolonging drugs; however, QT prolonging drugs have been associated with TdP in patients with bradycardia. Clarithromycin is associated with an established risk for QT prolongation and TdP.
Voriconazole: (Major) In general, do not initiate ozanimod in patients taking voriconazole due to the risk of additive bradycardia, QT prolongation, and torsade de pointes (TdP). If treatment initiation is considered, seek advice from a cardiologist. Ozanimod initiation may result in a transient decrease in heart rate and atrioventricular conduction delays. Ozanimod has not been studied in patients taking concurrent QT prolonging drugs; however, QT prolonging drugs have been associated with TdP in patients with bradycardia. Voriconazole has been associated with QT prolongation and rare cases of TdP.
Vorinostat: (Major) In general, do not initiate ozanimod in patients taking vorinostat due to the risk of additive bradycardia, QT prolongation, and torsade de pointes (TdP). If treatment initiation is considered, seek advice from a cardiologist. Ozanimod initiation may result in a transient decrease in heart rate and atrioventricular conduction delays. Ozanimod has not been studied in patients taking concurrent QT prolonging drugs; however, QT prolonging drugs have been associated with TdP in patients with bradycardia. Vorinostat therapy is associated with a risk of QT prolongation.
Vortioxetine: (Major) Coadministration of ozanimod with vortioxetine is not recommended due to the potential for hypertensive crisis and serotonin syndrome. If coadministration is necessary, closely monitor patients for hypertension and serotonergic effects. An active metabolite of ozanimod inhibits MAO-B, which may increase the potential for hypertensive crisis and serotonin syndrome. Vortioxetine may increase blood pressure or cause serotonergic side effects by increasing serotonin concentrations.
Yellow Fever Vaccine, Live: (Major) Avoid the use of live vaccines and live attenuated vaccines during ozanimod treatment and for up to 3 months after discontinuation of ozanimod treatment. Live vaccinations may be less effective during ozanimod treatment and also may carry the risk of infection.
Ziprasidone: (Major) In general, do not initiate ozanimod in patients taking ziprasidone due to the risk of additive bradycardia, QT prolongation, and torsade de pointes (TdP). Additionally, there is a potential for hypertensive crisis or serotonin syndrome. If treatment initiation is considered, seek advice from a cardiologist and monitor for hypertension and serotonergice effects. An active metabolite of ozanimod inhibits MAO-B, which may increase the potential for hypertensive crisis or serotonin syndrome. Ozanimod may also result in a transient decrease in heart rate and atrioventricular conduction delays. Ozanimod has not been studied in patients taking concurrent QT prolonging drugs; however, QT prolonging drugs have been associated with TdP in patients with bradycardia. Ziprasidone causes QT prolongation; there are postmarketing reports of TdP and serotonin syndrome in patients with multiple confounding factors.
Zolmitriptan: (Major) Coadministration of ozanimod with serotonin receptor agonists "triptans" is not recommended due to the potential for hypertensive crisis or serotonin syndrome. If coadministration is necessary, closely monitor patients for hypertension and serotonergic effects. An active metabolite of ozanimod inhibits MAO-B, which may increase the potential for hypertensive crisis or serotonin syndrome. Serotonin receptor agonists may increase blood pressure by increasing serotonin concentrations.
Ozanimod is a sphingosine 1-phosphate (S1P) receptor modulator that binds with high affinity to S1P receptors 1 and 5. Ozanimod blocks the capacity of lymphocytes to egress from lymph nodes, reducing the number of lymphocytes in peripheral blood. The mechanism by which ozanimod exerts therapeutic effects in multiple sclerosis and ulcerative colitis is unknown but may involve the reduction of lymphocyte migration into the central nervous system and intestine.
Ozanimod is administered orally. The mean (coefficient of variation %) apparent volume of distribution of ozanimod (Vz/F) is 5,590 L (27%). Human plasma proteins binding of ozanimod and its major active metabolites, CC112273 and CC1084037, is approximately 98.2%, 99.8%, and 99.3%, respectively. Ozanimod is metabolized by multiple enzymes to form circulating major active metabolites (e.g., CC112273 and CC1084037) and minor active metabolites (e.g., RP101988, RP101075, and RP112509) with similar activity and selectivity for S1P1 and S1P5 receptors. Ozanimod is metabolized by ALDH/ADH to form carboxylate metabolite RP101988 and by CYP3A4 to form RP101075. RP101075 is then metabolized either by NAT-2 to form a minor active metabolite RP101442 or by MAO-B to form CC112273. CC112273 is then metabolized by CYP2C8 to form RP112509 or reduced to form CC1084037. CC1084037 is metabolized by AKR 1C1/1C2 and/or 3 beta-and 11 beta-HSD to form CC112273. The interconversion between CC112273 and CC1084037 favors CC112273. Approximately 94% of circulating total active drug exposure is represented by ozanimod (6%), CC112273 (73%), and CC1084037 (15%), in humans. Following a single oral dose of radiolabeled ozanimod 0.92 mg, approximately 26% of the radioactivity was recovered in urine and 37% in feces, primarily composed of inactive metabolites. The mean (CV%) plasma half-life of ozanimod is approximately 21 hours (15%). The mean (CV%) effective half-life of CC112273 and its direct interconverting metabolite CC1084037 was approximately 11 days (104%) in relapsing MS patients. The mean (CV%) apparent oral clearance for ozanimod was approximately 192 L/hour.
Affected cytochrome P450 isoenzymes and drug transporters: CYP2C8, BCRP, CYP3A4
Ozanimod is metabolized by multiple enzymes to form its circulating major active metabolites (e.g., CC112273 and CC1084037) and minor active metabolites (e.g., RP101988, RP101075, and RP112509). The major active metabolite CC112273 is metabolized by CYP2C8. Ozanimod is metabolized by CYP3A4 to form the minor metabolite RP101075. Coadministration of ozanimod with strong CYP2C8 inhibitors or BCRP inhibitors increases the exposure of the active metabolites and should be avoided. Administration of ozanimod with strong CYP2C8 inducers decreases the exposure of the active metabolites and is likely to result in reduced efficacy.
MAO-B inhibition:
In vitro, the metabolites CC112273 and CC1084037 inhibited monoamine oxidase type B (MAO-B; IC50 values of 5.72 nM and 58 nM, respectively) with more than 1,000-fold selectivity over MAO-A.
-Route-Specific Pharmacokinetics
Oral Route
The maximum concentration (Cmax) and AUC of ozanimod and its major metabolite, CC112273, increase proportionally over the oral dose range of 0.46 to 0.92 mg. The time to maximum concentration (Tmax) of ozanimod is approximately 6 to 8 hours. Cmax, AUC, time to steady-state, and accumulation ratio for ozanimod are 0.244 ng/mL (coefficient of variation 31.8%), 4.46 ng x hour/mL (31.8%), 102 hours (28.2%), and 2.4 (21.1%), respectively. Cmax, AUC, time to steady-state, and accumulation ratio for CC112273 are 6.98 ng/mL (42.7%), 143.77 ng x hour/mL (39.2%), 45 days (45%), and 16 (101%), respectively. No clinically significant differences in the Cmax and AUC of ozanimod were observed following administration with a high fat, high-calorie meal.
-Special Populations
Hepatic Impairment
Mean exposures (AUClast) of ozanimod and active metabolites CC112273 and CC1084037 increased by 60%, 98%, and 107%, respectively, in subjects with mild hepatic impairment (Child-Pugh class A, n = 8) compared to healthy controls (n = 8) following an 8-day titration regimen of once daily doses of ozanimod 0.23 mg on days 1 to 3, 0.46 mg on days 5 to 7, and 0.92 mg on day 8. Mean exposures (AUClast) of ozanimod and active metabolites CC112273 and CC1084037 increased by 17%, 38%, and 61%, respectively, in subjects with moderate hepatic impairment (Child-Pugh class B, n = 8) compared to healthy controls following the same 8-day titration regimen. The pharmacokinetic parameters of ozanimod or its active metabolites have not been studied in patients with severe hepatic impairment (Child-Pugh class C).
Renal Impairment
The AUC for ozanimod and CC112273 were approximately 27% higher and 23% lower, respectively, following a single oral dose of 0.23 mg of ozanimod in subjects with end-stage renal disease (n = 8) compared to subjects with normal renal function (n = 8). Based on this trial, renal impairment has no clinically important effects on pharmacokinetics of ozanimod or CC112273.
Geriatric
There is no meaningful difference in the pharmacokinetics of ozanimod in older adult patients with ulcerative colitis. Population pharmacokinetic analyses showed that AUC of CC112273 was approximately 3% to 4% and 27% greater in geriatric patients older than 65 years compared to adults 45 to 65 years and 18 to 44 years, respectively.
Gender Differences
Gender did not affect the pharmacokinetics of ozanimod.
Ethnic Differences
Exposure (Cmax and AUC) to ozanimod was unchanged following repeated dosing of 0.96 mg in Japanese subjects (n = 10) compared to Caucasian subjects (n = 12). Cmax and AUC of the CC112273 metabolite were approximately 28% and 43% higher, respectively, in Japanese subjects. These differences are not considered clinically meaningful.
Other
Tobacco smoking
Steady-state exposure (AUC) of the metabolite CC112273 was approximately 50% lower in smokers than in nonsmokers. This reduction in exposure did not result in meaningful differences in absolute lymphocyte count reduction or an apparent impact on clinical efficacy.