Voclosporin is an oral calcineurin-inhibitor approved for use in adult patients with lupus nephritis receiving other immunosuppressant therapies (e.g., mycophenolate mofetil, corticosteroids). Voclosporin is structurally similar to cyclosporine except for a methyl group addition to the aminoacid-1 residue, which confers a four-fold increase in potency. This structural change alters the metabolic pathway of voclosporin resulting in faster elimination, lower metabolite exposure, and decreased risk of adverse reactions compared to cyclosporine. Due to its more predictable pharmacokinetic and pharmacodynamic profile compared to cyclosporine and tacrolimus, voclosporin may be administered as a fixed dose without the need for therapeutic drug monitoring. Voclosporin carries a boxed warning for malignancies and serious infections. Voclosporin was FDA-approved in January 2021.
General Administration Information
For storage information, see the specific product information within the How Supplied section.
Route-Specific Administration
Oral Administration
-Patients should avoid grapefruit or drinking grapefruit juice while taking voclosporin.
Oral Solid Formulations
-Administer whole; do not open, chew, divide, or crush capsules.
-Have patient take on an empty stomach as close to a 12-hour schedule as possible, with a minimum of 8 hours between doses.
-Missed doses: If a dose is missed, administer it as soon as possible within 4 hours after missing the dose. If it is beyond the 4-hour time period, skip the dose and have the patient take the next dose at the regularly scheduled time. Do not double doses.
Acute and chronic nephrotoxicity may occur with voclosporin therapy, as with other calcineurin-inhibitors. Reductions in glomerular filtration rate were reported in 26% of patients treated with voclosporin 23.7 mg twice daily compared to 9% of patients treated with placebo. Renal impairment and acute kidney injury were reported in 6% and 3%, respectively, of voclosporin patients compared to 3% and 1%, respectively, of placebo patients. The most commonly reported adverse reaction in clinical trials was a reduction in the glomerular filtration rate, which was reported in 70 patients (37.1 per 100 patient-years) treated with voclosporin 23.7 mg twice daily, 27 patients (48.7 per 100 patient-years) treated with voclosporin 39.5 mg twice daily, and 25 patients (11.3 per 100 patient-years) treated with placebo. Among the 70 patients treated with voclosporin 23.7 mg, reductions in glomerular filtration rate occurred within the first 3 months of therapy for 50 patients (71%). Of the 50 patients that experienced decreased glomerular filtration rates within 3 months, 39 patients (78%) had resolution or improvement following voclosporin dose modification and 25 of the 39 patients (64%) experienced the resolution or improvement within 1 month of dose adjustment. Ten patients (14%) treated with voclosporin 23.7 mg permanently discontinued treatment due to glomerular filtration rate reductions; 4 (40%) of these patients experienced resolution 3 months after treatment discontinuation. Adverse renal reactions (defined as renal impairment, acute kidney injury, increased serum creatinine, azotemia, renal failure, oliguria, and proteinuria) were reported in 26 patients (11.3 per 100 patient-years) treated with voclosporin 23.7 mg, 11 patients (16.5 per 100 patient-years) treated with voclosporin 39.5 mg, and 22 patients (9.5 per 100 patient-years) treated with placebo. Serious renal adverse reactions were reported in 13 patients (5.6 per 100 patient-years) taking voclosporin 23.7 mg twice daily and 9 patients (3.7 per 100 patient-years) taking placebo; no patients taking voclosporin 39.5 mg experienced serious renal adverse reactions. The most frequently reported serious renal adverse reactions were acute kidney injury and renal impairment.
During clinical trials, hyperkalemia was reported in 5 patients (2.1 per 100 patient-years) treated with voclosporin 23.7 mg twice daily, 1 patient (1.4 per 100 patient-years) treated with voclosporin 39.5 mg twice daily, and 2 patients (0.8 per 100 patient-years) treated with placebo.
Hypertension was reported in 19% of patients taking voclosporin 23.7 mg twice daily compared to 9% of patients taking placebo during clinical trials. Hypertension was reported in 51 patients (25.5 per 100 patient-years) treated with voclosporin 23.7 mg twice daily, 16 patients (26 per 100 patient-years) treated with voclosporin 39.5 mg twice daily, and 23 patients (10.3 per 100 patient-years) treated with placebo. Serious hypertension was reported in 5 patients (2.1 per 100 patient-years) treated with voclosporin 23.7 mg, 2 patients (2.8 per 100 patient-years) treated with voclosporin 39.5 mg, and 1 patient (0.4 per 100 patient-years) treated with placebo.
QT prolongation was reported in 2 patients (0.9 per 100 patient-years) treated with voclosporin 23.7 mg twice daily, 1 patient (1.4 per 100 patient-years) treated with voclosporin 39.5 mg twice daily, and no patients treated with placebo during clinical trials.
Like other immunosuppressants, voclosporin may increase the risk for serious infection, including bacterial, viral, protozoal, fungal and opportunistic infections. Urinary tract infection was reported in 10% of voclosporin patients compared to 6% of placebo patients in clinical trials. In clinical trials, infections were common and were reported in 166 patients (135.2 per 100 patient-years) treated with voclosporin 23.7 mg twice daily, 58 patients (167.5 per 100 patient-years) treated with voclosporin 39.5 mg twice daily, and 146 patients (107.4 per 100 patient-years) treated with placebo during clinical trials. The most commonly reported infections were upper respiratory tract infections, urinary tract infections, viral upper respiratory tract infections, and herpes zoster. Serious infections were reported in 27 patients (11.9 per 100 patient-years) treated with voclosporin 23.7 mg, 10 patients (14.4 per 100 patient-years) treated with voclosporin 39.5 mg twice daily, and 27 patients (12 per 100 patient-years) treated with placebo. The most frequent serious infections were pneumonia, gastroenteritis, and urinary tract infections. Opportunistic infections were reported in 3 patients (1.3 per 100 patient-years) treated with voclosporin 23.7 mg, 1 patient (1.4 per 100 patient-years) treated with voclosporin 39.5 mg twice daily, and 2 patients (0.9 per 100 patient-years) treated with placebo. The most common opportunistic infections were cytomegalovirus chorioretinitis, cytomegalovirus infection, and herpes zoster.
Voclosporin, like other calcineurin-inhibitors, may cause neurotoxicity. In clinical studies, nervous system disorders were reported in 74 patients (38.9 per 100 patient-years) treated with voclosporin 23.7 mg twice daily, 24 patients (42.5 per 100 patient-years) treated with voclosporin 39.5 mg twice daily, and 44 patients (21.6 per 100 patient-years) treated with placebo during clinical trials. The most commonly reported neurological adverse reactions were headache (15%), tremor (3%), dizziness, post-herpetic neuralgia (neuropathic pain), migraine, paresthesias, hypoesthesia, seizures, tension headache, and disturbance in attention. Serious nervous system disorders were reported in 9 patients (3.9 per 100 patient-years) treated with voclosporin 23.7 mg, 3 patients (4.3 per 100 patient-years) treated with voclosporin 39.5 mg twice daily, and 2 patients (0.9 per 100 patient-years) treated with placebo during clinical trials. The most frequently reported serious nervous system disorders were headache, migraine, seizures, and posterior reversible encephalopathy syndrome (PRES). Monitor for neurologic abnormalities during treatment; if neurotoxicity occurs, consider dosage reduction or drug discontinuation.
Gastrointestinal adverse reactions reported during clinical trials and at incidences higher with voclosporin use vs. placebo included diarrhea (19%), upper abdominal pain (7%), abdominal pain (5%), dyspepsia (6%), mouth or oral ulceration (4%) and anorexia/decreased appetite (3%).
Anemia was reported in 12% of voclosporin patients compared to 6% of placebo patients in clinical trials. Cases of pure red cell aplasia (PRCA) have been reported in patients treated with another calcineurin-inhibitor immunosuppressant. All of these patients reported risk factors for PRCA such as parvovirus B19 infection, underlying disease, or concomitant medications associated with PRCA. A mechanism for calcineurin-inhibitor-induced PRCA has not been elucidated. If PRCA is diagnosed, consider discontinuation of voclosporin.
General adverse reactions reported during clinical trials with voclosporin and at incidences higher than with placebo included cough (11%), alopecia (6%), and fatigue (4%).
Immunosuppressants, including voclosporin, increase the risk of developing lymphoma, new primary malignancy, and other malignancies, particularly of the skin. The risk appears to be related to the intensity and duration of immunosuppression, as opposed to the use of any specific agent. In clinical trials, malignancies were reported in 4 patients (1.7 per 100 patient-years) treated with voclosporin 23.7 mg twice daily; there were no reported malignancies in patients treated with voclosporin 39.5 mg twice daily or in patients treated with placebo. The reported malignancies were single occurrences of stage 0 cervical cancer (cervical carcinoma), skin cancer (skin neoplasm), pyoderma gangrenosum, and breast tumor excision.
Voclosporin is contraindicated in patients with known serious or severe hypersensitivity reaction to voclosporin or any of its excipients.
Patients receiving immunosuppressants, such as voclosporin, are at increased risk for the development of lymphoma, new primary malignancy, and other malignancies, particularly skin cancer. Risk of developing a malignancy appears to be related to the intensity and duration of immunosuppression rather than the specific immunosuppressive agent. Patients should be advised to avoid or limit sunlight (UV) exposure and artificial UV light (e.g., tanning beds, sun lamps) by wearing protective clothing and using a broad spectrum sunscreen with a high protection factor (SPF 30 or higher). Patients should be examined for any skin changes.
As with any immunosuppressant, an increased susceptibility to infection may occur with voclosporin therapy. The risk of bacterial infection, viral infection, protozoal infection, and fungal infection, including opportunistic infections, may be increased with voclosporin use and may result in serious and fatal outcomes. Reported viral infections include cytomegalovirus and herpes infection. Patients should be monitored for the development of infection and instructed to promptly report signs of infection. Use the lowest effective dose needed to maintain therapeutic response.
Acute and chronic nephrotoxicity may occur with voclosporin therapy, as with other calcineurin-inhibitors. Impaired renal function, renal failure, elevated serum creatinine, acute kidney injury, azotemia, oliguria, and proteinuria have been reported with voclosporin. Prior to initiation of voclosporin therapy, a baseline estimate glomerular filtration rate (eGFR) should be obtained; eGFR must also be closely monitored during therapy. Assess eGFR every 2 weeks for the first month of therapy, then every 4 weeks for the duration of treatment, and adjust voclosporin dose or discontinue therapy as indicated by eGFR monitoring. A persistent decrease of eGFR should prompt evaluation of the patient for chronic calcineurin-inhibitor nephrotoxicity. The risk of acute or chronic nephrotoxicity is increased in patients with renal impairment with a baseline eGFR of 45 mL/minute/1.73 m2 or less; thus, voclosporin therapy is not recommended in these patients unless the benefits exceed the risks. The risk of nephrotoxicity is also increased when voclosporin coadministered with other nephrotoxic drugs. Nephrotoxicity risk may also be increased with treatment duration beyond 1 year; safety and efficacy of voclosporin therapy for more than 1 year has not been established.
Voclosporin exposure is increased in patients with hepatic disease and in patients taking select concomitant medications, which may increase the risk for drug-related toxicity. Avoid voclosporin therapy in patients with severe hepatic impairment (Child-Pugh C). Since voclosporin elimination is reduced in patients with hepatic impairment, a dose reduction is recommended for patients with mild (Child-Pugh A) or moderate (Child-Pugh B) hepatic impairment. Patients concomitantly using strong CYP3A4 inhibitors (e.g., ketoconazole, itraconazole, clarithromycin) should not receive voclosporin. Dosage adjustments may be necessary in some patients based on other concomitant medications; review drug-drug interactions.
Hypertension is a common adverse reaction to voclosporin therapy and antihypertensive therapy may be required. Blood pressure should be checked prior to initiation of therapy, then every 2 weeks for the first month, and as clinically indicated thereafter. Do not initiate voclosporin in patients with a blood pressure greater than 165/105 mmHg or with hypertensive crisis/emergency. Voclosporin, similar to other calcineurin inhibitors, has also been reported to cause hyperkalemia. Monitor serum potassium levels periodically during treatment. Some antihypertensive agents may increase the risk of hyperkalemia, so cautious use of potassium-sparing diuretics, ACE inhibitors, and angiotensin receptor blockers is warranted. In addition, calcium-channel blockers, such as diltiazem and verapamil, may increase voclosporin blood concentrations requiring a reduction in voclosporin dose. In patients who develop new-onset hypertension or an exacerbation of pre-existing hypertension, consider voclosporin dose reduction and/or antihypertensive therapy. Discontinuation of voclosporin therapy may be needed in patients who experience blood pressure elevations that do not respond to voclosporin dose reduction or other appropriate medical interventions.
Voclosporin, like other calcineurin-inhibitors, may cause neurotoxicity. The most severe neurotoxicities include posterior reversible encephalopathy syndrome (PRES), delirium, seizure, and coma; others include tremors, paresthesias, headache, mental status changes, and changes in motor and sensory functions. Monitor for neurologic symptoms and consider dosage reduction or discontinuation of voclosporin if neurotoxicity occurs.
Voclosporin caused dose-dependent QT prolongation following single-dose administration at a dose higher than the recommended lupus nephritis therapeutic dose. Coadministration of voclosporin and other drugs known to prolong the QT interval may result in clinically significant QT prolongation. The risk of torsade de pointes and sudden death may be increased in patients who have bradycardia, hypokalemia, hypomagnesemia, are receiving medications that prolong the QT interval, or a congenital long QT syndrome.
Avoid vaccination with live attenuated vaccines (e.g., intranasal influenza, MMR, oral polio, BCG, yellow fever, varicella, and TY21a typhoid vaccines) during voclosporin therapy due to the possibility of secondary transmission of infection by the vaccine. While vaccination with inactivated vaccines appears to be safe, the immunogenic response may not be sufficient when administered during voclosporin therapy.
Pure red cell aplasia (PRCA) has been reported in patients treated with another calcineurin inhibitor immunosuppressant. A mechanism for calcineurin-inhibitor-induced PRCA has not been elucidated. Risk factors for PRCA include parvovirus B19 infection, underlying disease, or concomitant medications associated with PRCA. Consider discontinuation of voclosporin in patients diagnosed with PRCA.
Due to the alcohol content of the drug formulation, avoid use of voclosporin during pregnancy. Available data on the use of voclosporin in pregnant patients are insufficient to determine whether there is a drug-associated risk for major birth defects, miscarriage, or adverse maternal or fetal outcomes. Based on animal data, there is a potential for fetal harm. In animal reproductive studies, oral administration of either voclosporin or a 50:50 mixture of voclosporin and its cis-isomer was embryocidal and fetocidal in rats and rabbits at doses 15-times and 1-times, respectively, the maximum recommended human dose (MRHD) of 23.7 mg twice daily. There were no treatment-related fetal malformations or variations; however, a reduction in ossifications sites in the metatarsal bones were observed in rat pups at 15-times the MRHD. Reductions in placental and fetal body weights occurred in rabbits at 0.1 to 0.3-times the MRHD and in rats at 15-times the MRHD. Voclosporin transferred across the placenta in pregnant rats. Maternal toxicity consisting of body weight reductions occurred in rats and at some doses in rabbits. Dystocia occurred at 12-times the MRHD in rats resulting in reductions in the mean number of total pups delivered and surviving pups per litter; however, voclosporin did not have an effect on postnatal growth and development. The voclosporin formulation contains 21.6 mg of dehydrated ethanol per capsule for a total daily dose of 129.4 mg/day. Alcohol exposure during pregnancy has been associated with fetal harm including central nervous system abnormalities, behavioral disorders, and impaired intellectual development; there is no safe dose of alcohol exposure during pregnancy.
Avoid use of voclosporin during breast-feeding and for at least 7 days (approximately 6 half-lives) after the last dose of voclosporin. There are no available data on the presence of voclosporin in human milk, the effects on the breastfed infant, or the effects on milk production. Voclosporin is present in the milk of lactating rats. Due to the potential risk of serious adverse reactions in the nursing child, such as serious infections, breast-feeding is not recommended during treatment.
Cautious dose selection recommended for geriatric patients with initial doses at the low end of the voclosporin dosage range. The number of patients 65 and older enrolled in clinical studies were insufficient to determine if treatment response differed from that of younger adult patients. No differences in voclosporin response between geriatric and younger patients have been reported with other clinical experience.
For the treatment of active lupus nephritis in combination with a background immunosuppressive therapy regimen:
Oral dosage:
Adults: 23.7 mg PO twice daily initially; used in combination with mycophenolate mofetil and corticosteroids. Give on an empty stomach every 12 hours, with a minimum of 8 hours between doses. Continued dosage is based on patient's eGFR; adjust accordingly. Consider voclosporin discontinuation if therapeutic benefit not experienced by 24 weeks. Safety and efficacy have not been established beyond 1 year of therapy. LIMIT OF USE: Safety and efficacy of voclosporin in combination with cyclophosphamide has not been established; therefore, use of voclosporin in a patient taking cyclophosphamide is not recommended.
Maximum Dosage Limits:
-Adults
47.4 mg/day PO.
-Geriatric
47.4 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 and Moderate hepatic impairment (Child-Pugh A and Child-Pugh B): Reduce to 15.8 mg PO twice daily.
Severe hepatic impairment (Child-Pugh C): Use not recommended.
Patients with Renal Impairment Dosing
Dosage adjustments of voclosporin are recommended based on eGFR. Assess eGFR at baseline, then every 2 weeks for the first month and every 4 weeks thereafter.
Baseline eGFR 45 mL/minute/1.73 m2 or less:
-Voclosporin has not been studied in this patient population; use is not recommended unless benefit exceeds increased risk for acute or chronic nephrotoxicity.
-If a decision is made to initiate therapy, the recommended starting dose is 15.8 mg PO twice daily.
Dose Adjustments After Therapy Initiation:
eGFR less than 60 mL/minute/1.73 m2 and reduced by more than 20% and less than 30% from baseline:
-Reduce dose by 7.9 mg PO twice a day.
-Reassess eGFR within 2 weeks. If eGFR still reduced from baseline by more than 20%, then reduce dose again by 7.9 mg PO twice a day.
eGFR less than 60 mL/minute/1.73 m2 and reduced by 30% or more from baseline:
-Discontinue voclosporin.
-Reassess eGFR within 2 weeks. If eGFR has returned to 80% or more of baseline, then may consider restarting voclosporin at 7.9 mg PO twice daily.
For patients who require dosage reductions related to eGFR, dosage increases of 7.9 mg twice daily may be considered for each eGFR measurement that is 80% or more of baseline; but not to exceed 23.7 mg PO twice daily.
*non-FDA-approved indication
Abacavir; Dolutegravir; Lamivudine: (Moderate) Monitor for increased toxicity of dolutegravir if coadministered with voclosporin. Concurrent use may increase the plasma concentrations of dolutegravir. Dolutegravir is a P-gp substrate and voclosporin is a P-gp inhibitor.
Acetaminophen; Ibuprofen: (Moderate) Concomitant use of voclosporin and nonsteroidal anti-inflammatory drugs (NSAIDs) may result in additive nephrotoxicity. Monitor for renal toxicity if concomitant use is required.
Acyclovir: (Moderate) Concomitant use of voclosporin and acyclovir may result in additive nephrotoxicity. Monitor for renal toxicity if concomitant use is required.
Adagrasib: (Contraindicated) Concomitant use of voclosporin and adagrasib is contraindicated; concomitant use may increase the exposure of voclosporin and the risk of voclosporin-related adverse effects such as nephrotoxicity, hypertension, and QT prolongation. Concomitant use may also result in additive risk for QT/QTc prolongation and torsade de pointes (TdP). Voclosporin is a sensitive CYP3A substrate, adagrasib is a strong CYP3A inhibitor, and both medications have been associated with QT interval prolongation. Coadministration with another strong CYP3A inhibitor increased voclosporin exposure by approximately 19-fold.
Adefovir: (Moderate) Concomitant use of voclosporin and adefovir dipivoxil may result in additive nephrotoxicity. Monitor for renal toxicity if concomitant use is required.
Afatinib: (Moderate) If the concomitant use of voclosporin and afatinib is necessary, monitor for afatinib-related adverse reactions. If the original dose of afatinib is not tolerated, consider reducing the daily dose of afatinib by 10 mg; resume the previous dose of afatinib as tolerated after discontinuation of voclosporin. The manufacturer of afatinib recommends permanent discontinuation of therapy for severe or intolerant adverse drug reactions at a dose of 20 mg per day, but does not address a minimum dose otherwise. Afatinib is a P-gp substrate and voclosporin is a P-gp inhibitor. Administration with another P-gp inhibitor, given 1 hour before a single dose of afatinib, increased afatinib exposure by 48%; there was no change in afatinib exposure when the P-gp inhibitor was administered at the same time as afatinib or 6 hours later. In healthy subjects, the relative bioavailability for AUC and Cmax of afatinib was 119% and 104%, respectively, when coadministered with the same P-gp inhibitor, and 111% and 105% when the inhibitor was administered 6 hours after afatinib. The manufacturer of voclosporin recommends to reduce dosage of certain P-gp substrates with a narrow therapeutic window when co-administered with voclosporin.
Aldesleukin, IL-2: (Major) Avoid concomitant use of voclosporin and aldesleukin; coadministration may result in additive nephrotoxicity. Monitor for renal toxicity if concomitant use is required.
Alfuzosin: (Moderate) Concomitant use of voclosporin and alfuzosin may increase the risk of QT prolongation. Consider interventions to minimize the risk of progression to torsades de pointes (TdP), such as ECG monitoring and correcting electrolyte abnormalities, particularly in patients with additional risk factors for TdP. Voclosporin has been associated with QT prolongation at supratherapeutic doses. Alfuzosin may prolong the QT interval in a dose-dependent manner.
Amikacin: (Moderate) Concomitant use of voclosporin and aminoglycosides may result in additive nephrotoxicity. Monitor for renal toxicity if concomitant use is required.
Aminoglycosides: (Moderate) Concomitant use of voclosporin and aminoglycosides may result in additive nephrotoxicity. Monitor for renal toxicity if concomitant use is required.
Amiodarone: (Major) Concomitant use of amiodarone and voclosporin 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. The degree of QT prolongation associated with voclosporin is not clinically significant when administered within the recommended dosage range; QT prolongation has been described at 3 times the maximum recommended dose. Due to the extremely long half-life of amiodarone, a drug interaction is possible for days to weeks after drug discontinuation.
Amisulpride: (Major) Monitor the ECG in patients taking amisulpride with voclosporin due to the risk of additive QT prolongation. Amisulpride causes dose- and concentration-dependent QT prolongation. Voclosporin has been associated with QT prolongation at supratherapeutic doses.
Amlodipine; Atorvastatin: (Moderate) Monitor for an increase in atorvastatin-related adverse reactions, including myopathy and rhabdomyolysis, if coadministration with voclosporin is necessary. Concomitant use may increase atorvastatin exposure. Atorvastatin is a P-gp and OATP1B1 substrate; voclosporin is a P-gp and OATP1B1 inhibitor.
Amlodipine; Celecoxib: (Moderate) Concomitant use of voclosporin and nonsteroidal anti-inflammatory drugs (NSAIDs) may result in additive nephrotoxicity. Monitor for renal toxicity if concomitant use is required.
Amobarbital: (Major) Avoid coadministration of voclosporin with amobarbital. Coadministration may decrease voclosporin exposure resulting in decreased efficacy. Voclosporin is a sensitive CYP3A4 substrate and amobarbital is a moderate CYP3A4 inducer. Coadministration with moderate CYP3A4 inducers is predicted to decrease voclosporin exposure by 70%.
Amoxicillin; Clarithromycin; Omeprazole: (Contraindicated) Concomitant use of voclosporin and clarithromycin is contraindicated; concomitant use may increase the exposure of voclosporin and the risk of voclosporin-related adverse effects such as nephrotoxicity, hypertension, and QT prolongation. Additive QT prolongation may also occur. Voclosporin is a sensitive CYP3A4 substrate and clarithromycin is a strong CYP3A4 inhibitor that has been associated with QT prolongation. Coadministration with another strong CYP3A4 inhibitor increased voclosporin exposure by approximately 19-fold.
Amphotericin B lipid complex (ABLC): (Moderate) Concomitant use of voclosporin and amphotericin B may result in additive nephrotoxicity. Monitor for renal toxicity if concomitant use is required.
Amphotericin B liposomal (LAmB): (Moderate) Concomitant use of voclosporin and amphotericin B may result in additive nephrotoxicity. Monitor for renal toxicity if concomitant use is required.
Amphotericin B: (Moderate) Concomitant use of voclosporin and amphotericin B may result in additive nephrotoxicity. Monitor for renal toxicity if concomitant use is required.
Anagrelide: (Major) Avoid concomitant use of voclosporin and anagrelide due to the risk of additive QT prolongation. Torsade de pointes (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. Voclosporin has been associated with QT prolongation at supratherapeutic doses.
Apalutamide: (Major) Avoid coadministration of voclosporin with apalutamide. Coadministration may decrease voclosporin exposure resulting in decreased efficacy. Voclosporin is a sensitive CYP3A4 substrate and apalutamide is a strong CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer decreased voclosporin exposure by 87%.
Apomorphine: (Moderate) Concomitant use of voclosporin and apomorphine may increase the risk of QT prolongation. Consider interventions to minimize the risk of progression to torsades de pointes (TdP), such as ECG monitoring and correcting electrolyte abnormalities, particularly in patients with additional risk factors for TdP. Voclosporin has been associated with QT prolongation at supratherapeutic doses. Dose-related QTc prolongation is associated with therapeutic apomorphine exposure.
Aprepitant, Fosaprepitant: (Major) Reduce the voclosporin dosage to 15.8 mg PO in the morning and 7.9 mg PO in the evening if coadministered with aprepitant, fosaprepitant. Concomitant use may increase voclosporin exposure and the risk of voclosporin-related adverse effects such as nephrotoxicity, hypertension, and QT prolongation. Voclosporin is a sensitive CYP3A4 substrate and aprepitant, fosaprepitant is a moderate CYP3A4 inhibitor when administered as a 3 day oral regimen; single oral and IV doses have not been shown to alter concentrations of CYP3A4 substrates. Coadministration with moderate CYP3A4 inhibitors is predicted to increase voclosporin exposure by 3-fold.
Aripiprazole: (Moderate) Concomitant use of aripiprazole and voclosporin may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP. The degree of QT prolongation associated with voclosporin is not clinically significant when administered within the recommended dosage range; QT prolongation has been described at 3 times the maximum recommended dose.
Arsenic Trioxide: (Major) Avoid concomitant use of arsenic trioxide and voclosporin due to the risk of additive QT prolongation; discontinue or select an alternative drug that does not prolong the QT interval prior to starting arsenic trioxide therapy. If concomitant use is unavoidable, frequently monitor electrocardiograms. Torsade de pointes (TdP), QT interval prolongation, and complete atrioventricular block have been reported with arsenic trioxide use. Voclosporin has been associated with QT prolongation at supratherapeutic doses.
Artemether; Lumefantrine: (Major) Avoid concomitant use of artemether; lumefantrine and voclosporin due to the risk of additive QT prolongation. Consider ECG monitoring if voclosporin must be used with or after artemether; lumefantrine treatment. Artemether; lumefantrine is associated with prolongation of the QT interval. Voclosporin has been associated with QT prolongation at supratherapeutic doses.
Asenapine: (Major) Avoid concomitant use of asenapine and voclosporin due to the risk of additive QT prolongation. Asenapine has been associated with QT prolongation. Voclosporin has been associated with QT prolongation at supratherapeutic doses.
Aspirin, ASA; Butalbital; Caffeine: (Major) Avoid coadministration of voclosporin with butalbital. Coadministration may decrease voclosporin exposure resulting in decreased efficacy. Voclosporin is a sensitive CYP3A4 substrate and butalbital is a moderate CYP3A4 inducer. Coadministration with moderate CYP3A4 inducers is predicted to decrease voclosporin exposure by 70%.
Atazanavir: (Contraindicated) Concomitant use of voclosporin and atazanavir is contraindicated; concomitant use may increase the exposure of voclosporin and the risk of voclosporin-related adverse effects such as nephrotoxicity, hypertension, and QT prolongation. Voclosporin is a sensitive CYP3A4 substrate and atazanavir is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased voclosporin exposure by approximately 19-fold.
Atazanavir; Cobicistat: (Contraindicated) Concomitant use of voclosporin and atazanavir is contraindicated; concomitant use may increase the exposure of voclosporin and the risk of voclosporin-related adverse effects such as nephrotoxicity, hypertension, and QT prolongation. Voclosporin is a sensitive CYP3A4 substrate and atazanavir is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased voclosporin exposure by approximately 19-fold. (Contraindicated) Concomitant use of voclosporin and cobicistat is contraindicated; concomitant use may increase the exposure of voclosporin and the risk of voclosporin-related adverse effects such as nephrotoxicity, hypertension, and QT prolongation. Voclosporin is a sensitive CYP3A4 substrate and cobicistat is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased voclosporin exposure by approximately 19-fold.
Atogepant: (Major) Limit the dose of atogepant to 10 or 30 mg PO once daily for episodic migraine or 30 mg PO once daily for chronic migraine if coadministered with voclosporin. Concurrent use may increase atogepant exposure and the risk of adverse effects. Atogepant is a substrate of OATP1B1 and OATP1B3 and voclosporin is an OATP inhibitor. Coadministration with an OATP1B1/3 inhibitor resulted in a 2.85-fold increase in atogepant overall exposure and a 2.23-fold increase in atogepant peak concentration.
Atomoxetine: (Moderate) Concomitant use of atomoxetine and voclosporin may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP. The degree of QT prolongation associated with voclosporin is not clinically significant when administered within the recommended dosage range; QT prolongation has been described at 3 times the maximum recommended dose.
Atorvastatin: (Moderate) Monitor for an increase in atorvastatin-related adverse reactions, including myopathy and rhabdomyolysis, if coadministration with voclosporin is necessary. Concomitant use may increase atorvastatin exposure. Atorvastatin is a P-gp and OATP1B1 substrate; voclosporin is a P-gp and OATP1B1 inhibitor.
Azithromycin: (Major) Concomitant use of voclosporin and azithromycin 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. The degree of QT prolongation associated with voclosporin is not clinically significant when administered within the recommended dosage range; QT prolongation has been described at 3 times the maximum recommended dose.
Bacillus Calmette-Guerin Vaccine, BCG: (Major) Live virus vaccines should generally not be administered to an immunosuppressed patient. Live virus vaccines may induce the illness they are intended to prevent and are generally contraindicated for use during immunosuppressive treatment. The immune response of the immunocompromised patient to vaccines may be decreased, even despite alternate vaccination schedules or more frequent booster doses. If immunization is necessary, choose an alternative to live vaccination, or, consider a delay or change in the immunization schedule. Practitioners should refer to the most recent CDC guidelines regarding vaccination of patients who are receiving drugs that adversely affect the immune system.
Bedaquiline: (Major) Monitor ECGs if bedaquiline is coadministered with voclosporin. Discontinue bedaquiline if evidence of serious ventricular arrhythmia or QTcF interval greater than 500 msec. Bedaquiline prolongs the QT interval. Voclosporin has been associated with QT prolongation at supratherapeutic doses.
Berotralstat: (Major) Reduce the voclosporin dosage to 15.8 mg PO in the morning and 7.9 mg PO in the evening if coadministered with berotralstat. Concomitant use may increase voclosporin exposure and the risk of voclosporin-related adverse effects such as nephrotoxicity, hypertension, and QT prolongation. Voclosporin is a sensitive CYP3A substrate and berotralstat is a moderate CYP3A inhibitor. Coadministration with moderate CYP3A inhibitors is predicted to increase voclosporin exposure by 3-fold.
Betrixaban: (Major) Avoid betrixaban use in patients with severe renal impairment receiving voclosporin. Reduce betrixaban dosage to 80 mg PO once followed by 40 mg PO once daily in all other patients receiving voclosporin. Concurrent use may increase betrixaban exposure resulting in an increased bleeding risk; monitor patients closely for signs and symptoms of bleeding. Betrixaban is a P-gp substrate; voclosporin is a P-gp inhibitor. Coadministration of other P-gp inhibitors increased betrixaban exposure by 2 to 3 fold.
Bexarotene: (Major) Avoid coadministration of voclosporin with bexarotene. Coadministration may decrease voclosporin exposure resulting in decreased efficacy. Voclosporin is a sensitive CYP3A4 substrate and bexarotene is a moderate CYP3A4 inducer. Coadministration with moderate CYP3A4 inducers is predicted to decrease voclosporin exposure by 70%.
Bictegravir; Emtricitabine; Tenofovir Alafenamide: (Moderate) Coadministration of tenofovir alafenamide and voclosporin may result in increased plasma concentrations of tenofovir leading to an increase in tenofovir-related adverse effects. Concomitant use may also may result in additive nephrotoxicity. Monitor for renal toxicity if concomitant use is required. Tenofovir alafenamide is a P-gp substrate and voclosporin is a P-gp inhibitor.
Bismuth Subcitrate Potassium; Metronidazole; Tetracycline: (Moderate) Concomitant use of metronidazole and voclosporin may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP. The degree of QT prolongation associated with voclosporin is not clinically significant when administered within the recommended dosage range; QT prolongation has been described at three times the maximum recommended dose.
Bismuth Subsalicylate; Metronidazole; Tetracycline: (Moderate) Concomitant use of metronidazole and voclosporin may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP. The degree of QT prolongation associated with voclosporin is not clinically significant when administered within the recommended dosage range; QT prolongation has been described at three times the maximum recommended dose.
Bosentan: (Major) Avoid coadministration of voclosporin with bosentan. Coadministration may decrease voclosporin exposure resulting in decreased efficacy. Voclosporin is a sensitive CYP3A4 substrate and bosentan is a moderate CYP3A4 inducer. Coadministration with moderate CYP3A4 inducers is predicted to decrease voclosporin exposure by 70%.
Brincidofovir: (Moderate) Postpone the administration of voclosporin for at least three hours after brincidofovir administration and increase monitoring for brincidofovir-related adverse reactions (i.e., elevated hepatic enzymes and bilirubin, diarrhea, other gastrointestinal adverse events) if concomitant use of brincidofovir and voclosporin is necessary. Brincidofovir is an OATP1B1 substrate and voclosporin is an OATP1B1 inhibitor. In a drug interaction study, the mean AUC and Cmax of brincidofovir increased by 374% and 269%, respectively, when administered with another OATP1B1 inhibitor.
Bupivacaine; Meloxicam: (Moderate) Concomitant use of voclosporin and nonsteroidal anti-inflammatory drugs (NSAIDs) may result in additive nephrotoxicity. Monitor for renal toxicity if concomitant use is required.
Buprenorphine: (Major) Concomitant use of voclosporin and buprenorphine 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. The degree of QT prolongation associated with voclosporin is not clinically significant when administered within the recommended dosage range; QT prolongation has been described at 3 times the maximum recommended dose.
Buprenorphine; Naloxone: (Major) Concomitant use of voclosporin and buprenorphine 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. The degree of QT prolongation associated with voclosporin is not clinically significant when administered within the recommended dosage range; QT prolongation has been described at 3 times the maximum recommended dose.
Butalbital; Acetaminophen: (Major) Avoid coadministration of voclosporin with butalbital. Coadministration may decrease voclosporin exposure resulting in decreased efficacy. Voclosporin is a sensitive CYP3A4 substrate and butalbital is a moderate CYP3A4 inducer. Coadministration with moderate CYP3A4 inducers is predicted to decrease voclosporin exposure by 70%.
Butalbital; Acetaminophen; Caffeine: (Major) Avoid coadministration of voclosporin with butalbital. Coadministration may decrease voclosporin exposure resulting in decreased efficacy. Voclosporin is a sensitive CYP3A4 substrate and butalbital is a moderate CYP3A4 inducer. Coadministration with moderate CYP3A4 inducers is predicted to decrease voclosporin exposure by 70%.
Butalbital; Acetaminophen; Caffeine; Codeine: (Major) Avoid coadministration of voclosporin with butalbital. Coadministration may decrease voclosporin exposure resulting in decreased efficacy. Voclosporin is a sensitive CYP3A4 substrate and butalbital is a moderate CYP3A4 inducer. Coadministration with moderate CYP3A4 inducers is predicted to decrease voclosporin exposure by 70%.
Butalbital; Aspirin; Caffeine; Codeine: (Major) Avoid coadministration of voclosporin with butalbital. Coadministration may decrease voclosporin exposure resulting in decreased efficacy. Voclosporin is a sensitive CYP3A4 substrate and butalbital is a moderate CYP3A4 inducer. Coadministration with moderate CYP3A4 inducers is predicted to decrease voclosporin exposure by 70%.
Cabotegravir; Rilpivirine: (Moderate) Concomitant use of voclosporin and rilpivirine may increase the risk of QT prolongation. Consider interventions to minimize the risk of progression to torsades de pointes (TdP), such as ECG monitoring and correcting electrolyte abnormalities, particularly in patients with additional risk factors for TdP. Both voclosporin and rilpivirine have been associated with QT prolongation at supratherapeutic doses.
Carbamazepine: (Major) Avoid coadministration of voclosporin with carbamazepine. Coadministration may decrease voclosporin exposure resulting in decreased efficacy. Voclosporin is a sensitive CYP3A4 substrate and carbamazepine is a strong CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer decreased voclosporin exposure by 87%.
Carboplatin: (Moderate) Concomitant use of voclosporin and carboplatin may result in additive nephrotoxicity. Monitor for renal toxicity if concomitant use is required.
Celecoxib: (Moderate) Concomitant use of voclosporin and nonsteroidal anti-inflammatory drugs (NSAIDs) may result in additive nephrotoxicity. Monitor for renal toxicity if concomitant use is required.
Celecoxib; Tramadol: (Moderate) Concomitant use of voclosporin and nonsteroidal anti-inflammatory drugs (NSAIDs) may result in additive nephrotoxicity. Monitor for renal toxicity if concomitant use is required.
Cenobamate: (Major) Avoid coadministration of voclosporin with cenobamate. Coadministration may decrease voclosporin exposure resulting in decreased efficacy. Voclosporin is a sensitive CYP3A4 substrate and cenobamate is a moderate CYP3A4 inducer. Coadministration with moderate CYP3A4 inducers is predicted to decrease voclosporin exposure by 70%.
Ceritinib: (Contraindicated) Concomitant use of voclosporin and ceritinib is contraindicated; concomitant use may increase the exposure of voclosporin and the risk of voclosporin-related adverse effects such as nephrotoxicity, hypertension, and QT prolongation. Additive QT prolongation may also occur. Voclosporin is a sensitive CYP3A4 substrate and ceritinib is a strong CYP3A4 inhibitor that has been associated with concentration-dependent QT prolongation. Coadministration with another strong CYP3A4 inhibitor increased voclosporin exposure by approximately 19-fold.
Chikungunya Vaccine, Live: (Major) Live virus vaccines should generally not be administered to an immunosuppressed patient. Live virus vaccines may induce the illness they are intended to prevent and are generally contraindicated for use during immunosuppressive treatment. The immune response of the immunocompromised patient to vaccines may be decreased, even despite alternate vaccination schedules or more frequent booster doses. If immunization is necessary, choose an alternative to live vaccination, or, consider a delay or change in the immunization schedule. Practitioners should refer to the most recent CDC guidelines regarding vaccination of patients who are receiving drugs that adversely affect the immune system.
Chloramphenicol: (Contraindicated) Concomitant use of voclosporin and chloramphenicol is contraindicated; concomitant use may increase the exposure of voclosporin and the risk of voclosporin-related adverse effects such as nephrotoxicity, hypertension, and QT prolongation. Voclosporin is a sensitive CYP3A4 substrate and chloramphenicol is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased voclosporin exposure by approximately 19-fold.
Chloroquine: (Major) Avoid concomitant use of chloroquine and voclosporin due to the risk of additive QT prolongation. Monitor ECG and electrolytes and avoid other non-essential QT prolonging drugs if use together is required. 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. Voclosporin has been associated with QT prolongation at supratherapeutic doses.
Chlorpheniramine; Ibuprofen; Pseudoephedrine: (Moderate) Concomitant use of voclosporin and nonsteroidal anti-inflammatory drugs (NSAIDs) may result in additive nephrotoxicity. Monitor for renal toxicity if concomitant use is required.
Chlorpromazine: (Major) Use caution if chlorpromazine is coadministered with voclosporin due to the risk of additive QT prolongation. Chlorpromazine is associated with an established risk of QT prolongation and torsade de pointes (TdP). Voclosporin has been associated with QT prolongation at supratherapeutic doses.
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.
Cidofovir: (Contraindicated) Concomitant use of cidofovir and voclosporin is contraindicated due to the increased risk of nephrotoxicity. Voclosporin must be discontinued at least 7 days prior to starting therapy with cidofovir.
Ciprofloxacin: (Major) Reduce the voclosporin dosage to 15.8 mg PO in the morning and 7.9 mg PO in the evening if coadministered with ciprofloxacin. Concomitant use may increase voclosporin exposure and the risk of voclosporin-related adverse effects such as nephrotoxicity, hypertension, and QT prolongation. Additive QT prolongation may also occur. Voclosporin is a sensitive CYP3A4 substrate and ciprofloxacin is a moderate CYP3A4 inhibitor that is associated with rare cases of QT prolongation and torsade de pointes (TdP). Coadministration with moderate CYP3A4 inhibitors is predicted to increase voclosporin exposure by 3-fold.
Cisapride: (Contraindicated) Concomitant use of voclosporin and cisapride is contraindicated due to the potential for QT prolongation and torsade de pointes (TdP). QT prolongation and ventricular arrhythmias, including TdP and death, have been reported with cisapride. Voclosporin has been associated with QT prolongation at supratherapeutic doses.
Cisplatin: (Moderate) Concomitant use of voclosporin and cisplatin may result in additive nephrotoxicity. Monitor for renal toxicity if concomitant use is required.
Citalopram: (Major) Concomitant use of voclosporin and citalopram 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. The degree of QT prolongation associated with voclosporin is not clinically significant when administered within the recommended dosage range; QT prolongation has been described at 3 times the maximum recommended dose.
Clarithromycin: (Contraindicated) Concomitant use of voclosporin and clarithromycin is contraindicated; concomitant use may increase the exposure of voclosporin and the risk of voclosporin-related adverse effects such as nephrotoxicity, hypertension, and QT prolongation. Additive QT prolongation may also occur. Voclosporin is a sensitive CYP3A4 substrate and clarithromycin is a strong CYP3A4 inhibitor that has been associated with QT prolongation. Coadministration with another strong CYP3A4 inhibitor increased voclosporin exposure by approximately 19-fold.
Clindamycin: (Moderate) Concomitant use of voclosporine and clindamycin may result in additive nephrotoxicity. Monitor for renal toxicity if concomitant use is required.
Clofarabine: (Moderate) Concomitant use of voclosporin and clofarabine may result in additive nephrotoxicity. Monitor for renal toxicity if concomitant use is required.
Clofazimine: (Moderate) Concomitant use of clofazimine and voclosporin may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP. The degree of QT prolongation associated with voclosporin is not clinically significant when administered within the recommended dosage range; QT prolongation has been described at 3 times the maximum recommended dose.
Clozapine: (Moderate) Concomitant use of voclosporin and clozapine may increase the risk of QT prolongation. Consider interventions to minimize the risk of progression to torsades de pointes (TdP), such as ECG monitoring and correcting electrolyte abnormalities, particularly in patients with additional risk factors for TdP. Voclosporin has been associated with QT prolongation at supratherapeutic doses. Treatment with clozapine has been associated with QT prolongation, TdP, cardiac arrest, and sudden death.
Cobicistat: (Contraindicated) Concomitant use of voclosporin and cobicistat is contraindicated; concomitant use may increase the exposure of voclosporin and the risk of voclosporin-related adverse effects such as nephrotoxicity, hypertension, and QT prolongation. Voclosporin is a sensitive CYP3A4 substrate and cobicistat is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased voclosporin exposure by approximately 19-fold.
Cobimetinib: (Moderate) Monitor for an increase in cobimetinib-related adverse reactions if coadministration with voclosporin is necessary. Concomitant use may increase cobimetinib exposure. In vitro, cobimetinib is a P-glycoprotein; voclosporin is a P-gp inhibitor. Drugs that inhibit P-gp may increase cobimetinib concentrations.
Codeine; Phenylephrine; Promethazine: (Moderate) Concomitant use of promethazine and voclosporin may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP. The degree of QT prolongation associated with voclosporin is not clinically significant when administered within the recommended dosage range; QT prolongation has been described at 3 times the maximum recommended dose.
Codeine; Promethazine: (Moderate) Concomitant use of promethazine and voclosporin may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP. The degree of QT prolongation associated with voclosporin is not clinically significant when administered within the recommended dosage range; QT prolongation has been described at 3 times the maximum recommended dose.
Colchicine: (Major) Avoid concomitant use of colchicine and voclosporin due to the risk for increased colchicine exposure which may increase the risk for adverse effects. Concomitant use is contraindicated in patients with renal or hepatic impairment. Additionally, this combination is contraindicated if colchicine is being used for cardiovascular risk reduction. If concomitant use is necessary outside of these scenarios, consider a colchicine dosage reduction. Specific dosage reduction recommendations are available for colchicine tablets for some indications; it is unclear if these dosage recommendations are appropriate for other products or indications. For colchicine tablets being used for gout prophylaxis, reduce the dose from 0.6 mg twice daily to 0.3 mg once daily or from 0.6 mg once daily to 0.3 mg once every other day. For colchicine tablets being used for gout treatment, reduce the dose from 1.2 mg followed by 0.6 mg to 0.6 mg without an additional dose. For colchicine tablets being used for Familial Mediterranean Fever, the maximum daily dose is 0.6 mg. Colchicine is a P-gp substrate and voclosporin is a P-gp inhibitor.
Conivaptan: (Major) Reduce the voclosporin dosage to 15.8 mg PO in the morning and 7.9 mg PO in the evening if coadministered with conivaptan. Concomitant use may increase voclosporin exposure and the risk of voclosporin-related adverse effects such as nephrotoxicity, hypertension, and QT prolongation. Voclosporin is a sensitive CYP3A substrate and conivaptan is a moderate CYP3A inhibitor. Coadministration with moderate CYP3A inhibitors is predicted to increase voclosporin exposure by 3-fold.
Crizotinib: (Major) Avoid coadministration of crizotinib and voclosporin due to the risk of QT prolongation. Voclosporin exposure and the risk for voclosporin-related adverse effects may also be increased. If concomitant use is unavoidable, monitor ECGs and electrolytes and reduce voclosporin dosage to 15.8 mg PO in the morning and 7.9 mg PO in the evening. An interruption of therapy, dose reduction, or discontinuation of therapy may be necessary for crizotinib if QT prolongation occurs. Voclosporin is a sensitive CYP3A4 substrate that is associated with QT prolongation at supratherapeutic doses. Crizotinib is a moderate CYP3A4 inhibitor that can cause concentration-dependent QT prolongation. Coadministration with moderate CYP3A4 inhibitors is predicted to increase voclosporin exposure by 3-fold.
Dabigatran: (Moderate) Monitor for an increase in dabigatran-related adverse reactions if coadministration with voclosporin is necessary in patients with creatinine clearance (CrCl) greater than 50 mL/min. Avoid coadministration in patients with CrCl less than 50 mL/min when dabigatran is administered for treatment or reduction in risk of recurrence of deep venous thrombosis (DVT) or pulmonary embolism (PE) or prophylaxis of DVT or PE following hip replacement surgery. Avoid coadministration in patients with CrCl less than 30 mL/min in patients with non-valvular atrial fibrillation. Serum concentrations of dabigatran are expected to be higher in patients with renal impairment compared to patients with normal renal function. Dabigatran is a P-glycoprotein substrate and voclosporin is a P-gp inhibitor.
Dabrafenib: (Major) Avoid coadministration of voclosporin with dabrafenib. Coadministration may decrease voclosporin exposure resulting in decreased efficacy. Voclosporin is a sensitive CYP3A4 substrate and dabrafenib is a moderate CYP3A4 inducer. Coadministration with moderate CYP3A4 inducers is predicted to decrease voclosporin exposure by 70%.
Danazol: (Major) Reduce the voclosporin dosage to 15.8 mg PO in the morning and 7.9 mg PO in the evening if coadministered with danazol. Concomitant use may increase voclosporin exposure and the risk of voclosporin-related adverse effects such as nephrotoxicity, hypertension, and QT prolongation. Voclosporin is a sensitive CYP3A4 substrate and danazol is a moderate CYP3A4 inhibitor. Coadministration with moderate CYP3A4 inhibitors is predicted to increase voclosporin exposure by 3-fold.
Darunavir: (Contraindicated) Concomitant use of voclosporin and darunavir is contraindicated; concomitant use may increase the exposure of voclosporin and the risk of voclosporin-related adverse effects such as nephrotoxicity, hypertension, and QT prolongation. Voclosporin is a sensitive CYP3A4 substrate and darunavir is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased voclosporin exposure by approximately 19-fold.
Darunavir; Cobicistat: (Contraindicated) Concomitant use of voclosporin and cobicistat is contraindicated; concomitant use may increase the exposure of voclosporin and the risk of voclosporin-related adverse effects such as nephrotoxicity, hypertension, and QT prolongation. Voclosporin is a sensitive CYP3A4 substrate and cobicistat is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased voclosporin exposure by approximately 19-fold. (Contraindicated) Concomitant use of voclosporin and darunavir is contraindicated; concomitant use may increase the exposure of voclosporin and the risk of voclosporin-related adverse effects such as nephrotoxicity, hypertension, and QT prolongation. Voclosporin is a sensitive CYP3A4 substrate and darunavir is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased voclosporin exposure by approximately 19-fold.
Darunavir; Cobicistat; Emtricitabine; Tenofovir alafenamide: (Contraindicated) Concomitant use of voclosporin and cobicistat is contraindicated; concomitant use may increase the exposure of voclosporin and the risk of voclosporin-related adverse effects such as nephrotoxicity, hypertension, and QT prolongation. Voclosporin is a sensitive CYP3A4 substrate and cobicistat is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased voclosporin exposure by approximately 19-fold. (Contraindicated) Concomitant use of voclosporin and darunavir is contraindicated; concomitant use may increase the exposure of voclosporin and the risk of voclosporin-related adverse effects such as nephrotoxicity, hypertension, and QT prolongation. Voclosporin is a sensitive CYP3A4 substrate and darunavir is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased voclosporin exposure by approximately 19-fold. (Moderate) Coadministration of tenofovir alafenamide and voclosporin may result in increased plasma concentrations of tenofovir leading to an increase in tenofovir-related adverse effects. Concomitant use may also may result in additive nephrotoxicity. Monitor for renal toxicity if concomitant use is required. Tenofovir alafenamide is a P-gp substrate and voclosporin is a P-gp inhibitor.
Dasatinib: (Moderate) Concomitant use of voclosporin and dasatinib may increase the risk of QT prolongation. Consider interventions to minimize the risk of progression to torsades de pointes (TdP), such as correcting electrolyte abnormalities and ECG monitoring, particularly in patients with additional risk factors for TdP. Voclosporin has been associated with QT prolongation at supratherapeutic doses. In vitro studies have shown that dasatinib has the potential to prolong the QT interval.
Degarelix: (Moderate) Concomitant use of voclosporin and degarelix may increase the risk of QT prolongation. Consider interventions to minimize the risk of progression to torsades de pointes (TdP), such as ECG monitoring and correcting electrolyte abnormalities, particularly in patients with additional risk factors for TdP. Voclosporin has been associated with QT prolongation at supratherapeutic doses. Androgen deprivation therapy (i.e., degarelix) may prolong the QT/QTc interval.
Delavirdine: (Contraindicated) Concomitant use of voclosporin and delavirdine is contraindicated; concomitant use may increase the exposure of voclosporin and the risk of voclosporin-related adverse effects such as nephrotoxicity, hypertension, and QT prolongation. Voclosporin is a sensitive CYP3A4 substrate and delavirdine is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased voclosporin exposure by approximately 19-fold.
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) Use caution if halogenated anesthetics are coadministered with voclosporin due to the risk of additive QT prolongation. Halogenated anesthetics can prolong the QT interval. Voclosporin has been associated with QT prolongation at supratherapeutic doses.
Deutetrabenazine: (Moderate) Concomitant use of voclosporin and deutetrabenazine may increase the risk of QT prolongation. Consider interventions to minimize the risk of progression to torsades de pointes (TdP), such as ECG monitoring and correcting electrolyte abnormalities, particularly in patients with additional risk factors for TdP. Voclosporin has been associated with QT prolongation at supratherapeutic doses. 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.
Dexmedetomidine: (Moderate) Concomitant use of dexmedetomidine and voclosporin may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP. The degree of QT prolongation associated with voclosporin is not clinically significant when administered within the recommended dosage range; QT prolongation has been described at 3 times the maximum recommended dose.
Dextromethorphan; Quinidine: (Major) Use caution if quinidine is coadministered with voclosporin due to the risk of additive QT prolongation. Quinidine administration is associated with QT prolongation and torsade de pointes (TdP). Voclosporin has been associated with QT prolongation at supratherapeutic doses.
Diclofenac: (Moderate) Concomitant use of voclosporin and nonsteroidal anti-inflammatory drugs (NSAIDs) may result in additive nephrotoxicity. Monitor for renal toxicity if concomitant use is required.
Diclofenac; Misoprostol: (Moderate) Concomitant use of voclosporin and nonsteroidal anti-inflammatory drugs (NSAIDs) may result in additive nephrotoxicity. Monitor for renal toxicity if concomitant use is required.
Diflunisal: (Moderate) Concomitant use of voclosporin and nonsteroidal anti-inflammatory drugs (NSAIDs) may result in additive nephrotoxicity. Monitor for renal toxicity if concomitant use is required.
Digoxin: (Moderate) Increase monitoring of serum digoxin concentrations and watch for potential signs and symptoms of clinical toxicity when starting, adjusting, or discontinuing voclosporin. Concurrent use may increase digoxin exposure. Digoxin is a P-gp substrate with a narrow therapeutic index and voclosporin is a P-gp inhibitor.
Diltiazem: (Major) Reduce the voclosporin dosage to 15.8 mg PO in the morning and 7.9 mg PO in the evening if coadministered with diltiazem. Concomitant use may increase voclosporin exposure and the risk of voclosporin-related adverse effects such as nephrotoxicity, hypertension, and QT prolongation. Voclosporin is a sensitive CYP3A4 substrate and diltiazem is a moderate CYP3A4 inhibitor. Coadministration with moderate CYP3A4 inhibitors is predicted to increase voclosporin exposure by 3-fold.
Diphenhydramine; Ibuprofen: (Moderate) Concomitant use of voclosporin and nonsteroidal anti-inflammatory drugs (NSAIDs) may result in additive nephrotoxicity. Monitor for renal toxicity if concomitant use is required.
Diphenhydramine; Naproxen: (Moderate) Concomitant use of voclosporin and nonsteroidal anti-inflammatory drugs (NSAIDs) may result in additive nephrotoxicity. Monitor for renal toxicity if concomitant use is required.
Disopyramide: (Major) Use caution if disopyramide is coadministered with voclosporin due to the risk of additive QT prolongation. Disopyramide administration is associated with QT prolongation and torsade de pointes (TdP). Voclosporin has been associated with QT prolongation at supratherapeutic doses.
Dofetilide: (Major) Concomitant use of dofetilide and voclosporin is not recommended as concurrent use may increase the risk of QT prolongation. Dofetilide, a Class III antiarrhythmic agent, is associated with a well-established risk of QT prolongation and TdP. Voclosporin has been associated with QT prolongation with supratherapeutic doses.
Dolasetron: (Moderate) Concomitant use of voclosporin and dolasetron may increase the risk of QT prolongation. Consider interventions to minimize the risk of progression to torsades de pointes (TdP), such as ECG monitoring and correcting electrolyte abnormalities, particularly in patients with additional risk factors for TdP. Voclosporin has been associated with QT prolongation at supratherapeutic doses. Dolasetron has been associated with a dose-dependent prolongation in the QT, PR, and QRS intervals on ECG.
Dolutegravir: (Moderate) Monitor for increased toxicity of dolutegravir if coadministered with voclosporin. Concurrent use may increase the plasma concentrations of dolutegravir. Dolutegravir is a P-gp substrate and voclosporin is a P-gp inhibitor.
Dolutegravir; Lamivudine: (Moderate) Monitor for increased toxicity of dolutegravir if coadministered with voclosporin. Concurrent use may increase the plasma concentrations of dolutegravir. Dolutegravir is a P-gp substrate and voclosporin is a P-gp inhibitor.
Dolutegravir; Rilpivirine: (Moderate) Concomitant use of voclosporin and rilpivirine may increase the risk of QT prolongation. Consider interventions to minimize the risk of progression to torsades de pointes (TdP), such as ECG monitoring and correcting electrolyte abnormalities, particularly in patients with additional risk factors for TdP. Both voclosporin and rilpivirine have been associated with QT prolongation at supratherapeutic doses. (Moderate) Monitor for increased toxicity of dolutegravir if coadministered with voclosporin. Concurrent use may increase the plasma concentrations of dolutegravir. Dolutegravir is a P-gp substrate and voclosporin is a P-gp inhibitor.
Donepezil: (Moderate) Concomitant use of voclosporin and donepezil may increase the risk of QT prolongation. Consider interventions to minimize the risk of progression to torsades de pointes (TdP), such as ECG monitoring and correcting electrolyte abnormalities, particularly in patients with additional risk factors for TdP. Voclosporin has been associated with QT prolongation at supratherapeutic doses. Case reports indicate that QT prolongation and TdP can occur during donepezil therapy.
Donepezil; Memantine: (Moderate) Concomitant use of voclosporin and donepezil may increase the risk of QT prolongation. Consider interventions to minimize the risk of progression to torsades de pointes (TdP), such as ECG monitoring and correcting electrolyte abnormalities, particularly in patients with additional risk factors for TdP. Voclosporin has been associated with QT prolongation at supratherapeutic doses. Case reports indicate that QT prolongation and TdP can occur during donepezil therapy.
Doravirine; Lamivudine; Tenofovir disoproxil fumarate: (Moderate) Coadministration of tenofovir disoproxil fumarate and voclosporin may result in increased plasma concentrations of tenofovir, leading to an increase in tenofovir-related adverse effects. Concomitant use may also may result in additive nephrotoxicity. Monitor for renal toxicity if concomitant use is required. Tenofovir disoproxil fumarate is a P-gp substrate and voclosporin is a P-gp inhibitor.
Doxorubicin Liposomal: (Major) Avoid coadministration of voclosporin with doxorubicin due to increased systemic exposure of doxorubicin resulting in increased treatment-related adverse reactions. Doxorubicin is a P-gp substrate and voclosporin is a P-gp inhibitor. Concurrent use of P-gp inhibitors with doxorubicin has resulted in clinically significant interactions.
Doxorubicin: (Major) Avoid coadministration of voclosporin with doxorubicin due to increased systemic exposure of doxorubicin resulting in increased treatment-related adverse reactions. Doxorubicin is a P-gp substrate and voclosporin is a P-gp inhibitor. Concurrent use of P-gp inhibitors with doxorubicin has resulted in clinically significant interactions.
Dronedarone: (Contraindicated) Concomitant use of voclosporin and dronedarone is contraindicated due to the potential for QT prolongation and torsade de pointes (TdP). Voclosporin exposure and the risk for voclosporin-related adverse effects may also be increased. If concomitant use is necessary, reduce the voclosporin dosage to 15.8 mg PO in the morning and 7.9 mg PO in the evening. Voclosporin is a sensitive CYP3A4 substrate that is associated with QT prolongation at supratherapeutic doses. Dronedarone is a moderate CYP3A4 inhibitor that is associated with a dose-related increase in the QTc interval. The dronedarone-induced increase in QTc is approximately 10 msec at doses of 400 mg twice daily (the FDA-approved dose) and up to 25 msec at doses of 1,600 mg twice daily. Coadministration with moderate CYP3A4 inhibitors is predicted to increase voclosporin exposure by 3-fold.
Droperidol: (Major) Avoid concomitant use of droperidol and voclosporin due to the risk of additive QT prolongation. If concomitant use is necessary, 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 torsade de pointes (TdP). Some cases have occurred in patients with no known risk factors for QT prolongation and some cases have been fatal. Voclosporin has been associated with QT prolongation at supratherapeutic doses.
Duvelisib: (Major) Reduce the voclosporin dosage to 15.8 mg PO in the morning and 7.9 mg PO in the evening if coadministered with duvelisib. Concomitant use may increase voclosporin exposure and the risk of voclosporin-related adverse effects such as nephrotoxicity, hypertension, and QT prolongation. Voclosporin is a sensitive CYP3A4 substrate and duvelisib is a moderate CYP3A4 inhibitor. Coadministration with moderate CYP3A4 inhibitors is predicted to increase voclosporin exposure by 3-fold.
Edoxaban: (Major) Consider an edoxaban dosage reduction for patients being treated for deep venous thrombosis (DVT) or pulmonary embolism (PE) if concomitant use of voclosporin is necessary. Concomitant use may increase edoxaban exposure; edoxaban is a P-gp substrate and voclosporin is a P-gp inhibitor. An edoxaban dose reduction to 30 mg PO once daily is recommended by the manufacturer for use with certain P-gp inhibitors; however, because use of concomitant P-gp inhibitors was limited to only certain drugs that inhibit P-gp in DVT/PE clinical trials, clinicians should use professional judgment and guide edoxaban dose adjustments based on patient response if coadministered with voclosporin. Based on clinical experience in patients with non-valvular atrial fibrillation no dose reduction is recommended for concomitant use of voclosporin. Increased concentrations of edoxaban may occur during concomitant use of voclosporin; monitor for increased adverse effects of edoxaban.
Efavirenz: (Major) Avoid coadministration of voclosporin with efavirenz. Coadministration may decrease voclosporin exposure resulting in decreased efficacy. Concomitant use may also increase the risk of QT prolongation. Voclosporin is a sensitive CYP3A4 substrate and efavirenz is a moderate CYP3A4 inducer. Coadministration with moderate CYP3A4 inducers is predicted to decrease voclosporin exposure by 70%.
Efavirenz; Emtricitabine; Tenofovir Disoproxil Fumarate: (Major) Avoid coadministration of voclosporin with efavirenz. Coadministration may decrease voclosporin exposure resulting in decreased efficacy. Concomitant use may also increase the risk of QT prolongation. Voclosporin is a sensitive CYP3A4 substrate and efavirenz is a moderate CYP3A4 inducer. Coadministration with moderate CYP3A4 inducers is predicted to decrease voclosporin exposure by 70%. (Moderate) Coadministration of tenofovir disoproxil fumarate and voclosporin may result in increased plasma concentrations of tenofovir, leading to an increase in tenofovir-related adverse effects. Concomitant use may also may result in additive nephrotoxicity. Monitor for renal toxicity if concomitant use is required. Tenofovir disoproxil fumarate is a P-gp substrate and voclosporin is a P-gp inhibitor.
Efavirenz; Lamivudine; Tenofovir Disoproxil Fumarate: (Major) Avoid coadministration of voclosporin with efavirenz. Coadministration may decrease voclosporin exposure resulting in decreased efficacy. Concomitant use may also increase the risk of QT prolongation. Voclosporin is a sensitive CYP3A4 substrate and efavirenz is a moderate CYP3A4 inducer. Coadministration with moderate CYP3A4 inducers is predicted to decrease voclosporin exposure by 70%. (Moderate) Coadministration of tenofovir disoproxil fumarate and voclosporin may result in increased plasma concentrations of tenofovir, leading to an increase in tenofovir-related adverse effects. Concomitant use may also may result in additive nephrotoxicity. Monitor for renal toxicity if concomitant use is required. Tenofovir disoproxil fumarate is a P-gp substrate and voclosporin is a P-gp inhibitor.
Elagolix: (Major) Avoid coadministration of voclosporin with elagolix. Coadministration may decrease voclosporin exposure resulting in decreased efficacy. Voclosporin is a sensitive CYP3A4 substrate and elagolix is a moderate CYP3A4 inducer. Coadministration with moderate CYP3A4 inducers is predicted to decrease voclosporin exposure by 70%.
Elagolix; Estradiol; Norethindrone acetate: (Major) Avoid coadministration of voclosporin with elagolix. Coadministration may decrease voclosporin exposure resulting in decreased efficacy. Voclosporin is a sensitive CYP3A4 substrate and elagolix is a moderate CYP3A4 inducer. Coadministration with moderate CYP3A4 inducers is predicted to decrease voclosporin exposure by 70%.
Elbasvir; Grazoprevir: (Contraindicated) Concomitant use of grazoprevir and voclosporin is contraindicated due to the potential for increased grazoprevir exposure. Grazoprevir is a substrate of OATP1B1; voclosporin is an inhibitor of OATP1B1.
Eliglustat: (Moderate) Concomitant use of voclosporin and eliglustat may increase the risk of QT prolongation. Consider interventions to minimize the risk of progression to torsades de pointes (TdP), such as ECG monitoring and correcting electrolyte abnormalities, particularly in patients with additional risk factors for TdP. Voclosporin has been associated with QT prolongation at supratherapeutic doses. Eliglustat is predicted to cause PR, QRS, and/or QT prolongation at significantly elevated plasma concentrations.
Eluxadoline: (Major) Reduce the dose of eluxadoline to 75 mg twice daily and monitor for eluxadoline-related adverse effects including decreased mental and physical acuity if coadministered with voclosporin. Coadministration may increase exposure of eluxadoline. Eluxadoline is an OATP1B1 substrate and voclosporin is a an OATP1B1 inhibitor. Coadministration with another OATP1B1 inhibitor increased the exposure of eluxadoline by 4.4-fold.
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Alafenamide: (Contraindicated) Concomitant use of voclosporin and cobicistat is contraindicated; concomitant use may increase the exposure of voclosporin and the risk of voclosporin-related adverse effects such as nephrotoxicity, hypertension, and QT prolongation. Voclosporin is a sensitive CYP3A4 substrate and cobicistat is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased voclosporin exposure by approximately 19-fold. (Moderate) Coadministration of tenofovir alafenamide and voclosporin may result in increased plasma concentrations of tenofovir leading to an increase in tenofovir-related adverse effects. Concomitant use may also may result in additive nephrotoxicity. Monitor for renal toxicity if concomitant use is required. Tenofovir alafenamide is a P-gp substrate and voclosporin is a P-gp inhibitor.
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Disoproxil Fumarate: (Contraindicated) Concomitant use of voclosporin and cobicistat is contraindicated; concomitant use may increase the exposure of voclosporin and the risk of voclosporin-related adverse effects such as nephrotoxicity, hypertension, and QT prolongation. Voclosporin is a sensitive CYP3A4 substrate and cobicistat is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased voclosporin exposure by approximately 19-fold. (Moderate) Coadministration of tenofovir disoproxil fumarate and voclosporin may result in increased plasma concentrations of tenofovir, leading to an increase in tenofovir-related adverse effects. Concomitant use may also may result in additive nephrotoxicity. Monitor for renal toxicity if concomitant use is required. Tenofovir disoproxil fumarate is a P-gp substrate and voclosporin is a P-gp inhibitor.
Emtricitabine; Rilpivirine; Tenofovir alafenamide: (Moderate) Coadministration of tenofovir alafenamide and voclosporin may result in increased plasma concentrations of tenofovir leading to an increase in tenofovir-related adverse effects. Concomitant use may also may result in additive nephrotoxicity. Monitor for renal toxicity if concomitant use is required. Tenofovir alafenamide is a P-gp substrate and voclosporin is a P-gp inhibitor. (Moderate) Concomitant use of voclosporin and rilpivirine may increase the risk of QT prolongation. Consider interventions to minimize the risk of progression to torsades de pointes (TdP), such as ECG monitoring and correcting electrolyte abnormalities, particularly in patients with additional risk factors for TdP. Both voclosporin and rilpivirine have been associated with QT prolongation at supratherapeutic doses.
Emtricitabine; Rilpivirine; Tenofovir Disoproxil Fumarate: (Moderate) Coadministration of tenofovir disoproxil fumarate and voclosporin may result in increased plasma concentrations of tenofovir, leading to an increase in tenofovir-related adverse effects. Concomitant use may also may result in additive nephrotoxicity. Monitor for renal toxicity if concomitant use is required. Tenofovir disoproxil fumarate is a P-gp substrate and voclosporin is a P-gp inhibitor. (Moderate) Concomitant use of voclosporin and rilpivirine may increase the risk of QT prolongation. Consider interventions to minimize the risk of progression to torsades de pointes (TdP), such as ECG monitoring and correcting electrolyte abnormalities, particularly in patients with additional risk factors for TdP. Both voclosporin and rilpivirine have been associated with QT prolongation at supratherapeutic doses.
Emtricitabine; Tenofovir alafenamide: (Moderate) Coadministration of tenofovir alafenamide and voclosporin may result in increased plasma concentrations of tenofovir leading to an increase in tenofovir-related adverse effects. Concomitant use may also may result in additive nephrotoxicity. Monitor for renal toxicity if concomitant use is required. Tenofovir alafenamide is a P-gp substrate and voclosporin is a P-gp inhibitor.
Emtricitabine; Tenofovir Disoproxil Fumarate: (Moderate) Coadministration of tenofovir disoproxil fumarate and voclosporin may result in increased plasma concentrations of tenofovir, leading to an increase in tenofovir-related adverse effects. Concomitant use may also may result in additive nephrotoxicity. Monitor for renal toxicity if concomitant use is required. Tenofovir disoproxil fumarate is a P-gp substrate and voclosporin is a P-gp inhibitor.
Encorafenib: (Major) Avoid concurrent use of encorafenib with voclosporin due to the risk for decreased voclosporin exposure and additive risk for QT/QTc prolongation and torsade de pointes (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. Voclosporin is a CYP3A substrate, encorafenib is a strong CYP3A inducer, and both medications have been associated with QT/QTc prolongation. Coadministration with another strong CYP3A inducer decreased voclosporin exposure by 87%. The degree of QT prolongation associated with voclosporin is not clinically significant when administered within the recommended dosage range; QT prolongation has been described at 3 times the maximum recommended dose.
Entrectinib: (Major) Avoid concomitant use of entrectinib and voclosporin due to the risk of additive QT prolongation. Entrectinib has been associated with QT prolongation. Voclosporin has been associated with QT prolongation at supratherapeutic doses.
Enzalutamide: (Major) Avoid coadministration of voclosporin with enzalutamide. Coadministration may decrease voclosporin exposure resulting in decreased efficacy. Voclosporin is a sensitive CYP3A4 substrate and enzalutamide is a strong CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer decreased voclosporin exposure by 87%.
Eribulin: (Major) Monitor ECG if eribulin is coadministered with voclosporin. Eribulin has been associated with QT prolongation. Voclosporin has been associated with QT prolongation at supratherapeutic doses.
Erythromycin: (Major) Reduce the voclosporin dosage to 15.8 mg PO in the morning and 7.9 mg PO in the evening if coadministered with erythromycin. Concomitant use may increase voclosporin exposure and the risk of voclosporin-related adverse effects such as nephrotoxicity, hypertension, and QT prolongation. Additive QT prolongation may also occur. Voclosporin is a sensitive CYP3A4 substrate and erythromycin is a moderate CYP3A4 inhibitor that is associated with QT prolongation and torsade de pointes (TdP). Coadministration with moderate CYP3A4 inhibitors is predicted to increase voclosporin exposure by 3-fold.
Escitalopram: (Moderate) Concomitant use of escitalopram and voclosporin may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP. The degree of QT prolongation associated with voclosporin is not clinically significant when administered within the recommended dosage range; QT prolongation has been described at 3 times the maximum recommended dose.
Eslicarbazepine: (Major) Avoid coadministration of voclosporin with eslicarbazepine. Coadministration may decrease voclosporin exposure resulting in decreased efficacy. Voclosporin is a sensitive CYP3A4 substrate and eslicarbazepine is a moderate CYP3A4 inducer. Coadministration with moderate CYP3A4 inducers is predicted to decrease voclosporin exposure by 70%.
Ethiodized Oil: (Moderate) Concomitant use of voclosporin and non-ionic contrast media may result in additive nephrotoxicity. Monitor for renal toxicity if concomitant use is required.
Etodolac: (Moderate) Concomitant use of voclosporin and nonsteroidal anti-inflammatory drugs (NSAIDs) may result in additive nephrotoxicity. Monitor for renal toxicity if concomitant use is required.
Etrasimod: (Moderate) Concomitant use of etrasimod and voclosporin may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP. The degree of QT prolongation associated with voclosporin is not clinically significant when administered within the recommended dosage range; QT prolongation has been described at 3 times the maximum recommended dose. Etrasimod 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.
Etravirine: (Major) Avoid coadministration of voclosporin with etravirine. Coadministration may decrease voclosporin exposure resulting in decreased efficacy. Voclosporin is a sensitive CYP3A4 substrate and etravirine is a moderate CYP3A4 inducer. Coadministration with moderate CYP3A4 inducers is predicted to decrease voclosporin exposure by 70%.
Everolimus: (Moderate) Monitor everolimus whole blood trough concentrations as appropriate and watch for everolimus-related adverse reactions if coadministration with voclosporin is necessary. The dose of everolimus may need to be reduced. Everolimus is a P-gp substrate and voclosporin is a P-gp inhibitor. Coadministration with P-gp inhibitors may decrease the efflux of everolimus from intestinal cells and increase everolimus blood concentrations.
Ezetimibe; Simvastatin: (Moderate) Monitor for an increase in simvastatin-related adverse reactions, including myopathy and rhabdomyolysis, if coadministration with voclosporin is necessary. Concomitant use may increase simvastatin exposure. Simvastatin is a P-gp and OATP1B1 substrate; voclosporin is a P-gp and OATP1B1 inhibitor.
Fedratinib: (Major) Reduce the voclosporin dosage to 15.8 mg PO in the morning and 7.9 mg PO in the evening if coadministered with fedratinib. Concomitant use may increase voclosporin exposure and the risk of voclosporin-related adverse effects such as nephrotoxicity, hypertension, and QT prolongation. Voclosporin is a sensitive CYP3A4 substrate and fedratinib is a moderate CYP3A4 inhibitor. Coadministration with moderate CYP3A4 inhibitors is predicted to increase voclosporin exposure by 3-fold.
Fenoprofen: (Moderate) Concomitant use of voclosporin and nonsteroidal anti-inflammatory drugs (NSAIDs) may result in additive nephrotoxicity. Monitor for renal toxicity if concomitant use is required.
Fexinidazole: (Major) Concomitant use of fexinidazole and voclosporin 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. The degree of QT prolongation associated with voclosporin is not clinically significant when administered within the recommended dosage range; QT prolongation has been described at 3 times the maximum recommended dose.
Fingolimod: (Moderate) Concomitant use of voclosporin and fingolimod may increase the risk of QT prolongation. Consider interventions to minimize the risk of progression to torsades de pointes (TdP), such as ECG monitoring and correcting electrolyte abnormalities, particularly in patients with additional risk factors for TdP. Voclosporin has been associated with QT prolongation at supratherapeutic doses. Fingolimod initiation results in decreased heart rate and may prolong the QT interval. Fingolimod has not been studied in patients treated with drugs that prolong the QT interval, but drugs that prolong the QT interval have been associated with cases of TdP in patients with bradycardia.
Flecainide: (Major) Concomitant use of voclosporin and flecainide 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. The degree of QT prolongation associated with voclosporin is not clinically significant when administered within the recommended dosage range; QT prolongation has been described at 3 times the maximum recommended dose.
Fluconazole: (Contraindicated) Concomitant use of voclosporin and fluconazole is contraindicated due to the risk for QT prolongation. Voclosporin exposure and the risk for voclosporin-related adverse effects may also be increased. If concomitant use is necessary, reduce the voclosporin dosage to 15.8 mg PO in the morning and 7.9 mg PO in the evening. Voclosporin is a sensitive CYP3A4 substrate that is associated with QT prolongation with supratherapeutic doses. Fluconazole is a moderate CYP3A4 inhibitor that has been associated with QT prolongation. Coadministration with moderate CYP3A4 inhibitors is predicted to increase voclosporin exposure by 3-fold.
Fluoxetine: (Moderate) Concomitant use of fluoxetine and voclosporin may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP. The degree of QT prolongation associated with voclosporin is not clinically significant when administered within the recommended dosage range; QT prolongation has been described at 3 times the maximum recommended dose.
Fluphenazine: (Minor) Concomitant use of voclosporin and fluphenazine may increase the risk of QT prolongation. Consider interventions to minimize the risk of progression to torsades de pointes (TdP), such as ECG monitoring and correcting electrolyte abnormalities, particularly in patients with additional risk factors for TdP. Voclosporin has been associated with QT prolongation at supratherapeutic doses. Fluphenazine is associated with a possible risk for QT prolongation.
Flurbiprofen: (Moderate) Concomitant use of voclosporin and nonsteroidal anti-inflammatory drugs (NSAIDs) may result in additive nephrotoxicity. Monitor for renal toxicity if concomitant use is required.
Fluvastatin: (Moderate) Monitor for an increase in fluvastatin-related adverse reactions, including myopathy and rhabdomyolysis, if coadministration with voclosporin is necessary. Concomitant use may increase fluvastatin exposure. Fluvastatin is a substrate of OATP1B3; voclosporin is an inhibitor of OATP1B3.
Fluvoxamine: (Major) Reduce the voclosporin dosage to 15.8 mg PO in the morning and 7.9 mg PO in the evening if coadministered with fluvoxamine. Concomitant use may increase voclosporin exposure and the risk of voclosporin-related adverse effects such as nephrotoxicity, hypertension, and QT prolongation. Additive QT prolongation may also occur. Voclosporin is a sensitive CYP3A4 substrate and fluvoxamine is a moderate CYP3A4 inhibitor that is associated with QT prolongation and torsade de pointes (TdP). Coadministration with moderate CYP3A4 inhibitors is predicted to increase voclosporin exposure by 3-fold.
Fosamprenavir: (Major) Reduce the voclosporin dosage to 15.8 mg PO in the morning and 7.9 mg PO in the evening if coadministered with fosamprenavir. Concomitant use may increase voclosporin exposure and the risk of voclosporin-related adverse effects such as nephrotoxicity, hypertension, and QT prolongation. Voclosporin is a sensitive CYP3A substrate and fosamprenavir is a moderate CYP3A inhibitor. Coadministration with moderate CYP3A inhibitors is predicted to increase voclosporin exposure by 3-fold.
Foscarnet: (Major) Avoid concomitant use of foscarnet and voclosporin due to the risk of additive QT prolongation and nephrotoxicity. Both QT prolongation and torsade de pointes (TdP) have been reported during postmarketing use of foscarnet. Voclosporin has been associated with QT prolongation at supratherapeutic doses.
Fosphenytoin: (Major) Avoid coadministration of voclosporin with fosphenytoin. Coadministration may decrease voclosporin exposure resulting in decreased efficacy. Voclosporin is a sensitive CYP3A4 substrate and fosphenytoin is a strong CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer decreased voclosporin exposure by 87%.
Fostemsavir: (Moderate) Concomitant use of voclosporin and fostemsavir may increase the risk of QT prolongation. Consider interventions to minimize the risk of progression to torsades de pointes (TdP), such as ECG monitoring and correcting electrolyte abnormalities, particularly in patients with additional risk factors for TdP. Voclosporin and fostemsavir have been associated with QT prolongation at supratherapeutic doses.
Ganciclovir: (Moderate) Concomitant use of voclosporin and ganciclovir may result in additive nephrotoxicity. Monitor for renal toxicity if concomitant use is required.
Gemifloxacin: (Moderate) Concomitant use of voclosporin and gemifloxacin may increase the risk of QT prolongation. Consider interventions to minimize the risk of progression to torsades de pointes (TdP), such as ECG monitoring and correcting electrolyte abnormalities, particularly in patients with additional risk factors for TdP. Voclosporin has been associated with QT prolongation at supratherapeutic doses. 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: (Moderate) Concomitant use of voclosporin and gemtuzumab may increase the risk of QT prolongation. If concomitant use is necessary and to minimize the risk of progression to TdP, monitor ECG and correct electrolyte abnormalities, particularly in patients with additional risk factors for TdP. Voclosporin has been associated with QT prolongation at supratherapeutic doses. Although QT interval prolongation has not been reported with gemtuzumab, it has been reported with other drugs that contain calicheamicin.
Gentamicin: (Moderate) Concomitant use of voclosporin and aminoglycosides may result in additive nephrotoxicity. Monitor for renal toxicity if concomitant use is required.
Gilteritinib: (Moderate) Concomitant use of voclosporin and gilteritinib may increase the risk of QT prolongation. Consider interventions to minimize the risk of progression to torsades de pointes (TdP), such as ECG monitoring and correcting electrolyte abnormalities, particularly in patients with additional risk factors for TdP. Voclosporin has been associated with QT prolongation at supratherapeutic doses. Gilteritinib has been associated with QT prolongation.
Glasdegib: (Major) Avoid concomitant use of glasdegib and voclosporin due to the risk of additive QT prolongation. If concomitant use is necessary, 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. Voclosporin has been associated with QT prolongation with supratherapeutic doses.
Glecaprevir; Pibrentasvir: (Moderate) Monitor for an increase in glecaprevir-related adverse reactions if coadministration with voclosporin is necessary. Concomitant use may increase glecaprevir exposure. Glecaprevir is an P-gp and OATP1B1/3 substrate; voclosporin is P-gp and OATP1B1/3 inhibitor. (Moderate) Monitor for an increase in pibrentasvir-related adverse effects if concomitant use of voclosporin is necessary. Concomitant use may increase pibrentasvir exposure. Pibrentasvir is a substrate of P-gp and voclosporin is a P-gp inhibitor.
Glyburide: (Moderate) Monitor for an increase in glyburide-related adverse reactions, such as hypoglycemia, if coadministration with voclosporin is necessary. Concomitant use may increase glyburide exposure. Glyburide is a substrate of OATP1B1/3; voclosporin is an OATP1B1/3 inhibitor.
Glyburide; Metformin: (Moderate) Monitor for an increase in glyburide-related adverse reactions, such as hypoglycemia, if coadministration with voclosporin is necessary. Concomitant use may increase glyburide exposure. Glyburide is a substrate of OATP1B1/3; voclosporin is an OATP1B1/3 inhibitor.
Goserelin: (Moderate) Concomitant use of voclosporin and goserelin may increase the risk of QT prolongation. Consider interventions to minimize the risk of progression to torsades de pointes (TdP), such as ECG monitoring and correcting electrolyte abnormalities, particularly in patients with additional risk factors for TdP. Voclosporin has been associated with QT prolongation at supratherapeutic doses. Androgen deprivation therapy (i.e., goserelin) may prolong the QT/QTc interval.
Granisetron: (Moderate) Concomitant use of voclosporin and granisetron may increase the risk of QT prolongation. Consider interventions to minimize the risk of progression to torsades de pointes (TdP), such as ECG monitoring and correcting electrolyte abnormalities, particularly in patients with additional risk factors for TdP. Voclosporin has been associated with QT prolongation at supratherapeutic doses. Granisetron has been associated with QT prolongation.
Grapefruit juice: (Contraindicated) Advise patients that the use of voclosporin and grapefruit juice is contraindicated; concomitant use may increase the exposure of voclosporin and the risk of voclosporin-related adverse effects such as nephrotoxicity, hypertension, and QT prolongation. Voclosporin is a sensitive CYP3A4 substrate and grapefruit juice is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased voclosporin exposure by approximately 19-fold.
Halogenated Anesthetics: (Major) Use caution if halogenated anesthetics are coadministered with voclosporin due to the risk of additive QT prolongation. Halogenated anesthetics can prolong the QT interval. Voclosporin has been associated with QT prolongation at supratherapeutic doses.
Haloperidol: (Moderate) Concomitant use of voclosporin and haloperidol may increase the risk of QT prolongation. Consider interventions to minimize the risk of progression to torsades de pointes (TdP), such as ECG monitoring and correcting electrolyte abnormalities, particularly in patients with additional risk factors for TdP. Voclosporin has been associated with QT prolongation at supratherapeutic doses. 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: (Moderate) Concomitant use of voclosporin and histrelin may increase the risk of QT prolongation. Consider interventions to minimize the risk of progression to torsades de pointes (TdP), such as ECG monitoring and correcting electrolyte abnormalities, particularly in patients with additional risk factors for TdP. Voclosporin has been associated with QT prolongation at supratherapeutic doses. Androgen deprivation therapy (i.e., histrelin) may prolong the QT/QTc interval.
Hydrocodone; Ibuprofen: (Moderate) Concomitant use of voclosporin and nonsteroidal anti-inflammatory drugs (NSAIDs) may result in additive nephrotoxicity. Monitor for renal toxicity if concomitant use is required.
Hydroxychloroquine: (Major) Concomitant use of voclosporin and hydroxychloroquine 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. The degree of QT prolongation associated with voclosporin is not clinically significant when administered within the recommended dosage range; QT prolongation has been described at 3 times the maximum recommended dose.
Hydroxyzine: (Moderate) Concomitant use of hydroxyzine and voclosporin may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP. The degree of QT prolongation associated with voclosporin is not clinically significant when administered within the recommended dosage range; QT prolongation has been described at 3 times the maximum recommended dose.
Ibuprofen: (Moderate) Concomitant use of voclosporin and nonsteroidal anti-inflammatory drugs (NSAIDs) may result in additive nephrotoxicity. Monitor for renal toxicity if concomitant use is required.
Ibuprofen; Famotidine: (Moderate) Concomitant use of voclosporin and nonsteroidal anti-inflammatory drugs (NSAIDs) may result in additive nephrotoxicity. Monitor for renal toxicity if concomitant use is required.
Ibuprofen; Oxycodone: (Moderate) Concomitant use of voclosporin and nonsteroidal anti-inflammatory drugs (NSAIDs) may result in additive nephrotoxicity. Monitor for renal toxicity if concomitant use is required.
Ibuprofen; Pseudoephedrine: (Moderate) Concomitant use of voclosporin and nonsteroidal anti-inflammatory drugs (NSAIDs) may result in additive nephrotoxicity. Monitor for renal toxicity if concomitant use is required.
Ibutilide: (Major) Use caution if ibutilide is coadministered with voclosporin due to the risk of additive QT prolongation. Voclosporin has been associated with QT prolongation at supratherapeutic doses. Ibutilide administration can cause QT prolongation and torsade de pointes (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.
Idelalisib: (Contraindicated) Concomitant use of voclosporin and idelalisib is contraindicated; concomitant use may increase the exposure of voclosporin and the risk of voclosporin-related adverse effects such as nephrotoxicity, hypertension, and QT prolongation. Voclosporin is a sensitive CYP3A4 substrate and idelalisib is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased voclosporin exposure by approximately 19-fold.
Iloperidone: (Major) Avoid concomitant use of iloperidone and voclosporin due to the risk of additive QT prolongation. Iloperidone has been associated with QT prolongation. Voclosporin has been associated with QT prolongation at supratherapeutic doses.
Imatinib: (Major) Reduce the voclosporin dosage to 15.8 mg PO in the morning and 7.9 mg PO in the evening if coadministered with imatinib. Concomitant use may increase voclosporin exposure and the risk of voclosporin-related adverse effects such as nephrotoxicity, hypertension, and QT prolongation. Voclosporin is a sensitive CYP3A4 substrate and imatinib is a moderate CYP3A4 inhibitor. Coadministration with moderate CYP3A4 inhibitors is predicted to increase voclosporin exposure by 3-fold.
Indinavir: (Contraindicated) Concomitant use of voclosporin and indinavir is contraindicated; concomitant use may increase the exposure of voclosporin and the risk of voclosporin-related adverse effects such as nephrotoxicity, hypertension, and QT prolongation. Voclosporin is a sensitive CYP3A4 substrate and indinavir is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased voclosporin exposure by approximately 19-fold.
Indomethacin: (Moderate) Concomitant use of voclosporin and nonsteroidal anti-inflammatory drugs (NSAIDs) may result in additive nephrotoxicity. Monitor for renal toxicity if concomitant use is required.
Inotuzumab Ozogamicin: (Major) Avoid concomitant use of inotuzumab and voclosporin due to the risk of additive QT prolongation. If concomitant use is necessary, obtain ECGs and electrolytes prior to the start of treatment and periodically during treatment. Inotuzumab has been associated with QT interval prolongation. Voclosporin has been associated with QT prolongation at supratherapeutic doses.
Intranasal Influenza Vaccine: (Major) Live virus vaccines should generally not be administered to an immunosuppressed patient. Live virus vaccines may induce the illness they are intended to prevent and are generally contraindicated for use during immunosuppressive treatment. The immune response of the immunocompromised patient to vaccines may be decreased, even despite alternate vaccination schedules or more frequent booster doses. If immunization is necessary, choose an alternative to live vaccination, or, consider a delay or change in the immunization schedule. Practitioners should refer to the most recent CDC guidelines regarding vaccination of patients who are receiving drugs that adversely affect the immune system.
Iodixanol: (Moderate) Concomitant use of voclosporin and non-ionic contrast media may result in additive nephrotoxicity. Monitor for renal toxicity if concomitant use is required.
Iohexol: (Moderate) Concomitant use of voclosporin and non-ionic contrast media may result in additive nephrotoxicity. Monitor for renal toxicity if concomitant use is required.
Iomeprol: (Moderate) Concomitant use of voclosporin and non-ionic contrast media may result in additive nephrotoxicity. Monitor for renal toxicity if concomitant use is required.
Ionic Contrast Media: (Moderate) Concomitant use of voclosporin and ionic contrast media may result in additive nephrotoxicity. Monitor for renal toxicity if concomitant use is required.
Iopamidol: (Moderate) Concomitant use of voclosporin and non-ionic contrast media may result in additive nephrotoxicity. Monitor for renal toxicity if concomitant use is required.
Iopromide: (Moderate) Concomitant use of voclosporin and non-ionic contrast media may result in additive nephrotoxicity. Monitor for renal toxicity if concomitant use is required.
Ioversol: (Moderate) Concomitant use of voclosporin and non-ionic contrast media may result in additive nephrotoxicity. Monitor for renal toxicity if concomitant use is required.
Isavuconazonium: (Major) Reduce the voclosporin dosage to 15.8 mg PO in the morning and 7.9 mg PO in the evening if coadministered with isavuconazonium. Concomitant use may increase voclosporin exposure and the risk of voclosporin-related adverse effects such as nephrotoxicity, hypertension, and QT prolongation. Voclosporin is a sensitive CYP3A4 substrate and isavuconazonium is a moderate CYP3A4 inhibitor. Coadministration with moderate CYP3A4 inhibitors is predicted to increase voclosporin exposure by 3-fold.
Isoflurane: (Major) Use caution if halogenated anesthetics are coadministered with voclosporin due to the risk of additive QT prolongation. Halogenated anesthetics can prolong the QT interval. Voclosporin has been associated with QT prolongation at supratherapeutic doses.
Isoniazid, INH; Pyrazinamide, PZA; Rifampin: (Major) Avoid coadministration of voclosporin with rifampin. Coadministration may decrease voclosporin exposure resulting in decreased efficacy. Voclosporin is a sensitive CYP3A4 substrate and rifampin is a strong CYP3A4 inducer. Coadministration with rifampin decreased voclosporin exposure by 87%.
Isoniazid, INH; Rifampin: (Major) Avoid coadministration of voclosporin with rifampin. Coadministration may decrease voclosporin exposure resulting in decreased efficacy. Voclosporin is a sensitive CYP3A4 substrate and rifampin is a strong CYP3A4 inducer. Coadministration with rifampin decreased voclosporin exposure by 87%.
Isosulfan Blue: (Moderate) Concomitant use of voclosporin and non-ionic contrast media may result in additive nephrotoxicity. Monitor for renal toxicity if concomitant use is required.
Itraconazole: (Contraindicated) Concomitant use of voclosporin and itraconazole is contraindicated; concomitant use may increase the exposure of voclosporin and the risk of voclosporin-related adverse effects such as nephrotoxicity, hypertension, and QT prolongation. Additive QT prolongation may also occur. Voclosporin is a sensitive CYP3A4 substrate and itraconazole is a strong CYP3A4 inhibitor that has been associated with QT prolongation. Coadministration with another strong CYP3A4 inhibitor increased voclosporin exposure by approximately 19-fold.
Ivosidenib: (Major) Avoid concomitant use of ivosidenib and voclosporin due to the risk of additive QT prolongation. If concomitant use is necessary, 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. Voclosporin has been associated with QT prolongation at supratherapeutic doses.
Ketoconazole: (Contraindicated) Avoid concomitant use of ketoconazole and voclosporin due to an increased risk for torsade de pointes (TdP) and QT/QTc prolongation. The degree of QT prolongation associated with voclosporin is not clinically significant when administered within the recommended dosage range; QT prolongation has been described at 3 times the maximum recommended dose. Concomitant use may also increase the exposure of voclosporin, further increasing the risk for adverse effects. Voclosporin is a sensitive CYP3A4 substrate and ketoconazole is a strong CYP3A4 inhibitor. Coadministration with ketoconazole increased voclosporin exposure by approximately 19-fold.
Ketoprofen: (Moderate) Concomitant use of voclosporin and nonsteroidal anti-inflammatory drugs (NSAIDs) may result in additive nephrotoxicity. Monitor for renal toxicity if concomitant use is required.
Ketorolac: (Moderate) Concomitant use of voclosporin and nonsteroidal anti-inflammatory drugs (NSAIDs) may result in additive nephrotoxicity. Monitor for renal toxicity if concomitant use is required.
Lamivudine; Tenofovir Disoproxil Fumarate: (Moderate) Coadministration of tenofovir disoproxil fumarate and voclosporin may result in increased plasma concentrations of tenofovir, leading to an increase in tenofovir-related adverse effects. Concomitant use may also may result in additive nephrotoxicity. Monitor for renal toxicity if concomitant use is required. Tenofovir disoproxil fumarate is a P-gp substrate and voclosporin is a P-gp inhibitor.
Lansoprazole; Amoxicillin; Clarithromycin: (Contraindicated) Concomitant use of voclosporin and clarithromycin is contraindicated; concomitant use may increase the exposure of voclosporin and the risk of voclosporin-related adverse effects such as nephrotoxicity, hypertension, and QT prolongation. Additive QT prolongation may also occur. Voclosporin is a sensitive CYP3A4 substrate and clarithromycin is a strong CYP3A4 inhibitor that has been associated with QT prolongation. Coadministration with another strong CYP3A4 inhibitor increased voclosporin exposure by approximately 19-fold.
Lapatinib: (Major) Monitor for an increase in lapatinib-related adverse reactions if coadministration with voclosporin is necessary; also monitor ECGs for QT prolongation and monitor electrolytes. Correct any electrolyte abnormalities prior to treatment. Lapatinib is a P-gp substrate that has been associated with concentration-dependent QT prolongation; ventricular arrhythmias and torsade de pointes (TdP) have also been reported in postmarketing experience. Voclosporin is a P-gp inhibitor that is associated with QT prolongation with supratherapeutic doses. Increased plasma concentrations of lapatinib are likely when administered with P-gp inhibitors.
Lefamulin: (Contraindicated) Concomitant use of voclosporin and oral lefamulin is contraindicated due to the potential for QT prolongation and torsade de pointes (TdP). Voclosporin exposure and the risk for voclosporin-related adverse effects may also be increased. Avoid use of lefamulin injection with voclosporin. If concurrent use of lefamulin injection is necessary, monitor ECG and reduce the voclosporin dosage to 15.8 mg PO in the morning and 7.9 mg PO in the evening. Voclosporin is a sensitive CYP3A4 substrate and P-gp inhibitor that is associated with QT prolongation at supratherapeutic doses. Oral lefamulin is a P-gp substrate and moderate CYP3A4 inhibitor that is associated with concentration dependent QTc prolongation. Coadministration with moderate CYP3A4 inhibitors is predicted to increase voclosporin exposure by 3-fold.
Lenacapavir: (Major) Reduce the voclosporin dosage to 15.8 mg PO in the morning and 7.9 mg PO in the evening if coadministered with lenacapavir. Concomitant use may increase voclosporin exposure and the risk of voclosporin-related adverse effects such as nephrotoxicity, hypertension, and QT prolongation. Voclosporin is a sensitive CYP3A substrate and lenacapavir is a moderate CYP3A inhibitor. Coadministration with moderate CYP3A inhibitors is predicted to increase voclosporin exposure by 3-fold.
Lenvatinib: (Major) Avoid concomitant use of lenvatinib and voclosporin due to the risk of additive QT prolongation. Prolongation of the QT interval has been reported with lenvatinib therapy. Voclosporin has been associated with QT prolongation at supratherapeutic doses.
Letermovir: (Major) Reduce the voclosporin dosage to 15.8 mg PO in the morning and 7.9 mg PO in the evening if coadministered with letermovir. Concomitant use may increase voclosporin exposure and the risk of voclosporin-related adverse effects such as nephrotoxicity, hypertension, and QT prolongation. Concomitant use may also increase letermovir exposure and adverse effects. Voclosporin is a sensitive CYP3A4 substrate and OATP1B1 inhibitor and letermovir is a moderate CYP3A4 inhibitor and OATP1B1 substrate. Coadministration with moderate CYP3A4 inhibitors is predicted to increase voclosporin exposure by 3-fold.
Leuprolide: (Moderate) Concomitant use of voclosporin and leuprolide may increase the risk of QT prolongation. Consider interventions to minimize the risk of progression to torsades de pointes (TdP), such as ECG monitoring and correcting electrolyte abnormalities, particularly in patients with additional risk factors for TdP. Voclosporin has been associated with QT prolongation at supratherapeutic doses. Androgen deprivation therapy (i.e., leuprolide) may prolong the QT/QTc interval.
Leuprolide; Norethindrone: (Moderate) Concomitant use of voclosporin and leuprolide may increase the risk of QT prolongation. Consider interventions to minimize the risk of progression to torsades de pointes (TdP), such as ECG monitoring and correcting electrolyte abnormalities, particularly in patients with additional risk factors for TdP. Voclosporin has been associated with QT prolongation at supratherapeutic doses. Androgen deprivation therapy (i.e., leuprolide) may prolong the QT/QTc interval.
Levofloxacin: (Moderate) Concomitant use of levofloxacin and voclosporin may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP. The degree of QT prolongation associated with voclosporin is not clinically significant when administered within the recommended dosage range; QT prolongation has been described at 3 times the maximum recommended dose.
Levoketoconazole: (Contraindicated) Avoid concomitant use of ketoconazole and voclosporin due to an increased risk for torsade de pointes (TdP) and QT/QTc prolongation. The degree of QT prolongation associated with voclosporin is not clinically significant when administered within the recommended dosage range; QT prolongation has been described at 3 times the maximum recommended dose. Concomitant use may also increase the exposure of voclosporin, further increasing the risk for adverse effects. Voclosporin is a sensitive CYP3A4 substrate and ketoconazole is a strong CYP3A4 inhibitor. Coadministration with ketoconazole increased voclosporin exposure by approximately 19-fold.
Lithium: (Moderate) Concomitant use of lithium and voclosporin may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP. The degree of QT prolongation associated with voclosporin is not clinically significant when administered within the recommended dosage range; QT prolongation has been described at 3 times the maximum recommended dose.
Live Vaccines: (Major) Live virus vaccines should generally not be administered to an immunosuppressed patient. Live virus vaccines may induce the illness they are intended to prevent and are generally contraindicated for use during immunosuppressive treatment. The immune response of the immunocompromised patient to vaccines may be decreased, even despite alternate vaccination schedules or more frequent booster doses. If immunization is necessary, choose an alternative to live vaccination, or, consider a delay or change in the immunization schedule. Practitioners should refer to the most recent CDC guidelines regarding vaccination of patients who are receiving drugs that adversely affect the immune system.
Lofexidine: (Major) Monitor ECG if lofexidine is coadministered with voclosporin due to the risk for additive QT prolongation. Lofexidine prolongs the QT interval. Voclosporin has been associated with QT prolongation at supratherapeutic doses.
Lonafarnib: (Contraindicated) Concomitant use of voclosporin and lonafarnib is contraindicated; concomitant use may increase the exposure of voclosporin and the risk of voclosporin-related adverse effects such as nephrotoxicity, hypertension, and QT prolongation. Voclosporin is a sensitive CYP3A4 substrate and lonafarnib is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased voclosporin exposure by approximately 19-fold.
Loperamide: (Moderate) Concomitant use of loperamide and voclosporin may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP. Concomitant use may also increase loperamide exposure and the risk for other loperamide-related adverse effects; loperamide is a P-gp substrate and voclosporin is a P-gp inhibitor. Coadministration with another P-gp inhibitor increased loperamide plasma concentrations by 2- to 3-fold.
Loperamide; Simethicone: (Moderate) Concomitant use of loperamide and voclosporin may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP. Concomitant use may also increase loperamide exposure and the risk for other loperamide-related adverse effects; loperamide is a P-gp substrate and voclosporin is a P-gp inhibitor. Coadministration with another P-gp inhibitor increased loperamide plasma concentrations by 2- to 3-fold.
Lopinavir; Ritonavir: (Contraindicated) Concomitant use of voclosporin and ritonavir is contraindicated; concomitant use may increase the exposure of voclosporin and the risk of voclosporin-related adverse effects such as nephrotoxicity, hypertension, and QT prolongation. Voclosporin is a sensitive CYP3A4 substrate and ritonavir is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased voclosporin exposure by approximately 19-fold. (Major) Avoid concomitant use of lopinavir and voclosporin due to the risk of additive QT prolongation. If concomitant use 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. Voclosporin has been associated with QT prolongation at supratherapeutic doses.
Lorlatinib: (Major) Avoid coadministration of voclosporin with lorlatinib. Coadministration may decrease voclosporin exposure resulting in decreased efficacy. Voclosporin is a sensitive CYP3A4 substrate and lorlatinib is a moderate CYP3A4 inducer. Coadministration with moderate CYP3A4 inducers is predicted to decrease voclosporin exposure by 70%.
Lovastatin: (Moderate) Monitor for an increase in lovastatin-related adverse reactions, including myopathy and rhabdomyolysis, if coadministration with voclosporin is necessary. Concomitant use may increase lovastatin exposure. Lovastatin is a substrate of P-gp; voclosporin is an inhibitor of P-gp.
Lumacaftor; Ivacaftor: (Major) Avoid coadministration of voclosporin with lumacaftor; ivacaftor. Coadministration may decrease voclosporin exposure resulting in decreased efficacy. Voclosporin is a sensitive CYP3A4 substrate and lumacaftor; ivacaftor is a strong CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer decreased voclosporin exposure by 87%.
Lumacaftor; Ivacaftor: (Major) Avoid coadministration of voclosporin with lumacaftor; ivacaftor. Coadministration may decrease voclosporin exposure resulting in decreased efficacy. Voclosporin is a sensitive CYP3A4 substrate and lumacaftor; ivacaftor is a strong CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer decreased voclosporin exposure by 87%.
Macimorelin: (Major) Avoid concomitant use of macimorelin and voclosporin due to the risk of additive QT prolongation. Use of these drugs together may increase the risk of developing torsade de pointes-type ventricular tachycardia. Allow a sufficient washout of drugs that are known to prolong the QT interval prior to administration of macimorelin. Treatment with macimorelin has been associated with an increase in the corrected QT (QTc) interval. Voclosporin has been associated with QT prolongation with supratherapeutic doses.
Mannitol: (Major) Avoid concomitant use of mannitol and voclosporin; coadministration may result in additive nephrotoxicity. Monitor for renal toxicity if concomitant use is required.
Maprotiline: (Moderate) Concomitant use of voclosporin and maprotiline may increase the risk of QT prolongation. Consider interventions to minimize the risk of progression to torsades de pointes (TdP), such as ECG monitoring and correcting electrolyte abnormalities, particularly in patients with additional risk factors for TdP. Voclosporin has been associated with QT prolongation at supratherapeutic doses. 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.
Maraviroc: (Moderate) Monitor for an increase in maraviroc-related adverse reactions if coadministration with voclosporin is necessary. Concomitant use may increase maraviroc exposure. Maraviroc is a P-gp and OATP1B1 substrate; voclosporin is a P-gp and OATP1B1 inhibitor.
Mavacamten: (Major) Avoid coadministration of voclosporin with mavacamten. Coadministration may decrease voclosporin exposure resulting in decreased efficacy. Voclosporin is a sensitive CYP3A substrate and mavacamten is a moderate CYP3A inducer. Coadministration with moderate CYP3A inducers is predicted to decrease voclosporin exposure by 70%.
Measles Virus; Mumps Virus; Rubella Virus; Varicella Virus Vaccine, Live: (Major) Live virus vaccines should generally not be administered to an immunosuppressed patient. Live virus vaccines may induce the illness they are intended to prevent and are generally contraindicated for use during immunosuppressive treatment. The immune response of the immunocompromised patient to vaccines may be decreased, even despite alternate vaccination schedules or more frequent booster doses. If immunization is necessary, choose an alternative to live vaccination, or, consider a delay or change in the immunization schedule. Practitioners should refer to the most recent CDC guidelines regarding vaccination of patients who are receiving drugs that adversely affect the immune system.
Measles/Mumps/Rubella Vaccines, MMR: (Major) Live virus vaccines should generally not be administered to an immunosuppressed patient. Live virus vaccines may induce the illness they are intended to prevent and are generally contraindicated for use during immunosuppressive treatment. The immune response of the immunocompromised patient to vaccines may be decreased, even despite alternate vaccination schedules or more frequent booster doses. If immunization is necessary, choose an alternative to live vaccination, or, consider a delay or change in the immunization schedule. Practitioners should refer to the most recent CDC guidelines regarding vaccination of patients who are receiving drugs that adversely affect the immune system.
Meclofenamate Sodium: (Moderate) Concomitant use of voclosporin and nonsteroidal anti-inflammatory drugs (NSAIDs) may result in additive nephrotoxicity. Monitor for renal toxicity if concomitant use is required.
Mefenamic Acid: (Moderate) Concomitant use of voclosporin and nonsteroidal anti-inflammatory drugs (NSAIDs) may result in additive nephrotoxicity. Monitor for renal toxicity if concomitant use is required.
Mefloquine: (Moderate) Monitor for an increase in mefloquine-related adverse effects if concomitant use of voclosporin is necessary. Concomitant use may increase mefloquine exposure and the risk of additive QT prolongation. Consider interventions to minimize the risk of progression to torsades de pointes (TdP), such as ECG monitoring and correcting electrolyte abnormalities, particularly in patients with additional risk factors for TdP. 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. Mefloquine is a P-gp substrate; voclosporin is a P-gp inhibitor that has been associated with QT prolongation at supratherapeutic doses.
Meloxicam: (Moderate) Concomitant use of voclosporin and nonsteroidal anti-inflammatory drugs (NSAIDs) may result in additive nephrotoxicity. Monitor for renal toxicity if concomitant use is required.
Mesalamine, 5-ASA: (Moderate) Concomitant use of voclosporin and mesalamine may result in additive nephrotoxicity. Monitor for renal toxicity if concomitant use is required.
Methadone: (Major) The need to coadminister methadone with drugs known to prolong the QT interval, such as voclosporin, should be done with extreme caution and a careful assessment of treatment risks versus benefits. Methadone is associated with an increased risk for QT prolongation and torsade de pointes (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. Voclosporin has been associated with QT prolongation at supratherapeutic doses.
Methohexital: (Major) Avoid coadministration of voclosporin with methohexital. Coadministration may decrease voclosporin exposure resulting in decreased efficacy. Voclosporin is a sensitive CYP3A4 substrate and methohexital is a moderate CYP3A4 inducer. Coadministration with moderate CYP3A4 inducers is predicted to decrease voclosporin exposure by 70%.
Metronidazole: (Moderate) Concomitant use of metronidazole and voclosporin may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP. The degree of QT prolongation associated with voclosporin is not clinically significant when administered within the recommended dosage range; QT prolongation has been described at three times the maximum recommended dose.
Midostaurin: (Major) Consider interval assessments of QT by EKG if midostaurin is taken concurrently with voclosporin. QT prolongation was reported in patients who received midostaurin in clinical trials. Voclosporin has been associated with QT prolongation at supratherapeutic doses.
Mifepristone: (Contraindicated) Concomitant use of voclosporin and mifepristone is contraindicated; concomitant use may increase the exposure of voclosporin and the risk of voclosporin-related adverse effects such as nephrotoxicity, hypertension, and QT prolongation. Additive QT prolongation may also occur. Voclosporin is a sensitive CYP3A4 substrate and mifepristone is a strong CYP3A4 inhibitor that has been associated with QT prolongation. Coadministration with another strong CYP3A4 inhibitor increased voclosporin exposure by approximately 19-fold.
Mirtazapine: (Moderate) Concomitant use of mirtazapine and voclosporin may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP. The degree of QT prolongation associated with voclosporin is not clinically significant when administered within the recommended dosage range; QT prolongation has been described at 3 times the maximum recommended dose.
Mitotane: (Major) Avoid coadministration of voclosporin with mitotane. Coadministration may decrease voclosporin exposure resulting in decreased efficacy. Voclosporin is a sensitive CYP3A4 substrate and mitotane is a strong CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer decreased voclosporin exposure by 87%.
Mobocertinib: (Major) Concomitant use of mobocertinib and voclosporin 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. The degree of QT prolongation associated with voclosporin is not clinically significant when administered within the recommended dosage range; QT prolongation has been described at 3 times the maximum recommended dose.
Morphine: (Moderate) Monitor for an increase in morphine-related adverse reactions, including hypotension, sedation, and respiratory depression, if coadministration with voclosporin is necessary; decrease the morphine dose if indicated. Morphine is a P-gp substrate and voclosporin is a P-gp inhibitor. Coadministration with P-gp inhibitors can increase morphine exposure by about 2-fold.
Morphine; Naltrexone: (Moderate) Monitor for an increase in morphine-related adverse reactions, including hypotension, sedation, and respiratory depression, if coadministration with voclosporin is necessary; decrease the morphine dose if indicated. Morphine is a P-gp substrate and voclosporin is a P-gp inhibitor. Coadministration with P-gp inhibitors can increase morphine exposure by about 2-fold.
Moxifloxacin: (Major) Avoid concomitant use of moxifloxacin and voclosporin due to the risk of additive QT prolongation and torsade de pointes (TdP). 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. Voclosporin has been associated with QT prolongation at supratherapeutic doses.
Nabumetone: (Moderate) Concomitant use of voclosporin and nonsteroidal anti-inflammatory drugs (NSAIDs) may result in additive nephrotoxicity. Monitor for renal toxicity if concomitant use is required.
Nafcillin: (Major) Avoid coadministration of voclosporin with nafcillin. Coadministration may decrease voclosporin exposure resulting in decreased efficacy. Voclosporin is a sensitive CYP3A4 substrate and nafcillin is a moderate CYP3A4 inducer. Coadministration with moderate CYP3A4 inducers is predicted to decrease voclosporin exposure by 70%.
Naldemedine: (Moderate) Monitor for potential naldemedine-related adverse reactions if coadministered with voclosporin. The plasma concentrations of naldemedine may be increased during concurrent use. Naldemedine is a P-gp substrate; voclosporin is a P-gp inhibitor.
Nanoparticle Albumin-Bound Sirolimus: (Major) Avoid concomitant use of sirolimus and voclosporin. Coadministration may increase sirolimus concentrations and increase the risk for sirolimus-related adverse effects. Sirolimus is a P-gp substrate and voclosporin is a P-gp inhibitor.
Naproxen: (Moderate) Concomitant use of voclosporin and nonsteroidal anti-inflammatory drugs (NSAIDs) may result in additive nephrotoxicity. Monitor for renal toxicity if concomitant use is required.
Naproxen; Esomeprazole: (Moderate) Concomitant use of voclosporin and nonsteroidal anti-inflammatory drugs (NSAIDs) may result in additive nephrotoxicity. Monitor for renal toxicity if concomitant use is required.
Naproxen; Pseudoephedrine: (Moderate) Concomitant use of voclosporin and nonsteroidal anti-inflammatory drugs (NSAIDs) may result in additive nephrotoxicity. Monitor for renal toxicity if concomitant use is required.
Nefazodone: (Contraindicated) Concomitant use of voclosporin and nefazodone is contraindicated; concomitant use may increase the exposure of voclosporin and the risk of voclosporin-related adverse effects such as nephrotoxicity, hypertension, and QT prolongation. Voclosporin is a sensitive CYP3A4 substrate and nefazodone is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased voclosporin exposure by approximately 19-fold.
Nelfinavir: (Contraindicated) Concomitant use of voclosporin and nelfinavir is contraindicated; concomitant use may increase the exposure of voclosporin and the risk of voclosporin-related adverse effects such as nephrotoxicity, hypertension, and QT prolongation. Voclosporin is a sensitive CYP3A4 substrate and nelfinavir is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased voclosporin exposure by approximately 19-fold.
Neomycin: (Moderate) Concomitant use of voclosporin and neomycin may result in additive nephrotoxicity. Monitor for renal toxicity if concomitant use is required.
Netupitant, Fosnetupitant; Palonosetron: (Major) Reduce the voclosporin dosage to 15.8 mg PO in the morning and 7.9 mg PO in the evening if coadministered with netupitant. Concomitant use may increase voclosporin exposure and the risk of voclosporin-related adverse effects such as nephrotoxicity, hypertension, and QT prolongation. Voclosporin is a sensitive CYP3A4 substrate and netupitant is a moderate CYP3A4 inhibitor. Coadministration with moderate CYP3A4 inhibitors is predicted to increase voclosporin exposure by 3-fold.
Nilotinib: (Major) Avoid coadministration of voclosporin and nilotinib due to the risk of QT prolongation. Voclosporin exposure and the risk for voclosporin-related adverse effects may also be increased. If concomitant use is necessary, reduce the voclosporin dosage to 15.8 mg PO in the morning and 7.9 mg PO in the evening. Voclosporin is a sensitive CYP3A4 substrate that is associated with QT prolongation at supratherapeutic doses. Nilotinib is a moderate CYP3A4 inhibitor that has been associated with sudden death and QT prolongation. Coadministration with moderate CYP3A4 inhibitors is predicted to increase voclosporin exposure by 3-fold.
Nirmatrelvir; Ritonavir: (Contraindicated) Concomitant use of ritonavir-boosted nirmatrelvir and voclosporin is contraindicated due to the potential for acute or chronic nephrotoxicity; consider an alternative COVID-19 therapy. Coadministration may increase voclosporin exposure resulting in increased toxicity. Voclosporin is a sensitive CYP3A4 substrate and nirmatrelvir is a CYP3A inhibitor. (Contraindicated) Concomitant use of voclosporin and ritonavir is contraindicated; concomitant use may increase the exposure of voclosporin and the risk of voclosporin-related adverse effects such as nephrotoxicity, hypertension, and QT prolongation. Voclosporin is a sensitive CYP3A4 substrate and ritonavir is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased voclosporin exposure by approximately 19-fold.
Non-Ionic Contrast Media: (Moderate) Concomitant use of voclosporin and non-ionic contrast media may result in additive nephrotoxicity. Monitor for renal toxicity if concomitant use is required.
Nonsteroidal antiinflammatory drugs: (Moderate) Concomitant use of voclosporin and nonsteroidal anti-inflammatory drugs (NSAIDs) may result in additive nephrotoxicity. Monitor for renal toxicity if concomitant use is required.
Ofloxacin: (Moderate) Concomitant use of ofloxacin and voclosporin may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP. The degree of QT prolongation associated with voclosporin is not clinically significant when administered within the recommended dosage range; QT prolongation has been described at 3 times the maximum recommended dose.
Olanzapine: (Moderate) Concomitant use of voclosporin and olanzapine may increase the risk of QT prolongation. Consider interventions to minimize the risk of progression to torsades de pointes (TdP), such as ECG monitoring and correcting electrolyte abnormalities, particularly in patients with additional risk factors for TdP. Voclosporin has been associated with QT prolongation at supratherapeutic doses. Limited data, including some case reports, suggest that olanzapine may be associated with a significant prolongation of the QTc interval.
Olanzapine; Fluoxetine: (Moderate) Concomitant use of fluoxetine and voclosporin may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP. The degree of QT prolongation associated with voclosporin is not clinically significant when administered within the recommended dosage range; QT prolongation has been described at 3 times the maximum recommended dose. (Moderate) Concomitant use of voclosporin and olanzapine may increase the risk of QT prolongation. Consider interventions to minimize the risk of progression to torsades de pointes (TdP), such as ECG monitoring and correcting electrolyte abnormalities, particularly in patients with additional risk factors for TdP. Voclosporin has been associated with QT prolongation at supratherapeutic doses. Limited data, including some case reports, suggest that olanzapine may be associated with a significant prolongation of the QTc interval.
Olanzapine; Samidorphan: (Moderate) Concomitant use of voclosporin and olanzapine may increase the risk of QT prolongation. Consider interventions to minimize the risk of progression to torsades de pointes (TdP), such as ECG monitoring and correcting electrolyte abnormalities, particularly in patients with additional risk factors for TdP. Voclosporin has been associated with QT prolongation at supratherapeutic doses. Limited data, including some case reports, suggest that olanzapine may be associated with a significant prolongation of the QTc interval.
Omeprazole; Amoxicillin; Rifabutin: (Major) Avoid coadministration of voclosporin with rifabutin. Coadministration may decrease voclosporin exposure resulting in decreased efficacy. Voclosporin is a sensitive CYP3A4 substrate and rifabutin is a moderate CYP3A4 inducer. Coadministration with moderate CYP3A4 inducers is predicted to decrease voclosporin exposure by 70%.
Ondansetron: (Major) Concomitant use of voclosporin and ondansetron 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. Do not exceed 16 mg of IV ondansetron in a single dose; the degree of QT prolongation associated with ondansetron significantly increases above this dose. The degree of QT prolongation associated with voclosporin is not clinically significant when administered within the recommended dosage range; QT prolongation has been described at 3 times the maximum recommended dose.
Osilodrostat: (Moderate) Concomitant use of voclosporin and osilodrostat may increase the risk of QT prolongation. Consider interventions to minimize the risk of progression to torsades de pointes (TdP), such as ECG monitoring and correcting electrolyte abnormalities, particularly in patients with additional risk factors for TdP. Voclosporin has been associated with QT prolongation at supratherapeutic doses. Osilodrostat is associated with dose-dependent QT prolongation.
Osimertinib: (Major) Avoid concomitant use of osimertinib and voclosporin if possible due to the risk of additive QT prolongation and torsade de pointes (TdP). If concomitant use is necessary, periodically monitor ECGs and electrolytes; an interruption of osimertinib therapy with dose reduction or discontinuation may be necessary if QT prolongation occurs. Concentration-dependent QTc prolongation occurred during clinical trials of osimertinib. Voclosporin has been associated with QT prolongation at supratherapeutic doses.
Oxaliplatin: (Major) Monitor ECGs and electrolytes in patients receiving oxaliplatin concomitantly with voclosporin; correct electrolyte abnormalities prior to administration of oxaliplatin. QT prolongation and ventricular arrhythmias including fatal torsade de pointes have been reported with oxaliplatin use in postmarketing experience. Voclosporin has been associated with QT prolongation at supratherapeutic doses.
Oxaprozin: (Moderate) Concomitant use of voclosporin and nonsteroidal anti-inflammatory drugs (NSAIDs) may result in additive nephrotoxicity. Monitor for renal toxicity if concomitant use is required.
Ozanimod: (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.
Pacritinib: (Major) Concomitant use of pacritinib and voclosporin 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. The degree of QT prolongation associated with voclosporin is not clinically significant when administered within the recommended dosage range; QT prolongation has been described at 3 times the maximum recommended dose.
Paliperidone: (Major) Avoid concomitant use of paliperidone with voclosporin due to the risk of additive QT prolongation and torsade de pointes (TdP). Paliperidone has been associated with QT prolongation; TdP and ventricular fibrillation have been reported in the setting of overdose. Voclosporin has been associated with QT prolongation at supratherapeutic doses.
Pamidronate: (Moderate) Concomitant use of voclosporin and pamidronate may result in additive nephrotoxicity. Monitor for renal toxicity if concomitant use is required.
Panobinostat: (Major) Avoid concomitant use of panobinostat with voclosporin due to the risk of additive QT prolongation. QT prolongation has been reported with panobinostat. Voclosporin has been associated with QT prolongation at supratherapeutic doses.
Paromomycin: (Moderate) Concomitant use of voclosporin and aminoglycosides may result in additive nephrotoxicity. Monitor for renal toxicity if concomitant use is required.
Pasireotide: (Moderate) Concomitant use of voclosporin and pasireotide may increase the risk of QT prolongation. Consider interventions to minimize the risk of progression to torsades de pointes (TdP), such as ECG monitoring and correcting electrolyte abnormalities, particularly in patients with additional risk factors for TdP. Voclosporin has been associated with QT prolongation at supratherapeutic doses. QT prolongation has occurred with pasireotide at therapeutic and supra-therapeutic doses.
Pazopanib: (Major) Avoid concomitant use of pazopanib and voclosporin due to the potential for increase pazopanib exposure and risk of additive QT prolongation. If concomitant use is necessary, monitor ECGs and electrolytes; correct hypokalemia, hypomagnesemia, and hypocalcemia. Pazopanib is a P-gp substrate that has been associated with QT prolongation. Voclosporin is a P-gp inhibitor that has been associated with QT prolongation with supratherapeutic doses.
Pentamidine: (Major) Use caution if pentamidine is coadministered with voclosporin due to the risk of additive QT prolongation. Concomitant use may also result in additive nephrotoxicity; monitor for renal toxicity if concomitant use is required. Systemic pentamidine has been associated with QT prolongation. Voclosporin has been associated with QT prolongation at supratherapeutic doses.
Perphenazine: (Minor) Concomitant use of voclosporin and perphenazine may increase the risk of QT prolongation. Consider interventions to minimize the risk of progression to torsades de pointes (TdP), such as ECG monitoring and correcting electrolyte abnormalities, particularly in patients with additional risk factors for TdP. Voclosporin has been associated with QT prolongation at supratherapeutic doses. Perphenazine is associated with a possible risk for QT prolongation.
Perphenazine; Amitriptyline: (Minor) Concomitant use of voclosporin and perphenazine may increase the risk of QT prolongation. Consider interventions to minimize the risk of progression to torsades de pointes (TdP), such as ECG monitoring and correcting electrolyte abnormalities, particularly in patients with additional risk factors for TdP. Voclosporin has been associated with QT prolongation at supratherapeutic doses. Perphenazine is associated with a possible risk for QT prolongation.
Pexidartinib: (Major) Avoid coadministration of voclosporin with pexidartinib. Coadministration may decrease voclosporin exposure resulting in decreased efficacy. Voclosporin is a sensitive CYP3A4 substrate and pexidartinib is a moderate CYP3A4 inducer. Coadministration with moderate CYP3A4 inducers is predicted to decrease voclosporin exposure by 70%.
Phenobarbital: (Major) Avoid coadministration of voclosporin with phenobarbital. Coadministration may decrease voclosporin exposure resulting in decreased efficacy. Voclosporin is a sensitive CYP3A4 substrate and phenobarbital is a strong CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer decreased voclosporin exposure by 87%.
Phenobarbital; Hyoscyamine; Atropine; Scopolamine: (Major) Avoid coadministration of voclosporin with phenobarbital. Coadministration may decrease voclosporin exposure resulting in decreased efficacy. Voclosporin is a sensitive CYP3A4 substrate and phenobarbital is a strong CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer decreased voclosporin exposure by 87%.
Phenytoin: (Major) Avoid coadministration of voclosporin with phenytoin. Coadministration may decrease voclosporin exposure resulting in decreased efficacy. Voclosporin is a sensitive CYP3A4 substrate and phenytoin is a strong CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer decreased voclosporin exposure by 87%.
Pimavanserin: (Major) Avoid concomitant use of pimavanserin and voclosporin due to the risk of additive QT prolongation. Pimavanserin prolongs the QT interval. Voclosporin has been associated with QT prolongation at supratherapeutic doses.
Pimozide: (Contraindicated) Concomitant use of voclosporin and pimozide is contraindicated due to the potential for QT prolongation and torsade de pointes (TdP). Pimozide is associated with a well-established risk of QT prolongation and TdP. Voclosporin has been associated with QT prolongation at supratherapeutic doses.
Piroxicam: (Moderate) Concomitant use of voclosporin and nonsteroidal anti-inflammatory drugs (NSAIDs) may result in additive nephrotoxicity. Monitor for renal toxicity if concomitant use is required.
Pitavastatin: (Moderate) Monitor for an increase in pitavastatin-related adverse reactions, including myopathy and rhabdomyolysis, if coadministration with voclosporin is necessary. Concomitant use may increase pitavastatin exposure. Pitavastatin is a P-gp and OATP1B1 substrate; voclosporin is a P-gp and OATP1B1 inhibitor.
Pitolisant: (Major) Avoid concomitant use of pitolisant and voclosporin due to the risk of additive QT prolongation. Pitolisant prolongs the QT interval. Voclosporin has been associated with QT prolongation at supratherapeutic doses.
Plazomicin: (Moderate) Concomitant use of voclosporin and aminoglycosides may result in additive nephrotoxicity. Monitor for renal toxicity if concomitant use is required.
Ponesimod: (Major) In general, do not initiate ponesimod in patients taking voclosporin due to the risk of additive bradycardia, QT prolongation, and torsade de pointes (TdP); additive immunosuppression may also occur which may extend the duration or severity of immune suppression. If treatment initiation is considered, seek advice from a cardiologist and monitor for signs and symptoms of infection. Ponesimod initiation may result in a transient decrease in heart rate and atrioventricular conduction delays. Ponesimod 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 voclosporin may prolong the QT interval.
Posaconazole: (Contraindicated) Concomitant use of voclosporin and posaconazole is contraindicated as use may increase the exposure of voclosporin and the risk of voclosporin-related adverse effects such as nephrotoxicity, hypertension, and QT prolongation. Concomitant use may also increase the risk for posaconazole-related adverse effects and result in additive QT prolongation. Voclosporin is a sensitive CYP3A4 substrate and P-gp inhibitor and posaconazole is a strong CYP3A4 inhibitor and P-gp substrate that has been associated with QT prolongation. Coadministration with another strong CYP3A4 inhibitor increased voclosporin exposure by approximately 19-fold.
Pralsetinib: (Major) Avoid concomitant use of voclosporin with pralsetinib due to the risk of increased pralsetinib exposure which may increase the risk of adverse reactions. If concomitant use is necessary, reduce the daily dose of pralsetinib by 100 mg. Pralsetinib is a P-gp substrate and voclosporin is a P-gp inhibitor. Coadministration with another P-gp inhibitor increased the overall exposure of pralsetinib by 81%.
Pravastatin: (Moderate) Monitor for an increase in pravastatin-related adverse reactions, including myopathy and rhabdomyolysis, if coadministration with voclosporin is necessary. Concomitant use may increase pravastatin exposure. Pravastatin is an OATP1B1/3 substrate; voclosporin is an OATP1B1/3 inhibitor.
Primaquine: (Moderate) Concomitant use of voclosporin and primaquine may increase the risk of QT prolongation. Consider interventions to minimize the risk of progression to torsades de pointes (TdP), such as ECG monitoring and correcting electrolyte abnormalities, particularly in patients with additional risk factors for TdP. Voclosporin has been associated with QT prolongation at supratherapeutic doses. Primaquine is also associated with QT interval prolongation.
Primidone: (Major) Avoid coadministration of voclosporin with primidone. Coadministration may decrease voclosporin exposure resulting in decreased efficacy. Voclosporin is a sensitive CYP3A4 substrate and primidone is a strong CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer decreased voclosporin exposure by 87%.
Probenecid; Colchicine: (Major) Avoid concomitant use of colchicine and voclosporin due to the risk for increased colchicine exposure which may increase the risk for adverse effects. Concomitant use is contraindicated in patients with renal or hepatic impairment. Additionally, this combination is contraindicated if colchicine is being used for cardiovascular risk reduction. If concomitant use is necessary outside of these scenarios, consider a colchicine dosage reduction. Specific dosage reduction recommendations are available for colchicine tablets for some indications; it is unclear if these dosage recommendations are appropriate for other products or indications. For colchicine tablets being used for gout prophylaxis, reduce the dose from 0.6 mg twice daily to 0.3 mg once daily or from 0.6 mg once daily to 0.3 mg once every other day. For colchicine tablets being used for gout treatment, reduce the dose from 1.2 mg followed by 0.6 mg to 0.6 mg without an additional dose. For colchicine tablets being used for Familial Mediterranean Fever, the maximum daily dose is 0.6 mg. Colchicine is a P-gp substrate and voclosporin is a P-gp inhibitor.
Procainamide: (Major) Use caution if procainamide is coadministered with voclosporin due to the risk of additive QT prolongation. Procainamide is associated with a well-established risk of QT prolongation and torsade de pointes (TdP). Voclosporin has been associated with QT prolongation at supratherapeutic doses.
Prochlorperazine: (Minor) Concomitant use of voclosporin and prochlorperazine may increase the risk of QT prolongation. Consider interventions to minimize the risk of progression to torsades de pointes (TdP), such as ECG monitoring and correcting electrolyte abnormalities, particularly in patients with additional risk factors for TdP. Voclosporin has been associated with QT prolongation at supratherapeutic doses. Prochlorperazine is associated with a possible risk for QT prolongation.
Promethazine: (Moderate) Concomitant use of promethazine and voclosporin may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP. The degree of QT prolongation associated with voclosporin is not clinically significant when administered within the recommended dosage range; QT prolongation has been described at 3 times the maximum recommended dose.
Promethazine; Dextromethorphan: (Moderate) Concomitant use of promethazine and voclosporin may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP. The degree of QT prolongation associated with voclosporin is not clinically significant when administered within the recommended dosage range; QT prolongation has been described at 3 times the maximum recommended dose.
Promethazine; Phenylephrine: (Moderate) Concomitant use of promethazine and voclosporin may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP. The degree of QT prolongation associated with voclosporin is not clinically significant when administered within the recommended dosage range; QT prolongation has been described at 3 times the maximum recommended dose.
Propafenone: (Major) Concomitant use of voclosporin and propafenone 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. The degree of QT prolongation associated with voclosporin is not clinically significant when administered within the recommended dosage range; QT prolongation has been described at 3 times the maximum recommended dose.
Quetiapine: (Major) Concomitant use of voclosporin and quetiapine 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. The degree of QT prolongation associated with voclosporin is not clinically significant when administered within the recommended dosage range; QT prolongation has been described at 3 times the maximum recommended dose.
Quinidine: (Major) Use caution if quinidine is coadministered with voclosporin due to the risk of additive QT prolongation. Quinidine administration is associated with QT prolongation and torsade de pointes (TdP). Voclosporin has been associated with QT prolongation at supratherapeutic doses.
Quinine: (Major) Avoid concomitant use of quinine and voclosporin due to the risk of additive QT prolongation. Quinine has been associated with QT prolongation and rare cases of torsade de pointes (TdP). Voclosporin has been associated with QT prolongation at supratherapeutic doses.
Quizartinib: (Major) Concomitant use of quizartinib and voclosporin 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. The degree of QT prolongation associated with voclosporin is not clinically significant when administered within the recommended dosage range; QT prolongation has been described at 3 times the maximum recommended dose.
Ranolazine: (Moderate) Monitor for an increase in ranolazine-related adverse reactions if coadministration with voclosporin is necessary and consider a ranolazine dosage reduction. Concomitant use may increase ranolazine exposure and the risk of QT prolongation. Ranolazine is a P-gp substrate that is associated with dose- and plasma concentration-related increases in the QTc interval; voclosporin is a P-gp inhibitor that has been associated with QT prolongation at supratherapeutic doses.
Relugolix: (Major) Avoid concomitant use of relugolix and oral voclosporin. Concomitant use may increase relugolix exposure and the risk of relugolix-related adverse effects. Additive QT prolongation may also occur. If concomitant use is necessary, administer voclosporin at least six hours after relugolix and monitor for adverse reactions. Alternatively, relugolix therapy may be interrupted for up to 14 days if a short course of voclosporin is required; if treatment is interrupted for more than seven days, resume relugolix with a 360 mg loading dose followed by 120 mg once daily. Relugolix is a P-gp substrate that may prolong the QT/QTc interval; voclosporin is a P-gp inhibitor that has been associated with QT prolongation at supratherapeutic doses.
Relugolix; Estradiol; Norethindrone acetate: (Major) Avoid concomitant use of relugolix and oral voclosporin. Concomitant use may increase relugolix exposure and the risk of relugolix-related adverse effects. Additive QT prolongation may also occur. If concomitant use is necessary, administer voclosporin at least six hours after relugolix and monitor for adverse reactions. Alternatively, relugolix therapy may be interrupted for up to 14 days if a short course of voclosporin is required; if treatment is interrupted for more than seven days, resume relugolix with a 360 mg loading dose followed by 120 mg once daily. Relugolix is a P-gp substrate that may prolong the QT/QTc interval; voclosporin is a P-gp inhibitor that has been associated with QT prolongation at supratherapeutic doses.
Repotrectinib: (Major) Avoid coadministration of voclosporin with repotrectinib. Concomitant use may decrease voclosporin exposure and efficacy and may increase repotrectinib exposure and the risk for repotrectinib-related adverse effects. Voclosporin is a CYP3A substrate and P-gp inhibitor; repotrectinib is a P-gp substrate and moderate CYP3A inducer. Coadministration with moderate CYP3A inducers is predicted to decrease voclosporin exposure by 70%.
Resmetirom: (Major) Avoid concomitant use of resmetirom and voclosporin due to the risk for increased resmetirom exposure which may increase the risk for resmetirom-related adverse effects. Resmetirom is an OATP1B1 substrate and voclosporin is an OATP1B1 inhibitor.
Revefenacin: (Major) Avoid concomitant use of revefenacin and voclosporin. Concomitant use may increase exposure to the active metabolite of revefenacin and the risk for anticholinergic adverse effects. The active metabolite of revefenacin is a substrate of OATP1B1; voclosporin is an inhibitor of OATP1B1.
Ribociclib: (Contraindicated) Concomitant use of voclosporin and ribociclib is contraindicated; concomitant use may increase the exposure of voclosporin and the risk of voclosporin-related adverse effects such as nephrotoxicity, hypertension, and QT prolongation. Additive QT prolongation may also occur. Voclosporin is a sensitive CYP3A4 substrate and ribociclib is a strong CYP3A4 inhibitor that has been associated with concentration-dependent QT prolongation. Coadministration with another strong CYP3A4 inhibitor increased voclosporin exposure by approximately 19-fold.
Ribociclib; Letrozole: (Contraindicated) Concomitant use of voclosporin and ribociclib is contraindicated; concomitant use may increase the exposure of voclosporin and the risk of voclosporin-related adverse effects such as nephrotoxicity, hypertension, and QT prolongation. Additive QT prolongation may also occur. Voclosporin is a sensitive CYP3A4 substrate and ribociclib is a strong CYP3A4 inhibitor that has been associated with concentration-dependent QT prolongation. Coadministration with another strong CYP3A4 inhibitor increased voclosporin exposure by approximately 19-fold.
Rifabutin: (Major) Avoid coadministration of voclosporin with rifabutin. Coadministration may decrease voclosporin exposure resulting in decreased efficacy. Voclosporin is a sensitive CYP3A4 substrate and rifabutin is a moderate CYP3A4 inducer. Coadministration with moderate CYP3A4 inducers is predicted to decrease voclosporin exposure by 70%.
Rifampin: (Major) Avoid coadministration of voclosporin with rifampin. Coadministration may decrease voclosporin exposure resulting in decreased efficacy. Voclosporin is a sensitive CYP3A4 substrate and rifampin is a strong CYP3A4 inducer. Coadministration with rifampin decreased voclosporin exposure by 87%.
Rifapentine: (Major) Avoid coadministration of voclosporin with rifapentine. Coadministration may decrease voclosporin exposure resulting in decreased efficacy. Voclosporin is a sensitive CYP3A4 substrate and rifapentine is a strong CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer decreased voclosporin exposure by 87%.
Rifaximin: (Moderate) Monitor for an increase in rifaximin-related adverse reactions if coadministration with voclosporin is necessary. Concomitant use may increase rifaximin exposure. In patients with hepatic impairment, a potential additive effect of reduced metabolism may further increase systemic rifaximin exposure. Rifaximin is a P-gp substrate and voclosporin is a P-gp inhibitor. Coadministration with another P-gp inhibitor increased rifaximin overall exposure by 124-fold.
Rilpivirine: (Moderate) Concomitant use of voclosporin and rilpivirine may increase the risk of QT prolongation. Consider interventions to minimize the risk of progression to torsades de pointes (TdP), such as ECG monitoring and correcting electrolyte abnormalities, particularly in patients with additional risk factors for TdP. Both voclosporin and rilpivirine have been associated with QT prolongation at supratherapeutic doses.
Rimegepant: (Major) Avoid a second dose of rimegepant within 48 hours if coadministered with voclosporin; concurrent use may increase rimegepant exposure. Rimegepant is a P-gp substrate and voclosporin is a P-gp inhibitor.
Risperidone: (Moderate) Concomitant use of voclosporin and risperidone may increase the risk of QT prolongation. Consider interventions to minimize the risk of progression to torsades de pointes (TdP), such as ECG monitoring and correcting electrolyte abnormalities, particularly in patients with additional risk factors for TdP. Voclosporin has been associated with QT prolongation at supratherapeutic doses. Risperidone has been associated with a possible risk for QT prolongation and/or TdP, primarily in the overdose setting.
Ritlecitinib: (Major) Reduce the voclosporin dosage to 15.8 mg PO in the morning and 7.9 mg PO in the evening if coadministered with ritlecitinib. Concomitant use may increase voclosporin exposure and the risk of voclosporin-related adverse effects such as nephrotoxicity, hypertension, and QT prolongation. Voclosporin is a sensitive CYP3A substrate and ritlecitinib is a moderate CYP3A inhibitor. Coadministration with moderate CYP3A inhibitors is predicted to increase voclosporin exposure by 3-fold.
Ritonavir: (Contraindicated) Concomitant use of voclosporin and ritonavir is contraindicated; concomitant use may increase the exposure of voclosporin and the risk of voclosporin-related adverse effects such as nephrotoxicity, hypertension, and QT prolongation. Voclosporin is a sensitive CYP3A4 substrate and ritonavir is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased voclosporin exposure by approximately 19-fold.
Romidepsin: (Moderate) Concomitant use of voclosporin and romidepsin may increase the risk of QT prolongation. Consider interventions to minimize the risk of progression to torsades de pointes (TdP), such as ECG monitoring and correcting electrolyte abnormalities, particularly in patients with additional risk factors for TdP. Voclosporin has been associated with QT prolongation at supratherapeutic doses. Romidepsin has been reported to prolong the QT interval.
Rosuvastatin: (Moderate) Monitor for an increase in rosuvastatin-related adverse reactions, including myopathy and rhabdomyolysis, during concomitant use with voclosporin. Concurrent use may increase rosuvastatin exposure. Rosuvastatin is a substrate of the drug transporter OATP1B1/3 and voclosporin is an OATP1B1/3 inhibitor.
Rosuvastatin; Ezetimibe: (Moderate) Monitor for an increase in rosuvastatin-related adverse reactions, including myopathy and rhabdomyolysis, during concomitant use with voclosporin. Concurrent use may increase rosuvastatin exposure. Rosuvastatin is a substrate of the drug transporter OATP1B1/3 and voclosporin is an OATP1B1/3 inhibitor.
Rotavirus Vaccine: (Major) Live virus vaccines should generally not be administered to an immunosuppressed patient. Live virus vaccines may induce the illness they are intended to prevent and are generally contraindicated for use during immunosuppressive treatment. The immune response of the immunocompromised patient to vaccines may be decreased, even despite alternate vaccination schedules or more frequent booster doses. If immunization is necessary, choose an alternative to live vaccination, or, consider a delay or change in the immunization schedule. Practitioners should refer to the most recent CDC guidelines regarding vaccination of patients who are receiving drugs that adversely affect the immune system.
Saquinavir: (Contraindicated) Concomitant use of voclosporin and saquinavir is contraindicated as use may increase the exposure of voclosporin and the risk of voclosporin-related adverse effects such as nephrotoxicity, hypertension, and QT prolongation. Concomitant use may also increase the risk for saquinavir-related adverse effects and result in additive QT prolongation. Voclosporin is a sensitive CYP3A4 substrate and P-gp inhibitor and saquinavir is a strong CYP3A4 inhibitor and P-gp substrate that has been associated with QT prolongation. Coadministration with another strong CYP3A4 inhibitor increased voclosporin exposure by approximately 19-fold.
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.
Secobarbital: (Major) Avoid coadministration of voclosporin with secobarbital. Coadministration may decrease voclosporin exposure resulting in decreased efficacy. Voclosporin is a sensitive CYP3A4 substrate and secobarbital is a moderate CYP3A4 inducer. Coadministration with moderate CYP3A4 inducers is predicted to decrease voclosporin exposure by 70%.
Selpercatinib: (Major) Monitor ECGs more frequently for QT prolongation if coadministration of voclosporin with selpercatinib is necessary due to the risk of additive QT prolongation. Concentration-dependent QT prolongation has been observed with selpercatinib therapy. Voclosporin has been associated with QT prolongation at supratherapeutic doses.
Sertraline: (Moderate) Concomitant use of sertraline and voclosporin may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP. The degree of QT prolongation associated with voclosporin is not clinically significant when administered within the recommended dosage range; QT prolongation has been described at 3 times the maximum recommended dose. The degree of QT prolongation associated with sertraline is not clinically significant when administered within the recommended dosage range; QT prolongation has been described at 2 times the maximum recommended dose.
Sevoflurane: (Major) Use caution if halogenated anesthetics are coadministered with voclosporin due to the risk of additive QT prolongation. Halogenated anesthetics can prolong the QT interval. Voclosporin has been associated with QT prolongation at supratherapeutic doses.
Silodosin: (Major) Avoid coadministration of silodosin and voclosporin due to the potential for increased silodosin exposure. In vitro data indicate that silodosin is a P-glycoprotein substrate; voclosporin is a P-gp inhibitor.
Simvastatin: (Moderate) Monitor for an increase in simvastatin-related adverse reactions, including myopathy and rhabdomyolysis, if coadministration with voclosporin is necessary. Concomitant use may increase simvastatin exposure. Simvastatin is a P-gp and OATP1B1 substrate; voclosporin is a P-gp and OATP1B1 inhibitor.
Siponimod: (Major) In general, do not initiate treatment with siponimod in patients receiving voclosporin due to the potential for QT prolongation. Consult a cardiologist regarding appropriate monitoring if siponimod use is required. Siponimod therapy prolonged the QT interval at recommended doses in a clinical study. Voclosporin has been associated with QT prolongation at supratherapeutic doses.
Sirolimus: (Moderate) Monitor sirolimus concentrations and adjust sirolimus dosage as appropriate during concomitant use of voclosporin. Coadministration may increase sirolimus concentrations and the risk for sirolimus-related adverse effects. Sirolimus is a P-gp substrate and voclosporin is a P-gp inhibitor.
Smallpox and Monkeypox Vaccine, Live, Nonreplicating: (Major) Live virus vaccines should generally not be administered to an immunosuppressed patient. Live virus vaccines may induce the illness they are intended to prevent and are generally contraindicated for use during immunosuppressive treatment. The immune response of the immunocompromised patient to vaccines may be decreased, even despite alternate vaccination schedules or more frequent booster doses. If immunization is necessary, choose an alternative to live vaccination, or, consider a delay or change in the immunization schedule. Practitioners should refer to the most recent CDC guidelines regarding vaccination of patients who are receiving drugs that adversely affect the immune system.
Smallpox Vaccine, Vaccinia Vaccine: (Major) Live virus vaccines should generally not be administered to an immunosuppressed patient. Live virus vaccines may induce the illness they are intended to prevent and are generally contraindicated for use during immunosuppressive treatment. The immune response of the immunocompromised patient to vaccines may be decreased, even despite alternate vaccination schedules or more frequent booster doses. If immunization is necessary, choose an alternative to live vaccination, or, consider a delay or change in the immunization schedule. Practitioners should refer to the most recent CDC guidelines regarding vaccination of patients who are receiving drugs that adversely affect the immune system.
Sodium Stibogluconate: (Moderate) Concomitant use of sodium stibogluconate and voclosporin may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP. The degree of QT prolongation associated with voclosporin is not clinically significant when administered within the recommended dosage range; QT prolongation has been described at 3 times the maximum recommended dose.
Sofosbuvir; Velpatasvir; Voxilaprevir: (Major) Avoid concomitant use of voxilaprevir and voclosporin. Concomitant use may increase voxilaprevir exposure and the risk of voxilaprevir-related adverse reactions. Voxilaprevir is a substrate of OATP1B1; voclosporin is an OATP1B1 inhibitor.
Solifenacin: (Moderate) Concomitant use of voclosporin and solifenacin may increase the risk of QT prolongation. Consider interventions to minimize the risk of progression to torsades de pointes (TdP), such as ECG monitoring and correcting electrolyte abnormalities, particularly in patients with additional risk factors for TdP. Voclosporin has been associated with QT prolongation at supratherapeutic doses. Solifenacin has been associated with dose-dependent prolongation of the QT interval. TdP has been reported with postmarketing use of solifenacin, although causality was not determined.
Sorafenib: (Major) Avoid concomitant use of sorafenib and voclosporin due to the risk of additive QT prolongation. If concomitant use is necessary, monitor ECGs and correct electrolyte abnormalities. An interruption or discontinuation of sorafenib therapy may be necessary if QT prolongation occurs. Sorafenib is associated with QTc prolongation. Voclosporin has been associated with QT prolongation at supratherapeutic doses.
Sotalol: (Major) Concomitant use of voclosporin and sotalol 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. The degree of QT prolongation associated with voclosporin is not clinically significant when administered within the recommended dosage range; QT prolongation has been described at 3 times the maximum recommended dose.
Sotorasib: (Major) Avoid coadministration of voclosporin with sotorasib. Coadministration may decrease voclosporin exposure resulting in decreased efficacy. Voclosporin is a sensitive CYP3A4 substrate and sotorasib is a moderate CYP3A4 inducer. Coadministration with moderate CYP3A4 inducers is predicted to decrease voclosporin exposure by 70%.
St. John's Wort, Hypericum perforatum: (Major) Avoid coadministration of voclosporin with St. John's Wort. Coadministration may decrease voclosporin exposure resulting in decreased efficacy. Voclosporin is a sensitive CYP3A4 substrate and St. John's Wort is a strong CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer decreased voclosporin exposure by 87%.
Streptomycin: (Moderate) Concomitant use of voclosporin and aminoglycosides may result in additive nephrotoxicity. Monitor for renal toxicity if concomitant use is required.
Streptozocin: (Moderate) Concomitant use of voclosporin and streptozocin may result in additive nephrotoxicity. Monitor for renal toxicity if concomitant use is required.
Sulindac: (Moderate) Concomitant use of voclosporin and nonsteroidal anti-inflammatory drugs (NSAIDs) may result in additive nephrotoxicity. Monitor for renal toxicity if concomitant use is required.
Sumatriptan; Naproxen: (Moderate) Concomitant use of voclosporin and nonsteroidal anti-inflammatory drugs (NSAIDs) may result in additive nephrotoxicity. Monitor for renal toxicity if concomitant use is required.
Sunitinib: (Moderate) Concomitant use of voclosporin and sunitinib may increase the risk of QT prolongation. Consider interventions to minimize the risk of progression to torsades de pointes (TdP), such as ECG monitoring and correcting electrolyte abnormalities, particularly in patients with additional risk factors for TdP. Voclosporin has been associated with QT prolongation at supratherapeutic doses. Sunitinib can prolong the QT interval.
Talazoparib: (Moderate) Monitor for an increase in talazoparib-related adverse reactions if coadministration with voclosporin is necessary. Talazoparib is a P-gp substrate and voclosporin is a P-gp inhibitor.
Tamoxifen: (Moderate) Concomitant use of tamoxifen and voclosporin may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP. The degree of QT prolongation associated with voclosporin is not clinically significant when administered within the recommended dosage range; QT prolongation has been described at 3 times the maximum recommended dose.
Telavancin: (Moderate) Concomitant use of voclosporin and telavancin may increase the risk of QT prolongation and additive nephrotoxicity. Consider interventions to minimize the risk of progression to torsades de pointes (TdP), such as ECG monitoring and correcting electrolyte abnormalities, particularly in patients with additional risk factors for TdP. Additionally, monitor for renal toxicity if concomitant use is required. Voclosporin has been associated with QT prolongation at supratherapeutic doses. Telavancin has been associated with QT prolongation.
Temsirolimus: (Moderate) Monitor for an increase in temsirolimus-related adverse reactions if coadministration with voclosporin is necessary due to the risk of increased temsirolimus exposure. Temsirolimus is a P-gp substrate and voclosporin is a P-gp inhibitor. Coadministration is likely to increase plasma concentrations of temsirolimus.
Tenofovir Alafenamide: (Moderate) Coadministration of tenofovir alafenamide and voclosporin may result in increased plasma concentrations of tenofovir leading to an increase in tenofovir-related adverse effects. Concomitant use may also may result in additive nephrotoxicity. Monitor for renal toxicity if concomitant use is required. Tenofovir alafenamide is a P-gp substrate and voclosporin is a P-gp inhibitor.
Tenofovir Alafenamide: (Moderate) Coadministration of tenofovir alafenamide and voclosporin may result in increased plasma concentrations of tenofovir leading to an increase in tenofovir-related adverse effects. Concomitant use may also may result in additive nephrotoxicity. Monitor for renal toxicity if concomitant use is required. Tenofovir alafenamide is a P-gp substrate and voclosporin is a P-gp inhibitor.
Tenofovir Disoproxil Fumarate: (Moderate) Coadministration of tenofovir disoproxil fumarate and voclosporin may result in increased plasma concentrations of tenofovir, leading to an increase in tenofovir-related adverse effects. Concomitant use may also may result in additive nephrotoxicity. Monitor for renal toxicity if concomitant use is required. Tenofovir disoproxil fumarate is a P-gp substrate and voclosporin is a P-gp inhibitor.
Tetrabenazine: (Major) Avoid concomitant use of tetrabenazine and voclosporin due to the risk of additive QT prolongation. Tetrabenazine causes a small increase in the corrected QT interval (QTc). Voclosporin has been associated with QT prolongation at supratherapeutic doses.
Thioridazine: (Contraindicated) Concomitant use of voclosporin and thioridazine is contraindicated due to the potential for QT prolongation and torsade de pointes (TdP). Thioridazine is associated with a well-established risk of QT prolongation and TdP. Voclosporin has been associated with QT prolongation at supratherapeutic doses.
Ticagrelor: (Moderate) Monitor for increased bleeding if ticagrelor is coadministered with voclosporin as concurrent use may increase the exposure of ticagrelor. Ticagrelor is a P-gp substrate and voclosporin is a P-gp inhibitor.
Tipranavir: (Contraindicated) Concomitant use of voclosporin and tipranavir is contraindicated as use may increase the exposure of voclosporin and the risk of voclosporin-related adverse effects such as nephrotoxicity, hypertension, and QT prolongation. Concomitant use may also increase tipranavir exposure and adverse effects. Voclosporin is a sensitive CYP3A4 substrate and P-gp inhibitor and tipranavir is a strong CYP3A4 inhibitor and P-gp substrate. Coadministration with another strong CYP3A4 inhibitor increased voclosporin exposure by approximately 19-fold.
Tobramycin: (Moderate) Concomitant use of voclosporin and aminoglycosides may result in additive nephrotoxicity. Monitor for renal toxicity if concomitant use is required.
Tolmetin: (Moderate) Concomitant use of voclosporin and nonsteroidal anti-inflammatory drugs (NSAIDs) may result in additive nephrotoxicity. Monitor for renal toxicity if concomitant use is required.
Tolterodine: (Moderate) Concomitant use of voclosporin and tolterodine may increase the risk of QT prolongation. Consider interventions to minimize the risk of progression to torsades de pointes (TdP), such as ECG monitoring and correcting electrolyte abnormalities, particularly in patients with additional risk factors for TdP. Voclosporin has been associated with QT prolongation at supratherapeutic doses. Tolterodine has been associated with dose-dependent prolongation of the QT interval, especially in poor CYP2D6 metabolizers.
Topotecan: (Major) Avoid coadministration of voclosporin with oral topotecan due to increased topotecan exposure; voclosporin may be administered with intravenous topotecan. Oral topotecan is a substrate of the P-gp and voclosporin is a P-gp inhibitor. Coadministration increases the risk of topotecan-related adverse reactions. Oral administration within 4 hours of another P-gp inhibitor increased the dose-normalized AUC of topotecan lactone and total topotecan 2-fold to 3-fold compared to oral topotecan alone.
Toremifene: (Major) Avoid concomitant use of toremifene and voclosporin due to the risk of additive QT prolongation. If concomitant use is necessary, closely monitor ECGs and electrolytes. Toremifene has been shown to prolong the QTc interval in a dose- and concentration-related manner. Voclosporin has been associated with QT prolongation at supratherapeutic doses.
Trandolapril; Verapamil: (Major) Reduce the voclosporin dosage to 15.8 mg PO in the morning and 7.9 mg PO in the evening if coadministered with verapamil. Concomitant use may increase voclosporin exposure and the risk of voclosporin-related adverse effects such as nephrotoxicity, hypertension, and QT prolongation. Voclosporin is a sensitive CYP3A4 substrate and verapamil is a moderate CYP3A4 inhibitor. Coadministration with verapamil increased voclosporin exposure by 2.7-fold.
Trazodone: (Major) Concomitant use of voclosporin and trazodone 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. The degree of QT prolongation associated with voclosporin is not clinically significant when administered within the recommended dosage range; QT prolongation has been described at 3 times the maximum recommended dose.
Triclabendazole: (Moderate) Concomitant use of triclabendazole and voclosporin may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP. The degree of QT prolongation associated with voclosporin is not clinically significant when administered within the recommended dosage range; QT prolongation has been described at 3 times the maximum recommended dose.
Trifluoperazine: (Minor) Concomitant use of voclosporin and trifluoperazine may increase the risk of QT prolongation. Consider interventions to minimize the risk of progression to torsades de pointes (TdP), such as ECG monitoring and correcting electrolyte abnormalities, particularly in patients with additional risk factors for TdP. Voclosporin has been associated with QT prolongation at supratherapeutic doses. Trifluoperazine is associated with a possible risk for QT prolongation.
Triptorelin: (Moderate) Concomitant use of voclosporin and triptorelin may increase the risk of QT prolongation. Consider interventions to minimize the risk of progression to torsades de pointes (TdP), such as ECG monitoring and correcting electrolyte abnormalities, particularly in patients with additional risk factors for TdP. Voclosporin has been associated with QT prolongation t supratherapeutic doses. Androgen deprivation therapy (i.e., triptorelin) may prolong the QT/QTc interval.
Tucatinib: (Contraindicated) Concomitant use of voclosporin and tucatinib is contraindicated; concomitant use may increase the exposure of voclosporin and the risk of voclosporin-related adverse effects such as nephrotoxicity, hypertension, and QT prolongation. Voclosporin is a sensitive CYP3A4 substrate and tucatinib is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased voclosporin exposure by approximately 19-fold.
Typhoid Vaccine: (Major) Live virus vaccines should generally not be administered to an immunosuppressed patient. Live virus vaccines may induce the illness they are intended to prevent and are generally contraindicated for use during immunosuppressive treatment. The immune response of the immunocompromised patient to vaccines may be decreased, even despite alternate vaccination schedules or more frequent booster doses. If immunization is necessary, choose an alternative to live vaccination, or, consider a delay or change in the immunization schedule. Practitioners should refer to the most recent CDC guidelines regarding vaccination of patients who are receiving drugs that adversely affect the immune system.
Ubrogepant: (Major) Limit the initial and second dose of ubrogepant to 50 mg if coadministered with voclosporin. Concurrent use may increase ubrogepant exposure and the risk of adverse effects. Ubrogepant is a P-gp substrate; voclosporin is a P-gp inhibitor.
Valacyclovir: (Moderate) Concomitant use of voclosporin and valacyclovir may result in additive nephrotoxicity. Monitor for renal toxicity if concomitant use is required.
Valganciclovir: (Moderate) Concomitant use of voclosporin and valganciclovir may result in additive nephrotoxicity. Monitor for renal toxicity if concomitant use is required.
Vancomycin: (Moderate) Concomitant use of voclosporin and vancomycin may result in additive nephrotoxicity. Monitor for renal toxicity if concomitant use is required.
Vandetanib: (Major) Avoid concomitant use of vandetanib and voclosporin due to the risk of additive QT prolongation and torsade de pointes (TdP). If concomitant use is necessary, monitor ECGs and electrolytes; correct hypocalcemia, hypokalemia, and hypomagnesemia prior to vandetanib administration. An interruption of vandetanib therapy or dose reduction may be necessary is QT prolongation occurs. Vandetanib can prolong the QT interval in a concentration-dependent manner; TdP and sudden death have been reported in patients receiving vandetanib. Voclosporin has been associated with QT prolongation at supratherapeutic doses.
Vardenafil: (Moderate) Concomitant use of vardenafil and voclosporin may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP. The degree of QT prolongation associated with voclosporin is not clinically significant when administered within the recommended dosage range; QT prolongation has been described at 3 times the maximum recommended dose.
Varicella-Zoster Virus Vaccine, Live: (Major) Live virus vaccines should generally not be administered to an immunosuppressed patient. Live virus vaccines may induce the illness they are intended to prevent and are generally contraindicated for use during immunosuppressive treatment. The immune response of the immunocompromised patient to vaccines may be decreased, even despite alternate vaccination schedules or more frequent booster doses. If immunization is necessary, choose an alternative to live vaccination, or, consider a delay or change in the immunization schedule. Practitioners should refer to the most recent CDC guidelines regarding vaccination of patients who are receiving drugs that adversely affect the immune system.
Vemurafenib: (Major) Avoid concomitant use of vemurafenib and voclosporin due to the risk of additive QT prolongation. Vemurafenib has been shown to prolong the QT interval in a concentration-dependent manner. The ECG changes occurred within the first month of treatment. Voclosporin has been associated with QT prolongation at supratherapeutic doses.
Venetoclax: (Major) Reduce the dose of venetoclax by at least 50% and monitor for venetoclax toxicity (e.g., hematologic toxicity, GI toxicity, and tumor lysis syndrome) if coadministered with voclosporin due to the potential for increased venetoclax exposure. Resume the original venetoclax dose 2 to 3 days after discontinuation of voclosporin. Venetoclax is a P-gp substrate; voclosporin is a P-gp inhibitor. Coadministration with a single dose of another P-gp inhibitor increased venetoclax exposure by 78% in a drug interaction study.
Venlafaxine: (Moderate) Concomitant use of venlafaxine and voclosporin may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP. The degree of QT prolongation associated with voclosporin is not clinically significant when administered within the recommended dosage range; QT prolongation has been described at 3 times the maximum recommended dose.
Verapamil: (Major) Reduce the voclosporin dosage to 15.8 mg PO in the morning and 7.9 mg PO in the evening if coadministered with verapamil. Concomitant use may increase voclosporin exposure and the risk of voclosporin-related adverse effects such as nephrotoxicity, hypertension, and QT prolongation. Voclosporin is a sensitive CYP3A4 substrate and verapamil is a moderate CYP3A4 inhibitor. Coadministration with verapamil increased voclosporin exposure by 2.7-fold.
Vincristine Liposomal: (Moderate) Monitor for vincristine-related adverse reactions if coadministration of voclosporin is necessary as concurrent use may increase vincristine exposure. Vincristine is a P-gp substrate and voclosporin is a P-gp inhibitor.
Vincristine: (Moderate) Monitor for vincristine-related adverse reactions if coadministration of voclosporin is necessary as concurrent use may increase vincristine exposure. Vincristine is a P-gp substrate and voclosporin is a P-gp inhibitor.
Vonoprazan; Amoxicillin; Clarithromycin: (Contraindicated) Concomitant use of voclosporin and clarithromycin is contraindicated; concomitant use may increase the exposure of voclosporin and the risk of voclosporin-related adverse effects such as nephrotoxicity, hypertension, and QT prolongation. Additive QT prolongation may also occur. Voclosporin is a sensitive CYP3A4 substrate and clarithromycin is a strong CYP3A4 inhibitor that has been associated with QT prolongation. Coadministration with another strong CYP3A4 inhibitor increased voclosporin exposure by approximately 19-fold.
Voriconazole: (Contraindicated) Concomitant use of voclosporin and voriconazole is contraindicated; concomitant use may increase the exposure of voclosporin and the risk of voclosporin-related adverse effects such as nephrotoxicity, hypertension, and QT prolongation. Additive QT prolongation may also occur. Voclosporin is a sensitive CYP3A4 substrate and voriconazole is a strong CYP3A4 inhibitor that has been associated with QT prolongation and rare cases of torsade de pointes (TdP). Coadministration with another strong CYP3A4 inhibitor increased voclosporin exposure by approximately 19-fold.
Vorinostat: (Moderate) Concomitant use of voclosporin and vorinostat may increase the risk of QT prolongation. Consider interventions to minimize the risk of progression to torsade de pointes (TdP), such as ECG monitoring and correcting electrolyte abnormalities, particularly in patients with additional risk factors for TdP. Voclosporin has been associated with QT prolongation at supratherapeutic doses. Vorinostat therapy is associated with a risk of QT prolongation.
Voxelotor: (Major) Reduce the voclosporin dosage to 15.8 mg PO in the morning and 7.9 mg PO in the evening if coadministered with voxelotor. Concomitant use may increase voclosporin exposure and the risk of voclosporin-related adverse effects such as nephrotoxicity, hypertension, and QT prolongation. Voclosporin is a sensitive CYP3A substrate and voxelotor is a moderate CYP3A inhibitor. Coadministration with moderate CYP3A inhibitors is predicted to increase voclosporin exposure by 3-fold.
Yellow Fever Vaccine, Live: (Major) Live virus vaccines should generally not be administered to an immunosuppressed patient. Live virus vaccines may induce the illness they are intended to prevent and are generally contraindicated for use during immunosuppressive treatment. The immune response of the immunocompromised patient to vaccines may be decreased, even despite alternate vaccination schedules or more frequent booster doses. If immunization is necessary, choose an alternative to live vaccination, or, consider a delay or change in the immunization schedule. Practitioners should refer to the most recent CDC guidelines regarding vaccination of patients who are receiving drugs that adversely affect the immune system.
Ziprasidone: (Major) Avoid concomitant use of ziprasidone and voclosporin due to the risk of additive QT prolongation. Clinical trial data indicate that ziprasidone causes QT prolongation; there are postmarketing reports of torsade de pointes (TdP) in patients with multiple confounding factors. Voclosporin has been associated with QT prolongation at supratherapeutic doses.
Zoledronic Acid: (Moderate) Concomitant use of voclosporin and zoledronic acid may result in additive nephrotoxicity. Monitor for renal toxicity if concomitant use is required.
Voclosporin is a calcineurin inhibitor immunosuppressant. The mechanism of voclosporin suppression of calcineurin has not been fully established. Activation of lymphocytes involves an increase in intracellular calcium concentrations that bind to the calcineurin regulatory site and activate calmodulin binding catalytic subunit and through dephosphorylation activates the transcription factor, Nuclear Factor of Activated T-Cell Cytoplasmic (NFATc). The immunosuppressant activity results in inhibition of lymphocyte proliferation, T-cell cytokine production, and expression of T-cell activation surface antigens. Studies in animal models also support a non-immunological role for calcineurin inhibition in kidney function to stabilize actin cytoskeleton and stress fibers in podocytes leading to increased podocyte integrity in glomeruli.
Voclosporin is administered orally. Voclosporin inhibits calcineurin in a dose-dependent manner up to a maximum dose of 1 mg/kg, with little to no lag time between the time to maximum concentration and time to maximum calcineurin inhibition. Plasma protein binding is 97% and the apparent volume of distribution (Vd) is 2,154 L. Voclosporin partitions extensively into red blood cells. The distribution of voclosporin between whole blood and plasma is both concentration- and temperature-dependent. Metabolism of voclosporin occurs primarily via the hepatic cytochrome P450 isoenzyme CYP3A4. Voclosporin accounts for the majority of its pharmacologic activity and is the primary circulating component, while its major metabolite is approximately 8-fold less potent than the parent molecule and accounts for 16.7% of total whole blood voclosporin exposure. After oral administration of a single, radiolabeled 70 mg voclosporin dose, 92.7% (5% as unchanged voclosporin) of the radioactivity was recovered in the feces and 2.1% (0.25% as unchanged voclosporin) in the urine. Mean terminal half-life at steady-state is approximately 30 hours (24.9 to 36.5 hours) and mean apparent clearance is 63.6 L/hour.
Affected cytochrome P450 isoenzymes and drug transporters: CYP3A4, OATP1B1, OATP1B3, P-glycoprotein (P-gp)
Voclosporin is a sensitive CYP3A4 substrate and may be a P-gp substrate. It is a weak P-gp inhibitor and, based on in vitro studies, an inhibitor of OATP1B1 and OATP1B3. Voclosporin is CYP3A4 inhibitor; however, no clinically meaningful drug interaction was identified when coadministered with midazolam, a sensitive CYP3A4 substrate. Coadministration of voclosporin with strong CYP3A4 inhibitors is contraindicated; dosage reductions are necessary when coadministered with moderate CYP3A4 inhibitors. Avoid use with strong or moderate CYP3A4 inducers as concomitant use decreases voclosporin concentrations. Voclosporin may increase the exposure of P-gp substrates; thus, it is recommended to reduce the dosage of P-gp substrates with a narrow therapeutic range during coadministration. Although there are no clinical studies evaluating concurrent administration, voclosporin has the potential to increase exposures of OATP1B1 substrates, such as HMG-CoA reductase inhibitors (statins). Monitor for adverse reactions if voclosporin is coadministered with OATP1B1 substrates.
-Route-Specific Pharmacokinetics
Oral Route
Following twice daily oral administration, there is an approximate 2-fold accumulation and steady-state is achieved after 6 days. When voclosporin is administered on an empty stomach, the median Tmax is 1.5 hours (1 to 4). Voclosporin administration with either a low- or high-fat meal results in a 29% to 53% reduction in Cmax and 15% to 25% reduction in AUC; thus, the drug should be given on an empty stomach.
-Special Populations
Hepatic Impairment
In patients with mild (Child-Pugh A) and moderate (Child-Pugh B) hepatic impairment, there was an approximate 1.5- to 2-fold increase in Cmax and AUC; dosage adjustments are recommended. The effect of severe hepatic impairment (Child-Pugh C) on voclosporin pharmacokinetics is unknown and use in these patients is not recommended.
Renal Impairment
Voclosporin Cmax and AUC were found to be similar between volunteers with normal renal function (CrCl 90 mL/minute or greater), mild renal impairment (CrCl 60 to 89 mL/minute) and moderate renal impairment (CrCl 30 to 59 mL/minute). Volunteers with severe renal impairment (CrCl less than 30 mL/minute) had a 1.5-fold increase in Cmax and 2-fold increase in AUC. The effect of end-stage renal disease with or without hemodialysis on voclosporin pharmacokinetics is unknown. Dosage adjustments of voclosporin are recommended based on estimated glomerular filtration rate (eGFR).
Geriatric
Clinical studies did not include a sufficient number of patients aged 65 and older to determine whether this patient population differs from younger patients with regard to voclosporin pharmacokinetics or response. There were no clinically significant differences in the pharmacokinetics of voclosporin based on age (18 to 66 years).
Gender Differences
Gender was not shown to have a clinically significant effect on voclosporin pharmacokinetics.
Ethnic Differences
Race (Asian, Black, White, other) was not shown to have a clinically significant effect on voclosporin pharmacokinetics.
Obesity
Body weight (range, 37 kg up to 133 kg) was not shown to have a clinically significant effect on voclosporin pharmacokinetics.