Lasmiditan is an oral serotonin receptor 5-HT1F agonist indicated for acute treatment of migraine with or without aura in adults. In 2 randomized, double-blind, placebo-controlled trials, lasmiditan (n = 3,743) significantly increased freedom from pain and bothersome migraine symptoms (i.e., photophobia, phonophobia, or nausea) at 2 hours. When compared to placebo, pain freedom at 2 hours occurred in more lasmiditan-treated patients; the differences in pain freedom at 2 hours between lasmiditan and placebo groups were 7.3% for lasmiditan 50 mg (p less than 0.006), 10.4% and 13% for lasmiditan 100 mg (p less than 0.001), and 16.5% and 17.8% for lasmiditan 200 mg (p less than 0.001). Additionally, lasmiditan alleviated bothersome migraine symptoms at 2 hours in significantly more patients; the differences in most bothersome symptom freedom at 2 hours between lasmiditan and placebo groups were 7.6% for lasmiditan 50 mg (p = 0.014), 10.8% and 11.6% for lasmiditan 100 mg (p less than 0.001), and 11.1% and 15.5% for lasmiditan 200 mg (p less than 0.001). Lasmiditan may cause CNS depression and significant driving impairment. Potentially hazardous activities requiring complete mental alertness, such as driving or operating machinery, must be avoided for at least 8 hours after each dose of lasmiditan. Lasmiditan does not activate 5-HT1B receptors in peripheral blood vessels, including coronary arteries, and does not induce vasoconstriction.
General Administration Information
For storage information, see the specific product information within the How Supplied section.
Route-Specific Administration
Oral Administration
-Administer with or without food.
-Swallow tablets whole. Do not split, crush, or chew.
Lasmiditan may cause CNS depression, including dizziness and drowsiness. In 2 placebo-controlled phase 3 trials, dizziness occurred in 9% of patients receiving lasmiditan 50 mg (n = 654), 15% of patients receiving lasmiditan 100 mg (n = 1,265), and 17% of patients receiving lasmiditan 200 mg (n = 1,258) compared to 3% of patients receiving placebo (n = 1,262). Dizziness occurred more frequently in geriatric patients who were 65 years and older (19% lasmiditan vs. 2% placebo) compared to patients younger than 65 years (14% lasmiditan vs. 3% placebo). Dizziness was the most common adverse event leading to lasmiditan discontinuation in a long-term safety study (more than 2%). Drowsiness occurred in 6% of patients receiving lasmiditan 50 mg and 100 mg and 7% of patients receiving lasmiditan 200 mg compared to 2% of patients receiving placebo. A single dose of lasmiditan 50 mg, 100 mg, or 200 mg significantly impaired driving ability. More sleepiness was reported at 8 hours after a single lasmiditan dose compared to placebo. Advise patients not to engage in potentially hazardous activities requiring complete mental alertness, such as driving or operating machinery, for at least 8 hours after each dose of lasmiditan. Patients who are unable to follow these instructions should not receive lasmiditan. Patients may not be able to asses their own driving competence and the degree of impairment caused by lasmiditan. Additionally, paresthesias (including oral paresthesia, hypoesthesia, and oral hypoesthesia) occurred in 3% of patients receiving lasmiditan 50 mg, 7% of patients receiving lasmiditan 100 mg, and 9% of patients receiving lasmiditan 200 mg compared to 2% of patients receiving placebo. Vertigo, abnormal feeling, anxiety, tremor, restlessness, sleep abnormalities including sleep disturbance and abnormal dreams, cognitive changes, confusion, euphoria, and hallucinations were reported in less than 2% of lasmiditan-treated patients during clinical trials. Overuse of acute migraine drugs for 10 or more days per month may lead to exacerbation of headache (i.e., medication overuse headache). Medication overuse headache may present as migraine-like daily headaches or as a marked increase in frequency of migraine attacks. Withdrawal of the overused drugs and treatment of withdrawal symptoms, which often includes a transient worsening of headache, may be necessary.
Hypersensitivity reactions, including angioedema, rash, and photosensitivity, were observed in 0.2% of patients during treatment with lasmiditan in clinical trials. Initiate appropriate therapy and discontinue lasmiditan if a serious or severe hypersensitivity reaction occurs.
Palpitations and chest discomfort were reported in less than 2% of lasmiditan-treated patients during clinical trials. A mean decrease in heart rate of 5 to 10 beats per minute was reported among patients treated with lasmiditan compared to a 2 to 5 beat per minute decrease among patients treated with placebo. A mean increase in ambulatory systolic and diastolic blood pressure of approximately 2 to 3 mmHg from baseline occurred 1 hour after administration of lasmiditan 200 mg to non-elderly healthy volunteers compared to a mean increase of up to 1 mmHg for placebo. A mean increase in ambulatory systolic blood pressure of 7 mmHg from baseline occurred 1 hour after administration of lasmiditan 200 mg to healthy volunteers older than 65 years compared to a mean increase of 4 mmHg for placebo. At 2 hours post-dose, there were no increases in mean blood pressure with lasmiditan compared to placebo. Consider evaluating heart rate and/or blood pressure after administration of lasmiditan in patients for whom these changes may not be tolerated.
In 2 placebo-controlled phase 3 trials, fatigue (including asthenia and malaise) occurred in 4% of patients receiving lasmiditan 50 mg (n = 654), 5% of patients receiving lasmiditan 100 mg (n = 1,265), and 6% of patients receiving lasmiditan 200 mg (n = 1,258) compared to 1% of patients receiving placebo (n = 1,262). Lethargy, feeling hot, or feeling cold was reported in less than 2% of lasmiditan-treated patients during clinical trials.
In 2 placebo-controlled phase 3 trials, nausea and/or vomiting occurred in 3% of patients receiving lasmiditan 50 mg (n = 654) and 4% of patients receiving lasmiditan 100 mg (n = 1,265) and 200 mg (n = 1,258) compared to 2% of patients receiving placebo (n = 1,262).
In 2 placebo-controlled phase 3 trials, muscle weakness occurred in 1% of patients receiving lasmiditan 50 mg (n = 654) and 100 mg (n = 1,265) and 2% of patients receiving lasmiditan 200 mg (n = 1,258) compared to 0% of patients receiving placebo (n = 1,262). Muscle spasm, limb discomfort, and incoordination were reported in less than 2% of lasmiditan-treated patients during clinical trials.
In clinical trials, reactions consistent with serotonin syndrome were reported in patients receiving lasmiditan who were not taking any other drugs associated with serotonin syndrome. Serotonin syndrome may also occur with lasmiditan during concurrent use with other serotonergic drugs, such as SSRIs, SNRIs, tricyclic antidepressants, and MAOIs. Serotonin syndrome symptoms may include mental status changes (e.g., agitation, hallucinations, coma), autonomic instability (e.g., tachycardia, labile blood pressure, hyperthermia), neuromuscular signs (e.g., hyperreflexia, incoordination), and/or gastrointestinal signs and symptoms (e.g., nausea, vomiting, diarrhea). The onset of symptoms usually occurs within minutes to hours of receiving a new or a higher dose of a serotonergic medication. Discontinue lasmiditan if serotonin syndrome is suspected.
Visual impairment and speech abnormalities were reported in less than 2% of lasmiditan-treated patients during clinical trials.
Dyspnea was reported in less than 2% of lasmiditan-treated patients during clinical trials.
Lasmiditan may cause significant driving impairment. Advise patients not to engage in potentially hazardous activities requiring complete mental alertness, such as driving or operating machinery, for at least 8 hours after each dose of lasmiditan. Patients who are unable to follow these instructions should not receive lasmiditan. Patients may not be able to asses their own driving competence and the degree of impairment caused by lasmiditan. Use lasmiditan with caution in combination with alcohol or other CNS depressants.
Lasmiditan was associated with decreases in heart rate during clinical trials. Consider evaluating heart rate after lasmiditan administration in patients for whom a decrease in heart rate may not be tolerated, including patients taking other medications that lower the heart rate. Additionally, lasmiditan may increase blood pressure after a single dose. Consider evaluating blood pressure after lasmiditan administration in patients for whom an increase in systolic and/or diastolic blood pressure may not be tolerated. Lasmiditan has not been well studied in patients with ischemic cardiac disease.
Lasmiditan has not been studied in patients with severe hepatic disease (Child-Pugh class C), and its use in these patients is not recommended.
There are no adequate data on the developmental risk associated with lasmiditan use during human pregnancy. Skeletal and visceral malformations, increased embryofetal and offspring mortality, and decreased fetal body weight occurred in pregnant rabbits and rats at maternal exposures less than or more than, respectively, those observed clinically. Data suggest that women with migraine may be at increased risk for preeclampsia and gestational hypertension during pregnancy. There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to lasmiditan during pregnancy. Health care providers are encouraged to register pregnant patients, or pregnant women may enroll themselves in the registry by calling 1-833-464-4724 or visiting www.migrainepregnancyregistry.com.
There are no data on the presence of lasmiditan in human milk, the effects on the breast-fed infant, or the effects on milk production. Consider the developmental and health benefits of breast-feeding along with the mother's clinical need for lasmiditan and any potential adverse effects on the breast-fed infant from lasmiditan or the underlying maternal condition. Lasmiditan and/or its metabolites were excreted in the milk of lactating rats at concentrations approximately 3 times those in maternal plasma after oral administration.
Guideline indications for initiating acute treatment with lasmiditan:
-Contraindications to or inability to tolerate serotonin-receptor agonists ("triptans") or
-Inadequate response to at least 2 oral triptans, as determined by either health care provider attestation or a validated acute treatment patient-reported outcome questionnaire (e.g., mTOQ, Migraine-ACT, PPMQ-R, FIS, PGIC).
Guideline criteria for continuation of acute treatment with lasmiditan: -Continue coverage until at least 3 attacks are treated to assess efficacy and tolerability.
-Base treatment continuation decisions on the average monthly headache frequency and clinical assessment of improvement by a health care provider or response to a validated acute treatment patient-reported outcome questionnaire.
For the acute treatment of migraine with or without aura:
Oral dosage:
Adults: 50, 100, or 200 mg PO as a single dose. Do not exceed more than 1 dose in 24 hours. A second dose has not been shown to be effective for the same migraine attack. The safety of treating an average of more than 4 migraine attacks within 30 days has not been established. Guidelines classify lasmiditan as having established efficacy for the treatment of acute migraine.
Maximum Dosage Limits:
-Adults
200 mg/day PO.
-Geriatric
200 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
No dosage adjustment is needed in mild or moderate hepatic impairment (Child-Pugh class A or B). Lasmiditan has not been studied in patients with severe hepatic impairment (Child-Pugh class C), and its use in these patients is not recommended.
Patients with Renal Impairment Dosing
Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are needed.
*non-FDA-approved indication
Abacavir; Dolutegravir; Lamivudine: (Moderate) Monitor for increased toxicity of dolutegravir if coadministered with lasmiditan. Concurrent use may increase the plasma concentrations of dolutegravir. Dolutegravir is a P-gp substrate and lasmiditan is a P-gp inhibitor.
Acebutolol: (Moderate) Monitor heart rate if lasmiditan is coadministered with beta-blockers as concurrent use may increase the risk for bradycardia. Lasmiditan has been associated with lowering of heart rate. In a drug interaction study, addition of a single 200 mg dose of lasmiditan to a beta-blocker (propranolol) decreased heart rate by an additional 5 beats per minute.
Acetaminophen; Aspirin; Diphenhydramine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lasmiditan and sedating H1-blockers. Concurrent use may result in additive CNS depression.
Acetaminophen; Caffeine; Dihydrocodeine: (Moderate) Concomitant use of dihydrocodeine with lasmiditan may cause excessive sedation, somnolence, and serotonin syndrome. Limit the use of dihydrocodeine with lasmiditan to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression and serotonin syndrome. Avoid prescribing dihydrocodeine cough medications in patients taking lasmiditan.
Acetaminophen; Caffeine; Pyrilamine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lasmiditan and sedating H1-blockers. Concurrent use may result in additive CNS depression.
Acetaminophen; Chlorpheniramine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lasmiditan and sedating H1-blockers. Concurrent use may result in additive CNS depression.
Acetaminophen; Chlorpheniramine; Dextromethorphan: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lasmiditan and sedating H1-blockers. Concurrent use may result in additive CNS depression. (Moderate) Serotonin syndrome may occur during coadministration of lasmiditan and dextromethorphan. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome, particularly after a dose increase or the addition of other serotonergic medications to an existing regimen. Discontinue all serotonergic agents if serotonin syndrome occurs and implement appropriate medical management.
Acetaminophen; Chlorpheniramine; Dextromethorphan; Phenylephrine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lasmiditan and sedating H1-blockers. Concurrent use may result in additive CNS depression. (Moderate) Serotonin syndrome may occur during coadministration of lasmiditan and dextromethorphan. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome, particularly after a dose increase or the addition of other serotonergic medications to an existing regimen. Discontinue all serotonergic agents if serotonin syndrome occurs and implement appropriate medical management.
Acetaminophen; Chlorpheniramine; Dextromethorphan; Pseudoephedrine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lasmiditan and sedating H1-blockers. Concurrent use may result in additive CNS depression. (Moderate) Serotonin syndrome may occur during coadministration of lasmiditan and dextromethorphan. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome, particularly after a dose increase or the addition of other serotonergic medications to an existing regimen. Discontinue all serotonergic agents if serotonin syndrome occurs and implement appropriate medical management.
Acetaminophen; Chlorpheniramine; Phenylephrine : (Moderate) Monitor for excessive sedation and somnolence during coadministration of lasmiditan and sedating H1-blockers. Concurrent use may result in additive CNS depression.
Acetaminophen; Codeine: (Moderate) Concomitant use of codeine with lasmiditan may cause excessive sedation, somnolence, and serotonin syndrome. Limit the use of codeine with lasmiditan to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression and serotonin syndrome. Avoid prescribing codeine cough medications in patients taking lasmiditan.
Acetaminophen; Dextromethorphan: (Moderate) Serotonin syndrome may occur during coadministration of lasmiditan and dextromethorphan. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome, particularly after a dose increase or the addition of other serotonergic medications to an existing regimen. Discontinue all serotonergic agents if serotonin syndrome occurs and implement appropriate medical management.
Acetaminophen; Dextromethorphan; Doxylamine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lasmiditan and sedating H1-blockers. Concurrent use may result in additive CNS depression. (Moderate) Serotonin syndrome may occur during coadministration of lasmiditan and dextromethorphan. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome, particularly after a dose increase or the addition of other serotonergic medications to an existing regimen. Discontinue all serotonergic agents if serotonin syndrome occurs and implement appropriate medical management.
Acetaminophen; Dextromethorphan; Guaifenesin; Phenylephrine: (Moderate) Serotonin syndrome may occur during coadministration of lasmiditan and dextromethorphan. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome, particularly after a dose increase or the addition of other serotonergic medications to an existing regimen. Discontinue all serotonergic agents if serotonin syndrome occurs and implement appropriate medical management.
Acetaminophen; Dextromethorphan; Guaifenesin; Pseudoephedrine: (Moderate) Serotonin syndrome may occur during coadministration of lasmiditan and dextromethorphan. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome, particularly after a dose increase or the addition of other serotonergic medications to an existing regimen. Discontinue all serotonergic agents if serotonin syndrome occurs and implement appropriate medical management.
Acetaminophen; Dextromethorphan; Phenylephrine: (Moderate) Serotonin syndrome may occur during coadministration of lasmiditan and dextromethorphan. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome, particularly after a dose increase or the addition of other serotonergic medications to an existing regimen. Discontinue all serotonergic agents if serotonin syndrome occurs and implement appropriate medical management.
Acetaminophen; Dextromethorphan; Pseudoephedrine: (Moderate) Serotonin syndrome may occur during coadministration of lasmiditan and dextromethorphan. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome, particularly after a dose increase or the addition of other serotonergic medications to an existing regimen. Discontinue all serotonergic agents if serotonin syndrome occurs and implement appropriate medical management.
Acetaminophen; Diphenhydramine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lasmiditan and sedating H1-blockers. Concurrent use may result in additive CNS depression.
Acetaminophen; Hydrocodone: (Moderate) Concomitant use of hydrocodone with lasmiditan may cause excessive sedation, somnolence, and serotonin syndrome. Limit the use of hydrocodone with lasmiditan to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression and serotonin syndrome. Avoid prescribing hydrocodone cough medications in patients taking lasmiditan.
Acetaminophen; Oxycodone: (Moderate) Concomitant use of oxycodone with lasmiditan may cause excessive sedation, somnolence, and serotonin syndrome. Limit the use of oxycodone with lasmiditan to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression and serotonin syndrome.
Acetaminophen; Pamabrom; Pyrilamine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lasmiditan and sedating H1-blockers. Concurrent use may result in additive CNS depression.
Acrivastine; Pseudoephedrine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lasmiditan and sedating H1-blockers. Concurrent use may result in additive CNS depression.
Afatinib: (Moderate) If the concomitant use of lasmiditan 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 lasmiditan. 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 lasmiditan 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.
Alfentanil: (Moderate) Concomitant use of alfentanil with lasmiditan may cause excessive sedation, somnolence, and serotonin syndrome. Limit the use of alfentanil with lasmiditan to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression and serotonin syndrome.
Almotriptan: (Moderate) Serotonin syndrome may occur during coadministration of lasmiditan and serotonin-receptor agonists. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome, particularly after a dose increase or the addition of other serotonergic medications to an existing regimen. Discontinue all serotonergic agents if serotonin syndrome occurs and implement appropriate medical management.
Alprazolam: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lasmiditan and benzodiazepines. Concurrent use may result in additive CNS depression.
Amitriptyline: (Moderate) Monitor for excessive sedation, somnolence, and serotonin syndrome during coadministration of lasmiditan and tricyclic antidepressants. Inform patients taking this combination of the risks and symptoms of excessive CNS depression and serotonin syndrome, particularly after a dose increase or the addition of other serotonergic medications to an existing regimen. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
Amlodipine: (Moderate) Monitor heart rate if lasmiditan is coadministered with calcium-channel blockers as concurrent use may increase the risk for bradycardia. Lasmiditan has been associated with lowering of heart rate. In a drug interaction study, addition of a single 200 mg dose of lasmiditan to another heart rate lowering drug decreased heart rate by an additional 5 beats per minute.
Amlodipine; Atorvastatin: (Moderate) Monitor for an increase in atorvastatin-related adverse reactions, including myopathy and rhabdomyolysis, if coadministration with lasmiditan is necessary. Concomitant use may increase atorvastatin exposure. Atorvastatin is a P-gp substrate; lasmiditan is a P-gp inhibitor. (Moderate) Monitor heart rate if lasmiditan is coadministered with calcium-channel blockers as concurrent use may increase the risk for bradycardia. Lasmiditan has been associated with lowering of heart rate. In a drug interaction study, addition of a single 200 mg dose of lasmiditan to another heart rate lowering drug decreased heart rate by an additional 5 beats per minute.
Amlodipine; Benazepril: (Moderate) Monitor heart rate if lasmiditan is coadministered with calcium-channel blockers as concurrent use may increase the risk for bradycardia. Lasmiditan has been associated with lowering of heart rate. In a drug interaction study, addition of a single 200 mg dose of lasmiditan to another heart rate lowering drug decreased heart rate by an additional 5 beats per minute.
Amlodipine; Celecoxib: (Moderate) Monitor heart rate if lasmiditan is coadministered with calcium-channel blockers as concurrent use may increase the risk for bradycardia. Lasmiditan has been associated with lowering of heart rate. In a drug interaction study, addition of a single 200 mg dose of lasmiditan to another heart rate lowering drug decreased heart rate by an additional 5 beats per minute.
Amlodipine; Olmesartan: (Moderate) Monitor heart rate if lasmiditan is coadministered with calcium-channel blockers as concurrent use may increase the risk for bradycardia. Lasmiditan has been associated with lowering of heart rate. In a drug interaction study, addition of a single 200 mg dose of lasmiditan to another heart rate lowering drug decreased heart rate by an additional 5 beats per minute.
Amlodipine; Valsartan: (Moderate) Monitor heart rate if lasmiditan is coadministered with calcium-channel blockers as concurrent use may increase the risk for bradycardia. Lasmiditan has been associated with lowering of heart rate. In a drug interaction study, addition of a single 200 mg dose of lasmiditan to another heart rate lowering drug decreased heart rate by an additional 5 beats per minute.
Amlodipine; Valsartan; Hydrochlorothiazide, HCTZ: (Moderate) Monitor heart rate if lasmiditan is coadministered with calcium-channel blockers as concurrent use may increase the risk for bradycardia. Lasmiditan has been associated with lowering of heart rate. In a drug interaction study, addition of a single 200 mg dose of lasmiditan to another heart rate lowering drug decreased heart rate by an additional 5 beats per minute.
Amobarbital: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lasmiditan and barbiturates. Concurrent use may result in additive CNS depression.
Amoxapine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lasmiditan and amoxapine. Concurrent use may result in additive CNS depression.
Amphetamine: (Moderate) Serotonin syndrome may occur during coadministration of lasmiditan and amphetamines. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly after a dose increase or the addition of other serotonergic medications to an existing regimen. Discontinue all serotonergic agents if serotonin syndrome occurs and implement appropriate medical management.
Amphetamine; Dextroamphetamine: (Moderate) Serotonin syndrome may occur during coadministration of lasmiditan and amphetamines. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly after a dose increase or the addition of other serotonergic medications to an existing regimen. Discontinue all serotonergic agents if serotonin syndrome occurs and implement appropriate medical management.
Amphetamines: (Moderate) Serotonin syndrome may occur during coadministration of lasmiditan and amphetamines. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly after a dose increase or the addition of other serotonergic medications to an existing regimen. Discontinue all serotonergic agents if serotonin syndrome occurs and implement appropriate medical management.
Apomorphine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lasmiditan and apomorphine. Concurrent use may result in additive CNS depression. Dopaminergic agents, such as apomorphine, have also been associated with sudden sleep onset during activities of daily living such as driving, which has resulted in accidents in some cases. Prescribers should re-assess patients for drowsiness or sleepiness regularly throughout treatment, especially since events may occur well after the start of treatment.
Aripiprazole: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lasmiditan and aripiprazole. Concurrent use may result in additive CNS depression.
Asenapine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lasmiditan and asenapine. Concurrent use may result in additive CNS depression.
Aspirin, ASA; Butalbital; Caffeine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lasmiditan and barbiturates. Concurrent use may result in additive CNS depression.
Aspirin, ASA; Caffeine; Orphenadrine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lasmiditan and orphenadrine. Concurrent use may result in additive CNS depression.
Aspirin, ASA; Carisoprodol; Codeine: (Moderate) Concomitant use of codeine with lasmiditan may cause excessive sedation, somnolence, and serotonin syndrome. Limit the use of codeine with lasmiditan to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression and serotonin syndrome. Avoid prescribing codeine cough medications in patients taking lasmiditan. (Moderate) Monitor for excessive sedation and somnolence during coadministration of lasmiditan and carisoprodol. Concurrent use may result in additive CNS depression.
Aspirin, ASA; Oxycodone: (Moderate) Concomitant use of oxycodone with lasmiditan may cause excessive sedation, somnolence, and serotonin syndrome. Limit the use of oxycodone with lasmiditan to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression and serotonin syndrome.
Atenolol: (Moderate) Monitor heart rate if lasmiditan is coadministered with beta-blockers as concurrent use may increase the risk for bradycardia. Lasmiditan has been associated with lowering of heart rate. In a drug interaction study, addition of a single 200 mg dose of lasmiditan to a beta-blocker (propranolol) decreased heart rate by an additional 5 beats per minute.
Atenolol; Chlorthalidone: (Moderate) Monitor heart rate if lasmiditan is coadministered with beta-blockers as concurrent use may increase the risk for bradycardia. Lasmiditan has been associated with lowering of heart rate. In a drug interaction study, addition of a single 200 mg dose of lasmiditan to a beta-blocker (propranolol) decreased heart rate by an additional 5 beats per minute.
Atorvastatin: (Moderate) Monitor for an increase in atorvastatin-related adverse reactions, including myopathy and rhabdomyolysis, if coadministration with lasmiditan is necessary. Concomitant use may increase atorvastatin exposure. Atorvastatin is a P-gp substrate; lasmiditan is a P-gp inhibitor.
Atropine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lasmiditan and atropine. Concurrent use may result in additive CNS depression.
Atropine; Difenoxin: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lasmiditan and atropine. Concurrent use may result in additive CNS depression.
Baclofen: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lasmiditan and baclofen. Concurrent use may result in additive CNS depression.
Barbiturates: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lasmiditan and barbiturates. Concurrent use may result in additive CNS depression.
Belladonna; Opium: (Moderate) Concomitant use of opium with lasmiditan may cause excessive sedation, somnolence, and serotonin syndrome. Limit the use of opium with lasmiditan to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression and serotonin syndrome.
Benzhydrocodone; Acetaminophen: (Moderate) Concomitant use of benzhydrocodone with lasmiditan may cause excessive sedation, somnolence, and serotonin syndrome. Limit the use of benzhydrocodone with lasmiditan to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression and serotonin syndrome.
Benzodiazepines: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lasmiditan and benzodiazepines. Concurrent use may result in additive CNS depression.
Benzoic Acid; Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate: (Moderate) Serotonin syndrome may occur during coadministration of lasmiditan and methylene blue. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome, particularly after a dose increase or the addition of other serotonergic medications to an existing regimen. Discontinue all serotonergic agents if serotonin syndrome occurs and implement appropriate medical management.
Benzphetamine: (Moderate) Serotonin syndrome may occur during coadministration of lasmiditan and amphetamines. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly after a dose increase or the addition of other serotonergic medications to an existing regimen. Discontinue all serotonergic agents if serotonin syndrome occurs and implement appropriate medical management.
Beta-blockers: (Moderate) Monitor heart rate if lasmiditan is coadministered with beta-blockers as concurrent use may increase the risk for bradycardia. Lasmiditan has been associated with lowering of heart rate. In a drug interaction study, addition of a single 200 mg dose of lasmiditan to a beta-blocker (propranolol) decreased heart rate by an additional 5 beats per minute.
Betaxolol: (Moderate) Monitor heart rate if lasmiditan is coadministered with beta-blockers as concurrent use may increase the risk for bradycardia. Lasmiditan has been associated with lowering of heart rate. In a drug interaction study, addition of a single 200 mg dose of lasmiditan to a beta-blocker (propranolol) decreased heart rate by an additional 5 beats per minute.
Betrixaban: (Major) Avoid betrixaban use in patients with severe renal impairment receiving lasmiditan. Reduce betrixaban dosage to 80 mg PO once followed by 40 mg PO once daily in all other patients receiving lasmiditan. 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; lasmiditan is a P-gp inhibitor. Coadministration of other P-gp inhibitors increased betrixaban exposure by 2 to 3-fold.
Bictegravir; Emtricitabine; Tenofovir Alafenamide: (Moderate) Coadministration of tenofovir alafenamide with lasmiditan may result in increased plasma concentrations of tenofovir leading to an increase in tenofovir-related adverse effects. Tenofovir alafenamide is a P-gp substrate and lasmiditan is a P-gp inhibitor.
Bisoprolol: (Moderate) Monitor heart rate if lasmiditan is coadministered with beta-blockers as concurrent use may increase the risk for bradycardia. Lasmiditan has been associated with lowering of heart rate. In a drug interaction study, addition of a single 200 mg dose of lasmiditan to a beta-blocker (propranolol) decreased heart rate by an additional 5 beats per minute.
Bisoprolol; Hydrochlorothiazide, HCTZ: (Moderate) Monitor heart rate if lasmiditan is coadministered with beta-blockers as concurrent use may increase the risk for bradycardia. Lasmiditan has been associated with lowering of heart rate. In a drug interaction study, addition of a single 200 mg dose of lasmiditan to a beta-blocker (propranolol) decreased heart rate by an additional 5 beats per minute.
Brexpiprazole: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lasmiditan and brexpiprazole. Concurrent use may result in additive CNS depression.
Brimonidine; Timolol: (Moderate) Monitor heart rate if lasmiditan is coadministered with beta-blockers as concurrent use may increase the risk for bradycardia. Lasmiditan has been associated with lowering of heart rate. In a drug interaction study, addition of a single 200 mg dose of lasmiditan to a beta-blocker (propranolol) decreased heart rate by an additional 5 beats per minute.
Brompheniramine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lasmiditan and sedating H1-blockers. Concurrent use may result in additive CNS depression.
Brompheniramine; Dextromethorphan; Phenylephrine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lasmiditan and sedating H1-blockers. Concurrent use may result in additive CNS depression. (Moderate) Serotonin syndrome may occur during coadministration of lasmiditan and dextromethorphan. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome, particularly after a dose increase or the addition of other serotonergic medications to an existing regimen. Discontinue all serotonergic agents if serotonin syndrome occurs and implement appropriate medical management.
Brompheniramine; Phenylephrine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lasmiditan and sedating H1-blockers. Concurrent use may result in additive CNS depression.
Brompheniramine; Pseudoephedrine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lasmiditan and sedating H1-blockers. Concurrent use may result in additive CNS depression.
Brompheniramine; Pseudoephedrine; Dextromethorphan: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lasmiditan and sedating H1-blockers. Concurrent use may result in additive CNS depression. (Moderate) Serotonin syndrome may occur during coadministration of lasmiditan and dextromethorphan. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome, particularly after a dose increase or the addition of other serotonergic medications to an existing regimen. Discontinue all serotonergic agents if serotonin syndrome occurs and implement appropriate medical management.
Buprenorphine: (Moderate) Concomitant use of buprenorphine with lasmiditan may cause excessive sedation, somnolence, and serotonin syndrome. Limit the use of buprenorphine with lasmiditan to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression and serotonin syndrome.
Buprenorphine; Naloxone: (Moderate) Concomitant use of buprenorphine with lasmiditan may cause excessive sedation, somnolence, and serotonin syndrome. Limit the use of buprenorphine with lasmiditan to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression and serotonin syndrome.
Bupropion: (Moderate) Serotonin syndrome may occur during coadministration of lasmiditan and bupropion. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly after a dose increase or the addition of other serotonergic medications to an existing regimen. Discontinue all serotonergic agents if serotonin syndrome occurs and implement appropriate medical management.
Bupropion; Naltrexone: (Moderate) Serotonin syndrome may occur during coadministration of lasmiditan and bupropion. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly after a dose increase or the addition of other serotonergic medications to an existing regimen. Discontinue all serotonergic agents if serotonin syndrome occurs and implement appropriate medical management.
Buspirone: (Moderate) Serotonin syndrome may occur during coadministration of lasmiditan and buspirone. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly after a dose increase or the addition of other serotonergic medications to an existing regimen. Discontinue all serotonergic agents if serotonin syndrome occurs and implement appropriate medical management.
Butalbital; Acetaminophen: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lasmiditan and barbiturates. Concurrent use may result in additive CNS depression.
Butalbital; Acetaminophen; Caffeine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lasmiditan and barbiturates. Concurrent use may result in additive CNS depression.
Butalbital; Acetaminophen; Caffeine; Codeine: (Moderate) Concomitant use of codeine with lasmiditan may cause excessive sedation, somnolence, and serotonin syndrome. Limit the use of codeine with lasmiditan to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression and serotonin syndrome. Avoid prescribing codeine cough medications in patients taking lasmiditan. (Moderate) Monitor for excessive sedation and somnolence during coadministration of lasmiditan and barbiturates. Concurrent use may result in additive CNS depression.
Butalbital; Aspirin; Caffeine; Codeine: (Moderate) Concomitant use of codeine with lasmiditan may cause excessive sedation, somnolence, and serotonin syndrome. Limit the use of codeine with lasmiditan to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression and serotonin syndrome. Avoid prescribing codeine cough medications in patients taking lasmiditan. (Moderate) Monitor for excessive sedation and somnolence during coadministration of lasmiditan and barbiturates. Concurrent use may result in additive CNS depression.
Butorphanol: (Moderate) Concomitant use of butorphanol with lasmiditan may cause excessive sedation, somnolence, and serotonin syndrome. Limit the use of butorphanol with lasmiditan to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression and serotonin syndrome.
Calcium, Magnesium, Potassium, Sodium Oxybates: (Moderate) Monitor for excessive sedation, somnolence, and serotonin syndrome during coadministration of lasmiditan and sodium oxybate. Inform patients taking this combination of the risks and symptoms of excessive CNS depression and serotonin syndrome, particularly after a dose increase or the addition of other serotonergic medications to an existing regimen. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
Calcium-channel blockers: (Moderate) Monitor heart rate if lasmiditan is coadministered with calcium-channel blockers as concurrent use may increase the risk for bradycardia. Lasmiditan has been associated with lowering of heart rate. In a drug interaction study, addition of a single 200 mg dose of lasmiditan to another heart rate lowering drug decreased heart rate by an additional 5 beats per minute.
Cannabidiol: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lasmiditan and cannabidiol. Concurrent use may result in additive CNS depression.
Capsaicin; Metaxalone: (Moderate) Monitor for excessive sedation, somnolence, and serotonin syndrome during coadministration of lasmiditan and metaxalone. Inform patients taking this combination of the risks and symptoms of excessive CNS depression and serotonin syndrome, particularly after a dose increase or the addition of other serotonergic medications to an existing regimen. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
Carbidopa; Levodopa: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lasmiditan and levodopa. Concurrent use may result in additive CNS depression. Dopaminergic agents, such as levodopa, have also been associated with sudden sleep onset during activities of daily living such as driving, which has resulted in accidents in some cases. Prescribers should re-assess patients for drowsiness or sleepiness regularly throughout treatment, especially since events may occur well after the start of treatment.
Carbidopa; Levodopa; Entacapone: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lasmiditan and entacapone. Concurrent use may result in additive CNS depression. Dopaminergic agents, such as entacapone, have also been associated with sudden sleep onset during activities of daily living such as driving, which has resulted in accidents in some cases. Prescribers should re-assess patients for drowsiness or sleepiness regularly throughout treatment, especially since events may occur well after the start of treatment. (Moderate) Monitor for excessive sedation and somnolence during coadministration of lasmiditan and levodopa. Concurrent use may result in additive CNS depression. Dopaminergic agents, such as levodopa, have also been associated with sudden sleep onset during activities of daily living such as driving, which has resulted in accidents in some cases. Prescribers should re-assess patients for drowsiness or sleepiness regularly throughout treatment, especially since events may occur well after the start of treatment.
Carbinoxamine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lasmiditan and sedating H1-blockers. Concurrent use may result in additive CNS depression.
Cariprazine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lasmiditan and cariprazine. Concurrent use may result in additive CNS depression.
Carisoprodol: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lasmiditan and carisoprodol. Concurrent use may result in additive CNS depression.
Carteolol: (Moderate) Monitor heart rate if lasmiditan is coadministered with beta-blockers as concurrent use may increase the risk for bradycardia. Lasmiditan has been associated with lowering of heart rate. In a drug interaction study, addition of a single 200 mg dose of lasmiditan to a beta-blocker (propranolol) decreased heart rate by an additional 5 beats per minute.
Carvedilol: (Moderate) Monitor heart rate if lasmiditan is coadministered with beta-blockers as concurrent use may increase the risk for bradycardia. Lasmiditan has been associated with lowering of heart rate. In a drug interaction study, addition of a single 200 mg dose of lasmiditan to a beta-blocker (propranolol) decreased heart rate by an additional 5 beats per minute.
Celecoxib; Tramadol: (Moderate) Concomitant use of tramadol with lasmiditan may cause excessive sedation, somnolence, and serotonin syndrome. Limit the use of tramadol with lasmiditan to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression and serotonin syndrome.
Cenobamate: (Moderate) Monitor for excessive sedation and somnolence during coadministration of cenobamate and lasmiditan. Concurrent use may result in additive CNS depression.
Ceritinib: (Major) Avoid concomitant use of ceritinib with lasmiditan if possible due to the risk of additive bradycardia. Both ceritinib and lasmiditan can cause bradycardia. An interruption of ceritinib therapy, dose reduction, or discontinuation of therapy may be necessary if bradycardia occurs. In a drug interaction study, addition of a single 200 mg dose of lasmiditan to another heart rate lowering drug decreased heart rate by an additional 5 beats per minute.
Chlophedianol; Dexbrompheniramine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lasmiditan and sedating H1-blockers. Concurrent use may result in additive CNS depression.
Chlophedianol; Dexchlorpheniramine; Pseudoephedrine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lasmiditan and sedating H1-blockers. Concurrent use may result in additive CNS depression.
Chlorcyclizine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lasmiditan and sedating H1-blockers. Concurrent use may result in additive CNS depression.
Chlordiazepoxide: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lasmiditan and benzodiazepines. Concurrent use may result in additive CNS depression.
Chlordiazepoxide; Amitriptyline: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lasmiditan and benzodiazepines. Concurrent use may result in additive CNS depression. (Moderate) Monitor for excessive sedation, somnolence, and serotonin syndrome during coadministration of lasmiditan and tricyclic antidepressants. Inform patients taking this combination of the risks and symptoms of excessive CNS depression and serotonin syndrome, particularly after a dose increase or the addition of other serotonergic medications to an existing regimen. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
Chlordiazepoxide; Clidinium: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lasmiditan and benzodiazepines. Concurrent use may result in additive CNS depression.
Chlorpheniramine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lasmiditan and sedating H1-blockers. Concurrent use may result in additive CNS depression.
Chlorpheniramine; Codeine: (Moderate) Concomitant use of codeine with lasmiditan may cause excessive sedation, somnolence, and serotonin syndrome. Limit the use of codeine with lasmiditan to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression and serotonin syndrome. Avoid prescribing codeine cough medications in patients taking lasmiditan. (Moderate) Monitor for excessive sedation and somnolence during coadministration of lasmiditan and sedating H1-blockers. Concurrent use may result in additive CNS depression.
Chlorpheniramine; Dextromethorphan: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lasmiditan and sedating H1-blockers. Concurrent use may result in additive CNS depression. (Moderate) Serotonin syndrome may occur during coadministration of lasmiditan and dextromethorphan. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome, particularly after a dose increase or the addition of other serotonergic medications to an existing regimen. Discontinue all serotonergic agents if serotonin syndrome occurs and implement appropriate medical management.
Chlorpheniramine; Dextromethorphan; Phenylephrine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lasmiditan and sedating H1-blockers. Concurrent use may result in additive CNS depression. (Moderate) Serotonin syndrome may occur during coadministration of lasmiditan and dextromethorphan. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome, particularly after a dose increase or the addition of other serotonergic medications to an existing regimen. Discontinue all serotonergic agents if serotonin syndrome occurs and implement appropriate medical management.
Chlorpheniramine; Dextromethorphan; Pseudoephedrine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lasmiditan and sedating H1-blockers. Concurrent use may result in additive CNS depression. (Moderate) Serotonin syndrome may occur during coadministration of lasmiditan and dextromethorphan. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome, particularly after a dose increase or the addition of other serotonergic medications to an existing regimen. Discontinue all serotonergic agents if serotonin syndrome occurs and implement appropriate medical management.
Chlorpheniramine; Hydrocodone: (Moderate) Concomitant use of hydrocodone with lasmiditan may cause excessive sedation, somnolence, and serotonin syndrome. Limit the use of hydrocodone with lasmiditan to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression and serotonin syndrome. Avoid prescribing hydrocodone cough medications in patients taking lasmiditan. (Moderate) Monitor for excessive sedation and somnolence during coadministration of lasmiditan and sedating H1-blockers. Concurrent use may result in additive CNS depression.
Chlorpheniramine; Ibuprofen; Pseudoephedrine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lasmiditan and sedating H1-blockers. Concurrent use may result in additive CNS depression.
Chlorpheniramine; Phenylephrine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lasmiditan and sedating H1-blockers. Concurrent use may result in additive CNS depression.
Chlorpheniramine; Pseudoephedrine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lasmiditan and sedating H1-blockers. Concurrent use may result in additive CNS depression.
Chlorpromazine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lasmiditan and chlorpromazine. Concurrent use may result in additive CNS depression.
Chlorzoxazone: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lasmiditan and chlorzoxazone. Concurrent use may result in additive CNS depression.
Citalopram: (Moderate) Serotonin syndrome may occur during coadministration of lasmiditan and selective serotonin reuptake inhibitors. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome, particularly after a dose increase or the addition of other serotonergic medications to an existing regimen. Discontinue all serotonergic agents if serotonin syndrome occurs and implement appropriate medical management.
Clemastine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lasmiditan and sedating H1-blockers. Concurrent use may result in additive CNS depression.
Clevidipine: (Moderate) Monitor heart rate if lasmiditan is coadministered with calcium-channel blockers as concurrent use may increase the risk for bradycardia. Lasmiditan has been associated with lowering of heart rate. In a drug interaction study, addition of a single 200 mg dose of lasmiditan to another heart rate lowering drug decreased heart rate by an additional 5 beats per minute.
Clomipramine: (Moderate) Monitor for excessive sedation, somnolence, and serotonin syndrome during coadministration of lasmiditan and tricyclic antidepressants. Inform patients taking this combination of the risks and symptoms of excessive CNS depression and serotonin syndrome, particularly after a dose increase or the addition of other serotonergic medications to an existing regimen. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
Clonazepam: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lasmiditan and benzodiazepines. Concurrent use may result in additive CNS depression.
Clonidine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lasmiditan and clonidine. Concurrent use may result in additive CNS depression. Additionally, monitor heart rate if lasmiditan is coadministered with clonidine as concurrent use may increase the risk for bradycardia. Lasmiditan has been associated with lowering of heart rate. In a drug interaction study, addition of a single 200 mg dose of lasmiditan to another heart rate lowering drug decreased heart rate by an additional 5 beats per minute.
Clorazepate: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lasmiditan and benzodiazepines. Concurrent use may result in additive CNS depression.
Clozapine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lasmiditan and clozapine. Concurrent use may result in additive CNS depression.
Cobimetinib: (Moderate) Monitor for an increase in cobimetinib-related adverse reactions if coadministration with lasmiditan is necessary. Concomitant use may increase cobimetinib exposure. In vitro, cobimetinib is a P-glycoprotein substrate; lasmiditan is a P-gp inhibitor.
Codeine: (Moderate) Concomitant use of codeine with lasmiditan may cause excessive sedation, somnolence, and serotonin syndrome. Limit the use of codeine with lasmiditan to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression and serotonin syndrome. Avoid prescribing codeine cough medications in patients taking lasmiditan.
Codeine; Guaifenesin: (Moderate) Concomitant use of codeine with lasmiditan may cause excessive sedation, somnolence, and serotonin syndrome. Limit the use of codeine with lasmiditan to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression and serotonin syndrome. Avoid prescribing codeine cough medications in patients taking lasmiditan.
Codeine; Guaifenesin; Pseudoephedrine: (Moderate) Concomitant use of codeine with lasmiditan may cause excessive sedation, somnolence, and serotonin syndrome. Limit the use of codeine with lasmiditan to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression and serotonin syndrome. Avoid prescribing codeine cough medications in patients taking lasmiditan.
Codeine; Phenylephrine; Promethazine: (Moderate) Concomitant use of codeine with lasmiditan may cause excessive sedation, somnolence, and serotonin syndrome. Limit the use of codeine with lasmiditan to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression and serotonin syndrome. Avoid prescribing codeine cough medications in patients taking lasmiditan.
Codeine; Promethazine: (Moderate) Concomitant use of codeine with lasmiditan may cause excessive sedation, somnolence, and serotonin syndrome. Limit the use of codeine with lasmiditan to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression and serotonin syndrome. Avoid prescribing codeine cough medications in patients taking lasmiditan.
Colchicine: (Major) Avoid concomitant use of colchicine and lasmiditan 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 lasmiditan is a P-gp inhibitor.
Cyclobenzaprine: (Moderate) Monitor for excessive sedation, somnolence, and serotonin syndrome during coadministration of lasmiditan and cyclobenzaprine. Inform patients taking this combination of the risks and symptoms of excessive CNS depression and serotonin syndrome, particularly after a dose increase or the addition of other serotonergic medications to an existing regimen. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
Cyclosporine: (Moderate) Closely monitor cyclosporine whole blood trough concentrations as appropriate and watch for cyclosporine-related adverse reactions if coadministration with lasmiditan is necessary. The dose of cyclosporine may need to be adjusted. Concurrent use may increase cyclosporine exposure causing an increased risk for cyclosporine-related adverse events. Cyclosporine is a P-gp substrate and lasmiditan is a P-gp inhibitor.
Cyproheptadine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lasmiditan and sedating H1-blockers. Concurrent use may result in additive CNS depression.
Dabigatran: (Moderate) Monitor for an increase in dabigatran-related adverse reactions if coadministration with lasmiditan is necessary in patients with creatinine clearance (CrCl) greater than 50 mL/minute. Avoid coadministration in patients with CrCl less than 50 mL/minute 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/minute 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-gp substrate and lasmiditan is a P-gp inhibitor.
Dantrolene: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lasmiditan and dantrolene. Concurrent use may result in additive CNS depression.
Darunavir; Cobicistat; Emtricitabine; Tenofovir alafenamide: (Moderate) Coadministration of tenofovir alafenamide with lasmiditan may result in increased plasma concentrations of tenofovir leading to an increase in tenofovir-related adverse effects. Tenofovir alafenamide is a P-gp substrate and lasmiditan is a P-gp inhibitor.
Desipramine: (Moderate) Monitor for excessive sedation, somnolence, and serotonin syndrome during coadministration of lasmiditan and tricyclic antidepressants. Inform patients taking this combination of the risks and symptoms of excessive CNS depression and serotonin syndrome, particularly after a dose increase or the addition of other serotonergic medications to an existing regimen. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
Desvenlafaxine: (Moderate) Serotonin syndrome may occur during coadministration of lasmiditan and serotonin norepinephrine reuptake inhibitors. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome, particularly after a dose increase or the addition of other serotonergic medications to an existing regimen. Discontinue all serotonergic agents if serotonin syndrome occurs and implement appropriate medical management.
Deutetrabenazine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lasmiditan and deutetrabenazine. Concurrent use may result in additive CNS depression.
Dexbrompheniramine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lasmiditan and sedating H1-blockers. Concurrent use may result in additive CNS depression.
Dexbrompheniramine; Pseudoephedrine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lasmiditan and sedating H1-blockers. Concurrent use may result in additive CNS depression.
Dexchlorpheniramine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lasmiditan and sedating H1-blockers. Concurrent use may result in additive CNS depression.
Dexchlorpheniramine; Dextromethorphan; Pseudoephedrine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lasmiditan and sedating H1-blockers. Concurrent use may result in additive CNS depression. (Moderate) Serotonin syndrome may occur during coadministration of lasmiditan and dextromethorphan. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome, particularly after a dose increase or the addition of other serotonergic medications to an existing regimen. Discontinue all serotonergic agents if serotonin syndrome occurs and implement appropriate medical management.
Dexmedetomidine: (Moderate) Although CNS depression is a desired effect of dexmedetomidine, patients also receiving lasmiditan should be closely monitored for additive effects that may prolong recovery after administration of dexmedetomidine.
Dexmethylphenidate: (Moderate) Serotonin syndrome may occur during coadministration of lasmiditan and methylphenidate derivatives. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome, particularly after a dose increase or the addition of other serotonergic medications to an existing regimen. Discontinue all serotonergic agents if serotonin syndrome occurs and implement appropriate medical management.
Dextroamphetamine: (Moderate) Serotonin syndrome may occur during coadministration of lasmiditan and amphetamines. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly after a dose increase or the addition of other serotonergic medications to an existing regimen. Discontinue all serotonergic agents if serotonin syndrome occurs and implement appropriate medical management.
Dextromethorphan: (Moderate) Serotonin syndrome may occur during coadministration of lasmiditan and dextromethorphan. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome, particularly after a dose increase or the addition of other serotonergic medications to an existing regimen. Discontinue all serotonergic agents if serotonin syndrome occurs and implement appropriate medical management.
Dextromethorphan; Bupropion: (Moderate) Serotonin syndrome may occur during coadministration of lasmiditan and bupropion. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly after a dose increase or the addition of other serotonergic medications to an existing regimen. Discontinue all serotonergic agents if serotonin syndrome occurs and implement appropriate medical management. (Moderate) Serotonin syndrome may occur during coadministration of lasmiditan and dextromethorphan. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome, particularly after a dose increase or the addition of other serotonergic medications to an existing regimen. Discontinue all serotonergic agents if serotonin syndrome occurs and implement appropriate medical management.
Dextromethorphan; Diphenhydramine; Phenylephrine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lasmiditan and sedating H1-blockers. Concurrent use may result in additive CNS depression. (Moderate) Serotonin syndrome may occur during coadministration of lasmiditan and dextromethorphan. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome, particularly after a dose increase or the addition of other serotonergic medications to an existing regimen. Discontinue all serotonergic agents if serotonin syndrome occurs and implement appropriate medical management.
Dextromethorphan; Guaifenesin: (Moderate) Serotonin syndrome may occur during coadministration of lasmiditan and dextromethorphan. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome, particularly after a dose increase or the addition of other serotonergic medications to an existing regimen. Discontinue all serotonergic agents if serotonin syndrome occurs and implement appropriate medical management.
Dextromethorphan; Guaifenesin; Phenylephrine: (Moderate) Serotonin syndrome may occur during coadministration of lasmiditan and dextromethorphan. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome, particularly after a dose increase or the addition of other serotonergic medications to an existing regimen. Discontinue all serotonergic agents if serotonin syndrome occurs and implement appropriate medical management.
Dextromethorphan; Guaifenesin; Pseudoephedrine: (Moderate) Serotonin syndrome may occur during coadministration of lasmiditan and dextromethorphan. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome, particularly after a dose increase or the addition of other serotonergic medications to an existing regimen. Discontinue all serotonergic agents if serotonin syndrome occurs and implement appropriate medical management.
Dextromethorphan; Quinidine: (Moderate) Serotonin syndrome may occur during coadministration of lasmiditan and dextromethorphan. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome, particularly after a dose increase or the addition of other serotonergic medications to an existing regimen. Discontinue all serotonergic agents if serotonin syndrome occurs and implement appropriate medical management.
Diazepam: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lasmiditan and benzodiazepines. Concurrent use may result in additive CNS depression.
Difelikefalin: (Moderate) Monitor for dizziness, somnolence, mental status changes, and gait disturbances if concomitant use of difelikefalin with CNS depressants is necessary. Concomitant use may increase the risk for these adverse reactions.
Digoxin: (Moderate) Increase monitoring of serum digoxin concentrations and watch for potential signs and symptoms of clinical toxicity when starting, adjusting, or discontinuing lasmiditan. Concurrent use may increase digoxin exposure. Digoxin is a P-gp substrate with a narrow therapeutic index and lasmiditan is a P-gp inhibitor. Lasmiditan has also been associated with a lowering of heart rate (approximately 5 to 10 beats per minute), which may be additive to digoxin's effect on heart rate. Use this combination with caution if this magnitude of heart rate decrease may pose a concern for the patient.
Diltiazem: (Moderate) Monitor heart rate if lasmiditan is coadministered with calcium-channel blockers as concurrent use may increase the risk for bradycardia. Lasmiditan has been associated with lowering of heart rate. In a drug interaction study, addition of a single 200 mg dose of lasmiditan to another heart rate lowering drug decreased heart rate by an additional 5 beats per minute.
Dimenhydrinate: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lasmiditan and sedating H1-blockers. Concurrent use may result in additive CNS depression.
Diphenhydramine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lasmiditan and sedating H1-blockers. Concurrent use may result in additive CNS depression.
Diphenhydramine; Ibuprofen: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lasmiditan and sedating H1-blockers. Concurrent use may result in additive CNS depression.
Diphenhydramine; Naproxen: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lasmiditan and sedating H1-blockers. Concurrent use may result in additive CNS depression.
Diphenhydramine; Phenylephrine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lasmiditan and sedating H1-blockers. Concurrent use may result in additive CNS depression.
Diphenoxylate; Atropine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lasmiditan and atropine. Concurrent use may result in additive CNS depression.
Dolasetron: (Moderate) Serotonin syndrome may occur during coadministration of lasmiditan and serotonin-receptor antagonists. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome, particularly after a dose increase or the addition of other serotonergic medications to an existing regimen. Discontinue all serotonergic agents if serotonin syndrome occurs and implement appropriate medical management.
Dolutegravir: (Moderate) Monitor for increased toxicity of dolutegravir if coadministered with lasmiditan. Concurrent use may increase the plasma concentrations of dolutegravir. Dolutegravir is a P-gp substrate and lasmiditan is a P-gp inhibitor.
Dolutegravir; Lamivudine: (Moderate) Monitor for increased toxicity of dolutegravir if coadministered with lasmiditan. Concurrent use may increase the plasma concentrations of dolutegravir. Dolutegravir is a P-gp substrate and lasmiditan is a P-gp inhibitor.
Dolutegravir; Rilpivirine: (Moderate) Monitor for increased toxicity of dolutegravir if coadministered with lasmiditan. Concurrent use may increase the plasma concentrations of dolutegravir. Dolutegravir is a P-gp substrate and lasmiditan is a P-gp inhibitor.
Doravirine; Lamivudine; Tenofovir disoproxil fumarate: (Moderate) Coadministration of tenofovir disoproxil fumarate with lasmiditan may result in increased plasma concentrations of tenofovir, leading to an increase in tenofovir-related adverse effects. Tenofovir disoproxil fumarate is a P-gp substrate and lasmiditan is a P-gp inhibitor.
Dorzolamide; Timolol: (Moderate) Monitor heart rate if lasmiditan is coadministered with beta-blockers as concurrent use may increase the risk for bradycardia. Lasmiditan has been associated with lowering of heart rate. In a drug interaction study, addition of a single 200 mg dose of lasmiditan to a beta-blocker (propranolol) decreased heart rate by an additional 5 beats per minute.
Doxepin: (Moderate) Monitor for excessive sedation, somnolence, and serotonin syndrome during coadministration of lasmiditan and tricyclic antidepressants. Inform patients taking this combination of the risks and symptoms of excessive CNS depression and serotonin syndrome, particularly after a dose increase or the addition of other serotonergic medications to an existing regimen. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
Doxorubicin Liposomal: (Major) Avoid coadministration of lasmiditan with doxorubicin due to the risk for increased systemic exposure of doxorubicin that may result in increased treatment-related adverse reactions. Doxorubicin is a P-gp substrate and lasmiditan is a P-gp inhibitor. Concurrent use of P-gp inhibitors with doxorubicin has resulted in clinically significant interactions.
Doxorubicin: (Major) Avoid coadministration of lasmiditan with doxorubicin due to the risk for increased systemic exposure of doxorubicin that may result in increased treatment-related adverse reactions. Doxorubicin is a P-gp substrate and lasmiditan is a P-gp inhibitor. Concurrent use of P-gp inhibitors with doxorubicin has resulted in clinically significant interactions.
Doxylamine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lasmiditan and sedating H1-blockers. Concurrent use may result in additive CNS depression.
Doxylamine; Pyridoxine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lasmiditan and sedating H1-blockers. Concurrent use may result in additive CNS depression.
Droperidol: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lasmiditan and droperidol. Concurrent use may result in additive CNS depression.
Duloxetine: (Moderate) Serotonin syndrome may occur during coadministration of lasmiditan and serotonin norepinephrine reuptake inhibitors. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome, particularly after a dose increase or the addition of other serotonergic medications to an existing regimen. Discontinue all serotonergic agents if serotonin syndrome occurs and implement appropriate medical management.
Edoxaban: (Major) Consider an edoxaban dosage reduction for patients being treated for deep venous thrombosis (DVT) or pulmonary embolism (PE) if concomitant use of lasmiditan is necessary. Concomitant use may increase edoxaban exposure; edoxaban is a P-gp substrate and lasmiditan 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 lasmiditan. Based on clinical experience in patients with non-valvular atrial fibrillation no dose reduction is recommended for concomitant use of lasmiditan. Increased concentrations of edoxaban may occur during concomitant use of lasmiditan; monitor for increased adverse effects of edoxaban.
Efavirenz; Emtricitabine; Tenofovir Disoproxil Fumarate: (Moderate) Coadministration of tenofovir disoproxil fumarate with lasmiditan may result in increased plasma concentrations of tenofovir, leading to an increase in tenofovir-related adverse effects. Tenofovir disoproxil fumarate is a P-gp substrate and lasmiditan is a P-gp inhibitor.
Efavirenz; Lamivudine; Tenofovir Disoproxil Fumarate: (Moderate) Coadministration of tenofovir disoproxil fumarate with lasmiditan may result in increased plasma concentrations of tenofovir, leading to an increase in tenofovir-related adverse effects. Tenofovir disoproxil fumarate is a P-gp substrate and lasmiditan is a P-gp inhibitor.
Eletriptan: (Moderate) Serotonin syndrome may occur during coadministration of lasmiditan and serotonin-receptor agonists. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome, particularly after a dose increase or the addition of other serotonergic medications to an existing regimen. Discontinue all serotonergic agents if serotonin syndrome occurs and implement appropriate medical management.
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Alafenamide: (Moderate) Coadministration of tenofovir alafenamide with lasmiditan may result in increased plasma concentrations of tenofovir leading to an increase in tenofovir-related adverse effects. Tenofovir alafenamide is a P-gp substrate and lasmiditan is a P-gp inhibitor.
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Disoproxil Fumarate: (Moderate) Coadministration of tenofovir disoproxil fumarate with lasmiditan may result in increased plasma concentrations of tenofovir, leading to an increase in tenofovir-related adverse effects. Tenofovir disoproxil fumarate is a P-gp substrate and lasmiditan is a P-gp inhibitor.
Emtricitabine; Rilpivirine; Tenofovir alafenamide: (Moderate) Coadministration of tenofovir alafenamide with lasmiditan may result in increased plasma concentrations of tenofovir leading to an increase in tenofovir-related adverse effects. Tenofovir alafenamide is a P-gp substrate and lasmiditan is a P-gp inhibitor.
Emtricitabine; Rilpivirine; Tenofovir Disoproxil Fumarate: (Moderate) Coadministration of tenofovir disoproxil fumarate with lasmiditan may result in increased plasma concentrations of tenofovir, leading to an increase in tenofovir-related adverse effects. Tenofovir disoproxil fumarate is a P-gp substrate and lasmiditan is a P-gp inhibitor.
Emtricitabine; Tenofovir alafenamide: (Moderate) Coadministration of tenofovir alafenamide with lasmiditan may result in increased plasma concentrations of tenofovir leading to an increase in tenofovir-related adverse effects. Tenofovir alafenamide is a P-gp substrate and lasmiditan is a P-gp inhibitor.
Emtricitabine; Tenofovir Disoproxil Fumarate: (Moderate) Coadministration of tenofovir disoproxil fumarate with lasmiditan may result in increased plasma concentrations of tenofovir, leading to an increase in tenofovir-related adverse effects. Tenofovir disoproxil fumarate is a P-gp substrate and lasmiditan is a P-gp inhibitor.
Entacapone: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lasmiditan and entacapone. Concurrent use may result in additive CNS depression. Dopaminergic agents, such as entacapone, have also been associated with sudden sleep onset during activities of daily living such as driving, which has resulted in accidents in some cases. Prescribers should re-assess patients for drowsiness or sleepiness regularly throughout treatment, especially since events may occur well after the start of treatment.
Escitalopram: (Moderate) Serotonin syndrome may occur during coadministration of lasmiditan and selective serotonin reuptake inhibitors. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome, particularly after a dose increase or the addition of other serotonergic medications to an existing regimen. Discontinue all serotonergic agents if serotonin syndrome occurs and implement appropriate medical management.
Esmolol: (Moderate) Monitor heart rate if lasmiditan is coadministered with beta-blockers as concurrent use may increase the risk for bradycardia. Lasmiditan has been associated with lowering of heart rate. In a drug interaction study, addition of a single 200 mg dose of lasmiditan to a beta-blocker (propranolol) decreased heart rate by an additional 5 beats per minute.
Estazolam: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lasmiditan and benzodiazepines. Concurrent use may result in additive CNS depression.
Eszopiclone: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lasmiditan and eszopiclone. Concurrent use increases the risk for CNS depression and complex sleep-related behaviors (e.g., driving, talking, eating, or performing other activities while not fully awake). Patients should be instructed to contact their provider immediately if these symptoms or behaviors occur.
Ethanol: (Major) Advise patients to avoid alcohol consumption while taking CNS depressants. Alcohol consumption may result in additive CNS depression.
Etomidate: (Moderate) Although CNS depression is a desired effect of general anesthetics, patients also receiving lasmiditan should be closely monitored for additive effects that may prolong recovery after administration of a general anesthetic.
Everolimus: (Moderate) Monitor everolimus whole blood trough concentrations as appropriate and watch for everolimus-related adverse reactions if coadministration with lasmiditan is necessary. The dose of everolimus may need to be reduced. Everolimus is a P-glycoprotein (P-gp) substrate and lasmiditan 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 lasmiditan is necessary. Concomitant use may increase simvastatin exposure. Simvastatin is a P-gp substrate; lasmiditan is a P-gp inhibitor.
Felodipine: (Moderate) Monitor heart rate if lasmiditan is coadministered with calcium-channel blockers as concurrent use may increase the risk for bradycardia. Lasmiditan has been associated with lowering of heart rate. In a drug interaction study, addition of a single 200 mg dose of lasmiditan to another heart rate lowering drug decreased heart rate by an additional 5 beats per minute.
Fenfluramine: (Moderate) Use fenfluramine and lasmiditan with caution due to an increased risk of serotonin syndrome and additive CNS depression. Monitor for excessive sedation, somnolence, and serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
Fentanyl: (Moderate) Concomitant use of fentanyl with lasmiditan may cause excessive sedation, somnolence, and serotonin syndrome. Limit the use of fentanyl with lasmiditan to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression and serotonin syndrome.
Fexinidazole: (Major) Avoid concomitant use of fexinidazole and medications that cause bradycardia, such as lasmiditan, especially in patients with additional risk factors for torsade de pointes (TdP). Coadministration may increase the risk of QT/QTc prolongation and TdP. Fexinidazole is known to prolong the QT interval and medications that may cause bradycardia can increase the risk for TdP in patients with a prolonged QT/QTc interval.
Flibanserin: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lasmiditan and flibanserin. Concurrent use may result in additive CNS depression.
Fluoxetine: (Moderate) Serotonin syndrome may occur during coadministration of lasmiditan and selective serotonin reuptake inhibitors. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome, particularly after a dose increase or the addition of other serotonergic medications to an existing regimen. Discontinue all serotonergic agents if serotonin syndrome occurs and implement appropriate medical management.
Fluphenazine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lasmiditan and fluphenazine. Concurrent use may result in additive CNS depression.
Flurazepam: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lasmiditan and benzodiazepines. Concurrent use may result in additive CNS depression.
Fluvoxamine: (Moderate) Serotonin syndrome may occur during coadministration of lasmiditan and selective serotonin reuptake inhibitors. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome, particularly after a dose increase or the addition of other serotonergic medications to an existing regimen. Discontinue all serotonergic agents if serotonin syndrome occurs and implement appropriate medical management.
Food: (Major) Advise patients to avoid cannabis use while taking CNS depressants due to the risk for additive CNS depression and potential for other cognitive adverse reactions.
Frovatriptan: (Moderate) Serotonin syndrome may occur during coadministration of lasmiditan and serotonin-receptor agonists. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome, particularly after a dose increase or the addition of other serotonergic medications to an existing regimen. Discontinue all serotonergic agents if serotonin syndrome occurs and implement appropriate medical management.
Gabapentin: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lasmiditan and gabapentin. Concurrent use may result in additive CNS depression.
General anesthetics: (Moderate) Although CNS depression is a desired effect of general anesthetics, patients also receiving lasmiditan should be closely monitored for additive effects that may prolong recovery after administration of a general anesthetic.
Glecaprevir; Pibrentasvir: (Moderate) Caution is advised with coadministration of glecaprevir and lasmiditan as increased plasma concentrations of glecaprevir may occur resulting in increased risk of glecaprevir-related adverse events. Glecaprevir is a substrate of P-gp and lasmiditan is a P-gp inhibitor. (Moderate) Monitor for an increase in pibrentasvir-related adverse effects if concomitant use of lasmiditan is necessary. Concomitant use may increase pibrentasvir exposure. Pibrentasvir is a substrate of P-gp and lasmiditan is a P-gp inhibitor.
Granisetron: (Moderate) Serotonin syndrome may occur during coadministration of lasmiditan and serotonin-receptor antagonists. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome, particularly after a dose increase or the addition of other serotonergic medications to an existing regimen. Discontinue all serotonergic agents if serotonin syndrome occurs and implement appropriate medical management.
Guanfacine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lasmiditan and guanfacine. Concurrent use may result in additive CNS depression.
Haloperidol: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lasmiditan and haloperidol. Concurrent use may result in additive CNS depression.
Homatropine; Hydrocodone: (Moderate) Concomitant use of hydrocodone with lasmiditan may cause excessive sedation, somnolence, and serotonin syndrome. Limit the use of hydrocodone with lasmiditan to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression and serotonin syndrome. Avoid prescribing hydrocodone cough medications in patients taking lasmiditan.
Hydrocodone: (Moderate) Concomitant use of hydrocodone with lasmiditan may cause excessive sedation, somnolence, and serotonin syndrome. Limit the use of hydrocodone with lasmiditan to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression and serotonin syndrome. Avoid prescribing hydrocodone cough medications in patients taking lasmiditan.
Hydrocodone; Ibuprofen: (Moderate) Concomitant use of hydrocodone with lasmiditan may cause excessive sedation, somnolence, and serotonin syndrome. Limit the use of hydrocodone with lasmiditan to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression and serotonin syndrome. Avoid prescribing hydrocodone cough medications in patients taking lasmiditan.
Hydromorphone: (Moderate) Concomitant use of hydromorphone with lasmiditan may cause excessive sedation, somnolence, and serotonin syndrome. Limit the use of hydromorphone with lasmiditan to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression and serotonin syndrome.
Hydroxyzine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lasmiditan and sedating H1-blockers. Concurrent use may result in additive CNS depression.
Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate; Sodium Biphosphate: (Moderate) Serotonin syndrome may occur during coadministration of lasmiditan and methylene blue. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome, particularly after a dose increase or the addition of other serotonergic medications to an existing regimen. Discontinue all serotonergic agents if serotonin syndrome occurs and implement appropriate medical management.
Ibuprofen; Oxycodone: (Moderate) Concomitant use of oxycodone with lasmiditan may cause excessive sedation, somnolence, and serotonin syndrome. Limit the use of oxycodone with lasmiditan to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression and serotonin syndrome.
Iloperidone: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lasmiditan and iloperidone. Concurrent use may result in additive CNS depression.
Imipramine: (Moderate) Monitor for excessive sedation, somnolence, and serotonin syndrome during coadministration of lasmiditan and tricyclic antidepressants. Inform patients taking this combination of the risks and symptoms of excessive CNS depression and serotonin syndrome, particularly after a dose increase or the addition of other serotonergic medications to an existing regimen. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
Isocarboxazid: (Moderate) Monitor for excessive sedation, somnolence, and serotonin syndrome during coadministration of lasmiditan and isocarboxazid. Inform patients taking this combination of the risks and symptoms of excessive CNS depression and serotonin syndrome, particularly after a dose increase or the addition of other serotonergic medications to an existing regimen. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
Isoflurane: (Moderate) Although CNS depression is a desired effect of general anesthetics, patients also receiving lasmiditan should be closely monitored for additive effects that may prolong recovery after administration of a general anesthetic.
Isradipine: (Moderate) Monitor heart rate if lasmiditan is coadministered with calcium-channel blockers as concurrent use may increase the risk for bradycardia. Lasmiditan has been associated with lowering of heart rate. In a drug interaction study, addition of a single 200 mg dose of lasmiditan to another heart rate lowering drug decreased heart rate by an additional 5 beats per minute.
Ivabradine: (Moderate) Monitor heart rate if lasmiditan is coadministered with ivabradine as concurrent use may increase the risk for bradycardia. Lasmiditan has been associated with lowering of heart rate. In a drug interaction study, addition of a single 200 mg dose of lasmiditan to another heart rate lowering drug decreased heart rate by an additional 5 beats per minute.
Ketamine: (Moderate) Although CNS depression is a desired effect of general anesthetics, patients also receiving lasmiditan should be closely monitored for additive effects that may prolong recovery after administration of a general anesthetic.
Labetalol: (Moderate) Monitor heart rate if lasmiditan is coadministered with beta-blockers as concurrent use may increase the risk for bradycardia. Lasmiditan has been associated with lowering of heart rate. In a drug interaction study, addition of a single 200 mg dose of lasmiditan to a beta-blocker (propranolol) decreased heart rate by an additional 5 beats per minute.
Lamivudine; Tenofovir Disoproxil Fumarate: (Moderate) Coadministration of tenofovir disoproxil fumarate with lasmiditan may result in increased plasma concentrations of tenofovir, leading to an increase in tenofovir-related adverse effects. Tenofovir disoproxil fumarate is a P-gp substrate and lasmiditan is a P-gp inhibitor.
Lapatinib: (Moderate) Monitor for an increase in lapatinib-related adverse reactions if coadministration with lasmiditan is necessary. Lapatinib is a P-gp substrate and lasmiditan is a P-gp inhibitor. Increased plasma concentrations of lapatinib are likely.
Lefamulin: (Major) Avoid coadministration of lasmiditan with oral lefamulin unless the benefits outweigh the risks as concurrent use may increase lefamulin exposure and adverse effects; lasmiditan may be administered with intravenous lefamulin. Lefamulin is a P-gp substrate and lasmiditan is a P-gp inhibitor.
Lemborexant: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lemborexant and lasmiditan. Dosage adjustments of lemborexant and lasmiditan may be necessary when administered together because of potentially additive CNS effects. The risk of next-day impairment, including impaired driving, is increased if lemborexant is taken with other CNS depressants.
Levamlodipine: (Moderate) Monitor heart rate if lasmiditan is coadministered with calcium-channel blockers as concurrent use may increase the risk for bradycardia. Lasmiditan has been associated with lowering of heart rate. In a drug interaction study, addition of a single 200 mg dose of lasmiditan to another heart rate lowering drug decreased heart rate by an additional 5 beats per minute.
Levobunolol: (Moderate) Monitor heart rate if lasmiditan is coadministered with beta-blockers as concurrent use may increase the risk for bradycardia. Lasmiditan has been associated with lowering of heart rate. In a drug interaction study, addition of a single 200 mg dose of lasmiditan to a beta-blocker (propranolol) decreased heart rate by an additional 5 beats per minute.
Levodopa: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lasmiditan and levodopa. Concurrent use may result in additive CNS depression. Dopaminergic agents, such as levodopa, have also been associated with sudden sleep onset during activities of daily living such as driving, which has resulted in accidents in some cases. Prescribers should re-assess patients for drowsiness or sleepiness regularly throughout treatment, especially since events may occur well after the start of treatment.
Levomilnacipran: (Moderate) Serotonin syndrome may occur during coadministration of lasmiditan and serotonin norepinephrine reuptake inhibitors. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome, particularly after a dose increase or the addition of other serotonergic medications to an existing regimen. Discontinue all serotonergic agents if serotonin syndrome occurs and implement appropriate medical management.
Levorphanol: (Moderate) Concomitant use of levorphanol with lasmiditan may cause excessive sedation, somnolence, and serotonin syndrome. Limit the use of levorphanol with lasmiditan to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression and serotonin syndrome.
Linezolid: (Moderate) Serotonin syndrome may occur during coadministration of lasmiditan and linezolid. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome, particularly after a dose increase or the addition of other serotonergic medications to an existing regimen. Discontinue all serotonergic agents if serotonin syndrome occurs and implement appropriate medical management.
Lisdexamfetamine: (Moderate) Serotonin syndrome may occur during coadministration of lasmiditan and amphetamines. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly after a dose increase or the addition of other serotonergic medications to an existing regimen. Discontinue all serotonergic agents if serotonin syndrome occurs and implement appropriate medical management.
Lithium: (Moderate) Serotonin syndrome may occur during coadministration of lasmiditan and lithium. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome, particularly after a dose increase or the addition of other serotonergic medications to an existing regimen. Discontinue all serotonergic agents if serotonin syndrome occurs and implement appropriate medical management.
Lofexidine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lasmiditan and lofexidine. Concurrent use may result in additive CNS depression.
Loperamide: (Moderate) Monitor for loperamide-associated adverse reactions, such as CNS effects and cardiac toxicities (i.e., syncope, ventricular tachycardia, QT prolongation, torsade de pointes, cardiac arrest), if coadministered with lasmiditan. Concurrent use may increase loperamide exposure. Loperamide is a P-gp substrate and lasmiditan is a P-gp inhibitor. Coadministration with another P-gp inhibitor increased loperamide plasma concentrations by 2- to 3-fold.
Loperamide; Simethicone: (Moderate) Monitor for loperamide-associated adverse reactions, such as CNS effects and cardiac toxicities (i.e., syncope, ventricular tachycardia, QT prolongation, torsade de pointes, cardiac arrest), if coadministered with lasmiditan. Concurrent use may increase loperamide exposure. Loperamide is a P-gp substrate and lasmiditan is a P-gp inhibitor. Coadministration with another P-gp inhibitor increased loperamide plasma concentrations by 2- to 3-fold.
Lorazepam: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lasmiditan and benzodiazepines. Concurrent use may result in additive CNS depression.
Lorcaserin: (Moderate) Serotonin syndrome may occur during coadministration of lasmiditan and lorcaserin. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome, particularly after a dose increase or the addition of other serotonergic medications to an existing regimen. Discontinue all serotonergic agents if serotonin syndrome occurs and implement appropriate medical management.
Lovastatin: (Moderate) Monitor for an increase in lovastatin-related adverse reactions, including myopathy and rhabdomyolysis, if coadministration with lasmiditan is necessary. Concomitant use may increase lovastatin exposure. Lovastatin is a P-gp substrate; lasmiditan is a P-gp inhibitor.
Loxapine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lasmiditan and loxapine. Concurrent use may result in additive CNS depression.
Lumateperone: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lumateperone and lasmiditan. Concurrent use may result in additive CNS depression.
Lurasidone: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lasmiditan and lurasidone. Concurrent use may result in additive CNS depression.
Maprotiline: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lasmiditan and maprotiline. Concurrent use may result in additive CNS depression.
Maraviroc: (Moderate) Monitor for an increase in maraviroc-related adverse reactions if coadministration with lasmiditan is necessary. Concomitant use may increase maraviroc exposure. Maraviroc is a P-gp substrate; lasmiditan is a P-gp inhibitor.
Meclizine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lasmiditan and sedating H1-blockers. Concurrent use may result in additive CNS depression.
Mefloquine: (Moderate) Monitor for an increase in mefloquine-related adverse effects if concomitant use of lasmiditan is necessary. Concomitant use may increase mefloquine exposure. Mefloquine is a P-gp substrate and lasmiditan is a P-gp inhibitor.
Melatonin: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lasmiditan and melatonin. Concurrent use may result in additive CNS depression.
Meperidine: (Moderate) Concomitant use of meperidine with lasmiditan may cause excessive sedation, somnolence, and serotonin syndrome. Limit the use of meperidine with lasmiditan to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression and serotonin syndrome.
Meprobamate: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lasmiditan and meprobamate. Concurrent use may result in additive CNS depression.
Metaxalone: (Moderate) Monitor for excessive sedation, somnolence, and serotonin syndrome during coadministration of lasmiditan and metaxalone. Inform patients taking this combination of the risks and symptoms of excessive CNS depression and serotonin syndrome, particularly after a dose increase or the addition of other serotonergic medications to an existing regimen. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
Methadone: (Moderate) Concomitant use of methadone with lasmiditan may cause excessive sedation, somnolence, and serotonin syndrome. Limit the use of methadone with lasmiditan to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression and serotonin syndrome.
Methamphetamine: (Moderate) Serotonin syndrome may occur during coadministration of lasmiditan and amphetamines. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly after a dose increase or the addition of other serotonergic medications to an existing regimen. Discontinue all serotonergic agents if serotonin syndrome occurs and implement appropriate medical management.
Methenamine; Sodium Acid Phosphate; Methylene Blue; Hyoscyamine: (Moderate) Serotonin syndrome may occur during coadministration of lasmiditan and methylene blue. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome, particularly after a dose increase or the addition of other serotonergic medications to an existing regimen. Discontinue all serotonergic agents if serotonin syndrome occurs and implement appropriate medical management.
Methocarbamol: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lasmiditan and methocarbamol. Concurrent use may result in additive CNS depression.
Methohexital: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lasmiditan and barbiturates. Concurrent use may result in additive CNS depression.
Methyldopa: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lasmiditan and methyldopa. Concurrent use may result in additive CNS depression.
Methylene Blue: (Moderate) Serotonin syndrome may occur during coadministration of lasmiditan and methylene blue. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome, particularly after a dose increase or the addition of other serotonergic medications to an existing regimen. Discontinue all serotonergic agents if serotonin syndrome occurs and implement appropriate medical management.
Methylphenidate Derivatives: (Moderate) Serotonin syndrome may occur during coadministration of lasmiditan and methylphenidate derivatives. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome, particularly after a dose increase or the addition of other serotonergic medications to an existing regimen. Discontinue all serotonergic agents if serotonin syndrome occurs and implement appropriate medical management.
Methylphenidate: (Moderate) Serotonin syndrome may occur during coadministration of lasmiditan and methylphenidate derivatives. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome, particularly after a dose increase or the addition of other serotonergic medications to an existing regimen. Discontinue all serotonergic agents if serotonin syndrome occurs and implement appropriate medical management.
Metoclopramide: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lasmiditan and metoclopramide. Concurrent use may result in additive CNS depression.
Metoprolol: (Moderate) Monitor heart rate if lasmiditan is coadministered with beta-blockers as concurrent use may increase the risk for bradycardia. Lasmiditan has been associated with lowering of heart rate. In a drug interaction study, addition of a single 200 mg dose of lasmiditan to a beta-blocker (propranolol) decreased heart rate by an additional 5 beats per minute.
Metoprolol; Hydrochlorothiazide, HCTZ: (Moderate) Monitor heart rate if lasmiditan is coadministered with beta-blockers as concurrent use may increase the risk for bradycardia. Lasmiditan has been associated with lowering of heart rate. In a drug interaction study, addition of a single 200 mg dose of lasmiditan to a beta-blocker (propranolol) decreased heart rate by an additional 5 beats per minute.
Midazolam: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lasmiditan and benzodiazepines. Concurrent use may result in additive CNS depression.
Milnacipran: (Moderate) Serotonin syndrome may occur during coadministration of lasmiditan and serotonin norepinephrine reuptake inhibitors. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome, particularly after a dose increase or the addition of other serotonergic medications to an existing regimen. Discontinue all serotonergic agents if serotonin syndrome occurs and implement appropriate medical management.
Mirtazapine: (Moderate) Monitor for excessive sedation, somnolence, and serotonin syndrome during coadministration of lasmiditan and mirtazapine. Inform patients taking this combination of the risks and symptoms of excessive CNS depression and serotonin syndrome, particularly after a dose increase or the addition of other serotonergic medications to an existing regimen. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
Molindone: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lasmiditan and molindone. Concurrent use may result in additive CNS depression.
Morphine: (Moderate) Monitor for an increase in morphine-related adverse reactions, including hypotension, sedation, and respiratory depression, if coadministration with lasmiditan is necessary; decrease the dose of morphine as necessary. Morphine is a P-gp substrate and lasmiditan 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 lasmiditan is necessary; decrease the dose of morphine as necessary. Morphine is a P-gp substrate and lasmiditan is a P-gp inhibitor. Coadministration with P-gp inhibitors can increase morphine exposure by about 2-fold.
Nabilone: (Moderate) Concomitant administration of lasmiditan and other CNS depressant drugs has not been evaluated in clinical studies. Because of the potential of lasmiditan to cause sedation, as well as other cognitive and/or neuropsychiatric adverse reactions, lasmiditan should be used with caution if used in combination with alcohol or other CNS depressants.
Nadolol: (Moderate) Monitor heart rate if lasmiditan is coadministered with beta-blockers as concurrent use may increase the risk for bradycardia. Lasmiditan has been associated with lowering of heart rate. In a drug interaction study, addition of a single 200 mg dose of lasmiditan to a beta-blocker (propranolol) decreased heart rate by an additional 5 beats per minute.
Nalbuphine: (Moderate) Concomitant use of nalbuphine with lasmiditan may cause excessive sedation, somnolence, and serotonin syndrome. Limit the use of nalbuphine with lasmiditan to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression and serotonin syndrome.
Naldemedine: (Moderate) Monitor for naldemedine-related adverse reactions if coadministered with lasmiditan. Naldemedine plasma concentrations may increase during concomitant use. Naldemedine is a P-gp substrate; lasmiditan is a P-gp inhibitor.
Nanoparticle Albumin-Bound Sirolimus: (Major) Avoid concomitant use of sirolimus and lasmiditan. Coadministration may increase sirolimus concentrations and increase the risk for sirolimus-related adverse effects. Sirolimus is a P-gp substrate and lasmiditan is a P-gp inhibitor.
Naratriptan: (Moderate) Serotonin syndrome may occur during coadministration of lasmiditan and serotonin-receptor agonists. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome, particularly after a dose increase or the addition of other serotonergic medications to an existing regimen. Discontinue all serotonergic agents if serotonin syndrome occurs and implement appropriate medical management.
Nebivolol: (Moderate) Monitor heart rate if lasmiditan is coadministered with beta-blockers as concurrent use may increase the risk for bradycardia. Lasmiditan has been associated with lowering of heart rate. In a drug interaction study, addition of a single 200 mg dose of lasmiditan to a beta-blocker (propranolol) decreased heart rate by an additional 5 beats per minute.
Nebivolol; Valsartan: (Moderate) Monitor heart rate if lasmiditan is coadministered with beta-blockers as concurrent use may increase the risk for bradycardia. Lasmiditan has been associated with lowering of heart rate. In a drug interaction study, addition of a single 200 mg dose of lasmiditan to a beta-blocker (propranolol) decreased heart rate by an additional 5 beats per minute.
Nefazodone: (Moderate) Monitor for excessive sedation, somnolence, and serotonin syndrome during coadministration of lasmiditan and nefazodone. Inform patients taking this combination of the risks and symptoms of excessive CNS depression and serotonin syndrome, particularly after a dose increase or the addition of other serotonergic medications to an existing regimen. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
Nicardipine: (Moderate) Monitor heart rate if lasmiditan is coadministered with calcium-channel blockers as concurrent use may increase the risk for bradycardia. Lasmiditan has been associated with lowering of heart rate. In a drug interaction study, addition of a single 200 mg dose of lasmiditan to another heart rate lowering drug decreased heart rate by an additional 5 beats per minute.
NIFEdipine: (Moderate) Monitor heart rate if lasmiditan is coadministered with calcium-channel blockers as concurrent use may increase the risk for bradycardia. Lasmiditan has been associated with lowering of heart rate. In a drug interaction study, addition of a single 200 mg dose of lasmiditan to another heart rate lowering drug decreased heart rate by an additional 5 beats per minute.
Nimodipine: (Moderate) Monitor heart rate if lasmiditan is coadministered with calcium-channel blockers as concurrent use may increase the risk for bradycardia. Lasmiditan has been associated with lowering of heart rate. In a drug interaction study, addition of a single 200 mg dose of lasmiditan to another heart rate lowering drug decreased heart rate by an additional 5 beats per minute.
Nisoldipine: (Moderate) Monitor heart rate if lasmiditan is coadministered with calcium-channel blockers as concurrent use may increase the risk for bradycardia. Lasmiditan has been associated with lowering of heart rate. In a drug interaction study, addition of a single 200 mg dose of lasmiditan to another heart rate lowering drug decreased heart rate by an additional 5 beats per minute.
Nortriptyline: (Moderate) Monitor for excessive sedation, somnolence, and serotonin syndrome during coadministration of lasmiditan and tricyclic antidepressants. Inform patients taking this combination of the risks and symptoms of excessive CNS depression and serotonin syndrome, particularly after a dose increase or the addition of other serotonergic medications to an existing regimen. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
Olanzapine: (Moderate) Monitor for excessive sedation, somnolence, and serotonin syndrome during coadministration of lasmiditan and olanzapine. Inform patients taking this combination of the risks and symptoms of excessive CNS depression and serotonin syndrome, particularly after a dose increase or the addition of other serotonergic medications to an existing regimen. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
Olanzapine; Fluoxetine: (Moderate) Monitor for excessive sedation, somnolence, and serotonin syndrome during coadministration of lasmiditan and olanzapine. Inform patients taking this combination of the risks and symptoms of excessive CNS depression and serotonin syndrome, particularly after a dose increase or the addition of other serotonergic medications to an existing regimen. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. (Moderate) Serotonin syndrome may occur during coadministration of lasmiditan and selective serotonin reuptake inhibitors. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome, particularly after a dose increase or the addition of other serotonergic medications to an existing regimen. Discontinue all serotonergic agents if serotonin syndrome occurs and implement appropriate medical management.
Olanzapine; Samidorphan: (Moderate) Monitor for excessive sedation, somnolence, and serotonin syndrome during coadministration of lasmiditan and olanzapine. Inform patients taking this combination of the risks and symptoms of excessive CNS depression and serotonin syndrome, particularly after a dose increase or the addition of other serotonergic medications to an existing regimen. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
Oliceridine: (Moderate) Concomitant use of oliceridine with lasmiditan may cause excessive sedation and somnolence. Limit the use of oliceridine with lasmiditan to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Also monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome.
Olmesartan; Amlodipine; Hydrochlorothiazide, HCTZ: (Moderate) Monitor heart rate if lasmiditan is coadministered with calcium-channel blockers as concurrent use may increase the risk for bradycardia. Lasmiditan has been associated with lowering of heart rate. In a drug interaction study, addition of a single 200 mg dose of lasmiditan to another heart rate lowering drug decreased heart rate by an additional 5 beats per minute.
Ondansetron: (Moderate) Serotonin syndrome may occur during coadministration of lasmiditan and serotonin-receptor antagonists. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome, particularly after a dose increase or the addition of other serotonergic medications to an existing regimen. Discontinue all serotonergic agents if serotonin syndrome occurs and implement appropriate medical management.
Opicapone: (Moderate) Because of the potential of lasmiditan to cause sedation, as well as other cognitive and/or neuropsychiatric adverse reactions, lasmiditan should be used with caution in combination with other drugs having CNS depressant effects, such as opicapone. COMT inhibitors, such as opicapone, have also been associated with sudden sleep onset during activities of daily living such as driving, which has resulted in accidents in some cases. Prescribers should re-assess patients for drowsiness or sleepiness regularly throughout treatment, especially since events may occur well after the start of treatment. Patients should be advised to avoid driving or other tasks requiring mental alertness until they know how the combination affects them.
Orphenadrine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lasmiditan and orphenadrine. Concurrent use may result in additive CNS depression.
Oxazepam: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lasmiditan and benzodiazepines. Concurrent use may result in additive CNS depression.
Oxycodone: (Moderate) Concomitant use of oxycodone with lasmiditan may cause excessive sedation, somnolence, and serotonin syndrome. Limit the use of oxycodone with lasmiditan to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression and serotonin syndrome.
Oxymorphone: (Moderate) Concomitant use of oxymorphone with lasmiditan may cause excessive sedation, somnolence, and serotonin syndrome. Limit the use of oxymorphone with lasmiditan to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression and serotonin syndrome.
Ozanimod: (Major) Coadministration of ozanimod with lasmiditan is not recommended; monitor patients for hypertension if used together. An active metabolite of ozanimod inhibits MAO-B, creating potential for hypertensive crisis when give with medications that increase serotonin, such as lasmiditan.
Paliperidone: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lasmiditan and paliperidone. Concurrent use may result in additive CNS depression.
Palonosetron: (Moderate) Serotonin syndrome may occur during coadministration of lasmiditan and serotonin-receptor antagonists. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome, particularly after a dose increase or the addition of other serotonergic medications to an existing regimen. Discontinue all serotonergic agents if serotonin syndrome occurs and implement appropriate medical management.
Paroxetine: (Moderate) Serotonin syndrome may occur during coadministration of lasmiditan and selective serotonin reuptake inhibitors. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome, particularly after a dose increase or the addition of other serotonergic medications to an existing regimen. Discontinue all serotonergic agents if serotonin syndrome occurs and implement appropriate medical management.
Pazopanib: (Major) Avoid coadministration of pazopanib and lasmiditan due to the potential for increased pazopanib exposure. Pazopanib is a P-gp substrate; lasmiditan is a P-gp inhibitor. Consider selection of an alternative concomitant medication with no or minimal potential to inhibit P-gp.
Pentazocine; Naloxone: (Moderate) Concomitant use of pentazocine with lasmiditan may cause excessive sedation, somnolence, and serotonin syndrome. Limit the use of pentazocine with lasmiditan to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression and serotonin syndrome.
Pentobarbital: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lasmiditan and barbiturates. Concurrent use may result in additive CNS depression.
Perampanel: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lasmiditan and perampanel. Concurrent use may result in additive CNS depression.
Perindopril; Amlodipine: (Moderate) Monitor heart rate if lasmiditan is coadministered with calcium-channel blockers as concurrent use may increase the risk for bradycardia. Lasmiditan has been associated with lowering of heart rate. In a drug interaction study, addition of a single 200 mg dose of lasmiditan to another heart rate lowering drug decreased heart rate by an additional 5 beats per minute.
Perphenazine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lasmiditan and perphenazine. Concurrent use may result in additive CNS depression.
Perphenazine; Amitriptyline: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lasmiditan and perphenazine. Concurrent use may result in additive CNS depression. (Moderate) Monitor for excessive sedation, somnolence, and serotonin syndrome during coadministration of lasmiditan and tricyclic antidepressants. Inform patients taking this combination of the risks and symptoms of excessive CNS depression and serotonin syndrome, particularly after a dose increase or the addition of other serotonergic medications to an existing regimen. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
Phenelzine: (Major) Avoid coadministration of lasmiditan and phenelzine due to the risk of serotonin syndrome. Additionally, additive CNS depression may occur. If concomitant use is unavoidable, use the lowest appropriate medication dosages, and monitor for excessive sedation, somnolence, and serotonin syndrome. Inform patients taking this combination of the risks and symptoms of excessive CNS depression and serotonin syndrome, particularly after a dose increase or the addition of other serotonergic medications to an existing regimen. Discontinue all serotonergic agents if serotonin syndrome occurs and implement appropriate medical management.
Phenobarbital: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lasmiditan and barbiturates. Concurrent use may result in additive CNS depression.
Phenobarbital; Hyoscyamine; Atropine; Scopolamine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lasmiditan and atropine. Concurrent use may result in additive CNS depression. (Moderate) Monitor for excessive sedation and somnolence during coadministration of lasmiditan and barbiturates. Concurrent use may result in additive CNS depression. (Moderate) Monitor for excessive sedation and somnolence during coadministration of lasmiditan and scopolamine. Concurrent use may result in additive CNS depression.
Pimavanserin: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lasmiditan and pimavanserin. Concurrent use may result in additive CNS depression.
Pimozide: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lasmiditan and pimozide. Concurrent use may result in additive CNS depression.
Pindolol: (Moderate) Monitor heart rate if lasmiditan is coadministered with beta-blockers as concurrent use may increase the risk for bradycardia. Lasmiditan has been associated with lowering of heart rate. In a drug interaction study, addition of a single 200 mg dose of lasmiditan to a beta-blocker (propranolol) decreased heart rate by an additional 5 beats per minute.
Pitavastatin: (Moderate) Monitor for an increase in pitavastatin-related adverse reactions, including myopathy and rhabdomyolysis, if coadministration with lasmiditan is necessary. Concomitant use may increase pitavastatin exposure. Pitavastatin is a P-gp substrate; lasmiditan is a P-gp inhibitor.
Ponesimod: (Major) Avoid concomitant use of ponesimod and medications that may decrease heart rate such as lasmiditan due to the risk for severe bradycardia and heart block. Consider consultation from a cardiologist if concomitant use is necessary.
Posaconazole: (Moderate) Monitor for an increase in posaconazole-related adverse reactions if coadministration with lasmiditan is necessary. Concomitant use may increase posaconazole exposure. Posaconazole is a P-gp substrate; lasmiditan is a P-gp inhibitor.
Pralsetinib: (Major) Avoid concomitant use of lasmiditan 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 lasmiditan is a P-gp inhibitor. Coadministration with another P-gp inhibitor increased the overall exposure of pralsetinib by 81%.
Pramipexole: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lasmiditan and pramipexole. Concurrent use may result in additive CNS depression. Dopaminergic agents, such as pramipexole, have also been associated with sudden sleep onset during activities of daily living such as driving, which has resulted in accidents in some cases. Prescribers should re-assess patients for drowsiness or sleepiness regularly throughout treatment, especially since events may occur well after the start of treatment.
Pregabalin: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lasmiditan and pregabalin. Concurrent use may result in additive CNS depression.
Primidone: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lasmiditan and barbiturates. Concurrent use may result in additive CNS depression.
Probenecid; Colchicine: (Major) Avoid concomitant use of colchicine and lasmiditan 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 lasmiditan is a P-gp inhibitor.
Prochlorperazine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lasmiditan and prochlorperazine. Concurrent use may result in additive CNS depression.
Promethazine; Dextromethorphan: (Moderate) Serotonin syndrome may occur during coadministration of lasmiditan and dextromethorphan. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome, particularly after a dose increase or the addition of other serotonergic medications to an existing regimen. Discontinue all serotonergic agents if serotonin syndrome occurs and implement appropriate medical management.
Propofol: (Moderate) Although CNS depression is a desired effect of general anesthetics, patients also receiving lasmiditan should be closely monitored for additive effects that may prolong recovery after administration of a general anesthetic.
Propranolol: (Moderate) Monitor heart rate if lasmiditan is coadministered with beta-blockers as concurrent use may increase the risk for bradycardia. Lasmiditan has been associated with lowering of heart rate. In a drug interaction study, addition of a single 200 mg dose of lasmiditan to a beta-blocker (propranolol) decreased heart rate by an additional 5 beats per minute.
Protriptyline: (Moderate) Monitor for excessive sedation, somnolence, and serotonin syndrome during coadministration of lasmiditan and tricyclic antidepressants. Inform patients taking this combination of the risks and symptoms of excessive CNS depression and serotonin syndrome, particularly after a dose increase or the addition of other serotonergic medications to an existing regimen. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
Pseudoephedrine; Triprolidine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lasmiditan and sedating H1-blockers. Concurrent use may result in additive CNS depression.
Quazepam: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lasmiditan and benzodiazepines. Concurrent use may result in additive CNS depression.
Quetiapine: (Moderate) Monitor for excessive sedation, somnolence, and serotonin syndrome during coadministration of lasmiditan and quetiapine. Inform patients taking this combination of the risks and symptoms of excessive CNS depression and serotonin syndrome, particularly after a dose increase or the addition of other serotonergic medications to an existing regimen. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
Ramelteon: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lasmiditan and ramelteon. Concurrent use may result in additive CNS depression.
Ranolazine: (Moderate) Monitor for an increase in ranolazine-related adverse reactions if coadministration with lasmiditan is necessary and consider a ranolazine dosage adjustment. Concomitant use may increase ranolazine exposure. Ranolazine is a P-gp substrate; lasmiditan is a P-gp inhibitor.
Rasagiline: (Moderate) Monitor for excessive sedation, somnolence, and serotonin syndrome during coadministration of lasmiditan and rasagiline. Inform patients taking this combination of the risks and symptoms of excessive CNS depression and serotonin syndrome, particularly after a dose increase or the addition of other serotonergic medications to an existing regimen. Dopaminergic agents, such as rasagiline, have also been associated with sudden sleep onset during activities of daily living such as driving, which has resulted in accidents in some cases. Prescribers should re-assess patients for drowsiness or sleepiness regularly throughout treatment, especially since events may occur well after the start of treatment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
Relugolix: (Major) Avoid concomitant use of relugolix and lasmiditan. Concomitant use may increase relugolix exposure and the risk of relugolix-related adverse effects. If use together is unavoidable, administer relugolix first and separate dosing by at least 6 hours. Alternatively, relugolix therapy may be interrupted for up to 14 days if a short course of lasmiditan is required; if treatment is interrupted for more than 7 days, resume relugolix with a 360 mg loading dose followed by 120 mg once daily. Relugolix is a P-gp substrate and lasmiditan is a P-gp inhibitor.
Relugolix; Estradiol; Norethindrone acetate: (Major) Avoid concomitant use of relugolix and lasmiditan. Concomitant use may increase relugolix exposure and the risk of relugolix-related adverse effects. If use together is unavoidable, administer relugolix first and separate dosing by at least 6 hours. Alternatively, relugolix therapy may be interrupted for up to 14 days if a short course of lasmiditan is required; if treatment is interrupted for more than 7 days, resume relugolix with a 360 mg loading dose followed by 120 mg once daily. Relugolix is a P-gp substrate and lasmiditan is a P-gp inhibitor.
Remifentanil: (Moderate) Concomitant use of remifentanil with lasmiditan may cause excessive sedation, somnolence, and serotonin syndrome. Limit the use of remifentanil with lasmiditan to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression and serotonin syndrome.
Remimazolam: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lasmiditan and benzodiazepines. Concurrent use may result in additive CNS depression.
Repotrectinib: (Major) Avoid coadministration of repotrectinib with lasmiditan due to increased repotrectinib exposure which may increase the risk for repotrectinib-related adverse effects. Repotrectinib is a P-gp substrate and lasmiditan is a P-gp inhibitor.
Rifaximin: (Moderate) Monitor for an increase in rifaximin-related adverse reactions if coadministration with lasmiditan 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 lasmiditan is a P-gp inhibitor. Coadministration with another P-gp inhibitor increased rifaximin overall exposure by 124-fold.
Rimegepant: (Major) Avoid a second dose of rimegepant within 48 hours if coadministered with lasmiditan; concurrent use may increase rimegepant exposure. Rimegepant is a P-gp substrate and lasmiditan is a P-gp inhibitor.
Risperidone: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lasmiditan and risperidone. Concurrent use may result in additive CNS depression.
Rizatriptan: (Moderate) Serotonin syndrome may occur during coadministration of lasmiditan and serotonin-receptor agonists. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome, particularly after a dose increase or the addition of other serotonergic medications to an existing regimen. Discontinue all serotonergic agents if serotonin syndrome occurs and implement appropriate medical management.
Ropinirole: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lasmiditan and ropinirole. Concurrent use may result in additive CNS depression. Dopaminergic agents, such as ropinirole, have also been associated with sudden sleep onset during activities of daily living such as driving, which has resulted in accidents in some cases. Prescribers should re-assess patients for drowsiness or sleepiness regularly throughout treatment, especially since events may occur well after the start of treatment.
Rotigotine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lasmiditan and rotigotine. Concurrent use may result in additive CNS depression. Dopaminergic agents, such as rotigotine, have also been associated with sudden sleep onset during activities of daily living such as driving, which has resulted in accidents in some cases. Prescribers should re-assess patients for drowsiness or sleepiness regularly throughout treatment, especially since events may occur well after the start of treatment.
Safinamide: (Moderate) Monitor for excessive sedation, somnolence, and serotonin syndrome during coadministration of lasmiditan and safinamide. Inform patients taking this combination of the risks and symptoms of excessive CNS depression and serotonin syndrome, particularly after a dose increase or the addition of other serotonergic medications to an existing regimen. Dopaminergic agents, such as safinamide, have also been associated with sudden sleep onset during activities of daily living such as driving, which has resulted in accidents in some cases. Prescribers should re-assess patients for drowsiness or sleepiness regularly throughout treatment, especially since events may occur well after the start of treatment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
Saquinavir: (Moderate) Monitor for an increase in saquinavir-related adverse reactions if coadministration with lasmiditan is necessary. Concomitant use may increase saquinavir exposure. Saquinavir is a P-gp substrate; lasmiditan is a P-gp inhibitor.
Scopolamine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lasmiditan and scopolamine. Concurrent use may result in additive CNS depression.
Secobarbital: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lasmiditan and barbiturates. Concurrent use may result in additive CNS depression.
Sedating H1-blockers: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lasmiditan and sedating H1-blockers. Concurrent use may result in additive CNS depression.
Selective serotonin reuptake inhibitors: (Moderate) Serotonin syndrome may occur during coadministration of lasmiditan and selective serotonin reuptake inhibitors. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome, particularly after a dose increase or the addition of other serotonergic medications to an existing regimen. Discontinue all serotonergic agents if serotonin syndrome occurs and implement appropriate medical management.
Selegiline: (Moderate) Monitor for excessive sedation, somnolence, and serotonin syndrome during coadministration of lasmiditan and selegiline. Inform patients taking this combination of the risks and symptoms of excessive CNS depression and serotonin syndrome, particularly after a dose increase or the addition of other serotonergic medications to an existing regimen. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
Serdexmethylphenidate; Dexmethylphenidate: (Moderate) Serotonin syndrome may occur during coadministration of lasmiditan and methylphenidate derivatives. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome, particularly after a dose increase or the addition of other serotonergic medications to an existing regimen. Discontinue all serotonergic agents if serotonin syndrome occurs and implement appropriate medical management.
Serotonin norepinephrine reuptake inhibitors: (Moderate) Serotonin syndrome may occur during coadministration of lasmiditan and serotonin norepinephrine reuptake inhibitors. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome, particularly after a dose increase or the addition of other serotonergic medications to an existing regimen. Discontinue all serotonergic agents if serotonin syndrome occurs and implement appropriate medical management.
Serotonin-Receptor Agonists: (Moderate) Serotonin syndrome may occur during coadministration of lasmiditan and serotonin-receptor agonists. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome, particularly after a dose increase or the addition of other serotonergic medications to an existing regimen. Discontinue all serotonergic agents if serotonin syndrome occurs and implement appropriate medical management.
Serotonin-Receptor Antagonists: (Moderate) Serotonin syndrome may occur during coadministration of lasmiditan and serotonin-receptor antagonists. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome, particularly after a dose increase or the addition of other serotonergic medications to an existing regimen. Discontinue all serotonergic agents if serotonin syndrome occurs and implement appropriate medical management.
Sertraline: (Moderate) Serotonin syndrome may occur during coadministration of lasmiditan and selective serotonin reuptake inhibitors. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome, particularly after a dose increase or the addition of other serotonergic medications to an existing regimen. Discontinue all serotonergic agents if serotonin syndrome occurs and implement appropriate medical management.
Sevoflurane: (Moderate) Although CNS depression is a desired effect of general anesthetics, patients also receiving lasmiditan should be closely monitored for additive effects that may prolong recovery after administration of a general anesthetic.
Silodosin: (Major) Avoid coadministration of silodosin and lasmiditan due to the potential for increased silodosin exposure. Consider if an alternative to silodosin will be appropriate for the patient. In vitro data indicate that silodosin is a P-glycoprotein substrate; lasmiditan is a P-gp inhibitor.
Simvastatin: (Moderate) Monitor for an increase in simvastatin-related adverse reactions, including myopathy and rhabdomyolysis, if coadministration with lasmiditan is necessary. Concomitant use may increase simvastatin exposure. Simvastatin is a P-gp substrate; lasmiditan is a P-gp inhibitor.
Sirolimus: (Moderate) Monitor sirolimus concentrations and adjust sirolimus dosage as appropriate during concomitant use of lasmiditan. Coadministration may increase sirolimus concentrations and the risk for sirolimus-related adverse effects. Sirolimus is a P-gp substrate and lasmiditan is a P-gp inhibitor.
Sodium Oxybate: (Moderate) Monitor for excessive sedation, somnolence, and serotonin syndrome during coadministration of lasmiditan and sodium oxybate. Inform patients taking this combination of the risks and symptoms of excessive CNS depression and serotonin syndrome, particularly after a dose increase or the addition of other serotonergic medications to an existing regimen. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
Sotalol: (Moderate) Monitor heart rate if lasmiditan is coadministered with beta-blockers as concurrent use may increase the risk for bradycardia. Lasmiditan has been associated with lowering of heart rate. In a drug interaction study, addition of a single 200 mg dose of lasmiditan to a beta-blocker (propranolol) decreased heart rate by an additional 5 beats per minute.
St. John's Wort, Hypericum perforatum: (Moderate) Serotonin syndrome may occur during coadministration of lasmiditan and St. John's Wort. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome, particularly after a dose increase or the addition of other serotonergic medications to an existing regimen. Discontinue all serotonergic agents if serotonin syndrome occurs and implement appropriate medical management.
Stiripentol: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lasmiditan and stiripentol. Concurrent use may result in additive CNS depression.
Sufentanil: (Moderate) Concomitant use of sufentanil with lasmiditan may cause excessive sedation, somnolence, and serotonin syndrome. Limit the use of sufentanil with lasmiditan to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression and serotonin syndrome.
Sumatriptan: (Moderate) Serotonin syndrome may occur during coadministration of lasmiditan and serotonin-receptor agonists. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome, particularly after a dose increase or the addition of other serotonergic medications to an existing regimen. Discontinue all serotonergic agents if serotonin syndrome occurs and implement appropriate medical management.
Sumatriptan; Naproxen: (Moderate) Serotonin syndrome may occur during coadministration of lasmiditan and serotonin-receptor agonists. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome, particularly after a dose increase or the addition of other serotonergic medications to an existing regimen. Discontinue all serotonergic agents if serotonin syndrome occurs and implement appropriate medical management.
Suvorexant: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lasmiditan and suvorexant. Concurrent use may result in additive CNS depression.
Talazoparib: (Moderate) Monitor for an increase in talazoparib-related adverse reactions if coadministration with lasmiditan is necessary. Talazoparib is a P-gp substrate and lasmiditan is a P-gp inhibitor.
Tapentadol: (Moderate) Concomitant use of tapentadol with lasmiditan may cause excessive sedation, somnolence, and serotonin syndrome. Limit the use of tapentadol with lasmiditan to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression and serotonin syndrome.
Tasimelteon: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lasmiditan and tasimelteon. Concurrent use may result in additive CNS depression.
Tedizolid: (Moderate) Serotonin syndrome may occur during coadministration of lasmiditan and tedizolid. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome, particularly after a dose increase or the addition of other serotonergic medications to an existing regimen. Discontinue all serotonergic agents if serotonin syndrome occurs and implement appropriate medical management.
Telmisartan; Amlodipine: (Moderate) Monitor heart rate if lasmiditan is coadministered with calcium-channel blockers as concurrent use may increase the risk for bradycardia. Lasmiditan has been associated with lowering of heart rate. In a drug interaction study, addition of a single 200 mg dose of lasmiditan to another heart rate lowering drug decreased heart rate by an additional 5 beats per minute.
Temazepam: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lasmiditan and benzodiazepines. Concurrent use may result in additive CNS depression.
Temsirolimus: (Moderate) Monitor for an increase in temsirolimus-related adverse reactions if coadministration with lasmiditan is necessary due to the risk of increased temsirolimus exposure. Temsirolimus is a P-gp substrate and lasmiditan is a P-gp inhibitor. Coadministration is likely to increase plasma concentrations of temsirolimus.
Tenofovir Alafenamide: (Moderate) Coadministration of tenofovir alafenamide with lasmiditan may result in increased plasma concentrations of tenofovir leading to an increase in tenofovir-related adverse effects. Tenofovir alafenamide is a P-gp substrate and lasmiditan is a P-gp inhibitor.
Tenofovir Alafenamide: (Moderate) Coadministration of tenofovir alafenamide with lasmiditan may result in increased plasma concentrations of tenofovir leading to an increase in tenofovir-related adverse effects. Tenofovir alafenamide is a P-gp substrate and lasmiditan is a P-gp inhibitor.
Tenofovir Disoproxil Fumarate: (Moderate) Coadministration of tenofovir disoproxil fumarate with lasmiditan may result in increased plasma concentrations of tenofovir, leading to an increase in tenofovir-related adverse effects. Tenofovir disoproxil fumarate is a P-gp substrate and lasmiditan is a P-gp inhibitor.
Tetrabenazine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lasmiditan and tetrabenazine. Concurrent use may result in additive CNS depression.
Thalidomide: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lasmiditan and thalidomide. Concurrent use may result in additive CNS depression.
Thioridazine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lasmiditan and thioridazine. Concurrent use may result in additive CNS depression.
Thiothixene: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lasmiditan and thiothixene. Concurrent use may result in additive CNS depression.
Ticagrelor: (Moderate) Monitor for increased bleeding if ticagrelor is coadministered with lasmiditan as concurrent use may increase the exposure of ticagrelor. Ticagrelor is a P-gp substrate and lasmiditan is a P-gp inhibitor.
Timolol: (Moderate) Monitor heart rate if lasmiditan is coadministered with beta-blockers as concurrent use may increase the risk for bradycardia. Lasmiditan has been associated with lowering of heart rate. In a drug interaction study, addition of a single 200 mg dose of lasmiditan to a beta-blocker (propranolol) decreased heart rate by an additional 5 beats per minute.
Tipranavir: (Moderate) Monitor for an increase in tipranavir-related adverse reactions if coadministration with lasmiditan is necessary. Concomitant use may increase tipranavir exposure. Tipranavir is a P-gp substrate; lasmiditan is a P-gp inhibitor.
Tizanidine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lasmiditan and tizanidine. Concurrent use may result in additive CNS depression.
Tolcapone: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lasmiditan and tolcapone. Concurrent use may result in additive CNS depression. Dopaminergic agents, such as tolcapone, have also been associated with sudden sleep onset during activities of daily living such as driving, which has resulted in accidents in some cases. Prescribers should re-assess patients for drowsiness or sleepiness regularly throughout treatment, especially since events may occur well after the start of treatment.
Topotecan: (Major) Avoid coadministration of lasmiditan with oral topotecan due to increased topotecan exposure; lasmiditan may be administered with intravenous topotecan. Coadministration increases the risk of topotecan-related adverse reactions. Oral topotecan is a substrate of the P-gp and lasmiditan is a P-gp inhibitor. 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.
Tramadol: (Moderate) Concomitant use of tramadol with lasmiditan may cause excessive sedation, somnolence, and serotonin syndrome. Limit the use of tramadol with lasmiditan to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression and serotonin syndrome.
Tramadol; Acetaminophen: (Moderate) Concomitant use of tramadol with lasmiditan may cause excessive sedation, somnolence, and serotonin syndrome. Limit the use of tramadol with lasmiditan to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression and serotonin syndrome.
Trandolapril; Verapamil: (Moderate) Monitor heart rate if lasmiditan is coadministered with calcium-channel blockers as concurrent use may increase the risk for bradycardia. Lasmiditan has been associated with lowering of heart rate. In a drug interaction study, addition of a single 200 mg dose of lasmiditan to another heart rate lowering drug decreased heart rate by an additional 5 beats per minute.
Tranylcypromine: (Major) Avoid coadministration of lasmiditan and tranylcypromine due to the risk of serotonin syndrome. Additionally, additive CNS depression may occur. If concomitant use is unavoidable, use the lowest appropriate medication dosages, and monitor for excessive sedation, somnolence, and serotonin syndrome. Inform patients taking this combination of the risks and symptoms of excessive CNS depression and serotonin syndrome, particularly after a dose increase or the addition of other serotonergic medications to an existing regimen. Discontinue all serotonergic agents if serotonin syndrome occurs and implement appropriate medical management.
Trazodone: (Moderate) Monitor for excessive sedation, somnolence, and serotonin syndrome during coadministration of lasmiditan and trazodone. Inform patients taking this combination of the risks and symptoms of excessive CNS depression and serotonin syndrome, particularly after a dose increase or the addition of other serotonergic medications to an existing regimen. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
Triazolam: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lasmiditan and benzodiazepines. Concurrent use may result in additive CNS depression.
Tricyclic antidepressants: (Moderate) Monitor for excessive sedation, somnolence, and serotonin syndrome during coadministration of lasmiditan and tricyclic antidepressants. Inform patients taking this combination of the risks and symptoms of excessive CNS depression and serotonin syndrome, particularly after a dose increase or the addition of other serotonergic medications to an existing regimen. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
Trifluoperazine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lasmiditan and trifluoperazine. Concurrent use may result in additive CNS depression.
Trimipramine: (Moderate) Monitor for excessive sedation, somnolence, and serotonin syndrome during coadministration of lasmiditan and tricyclic antidepressants. Inform patients taking this combination of the risks and symptoms of excessive CNS depression and serotonin syndrome, particularly after a dose increase or the addition of other serotonergic medications to an existing regimen. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
Triprolidine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lasmiditan and sedating H1-blockers. Concurrent use may result in additive CNS depression.
Ubrogepant: (Major) Limit the initial and second dose of ubrogepant to 50 mg if coadministered with lasmiditan. Concurrent use may increase ubrogepant exposure and the risk of adverse effects. Ubrogepant is a P-gp substrate and lasmiditan is a P-gp inhibitor.
Valerian, Valeriana officinalis: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lasmiditan and valerian. Concurrent use may result in additive CNS depression.
Valproic Acid, Divalproex Sodium: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lasmiditan and valproic acid. Concurrent use may result in additive CNS depression.
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 lasmiditan due to the potential for increased venetoclax exposure. Resume the original venetoclax dose 2 to 3 days after discontinuation of lasmiditan. Venetoclax is a P-gp substrate; lasmiditan 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) Serotonin syndrome may occur during coadministration of lasmiditan and serotonin norepinephrine reuptake inhibitors. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome, particularly after a dose increase or the addition of other serotonergic medications to an existing regimen. Discontinue all serotonergic agents if serotonin syndrome occurs and implement appropriate medical management.
Verapamil: (Moderate) Monitor heart rate if lasmiditan is coadministered with calcium-channel blockers as concurrent use may increase the risk for bradycardia. Lasmiditan has been associated with lowering of heart rate. In a drug interaction study, addition of a single 200 mg dose of lasmiditan to another heart rate lowering drug decreased heart rate by an additional 5 beats per minute.
Vilazodone: (Moderate) Serotonin syndrome may occur during coadministration of lasmiditan and vilazodone. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome, particularly after a dose increase or the addition of other serotonergic medications to an existing regimen. Discontinue all serotonergic agents if serotonin syndrome occurs and implement appropriate medical management.
Vincristine Liposomal: (Moderate) Monitor for vincristine-related adverse reactions if coadministration of lasmiditan is necessary as concurrent use may increase vincristine exposure. Vincristine is a P-gp substrate and lasmiditan is a P-gp inhibitor.
Vincristine: (Moderate) Monitor for vincristine-related adverse reactions if coadministration of lasmiditan is necessary as concurrent use may increase vincristine exposure. Vincristine is a P-gp substrate and lasmiditan is a P-gp inhibitor.
Vortioxetine: (Moderate) Serotonin syndrome may occur during coadministration of lasmiditan and vortioxetine. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome, particularly after a dose increase or the addition of other serotonergic medications to an existing regimen. Discontinue all serotonergic agents if serotonin syndrome occurs and implement appropriate medical management.
Zaleplon: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lasmiditan and zaleplon. Concurrent use increases the risk for CNS depression and complex sleep-related behaviors (e.g., driving, talking, eating, or performing other activities while not fully awake). Patients should be instructed to contact their provider immediately if these symptoms or behaviors occur.
Ziprasidone: (Moderate) Monitor for excessive sedation, somnolence, and serotonin syndrome during coadministration of lasmiditan and ziprasidone. Inform patients taking this combination of the risks and symptoms of excessive CNS depression and serotonin syndrome, particularly after a dose increase or the addition of other serotonergic medications to an existing regimen. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
Zolmitriptan: (Moderate) Serotonin syndrome may occur during coadministration of lasmiditan and serotonin-receptor agonists. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome, particularly after a dose increase or the addition of other serotonergic medications to an existing regimen. Discontinue all serotonergic agents if serotonin syndrome occurs and implement appropriate medical management.
Zolpidem: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lasmiditan and zolpidem. Concurrent use increases the risk for CNS depression and complex sleep-related behaviors (e.g., driving, talking, eating, or performing other activities while not fully awake). Patients should be instructed to contact their provider immediately if these symptoms or behaviors occur.
Zuranolone: (Major) Avoid the use of multiple sedating agents due to the risk for additive CNS depression. If use is necessary, consider a downward dosage adjustment of either or both medications, especially in patients with additional risk factors for sedation-related harm.
Lasmiditan is a highly selective 5-HT1F receptor agonist. It decreases activation and sensitization of the trigeminal nerve system within the meninges by acting centrally on trigeminal neurons and peripherally on primary trigeminal afferents and cell bodies within the trigeminal ganglion. Lasmiditan does not activate 5-HT1B receptors in peripheral blood vessels, including coronary arteries, and does not induce vasoconstriction.
Lasmiditan is administered orally. Plasma protein binding is approximately 55% to 60% and independent of concentration between 15 and 500 ng/mL. Lasmiditan undergoes hepatic and extrahepatic metabolism by ketone reduction primarily by non-cytochrome P450 enzymes. Lasmiditan is also metabolized to M7 (through oxidation) and M18 (combination of M7 and M8 pathways); these metabolits are considered pharmacologically inactive. Unchanged lasmiditan accounts for 3% of the dose recovered in urine. The metabolite S-M8 represents approximately 66% of the dose in urine, with the majority of recovery within 48 hours postdose. The geometric mean half-life of lasmiditan is approximately 5.7 hours. There were no differences in lasmiditan pharmacokinetics during a migraine attack compared to the interictal period.
Affected cytochrome P450 isoenzymes and drug transporters: CYP2D6, P-gp, BCRP, MATE1, MATE2-K, OCT1
Lasmiditan is a substrate for P-gp in vitro. Lasmiditan is an inhibitor of CYP2D6 in vitro; however, clinically significant inhibition is unlikely to occur. Lasmiditan also inhibits P-gp, BCRP, OCT1, MATE1, and MATE2-K in vitro. No change in substrate pharmacokinetics was observed in a drug interaction study with an OCT1 substrate.
-Route-Specific Pharmacokinetics
Oral Route
Lasmiditan is rapidly absorbed with a median Tmax of 1.8 hours after oral administration. Coadministration of lasmiditan with a high-fat meal increased Cmax and AUC values by 22% and 19%, respectively, and delayed the median Tmax by 1 hour. These differences in exposure are not expected to be clinically significant.
-Special Populations
Hepatic Impairment
In subjects with mild and moderate haptic impairment (Child-Pugh classes A and B), the AUC of lasmiditan increased by 11% and 35%, respectively, compared to subjects with normal hepatic function. Cmax was 19% and 33% higher in patients with mild and moderate impairment, respectively. These differences are not expected to be clinically significant. Lasmiditan has not been studied in patients with severe hepatic impairment.
Renal Impairment
The AUC and Cmax of lasmiditan increased by 18% and 13%, respectively, in patients with severe renal impairment (eGFR less than 30 mL/minute/1.73 m2) compared to subjects with normal renal function. No lasmiditan dose adjustment is required based on renal function.
Geriatric
Lasmiditan AUC and Cmax increased by 26% and 21%, respectively, in subjects 65 years and older compared to subjects 45 years or younger.
Gender Differences
Gender did not have a significant effect on the pharmacokinetics of lasmiditan.
Ethnic Differences
Race or ethnicity did not have a significant effect on the pharmacokinetics of lasmiditan.
Obesity
Body weight did not have a significant effect on the pharmacokinetics of lasmiditan.