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Interactions between Binimetinib and Daridorexant

1 drug interaction and 11 additional warnings found for the following 2 drugs:

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Drug interactions

Moderate drug interactions

Moderate:

binimetinib daridorexant

Applies to: binimetinib and daridorexant
Monitor

Coadministration with inhibitors of P-glycoprotein (P-gp), uridine diphosphate glucuronosyltransferase (UGT) 1A1 or 2B7, and/or breast cancer resistance protein (BCRP) may increase the plasma levels and risk of adverse effects of binimetinib. The proposed mechanism involves the reduced metabolic clearance of binimetinib through inhibition of P-gp, UGT 1A1, UGT 2B7, and/or BCRP. The clinical significance of this interaction is unknown as no clinically relevant drug interactions have been demonstrated with binimetinib.

Management

Until further information is available, caution is recommended if binimetinib must be used concomitantly with P-gp, UGT 1A1, UGT 2B7, and/or BCRP inhibitors. Binimetinib should be monitored more closely whenever a P-gp, UGT 1A1, UGT 2B7, and/or BCRP inhibitor is added to or withdrawn from therapy, and the binimetinib dosage adjusted as necessary.

References (3)
  1. Cerner Multum, Inc. "UK Summary of Product Characteristics."
  2. Cerner Multum, Inc. "Australian Product Information."
  3. (2018) "Product Information. Mektovi (binimetinib)." Array BioPharma Inc.

Food/lifestyle interactions

Moderate food/lifestyle interactions

Moderate:

daridorexant Food/Lifestyle

Applies to: daridorexant
Generally avoid

Grapefruit juice may increase the plasma concentrations of daridorexant, which is primarily metabolized by CYP450 3A4. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruit. Inhibition of hepatic CYP450 3A4 may also contribute. The interaction has not been studied with grapefruit juice but has been reported for other CYP450 3A4 inhibitors. Per physiologically based pharmacokinetic (PBPK) analysis, concomitant use of itraconazole, a potent CYP450 3A4 inhibitor, increased daridorexant systemic exposure (AUC) by more than 400%. When a 25 mg daridorexant dose was coadministered with multiple 240 mg doses of diltiazem, a moderate CYP450 3A4 inhibitor, daridorexant peak plasma concentration (Cmax) and AUC increased by 1.4- and 2.4-fold, respectively. In general, the effect of grapefruit juice is concentration-, dose- and preparation-dependent, and can vary widely among brands. Certain preparations of grapefruit juice (e.g., high dose, double strength) have sometimes demonstrated potent inhibition of CYP450 3A4, while other preparations (e.g., low dose, single strength) have typically demonstrated moderate inhibition. Increased exposure to daridorexant may increase the risk of adverse reactions such as central nervous system (CNS) depression, sleep paralysis, hallucinations, complex sleep behaviors, worsening of depression or suicidal ideation, or headache. After administration of a high-fat, high-calorie meal, daridorexant Cmax decreased by 16% (no effect on AUC) and the time to maximum concentration (Tmax) was delayed by 1.3 hours.

Generally avoid

Alcohol may potentiate the pharmacologic effects of daridorexant. Coadministration of daridorexant (50 mg) with alcohol led to additive effects on psychomotor performance. Use in combination may result in an increased risk of complex sleep-related behaviors (e.g., "sleep driving"), additive central nervous system (CNS) depression, and/or impairment of psychomotor performance.

Management

Consumption of grapefruit, grapefruit juice, or supplements that contain grapefruit during treatment with daridorexant should generally be avoided. Some authorities suggest avoiding grapefruit or grapefruit juice consumption specifically in the evening. Patients should avoid the consumption of alcohol during treatment with daridorexant. The manufacturer makes no recommendation regarding administration with food; however, the time to sleep onset may be delayed if taken with or soon after a meal.

References (3)
  1. (2024) "Product Information. Quviviq (daridorexant)." Idorsia Pharmaceuticals UK Ltd
  2. (2024) "Product Information. Quviviq (daridorexant)." Idorsia Pharmaceuticals US Inc., SUPPL-12
  3. (2024) "Product Information. Quviviq (daridorexant)." Innomar Strategies Inc

Disease interactions

10 potential interactions Applies to: 9 conditions, including Depression, Narcolepsy, Cardiomyopathy, Liver Disease, and Drug Dependence.

Alcoholism

Moderate:

daridorexant

Daridorexant has a moderate potential interaction with Alcoholism.

Patients with a history of abuse or addiction to alcohol or other substances may be at increased risk for abuse of or addiction to daridorexant and should be monitored closely.

Cardiomyopathy

Moderate:

binimetinib

Binimetinib has a moderate potential interaction with Cardiomyopathy.

Cardiomyopathy, manifesting as left ventricular dysfunction associated with symptomatic or asymptomatic decreases in ejection fraction, has been reported in patients treated with binimetinib in combination with encorafenib. The median time to first occurrence of left ventricular dysfunction (any grade) in patients receiving treatment was 3.6 months (range 0 to 21 months). Cardiomyopathy resolved in 87% of the patients. Ejection fraction should be assessed by echocardiogram or MUGA scan prior to initiating treatment, one month after initiating treatment, and then every 2 to 3 months during treatment. The safety of this therapy has not been established in patients with a baseline ejection fraction that is either below 50% or below the institutional lower limit of normal (LLN). Patients with cardiovascular risk factors should be monitored closely when treated with binimetinib.

Depression

Moderate:

daridorexant

Daridorexant has a moderate potential interaction with Depression.

Daridorexant can worsen depression and suicidal thoughts and actions and should be used with caution in patients with depression. These patients should be monitored closely and any preventive measures should be taken.

Drug Dependence

Moderate:

daridorexant

Daridorexant has a moderate potential interaction with Drug Dependence.

Patients with a history of abuse or addiction to alcohol or other substances may be at increased risk for abuse of or addiction to daridorexant and should be monitored closely.

Glaucoma/Intraocular Hypertension

Moderate:

binimetinib

Binimetinib has a moderate potential interaction with Glaucoma/Intraocular Hypertension.

Retinal vein occlusion (RVO) is a known class- related adverse reaction of MEK inhibitors and may occur in patients treated with binimetinib in combination with encorafenib. The safety of binimetinib has not been established in patients with a history of RVO or current risk factors for RVO including uncontrolled glaucoma or a history of hyperviscosity or hypercoagulability syndromes. An ophthalmologic evaluation should be performed for patient reporting acute vision loss or other visual disturbance within 24 hours. Treatment should be discontinued in patients with documented RVO.

Liver Disease

Moderate:

binimetinib

Binimetinib has a moderate potential interaction with Liver Disease.

Binimetinib concentrations may increase in patients with moderate or severe hepatic impairment. Reduce the dose of binimetinib for patients with moderate (total bilirubin > 1.5 and = 3 × ULN and any AST) or severe (total bilirubin levels > 3 × ULN and any AST) hepatic impairment. Dose adjustment is not recommended in patients with mild hepatic impairment (total bilirubin > 1 and = 1.5 × ULN and any AST or total bilirubin = ULN and AST > ULN).

Moderate:

daridorexant

Daridorexant has a moderate potential interaction with Liver Disease.

Daridorexant is not recommended in patients with severe hepatic dysfunction. The maximum recommended dosage in patients with moderate hepatic dysfunction is 25 mg once per night.

Narcolepsy

Major:

daridorexant

Daridorexant has a major potential interaction with Narcolepsy.

Daridorexant is contraindicated in patients with narcolepsy.

Pulmonary Impairment

Moderate:

daridorexant

Daridorexant has a moderate potential interaction with Pulmonary Impairment.

Daridorexant is a respiratory depressant and should be used with caution if prescribed to patients with impaired respiratory function. This drug has not been studied in patients with moderate to severe sleep apnea requiring CPAP or in patients with severe chronic obstructive pulmonary disease (COPD).

Retinal Disorders

Moderate:

binimetinib

Binimetinib has a moderate potential interaction with Retinal Disorders.

Retinal vein occlusion (RVO) is a known class- related adverse reaction of MEK inhibitors and may occur in patients treated with binimetinib in combination with encorafenib. The safety of binimetinib has not been established in patients with a history of RVO or current risk factors for RVO including uncontrolled glaucoma or a history of hyperviscosity or hypercoagulability syndromes. An ophthalmologic evaluation should be performed for patient reporting acute vision loss or other visual disturbance within 24 hours. Treatment should be discontinued in patients with documented RVO.

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More resources

binimetinib

A total of 208 drugs are known to interact with binimetinib.

daridorexant

A total of 778 drugs are known to interact with daridorexant.

Drug Interaction Classification

These classifications are only a guideline. The relevance of a particular drug interaction to a specific individual is difficult to determine. Always consult your healthcare provider before starting or stopping any medication.
Major Highly clinically significant. Avoid combinations; the risk of the interaction outweighs the benefit.
Moderate Moderately clinically significant. Usually avoid combinations; use it only under special circumstances.
Minor Minimally clinically significant. Minimize risk; assess risk and consider an alternative drug, take steps to circumvent the interaction risk and/or institute a monitoring plan.
Unknown No interaction information available.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

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