Drug Interactions between Nuedexta and thalidomide

GENERALLY AVOID: Coadministration with potent CYP450 2D6 inhibitors (e.g., quinidine, terbinafine) may significantly increase the plasma concentrations of dextromethorphan in patients who are extensive metabolizers of this isoenzyme (approximately 93% of Caucasians and more than 98% of Asians and individuals of African descent). The proposed mechanism is inhibition of the CYP450 2D6-mediated O-demethylation of dextromethorphan. Studies in humans have shown an increase in systemic exposure of dextromethorphan of up to 43-fold when given concurrently with quinidine. Increased plasma concentrations increase the risk of dextromethorphan-related adverse effects (e.g., agitation, confusion, tremor, insomnia, diarrhea, and respiratory depression) and serotonin syndrome. However, this interaction has also been used clinically, with dextromethorphan in combination with quinidine indicated by some authorities for the treatment of pseudobulbar affect. Data evaluating the impact of this interaction in patients who are poor metabolizers of CYP450 2D6 are limited; most studies include extensive metabolizers of this isoenzyme. It is expected that poor metabolizers would have elevated dextromethorphan levels without concurrent quinidine

MANAGEMENT: The combination of dextromethorphan with potent CYP450 2D6 inhibitors should be generally avoided. Some manufacturers consider the concomitant use of dextromethorphan and selective serotonin reuptake inhibitors contraindicated. If use is considered necessary, the patient should be monitored for signs of dextromethorphan adverse effects (e.g., agitation, confusion, tremor, insomnia, diarrhea, and respiratory depression) and serotonin syndrome, and advised to notify their health care professional if these adverse effects develop or worsen. Dose reduction of dextromethorphan may also be required.

MONITOR: Thalidomide can cause bradycardia and may have additive effects with other drugs that decrease heart rate. Cases of bradycardia have been associated with thalidomide use, some requiring medical interventions. The clinical significance and underlying etiology of the bradycardia observed with thalidomide treatment have not been established. However, the potential for additive bradycardic effects should be considered when used with other drugs that slow cardiac conduction such as beta-blockers, calcium channel blockers, digitalis, flecainide, moricizine, and propafenone. Non-cardiac drugs that may also cause bradycardia include atazanavir, lacosamide, lithium, mefloquine, succinylcholine, H2-receptor antagonists, tricyclic antidepressants, and anticholinesterase or cholinergic agents. Because bradycardia is a risk factor for torsade de pointes arrhythmia, concerns also exist when thalidomide is used with drugs that prolong the QT interval or cause torsade de pointes.

MANAGEMENT: Caution is advised when thalidomide is used with drugs that can slow the heart rate or induce torsade de pointes arrhythmia. Patients should be monitored for bradycardia, atrioventricular block and syncope, and advised to seek medical attention if they experience dizziness, lightheadedness, fainting, shortness of breath, or slow or irregular heartbeat. A dose reduction of thalidomide or discontinuation may be required.

MONITOR: Thalidomide can commonly cause drowsiness/sedation and may have additive effects with other drugs that cause central nervous system (CNS) depression.

MANAGEMENT: Caution is advised when thalidomide is used with other CNS depressants such as anticonvulsants, antihistamines, antidepressants, antipsychotics, anxiolytics, opioids, and sedatives/hypnotics. Patients should be advised to avoid hazardous activities requiring mental alertness and motor coordination until they know how these agents affect them, and to notify their physician if they experience excessive or prolonged CNS effects that interfere with their normal activities. Dosage reductions may be necessary. Thalidomide should preferably be administered at bedtime to reduce the impact of somnolence. Alcohol use is not recommended.