Drug Interaction Report

MONITOR: Coadministration with alcohol or other central nervous system (CNS) depressants may enhance the sedative effects of mitotane and increase the likelihood and/or severity of central nervous system (CNS) side effects. In clinical studies and post marketing reports, CNS side effects occurred in 40% of patients, primarily consisting of depression as manifested by lethargy and somnolence (25%), and dizziness or vertigo (15%). Mitotane plasma concentrations exceeding 20 mcg/mL are associated with a greater incidence of severe neurologic toxicity. Clinical data are not available for the concomitant use of mitotane with other CNS depressants.

MANAGEMENT: Caution and clinical monitoring for increased CNS adverse effects is advised if mitotane is coadministered with alcohol, other CNS depressants, or agents that cause dizziness or vertigo. Patients should not drive, operate machinery, or engage in hazardous activities requiring mental alertness and motor coordination until they know how the medications affect them. In addition, more frequent monitoring of serum mitotane levels may be considered.

ADJUST DOSING INTERVAL: Fat-rich food enhances the absorption of mitotane. One study evaluated blood levels of mitotane (o,p'-DDD) after subjects ingested a single dose of 2 g administered using various delivery vehicles (e.g., tablets, granules, milk, chocolate or oil emulsion). Mitotane plasma levels were significantly higher for milk, chocolate, and oil emulsion when compared to those who received tablets or granules alone. In the same study, mitotane levels were evaluated in subjects following long-term treatment (total dose of 200 g over 30 to 60 days) in tablet, oil emulsion, or milk formulations. Significantly higher mean plasma levels were recorded in subjects who received mitotane as an oil emulsion or mixed in milk, when compared to tablets alone. Additionally, the recovery of o,p'-DDD from the feces was about 5 times higher in subjects who received tablets alone, suggesting absorption was reduced when compared to subjects who received mitotane mixed with a fat-rich vehicle (e.g., oil emulsion or milk).

GENERALLY AVOID: Concomitant use of mitotane with central nervous system (CNS) depressants, including alcohol, may potentiate adverse effects such as somnolence and sedation.

MANAGEMENT: According to product labeling, mitotane tablets should be taken during meals containing fat-rich food (e.g., milk, chocolate, or oil) and with a full glass of water. Patients should be advised to avoid or limit consumption of alcohol and to avoid activities requiring mental alertness such as driving or operating hazardous machinery until they know how the medication affects them.

GENERALLY AVOID: Concomitant use of esketamine with central nervous system (CNS) depressants such as alcohol may increase sedation and impairment of attention, judgment, thinking, reaction speed, and psychomotor skills.

ADJUST DOSING INTERVAL: Nausea and vomiting may occur following intranasal administration of esketamine. In clinical studies, nausea and vomiting were reported in approximately 25% and 10% of esketamine-treated patients, respectively.

MANAGEMENT: Patients receiving esketamine should be advised to avoid or limit the consumption of alcohol. In addition, to help prevent nausea and vomiting, patients should be advised not to eat for at least 2 hours before intranasal administration of esketamine and not to drink liquids for at least 30 minutes prior to administration.