Drug Interactions between mitotane and Vitrakvi
This report displays the potential drug interactions for the following 2 drugs:
- mitotane
- Vitrakvi (larotrectinib)
Interactions between your drugs
mitotane larotrectinib
Applies to: mitotane and Vitrakvi (larotrectinib)
GENERALLY AVOID: Coadministration with potent inducers of CYP450 3A4 and/or P-glycoprotein (P-gp) may significantly decrease the plasma concentrations of larotrectinib. According to the prescribing information, larotrectinib is metabolized primarily by the CYP450 3A4 isoenzyme and is a substrate of the P-gp and BCRP efflux transporters in vitro. When a single 100 mg dose of larotrectinib was coadministered with rifampin (600 mg once daily for 11 days), a potent CYP450 3A4 and P-gp inducer, larotrectinib peak plasma concentration (Cmax) and systemic exposure (AUC) decreased by 71% and 81%, respectively, compared to administration of larotrectinib alone. Reduced efficacy of larotrectinib may occur.
MANAGEMENT: Concomitant use of larotrectinib with potent CYP450 3A4 and/or P-gp inducers should generally be avoided. If coadministration is required, the manufacturer recommends doubling the larotrectinib dose. After the inducer has been discontinued for 3 to 5 elimination half-lives, the larotrectinib dose that was taken prior to initiating the inducer may be resumed.
References
- Cerner Multum, Inc. "UK Summary of Product Characteristics."
- Cerner Multum, Inc. "Australian Product Information."
- (2018) "Product Information. Vitrakvi (larotrectinib)." Bayer Pharmaceutical Inc
Drug and food interactions
mitotane food
Applies to: mitotane
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.
References
- (2023) "Product Information. Lysodren (mitotane)." HRA Pharma America
- (2023) "Product Information. Lysodren (mitotane)." Medunik Canada
- (2023) "Product Information. Lysodren (mitotane)." HRA Pharma UK & Ireland Ltd
- Moolenaar AJ, van Slooten H, van Seters AP, Smeenk D (2023) Blood levels of o,p-DDD following administration in various vehicles after a single dose and during long-term treatment https://link.springer.com/article/10.1007/BF00258213
larotrectinib food
Applies to: Vitrakvi (larotrectinib)
GENERALLY AVOID: Grapefruit juice may increase the plasma concentrations of larotrectinib. The proposed mechanism is inhibition of CYP450 3A4-mediated metabolism of larotrectinib by certain compounds present in grapefruit. When a single 100 mg dose of larotrectinib was coadministered with itraconazole, a potent CYP450 3A4 inhibitor, larotrectinib peak plasma concentration (Cmax) and systemic exposure (AUC) increased by 2.8- and 4.3-fold, respectively, compared to administration of larotrectinib alone. The interaction has not been studied with grapefruit juice. 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 larotrectinib may increase the risk of adverse effects such as neurotoxicity (delirium, dysarthria, dizziness, gait disturbance, paraesthesia, encephalopathy, memory impairment, tremor) and hepatotoxicity (elevations in liver transaminases).
Food does not alter the pharmacokinetics of larotrectinib to a clinically significant extent. When a single 100 mg dose of larotrectinib was administered with a high-fat meal (approximately 900 calories; 58 g carbohydrate, 56 g fat, 43 g protein) in healthy study subjects, larotrectinib peak plasma concentration (Cmax) was reduced by 35% while systemic exposure (AUC) was similar compared to administration in the fasted state.
MANAGEMENT: Larotrectinib may be taken with or without food. Patients should avoid the consumption of grapefruit and grapefruit juice during treatment.
References
- (2018) "Product Information. Vitrakvi (larotrectinib)." Bayer Pharmaceutical Inc
Therapeutic duplication warnings
No warnings were found for your selected drugs.
Therapeutic duplication warnings are only returned when drugs within the same group exceed the recommended therapeutic duplication maximum.
See also
Drug Interaction Classification
Highly clinically significant. Avoid combinations; the risk of the interaction outweighs the benefit. | |
Moderately clinically significant. Usually avoid combinations; use it only under special circumstances. | |
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. | |
No interaction information available. |
Further information
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