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Drug Interactions between amoxicillin / clarithromycin / vonoprazan and tepotinib

This report displays the potential drug interactions for the following 2 drugs:

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Interactions between your drugs

Major

clarithromycin tepotinib

Applies to: amoxicillin / clarithromycin / vonoprazan and tepotinib

GENERALLY AVOID: Coadministration with dual potent inhibitors of CYP450 3A4 and P-glycoprotein (P-gp) may increase the plasma concentrations of tepotinib, which may increase the incidence and severity of adverse reactions such as interstitial lung disease/pneumonitis, hepatotoxicity, edema, nausea, vomiting, diarrhea, constipation, and musculoskeletal pain. Tepotinib is a substrate of both CYP450 3A4 isoenzyme and P-gp efflux transporter. However, the effect of strong CYP450 3A4 inhibitors or P-gp inhibitors on tepotinib has not been studied clinically.

MANAGEMENT: Concomitant use of tepotinib with potent CYP450 3A4 and P-gp inhibitors should generally be avoided.

References (2)
  1. (2021) "Product Information. Tepmetko (tepotinib)." EMD Serono Inc
  2. (2022) "Product Information. Tepmetko (tepotinib)." Merck Healthcare Pty Ltd, A001-0122
Minor

amoxicillin clarithromycin

Applies to: amoxicillin / clarithromycin / vonoprazan and amoxicillin / clarithromycin / vonoprazan

Although some in vitro data indicate synergism between macrolide antibiotics and penicillins, other in vitro data indicate antagonism. When these drugs are given together, neither has predictable therapeutic efficacy. Data are available for erythromycin, although theoretically this interaction could occur with any macrolide. Except for monitoring of the effectiveness of antibiotic therapy, no special precautions appear to be necessary.

References (3)
  1. Strom J (1961) "Penicillin and erythromycin singly and in combination in scarlatina therapy and the interference between them." Antibiot Chemother, 11, p. 694-7
  2. Cohn JR, Jungkind DL, Baker JS (1980) "In vitro antagonism by erythromycin of the bactericidal action of antimicrobial agents against common respiratory pathogens." Antimicrob Agents Chemother, 18, p. 872-6
  3. Penn RL, Ward TT, Steigbigel RT (1982) "Effects of erythromycin in combination with penicillin, ampicillin, or gentamicin on the growth of listeria monocytogenes." Antimicrob Agents Chemother, 22, p. 289-94

Drug and food interactions

Moderate

tepotinib food

Applies to: tepotinib

ADJUST DOSING INTERVAL: Food enhances the oral bioavailability of tepotinib. When tepotinib was administered after a high-fat, high-calorie meal (approximately 800 to 1000 calories; 150 calories from protein, 250 calories from carbohydrate, 500 to 600 calories from fat), tepotinib peak plasma concentration (Cmax) and systemic exposure (AUC) increased by 2-fold and 1.6-fold, respectively, compared to administration under fasted conditions.

MANAGEMENT: Tepotinib should be administered with food at approximately the same time each day.

References (1)
  1. (2021) "Product Information. Tepmetko (tepotinib)." EMD Serono Inc
Minor

clarithromycin food

Applies to: amoxicillin / clarithromycin / vonoprazan

Grapefruit juice may delay the gastrointestinal absorption of clarithromycin but does not appear to affect the overall extent of absorption or inhibit the metabolism of clarithromycin. The mechanism of interaction is unknown but may be related to competition for intestinal CYP450 3A4 and/or absorptive sites. In an open-label, randomized, crossover study consisting of 12 healthy subjects, coadministration with grapefruit juice increased the time to reach peak plasma concentration (Tmax) of both clarithromycin and 14-hydroxyclarithromycin (the active metabolite) by 80% and 104%, respectively, compared to water. Other pharmacokinetic parameters were not significantly altered. This interaction is unlikely to be of clinical significance.

References (1)
  1. Cheng KL, Nafziger AN, Peloquin CA, Amsden GW (1998) "Effect of grapefruit juice on clarithromycin pharmacokinetics." Antimicrob Agents Chemother, 42, p. 927-9

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

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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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