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Drug Interactions between amoxicillin / clarithromycin / omeprazole and sonidegib

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

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Interactions between your drugs

Major

clarithromycin sonidegib

Applies to: amoxicillin / clarithromycin / omeprazole and sonidegib

GENERALLY AVOID: Coadministration with potent inhibitors of CYP450 3A4 may significantly increase the plasma concentrations of sonidegib, which is primarily metabolized by the isoenzyme. In 15 healthy volunteers, administration of a single 800 mg dose of sonidegib five days after starting treatment with the potent CYP450 3A4 inhibitor ketoconazole (200 mg orally twice daily for 14 days) increased mean sonidegib peak plasma concentration (Cmax) and systemic exposure (AUC) by 1.5- and 2.2-fold, respectively, compared to administration of sonidegib alone. Simulations using physiologically-based pharmacokinetic (PBPK) models suggest that sonidegib steady-state AUC would similarly increase in cancer patients taking sonidegib 200 mg once daily with a potent CYP450 3A4 inhibitor for 14 days.

MANAGEMENT: Concomitant use of sonidegib with potent CYP450 3A4 inhibitors should generally be avoided.

References

  1. (2015) "Product Information. Odomzo (sonidegib)." Novartis Pharmaceuticals

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Minor

amoxicillin clarithromycin

Applies to: amoxicillin / clarithromycin / omeprazole and amoxicillin / clarithromycin / omeprazole

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

  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

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Minor

clarithromycin omeprazole

Applies to: amoxicillin / clarithromycin / omeprazole and amoxicillin / clarithromycin / omeprazole

Clarithromycin may increase and prolong the omeprazole plasma concentration. The mechanism may be related to clarithromycin inhibition of hepatic cytochrome P450 enzymes responsible for omeprazole metabolism. Coadministration of omeprazole may result in an increase in clarithromycin and 14-(R)-hydroxyclarithromycin plasma concentrations. These increases may be due to the effect of omeprazole on gastric pH.

References

  1. Zhou Q, Yamamoto I, Fukuda T, Ohno M, Sumida A, Azuma J (1999) "CYP2C19 genotypes and omeprazole metabolism after single and repeated dosing when combined with clarithromycin." Eur J Clin Pharmacol, 55, p. 43-7
  2. Gustavson LE, Kaiser JF, Edmonds AL, Locke CS, DeBartolo ML, Schneck DW (1995) "Effect of omeprazole on concentrations of clarithromycin in plasma and gastric tissue at steady state." Antimicrob Agents Chemother, 39, p. 2078-83
  3. Furuta T, Ohashi K, Kobayashi K, Iida I, Yoshida H, Shirai N, Takashima M, Kosuge K, Hanai H, Chiba K, Ishizaki T, Kaneko E (1999) "Effects of clarithromycin on the metabolism of omeprazole in relation to CYP2C19 genotype status in humans." Clin Pharmacol Ther, 66, p. 265-74

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Minor

omeprazole sonidegib

Applies to: amoxicillin / clarithromycin / omeprazole and sonidegib

Coadministration with proton pump inhibitors or H2-receptor antagonists may decrease the plasma concentrations of sonidegib. The mechanism of interaction has not been described. Based on population pharmacokinetic analysis, concomitant administration of sonidegib with a proton pump inhibitor or H2-receptor antagonist decreases mean sonidegib steady-state systemic exposure (AUC) by approximately one-third. The clinical relevance of this interaction is unknown.

References

  1. (2015) "Product Information. Odomzo (sonidegib)." Novartis Pharmaceuticals

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Drug and food interactions

Moderate

sonidegib food

Applies to: sonidegib

ADJUST DOSING INTERVAL: Food significantly increases the oral bioavailability of sonidegib. According to the product labeling, administration of sonidegib with a high-fat meal (approximately 1000 calories; 50% from fat) increased mean sonidegib peak plasma concentration (Cmax) and systemic exposure (AUC) by 7.4- to 7.8-fold.

GENERALLY AVOID: Grapefruit juice may increase the plasma concentrations of sonidegib. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruit. 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 sonidegib may increase the risk of adverse effects such as musculoskeletal toxicity, fatigue, nausea, vomiting, diarrhea, anorexia, weight loss, alopecia, pruritus, and dysgeusia.

MANAGEMENT: Sonidegib should be administered on an empty stomach, at least 1 hour before or 2 hours after a meal. Patients should avoid consumption of grapefruit or grapefruit juice during treatment with sonidegib.

References

  1. (2015) "Product Information. Odomzo (sonidegib)." Novartis Pharmaceuticals

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Minor

clarithromycin food

Applies to: amoxicillin / clarithromycin / omeprazole

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

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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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