Drug Interactions between amoxicillin / clarithromycin / omeprazole and pralsetinib
This report displays the potential drug interactions for the following 2 drugs:
- amoxicillin/clarithromycin/omeprazole
- pralsetinib
Interactions between your drugs
clarithromycin pralsetinib
Applies to: amoxicillin / clarithromycin / omeprazole and pralsetinib
GENERALLY AVOID: Coadministration with a combined P-glycoprotein (P-gp) and potent CYP450 3A inhibitor may significantly increase the plasma concentrations of pralsetinib, which is primarily metabolized by the CYP450 3A isoenzyme. In vitro studies have shown pralsetinib is a time-dependent inhibitor of CYP450 3A4/5 isoenzymes and a P-gp inhibitor at clinically relevant concentrations. Drug interactions studies have shown single dose administration of pralsetinib 200 mg with itraconazole, a P-gp and potent CYP450 3A4 inhibitor, increased pralsetinib peak plasma concentration (Cmax) and systemic exposure (AUC) by 84% and 251%, respectively. Increased exposure to pralsetinib may increase the risk of serious adverse effects such as interstitial lung disease/pneumonitis, liver transaminase elevations, hypertension, and hemorrhage.
MANAGEMENT: Concomitant use of pralsetinib with a combined P-gp and potent CYP450 3A inhibitor should be avoided when possible. If coadministration is necessary, the manufacturer recommends reducing the dose of pralsetinib to 200 mg once daily for patients receiving 300 or 400 mg once daily and reducing the pralsetinib dose to 100 mg once daily for patients receiving 200 mg once daily. Following discontinuation of the combined P-gp and potent CYP450 3A inhibitor, and after an appropriate washout period (3 to 5 elimination half-lives), the pralsetinib dose taken prior to initiating the combined P-gp and potent CYP450 3A4 inhibitor may be resumed.
References
- Cerner Multum, Inc. "UK Summary of Product Characteristics."
- (2020) "Product Information. Gavreto (pralsetinib)." Blueprint Medicines Corporation
- (2023) "Product Information. Gavreto (pralsetinib)." Roche Products Pty Ltd, GAVRETO 20230406
omeprazole pralsetinib
Applies to: amoxicillin / clarithromycin / omeprazole and pralsetinib
MONITOR: Coadministration with pralsetinib may alter the plasma concentrations of drugs that are substrates of CYP450 2C8, 2C9, 3A4, and/or 3A5. In vitro studies indicate that pralsetinib is both an inhibitor as well as an inducer of CYP450 2C8, 2C9, 3A4, and 3A5. Therefore, pralsetinib may decrease clearance via inhibition or increase clearance via induction of these isoenzymes, resulting in increased or decreased plasma concentrations of agents that are metabolized by one or more of these isoenzymes. Clinical and pharmacokinetic data are currently lacking.
MANAGEMENT: Caution is advised if pralsetinib is used concomitantly with drugs that are substrates of CYP450 2C8, 2C9, 3A4, and/or 3A5, particularly sensitive substrates or those with a narrow therapeutic range. Some authorities recommend avoiding coadministration of pralsetinib with CYP450 2C8, 2C9, 3A4, and/or 3A5 substrates for which minimal concentration changes may lead to therapeutic failure or serious toxicities. If coadministration is required, dosage adjustments as well as clinical and laboratory monitoring may be appropriate whenever pralsetinib is added to or withdrawn from therapy. The prescribing information for concomitant medications should be consulted to assess the benefits versus risks of coadministration and for any dosage adjustments that may be required.
References
- (2023) "Product Information. Gavreto (pralsetinib)." Roche Products Pty Ltd, GAVRETO 20230406
- (2023) "Product Information. Gavreto (pralsetinib)." Roche Products Ltd
- (2023) "Product Information. Gavreto (pralsetinib)." Genentech
- (2021) "Product Information. Gavreto (pralsetinib)." Hoffmann-La Roche Limited
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
- Strom J (1961) "Penicillin and erythromycin singly and in combination in scarlatina therapy and the interference between them." Antibiot Chemother, 11, p. 694-7
- 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
- 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
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
- 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
- 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
- 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
Drug and food interactions
pralsetinib food
Applies to: pralsetinib
ADJUST DOSING INTERVAL: Food significantly increases the oral bioavailability of pralsetinib. According to the product labeling, administration of pralsetinib with a high-fat meal (approximately 800 to 1000 calories; 50% to 60% from fat) increased mean pralsetinib peak plasma concentration (Cmax) and systemic exposure (AUC) by 104% and 122%, respectively. The median time to maximum concentration (Tmax) was delayed from 4 to 8.5 hours.
GENERALLY AVOID: Grapefruit juice may increase the plasma concentrations of pralsetinib. 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 pralsetinib may increase the risk of adverse effects such as musculoskeletal toxicity, fatigue, constipation, hypertension, and pneumonia.
MANAGEMENT: Pralsetinib should be administered on an empty stomach, at least 2 hours after or 1 hour before a meal. Patients should avoid consumption of grapefruit or grapefruit juice during treatment with pralsetinib.
References
- Cerner Multum, Inc. "UK Summary of Product Characteristics."
- (2020) "Product Information. Gavreto (pralsetinib)." Blueprint Medicines Corporation
- (2023) "Product Information. Gavreto (pralsetinib)." Roche Products Pty Ltd, GAVRETO 20230406
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
- 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
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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