Drug Interactions between amoxicillin / clarithromycin / omeprazole and selumetinib
This report displays the potential drug interactions for the following 2 drugs:
- amoxicillin/clarithromycin/omeprazole
- selumetinib
Interactions between your drugs
clarithromycin selumetinib
Applies to: amoxicillin / clarithromycin / omeprazole and selumetinib
GENERALLY AVOID: Coadministration with potent or moderate inhibitors of CYP450 3A4 may increase the plasma concentrations of selumetinib, which is primarily metabolized by CYP450 3A4 and to a lesser extent by CYP450 2C19, 1A2, 2C9, 2E1, and 3A5. Selumetinib also undergoes glucuronidation by UGT1A1 and UGT1A3. When coadministered with itraconazole, a potent CYP450 3A4 inhibitor, selumetinib peak plasma concentration (Cmax) and systemic exposure (AUC) increased by 19% and 49%, respectively. When coadministered with fluconazole, a potent CYP450 2C19 and moderate CYP450 3A4 inhibitor, selumetinib Cmax and AUC increased by 26% and 53%, respectively. Concomitant use of erythromycin, a moderate CYP450 3A4 inhibitor, is predicted to increase selumetinib Cmax and AUC by 23% and 41%, respectively. Although not studied, inhibition of CYP450 3A4 may also increase the plasma concentrations of N-desmethyl selumetinib, an active metabolite that is generated primarily by CYP450 2C19 and 1A2 and metabolized via the same routes as selumetinib. N-desmethyl selumetinib represents less than 10% of selumetinib levels in human plasma, but is approximately 3 to 5 times more potent than the parent compound and contributes about 21% to 35% of the overall pharmacologic activity. Increased exposures to selumetinib and N-desmethyl selumetinib may increase the risk and/or severity of serious adverse effects such as cardiomyopathy (decrease in left ventricular ejection fraction by 10% or more below baseline), ocular toxicity (blurred vision, photophobia, cataracts, ocular hypertension, retinal pigment epithelial detachment, retinal vein occlusion), gastrointestinal toxicity (diarrhea, colitis), skin toxicity (dermatitis acneiform, maculopapular rash, eczema), and musculoskeletal toxicity (creatine phosphokinase elevations, myalgia, rhabdomyolysis).
MANAGEMENT: Concomitant use of selumetinib with potent or moderate CYP450 3A4 inhibitors should generally be avoided. If coadministration is required, a reduction in the dosage of selumetinib is recommended. Patients receiving selumetinib 25 mg/m2 twice daily should have the dosage reduced to 20 mg/m2 twice daily, and those receiving 20 mg/m2 twice daily should have the dosage reduced to 15 mg/m2 twice daily. Further dosage adjustments should be made according to clinical response and tolerance. Please refer to the product labeling for more detailed information on dosing adjustments. After discontinuation of the strong or moderate CYP450 3A4 inhibitor for 3 elimination half-lives, the selumetinib dosage that was taken prior to initiating the inhibitor may be resumed.
References (1)
- (2020) "Product Information. Koselugo (selumetinib)." Astra-Zeneca Pharmaceuticals
omeprazole selumetinib
Applies to: amoxicillin / clarithromycin / omeprazole and selumetinib
MONITOR: Coadministration with potent or moderate inhibitors of CYP450 2C19 may increase the plasma concentrations of selumetinib, which is primarily metabolized by CYP450 3A4 and to a lesser extent by CYP450 2C19, 1A2, 2C9, 2E1, and 3A5. Selumetinib's active metabolite, N-desmethyl selumetinib, is generated by CYP450 2C19 and 1A2 with additional contribution by CYP450 2C9 and 2A6, and metabolized through the same routes as selumetinib. N-desmethyl selumetinib represents less than 10% of selumetinib levels in human plasma, but is approximately 3 to 5 times more potent than the parent compound, contributing to about 21% to 35% of the overall pharmacologic activity. When coadministered with fluconazole, a potent CYP450 2C19 and moderate CYP450 3A4 inhibitor, selumetinib peak plasma concentration (Cmax) and systemic exposure (AUC) increased by 26% and 53%, respectively. Concomitant use of fluoxetine, a potent CYP450 2C19 and 2D6 inhibitor, is predicted to increase selumetinib AUC by 30 to 40% and Cmax by 20%. Increased exposures to selumetinib may increase the risk and/or severity of serious adverse effects such as cardiomyopathy (decrease in left ventricular ejection fraction by 10% or more below baseline), ocular toxicity (blurred vision, photophobia, cataracts, ocular hypertension, retinal pigment epithelial detachment, retinal vein occlusion), gastrointestinal toxicity (diarrhea, colitis), skin toxicity (dermatitis acneiform, maculopapular rash, eczema), and musculoskeletal toxicity (creatine phosphokinase elevations, myalgia, rhabdomyolysis).
MANAGEMENT: Caution is advised when selumetinib is used with potent or moderate CYP450 2C19 inhibitors.
References (2)
- Cerner Multum, Inc. "UK Summary of Product Characteristics."
- (2020) "Product Information. Koselugo (selumetinib)." Astra-Zeneca Pharmaceuticals
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 (3)
- 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 (3)
- 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
selumetinib food
Applies to: selumetinib
GENERALLY AVOID: Grapefruit juice may increase the plasma concentrations of selumetinib, which undergoes metabolism primarily by CYP450 3A4 and to a lesser extent by CYP450 2C19, 1A2, 2C9, 2E1 and 3A5, as well as glucuronidation by UGT1A1 and UGT1A3. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruit. Inhibition of hepatic CYP450 3A4 may also contribute. The interaction has not been studied with grapefruit juice, but has been reported for other CYP450 3A4 inhibitors. When coadministered with itraconazole, a potent CYP450 3A4 inhibitor, selumetinib peak plasma concentration (Cmax) and systemic exposure (AUC) increased by 19% and 49%, respectively. When coadministered with fluconazole, a potent CYP450 2C19 and moderate CYP450 3A4 inhibitor, selumetinib Cmax and AUC increased by 26% and 53%, respectively. Concomitant use of erythromycin, a moderate CYP450 3A4 inhibitor, is predicted to increase selumetinib Cmax and AUC by 23% and 41%, respectively. 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 selumetinib may increase the risk and/or severity of serious adverse effects such as cardiomyopathy (decrease in left ventricular ejection fraction by 10% or more below baseline), ocular toxicity (blurred vision, photophobia, cataracts, ocular hypertension, retinal pigment epithelial detachment, retinal vein occlusion), gastrointestinal toxicity (diarrhea, colitis), skin toxicity (dermatitis acneiform, maculopapular rash, eczema), and musculoskeletal toxicity (creatine phosphokinase elevations, myalgia, rhabdomyolysis).
MANAGEMENT: Patients should avoid consumption of grapefruit, grapefruit juice, or supplements that contain grapefruit during treatment with selumetinib.
References (2)
- (2024) "Product Information. Koselugo (selumetinib)." Alexion Pharmaceuticals Inc
- (2024) "Product Information. Koselugo (selumetinib)." AstraZeneca UK Ltd
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
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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