Drug Interactions between Omeclamox-Pak and sildenafil
This report displays the potential drug interactions for the following 2 drugs:
- Omeclamox-Pak (amoxicillin/clarithromycin/omeprazole)
- sildenafil
Interactions between your drugs
clarithromycin sildenafil
Applies to: Omeclamox-Pak (amoxicillin / clarithromycin / omeprazole) and sildenafil
ADJUST DOSE: Coadministration with potent inhibitors of CYP450 3A4 may significantly increase the plasma concentrations of sildenafil, which is primarily metabolized by the isoenzyme. The possibility of prolonged and/or increased pharmacologic effects of sildenafil should be considered. In 14 healthy volunteers, the potent CYP450 3A4 inhibitor ritonavir (500 mg twice a day for 7 days) increased mean peak plasma concentration (Cmax) and area under the concentration-time curve (AUC) of sildenafil (100 mg single dose) by 300% and 1000%, respectively, compared to sildenafil given alone. At 24 hours, sildenafil plasma levels were still approximately 200 ng/mL as opposed to about 5 ng/mL with sildenafil alone. In a parallel study, saquinavir (SGC 1200 mg three times a day for 7 days) increased single-dose sildenafil Cmax and AUC by 140% and 210%, respectively, in 14 healthy volunteers. No change in safety or tolerability of sildenafil was observed with either protease inhibitor. In six HIV-infected patients stabilized on triple antiretroviral therapy containing indinavir (800 mg three times a day), the AUC of a single 25 mg dose of sildenafil was 4.4 times higher than dose-normalized data from historical controls. The patients experienced headache, flushing, dyspepsia and rhinitis, and there was a mean maximal decrease in blood pressure of 14/10 mmHg. The interaction was also suspected in the death of a 47-year-old man who used sildenafil (25 mg) during treatment with ritonavir and saquinavir. Another CYP450 3A4 inhibitor, erythromycin (500 mg twice daily for 5 days), increased single-dose sildenafil AUC by 182%.
MANAGEMENT: Caution is advised if sildenafil is coadministered with potent CYP450 3A4 inhibitors. Dosage adjustments may be appropriate for sildenafil whenever a CYP450 3A4 inhibitor is added to or withdrawn from therapy based on efficacy and side effects. For the treatment of erectile dysfunction, an initial sildenafil dosage of 25 mg should be considered in patients treated concomitantly with potent CYP450 3A4 inhibitors. Patients should be advised to promptly notify their physician if they experience pain or tightness in the chest or jaw, irregular heartbeat, nausea, shortness of breath, visual disturbances, syncope, or prolonged erection (greater than 4 hours). For the treatment of pulmonary arterial hypertension, a dosage adjustment for sildenafil should be considered during coadministration with some CYP450 3A4 inhibitors such as erythromycin, saquinavir, telithromycin, and nefazodone. However, use with more potent CYP450 3A4 inhibitors such as ritonavir, ketoconazole, itraconazole, or clarithromycin is not recommended. Some authorities consider the use of very potent CYP450 3A4 inhibitors with sildenafil to be contraindicated in patients with pulmonary arterial hypertension. When sildenafil is used for the treatment of pulmonary hypertension, the manufacturer of itraconazole recommends avoiding concomitant use during and for 2 weeks after treatment with itraconazole.
References
- (2002) "Product Information. Sporanox (itraconazole)." Janssen Pharmaceuticals
- (2001) "Product Information. Viagra (sildenafil)." Pfizer U.S. Pharmaceuticals
- Nandwani R, Gourlay Y (1999) "Possible interaction between sildenafil and HIV combination therapy." Lancet, 353, p. 840
- Hall MCS, Ahmad S (1999) "Interaction between sildenafil and HIV-1 combination therapy." Lancet, 353, p. 2071-2
- Merry C, Barry MG, Ryan M, Tjia JF, Hennessy M, Eagling VA, Mulcahy F, Back DJ (1999) "Interaction of sildenafil and indinavir when co-administered to HIV-positive patients." AIDS, 13, f101-7
- Warrington JS, Shader RI, vonMoltke LL, Greenblatt DJ (2000) "In vitro biotransformation of sildenafil (Viagra): Identification of human cytochromes and potential drug interactions." Drug Metab Disposition, 28, p. 392-7
- Muirhead GJ, Wulff MB, Fielding A, Kleinermans D, Buss N (2000) "Pharmacokinetic interactions between sildenafil and saquinavir/ritonavir." Br J Clin Pharmacol, 50, p. 99-107
- Hyland R, Roe GH, Jones BC, Smith DA (2001) "Identification of the cytochrome P450 enzymes involved in the N-demethylation of sildenafil." Br J Clin Pharmaacol, 51, p. 239-48
- (2005) "Product Information. Revatio (sildenafil)." Pfizer U.S. Pharmaceuticals Group
- Cerner Multum, Inc. "UK Summary of Product Characteristics."
- Cerner Multum, Inc. "Australian Product Information."
- (2022) "Product Information. Voquezna Dual Pak (amoxicillin-vonoprazan)." Phathom Pharmaceuticals, Inc
- (2022) "Product Information. Voquezna Triple Pak (amoxicillin/clarithromycin/vonoprazan)." Phathom Pharmaceuticals, Inc
amoxicillin clarithromycin
Applies to: Omeclamox-Pak (amoxicillin / clarithromycin / omeprazole) and Omeclamox-Pak (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: Omeclamox-Pak (amoxicillin / clarithromycin / omeprazole) and Omeclamox-Pak (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
sildenafil food
Applies to: sildenafil
GENERALLY AVOID: Coadministration with grapefruit juice may slightly increase the oral bioavailability and delay the onset of action of sildenafil. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruits. In a randomized, crossover study with 24 healthy male volunteers, ingestion of 250 mL of grapefruit juice one hour before and concurrently with a 50 mg dose of sildenafil increased the mean area under the plasma concentration-time curve (AUC) of sildenafil and its pharmacologically active N-desmethyl metabolite by 23% and 24%, respectively, compared to water. Peak plasma concentrations (Cmax) were unaltered, but the time to reach sildenafil Cmax was prolonged by 0.25 hour. The observed increase in sildenafil bioavailability is unlikely to be of clinical significance in most individuals. However, pharmacokinetic interactions involving grapefruit juice are often subject to a high degree of interpatient variability and may be significant in the occasional susceptible patient. Indeed, one subject in the study had a 2.6-fold increase in sildenafil concentrations.
MANAGEMENT: It may be advisable to avoid administration of sildenafil with grapefruit juice to prevent potential toxicity and delay in onset of action.
References
- Jetter A, Kinzig-Schippers M, Walchner-Bonjean M, et al. (2002) "Effects of grapefruit juice on the pharmacokinetics of sildenafil." Clin Pharmacol Ther, 71, p. 21-29
clarithromycin food
Applies to: Omeclamox-Pak (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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