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Drug Interactions between allopurinol and amoxicillin / clarithromycin / omeprazole

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

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Interactions between your drugs

Moderate

allopurinol amoxicillin

Applies to: allopurinol and amoxicillin / clarithromycin / omeprazole

MONITOR: Coadministration of allopurinol with ampicillin or amoxicillin may increase the risk of skin rash and hypersensitivity. The mechanism of interaction is unknown, and it is unclear whether the condition of hyperuricemia or the actual exposure to allopurinol is responsible. In a retrospective study, 15 out of 67 patients (22%) who took ampicillin with allopurinol developed a skin rash, compared to 94 out of 1257 patients (7.5%) who took ampicillin without allopurinol. An updated study by the same group of investigators consisted of 252 patients who took ampicillin with allopurinol and 4434 who took ampicillin alone. The incidence of rash was 13.9% in the allopurinol group and 5.7% in the ampicillin-only group. Similar results were reported for amoxicillin. Specifically, 8 out of 36 patients (22%) treated concomitantly with allopurinol developed a rash, compared to 52 out of 887 patients (5.9%) on amoxicillin without allopurinol.

MANAGEMENT: Closer monitoring for the development of skin rash is recommended if ampicillin or amoxicillin are used concurrently with allopurinol. Some authorities suggest using an alternative to ampicillin or amoxicillin in patients receiving allopurinol when possible. Patients should be advised to promptly report any signs of skin hypersensitivity, including rash, pruritus, fever, or chills.

References (8)
  1. Singer JZ, Wallace SL (1986) "The allopurinol hypersensitivity syndrome." Arthritis Rheum, 29, p. 82-7
  2. Boston Collaborative Drug Surveillance Program (1972) "Excess of ampicillin rashes associated with allopurinol or hyperuricemia." N Engl J Med, 286, p. 505-7
  3. (2022) "Product Information. Zyloprim (allopurinol)." Glaxo Wellcome
  4. Jick H, Porter JB (1981) "Potentiation of ampicillin skin reactions by allopurinol or hyperuricemia." J Clin Pharmacol, 21, p. 456-8
  5. (2024) "Product Information. Allopurinol (Sandoz) (allopurinol)." Sandoz Pty Ltd
  6. (2021) "Product Information. Zyloric (allopurinol)." Aspen Pharma Trading Ltd
  7. (2021) "Product Information. Zyloprim (allopurinol)." AA Pharma Inc, 248178
  8. (2024) "Product Information. Allopurinol (allopurinol)." Actavis U.S. (Purepac Pharmaceutical Company)
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 (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
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 (3)
  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

Drug and food interactions

Moderate

allopurinol food

Applies to: allopurinol

ADJUST DOSING INTERVAL: The tolerability of allopurinol may be improved by giving it after a meal. Additionally, when the dose is greater than 300 mg, dividing the total daily dose into smaller doses administered more often may be appropriate to help minimize gastrointestinal irritation.

MONITOR: Concomitant use of allopurinol with central nervous system (CNS) depressants, including alcohol, may potentiate adverse effects such as somnolence and sedation.

MANAGEMENT: To improve tolerability, some manufacturers suggest administering allopurinol after a meal. Additionally, if the daily dose is greater than 300 mg, administering allopurinol in divided doses may help reduce gastrointestinal intolerance. Patients should also be counseled to avoid or limit consumption of alcohol and to avoid activities requiring mental alertness such as driving or operating hazardous machinery until they know how the medication affects them.

References (4)
  1. (2024) "Product Information. Allopurinol (Sandoz) (allopurinol)." Sandoz Pty Ltd
  2. (2021) "Product Information. Zyloric (allopurinol)." Aspen Pharma Trading Ltd
  3. (2021) "Product Information. Zyloprim (allopurinol)." AA Pharma Inc, 248178
  4. (2024) "Product Information. Allopurinol (allopurinol)." Actavis U.S. (Purepac Pharmaceutical Company)
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)
  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

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