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Drug Interactions between allopurinol and ampicillin / probenecid

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

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Interactions between your drugs

Moderate

ampicillin allopurinol

Applies to: ampicillin / probenecid and allopurinol

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

ampicillin probenecid

Applies to: ampicillin / probenecid and ampicillin / probenecid

Probenecid may increase the plasma concentrations and half-lives of penicillins. The mechanism is competitive inhibition by probenecid of the renal tubular secretion of penicillins. While this interaction is often exploited to enhance the antibacterial effect of penicillins, toxicity may occur and should be considered if high penicillin dosages are administered intravenously.

References (6)
  1. Sommers DK, Schoeman HS (1987) "Drug interactions with urate excretion in man?" Eur J Clin Pharmacol, 32, p. 499-502
  2. Waller ES, Sharanevych MA, Yakatan GJ (1982) "The effect of probenecid on nafcillin disposition." J Clin Pharmacol, 22, p. 482-9
  3. Shanson DC, McNabb R, Hajipieris P (1984) "The effect of probenecid on serum amoxycillin concentrations up to 18 hours after a single 3g oral dose of amoxycillin: possible implications for preventing endocarditis." J Antimicrob Chemother, 13, p. 629-32
  4. Sutherland R, Croydon EA, Rolinson GN (1972) "Amoxycillin: a new semi-synthetic penicillin." Br Med J, 3, p. 13-6
  5. Allen MB, Fitzpatrick RW, Barratt A, Cole RB (1990) "The use of probenecid to increase the serum amoxycillin levels in patients with bronchiectasis." Respir Med, 84, p. 143-6
  6. Gibaldi M, Schwartz MA (1968) "Apparent effect of probenecid on the distribution of penicillins in man." Clin Pharmacol Ther, 9, p. 345-9
Minor

allopurinol probenecid

Applies to: allopurinol and ampicillin / probenecid

The renal excretion allopurinol's active metabolite, oxypurinol, may be increased when coadministered with probenecid and/or large doses of salicylates (e.g., aspirin). At the same time, both probenecid and large doses of salicylates may have a hypouricemic effect; allopurinol may also inhibit probenecid metabolism. The clinical significance of this interaction is unknown. Patients should be monitored for altered effects of both allopurinol and probenecid.

References (10)
  1. Elion GB, Yu TF, Gutman AB, Hitchings GH (1968) "Renal clearance of oxipurinol, the chief metabolite of allopurinol." Am J Med, 45, p. 69-77
  2. Tjandramaga TB, Cucinell SA, Israili ZH, et al. (1972) "Observations on the disposition of probenecid in patients receiving allopurinol." Pharmacology, 8, p. 259-72
  3. Kelley WN (1976) "Current therapy of gout and hyperuricemia." Hosp Pract, 11, p. 69-76
  4. Stocker S (2011) "Pharmacokinetic and pharmacodynamic interaction between allopurinol and probenecid in patients with gout" J Rheumatol, 38, p. 904-910
  5. Reinders M (2007) "Biochemical effectiveness of allopurinol and allopurinol-probenecid in previously benzbromarone-treated gout patients" Clin Rheumatol, 26, p. 1459-1465
  6. Price GE (1963) "The Effects of Oral Salicylate on Serum Uric Acid Levels" Can Med Assoc J, 88, p. 1065-1067
  7. (2024) "Product Information. Allopurinol (Sandoz) (allopurinol)." Sandoz Pty Ltd
  8. (2021) "Product Information. Zyloric (allopurinol)." Aspen Pharma Trading Ltd
  9. (2021) "Product Information. Zyloprim (allopurinol)." AA Pharma Inc, 248178
  10. (2024) "Product Information. Allopurinol (allopurinol)." Actavis U.S. (Purepac Pharmaceutical Company)

Drug and food/lifestyle interactions

Moderate

ampicillin food/lifestyle

Applies to: ampicillin / probenecid

ADJUST DOSING INTERVAL: Certain penicillins may exhibit reduced gastrointestinal absorption in the presence of food. The therapeutic effect of the antimicrobial may be reduced.

MANAGEMENT: The interacting penicillin should be administered one hour before or two hours after meals. Penicillin V and amoxicillin are not affected by food and may be given without regard to meals.

References (6)
  1. Neu HC (1974) "Antimicrobial activity and human pharmacology of amoxicillin." J Infect Dis, 129, s123-31
  2. Welling PG, Huang H, Koch PA, Madsen PO (1977) "Bioavailability of ampicillin and amoxicillin in fasted and nonfasted subjects." J Pharm Sci, 66, p. 549-52
  3. McCarthy CG, Finland M (1960) "Absorption and excretion of four penicillins." N Engl J Med, 263, p. 315-26
  4. Cronk GA, Wheatley WB, Fellers GF, Albright H (1960) "The relationship of food intake to the absorption of potassium alpha-phenoxyethyl penicillin and potassium phenoxymethyl penicillin from the gastrointestinal tract." Am J Med Sci, 240, p. 219-25
  5. Klein JO, Sabath LD, Finland M (1963) "Laboratory studies on oxacillin. I: in vitro activity against staphylococci and some other bacterial pathogens. II: absorption and urinary excretion in normal young." Am J Med Sci, 245, p. 399-411
  6. Neuvonen PJ, Elonen E, Pentikainen PJ (1977) "Comparative effect of food on absorption of ampicillin and pivampicillin." J Int Med Res, 5, p. 71-6
Moderate

allopurinol food/lifestyle

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)

Therapeutic duplication warnings

Therapeutic duplication is the use of more than one medicine from the same drug category or therapeutic class to treat the same condition. This can be intentional in cases where drugs with similar actions are used together for demonstrated therapeutic benefit. It can also be unintentional in cases where a patient has been treated by more than one doctor, or had prescriptions filled at more than one pharmacy, and can have potentially adverse consequences.

Duplication

Anti-gout agents

Therapeutic duplication

The recommended maximum number of medicines in the 'anti-gout agents' category to be taken concurrently is usually one. Your list includes two medicines belonging to the 'anti-gout agents' category:

  • allopurinol
  • ampicillin/probenecid

Note: In certain circumstances, the benefits of taking this combination of drugs may outweigh any risks. Always consult your healthcare provider before making changes to your medications or dosage.

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.

Medical Disclaimer