Allopurinol is a medicine that lowers the amount of uric acid in the blood. It is used to treat gout and prevent its flares, as well as uric acid kidney stones. Its effects take a few weeks to develop and the dose is adjusted by your doctor.
Also known as: Zyloric
Combining Amoxicillin and Allopurinol increases the incidence of skin rashes.
As with ampicillin, the allopurinol label lists "amoxicillin" among the drugs that "may increase the risk of serious skin reactions" (section 7.1) and recommends "discontinuing allopurinol immediately if a skin rash develops". The mechanism is shared with ampicillin — penicillins are believed to increase skin reactivity to allopurinol, possibly through alteration of the gut microbiota or accumulation of the oxypurinol metabolite. The combination is frequent in practice (gout prophylaxis during antibiotic therapy for respiratory or urinary infection). The rash is usually maculopapular and benign, but can progress to severe reactions (DRESS, Stevens-Johnson syndrome). Start allopurinol and the antibiotic at different times whenever possible; if the patient is already on allopurinol, advise them to watch their skin while taking amoxicillin; if a rash appears, stop both and use an alternative antibiotic (macrolide, doxycycline) or reintroduce allopurinol after resolution, with vigilance.
Allopurinol + amoxicillin: increased risk of severe skin reaction. Watch for skin rash and stop if it appears.
Increased cutaneous hypersensitivity reactivity when coadministered; mechanism not fully established.
Skin status, signs of hypersensitivity.
Generalized rash, fever, mucosal involvement.
Watch for a rash; consider an antibiotic alternative or adjust allopurinol if the eruption is significant.
DailyMed/FDA (NIH/NLM) — approved Amoxicillin label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=57e56202-950b-10f6-e063-6394a90a4912 ; approved Allopurinol label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=b6c5b5c0-b1cb-44c0-a849-5d317e6fa300
Combining Ampicillin and Allopurinol increases the incidence of skin rashes.
The allopurinol label documents that "the following drugs may increase the risk of serious skin reactions: bendamustine, thiazide diuretics, ampicillin and amoxicillin" (section 7.1) and warns that "hypersensitivity reactions to allopurinol may be increased in patients with decreased kidney function receiving thiazide diuretics and allopurinol concurrently". The mechanism is not fully known, but ampicillin seems to increase skin reactivity during allopurinol therapy — possibly related to accumulation of the oxypurinol metabolite in the skin. The reaction is not a penicillin allergy but a maculopapular exanthema that can be severe (including hypersensitivity syndrome/DRESS). If a skin eruption appears when starting the combination, stop both and reassess; do not reintroduce allopurinol if the reaction was severe. In patients who need both, start separately, with weeks in between, and watch the skin.
Allopurinol + ampicillin: increased risk of severe skin reaction. Watch for skin rash; stop allopurinol at first sign.
Mechanism not fully established; increased cutaneous hypersensitivity reactivity when coadministered.
Skin status (eruption, extent, pruritus), signs of hypersensitivity.
Generalized rash, fever, mucosal involvement (hypersensitivity syndrome).
Watch for a rash; consider an alternative antibiotic or stop allopurinol if the eruption is extensive or pruritic; assess penicillin cross-reactivity.
DailyMed/FDA (NIH/NLM) — approved Ampicillin label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=402e7cc7-5ae8-c113-e063-6394a90aa54a ; approved Allopurinol label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=b6c5b5c0-b1cb-44c0-a849-5d317e6fa300
Two xanthine oxidase inhibitors: no benefit and increased risk of hypersensitivity reactions.
Allopurinol and febuxostat act by the same mechanism — xanthine oxidase inhibition — and combining them adds no efficacy in controlling hyperuricaemia, but can increase the risk of hypersensitivity reactions (including hypersensitivity syndrome and, rarely, severe skin reactions). In practice the combination is not used: the patient should be on a single xanthine oxidase inhibitor, at the titrated dose, with gout flare prophylaxis in the first months and uric acid monitoring. If intolerance to one occurs, switching to the other is considered, never combining them.
Two xanthine oxidase inhibitors: no benefit and increased risk of hypersensitivity reactions. Do not combine.
Overlapping mechanism (xanthine oxidase inhibition) and risk profile of severe cutaneous reactions.
Watch for skin rash and hypersensitivity symptoms.
Skin rash, pruritus, fever, hypersensitivity syndrome symptoms.
Do not combine; choose only one xanthine oxidase inhibitor.
DailyMed (FDA) — approved Allopurinol label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=b6c5b5c0-b1cb-44c0-a849-5d317e6fa300 ; approved Febuxostat label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=f2c338dc-5bab-49f4-a4ac-d8dea8afeea5 — additional reference: Prontuário Terapêutico do INFARMED (11th ed., 2012)
Severe myelosuppression. Allopurinol inhibits Azathioprine metabolism, with risk of severe leucopenia and infections.
Azathioprine is an inactive prodrug converted to 6-mercaptopurine, which is then metabolised by xanthine oxidase to inactive thiouric acid. Allopurinol inhibits xanthine oxidase and shifts metabolism towards cytotoxic 6-thioguanine nucleotides: the consequence is accumulation of active metabolites with severe, sometimes fatal, myelosuppression. The approved azathioprine label recommends reducing the dose to one quarter of the usual dose when allopurinol is added. Monitor the blood count frequently (weekly in the first weeks) and adjust the dose based on neutrophils and platelets; also monitor liver function.
Xanthine oxidase inhibitor + azathioprine: allopurinol blocks azathioprine metabolism and greatly raises its levels, with risk of severe myelosuppression and infections. If unavoidable, reduce azathioprine to about 25% of the dose and monitor the blood count.
Xanthine oxidase (inhibited by Allopurinol) inactivates the active metabolite 6-mercaptopurine.
Full blood count every 1–2 weeks when starting the combination.
Fever, recurrent infections, sore throat, spontaneous bruising.
Reduce Azathioprine to about 25% of the usual dose and monitor the full blood count.
DailyMed/FDA (NIH/NLM) — approved Allopurinol label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=b6c5b5c0-b1cb-44c0-a849-5d317e6fa300 ; approved Azathioprine label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=5116b22b-1460-5535-e063-6394a90acbe5
Alcohol raises serum urate and may trigger gout flares.
Limit or avoid alcohol, especially beer.
EMC-UK (MHRA) — approved Allopurinol SmPC: https://www.medicines.org.uk/emc/product/100235/smpc
Prior severe reaction to allopurinol contraindicates reintroduction.
Contraindicated; consider an alternative (febuxostat) with caution.
EMC-UK (MHRA) — approved Allopurinol SmPC: https://www.medicines.org.uk/emc/product/100235/smpc
Reduced renal excretion increases the risk of allopurinol hypersensitivity.
Adjust dose to renal function and monitor.
EMC-UK (MHRA) — approved Allopurinol SmPC: https://www.medicines.org.uk/emc/product/100235/smpc
Limited data; use in pregnancy only if benefit justifies risk.
Use only if necessary, at the lowest effective dose.
Limited data; prefer to avoid during breastfeeding.
Maintain effective contraception; limited conception data.
EMC-UK (MHRA) — approved Allopurinol SmPC: https://www.medicines.org.uk/emc/product/100235/smpc
Clinical and educational support tool. The information does not replace a medical prescription or the opinion of a qualified healthcare professional.
Reduces uric acid production by inhibiting xanthine oxidase, the enzyme that converts hypoxanthine to xanthine and xanthine to uric acid. This inhibition lowers serum and urinary uric acid, preventing urate deposits (gout flares, tophi, lithiasis) and uric acid nephropathy.
Allopurinol and its principal active metabolite, oxypurinol (alloxanthine), are both inhibitors of xanthine oxidase. Oxypurinol is also eliminated by tubular reabsorption, extending the inhibitory effect beyond the half-life of the parent drug.
Allopurinol is approximately 90% absorbed from the gastrointestinal tract. Peak plasma levels generally occur at 1.5 hours (allopurinol) and 4.5 hours (oxypurinol). After a single oral 300 mg dose, maximum plasma levels are about 3 mcg/mL of allopurinol and 6.5 mcg/mL of oxypurinol.
Allopurinol is metabolised to the active metabolite oxypurinol, also a xanthine oxidase inhibitor. Approximately 20% of ingested allopurinol is excreted in the faeces; oxypurinol is eliminated primarily unchanged in urine by glomerular filtration and tubular reabsorption.
The half-life of allopurinol is approximately 1–2 hours; that of its active metabolite oxypurinol is about 15 hours after an oral dose.
Medicines from the same therapeutic group (ATC classification) or the same pharmacological class.
