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
Severe myelosuppression. Allopurinol inhibits Azathioprine metabolism, with risk of severe leucopenia and infections.
Azathioprine is converted to the active metabolite 6-mercaptopurine, which is inactivated by xanthine oxidase; allopurinol inhibits that enzyme and markedly increases 6-mercaptopurine concentrations, with a risk of severe myelosuppression (pancytopenia), fever, serious infections and, in extreme cases, death. QUADRO 2 of Annex 7 lists allopurinol among the drugs that increase azathioprine toxicity, and the labels of both drugs strongly discourage the combination. When the combination is clinically essential (e.g. gout in a transplant patient or with inflammatory bowel disease), the azathioprine dose should be reduced to about 25% of the usual dose, with very close blood count monitoring in the first weeks. Starting allopurinol in patients stabilised on azathioprine without reassessing the dose should also be avoided.
Allopurinol + azathioprine: allopurinol inhibits the xanthine oxidase that metabolises azathioprine — severe and potentially fatal myelosuppression; contraindicated or requires a 75% dose reduction.
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.
Prontuário Terapêutico do INFARMED (11th ed., 2012) — Annex 7, QUADRO 2 (Allopurinol)
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)
Acenocoumarol + allopurinol: allopurinol may potentiate the anticoagulant effect of coumarins — watch INR when starting allopurinol.
QUADRO 2 (Warfarin) explicitly refers "See also: Alcohol, Allopurinol", recognising the potential interaction of allopurinol with coumarin anticoagulants (increased anticoagulant effect, possibly via metabolic inhibition).
Monitor INR after starting or changing the allopurinol dose.
Elevated INR or bleeding after starting allopurinol.
When starting allopurinol, monitor INR and adjust the anticoagulant dose if needed.
Prontuário Terapêutico do INFARMED (11th ed., 2012) — Annex 7, Table 2 (Oral anticoagulants: Acenocoumarol — see Warfarin; Allopurinol)
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
100 to 200 mg/day in moderate and 100 mg on alternate days in severe renal impairment; increased risk of toxicity (skin rashes).
Reduce the dose according to the degree of renal impairment; watch for skin rashes.
Prontuário Terapêutico do INFARMED (11th ed., 2012) — Annex 4, Drugs and renal impairment: 100 to 200 mg/day in moderate and 100 mg on alternate days in severe renal impairment; increased risk of toxicity (skin rashes).
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 ; Prontuário Terapêutico do INFARMED (11th ed., 2012) — Annex 2, Drugs and Breastfeeding: Present in milk; it is not known whether it is harmful.
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.
