chapter
Antigout drugs
Pages 6

Pyrazinamide should not be used in patients with gout

ALLOPURINOL ANTICANCER AND IMMUNOMODULATING DRUGS

ALLOPURINOL AZATHIOPRINE/ MERCAPTOPURINE

≠ mercaptopurine levels, with risk of toxicity (e.g. myelosuppression, pancreatitis)

Azathioprine is metabolized to mercaptopurine. Allopurinol inhibits hepatic metabolism of mercaptopurine

↓ doses of azathioprine and mercaptopurine by up to threequarters and monitor FBC, LFTs and amylase carefully

ALLOPURINOL CAPECITABINE/ FLUOROURACIL

Possible ↓ efficacy of capecitabine Capecitabine is a prodrug for fluorouracil; uncertain at which point allopurinol acts on the metabolic pathway

Manufacturers recommend avoiding co-administration

ALLOPURINOL CICLOSPORIN Ciclosporin levels may be ≠ Uncertain Monitor renal function closely ALLOPURINOL CYCLOPHOSPHAMIDE ≠ risk of bone marrow suppression Uncertain but allopurinol seems to

≠ cyclophosphamide levels Monitor FBC closely

ALLOPURINOL ANTICOAGULANTS – ORAL Uncommon instances of ≠ anticoagulant effect in patients on warfarin who started allopurinol

Allopurinol possibly ↓ hepatic metabolism of warfarin but considerable individual variation

Monitor INR closely when allopurinol is first started

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MUSCULOSKELETAL DRUGS ANTIGOUT DRUGS Colchicine

period of several weeks. 300 mg/day allopurinol does not seem to have this effect

Uncertain Monitor carbamazepine levels in patients taking long-term, high-dose allopurinol

ALLOPURINOL PHENYTOIN Phenytoin levels may be ≠ in some patients

Uncertain Monitor phenytoin levels

ALLOPURINOL ANTIHYPERTENSIVES AND HEART FAILURE DRUGS – ACE INHIBITORS

Risk of serious hypersensitivity with captopril and enalapril

Uncertain. Both drugs can cause hypersensitivity reactions

Warn patient to look for clinical features of hypersensitivity and Stevens-Johnson syndrome

ALLOPURINOL ANTIVIRALS – DIDANOSINE Didanosine levels may be ≠ Uncertain Watch for the early signs of toxicity ALLOPURINOL BRONCHODILATORS –

THEOPHYLLINE ≠ theophylline levels Allopurinol inhibits xanthine

oxidase Watch for early features of toxicity of theophylline (headache, nausea)

ALLOPURINOL DIURETICS – THIAZIDES Possible ≠ risk of severe allergic reactions when allopurinol is given with thiazides in the presence of renal impairment

Uncertain Caution in co-administering allopurinol with thiazides in the presence of renal insufficiency

COLCHICINE

COLCHICINE ANTIBIOTICS

COLCHICINE MACROLIDES Case reports of colchicine toxicity when macrolides were added

Uncertain; macrolides possibly inhibit hepatic metabolism of colchicine. Clarithromycin and erythromycin both inhibit intestinal P-gp, which may ≠ bioavailability of colchicine

Monitor FBC and renal function closely

COLCHICINE PYRAZINAMIDE ↓ efficacy of antigout drugs Pyrazinamide can induce hyperuricaemia

Pyrazinamide should not be used in patients with gout

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Mechanism Precautions

DRUGS – CICLOSPORIN

myopathy). ≠ penetration of ciclosporin through blood-brain barrier and ≠ risk of neurotoxicity

Competitive inhibition of P-gp with ≠ penetrations of ciclosporin to tissues. Ciclosporin inhibits transport of colchicine

Avoid concurrent use

PROBENECID PROBENECID ACE INHIBITORS ≠ plasma concentrations of

captopril and enalapril; uncertain clinical significance

Renal excretion of captopril and enalapril ↓ by probenecid

Monitor BP closely

PROBENECID ANALGESICS – NSAIDS Probenecid ≠ levels of indometacin and ketorolac and possibly dexketoprofen, ketoprofen, naproxen, tenoxicam and tiaprofenic acid

Probenecid competitively inhibits renal metabolism of these NSAIDs

Watch for signs of toxicity of these NSAIDs. Consider using an alternative NSAID. The manufacturers of ketorolac advise avoiding co-administration of ketorolac and probenecid

PROBENECID ANTIBIOTICS PROBENECID CEPHALOSPORINS ≠ cephalosporin levels Uncertain Watch for ≠ incidence of side-effects

of antibiotic

PROBENECID DAPSONE ≠ dapsone levels, with risk of bone marrow suppression

Uncertain Monitor FBC closely

PROBENECID MEROPENEM ≠ meropenem levels Uncertain Manufacturers recommend avoiding co-administration

PROBENECID NITROFURANTOIN ↓ efficacy of nitrofurantoin in urinary tract infections

↓ urinary excretion Watch for poor response to nitrofurantoin

PROBENECID PENICILLINS ≠ penicillin levels Uncertain Watch for ≠ incidence of side-effects of antibiotic

PROBENECID PYRAZINAMIDE ↓ efficacy of antigout drugs Pyrazinamide can induce hyperuricaemia

Pyrazinamide should not be used in patients with gout

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MUSCULOSKELETAL DRUGS ANTIGOUT DRUGS Probenecid

Uncertain Watch for ≠ incidence of sideeffects. Moxifloxacin, ofloxacin and sparfloxacin do not seem to interact and could be used as alternative therapy

PROBENECID ANTICANCER AND IMMUNOMODULATING DRUGS

PROBENECID AMINOSALICYLATES Aminosalicylate levels are ≠ by probenecid

Probenecid competes with aminosalicylate for active renal excretion

Watch for early features of toxicity of aminosalicylate. Consider ↓ dose of aminosalicylate

PROBENECID METHOTREXATE ≠ methotrexate levels Probenecid ↓ elimination of methotrexate renally by interfering with tubular secretion in the proximal tubule and also ↓ protein binding of methotrexate (a relatively minor effect). Probenecid competes with methotrexate for renal elimination

Avoid co-administration if possible; if not possible, ↓ dose of methotrexate and monitor FBC closely

PROBENECID PEMETREXED ≠ pemetrexed levels Probable ↓ renal excretion of pemetrexed

Avoid co-administration where possible. If both need to be given, monitor FBC and renal function closely and watch for gastrointestinal disturbances and features of myopathy

PROBENECID ANTIDIABETIC DRUGS

PROBENECID METFORMIN ≠ level of metformin and risk of lactic acidosis. The onset of lactic acidosis is often subtle with symptoms of malaise, myalgia, respiratory distress and ≠ nonspecific abdominal distress. There may be hypothermia and resistant bradyarrhythmias

↓ renal excretion of metformin Watch for hypoglycaemia and lactic acidosis. Warn patients about hypoglycaemia ➣ For signs and symptoms of hypoglycaemia, see Clinical Features of Some Adverse Drug Interactions, Hypoglycaemia

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glimepride

Attributed to ↓ renal excretion of sulphonylureas by probenecid. Probenecid is also an inhibitor of CYP2C9 isoenzymes

PROBENECID ANTIPLATELET AGENTS Aspirin possibly ↓ efficacy of probenecid

Uncertain Watch for poor response to probenecid

PROBENECID ANTIVIRALS

PROBENECID ANTIVIRALS ≠ levels of aciclovir, valaciclovir and ganciclovir

Competitive inhibition of renal excretion

Care with co-administering probenecid with high-dose antivirals

PROBENECID ZIDOVUDINE ≠ levels of zidovudine with cases of toxicity

↓ hepatic metabolism of zidovudine

Avoid co-administration if possible; if not possible, ↓ dose of zidovudine

PROBENECID SODIUM PHENYLBUTYRATE

Possibly ≠ sodium phenylbutyrate levels

Possibly ↓ excretion of sodium phenylbutyrate

Watch for signs of sodium phenylbutyrate toxicity. Monitor FBC, U&Es and ECG

SULFINPYRAZONE

SULFINPYRAZONE ANTIBIOTICS

SULFINPYRAZONE NITROFURANTOIN ↓ renal excretion of nitrofurantoin, which ↓ its efficacy in urinary tract infections

Uncertain Watch for poor response to nitrofurantoin

SULFINPYRAZONE PENICILLINS ≠ penicillin levels Uncertain Watch for ≠ incidence of side-effects SULFINPYRAZONE PYRAZINAMIDE ↓ efficacy of antigout drugs Pyrazinamide can induce

hyperuricaemia Pyrazinamide should not be used in patients with gout

SULFINPYRAZONE ANTICANCER AND IMMUNOMODULATING DRUGS – CICLOSPORIN

Cases of ↓ ciclosporin levels with transplant rejection

Uncertain Watch for ↓ efficacy of ciclosporin

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MUSCULOSKELETAL DRUGS ANTIGOUT DRUGS Sulphinpyrazone

Uncertain; possibly displacement of anticoagulant from plasma proteins, possibly inhibition of CYP2C9-mediated metabolism of warfarin

Monitor INR at least weekly until stable

SULFINPYRAZONE ANTIDIABETIC DRUGS

SULPHINPYRAZONE NATEGLINIDE ≠ blood levels of nateglinide Sulphinpyrazone is a selective CYP2C9 inhibitor

Need to monitor blood sugar weekly in patients receiving both drugs. Warn patients about hypoglycaemia ➣ For signs and symptoms of hypoglycaemia, see Clinical Features of Some Adverse Drug Interactions, Hypoglycaemia

SULFINPYRAZONE SULPHONYLUREAS ≠ hypoglycaemic effect of sulphonylureas

Uncertain Monitor blood glucose regularly

SULFINPYRAZONE ANTIEPILEPTICS Phenytoin levels may be ≠ in some patients

Uncertain Monitor phenytoin levels

SULFINPYRAZONE ANTIPLATELET AGENTS High-dose aspirin antagonizes the urate-lowering effect of sulfinpyrazone

Salicylates block the sulfinpyrazoneinduced inhibition of renal tubular reabsorption of urate

Avoid long-term co-administration of high-dose aspirin with sulfinpyrazone. Low-dose aspirin does not seem to have this effect

SULFINPYRAZONE BETA-BLOCKERS Antihypertensive effects of oxprenolol ↓ by sulfinpyrazone

Unknown Monitor PR and BP closely; consider starting an alternative beta-blocker

SULFINPYRAZONE BRONCHODILATORS – THEOPHYLLINE

↓ theophylline levels Due to ≠ demethylation and hydroxylation, and thus ≠ clearance of theophylline

May need to ≠ dose of theophylline by 25%

SULFINPYRAZONE CALCIUM CHANNEL BLOCKERS

Serum concentrations of verapamil are significantly ↓ when it is co-administered with sulfinpyrazone

Uncertain, but presumed to be due to ≠ hepatic metabolism

Monitor PR and BP closely; watch for poor response to verapamil