Probenecid

Oral
Hyperuricaemia with gout
Adult: 250 mg bid for 1 wk, followed by 500 mg bid thereafter. Further increases of up to 2 g daily by increments of 500 mg every 4 wk may be given if needed.
Renal impairment:

CrCl (ml/min)	Dosage Recommendation
<30	Avoid use.

Oral
Adjunct to antibacterial therapy
Adult: 500 mg 4 times daily. Treatment of uncomplicated gonorrhoea: 1 g as a single dose together w/ an oral antibacterial, or 30 min before an injected antibacterial.
Child: ≥2 yr ≤50 kg: Initially, 25 mg/kg (700 mg/m²) followed by 40 mg/kg (1,200 mg/m²) in 4 divided doses.
Renal impairment: Contraindicated.

Should be taken with food. Take w/ meals or antacids. Ensure adequate fluid intake.

History of uric acid renal calculi or blood disorders; gout patients w/ severe renal impairment. Antibacterial adjunct in patients w/ renal impairment. Childn <2 yr. Concomitant use w/ salicylates.

Patient w/ history of peptic ulcer. Pregnancy and lactation. Patient Counselling Maintain adequate fluid intake (2-3 L/day). Monitoring Parameters Monitor uric acid, renal function, CBC.

Nausea, vomiting, anorexia, headache, sore gums, flushing, alopecia, dizziness, anaemia, urinary frequency; hypersensitivity reactions w/ fever, dermatitis, pruritus, urticaria; leucopenia, hepatic necrosis, nephrotic syndrome, aplastic anaemia, haemolytic anaemia; precipitation of acute gout.
Potentially Fatal: Severe hypersensitivity reactions (e.g. Stevens-Johnson syndrome) and anaphylaxis.

Symptoms: CNS stimulation, convulsions, resp failure. Management: Symptomatic and supportive treatment along w/ gastric lavage. IV short-acting barbiturates may be given.

May potentiate methotrexate toxicity. May increase peak plasma concentrations of paracetamol, naproxen, indometacin, ketoprofen, meclofenamate, lorazepam, rifampicin, aciclovir, ganciclovir and zidovudine. May decrease the renal excretion of conjugated sulfonamides. May prolong or enhance the action of oral sulfonylureas thereby increasing the risk of hypoglycaemia. Pyrazinamide may antagonise the uricosuric action of probenecid.
Potentially Fatal: Salicylates antagonise the uricosuric action of probenecid.

May give false positive results w/ some tests for glucose in the urine. Reduces the excretion of some iodinated contrast media and may interfere w/ laboratory tests by decreasing the excretion of aminohippuric acid, phenolsulfonphthalein, and sulfobromophthalein.

Probenecid competitively inhibits the reabsorption of uric acid at the proximal convoluted tubule, thereby promoting its excretion and reducing serum uric acid levels. It increases plasma levels of weak organic acids (e.g. penicillins, cephalosporins, or other β-lactam antibiotics) by competitively inhibiting their renal tubular secretion.
Absorption: Rapidly and completely absorbed from the GI tract. Time to peak plasma concentration: 2-4 hr.
Distribution: Crosses the placenta; concentrations in the CSF are approx 2% of plasma concentrations. Plasma protein binding: 85-95%.
Metabolism: Slowly metabolised by the liver to probenecid monoacyl glucuronide, 2 monohydroxylated compounds, a carboxylated metabolite and an N-depropylated compound.
Excretion: Via urine, mainly as metabolites. Plasma half-life: <5 to >8 hr.

Oral: Store between 20-25°C. Protect from light.

Hyperuricemia & Gout Preparations

M04AB01 - probenecid ; Belongs to the class of preparations increasing uric acid excretion. Used in the treatment of gout.