Probenecid

Indications

Probenecid is used for: Hyperuricaemia with gout, Adjunct to antibacterial therapy

Adult Dose

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. 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 Dose

Oral Adjunct to antibacterial therapy 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 Dose

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

Administration

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

Contra Indications

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.

Precautions

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.

Pregnancy-Lactation

Interactions

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.

Adverse Effects

Side effects of Probenecid : 1-10% Headache Nausea Vomiting Loss of appetite GI upset Rash Flushing Dizziness Fever Aplastic anemia Hemolytic anemia Leukopenia Renal calculi Nephrotic syndrome (rare) Exacerbation of gout Gouty arthritis Hepatic necrosis (rare)

Mechanism of Action

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 beta-lactam antibiotics) by competitively inhibiting their renal tubular secretion.