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Penicillins: Drug-Drug Interactions

Allopurinol

The risk of rashes caused by aminopenicillins does not seem to be increased by parallel treatment with allopurinol, as had been suggested before.

Aminoglycosides

High doses of parenteral penicillin can inactivate aminoglycosides. In patients receiving low doses of aminoglycosides because of reduced renal function this can be clinically important. Parenteral administration of these drugs in neonatal dosages does not seem to produce relevant inactivation, and so temporal separation of the infusions is not required. Piperacillin protected against aminoglycoside nephrotoxicity without reducing its blood concentration; this was possibly a protective effect of co-administered mineral salts.

Penicillins: Drug-Drug Interactions

Ciclosporin

In a study in lung transplant recipients, ciclosporin nephrotoxicity was potentiated by nafcillin.

Methotrexate

Beta-lactams are weak organic acids that compete with the renal tubular secretion of methotrexate and its metabolites and reduce their clearance, leading to methotrexate toxicity. Consecutive aplastic crises have been described, particularly in patients with impaired renal clearance. In contrast, co-administration of flucloxacillin in another study produced a significant but not clinically important reduction in methotrexate AUC.

The more basic interactions between piperacillin and methotrexate and its major metabolite 7-hydroxymetho-trexate have been studied in rabbits. The interaction was mainly caused by reduced renal clearance of both methotrexate and its metabolite.

The authors concluded that renal function in patients taking this combination should be monitored, with adequate fluid intake, especially in elderly patients, because dehydration may accelerate the occurrence of toxicity.

Penicillins: Drug-Drug Interactions

Phenytoin

Competitive albumin binding of drugs with high serum protein affinity can increase pharmacologically active unbound concentrations and enhance the metabolism of low clearance drugs. In vitro data suggest a significant increase in unbound phenytoin concentration by high doses of oxacillin, especially with hypoalbuminemia or uremia.

Penicillins: Drug-Drug Interactions

Interference with Diagnostic Tests

Pseudoproteinuria

Patients who take penicillin G or ureidopenicillin derivatives in doses over 5 g/day develop pseudoproteinuria. Proteinuria should be evaluated by a bromphenol blue test (Albustix) or after urine dialysis.

17-ketosteroids

High-dosage penicillin produces abnormally high concentrations of 17-ketogenic steroids in the blood and high concentrations of 17-ketosteroid in the urine.

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