Summary
Probenecid significantly increases cidofovir plasma concentrations and reduces its renal clearance, potentially leading to enhanced nephrotoxicity. This interaction requires careful monitoring and possible dose adjustments when these medications are used together.
Introduction
Probenecid is a uricosuric agent primarily used to treat gout and hyperuricemia by blocking uric acid reabsorption in the kidneys. It also inhibits organic anion transporters, affecting the elimination of various drugs. Cidofovir is an antiviral medication belonging to the nucleotide analog class, primarily used to treat cytomegalovirus (CMV) retinitis in immunocompromised patients, particularly those with HIV/AIDS. Both drugs are eliminated through the kidneys, making their interaction clinically significant.
Mechanism of Interaction
The interaction between probenecid and cidofovir occurs through inhibition of renal tubular secretion. Probenecid blocks organic anion transporters (OAT1 and OAT3) in the proximal tubules of the kidneys, which are responsible for the active secretion of cidofovir. This inhibition leads to decreased renal clearance of cidofovir, resulting in increased plasma concentrations and prolonged elimination half-life. The reduced clearance can lead to accumulation of cidofovir in renal tissues, potentially increasing the risk of nephrotoxicity.
Risks and Symptoms
The primary clinical risk of this interaction is enhanced nephrotoxicity from cidofovir accumulation. Cidofovir is inherently nephrotoxic, and increased exposure due to probenecid co-administration can lead to acute kidney injury, proteinuria, and electrolyte imbalances. Patients may experience decreased creatinine clearance, elevated serum creatinine, and potential progression to chronic kidney disease. The risk is particularly elevated in patients with pre-existing kidney disease, dehydration, or concurrent use of other nephrotoxic medications. Additionally, increased cidofovir levels may enhance other dose-related adverse effects including neutropenia and metabolic acidosis.
Management and Precautions
When probenecid and cidofovir must be used together, close monitoring of renal function is essential. Baseline and regular assessment of serum creatinine, blood urea nitrogen, creatinine clearance, and urinalysis should be performed. Consider reducing cidofovir dose by 50% when co-administered with probenecid, though specific dosing guidelines should be confirmed with current prescribing information. Ensure adequate hydration and consider pre-hydration with normal saline. Monitor for signs of nephrotoxicity including decreased urine output, edema, and electrolyte abnormalities. Discontinue cidofovir if significant renal impairment develops. Alternative antiviral agents should be considered when possible to avoid this interaction entirely.
Probenecid interactions with food and lifestyle
Probenecid should be taken with food or milk to reduce gastrointestinal irritation and improve tolerance. Adequate fluid intake (at least 2-3 liters per day) is recommended to prevent kidney stone formation, as probenecid can increase uric acid excretion in urine. Alcohol consumption should be limited or avoided, as alcohol can increase uric acid levels and counteract the uric acid-lowering effects of probenecid, potentially reducing its effectiveness in treating gout.
