cidofovir

Cidofovir is an antiviral agent used primarily for cytomegalovirus (CMV) infections in immunocompromised patients, especially CMV retinitis in people with AIDS. It is a nucleotide analogue of cytosine phosphonate that inhibits viral DNA synthesis.

Mechanism of action: Cidofovir is phosphorylated intracellularly to cidofovir diphosphate, which inhibits viral DNA polymerase with higher affinity than cellular polymerases. This interference reduces replication of CMV and other DNA viruses in which the polymerase is inhibited by cidofovir.

Indications and spectrum: The drug is active against CMV and shows activity against other members of the herpesviridae family in some contexts. Clinically, it is used for CMV retinitis and other CMV infections in immunocompromised patients, particularly when there is resistance or intolerance to first-line agents.

Administration and pharmacokinetics: Cidofovir is given by intravenous infusion. A typical regimen for CMV retinitis involves an initial period of frequent dosing followed by less frequent maintenance doses; however, the exact schedule varies by indication and patient. The drug is eliminated mainly by the kidneys, with renal clearance being a key determinant of its disposition. Because of renal excretion, renal function strongly influences dosing and safety.

Adverse effects and safety: Nephrotoxicity is the most important dose-limiting adverse effect and requires careful monitoring of renal function. Other potential adverse effects include proteinuria and electrolyte disturbances. Because of the risk to kidneys, cidofovir is usually given with hydration and, in many regimens, coadministration of probenecid to reduce renal tubular uptake and toxicity.

Precautions and contraindications: Use is generally avoided or used with extreme caution in patients with significant renal impairment. Cidofovir can interact with other nephrotoxic drugs, and renal function should be monitored before and during treatment. Pregnancy and lactation require careful consideration of risks and benefits.

Regulatory status: Cidofovir was approved for CMV retinitis and certain CMV infections in immunocompromised patients. Its use is often limited by nephrotoxicity and the availability of alternative therapies.