Cidofovir is an antiviral medication that belongs to the class of nucleotide analogs. It is primarily used in the treatment of various viral infections, particularly those caused by DNA viruses.
Mechanism of Action Cidofovir is a synthetic acyclic nucleoside phosphonate analog of deoxycytidine monophosphate. Unlike some other antiviral agents that require initial phosphorylation by viral enzymes, cidofovir is phosphorylated intracellularly by host cellular kinases into its active diphosphate form, cidofovir diphosphate. This active metabolite then competitively inhibits viral DNA polymerases. By mimicking a natural nucleotide, cidofovir diphosphate can be incorporated into the growing viral DNA chain, leading to chain termination and inhibition of viral DNA synthesis. This mechanism provides broad-spectrum activity against several DNA viruses, including cytomegalovirus (CMV), herpes simplex virus (HSV), varicella-zoster virus (VZV), Epstein-Barr virus (EBV), adenovirus, and human papillomavirus (HPV).
Indications The primary approved indication for intravenous cidofovir is the treatment of cytomegalovirus (CMV) retinitis in patients with acquired immunodeficiency syndrome (AIDS). Due to its significant potential for nephrotoxicity, it is typically reserved for cases where other treatments are contraindicated, ineffective, or have failed.
Cidofovir is also used off-label for a variety of other conditions, often in immunocompromised patients, including:
- Treatment of progressive multifocal leukoencephalopathy (PML), a rare demyelinating disease of the central nervous system caused by the JC virus.
- Cutaneous and anogenital warts caused by human papillomavirus (HPV), often administered topically or intralesionally.
- Molluscum contagiosum, particularly in immunocompromised individuals, applied topically.
- Adenovirus infections, especially in immunocompromised patients such as stem cell transplant recipients, where it may be used intravenously or as a nebulized solution.
- Oropharyngeal papillomatosis.
Administration Cidofovir is typically administered intravenously, usually accompanied by aggressive intravenous hydration with normal saline and co-administration of probenecid. Probenecid is given to reduce the drug's nephrotoxic potential by competitively inhibiting its active tubular secretion in the kidneys. It can also be compounded into topical formulations (e.g., gels, creams) for dermatological use or administered intralesionally for localized lesions, depending on the indication.
Adverse Effects The most significant and dose-limiting adverse effect of cidofovir is nephrotoxicity, which can manifest as elevated serum creatinine, proteinuria, and Fanconi syndrome. To mitigate this risk, patients undergo pre-hydration and receive probenecid. Other common adverse effects include:
- Neutropenia (decreased white blood cell count)
- Ocular hypotony (reduced intraocular pressure), which can lead to vision changes.
- Metabolic acidosis
- Fever
- Headache
- Nausea and vomiting
- Asthenia (weakness)
- Alopecia (hair loss)
Contraindications Cidofovir is contraindicated in patients with a history of severe hypersensitivity to cidofovir or probenecid. It is also contraindicated in patients with significant renal impairment, typically defined by a baseline serum creatinine greater than 1.5 mg/dL or a calculated creatinine clearance less than 55 mL/min (specific cutoffs may vary based on clinical guidelines). Due to its teratogenic potential, it is contraindicated in pregnancy unless the potential benefits clearly outweigh the risks. Regular monitoring of renal function, blood counts, and intraocular pressure is crucial during treatment.