CIDOFOVIR
Clinical safety rating: avoid
Contraindicated (not allowed)
Cidofovir is a nucleotide analog that inhibits viral DNA polymerase by competing with deoxycytidine triphosphate for incorporation into viral DNA, resulting in chain termination and inhibition of viral replication.
| Metabolism | Cidofovir is phosphorylated intracellularly to its active metabolite, cidofovir diphosphate. It is not significantly metabolized by hepatic enzymes and is primarily eliminated unchanged by the kidneys via glomerular filtration and active tubular secretion. |
| Excretion | Renal excretion of unchanged drug via glomerular filtration and tubular secretion accounts for approximately 90% of the administered dose. Biliary/fecal elimination is minimal (<5%). |
| Half-life | Terminal elimination half-life is approximately 2.5 hours. However, the intracellular half-life of the active diphosphate metabolite is >48 hours, supporting once-weekly dosing. |
| Protein binding | Less than 6% bound to plasma proteins. |
| Volume of Distribution | Volume of distribution is approximately 0.5 L/kg, indicating limited tissue distribution, consistent with a hydrophilic compound that does not extensively cross cell membranes (except via active transport into renal tubular cells). |
| Bioavailability | Oral bioavailability is negligible (<5%); therefore, cidofovir is only administered intravenously. |
| Onset of Action | Intravenous administration: antiviral effect begins within 24–48 hours based on reduction in viral DNA load. No other routes are clinically relevant. |
| Duration of Action | Antiviral effect persists for 7–10 days after a single dose due to long intracellular half-life of the active metabolite. Dosing interval is weekly. |
5 mg/kg intravenously once weekly for 2 weeks, then 5 mg/kg every 2 weeks. Administer with probenecid 2 g orally 3 hours before dose, then 1 g at 2 and 8 hours after dose. Hydrate with 1 L normal saline before infusion.
| Dosage form | SOLUTION |
| Renal impairment | Contraindicated if serum creatinine >1.5 mg/dL, calculated creatinine clearance ≤55 mL/min, or urine protein ≥100 mg/dL. For CrCl 41-55 mL/min: reduce dose to 3 mg/kg. For CrCl 30-40 mL/min: 1.5 mg/kg. Do not use if CrCl <30 mL/min. |
| Liver impairment | No specific Child-Pugh adjustments are recommended; use with caution in hepatic impairment due to potential nephrotoxicity. No dose adjustment guidelines exist. |
| Pediatric use | Not approved for pediatric use. Safety and efficacy not established. No standard weight-based dosing. |
| Geriatric use | Use with caution; select dose based on renal function. Consider age-related decline in renal function; monitor serum creatinine and CrCl closely. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Probenecid is required during administration to reduce nephrotoxicity and other nephrotoxic drugs should be avoided Causes severe nephrotoxicity requires pre-hydration and renal function monitoring.
| Breastfeeding | Excreted in human milk; M/P ratio unknown. Potential for serious adverse reactions in nursing infants (nephrotoxicity, neutropenia). Discontinue breastfeeding or discontinue drug, considering importance to mother. |
| Teratogenic Risk | Pregnancy category C. Animal studies show embryotoxicity and teratogenicity at subtoxic doses. First trimester exposure associated with increased risk of congenital malformations (craniofacial, skeletal, cardiovascular). Second/third trimester use may cause reversible fetal nephrotoxicity and ototoxicity. Avoid in pregnancy unless benefit outweighs risk. |
■ FDA Black Box Warning
WARNING: Renal toxicity, neutropenia, and carcinogenicity. Cidofovir is contraindicated in patients with a serum creatinine level >1.5 mg/dL, a calculated creatinine clearance ≤55 mL/min, or a urine protein ≥100 mg/dL (equivalent to ≥2+ proteinuria). Acute renal failure can occur. Neutropenia may be dose-limiting. Cidofovir is carcinogenic in animals and should be considered a potential human carcinogen.
| Common Effects | Nephrotoxicity |
| Serious Effects |
["Hypersensitivity to cidofovir or any component of the formulation","Pre-existing severe renal impairment (serum creatinine >1.5 mg/dL, creatinine clearance ≤55 mL/min, or urine protein ≥100 mg/dL)","Concurrent or recent use of nephrotoxic agents (e.g., aminoglycosides, amphotericin B, foscarnet, intravenous pentamidine, vancomycin, nonsteroidal anti-inflammatory drugs [NSAIDs])","Pregnancy (based on animal data showing teratogenicity)"]
| Precautions | ["Renal toxicity: Monitor serum creatinine and urine protein before each dose; dose adjustment or discontinuation may be necessary.","Neutropenia: Monitor neutrophil counts; dose adjustment or use of granulocyte colony-stimulating factor (G-CSF) may be required.","Ocular hypotony: Monitor intraocular pressure, especially with intravitreal administration.","Carcinogenicity: Long-term risk of malignancy; use only when benefits outweigh risks.","Embryo-fetal toxicity: May cause fetal harm; advise females of reproductive potential to use effective contraception.","Fanconi syndrome: Report any signs of renal tubular damage."] |
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| Fetal Monitoring | Monitor maternal renal function (serum Cr, urine protein), CBC with differential, liver enzymes every 2 weeks. Fetal ultrasound for anomalies if exposure occurs in first trimester. Monitor newborn for renal function and hearing impairment if exposed in utero. |
| Fertility Effects | Animal studies show reduced spermatogenesis and ovarian atrophy at high doses. No human data on fertility impairment; advise reproductive-aged patients to use effective contraception during and for 3 months after therapy. |