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. |
| Molecular Weight | 279.2 |
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 | Cidofovir is embryotoxic in animal studies and should be avoided in the first trimester unless benefit outweighs risk. It is classified as Pregnancy Category C. |
| 2nd trimester | Use with caution; potential for fetal harm. Only if clearly needed and no safer alternative. |
| 3rd trimester | Same as second trimester; risk of fetal toxicity remains. |
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.
| Placental transfer | Cidofovir crosses the placenta in animal models; limited human data suggest transfer occurs. |
| Breastfeeding | Cidofovir is excreted in rat milk; unknown in humans. Due to potential for toxicity and long half-life, breastfeeding is not recommended during therapy and for at least 48 hours after the last dose. |
■ 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 |
Severe renal impairment (creatinine clearance <15 mL/min or requiring dialysis)History of clinically significant hypersensitivity to cidofovir or any component of the formulationConcurrent use of nephrotoxic agents (e.g., aminoglycosides, amphotericin B, foscarnet) unless absolutely necessaryPregnancy (Category C; avoid unless benefit outweighs risk)
| 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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| Lactation Rating | L5 - Contraindicated |
| 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. |
| 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. |
| Food/Dietary | No specific food interactions. Probenecid should be taken with food to reduce gastrointestinal upset. Avoid alcohol and grapefruit juice due to lack of data, but no known interactions. |
| Clinical Pearls | Cidofovir is a nephrotoxic antiviral requiring probenecid coadministration to reduce renal accumulation. Monitor serum creatinine and urine protein before each dose; dose reduction or discontinuation for renal impairment. Contraindicated with concurrent nephrotoxic drugs. Administered intravenously only. Hydration and probenecid pretreatment essential. |
| Patient Advice | This medication can cause serious kidney damage; you must drink plenty of fluids before and after each dose. · You will receive probenecid and IV fluids to protect your kidneys; take probenecid exactly as directed with food to reduce nausea. · Report any signs of kidney problems: decreased urination, swelling, or blood in urine. · Avoid taking other medications that can harm kidneys (e.g., NSAIDs, aminoglycosides) unless approved by your doctor. · Regular blood and urine tests are required to monitor kidney function. · This drug is given intravenously only; do not miss appointments. · Inform your doctor if you are pregnant or planning pregnancy; cidofovir may harm the fetus. |