VISTIDE
Clinical safety rating: caution
Comprehensive clinical and safety monograph for VISTIDE (VISTIDE).
Cidofovir is a nucleotide analogue that inhibits viral DNA polymerase by incorporating into viral DNA and causing chain termination, with selectivity for cytomegalovirus (CMV) DNA polymerase.
| Metabolism | Minimal hepatic metabolism; primarily excreted unchanged in the urine via renal tubular secretion and glomerular filtration. |
| Excretion | Primarily renal excretion via glomerular filtration and active tubular secretion. Approximately 90-95% of the dose is excreted unchanged in the urine within 24 hours. Biliary/fecal excretion accounts for <5%. |
| Half-life | Terminal elimination half-life is approximately 1.5-2 hours in patients with normal renal function. In patients with renal impairment, the half-life can extend to 5-10 hours or longer, necessitating dose adjustment based on creatinine clearance. |
| Protein binding | Less than 5% bound to plasma proteins. Binding is negligible and not clinically significant. |
| Volume of Distribution | Steady-state volume of distribution is approximately 0.3-0.5 L/kg, indicating distribution primarily into extracellular fluid and tissues, but limited intracellular accumulation except in renal tubules. |
| Bioavailability | Intravenous route only; oral bioavailability is negligible (<5%) due to poor gastrointestinal absorption. Not administered orally. |
| Onset of Action | Intravenous infusion: Clinical antiviral effect typically observed within 1-2 days, with reduction in CMV DNA levels measurable after 1-3 doses. |
| Duration of Action | Antiviral effect persists for 1-2 weeks after a single dose due to prolonged intracellular active metabolite (cidofovir diphosphate) with a half-life of 30-100 hours. However, dosing interval is typically every other week due to nephrotoxicity concerns. |
| Molecular Weight | 279.18 |
5 mg/kg intravenously once weekly for 2 consecutive weeks, then every other week thereafter.
| Dosage form | SOLUTION |
| Renal impairment | Contraindicated in patients with serum creatinine >1.5 mg/dL, creatinine clearance ≤55 mL/min, or urine protein ≥100 mg/dL. No dose adjustment is recommended; if renal function deteriorates to these levels during therapy, discontinue VISTIDE. |
| Liver impairment | No specific adjustments provided for hepatic impairment. Use with caution in patients with hepatic dysfunction. |
| Pediatric use | Safety and efficacy not established in pediatric patients. |
| Geriatric use | No specific geriatric dose adjustments; use with caution due to age-related renal function decline. |
| 1st trimester | Contraindicated due to teratogenic effects observed in animal studies; avoid use in first trimester unless no safer alternative and clearly needed. |
| 2nd trimester | Use only if potential benefit justifies potential risk to fetus; cidofovir is embryotoxic in animals and may cause nephrotoxicity. |
| 3rd trimester | Use only if clearly needed; risk of fetal nephrotoxicity and teratogenicity unknown but possible due to placental transfer. |
Clinical note
Comprehensive clinical and safety monograph for VISTIDE (VISTIDE).
| Placental transfer | Cidofovir crosses the placenta in humans; however, exact extent is not well documented. Animal studies confirm placental transfer. |
| Breastfeeding | Not recommended during breastfeeding due to potential for serious adverse effects in nursing infant, including nephrotoxicity and carcinogenicity. |
■ FDA Black Box Warning
Renal impairment: Cidofovir is nephrotoxic and can lead to acute renal failure. Dose adjustment, hydration, and probenecid co-administration are required. Neutropenia: May cause severe neutropenia. Contraindicated in patients with pre-existing severe renal impairment (serum creatinine >1.5 mg/dL, creatinine clearance ≤55 mL/min, or urine protein ≥100 mg/dL).
| Serious Effects |
History of hypersensitivity to cidofovir or any component of the formulationSevere renal impairment (creatinine clearance ≤55 mL/min)Concurrent use with other nephrotoxic agents (e.g., aminoglycosides, amphotericin B, foscarnet, intravenous pentamidine, vancomycin)Pregnancy (unless benefit outweighs risk; considered contraindicated in first trimester)Breastfeeding (contraindicated per manufacturer)
| Precautions | Renal toxicity: Monitor renal function (serum creatinine, urine protein) before each dose; use with probenecid and hydration. Neutropenia: Monitor neutrophil counts. Ocular toxicity: May cause iritis, uveitis, or hypotony. Carcinogenicity: Potential for carcinogenesis in animals. Use in pregnancy: Category C; avoid unless benefit outweighs risk. |
| Food/Dietary |
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| Lactation Rating | L5 (Contraindicated) |
| Teratogenic Risk | Cidofovir is embryotoxic and teratogenic in animal studies. In pregnant women, use only if benefit outweighs risk. First trimester: avoid unless essential; may cause developmental abnormalities. Second and third trimesters: limited data; potential for fetal nephrotoxicity and ototoxicity. Should be used with extreme caution. |
| Fetal Monitoring | Monitor renal function (serum creatinine, urine protein) weekly; complete blood count with differential; liver function tests; monitor for metabolic acidosis. Fetal ultrasound to assess growth and anatomy. In neonates, monitor for renal impairment and neutropenia. |
| Fertility Effects | Cidofovir may impair fertility in males and females based on animal studies showing testicular atrophy and ovarian effects. In humans, effects on fertility are not well studied. |
| No specific food interactions; maintain adequate hydration; avoid grapefruit juice as it may interfere with drug metabolism (theoretical based on CYP inhibition). |
| Clinical Pearls | Administer with probenecid to reduce nephrotoxicity; monitor renal function closely; requires IV infusion over 1 hour; dose adjustment needed for renal impairment; contraindicated in patients with creatinine clearance ≤0.5 mL/min/kg; not recommended for use with other nephrotoxic drugs. |
| Patient Advice | You must take probenecid before and after each VISTIDE infusion to protect your kidneys. · Drink plenty of fluids before and after treatment to stay hydrated. · Tell your healthcare provider if you have kidney disease, are taking other medicines that can affect kidneys, or are pregnant. · Report any signs of kidney problems (decreased urination, swelling, fatigue) or allergic reactions immediately. · VISTIDE can cause birth defects; use effective contraception during treatment and for at least 1 month after last dose. |