CYTOVENE
Clinical safety rating: caution
Comprehensive clinical and safety monograph for CYTOVENE (CYTOVENE).
Ganciclovir is a synthetic guanosine analog that inhibits viral DNA synthesis by competitively inhibiting viral DNA polymerase and by incorporation into viral DNA, causing chain termination. It is phosphorylated intracellularly to ganciclovir triphosphate, which is active against cytomegalovirus (CMV).
| Metabolism | Ganciclovir is not significantly metabolized in the liver. It is primarily eliminated unchanged by renal excretion via glomerular filtration and tubular secretion. The main metabolic pathway is intracellular phosphorylation to the active triphosphate form. |
| Excretion | Primarily renal excretion as unchanged drug (>90%); 1-2% biliary/fecal |
| Half-life | Terminal elimination half-life: 3-4 hours in normal renal function; prolonged to 28-40 hours in severe renal impairment (CrCl <10 mL/min) |
| Protein binding | 1–2% bound to plasma proteins (relatively low; binding is concentration-independent) |
| Volume of Distribution | 0.74 L/kg (0.5–1.2 L/kg); suggests distribution into total body water with tissue penetration including CNS |
| Bioavailability | Oral: ~5% under fasting conditions; increased to 9-15% with fatty meal; IV: 100% |
| Onset of Action | IV: Immediate inhibition of viral replication; Oral: 2–4 weeks to reduce viral shedding and symptoms in CMV retinitis |
| Duration of Action | IV: Antiviral effect persists for 8–12 hours after dosing; Oral: Sustained suppression with maintenance dosing; clinical effect wanes upon discontinuation |
Induction: 5 mg/kg IV every 12 hours for 14-21 days; maintenance: 5 mg/kg IV once daily for 7 days per week or 6 mg/kg IV once daily for 5 days per week
| Dosage form | INJECTABLE |
| Renal impairment | CrCl ≥60 mL/min: no adjustment; CrCl 40-59: 5 mg/kg IV every 12 hours; CrCl 20-39: 2.5 mg/kg IV every 12 hours; CrCl 10-19: 2.5 mg/kg IV every 24 hours; CrCl <10: 1.25 mg/kg IV three times per week after hemodialysis |
| Liver impairment | No specific Child-Pugh-based dose adjustments recommended; caution in severe hepatic impairment |
| Pediatric use | Induction: 5 mg/kg IV every 12 hours for 14-21 days; maintenance: 5 mg/kg IV once daily for 7 days per week or 6 mg/kg IV once daily for 5 days per week; adjust dose based on renal function with modified Schwartz formula |
| Geriatric use | Dose selection based on renal function; monitor for increased risk of nephrotoxicity, myelosuppression, and neurotoxicity |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for CYTOVENE (CYTOVENE).
| Breastfeeding | No human data available; ganciclovir present in animal milk. M/P ratio unknown. Due to risk of serious adverse effects in nursing infants, breastfeeding is contraindicated during therapy and for at least 72 hours after last dose. |
| Teratogenic Risk | FDA Category C. First trimester: Associated with teratogenic effects including microcephaly, hydrocephalus, microphthalmia, chorioretinitis, and auditory nerve damage. Second and third trimesters: Risk of fetal toxicity including bone marrow suppression and potential for long-term neurodevelopmental effects, particularly with high doses. Spermatogenesis and male fertility may be reversibly suppressed; animal studies show impaired spermatogenesis and reduced fertility in males. |
■ FDA Black Box Warning
Granulocytopenia, anemia, and thrombocytopenia have been observed in patients treated with ganciclovir. Ganciclovir should not be used in patients with a history of hypersensitivity to acyclovir or to ganciclovir. Ganciclovir has been shown to be carcinogenic in animals and to cause impairment of fertility. Cytovene is indicated for the treatment of CMV retinitis only. Cytovene is indicated for the prevention of CMV disease in transplant recipients only.
| Serious Effects |
["Absolute: Hypersensitivity to ganciclovir or acyclovir","Absolute: Severe neutropenia (ANC < 500 cells/µL) unless benefits outweigh risks","Absolute: Severe thrombocytopenia (platelet count < 25,000/µL) unless benefits outweigh risks","Relative: Pregnancy (due to teratogenicity; use only if clearly needed)","Relative: Lactation (discontinue breastfeeding or discontinue drug)"]
| Precautions | ["Hematologic toxicity: Severe leukopenia, neutropenia, anemia, thrombocytopenia, and pancytopenia may occur. Monitor blood counts frequently.","Renal impairment: Dose adjustment is required based on creatinine clearance. Elderly patients and those receiving nephrotoxic drugs are at increased risk.","Reproductive potential: Ganciclovir is mutagenic and teratogenic in animals. Advise patients of potential risk to fetus and use effective contraception.","Carcinogenesis: Ganciclovir is carcinogenic in animals; avoid prolonged exposure.","Fertility impairment: Ganciclovir may cause temporary or permanent inhibition of spermatogenesis in males and suppression of fertility in females."] |
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| Fetal Monitoring | Monitor complete blood count (CBC) with differential and platelet count frequently due to hematologic toxicity. Serum creatinine and BUN for renal function. Fetal ultrasound to assess growth and anatomy. In neonates exposed in utero: long-term audiology, ophthalmology, and neurodevelopmental assessments. |
| Fertility Effects | Reversible inhibition of spermatogenesis in males; may cause reduced sperm counts and motility. Animal studies show ovarian suppression and impaired fertility in females. Effect on human female fertility unknown. |