Trade Names:Cytovene- Capsules 250 mg- Capsules 500 mg- Injection, lyophilized powder for solution 500 mg (as sodium)/vial
Trade Names:Ganciclovir- Capsules 250 mg- Capsules 500 mg
Trade Names:Vitrasert- Intravitreal implant 4.5 mg
Trade Names:Zirgan- Ophthalmic gel 0.15%
Inhibits cytomegalovirus (CMV) and other virus replication by competitive inhibition of viral DNA polymerases and direct incorporation into viral DNA.
AUC 0-24 is approximately 15.9 mcg•h/mL (oral); approximately 22.1 to 26.8 mcg•h/mL (IV). Fasting absolute bioavailability is approximately 5%; absolute bioavailability following food is 6% to 9% (oral). C max is approximately 1.02 to 1.18 mcg/mL (oral); approximately 8.27 to 9 mcg/mL (IV). Time to steady state is 24 h (oral).
Approximately 1% to 2% bound to plasma proteins; Vd ss is approximately 0.74 L/kg (IV).
Major route is renal excretion of unchanged drug by glomerular filtration and active tubular secretion. Half-life is approximately 3.5 h (IV) to 4.8 h (oral). Systemic Cl is approximately 3.52 mL/min/kg.
Cl is about 128 mL/min; half-life is about 4.6 h.CrCl 25 to 49 mL/min
Cl is approximately 57 mL/min; half-life is approximately 4.4 h.CrCl less than 25 mL/min
Cl is approximately 30 mL/min; half-life is approximately 10.7 h.Hemodialysis
Reduces ganciclovir by about 50% after IV administration.Elderly
No studies have been conducted in patients older than 65 yr of age.Children9 mo to 12 yr of age
Vd ss was approximately 0.64 L/kg; C max was approximately 7.9 mcg/mL; systemic Cl was approximately 4.7 mL/min/kg; half-life was approximately 2.4 h.Neonates (2 to 49 days of age)
C max was approximately 5.5 to 7 mcg/mL; systemic Cl was approximately 3.14 to 3.56 mL/min/kg; half-life was approximately 2.4 h.Gender
No differences between men and women were observed.Race
Black and Hispanic patients trend toward a lower AUC 0-8 and steady-state C max .
Treatment of CMV retinitis in immunocompromised patients, including patients with AIDS; prevention of CMV disease in organ transplant patients at risk for CMV.Oral
Alternative to the IV formulation for maintenance treatment of CMV retinitis in immunocompromised patients, including patients with AIDS, in whom retinitis is stable following appropriate induction therapy and for whom the risk of more rapid progression is balanced by the benefit associated with avoiding daily IV infusions; prevention of CMV disease in solid organ transplant recipients and in individuals with advanced HIV infection at risk for developing CMV disease.Intravitreal implant
For the treatment of CMV retinitis in patients with AIDS.Ophthalmic gel
For the treatment of acute herpetic keratitis (dendritic ulcers).
Treatment of other CMV infections (eg, pneumonitis, gastroenteritis, hepatitis) in some immunocompromised patients.
Hypersensitivity to ganciclovir or acyclovir; patients with any contraindications for ocular surgery, such as external infection or severe thrombocytopenia (implant).
Ophthalmic gel Instill 1 drop in the affected eye(s) 5 times per day (approximately every 3 h while awake) until the corneal ulcer heals, and then 1 drop 3 times per day for 7 days.CMV RetinitisAdults IV Induction
5 mg/kg over 1 h every 12 h for 14 to 21 days.Maintenance
5 mg/kg over 1 h once daily 7 days per wk or 6 mg/kg over 1 h once daily 5 days per wk (max, 6 mg/kg over 1 h).PO
Following induction treatment with IV ganciclovir, the recommended maintenance dosage of oral ganciclovir is 1,000 mg 3 times/day with food. Alternatively, the dosing regimen of 500 mg 6 times/day every 3 h with food, during waking hours, may be used.Intravitreal implant
4.5 mg insert designed to release the drug over 5 to 8 mo.CMV Prevention in Transplant RecipientsAdults
IV 5 mg/kg over 1 h every 12 h for 7 to 14 days, followed by 5 mg/kg once daily 7 days per wk or 6 mg/kg once daily 5 days per wk. PO 1,000 mg 3 times/day with food.CMV Prevention in Advanced HIV InfectionAdults
PO 1,000 mg 3 times daily with food.Decreased Renal FunctionAdults IV Induction
Store capsules and implant at 59° to 86°F. Protect implant from freezing, excessive heat and light. Store vials below 104°F; refrigerate diluted solution for infusion and discard after 24 h. Store ophthalmic gel at 59° to 77°F.
May increase serum creatinine.Cytotoxic drugs
May cause added toxicity.Didanosine
Ganciclovir may increase didanosine plasma levels. Ganciclovir levels may be decreased when administered 2 h after didanosine but not when given simultaneously.Imipenem-cilastatin
May cause generalized seizures.Probenecid
May reduce renal Cl and increase serum levels of ganciclovir.Zidovudine
Zidovudine and ganciclovir can cause granulocytopenia; combination therapy at full dose may not be tolerated.
None well documented.
Hypertension, vasodilatation; cardiac arrest, cardiac conduction abnormality, stroke, torsades de pointes, vasculitis, ventricular tachycardia (postmarketing).
Neuropathy (21%); abnormal dreams, abnormal thinking, confusion, depression, dizziness, headache, seizures, somnolence, tremor; encephalopathy, extrapyramidal reaction, facial palsy, hallucinations, intracranial hypertension, rhabdomyolysis (postmarketing).
Sweating (14%); pruritus (10%); alopecia; exfoliative dermatitis, Stevens-Johnson syndrome (postmarketing).
Diarrhea (48%); anorexia (19%); vomiting (14%); GI perforation, pancreatitis; intestinal ulceration (postmarketing).
CrCl decreased, kidney failure, kidney function abnormal; hemolytic uremic syndrome, renal tubular disorder, testicular hypertrophy (postmarketing).
Leukopenia (41%); anemia (25%); thrombocytopenia (6%); pancytopenia; hemolytic anemia (postmarketing).
Abnormal LFT results; hepatic failure, hepatitis (postmarketing).
Allergic reaction, anaphylactic reaction (postmarketing).
Creatinine increased, increased AST and ALT; hypercalcemia, hyponatremia (postmarketing).
Weight loss; SIADH (postmarketing).
Arthralgia, leg cramps, myalgia, myasthenia; peripheral ischemia, rhabdomyolysis (postmarketing)
Blurred vision (60%); eye irritation (20%); conjunctival hyperemia, punctate keratitis (5%).Implant
Retinal detachments, visual acuity loss, vitreous hemorrhage (10% to 20%); cataract formation/lens opacities, hyphemas, intraocular pressure spikes, macular abnormalities, optic disc/nerve changes, uveitis (1% to 5%).IV/Oral
Retinal detachment (8%); oculomotor nerve paralysis (postmarketing).
Dyspnea, increased cough; bronchospasm, pulmonary fibrosis (postmarketing).
Fever (48%); sepsis (15%); infection (13%); chills (10%); catheter infection (9%); catheter sepsis (8%); multiple organ failure.
WarningsIV and oral use Animal data
In animal studies, ganciclovir was carcinogenic, teratogenic, and caused aspermatogenesis.Hematological
The clinical toxicity of ganciclovir includes granulocytopenia, anemia, and thrombocytopenia.Oral capsules
Associated with risk of rapid rate of CMV retinitis progression and should be used as maintenance therapy only in patients who benefit from avoiding daily IV infusions.
Monitor CBC and platelet counts frequently, especially in patients in whom ganciclovir or other nucleoside analogues have previously resulted in leukopenia, or those with neutrophil counts less than 1,000 cells/mcL. Monitor serum creatinine or CrCl to allow for dosage adjustment in renally impaired patients. Monitor for extraocular CMV disease.
Category C .
Safety and efficacy not established in children younger than 2 yr of age (ophthalmic gel); younger than 9 yr of age (implant); younger than 13 yr of age (capsules). Safety and efficacy has not been established in children; however, pharmacokinetic and clinical studies have been conducted in children and neonates (IV).
Dose selection should be cautious, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease.
Use drug cautiously and adjust dose. Carefully monitor renal function, especially when other nephrotoxic drugs are given.
Use drug with caution in patients with preexisting cytopenias; granulocytopenia is common.
Accompany administration with adequate hydration because ganciclovir is excreted by the kidneys.
Phlebitis and/or pain may occur at the site of IV infusion.
Potential complications may include vitreous loss, vitreous hemorrhage, cataract formation, retinal detachment, uveitis, endophthalmitis, and decrease in visual acuity.
Has occurred; relationship to drug undetermined.
Acute renal failure, central retinal artery occlusion, hepatitis, irreversible pancytopenia, persistent bone marrow suppression (neutropenia and thrombocytopenia), renal toxicity, reversible neutropenia or granulocytopenia, seizure, temporary loss of vision, worsening GI symptoms, worsening of hematuria.
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