No

Antiviral Agent

Parenteral: Treatment of CMV retinitis in immunocompromised individuals, including patients with acquired immunodeficiency syndrome; prophylaxis of CMV infection in transplant patients; may be given in combination with foscarnet in patients who relapse after monotherapy with either drug

Oral: Alternative to the I.V. 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 I.V. infusions.

Implant: Treatment of CMV retinitis

C

Absolute neutrophil count <500/mm³; platelet count <25,000/mm³; known hypersensitivity to ganciclovir or acyclovir

Dosage adjustment or interruption of ganciclovir therapy may be necessary in patients with neutropenia and/or thrombocytopenia and patients with impaired renal function. Use with extreme caution in children since long-term safety has not been determined and due to ganciclovir's potential for long-term carcinogenic and adverse reproductive effects; ganciclovir may adversely affect spermatogenesis and fertility; due to its mutagenic potential, contraceptive precautions for female and male patients need to be followed during and for at least 90 days after therapy with the drug; take care to administer only into veins with good blood flow.

>10%:

Central nervous system: Fever (38% to 48%)

Dermatologic: Rash (15% - oral, 10% - I.V.)

Gastrointestinal: Abdominal pain (17% to 19%), diarrhea (40%), nausea (25%), anorexia (15%), vomiting (13%)

Hematologic: Anemia (20% to 25%), leukopenia (30% to 40%)

1% to 10%:

Central nervous system: Confusion, neuropathy (8% to 9%), headache (4%)

Dermatologic: Pruritus (5%)

Hematologic: Thrombocytopenia (6%), neutropenia with ANC <500/mm³ (5% - oral, 14% - I.V.)

Neuromuscular & skeletal: Paresthesia (6% to 10%), weakness (6%)

Miscellaneous: Sepsis (4% - oral, 15% - I.V.)

<1%: Arrhythmia, hypertension, hypotension, edema, ataxia, dizziness, nervousness, psychosis, malaise, coma, seizures, alopecia, urticaria, eosinophilia, hemorrhage, increased LFTs, increased serum creatinine, azotemia, inflammation or pain at injection site, tremor, retinal detachment, visual loss, hyphema, uveitis (intravitreal implant), creatinine increased 2.5%, dyspnea

Symptoms of overdose include neutropenia, vomiting, hypersalivation, bloody diarrhea, cytopenia, testicular atrophy

Treatment is supportive; hemodialysis removes 50% of drug; hydration may be of some benefit

Decreased effect: Didanosine: A decrease in steady-state ganciclovir AUC may occur

Increased toxicity:

Immunosuppressive agents may increase cytotoxicity of ganciclovir

Imipenem/cilastatin may increase seizure potential

Zidovudine: Oral ganciclovir increased the AUC of zidovudine, although zidovudine decreases steady state levels of ganciclovir. Since both drugs have the potential to cause neutropenia and anemia, some patients may not tolerate concomitant therapy with these drugs at full dosage.

Probenecid: The renal clearance of ganciclovir is decreased in the presence of probenecid

Didanosine levels are increased with concurrent ganciclovir

Other nephrotoxic drugs (eg, amphotericin and cyclosporine) may have additive nephrotoxicity with ganciclovir

Preparation should take place in a vertical laminar flow hood with the same precautions as antineoplastic agents

Intact vials should be stored at room temperature and protected from temperatures >40°C

Reconstitute powder with sterile water not bacteriostatic water because parabens may cause precipitation

Reconstituted solution is stable for 12 hours at room temperature, however, conflicting data indicates that reconstituted solution is stable for 60 days under refrigeration (4°C)

Drug product should be reconstituted immediately before use and any unused portion should be discarded

Stability of parenteral admixture at room temperature (25°C) and at refrigeration temperature (4°C): 5 days

An in-line filter of 0.22-5 micron is recommended during the infusion of all ganciclovir solutions

Ganciclovir is phosphorylated to a substrate which competitively inhibits the binding of deoxyguanosine triphosphate to DNA polymerase resulting in inhibition of viral DNA synthesis

Absorption: Oral: Absolute bioavailability under fasting conditions: 5% and following food: 6% to 9%; following fatty meal: 28% to 31%

Distribution: V_d: 15.26 L/1.73 m²; widely distributed to all tissues including CSF and ocular tissue

Protein binding: 1% to 2%

Half-life: 1.7-5.8 hours; increases with impaired renal function

End-stage renal disease: 5-28 hours

Elimination: Majority (80% to 99%) excreted as unchanged drug in the urine

CMV retinitis: Slow I.V. infusion (dosing is based on total body weight):

Children >3 months and Adults:

Induction therapy: 5 mg/kg/dose every 12 hours for 14-21 days followed by maintenance therapy

Maintenance therapy: 5 mg/kg/day as a single daily dose for 7 days/week or 6 mg/kg/day for 5 days/week

CMV retinitis: Oral: 1000 mg 3 times/day with food or 500 mg 6 times/day with food

Prevention of CMV disease in patients with advanced HIV infection and normal renal function: Oral: 1000 mg 3 times/day with food

Prevention of CMV disease in transplant patients: Same initial and maintenance dose as CMV retinitis except duration of initial course is 7-14 days, duration of maintenance therapy is dependent on clinical condition and degree of immunosuppression

Intravitreal implant: One implant for 5- to 8-month period; following depletion of ganciclovir, as evidenced by progression of retinitis, implant may be removed and replaced

Dosing adjustment in renal impairment:

I.V. (Induction):

Cl_cr 50-69 mL/minute: Administer 2.5 mg/kg/dose every 12 hours

Cl_cr 25-49 mL/minute: Administer 2.5 mg/kg/dose every 24 hours

Cl_cr 10-24 mL/minute: Administer 1.25 mg/kg/dose every 24 hours

Cl_cr <10 mL/minute: Administer 1.25 mg/kg/dose 3 times/week following hemodialysis

I.V. (Maintenance):

Cl_cr 50-69 mL/minute: Administer 2.5 mg/kg/dose every 24 hours

Cl_cr 25-49 mL/minute: Administer 1.25 mg/kg/dose every 24 hours

Cl_cr 10-24 mL/minute: Administer 0.625 mg/kg/dose every 24 hours

Cl_cr <10 mL/minute: Administer 0.625 mg/kg/dose 3 times/week following hemodialysis

Oral:

Cl_cr 50-69 mL/minute: Administer 1500 mg/day or 500 mg 3 times/day

Cl_cr 25-49 mL/minute: Administer 1000 mg/day or 500 mg twice daily

Cl_cr 10-24 mL/minute: Administer 500 mg/day

Cl_cr <10 mL/minute: Administer 500 mg 3 times/week following hemodialysis

Hemodialysis effects: Dialyzable (50%) following hemodialysis; administer dose postdialysis. During peritoneal dialysis, dose as for Cl_cr <10 mL/minute. During continuous arteriovenous or venovenous hemofiltration (CAVH/CAVHD), administer 2.5 mg/kg/dose every 24 hours.

CBC with differential and platelet count, serum creatinine, ophthalmologic exams

May cause confusion; may rarely cause nervousness or psychosis

Leukopenia is common; use caution with clozapine and carbamazepine

No information available to require special precautions

No effects or complications reported

Ganciclovir is not a cure for CMV retinitis. For oral administration, take as directed and maintain adequate hydration (2-3 L/day of fluids unless instructed to restrict fluid intake). You will need frequent blood tests and regular ophthalmic exams while taking this drug. You may experience increased susceptibility to infection; avoid crowds or exposure to infectious persons. You may experience photosensitivity; use sunscreen, wear protective clothing and eyewear, and avoid direct sunlight. Report fever, chills, unusual bleeding or bruising, infection, or unhealed sores or white plaques in mouth. Pregnancy/breast-feeding precautions: Inform prescriber if you are pregnant. Males and females should use appropriate barrier contraceptive measures during and for 60-90 days following end of therapy. Do not breast-feed.

Must be prepared in vertical flow hood; use chemotherapy precautions during administration; discard appropriately

Capsule: 250 mg

Implant, intravitreal: 4.5 mg released gradually over 5-8 months

Powder for injection, lyophilized: 500 mg (10 mL)

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