Professional Information

Ganciclovir

( DHPG ) Pronouncation: (gan-SIGH-kloe-VIHR)
Class: Antiviral, Ophthalmic

Trade Names:
Cytovene
- Capsules 250 mg
- Capsules 500 mg
- Powder for Injection, lyophilized 500 mg (as sodium)/vial

Trade Names:
Vitrasert
- Implant 4.5 mg

Pharmacology

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Inhibits cytomegalovirus (CMV) and other virus replication by competitive inhibition of viral DNA polymerases and direct incorporation into viral DNA.

Pharmacokinetics

Absorption

AUC _0-24 is approximately 15.9ߙmcg•h/mL (oral); approximately 22.1 to 26.8ߙmcg•h/mL (IV). Fasting absolute bioavailability is approximately 5%. Absolute bioavailability following food is 6% to 9%. 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.

Distribution

Approximately 1% to 2% bound to plasma proteins. Vd _ss is about 0.74ߙL/kg.

Elimination

Major route is renal excretion of unchanged drug by glomerular filtration and active tubular secretion. T _½ is about 3.5 to 4.8ߙh. Systemic Cl is about 3.52 mL/min/kg. Hemodialysis reduces plasma concentration by about 50%.

Special Populations

Renal Function Impairment
CrCl 25 to 49 mL/min

Cl is about 57 mL/min; t _½ is about 4.4 h.

CrCl less than 25 mL/min

Cl is about 30 mL/min; t _½ is about 10.7 h.

Children
9 mo to 12 yr of age

Vd _ss was about 0.64 L/kg; C _max was about 7.9ߙmcg/mL; systemic Cl was about 4.7 mL/min/kg; t _½ was about 2.4 h.

Neonates (2 to 49 days of age)

C _max was about 5.5 to 7 mcg/mL; systemic Cl was about 3.14 to 3.56ߙmL/min/kg; t _½ was about 2.4 h.

Race

Black/Hispanic patients trend toward a lower AUC _0-8 and steady-state C _max .

Indications and Usage

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.

Unlabeled Uses

Treatment of other CMV infections (eg, pneumonitis, gastroenteritis, hepatitis) in some immunocompromised patients.

Contraindications

Hypersensitivity to acyclovir.

Dosage and Administration

CMV Retinitis
Adults

IV Induction: 5 mg/kg over 1ߙh every 12ߙh for 14 to 21 days. Maintenance: 5ߙmg/kg over 1 h every day or 6 mg/kg over 1 h/day 5ߙdays/wk (max, 6 mg/kg over 1 h). PO Following induction treatment, the recommended maintenance dose of oral ganciclovir is 1,000ߙmg 3 times/day with food. Alternatively, the dosing regimen of 500 mg 6 times/day every 3ߙh with food, during waking hours, may be used.

CMV Prevention in Transplant Recipients
Adults

IV 5 mg/kg over 1 h every 12 h for 7 to 14 days, followed by 5 mg/kg once daily 7ߙdays/wk or 6 mg/kg once daily 5 days/wk. PO ߙ1,000ߙmg 3 times/day with food.

CMV Prevention in Advanced HIV Infection
Adults

PO 1,000 mg 3 times daily with food.

Decreased Renal Function
Adults

IV Induction: 5 mg/kg every 12 h (CrCl at least 70 mL/min); 2.5 mg/kg every 12 h (CrCl 50 to 69 mL/min); 2.5 mg/kg every 24 h (CrCl 25 to 49ߙmL/min); 1.25 mg/kg every 24 h (CrCl 10 to 24ߙmL/min); 1.25ߙmg/kg 3 times a week following hemodialysis (CrCl less than 10ߙmL/min). Maintenance: 5 mg/kg every 24 h (CrCl at leastߙ70ߙmL/min); 2.5 mg/kg every 24 h (CrCl 50 to 69ߙmL/min); 1.25 mg/kg every 24 h (CrCl 25 to 49ߙmL/min); 0.625 mg/kg every 24 h (CrCl 10 to 24ߙmL/min); 0.625 mg/kg 3ߙtimes a week following hemodialysis (CrCl less than 10ߙmL/min). PO 1,000ߙmg 3 times daily or 500ߙmg every 3 h, 6ߙtimes/day (CrCl at least 70 mL/min); 1,500ߙmg every day or 500 mg 3 times daily (CrCl 50 to 69ߙmL/min); 1,000 mg every day or 500 mg twice daily (CrCl 25 to 49ߙmL/min); 500 mg every day (CrCl 10ߙto 24); 500ߙmg 3 times/wk, following hemodialysis (less than 10ߙmL/min).

General Advice

For IV infusion only. Not for intradermal, subcutaneous, IM, IV bolus, or intraarterial administration.
Reconstitute with 10 mL sterile water for injection (do not use bacteriostatic water or other solutions), and shake well to dissolve drug.

Drug Interactions

Amphotericin B, cyclosporine, nephrotoxic drugs

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.

Incompatibility

Do not mix with other drugs.

Laboratory Test Interactions

None well documented.

Adverse Reactions

CNS

Headache; confusion.

Dermatologic

Rash; phlebitis or pain at injection site.

Genitourinary

Renal toxicity.

Hematologic

Granulocytopenia; thrombocytopenia; anemia.

Hepatic

Abnormal LFT results.

Miscellaneous

Sepsis; fever.

Precautions

Warnings

Animal data

Aspermatogenesis, carcinogenic, teratogenic.

Hematological

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.

Pregnancy

Category C .

Lactation

Undetermined.

Children

Safety and efficacy not established.

Renal Function

Use drug cautiously and adjust dose. Carefully monitor renal function, especially when other nephrotoxic drugs are given.

Carcinogenesis

Ganciclovir is potentially carcinogenic.

Cytopenia

Use drug with caution in patients with preexisting cytopenias; granulocytopenia is common.

Hydration

Accompany administration by adequate hydration because ganciclovir is excreted by the kidneys.

Retinal detachment

Has occurred; relationship to drug undetermined.

Overdosage

Symptoms

Neutropenia, emesis, hypersalivation, anorexia, bloody diarrhea, inactivity, cytopenia, elevated LFT results, elevated BUN and serum creatinine, testicular atrophy, death.

Patient Information

Give patient and family members instructions regarding handling of ganciclovir and proper disposal techniques when drug is to be administered at home.
Inform patient that it is important to drink plenty of fluids.
Teach patient for CMV retinitis that drug is not a cure, but it may help to keep symptoms from getting worse.
Advise CMV retinitis patients to have regular ophthalmologic examinations at least every 6 wk during treatment.
Instruct patients to use barrier form of contraception for at least 90 days after treatment because ganciclovir is potentially teratogenic.
Explain to men that drug may cause temporary or permanent male infertility.
Tell patient to avoid crowds and people with infections.
Instruct patient to report the following symptoms to health care provider: headache, mental status changes, rash, pain at injection site, fever, nausea, unusual bleeding or bruising, black tarry stools, other physical complaints.