Ganciclovir sodium
(DHPG)
Ganciclovir sodium (Cytovene)
DHPG (Cytovene)
Ganciclovir sodium
(gan- SYE-kloh-veer)
Pregnancy Category: C Cytovene Vitrasert (Rx)

Classification: Antiviral

See Also: See also Antiviral Agents .

Action/Kinetics: Upon entry into viral cells infected by CMV, ganciclovir is converted to ganciclovir triphosphate by the CMV. Ganciclovir triphosphate inhibits viral DNA synthesis by competitive inhibition of viral DNA polymerases and direct incorporation into viral DNA; this results in eventual termination of viral DNA elongation. Ganciclovir is active against CMV, herpes simplex virus-1 and -2, Epstein-Barr virus, and varicella zoster virus. Use of the intraocular implant causes a significantly slower disease progression than did those treated with IV ganciclovir. t 1/2: Approximately 2.9 hr. Believed to cross the blood-brain barrier. Most excreted unchanged through the urine. Renal impairment increases the t 1/2 of the drug; make dosage adjustments based on C _CR.

Uses: IV: Immunocompromised clients with CMV retinitis, including AIDS clients. Diagnosis may be confirmed by culture of CMV from the blood, urine, or throat; note that a negative CMV culture does not rule out CMV retinitis. Prevention of CMV disease in transplant clients at risk; duration of treatment depends on duration and degree of immunosuppression. Investigational: Treatment of CMV infections (e.g., gastroenteritis, hepatitis, pneumonitis) in immunocompromised clients.
PO: Alternative to IV for maintenance treatment of CMV retinitis inimmunocompromised (including AIDS) clients. Prevention of CMV disease in clients with advanced HIV infection at risk for developing CMV disease.  Intraocular implant: CMV retinitis in those with AIDS.

Contraindications: Hypersensitivity to acyclovir or ganciclovir. Lactation. Use when the absolute neutrophil count is less than 500/mm ³ or the platelet count is less than 25,000/mm ³.

Special Concerns: Safety and effectiveness of ganciclovir have not been established for nonimmunocompromised clients, treatment of other CMV infections such as pneumonitis or colitis, or congenital or neonatal CMV disease. Use with caution in impaired renal function, in elderly clients, or with preexisting cytopenias or with a history of cytopenic reactions to other drugs, chemicals, or irradiation. Use in children only if potential benefits outweigh potential risks, including carcinogenicity and reproductive toxicity. Not a cure for CMV retinitis and progression of the disease may continue in immunocompromised clients. Treatment with AZT and ganciclovir (e.g., in AIDS clients) will likely not be tolerated and lead to severe granulocytopenia.

Side Effects: Hematologic: Granulocytopenia, thrombocytopenia, neutropenia (may be irreversible), eosinophilia, leukopenia, anemia, hypochromic anemia, bone marrow depression, pancytopenia, leukemia, lymphoma. CNS: Ataxia, coma neuropathy, confusion, abnormal dreams or thoughts, dizziness, headache, paresthesia, psychosis, nervousness, somnolence, tremor, agitation, amnesia, anxiety, depression, euphoria, hypertonia, hypesthesia, insomnia, manic reaction, seizures trismus, emotional lability. GI: N&V;, aphthous stomatitis, diarrhea, anorexia, dry mouth, GI hemorrhage, pancreatitis abdominal pain, flatulence, dyspepsia, constipation, dysphagia, esophagitis, eructation, fecal incontinence, melena, mouth ulceration, tongue disorder, hepatitis, weight loss. CV: Hypertension or hypotension, arrhythmias, phlebitis, deep thrombophlebitis, cardiac arrest, intracranial hypertension, MI, stroke pericarditis, vasodilation, migraine. Body as a whole: Fever (most common), chills, edema, infections, malaise, sepsis, multiple organ failure asthenia, enlarged abdomen, abscess, back pain, cellulitis, chest pain, facial edema, neck pain or rigidity. Dermatologic: Rash (most common), alopecia, pruritus, urticaria, sweating, acne, dry skin, fixed eruption, herpes simplex, maculopapular rash, skin discoloration, vesiculobullous rash, photosensitivity, phototoxicity. GU: Hematuria, breast pain, kidney failure, abnormal kidney function, urinary frequency, UTI. At injection site: Catheter infection, catheter sepsis, inflammation or pain, abscess, edema, hemorrhage, phlebitis. Musculoskeletal: Arthralgia, bone pain, leg cramps, myalgia, myasthenia. Ophthalmologic: Abnormal vision, amblyopia, blindness, conjunctivitis, eye pain, glaucoma, retinitis, photophobia, cataracts, vitreous disorder. Respiratory: Dyspnea, increased cough, pneumonia. Hepatic: Cholestasis, cholangitis. Miscellaneous: Abnormal gait, decreased libido, deafness, anaphylaxis taste perversion, tinnitus, acidosis, congenital anomaly, encephalopathy, impotence, transverse myelitis, infertility, splenomegaly, Stevens-Johnson syndrome, unexplained death retinal detachment in CMV retinitis clients.

Laboratory Test Alterations: or Serum creatinine. BUN, alkaline phosphatase, CPK, LDH, AST, ALT. Blood glucose. Abnormal LFT. Hypokalemia, hyponatremia.

Overdose Management: Symptoms: Neutropenia. Possibility of hypersalivation, anorexia, vomiting, bloody diarrhea, inactivity, cytopenia, testicular atrophy, increased BUN and LFT results. Treatment: Hydration, hemodialysis.

Drug Interactions: Adriamycin / Additive cytotoxicity in rapidly dividing cells Amphotericin B / Additive cytotoxicity in rapidly dividing cells; also, serum creatinine levels Cyclosporine / Serum creatinine levels Dapsone / Additive cytotoxicity in rapidly dividing cells Flucytosine / Additive cytotoxicity in rapidly dividing cells Imipenem/Cilastatin combination / Possibility of seizures Pentamidine / Additive cytotoxicity in rapidly dividing cells Probenecid / Effect of ganciclovir R/T renal excretion Sulfamethoxazole/Trimethoprim combinations / Additive cytotoxicity in rapidly dividing cells Vinblastine / Additive cytotoxicity in rapidly dividing cells Vincristine / Additive cytotoxicity in rapidly dividing cells AZT / Risk of granulocytopenia and anemia

How Supplied: Powder for injection: 500 mg; Capsules: 250 mg, 500 mg; Implant: 4.5 mg

Dosage
?IV Infusion, Capsules CMV retinitis.
Induction treatment: 5 mg/kg over 1 hr q 12 hr for 14-21 days in clients with normal renal function. Do not use PO treatment for induction. Maintenance, IV: 5 mg/kg over 1 hr by IV infusion daily for 7 days or 6 mg/kg/day for 5 days each week. Dosage must be reduced in clients with renal impairment. Maintenance, PO: 1,000 mg t.i.d. with food. Or, 500 mg 6 times/day q 3 hr with food during waking hours.
Prevention of CMV retinitis in those with advanced HIV infection and normal renal function.
1,000 mg t.i.d. with food.
Prophylaxis of CMV disease in transplant clients.
Initial dose, IV: 5 mg/kg over 1 hr q 12 hr for 7-14 days. Maintenance: 5 mg/kg/day on 7 days each week (or 6 mg/kg/day on 5 days each week).