(gan SYE kloe veer)
Treatment of CMV retinitis in immunocompromised individuals, including patients with acquired immunodeficiency syndrome; prophylaxis of CMV infection in transplant patients
Hypersensitivity to ganciclovir, acyclovir, or any component of the formulation
The clinical toxicity of ganciclovir IV includes granulocytopenia, anemia and thrombocytopenia. In animal studies ganciclovir was carcinogenic, teratogenic and caused aspermatogenesis.
Appropriate use:Ganciclovir IV is indicated for use only in the treatment of cytomegalovirus (CMV) retinitis in immunocompromised patients and for the prevention of CMV disease in transplant patients at risk for CMV disease
Carcinogenic/teratogenic:In animal studies ganciclovir was carcinogenic, teratogenic and caused aspermatogenesis
CMV retinitis:
Manufacturers labeling:
Induction therapy: IV (slow infusion): 5 mg/kg/dose every 12 hours for 14 to 21 days followed by maintenance therapy
Maintenance therapy: IV (slow infusion): 5 mg/kg/day as a single daily dose for 7 days/week or 6 mg/kg/day for 5 days/week
Alternate dosing (HHS [OI adult 2015]):
Peripheral lesions (alternative to preferred therapy): IV: Induction: 5 mg/kg/dose every 12 hours for 14 to 21 days followed by chronic maintenance (secondary prophylaxis)
Immediate sight-threatening lesions (adjacent to the optic nerve or fovea): Intravitreal injection (off-label route): Induction therapy: 2 mg of an extemporaneously prepared solution administered as intravitreal injections for 1 to 4 doses over a period of 7 to 10 days; administer with a concomitant systemically administered agent (oral valganciclovir preferred).
CMV disease, chronic maintenance (secondary prophylaxis) in HIV-infected patients (off-label use; alternative to preferred therapy): IV: 5 mg/kg/dose 5 to 7 times weekly; continue until sustained CD4 count >100 cells/mm3 in response to ART for 3 to 6 months; discontinue only after consultation with an ophthalmologist) (HHS [OI adult 2015]).
CMV disease, prophylaxis (secondary) in transplant patients: IV (slow infusion): 5 mg/kg/dose every 12 hours for 7 to 14 days, duration of maintenance therapy is dependent on clinical condition and degree of immunosuppression
CMV esophagitis or colitis in HIV-infected patients (off-label use): IV: 5 mg/kg/dose every 12 hours, then change to oral valganciclovir therapy once oral therapy is tolerated; total duration of therapy: 21 to 42 days or until symptom resolution (HHS [OI adult 2015])
CMV neurological disease in HIV-infected patients (off-label use): IV: 5 mg/kg/dose every 12 hours plus foscarnet until symptoms improve (HHS [OI adult 2015])
Varicella-zoster: Acute retinal necrosis (ARN) in HIV-infected patients (off-label use): Intravitreal injection (off-label route): 2 mg of an extemporaneously prepared solution administered as an intravitreal injection twice weekly for 1 to 2 doses in combination with IV acyclovir for 10 to 14 days, followed by valacyclovir for 6 weeks (HHS [OI adult 2015])
Varicella-zoster: Progressive outer retinal necrosis in HIV-infected patients (off-label use): IV: 5 mg/kg/dose every 12 hours (with or without IV foscarnet) plus intravitreal ganciclovir and/or intravitreal foscarnet (HHS [OI adult 2015])
Refer to adult dosing.
CMV retinitis:
Children: IV (slow infusion): Manufacturers labeling:
Induction therapy: 5 mg/kg/dose every 12 hours for 14 to 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
Adolescents: Refer to adult dosing.
CMV disease, chronic maintenance (secondary prophylaxis) in HIV-exposed/-infected patients (off-label use):
Infants and Children: IV: 5 mg/kg/dose daily (CDC 2009)
Adolescents (alternative to preferred therapy): Refer to adult dosing.
CMV disease, prophylaxis (secondary) in transplant patients: Children: IV (slow infusion): Refer to adult dosing.
CMV esophagitis or colitis in HIV-infected patients (off-label use): Adolescents: Refer to adult dosing.
CMV neurological disease in HIV-exposed/-infected patients (off-label use): Infants, Children, and Adolescents: IV: Refer to adult dosing.
Varicella-zoster: Acute retinal necrosis (ARN) in HIV-infected patients (off-label use): Adolescents: Refer to adult dosing.
Varicella-zoster: Progressive outer retinal necrosis in HIV-exposed/-infected patients (off-label use):
Infants and Children: IV: 5 mg/kg/dose every 12 hours plus systemic foscarnet and intravitreal ganciclovir or intravitreal foscarnet (CDC 2009)
Adolescents: Refer to adult dosing.
IV (Induction):
CrCl 50 to 69 mL/minute: Administer 2.5 mg/kg/dose every 12 hours.
CrCl 25 to 49 mL/minute: Administer 2.5 mg/kg/dose every 24 hours.
CrCl 10 to 24 mL/minute: Administer 1.25 mg/kg/dose every 24 hours.
CrCl <10 mL/minute: Administer 1.25 mg/kg/dose 3 times/week following hemodialysis.
IV (Maintenance):
CrCl 50 to 69 mL/minute: Administer 2.5 mg/kg/dose every 24 hours.
CrCl 25 to 49 mL/minute: Administer 1.25 mg/kg/dose every 24 hours.
CrCl 10 to 24 mL/minute: Administer 0.625 mg/kg/dose every 24 hours
CrCl <10 mL/minute: Administer 0.625 mg/kg/dose 3 times/week following hemodialysis.
Intermittent hemodialysis (IHD) (administer after hemodialysis on dialysis days): Dialyzable (50%): CMV Infection: IV: Induction: 1.25 mg/kg every 48 to 72 hours; Maintenance: 0.625 mg/kg every 48 to 72 hours. Note: Dosing dependent on the assumption of 3 times/week, complete IHD sessions.
Peritoneal dialysis (PD): Dose as for CrCl <10 mL/minute.
Continuous renal replacement therapy (CRRT) (Heintz 2009; Trotman 2005): Drug clearance is highly dependent on the method of renal replacement, filter type, and flow rate. Appropriate dosing requires close monitoring of pharmacologic response, signs of adverse reactions due to drug accumulation, as well as drug concentrations in relation to target trough (if appropriate). The following are general recommendations only (based on dialysate flow/ultrafiltration rates of 1 to 2 L/hour and minimal residual renal function) and should not supersede clinical judgment: CMV Infection:
CVVH: IV: Induction: 2.5 mg/kg every 24 hours; Maintenance: 1.25 mg/kg every 24 hours
CVVHD/CVVHDF: IV: Induction: 2.5 mg/kg every 12 hours; Maintenance: 2.5 mg/kg every 24 hours
No dosage adjustment provided in manufacturer 's labeling.
Hazardous agent; use appropriate precautions for handling and disposal (NIOSH 2014 [group 2]).
Reconstitute 500 mg vial with 10 mL unpreserved sterile water not bacteriostatic water because parabens may cause precipitation. Typically, dilute in 100 mL D5W or NS to a concentration ≤10 mg/mL for infusion.
For IV infusion; should not be administered by IM, SubQ, or rapid IVP. Administer by slow IV infusion over at least 1 hour. Too rapid infusion can cause increased toxicity and excessive plasma levels. Flush line well with NS before and after administration.
Hazardous agent; use appropriate precautions for handling and disposal (NIOSH 2014 [group 2]).
Some products may contain sodium.
Store intact vials at temperatures below 40 ‚ °C (104 ‚ °F). 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). Stability of parenteral admixture in D5W or NS at room temperature (25 ‚ °C) and at refrigeration temperature (4 ‚ °C) for 35 days has been reported. However, the manufacturer recommends use within 24 hours of preparation.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution Reconstituted, Intravenous:
Cytovene: 500 mg (1 ea)
Generic: 500 mg (1 ea)
Stable in D5W, LR, NS; incompatible with paraben preserved bacteriostatic water for injection (may cause precipitation).
Y-site administration: Incompatible with amifostine, amsacrine, aztreonam, cefepime, cytarabine, doxorubicin, fludarabine, foscarnet, gemcitabine, ondansetron, piperacillin/tazobactam, vinorelbine.
Imipenem: Ganciclovir-Valganciclovir may enhance the adverse/toxic effect of Imipenem. Specifically, the risk of seizures may be increased. Management: Avoid concomitant use of these agents unless the prospective benefits of therapy outweigh the risks. Consider therapy modification
Mycophenolate: May increase the serum concentration of Ganciclovir-Valganciclovir. Ganciclovir-Valganciclovir may increase the serum concentration of Mycophenolate. Monitor therapy
Probenecid: May increase the serum concentration of Ganciclovir-Valganciclovir. Monitor therapy
Reverse Transcriptase Inhibitors (Nucleoside): Ganciclovir-Valganciclovir may enhance the adverse/toxic effect of Reverse Transcriptase Inhibitors (Nucleoside). Hematologic toxicity with zidovudine is of particular concern. Ganciclovir-Valganciclovir may increase the serum concentration of Reverse Transcriptase Inhibitors (Nucleoside). Management: Monitor patients receiving any of these combination closely for toxicity of the reverse transcriptase inhibitor. Avoid zidovudine. Intravitreal implants would not be affected. Exceptions: Stavudine. Consider therapy modification
Tenofovir Products: May increase the serum concentration of Ganciclovir-Valganciclovir. Ganciclovir-Valganciclovir may increase the serum concentration of Tenofovir Products. Monitor therapy
CBC with differential and platelet count, serum creatinine
>10%:
Dermatologic: Diaphoresis (12%)
Gastrointestinal: Diarrhea (44%), anorexia (14%), vomiting (13%)
Hematologic & oncologic: Thrombocytopenia (57%), leukopenia (41%), anemia (16% to 26%), neutropenia (ANC <500/mm3: 12% to 14%)
Infection: Sepsis (15%)
Ophthalmic: Retinal detachment (11%; relationship to ganciclovir not established)
Renal: Increased serum creatinine (2% to 14%)
Miscellaneous: Fever (48%)
1% to 10%:
Central nervous system: Chills (10%), neuropathy (9%)
Dermatologic: Pruritus (5%)
<1% (Limited to important or life-threatening): Alopecia, brain disease, bronchospasm, cardiac arrhythmia, cataract, cholestasis, coma, dyspnea, edema, eosinophilia, exfoliative dermatitis, extrapyramidal reaction, hemorrhage, hepatic failure, hepatitis, hypersensitivity reaction (including anaphylaxis), pancreatitis, pancytopenia, psychosis, pulmonary fibrosis, renal failure, rhabdomyolysis, seizure, SIADH (syndrome of inappropriate antidiuretic hormone secretion), Stevens-Johnson syndrome, torsades de pointes, urticaria, vision loss
Cl is about 128 mL/min; half-life is about 4.6 h.
CrCl 25 to 49 mL/minCl is approximately 57 mL/min; half-life is approximately 4.4 h.
CrCl less than 25 mL/minCl is approximately 30 mL/min; half-life is approximately 10.7 h.
HemodialysisReduces ganciclovir by about 50% after IV administration.
Concerns related to adverse effects:
- Blood dyscrasias: [US Boxed Warning]: Granulocytopenia (neutropenia), anemia, and thrombocytopenia may occur. Dosage adjustment or interruption of therapy may be necessary in patients with neutropenia and/or thrombocytopenia.
- Carcinogenic/teratogenic: [US Boxed Warning]: Animal studies have demonstrated carcinogenic and teratogenic effects, and inhibition of spermatogenesis; contraceptive precautions for female and male patients need to be followed during and for at least 90 days after therapy with the drug.
Disease-related concerns:
- Renal impairment: Use with caution in patients with renal impairment; dosage adjustment or interruption of therapy may be necessary.
Special handling:
- Hazardous agent: Use appropriate precautions for handling and disposal (NIOSH 2014 [group 2]).
Other warnings/precautions:
- Administration: Take care to administer only into veins with good blood flow.
- Appropriate use: [US Boxed Warning]: Indicated only for treatment of CMV retinitis in the immunocompromised patient and CMV prevention in transplant patients at risk.
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[U.S. Boxed Warning]: Animal studies have demonstrated carcinogenic and teratogenic effects, and inhibition of spermatogenesis. Female patients should use effective contraception during therapy; male patients should use a barrier contraceptive during and for at least 90 days after therapy.
Ganciclovir is phosphorylated to a substrate which competitively inhibits the binding of deoxyguanosine triphosphate to DNA polymerase resulting in inhibition of viral DNA synthesis
Vd: Children 9 months to 12 years: 0.64 ‚ ± 0.22 L/kg; Adults: 0.74 ‚ ± 0.15 L/kg; widely to all tissues including CSF and ocular tissue
Urine (80% to 99% as unchanged drug)
Prolonged with renal impairment
Neonates 2-49 days of age: 2.4 hours
Children 9 months to 12 years: 2.4 ‚ ± 0.7 hours
Adults: Mean: 2.5-3.6 hours (range: 1.7-5.8 hours)
1% to 2%
- Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)
- Patient may experience dizziness, fatigue, lack of appetite, nausea, vomiting, or diarrhea. Have patient report immediately to prescriber signs of infection, bruising, bleeding, loss of strength and energy, sweating a lot, illogical thinking, urinary retention, change in amount of urine passed, change in balance, hallucinations, depression; black, tarry, or bloody stools; burning or numbness feeling; seizures; severe abdominal pain; vision changes; vomiting blood; or injection site irritation (HCAHPS).
- Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.
Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for healthcare professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience and judgment in diagnosing, treating and advising patients.