Dosing & Uses
Dosage Forms & Strengths
injection, lyophilized powder for reconstitution
- 500mg
CMV Retinitis
Indicated for the treatment of cytomegalovirus (CMV) retinitis in immunocompromised adults, including patients with acquired immunodeficiency syndrome (AIDS)
Induction: 5 mg/kg IV q12hr, infused over 1 hr for 14-21 days
Maintenance
- Following induction treatment, 5 mg/kg IV qDay OR
- 6 mg/kg IV qDay for 5 days/week
CMV Prevention in Transplant Recipients
Indicated for the prevention of CMV disease in adult transplant recipients at risk for CMV disease
Induction: 5 mg/kg IV qDay infused over 1 hr for 7-14 days
Maintenance
- 5 mg/kg IV qDay for 100-120 days after transplant OR
- 6 mg/kg IV qDay for 5 day/week for 100-120 days after transplant
CMV Prevention in HIV Infected (Off-label)
1000 mg PO TID (primary/recurrence)
5-6 mg/kg 5-7x/week IV (recurrence)
CMV Colitis or Esophagitis in HIV-Infected Patients (Off-label)
Treat initially with ganciclovir 5 mg/kg/dose IV q12hr; once therapy is tolerated, change to valganciclovir 900 mg PO q12hr for 21-42 days or until signs and symptoms have resolved
Dosage Modifications
Renal impairment
- Induction dose
- CrCl 50-69 mL/min: 2.5 mg/kg IV q12hr
- CrCl 25-49 mL/min: 2.5 mg/kg IV qDay
- CrCl 10-24 mL/min: 1.25 mg/kg IV qDay
- CrCl <10 mL/min: 1.25 mg/kg IV 3 x per week following hemodialysis
- Maintenance dose
- CrCl 50-69 mL/min: 2.5 mg/kg IV qDay
- CrCl 25-49 mL/min: 1.25 mg/kg IV qDay
- CrCl 10-24 mL/min: 0.625 mg/kg IV qDay
- CrCl <10 mL/min: 0.625 mg/kg IV 3 x per week following hemodialysis
Dosage Forms & Strengths
injection, lyophilized powder for reconstitution
- 500mg
CMV Prevention in HIV-infected (off-label)
5 mg/kg IV qDay (recurrence)
Interactions
Interaction Checker
No Results
Contraindicated
Serious - Use Alternative
Significant - Monitor Closely
Minor
Adverse Effects
>10%
Neutropenia w/ ANC <1000/cu.mm (25-50%)
Thrombocytopenia (20%)
1-10%
Elevated LFTs
Anemia
Confusion
Headache
Nausea/vomiting
Neuropathy
Paresthesia
Pruritus
Retinal detachment,
Rash
Sepsis
Weakness
Frequency Not Defined
Blood and lymphatic disorders: Pancytopenia, bone marrow failure
Cardiac disorders: Arrhythmias
Ear and labyrinth disorders: Tinnitus, ear pain, deafness
Eye disorders: Visual impairment, vitreous disorders, eye pain, conjunctivitis, macular edema
Gastrointestinal disorders: Abdominal pain, dyspepsia, flatulence, constipation, mouth ulceration, dysphagia, abdominal distention, pancreatitis, gastrointestinal perforation, eructation, dry mouth
General disorders and administration site conditions: Fatigue, injection site inflammation, edema, pain, malaise, asthenia, chest pain, multiple organ failure
Blood Immune system disorders: Hypersensitivity Infections and infestations: Candida infections including oral candidiasis, upper respiratory infection, influenza, urinary tract infections, cellulitis
Investigations: Blood alkaline phosphatase increased, hepatic function abnormal, aspartate aminotransferase increased, alanine aminotransferase increased, creatinine clearance decreased
Metabolism and nutrition disorders: Weight decreased
Musculoskeletal and connective tissue disorders: Back pain, myalgia, arthralgia, muscle spasms, leg cramps, myasthenia
Nervous system disorders: Headache, insomnia, dizziness, paresthesia, hypoaesthesia, seizures, somnolence, dysgeusia (taste disturbance), tremor
Psychiatric disorders: Depression, confusional state, anxiety, agitation, psychotic disorder, thinking abnormal, abnormal dreams
Renal and urinary disorders: Kidney failure, renal function abnormal, urinary frequency, hematuria
Respiratory, thoracic and mediastinal disorders: Cough, dyspnea
Skin and subcutaneous tissues disorders: Dermatitis, alopecia, dry skin, urticaria, rash
Vascular disorders: Hypotension, hypertension, phlebitis, vasodilation
Postmarketing Reports
Hemolytic anemia, agranulocytosis, granulocytopenia
Cardiac arrest, conduction disorder, torsade de pointes, ventricular tachycardia
Congenital anomaly
Inappropriate antidiuretic hormone secretion
Cataracts, dry eyes
Intestinal ulcer
Cholelithiasis, cholestasis, hepatic failure, hepatitis
Anaphylactic reaction, allergic reaction, vasculitis
Blood triglycerides increased
Acidosis, hypercalcemia, hyponatremia Arthritis, rhabdomyolysis
Dysesthesia, dysphasia, extrapyramidal disorder, facial paralysis, amnesia, anosmia, myelopathy, cerebrovascular accident, third cranial nerve paralysis, aphasia, encephalopathy, intracranial hypertension
Irritability, hallucinations
Renal tubular disorder, hemolytic uremic syndrome
Infertility, testicular hypotrophy
Bronchospasm, pulmonary fibrosis
Exfoliative dermatitis, Stevens Johnson syndrome Peripheral ischemia
Warnings
Black Box Warnings
Hematologic toxicity: Granulocytopenia, anemia, thrombocytopenia, and pancytopenia reported
Impairment of fertility: Based on animal data and limited human data, ganciclovir may cause temporary or permanent inhibition of spermatogenesis in males and suppression of fertility in females
Fetal toxicity: Based on animal data, ganciclovir has the potential to cause birth defects in humans
Mutagenesis and carcinogenesis: Based on animal data, ganciclovir has the potential to cause cancers in humans
Contraindications
Hypersensitivity reaction (eg, anaphylaxis) to ganciclovir, valganciclovir, or any component of the formulation
Cautions
Also see Black Box Warnings
Granulocytopenia (neutropenia), anemia, thrombocytopenia and pancytopenia observed; not recommended if the absolute neutrophil count (ANC) <500 cells/mcL, hemoglobin <8 g/dL, or the platelet count <25,000 cells/mcL
Exercise caution patients with pre-existing cytopenias and in patients receiving myelosuppressive drugs or irradiation
Renal impairment should be used with caution in patients with impaired renal function because the half-life and plasma/serum concentrations of ganciclovir will be increased due to reduced renal clearance; increased serum creatinine levels have been reported in elderly patients and in transplant recipients receiving concomitant nephrotoxic medications (eg, cyclosporine and amphotericin B); monitor renal function during therapy is essential, especially for elderly patients and those patients receiving concomitant agents that may cause nephrotoxicity
Based on animal data and limited human data, recommended human dose (RHD) may cause temporary or permanent inhibition of spermatogenesis in males, and may cause suppression of fertility in females (see Pregnancy)
Fetal toxicity may occur when administered to pregnant women based on findings in animal studies (see Pregnancy)
Animal data indicate that ganciclovir is mutagenic and carcinogenic, may potentially be carcinogenic in humans
Drug interactions overview
- Coadministration with imipenem-cilastatin is not recommended because generalized seizures reported
- Monitor renal function when coadministered with cyclosporine or amphotericin B because of potential increase in serum creatinine
- Based on increased risk, monitor for hematological and renal toxicity when concomitantly using mycophenolate mofetil with ganciclovir
- Other drugs associated with myelosuppression or nephrotoxicity: Consider only if the potential benefits outweigh the risks
- Coadministration with didanosine will potentially increase plasma levels and toxicities of didanosine; closely monitor
- Concomitant use with probenecid may increase ganciclovir levels; consider reducing dose of ganciclovir and monitor possible toxicities
Pregnancy & Lactation
Pregnancy
Placental transfer of ganciclovir has been shown to occur based on ex vivo experiments with human placenta and in at least 1 case report in a pregnant woman; however, no adequate human data are available to establish whether ganciclovir poses a risk to pregnancy outcomes
In animal studies, ganciclovir caused maternal and fetal toxicity and embryo-fetal mortality in pregnant mice and rabbits as well as teratogenicity in rabbits at exposures 2 times the exposure at the recommended human dose (RHD)
Disease-associated maternal and/or embryo-fetal risk
- Most maternal CMV infections are asymptomatic or they may be associated with a self-limited mononucleosis-like syndrome; however, in immunocompromised patients, CMV infections may be symptomatic and may result in significant maternal morbidity and mortality
- CMV fetal transmission results from maternal viremia and transplacental infection
- Perinatal infection can also occur from exposure of the neonate to CMV shedding in the genital tract ~10% of children with congenital CMV infection are symptomatic at birth
- Mortality in symptomatic infants is ~10% and ~50-90% of symptomatic surviving newborns experience significant morbidity, including mental retardation, sensorineural hearing loss, microcephaly, seizures, and other medical problems
- Risk of congenital CMV infection resulting from primary maternal CMV infection may be higher and of greater severity than that resulting from maternal reactivation of CMV infection
Contraception
- Test for pregnancy in females of reproductive potential before initiating treatment
- Females: Because of ganciclovir’s mutagenic and teratogenic potential, use effective contraception during treatment and for at least 30 days following treatment
- Males: Because of ganciclovir’s mutagenic and teratogenic potential, use barrier contraception during treatment and for at least 90 days following treatment
Infertility
- Based on animal data and limited human data, may cause temporary or permanent inhibition of spermatogenesis in males, and may cause suppression of fertility in females at recommended human dose (RHD); advise patients that fertility may be impaired with use
Lactation
No data are available regarding the presence of ganciclovir in human milk, the effects on the breastfed infant, or the effects on milk production
Ganciclovir was present in milk in lactating rats following administration
Breastfeeding is not recommended during treatment owing to the potential for serious adverse reactions in nursing infants
Pregnancy Categories
A:Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B:May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C:Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D:Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X:Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA:Information not available.
Pharmacology
Mechanism of Action
Inhibits of viral DNA polymerases resulting in chain termination
Absorption
AUC: 22.1-26.8 mcg·hr/mL
Distribution
Vd (steady-state): 0.74 L/kg
Diffuses across the placenta
Protein binding: 1-2% over ganciclovir concentrations of 0.5-51 mcg/mL
Elimination
Clearance: 3.2 mL/min/kg (renal); 3.52 mL/min/kg (systemic)
Administration
IV Compatibilities
Solution: compatible w/ most common solvents
Y-site (partial list): allopurinol, fluconazole, linezolid, propofol
IV Incompatibilities
Y-site: aldesleukin, amifostine, amsacrine, aztreonam, cefepime, cisatracurium(?), cytarabine, doxorubicin, fludarabine, foscarnet, gemcitabine, ondansetron, piperacillin/tazobactam, sargramostim, tacrolimus, vinorelbine
IV Preparation
Reconstitute vial with 10 mL of Sterile Water for Injection
Do not use bacteriostatic water for injection containing parabens; it is incompatible with ganciclovir and may cause precipitation
Gently swirl the vial in order to ensure complete wetting of the product; continue swirling until a clear reconstituted solution is obtained
Visually inspect solution for particulate matter and discoloration prior to proceeding with infusion
Discard the vial if particulate matter or discoloration is observed
IV Administration
Also see Storage
Same precautions as antineoplastic agents should be followed with ganciclovir
Do not administer IM, SC, rapid infusion or IVP
Administer by slow IV infusion over at least 1 hr at a final concentration not to exceed 10 mg/mL
Too rapid infusion can cause increased toxicity and excessive plasma levels
Handling and disposal
- Exercise caution in the handling and preparation of solutions
- Reconstituted solutions are alkaline (pH 11)
- Avoid direct contact of the skin or mucous membranes with solution
- If such contact occurs, wash thoroughly with soap and water; rinse eyes thoroughly with plain water
- Wearing disposable gloves is recommended
- Because ganciclovir shares some of the properties of antitumor agents (eg, carcinogenicity and mutagenicity), consideration should be given to handling and disposal according to guidelines issued for antineoplastic drugs
Storage
Unused vials: Store at 25°C (77°F); excursions permitted to 15-30°C (59-86°F)
Reconstituted vials: Store at 25°C (77°F) for no longer than 12 hr; do not refrigerate or freeze
Diluted solutions: Refrigerate at 2-8°C (36-46°F) for no longer than 24 hr; do not freeze
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Patient Handout
Formulary
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Adding plans allows you to:
- View the formulary and any restrictions for each plan.
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- Compare formulary status to other drugs in the same class.
- Access your plan list on any device – mobile or desktop.
