Zirgan

Nucleoside and Nucleotide DNA Polymerase Inhibitor Antivirals
Ophthalmological Antiviral Agents

 
Perform frequent hematologic monitoring in patients during treatment and do not administer if the absolute neutrophil count (ANC) is less than 500 cells/mm3, hemoglobin is less than 8 g/dL, or the platelet count is less than 25,000 cells/mm3.Use caution when handling and preparing parenteral solutions.
Hazardous Drugs Classification
NIOSH 2016 List: Group 2
NIOSH (Draft) 2020 List: Table 1
Observe and exercise appropriate precautions for handling, preparation, administration, and disposal of hazardous drugs.
INJECTABLE: Use double chemotherapy gloves and a protective gown. Prepare in a biological safety cabinet or compounding aseptic containment isolator with a closed system drug transfer device. Eye/face and respiratory protection may be needed during preparation and administration.
ORAL CAPSULES: Use gloves to handle. Cutting, crushing, or otherwise manipulating capsules will increase exposure and require additional protective equipment. Eye/face and respiratory protection may be needed during preparation and administration.
TOPICAL: Use double chemotherapy gloves and protective gown. Eye/face and respiratory protection may be needed during preparation and administration.

Use caution when preparing and administering the product to avoid direct contact with skin. If contact occurs, wash the area thoroughly with soap and water. Ganciclovir solution for injection is alkaline and may cause irritation.
Do NOT administer by rapid infusion or injection; toxicity may be increased.
Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit; the solution should be colorless. Discard if discoloration or particulate matter is observed.

Reconstitution
Reconstitute 500 mg vials with 10 mL of Sterile Water for Injection. Do NOT use Bacteriostatic Water for Injection containing parabens or precipitation may occur.
Gently swirl vial until a clear reconstituted solution is obtained.
Storage: Reconstituted vials are stable at room temperature 25 degrees C (77 degrees F) for 12 hours. Do not refrigerate or freeze. Discard any unused portion of the reconstituted solution.
 
Dilution
Withdraw appropriate dose of reconstituted solution and dilute with 50 to 250 mL of a compatible IV infusion solution including 0.9% Sodium Chloride Injection, 5% Dextrose Injection, Ringer's Solution for Injection, or Lactated Ringer's Injection. Infusion concentrations greater than 10 mg/mL are not recommended.
Storage: Once further diluted in an IV solution, use within 24 hours to reduce the risk of bacterial contamination. Refrigerate the diluted infusion solution at 2 to 8 degrees C (36 to 46 degrees F). Do not freeze.
 
Premixed IV solution
Dilution is not required.
Solution does not contain preservatives and is for single use only. Any unused portion must be discarded.
 
Intermittent IV Infusion
Infuse slowly over 1 hour at a constant rate via a large peripheral or central vein with adequate blood flow to permit rapid dilution and distribution. The infusion should be accompanied by adequate hydration.
A controlled-infusion device is recommended for highly concentrated solutions.

Intravitreal injection†
NOTE: Ganciclovir is not approved by the FDA for administration via intravitreal injection.
Reconstitute and dilute ganciclovir IV powder in 0.9% NaCl Injection to a concentration of 2 mg/0.04 mL to 2 mg/0.1 mL. Doses of 5 mg/0.1 mL have also been used in adults.
Inject appropriate dose intravitreally using a tuberculin syringe.

Ganciclovir ophthalmic gel is for topical ophthalmic use only.
To avoid contamination or the spread of infection, do not use dropper for more than 1 person.
Do not to touch the tip of the dropper to the eye, fingertips, or other surface to prevent contamination.
Instruct patient on proper instillation of eye gel (see Patient Information).
Wash hands before and after use. Tilt the head back slightly and pull the lower eyelid down with the index finger to form a pouch. Squeeze the prescribed number of drops into the pouch. Close eyes to spread drops.
Patients should not wear contact lenses while using ganciclovir ophthalmic gel.

retinal detachment / Delayed / 8.0-11.0
hemolytic anemia / Delayed / 0-1.0
cranial nerve palsies / Delayed / 0-1.0
stroke / Early / 0-1.0
increased intracranial pressure / Early / 0-1.0
hemolytic-uremic syndrome / Delayed / 0-1.0
anaphylactoid reactions / Rapid / 0-1.0
Stevens-Johnson syndrome / Delayed / 0-1.0
exfoliative dermatitis / Delayed / 0-1.0
hepatic failure / Delayed / 0-1.0
bronchospasm / Rapid / 0-1.0
pulmonary fibrosis / Delayed / 0-1.0
rhabdomyolysis / Delayed / 0-1.0
cardiac arrest / Early / 0-1.0
torsade de pointes / Rapid / 0-1.0
vasculitis / Delayed / 0-1.0
keratitis / Delayed / 5.0
pancytopenia / Delayed / Incidence not known
agranulocytosis / Delayed / Incidence not known
GI perforation / Delayed / Incidence not known
pancreatitis / Delayed / Incidence not known
seizures / Delayed / Incidence not known
renal failure (unspecified) / Delayed / Incidence not known
new primary malignancy / Delayed / Incidence not known
teratogenesis / Delayed / Incidence not known
hearing loss / Delayed / Incidence not known
arrhythmia exacerbation / Early / Incidence not known
ventricular tachycardia / Early / Incidence not known
visual impairment / Early / Incidence not known
macular edema / Delayed / Incidence not known
SIADH / Delayed / Incidence not known

blurred vision / Early / 60.0-60.0
thrombocytopenia / Delayed / 3.0-57.0
leukopenia / Delayed / 29.0-41.0
neutropenia / Delayed / 3.0-29.0
anemia / Delayed / 2.0-26.0
peripheral neuropathy / Delayed / 8.0-9.0
conjunctival hyperemia / Early / 5.0-5.0
hallucinations / Early / 0-1.0
memory impairment / Delayed / 0-1.0
aphasia / Delayed / 0-1.0
cholelithiasis / Delayed / 0-1.0
elevated hepatic enzymes / Delayed / 0-1.0
cholestasis / Delayed / 0-1.0
hepatitis / Delayed / 0-1.0
dyspnea / Early / 0-1.0
metabolic acidosis / Delayed / 0-1.0
hypertriglyceridemia / Delayed / 0-1.0
hyponatremia / Delayed / 0-1.0
hypercalcemia / Delayed / 0-1.0
bleeding / Early / Incidence not known
bone marrow suppression / Delayed / Incidence not known
stomatitis / Delayed / Incidence not known
constipation / Delayed / Incidence not known
depression / Delayed / Incidence not known
dysphagia / Delayed / Incidence not known
confusion / Early / Incidence not known
urinary retention / Early / Incidence not known
hematuria / Delayed / Incidence not known
phlebitis / Rapid / Incidence not known
clastogenesis / Delayed / Incidence not known
infertility / Delayed / Incidence not known
candidiasis / Delayed / Incidence not known
edema / Delayed / Incidence not known
chest pain (unspecified) / Early / Incidence not known
testicular atrophy / Delayed / Incidence not known
myasthenia / Delayed / Incidence not known
hypotension / Rapid / Incidence not known
hypertension / Early / Incidence not known
peripheral vasodilation / Rapid / Incidence not known
conjunctivitis / Delayed / Incidence not known
cataracts / Delayed / Incidence not known

fever / Early / 38.0-48.0
diarrhea / Early / 41.0-44.0
ocular irritation / Rapid / 20.0-20.0
anorexia / Delayed / 14.0-15.0
infection / Delayed / 0-15.0
vomiting / Early / 13.0-13.0
hyperhidrosis / Early / 11.0-12.0
chills / Rapid / 7.0-10.0
pruritus / Rapid / 5.0-6.0
irritability / Delayed / 0-1.0
dysesthesia / Delayed / 0-1.0
cough / Delayed / 0-1.0
xerophthalmia / Early / 0-1.0
xerostomia / Early / Incidence not known
dysgeusia / Early / Incidence not known
eructation / Early / Incidence not known
flatulence / Early / Incidence not known
dyspepsia / Early / Incidence not known
abdominal pain / Early / Incidence not known
nausea / Early / Incidence not known
weight loss / Delayed / Incidence not known
paresthesias / Delayed / Incidence not known
drowsiness / Early / Incidence not known
headache / Early / Incidence not known
fatigue / Early / Incidence not known
anxiety / Delayed / Incidence not known
hypoesthesia / Delayed / Incidence not known
tremor / Early / Incidence not known
insomnia / Early / Incidence not known
dizziness / Early / Incidence not known
increased urinary frequency / Early / Incidence not known
injection site reaction / Rapid / Incidence not known
xerosis / Delayed / Incidence not known
alopecia / Delayed / Incidence not known
urticaria / Rapid / Incidence not known
rash / Early / Incidence not known
spermatogenesis inhibition / Delayed / Incidence not known
influenza / Delayed / Incidence not known
malaise / Early / Incidence not known
anosmia / Delayed / Incidence not known
otalgia / Early / Incidence not known
tinnitus / Delayed / Incidence not known
myalgia / Early / Incidence not known
arthralgia / Delayed / Incidence not known
muscle cramps / Delayed / Incidence not known
back pain / Delayed / Incidence not known
ocular pain / Early / Incidence not known

Use systemic ganciclovir with caution in patients with bone marrow suppression or to those who are receiving other myelosuppressive chemotherapy or radiation therapy. Severe anemia, leukopenia, neutropenia, pancytopenia, and thrombocytopenia have been reported during ganciclovir therapy. The frequency and severity of these events vary widely in different patient populations. Patients with neutropenia (absolute neutrophil count (ANC) less than 500 cells/mm3), anemia (hemoglobin less than 8 g/dL), or thrombocytopenia (platelet count less than 25,000 cells/mm3) should not receive the drug. Complete blood counts with differential and platelet counts should be performed frequently, especially in patients who have experienced previous drug-induced leukopenia or in patients with a baseline ANC less than 1,000 cells/mm3. The manufacturer notes that ganciclovir should only be used as indicated within the prescribing information; avoid unnecessary use.

Take care to avoid accidental exposure to ganciclovir during preparation, handling or administration, due to the potential mutagenicity and alkaline pH of intravenous ganciclovir. Although human data are not available, the development of neoplastic disease is a potential risk to consider during ganciclovir therapy based on animal carcinogenicity data. The use of protective gowns, gloves and goggles is recommended. Avoid direct contact of ganciclovir solution with skin or mucous membranes. If skin contact occurs, wash thoroughly with soap and water. Following ocular exposure, rinse eyes thoroughly with plain water. Consider handling and disposing of ganciclovir according to guidelines issued for antineoplastic agents. There is no agreement that all the procedures recommended in the guidelines are necessary or appropriate for ganciclovir. The manufacturer notes that ganciclovir should only be used as indicated within the prescribing information; avoid unnecessary use.

Ganciclovir is associated with reproductive risk. The drug can be teratogenic if taken by the father near the time of conception (male-mediated teratogenicity) or by the mother during pregnancy. Discuss contraception requirements with the patient. Females should use effective contraception during and for at least 30 days after treatment with ganciclovir. Males must use a condom during and for at least 90 days after treatment. Females of reproductive potential should undergo pregnancy testing prior to initiation of ganciclovir. In addition, based on animal and limited human data, ganciclovir may cause temporary or permanent inhibition of spermatogenesis and subsequent infertility. Animal studies also indicate that suppression of fertility in females may occur.
 

There are no adequate and well-controlled human studies evaluating use of ganciclovir during pregnancy; however, based on data from animal studies, ganciclovir may be teratogenic or embryotoxic at doses recommended for human use. If considering use of ganciclovir in a pregnant female, consider that most maternal CMV infections are subclinical or may be associated with mononucleosis-like syndrome. However, in immunocompromised patients, CMV infections are often symptomatic and associated with significant morbidity and mortality. Also consider that the risk and severity of congenital CMV infection appear to be higher in infants born to mother with primary CMV infection than in those born to mothers with reactivation of the disease. Of the newborns who are infected with CMV, only 10% are symptomatic at birth and the mortality rate among symptomatic infants is about 10%; however, approximately 50% to 90% of the surviving infants may experience significant problems, including sensorineural hearing loss, mental retardation, and other neurologic defects. It is not known if topically administered ophthalmic ganciclovir could result in significant systemic absorption; therefore, the manufacturer recommends the administration of ophthalmic ganciclovir to pregnant women only if the potential benefit to the mother outweighs the potential risk to the fetus.

Cytovene, Zirgan

Rx

Synthetic purine nucleoside analog antiviral
Used for prevention and treatment of CMV; ophthalmic gel approved for acute herpetic keratitis
Dose adjustment may be required for hematological toxicity (neutropenia, thrombocytopenia)
.

5 mg/kg/dose IV every 12 hours for 14 to 21 days as an initial therapy. Systemic therapy may be combined with intravitreal ganciclovir or foscarnet for immediate sight-threatening lesions (i.e., within 1,500 microns of the fovea). Follow with chronic maintenance therapy.

5 mg/kg/dose IV every 12 hours for 14 to 21 days as an initial therapy. Systemic therapy may be combined with intravitreal ganciclovir or foscarnet for immediate sight-threatening lesions (i.e., within 1,500 microns of the fovea). Follow with chronic maintenance therapy.

5 mg/kg/dose IV every 12 hours for 14 to 21 days; may increase dose to 7.5 mg/kg/dose IV every 12 hours if needed. Consider adding IV foscarnet for sight-threatening disease. Follow with chronic maintenance therapy.

2 mg intravitreally once weekly until lesion inactivity is achieved for patients with immediate sight-threatening lesions (i.e., within 1,500 microns of the fovea). Intravitreal injections are given to achieve rapid high intraocular drug concentrations and should be administered in combination with systemic induction therapy.

2 mg intravitreally once weekly until lesion inactivity is achieved for patients with immediate sight-threatening lesions (i.e., within 1,500 microns of the fovea). Intravitreal injections are given to achieve rapid high intraocular drug concentrations and should be administered in combination with systemic induction therapy.

5 mg/kg/dose IV every 12 hours for 7 to 14 days, followed by maintenance therapy of 5 mg/kg/dose IV daily for 7 days per week or 6 mg/kg/dose IV daily for 5 days per week through day 100 to 120 post-transplant. Other studies have examined similar doses starting 5 to 7 days prior to transplantation. Regimens are transplant center and recipient specific; high dose acyclovir or other co-therapies may be utilized.

5 mg/kg/dose IV twice daily for 5 to 7 days starting at engraftment, followed by 5 mg/kg/dose IV once daily through day 100 post-transplant. Monitor ANC at least twice weekly during ganciclovir therapy. Regimens are transplant center and recipient specific; consult local protocols.

5 mg/kg/dose IV twice daily for 7 to 14 days, followed by 5 mg/kg/dose IV once daily 7 days per week or 6 mg/kg/dose IV once daily 5 days per week is the FDA-approved dosage. 5 mg/kg/dose IV once daily starting within 10 days post-transplant and continuing for 3 months has been recommended. Studies have been conducted in recipients of kidney, kidney-pancreas, heart, heart-lung, liver, lung, and pancreas transplants.

5 mg/kg/dose IV once daily starting within 10 days post-transplant and continuing for up to 3 months has been recommended. Some protocols may extend therapy up to 6 months in highest risk patients. Regimens vary by transplant center, type of transplant, and recipient characteristics; consult local protocols. CMV hyperimmune globulin may be added to the ganciclovir regimen and/or the duration of IV therapy may vary.

5 mg/kg/day IV for the length of ATG therapy, followed by oral ganciclovir for 3 to 4 months, significantly reduced the incidence of CMV disease in patients who also were treated with ATG.

5 mg/kg/dose IV twice daily for 7 to 14 days for allogeneic transplant recipients or for 7 days for autologous transplant recipients, then 5 mg/kg/dose IV once daily for maintenance. Continue maintenance therapy until CMV detection methods are negative. The minimum length of therapy is 2 weeks for autologous HCT; for allogenic HCT, the minimum is 2 weeks when 14-day induction is used or 3 weeks when a 7-day induction is used. Preemptive therapy is recommended for all allogeneic transplant recipients with evidence of CMV infection in blood by antigenemia, PCR for CMV DNA, or detection of CMV mRNA and for CMV seropositive autologous transplant recipients at high risk when CMV antigenemia is at least 5 cells/slide (or any level for recipients of CD34+ selected grafts). Regimens are transplant center and recipient specific; consult local protocols.

5 mg/kg/dose IV twice daily for 7 to 14 days for allogeneic transplant recipients or for 7 days for autologous transplant recipients, then 5 mg/kg/dose IV once daily for maintenance. Continue maintenance therapy until CMV detection methods are negative. The minimum length of therapy is 2 weeks for autologous HCT; for allogenic HCT, the minimum is 2 weeks when 14-day induction is used or 3 weeks when a 7-day induction is used. Preemptive therapy is recommended for all allogeneic transplant recipients with evidence of CMV infection in blood by antigenemia, PCR for CMV DNA, or detection of CMV mRNA and for CMV seropositive autologous transplant recipients at high risk when CMV antigenemia is at least 5 cells/slide (or any level for recipients of CD34+ selected grafts). Regimens are transplant center and recipient specific; consult local protocols.

5 mg/kg/dose IV twice daily for 7 to 14 days, then 5 mg/kg/dose IV once daily for 1 to 2 weeks or until the indicator test is negative. The minimum length of therapy is 2 weeks. Preemptive therapy is recommended when allogeneic transplant recipients, patients receiving steroids for GVHD, or patients who received CMV therapy less than 100 days after HCT have an antigenemia at least 5 cells/slide or at least 2 consecutive positive viremia or PCR tests. Regimens are transplant center and recipient specific; consult local protocols.

5 mg/kg/dose IV twice daily for 7 to 14 days, then 5 mg/kg/dose IV once daily for 1 to 2 weeks or until the indicator test is negative. The minimum length of therapy is 2 weeks. Preemptive therapy is recommended when allogeneic transplant recipients, patients receiving steroids for GVHD, or patients who received CMV therapy less than 100 days after HCT have an antigenemia at least 5 cells/slide or at least 2 consecutive positive viremia or PCR tests. Regimens are transplant center and recipient specific; consult local protocols.

1 drop in the affected eye(s) 5 times daily, approximately every 3 hours while awake, until corneal ulcer heals, then 1 drop in the affected eye(s) 3 times daily for 7 days.

1 drop in the affected eye(s) 5 times daily, approximately every 3 hours while awake, until corneal ulcer heals, then 1 drop in the affected eye(s) 3 times daily for 7 days.

Following induction therapy for CMV retinitis, give chronic maintenance therapy of 5 mg/kg/dose IV daily for 7 days per week or 6 mg/kg/dose IV daily for 5 days per week; may switch to oral valganciclovir when the patient is clinically improving and there are no concerns about absorption. The duration of maintenance therapy depends on the immune status of the patient. For patients with HIV who have had a sustained immune response to highly active antiretroviral therapy (i.e., CD4 counts greater than 100 cells/mm3 for 3 to 6 months), have been on CMV treatment for at least 3 to 6 months, and have no active lesions, secondary CMV retinitis prophylaxis may be discontinued after consultation with an ophthalmologist. Maintenance therapy should be restarted if subsequent CD4 counts drop to less than 100 cells/mm3, as relapse occurs most frequently in those patients whose counts decrease to less than 50 cells/mm3 after stopping treatment. However, because relapses may occur at any CD4 count, all patients who have had maintenance CMV therapy discontinued should continue to undergo regular ophthalmologic monitoring (every 3 months) for early detection of CMV relapse (as well as for immune reconstitution uveitis).

Following induction therapy for CMV retinitis, give chronic maintenance therapy of 5 mg/kg/dose IV daily; may switch to oral valganciclovir when the patient is clinically improving and there are no concerns about absorption. The duration of maintenance therapy depends on the immune status of the patient. For patients with HIV who have had a sustained immune response to highly active antiretroviral therapy (i.e., CD4 counts greater than 100 cells/mm3 for 3 to 6 months), have been on CMV treatment for at least 3 to 6 months, and have no active lesions, secondary CMV retinitis prophylaxis may be discontinued after consultation with an ophthalmologist. Maintenance therapy should be restarted if subsequent CD4 counts drop to less than 100 cells/mm3, as relapse occurs most frequently in those patients whose counts decrease to less than 50 cells/mm3 after stopping treatment. However, because relapses may occur at any CD4 count, all patients who have had maintenance CMV therapy discontinued should continue to undergo regular ophthalmologic monitoring (every 3 months) for early detection of CMV relapse (as well as for immune reconstitution uveitis).

5 mg/kg/dose IV once daily is recommended as the preferred regimen in the HIV guidelines after induction therapy. Treatment duration depends on the immune status of the patient. Discontinuation of secondary prophylaxis may be considered in children who have received at least 6 months of highly active antiretroviral therapy with a sustained increase (more than 6 months) in CD4 percentage of at least 15% (pediatric patients younger than 5 years) or CD4 count more than 100 cells/mm3 (children 6 years and older). For retinitis, the decision to discontinue secondary prophylaxis should be made in consultation with an ophthalmologist. Routine follow-up (every 3 to 6 months) with an ophthalmologist is recommended. Restart maintenance therapy if CD4 percentage is less than 15% in pediatric patients younger than 5 years or if CD4 count is less than 100 cells/mm3 in children 6 years and older.

2 mg intravitreally twice weekly for 3 weeks then weekly thereafter; alternately, 5 mg intravitreal injection once weekly has been studied.

5 mg/kg/dose IV every 12 hours is recommended by the Infectious Diseases Society of America (IDSA). Although no duration is given for ganciclovir, 10 to 15 days duration of therapy is recommended for acyclovir.

5 mg/kg/dose IV every 12 hours. The American Academy of Pediatrics (AAP) recommends ganciclovir as the first line alternative when IV acyclovir is unavailable for patients with herpes simplex/varicella zoster infections in immunocompromised hosts and patients unable to tolerate oral acyclovir or valacyclovir.

6 mg/kg/dose IV every 12 hours. The American Academy of Pediatrics (AAP) recommends ganciclovir as the first line alternative when IV acyclovir is unavailable for patients with suspected or proven neonatal herpes simplex disease and herpes simplex/varicella zoster infections in immunocompromised hosts and patients unable to tolerate oral acyclovir or valacyclovir.

5 mg/kg/dose IV every 12 hours plus IV foscarnet (to stabilize the disease and maximize response); optimal duration has not been established. Routine maintenance therapy is not recommended unless there is concurrent retinitis, there have already been recurrent infections, or severe disease was present initially.

5 mg/kg/dose IV every 12 hours plus IV foscarnet (to stabilize the disease and maximize response). Continue treatment until there is symptomatic improvement, then follow with secondary prophylaxis (chronic maintenance therapy). Acutely, single drug therapy with ganciclovir is not recommended due to therapeutic failures.

6 mg/kg/dose IV every 12 hours for 6 weeks. If during the 6 weeks of therapy an infant is identified as HIV-infected, some experts recommend extending the course of therapy beyond 6 weeks.

5 mg/kg/dose IV every 12 hours for a minimum of 14 days or until all CNS symptoms have resolved is recommended by the IDSA.

5 mg/kg/dose IV every 12 hours is recommended by the HIV guidelines for 21 to 42 days or until resolution of signs and symptoms; when patient can tolerate PO, switch to oral valganciclovir to complete therapy. Maintenance therapy is usually not necessary, but should be considered after relapse.

5 mg/kg/dose IV every 12 hours is recommended in the HIV guidelines. Therapy may be switched to oral valganciclovir once the patient can tolerate PO therapy. The total duration of therapy should be 21 to 42 days or until resolution of signs and symptoms.

5 mg/kg/dose IV every 12 hours for 14 to 21 days is recommended in the HIV guidelines for patients with disseminated disease; the dosage may be increased to 7.5 mg/kg/dose IV every 12 hours if needed.

In a small randomized, placebo-controlled trial, BMT patients with biopsy-documented CMV infection of the GI tract were treated with ganciclovir 2.5 mg/kg/dose IV every 8 hours for 14 days and did not demonstrate a superior clinical response or endoscopic appearance compared to the placebo group. Cultures were negative more often, however, in the ganciclovir group.

Experience is limited in HIV-infected patients. 5 mg/kg/dose IV every 12 hours is suggested by the HIV guidelines; however, optimal duration has not been established. In an open trial in BMT patients, ganciclovir 2.5 mg/kg/dose IV every 8 hours for 14 days, in combination with intravenous CMV-IVIG (on days 1, 2, 7, and 14) was studied. In patients who were still symptomatic, a maintenance dose of 5 mg/kg/dose IV once daily was given for an additional 14 days with CMV-IVIG on day 21. Twelve of 25 patients died a median of 12 days after treatment. In another trial in BMT patients, ganciclovir 2.5 mg/kg/dose IV every 8 hours for 20 days, then 5 mg/kg/dose IV once daily 3 to 5 times per week for 20 additional doses in combination with IV immune globulin was evaluated. Combination therapy was successful in 7 of 10 patients.

5 mg/kg/dose IV every 12 hours. For HIV-infected patients, treatment should be considered in patients with well-documented, histologic evidence of CMV pneumonitis. Data for treating CMV pneumonitis in HIV-infected patients is limited and the optimal duration of therapy has not been established. In 3 pediatric patients who developed CMV pneumonitis after allogenic stem cell transplant, 5 mg/kg/dose IV every 12 hours for 14 days, then 5 mg/kg/dose IV once daily for 5 to 7 days each week for 3 weeks was used. Intravenous immunoglobulin was given in addition to ganciclovir in all patients for part of the study period. Two of the 3 patients that developed CMV pneumonitis died; 1 of multiorgan failure and 1 of acute graft versus host disease.

5 mg/kg/dose IV every 12 hours for 14 to 21 days. For HIV-infected patients with disseminated disease, the dose may be increased to 7.5 mg/kg/dose IV every 12 hours if needed. 5 mg/kg/dose IV every 12 hours for 14 days, then 5 mg/kg/dose IV once daily for 5 to 7 days each week for 3 weeks was used in 3 pediatric patients who developed CMV pneumonitis after allogenic stem cell transplant. Intravenous immunoglobulin was given in addition to ganciclovir in all patients with CMV infection for part of the study period, and then only in patients with subnormal IgG. Two of the 3 patients that developed CMV pneumonitis died; 1 of multiorgan failure and 1 of acute graft versus host disease.

6 mg/kg/dose IV every 12 hours for 6 weeks. Dosage adjustments for the development of neutropenia may be required. This regimen is also recommended by the CDC for HIV-infected neonates; if a neonate is confirmed as being HIV-positive during the 6-week treatment course, some experts recommend extending the treatment course beyond 6 weeks. Clinical practice guidelines recommend antiviral treatment only for symptomatic neonates (first 30 days of life) with severe symptomatic focal organ disease or CNS disease.

5 mg/kg/dose IV every 12 hours plus ganciclovir intravitreal injection and/or foscarnet intravitreal injection. The optimal duration has not been defined; duration should be determined clinically in consultation with an ophthalmologist.

5 mg/kg/dose IV every 12 hours plus ganciclovir intravitreal injection and/or foscarnet intravitreal injection. The optimal duration has not been defined; duration should be determined clinically in consultation with an ophthalmologist.

5 mg/kg/dose IV every 12 hours plus IV foscarnet plus ganciclovir intravitreal injection and/or foscarnet intravitreal injection. The optimal duration has not been defined; duration should be determined clinically in consultation with an ophthalmologist.

2 mg/0.05 mL intravitreal injection twice weekly, with or without foscarnet intravitreal injection, in combination with systemic therapy (i.e., ganciclovir or acyclovir). The optimal duration has not been defined; duration should be determined clinically in consultation with an ophthalmologist.

2 mg/0.05 mL intravitreal injection twice weekly, with or without foscarnet intravitreal injection, in combination with systemic therapy (i.e., ganciclovir or acyclovir). The optimal duration has not been defined; duration should be determined clinically in consultation with an ophthalmologist.

2 mg/0.05 mL intravitreal injection twice weekly, with or without foscarnet intravitreal injection, in combination with systemic therapy (i.e., acyclovir or ganciclovir plus foscarnet). The optimal duration has not been defined; duration should be determined clinically in consultation with an ophthalmologist.

5 mg/kg/dose IV every 12 hours for 3 weeks is recommended by the HIV guidelines.

5 mg/kg/dose IV every 12 hours may be useful as an adjunct to chemotherapy and antiretroviral therapy.

2 mg/0.05 mL intravitreal injections given twice weekly until evidence of treatment response. Administer in combination with 10 to 14 days of IV acyclovir, then at least 14 weeks of oral valacyclovir is recommended by the HIV guidelines. Involvement of an experienced ophthalmologist is recommended.

2 mg/0.05 mL intravitreal injections given twice weekly until evidence of treatment response. Administer in combination with 10 to 14 days of IV acyclovir, then at least 14 weeks of oral valacyclovir is recommended by the HIV guidelines. Involvement of an experienced ophthalmologist is recommended.

5 mg/kg/dose IV every 12 hours. The American Academy of Pediatrics (AAP) recommends ganciclovir as the first line alternative when IV acyclovir is unavailable for herpes simplex/varicella zoster infections in immunocompromised hosts and patients unable to tolerate oral acyclovir or valacyclovir.

6 mg/kg/dose IV every 12 hours. The American Academy of Pediatrics (AAP) recommends ganciclovir as the first line alternative when IV acyclovir is unavailable in suspected or proven neonatal herpes simplex disease or herpes simplex/varicella zoster infections in immunocompromised hosts.

6 mg/kg/dose IV every 12 hours. The American Academy of Pediatrics (AAP) recommends ganciclovir as the first line alternative when IV acyclovir is unavailable in cases of suspected or proven neonatal herpes simplex disease.

5 mg/kg/dose IV every 12 hours for 1 to 3 weeks, followed by a maintenance dose of 5 mg/kg/dose IV once daily to 5 times weekly has been effective in small studies and case reports of immunocompromised adult patients with HHV-6 encephalitis. Ganciclovir alone or in combination with foscarnet is suggested as reasonable by the IDSA due to the lack of other therapeutic options.

5 mg/kg/dose IV every 12 hours for 1 to 3 weeks, followed by a maintenance dose of 5 mg/kg/dose IV once daily to 5 times weekly, has been effective in small studies and case reports of pediatric and adult patients with HHV-6 encephalitis. Higher doses of ganciclovir (18 to 24 mg/kg/day) have also been used in children, without side effects. Ganciclovir alone or in combination with foscarnet is suggested as reasonable by the IDSA due to the lack of other therapeutic options.

†Indicates off-label use

No dosage adjustment necessary.

Modify dosage for intravenous induction therapy and maintenance therapy based on creatinine clearance (CrCl).
Adults:
Intravenous dosage adjustments (induction)
CrCl 70 mL/minute or more: no dosage adjustment needed.
CrCl 50 to 69 mL/minute: 2.5 mg/kg/dose IV every 12 hours.
CrCl 25 to 49 mL/minute: 2.5 mg/kg/dose IV every 24 hours.
CrCl 10 to 24 mL/minute: 1.25 mg/kg/dose IV every 24 hours.
CrCl less than 10 mL/minute: 1.25 mg/kg/dose IV 3 times a week after hemodialysis.
 
Intravenous dosage adjustments (maintenance)
CrCl 70 mL/minute or more: no dosage adjustment needed.
CrCl 50 to 69 mL/minute: 2.5 mg/kg/dose IV every 24 hours.
CrCl 25 to 49 mL/minute: 1.25 mg/kg/dose IV every 24 hours.
CrCl 10 to 24 mL/minute: 0.625 mg/kg/dose IV every 24 hours.
CrCl less than 10 mL/minute: 0.625 mg/kg/dose IV 3 times a week after hemodialysis.
 
Intermittent hemodialysis or Peritoneal dialysis
1.25 mg/kg/dose IV 3 times per week. Give all doses after dialysis sessions.
 
Continuous renal replacement therapy
Intravenous dosage adjustments (induction): 2.5 mg/kg/dose IV every 24 hours.
Intravenous dosage adjustments (maintenance): 1.25 mg/kg/dose IV every 24 hours.
 
Pediatrics:
Intravenous dosage adjustments (induction)
GFR 30 to 50 mL/minute/1.73 m2: 2.5 mg/kg/dose IV every 24 hours.
GFR 10 to 29 mL/minute/1.73 m2: 1.25 mg/kg/dose IV every 24 hours.
GFR less than 10 mL/minute/1.73 m2: 1.25 mg/kg/dose IV 3 times a week.
 
Intravenous dosage adjustments (maintenance)
GFR 30 to 50 mL/minute/1.73 m2: 1.25 mg/kg/dose IV every 24 hours.
GFR 10 to 29 mL/minute/1.73 m2: 0.625 mg/kg/dose IV every 24 hours.
GFR less than 10 mL/minute/1.73 m2: 0.625 mg/kg/dose IV 3 times a week.
 
Intermittent hemodialysis or Peritoneal dialysis
Give all doses after dialysis sessions.
Intravenous dosage adjustments (induction): 1.25 mg/kg/dose IV 3 times per week.
Intravenous dosage adjustments (maintenance): 0.625 mg/kg/dose IV 3 times per week.
 
Continuous renal replacement therapy
Intravenous dosage adjustments (induction): 2.5 mg/kg/dose IV every 24 hours.
Intravenous dosage adjustments (maintenance): 1.25 mg/kg/dose IV every 24 hours.

Abacavir; Lamivudine, 3TC; Zidovudine, ZDV: (Major) Coadministration of ganciclovir and zidovudine may increase the hematologic toxicity (e.g., neutropenia, anemia) of zidovudine. Some patients may not tolerate concomitant therapy with these drugs at full dosage. If concomitant use is necessary, monitor hematologic parameters closely.
Acetaminophen; Ibuprofen: (Minor) Concurrent use of nephrotoxic agents, such as NSAIDs, with ganciclovir should be done cautiously to avoid additive nephrotoxicity. Monitor renal function carefully if concomitant therapy is required.
Aldesleukin, IL-2: (Moderate) Aldesleukin may cause nephrotoxicity. Concurrent administration of drugs possessing nephrotoxic effects, such as ganciclovir, with Aldesleukin, IL-2 may increase the risk of kidney dysfunction.
Aminoglycosides: (Major) Concurrent use of nephrotoxic agents, such as the aminoglycosides, with ganciclovir should be done cautiously to avoid additive nephrotoxicity.
Amlodipine; Celecoxib: (Minor) Concurrent use of nephrotoxic agents, such as NSAIDs, with ganciclovir should be done cautiously to avoid additive nephrotoxicity. Monitor renal function carefully if concomitant therapy is required.
Amphotericin B lipid complex (ABLC): (Moderate) Use caution and monitor renal function when ganciclovir is coadministered with amphotericin B because of the potential increase in serum creatinine. Acute renal failure may occur in patients concomitantly receiving potential nephrotoxic drugs.
Amphotericin B liposomal (LAmB): (Moderate) Use caution and monitor renal function when ganciclovir is coadministered with amphotericin B because of the potential increase in serum creatinine. Acute renal failure may occur in patients concomitantly receiving potential nephrotoxic drugs.
Amphotericin B: (Moderate) Use caution and monitor renal function when ganciclovir is coadministered with amphotericin B because of the potential increase in serum creatinine. Acute renal failure may occur in patients concomitantly receiving potential nephrotoxic drugs.
Aprotinin: (Moderate) The manufacturer recommends using aprotinin cautiously in patients that are receiving drugs that can affect renal function, such as ganciclovir, as the risk of renal impairment may be increased.
Bacitracin: (Minor) Concurrent use of nephrotoxic agents, including systemic bacitracin, with ganciclovir should be done cautiously to avoid additive nephrotoxicity.
Bictegravir; Emtricitabine; Tenofovir Alafenamide: (Moderate) Monitor for changes in serum creatinine and adverse reactions, such as lactic acidosis or hepatotoxicity if emtricitabine is administered in combination with nephrotoxic agents, such as ganciclovir. Consider the potential for drug interaction prior to and during concurrent use of these medications. Both emtricitabine and ganciclovir are excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. While no drug interactions due to competition for renal excretion have been observed, coadministration of these medications may increase concentrations of both drugs.
Bupivacaine; Meloxicam: (Minor) Concurrent use of nephrotoxic agents, such as NSAIDs, with ganciclovir should be done cautiously to avoid additive nephrotoxicity. Monitor renal function carefully if concomitant therapy is required.
Capreomycin: (Major) Since capreomycin is eliminated by the kidney, coadministration with other potentially nephrotoxic drugs, including ganciclovir, may increase serum concentrations of either drug. Theoretically, the chronic coadministration of these drugs may increase the risk of developing nephrotoxicity, even in patients who have normal renal function. Monitor patients for changes in renal function if these drugs are coadministered.
Celecoxib: (Minor) Concurrent use of nephrotoxic agents, such as NSAIDs, with ganciclovir should be done cautiously to avoid additive nephrotoxicity. Monitor renal function carefully if concomitant therapy is required.
Celecoxib; Tramadol: (Minor) Concurrent use of nephrotoxic agents, such as NSAIDs, with ganciclovir should be done cautiously to avoid additive nephrotoxicity. Monitor renal function carefully if concomitant therapy is required.
Chlorpheniramine; Ibuprofen; Pseudoephedrine: (Minor) Concurrent use of nephrotoxic agents, such as NSAIDs, with ganciclovir should be done cautiously to avoid additive nephrotoxicity. Monitor renal function carefully if concomitant therapy is required.
Cidofovir: (Contraindicated) The administration of cidofovir with another potentially nephrotoxic agent, such as ganciclovir, is contraindicated. Ganciclovir should be discontinued at least 7 days prior to beginning cidofovir.
Cisplatin: (Moderate) Concomitant use of cisplatin and ganciclovir should be considered only if the potential benefits outweigh the risks of increased treatment-related toxicities. If coadministration is necessary, closely monitor for treatment-related adverse reactions. Ganciclovir is eliminated renally and cisplatin can cause nephrotoxicity, which may result in increased plasma concentrations of ganciclovir. Side effects such as nephrotoxicity and myelosuppression may be additive.
Clindamycin: (Moderate) Concomitant use of ganciclovir and clindamycin may result in additive nephrotoxicity. Monitor for renal toxicity if concomitant use is required.
Clofarabine: (Moderate) Concomitant use of clofarabine and ganciclovir may result in altered clofarabine levels because both agents are a substrate of OCT1. Therefore, monitor for signs of clofarabine toxicity such as gastrointestinal toxicity (e.g., nausea, vomiting, diarrhea, mucosal inflammation), hematologic toxicity, and skin toxicity (e.g., hand and foot syndrome, rash, pruritus) in patients also receiving OCT1 substrates.
Colistimethate, Colistin, Polymyxin E: (Major) Theoretically, chronic coadministration may increase the risk of developing nephrotoxicity, even in patients who have normal renal function. Monitor patients for changes in renal function during concurrent use. Since colistimethate sodium is eliminated by the kidney, coadministration with other potentially nephrotoxic drugs, including ganciclovir, may increase serum concentrations of either drug.
Colistin: (Major) Theoretically, chronic coadministration may increase the risk of developing nephrotoxicity, even in patients who have normal renal function. Monitor patients for changes in renal function during concurrent use. Since colistimethate sodium is eliminated by the kidney, coadministration with other potentially nephrotoxic drugs, including ganciclovir, may increase serum concentrations of either drug.
Cyclosporine: (Moderate) Use caution and monitor renal function when ganciclovir is coadministered with cyclosporine because of the potential increase in serum creatinine. Acute renal failure may occur in patients concomitantly receiving potential nephrotoxic drugs.
Dapsone: (Moderate) Use ganciclovir and dapsone together only if the potential benefits outweigh the risks; bone marrow suppression, spermatogenesis inhibition, skin toxicity, and gastrointestinal toxicity may be additive as both drugs inhibit rapidly dividing cells.
Darunavir; Cobicistat; Emtricitabine; Tenofovir alafenamide: (Moderate) Monitor for changes in serum creatinine and adverse reactions, such as lactic acidosis or hepatotoxicity if emtricitabine is administered in combination with nephrotoxic agents, such as ganciclovir. Consider the potential for drug interaction prior to and during concurrent use of these medications. Both emtricitabine and ganciclovir are excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. While no drug interactions due to competition for renal excretion have been observed, coadministration of these medications may increase concentrations of both drugs.
Dichlorphenamide: (Major) Use of dichlorphenamide and ganciclovir is not recommended because of an increased risk of ganciclovir-related adverse effects. Monitor closely for signs of drug toxicity if use together cannot be avoided. For example, the main toxicities of ganciclovir are myelosuppresion or nephrotoxicity. Monitor blood counts and renal function, since increased ganciclovir exposure is possible. Dichlorphenamide inhibits OAT1. Ganciclovir is an OAT1 substrate. Additionally, metabolic acidosis is associated with the use of dichlorphenamide and has been reported with the postmarketing use of ganciclovir. Measure sodium bicarbonate concentrations at baseline and periodically during dichlorphenamide treatment. If metabolic acidosis occurs or persists, consider reducing the dose or discontinuing dichlorphenamide therapy.
Diclofenac: (Minor) Concurrent use of nephrotoxic agents, such as NSAIDs, with ganciclovir should be done cautiously to avoid additive nephrotoxicity. Monitor renal function carefully if concomitant therapy is required.
Diclofenac; Misoprostol: (Minor) Concurrent use of nephrotoxic agents, such as NSAIDs, with ganciclovir should be done cautiously to avoid additive nephrotoxicity. Monitor renal function carefully if concomitant therapy is required.
Didanosine, ddI: (Moderate) Ganciclovir can increase the AUC and Cmax of didanosine, ddI when given concurrently. Patients should be monitored closely for didanosine toxicity when receiving ganciclovir concurrently.
Diflunisal: (Minor) Concurrent use of nephrotoxic agents, such as NSAIDs, with ganciclovir should be done cautiously to avoid additive nephrotoxicity. Monitor renal function carefully if concomitant therapy is required.
Diphenhydramine; Ibuprofen: (Minor) Concurrent use of nephrotoxic agents, such as NSAIDs, with ganciclovir should be done cautiously to avoid additive nephrotoxicity. Monitor renal function carefully if concomitant therapy is required.
Diphenhydramine; Naproxen: (Minor) Concurrent use of nephrotoxic agents, such as NSAIDs, with ganciclovir should be done cautiously to avoid additive nephrotoxicity. Monitor renal function carefully if concomitant therapy is required.
Doravirine; Lamivudine; Tenofovir disoproxil fumarate: (Moderate) Concurrent use of nephrotoxic agents with ganciclovir should be done cautiously to avoid additive nephrotoxicity. Other nephrotoxic agents include tenofovir.
Doxorubicin Liposomal: (Moderate) Use ganciclovir and doxorubicin together only if the potential benefits outweigh the risks; bone marrow suppression, spermatogenesis inhibition, skin toxicity, and gastrointestinal toxicity may be additive as both drugs inhibit rapidly dividing cells.
Doxorubicin: (Moderate) Use ganciclovir and doxorubicin together only if the potential benefits outweigh the risks; bone marrow suppression, spermatogenesis inhibition, skin toxicity, and gastrointestinal toxicity may be additive as both drugs inhibit rapidly dividing cells.
Efavirenz; Emtricitabine; Tenofovir Disoproxil Fumarate: (Moderate) Concurrent use of nephrotoxic agents with ganciclovir should be done cautiously to avoid additive nephrotoxicity. Other nephrotoxic agents include tenofovir. (Moderate) Monitor for changes in serum creatinine and adverse reactions, such as lactic acidosis or hepatotoxicity if emtricitabine is administered in combination with nephrotoxic agents, such as ganciclovir. Consider the potential for drug interaction prior to and during concurrent use of these medications. Both emtricitabine and ganciclovir are excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. While no drug interactions due to competition for renal excretion have been observed, coadministration of these medications may increase concentrations of both drugs.
Efavirenz; Lamivudine; Tenofovir Disoproxil Fumarate: (Moderate) Concurrent use of nephrotoxic agents with ganciclovir should be done cautiously to avoid additive nephrotoxicity. Other nephrotoxic agents include tenofovir.
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Alafenamide: (Moderate) Monitor for changes in serum creatinine and adverse reactions, such as lactic acidosis or hepatotoxicity if emtricitabine is administered in combination with nephrotoxic agents, such as ganciclovir. Consider the potential for drug interaction prior to and during concurrent use of these medications. Both emtricitabine and ganciclovir are excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. While no drug interactions due to competition for renal excretion have been observed, coadministration of these medications may increase concentrations of both drugs.
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Disoproxil Fumarate: (Moderate) Concurrent use of nephrotoxic agents with ganciclovir should be done cautiously to avoid additive nephrotoxicity. Other nephrotoxic agents include tenofovir. (Moderate) Monitor for changes in serum creatinine and adverse reactions, such as lactic acidosis or hepatotoxicity if emtricitabine is administered in combination with nephrotoxic agents, such as ganciclovir. Consider the potential for drug interaction prior to and during concurrent use of these medications. Both emtricitabine and ganciclovir are excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. While no drug interactions due to competition for renal excretion have been observed, coadministration of these medications may increase concentrations of both drugs.
Emtricitabine: (Moderate) Monitor for changes in serum creatinine and adverse reactions, such as lactic acidosis or hepatotoxicity if emtricitabine is administered in combination with nephrotoxic agents, such as ganciclovir. Consider the potential for drug interaction prior to and during concurrent use of these medications. Both emtricitabine and ganciclovir are excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. While no drug interactions due to competition for renal excretion have been observed, coadministration of these medications may increase concentrations of both drugs.
Emtricitabine; Rilpivirine; Tenofovir alafenamide: (Moderate) Monitor for changes in serum creatinine and adverse reactions, such as lactic acidosis or hepatotoxicity if emtricitabine is administered in combination with nephrotoxic agents, such as ganciclovir. Consider the potential for drug interaction prior to and during concurrent use of these medications. Both emtricitabine and ganciclovir are excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. While no drug interactions due to competition for renal excretion have been observed, coadministration of these medications may increase concentrations of both drugs.
Emtricitabine; Rilpivirine; Tenofovir Disoproxil Fumarate: (Moderate) Concurrent use of nephrotoxic agents with ganciclovir should be done cautiously to avoid additive nephrotoxicity. Other nephrotoxic agents include tenofovir. (Moderate) Monitor for changes in serum creatinine and adverse reactions, such as lactic acidosis or hepatotoxicity if emtricitabine is administered in combination with nephrotoxic agents, such as ganciclovir. Consider the potential for drug interaction prior to and during concurrent use of these medications. Both emtricitabine and ganciclovir are excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. While no drug interactions due to competition for renal excretion have been observed, coadministration of these medications may increase concentrations of both drugs.
Emtricitabine; Tenofovir alafenamide: (Moderate) Monitor for changes in serum creatinine and adverse reactions, such as lactic acidosis or hepatotoxicity if emtricitabine is administered in combination with nephrotoxic agents, such as ganciclovir. Consider the potential for drug interaction prior to and during concurrent use of these medications. Both emtricitabine and ganciclovir are excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. While no drug interactions due to competition for renal excretion have been observed, coadministration of these medications may increase concentrations of both drugs.
Emtricitabine; Tenofovir Disoproxil Fumarate: (Moderate) Concurrent use of nephrotoxic agents with ganciclovir should be done cautiously to avoid additive nephrotoxicity. Other nephrotoxic agents include tenofovir. (Moderate) Monitor for changes in serum creatinine and adverse reactions, such as lactic acidosis or hepatotoxicity if emtricitabine is administered in combination with nephrotoxic agents, such as ganciclovir. Consider the potential for drug interaction prior to and during concurrent use of these medications. Both emtricitabine and ganciclovir are excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. While no drug interactions due to competition for renal excretion have been observed, coadministration of these medications may increase concentrations of both drugs.
Entecavir: (Moderate) Entecavir may affect renal function and should be used cautiously in combination with other drugs that may also affect renal function including ganciclovir.
Etodolac: (Minor) Concurrent use of nephrotoxic agents, such as NSAIDs, with ganciclovir should be done cautiously to avoid additive nephrotoxicity. Monitor renal function carefully if concomitant therapy is required.
Fenoprofen: (Minor) Concurrent use of nephrotoxic agents, such as NSAIDs, with ganciclovir should be done cautiously to avoid additive nephrotoxicity. Monitor renal function carefully if concomitant therapy is required.
Flucytosine: (Moderate) Use ganciclovir and flucytosine together only if the potential benefits outweigh the risks; bone marrow suppression, spermatogenesis inhibition, skin toxicity, and gastrointestinal toxicity may be additive as both drugs inhibit rapidly dividing cells.
Flurbiprofen: (Minor) Concurrent use of nephrotoxic agents, such as NSAIDs, with ganciclovir should be done cautiously to avoid additive nephrotoxicity. Monitor renal function carefully if concomitant therapy is required.
Hyaluronidase, Recombinant; Immune Globulin: (Moderate) Immune Globulin (IG) products have been reported to be associated with renal dysfunction, acute renal failure, osmotic nephrosis, and death. Patients predisposed to acute renal failure include patients receiving known nephrotoxic drugs like ganciclovir. Coadminister IG products at the minimum concentration available and the minimum rate of infusion practicable. Also, closely monitor renal function.
Hydrocodone; Ibuprofen: (Minor) Concurrent use of nephrotoxic agents, such as NSAIDs, with ganciclovir should be done cautiously to avoid additive nephrotoxicity. Monitor renal function carefully if concomitant therapy is required.
Hydroxyurea: (Moderate) Use ganciclovir and hydroxyurea together only if the potential benefits outweigh the risks; bone marrow suppression, spermatogenesis inhibition, skin toxicity, and gastrointestinal toxicity may be additive as both drugs inhibit rapidly dividing cells.
Ibuprofen: (Minor) Concurrent use of nephrotoxic agents, such as NSAIDs, with ganciclovir should be done cautiously to avoid additive nephrotoxicity. Monitor renal function carefully if concomitant therapy is required.
Ibuprofen; Famotidine: (Minor) Concurrent use of nephrotoxic agents, such as NSAIDs, with ganciclovir should be done cautiously to avoid additive nephrotoxicity. Monitor renal function carefully if concomitant therapy is required.
Ibuprofen; Oxycodone: (Minor) Concurrent use of nephrotoxic agents, such as NSAIDs, with ganciclovir should be done cautiously to avoid additive nephrotoxicity. Monitor renal function carefully if concomitant therapy is required.
Ibuprofen; Pseudoephedrine: (Minor) Concurrent use of nephrotoxic agents, such as NSAIDs, with ganciclovir should be done cautiously to avoid additive nephrotoxicity. Monitor renal function carefully if concomitant therapy is required.
Imipenem; Cilastatin: (Major) Avoid concomitant use of imipenem; cilastatin and ganciclovir unless the potential benefits outweigh the risks. Generalized seizures have occurred in patients who were receiving imipenem; cilastatin concomitantly with ganciclovir.
Imipenem; Cilastatin; Relebactam: (Major) Avoid concomitant use of imipenem; cilastatin and ganciclovir unless the potential benefits outweigh the risks. Generalized seizures have occurred in patients who were receiving imipenem; cilastatin concomitantly with ganciclovir.
Immune Globulin IV, IVIG, IGIV: (Moderate) Immune Globulin (IG) products have been reported to be associated with renal dysfunction, acute renal failure, osmotic nephrosis, and death. Patients predisposed to acute renal failure include patients receiving known nephrotoxic drugs like ganciclovir. Coadminister IG products at the minimum concentration available and the minimum rate of infusion practicable. Also, closely monitor renal function.
Indomethacin: (Minor) Concurrent use of nephrotoxic agents, such as NSAIDs, with ganciclovir should be done cautiously to avoid additive nephrotoxicity. Monitor renal function carefully if concomitant therapy is required.
Inotersen: (Moderate) Use caution with concomitant use of inotersen and ganciclovir due to the risk of glomerulonephritis and nephrotoxicity.
Ketoprofen: (Minor) Concurrent use of nephrotoxic agents, such as NSAIDs, with ganciclovir should be done cautiously to avoid additive nephrotoxicity. Monitor renal function carefully if concomitant therapy is required.
Ketorolac: (Minor) Concurrent use of nephrotoxic agents, such as NSAIDs, with ganciclovir should be done cautiously to avoid additive nephrotoxicity. Monitor renal function carefully if concomitant therapy is required.
Lamivudine, 3TC; Zidovudine, ZDV: (Major) Coadministration of ganciclovir and zidovudine may increase the hematologic toxicity (e.g., neutropenia, anemia) of zidovudine. Some patients may not tolerate concomitant therapy with these drugs at full dosage. If concomitant use is necessary, monitor hematologic parameters closely.
Lamivudine; Tenofovir Disoproxil Fumarate: (Moderate) Concurrent use of nephrotoxic agents with ganciclovir should be done cautiously to avoid additive nephrotoxicity. Other nephrotoxic agents include tenofovir.
Mannitol: (Major) Avoid use of mannitol and ganciclovir, if possible. Concomitant administration of nephrotoxic drugs, such as ganciclovir, increases the risk of renal failure after administration of mannitol.
Maribavir: (Major) Avoid concomitant use of maribavir and ganciclovir. Maribavir may antagonize the antiviral activity of ganciclovir by inhibiting human CMV pUL97 kinase, which is required for activation of ganciclovir.
Meclofenamate Sodium: (Minor) Concurrent use of nephrotoxic agents, such as NSAIDs, with ganciclovir should be done cautiously to avoid additive nephrotoxicity. Monitor renal function carefully if concomitant therapy is required.
Mefenamic Acid: (Minor) Concurrent use of nephrotoxic agents, such as NSAIDs, with ganciclovir should be done cautiously to avoid additive nephrotoxicity. Monitor renal function carefully if concomitant therapy is required.
Meloxicam: (Minor) Concurrent use of nephrotoxic agents, such as NSAIDs, with ganciclovir should be done cautiously to avoid additive nephrotoxicity. Monitor renal function carefully if concomitant therapy is required.
Mycophenolate: (Moderate) The systemic concentration of ganciclovir and the glucuronide metabolite of mycophenolate are increased in the presence of renal impairment. Concomitant use may result in competition for tubular secretion, which could further increase the systemic exposures. Thus, adverse effects from increased serum concentrations may be anticipated; blood cell count monitoring is recommended.
Nabumetone: (Minor) Concurrent use of nephrotoxic agents, such as NSAIDs, with ganciclovir should be done cautiously to avoid additive nephrotoxicity. Monitor renal function carefully if concomitant therapy is required.
Naproxen: (Minor) Concurrent use of nephrotoxic agents, such as NSAIDs, with ganciclovir should be done cautiously to avoid additive nephrotoxicity. Monitor renal function carefully if concomitant therapy is required.
Naproxen; Esomeprazole: (Minor) Concurrent use of nephrotoxic agents, such as NSAIDs, with ganciclovir should be done cautiously to avoid additive nephrotoxicity. Monitor renal function carefully if concomitant therapy is required.
Naproxen; Pseudoephedrine: (Minor) Concurrent use of nephrotoxic agents, such as NSAIDs, with ganciclovir should be done cautiously to avoid additive nephrotoxicity. Monitor renal function carefully if concomitant therapy is required.
Nitisinone: (Moderate) Monitor for increased ganciclovir-related adverse effects. Coadministration may increase ganciclovir exposure resulting in increased adverse effects. Nitisinone inhibits OAT1. Ganciclovir is an OAT1 substrate.
Nonsteroidal antiinflammatory drugs: (Minor) Concurrent use of nephrotoxic agents, such as NSAIDs, with ganciclovir should be done cautiously to avoid additive nephrotoxicity. Monitor renal function carefully if concomitant therapy is required.
Oxaprozin: (Minor) Concurrent use of nephrotoxic agents, such as NSAIDs, with ganciclovir should be done cautiously to avoid additive nephrotoxicity. Monitor renal function carefully if concomitant therapy is required.
Pentamidine: (Moderate) Use ganciclovir with pentamidine only if the potential benefits are judged to outweigh the risks. Concurrent use of agents that inhibit rapidly dividing cell populations (i.e., bone marrow, spermatogonia, germinal layers of the skin, gastrointestinal mucosa) with ganciclovir should be done cautiously, in order to avoid additive toxicity. Additive nephrotoxicity may be seen with the combination of pentamidine and other agents that cause nephrotoxicity, including ganciclovir.
Piroxicam: (Minor) Concurrent use of nephrotoxic agents, such as NSAIDs, with ganciclovir should be done cautiously to avoid additive nephrotoxicity. Monitor renal function carefully if concomitant therapy is required.
Polymyxin B: (Minor) Concurrent use of nephrotoxic agents, such as polymyxin b, with ganciclovir should be done cautiously to avoid additive nephrotoxicity.
Probenecid: (Moderate) Ganciclovir should be used with probenecid with caution. Probenecid can inhibit renal tubular secretion of ganciclovir, possibly potentiating ganciclovir toxicity. Patients should be monitored for increased ganciclovir toxicity when taking probenecid with ganciclovir.
Probenecid; Colchicine: (Moderate) Ganciclovir should be used with probenecid with caution. Probenecid can inhibit renal tubular secretion of ganciclovir, possibly potentiating ganciclovir toxicity. Patients should be monitored for increased ganciclovir toxicity when taking probenecid with ganciclovir.
Sulfamethoxazole; Trimethoprim, SMX-TMP, Cotrimoxazole: (Moderate) Use ganciclovir and sulfamethoxazole; trimethoprim together only if the potential benefits outweigh the risks; bone marrow suppression, spermatogenesis inhibition, skin toxicity, and gastrointestinal toxicity may be additive as both drugs inhibit rapidly dividing cells.
Sulindac: (Minor) Concurrent use of nephrotoxic agents, such as NSAIDs, with ganciclovir should be done cautiously to avoid additive nephrotoxicity. Monitor renal function carefully if concomitant therapy is required.
Sumatriptan; Naproxen: (Minor) Concurrent use of nephrotoxic agents, such as NSAIDs, with ganciclovir should be done cautiously to avoid additive nephrotoxicity. Monitor renal function carefully if concomitant therapy is required.
Tacrolimus: (Moderate) Use ganciclovir and tacrolimus together only if the potential benefits outweigh the risks. Monitor renal function when ganciclovir is coadministered with tacrolimus because of the potential increase in serum creatinine. Acute renal failure may occur in patients concomitantly receiving potential nephrotoxic drugs.
Talimogene Laherparepvec: (Major) Consider the risks and benefits of treatment with talimogene laherparepvec before administering acyclovir or other antivirals to prevent or manage herpetic infection. Talimogene laherparepvec is a live, attenuated herpes simplex virus that is sensitive to acyclovir; coadministration with antiviral agents may cause a decrease in efficacy.
Telavancin: (Moderate) Concurrent or sequential use of telavancin with other potentially nephrotoxic drugs such as ganciclovir may lead to additive nephrotoxicity. Closely monitor renal function and adjust telavancin doses based on calculated creatinine clearance.
Tenofovir Alafenamide: (Moderate) Monitor for changes in renal function if tenofovir alafenamide is administered in combination with a nephrotoxic agent, such as ganciclovir. Tenofovir is primarily excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. Coadministration of tenofovir alafenamide with a drug that reduces renal function or competes for active tubular secretion may increase concentrations of tenofovir and other renally eliminated drugs; thus, increasing the risk of developing renal-related adverse reactions.
Tenofovir Disoproxil Fumarate: (Moderate) Concurrent use of nephrotoxic agents with ganciclovir should be done cautiously to avoid additive nephrotoxicity. Other nephrotoxic agents include tenofovir.
Tolmetin: (Minor) Concurrent use of nephrotoxic agents, such as NSAIDs, with ganciclovir should be done cautiously to avoid additive nephrotoxicity. Monitor renal function carefully if concomitant therapy is required.
Trimethoprim: (Moderate) Use ganciclovir and sulfamethoxazole; trimethoprim together only if the potential benefits outweigh the risks; bone marrow suppression, spermatogenesis inhibition, skin toxicity, and gastrointestinal toxicity may be additive as both drugs inhibit rapidly dividing cells.
Valdecoxib: (Minor) Concurrent use of nephrotoxic agents, such as NSAIDs, with ganciclovir should be done cautiously to avoid additive nephrotoxicity. Monitor renal function carefully if concomitant therapy is required.
Vancomycin: (Moderate) Concurrent use of nephrotoxic agents, such as vancomycin, with ganciclovir should be done cautiously to avoid additive nephrotoxicity. Renal function should be monitored closely and vancomycin doses should be adjusted according to vancomycin serum concentrations.
Vinca alkaloids: (Moderate) Use ganciclovir and vinca alkaloids together only if the potential benefits outweigh the risks; bone marrow suppression, spermatogenesis inhibition, skin toxicity, and gastrointestinal toxicity may be additive as both drugs inhibit rapidly dividing cells.
Voclosporin: (Moderate) Concomitant use of voclosporin and ganciclovir may result in additive nephrotoxicity. Monitor for renal toxicity if concomitant use is required.
Zidovudine, ZDV: (Major) Coadministration of ganciclovir and zidovudine may increase the hematologic toxicity (e.g., neutropenia, anemia) of zidovudine. Some patients may not tolerate concomitant therapy with these drugs at full dosage. If concomitant use is necessary, monitor hematologic parameters closely.

Cytovene/Ganciclovir Intravenous Inj Pwd F/Sol: 500mg
Ganciclovir Intravenous Inj Sol: 1mL, 2mg, 50mg
Zirgan Ophthalmic Gel: 0.15%

10 mg/kg/day IV; 5 drops/day ophthalmic gel in each affected eye.

10 mg/kg/day IV; 5 drops/day ophthalmic gel in each affected eye.

Safety and efficacy have not been established for IV dosing; however, 10 mg/kg/day IV has been used off-label for the treatment of CMV infection. 5 drops/day ophthalmic gel in each affected eye.

2 to 12 years: Safety and efficacy have not been established for IV dosing; however, doses up to 15 mg/kg/day IV have been used off-label for the treatment of CMV infection. 5 drops/day ophthalmic gel in each affected eye.
1 year: Safety and efficacy have not been established; however, doses up to 15 mg/kg/day IV have been used off-label for the treatment of CMV infection.

Safety and efficacy have not been established; however, doses up to 15 mg/kg/day IV have been used off-label for the treatment of CMV infection.

Safety and efficacy have not been established; however, doses of 12 mg/kg/day IV have been used off-label for the treatment of congenital CMV disease.

Ganciclovir is a synthetic analog of 2'-deoxyguanosine and inhibits the replication of human cytomegalovirus (CMV). In CMV-infected cells, ganciclovir is initially phosphorylated to ganciclovir monophosphate by the viral protein kinase pUL97. Further phosphorylation by protein kinases produces ganciclovir triphosphate. Ganciclovir triphosphate inhibits viral DNA synthesis by competitive inhibition of viral DNA polymerases and incorporation into viral DNA resulting in eventual termination of viral DNA elongation. Since phosphorylation is dependent upon viral protein kinases, ganciclovir is preferentially metabolized in virus-infected cells. Ganciclovir triphosphate concentrations may be 100-fold greater in CMV-infected cells than in uninfected cells. As sensitivity tests vary due to many factors, the concentration of ganciclovir to inhibit the growth of virus in cell culture by 50% (IC50) ranges from 0.02—3.48 mcg/mL. Ganciclovir inhibits mammalian cell proliferation (CIC50) in vitro at higher concentrations ranging from 30—725 mcg/mL; however, bone marrow cells are more sensitive (CIC50 0.028—0.7 mcg/mL).
 
Resistance to ganciclovir may occur after prolonged treatment with valganciclovir by selection of mutations in either the viral protein kinase (UL97) and/or in the viral polymerase gene (UL54). Virus with mutations in the UL97 gene is resistant to ganciclovir alone, whereas virus with mutations in the UL54 gene may show cross-resistance to other antiviral agents with a similar mechanism of action. The current definition of CMV resistance to ganciclovir in vitro is IC50 >= 1.5 mcg/mL. CMV resistance to ganciclovir has been observed in individuals with AIDS and CMV retinitis who have never received ganciclovir therapy.

Ganciclovir is administered intravenously, by topical ophthalmic administration, and by intravitreal injection. Ganciclovir crosses the blood-brain barrier, producing CSF concentrations that average about 40% (range 24% to 70%) of plasma concentrations. Ganciclovir crosses the placenta. It is not known if ganciclovir is excreted into breast milk. Protein binding is roughly 1% to 2%. Ganciclovir undergoes little or no metabolism. Ganciclovir is excreted primarily in the urine, with about 90% excreted unchanged by glomerular filtration and active tubular secretion.
 
Affected cytochrome P450 isoenzymes: none

Following IV administration of ganciclovir, distribution into body tissues and fluids is extensive including significant intraocular penetration. The half-life in patients with normal renal function is about 3.5 hours following IV administration.

Ophthalmic Route
Minimal systemic exposure is expected with topical ophthalmic administration of ganciclovir gel.

There are no adequate and well-controlled human studies evaluating use of ganciclovir during pregnancy; however, based on data from animal studies, ganciclovir may be teratogenic or embryotoxic at doses recommended for human use. If considering use of ganciclovir in a pregnant female, consider that most maternal CMV infections are subclinical or may be associated with mononucleosis-like syndrome. However, in immunocompromised patients, CMV infections are often symptomatic and associated with significant morbidity and mortality. Also consider that the risk and severity of congenital CMV infection appear to be higher in infants born to mother with primary CMV infection than in those born to mothers with reactivation of the disease. Of the newborns who are infected with CMV, only 10% are symptomatic at birth and the mortality rate among symptomatic infants is about 10%; however, approximately 50% to 90% of the surviving infants may experience significant problems, including sensorineural hearing loss, mental retardation, and other neurologic defects. It is not known if topically administered ophthalmic ganciclovir could result in significant systemic absorption; therefore, the manufacturer recommends the administration of ophthalmic ganciclovir to pregnant women only if the potential benefit to the mother outweighs the potential risk to the fetus.

Ganciclovir is associated with reproductive risk. The drug can be teratogenic if taken by the father near the time of conception (male-mediated teratogenicity) or by the mother during pregnancy. Discuss contraception requirements with the patient. Females should use effective contraception during and for at least 30 days after treatment with ganciclovir. Males must use a condom during and for at least 90 days after treatment. Females of reproductive potential should undergo pregnancy testing prior to initiation of ganciclovir. In addition, based on animal and limited human data, ganciclovir may cause temporary or permanent inhibition of spermatogenesis and subsequent infertility. Animal studies also indicate that suppression of fertility in females may occur.