Ganciclovir

>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

Blood and lymphatic disorders: Hemolytic anemia, agranulocytosis, granulocytopenia

Cardiac disorders: Cardiac arrest, conduction disorder, torsade de pointes, ventricular tachycardia

Congenital, familial and genetic disorders: Congenital anomaly

Endocrine disorders: Inappropriate antidiuretic hormone secretion

Eye disorders: Cataracts, dry eyes

Gastrointestinal disorders: Intestinal ulcer

Hepatobiliary disorders: Cholelithiasis, cholestasis, hepatic failure, hepatitis

Immune system disorders: Anaphylactic reaction, allergic reaction, vasculitis

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

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.

Take ganciclovir exactly as directed by your doctor. If you do not understand these directions, ask your pharmacist, nurse, or doctor to explain them to you.

Take each oral dose with a full glass of water.

Take each oral dose with food to increase the absorption of the drug in your body.

Your healthcare provider will administer injectable ganciclovir as an intravenous (into a vein) infusion.

If you are injecting ganciclovir at home, your healthcare provider will give you detailed instructions on how and where to inject the medication. If you do not understand these directions, do not attempt to inject the medication. Contact your healthcare provider for further instructions.

Do not use any ganciclovir that is discolored, has particles in it, or looks different from your previous doses. Throw away any unused ganciclovir after the amount of time determined by your pharmacist or doctor.

Take all of the ganciclovir that has been prescribed for you even if you begin to feel better. Your symptoms may start to improve before the infection is completely treated.

Your doctor may want you to have blood tests, eye exams, or other evaluations during treatment with ganciclovir to monitor progress and side effects.

Store oral ganciclovir at room temperature away from moisture and heat.

Dispose of used needles and syringes in a puncture resistant container out of the reach of children.

Your healthcare provider will store injectable ganciclovir as directed by the manufacturer or give you detailed storage instructions if you are storing the medication at home.

Seek emergency medical attention if an overdose is suspected.

Symptoms of a ganciclovir overdose include seizures, diarrhea, kidney damage (decreased urine production), liver damage (yellowing of the skin or eyes, abdominal pain), and bone marrow damage (paleness, increased chance of infection, fever and chills).

If a dose of oral ganciclovir is missed, take the missed dose as soon as you remember. If it is almost time for the next dose, skip that dose and take only your next regularly scheduled dose. Do not take a double dose of this medication.

Contact your healthcare provider if you miss a dose of injectable ganciclovir.

Included as part of the PRECAUTIONS section.

The Vitrasert (ganciclovir) Implant is indicated for the treatment of CMV retinitis in patients with acquired immunodeficiency syndrome (AIDS).

The diagnosis of CMV retinitis is ophthalmologic and should be made by indirect ophthalmoscopy. Other conditions in the differential diagnosis of CMV retinitis include candidiasis, toxoplasmosis, histoplasmosis, retinal scars, and cotton wool spots, any of which may produce a retinal appearance similar to CMV. For this reason, it is essential that the diagnosis of CMV be established by a physician familiar with the retinal presentation of these conditions. The Vitrasert (ganciclovir) Implant is for intravitreal implantation only.

Clinical Trials

In a randomized, controlled parallel group trial conducted between May 1993 and December 1994, treatment with the Vitrasert (ganciclovir) Implant was compared to treatment with intravenous ganciclovir (Cytovene-IV; Roche) in 188 patients with AIDS and newly diagnosed CMV retinitis. Patients randomized to the Cytovene-IV treatment group received Cytovene-IV solution at induction doses (5 mg/kg twice daily) for 14 days, followed by maintenance dosing (5 mg/kg once daily). Based on masked assessment of fundus photographs, the median time to progression was approximately 210 days for the Vitrasert (ganciclovir) Implant treatment group compared to approximately 120 days for the intravenous ganciclovir treatment group.

Ganciclovir is a prescription medication used to treat cytomegalovirus (CMV) retinitis (eye infection that can cause blindness). It is also used to prevent cytomegalovirus (CMV) disease.

Ganciclovir is a prescription medication used in patients whose immune system is not working properly such as patients who have acquired immunodeficiency syndrome (AIDS) or who have received an organ transplant.

This medication may be prescribed for other uses. Ask your doctor or pharmacist for more information.

During clinical trials, the most frequent adverse events seen in patients treated with the Vitrasert (ganciclovir) Implant involved the eye.

During the first two months following implantation, visual acuity loss of 3 lines or more, vitreous hemorrhage, and retinal detachments occurred in approximately 10-20% of patients. Cataract formation/lens opacities, macular abnormalities, intraocular pressure spikes, optic disk/nerve changes, hyphemas and uveitis occurred in approximately 1-5%.

Adverse events with an incidence of less than 1% were: retinopathy, anterior chamber cell and flare, synechia, hemorrhage (other than vitreous), cotton wool spots, keratopathy, astigmatism, endophthalmitis, microangiopathy, sclerosis, choroiditis, chemosis, phthisis bulbi, angle closure glaucoma with anterior chamber shallowing, vitreous detachment, vitreous traction, hypotony, severe post-operative inflammation, retinal tear, retinal hole, corneal dellen, choroidal folds, pellet extrusion from scleral wound, and gliosis.

Read the entire FDA prescribing information for Vitrasert (Ganciclovir)

Administration

Ophthalmic Administration

Apply 0.15% ophthalmic gel topically to the eye.1

To avoid contaminating the ophthalmic gel, do not allow tip of dispensing dropper to touch any surface.1

Dosage

Pediatric Patients

Children ≥2 years of age with dendritic ulcers: Instill 1 drop of 0.15% ophthalmic gel into affected eye 5 times daily (approximately every 3 hours while awake) until corneal ulcer heals.1 Then, instill 1 drop 3 times daily for 7 additional days.1

Children ≥2 years of age with geographic ulcers†: Some experts state use same dosage recommended for dendritic ulcers.7

Adults

Dendritic ulcers: Instill 1 drop of 0.15% ophthalmic gel into affected eye 5 times daily (approximately every 3 hours while awake) until corneal ulcer heals.1 Then, instill 1 drop 3 times daily for 7 additional days.1

Geographic ulcers†: Some experts state use same dosage recommended for dendritic ulcers.7

Special Populations

No special population dosage recommendations.1

Carcinogenesis, Mutagenesis, Impairment of Fertility

Carcinogenesis, Mutagenesis
Ganciclovir was carcinogenic in mice at the same mean drug exposure in humans as at the RHD (5 mg/kg). At the dose of 1000 mg/kg/day (1.4 times the exposure at the RHD) there was a significant increase in the incidence of tumors of the preputial gland in males, forestomach (nonglandular mucosa) in males and females, and reproductive tissues (ovaries, uterus, mammary gland, clitoral gland and vagina) and liver in females. At the dose of 20 mg/kg/day (0.1 times the exposure at the RHD), a slightly increased incidence of tumors was noted in the preputial and harderian glands in males, forestomach in males and females, and liver in females. No carcinogenic effect was observed in mice administered Ganciclovir at 1 mg/kg/day (exposure estimated as 0.01 times the RHD).  Except for histiocytic sarcoma of the liver, Ganciclovir-induced tumors were generally of epithelial or vascular origin. Although the preputial and clitoral glands, forestomach and harderian glands of mice do not have human counterparts, Ganciclovir should be considered a potential carcinogen in humans.

Ganciclovir increased mutations in mouse lymphoma cells and DNA damage in human lymphocytes in vitro at concentrations of 50 to 500 and 250 to 2000 μg/mL, respectively. In the mouse micronucleus assay, Ganciclovir was clastogenic at doses of 150 and 500 mg/kg (2.8 to 10 times the exposure at the RHD) but not at doses of 50 mg/kg (exposure approximately comparable to the RHD). Ganciclovir was not mutagenic in the Ames Salmonella assay at concentrations of 500 to 5000 μg/mL.

Impairment of Fertility
Ganciclovir caused decreased mating behavior, decreased fertility, and an increased incidence of embryolethality in female mice following doses of 90 mg/kg/day (exposures approximately 1.7 times the RHD). Ganciclovir caused decreased fertility in male mice and hypospermatogenesis in mice and dogs following daily oral or intravenous administration of doses ranging from 0.2 to 10 mg/kg. Systemic drug exposure (AUC) at the lowest dose showing toxicity in each species ranged from 0.03 to 0.1 times the exposure at the RHD.

Ganciclovir INJECTION is supplied as a sterile, unpreserved, colorless solution in a single-dose polymeric bag containing 500 mg Ganciclovir in 250 mL of solution (2 mg/mL) sealed with a Twist Off port from Technoflex, and oversealed in an aluminum pouch (NDC 51754-2500-1). Follow guidelines for handling and disposal for cytotoxic drugs.1

The premix flexible plastic container bag contains no preservative; any unused portion should be discarded [see Dosage and Administration (2.6)].  

Gently shaking should redissolve any crystals that may have formed during transportation and/or storage at temperatures lower than recommended. The solution must be clear at the time of use.

Storage

Store at 20°C to 25°C (68°F to 77°F); excursions permitted to 15° to 30°C (59° to 86°F) [see USP Controlled Room Temperature].

Applies to ganciclovir ophthalmic: intraocular implant, ophthalmic gel

General

The following side effects are for the ophthalmic gel only; if available, the manufacturer product information for the intraocular implant should be consulted for additional information.

Ocular

Very common (10% or more): Blurred vision (60%), eye irritation (20%), transient burning/stinging sensations
Common (1% to 10%): Punctate keratitis, conjunctival hyperemia[Ref]

Some side effects of ganciclovir ophthalmic may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA.

2 years or older: Instill 1 drop in the affected eye 5 times a day (about every 3 hours while awake) until corneal ulcer heals, and then 1 drop 3 times a day for 7 days.

Use: For the treatment of acute herpetic keratitis (dendritic ulcers)