Ganciclovir

What is Ganciclovir?

• Ganciclovir (Cytovene) is a nucleoside analogue CMV DNA polymerase inhibitor used to prevent or treat cytomegalovirus infections that may occur when the body's immune system is suppressed. In gene therapy, ganciclovir is used with an altered herpes simplex virus-1 gene to kill advanced melanoma cells and brain tumor cells.

Ganciclovir structure

Ganciclovir Structural Formulae

Ganciclovir ball-and-stick

What are the uses of this medicine?

Ganciclovir (Cytovene) is used for:

• the treatment of cytomegalovirus (CMV) retinitis in immunocompromised adult patients, including patients with acquired immunodeficiency syndrome
• the prevention of CMV disease in adult transplant recipients at risk for CMV disease

How does this medicine work?

• Ganciclovir (gan sye' kloe vir) is an acyclic guanosine nucleoside analogue structurally related to acyclovir which has antiviral activity against many herpes viruses, including herpes simplex 1 and 2, Epstein-Barr virus and varicella-zoster, but is used largely in the therapy of cytomegalovirus (CMV) infections.
• Ganciclovir is phosphorylated intracellularly by viral kinases and the resultant triphosphate competes with guanosine for incorporation into viral DNA, blocking viral DNA polymerase activity.
• Because of the requirement for activation by viral kinases, ganciclovir is not active in non-infected cells.
• Ganciclovir is not well absorbed orally and must be given parenterally to achieved adequate levels for maximal antiviral effect.
• Valganciclovir (val" gan sye' kloe vir) is the L-valyl ester prodrug of ganciclovir which is well absorbed orally and rapidly converted to ganciclovir by intracellular hydrolases.
• Ganciclovir and valganciclovir are indicated for therapy and prophylaxis of severe CMV infections.

Who Should Not Use this medicine ?

This medicine cannot be used in patients with:

• a clinically significant hypersensitivity reaction (e.g., anaphylaxis) to ganciclovir, valganciclovir or acyclovir.

What drug interactions can this medicine cause?

• Tell your doctor and pharmacist what other prescription and nonprescription medications, vitamins, nutritional supplements, and herbal products you are taking or plan to take.

Be sure to mention the following:

• anticoagulants ('blood thinners') such as warfarin (Coumadin);cancer chemotherapy medications
• dapsone
• flucytosine (Ancobon)
• heparin
• immunosuppressants such as azathioprine (Azasan, Imuran), cyclosporine (Neoral, Sandimmune), methotrexate (Rheumatrex), sirolimus (Rapamune), and tacrolimus (Prograf)
• interferons (Infergen, Intron A, PEGASYS, PEG-Intron, Roferon-A)
• medications to treat human immunodeficiency virus (HIV) and acquired immunodeficiency syndrome (AIDS) including didanosine (Videx) , zalcitabine (HIVID), or zidovudine (Retrovir, AZT)
• nonsteroidal anti-inflammatory drugs to treat pain and swelling such as aspirin, ibuprofen (Advil, Motrin), naproxen (Aleve, Naprosyn), and others pentamidine (NebuPent, Pentam)
• pyrimethamine (Daraprim, in Fansidar)
• steroids such as dexamethasone (Decadron), prednisone (Deltasone), or others
• trimethoprim/sulfamethoxazole (co-trimoxazole, Bactrim, Septra)
• aminoglycoside antibiotics such as amikacin (Amikin), gentamicin (Garamycin), neomycin (New-Rx, New-Fradin), netilmicin (Netromycin), streptomycin, tobramycin (Nebcin, Tobi), and others
• amphotericin B (Fungizone)
• captopril (Capoten, in Capozide)
• diuretics ('water pills')
• foscarnet (Foscavir)
• gold compounds such as auranofin (Ridaura) or aurothioglucose (Solganal)
• imipenem-cilastatin (Primaxin)
• immune globulin (gamma globulin, BayGam, Carimmune, Gammagard, others)
• methicillin (Staphcillin)
• muromonab-CD3 (OKT3)
• mycophenolate mofetil (CellCept)
• nitrates such as isosorbide dinitrate (Isordil, Sorbitrate) or nitroglycerin products; penicillamine (Cuprimine, Depen)
• primaquine
• probenecid
• rifampin (Rifadin, Rimactane)
• other nucleoside analogues such as acyclovir (Zovirax), famciclovir (Famvir), and ribavirin (Copegus, Rebetol, Virazole, in Rebetron)

Is this medicine FDA approved?

• Ganciclovir was approved for use in the United States in 1994 and is available in a parenteral formulation in generic forms and under the brand name of Cytovene.

How should this medicine be used?

Recommended dosage: Recommended Dosage for Treatment of CMV Retinitis in Adult Patients with Normal Renal Function: Induction Dosage:

• The recommended initial dosage of Ganciclovir Injection for patients with normal renal function is 5 mg/kg (given intravenously at a constant rate over 1 hour) every 12 hours for 14 to 21 days.

Maintenance Dosage:

• Following induction treatment, the recommended maintenance dosage of Ganciclovir Injection is 5 mg/kg (given intravenously at a constant rate over 1 hour) once daily for 7 days per week, or 6 mg/kg once daily for 5 days per week.

Recommended Dosage for Prevention of CMV Disease in Adult Transplant Recipients with Normal Renal Function: Induction Dosage:

• The recommended initial dosage of Ganciclovir Injection for patients with normal renal function is 5 mg/kg (given intravenously at a constant rate over 1 hour) every 12 hours for 7 to 14 days.

Maintenance Dosage:

• Following induction, the recommended maintenance dosage of GANCICLOVIR INJECTIONS is 5 mg/kg (given intravenously at a constant rate over 1 hour) once daily for 7 days per week, or 6 mg/kg once daily for 5 days per week until 100 to 120 days post-transplantation.

Administration:

• Ganciclovir Injection comes as a powder to be mixed with liquid and injected intravenously (into a vein).
• It is usually given every 12 hours.
• You may receive Ganciclovir Injection in a hospital, or you may administer the medication at home.
• If you will be receiving Ganciclovir Injection at home, your healthcare provider will show you how to use the medication.
• Ganciclovir is also available in slow-release formulations for insertion into the vitreous humour of the eye, as treatment for CMV retinitis (associated with HIV infection).
• A topical ophthalmic gel preparation of ganciclovir (Zirgan) was recently approved for the treatment of acute herpes simplex keratitis.

What are the dosage forms and brand names of this medicine?

This medicine is available in fallowing doasage form:

• As Injection: 500 mg ganciclovir in 250 mL (2 mg per mL) solution in a single-dose bag for intravenous use.

This medicine is available in fallowing brand namesː

• Cytovene

What side effects can this medication cause?

The most common side effects of this medicine include:

• fever
• diarrhea
• leukopenia
• anemia
• catheter-related events (including catheter infection and catheter sepsis)
• elevated creatinine levels
• Sepsis
• Anorexia
• Vomiting
• Infection
• Sweating
• Chills
• Neuropathy
• Thrombocytopenia
• Pruritus

Ganciclovir may cause serious side effects which may include:

• unusual tiredness or weakness
• pale skin
• fast or irregular heartbeat
• shortness of breath
• numbness, pain, burning, or tingling in the hands or feet
• vision changes
• decreased urination

What special precautions should I follow?

• Granulocytopenia (neutropenia), anemia, thrombocytopenia, and pancytopenia have been reported with use of ganciclovir. Avoid the use of Ganciclovir Injection if absolute neutrophil count is less than 500 cells/µL, hemoglobin is less than 8 g/dL, or platelet count is less than 25,000 cells/µL. Use with caution in patients with pre-existing cytopenias or in patients receiving myelosuppressive drugs or irradiation. Monitor with frequent complete blood and platelet counts.
• Increased serum creatinine levels have been observed with the use of ganciclovir, particularly in elderly patients and transplant patients receiving concomitant nephrotoxic drugs. Monitor renal function during therapy with Ganciclovir Injection, particularly in elderly patients and in patients taking other nephrotoxic drugs, and reduce dosage in patients with renal impairment.
• Based on animal studies, Ganciclovir Injection may cause temporary or permanent female and male infertility. Advise patients that fertility may be impaired with use of Ganciclovir Injection
• Ganciclovir Injection may cause fetal toxicity when administered to pregnant women based on findings in animal studies. Women of childbearing potential should be advised to use effective contraception during treatment and for at least 30 days following treatment with Ganciclovir Injection. Similarly, men should be advised to practice barrier contraception during and for at least 90 days following treatment with Ganciclovir Injection.
• Based on animal studies, Ganciclovir Injection is potentially mutagenic and carcinogenic.
• Advise patients with CMV retinitis to have frequent ophthalmological examinations while being treated with Ganciclovir Injection to monitor disease status and for other retinal abnormalities. More frequent ophthalmological follow-up may be needed in some cases.
• Advise nursing mothers that breastfeeding is not recommended during treatment with Ganciclovir Injection because of the potential for serious adverse events in nursing infants and because HIV can be passed to the baby in breast milk.
• Ganciclovir is a nucleoside analogue and antiviral agent used in therapy of cytomegalovirus infections. Valganciclovir is the valyl ester prodrug of ganciclovir which can be given orally. When given intravenously, ganciclovir can cause mild, transient and asymptomatic elevations in serum aminotransferase levels, but neither ganciclovir nor valganciclovir have been associated with clinically apparent liver injury.

What to do in case of emergency/overdose?

Symptoms of overdosage may include:

• irreversible pancytopenia, acute renal failure requiring hemodialysis, neutropenia, thrombocytopenia, hepatitis, and seizures

Management of overdosage:

• In case of overdose, call the poison control helpline of your country. In the United States, call 1-800-222-1222.

• Overdose related information is also available online at poisonhelp.org/help.
• In the event that the victim has collapsed, had a seizure, has trouble breathing, or can't be awakened, immediately call emergency services. In the United States, call 911.
• Since ganciclovir is dialyzable, dialysis may be useful in reducing serum concentrations.
• Adequate hydration should be maintained.
• The use of hematopoietic growth factors should be considered in patients with cytopenias.

Can this medicine be used in pregnancy?

• Based on findings in animal studies, Ganciclovir Injection may cause fetal toxicity.
• Females of reproductive potential should use effective contraception during treatment and for at least 30 days following treatment with Ganciclovir Injection.
• Males should practice barrier contraception during treatment and for at least 90 days following treatment with Ganciclovir Injection.

Can this medicine be used in children?

• Safety and efficacy of Ganciclovir Injection have not been established in pediatric patients.

What are the active and inactive ingredients in this medicine?

Active ingredient:

• GANCICLOVIR

Inactive ingredients:

• SODIUM CHLORIDE
• SODIUM HYDROXIDE
• HYDROCHLORIC ACID

Who manufactures and distributes this medicine?

Manufactured and distributed by:

• Exela Pharma Sciences
• Lenoir, NC

What should I know about storage and disposal of this medication?

• Store at 20°C to 25°C (68°F to 77°F); excursions permitted to 15° to 30°C (59° to 86°F).

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Drugs for Herpes Virus

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• Dailymed label info on Ganciclovir
• FDA Ganciclovir