Cytovene

Distribution: widely, to all tissues including CSF & ocular tissue

Vd: 15.26 L/1.73 sq.meter

Protein Bound: 1-2%

Bioavailability: oral: fasting: 5%; following food: 6-9%; following fatty meal: 28-31%

Half-life, elimination: 1.7-5.8 hr; prolonged with renal impairment; end-stage renal disease: 5-28 hr

Excretion: urine (80-99% as unchanged drug)

Mechanism of Action

Inhibits of viral DNA polymerases resulting in chain termination

There are no restrictions on food, beverages, or activity during treatment with ganciclovir unless otherwise directed by your doctor.

Before taking ganciclovir, tell your doctor if you are taking any of the following drugs:

• zidovudine (Retrovir, AZT);
• didanosine (Videx);
• probenecid (Benemid); or
• imipenem-cilastatin (Primaxin).

You may not be able to take ganciclovir, or you may require a dosage adjustment or special monitoring if you are taking any of the medicines listed above.

Drugs other than those listed here may also interact with ganciclovir. Talk to your doctor and pharmacist before taking any prescription or over-the-counter medicines, including herbal products.

Serious side effects have been reported with ganciclovir. See the “Ganciclovir Precautions” section.

Capsules and Injection:

Common side effects of ganciclovir include the following:

• change in blood counts
• fever
• infection
• chills
• diarrhea
• loss of appetite
• vomiting
• neuropathy (weakness, numbness and pain, usually in your hands and feet)
• sweating
• itching
• retinal detachment (separation)

Ophthalmic Gel:

• blurred vision
• eye irritation
• watery eyes
• eyes sensitive to light
• red eye
• change in vision

This is not a complete list of ganciclovir side effects. Ask your doctor or pharmacist for more information.

Tell your doctor if you have any side effect that bothers you or that does not go away.

Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

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.

Antiviral; purine nucleoside analog of guanine.1 2 3 8 9 10 11 12

Cytomegalovirus (CMV) Infections

Treatment of CMV retinitis in immunocompromised patients, including HIV-infected patients.1 5 11 21 28 100 103 104 105 117 118 126 127 139 164 174 175 187 207 225 243 268 ganciclovir is not curative; stabilization or improvement of ocular manifestations may occur, but progression of retinitis is possible during or following treatment.1 4 5 8 9 11 13 21 27 28 63 65 77 94 100 120 126 128 139 167 168

Drugs of choice for initial induction and maintenance therapy of CMV retinitis are IV ganciclovir, IV foscarnet, IV cidofovir, oral valganciclovir, or intravitreal fomivirsen.268 319 322 331 A regimen of both ganciclovir and foscarnet is used for treatment of CMV retinitis in patients who have relapsed following monotherapy with either drug.268 319 322 331

Primary prevention (primary prophylaxis) of CMV disease in HIV-infected patients at risk for the disease, including adults, adolescents, and children who are positive for CMV antibody and have CD4+ T-cell counts <50/mm3.317 320 321 322 USPHS/IDSA recommends oral ganciclovir as the drug of choice for primary CMV prophylaxis in these patients.317

Long-term suppressive or maintenance therapy (secondary prophylaxis) of recurrent CMV disease in HIV-infected adults, adolescents, or children.317 USPHS/IDSA recommends IV ganciclovir or IV foscarnet as drugs of choice for such prophylaxis.317

Prevention of CMV disease in solid organ transplant recipients and bone marrow transplant (BMT) recipients at risk for the disease.1 268 271 283 284 286 287 304 305 307 313 324

Has been used in immunocompromised patients for parenteral treatment of extraocular CMV infections, including GI infections†,3 4 5 6 8 11 16 20 21 26 68 69 70 76 77 92 102 108 110 122 134 146 166 193 194 207 pneumonitis†,3 4 5 8 10 11 15 16 17 18 19 20 21 33 43 64 72 73 74 106 107 108 109 110 111 121 122 137 140 145 146 147 149 151 154 159 180 188 193 198 199 200 201 202 207 219 220 225 nervous system†,4 5 8 11 21 110 165 207 231 hepatobiliary†,4 5 8 20 21 68 106 108 146 166 219 or cardiac†110 171 220 CMV infections.3 5 8 15 19 108 140 Safety and efficacy have not been established for extraocular CMV infections;1 2 use in these infections should be limited to severe and/or potentially life-threatening infections when potential benefits outweigh risks.3 6 15 16 72 106 107 110 134 146 219 262

Safety and efficacy not established for treatment of congenital or neonatal CMV disease or for treatment of CMV infections in immunocompetent patients.1

General

• Frequent monitoring of neutrophil and platelet counts is necessary during ganciclovir induction and maintenance therapy.1 2 20 191

• Dosage adjustment and/or interruption of ganciclovir therapy may be necessary if hematologic abnormalities occur.1 2

• Ganciclovir should be withheld if the ANC declines to <500/mm3 or the platelet count declines to <25,000/mm3 and should not be resumed until there is evidence of bone marrow recovery.1 2

Administration

Administer orally or by slow IV infusion.1 2

Do not administer by rapid IV infusion or direct IV injection since potentially toxic plasma ganciclovir concentrations may result.1 2 In addition, do not administer by IM or sub-Q injection.1 2

Can be administered via a commercially available intravitreal implant for treatment of CMV retinitis.323 340 Although ganciclovir has been administered by intravitreal injection† for the treatment of ocular infections,4 5 8 67 84 117 129 135 170 209 safety and efficacy of intravitreal injection of solutions made from the powder for IV infusion have not been established.4 5 8 67 170

Oral Administration

Administer orally with food.1

Oral ganciclovir should be used only for prevention of CMV disease in HIV-infected patients or transplant recipients at risk for the disease or for maintenance treatment of CMV retinitis in patients in whom the disease is stable following initial IV induction therapy.1

IV Infusion

For solution and drug compatibility information see Compatibility under Stability.

Handle the powder and reconstituted and diluted solutions cautiously because of the high pH of the solutions and because of the mutagenic and/or carcinogenic potential of the drug.1 2 Use protective equipment (e.g., latex gloves, protective eyewear).1 2

Since ganciclovir shares some of the properties of cytotoxic drugs, consider consulting specialized references for procedures for proper handling and disposal of antineoplastics, although there is no general agreement that all of the procedures recommended in such guidelines are necessary or appropriate.1 2

Because of the high pH of ganciclovir solutions, a vein with adequate blood flow should be used to allow for rapid dilution and distribution of the drug, which may minimize risk of phlebitis.1 2

For intermittent IV infusion, reconstitute 500-mg vial by adding 10 mL of sterile water for injection to provide a solution containing 50 mg/mL.1 2 Bacteriostatic water for injection containing parabens should not be used.1 2 Shake vial well to ensure complete dissolution of the drug.1 2

The appropriate dose of reconstituted solution should then be withdrawn from the vial and diluted in 50–250 (usually 100) mL of a compatible IV infusion solution.1 2 8 For use in fluid-restricted patients, the appropriate dose of reconstituted solution may be diluted to a concentration ≤10 mg/mL; use of more concentrated solutions is not recommended.1 2 8 191

Administer by slow IV infusion over 1 hour, either via a large peripheral or central vein,4 190 at a constant rate of administration.1 2

For highly concentrated solutions (e.g., 5–10 mg/mL), a controlled-infusion device (e.g., pump) is recommended.8 262

Dosage

Available as ganciclovir and ganciclovir sodium; dosage expressed in terms of ganciclovir.1 2

Because the risk of toxicity may be increased with higher doses and/or more rapid infusion,1 2 recommended doses, frequencies of administration, and rate of IV infusion should not be exceeded.1 2

Pediatric Patients

Maintenance therapy in children >3 months of age†: after an initial IV induction regimen, 1 g 3 times daily.1 191 Alternatively, 500 mg 6 times daily (every 3 hours while awake).1 191

Initial induction therapy in children >3 months of age†: 5 mg/kg every 12 hours for 14–21 days.1 191

Maintenance treatment in children >3 months of age†: 5 mg/kg once daily.1 2 5 20 191 216 268 Alternatively, 6 mg/kg once daily 5 days weekly.1 2 71 106 191 262 268

Infants and children†: 30 mg/kg 3 times daily.317

Adolescents: 1 g 3 times daily.317

1 g 3 times daily.317 Initiate secondary prophylaxis after initial induction treatment.317

Infants and children†: 5 mg/kg daily.317

Adolescents: 5–6 mg/kg once daily 5–7 days each week.317

Consideration can be given to discontinuing secondary CMV prophylaxis in adolescents with sustained (e.g., for ≥6 months) increase in CD4+ T-cell counts to >100–150/mm3 in response to potent antiretroviral therapy.317 This decision should be made in consultation with an ophthalmologist and factors such as the magnitude and duration of CD4+ T-cell increase, anatomic location of the retinal lesion, vision in the contralateral eye, and feasibility of regular ophthalmic monitoring should be considered.317 Relapse of CMV retinitis could occur following discontinuance of secondary prophylaxis, especially in those whose CD4+ T-cell count decreases to <50/mm3; relapse has been reported rarely in those with CD4+ T-cell counts >100/mm3.317

Reinitiate secondary CMV prophylaxis if CD4+ T-cell count decreases to <100–150/mm3.317

Adults

Maintenance therapy after an initial IV induction regimen: 1 g 3 times daily.1 Alternatively, 500 mg 6 times daily (every 3 hours while awake).1

Initial induction therapy: 5 mg/kg every 12 hours for 14–21 days.1 191

Maintenance therapy: 5 mg/kg once daily.1 2 5 20 191 216 268 Alternatively, 6 mg/kg once daily 5 days weekly.1 2 71 106 191 262 268

1 g 3 times daily.1 317

1 g 3 times daily.317 Initiate secondary prophylaxis after initial induction treatment.317

5–6 mg/kg once daily 5–7 days each week.317

Consideration can be given to discontinuing secondary CMV prophylaxis in adults with sustained (e.g., for ≥6 months) increase in CD4+ T-cell counts to >100–150/mm3 in response to potent antiretroviral therapy.317 This decision should be made in consultation with an ophthalmologist and factors such as the magnitude and duration of CD4+ T-cell increase, anatomic location of the retinal lesion, vision in the contralateral eye, and feasibility of regular ophthalmic monitoring should be considered.317 Relapse of CMV retinitis could occur following discontinuance of secondary prophylaxis, especially in those whose CD4+ T-cell count decreases to <50/mm3; relapse has been reported rarely in those with CD4+ T-cell counts >100/mm3.317

Reinitiate secondary CMV prophylaxis if CD4+ T-cell count decreases to <100–150/mm3.317

1 g 3 times daily.1

Initially, 5 mg/kg every 12 hours for 7–14 days, then 5 mg/kg once daily 7 days per week or 6 mg/kg once daily 5 days per week.1

Duration of ganciclovir maintenance in organ transplant recipients depends on several factors including the duration and degree of immunosuppression.1 283 302 303 Bone marrow allograft recipients have received IV ganciclovir for up to 100–120 days following transplantation.1 271 284 In cardiac allograft recipients, ganciclovir should be continued for >28 days in patients to prevent late development of CMV disease.1 283 Liver transplant recipients have received oral ganciclovir for up to 98 days following transplantation.1 325

Special Populations

Renal Impairment

In patients with impaired renal function, doses and/or frequency of administration of oral or IV ganciclovir must be modified in response to the degree of impairment.1 2 5 6 9 11 28 33 191 346 Dosage should be based on the patient’s measured or estimated Clcr.1 2

Geriatric Patients

Select dosage with caution because of age-related decreases in renal function.1 2 (See Renal Impairment under Dosage and Administration.)

Nephrotoxic Drugs

Possible increased risk of adverse effects; use concomitantly with caution and closely monitor renal function.1

Specific Drugs

Ganciclovir is an antiviral. It is used to treat infections caused by viruses.

Ganciclovir is used to treat the symptoms of cytomegalovirus (CMV) infection of the eyes in people whose immune system is not working fully. This includes patients with acquired immune deficiency syndrome (AIDS). Ganciclovir will not cure this eye infection, but it may help to keep the symptoms from becoming worse. It is also used to help prevent CMV infection in patients who receive organ or bone marrow transplants, as well as in patients with advanced human immunodeficiency virus (HIV) infection. Ganciclovir may be used for other serious CMV infections as determined by your doctor. However, it does not work in treating certain viruses, such as the common cold or the flu.

This medicine may cause some serious side effects, including anemia and other blood problems. Before you begin treatment with ganciclovir, you and your doctor should talk about the good this medicine will do as well as the risks of using it.

Ganciclovir is to be administered only by or under the supervision of your doctor.

If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.