Cymevene

/ Tzamal

CAUTION: DO NOT ADMINISTER CYMEVENE-IV SOLUTION BY RAPID OR BOLUS INTRAVENOUS INJECTION. THE TOXICITY OF CYMEVENE-IV MAY BE INCREASED AS A RESULT OF EXCESSIVE PLASMA LEVELS.
CAUTION: INTRAMUSCULAR OR SUBCUTANEOUS INJECTION OF
RECONSTITUTED CYMEVENE-IV SOLUTION MAY RESULT IN SEVERE TISSUE
IRRITATION DUE TO HIGH pH (11).
THE RECOMMENDED DOSE FOR CYMEVENE-IV SOLUTION SHOULD NOT BE
EXCEEDED. THE RECOMMENDED INFUSION RATE FOR CYMEVENE-IV SOLUTION SHOULD NOT BE EXCEEDED.
For Treatment of CMV Retinitis in Patients With Normal Renal Function
Induction Treatment: The recommended initial dosage 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 Treatment: Following induction treatment, the recommended maintenance dosage of CYMEVENE-IV solution is 5 mg/kg given as a constant-rate intravenous infusion over 1 hour once daily, 7 days per week, or 6 mg/kg once daily, 5 days per week. For patients who experience progression of CMV retinitis while receiving maintenance treatment with CYMEVENE-IV, reinduction treatment is recommended.
For the Prevention of CMV Disease in Transplant Recipients With Normal Renal Function
The recommended initial dosage of CYMEVENE-IV solution 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, followed by 5 mg/kg once daily, 7 days per week or 6 mg/kg once daily, 5 days per week.
The duration of treatment with CYMEVENE-IV solution in transplant recipients is
dependent upon the duration and degree of immunosuppression. In controlled clinical trials in bone marrow allograft recipients, treatment with CYMEVENE-IV was continued until day 100 to 120 posttransplantation. CMV disease occurred in several patients who discontinued treatment with CYMEVENE-IV solution prematurely. In heart allograft recipients, the onset of newly diagnosed CMV disease occurred after treatment with CYMEVENE-IV was stopped at day 28 posttransplant, suggesting that continued dosing may be necessary to prevent late occurrence of CMV disease in this patient population.
Renal Impairment: For patients with impairment of renal function, refer to prescribing information.
See prescribing information for full details.

For the prevention of CMV disease in solid organ transplant recipients and in individuals with advanced HIV infection at risk for developing CMV disease. Also indicated as an alternative to the intravenous formulation for maintenance treatment of CMV retinitis in immunocompromised patients, including patients with AIDS, in whom retinitis is stable following appropriate induction therapy and for whom the risk of more rapid progression is balanced by the benefit associated with avoiding daily I.V. infusions.

Patients with hypersensitivity to ganciclovir or acyclovir.

Warning: The clinical toxicity of Cymevene-IV includes granulocytopenia, anemia and thrombocytopenia.  In animal studies ganciclovir was carcinogenic, teratogenic and caused aspermatogenesis.
Hematologic: CYMEVENE-IV should not be administered if the absolute neutrophil count is less than 500 cells/µL or the platelet count is less than 25,000 cells/µL. Granulocytopenia (neutropenia), anemia and thrombocytopenia have been observed in patients treated with CYMEVENE-IV. The frequency and severity of these events vary widely in different patient populations.
CYMEVENE-IV should, therefore, be used with caution in patients with pre-existing cytopenias or with a history of cytopenic reactions to other drugs, chemicals or irradiation.
Granulocytopenia usually occurs during the first or second week of treatment but may occur at any time during treatment. Cell counts usually begin to recover within 3 to 7 days of discontinuing drug. Colony-stimulating factors have been shown to increase neutrophil and white blood cell counts in patients receiving CYMEVENE-IV solution for treatment of CMV retinitis.
Impairment of Fertility: Animal data indicate that administration of ganciclovir causes inhibition of spermatogenesis and subsequent infertility. These effects were reversible at lower doses and irreversible at higher doses. Although data in humans have not been obtained regarding this effect, it is considered probable that ganciclovir at the recommended doses causes temporary or permanent inhibition of spermatogenesis. Animal data also indicate that suppression of fertility in females may occur.
Teratogenesis: Because of the mutagenic and teratogenic potential of ganciclovir, women of childbearing potential should be advised to use effective contraception during treatment. Similarly, men should be advised to practice barrier contraception during and for at least 90 days following treatment with CYMEVENE-IV.
See prescribing information for full details.

Fever, infection, chills, sepsis, diarrhea, anorexia, vomiting, leukopenia, anemia, thrombocytopenia, neuropathy, sweating, pruritus.
See prescribing information for full details.

Didanosine: Ganciclovir pharmacokinetics were not affected by didanosine. In neither study were there significant changes in the renal clearance of either drug.
Zidovudine: Since both zidovudine and ganciclovir have the potential to cause neutropenia and anemia, some patients may not tolerate concomitant therapy with these drugs at full dosage.
Probenecid: No drugdrug interaction studies have been conducted with IV ganciclovir and probenecid.
Imipenem-cilastatin: Generalized seizures have been reported in patients who received ganciclovir and imipenem-cilastatin. These drugs should not be used concomitantly unless the potential benefits outweigh the risks.
Other Medications: It is possible that drugs that inhibit replication of rapidly dividing cell populations such as bone marrow, spermatogonia and germinal layers of skin and gastrointestinal mucosa may have additive toxicity when administered concomitantly with ganciclovir. Therefore, drugs such as dapsone, pentamidine, flucytosine, vincristine, vinblastine, adriamycin, amphotericin B, trimethoprim/sulfamethoxazole combinations or other nucleoside analogues, should be considered for concomitant use with ganciclovir only if the potential benefits are judged to outweigh the risks.
See prescribing information for full details.

Pregnancy: Category C. Ganciclovir may be teratogenic or embryotoxic at dose levels recommended for human use. There are no adequate and well-controlled studies in pregnant women. CYMEVENEIV should be used during pregnancy only if the potential benefits justify the potential risk to the fetus.
Lactation: Mothers should be instructed to discontinue nursing if they are receiving CYMEVENE-IV. The minimum interval before nursing can safely be resumed after the last dose of CYMEVENE-IV is unknown.
See prescribing information for full details.

Overdosage with CYMEVENE-IV has been reported in 17 patients (13 adults and 4 children under 2 years of age). Five patients experienced no adverse events following overdosage at the following doses: 7 doses of 11 mg/kg over a 3-day period (adult), single dose of 3500 mg (adult), single dose of 500 mg (72.5 mg/kg) followed by 48 hours of peritoneal dialysis (4-month-old), single dose of approximately 60 mg/kg followed by exchange transfusion (18-month-old), 2 doses of 500 mg instead of 31 mg (21-month-old).
Irreversible pancytopenia developed in 1 adult with AIDS and CMV colitis after receiving 3000 mg of CYMEVENE-IV solution on each of 2 consecutive days. He experienced worsening GI symptoms and acute renal failure that required short-term dialysis.
Pancytopenia developed and persisted until his death from a malignancy several months later. Other adverse events reported following overdosage included: persistent bone marrow suppression (1 adult with neutropenia and thrombocytopenia after a single dose of 6000 mg), reversible neutropenia or granulocytopenia (4 adults, overdoses ranging from 8 mg/kg daily for 4 days to a single dose of 25 mg/kg), hepatitis (1 adult receiving 10 mg/kg daily, and one 2 kg infant after a single 40 mg dose), renal toxicity (1 adult with transient worsening of hematuria after a single 500 mg dose, and 1 adult with elevated creatinine (5.2 mg/dL) after a single 5000 to 7000 mg dose), and seizure (1 adult with known seizure disorder after 3 days of 9 mg/kg). In addition, 1 adult received 0.4 mL (instead of 0.1 mL) CYMEVENE-IV solution by intravitreal injection, and experienced temporary loss of vision and central retinal artery occlusion secondary to increased intraocular pressure related to the injected fluid volume.
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.