Cymevene 500mg Freeze dried powder

CYMEVENE is indicated for the treatment of cytomegalovirus disease (CMV) in immuno-compromised patients u2265 12 years of age.

CYMEVENE is indicated for the prevention of CMV disease using pre-emptive therapy in patients with medicine-induced immunosuppression following organ transplantation or cancer chemotherapy in patients u2265 12 years of age.

CYMEVENE is also indicated for the prevention of CMV disease using universal prophylaxis in patients with medicine-induced immunosuppression following organ transplantation or cancer chemotherapy in patients u2265 12 years of age.

Because of individual patient variations in the clinical response to CMV infections and the sensitivity to the myelosuppressive effects of CYMEVENE, the treatment of each patient should be considered individually. Changes in dose should be based on frequent clinical and haematological assessment. Due to the myelosuppressive nature of CYMEVENE, it is recommended that white blood cell counts be performed every two days for the first fourteen days of CYMEVENE administration.

Table 3 Dose and duration of therapy

Indication Dose and duration of therapy

Treatment of CMV disease

Patients u2265 12 years with normal renal function* Induction treatment: 5 mg/kg every 12 hours for 14 - 21 days. Maintenance treatment: For immunocompromised patients at risk of relapse maintenance therapy may be given. 5 mg/kg once daily on 7 days per week or 6 mg/kg once daily on 5 days per week. The duration of maintenance treatment should be determined on an individual basis.

Treatment of disease progression: Any patient, in whom CMV disease progresses, either while on maintenance treatment or because treatment with CYMEVENE has been withdrawn, may be re-treated using the induction treatment regimen.

Prevention of CMV disease using pre-emptive therapy

Patients u2265 12 years with normal renal function* Induction treatment: 5 mg/kg every 12 hours for 7 u2013 14 days. Maintenance treatment: 5 mg/kg once daily on 7 days per week or 6 mg/kg once daily on 5 days per week. The duration of maintenance treatment is based on the risk of CMV disease and should be determined on an individual basis.

Prevention of CMV disease using universal prophylaxis

Patients >16 years of age with normal renal function* 5 mg/kg once daily on 7 days per week or 6 mg/kg once daily on 5 days per week. The duration of universal prophylaxis is based on the risk of CMV disease and should be determined on an individual basis.

Prevention of CMV disease using universal prophylaxis

Patients > 12 years of age See Special Dosage Instructions

* For dosing in patients with renal impairment refer to Special Dosage Instructions

• Pregnancy and lactation.
• Patients with known hypersensitivity to ganciclovir, valganciclovir or to any of the excipients.
• Absolute neutrophil count less than 500 cells/u03bcuf06c, and/or a platelet count less than 25 000 cells/u03bcuf06c, and/or haemoglobin less than 8 g/duf06c. (see WARNINGS AND SPECIAL PRECAUTIONS, Special dosage instructions).
• CYMEVENE is not indicated for the treatment of congenital or neonatal CMV infections.
• Treatment with myelosuppressive medicines.

• Cross hypersensitivity: Due to the similarity of the chemical structure of ganciclovir and that of aciclovir and penciclovir, a cross-hypersensitivity reaction between these medicines is possible. Caution should therefore be used when prescribing CYMEVENE to patients with known hypersensitivity to aciclovir or penciclovir, (or to their prodrugs, valaciclovir or famciclovir respectively).
• Myelosuppression: CYMEVENE should be used with caution in patients with pre-existing haematological cytopenia or a history of drug-related haematological cytopenia and in patients receiving radiotherapy.
• Severe leukopenia, neutropenia, anaemia, thrombocytopenia, pancytopenia, bone marrow failure and aplastic anaemia have been observed in patients treated with CYMEVENE. Therapy should not be initiated or continued if the absolute neutrophil count is less than 500 cells/u03bcuf06c, and/or the platelet count is less than 25 000 cells/u03bcuf06c, and/or the haemoglobin is less than 8 g/duf06c (see CONTRAINDICATIONS and SIDE-EFFECTS).
• Mutagenicity, carcinogenicity teratogenicity, fertility and contraception: In animal studies ganciclovir was found to be mutagenic, teratogenic, carcinogenic and to impair fertility. CYMEVENE should therefore be considered a potential teratogen and carcinogen in humans with the potential to cause birth defects and cancers. Temporary and permanent inhibition of spermatogenesis in male animals and permanent suppression of fertility in female animals have occurred. Because of the teratogenicity observed in animals, women of childbearing potential should use effective contraception during treatment. Men should be advised to practice barrier contraception during treatment and for 90 days following treatment. Based on clinical and non-clinical studies, CYMEVENE may cause temporary or permanent inhibition of spermatogenesis (see PREGNANCY AND LACTATION and SIDE-EFFECTS).
• It is recommended that complete blood counts and platelet counts be frequently monitored in all patients during therapy, particularly in patients with renal impairment. In patients with severe leukopenia, neutropenia, anaemia and/or thrombocytopenia, treatment with haematopoietic growth factors and/or dose interruption of therapy is recommended (see CONTRAINDICATIONS and SIDE-EFFECTS). In patients with impaired renal function, dosage adjustments based on creatinine clearance is required (see Special dosage instructions and Pharmacokinetics in special populations).

• Seizures have been reported in patients taking imipenem-cilastatin and ganciclovir. CYMEVENE should not be used concomitantly with imipenem-cilastatin unless there is no other appropriate treatment option (see WARNINGS AND SPECIAL PRECAUTIONS).
• Zidovudine and CYMEVENE each have the potential to cause neutropenia and anaemia. Some patients may not tolerate concomitant therapy at full dosage (see WARNINGS AND SPECIAL PRECAUTIONS).
• Didanosine plasma concentrations may increase during concomitant use with CYMEVENE, thus patients should be monitored for didanosine toxicity (see WARNINGS AND SPECIAL PRECAUTIONS).
• Concomitant use of other medicines that are known to be myelosuppressive or associated with renal impairment with CYMEVENE may result in added toxicity (see WARNINGS AND SPECIAL PRECAUTIONS).

Females and Males of Reproductive Potential

Fertility: Temporary and permanent inhibition of spermatogenesis in male animals and permanent suppression of fertility in female animals have occurred. Based on the occurrence of aspermatogenesis at ganciclovir exposures below therapeutic levels in animal studies, it is considered likely that ganciclovir may cause temporary or permanent inhibition of human spermatogenesis.

In a clinical study of renal transplant patients receiving valganciclovir (which is a pro-drug of ganciclovir) for CMV prophylaxis for up to 200 days were compared to an untreated control group. Spermatogenesis was inhibited during treatment with valganciclovir. At follow-up, approximately 6 months after treatment discontinuation, the mean sperm density in treated patients was comparable to that observed in the untreated control group. In valganciclovir treated patients, all patients with normal sperm density (n = 7) and 8/13 patients with low sperm density at baseline, recovered to normal counts after treatment cessation. In the control group, all patients with normal sperm density (n = 6) and 2/4 patients with low sperm density at baseline, had normal density at the end of follow-up.

Contraception: Women of reproductive potential should be advised to use effective contraception during and for at least 30 days after treatment with CYMEVENE. Sexually active men are advised to use condoms during and for at least 90 days after cessation of treatment with CYMEVENE, unless it is certain that the female partner is not at risk of becoming pregnant.

Pregnancy: CYMEVENE is contraindicated in pregnancy and lactation. Please refer to CONTRAINDICATIONS and WARNINGS AND SPECIAL PRECAUTIONS. In animal studies ganciclovir was associated with reproductive toxicity and teratogenicity. The safety of CYMEVENE in pregnant women has not been established. Ganciclovir readily diffuses across the human placenta. The safe use of CYMEVENE during labour and delivery has not been established.

Lactation: Women on treatment with CYMEVENE must be advised not to breastfeed their infants. Peri- and postnatal development has not been studied with ganciclovir but the possibility of ganciclovir being excreted in breast milk and causing serious adverse reactions in the breastfeeding infant cannot be excluded. Human data are not available but animal data indicates that ganciclovir is excreted in the milk of lactating rats.

No studies on the effect on the ability to drive and use machines have been performed. Based on the adverse reaction profile, ganciclovir may influence the ability to drive and use machines. Adverse reactions for example seizures, dizziness, visual impairment, fatigue and confusion may occur in patients receiving CYMEVENE. If they occur, such effects may affect tasks requiring alertness, including the patient's ability to drive and operate machinery.

HIV infected patients Valganciclovir is a pro-drug of ganciclovir, and adverse reactions associated with valganciclovir can be expected to occur with ganciclovir. Therefore, adverse drug reactions reported with IV or oral ganciclovir (no longer available) or with valganciclovir are included in the table of adverse reactions (see Table 5). In patients treated with ganciclovir/valganciclovir the most serious and frequent adverse drug reactions are haematological reactions and include neutropenia, anaemia and thrombocytopenia. The frequencies presented in the table of adverse reactions are derived from a pooled population of HIV-infected patients (n=1704) receiving maintenance therapy with ganciclovir (GAN1697, GAN1653, GAN2304, GAN1774, GAN2226, AVI034, GAN041) or valganciclovir (WV15376, WV15705).

Overdose experience with IV ganciclovir: Reports of overdoses with intravenous ganciclovir, some with fatal outcomes, have been received from clinical trials and during post-marketing experience. The majority of patients experienced one or more of the following adverse events: Haematological toxicity: myelosuppression including pancytopenia, medullary aplasia, leukopenia, neutropenia, granulocytopenia thrombocytopenia. Hepatotoxicity: hepatitis, liver function disorder. Renal toxicity: worsening of haematuria in a patient with pre-existing renal impairment, acute renal failure, elevated creatinine. Gastrointestinal toxicity: abdominal pain, diarrhoea, vomiting. Neurotoxicity: generalised tremor, convulsion. An excessive volume of IV ganciclovir solution given by intravitreal injection caused a temporary loss of vision and central retinal artery occlusion due to increased intraocular pressure related to the injected fluid volume. Haemodialysis and hydration may be of benefit in reducing blood plasma levels in patients who receive an overdose of ganciclovir (see Pharmacokinetics in Special Populations).