Cymevene Adverse Reactions

Clinical Trials: 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 Tables 5a and 5b).
In patients treated with ganciclovir/valganciclovir, the most serious and frequent adverse drug reactions are hematological reactions and include neutropenia, anemia 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). Exception is made for agranulocytosis, granulocytopenia and anaphylactic reaction; the frequencies of which are derived from post-marketing experience. Frequencies are presented as percentages and as CIOMS frequency categories defined as very common (≥1/10), common (≥1/100 to <1/10), uncommon (≥1/1,000 to <1/100), rare (≥1/10,000 to <1/1,000) and very rare (<1/10,000).
The overall safety profile of ganciclovir/valganciclovir is consistent in HIV and transplant populations except that retinal detachment has only been reported in HIV patients with CMV retinitis. However, there are some differences in the frequency of certain reactions. Intravenous ganciclovir is associated with a lower risk of diarrhea compared to oral valganciclovir. Pyrexia, candida infections, depression, severe neutropenia (ANC <500 μL) and skin reactions are reported more frequently in patients with HIV. Renal and hepatic dysfunction is reported more frequently in organ transplant recipients.
Pediatric population: Based on the cumulative experience, including valganciclovir pediatric studies, the overall safety profile of ganciclovir in the pediatric population appears similar to the safety profile established in adults. There is a higher risk of hematological cytopenias in neonates and infants (see Use in Children under Precautions). (See Tables 5a and 5b.)

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Description of selected adverse reactions: Neutropenia: The risk of neutropenia is not predictable on the basis of the number of neutrophils before treatment. Neutropenia usually occurs during the first or second week of induction therapy. The cell count usually normalizes within 2 to 5 days after discontinuation of the drug or dose reduction (see Precautions).
Thrombocytopenia: Patients with low baseline platelet counts (<100,000/μL) have an increased risk of developing thrombocytopenia. Patients with iatrogenic immunosuppression due to treatment with immunosuppressive drugs are at greater risk of thrombocytopenia than patients with HIV (see Precautions). Severe thrombocytopenia may be associated with potentially life-threatening bleeding.
Laboratory Abnormalities: Laboratory abnormalities in HIV infected patients: Laboratory abnormalities reported from three clinical trials in HIV infected patients receiving intravenous ganciclovir as maintenance treatment for CMV retinitis are listed as follows in Table 6. One hundred seventy-nine patients were eligible for the laboratory abnormality analysis. (See Table 6.)

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Postmarketing Experience: Safety reports from the postmarketing setting are consistent with safety data from clinical trials with ganciclovir and valganciclovir (see Tables 5a and 5b as previously mentioned).