Valgan 450 Adverse Reactions

Summary of the safety profile: Valganciclovir is a prodrug of ganciclovir, which is rapidly and extensively metabolised to ganciclovir after oral administration. The undesirable effects known to be associated with ganciclovir use can be expected to occur with valganciclovir. All of the undesirable effects observed with valganciclovir clinical studies have been previously observed 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.
In patients treated with valganciclovir/ganciclovir 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 patients (n=1704) receiving maintenance therapy with ganciclovir (GAN 1697, GAN 1653, 2304, GAN 1774, GAN 2226, AVI 034, GAN 041) or valganciclovir (WV15376, WV15705). Exception is made for anaphylactic reaction, agranulocytosis and granulocytopenia 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 patients with CMV retinitis. However, there are some differences in the frequency of certain reactions. Valganciclovir is associated with a higher risk of diarrhea compared to intravenous ganciclovir. Pyrexia, candida infections, depression, severe neutropenia (ANC <500/μL) [2, 6, 44, 49] and skin reactions are reported more frequently in patients with HIV. Renal and hepatic dysfunction are reported more frequently in organ transplant recipients. (See Table 4.)

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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. Cell counts usually begin to recover within 3 to 7 days of discontinuing drug (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.
Influence of treatment duration or indication on adverse reactions: Severe neutropenia (ANC <500/μL) is seen more frequently in CMV retinitis patients (16%) undergoing treatment with valganciclovir than in solid organ transplant patients receiving valganciclovir or oral ganciclovir. In patients receiving valganciclovir or oral ganciclovir until Day 100 post-transplant, the incidence of severe neutropenia was 5% and 3% respectively, whilst in patients receiving valganciclovir until Day 200 post-transplant the incidence of severe neutropenia was 10%.
There was a greater increase in serum creatinine seen in solid organ transplant patients treated until Day 100 or Day 200 post-transplant with both valganciclovir and oral ganciclovir when compared to CMV retinitis patients. However, impaired renal function is a feature more frequent in solid organ transplantation patients.
The overall safety profile of Valganciclovir did not change with the extension of prophylaxis up to 200 days in high risk kidney transplant patients. Leukopenia was reported with a slightly higher incidence in the 200 days arm while the incidence of neutropenia, anaemia and thrombocytopenia were similar in both arms.
Laboratory Abnormalities: Laboratory abnormalities reported in adults CMV retinitis patients and solid organ transplant patients receiving valganciclovir until Day 100 post-tranplant are listed as follows. The incidence of laboratory abnormalities was comparable with the extension of prophylaxis up to 200 days in high risk kidney transplant patients. (See Table 5.)

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Severe neutropenia (ANC <500 /μl) is seen more frequently in CMV retinitis patients (16%) undergoing treatment with valganciclovir than in solid organ transplant patients receiving valganciclovir (5%) or oral ganciclovir (3%) until Day 100 post-transplant or valganciclovir (10%) until Day 200 post-transplant. There was a greater increase in serum creatinine seen in solid organ transplant patients treated until Day 100 or Day 200 post-transplant with both valganciclovir and oral ganciclovir when compared to CMV retinitis patients. Impaired renal function is a feature common to solid organ transplantation patients.
The overall safety profile of Valganciclovir did not change with the extension of prophylaxis up to 200 days in high risk kidney transplant patients. Leukopenia was reported with a slightly higher incidence in the 200 days arm while the incidence of neutropenia, anaemia and thrombocytopenia were similar in both arms.
The incidence of adverse events in this patient population from the clinical study is shown in Tables 6 and 7. Table 6 shows adverse events occurring in the first 100 days of the study when all patients were receiving valganciclovir prophylaxis. While, Table 7 shows adverse events occurring after day 100 of the study when only patients in the 200 days arm were receiving valganciclovir (patients in the 100 day arm were receiving placebo). (See Tables 6 and 7.)

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Post Marketing Experience: Safety reports from the postmarketing setting are consistent with the safety data from clinical trials with valganciclovir and ganciclovir (see previously mentioned Table).