Summary of the safety profile Valganciclovir is a pro-drug of ganciclovir, and adverse reactions associated with valganciclovir can be expected to occur with ganciclovir. Oral ganciclovir is no longer available but adverse reactions reported with its use can also be expected to occur in patients receiving intravenous ganciclovir.
Therefore, adverse drug reactions reported with intravenous or oral ganciclovir or with valganciclovir are included in the table of adverse reactions. 4). Other adverse drug reactions are presented in the table below. The frequencies presented in the table of adverse reactions are derived from a pooled population of HIV-infected patients (n = 1,704) receiving maintenance therapy with ganciclovir or valganciclovir.
Exception is made for agranulocytosis, granulocytopenia and anaphylactic reaction; the frequencies of which are derived from post-marketing experience. Adverse reactions are listed according to MedDRA system organ class. Frequency categories are defined using the following convention: 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 diarrhoea 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 are reported more frequently in organ transplant recipients. Tabulated list of adverse reactions System Organ Class (MedDRA) Frequency ADR Very common Candida infections including oral candidiasis, upper respiratory tract infection Infections and infestations Common sepsis, influenza, urinary tract infection, cellulitis Very common neutropenia, anaemiaBlood and lymphatic system disorders Common thrombocytopenia, leukopenia, pancytopenia System Organ Class (MedDRA) Frequency ADR Uncommon bone marrow failure Rare aplastic anaemia, agranulocytosis*, granulocytopenia* Common hypersensitivityImmune system disorders Rare anaphylactic reaction* Very common decreased appetiteMetabolic and nutrition disorders Common weight decreased Common depression, confusional state, anxietyPsychiatric disorders Uncommon agitation, psychotic disorder, thinking abnormal, hallucinations Very common headache Common insomnia, neuropathy peripheral, dizziness, paraesthesia, hypoaesthesia, seizure, dysgeusia (taste disturbance) Nervous system disorders Uncommon tremor Eye disorders Common visual impairment, retinal detachment, vitreous floaters, eye pain, conjunctivitis, macular oedema Common ear painEar and labyrinth disorders Uncommon deafness Cardiac disorders Uncommon arrhythmia Vascular disorders Common hypotension Respiratory, thoracic and mediastinal disorders Very common Cough, dyspnoea Very common diarrhoea, nausea, vomiting, abdominal painGastrointestinal disorders Common dyspepsia, flatulence, abdominal pain upper, constipation, mouth ulceration, dysphagia, abdominal distention, pancreatitis Hepatobiliary disorders Common blood alkaline phosphatase increased, hepatic function abnormal, aspartate aminotransferase increased, alanine aminotransferase increased Very common dermatitis Common night sweats, pruritus, rash, alopecia Skin and subcutaneous tissue disorders Uncommon dry skin, urticaria Musculoskeletal and connective tissue disorders Common back pain, myalgia, arthralgia, muscle spasms Common renal impairment, creatinine clearance renal decreased, blood creatinine increased Renal and urinary disorders Uncommon renal failure, haematuria System Organ Class (MedDRA) Frequency ADR Reproductive system and breast disorders Uncommon infertility male Very common pyrexia, fatigue Common injection site reaction, pain, chills, malaise, asthenia General disorders and administration site conditions Uncommon chest pain *The frequencies of these adverse reactions are derived from post-marketing experience; all other frequency categories are based on the frequency recorded in clinical trials.
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 and following administration of a cumulative dose of ≤ 200 mg/kg.
4). Severe neutropenia Severe neutropenia was reported more frequently in HIV patients (14%) receiving maintenance therapy with valganciclovir, oral or intravenous ganciclovir (n = 1,704) than in 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%.
Thrombocytopenia Patients with low baseline platelet counts (< 100,000/μL) have an increased risk of developing thrombocytopenia. 4). Severe thrombocytopenia may be associated with potentially life-threatening bleeding. 4 […]