1 Name of Medicine
Valganciclovir (as hydrochloride).
2 Qualitative and Quantitative Composition
Valcyte is available as film-coated tablets and as powder for oral solution.
Each film coated tablet contains 496.3 mg valganciclovir HCl (corresponding to 450 mg valganciclovir).
The powder is reconstituted to form an oral solution, containing 55 mg valganciclovir HCl per mL (equivalent to 50 mg valganciclovir).
Excipients with known effect. The powder for oral solution contains a total of 0.188 mg/mL sodium.
For the full list of excipients, see Section 6.1. List of Excipients.
3 Pharmaceutical Form
Valcyte tablets. Valcyte (valganciclovir HCl) is available as 450 mg pink convex oval tablets with "VGC" on one side and "450" on the other side. Each film-coated tablet contains 450 mg valganciclovir. Valcyte is supplied in bottles of 60 tablets.
Valcyte powder for oral solution. Valcyte powder is white to slightly yellow. The reconstituted solution contains 50 mg/mL valganciclovir and appears clear, colourless to brownish-yellow in colour.
4 Clinical Particulars
4.9 Overdose
Overdose experience with valganciclovir and intravenous ganciclovir. It is expected that an overdose of valganciclovir could also possibly result in increased renal toxicity (see Section 4.4 Special Warnings and Precautions for Use; Section 4.2 Dose and Method of Administration).
Overdose experience with intravenous ganciclovir. Reports of overdoses with intravenous ganciclovir, some with fatal outcomes, have been received from clinical trials and during post-marketing experience. In some of these cases no adverse events were reported. The majority of patients experienced one or more of the following adverse events.
Haematological toxicity. Myelosuppression including pancytopenia, bone marrow failure, leukopenia, neutropenia, granulocytopenia.
Hepatotoxicity. Hepatitis, liver function disorder.
Renal toxicity. Worsening of haematuria in a patient with pre-existing renal impairment, acute renal failure, and elevated creatinine.
Gastrointestinal toxicity. Abdominal pain, diarrhoea, vomiting.
Neurotoxicity. Generalised tremor, seizure.
Haemodialysis and hydration may be of benefit in reducing blood plasma levels in patients who receive an overdose of valganciclovir.
Treatment of overdose should consist of general supportive measures.
For information on the management of overdose, contact the Poisons Information Centre on 131126 (Australia).
5 Pharmacological Properties
5.3 Preclinical Safety Data
Ganciclovir was genotoxic and carcinogenic in animal studies.
Carcinogenicity. Ganciclovir was genotoxic and carcinogenic in animal studies. Valcyte should be considered a potential carcinogen in humans with the potential to cause cancers. No long-term carcinogenicity studies have been conducted with valganciclovir. However, upon oral administration, valganciclovir is rapidly and extensively converted to ganciclovir.
Toxicity in mice, dogs and rats was primarily characterised by testicular atrophy. Male infertility occurred at doses of 2 mg/kg/day and above which was consistent with the infertility and testicular atrophy seen in toxicity studies with doses between 2 and 10 mg/kg/day. In females, a more complex range of effects were induced which were characterised by embryo-foetal abnormalities and embryo-foetal losses in mice and rabbits and in multi-dose studies, by toxic and eventually carcinogenic changes to the reproductive system in mice.
Ganciclovir was carcinogenic in the mouse after oral doses of 20 mg/kg/day for 18 months and 1000 mg/kg/day for 15 months. All ganciclovir-induced tumours were of haematopoietic, epithelial or vascular origin. Epithelial tumours involved a wide variety of tissues, including the female reproductive organs, pancreas, gastrointestinal tract and skin, as well as rodent specific glands (perputial, clitoral and Harderian). Vascular tumours were observed in females, mainly in the reproductive organs, but also in the mesenteric lymph nodes and liver. No carcinogenic effects occurred at 1 mg/kg/day. Based on data on plasma drug concentrations, exposure of humans to ganciclovir would be similar to or greater than the exposure of mice in the above study at 1000 mg/kg/day. This potential is likely to be markedly greater in children, as cell division occurs more rapidly in children.
Genotoxicity. Valganciclovir increased mutations in mouse lymphoma cells and was clastogenic in the mouse micronucleus assay. Valganciclovir was not mutagenic in the Ames Salmonella assay.
Ganciclovir increased mutations in mouse lymphoma cells and DNA damage in human lymphocytes in vitro. Ganciclovir was clastogenic in the mouse micronucleus assay. Ganciclovir was not mutagenic in the Ames Salmonella assay.
6 Pharmaceutical Particulars
6.7 Physicochemical Properties
Chemical structure.
https://stagingapi.mims.com/au/public/v2/images/fullchemgif/CSVALGAN.gif CAS number. 175865-59-5.
The chemical name for valganciclovir hydrochloride is L-valine, 2-[(2-amino-1,6-dihydro-6-oxo-9H-purin-9-yl) methoxy]-3-hydroxypropyl ester, monohydrochloride. The molecular formula is C14H22N6O5.HCl and molecular weight is 390.83.
Valganciclovir hydrochloride (valganciclovir HCl) is the hydrochloride salt of the L-valyl ester of ganciclovir. Ganciclovir is a synthetic nucleoside analogue of guanine.
Valganciclovir HCl is a white to off-white crystalline powder.
Valganciclovir HCl is a polar hydrophilic compound with a solubility of 70 mg/mL in water at 25°C at a pH of 7.0 and an n-octanol/water partition coefficient of 0.0095 at pH 7.0. The pKa for valganciclovir is 7.6.
7 Medicine Schedule (Poisons Standard)
Schedule 4 - Prescription Only Medicine.
Summary Table of Changes
https://stagingapi.mims.com/au/public/v2/images/fulltablegif/VALCYTST.gif
