The most common adverse reactions (ARs) reported in at least one indication by patients treated with valaciclovir in clinical trials were headache and nausea. More serious ARs such as thrombotic thrombocytopenic purpura/haemolytic uraemic syndrome, acute renal failure and neurological disorders are discussed in greater detail in other sections of the label.
Undesirable effects are listed as follows by body system organ class and by frequency.
The following frequency categories are used for classification of adverse effects: 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, Very rare ≤1/10,000.
Clinical trial data have been used to assign frequency categories to ARs if, in the trials, there was evidence of an association with valaciclovir.
For ARs identified from postmarketing experience, but not observed in clinical trials, the most conservative value of point estimate ("rule of three") has been used to assign the AR frequency category. For ARs identified as associated with valaciclovir from post-marketing experience, and observed in clinical trials, study incidence has been used to assign the AR frequency category. The clinical trial safety database is based on 5855 subjects exposed to valaciclovir in clinical trials covering multiple indications (treatment of herpes zoster, treatment/suppression of genital herpes & treatment of cold sores).
Clinical Trial Data: Nervous system disorders: Very common: Headache.
Gastrointestinal disorders: Common: Nausea.
Post Marketing Data: Blood and lymphatic system disorders: Uncommon: Leucopenia, thrombocytopenia.
Leucopenia is mainly reported in immunocompromised patients.
Immune system disorders: Rare: Anaphylaxis.
Psychiatric and nervous system disorders: Common: Dizziness.
Uncommon: Confusion, hallucinations, decreased consciousness, tremor, agitation.
Rare: Ataxia, dysarthria, convulsions, encephalopathy, coma, psychotic symptoms, delirium.
Neurological disorders, sometimes severe, may be linked to encephalopathy and include confusion, agitation, convulsions, hallucinations, coma. These events are generally reversible and usually seen in patients with renal impairment or with other predisposing factors (see Precautions). In organ transplant patients receiving high doses (8 g daily) of valaciclovir for CMV prophylaxis, neurological reactions occurred more frequently compared with lower doses used for other indications.
Respiratory, thoracic and mediastinal disorders: Uncommon: Dyspnoea.
Gastrointestinal disorders: Common: Vomiting, diarrhoea. Uncommon: Abdominal discomfort.
Hepato-biliary disorders: Uncommon: Reversible increases in liver function tests (e.g. bilirubin, liver enzymes).
Skin and subcutaneous tissue disorders: Common: Rashes including photosensitivity, pruritus. Uncommon: Urticaria.
Renal and urinary disorders: Uncommon: Renal pain, haematuria (often associated with other renal events).
Rare: Renal impairment, acute renal failure (especially in elderly patients or in patients with renal impairment receiving higher than the recommended doses).
Renal pain may be associated with renal failure.
Intratubular precipitation of aciclovir crystals in the kidney has also been reported. Adequate fluid intake should be ensured during treatment (see Precautions).
Additional information on special populations: There have been reports of renal insufficiency, microangiopathic haemolytic anaemia and thrombocytopenia (sometimes in combination) in severely immunocompromised adult patients, particularly those with advanced HIV disease, receiving high doses (8 g daily) of valaciclovir for prolonged periods in clinical trials. These findings have also been observed in patients not treated with valaciclovir who have the same underlying or concurrent conditions.