Adverse reactions : תופעות לוואי

4.8     Undesirable effects

The most common adverse reactions (ARs) reported in at least one indication by patients treated with Valtrex in clinical trials were headache and nausea. More serious ARs such as thrombotic thrombocytopenic purpura/haemolytic uraemic syndrome, acute renal failure, neurological disorders and DRESS (see section 4.4) are discussed in greater detail in other sections of the label.

Undesirable effects are listed below 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 < 1/1000,
Very rare        < 1/10,000
Not known        (Cannot be estimated from the available data)

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 post marketing 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 section 4.4). In organ transplant patients receiving high doses (8000 mg daily) of Valtrex 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
Rare:            Angioedema
Not known:       Drug reaction with eosinophilia and systemic symptoms (DRESS) (see section 4.4) 
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).
Not known        Tubulointerstitial nephritis.

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 section 4.4).

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 (8000 mg 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.

Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. any suspected adverse events should be reported to the Ministry of Health according to the National Regulation by using an online form https://sideeffects.health.gov.il
Additionally, you should also report to GSK Israel (il.safety@gsk.com).