Classification of expected frequencies: Very common (≥10%), Common (≥1% to <10% ), Uncommon (≥0.1% to <1%); Rare (≥0.01% to <0.1%); Very rare (<0.01%); Not Known (cannot be estimated from the available data).
Congenital, Family and Genetic Disorders:
Congenital malformations, neurodevelopmental disorders (see Warnings, Precautions and Use in Pregnancy & Lactation).
Haematological and Lymphatic System Disorders:
Common: Anaemia, thrombocytopenia.
Cases of dose-related thrombocytopenia, usually discovered systemically and without any clinical repercussions, have been described.
In the case of asymptomatic thrombocytopenia, if the platelet count and control of epileptic disease so allow a decrease in the dosage of this medicinal product alone frequently results in the regression of thrombocytopenia.
Uncommon: Leucopenia, pancytopenia.
Rare: Global aplastic anaemia or pure red cell aplasia, agranulocytosis, macrocytic anaemia, macrocytosis.
Common: Weight gain.*
Rare: Decrease of at least one clotting factor, abnormal coagulation tests (such as prolonged prothrombin time, prolonged activated partial thromboplastin time, prolonged thrombin time, increased INR) (see Warnings, Precautions and Use in Pregnancy & Lactation), vitamin B8
(biotin) deficiency/biotinidase deficiency.
*Given that weight gain is a risk factor for the onset of polycystic ovary syndrome, patients weight must be carefully monitored (see Warnings and Precautions).
Nervous System Disorders:
Very common: Tremors.
Common: Extrapyramidal disorders, stupor*, sedation, convulsion*, memory impairment, headache, nystagmus.
Uncommon: Coma*, encephalopathy*, lethargy, reversible parkinsonian syndromes, ataxia, paresthesia.
Rare: Insidious and progressive cognitive disorders (that may be associated with dementia) reversible a few weeks to months after discontinuation of treatment.
*Cases of stupor or lethargy sometimes leading to a transient coma (encephalopathy) with valproate have been observed regressing upon treatment disconinuation or dose reduction. These conditions occur most frequently during polytherapies (especially phenobarbital and topiramate) or sudden increase in valproate doses.
Ear and Labyrinth Disorders:
Common: Hearing loss.
Respiratory, Thoracic and Mediastinal Disorders:
Uncommon: Pleural effusion.
Very common: Nausea.
Common: Vomiting, gingival disorders (mainly gingival hyperplasia), stomatitis, epigastric pain, diarrhoea that may occur in some patients at the start of treatment, but usually disappear after a few days without discontinuing treatment.
Uncommon: Pancreatitis sometimes fatal and that requires early treatment discontinuation (see Warnings and Precautions).
Renal and Urinary Disorders:
Uncommon: Renal insufficiency.
Rare: Enuresis, urinary incontinence, tubulointerstitial nephritis.
Skin and Subcutaneous Tissue Disorders:
Common: Transient and/or dose-dependent, hair loss.
Uncommon: Angioedema, skin reactions, hair disorders (such as abnormal hair texture, changes in hair colour, abnormal hair growth).
Rare: Lyell syndrome (toxic epidermal necrolysis), Stevens-Johnson syndrome, erythema multiforme, DRESS (Drug Rash with Eosinophilia and Systemic Symptoms) syndrome.
Uncommon: Syndrome of inappropriate antidiuretic hormone secretion (SIADH), hyperandrogenism (hirsutism, virilization, acne, adrogenic, alopecia and/or increased androgenic hormone levels).
Rare: Hypothyroidism (see Use in Pregnancy & Lactation).
Metabolic and Nutritional Disorders:
Rare: Hyperammonaemia*(see Warnings and Precautions).
*Cases of isolated and moderate hyperammonaemia without change in liver function tests may occur, especially in case of polytherapy and should not cause treatment discontinuation.
However cases of hyperammonaemia with neurological symptoms (including coma) have also been reported thereby requiring further investigations (see Warnings and Precautions).
Benign, Malignant and Unspecified Tumour (including Cysts and Polyps):
Rare: Myelodysplastic syndrome.
Common bleeding (see Warnings, Precautions and Adverse Reactions).
General Disorders and Administration Site Anomalies:
Common: Within minutes following the injection, nausea or dizziness may occur which spontaneously disappear within a few minutes.
Uncommon: Hypothermia, non-severe peripheral oedema.
Unknown: Risk of local tissue necrosis in case of repeated injections.
Common: Liver dysfunction (see Warnings and Precautions).
Reproductive Organ and Breast Disorders:
Common: Menstrual irregularities.
Rare: Impact on spermatogenesis (reduction in sperm mobility in particular) (see Precautions) polycystic ovaries.
Musculoskeletal and Systemic Disorders:
Uncommon: Decreased bone mineral density, osteopenia, osteoporosis and fractures in patients treated long term with Sodium Valproate Aguettant. The way that SODIUM VALPROATE AGUETTANT acts on bone metabolism is not known.
Rare: Systemic lupus erythematosus (see Warnings and Precautions), rhabdomyolysis (see Warnings and Precautions).
Common: Confusion, hallucinations*, aggression*, agitation*, attention disorders*.
Rare: Abnormal behaviour*, psychomotor hyperactivity*, learning difficulties*.
*These reactions are mostly seen in the paediatric population.
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. Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system.