|The following CIOMS frequency rating is used, when applicable: 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); not known (cannot be estimated from the available data).
Congenital and familial/genetic disorders: (see section 4.6 Fertility, pregnancy and lactation)Hepato-biliary disorders: Common: liver injury (see section 4.4.1 Warnings)Severe liver damage, including hepatic failure sometimes resulting in death, has been reported (see also sections 4.2, 4.3 and 4.4.1). Increased liver enzymes are common, particularly early in treatment, and may be transient (see section 4.4.1).|
Gastrointestinal disordersVery common: nausea, Common: gastralgia, diarrhoea The above three adverse events frequently occur at the start of treatment, but they usually disappear after a few days without discontinuing treatment. These problems can usually be overcome by taking Epilim with or after food or by using Enteric Coated Epilim (Epilim Gastro-resistant tablets).Uncommon: pancreatitis, sometimes lethal (see section 4.4 Special Warnings and Special Precautions for Use).
Nervous system disorders: Very common: tremorCommon: extrapyramidal disorder, stupor*, somnolence, convulsion*, memory impairment, headache, nystagmus, Uncommon: coma*, encephalopathy, lethargy* (see below), reversible parkinsonism, ataxia, paresthesia.Rare: reversible dementia associated with reversible cerebral atrophy, cognitive disorder.Sedation has been reported occasionally, usually when in combination with other anticonvulsants. In monotherapy it occurred early in treatment on rare occasions and is usually transient. *Rare cases of lethargy occasionally progressing to stupor, sometimes with associated hallucinations or convulsions have been reported. Encephalopathy and coma have very rarely been observed. These cases have often been associated with too high a starting dose or too rapid a dose escalation or concomitant use of other anticonvulsants, notably phenobarbital or topiramate. They have usually been reversible on withdrawal of treatment or reduction of dosage.An increase in alertness may occur; this is generally beneficial but occasionally aggression, hyperactivity and behavioural deterioration have been reported.
Psychiatric disorder:Common: confusional state, aggression*, agitation*, disturbance in attention* Rare: abnormal behaviour*, psychomotor hyperactivity*, learning disorder**These ADRs are principally observed in the paediatric population.
Metabolic disorders:Common: hyponatraemia.Rare: hyperammonaemia* (see section 4.4.2 Precautions)*Cases of isolated and moderate hyperammonaemia without change in liver function tests may occur, are usually transient and should not cause treatment discontinuation. However, they may present clinically as vomiting, ataxia, and increasing clouding of consciousness. Should these symptoms occur Epilim should be discontinued. Hyperammonaemia associated with neurological symptoms has also been reported (see section 4.4.2 Precautions). In such cases further investigations should be considered.
Endocrine Disorders:Uncommon: Syndrome of Inappropriate Secretion of ADH (SIADH)Rare: hypothyroidism (see section 4.6 Fertility, pregnancy and lactation)
Blood and lymphatic system disorders: Common: anaemia, thrombocytopenia, (see section 4.4.2 Precautions). Uncommon: pancytopenia, leucopenia The blood picture returned to normal when the drug was discontinued. Rare: bone marrow failure, including pure red cell aplasia.agranulocytosis, anaemia macrocytic, macrocytosis.Isolated findings of a reduction in blood fibrinogen and/or an increase in prothrombin time have been reported, usually without associated clinical signs and particularly with high doses (Epilim has an inhibitory effect on the second phase of platelet aggregation). Spontaneous bruising or bleeding is an indication for withdrawal of medication pending investigations (see also section 4.6 Fertility, pregnancy and lactation).
Skin and subcutaneous tissue disorders:Common: hypersensitivity, transient and/or dose related alopecia (hair loss).. Regrowth normally begins within six months, although the hair may become more curly than previously. Uncommon: angioedema, rashHirsutism and acne have been very rarely reported.Rare: toxic epidermal necrolysis, Stevens-Johnson syndrome, erythema multiforme, Drug Rash with Eosinophilia and Systemic Symptoms (DRESS) syndrome.
Reproductive system and breast disorders:Common: dysmenorrheaUncommon: amenorrheaRare: male infertility, polycystic ovariesVery rarely gynaecomastia has occurred.
Vascular disorders: Common: haemorrhage (see section 4.4.2 Precautions and 4.6 Fertility, pregnancy and lactation).Uncommon: vasculitis
Ear and labyrinth disorders: Common: Deafness, a cause and effect relationship has not been established.
Renal and urinary disorders: Rare: enuresis, reversible Fanconi syndrome (a defect in proximal renal tubular function giving rise to glycosuria, amino aciduria, phosphaturia, and uricosuria) associated with Epilim therapy, but the mode of action is as yet unclear.
General disorders and administration site conditions: Uncommon: non-severe oedema peripheral
Musculoskeletal and connective tissue disorders: Uncommon: bone mineral density decreased, osteopenia, osteoporosis and fractures in patients on long-term therapy with Epilim. The mechanism by which Epilim affects bone metabolism has not been identified.Rare: systemic lupus erythematosus (see section 4.4.2 Precautions)
Respiratory, thoracic and mediastinal disorders:Uncommon: pleural effusion
Investigations:Common: Weight increased*Rare: Coagulation factors decreased (at least one), abnormal coagulation tests (such as prothrombin time prolonged, activated partial thromboplastin time prolonged, thrombin time prolonged, INR prolonged).*Weight increase should be carefully monitored since it is a factor for polycystic ovary syndrome (see section 4.4.2 Precautions)
Neoplasms benign, malignant and unspecified (including cysts and polyps):Rare: myelodysplastic syndromeReporting of suspected adverse reactionsReporting 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 Yellow Card Scheme at: www.mhra.gov.uk/yellowcard