ORPHACOL

Lactation Amenorrhea Combination with other anti-epileptic drugs Carnitine palmitoyltransferase deficiency Diabetes Child under 17 kg Child under 6 years of age Child between and 15 years Female child or adolescent Severe epilepsy Male of childbearing age Hypocarnitinaemia Renal impairment Surgical intervention Brain injury Dispersed erythematous lupus Mitochondriopathy Newborn exposed in utero to the medicine Pregnant or likely partner Hemodialysis patient Patients with POLG mutations, family history (de) Patients on combination therapy High dose treated patient Patient treated as relays of an immediate release form Elderly Subject at risk of hepatopathies Subject at risk of hypocarnitinaemia Suspicion of POLG gene mutations Hereditary metabolic disorder.

Valproic acid

Mechanism of action Valproic acid is an antiepileptic.

It exerts its pharmacological effects mainly in the central nervous system.

These anticonvulsive properties are exercised against a wide variety of types of seizures in animals and epilepsy in humans.

Experimental and clinical studies of valproic acid suggest two types of anticonvulsive action.

The first is a direct pharmacological effect in relation to valproic acid concentrations in plasma and brain.

The second is apparently indirect and likely in relation to persistent valproic acid metabolites in the brain, or with neurotransmitter changes, or with direct membrane effects.

The most commonly accepted hypothesis is the hypothesis of gamma-aminobutyric acid (GABA), the rate of which increases after administration of valproic acid.

Valproic acid decreases the duration of intermediate sleep phases with a concomitant increase in slow sleep.

• Hyponatremia (Common)
• Reduced sperm mobility (Rare)
• Macrocytosis (Rare)
• Hyperammonaemia (Rare)
• Coagulation factors (decrease) (Rare)
• Serum carnitine (decrease)
• INR (increase)
• Thrombin time (longening)
• Cep time activated (elongation)
• Prothrombin time increased Alopecia (Common)
• Skin reaction (Uncommon)
• Nail bed disorders (Common)
• Hair disorder (Uncommon)
• Onychopathy (Common)
• Hair disorder (Uncommon)
• Lyell's syndrome (Rare)
• Polymorphic Erythema (Rare)
• Stevens-Johnson Syndrome (Rare)
• Skin hyperpigmentation Hair pulverization (abnormal)
• Hair colour (change)
• Acne Hypothermia (Uncommon)
• Peripheral edema (Uncommon)
• Hyperandrogeneity (Uncommon)
• Inappropriate antidiuretic hormone secretion syndrome (IADH) (Uncommon)
• Hypothyroidism (Rare)
• Virilization Hirsutism Menstrual irregularity (Common)
• Amenorrhea (Uncommon)
• Polycystic ovary (Rare)
• Haemorrhage (Common)
• Leucopenia (Uncommon)
• Thrombocytopenia (Common)
• Pancytopenia (Uncommon)
• Anemia (Common)
• Erythrocyte aplasia (Rare)
• Cardiac aplasia (Rare)
• Agranulocytosis (Rare)
• Myelodysplastic syndrome (Rare)
• Macrocytic anaemia (Rare)
• Neutrophils with Pelger-Huët's Anomaly Hepatitis (Common)
• Angioedema (Uncommon)
• Dispersed erythematous lupus (Rare)
• Drug hypersensitivity (Rare)
• DRESS syndrome (Rare)
• Neurodevelopmental disorder Congenital malformation
• Weight (increase) (Common)
• Vitamin B8 deficiency (Rare)
• Obesity (Rare)
• Biotinidase deficiency (Rare)
• Nystagmus (Common)
• Diplopia (Rare)
• Feeling dizzy (Common)
• Deafness (Common)
• Stomatitis (Common)
• Gingival disorder (Common)
• Gingival hyperplasia
• Attention disorder (Common)
• Stupid (Common)
• Hallucination (Common)
• Lethargy (Uncommon)
• Mental confusion (Common)
• Aggressiveness (Common)
• Agitation (Common)
• Learning difficulty (Rare)
• Behavioural disorder (Rare)
• Cognitive disorder (Rare)
• Dementia Skin vasculitis (Uncommon)
• Leukocytoclase vasculitis Nausea (Very common)
• Epigastric pain (Common)
• Vomiting (Common)
• Diarrhoea (Common)
• Pancreatitis (Uncommon)
• Osteoporosis (Uncommon)
• Osteopenia (Uncommon)
• Fracture (Uncommon)
• Rhabdomyolysis (Rare)
• Headache (Common)
• Trembling (Very common)
• Convulsions (Common)
• Parkinsonian syndrome (Uncommon)
• Sedation (Common)
• Paraesthesia (Uncommon)
• Memory Disorder (Common)
• Ataxia (Uncommon)
• Coma (Uncommon)
• Encephalopathy (Uncommon)
• Extrapyramidal disorder (Common)
• Psychomotor hyperactivity (Rare)
• Neurological disorder
• Pleural effusion (Uncommon)
• Renal impairment (Uncommon)
• Urinary incontinence (Common)
• Enuresis (Rare)
• Tubulo-interstitial nephropathy (Rare)
• Fanconi syndrome (Rare).

For external use only.

Do not use more than one acne product at a time.

After area is wet with

Blemfree™ Cleansing Wash Concentrate has foamed, tap Blemfree™ Cleansing Spheres with fingertips and massage in small circles for 60 seconds.

Proceed to rinse step.