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DYZANTIL is a brand name for Valproate (also known as Valproic Acid). The medicine, its uses, side effects and dosage are the same regardless of brand.
Used for: Female patients: • For all female patients aged under 55 years: For the treatment of generalised, partial or other epilepsy only when there is no other effective or tolerated treatment. • For all female patients aged over 55 years: For the treatment of generalised, partial or other epilepsy. Male patients: • For all…
Verbatim from this product's MHRA label. Tap a section to expand.
Posology Dyzantil is a prolonged release formulation which reduces peak concentration and ensures more even plasma concentrations throughout the day. Dyzantil may be given once or twice daily. Daily dosage requirements vary according to age and body weight.
Dosage Usual requirements are as follows:
Adults Dosage should start at 600 mg daily increasing by 200 mg at three-day intervals until control is achieved. e. 20 – 30 mg/kg/day body weight. Where adequate control is not achieved within this range, the dose may be further increased to 2500 mg per day.
Special populations Paediatric population Children over 20 kg Initial dosage should be 400 mg/day (irrespective of weight) with spaced increases until control is achieved; this is usually within the range 20 – 30 mg/kg body weight per day.
Where adequate control is not achieved within this range the dose may be increased to 35 mg/kg body weight per day. In children requiring doses higher than 40 mg/kg/day, clinical chemistry and haematological parameters should be monitored.
Children under 20 kg An alternative formulation of sodium valproate should be used in this group of patients, due to the tablet size and the need for dose titration. Liquid formulations of sodium valproate are available which would be more suitable for this patient group.
Elderly Although the pharmacokinetics of valproate are modified in the elderly, they have limited clinical significance and dosage should be determined by seizure control. The volume of distribution is increased in the elderly and because of decreased binding to serum albumin, the proportion of free drug is increased.
This will affect the clinical interpretation of plasma valproic acid levels. Renal impairment It may be necessary in patients with renal insufficiency to decrease the dosage, or to increase the dosage in patients on haemodialysis. 9).
4). 8). 4). Salicylates should not be used in children under 16 years of age (see aspirin/salicylate product information on Reye’s syndrome). 1). 6). Valproate must be supervised by a specialist experienced in the management of epilepsy.
6). Where possible, existing female children and women of childbearing potential aged under 55 years should be switched to another treatment unless two specialists independently consider and document there is no other effective or tolerated treatment.
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).
4) Psychiatric disorders Confusional state Hallucinations Aggression Agitation Disturbance in attention Abnormal behaviour Psychomotor hyperactivity Learning disorder Nervous system disorders Tremor Extrapyramidal disorder Stupor Somnolence Convulsion Memory impairment Headache Nystagmus Coma Encephalopathy Lethargy Reversible parkinsonism Ataxia Paraesthesia Aggravated convulsions Reversible dementia associated with reversible cerebral atrophy Cognitive disorder Eye disorders Diplopia Ear and labyrinth disorders Deafness Vascular disorders Haemorrhage Vasculitis Respiratory, thoracic and mediastinal disorders Pleural effusion (eosinophilic) Gastrointestin al disorders Nausea Vomiting Gingival disorder (mainly gingival hyperplasia) Stomatitis Gastralgia Diarrhoea Pancreatitis (sometimes fatal) Hepatobiliary disorders Liver injury Increased liver enzymes Hepatic failure, sometimes fatal SOC Very Common Common Uncommon Rare Very rare Not known Skin and subcutaneous tissue disorders Hypersensitivit y Transient and/or dose related alopecia Nail and nail bed disorders.
6). General disorders and administratio n site conditions Hypothermia Peripheral oedema Investigations Coagulation factors decreased abnormal coagulation tests4 1 Includes pure red cell aplasia, agranulocytosis, macrocytic anaemia and macrocytosis.
2 Includes hirsutism, virilism, acne, male pattern alopecia, and/or androgen increase. 3 Includes abnormal hair texture, hair colour changes and/or abnormal hair growth. 4 Includes prothrombin time prolonged, activated partial thromboplastin time prolonged, thrombin time prolonged and/or INR prolonged.
Description of selected adverse reactions Blood and lymphatic system disorders:
Although there is no specific evidence of sudden recurrence of underlying symptoms following withdrawal of valproate, discontinuation should normally only be done under the supervision of a specialist in a gradual manner. This is due to the possibility of sudden alterations in plasma concentrations giving rise to a recurrence of symptoms.
NICE has advised that generic switching of valproate preparations is not normally recommended due to the clinical implications of possible variations in plasma concentrations. 1 Special warnings Liver dysfunction: Conditions of occurrence: Severe liver damage, including hepatic failure sometimes resulting in fatalities, has been very rarely reported.
4) or degenerative disease associated with mental retardation. After the age of 3 years, the incidence of occurrence is significantly reduced and progressively decreases with age. 5). Additionally, salicylates should not be used in children under 16 years of age (see aspirin/salicylate product information on Reye’s syndrome).
5). In most cases, such liver damage occurred during the first 6 months of therapy, the period of maximum risk being 2 – 12 weeks.
Suggestive signs:
Clinical symptoms are essential for early diagnosis. In particular, the following conditions, which may precede jaundice, should be taken into consideration, especially in patients at risk (see above: ‘Conditions of occurrence’): - non-specific symptoms, usually of sudden onset, such as asthenia, malaise, anorexia, lethargy, oedema and drowsiness, which are sometimes associated with repeated vomiting and abdominal pain.
- in patients with epilepsy, recurrence of seizures. These are an indication for immediate withdrawal of the drug. Patients (or their family for children) should be instructed to report immediately any such signs to a physician should they occur.
6). 6). 1. • Active liver disease or personal or family history of severe hepatic dysfunction, especially drug related. 4). • Porphyria. g. 4). 4).
Not medical advice. Always read the patient information leaflet and follow your prescriber or pharmacist.
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4). 4). Valproate should preferably be prescribed as monotherapy and at the lowest effective dose, if possible as a prolonged-release formulation. 6). 6). 3). 5) When starting Dyzantil in patients already on other anti-convulsants, these should be tapered slowly; initiation of Dyzantil therapy should then be gradual, with target dose being reached after about 2 weeks.
g. phenytoin, phenobarbital and carbamazepine. Once known enzyme inducers have been withdrawn it may be possible to maintain seizure control on a reduced dose of Dyzantil. When barbiturates are being administered concomitantly, and particularly if sedation is observed (particularly in children), the dosage of barbiturate should be reduced.
Optimum dosage is mainly determined by seizure control and routine measurement of plasma levels is unnecessary. 2). Method of administration Dyzantil 300 mg prolonged-release tablets are for oral administration. The tablets should be swallowed whole and […]
The haematological profile returned to normal when the drug was discontinued. 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 (sodium valproate has an inhibitory effect on the second phase of platelet aggregation).
4). 4). 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 valproate should be discontinued. Hyperammonaemia associated with neurological symptoms has also been reported. 4).
Nervous system disorders:
Sedation has been reported occasionally, usually when in combination with other anti-convulsants. 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 anti-convulsants, 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.
Gastrointestinal disorders:
Common gastrointestinal adverse events, such as nausea and vomiting, frequently occur at the start of treatment, but usually disappear after a few days without discontinuing treatment. These problems can usually be overcome by taking sodium valproate with or after food.
Hepatobiliary disorders:
Increased liver enzymes are common, particularly early in treatment, and may be transient. Severe liver damage, including hepatic failure sometimes resulting in death, has been reported.
Skin and subcutaneous tissue disorders:
Hair regrowth normally begins within six months, although the hair may become curlier than previously.
Musculoskeletal and connective tissue disorders:
There is a higher risk of osteoporosis and […]
Investigations, including clinical examination and biological assessment of liver function, should be undertaken immediately.
Detection:
Liver function should be measured before therapy and then periodically monitored during the first 6 months of therapy, especially for patients at risk and those with a prior history of liver disease. 5). Amongst usual investigations, tests which reflect protein synthesis, particularly prothrombin rate, are most relevant.
Confirmation of an abnormally low prothrombin rate, particularly in association with other biological abnormalities (significant decrease in fibrinogen and coagulation factors; increased bilirubin level and raised transaminases) requires cessation of Dyzantil therapy.
As a matter of precaution and in case they are taken concomitantly salicylates should also be discontinued since they employ the same metabolic pathway. As with most anti-epileptic drugs, increased liver enzymes are common, particularly at the beginning of therapy; they are also transient.
More extensive biological investigations (including prothrombin rate) are recommended in these patients; a reduction in dosage may be considered when appropriate and tests should be repeated as necessary.
Patients with known or suspected mitochondrial disease:
Valproate may trigger or worsen clinical signs of underlying mitochondrial diseases caused by mutations of mitochondrial DNA as well as the nuclear encoded POLG gene. g. Alpers- Huttenlocher Syndrome. POLG-related disorders should be suspected in patients with a family history or suggestive symptoms of a POLG-related disorder, including but not limited to unexplained encephalopathy, refractory epilepsy (focal, myoclonic), status epilepticus at presentation, developmental delays, psychomotor regression, axonal sensorimotor neuropathy, myopathy cerebellar ataxia, ophthalmoplegia, or complicated migraine with occipital aura.
3). 4).
Patients at risk of hypocarnitinaemia:
Valproate administration may trigger occurrence or worsening of hypocarnitinaemia that can result in hyperammonaemia (that may lead to hyperammonemic encephalopathy). Other symptoms such as liver toxicity, hypoketotic hypoglycaemia, myopathy including cardiomyopathy, rhabdomyolysis, Fanconi syndrome have been observed, mainly in patients with risk factors for hypocarnitinaemia or pre-existing hypocarnitinaemia.
Patients at increased risk for symptomatic hypocarnitinaemia when treated with valproate […]