Generic Drug Therapeutic Class: Neurology-Psychiatry
Active ingredients: Sodium Divalproate
laboratory: Sanofi-Aventis France
Box of 90
In the adult
Treatments of manic episodes of bipolar disorder in case of contraindications or intolerance to lithium. Continuation of treatment after the manic episode may be considered in patients who responded to sodium divalproate during the acute episode.
Dosage DEPAKOTE 250 mg gastroresistant tablet Box of 90
Manic episodes of bipolar disorder:
The daily dosage will be established and controlled individually by the doctor.
The recommended starting dose is 750 mg daily. In addition, in clinical trials, an initial dose of 20 mg / kg of sodium divalproate also showed a satisfactory safety profile.
The dosage will then be increased as quickly as possible to reach the minimum effective dose. The daily dosage should be tailored to each patient's clinical response to establish the minimum effective individual dose.
The average dosage is usually between 1000 and 2000 mg of sodium divalproate per day.
Patients receiving doses greater than 45 mg / kg / day should be carefully monitored.
Continuation of therapy following the manic episode of bipolar disorder should be individually adjusted using the minimum effective dose.
In the elderly
Changes in pharmacokinetic parameters were observed in this population (decreased clearance of free valproate, decreased binding of valproate to proteins). Caution regarding dosage determination is therefore recommended. The initial dose should be reduced and the dosage determined according to the clinical response.
In children and adolescents
The safety and efficacy of DEPAKOTE in the treatment of manic episodes of bipolar disorder have not been evaluated in patients younger than 18 years of age.
In case of abnormal renal or hepatic function (see sections Contraindications and Warnings and precautions for use ).
· History of hypersensitivity to valproate, divalproate, valpromide, or to any of the constituents of the drug.
· Acute hepatitis.
· Chronic hepatitis.
· Personal or family history of severe hepatitis, especially medication.
· Porphyria liver.
· Combination with mefloquine, St. John's wort (see section 4.5 ).
Adverse effects Depakote
Congenital, familial and genetic disorders
· Teratogenic risk (see section on Pregnancy and lactation ).
Blood and lymphatic system disorders
· Cases of dose-dependent thrombocytopenia, usually of systematic discovery and without clinical repercussions, have been described.
· In cases of asymptomatic thrombocytopenia, if the platelet count and the disease control allow, the only decrease in the dosage of this drug allows the regression of this thrombocytopenia.
· Cases of fibrinogen decrease, or prolongation of bleeding time, usually without clinical repercussions, have been reported mainly at high doses. Valproate has an inhibitory effect for the 2nd phase of platelet aggregation. More rarely have been reported cases of anemia, macrocytosis and leukopenia and exceptionally cases of pancytopenia.
· Global medullary aplasia or pure aplasia of the red line.
Nervous system disorders
· Transient and / or dose-related adverse events have been reported: fine attitude tremor and sedation.
· Infrequent cases of ataxia have been reported.
· Sometimes irreversible extrapyramidal disorders that may include reversible Parkinson's syndromes.
· Very rare cases of insidious and progressive cognitive impairment (which may produce a complete picture of dementia syndrome), reversible a few weeks to a few months after stopping treatment, have been described.
· Confusional or convulsive states: a few cases of stuporous states or lethargy, sometimes leading to transient coma (encephalopathy) on valproate, have been observed, regressing at the end of treatment or the reduction of doses. These conditions occur most often during combination therapies (phenobarbital or topiramate in particular) or sudden increase in doses of valproate.
· Isolated and moderate hyperammonemia without modification of hepatic bioassays is frequently observed, especially in combination therapy, and should not interrupt treatment.
· However, cases of hyperammonemia with neurologic symptoms (up to coma) have also been reported, requiring further investigation (see Warnings and Precautions ).
· Headaches have also been reported.
Affections of the ear and labyrinth
· Exceptionally, reversible or non-reversible hearing loss has been reported.
· Some subjects may have, at the beginning of treatment, digestive disorders (nausea, vomiting, gastralgia, diarrhea) which generally give up after a few days without interruption of the treatment.
· Very rare cases of pancreatitis have been reported requiring early discontinuation of treatment. Their evolution is sometimes fatal (see section Warnings and precautions for use ).
Renal and urinary disorders
· Exceptionally, cases of renal damage have been reported.
· Very rare cases of enuresis and urinary incontinence have been reported.
Skin and subcutaneous tissue disorders
· Passive and / or dose-dependent hair loss has been reported.
· Skin reactions such as exanthematous rash have been observed. Exceptional cases of Lyell syndrome, Stevens-Johnson syndrome, and erythema multiforme have also been reported.
Metabolism and nutrition disorders
· Very rare cases of hyponatremia.
· Inappropriate secretion syndrome of the anti-diuretic hormone (S IADH).
General disorders and administration site conditions
· Weight gain has been observed. As these are a risk factor for the occurrence of polycystic ovary syndrome, the weight of the patients should be carefully monitored (see Warnings and precautions for use ).
· Very rare cases of non-severe peripheral edema have been reported.
Immune system disorders
· Angioedema, DRESS syndrome (Drug Rash with Eosinophilia and Systemic Symptoms) or drug hypersensitivity syndrome.
· Hepatopathies (see section Warnings and precautions for use )
Disorders of reproductive organs and breast
· Amenorrhea and menstrual irregularities.
· An impact on spermatogenesis is evoked (decreased sperm motility in particular (see section on Pregnancy and breastfeeding )).
Musculoskeletal and systemic disorders
· Cases of decreased bone mineral density, osteopenia, osteoporosis and fractures have been reported in long-term patients treated with DEPAKOTE. The mode of action of DEPAKOTE on bone metabolism is not known.