Universal reference book for medicines
Product name: DEPAKINE ® (DEPAKINE ® )

Active substance: valproic acid

Type: Anticonvulsant drug

Manufacturer: SANOFI-AVENTIS FRANCE (France) manufactured by GRUPPO LEPETIT (Italy)
Composition, form of production and packaging

Lyophilizate for the preparation of a solution for intravenous administration in the form of compressed porous mass from white to almost white;
allowed the presence of individual fragments of mass; The applied solvent is a colorless transparent liquid.
1 f.

sodium valproate 400 mg

Solvent: water d / u - 4 ml.

400 mg - bottles of glass (1) complete with a solvent (1 pc.) - packings of cellular contoured plastic without covering (pallets) (1) - packs cardboard internal (4) - packs cardboard.

INSTRUCTION FOR THE SPECIALIST.

Description of the drug approved by the manufacturer for the printed edition of 2017.

PHARMACHOLOGIC EFFECT

Anticonvulsant drug.
Has an anticonvulsant effect, is effective in various forms of epilepsy.
Experimental and clinical data indicate the existence of two mechanisms of anticonvulsant action of the drug Depakin ® .
The first is a direct pharmacological action associated with the concentration of valproic acid in the blood plasma and brain tissues, which affects the GABA -ergic system, causing an increase in GABA concentration in the CNS and activating GABA-ergic transmission. The second - apparently, is an indirect pharmacological action associated with remaining in the brain metabolites of valproic acid, either with changes in neurotransmitters or direct exposure to cell membranes.
PHARMACOKINETICS

Suction

The bioavailability of valproic acid with an iv administration is 100%.
Usually, serum concentrations of valproic acid of 40-100 mg / l (300-700 μmol / L) are effective (determined before taking the first dose of the drug within 24 hours). With the justified need to achieve higher concentrations of valproic acid in blood plasma, the ratio of expected benefits and the risk of side effects, especially dose-dependent, should be weighed carefully. at concentrations of valproic acid of more than 100 mg / l, an increase in side effects is expected up to the development of intoxication.
When the plasma concentration of valproic acid is more than 150 mg / l, a dose reduction is required.

When the course of the drug C ss in the blood serum is achieved within 3-14 days.

Distribution

Binding to plasma proteins (mainly with albumin) is high (90-95%), dose-dependent and saturable.

V d depends on the age and is usually 0.13-0.23 l / kg body weight or in young people 0.13-0.19 l / kg body weight.

Valproic acid penetrates into the cerebrospinal fluid and into the brain.
The concentration of valproic acid in the cerebrospinal fluid is 10% of the corresponding concentration in the plasma.
Valproic acid penetrates into breast milk from nursing mothers.
In the equilibrium state, the concentration of valproic acid in breast milk is 1-10% of its plasma concentration.
Metabolism

Metabolized by beta, omega and omega-1 oxidation and conjugation with glucuronic acid.
Isolated more than 20 metabolites, metabolites after omega-oxidation have a hepatotoxic effect.
Valproic acid does not have an inducing effect on the isoenzymes of the cytochrome P450 system: unlike most other antiepileptic drugs, valproic acid does not affect the extent of both its own metabolism and the degree of metabolism of other drugs such as estrogens, progestogens and indirect anticoagulants.

Excretion

It is excreted mainly with urine after beta oxidation and conjugation.
T 1/2 is 15-17 hours. The plasma clearance of valproic acid in patients with epilepsy is 12.7 ml / min.
Pharmacokinetics in special clinical cases

In elderly patients, patients with renal and hepatic insufficiency, binding to plasma proteins decreases.
In severe renal failure, the concentration of the free (therapeutically active) fraction of valproic acid may increase to 8.5-20%.
With hypoproteinemia, the total concentration of valproic acid (free + associated with plasma proteins of the fraction) may not change, but may decrease due to an increase in the metabolism of free valproic acid fraction (not associated with blood plasma proteins).

When combined with antiepileptic drugs that induce microsomal liver enzymes, the plasma clearance of valproic acid increases, and T 1/2 decreases, the degree of their change depends on the degree of induction of microsomal liver enzymes with other antiepileptic drugs.

The values ​​of T 1/2 in children over the age of 2 months are close to those of adults.

In patients with liver disease, T 1/2 valproic acid increases.

Overdose showed an increase in T 1/2 to 30 h.

Only free valproic acid in the blood is subject to hemodialysis (10%).

Peculiarities of pharmacokinetics in pregnancy

With an increase in V d of valproic acid in the III trimester of pregnancy, its renal and hepatic clearance increases.
In this case, despite taking the drug in a constant dose, it is possible to reduce the concentration of valproic acid in the plasma. In addition, during pregnancy, a change in the degree of binding of valproic acid to blood plasma proteins is possible, which may lead to an increase in the serum content of the free (therapeutically active) fraction of valproic acid.
INDICATIONS

The injection dosage form of valproic acid is indicated for the temporary replacement of its oral dosage forms, the use of which is temporarily impossible.

Adults

As a monotherapy or in combination with other antiepileptic drugs:

- generalized epileptic seizures (clonic, tonic, tonic-clonic, absences, myoclonic, atonic);

- Lennox-Gastaut syndrome;

- partial epileptic seizures (partial seizures with or without secondary generalization).

Children

As a monotherapy or in combination with other antiepileptic drugs:

- generalized epileptic seizures (clonic, tonic, tonic-clonic, absences, myoclonic, atonic);

- Lennox-Gastaut syndrome;

- partial epileptic seizures (partial seizures with or without secondary generalization).

Preventing seizures at high temperature, when such prevention is necessary.

DOSING MODE

Simple replacement therapy (eg, before surgery)

After 4-6 hours after the last oral dose, I / O is injected with a solution diluted with sodium chloride solution for injection (0.9%):

-or in the form of continuous infusion of the previously used dose during the day;

-or in the form of 4 infusions, the duration of 1 hour (in this case with each infusion introduced 1/4 of the previously used daily dose).

The usual average dose is 20-30 mg / kg / day.

Situations requiring rapid achievement and maintenance of effective concentration of valproic acid in blood plasma

Intravenous bolus administration of the drug at a dose of 15 mg / kg for 5 minutes;
then the administration is continued as a constant IV infusion at a rate of 1 mg / kg / h, with a gradual correction of the rate of administration to provide a valproic acid concentration in the blood of about 75 mg / l. Further, the rate of administration changes depending on the clinical picture.
After discontinuation of the infusion, the transition to treatment with oral forms of the drug Depakin ® can occur with the use of the previous dose or dose, adjusted for the clinical condition of the patient.

Special patient groups

Female children and adolescents, women with childbearing potential and pregnant women: treatment with Depakin ® should be started under the supervision of a specialist with experience in the treatment of epilepsy and bipolar disorders.
Treatment should be started only if other treatments are ineffective or not tolerated, and with a regular review of treatment, the benefit / risk ratio should be carefully reassessed. The use of Depakin ® for monotherapy and at the lowest effective doses and, if possible, in sustained release dosage forms is preferred. During pregnancy, the daily dose should be divided, at least, into 2 single doses.
Although elderly patients have a change in the pharmacokinetics of valproic acid, they are of limited clinical relevance, and the dose of valproic acid in elderly patients should be selected in accordance with the achievement of control over epileptic seizures.

In patients with renal insufficiency and / or hypoproteinemia , the possibility of increasing the concentration of the free (therapeutically active) fraction of valproic acid in the blood serum should be taken into account, and, if necessary, to reduce the dose of valproic acid, guided by the dose selection, mainly on the clinical picture, and not on the total content valproic acid in the serum (free fraction and fraction associated with blood plasma proteins) to avoid possible errors in the selection of the dose.

SIDE EFFECT

Determination of the frequency of adverse reactions (WHO classification): very often (? 10%), often (? 1% and <10%), infrequently (? 0.1% and <1%), rarely (≥0.01% and <0.1%), very rarely (<0.01%) , the frequency is unknown (it is impossible to determine from the available data).

Congenital, hereditary and genetic disorders: teratogenic risk.

From the hemopoietic system: often - anemia, thrombocytopenia;
infrequently - pancytopenia, leukopenia, neutropenia. Leukopenia and pancytopenia can be both with depression of bone marrow hematopoiesis, and without it. After the drug is stopped, the blood picture returns to normal.
From the coagulation system: often - bleeding and hemorrhage;
rarely - reducing the content of clotting factors (at least one), the deviation from the norm of blood coagulability (such as an increase in prothrombin time, an increase in APTT, an increase in thrombin time, an increase in MHO). The emergence of spontaneous ecchymosis and bleeding requires withdrawal of the drug and clinical and laboratory examination.
From the nervous system: very often - a tremor;
often - extrapyramidal disorders, stupor *, drowsiness, convulsions *, memory problems, headache, nystagmus, dizziness (may occur several minutes after IV injection and disappear spontaneously within a few minutes); infrequently - coma *, encephalopathy *, lethargy *, reversible parkinsonism, ataxia, paresthesia, increased severity of seizures; rarely - reversible dementia, combined with reversible brain atrophy, cognitive disorders;frequency unknown - sedation.
* Stent and lethargy sometimes lead to transient coma / encephalopathy and were either isolated, or combined with increased frequency of convulsive attacks on the background of treatment, and also decreased with the withdrawal of the drug or with a decrease in its dose.
Most of these cases have been described against a background of combination therapy, especially with the simultaneous use of phenobarbital or topiramate, or after a dramatic increase in the dose of valproic acid.
From the side of the psyche: infrequently - the state of confusion, aggression **, agitation **, attention impairment **, depression (with the combination of valproic acid with other anticonvulsant drugs);
rarely - behavioral disorders **, psychomotor hyperactivity **, learning disability **, depression (with monotherapy with valproic acid).
** adverse reactions, mainly observed in patients of childhood.

From the senses: often - reversible and irreversible deafness;
frequency is unknown - diplopia.
From the side of the digestive system: very often - nausea;
often vomiting, gum changes (mainly gum hyperplasia), stomatitis, epigastric pain, diarrhea (which often occur in some patients at the beginning of treatment, but usually disappear after a few days and do not require discontinuation of therapy); infrequently - pancreatitis, sometimes with a fatal outcome (the development of pancreatitis is possible during the first 6 months of treatment, in the case of acute pain in the abdomen, it is necessary to control the activity of serum amylase); frequency unknown - abdominal cramps, anorexia, increased appetite. Frequent reactions from the digestive system can be reduced by taking the drug during or after a meal.
From the liver and biliary tract: often - liver damage, which is accompanied by a deviation from the norm of indicators of the functional state of the liver, such as a decrease in the prothrombin index, especially in combination with a significant decrease in fibrinogen and clotting factors, an increase in bilirubin concentration and an increase in hepatic transaminase activity in blood;
hepatic insufficiency, in exceptional cases with a fatal outcome. It is necessary to monitor patients for possible violations of liver function.
From the respiratory system: infrequently - pleural effusion.

From the side of the urinary system: infrequently - kidney failure;
rarely - enuresis, tubulointerstitial nephritis, reversible Fanconi syndrome (a complex of biochemical and clinical manifestations of renal tubular damage with violation of tubular reabsorption of phosphate, glucose, amino acids and bicarbonate), the development mechanism of which is still unclear.
From the immune system: often - hypersensitivity reactions, for example, urticaria;
infrequently - angioedema; rarely - a syndrome of drug rash with eosinophilia and systemic symptoms (DRESS-syndrome).
From the skin and subcutaneous tissues: often - transient or dose-related alopecia (including androgenic alopecia against the background of developed hyperandrogenism, polycystic ovary, as well as alopecia against the background of developed hypothyroidism), abnormalities from the nails and the nail bed;infrequent - rash, hair disorders (such as abnormal hair structure, hair color changes, abnormal hair growth [disappearance of waviness and curly hair or, conversely, the appearance of curly hair in persons with initially straight hair]);
rarely - toxic epidermal necrolysis, Stevens-Johnson syndrome, erythema multiforme).
From the musculoskeletal system and connective tissue: infrequent - decrease in bone mineral density, osteopenia, osteoporosis and fractures in patients taking valproic acid for a long time (the mechanism of valproic acid's influence on bone metabolism is not established);
systemic lupus erythematosus.
On the part of the endocrine system: infrequently - the syndrome of inadequate secretion of ADH, hyperandrogenism (hirsutism, virilization, acne, alopecia in masculine type and / or increasing concentrations of androgens in the blood);
rarely - hypothyroidism.
From the side of metabolism: often - hyponatremia, weight gain (because weight gain is a factor contributing to the development of polycystic ovary syndrome);rarely - hyperammonia *, obesity.

* There may be cases of isolated and moderate hyperammonemia without changing the indicators of liver function and the need for cessation of treatment.
Also reported the emergence of hyperammonemia, accompanied by the appearance of neurologic symptoms, incl. development of encephalopathy, vomiting, ataxia), which required the discontinuation of valproic acid and additional examination.
From the side of the vessels: infrequently - vasculitis.

On the part of the reproductive system: often - dysmenorrhea;
infrequently - amenorrhea; rarely - male infertility, polycystic ovary; frequency is unknown - dysmenorrhea, breast enlargement, galactorrhea.
Benign, malignant and vague tumors (including cysts and polyps): rarely - myelodysplastic syndrome.

Common disorders: infrequent - hypothermia, mild peripheral edema.

Laboratory and instrumental data: rarely - biotin deficiency / biotinidase deficiency.

CONTRAINDICATIONS

- Hypersensitivity to sodium valproate, valproic acid, semenatrium valproate, valpromide or to any of the auxiliary components of the drug;

acute hepatitis;

- chronic hepatitis;

- severe liver disease (especially drug-induced hepatitis) in an anamnesis of the patient and his close blood relatives;

- severe liver damage with lethal outcome when using valproic acid in close blood relatives of the patient;

- hepatic porphyria;

- established mitochondrial diseases caused by mutations of the nuclear gene encoding the mitochondrial enzyme-polimerase (POLG), for example, Alpers-Huttenlohera syndrome, and suspected diseases caused by defects of α-polymerase in children under 2 years of age;

- Patients with established disorders of urea carbamide (urea cycle);

- hemorrhagic diathesis, thrombocytopenia;

- combination with mefloquine;

- a combination with preparations of St. John's wort perfumed.

Carefully

- in children under 3 years of age (due to an increased risk of liver damage);


- liver and pancreatic disease in history;

- Pregnancy;

- congenital fermentopathy;

- oppression of bone marrow hematopoiesis (leukopenia, thrombocytopenia, anemia);

- Renal insufficiency (correction of doses is required);

- hypoproteinemia;

- simultaneous administration of several anticonvulsants (due to an increased risk of liver damage);

- simultaneous administration of drugs, provoking seizures or reduce seizure threshold, such as tricyclic antidepressants, selective serotonin reuptake inhibitor; phenothiazine derivatives, butyrophenone derivatives, chloroquine, bupropion, tramadol (risk of provoking seizures);
- simultaneous reception neuroleptics, MAO inhibitors, antidepressants, benzodiazepines (the ability of potentiating effects);
- simultaneous reception phenobarbital, primidone, phenytoin, lamotrigine, zidovudine, felbamate, olanzapine, propofol, aztreonam, acetylsalicylic acid, anticoagulants, cimetidine, erythromycin, carbapenems, rifampicin, nimodipine, rufinamida (especially in children), protease inhibitor (lopinavir, ritonavir ), cholestyramine (in connection with the pharmacokinetic interaction at the level of metabolism or binding to plasma proteins may change or plasma concentrations of these agents and / or valproic acid);
- simultaneous with carbamazepine (risk of potentiating the toxic effects of carbamazepine and lowering plasma concentrations of valproic acid);
- Simultaneous reception with topiramate and acetazolamide (risk of encephalopathy);
- in patients with carnitine palmitoyltransferase deficiency available (CBT) of type II (the higher the risk of rhabdomyolysis with valproic acid).
PREGNANCY AND LACTATION

The risk associated with the development of epileptic seizures during pregnancy. During pregnancy, the development of generalized tonic-clonic seizures, status epilepticus with hypoxia may be of particular risk for both the mother and the fetus, due to the possibility of death.
The risk associated with the use of the drug Depakine ® during pregnancy. Experimental studies of reproductive toxicity in mice, rats and rabbits have shown the presence of valproate teratogenicity.
Congenital malformations.The available clinical data demonstrated greater frequency of small and severe malformations, such as congenital neural tube defects, craniofacial deformities, malformations of the limbs and the cardiovascular system, hypospadias and multiple malformations affecting different organ systems in children born to mothers who had taken during pregnancy valproic acid, as compared with their frequency in the reception during pregnancy a number of other anti-epileptic drugs. Thus, the risk of congenital malformations in infants born to mothers with epilepsy, monotherapy with valproic acid during pregnancy was approximately 1.5, 2.3, 2.3 and 3.7 times higher compared to monotherapy with phenytoin, carbamazepine, phenobarbital and lamotrigine, respectively.
Meta-analysis involving register and cohort studies have shown that the incidence of congenital defects in babies born to mothers with epilepsy who received during pregnancy monotherapy valproic acid was 10.73% (95% confidence interval 8.16-13.29). This risk is greater than the risk of severe birth defects in the general population is 2-3%. This risk is dose-dependent. but the threshold dose below which there is no such risk, it is not possible to establish.
Impaired mental and physical development.It is shown that prenatal exposure to valproic acid could have adverse effects on mental and physical development of children exposed to such exposure. Apparently, this risk is dose-dependent, but the threshold dose below which there is no such risk, it is not possible to establish. The exact gestation period for the risk of these effects is not set, and the risk can not be excluded throughout the pregnancy. Studies of preschool children exposed in utero to valproic acid, has shown that up to 30-40% of these children had delays of early development (such as the delay in mastering the skills of walking and speech delay), and lower intellectual ability, poor language skills (on site speech and speech understanding), and memory problems.Intelligence Quotient (IQ index) determined in children aged 6 years of age with a history of in utero exposure to valproate had an average of 7-10 points lower than children exposed in utero effects of other anti-epileptic drugs. Although we can not exclude the role of other factors that could undesirably affect the intellectual development of children exposed in utero to valproic acid, it is clear that these children risk of intellectual disability can be independent of the index of IQ mother.can undesirably affect the intellectual development of children exposed in utero to valproic acid, it is clear that these children risk of intellectual disability can be independent of the index of IQ mother.can undesirably affect the intellectual development of children exposed in utero to valproic acid, it is clear that these children risk of intellectual disability can be independent of the index of IQ mother.
Data on long-term outcomes are limited.
There is evidence in favor of the fact that children exposed in utero effects of valproic acid have an increased risk of developing the spectrum of autistic disorders spectrum (approximately three-five-fold increase in risk), including children with autism.
Limited data support the fact that children exposed prenatally exposed to valproic acid, it has a greater likelihood of developing attention deficit / hyperactivity disorder (ADHD).
Valproate monotherapy and combination therapy with inclusion of valproic acid are associated with a poor outcome of pregnancy, but according to reports, combined antiepileptic therapy comprising valproic acid, associated with a higher risk of adverse outcome of pregnancy, compared with valproate monotherapy (i.e. the risk of abnormalities in the fetus is less than in the application of valproic acid, when used as monotherapy).
Risk factors for fetal malformations are a dose of 1000 mg / day (yet smaller dose does not exclude this risk) and a combination of valproic acid with other anticonvulsant.
In connection with the above, the drug Depakinum ®should not be used during pregnancy and in women with childbearing potential unless absolutely necessary, ie its use is possible only in situations where other antiepileptic drugs are ineffective or the patient can not tolerate them.
The question of the need for drug Depakine ® , or the possibility of rejection of his application must be resolved before the start of the drug or revised if a woman takes the drug Depakine ® , planning to become pregnant.
Women with childbearing potential must use effective contraception during treatment with Depakine ® .
Women with childbearing potential should be informed of the risks and benefits of the use of valproic acid during pregnancy.
If a woman is planning to become pregnant, or her pregnancy is diagnosed, it is necessary to reassess the need for treatment with valproic acid.
If, after reassessment of the benefit and risk ratio of treatment with Depakine ® should still be continued during pregnancy, it is recommended to apply it in the lowest effective daily dose divided into several stages. It should be noted that in pregnancy more preferred is the use of sustained release dosage forms of the drug than the other formulations.
Further, if possible, before pregnancy should begin further folic acid supplementation (5 mg / day), because folic acid can reduce the risk of neural tube defects. However, the currently available data do not support its preventive action against congenital malformations caused by the action of valproic acid.
There should be a constant (including in the III trimester) special prenatal diagnosis to detect possible defects forming the neural tube or other malformations of fetal development, including the detailed ultrasound.
Risk to newborns.It reported on the development of sporadic cases of hemorrhagic syndrome in newborns whose mothers took valproic acid during pregnancy. This hemorrhagic syndrome associated with thrombocytopenia, hypofibrinogenemia, and / or a decrease in the content of other blood coagulation factors. It was also reported on the development of afibrinogenemia, which could lead to death. This hemorrhagic syndrome should be distinguished from vitamin K deficiency caused by phenobarbital and other inducers of microsomal liver enzymes.
Therefore neonates whose mothers are treated with drugs valproic acid during pregnancy, it is essential to carry out coagulation tests (to determine the number of platelets in peripheral blood, the plasma concentration of fibrinogen, coagulation factors and coagulation).
It reported cases of hypoglycemia in newborns whose mothers took valproic acid in the III trimester of pregnancy.
Reported cases of hypothyroidism in newborns whose mothers took valproic acid during pregnancy.
In infants whose mothers took valproic acid III trimester of pregnancy can occur withdrawal syndrome (in particular the appearance of agitation, irritability, hyperreflexia, jitter, hyperkinesia, muscle tone disorders, tremor, seizures, and difficulty in feeding).
Fertility

In connection with the possibility of dysmenorrhea. amenorrhea, polycystic ovaries, increasing the concentration of testosterone in the blood may reduce fertility in women. In men, valproic acid can reduce sperm motility and fertility break. It was found that these fertility disorders are reversible after discontinuation of treatment.
Lactation
Excretion of valproic acid in breast milk is low, its concentration in milk is 1-10% of its serum concentration.
There are limited clinical data on the application of valproic acid at breastfeeding, and therefore the use of the drug is not recommended at this time.
Based on data from the literature and little clinical experience, it is possible to consider breastfeeding when monotherapy Depakine ® , but it should take into account the side-effect profile of the drug, especially caused them haematological disorders.
APPLICATION FOR VIOLATIONS OF THE FUNCTION OF KIDNEYS

Contra-indications: acute hepatitis; chronic hepatitis; severe liver disease (especially drug-induced hepatitis) in the history of the patient and his close blood relatives; severe liver damage with lethal when using valproic acid in close blood relatives of the patient; hepatic porphyria.
APPLICATION FOR CHILDREN

Precautions: children under 3 years because of the increased risk of liver damage.
SPECIAL INSTRUCTIONS

Before the start of the drug Depakinum ® and periodically during the first 6 months of treatment, especially in patients at risk of development of liver injury, be carried out of the liver function.
As with most anti-epileptic drugs, in the application of valproic acid, a slight increase in liver enzymes, especially at the beginning of treatment, which occurs without clinical symptoms and is transient. These patients need to conduct a more detailed study of biological parameters, including prothrombin index, and may require adjustment of dose, and if necessary re-examination of the clinical and laboratory.
Before therapy or surgery, in the case of spontaneous subcutaneous hematoma or hemorrhage determination is recommended bleeding time, number of formed elements in peripheral blood, including platelet count).
Severe liver disease
predisposing factors. Clinical experience suggests that patients at risk are patients receiving multiple antiepileptic drugs, children under 3 years with severe convulsive attacks, especially against brain damage, mental retardation and / or congenital metabolic or degenerative disease; Patients concurrently taking salicylates (as salicylates metabolised by the same pathway as that of valproic acid).
In children older than 3 years, the risk of liver damage is significantly reduced and progressively decreases with increasing patient age. In most cases, liver damage occurs during the first 6 months of treatment, most often between 2 and 12 weeks of treatment and generally when using valproic acid in a combination of antiepileptic therapy.
Symptoms suggestive of liver damage. For early diagnosis of liver damage necessarily clinical monitoring of patients. In particular should pay attention to the following symptoms that may precede the appearance of jaundice, especially in patients at risk:
- non-specific symptoms, especially sudden onset, such as asthenia, anorexia, lethargy, drowsiness, sometimes accompanied by repetitive vomiting and abdominal pain;
- the resumption of seizures in patients with epilepsy.
It should warn patients or their families (when using the drug children) that they should immediately report any of these symptoms your doctor. In case of these symptoms, patients should carry out a clinical examination immediately and laboratory research of liver function.
Identification.Determination of liver function tests should be performed before treatment and then periodically during the first 6 months of treatment. Among the conventional studies are most informative studies, reflecting the state of the protein-synthetic liver function, especially prothrombin index. Confirmation abnormal prothrombin index, especially in combination with abnormalities other laboratory parameters (significant reduction in fibrinogen and clotting factors, the increase in the concentration of bilirubin and an increase of transaminases), and the appearance of other symptoms indicating liver damage requires discontinuation of preparation Depakinum ® . For safety purposes, if patients took both salicylates and their reception should also be terminated.
Pancreatitis

There are registered rare cases of severe pancreatitis in children and adults, develop independently of the age and duration of treatment. There have been several cases of hemorrhagic pancreatitis with rapid progression of symptoms from disease or death.
Children are at increased risk of pancreatitis, with increasing age of the child, this risk is reduced. Severe seizures, neurological disorders or anticonvulsant therapy may be risk factors for pancreatitis. Liver failure, combined with pancreatitis increases the risk of death.
Patients who develop severe abdominal pain, nausea, vomiting and / or anorexia, should be immediately examined. If confirmed pancreatitis in
Alphabetical index of medicines:
A  B  V  G  D  E  J
Z  I  Y  K  L  M  N
O  P  R  S  T  U  F
H  C  CH  SH  E  U  Y
Rambler's Top100
Privacy policy:
Copyright 2009 - 2017. Universal reference book of medicines. All rights reserved.
When using site materials, an active hyperlink is required!