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

Active substance: valproic acid

Type: Anticonvulsant drug

Manufacturer: SANOFI WINTHROP INDUSTRIE (France)
Composition, form of production and packaging

Tablets of prolonged action, covered with a shell of almost white color, oblong, with risk from both sides.

1 tab.

sodium valproate * 199.8 mg

valproic acid * 87 mg

Auxiliary substances: methylhydroxypropyl cellulose 4000 mPa.s (hypromellose) 105.6 mg, ethylcellulose (20 mPa.s) 7.2 mg, sodium saccharin 6 mg, silicon dioxide colloid hydrated 32.4 mg methylhydroxypropylcellulose 6 mPa.s (hypromellose) 4.8 mg mg, 30% dispersion of polyacrylate - 16 mg, macrogol 6000 - 4.8 mg, talc - 4.8 mg, titanium dioxide - 0.8 mg.

50 pcs.
- Vials of polypropylene (2) - packs cardboard.
Tablets of prolonged action, covered with a shell of almost white color, oblong, with risk from both sides.

1 tab.

sodium valproate ** 333 mg

valproic acid ** 145 mg

Auxiliary substances: silicon dioxide colloidal anhydrous - 4 mg, methyl hydroxypropylcellulose 4000 mPa.s (hypromellose) - 176 mg, ethylcellulose (20 mPa.s) - 12 mg, sodium saccharin - 10 mg, silicon dioxide colloid hydrated - 50 mg, methylhydroxypropylcellulose 6 mPa.s (hypromellose) 7.2 mg, 30% dispersion of polyacrylate 24 mg, macrogol 6000 7.2 mg, talc 7.2 mg, titanium dioxide 1.2 mg.

30 pcs.
- vials of polypropylene (1) - packs cardboard.
* corresponds to 300 mg of valproic acid in 1 tab.

** corresponds to 500 mg of valproic acid in 1 tablet.

INSTRUCTION FOR THE SPECIALIST.

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

PHARMACHOLOGIC EFFECT

An anticonvulsant drug, has a central muscle relaxant and sedative effect.
It shows antiepileptic activity in all types of epilepsy.
The main mechanism of action, apparently, is associated with the influence of valproic acid on the GABA -ergic system: an increase in the GABA (GABA) content in the central nervous system and the activation of GABA -ergic transmission.

PHARMACOKINETICS

Suction

The bioavailability of sodium valproate and valproic acid when administered is close to 100%.

When taking Depakin ® chrono 500 mg tablets at a dose of 1000 mg / day C min in plasma is 44.7 ± 9.8 μg / ml, and C max in plasma is 81.6 ± 15.8 μg / ml.
T max in plasma is 6.58 ± 2.23 hours. C ss in plasma is achieved within 3-4 days of regular intake of the drug.
The average therapeutic range of serum concentrations of valproic acid is 50-100 mg / l.
With the justified need to achieve a higher concentration of valproic acid in blood plasma, the ratio of expected benefit and the risk of side effects, especially dose-dependent, should be weighed carefully. at a valproic acid concentration of more than 100 mg / l, an increase in side effects is expected up to the development of intoxication. At a plasma concentration of more than 150 mg / l, a dose reduction is required.
Compared to the enteric coated dosage form, the sustained-release tablet formulation in equivalent doses is characterized by the absence of a latent absorption time, prolonged by absorption, identical to bioavailability, less C max ( Cmax decrease of about 25%), but with more stable plateau phase from 4 to 14 hours after administration, a more linear correlation between dose and plasma concentration of the drug.

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 by the kidneys after beta oxidation and conjugation with glucuronic acid.
Less than 5% of valproic acid is excreted by the kidneys unchanged.
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 third 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

Adults

As a monotherapy or in combination with other antiepileptic drugs:

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

- Lennox-Gastaut syndrome;

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

Treatment and prevention of bipolar affective disorders.

Children

AT
as a monotherapy or in combination with other antiepileptic drugs:
- treatment of generalized epileptic seizures (clonic, tonic, tonic-clonic, absences, myoclonic, atonic);

- Lennox-Gastaut syndrome;

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

DOSING MODE

Depakin ® chrono is intended only for adults and children over 6 years old with a body weight of more than 17 kg.

Depakin ® chrono is a sustained release dosage form, this avoids the sudden rise in valproic acid concentration in the blood after taking the drug and prolongs the constant concentration of valproic acid in the blood for a day.

Long-acting tablets Depakin ® chrono 300 mg or 500 mg can be divided to facilitate the reception of an individually selected dose.

Tablets are taken without crushing or chewing them.

Epilepsy

The doctor chooses a daily dose individually.

To prevent the development of epileptic seizures, the drug should be used at the lowest effective dose (especially in pregnancy).

The daily dose is set according to the age and body weight of the patient.
A stepwise (gradual) increase in the dose is recommended until the minimum effective dose is reached.
There was no clear relationship between the daily dose, plasma concentration and therapeutic effect.
Therefore, the optimal dose should be set mainly on the clinical response. Determining the level of valproic acid in plasma can serve as a supplement to clinical observation if epilepsy is not controlled or there is a suspicion of side effects. The range of therapeutic concentration in the blood is usually 40-100 mg / l (300-700 μmol / l).
In monotherapy, the initial dose is usually 5-10 mg valproic acid per kg body weight, then gradually increase this dose every 4-7 days at a rate of 5 mg valproic acid per kg body weight to the dose necessary to achieve control of epileptic seizures.

Average daily doses (with prolonged use):

for children 6-14 years (body weight 20-30 kg) - 30 mg valproic acid / kg body weight (600-1200 mg);

for adolescents (body weight 40-60 kg) - 25 mg valproic acid / kg body weight (1000-1500 mg);

for adults and elderly patients (body weight from 60 kg and above) - an average of 20 mg valproic acid / kg body weight (1200-2100 mg).

Although the daily dose is determined depending on the age and body weight of the patient, a wide range of individual sensitivity to valproate should be taken into account.

If epilepsy can not be controlled at such doses, they can be increased under the control of the patient's condition and the concentration of valproic acid in the blood.
In some cases, the full therapeutic effect of valproic acid does not appear immediately, but develops within 4-6 weeks. Therefore, do not increase the daily dose above the recommended average daily dose before this time.
The daily dose can be divided into 1-2 administrations, preferably during meals.

Use in one dose is possible with well-controlled epilepsy.

Most patients who are already taking Depakin ® in a non-prolonged-release dosage form can be transferred to Depakin ® chrono immediately or for several days, and patients should continue to take the previously selected daily dose.

For patients who have taken antiepileptic drugs earlier, transfer to the drug Depakin ® chrono should be carried out gradually, reaching the optimal dose of the drug for about 2 weeks.
It should immediately reduce the dose of antiepileptic drug, which the patient took earlier, especially if it is phenobarbital. The abolition of the antiepileptic drug, which the patient took earlier, should be carried out gradually.
Because
other antiepileptic drugs can reversibly induce microsomal liver enzymes, should monitor the concentration of valproic acid in plasma 4-6 weeks after taking the last dose of these antiepileptic drugs and, if necessary (as the metabolic-inducing effect of these drugs decreases), reduce the daily dose of valproic acid.
If necessary, combinations of valproic acid with other antiepileptic drugs should be added gradually to treatment.

Manic episodes with bipolar disorders

Adults

The doctor chooses a daily dose individually.

The recommended initial daily dose is 750 mg.
In addition, clinical studies also show an acceptable safety profile for the initial dose of 20 mg of sodium valproate per kg of body weight.
Depakin ® chrono can be taken 1 or 2 times / day.
The dose should be increased as soon as possible until a minimum effective therapeutic dose is achieved, which causes the desired clinical effect.
The average daily dose is in the range of 1000-2000 mg of sodium valproate.

Patients receiving a daily dose of more than 45 mg / kg / day should be under close medical supervision.

When continuing treatment of manic episodes with bipolar disorders, the drug is used in an individually selected minimum effective dose.

Children and teens

The efficacy and safety of the drug in the treatment of manic episodes in bipolar disorders in patients younger than 18 years of age have not been evaluated.

Special patient groups

Children and adolescents of the female, women with childbearing potential and pregnant women: treatment with Depakin ® Chrono 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 importance, 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.
Of the liver and biliary tract: often - liver disease, which is accompanied by abnormal parameters of the functional state of the liver, such as reducing prothrombin index, especially when combined with a significant decrease in fibrinogen and coagulation factors, increased bilirubin concentration and an increase in liver transaminases blood; liver failure, in exceptional cases, with fatal consequences. Necessary to monitor patients for possible liver dysfunction.
The respiratory system: rarely - pleural effusion.
From the urinary system:rarely - renal failure; rarely - enuresis, tubulointerstitial nephritis, reversible Fanconi syndrome (complex biochemical and clinical manifestations of renal tubules with impaired tubular reabsorption of phosphate, glucose, amino acids and bicarbonate), of the mechanism of which is unclear.
Immune system: often - hypersensitivity reactions such as hives; infrequently - angioedema; rarely - syndrome drug rash with eosinophilia and systemic symptoms (DRESS-syndrome).
Skin and subcutaneous tissue disorders:often - transient and dose-dependent alopecia (including androgenic alopecia evolved against a background of hyperandrogenism, polycystic ovaries, and alopecia on the background of established hypothyroidism), disorders of the nail and nail bed; seldom - rash, disorders of the hair (such as disturbance of the normal structure of the hair, change in hair color, abnormal hair growth [disappearance of the undulations and hair curl, or, on the contrary, the appearance of the hair curl in patients with initially straight hair]); seldom - toxic epidermal necrolysis, Stevens-Johnson syndrome, erythema multiforme).
On the part of the musculoskeletal system and connective tissue:infrequently - decrease in bone mineral density, osteopenia, osteoporosis and fractures in patients receiving long valproic acid (mechanism of the effect of valproic acid on bone metabolism is not installed); systemic lupus erythematosus.
Endocrine system: infrequently - syndrome of inappropriate secretion of ADH, hyperandrogenism (hirsutism, virilization, acne, male pattern alopecia and / or an increase in androgen concentrations in the blood); rarely - hypothyroidism.
Metabolism: often - hyponatremia, increased body weight (weight gain as a factor contributing to the development of polycystic ovary syndrome); rarely - * hyperammonemia, obesity.
* May be cases isolated and moderate hyperammonemia without changes in liver function and the need to stop treatment. It was also reported the occurrence of hyperammonemia, accompanied by the appearance of neurological symptoms, including encephalopathy, emesis, ataxia), which required discontinuation of valproic acid and of the additional examination.
On the part of the vessels: infrequently - vasculitis.
On the part of the reproductive system: often - dysmenorrhea; infrequently - amenorrhea; rare - male infertility, polycystic ovary syndrome; frequency is unknown - dysmenorrhea, breast enlargement, galactorrhea.
Benign and malignant tumors of uncertain (including cysts and polyps): rarely - myelodysplastic syndrome.
General disorders: rarely - hypothermia, not heavy peripheral edema.
Laboratory and instrumental data: rarely - biotin deficiency / insufficiency biotinidase.
CONTRAINDICATIONS

- increased sensitivity to sodium valproate, valproic acid, valproate seminatriya, valpromidu or any of the auxiliary components of the formulation;
- 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;
- severe hepatic dysfunction;
- severe disorders of the pancreas;
- hepatic porphyria;
-? Set mitochondrial diseases caused by mutations in the nuclear gene encoding mitochondrial enzyme polymerase (POLG), for example, Alpers-Huttenlohera syndrome, and a suspicion of the disease caused by defects polymerase, in children younger than 2 years (relates to the use of medicines drug forms Depakinum ® , intended for children);
- Patients with urea cycle disorders set (urea cycle);
- Combination with mefloquine;
- a combination of Hypericum perforatum preparations;
- Children under 6 years of age (the risk of getting the tablet into the airway during swallowing).
Carefully

- liver and pancreas history;
- Pregnancy;

- congenital fermentopathy;
- inhibition of bone marrow hematopoiesis (leucopenia, thrombocytopenia, anemia);
- renal failure (dose adjustments);
- hypoproteinemia;
- simultaneous reception of several anticonvulsant drugs (because of the increased risk of liver disease);
- 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 (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

Pregnancy
drug Depakine ® Chrono should not be used in children and female adolescents, women of childbearing age and pregnant women, except in cases where other treatments are ineffective or not tolerated patient.
Women who are planning a pregnancy before conception should make every effort to transfer the patient to an appropriate alternative treatment, if possible.
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 ® Chrono 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. So 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.
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 autism spectrum disorders (approximately three-fold increase in risk), including infantile autism (about a five-fold increase in risk).
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 ®chrono 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 need of the drug Depakine ® Chrono or possible rejection of its application must be resolved before the start of the drug or revised if a woman takes the drug Depakine ® Chrono, planning to become pregnant.
Women should be informed of the need to plan the pregnancy and monitor its course.
Women with childbearing potential must use effective contraception during treatment with Depakine ®chrono.
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, depending on the evidence.
- the indication bipolar disorder should consider discontinuing treatment with valproic acid.
- the indication epilepsy question of continued treatment with valproic acid or its abolition decided, after reassessment, the ratio of benefits and risks. If after re-evaluation of risk benefit ratio and drug treatment Depakinum ®chrono still should 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.
Wherever possible, before pregnancy should further start 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.
Before birth. Before the birth the mother should spend coagulation tests, such as determination of the number of platelets, fibrinogen concentration and the coagulation time (APTT).
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.
Neonates whose mothers took valproic acid in the III trimester
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!