Valproic Acid
When ATH:
N03AG01
Characteristic.
White crystalline powder. The easily soluble in water and alcohol.
Pharmacological action.
Antiepileptic, miorelaksiruyuschee, sedation.
Application.
Various forms of generalized seizures: Small (absences), big (convulsive) and polymorphic; used in focal seizures, children tick.
Contraindications.
Hypersensitivity, incl. "Family" (death of close relatives in patients receiving valproic acid), liver and pancreas (some patients may be a significant reduction in metabolism in the liver), gyemorragichyeskii diatyez.
Restrictions apply.
Childhood (co-administration of several anticonvulsants), bone marrow aplasia.
Pregnancy and breast-feeding.
It contraindicated in I trimester of pregnancy. Perhaps in the II and III trimester of pregnancy, if the effect of therapy outweighs the potential risk to the fetus.
Category actions result in FDA - D. (There is evidence of the risk of adverse effects of drugs on the human fetus, obtained in research or practice, However, the potential benefits, associated with drugs in pregnant, may justify its use, in spite of the possible risk, if the drug is needed in life-threatening situations or severe disease, when safer agents should not be used or are ineffective.)
At the time of treatment should stop breastfeeding.
Side effects.
Nausea, vomiting, diarrhea, stomach ache, Anorexia or increased appetite, liver dysfunction, drowsiness, tremor, paresthesia, confusion, peripheral edema, bleeding, leukopenia, thrombocytopenia. In the long admission-temporary hair loss.
Cooperation.
The effect of increasing other anticonvulsants, sedatives and opiates. Diarrhoeal disorders rarely develop on the background of antispasmodics and envelop funds. Alcohol and other hepatotoxic agents increases the likelihood of liver damage, anticoagulants or acetylsalicylic acid is the risk of bleeding.
Dosing and Administration.
Inside, during or immediately after a meal. Daily intake for adults at the beginning of treatment is 0.3-0.6 g, within 1-2 weeks it gradually increased to 0.9-1.5 g, under dose for adults is 0.3-0.45 g. Daily dose for children is 15-50 mg/kg (in the beginning — 15 mg / kg, then a gradual increase of 5-10 mg/kg/week).
Cooperation
| Active substance | Description of interaction |
| Alprazolam | FMR: synergism. Against the background of valproic acid enhanced CNS depression. |
| Amitriptyline | FKV. Against the background of valproic acid (accelerates biotransformation) decreases clearance and increases the blood levels of. |
| Acetylsalicylic acid | FKV. FMR. It increases the level of the free fraction in plasma (displace from its association with proteins). Against the background of valproic acid increased antiplatelet effect and increases the risk of bleeding. |
| Buprenorphine | FMR: synergism. Against the background of valproic acid increases CNS depression. |
| Buspirone | FMR: synergism. Against the background of valproic acid enhanced CNS depression. |
| Warfarin | FMR: synergism. Against the background of valproic acid enhanced antiplatelet effect. |
| Haloperidol | FMR: antagonizm. Weakens effect (may lower the seizure threshold). Strengthens (mutually) depressive effect. |
| Gidroksizin | FMR: synergism. Against the background of valproic acid enhanced CNS depression. |
| Diazepam | FKV. Against the background of valproic acid content increases almost double the free fraction of blood (It is shown in healthy volunteers), decreased clearance and volume of distribution. |
| Droperidol | FMR: synergism. Against the background of valproic acid enhanced CNS depression. |
| Zidovudine | FKV. Against the background of valproic acid, inhibits the activity of glucuronosyltransferase, reduced clearance (on 38%). |
| Zolpidem | FMR: synergism. Against the background of valproic acid enhanced CNS depression. |
| Izofluran | FMR: synergism. Against the background of valproic acid enhanced CNS depression. |
| Imipramine | FMR. Against the background of valproic acid can cause generalized seizures. |
| Carbamazepine | FKV. FMR. Inducing hepatic microsomal enzymes, increases clearance and lowers plasma. Against the background of valproic acid, inhibitory CYP3A4, zamedlyaetsya biotransformation, increased levels of the active metabolite of carbamazepine-10.11-epoxy (suppressed its decay). |
| Quetiapine | FMR: synergism. Against the background of valproic acid enhanced CNS depression. |
| Ketamine | FMR: synergism. Against the background of valproic acid enhanced CNS depression. |
| Clarithromycin | FKV. FMR: synergism. As an inhibitor of CYP450 enzyme system slows the biotransformation, It increases the concentration in the blood and increases the effect of. |
| Klozapyn | FMR: synergism. It lowers the threshold for seizure activity. Against the background of valproic acid enhanced CNS depression. |
| Clonazepam | FMR. Co-administration may cause the state of absences (seizures in patients with a history of this type). |
| Codeine | FMR: synergism. Against the background of valproic acid increases CNS depression. |
| Lamotrigine | FKV. FMR. Against the background of valproate increases T1/2 (due to inhibition of liver enzymes and slowing metabolism) to 70 no (children-up to 45-55 h) and enhances the effect of, incl. side. |
| Levokarnitin | Against the background of valproic acid increases the need for carnitine. |
| Lorazepam | FKV. FMR. Against the background of valproic acid enhanced CNS depression, almost twice reduced Cl and more, than twice the rate of glucuronide. |
| Maprotilin | FMR. It lowers the threshold for seizure activity. Strengthens (mutually) depressive effect. |
| Mefloxin | FKV. It accelerates biotransformation and cnizhaet blood levels. |
| Midazolam | FMR: synergism. Against the background of valproic acid enhanced CNS depression. |
| Morphine sulfate | FMR: synergism. Against the background of valproic acid increases CNS depression. |
| Oxazepam | FMR: synergism. Against the background of valproic acid enhanced CNS depression. |
| Olanzapine | FMR: synergism. Against the background of valproic acid enhanced CNS depression. |
| Perfenazyn | FMR: synergism. Against the background of valproic acid enhanced CNS depression. |
| Prymydon | FKV. FMR. Against the background of valproic acid, severe CNS depression, caused by pentobarbital, formed from primidona. |
| Promethazine | FMR: synergism. Against the background of valproic acid enhanced CNS depression. |
| Propofol | FMR: synergism. Against the background of valproic acid enhanced CNS depression. |
| Risperidone | FMR: synergism. Against the background of valproic acid enhanced CNS depression. |
| Rifampicin | FKV. Induces biotransformation and increases clearance. |
| Tioridazin | FMR: synergism. Against the background of valproic acid enhanced CNS depression. |
| Topiramate | FKV. Several reduced (mutually) concentration in the blood. |
| Trifluoperazine | FMR: synergism. Against the background of valproic acid enhanced CNS depression. |
| Phenytoin | FKV. FMR. Induces biotransformation enzymes, especially glucuronosyltransferase, increases clearance. Against the background of valproic acid increases the concentration of the free fraction of blood (phenytoin is displaced from its association with proteins) and reducing the rate of degradation. If concomitant use increases the risk of sudden seizures. |
| Phenobarbital | FKV. FMR. Inducing liver enzymes, incl. glucuronosyltransferase, increases clearance. Against the background of valproic acid inhibits the biotransformation, elongates T1/2 and reduced plasma clearance. When there is a need for caution — there is a risk of CNS oppression expressed. |
| Fentanyl | FMR: synergism. Against the background of valproic acid increases CNS depression. |
| Flufenazin | FMR: synergism. Against the background of valproic acid enhanced CNS depression. |
| Xlordiazepoksid | FMR: synergism. Against the background of valproic acid enhanced CNS depression. |
| Chlorpromazine | FKV. Increases plasma levels. Against the background of valproic acid enhanced CNS depression. |
| Chlorprothixene | FMR: synergism. Against the background of valproic acid enhanced CNS depression. |
| Ethanol | FMR. It increases the likelihood of liver damage. Against the background of valproic acid enhanced CNS depression. |
| Ethosuximide | FKV. Against the background of valproic acid inhibits the biotransformation and may increase blood levels. |
