Primidonum

General characteristics. Structure:

Active ingredient: 250 mg of Primidonum in terms of 100% substance.

Excipients: potato starch, sodium carboxymethylstarch (крахмалгликолат sodium), povidone, calcium stearate.

Pharmacological properties:

Pharmacodynamics. Antiepileptic drug. On a chemical structure it is close to phenobarbital, but differs in stronger anticonvulsant action, without having the systemic oppressing effect on the central nervous system (CNS) and the expressed somnolent effect.

The mechanism of action is connected with oppression of transfer of excitement from pyramidal and segmented spinal ways on motor-neurons of a spinal cord.

Pharmacokinetics. Absorption in digestive tract bystry and full. Bioavailability - more than 90%. Time of achievement of the maximum concentration - 3 h. Distribution volume - 0,64-0,86 l/kg. It is metabolized in a liver with formation of 2 active metabolites: phenobarbital - 15-25% and a feniletilmalonamida. Communication of Primidonum with proteins of plasma - 20%, phenobarbital - 50%, and a feniletilmalonamida - is insignificant. Primidonum and it metaboli-you get into breast milk where their average concentration makes 75% of stable concentration in blood. Semi-removal time for Primidonum, phenobarbital and a feniletilmalonamid - 3-23, 75-126 and 10-25 h respectively.

It is removed by kidneys in the form of Primidonum - 64%, phenobarbital - 5,1%, a feniletilmalonamida - 6,6%.

Indications to use:

Treatment of big convulsive attacks (grand mal) and psychomotor (frontal lobe) epilepsy.

Treatment of partial and jacksonian epilepsy, myoclonic spasms and akinetic attacks.

Route of administration and doses:

Epilepsy. Treatment is appointed individually. In one cases there is enough use of Primidonum in monotherapy, in others the combined anticonvulsant therapy is necessary. Primidonum is usually appointed two times days.

Therapy begin with a dose 125 mg (1/2 tablets) once for the night. Each 3 days a dose increase on 125 mg to achievement 500 mg/days (2 таб / days). Then each 3 days poyovyshat a dose on 250 mg at adults and children from 9 years and on 125 mg at children of 3-9 years before achievement of control over spasms or to the maximum tolerable dose.

The maximum tolerable dose at adults and children since 9 years - 1500 mg/days (6 таб / days), at deyoty 3-9 years - 1000 mg/days (4 таб / days). Average daily maintenance doses:

Age	Dosage, mg
Adults and children since 9 years	750-1500
Children of 6-9 years	750-1000
Children of 3-6 years	500-750

The general daily dose is usually divided into two equal parts and accepted in the morning and in the evening. Purpose of a bigger dose can be shown by some patient when spasms arise more often. For example, if spasms arise at night, then appoint all dose or its most part in the evening; if spasms arise in connection with certain circumstances (for example, during periods), small increase in a dose during this period can be useful. 

Elderly patients. It is necessary to watch the elderly patients accepting Primidonum with it is reduced - ache function of kidneys.

The patients accepting other anticonvulsants. If at reception of other anticonvulsants, it is not possible to establish neobkhodi-my control of spasms, or there are heavy side effects, reception of Primidonum as addition to the appointed therapy or for its replacement is shown.

Use of Primidonum as addition of anticonvulsant therapy is begun gradually, according to the scheme described above. If desirable control of spasms is reached at the dose of Primidonum making a half from an average dose less it is possible to try to cancel the accompanying therapy. Such cancellation needs to be carried out gradually, within two weeks that can also demand increase in a dose of Primidonum for maintenance of control over spasms.

In order to avoid the epileptic status cancellation of the accompanying therapy cannot be carried out too quickly. However if the main part of the accompanying therapy was made by phenobarbital, for prevention of excessive drowsiness, cancellation of the last and increase in a dose of Primidonum need to be begun earlier.

Features of use:

Use during pregnancy and in the period of a lactation. It is considered that Primidonum can cause serious malformations At use it during pregnancy. At children whose mothers accepted Primidonum, inborn malformations, including inborn heart diseases, a sky crevice were noted; the states caused by deficit of folic acid at mother (including spina bifida, a micrencephalia and an anencephalia).

Primidonum should be applied during pregnancy for the purpose of treatment of epilepsy only according to strict indications if cancellation of therapy leads to emergence of risks or at impossibility of use of other methods of treatment.

Children whose mothers accepted Primidonum on late durations of gestation, can have symptoms of "cancellation".

Long anticonvulsant therapy can cause decrease in content of folates in blood. Because the need for folic acid during pregnancy increases, regular screening of patients of risk group and purpose of drugs of folic acid and B12 vitamin are necessary.

In certain cases anticonvulsant therapy during pregnancy caused disturbances of a blood coagulation in newborns. In this regard pregnant women need to use K1 vitamin drugs within the last month of pregnancy. For lack of such prevention in the period of families of the pregnant woman the newborn needs to enter 10 mg of K1 vitamin and 1 mg of Primidonum right after the birth. 

 During breastfeeding it is necessary to watch the child regarding gray-haired tivny effect.

It can be used in complex anticonvulsant therapy.

Primidonum it is expressed TsNS oppresses, and also it is partially metabolized to phenobarbital. At prolonged use there is a risk of stability, medicinal dependence and a syndrome of "cancellation" at the sharp termination of treatment.

In case of development of megaloblastny anemia it is necessary to stop reception and to begin treatment with folic acid and/or B12 vitamin.

Now appoint more rare in connection with the expressed side effects (is-other antiepileptic medicines - valproic acid, carbamazepine and others use). Primidonum, as well as other antiepileptic means can increase risk a cart - a niknoveniya of suicide thoughts and suicide behavior. Therefore during treatment for all patients observation for the purpose of early identification of disturbances or changes of behavior, and also suicide bents has to be established.

Influence on ability to manage vehicles, mechanisms. During treatment it is necessary to refrain from driving of motor transport and occupations other potentially dangerous types of activity demanding the increased concentration of attention and speed of psychomotor reactions.

Side effects:

The most frequent side effects of Primidonum are drowsiness and apathy, to - tory arise preferential at the beginning of therapy.

Also the vision disorder, nausea, a headache, dizziness, vomiting, a nystagmus and an ataxy which had passing character, even at a considerable vyra-of a zhennost were noted. In certain cases there can be idiosyncratic reactions which can be shown by the above described symptoms in an acute and severe form and demand therapy cancellation.

Frequency of side effects of drug is regarded as follows: very frequent:> 1/10; frequent:> 1/100, <1/10; infrequent:> 1/1000, <1/100; rare:> 1/10 000, <1/1000; very rare: <1/10 000; single: cannot be estimated at the available data.   

From the central and peripheral nervous system: often - apathy, an ataxy, a visual disturbance, a nystagmus; seldom - frustration of the personality, psychotic reactions. 

From blood and lymphatic system: seldom - megaloblastny anemia, narushe-a niya from blood.

From digestive tract: often - nausea; infrequently - vomiting.            

From a liver and biliary tract: seldom - increase in activity "pechenoch-ny" enzymes, including a gamma glutamiltranspeptidazu and an alkaline phosphatase.               

From musculoskeletal system: often - an arthralgia, osteomalacy. As well as concerning phenobarbital, palmar fibromatosis cases were noted.                            

From skin and hypodermic fabrics: infrequently - allergic reactions with preferential involvement of skin, including makulopapulezny, korepodobny and scarlatiniform rash; seldom - heavy reactions, including exfoliative dermatitis, Stephens-Johnson's syndrome, a toxic epidermal necrolysis and a lupus.            

The general: often - drowsiness; infrequently - a headache, dizziness. Owing to increase in a catabolism of vitamin D at prolonged use of Primidonum purpose of drugs of vitamin D can be required.

In exceptional cases, as well as at use of Phenytoinum or phenobarbital, the megaloblastny anemia demanding cancellation of Primidonum can develop. This state can give in to correction by treatment by folic acid and (or) B12 vitamin.

Interaction with other medicines:

Strengthens effect of somnolent medicines, derivative sulphonylurea, cyclophosphamide, a methotrexate.

Increasing activity of microsomal enzymes of a liver, accelerates metabolism and weakened - lyat effect of paracetamol, glucocorticosteroids and mineralokortikosteroid, indirect anticoagulants, tricyclic antidepressants, chloramphenicol, tsiklospo-Reena, a dakarbazina, foxglove glycosides (digoxin to a lesser extent), dizopirami-yes, doxycycline, left thyroxine, metronidazole, a meksiletin, quinidine, the phenopro-hair dryer, vitamin D, Aminophyllinum, caffeine, an okstrifillin, theophylline, peroral kontra-tseptiv.

Oppression of the central nervous system at a combination to alcohol, medicines to the central depremirutoshchy action amplifies.

Amphetamine slows down absorption in digestive tract of one of metabolites phenobarbital.

At a combination to inhibitors of a karboangidraza disturbance of bone formation can amplify.

Strengthens toxic action on a liver of medicines for the general anesthesia-enflurana, a halothane, a metoksifluran.

Reduces griseofulvin absorption that leads to reduction of its antifungal activity.

Guanadrel, гуанетидин, a haloperidol, локсапин, Maprotilinum, молиндон, fenotiazina, thioxanthenes reduce a convulsive threshold, oppress the central nervous system. Leykovorin in high doses weakens anticonvulsant action of Primidonum. Methylphenidate oppresses metabolism of Primidonum and increases its concentration in blood that can lead to development of toxic action. 

Phenylbutazone - effects of each other mutually weaken.

Hormones of a back share of a hypophysis increase risk of development of arrhythmias and coronary nedosta-accuracy.

At co-administration of medicines - stimulators of microsomal enzymes of a liver: phenobarbital, carbamazepine, rifampicin, ethanol (at the chronic use) metabolism of Primidonum accelerates and its efficiency decreases. The medicines having myelotoxic effect strengthen proyavle-a drug gematotoksichnost niya.

Contraindications:

Hypersensitivity, liver and/or renal failure, anemia, leukopenia, acute intermittent porphyria, pregnancy, the lactation period, children up to 3 years.

With care. Should appoint Primidonum with care children, the elderly, weakened patients, persons with a renal failure, a liver or breath, decrease in a dosage of drug is required.

Overdose:

Symptoms: dizziness, nausea, an ataxy, TsNS function oppression, including the attacks - this, a loss of consciousness, respiratory depression and a coma.

At overdose there can be a crystalluria which can be one of diagnostic characters of overdose of Primidonum.

Treatment: gastric lavage, purpose of absorbent carbon; symptomatic treatment.

Storage conditions:

In the dry, protected from light place at a temperature not above 25 °C. To store in the place, unavailable to children. A period of validity - 5 years. Not to use after a period of validity.

Issue conditions:

According to the recipe

Packaging:

Tablets of 250 mg. On 10 tablets in a blister strip packaging. 1, 2, 3, 4 or 5 blister strip packagings together with the application instruction in a pack from a cardboard.