Diphenine (Diphenine)

Composition Pharmacodynamics Indications Carefully Contraindications Dosing and Administration Side effects Form release / dosage
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Active substancePhenytoinPhenytoin
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  • Diphenine
    pills inwards 
    LUHANSKY HFZ, OJSC     Ukraine
  • Diphenine
    pills inwards 
    UZOLE-SIBERIAN CHEMICAL PLANT, OJSC     Russia
    • Dosage form: & nbsppills
    Composition:

    1 tablet contains:

    active substance: phenytoin 100 mg;

    Excipients: sodium bicarbonate, potato starch, talc, calcium stearate.

    Description:Tablets of white or almost white color are flat-cylindrical with a bevel.
    Pharmacotherapeutic group:antiepileptic agent
    ATX: & nbsp

    N.03.A.B.02   Phenytoin

    Pharmacodynamics:

    Diphenin shows an anticonvulsant effect without a pronounced hypnotic effect. The mechanism of anticonvulsant action of Diphenin is not fully established. It is believed that the specific effect of Diphenin is realized in epilepsy by reducing the excitability of neuronal epileptic focus and the effect on the neurotransmitters. The drug blocks sodium channels, prolongs their inactivation time, prevents the generation and spread of high-frequency discharges. The drug also exhibits antiarrhythmic action. The antiarrhythmic effects of diphenin are probably due to the normalization of the entry of sodium and calcium ions into Purkinje heart fiber cells. The drug depresses the anomalous automatism and the duration of the action potential in the His-Purkinje system due toreduction of repolarization time, and reduces the effective refractory period.

    Pharmacokinetics:

    Has the effect of "first pass" through the liver. Bioavailability is less than 50%. Penetrates into the cerebrospinal fluid, saliva, semen, gastric and intestinal juice, bile, breast milk, penetrates the placenta. To a large extent (up to 90% or more) binds to plasma proteins.

    The time to reach the maximum concentration of the drug in the blood serum is 1.5-3 hours. The therapeutic concentration of the drug in the serum is 10-20 μg / ml (40-80 μmol / l). Stable concentration is usually achieved on 5-10 days with an average daily dose. The serum concentration of Diphenin needed to achieve a therapeutic effect may depend on the type of epileptic seizures. In some cases it is possible to prevent epileptic seizures at a serum phenytoin concentration of 6-9 μg / ml (24-36 μmol / L). Thus, the effectiveness of treatment should be controlled not by the concentration of the drug in the serum, but by the clinical signs of the disease.

    Diphenin is metabolized by liver enzymes to inactive metabolites.The basic inactive metabolite is 5- (p-hydroxyphenyl) -5-phenylhydantoin. Possible cumulation of the drug and as a consequence - the development of unforeseen toxic effects.

    The half-life is 24 hours. It is excreted by the kidneys - 35-60%, with bile - 40-65%. Excretion increases with an alkaline reaction of urine.

    Indications:

    Diphenin is prescribed for the treatment of epilepsy, mainly large epileptic seizures (grand mal), accompanied by loss of consciousness, arbitrary urination, tonic convulsions, turning into clonic ones.

    In addition, the drug can be prescribed for cardiac arrhythmias due to an overdose of cardiac glycosides, some forms of Meniere's syndrome (due to overwhelming vestibular reflexes).

    Contraindications:

    Hypersensitivity.

    Heart failure, Morgagni-Adams-Stokes syndrome, atrioventricular block II-III st, sinouauric block, bradycardia.

    Diseases of the kidneys, liver.

    Cachexia.

    Porphyria.

    Pregnancy and lactation.

    Carefully:

    In patients with alcoholism, diabetes, systemic lupus erythematosus, with hyperthermia.

    Dosing and Administration:

    Diphenin is used orally during or immediately after a meal.

    Single dose for adults: - 1/2-1 tablet. Take 2-3 times a day. According to the indications, the daily dose is increased to 3-4 tablets. Higher doses for adults: single - 3 tablets, daily - 8 tablets.

    Use in children: up to 5 years - by 1/4 tablets 2 times a day, 5-8 years - on 1/4 tablets 3-4 times a day, over 8 years - on 1/2-1 pills 2 times a day.

    Side effects:

    From the nervous system: tremor, ataxia, dysarthria, diplopia, irritability, insomnia, dizziness.

    From the sense organs: nystagmus, pain in the eyes.

    From the digestive system: gastritis, decreased appetite, nausea, vomiting, gastralgia, constipation.

    On the part of the organs of hematopoiesis: leukopenia, aplastic anemia, megaloblastic, B12- Deficiency anemia, agranulocytosis, lymphadenopathy.

    Allergic reactions: skin rash, fever, multiple exudative erythema and toxicoderma.

    Other: polyarthritis, hirsutism, gingival hyperplasia, weight loss, change connective tissue (coarsening features, Dupuytren's contracture); with prolonged use (after 2-5 months) - violation of calcium-phosphorus metabolism, latent osteopathy, dyspnea.

    If the drug is abruptly withdrawn, withdrawal can occur.

    With the expressed side effects, the dose is gradually reduced or the use of Diphenin is stopped.
    Overdose:

    In the event of an overdose of the drug, it is possible to increase toxic side effects. Since there is no antidote, the use of activated carbon, laxatives and symptomatic therapy is recommended.

    With prolonged use, manifestations of hypersensitivity syndrome to the drug and severe suppression of the central nervous system are possible, which requires the drug to be withdrawn.

    Interaction:

    Enhances hepatotoxicity and lengthens the effect of paracetamol.

    Increases the toxicity of chlorpromazine and other derivatives of phenothiazine, reserpine, sulfonamides.

    Amiodarone increases the concentration of phenytoin in the blood.

    Antacids containing salts Al+3, Mg+2 and Ca2+; preparations for parenteral nutrition, sucralfate reduce bioavailability; calcium sulfate reduces absorption by 20%.

    Anticoagulants of indirect action, chloramphenicol, cimetidine, disulfiram, an antiviral vaccine, isoniazid, methylphenidate, phenylbutazone, ranitidine, salicylates, sulfonamides, fluconazole, ketoconazole, miconazole reduce metabolism, increase active concentrations in the blood and increase the anticonvulsant effect.

    Anticonvulsants (succinimide, carbamazepine), estrogen-containing contraceptives, glucocorticosteroids, mineralocorticosteroids, adrenocorticotropic hormone, ciclosporin, dacarbazine, glycogenides of digitalis, diopyramide, doxycycline, estrogens, furosemide, levodopa, myxylethin, quinidine, methadone, praziquantel, vitamin D, aminophylline, caffeine, oestrfillin, theophylline are metabolized more intensively (due to induction microsomal enzymes of the liver), resulting in a decrease in their concentration in the blood.

    Tricyclic antidepressants, bupropion, clozapine, haloperidol, loxapine, maprotiline, molindone, monoamine oxidase inhibitors, phenothiazines, pimozide, thioxanthenes, sulfinpyrazone reduce anticonvulsant action (therefore, a dose adjustment of phenytoin may be required).

    Phenytoin can increase blood glucose levels, and therefore reduces the effect of insulin and oral hypoglycemic agents; breaks the complexation of levothyroxine with plasma proteins by 15-25%.

    Barbiturates, primidon, fluoxetine, folic acid can change the concentration in the blood (there is a need for monitoring).

    Diazoxide reduces the hyperglycemic activity of phenytoin.

    Dopamine can promote the development of arrhythmia and lower blood pressure.

    Influrane, halothane, methoxyflurane - the use of phenytoin before anesthesia can increase the metabolism of anesthetic and the risk of developing hepatotoxicity and nephrotoxicity.

    Lidocaine and beta-blockers in combination with phenytoin can inhibit cardiac activity; thus significantly increasing the metabolism of lidocaine.

    Omeprazole, by inhibiting the cytochrome P450 system, reduces the metabolism of phenytoin.

    Rifampin stimulates metabolism in the liver.

    Trazodone raises concentrations in the blood.

    Valproic acid and phenytoin inhibit each other's metabolism, which can lead to increased hepatotoxicity.

    Phenobarbital and carbamazepine increase the elimination (mutually) of phenytoin.

    Isoniazid, acetylsalicylic acid, chloramphenicol and disulfiram inhibit metabolism, strengthening side effects.

    Special instructions:

    During treatment, careful selection of doses (in epilepsy, the concentration in the blood is determined for 7-10 daystreatment), as an increase in the dose may be accompanied by a disproportionate increase in plasma levels.

    During treatment it is necessary to control the content of Ca2+ and phosphorus in the blood serum. At the expressed by-effects the dose of a preparation reduce or stop treatment. Patients with impaired liver function, and elderly people need a correction of the dosing regimen.

    In acute alcohol intoxication, the concentration of Diphenin rises, while in chronic cases it decreases.

    Effect on the ability to drive transp. cf. and fur:During the period of treatment, it is necessary to refrain from driving motor vehicles and practicing potentially dangerous species, activities requiring increased concentration of attention and speed of psychomotor reactions.
    Form release / dosage:Tablets, 100 mg.
    Packaging:

    For 10 tablets in contour non-jammed packaging. 1 or

    2 contour non-jawed packages with instructions for medical use in a pack of cardboard.
    Storage conditions:

    In dry, dark place, out of reach of children at a temperature of 5 to 30 ° C.

    Shelf life:

    4 years.

    Do not use after the expiration date.

    Terms of leave from pharmacies:On prescription
    Registration number:P N 015685/01
    Date of registration:09.06.2009
    The owner of the registration certificate:LUHANSKY HFZ, OJSC LUHANSKY HFZ, OJSC Ukraine
    Manufacturer: & nbsp
    Information update date: & nbsp19.09.2015
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