Phenobarbital - instructions for use, dose, side effects, contraindications

Composition per one tablet:	5 mg	50 mg
Active substance:
phenobarbital	5 mg	50 mg
Excipients:
sugar (sucrose)	42.2 mg	14.8 mg
potato starch	11.3 mg	32.3 mg
calcium stearate	1.5 mg	2.9 mg

Description:

Tablets with a dosage of 5 mg white, flat-cylindrical with a bevel.

Tablets with a dosage of 50 mg white, flat-cylindrical with a facet and a risk.

Pharmacotherapeutic group:antiepileptic agent

ATX: & nbsp

N.03.A.A.02 Phenobarbital

Pharmacodynamics:

Anticonvulsants. Barbiturate long-acting.Interacts with barbiturate site GABA_A-benzodiazepine-barbiturate receptor complex and increases the sensitivity of GABA-receptors to the mediator (GABA), as a result, the duration of the neuronal canal opening for incoming chlorine ion currents increases and the intake of chloride ions into the cell increases. An increase in the content of chloride ions inside the neuron entails hyperpolarization of the cell membrane and lowers its excitability. As a result, the inhibitory effect of GABA and the inhibition of interneuronal transmission in different parts of the central nervous system are increased.

Anticonvulsant action is caused by activation of the GABAergic system, influence on the potential-dependent sodium channels, and also by suppression of the activity of glutamate, etc. Phenobarbital reduces the excitability of neurons in the epileptogenic focus and prevents the appearance and propagation of impulses. It blocks high-frequency repeated discharges of neurons (due to the influence of sodium ions on the current). Barbiturates also increase the threshold of electrical stimulation of the motor cortex of the cerebral cortex.

The antihyperbilirubinemic effect is presumably due to induction of the enzymeuridine adiphosphate glucuronyl transferase, which catalyzes the conjugation of bilirubin, which leads to a decrease in the concentration of free bilirubin in the serum.

May cause mild analgesia, but it is also possible to intensify the reaction to the pain stimulus.

It was shown that at therapeutic concentrations phenobarbital enhances GABAergic transmission, inhibits glutamatergic neurotransmission, especially mediated by glutamate alpha-amino-5-methylisoxazole-4-propionate (AMPA) -receptors. In high concentrations affects the current of sodium ions and blocks the current of calcium ions through the cell membranes (channels of L and N types).

Barbiturates have a non-selective inhibitory effect on the central nervous system. They suppress sensory areas of the cerebral cortex, reduce motor activity and cause drowsiness, sedation and sleep.

The sedative-hypnotic effect is mainly due to the inhibition of the activity of the cells of the ascending activating reticular formation of the brain stem, the nuclei of the thalamus, inhibition of the interaction of these structures with the cortex of the brain. The sleep caused by barbiturates differs in structure from physiological,the phase of rapid (paradoxical) sleep is shortened and stages 3 and 4 of slow sleep decrease. Sleeping effect develops within 0.5-1 hour (less often later), lasts 6-8 hours (up to 12 hours) and decreases after 2 weeks of admission.

In small doses has a calming effect and in combination with other drugs (spasmolytic, vasodilating) is effective in neurovegetative disorders.

At high doses (with an overdose) causes oppression of the centers of the medulla oblongata. Directly depresses the respiratory center (the degree of respiratory depression depends on the dose), reduces the volume of respiration and sensitivity of the respiratory center to carbon dioxide.

In conventional hypnotic doses, it has no significant effect on the cardiovascular system. In high doses lowers blood pressure (except for the central action - depression of the vasomotor center, the effect is mediated by the effect on the heart, ganglia, and also is associated with direct myotropic vasodilating action).

It has no direct damaging effect on the kidneys, but with acute poisoning, it is possible to develop oliguria or anuria, largely as a result of lowering blood pressure.

Reduces the tone of the smooth muscles of the gastrointestinal tract.

In hypnotic doses to a small extent reduces the intensity of metabolism in humans.

Slightly decreases body temperature due to a decrease in activity and inhibition of the central mechanisms of thermoregulation.

Pharmacokinetics:

Ingestion phenobarbital slowly and fully absorbed in the small intestine, bioavailability - 80%. The maximum concentration in the blood is reached in 1-2 hours after administration. Plasma binds to proteins: in adults - by 50%, in newborns - by 30-40%. The therapeutic concentration in the blood serum, optimal for manifestation anticonvulsant effect, is 10-40 μg / ml. The half-life from plasma in adults is 53-118 hours (79 hours on the average), in children and newborns (less than 48 hours), 60-180 hours, an average of 110 hours.

The drug is evenly distributed in different organs and tissues; the lowest concentrations of it are found in the brain tissues. It passes well through the placenta and is distributed throughout the fetal tissues (the highest concentrations are found in the placenta, liver and fetal brain), it penetrates into breast milk. Phenobarbital induces microsomal liver enzymes (isozymes CYP3A4, CYP3A5, CYP3A7).When applied for more than 3-5 days, barbiturates stimulate their own biotransformation (the rate of enzymatic reactions may increase by 10-12 times).

It is excreted slowly from the body, which creates the prerequisites for cumulation. Metabolized in the liver with the participation of microsomal enzymes with the formation of pharmacologically inactive metabolites. The elimination half-life is 2-4 days (for newborns up to 7 days). It is excreted by the kidneys in the form of glucuronides of metabolites and in unchanged form (25-50%). Excretion by the kidneys depends on the pH of the urine: with alkalinization of urine, the excretion in unchanged form increases and the concentration in the blood decreases more rapidly, while on acidification it vice versa.

If the renal function is impaired, the effect is significantly prolonged.

Indications:

Large and partial epileptic seizures, premedication, insomnia, hyperbilirubinemia in newborns and chronic cholestasis.

Contraindications:

- Hypersensitivity to the components of the drug (including other barbiturates);

- severe hepatic or renal insufficiency;

- diabetes;

- I trimester of pregnancy (teratogenic effect is possible);

- the period of breastfeeding;

- Myasthenia gravis;

- porphyria in the anamnesis (there may be an increase in symptoms due to the induction of enzymes responsible for the synthesis of porphyritis);

- alcoholism, drug and drug dependence (including in history);

- severe anemia;

- Respiratory diseases with dyspnea, obstructive syndrome.

Carefully:

- Depression and / or suicidal tendencies;

- bronchial asthma in history;

- impaired liver and / or kidney function;

- hyperkinesis;

- hyperthyroidism (there may be an increase in symptoms, because barbiturates displace thyroxine, associated with plasma proteins);

- hypofunction of the adrenal glands (possible weakening of the systemic action of exogenous and endogenous hydrocortisone under the action of barbiturates);

- acute or persistent pain (paradoxical agitation may occur or important symptoms may masquerade);

- pregnancy (II and III trimester);

- childhood.

Pregnancy and lactation:

Application during pregnancy is possible only on strict indications, if other means can not be used.

The intake of barbiturates by pregnant women is the cause of an increase in the frequency of abnormalities of the fetus.

In newborns, whose mothers were taking phenobarbital in the third trimester of pregnancy, the development of physical dependence and withdrawal syndrome is possible (there are reports of the development of an acute withdrawal syndrome manifested in epileptic seizures and excessive excitability immediately after birth or within 14 days in newborns exposed to prolonged intrauterine exposure to barbiturates).

The use of phenobarbital as an anticonvulsant during pregnancy can lead to a clotting disorder (associated with vitamin K deficiency) in newborns, which can cause bleeding in the neonatal period (usually the first day after childbirth). Use during labor can cause respiratory depression in a newborn, especially premature (in connection with the underdevelopment of liver function).

For the duration of treatment, breastfeeding should stop (penetrates into breast milk and may cause CNS depression in infants).

Dosing and Administration:

Inside.

The dosage regimen is set strictly individually depending on the indications, the course of the disease, tolerability, age, etc. Treatment should be started with the lowest effective dose corresponding to a particular form of pathology.In patients with impaired liver and / or kidney function, elderly and weakened patients, treatment should begin with smaller doses.

As an antiepileptic agent adults are prescribed, starting with a dose of 50 mg 2 times a day and gradually increasing the dose until the seizures stop, but no more than 0.5 g per day. Then the dose is gradually reduced.

Children are prescribed medication in smaller doses according to their age (not exceeding the highest single and daily doses). Treatment is long. Stop taking phenobarbital with epilepsy should be gradual, as a sudden withdrawal of a drug can cause the development of a seizure and even epileptic status. Phenobarbital often prescribed in combination with other medicines. Usually these combinations are selected individually depending on the general condition of the patient.

The maximum single dose for adults is 0.2 g, the maximum daily dose is 0.5 g.

The dose for children is selected individually depending on the age, body weight of the child, 30-40 minutes before meals 2 times a day.

For children younger than 6 months, a single dose of 5 mg, a daily dose of 10 mg; 6 months-1 year-10 and 20 mg, respectively; at the age of 1 year-2 years - 20 and 40 mg respectively; 3-4 years - 30 and 60 mg; 5-6 years - 40 and 80 mg; 7-9 years old - 50 and 100 mg; 10-14 years - 75 and 150 mg respectively. Treatment is constant.With a decrease in liver function should be administered in smaller doses.

For children under the age of 3 years, the required number of tablets are ground to a powdered state, dissolved in a small amount of water and applied as a suspension.

As a hypnotic phenobarbital appoint an adult in a dose of 100-200 mg once for 30 min-1 h before bedtime. The duration of the hypnotic effect is 6-8 hours. Children, depending on their age, start at a dose of 5-7.5 mg.

Prolonged use of phenobarbital as a hypnotic and sedative should be avoided due to the possibility of its cumulation and the development of drug dependence. Hyperbilirubinemia:

children <12 years: 3-8 mg / kg / day in 2-3 doses, if necessary, increase the dose to 12 mg / kg / day; duration 3-5 days.

children> 12 years: 90-180 mg / day in 2-3 hours.

Premedication: Children older than 6 months-1-3 mg / kg for 1-1.5 h before surgery.

Side effects:

From the nervous system and sensory organs: drowsiness, lethargy, dizziness, ataxia, nystagmus, paradoxical reaction (especially in elderly and weakened patients - arousal), inhibition, irritability,headache, hand tremor, hallucinations, depression, nightmarish dreams, sleep disturbances, fainting, respiratory center depression, nervousness, anxiety, hyperkinesia (in children), impaired thinking process, aftereffects effect (asthenia, feeling of weakness, lethargy, decreased psychomotor reactions and concentration of attention).

From the musculoskeletal system: with prolonged use - violation of osteogenesis and development of rickets.

From the digestive system: nausea, vomiting, constipation, with prolonged use - a violation of liver function.

From the hematopoiesis: agranulocytosis, megaloblastic anemia (with prolonged use), thrombocytopenia.

From the cardiovascular system: lowering of blood pressure, bradycardia.

Allergic reactions: skin rash, urticaria, local edema (especially eyelids, cheeks or lips), shortness of breath, exfoliative dermatitis, malignant exudative erythema (Stevens-Johnson syndrome), possible fatal outcome.

Other: withdrawal syndrome: minor symptoms (within 8-12 hours after stopping the use of the drug) - anxiety, motor anxiety,muscle twitching, hand trembling, weakness, dizziness, blurred vision, nausea, vomiting, sleep disturbance, "nightmarish" dreams, orthostatic hypotension; the main symptoms (within 16 hours and lasts up to 5 days) - convulsions, hallucinations; with long-term use - drug dependence (mental and physical), violation of libido, impotence.

To avoid the development of the "withdrawal" syndrome, discontinuation of treatment should be gradual.

If any of the listed or new adverse reactions occur, consult a doctor as soon as possible.

Overdose:

Symptoms: nystagmus, ataxia, dizziness, headache, blockage, blurred speech, severe weakness, decreased or loss of reflexes, pronounced drowsiness or agitation, increased or decreased body temperature, respiratory depression, dyspnea, lowering blood pressure, narrowing of the pupils (alternating with paralytic enlargement), oliguria, tachi or bradycardia, cyanosis, confusion, cessation of brain electrical activity, pulmonary edema, coma, later pneumonia, arrhythmias, heart failure; when taking 2-10 g - a lethal outcome; in chronictoxicity - irritability, weakened ability to critical evaluation, sleep disorders, confusion.

Treatment: there is no specific antidote. Gastric lavage, reception of activated charcoal, conduct of detoxification therapy, symptomatic treatment, maintenance of vital body functions.

Interaction:

Phenobarbital is a potent inducer of the hepatic enzyme system containing cytochrome P450 (mainly isoenzyme CYP3A4). Induction by phenobarbital occurs when it is used in doses as low as 60 mg per day. This property is the basis of pharmacokinetic interactions with other drugs, i.e. phenobarbital boosts both its own metabolism and the metabolism of many other drugs undergoing biotransformation in the liver. The latter have different effects on the action of barbiturates. Phenytoin and valproic acid increase the content of phenobarbital in the blood serum.

Anticonvulsant effect of phenobarbital decreases with simultaneous reception with reserpine, increases when combined with amitriptyline, pialamide, diazepam, chlordiazepoxide.

Reduces the effectiveness of oral contraceptives and salicylates.

Reduces the blood levels of indirect anticoagulants, glucocorticosteroids, griseofulvin, doxycycline, estrogens and other drugs metabolized in the liver by the isoenzyme CYP3A4 and other cytochrome P450 isoenzymes (accelerates their destruction).

Strengthens the effect of alcohol, neuroleptics, narcotic analgesics, muscle relaxants, sedatives and hypnotics.

Acetazolamide, alkalinizing urine, reduces the reabsorption of phenobarbital in the kidneys and weakens its effect.

The hypnotic effect of phenobarbital decreases with simultaneous reception with atropine, belladonna extract, dextrose, thiamine, nicotinic acid, analeptics and psychostimulating drugs.

Reduces antibacterial activity of antibiotics and sulfonamides, antifungal action of griseofulvin.

Special instructions:

Being an inducer of microsomal enzymes of the liver, it increases its detoxification function, reduces the concentration of bilirubin in the blood serum. In patients with impaired liver function phenobarbital should be applied in a reduced dose.

Currently phenobarbital as a hypnotic is practically not used.

When dermatological complications appear phenobarbital should be canceled.

Hypersensitivity reactions are more common when there is a history of bronchial asthma, hives, angioedema, etc.

During treatment it is necessary to monitor the function of the liver, kidneys, a general blood test.

With caution, prescribe for depression (possibly worsening, especially in elderly patients).

It should be borne in mind that in elderly people and weakened patients with usual doses, there may be a marked agitation, depression or confusion.

In children, barbiturates can cause unusual arousal, irritability, hyperactivity.

The risk of dependence is increased with the use of large doses and with an increase in the duration of admission, as well as in patients with a drug and alcohol dependence in the anamnesis. The constant use of barbiturates in doses 3-4 times higher than therapeutic, leads to the development of physical dependence in 75% of patients. Cancellation should be carried out gradually, by reducing the dose for a long time to reduce the risk of withdrawal and "rejection" syndromes.A sudden cessation of reception with epilepsy can cause seizures or status epilepticus.

When using phenobarbital for the treatment of epilepsy, monitoring of its concentration in the blood is recommended. With long-term treatment, it is necessary to periodically determine the concentration of folate in the blood, monitor the pattern of peripheral blood, liver and kidney function.

If it is necessary to use barbiturates during childbirth, it is recommended to take delivery while the resuscitation equipment is ready.

Effect on the ability to drive transp. cf. and fur:

Do not use during work drivers of vehicles and people whose activities require a quick mental and physical reaction, and is also associated with increased concentration of attention and speed of psychomotor reactions.

Form release / dosage:

Tablets for children, 5 or 50 mg.

Packaging:

For 10 tablets in a planar cell package.

1 or 2 contour squares with instructions for use in a pack of cardboard.

1000 contour mesh packages with an equal number of instructions for use in a box of corrugated cardboard (for hospitals).

Storage conditions:

In accordance with the rules for the storage of psychotropic substances listed in Schedule III of the "List of narcotic drugs, psychotropic substances and their precursors subject to control in the Russian Federation". Store in a dark place at a temperature of no higher than 25 ° C.

Keep out of the reach of children.

Shelf life:

5 years.

Do not use after the expiration date.

Terms of leave from pharmacies:On prescription

Registration number:LP-000895

Date of registration:18.10.2011

The owner of the registration certificate:Anzhero-Sudzhensky Chemical-Pharmaceutical Plant, LLC Anzhero-Sudzhensky Chemical-Pharmaceutical Plant, LLC

Manufacturer: & nbsp

Anzhero-Sudzhensky Chemical-Pharmaceutical Plant, LLC Russia

Representation: & nbspASFARMA-ROS LLCASFARMA-ROS LLCRussia

Information update date: & nbsp19.09.2015

Illustrated instructions

Instructions

Phenobarbital (Phenobarbital)