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

Pharmacodynamics:Gabapentin has a structural relationship to the neurotransmitter gamma-aminobutyric acid (GABA), but the mechanism of its action is different from the mechanisms of action of some other substances interacting with GABAergic synapses, including valproate, barbiturates, benzodiazepines, inhibitors of GABA transaminases, GABA trap inhibitors, agonists GABA and predecessors GAMK. The binding site of gabapentin has been identified as the alpha2-delta subunit of potential-dependent calcium channels. Gabapentin in clinically usable concentrations, does not bind to other common receptors of drugs or brain neurotransmitters, including GABA-AA, GABA-AB, benzodiazepine, glutamate, glycine, or N-methyl-D-aspartate (NMDA) receptors. Gabapentin does not interact with sodium channels in vitro, and this is different from phenytoin and carbamazepine. Gabapentin partially reduces responses to the N-methyl-D-aspartate (NMDA) glutamate agonist in some in vitro test systems, but only at concentrations exceeding 100 μM that are not achieved in vivo. Gabapentin weakly reduces the release of monoamine neurotransmitters in vitro.

Pharmacokinetics:Suction

After oral administration Cmax gabapentin in plasma is achieved after 2-3 hours. The bioavailability of gabapentin is not proportional to the dose, When the dose is increased, it decreases. Absolute bioavailability when taking gabapentin in capsule form is about 60%. Simultaneous food intake, incl. with a high fat content, does not affect the pharmacokinetics.

Distribution

Pharmacokinetics does not change with repeated application; Css in plasma can be predicted based on the results of a single dose of the drug. Gabapentin practically does not bind to plasma proteins (<3%), the volume of distribution (Vd) is about 57.7 liters.

Metabolism

Metabolism is not affected. Does not induce oxidative liver enzymes with a mixed function involved in the metabolism of drugs. Excretion

The elimination of gabapentin from the plasma is linear. T1/2 does not depend on the dose and averages 5-7 hours. It is excreted exclusively with urine in unchanged form.

Pharmacokinetics in special clinical cases

The pharmacokinetics of gabapentin in children is studied at the age from 1 month to 12 years. It was found that the concentrations of gabapentin in the blood plasma of children older than 5 years are similar to the concentrations achieved in adults when calculating the dose per mg / kg of body weight. The clearance of gabapentin from plasma decreases in elderly people and in patients with impaired renal function. The rate of elimination constant, clearance from plasma and renal clearance are directly proportional to the creatinine clearance (CK). Gabapentin is removed from the plasma during hemodialysis. It is recommended that the dose be adjusted to patients with impaired renal function or who are on hemodialysis.

Indications:

Monotherapy of partial seizures in epilepsy with secondary generalization and without it in adults and children over 12 years of age (efficacy and safety of monotherapy in children under 12 years of age have not been established).

In the combination therapy of partial seizures with epilepsy with secondary generalization and without it in adults and children 12 years and older (for this dosage form).

Treatment of neuropathic pain in adults aged 18 years and older (efficacy and safety in patients younger than 18 years of age is not established).

Contraindications:Hypersensitivity to the components of the drug.

Children under 12 years (for this dosage form).

Carefully:renal failure, pancreatitis.

Pregnancy and lactation:

There is insufficient data on the use of gabapentin in pregnant women. Do not use gabapentin during pregnancy, if the potential benefit to the mother does not exceed the possible risk to the fetus. It is impossible to pinpoint whether gabapentin is associated with an increased risk of congenital malformations due to the presence of epilepsy itself and the use of concomitant antiepileptic drugs during pregnancy in all reported cases.

Gabapentin is excreted in breast milk. Since its effect on the infant is unknown, gabapentin can be used during breastfeeding only in cases where the benefits of taking the drug clearly outweigh the risk. For the duration of therapy it is necessary to stop breastfeeding.

Dosing and Administration:EGYPTENIN tablets are taken orally, regardless of food intake. The tablet should be swallowed whole, with enough liquid. If it is necessary to reduce the dose, cancel the drug or replace it with an alternative remedy, this should be done gradually for at least one week.

EGYPTENIN the film-coated tablets do not have any risks, therefore, they can not be divided in half, so when initial titration of the dose, as well as when the drug is administered in a dose of less than 600 mg, it is recommended to take the drug EGYPENTIN capsules 100 mg, 300 mg, 400 mg.

With partial seizures for adults and children over the age of 12 years, the effective dose is from 900 mg to 3600 mg per day. Therapy can begin with a dose of 300 mg 3 times a day on the first day or increase gradually to 900 mg according to the scheme:

1 day - 300 mg of the drug once a day;

Day 2 - 300 mg twice a day;

Day 3 - 300 mg 3 times a day.

Subsequently, the dose can be increased to a maximum of 3600 mg per day (divided into 3 equal doses). A good tolerability of the drug at doses up to 4800 mg / day was noted.

The maximum interval between doses with a three-time intake of the drug should not exceed 12 hours in order to avoid the resumption of seizures.

There is no need to monitor the concentration of gabapentin in plasma. EGYPTENIN can be used in combination with other anticonvulsants without taking into account changes in plasma concentration or concentration of other anticonvulsants in serum.

With neuropathic pain, adults are prescribed in an initial dose of 900 mg / day in 3 divided doses. If necessary, depending on the effect, the dose gradually (300 mg per day every 2-3 days) is increased to a maximum of 3600 mg / day. The minimum time to achieve a dose of 1800 mg per day is 1 week, to achieve a dose of 2,400 mg per day, it takes 2 weeks, and to achieve a dose of 3600 mg per day, it takes 3 weeks. Some patients may need a slower titration.

Treatment can begin immediately with a dose of 900 mg / day (300 mg 3 times a day) or within the first 3 days the dose can be increased gradually to 900 mg / sug according to the following scheme:

1 day - 300 mg of the drug once a day;

Day 2 - 300 mg twice a day;

Day 3 - 300 mg 3 times a day.

The efficacy of this drug has not been studied in the treatment neuropathic pain for more than 5 months. If the patient needs to take the drug for more than 5 months, the attending physician should assess the clinical condition of the patient and determine the need for additional therapy.If the patient's general condition is poor, for example, at a low body weight, after organ transplantation, etc., titration of the dose should be performed more slowly, using lower doses or longer intervals between dose increases.

elderly patients (older b5 s) in accordance with the age-related decrease QC patients with renal impairment (creatinine clearance less than 80 mL / min), as well as patients who are on hemodialysis, the therapeutic dose should be adjusted individually.

Recommended doses of gabapentin for renal dysfunction.

Creatinine clearance (ml / min)	The daily dose of gabapentin (mg) *
> 80 ml / min	900-2400
50-79	600-1800
30-49	300-900
15-29	150**-600
<15	150**-300

* The daily dose should be divided into 3 divided doses

** take 300 mg every other day

Patients who are on hemodialysis and have not previously taken gabapentin, it is recommended to appoint a saturating dose equal to 300-400 mg, then every 4 h of the hemodiagnosis session, appoint 200-300 mg of the drug.

In days free from dialysis, EGYPTENIN can not be accepted.

Capsules should be taken orally, without chewing and washing down with the necessary amount of liquid, regardless of food intake.

Side effects:Undesirable reactions are presented according to frequency: very often (> 1/10), often (> 1/100, <1/10), infrequently (> 1/1000, <1/100) and rarely (> 1/10 000; 1/1000).

From the cardiovascular system:

often: hypertension, symptoms of vasodilation; rarely: palpitations.

From the digestive system:

often - indigestion; rarely - nausea, vomiting, abdominal pain, increased appetite, dryness of the oral mucosa or pharynx, constipation or diarrhea, pancreatitis, increased activity of "liver" transaminases, hepatitis, jaundice. When appointed in conjunction with other antiepileptic drugs - flatulence, anorexia, gingivitis.

From the musculoskeletal system: rarely - myalgia, arthralgia, gait disturbance. When appointed in conjunction with other antiepileptic drugs - pain in the back, increased brittle bones.

From the side of the nervous system: often drowsiness, dizziness, ataxia, nystagmus (dose-dependent), increased fatigue, tremor, dysarthria, increased nervous excitability; rarely - headache, amnesia, depression; very rarely - disturbance of thinking, confusion, hallucinations, tics, paresthesia, hypoesthesia, asthenia, malaise, hyperkinesia; amplification, hypo- or areflexia, anxiety, hostility, choreoathetosis, dyskinesia, dystonia. When appointed in conjunction with others.antiepileptic drugs - insomnia.

From the respiratory system: rarely - rhinitis, bronchitis, pharyngitis. When appointed in conjunction with other antiepileptic drugs - cough, pneumonia. From the genitourinary system: rarely - urinary incontinence, acute renal failure. When appointed in conjunction with other antiepileptic drugs - reduced potency, infection of the urinary tract.

From the senses: rarely - visual impairment (diplopia, amblyopia), ringing in the ears.

From the hemopoiesis: rarely - leukopenia, thrombocytopenia.

Allergic reactions: rarely - skin rash, hives, itching, fever, angioedema, multiforme exudative erythema (including Stevens-Johnson syndrome).

Other: infrequent - purpura, weight gain; rarely - peripheral and generalized edema, discoloration of tooth enamel, alopecia, acne, face swelling, fluctuations in blood glycemin in patients with diabetes mellitus, pneumonia, respiratory tract infection, urinary tract infection, otitis media.

Children often observed aggressive behavior and hyperkinesis.

Post-registration experience: There have been recorded cases of sudden unexplained death, the relationship of which with treatment with gabapentin has not been established.

Other undesirable phenomena registered during the post-registration experience of the drug: acute renal failure, allergic reactions (including urticaria, multiforme erythema exudative (including Stevens-Johnson syndrome), angioedema), alopecia, fluctuations in glucose blood in patients with diabetes, chest pain, an increase in the volume of the mammary glands, gynecomastia, increased activity of liver enzymes, hallucinations, motor disorders (choreoathetosis, myoclonus, dyskinesia and dista Nia), palpitations, pancreatitis, thrombocytopenia, tinnitus, urinary incontinence.

After the abrupt withdrawal of therapy most often - anxiety, insomnia, nausea, pain of varying localization and sweating.

Overdose:

Symptoms: dizziness, double vision, speech disturbance, drowsiness, lethargy and diarrhea.

Treatment: gastric lavage, the appointment of activated charcoal, the conduct of symptomatic therapy.

Patients with severe renal insufficiency can be shown hemodialysis.

Interaction:With the joint administration of gabapentin and morphine, when morphine in the form of capsules with controlled release of 60 mg was taken 2 hours prior to gabapentin, an increase in AUC of gabapentin by 44% was observed, compared with monotherapy with gabapentin, which was accompanied by an increase in the pain threshold (cold pressor test). The clinical significance of these changes is not established. When gabapentin was administered 2 hours after morphine administration, there was no change in the pharmacokinetic parameters of morphine. The side effects of morphine when combined with gabapentin did not differ from those observed when taking morphine with placebo.

Interactions between gabapentin and phenytoin, carbamazepine, valproic acid, and phenobarbital have not been observed. The pharmacokinetics of gabapentin in the equilibrium state is the same in healthy people and patients receiving other antiepileptic drugs.

Gabapentin does not affect the pharmacokinetics and efficacy of oral contraceptives containing norethisterone and / or ethinyl estradiol. Means that neutralize the acidity of the stomach, containing magnesium or aluminum, reduce the bioavailability of gabapentin by 24%. It is recommended that gabapentin at least 2 hours after taking antacid preparations.

With the combination of cimetidine with gabapentin, the excretion of the latter by the kidneys slightly decreases, which probably has no clinical significance.

Other drugs that affect the central nervous system, as well as ethanol, are able to enhance the side effects of gabapentin on the CNS (eg, drowsiness, ataxia).

Probenecid does not affect renal excretion of gabapentin.

With the simultaneous administration of gabapentin at a dose of 125 mg with naproxen 250 mg, the absorption of gabapentin increases. Gabapentin does not affect the pharmacokinetic parameters of naproxen. Since these doses are lower than the therapeutic doses for both drugs, the degree of interaction within the recommended doses of the drugs is not known.

With simultaneous administration of gabapentin in doses of 125 to 500 mg with hydrocodone 10 mg decreases Cmax and AUC hydrocodone depending on the dose. The mechanism of this interaction has not been studied. Hydrocodone increases the AUC of gabapentin by 14%. The magnitude of the interaction with other doses is not known.

Special instructions:Reduce the dose, cancel the drug or substitute for another alternative means should be gradually over a minimum of 1 week.A sharp cessation of therapy can provoke an epileptic status.

As with the use of other antiepileptic drugs, in some patients the frequency of seizures may increase or new types of seizures may appear.

As with the use of other antiepileptic drugs, attempts to abolish intolerant anti-epileptic drugs with a view to switching to gabapentin monotherapy in refractory patients receiving several antiepileptic drugs rarely lead to success.

The drug is not considered effective in absences.

When the first signs of acute pancreatitis (prolonged pain in the abdominal cavity, nausea, repeated vomiting) should stop treatment with gabapentin. A thorough examination of the patient (clinical and laboratory tests) should be carried out for the purpose of early diagnosis of acute pancreatitis. When gabapentin was added to other anticonvulsants, false positive results were recorded in determining the total protein in the urine using semi-quantitative tests.

If positive results are obtained with such tests, it is recommended to use a more specific method of precipitation with sulfosalicylic acid or biuret breakdown.

Suicidal behavior is described in patients receiving antiepileptic drugs for some indications. Analysis of trials of antiepileptic drugs also revealed a slight increase in the risk of suicidal ideation and suicidal behavior. Existing data do not exclude the possibility of such an increased risk in the treatment of gabapentin. Therefore, it is necessary to monitor the appearance of signs of suicidal ideation and suicidal behavior in patients and, if necessary, prescribe appropriate treatment. Patients and patients assisting patients should be advised to seek medical help if signs of suicidal ideation and suicidal behavior occur.

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

Gabapentin may cause drowsiness, dizziness, and other such symptoms. Patients should be advised not to start work,requiring increased attention and speed of psychomotor reactions until the patient's individual reaction to the drug intake is determined (especially at the beginning of the course of treatment and with increasing doses).

Form release / dosage:Film coated tablets 600 mg and 800 mg.

Packaging:For 20 tablets in a blister of PVC / PVDC / / aluminum foil. 3 or 6 blisters in a cardboard box together with instructions for medical use.

Storage conditions:

Store at a temperature not exceeding 25 ° C.

Keep the drug out of the reach of children!

Shelf life:

Shelf life 2 years.

Do not use after the expiration date indicated on the package.

Terms of leave from pharmacies:On prescription

Registration number:PL-000879

Date of registration:18.10.2011 / 12.01.2015

The owner of the registration certificate:EGIS ZAO Pharmaceutical Plant EGIS ZAO Pharmaceutical Plant Hungary

Manufacturer: & nbsp

West Pharma Produces de Especialidades Farmaceuticas, S.A. Portugal

Representation: & nbspEGIS ZAO Pharmaceutical Plant EGIS ZAO Pharmaceutical Plant Hungary

Information update date: & nbsp12.01.2015

Illustrated instructions

Instructions

Egipentine (Egipentin)