Gabapentin

General characteristics. Structure:

Active agent: габапентин - 300 mg;
excipients: hydrophosphate calcium dihydrate of 60 mg, starch of potato 32 mg, macrogoal (polyethyleneglycol 6000) of 4 mg, magnesium stearate of 4 mg;
structure of the capsule: the case and a lid - titanium dioxide, dye quinolinic yellow, indigo dye a carmine - FD&C Blue 2, gelatin.

Description:
Capsules No. 0 of green color. Contents of capsules - powder of white or almost white color. Existence of lumps which when pressing by a glass stick are easily powdered is allowed.

Pharmacological properties:

Pharmacodynamics. Gabapentin on a structure is similar to the neurotransmitter piperidic acid (GAMK), however its mechanism of action differs from other drugs interacting with GAMK-receptors (valproic acid, barbiturates, benzodiazepines, GAMK-transaminase inhibitors, inhibitors of capture of GAMK, agonists of GAMK and pro-dosage forms of GAMK). It has no GAMK-ergichesky properties and does not influence for capture and metabolism of GAMK. Preliminary researches showed what габапентин communicates with α2-δ-субъединицей a voltage - dependent calcium channels and reduces the flow of calcium ions playing an important role in developing of neyropatichesky pain. Other mechanisms of action of a gabapentnn at neyropatichesky pain are reduction a glutamate - dependent death of neurons, increase in synthesis of GAMK, suppression of release of neurotransmitters of monoamine group. Gabapentin in clinically significant concentration does not contact the receptors sensitive to other medicines (M) or neurotransmitters, including receptors of GAMKA, GAMKV, benzodiazepine, a glutamate, glycine or N-methyl-d-aspartate. Unlike Phenytoinum and carbamazepine габапентин does not interact with natrium channels of in vitro. Gabapentin partially weakened effects of an agonist of glyutamatny receptors of N-methyl-d-aspartate in some in vitro tests, but only in concentration more than 100 µmol which is not reached in vivo. Gabapentin reduces emission of monoamine in vitro neurotransmitters a little.

Pharmacokinetics. Bioavailability of a gabapentin is not proportional to a dose. So, at increase in a dose it decreases. After intake the maximum concentration (Cmax) of a gabapentin in plasma is reached in 2-3 h. Absolute bioavailability of a gabapentin in capsules makes about 60%. Food, including with high content of fats, does not exert impact on pharmacokinetics. The elimination half-life (T1/2) from plasma does not depend on a dose and averages 5-7 h. The pharmacokinetics does not change at repeated use; equilibrium concentration in plasma can be predicted on the basis of results of a single dose of drug. Gabapentin practically does not contact proteins of plasma (<3 %) and has the volume of distribution of 57,7 l. It is removed only by kidneys in not changed look, is not exposed to metabolism. Drug does not induce the oxidizing enzymes of a liver with the mixed function participating in metabolism of medicines. The clearance of a gabapentin from plasma decreases at elderly people and patients with an impaired renal function. The removal speed constant, clearance from plasma and renal clearance are directly proportional to clearance of creatinine. Gabapentin leaves from plasma at a hemodialysis. At patients with an impaired renal function and the patients receiving treatment by a hemodialysis dose adjustment is recommended (see the Route of administration and doses).

Indications to use:

- epilepsy: partial spasms with secondary generalization and without it at adults and children are more senior than 12 years (monotherapy); partial spasms with secondary generalization and without it at adults (additional HP); the resistant form of epilepsy at children is more senior than 3 years (additional HP).
- neyropatichesky pain at adults (18 years are also more senior).

Route of administration and doses:

Inside, swallowing entirely, irrespective of meal and plentifully washing down with liquid. If it is necessary to lower a dose, to cancel drug or to replace it with alternative means, it should be done gradually within at least one week.
Neyropatichesky pain at adults
The initial daily dose makes 900 mg, divided into three receptions; if necessary the dose is gradually increased to maximum - 3600 mg/days. Treatment can be begun with a dose of 900 mg/days at once (300 mg 3 times a day) or during the first 3 days it is possible to increase a dose gradually to 900 mg a day according to the following scheme:
1st day:  300 mg of 1 times a day
2nd day:  300 mg 2 times a day
3rd day:  300 mg 3 times a day
Partial spasms
Adults and children of 12 years: An effective dose - from 900 to 3600 mg/days. Therapy it is possible to begin with a dose 300 mg 3 times a day in the first day or to increase gradually up to 900 mg according to the scheme described above (see the section "Neyropatichesky Pain at Adults"). In the subsequent the dose can be raised as much as possible to 3600 mg/days (divided into 3 equal receptions). The maximum interval between doses at triple administration of drug should not exceed 12 h in order to avoid resuming of spasms.
Selection of a dose at a renal failure.
The dose decline of a gabapentin according to the table is recommended to patients with a renal failure:

* appoint 300 mg every other day.
Recommendations for the patients who are on a hemodialysis.
Drug is recommended to appoint the patient who is on a hemodialysis who did not accept габапентин earlier in the sating dose 300-400 mg, and then to apply it on 200-300 mg each 4 h a hemodialysis.

Features of use:

Though the withdrawal with development of spasms at treatment gabapentiny is noted, nevertheless, the sharp termination of therapy by antiepileptic means at patients with partial spasms can provoke development of spasms (see the Route of administration and doses).
Gabapentin is not considered an effective remedy of treatment an absentia epileptica epilepsy.
At patients who need joint therapy by morphine increase in a dose of a gabapentin can be required. At the same time it is necessary to provide careful observation of patients regarding development of such sign of oppression of the central nervous system (CNS) as drowsiness. In this case the dose of a gabapentin or morphine has to be adequately lowered (see. "Interaction with other medicines").

Laboratory researches:
At addition of a gabapentin to other anticonvulsants false positive results when determining protein in urine by means of test strips of Ames N-Multistix SG® were registered. For definition of protein in urine it is recommended to use more specific method of precipitation sulphosalicylic acid.
Patients should avoid driving, and also the performance of work demanding speed of performance of psychomotor reactions.

Side effects:

Cardiovascular system: symptoms of a vazodilatation or increase in arterial pressure, heartbeat.
Digestive tract: a meteorism, anorexia, an ulitis, an abdominal pain, a lock, diseases of teeth (including discoloration of enamel of teeth), diarrhea, dyspepsia, increase in appetite, dryness in a mouth or a throat, nausea, vomiting, pancreatitis, increase in activity of "hepatic" transaminases, hepatitis, jaundice.
System of blood, lymphatic system: a purpura (most often it is described as the bruises arising at a physical injury), a leukopenia, thrombocytopenia.
Musculoskeletal system: an arthralgia, a dorsodynia, the increased fragility of bones, a mialgiya.
Nervous system: dizziness; headache; hyperkinesias; muscular dyskinesia and dystonia; choreoathetosis; easing or lack of tendon jerks; dysarthtia; ataxy; nystagmus; paresthesias; spasms; confusion of consciousness; increased fatigue; adynamy; amnesia; depression; disturbance of thinking; hostility; emotional lability; sleeplessness; alarm; drowsiness; hallucinations; tremor; tics; indisposition.
Respiratory system: rhinitis, pharyngitis, bronchitis, pneumonia, cough, short wind, respiratory infections.
Skin and hypodermic fabrics: acne, peripheral hypostases, allergic reactions: a skin itch, skin rash, a multiformny exudative erythema (including Stephens's syndrome - Johnson).
Urinogenital system: infection of uric ways, impotence, urine incontience, acute renal failure.
Sense bodys: vision disorder, amblyopia, diplopia, sonitus, otitis.
Others: fever, a viral infection, increase in body weight, lability of level of glucose in a blood plasma at patients with a diabetes mellitus, pain of various localization, a gynecomastia, increase in mammary glands, generalized hypostasis.

Interaction with other medicines:

Morphine: at joint reception of a gabapentin and morphine when morphine was accepted in 2 hours prior to reception of a gabapentin increase in average value of the area under a pharmacokinetic curve "concentration - time" (AUC) of a gabapentin for 44% in comparison with monotherapy gabapentiny was observed that was associated with increase in a pain threshold (the holodovy pressor test). Clinical value of this change is not established, pharmacokinetic characteristics of morphine at the same time did not change. Side effects of morphine at joint reception with gabapentiny did not differ from those at reception of morphine together with placebo.
Interaction between gabapentiny and phenobarbital, Phenytoinum, valproic acid and carbamazepine is noted. The pharmacokinetics of a gabapentin in an equilibrium state is identical at the healthy people and patients receiving other anticonvulsants. Simultaneous use of a gabapentin with the oral contraceptives containing Norethisteronum and/or ethinylestradiol was not followed by changes of pharmacokinetics of both components.
Simultaneous use of a gabapentin with the antacids containing aluminum and magnesium is followed by decrease in bioavailability of a gabapentin approximately for 20%. Gabapentin is recommended to accept approximately in 2 h after reception of an antacid.
Probenetsid does not influence renal excretion of a gabapentin.
Small decrease in renal excretion of a gabapentin at a concomitant use of Cimetidinum has probably no clinical value.

Contraindications:

Hypersensitivity to any of drug components, age up to 12 years (because of impossibility of exact dosing).
With care
Renal failure (see. "Route of administration and doses").

Use at pregnancy and a lactation:
There are no data on use of drug for pregnant women therefore габапентин it is necessary to use during pregnancy only if the estimated advantage for mother justifies possible risk for a fruit.
Gabapentin is brought with breast milk, its influence on the raised child is unknown therefore during treatment it is necessary to refuse breastfeeding.

Overdose:

Symptoms: dizziness, diplopia, disturbance of the speech, drowsiness, lethargy, diarrhea and strengthening of expressiveness of other side effects. Treatment: gastric lavage, reception of absorbent carbon, symptomatic therapy. The hemodialysis can be shown to patients with a heavy renal failure.

Storage conditions:

To store in the dry, protected from light place at a temperature not above 25 °C. To store in the place, unavailable to children. Period of validity: 2 years. Not to apply after a period of validity.

Issue conditions:

According to the recipe

Packaging:

On 10 or 15 capsules in a blister strip packaging from a film of the polyvinyl chloride and printing aluminum foil varnished.
On 3, 5, 10 blister strip packagings on 10 capsules or on 2, 4, 6 blister strip packagings on 15 capsules together with the application instruction place in a pack from a cardboard for a retail container.