Gabapentin

General characteristics. Structure:

Active agent: габапентин (in terms of 100% substance) 300,0 mg; excipients: calcium stearate of 4,2 mg, sodium carboxymethylstarch Type A of 4,2 mg, cellulose of microcrystallic 111,6 mg; structure of capsules: titanium dioxide of 2%, gelatin to 100%.
Description: solid gelatin capsules No. 0 of white color. Contents of capsules – powder, white or white with a yellowish shade.

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, transaminase GAMK-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 Gabapentin at neyropatichesky pain are reduction the glutamate of 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 receptors of other widespread drugs or neurotransmitters, including receptors of GAMKA, GAMKV, benzodiazepine, a glutamate, glycine or N-methyl-D-aspartate. Unlike Phenytoinum and carbamazepine Gabapentin does not interact with natrium channels of in vitro. Gabapentin partially weakened effects of an agonist of glutamate 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. Gabapentin's bioavailability is not proportional to a dose. So, at increase in a dose it decreases. After intake the maximum concentration (Cmax) of Gabapentin in plasma is reached in 2-3 h. Absolute bioavailability of Gabapentin in capsules makes about 60%. Food, including with high content of fats, does not exert impact on pharmacokinetics. Gabapentin's removal from plasma is best of all described by means of linear model. 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. Gabapentin's clearance 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 section "Route of Administration and Doses").

Indications to use:

· monotherapy or as an additional tool for treatment of partial spasms with secondary generalization or without it at adults and children since 12 years;
· 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 2400 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 is recommended to patients with a renal failure
Gabapentina according to the table:
Clearance of creatinine     Daily dose (mg/days)
>                                        80 900-2400
                                     50-79 600-1200
                                     30-49 300-600
                                     15-29 150*-300
<                                               15 150 *
* appoint 300 mg every other day
The recommendation for the patients who are on a hemodialysis the Patient who is on a hemodialysis who did not accept Gabapentin earlier drug is recommended to appoint 300-400 mg in the sating dose, 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 by Gabapentin is noted, nevertheless, the sharp termination of therapy by antiepileptic means at patients with partial spasms can provoke development of spasms (see the section "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 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 Gabapentin's dose or morphine has to be adequately lowered (see the section "Interaction with Other Medicines").
Laboratory researches At Gabapentin's addition to other anticonvulsants were registered false positive results when determining protein in urine by means of test strips of Ames N-Multistix SG®. 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:

At treatment of neuropathic pain Organism in general: accidental injuries, adynamy, dorsodynia, grippopodobny syndrome, headache, infection, pain of various localization, peripheral hypostases, increase in body weight; Digestive tract: a lock, diarrhea, dryness in a mouth, dyspepsia, a meteorism, nausea, vomiting, an abdominal pain; Nervous system: gait disturbance, amnesia, ataxy, confusion of consciousness, dizziness, hypesthesia, drowsiness, disturbance of thinking, tremor;
Respiratory system: short wind, pharyngitis;
Skin and hypodermic fabrics: skin rash;
Sense bodys: amblyopia.
At treatment of partial spasms
Organism in general: dorsodynia, exhaustion, fever, headache, viral infection, peripheral hypostases, increase in body weight, adynamy, febricula, face edema;
Cardiovascular system: symptoms of a vazodilatation or hypertensia;
Digestive tract: a lock, diseases of teeth, diarrhea, dyspepsia, increase in appetite, dryness in a mouth or a throat, nausea and/or vomiting, an abdominal pain, a meteorism, anorexia, an ulitis;
System of blood, lymphatic system: a leukopenia, a purpura (most often it was described as the bruises arising at a physical injury);
Musculoskeletal system: changes, mialgiya, arthralgias;
Nervous system: amnesia, ataxy, confusion of consciousness, incoordination, depression, dysarthtia, emotional lability, sleeplessness, nervousness, nystagmus, drowsiness, disturbance of thinking, tremor, twitching of muscles, dizziness, hyperkinesias; strengthening, easing or lack of reflexes, paresthesias, concern, hostility;
Respiratory system: cough, pharyngitis, rhinitis, pneumonia;
Skin and hypodermic fabrics: grazes, acne, skin itch, skin rash;
Sense bodys: amblyopia, diplopia, vision disorder;
Urinogenital system: infection of uric ways, impotence.

Interaction with other medicines:

Morphine: at joint reception of Gabapentin and morphine when morphine was accepted in 2 hours prior to Gabapentin's reception increase in average value of the area under a pharmacokinetic curve "concentration – time" Gabapentin's (AUC) for 44% in comparison with monotherapy by Gabapentin 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 Gabapentin did not differ from those at reception of morphine together with placebo. Interactions between Gabapentin and phenobarbital, Phenytoinum,
valproic acid and carbamazepine noted. Gabapentin's pharmacokinetics in an equilibrium state is identical at the healthy people and patients receiving other anticonvulsants.
Simultaneous use of Gabapentin with the oral contraceptives containing Norethisteronum and/or ethinylestradiol was not followed by changes of pharmacokinetics of both components. Simultaneous use of Gabapentin with the antacids containing aluminum and magnesium is followed by decrease in bioavailability of 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 Gabapentin.
Small decrease in renal excretion of Gabapentin at a concomitant use of Cimetidinum has probably no clinical value.

Contraindications:

Hypersensitivity to any of drug components, age to
12 years at partial spasms.
With care
Renal failure (see the section "Route of Administration and Doses").
Use at pregnancy and a lactation
There are no data on use of drug for pregnant women therefore Gabapentin 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, doubling in eyes, disturbance of the speech, drowsiness, a lethargy, diarrhea. Treatment: gastric lavage, reception of absorbent carbon, symptomatic therapy. The hemodialysis can be shown to patients with a heavy renal failure.

Storage conditions:

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

Issue conditions:

According to the recipe

Packaging:

Capsules of 300 mg. On 50 or 100 capsules in bank polymeric with a cover. On 10 or 15 capsules in a blister strip packaging. To bank, or 5 blister strip packagings on 10 capsules, or 3 blister strip packagings on 15 capsules together with the application instruction place in a pack from a cardboard.