Gabapentin capsules

Registration number: .ЛСР-000847/10

Trade name: Gabapentin.

International non-patented name (INN): gabapentin

Drug form: capsules.

Composition:

drug substance: gabapentin (adjusted to 100% compound) 300,0 mg;

excipients: calcium stearate 4,2 mg, sodium carboxymethyl starch Type A 4,2 mg, microcrystalline cellulose 111,6 mg;

composition of capsules: gelatin, titanium dioxide.

Description: hard white gelatine capsules # 0. Content of capsules is a white or white-yellowish powder.

Pharmacotherapeutic group: anti-epileptic medicine

АТХ code: М03АХ12.


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Pharmacological properties

Pharmacodynamics. Gabapentin is similar by its chemical structure to neuro-transmitter gamma-aminobutyric acid (GABA), but its mechanism of action is different from other drugs, reacting with GABA-receptors (valproic acid, barbiturates, benzodiazepines, GAMA-transaminase inhibitors, GABA uptake inhibitors, GABA agonists and pro-drug forms of GABA). It has no GABA-ergic properties and does not affect GABA uptake and metabolism. Preliminary studies showed that gabapentin binds with the α2-δ-sub-unit of voltage-dependent Ca-canals and decreases a calcium ions flow that play an important role in a neuropathy pain arising. Other mechanisms of the Gabapentin action on a neuropathy pain include: a decrease of the glutamate-dependent death of neurons, an increase of GABA synthesis, a suppression of the monoamine group neurotransmitters release. Gabapentin in clinically important concentrations not binds with receptors to other drugs or neurotransmitters, including GABAА, GABAВ, benzodiazepine, glutamate, glycine or N-methyl-D-aspartate receptors. Gabapentin does not interact (differently from phenytoin or carbamazepin) with Na-canals in vitro. Gabapentin partially decreased effects of N-methyl-D-aspartate (the agonist of glutamate receptors) in some tests in vitro, but only in concentrations higher than 100 umol (this concentration cannot be reached in vivo). Gabapentin somewhat decreases a monoamine neoritransmitters emission in vitro.

Pharmacokinetics. Bioavailability of Gabapentin is not proportional to its dosage. On increase of the dosage bioavailability decreases. After the ingestion the maximal concentration (Сmax) of Gabapentin is reached after 2-3 hours. The absolute bioavailability of Gabapentin in capsules is near 60%. Food (including fat food) does not affect a pharmacokinetics. Plasma clearance for Gabapentin is optimally described by linear model. A plasma half-life period (Т1/2) is dose-independent and its value is on average 5-7 hours. Pharmacokinetics not changes after the repeated use; equilibrium concentrations can be predicted on a base of the singe use of the drug. Gabapentin virtually not binds with plasma proteins (< 3 %) and has 57,7 l distribution volume. The drug is excreted only by kidneys (in unchanged form), without any metabolism. The drug does not induce hepatic oxidative enzymes with a mixed function (enzymes, playing a role in drugs metabolism). The Gabapentine clearance from decreases in elderly patients and patients with a decreased kidneys function. A constant of excretion rate of Gabapentin and its renal clearance are proportional to a creatinine clearance. Gamapentin is removed from plasma during the hemodialysis. A dose adjustment is recommended for patients treated by hemodialysis, (Refer to “Method of use and dosages”).

Indications

• monotherapy or as a additional aid in treatment of partial seizures with a secondary generalization or without it in adults or children (12 years old and older);

• neuropathy in adults (18 years old and older).

Contraindications

Increased individual sensitivity to any component of the drug; age under 12 years (in cases of partial seizures).

Use with caution

Renal insufficiency (Refer to “Method of use and dosages”).

Use during pregnancy and lactation

There are no data about the drug use in pregnant women, so Gabapentin has to be used during pregnancy only in cases, when predicted benefit for mother higher than the possible risk for fetus. Gabapentin excretes with breast milk and effect of this drug on a child is unknown, so the breast feeding during treatment has to be stopped.

Method of use and dosages

Capsules have to be ingested without chewing, independently from meals and with bug quantity of water. If it is necessary to decrease a dosage, to stop the drug use or to switch it on another drug, this has to be done gradually during a minimum one week.

Neuropathy pain in adults

The initial daily dosage is 900 mg, divided on three steps; if is is necessary, a dosage can be increased up to a maximal - 3600 mg/day. The treatment can be started from the dosage 900 mg/day (300 mg 3 times a day) or the dosage can be escalated during first 3 days by this scheme:

1st day: 300 mg one time a day; 2nd day: 300 mg two times a day; 3rd day: 300 mg three times a day.

Partial seizures

Adults and children older than 12 years: the effective dosage - 900 - 2400 mg/day. The treatment can be started from the dosage: 300 mg 3 times a day at first day, or the dosage can be escalated gradually up to 900 mg as described above (Refer to “Neuropathy pain in adults”). Than dosage can be escalated up to maximum 3600 mg/day (divided into three equal portions). A maximal interval between dosages (in three-times-a-day scheme) can not be over 12 hours to prevent a seizures recurrence.

Dose adjustment in a case of the renal insufficiency

A dosage for patients with the renal insufficiency can be decreased as described in the table:

Creatinine clearance

Daily dosage (mg/day)

> 80

900-2400

50-79

600-1200

30-49

300-600

15-29

150*-300

< 15

150*

* 300 mg per each second day

Recommendations for patients treated by hemodialysis

It is recommended to patients treated by hemodialysis if they are not used Gabapentin before to ingest a saturating dosage 300-400 mg, than ingest 200-300 mg per each 4 hours of hemodialysis.

Side effects

During the neuropathy pain treatment:

Body: accidental traumas, asthenia, back pain, flu-like syndrome, headache, infection, pain of the different localization, peripheral edemas, body mass increase;

Digestive tract: constipation, diarrea, mouth dryness, dyspepsia, meteorism, nausea, vomiting, stomach pain;

Nervous system: walking affection, amnesia, ataxia, mental confusion, dizziness, hypesthesia, drowsiness, thinking affection, tremor;

Respiratory system: breathlessness, pharyngitis;

Skin and subcutaneous structures: skin rash;

Sense organs: amblyopia.

During the partial seizures treatment:

Body: back pain, fatigue, fever, headache, virus infection, peripheral edemas, body mass increase, asthenia, common weakness,edema of face;

Cardiovascular system: vasodilation symptoms or hypertension;

Digestive tract:   constipation,  diseases of teeth, diarrhea, dyspepsia, appetite increase, mouth or pharynx dryness, nausea and/or vomiting, stomach pain, meteorism, anorexia, gingivitis;

Blood system, lymphatic system: leucopenia, purpura (most often described as bruises after the physical trauma);

Bone and musculature system: fractures, myalgias, arthralgias;

Nervous system:   amnesia, ataxia, mental confusion, coordination affection, depression, dysarthria, emotional lability, insomnia, nervousness, nystagmus, sleepiness, mental disorders, tremor, muscular fasciculations, dizziness, hyperkinesises; increase, decrease or absence of reflexes, parestesias, anxiety, hostility;

Respiratory system: cough, pharyngitis, rhinitis, pneumonia;

Skin and subcutaneous structures: abrasions, acne, skin inching, skin rash;

Sense organs: amblyopia, diplopia, visual impairment;

Genital-urinary system: urinary ways infection, impotence.

Over-dosage

Symptoms: dizziness, double vision, speech affection, sleepiness, lethargy, diarrhea.

Treatment: gastric lavage, activated charcoal use, symptomatic treatment. Patients with a severe renal insufficiency can be treated with gemodialysis.

Interaction with other medicines

Morphine: in concomitant use of Gabapentin with morphine, when morphin was used 2 hours before the Gabapentin use, an 44% increase of the Gabapentine AUC was observed in comparison to Gabapentin monotherapy, it was associated with the pain threshold increase (cold pressor test). A clinical importance of this effect was not established, pharmacokinetic characteristics of the morphine were not changed. Side effects of morphine used concomitantly with Gabapentin, were similar to those observed in concomitant use of morphine with a placebo.

Interaction between Gabapentin and phenobarbital, phenitoin, valproic acid, and carbamazepine was not observed. Equilibrium pharmacokinetics of Gabapentin is similar for healthy persons and for patients treated by other anti-convulsive drugs.

A concomitant use of Gabapentin with oral contraceptives (containing norethysteron and/or ethynil oestradiol) was not accompanied by pharmacokinetical changes of both components.

A concomitant use of Gabapentin with antacids containing magnesium and aluminum, is accompanied by a decrease of the Gabapentin bioavailability approximately by 20%. It is recommended to use a Gabapentin 2 hours after the antacid use.

Probenecid does not affect a renal excretion of Gabapentin.

A slight decrease of a renal excretion of Gabapentin in cases of concomitant use with cimetidine, probably, has no clinical importance.

Precautions

Even if a withdrawal syndrome with convulsions was not observed in Gabapentine treatment, but an acute stop of therapy by anti-epileptic drugs can provoke an arousal of convulsions (Refer to “Method of use and dosages”).

Gabapentin is not recognized as an effective treatment of the absence epilepsy.

A Gabapentine dosage may be increased for patients treated with morphine. In this case it is necessary to closely monitor a sign of the central nervous system (CNS) suppression - somnolence. In this case a Gabapentine dose or a morphine dose has to be adequately decreased (Refer to “Interaction with other medicines”).

Laboratory studies

During the concomitant use of Gabapentin and other anti-convulsive medicines false positive results of protein in urine were registered (testing by test strips Ames N-Multistix SG® ). For determination of protein in urine it is recommended to use more specific method (precipitation by sulfosalycilic acid).

Patients have to avoid a car driving and to perform activities where quick psycho-motoric reactions are needed.

Drug form

Capsules 300 mg.

Sealed polymer cans with 50 or 100 capsules. Blisters with 10 or 15 capsules. One can or 5 blisters with 10 capsules or 3 blisters with 15 capsules are packed into a carton box (with instruction).

Keeping conditions

Keep in protected from direct light place at temperature not higher than 25 °С. Keep out of the reach of children.

Shelf life

2 years. Do not use after the expiry date.

Selling conditions

By prescription.

 

Manufacturer

PIQ-PHARMA LLC., 129010, Russia, Moscow, Spassky blind alley, 2/1.

Manufactured by PIQ-PHARMA PRO LLC, 188663, Russia, Leningradskaya region, Vsevolozhsky district, Kuzmolovsky, Workshop # 92.

Claims have to e sent to

PIQ-PHARMA LLC. Phone/fax: +7-495-925-57-00.