Composition, form of production and packaging
Capsules hard gelatinous, в„–3, white; the contents of the capsules are white powder.
1 caps.
gabapentin 100 mg
Excipients: lactose, corn starch, talc, gelatin, titanium dioxide, iron oxide, yellow, iron oxide red.
10 pieces. - blisters (2) - packs of cardboard.
10 pieces. - blisters (5) - packs of cardboard.
10 pieces. - blisters (10) - packs of cardboard.
Capsules hard gelatinous, в„–1, yellow; the contents of the capsules are white powder.
1 caps.
gabapentin 300 mg
Excipients: lactose, corn starch, talc, gelatin, titanium dioxide, iron oxide, yellow, iron oxide red.
10 pieces. - blisters (2) - packs of cardboard.
10 pieces. - blisters (5) - packs of cardboard.
10 pieces. - blisters (10) - packs of cardboard.
Capsules hard gelatinous, в„–0, orange; the contents of the capsules are white powder.
1 caps.
gabapentin 400 mg
Excipients: lactose, corn starch, talc, gelatin, titanium oxide, iron oxide, yellow, iron oxide red.
10 pieces. - blisters (2) - packs of cardboard.
10 pieces. - blisters (5) - packs of cardboard.
10 pieces. - blisters (10) - packs of cardboard.
INSTRUCTION FOR THE SPECIALIST.
Description of the drug approved by the manufacturer for the printed edition of 2015.
PHARMACHOLOGIC EFFECT
Antiepileptic drug. Gabapentin is similar in structure to the neurotransmitter gamma-aminobutyric acid (GABA), but its mechanism of action differs from other drugs interacting with GABA receptors (valproate, barbiturates, benzodiazepines, GABA transaminase inhibitors, GABA capture inhibitors, GABA agonists and prodrugs of GABA ). It does not possess GABA-ergic properties and does not affect the capture and metabolism of GABA. Preliminary studies have shown that gabapentin binds to? 2 -? - subunit of voltage-dependent calcium channels and reduces the flow of calcium ions, which plays an important role in the occurrence of neuropathic pain.
Other mechanisms of action of gabapentin in neuropathic pain are a decrease in glutamate-dependent neuronal death, an increase in GABA synthesis, a suppression of the release of neurotransmitters of the monoamine group.
Gabapentin does not bind to receptors of other common drugs or neurotransmitters, including GABA receptors a , GABA 's , benzodiazepine, glutamate, glycine or N-methyl-D-asparaty at clinically significant concentrations. Unlike phenytoin and carbamazepine, gabapentin does not interact with sodium channels in vitro.Gabapentin partially attenuated the effects of the N-methyl-D-aspartate glutamate receptor agonist in some in vitro tests, but only at a concentration of more than 100 Ојmol, which is not achieved in vivo. Gabapentin somewhat reduces the release of monoamine neurotransmitters in vitro.
PHARMACOKINETICS
Suction and distribution
The bioavailability of gabapentin is not proportional to the dose. So, with an increase in the dose, it decreases. After ingestion C max gabapentin in plasma is achieved after 2-3 hours. Absolute bioavailability of gabapentin in capsules is about 60%. Food, incl. with a high fat content, does not affect the pharmacokinetics.
The elimination of gabapentin from plasma is best described using a linear model. T 1/2 from plasma is dose independent and averages 5-7 hours.
Pharmacokinetics does not change with repeated application; equilibrium concentrations 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%) and has V d - 57.7 l.
Metabolism and excretion
It is excreted exclusively by the kidneys in unchanged form, it is not metabolized. The drug does not induce oxidative liver enzymes with a mixed function involved in the metabolism of drugs.
Pharmacokinetics in special clinical cases
The clearance of gabapentin from plasma decreases in the elderly 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. Gabapentin is removed from the plasma during hemodialysis. In patients with impaired renal function and patients receiving hemodialysis treatment, dose adjustment is recommended.
INDICATIONS
- in the complex therapy of partial seizures with secondary generalization or without it in adults and children over 12 years of age;
- pain syndrome with diabetic neuropathy, postherpetic neuralgia in adults.
DOSING MODE
The drug is taken orally, regardless of food intake or with food. If you need to reduce the dose, cancel the drug or replace it with an alternative remedy, this should be done gradually for at least 1 week.
Neuropathic pain in adults
The initial dose is 900 mg / day in 3 divided doses; if necessary, the dose is gradually increased to a maximum of 3600 mg / day. Treatment can begin immediately with a dose of 900 mg / day (300 mg 3 times / day) or within the first 3 days the dose can be increased gradually to 900 mg / day as follows:
Day 1: 300 mg of the drug 1 time / day;
Day 2: 300 mg twice daily;
Day 3: 300 mg three times a day.
Partial cramps in adults and children from age 12
The effective dose is from 900 to 3600 mg / day. Therapy can begin with a dose of 300 mg 3 times / day on the first day or increase gradually to 900 mg according to the scheme described above. Subsequently, the dose may be increased to 3600 mg / day (divided into 3 equal doses). 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. It can be used in combination with other anticonvulsants without taking into account changes in plasma concentration or concentration of other antiepileptic drugs (PEP) in the serum.
Selection of a dose for renal failure
Patients with renal failure are recommended to reduce the dose of gabapentin according to the table:
CK (ml / min) Daily dose (mg / day) (in 3 divided doses)
> 80 900-3600
50-79 600-1800
30-49 300-900
15-29 150 * -600
<15 150 * -300
* - Assign 300 mg every other day.
Patients on hemodialysis who had not previously taken gabapentin should be prescribed a saturating dose of 300-400 mg, and then apply it to 200-300 mg every 4 hours of hemodialysis.
In weakened patients, as well as patients in severe general condition, with low body weight and after organ transplantation, the dose increase should be carried out gradually using a dosage of 100 mg.
SIDE EFFECT
The incidence of adverse reactions observed during clinical trials in patients with epilepsy (in complex therapy and with gabapentin monotherapy) and in patients with neuropathic pain is distributed in the following order: very often (more than 10% of cases), often ( 1% -10% of cases), infrequently (0.1% -1% of cases), rarely (0.01% -0.1% of cases), very rarely (less than 0.01% of cases, including reports of single side effects). Where there was a different incidence of side effects, the highest frequency was indicated. The incidence of adverse reactions noted in post-marketing observations can not be assessed on the basis of available data. In the data below, their frequency is indicated as "unknown". In each group, undesirable effects are presented in descending order of severity.
Infections and parasitic diseases: very often - viral diseases; often - pneumonia, respiratory diseases, urinary tract infections, infectious diseases, otitis media.
On the part of the hematopoiesis system: often - leukopenia; unknown - thrombocytopenia.
From the immune system: rarely - allergic reactions (including urticaria rash); unknown - drug rash with eosinophilia and systemic symptoms (DRESS syndrome).
From the side of metabolism and nutrition: often - anorexia, increased appetite.
From the side of the psyche: often - hostility, confusion and emotional lability, depression, anxiety, increased nervous excitability, disturbance of thinking; unknown - hallucinations .
From the nervous system: very often - drowsiness, dizziness, ataxia; often - convulsions, hyperkinesia, dysarthria, amnesia, tremor, sensitivity disorders such as paresthesia, decreased sensitivity, impaired coordination of movements, nystagmus, increased, decreased or absent reflexes; rarely - hypokinesia; unknown - other disorders of motor functions (including dyskinesia, dystonia).
From the side of the organ of vision: often - impaired vision, such as reduced visual acuity, double vision.
From the side of the hearing organ and labyrinthine disturbances: often - dizziness; unknown - ringing in the ears.
From the cardiovascular system: often - arterial hypertension, vasodilation; rarely - a heartbeat.
From the respiratory system: often - dyspnea, bronchitis, pharyngitis, cough, rhinitis.
On the part of the digestive system: often - vomiting, nausea, dental abnormalities, gingivitis, diarrhea, abdominal pain, dyspepsia, constipation, dry mouth and throat, flatulence; unknown - pancreatitis, hepatitis, jaundice.
From the skin and subcutaneous tissues: often - swelling of the face, hemorrhagic rash is most often described as bruising due to physical trauma, rash, itching, acne;Unknown - Stevens-Johnson syndrome, angioedema, erythema multiforme, alopecia.
From the musculoskeletal system and connective tissue: often - pain in the joints, muscle pain, back pain, convulsive twitching; unknown - myoclonus.
From the side of the kidneys and urinary tract: unknown - acute renal failure, urinary incontinence.
From the genitals and the breast: often - impotence; unknown - breast hypertrophy, gynecomastia.
General disorders and disorders at the injection site: very often - fatigue, fever; often - peripheral edema, gait disorders, asthenia, pain, malaise, flu-like syndrome;rarely - generalized edema; unknown - withdrawal syndrome (mainly anxiety, insomnia, nausea, pain, sweating), chest pain. Cases of sudden sudden death were reported when a causal relationship with gabapetpin treatment was not established.
From laboratory and instrumental studies: often - leukopenia, weight gain; rarely - increased levels of hepatic enzymes (ACT, ALT) and bilirubin; unknown - fluctuations in blood glucose levels in patients with diabetes.
Trauma, intoxication and complications of manipulation: often - accidental injury, fracture, abrasions.
In the treatment of gabapentin, there are reports of cases of acute pancreatitis. A causal relationship with gabapentin was not established.
There have been reports of cases of myopathy with an increase in the level of creatine kinase in patients in the terminal stage of renal failure who are on hemodialysis.
Respiratory tract infections, otitis media, bronchitis and convulsions in children have been reported only in clinical studies. In addition, in clinical studies in children in most cases, aggressive behavior and hyperkinesis were noted.
CONTRAINDICATIONS
acute pancreatitis;
- hereditary failure of galactase;
- deficiency of lactase;
- glucose-galactose malabsorption syndrome;
- Hypersensitivity to any of the components of the drug.
With caution: renal failure, psychotic diseases.
PREGNANCY AND LACTATION
The risk associated with epilepsy and antiepileptic drugs in general
In mothers receiving antiepileptic medicines, the risk of having children with congenital defects increases 2-3 times. The most frequently reported cases of birth of children with a hare lip, malformations of the cardiovascular system and neural tube defects. Complex therapy with several antiepileptic drugs increases the risk of congenital malformations more than monotherapy. Therefore, whenever possible, monotherapy is preferred. Women of childbearing age who need an anticonvulsant
therapy, it is necessary to consult a specialist. The need to continue treatment with anticonvulsant drugs should be reviewed in case of pregnancy planning. It should not be abruptly canceled
antiepileptic drugs, tk. this can lead to the resumption of convulsive seizures, which can have serious consequences for the health of the mother and child. The developmental delay in children born to women with epilepsy is rare. Differentiate, what are the reasons for the delay in development: genetic, social factors, a mother's disease with epilepsy, or the use of antiepileptic drugs, is not possible.
The risk associated with gabapentin
Data on the use of gabapentin in pregnant women are absent.
In animal studies, reproductive toxicity has been demonstrated. A potential risk to a person is not known. Gabapentin should not be used during pregnancy if the potential benefit to the mother does not outweigh the potential risk to the fetus.
Certain conclusions as to whether there is an increased risk of congenital malformations, if gabapentin was used during pregnancy, can not be made, since in every report on the use of gabapentin in pregnancy, there was epilepsy as such and concomitant therapy with antiepileptic drugs.
Gabapentin enters the mother's milk. Since the effect of gabapentin on children during breastfeeding is not known, caution should be exercised in prescribing gabapentin to a nursing mother. GABAPENTIN should be used in nursing mothers only if the potential benefit to the mother outweighs the potential risk to the fetus.
APPLICATION FOR FUNCTIONS OF THE LIVER
Patients with renal failure are recommended to reduce the dose of gabapentin according to the table:
Creatinine clearance (ml / min) Daily dose (mg / day) (in 3 divided doses)
> 80 900-3600
50-79 600-1800
30-49 300-900
15-29 150 * -600
<15 150 * -300
* - Assign 300 mg every other day.
Patients who are on hemodialysis who have not previously taken gabapentin, the drug is recommended to be prescribed in a saturating dose of 300-400 mg, and then apply it to 200-300 mg 4 h of hemodialysis.
APPLICATION FOR CHILDREN
Assign to children over 12 years. Influence on training, intelligence, and development of children and adolescents with long-term (more than 36 weeks) therapy with gabapentin has not been studied enough. Therefore, the benefits of long-term therapy should be evaluated in view of the potential risk of such treatment.
APPLICATION IN ELDERLY PATIENTS
In patients 65 years of age and older, no systematic studies with gabapentin have been performed. In a double-blind study, it was shown that patients with neuropathic pain at the age of 65 and older had a slightly higher percentage than younger patients who had drowsiness, peripheral edema, and asthenia. Along with these observations, clinical studies in this age group do not indicate that the profile of adverse events differs from those observed in younger patients.
SPECIAL INSTRUCTIONS
Suicide, suicidal thoughts or deterioration of the clinical picture
In patients receiving antiepileptic drugs for several indications, suicidal thoughts and behavior were recorded. A meta-analysis of randomized placebo-controlled trials of antiepileptic drugs also showed a slight increase in the risk of suicidal thoughts and behavior. The mechanism of this risk is not known, and the available data do not exclude the possibility of increasing the risk with gabapentin.
It is necessary to ensure close monitoring of patients to identify suicidal thoughts and behavior. When these signs appear, appropriate treatment should be prescribed.Patients and caregivers should be advised to consult a doctor if signs of suicidal thoughts or behavior appear.
Drug rash with eosinophilia and systemic manifestations (DRESS syndrome)
In patients taking antiepileptic drugs, including gabapentin, severe, life-threatening, systemic hypersensitivity reactions have been reported, such as a drug rash with eosinophilia and systemic symptoms (DRESS syndrome).
It should be noted that early manifestations of hypersensitivity, such as fever or lymphadenopathy (lymphadenopathy), may occur, even if there is no rash. If such signs or symptoms appear, you should immediately examine the patient. The use of gabapentin should be discontinued if an alternative cause of these symptoms can not be established.
If the patient undergoing treatment with gabapentin develops acute pancreatitis, gabapentin should be discontinued.
Although withdrawal syndrome in the treatment of gabapentin was not observed, it is not recommended to stop the treatment abruptly. Cancellation of any anticonvulsant in patients with epilepsy can provoke an epileptic status.
In the treatment of gabapentium, as with other anticonvulsant drugs, some patients may experience a seizure frequency or the appearance of new types of seizures.Monotherapy with gabapentin in the treatment of patients,
resistant to therapy with anticonvulsant drugs, is not successful, as with the use of other antiepileptic drugs.
Gabapentin is not effective in primary generalized seizures, such as absence, and may aggravate these seizures in some patients. GABAPENTIN should be used with caution in patients with mixed convulsive seizures, incl. with absans-epilepsy.
Patients 65 years of age or older
In patients 65 years of age and older, no systematic studies with gabapentin have been performed. In a double-blind study it showed that patients with neuropathic pain at the age of 65 years and older in a slightly higher percentage than in younger persons, observed somnolence, peripheral edema and asthenia. Along with these observations, clinical investigations in this age group do not indicate that adverse event profile different from that observed in younger patients.
Children 12 years and older
impact on learning, intelligence, and development in children and teenagers long-term (over 36 weeks) gabapentin therapy has been insufficiently studied. Therefore, the benefits of long-term therapy should be evaluated taking into account the potential risk of such treatment.
Laboratory indicators
When semi-quantitative determination of total protein in urine using test strips false-positive results can be obtained. In this case, it is recommended to confirm positive results by other analytical methods, for example, by Byureta, turbidimetric or dye-binding method, or use alternative methods from the beginning.
Preparation Gabagamma В® contains lactose. Patients with hereditary galactose intolerance, lactase deficiency or glucose-galactose malabsorption of the drug is contraindicated.
Effect on the ability to drive mechanisms and
Gabapentin may have minor or moderate influence on the ability to drive and use machines. The drug acts on the central nervous system and may cause drowsiness, dizziness and other symptoms. If these unwanted phenomena are expressed even in mild, they can be potentially dangerous when driving or operating machinery. The symptoms may appear more often in the beginning of treatment and when the dose is increased.
OVERDOSE
Symptoms: dizziness, double vision, impaired speech, drowsiness, lethargy, diarrhea, and increased severity of other side effects.
Treatment: gastric lavage, administration of activated charcoal, symptomatic therapy. Patients with severe renal insufficiency, hemodialysis may be indicated.
DRUG INTERACTION
In a study of healthy volunteers (n = 12) showed that when coadministered with morphine controlled release capsules 20 mg / caps. for 2 h to gabapentin, the increase observed average AUC of gabapentin by 44% compared with the same index without receiving morphine. Patients taking gabapentin and morphine together, must be monitored closely due to the risk of developing symptoms of CNS depression (drowsiness). Dose of gabapentin or morphine should be reduced with the appearance of symptoms.
Interactions between gabapentin and phenobarbital, phenytoin, carbamazepine or valproic acid was not observed. The equilibrium state pharmacokinetics of gabapentin is the same for healthy subjects and patients with epilepsy receiving other anticonvulsants.
The simultaneous use of gabapentin and oral contraceptives containing norethindrone and / or ethinyl estradiol, does not affect the pharmacokinetics of either component.
With simultaneous use of gabapentin with antacids that contain aluminum and magnesium, gabapentin bioavailability is reduced by 24%. It recommended taking gabapentin after about 2 hours after ingestion of antacids.
When receiving probenecid renal excretion of gabapentin is not changed.
When co-administered with cimetidine, a slight decrease in renal excretion of gabapentin that has no clinical significance.
TERMS OF RELEASE FROM PHARMACY
The drug is released by prescription.
TERMS AND CONDITIONS OF STORAGE
The drug should be stored out of reach of children at a temperature of no higher than 25 В° C. Shelf life - 3 years.
