Gabagamma - instructions for use, doses, side effects, contraindications

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 α₂-δ-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 in clinically significant concentrations does not bind to receptors of other common drugs or neurotransmitters, including GABA receptors_A, GABA_AT, benzodiazepine, glutamate, glycine or N-methyl-d-aspartate. Unlike phenytoin and carbamazepine gabapentin does not interact with sodium channels in vitro. Gabapentin partially attenuated the effects of the glutamate receptor agonist N-methyl- d-aspartate in some tests in vitro, but only at a concentration of more than 100 μmol, which is not achieved in vivo. Gabapentin slightly reduces the release of monoamine neurotransmitters in vitro.

Pharmacokinetics:

The bioavailability of gabapentin is not proportional to the dose. So, with an increase in the dose, it decreases. After oral administration, the maximum concentration (C_mOh) gabapentin in plasma is achieved after 2-3 hours. Absolute bioavailability of gabapentin in capsules is about 60%. Food, including those with a high fat content, does not affect the pharmacokinetics. The elimination of gabapentin from plasma is best described using a linear model. The half-life (T_1/2) from the plasma does not depend on the dose 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 a volume distribution of 57.7 liters. 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. 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. Gabapentin is removed from the plasma during hemodialysis. In patients with impaired renal function and patients receiving hemodialysis treatment, dose adjustment is recommended (see "Method of administration and dose").

Indications:

- Adults and children from the age of 12: in complex therapy of partial seizures with secondary generalization or without it;

- in adults: pain syndrome in diabetic neuropathy, postherpetic neuralgia.

Contraindications:

Hypersensitivity to any of the components of the drug, acute pancreatitis, hereditary galactose deficiency, lactase deficiency, glucose-galactose malabsorption.

Carefully:

Renal failure (see "Method of administration and dose"), 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 of several antiepileptic drugs increases the risk of congenital malformations more than monotherapy. Therefore, whenever possible, monotherapy is preferred. Women of childbearing age who need anticonvulsant therapy should consult a specialist.

The need to continue treatment with anticonvulsant drugs should be reviewed in case of pregnancy planning. It should not be drastically abolished 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, maternal 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 Do not use during pregnancy if the potential benefit to the mother does not outweigh the potential risk to the fetus.

Certain conclusions about whether there is an increased risk of congenital malformations, if during pregnancy was used gabapentin, can not be done, since in every report on the use of gabapentin in pregnancy, there was epilepsy per se, 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.

Dosing and Administration:

Inside, regardless of food intake or with food. 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.

In debilitated patients, and patients in severe general condition, low body weight and organ transplantation, increasing the dosage must be carried out gradually with dosage of 100 mg.

Neuropathic pain in adults

The initial dose is 900 mg / day in three divided doses; if necessary, the dose is gradually increased to a maximum of 3600 mg / day. Treatment may start with a dose of 900 mg / day (300 mg 3 times a day) or within the first 3 days the dose may be increased gradually to 900 mg a day according to the following scheme:

Day 1: 300 mg of the drug once a day

Day 2: 300 mg twice a day

3-th day: 300 mg 3 times a day

Partial cramps the adults and children from 12 years old

The effective dose is from 900 to 3600 mg / day. Therapy can be started with a dose of 300 mg three times a day on the first day and increased gradually to 900 mg according to the scheme described above (see.section "Neuropathic pain in adults"). 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 its 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:

Creatinine clearance (ml / min)	The daily dose (mg / day) for three 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.

Recommendations for patients on hemodialysis

Patients on hemodialysis who had 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.

In debilitated patients, and patients in severe general condition, low body weight and organ transplantation, increasing the dosage must be carried out gradually with dosage of 100 mg.

Side effects:

The incidence of adverse events observed during clinical trials that were conducted in patients with epilepsy (in complex therapy and monotherapy) and in patients with neuropathic pain, is distributed in the following order: very often (more than 10% of cases), often (in 1% - 10% of cases), infrequently (0.1% -1 % of cases), rarely (in 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.

For adverse reactions noted in post-marketing observations, the frequency can not be estimated from the available data; in the table, their frequency is indicated as "Frequency is unknown". In each group, undesirable effects are presented in descending order of severity.

Organs and Systems	Adverse Reactions
Infections and parasitic diseases
Often	Viral diseases
Often	Pneumonia, respiratory diseases, urinary tract infections, viral infections, otitis media
Violations lymphatic on the part of the blood and system
Often	Leukopenia
Frequency unknown	Thrombocytopenia
Immune system disorders
Infrequently	Syndrome hypersensitivity, allergic reactions (including urticaria rash)
Disorders from the metabolism and nutrition
Often	Anorexia, increased appetite
Violations psychoki
Often	Hostility, confusion and emotional lability, depression, anxiety, increased nervous excitability, impaired thinking
Frequency unknown	Hallucinations
Violations from fromTons of the nervous system
Often	Drowsiness, dizziness, ataxia
Often	Convulsions, hyperkinesis, dysarthria, amnesia, tremor, insomnia, headache, disorders sensitivity such as paresthesia, decreased sensitivity, impaired coordination of movements, nystagmus, increased, decreased or absent reflexes
Infrequently	Hypokinesia
Frequency unknown	Other disorders of motor functions (incl. choreoathetosis, dyskinesia, dystonia)
Disturbances on the part of the organ of sight
Often	Visual impairment, such as reduced visual acuity, double vision
Hearing disorders and labyrinthine disorders
Often	Dizziness
Frequency unknown	Tinnitus
Heart Disease
Infrequently	Heart palpitations
Vascular disorders
Often	Hypertension, vasodilation
Disturbances from the respiratory system of the chest and mediastinal organs
Often	Shortness of breath, bronchitis, pharyngitis, cough, rhinitis
Disorders from the side of the gastrointestinal tract
Often	Nausea, vomiting, dental problems, gingivitis, diarrhea, abdominal pain, indigestion, constipation, dry mouth and throat, flatulence
Frequency unknown	Pancreatitis
Disturbances from the liver and bile ducts
Frequency unknown	Hepatitis, jaundice
Disturbances from the skin and subcutaneous tissues
Often	Edema of the face, hemorrhagic rash, most often described as bruising due to physical trauma, rash, itching, acne
Frequency unknown	Drug rash with eosinophilia and systemic symptoms (DRESS syndrome), Stevens-Johnson syndrome, angioedema, erythema multiforme, alopecia
Disturbances from musculoskeletal and connective tissue
Often	Joint pain, muscle pain, back pain, convulsive twitching
Frequency unknown	Myoclonus, rhabdomyolysis
Renal impairment and urinary tract
Frequency unknown	Acute renal failure, incontinence
Violations of the genitals and mammary glandThreat
Often	Impotence
Frequency unknown	Hypertrophy of the breast, gynecomastia
General disorders and disorders at the site of administration
Often	Fatigue, fever
Often	Peripheral edema, gait disorders, asthenia, pain, malaise, flu-like syndrome
Infrequently	Generalized edema
Frequency unknown	The withdrawal syndrome, which manifests itself in the form of anxiety, insomnia, nausea, sweating, chest pain. There are reports of sudden sudden deaths, but the cause-and-effect relationship with gabapentin treatment has not been established
Laboratory and instrumental data
Often	Reduced leukocyte count in the blood, increase in body weight
Infrequently	Increase in the concentration of hepatic enzymes (ACT, ALT) and bilirubin
Frequency unknown	Fluctuations in blood glucose concentration in patients with diabetes mellitus, increased activity of creatine phosphokinase
Trauma, intoxication and complications of manipulation
Often	Accidental trauma, fracture, abrasions

In the treatment of gabapentin, there are reports of cases of acute pancreatitis.A causal relationship with gabapentin was not established.

Cases of myopathy with an increase in creatine kinase activity in patients in the terminal stage of renal failure on hemodialysis have been reported.

Respiratory tract infections, otitis media, bronchitis and convulsions in children have been reported only in clinical studies. In addition, clinical studies in children often noted hyperkinesis and aggressive behavior.

Overdose:

Symptoms: dizziness, diplopia, speech impairment, drowsiness, lethargy, diarrhea and increased severity of other side effects.

Treatment: gastric lavage, reception of activated charcoal, symptomatic therapy. Patients with severe renal insufficiency can be shown hemodialysis.

Interaction:

In a study involving healthy volunteers (n = 12), it was shown that when the morphine was concurrently administered in capsules with controlled release of 20 mg / caps 2 hours before gabapentin intake, an increase in the mean value of the area of the concentration-time curve was observed (AUC) gabapentin by 44% compared with this indicator without taking morphine.

Patients taking together morphine and gabapentin, should be carefully monitored in connection with the risk of developing symptoms of CNS depression (drowsiness). If such symptoms appear, the dose of gabapentin or morphine should be reduced.

Interactions between gabapentin and phenobarbital, phenytoin, valproic acid, or carbamazepine were not observed.

The equilibrium state of pharmacokinetics of gabapentin is the same for healthy individuals 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 any component.

With the simultaneous use of gabapentin with antacids containing aluminum and magnesium, the bioavailability of gabapentin is reduced by 24%. It is recommended that gabapentin approximately two hours after taking antacid preparations.

When taking probenecid, renal excretion of gabapentin does not change.

When combined with cimetidine, there is a slight decrease in renal excretion of gabapentin, which has no clinical significance.

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. Meta-analysis of randomized placebo-controlled trials 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 allow to 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, serious, 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 gabapentin, as with other anticonvulsant drugs, some patients may experience a seizure frequency or the appearance of new types of seizures. Monotherapy 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 seizures, including absent-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 studies in this age group do not indicate that the profile of adverse events differs from those observed in younger patients.

Children 12 years and over

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.

Laboratory indicators

When semiquantitative determination of the total protein in the urine with the help of test strips, false-positive results can be obtained.In this case, it is recommended to confirm the positive result by other analytical methods, for example, Buret's method, turbidimetric or dye-binding method, or use alternative methods from the very beginning. The drug Gababamma® contains lactose. Patients with hereditary intolerance to galactose, a deficiency of lactase or glucose-galactose malabsorption, the drug is contraindicated.

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

Gabapentin may have little or moderate influence on the ability to drive and work with machinery. The drug acts on the central nervous system and can cause drowsiness, dizziness and other symptoms. If these adverse events are expressed even mildly, they can be potentially dangerous when administered vehicles or the operation of machinery. Symptoms can appear more often at the beginning of treatment and with increasing doses.

Form release / dosage:Capsules, 100 mg, 300 mg and 400 mg.

Packaging:

10 capsules per blister for 2, 5 or 10 blisters in a cardboard box with instructions for use.

Storage conditions:

At a temperature of no higher than 25 ° C.

Keep out of the reach of children.

Shelf life:

3 years.

Do not use after the expiration date.

Terms of leave from pharmacies:On prescription

Registration number:LSR-002222/07

Date of registration:17.12.2007

Expiration Date:Unlimited

The owner of the registration certificate:Wörwag Pharma GmbH & Co. KG. KGWörwag Pharma GmbH & Co. KG. KG Germany

Manufacturer: & nbsp

ARTESAN PHARMA, GmbH & Co. KG. KG Germany

Representation: & nbspVEVWAG PHARMA GmbH & Co. KG VEVWAG PHARMA GmbH & Co. KG Germany

Information update date: & nbsp10.03.2017

Illustrated instructions

Instructions

Gabagamma® (Gabagamma®)