Tebantin - instructions for use, dose, side effects, contraindications

body: ferric oxide red oxide E172 (for doses of 300 mg and 400 mg), iron oxide pigment oxide yellow E172 (for doses of 300 mg and 400 mg), titanium dioxide E171, gelatin.

Description:

Contents of capsules:

White or almost white crystalline powder.

Capsules 100 mg

Capsules Coni-Snap® size # 3, cap: pinkish brown, body: white.

Capsules 300 mg

Capsules Coni-Snap® size 1, the lid: pinkish brown, body: light yellow.

Capsules 400 mg

Capsules Coni-Snap® size no. 0, cap: pinkish brown, body: yellowish orange.

Pharmacotherapeutic group:antiepileptic agent

ATX: & nbsp

N.03.A.X.12 Gabapentin

Pharmacodynamics:

Gabapentin is similar in structure to a neutron-transporter by gamma-aminobutyric acid (GABA). Is a lipophilic substance. However, its mechanism of action is different from that of some other drugs interacting with GABA receptors, including valproic acid preparations, barbiturates, benzodiazepines, GABA transferase inhibitors, GABA-capture inhibitors, GABA agonists and prodrugs of GABA: it does not possess GABAergic properties and does not affect the seizure and metabolism of GABA. Preliminary studies indicate that gabapentin communicates with α₂-δ subunit of potential-dependent calcium channels and inhibits the flow of calcium ions, which plays an important role in the occurrence of neuropathic pain.Other mechanisms involved in the action of gabapentin in neuropathic pain are: reduction of glutamate-dependent death of neurons, an increase in GABA synthesis, suppression of the release of neurotransmitters of the monoamine group. Gabapentin in clinically significant concentrations does not bind to the receptors of other common drugs or transmitters, including GABA receptors_A and 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 and modifies the activity of GABA synthetase and glutamate synthetase enzymes in vitro. The use of gabapentin in rats resulted in an increase in GABA metabolism in some parts of the brain; this effect was similar to that of valproic acid, although it was observed in other parts of the brain.The significance of these effects of gabapentin for its anticonvulsant activity is not established. In animals gabapentin easily penetrates into the brain tissue and prevents seizures caused by maximal electroshock, chemical preparations, including inhibitors of GABA synthesis, as well as caused by genetic factors.

Pharmacokinetics:

Absorption - Fast. After oral administration, the maximum concentration in the plasma (FROM_max) is achieved after 3 hours. When re-administered, the maximum concentration FROM_maxachieved approximately 1 hour faster (t_max) than with a single take. The bioavailability of gabapentin is not proportional to the dose: it decreases with increasing dose. Absolute bioavailability of gabapentin in capsules is about 60%. Food, including those with a high fat content, does not have a significant effect on the pharmacokinetics, in such cases there is a ~ 14% increase AUC and FROM_max. When taking the drug at a dose of 300 to 4800 mg, the average values FROM_max and AUC increased as the dose increased. The deviation from linearity in the case of both indices is very small at doses not exceeding 600 mg; at high doses, the increase is not so significant.

After ingestion of gabapentin, the single-dose plasma concentration of the drug in children aged 4 to 12 years is similar to that in adult patients. With repeated administration of the equilibrium state was achieved after 1-2 days and persisted throughout the course of treatment.

The following are pharmacokinetic parameters of gabapentin for repeated administration of the drug every 8 hours:

Pharmacokinetic options	300 mg (n=7)	400 mg (n=11)
FROM_max(mg / ml)	4,02 (24)	5,50 (21)
T_max (hour)	2,7(18)	2,1 (47)
T_1/2(hour)	5,2 (12)	6.1 (not spec.)
AUC (0-∞) (mg.h / ml)	24,8 (24)	33,3 (20)
Ae (%)	Absent	63,6 (14)

FROM_max - maximum concentration in the blood

T_max - time to reach FROM_max

T_1/2- half-life

AUC is the area under the concentration-time curve

Ae is the amount of gabapentin excreted in the urine

Metabolism: gabapentin practically not metabolized in the human body and does not induce oxidative liver enzymes with a mixed function involved in the metabolism of drugs.

Distribution: gabapentin practically does not bind to plasma proteins (less than 3%), the volume of distribution is 57.7 liters. The concentration of gabapentin in the cerebrospinal fluid is 20% of the plasma concentration in the equilibrium state.Passes through the blood-brain barrier, penetrates into breast milk.

Excretion: The removal of gabapentin from the plasma has a linear dependence. The half-life (T_1/2) is 5-7 hours, does not depend on the dose. The rate of elimination constant, clearance from plasma and renal clearance of gabapentin are directly proportional to the creatinine clearance. Gabapentin is excreted by the kidneys unchanged. It is removed from the plasma during hemodialysis.

Special patient groups

The clearance of gabapentin from plasma decreases in elderly patients and patients with impaired renal function, T_1/2 when the creatinine clearance is less than 30 ml / min. is about 52 hours. In patients with impaired renal function and patients on hemodialysis, dose adjustment is recommended.

Indications:

- Partial cramps with secondary generalization or without it in adults and children over 12 years of age as monotherapy or complementary therapy.

- Partial cramps with secondary generalization or without it in children from 3 to 12 years of age as adjunctive therapy.

- Neuropathic pain in patients older than 18 years. Efficacy and safety in patients under the age of 18 years are not established.

Contraindications:

- Hypersensitivity to any of the components of the drug;

acute pancreatitis;

- monotherapy in children aged 3 to 12 years;

- children under 3 years;

- lactation period;

- Lactase insufficiency, lactose intolerance, glucose-galactose malabsorption (in the drug form of the drug contains lactose).

Carefully:

Renal failure.

Pregnancy and lactation:

There are no data on the use of the drug in pregnant women, so gabapentin should be used during pregnancy only if the intended benefit to the mother justifies the possible risk to the fetus.

Gabapentin is excreted in breast milk, its effect on breastfed babies is unknown, therefore, while Tebantin® breastfeeding should be prescribed only if the benefit to the mother clearly outweighs the risk to the baby.

Dosing and Administration:

Teabantin® is administered internally, regardless of food intake or with food.

Capsules should be taken without chewing with a sufficient amount of liquid. With a three-fold administration, it should be borne in mind that the time between two doses should not exceed 12 hours.

Partial cramps:

Adults and children over 12 years of age: usually, antiepileptic effect is provided from 900 to 1200 mg / day. The desired therapeutic effect is achieved within a few days after titration.

Recommended dosing regimens:

A. 1st day: 300 mg gabapentin per day (1 capsule 300 mg once a day or 1 capsule 100 mg 3 times a day)

Day 2: 600 mg gabapentin per day (1 capsule 300 mg twice a day or 2 capsules 100 mg 3 times daily)

Day 3: 900 mg gabapentin per day (1 capsule 300 mg 3 times daily or 3 capsules 100 mg 3 times daily)

From the 4th day: the daily dose can be increased to 1200 mg, divided into 3 doses per day (for example, 1 capsule 400 mg 3 times a day).

B. Alternative dosing regimen: initial dose on the first day - 1 capsule 300 mg 3 times a day (corresponds to 900 mg gabapentin), after which the dose can be increased to 1200 mg / day.

Depending on the effect obtained, the dose can be increased by 300-400 mg / day, but not exceeding the total daily dose (with a three-time intake) of 2,400 mg, which is due to the lack of data on the effectiveness and safety of higher doses.

The use of the drug as an additional therapy in children aged 3-12 years and body weight over 17 kg:

Due to insufficient data on efficacy and safety, the drug is not recommended for children under 3 years of age and is not recommended for children aged 3 to 12 years as a monotherapy.

The recommended daily dose of the drug (divided into three doses) is 25-35 mg / kg / day. Table 1 contains recommended daily doses of gabapentin per kg of body weight.

The effective dose is achieved by titration according to the following scheme:

1st day: 10 mg / kg / day

2nd day: 20 mg / kg / day

Day 3: 30 mg / kg / day, according to the method given in the table. Then, if necessary, the daily dose of gabapentin (divided into three doses) may be increased to 35 mg / kg / day. Data from long-term clinical studies confirmed the good tolerability of doses in 40-50 mg / kg / day.

Table 1: Initial doses of gabapentin in children aged 3-12 years and body weight more 17 kg

Weight of child (kg)

Dose

1st day

2 nd day

Day 3

17-25

600 mg

200 mg

(1 per day)

200 mg

(2 times a day)

200 mg

(3 times a day)

>26

900 mg

300 mg

(1 per day)

300 mg

(2 times a day)

300 mg

(3 times a day)

Supportive doses of gabapentin in children aged 3-12 years and body weight of more than 17 kg

Weight, kg)	Total dose of mg / day
17-25	600
26-36	900
37-50	1200
51-72	1800

Treatment of neuropathic pain in adults (over 18 years)

The optimal therapeutic dose for the treatment of neuropathic pain is titrated by the attending physician on the basis of efficacy and tolerability. Depending on the individual reaction of the patient, the dose can reach 3600 mg / day.

Recommended dosing regimens:

A. Day 1: 300 mg of gabapentin per day (1 capsule 300 mg once a day or 1 capsule 100 mg 3 times a day)

Day 2: 600 mg of gabapentin per day (1 capsule 300 mg 2 times a day or 2 capsules 100 mg 3 times a day)

Day 3: 900 mg of gabapentin per day (1 capsule 300 mg 3 times a day or 3 capsules 100 mg 3 times a day)

B. Alternative dosing regimen with intensive pain: the initial dose on the first day - 1 capsule 300 mg 3 times a day (corresponds to 900 mg gabapentin), after which the dose can be increased for 7 days to 1800 mg / day.

In some cases, to achieve the desired analgesic effect, the dose can be raised to a maximum of 3600 mg / day, spreading it into three doses. (In clinical studies, during the first week, the dose was increased to 1800 mg, and for the second and third weeks, respectively, to 2,400 mg and 3600 mg.)

Weakened patients with low body weight or who underwent organ transplantation the dose can be increased strictly by 100 mg per day.

In elderly patients in accordance with the age-related decline in creatinine clearance, and in patients with renal insufficiency (creatinine clearance <80 ml / min) or on hemodialysis The therapeutic dose is selected individually according to the following scheme presented in Table 2.

Table 2: Recommended doses of gabapentin for decreased renal function

Creatinine clearance (ml / min)	*Total daily dose of gabapentin mg / day**
≥80 (normal ground clearance)	900-2400
50-79	600-1800
30-49	300-900
15-29	150**-600
<15	150**-300

* The daily dose should be divided into three doses

** Dose intake 3 x 100 mg every other day

Dosing regimen for hemodialysis: Patients who are on hemodialysis and have not previously taken gabapentin, it is recommended to appoint a saturating dose of 300-400 mg, then 200-300 mg every 4 hours of hemodialysis. In days free of hemodialysis, gabapentin can not be accepted.

Side effects:

When treating partial seizures

Are common: pain in the back, chest pain, fever, fatigue, flu-like syndrome, asthenia, malaise.

From the side nervous system: drowsiness, dizziness, headache, amnesia, ataxia, depression, emotional lability, increased nervous excitability,nystagmus (dose-dependent), tremor, muscle twitching, hyperkinesia, dysarthria, impaired coordination, hallucinations, motor disorders (choreoathetosis, dyskinesia, dystonia), impaired thinking, confusion, tics, paresthesia (dose-dependent), hyperkinesia, enhancement, weakening or lack of reflexes , anxiety, anxiety, hostility, insomnia.

From the digestive system: nausea, vomiting, abdominal pain, indigestion, increased appetite, dry mouth or throat, constipation, diarrhea, dental lesions, pancreatitis, hepatitis, jaundice, increased activity of "liver" transaminases, flatulence, anorexia, gingivitis.

From the side of the cardiovascular system: palpitation, symptoms of vasodilation. When prescribed with other drugs - increased blood pressure.

On the part of the hematopoiesis system: leukopenia, thrombocytopenia.

From the side of the musculoskeletal system: arthralgia, myalgia, fractures.

From the respiratory system: pharyngitis, rhinitis, with an appointment with other antiepileptic drugs - cough, pneumonia.

From the sense organs: visual impairment (amblyopia, diplopia), tinnitus.

From the side urogenital system: impotence, urinary incontinence, acute renal failure, an increase in the volume of mammary glands, gynecomastia, with the appointment of other antiepileptic drugs - urinary tract infection.

Allergic reactions: skin rash, itching, urticaria, fever, angioedema, multiforme exudative erythema (including Stevens-Johnson syndrome).

Other: purpura, weight gain, discoloration of the tooth enamel, facial edema, peripheral edema, generalized edema, acne, alopecia, fluctuations in blood glucose concentration in patients with diabetes mellitus.

In the treatment of neuropathic pain

Are common: accidental injuries, asthenia, back pain, flu-like syndrome, headache, infections, pain of different localization.

Co hand digestive system: constipation, diarrhea, indigestion, dry mouth, flatulence, nausea, vomiting, abdominal pain.

Diseases of the nervous system: gait disturbance, disorientation, paresthesia, drowsiness, impaired thinking, tremor.

Co hand respiratory system: shortness of breath, pharyngitis.

From the skin: skin rash.

From the side bodies feelings: amblyopia.

Other: peripheral edema, weight gain.

In addition, children under 12 years of age were noted for hostility and hyperkinesia when taking gabapentin as adjunctive therapy.

After the abrupt withdrawal of gabapentin therapy, anxiety, insomnia, nausea, pains of various localizations, sweating were most often noted.

Overdose:

Symptoms acute, life-threatening poisoning was not observed even after a daily intake of 49 g of the drug. When an overdose was observed dizziness, double vision, speech disturbance, drowsiness, lethargy and diarrhea.

Treatment: symptomatic. Patients with severe renal insufficiency can be shown hemodialysis.

Interaction:

Antiepileptic drugs: interactions between gabapentin and phenytoin, carbamazepine, valproic acid, and phenobarbital have not been observed. The pharmacokinetics of gabapentin in the equilibrium state is the same in healthy people and patients receiving other antiepileptic drugs.

Oral contraceptive drugs: gabapentin does not affect the pharmacokinetics and effectiveness of oral contraceptives containing norethisterone and / or ethinyl estradiol. However, the deterioration / cessation of the contraceptive effect of these drugs is possible when combining Tebantin® with other antiepileptic drugs that reduce the effectiveness of oral contraceptives.

Antacids: drugs that neutralize the acidity of the stomach, containing magnesium or aluminum, reduce the bioavailability of gabapentin by 24%. Capsules Tebantin® should be taken 2 hours after taking antacids.

Cimetidine: The combination of cimetidine with gabapentin somewhat reduces the excretion of the latter by the kidneys, which probably has no clinical significance.

Alcohol and other drugs that affect the central nervous system: can enhance undesirable side effects of gabapentin on the CNS (eg, drowsiness, ataxia).

Probenecid does not affect renal excretion of gabapentin.

Morphine: with the joint administration of gabapentin and morphine, when morphine in the form of capsules with controlled release of 60 mg was taken 2 hours before taking gabapentin there was an increase AUC gabapentin by 44% compared with monotherapy with gabapentin, which was accompanied by an increase in the pain threshold (cold pressor test). The clinical significance of these changes is not established. Gabapentin, administered 2 hours after the administration of morphine, did not alter the pharmacokinetic characteristics of morphine. The side effects of morphine when combined with gabapentin did not differ from those observed when taking morphine with placebo.

Laboratory results of protein determination in urine:

When gabapentin was added to other anticonvulsants, false positive results were recorded in determining the total protein in the urine using semi-quantitative tests. If positive results are obtained with such tests, it is recommended to use a more specific method of precipitation with sulfosalicylic acid or biuret breakdown.

Special instructions:

In the process of selecting the optimal therapeutic dose, there is no need to determine the concentration of the drug in the plasma.

The drug is ineffective for the treatment of absent epileptic seizures.

It is necessary to control the glucose level in the blood in patients with diabetes mellitus; sometimes there is a need to changeand dose of hypoglycemic drug.

When the first signs of acute pancreatitis (prolonged pain in the abdominal cavity, nausea, repeated vomiting) should stop treatment with gabapentin. The patient should be subjected to a thorough examination (clinical and laboratory tests) for the purpose of early diagnosis of acute pancreatitis.

With lactose intolerance, it should be noted that the 100 mg capsule contains 22.14 mg of lactose; 300 mg - 66.42 mg; 400 mg - 88.56 mg.

If necessary, reduce the dose, cancel the drug or replace it with an alternative drug should be gradually, for at least one week. A sharp cessation of therapy can provoke an epileptic status.

The safety and effectiveness of administration of gabapentin to children under 3 years of age as an adjunct therapy for epilepsy and in children under 12 years of age have not been established as monotherapy.

The safety and efficacy of neuropathy therapy in patients less than 18 years of age have not been established.

In the case of adult manifestations: drowsiness, ataxia, dizziness, increased fatigue, nausea and / or vomiting, weight gain, and in children: drowsiness, hyperkinesia and hostility,should stop treatment and consult with a doctor.

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

During the treatment period it is necessary to refrain from driving motor vehicles and practicing potentially dangerous activities that require an increased concentration of attention and speed of psychomotor reactions.

Form release / dosage:

Capsules, 100 mg, 300 mg and 400 mg.

Packaging:

10 capsules in a blister of PVC / PVDC film and aluminum foil.

5 or 10 blisters in a cardboard box with the attached instructions for use.

Storage conditions:

At a temperature of no higher than 25 ° C.

Keep out of the reach of children.

Shelf life:

5 years.

Do not use after the expiration date printed on the package.

Terms of leave from pharmacies:On prescription

Registration number:П N016052 / 01

Date of registration:25.11.2009

Expiration Date:Unlimited

The owner of the registration certificate:GEDEON RICHTER, OJSC GEDEON RICHTER, OJSC Hungary

Manufacturer: & nbsp

GEDEON RICHTER-RUS, CJSC Russia

GEDEON RICHTER, Ltd. Hungary

Representation: & nbspGEDEON RICHTER OJSC GEDEON RICHTER OJSC Hungary

Information update date: & nbsp28.12.2016

Illustrated instructions

Instructions

Tebantin® (Tebantin®)