Tebantin, 300mg capsules, 50pcs

Composition

1 capsule. contains: Active ingredients: gabapentin – 300 mg.

Auxiliary substances:

magnesium stearate,

pregelatinized starch,

talc,

lactose monohydrate.

Composition of the gelatin capsule:

gelatin,

iron oxide dye red (E 172),

iron oxide dye yellow (E 172),

titanium dioxide (E 172).

Pharmacological action

Gabapentin is similar in structure to the neurotransmitter gamma-aminobutyric acid (GABA). It is a lipophilic substance. Only its mechanism of action differs from that of some other similar drugs that interact with GABA receptors, including valproic acid preparations, barbiturates, benzodiazepines, GABA transferase inhibitors, GABA uptake inhibitors, GABA agonists and prodrug forms of GABA: it does not have GABA-ergic properties and does not affect GABA uptake and metabolism.

The results of preliminary studies indicate that gabapentin binds to_{the α2}-δ subunit of potential-dependent calcium channels and suppresses the flow of calcium ions, which plays an important role in the occurrence of neuropathic pain. There are also other mechanisms that are involved in the action of gabapentin in neuropathic pain: a decrease in glutamate-dependent neuronal death, an increase in GABA synthesis, and suppression of the release of monoamine group neurotransmitters.

Gabapentin in clinically significant concentrations does not bind to the receptors of other common drugs or transmitters, including GABA_A and GABA_B, benzodiazepine, glutamate, glycine or NMDA receptors.

Unlike phenytoin and carbamazepine, gabapentin does not interact with sodium channels in vitro. Gabapentin partially attenuated the effects of the NMDA glutamate receptor agonist in some in vitro tests, but only at concentrations greater than 100 mmol, which is not achieved in vivo. Gabapentin slightly reduces the release of monoamine neurotransmitters and modifies the activity of the enzymes GABA synthetase and glutamate synthetase in vitro.

When gabapetin was studied in rats, an increase in GABA metabolism was found in some areas of the brain; this effect was similar to that of valproic acid, although it was observed in other areas of the brain. The significance of these effects of gabapentin for its anticonvulsant activity has not been established. In animals, gabapentin easily penetrates the brain tissue and prevents seizures caused by maximum electric shock, chemical preparations, including GABA synthesis inhibitors, as well as due to genetic factors.

Pharmacokinetics

Suction

When taken orally, absorption is rapid. C_max is reached after 3 hours, regardless of the dose, with repeated doses, the time to reach C_max is 1 h. Bioavailability is not proportional to the dose: it decreases with increasing dose.

The absolute bioavailability of gabapentin in capsules is about 60%. Food intake (including those with a high fat content) does not significantly affect the pharmacokinetics, in such cases there is an increase in AUC and_cmax by 14%.

When taking the drug at a dose of 300-4800 mg, the average values with_max and AUC increase with increasing dose. The deviation from linearity for both indicators is very small at doses not exceeding 600 mg; at high doses, the increase is not so significant.

The pharmacokinetic parameters of gabapentin with repeated use of the drug every 8 hours are shown in Table 1.

Distribution

Gabapentin practically does not bind to plasma proteins (less than 3%), vd – 57.7 l. The concentration in the cerebrospinal fluid is 20% of the C_ss in plasma.

Penetrates through the BBB, is excreted in breast milk.

Metabolism

Ghabapentin is practically not metabolized in the human body and does not induce oxidative liver enzymes with mixed functions involved in drug metabolism.

Deduction

Plasma clearance after intravenous use is linear. T_1/2 – 5-7 hours, does not depend on the dose. The elimination rate constant, plasma clearance, and renal clearance of gabapentin are directly proportional to CC. Gabapentin is excreted unchanged by the kidneys. It is removed from the plasma by hemodialysis.

Pharmacokinetics in special clinical cases

When taking a single dose of gabapentin, the plasma concentration of the drug in children from 4 to 12 years is similar to that in adult patients. With repeated doses, the saturation stage is reached in 1-2 days and persists throughout the entire course of treatment.

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

Indications

• neuropathic pain in patients over 18 years of age (efficacy and safety in patients under 18 years of age have not been established).
• partial seizures with or without secondary generalization in adults and children over 12 years of age as monotherapy or additional therapy;
• partial seizures with or without secondary generalization in children from 3 to 12 years of age as additional therapy;

Use during pregnancy and lactation

Data on the use of the drug during pregnancy are not available, so Tebantin®should be used in pregnant women only if the intended benefit to the mother exceeds the possible risk to the fetus.

Gabapentin is excreted in breast milk. The effect of gabapentin on breastfed children is unknown, so if it is necessary to use the drug during lactation, breastfeeding should be discontinued.

Use in children

Contraindicated in children under 3 years of age.

The use of Tebantin® as monotherapy is contraindicated in children aged 3 to 12 years.

Contraindications

• monotherapy in children aged 3 to 12 years;
• children under 3 years of age;
• acute pancreatitis;
• lactase deficiency, lactose intolerance, glucose/galactose malabsorption (the dosage form of the drug contains lactose);
• hypersensitivity to the components of the drug.

Caution should be exercised when prescribing the drug to patients with renal insufficiency.

Use in patients with impaired renal function

Caution should be exercised when prescribing the drug to patients with renal insufficiency.

Recommended doses of gabapentin in patients with impaired renal function

*- take 100 mg of the drug 3 times a day every other day.

Patients who are on hemodialysis and have not previously taken gabapentin should be prescribed a saturating dose of 300-400 mg, then 200-300 mg of the drug should be prescribed every 4 hours of the hemodialysis session. Gabapentin should not be taken on dialysis-free days.

Use in elderly patients

In elderly patients, the dose should be selected individually in accordance with the age-related decrease in creatinine clearance.

Side effects

In the treatment of partial seizures

From the central nervous system and peripheral nervous system:  drowsiness, dizziness, headache, amnesia, ataxia, depression, emotional lability, increased nervous excitability, nystagmus (dose-dependent), tremor, muscle twitching, hyperkinesis, dysarthria, coordination disorders, hallucinations, movement disorders (choreoathetosis, dyskinesia, dystonia), impaired thinking, confusion, tics, paresthesia (dose-dependent), hyperkinesia, increased, weakened or absent reflexes, anxiety, restlessness, hostility, insomnia. In addition, children under 12 years of age showed hostility and hyperkinesia.

From the digestive system: nausea, vomiting, abdominal pain, dyspepsia, increased appetite, dry mouth or throat, constipation, diarrhea, tooth damage, pancreatitis, hepatitis, jaundice, increased activity of hepatic transaminases, flatulence, anorexia, gingivitis, discoloration of tooth enamel.

From the cardiovascular system: palpitations, symptoms of vasodilation. When prescribed with other drugs – increased blood pressure.

From the hematopoietic system: leukopenia, thrombocytopenia.

Musculoskeletal disorders: arthralgia, myalgia, fractures.

Respiratory system disorders: pharyngitis, rhinitis, when prescribed with other antiepileptic drugs – cough, pneumonia.

From the side of the senses: visual impairment (amblyopia, diplopia), tinnitus.

From the urinary system: urinary incontinence, acute renal failure, when prescribed with other antiepileptic drugs – urinary tract infection.

From the side of the reproductive system: impotence, breast enlargement, gynecomastia.

From the side of metabolism: weight gain, facial edema, peripheral edema, generalized edema, fluctuations in blood glucose concentration in patients with diabetes mellitus.

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

Dermatological reactions: purpura, acne, alopecia.

Other services: back pain, chest pain, fever, fatigue, flu-like syndrome, asthenia, malaise.

In the treatment of neuropathic pain

From the digestive system: constipation, diarrhea, dyspepsia, dry mouth, flatulence, nausea, vomiting, abdominal pain.

From the central nervous system and peripheral nervous system: gait disorders, disorientation, paresthesia, drowsiness, impaired thinking, tremor, headache.

Respiratory system disorders: shortness of breath, pharyngitis.

Dermatological reactions: skin rash.

From the side of the senses: amblyopia.

From the side of metabolism: peripheral edema, weight gain.

Other services: accidental injuries, asthenia, back pain, flu-like syndrome, headache, infections, pain of various localization.

After abrupt discontinuation of gabapentin therapy, anxiety, insomnia, nausea, pain of various localization, and increased sweating were most often noted.

Interaction

Interactions between gabapentin and phenytoin, carbamazepine, valproic acid, and phenobarbital were not observed. The pharmacokinetics of gabapentin at steady state are similar in healthy individuals and patients receiving other antiepileptic drugs.

Gabapentin does not affect the pharmacokinetics and efficacy of oral contraceptives containing norethisterone and/or ethinyl estradiol. However, reducing / stopping the contraceptive effect of these drugs is possible when Tebantin® is combined with other antiepileptic drugs that reduce the effectiveness of oral contraceptives.

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

When combined with gabapentin, cimetidine slightly reduces the excretion of the latter by the kidneys, which probably has no clinical significance.

Other drugs that affect the central nervous system, as well as ethanol, can increase the side effects of gabapentin on the central nervous system (for example, drowsiness, ataxia).

Probenecid does not affect the renal excretion of gabapentin.

When taking gabapentin and morphine together, when morphine in the form of controlled-release capsules of 60 mg was taken 2 hours before taking gabapentin, an increase in the AUC of gabapentin by 44% was observed, compared with monotherapy with gabapentin, which was accompanied by an increase in the pain threshold (cold pressor test). The clinical significance of these changes has not been established. When gabapentin was administered 2 hours after morphine use, no changes in the pharmacokinetic parameters of morphine were observed. Side effects of morphine when co-administered with gabapentin were not different from those observed when taking morphine with placebo.

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

How to take, course of use and dosage

In case of partial seizures in adults and children over 12 years of age, the anti-epileptic effect is provided by using the drug at a dose of 900-1200 mg / day. The optimal therapeutic effect is achieved within a few days after titration.

Recommended dosage regimens:

A. On day 1-300 mg of gabapentin (300 mg 1 time/day or 100 mg 3 times/day).

On day 2-600 mg of gabapentin (300 mg 2 times/day or 200 mg 3 times/day).

On day 3-900 mg of gabapentin (300 mg 3 times a day).

On day 4, the daily dose can be increased to 1200 mg in 3 divided doses (400 mg 3 times a day).

or

B. On day 1, the initial dose is 300 mg 3 times, i. e. 900 mg / day. Then the daily dose can be increased to 1200 mg.

Depending on the effect obtained, the dose can be increased by 300-400 mg/day, but not exceeding the total daily dose of 2400 mg (in 3 doses), which is due to insufficient data on the effectiveness and safety of the drug in higher doses.

As an adjunct therapy in children aged 3-12 years and weighing more than 17 kg, the recommended daily dose of the drug is 25-35 mg / kg / day in 3 divided doses. Table 2 shows the recommended daily doses of Tebantin® depending on the child’s body weight. The effective therapeutic dose is achieved by titration according to the following scheme:

Day 1-10 mg / kg / day

Day 2-20 mg / kg / day

Day 3-30 mg / kg/day, according to the method shown in the table. Then, if necessary, the daily dose of Tebantin® can be increased to 35 mg / kg / day in 3 divided doses. Data from long-term clinical studies confirmed the good tolerability of Tebantin® at doses of 40-50 mg / kg / day.

Table 2. Initial doses of gabapentin for children aged 3-12 years and weighing more than 17 kg.

Table 3. Maintenance doses of gabapentin for children aged 3-12 years and weighing more than 17 kg.

It is contraindicated to use the drug Tebantin® in children under 3 years of age and as monotherapy in children aged 3 to 12 years as monotherapy, because data on the effectiveness and safety of gabapentin for this category of patients are insufficient.

In the treatment of neuropathic pain in adults (over 18 years of age) The optimal therapeutic dose of Tebantin® is determined by titration, taking into account efficacy and tolerability. Depending on the individual response of the patient, the maximum dose can reach 3600 mg/day.

Recommended dosage regimens:

A. On day 1-300 mg of gabapentin (300 mg 1 time/day or 100 mg 3 times/day).

On day 2-600 mg of gabapentin (300 mg 2 times/day or 200 mg 3 times/day).

On day 3-900 mg of gabapentin (300 mg 3 times a day).

or

B. In case of intense pain, the initial dose on day 1 is 300 mg 3 times, i. e. 900 mg / day. Then, within 7 days, the daily dose can be increased to 1800 mg / day.

In some cases, to achieve the desired analgesic effect, the dose can be increased to a maximum of 3600 mg / day, distributed in 3 doses. In clinical trials, the dose was increased to 1800 mg during the first week, and to 2400 mg and 3600 mg during the second and third weeks, respectively.

In debilitated patients, patients with low body weight or who have undergone organ transplantation, the dose can be increased strictly by 100 mg / day.

In elderly patients, in accordance with the age-related decrease in creatinine clearance, patients with renal insufficiency (creatinine clearance less than 80 ml/min), as well as patients on hemodialysis, the therapeutic dose should be selected individually (Table 4).

Table 4. Recommended doses of gabapentin in patients with impaired renal function.

* the daily dose should be divided into 3 doses

* * take 100 mg of the drug 3 times a day every other day.

Patients who are on hemodialysis and have not previously taken gabapentin should be prescribed a saturating dose of 300-400 mg, then 200-300 mg of the drug should be prescribed every 4 hours of the hemodialysis session. Tebantin® should not be taken on dialysis-free days.

Capsules should be taken orally, without chewing and washed down with the necessary amount of liquid, regardless of food intake.

Overdose

Symptoms: dizziness, double vision, drowsiness, dysarthria, lethargy and diarrhea. Symptoms of acute, life-threatening poisoning were not observed even after a daily intake of 49 g of the drug.

Treatment: conducting symptomatic therapy. Hemodialysis may be indicated for patients with severe renal insufficiency.

Special instructions

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

The drug is ineffective in absences.

When using gabapentin, it is necessary to monitor blood glucose levels in patients with diabetes mellitus; sometimes it is necessary to change the dose of the hypoglycemic drug.

When the first signs of acute pancreatitis appear (prolonged abdominal pain, nausea, repeated vomiting), gabapentin treatment should be discontinued. A thorough examination of the patient (clinical and laboratory tests) should be performed in order to make an early diagnosis of acute pancreatitis.

In case of lactose intolerance, it should be noted that 1 capsule (100 mg) contains 22.14 mg of lactose,1 capsule (300 mg) – 66.42 mg of lactose, and 1 capsule (400 mg) – 88.56 mg of lactose.

Reduce the dose, discontinue the drug or replace it with another alternative remedy gradually for at least 1 week. Abrupt discontinuation of therapy can trigger an epileptic status.

In case of drowsiness, ataxia, dizziness, fatigue, nausea and/or vomiting, weight gain in adults, and drowsiness, hyperkinesia and hostility in children, you should stop taking the drug and consult your doctor.

Use in pediatrics

The safety and efficacy of gabapentin in children under 3 years of age as adjunctive therapy for epilepsy and in children under 12 years of age as monotherapy have not been established.

The safety and efficacy of neuropathic pain therapy in patients under 18 years of age have not been established.

Influence on the ability to drive vehicles and work with mechanisms

During treatment, patients should refrain from driving vehicles and engaging in potentially dangerous activities that require increased concentration of attention and speed of psychomotor reactions.

Form of production

Capsules

Storage conditions

At a temperature not exceeding 25 °C

Shelf life

5 years

Active ingredient

Gabapentin

Conditions of release from pharmacies

By prescription

Dosage form

Capsules

Purpose

Children as prescribed by a doctor, Adults as prescribed by a doctor

Indications

Epilepsy