Tebantin, 300 mg capsules 50 pcs

Gabapentin has a structure similar to the neurotransmitter gamma-aminobutyric acid (GABA). It is a lipophilic substance. However, the mechanism of action is different from that of some other similar GABA-receptor interacting drugs, including valproic acid, barbiturates, benzodiazepines, GABA transferase inhibitors, GABA capture inhibitors, GABA agonists and prodrug forms of GABA: it has no GABAergic properties and does not affect GABA capture and metabolism.

The results of preliminary studies suggest that gabapentin binds to the α₂-δ subunit of potential-dependent calcium channels and suppresses calcium ion flux, which plays an important role in causing neuropathic pain. There are also other mechanisms involved in the action of gabapentin in neuropathic pain: reduction of glutamate-dependent death of neurons, increase of GABA synthesis, suppression of monoamine group neurotransmitters release.

Gabapentin in clinically significant concentrations does not bind to 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 glutamate NMDA receptor agonist in some in vitro tests, but only at concentrations greater 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.

In a study of gabapetin in rats, it was found to increase GABA metabolism in some brain sites; this effect was similar to that of valproic acid, although observed in other brain sites. The significance of these effects of gabapentin for its anticonvulsant activity has not been established. In animals, gabapentin readily penetrates brain tissue and prevents seizures induced by maximal electroshock, chemicals including GABA synthesis inhibitors, and genetic factors.

Pharmacokinetics

Absorption

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

The absolute bioavailability of gabapentin in capsules is about 60%. Food intake (including high-fat) has no significant effect on pharmacokinetics; in such cases there is a 14% increase in AUC and C_max.

When the drug is taken at a dose of 300-4800 mg, the mean values of C_max and AUC increase as the dose is increased. The deviation from linearity for both values is very small at doses not exceeding 600 mg; at higher doses the increase is not so significant.

The pharmacokinetic parameters of gabapentin when repeatedly administered every 8 hours are shown in Table 1.

Distribution

Gabapentin is virtually unbound to plasma proteins (less than 3%), V_d is 57.7L. Concentration in cerebrospinal fluid is 20% of plasma C_ss.

It penetrates through the HEB and is excreted with breast milk.

Metabolism

Gabapentin is virtually unmetabolized in the human body and does not induce mixed function liver oxidative enzymes involved in drug metabolism.

Elevation

Elevation from plasma after IV administration is linear. T_1/2 is 5-7 h, independent of dose. The elimination rate constant, plasma clearance and renal clearance of gabapentin are directly proportional to CK. Gabapentin is excreted unchanged by the kidneys. It is eliminated from plasma by hemodialysis.

Pharmacokinetics in Special Clinical Cases

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

The plasma clearance of gabapentin is decreased in elderly patients and in patients with impaired renal function. When CKR is less than 30 ml/min, T_1/2 is about 52 h. Dose adjustment is recommended in patients with impaired renal function and patients on hemodialysis.

Indications

Active ingredient

How to take, the dosage

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

Recommended dosing regimens:

A. On Day 1, 300 mg of gabapentin (300 mg once daily or 100 mg three times daily).

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/day).

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

or

B. On day 1, the starting 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 to exceed the total daily dose of 2400 mg (in 3 doses), due to insufficient data on the effectiveness and safety of using the drug in higher doses.

As adjunctive 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 doses. Table 2 shows the recommended daily doses of Tebantin® depending on the body weight of the child. 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 given in the table. Thereafter, if necessary, the daily dose of Tebantine® can be increased to 35 mg/kg/day in 3 doses. The data of long-term clinical studies have confirmed good tolerability of Tebantin® in 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.

The use of Tebantin is contraindicated® in children younger than 3 years of age and as monotherapy in children aged 3 to 12 years as monotherapy becausebecause there is insufficient data on the efficacy and safety of gabapentin in this patient population.

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

The recommended dosing regimens:

A. On Day 1, 300 mg of gabapentin (300 mg once daily or 100 mg three times daily).

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/day).

or

B. For 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, divided into 3 doses. In clinical trials, the dose was increased to 1800 mg in the first week, and in the second and third weeks to 2400 mg and 3600 mg, respectively.

Patients who are weakened, patients with low body weight, or those who have undergone organ transplantation can have the dose increased strictly by 100 mg/day.

In elderly patients with age-related renal impairment, in patients with renal failure (CK lower than 80 ml/min), or in patients on hemodialysis, the therapeutic dose should be adjusted individually (Table 4).

Table 4: Recommended doses of gabapentin for renal impairment.

* The daily dose should be divided into 3 doses

** Take 100 mg of the drug 3 times daily.

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

The capsules should be taken orally without chewing and with as much liquid as necessary, regardless of meals.

Interaction

No interaction between gabapentin and phenytoin, carbamazepine, valproic acid and phenobarbital has been noted. Pharmacokinetics of gabapentin in equilibrium is similar in healthy people and patients receiving other antiepileptic drugs.

Gabapentin does not affect the pharmacokinetics and efficacy of oral contraceptive drugs containing norethisterone and/or ethinylestradiol. However, reduction/elimination of the contraceptive effect of these drugs is possible when combining Tebantin® with other antiepileptic drugs that reduce the effectiveness of oral contraceptives.

Magnesium or aluminum-containing agents that neutralize gastric acidity reduce the bioavailability of gabapentin by 24%. Tebantin® capsules should be taken 2 hours after taking antacids.

Combination of cimetidine with gabapentin slightly decreases excretion of the latter in the kidneys, which is probably not clinically relevant.

Other CNS medications, as well as ethanol, may increase CNS side effects of gabapentin (e.g. drowsiness, ataxia).

Probenecid does not affect renal excretion of gabapentin.

When gabapentin and morphine were co-administered, when morphine in the form of 60 mg controlled-release capsules was taken 2 hours prior to gabapentin administration, a 44% increase in gabapentin AUC was observed compared to gabapentin monotherapy, which was also accompanied by an increase in pain threshold (cold pressor test). The clinical significance of these changes has not been established. No changes in pharmacokinetic parameters of morphine were observed while using gabapentin 2 hours after morphine administration. Side effects of morphine when coadministered with gabapentin did not differ from those observed when morphine was given with placebo.

When gabapentin was added to other anticonvulsants, false-positive results were reported for urinary total protein determination using semi-quantitative tests. If positive results are obtained with such tests, it is recommended to use the more specific sulfosalicylic acid precipitation or biurette assay.

Special Instructions

There is no need to measure plasma concentrations of the drug when selecting the optimal therapeutic dose.

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 hypoglycemic drug.

The first signs of acute pancreatitis (prolonged abdominal pain, nausea, recurrent vomiting) should be discontinued with gabapentin. The patient should be thoroughly examined (clinical and laboratory tests) for early diagnosis of acute pancreatitis.

In case of lactose intolerance, note that 1 capsule (100 mg) contains 22.14 mg lactose, 1 capsule (300 mg) contains 66.42 mg lactose, and 1 capsule (400 mg) contains 88.56 mg lactose.

Dose reduction, withdrawal, or replacement with another alternative medication should be done gradually over a period of at least 1 week. Abrupt discontinuation of therapy may provoke epileptic status.

In adults, if drowsiness, ataxia, dizziness, increased fatigue, nausea and/or vomiting, weight gain, and in children, drowsiness, hyperkinesia, and hostility occur, the drug should be stopped and the physician should be consulted.

Pediatric Use

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

Impact on ability to drive motor transport and operate mechanisms

Patients must refrain from driving and engaging in potentially dangerous activities requiring increased concentration and quick psychomotor reactions during treatment.

Contraindications

Patients with renal insufficiency should use the drug with caution.

Perhaps with renal impairment

Patients with renal impairment should use the drug with caution.

Recommended doses of gabapentin in renal impairment

*- take 100 mg of the drug 3 times daily.

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

The use in elderly patients

The dose should be adjusted individually in elderly patients according to the age-related CK decline.

Side effects

In treatment of partial seizures

CNS and peripheral nervous system disorders: drowsiness, dizziness, headache, amnesia, ataxia, depression, emotional lability, increased nervous excitability, nystagmus (dose-dependent), tremor, muscle twitching, hyperkinesias, dysarthria, coordination disorders, hallucinations, Movement disorders (choreoathetosis, dyskinesia, dystonia), thought disorders, confusion, tics, paresthesias (dose-dependent), hyperkinesia, increased, decreased or absent reflexes, anxiety, restlessness, hostility, insomnia. In addition, hostility and hyperkinesia were noted in children younger than 12 years of age.

Digestive system disorders: nausea, vomiting, abdominal pain, dyspepsia, increased appetite, dry mouth or throat, constipation, diarrhea, dental lesions, pancreatitis, hepatitis, jaundice, increased liver transaminase activity, flatulence, anorexia, gingivitis, discolored teeth enamel.

Cardiovascular system: palpitation, symptoms of vasodilation. When prescribed with other drugs – increase in BP.

Hematopoietic system: leukopenia, thrombocytopenia.

Muscular system disorders: arthralgia, myalgia, fractures.

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

Sensory system disorders: visual impairment (amblyopia, diplopia), tinnitus.

Urinary system disorders: urinary incontinence, acute renal failure, if prescribed with other antiepileptic drugs – urinary tract infection.

In the sexual system: impotence, increase in the volume of the mammary glands, gynecomastia.

Metabolism disorders: weight gain, facial edema, peripheral edema, generalized edema, fluctuations of blood glucose concentration in diabetic patients.

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

Dermatological reactions: purpura, acne, alopecia.

Others: back pain, chest pain, fever, increased fatigue, flu-like syndrome, asthenia, malaise.

In the treatment of neuropathic pain

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

CNS and peripheral nervous system disorders: gait disturbance, disorientation, paresthesia, somnolence, thought disorder, tremor, headache.

Respiratory system: dyspnea, pharyngitis.

Dermatological reactions: skin rash.

Sensory system disorders: amblyopia.

Metabolic reactions: peripheral edema, weight gain.

Others: accidental injury, asthenia, back pain, flu-like syndrome, headache, infections, pain of various localization.

After abrupt withdrawal of therapy with gabapentin, the most frequently observed were restlessness, insomnia, nausea, pain of different localization, and increased sweating.

Overdose

Symptoms: dizziness, double vision, drowsiness, dysarthria, lethargy, and diarrhea. No symptoms of acute, life-threatening poisoning were observed even after daily administration of 49 g of the drug.

Treatment: with symptomatic therapy. Patients with severe renal failure may be indicated for hemodialysis.

Pregnancy use

There are no data on the use of the drug in pregnancy, therefore Tebantin® should be used in pregnant women only if the expected benefits to the mother exceed the possible risk to the fetus.

Gabapentin is excreted with the breast milk. The effect of gabapentin on breastfed children is unknown, so breastfeeding should be discontinued if the drug has to be used during lactation

Preventive use in children

Contraindicated in children under 3 years of age.

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

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