Gapentek^® (Capsules) Instructions for Use

ATC Code

N03AX12 (Gabapentin)

Active Substance

Gabapentin (Rec.INN registered by WHO)

Clinical-Pharmacological Group

Anticonvulsant drug

Pharmacotherapeutic Group

Anticonvulsant agent

Pharmacological Action

Anticonvulsant drug. Gabapentin is structurally related to the neurotransmitter gamma-aminobutyric acid (GABA), but its mechanism of action differs from that of some other drugs that interact with GABA receptors, including valproate, barbiturates, benzodiazepines, GABA transaminase inhibitors, GABA uptake inhibitors, GABA agonists, and GABA prodrugs. It does not possess GABAergic properties and does not affect the uptake and metabolism of GABA.

Preliminary studies have shown that Gabapentin binds to the α₂-δ subunit of voltage-gated 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: reduction of glutamate-dependent neuronal death, increased synthesis of GABA, suppression of the release of monoamine group neurotransmitters.

Gabapentin at clinically significant concentrations does not bind to receptors of other common drugs or neurotransmitters, including GABA_A, GABA_B, benzodiazepine, glutamate, glycine, or N-methyl-D-aspartate (NMDA) receptors. 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 in vitro tests, but only at concentrations above 100 µmol, which is not achieved in vivo. Gabapentin somewhat reduces the release of monoamine neurotransmitters in vitro.

Pharmacokinetics

Absorption

After oral administration, the C_max of gabapentin in plasma is reached in 2-3 hours. The bioavailability of gabapentin is not proportional to the dose, as it decreases with increasing dose. The absolute bioavailability of gabapentin in capsule form is about 60%. Concurrent food intake, including high-fat food, does not affect the pharmacokinetics.

Distribution

Pharmacokinetics does not change with repeated use; C_ss in plasma can be predicted based on the results of a single dose of the drug. Gabapentin is practically not bound to plasma proteins (<3%), V_d is about 57.7 L.

Metabolism

It is not metabolized. It does not induce mixed-function oxidative liver enzymes involved in drug metabolism.

Excretion

The elimination of gabapentin from plasma is linear. T_1/2 does not depend on the dose and averages 5-7 hours. It is excreted exclusively in the urine unchanged.

Pharmacokinetics in special clinical cases

Plasma concentrations of gabapentin in children aged 4 to 12 years have been found to be generally similar to those in adults.

The clearance of gabapentin from plasma is reduced in the elderly and in patients with impaired renal function. The elimination rate constant, plasma clearance, and renal clearance are directly proportional to CC. Gabapentin is removed from plasma by hemodialysis.

Indications

• Treatment of neuropathic pain in adults aged 18 years and older;
• Monotherapy of partial seizures with and without secondary generalization in adults and children over 12 years of age;
• As an adjunct in the treatment of partial seizures with and without secondary generalization in adults and children aged 3 years and older.

ICD codes

Dosage Regimen

Capsules

Gapentek^® is administered orally regardless of meals or with food. If it is necessary to reduce the dose, discontinue the drug, or replace it with an alternative agent, this should be done gradually over a minimum of one week.

For neuropathic pain, adults are prescribed an initial dose of 900 mg/day in 3 divided doses of equal amounts; if necessary, depending on the effect, the dose is gradually increased to a maximum of 3.6 g/day. Treatment can be started immediately with a dose of 900 mg/day (300 mg 3 times/day) or over the first 3 days the dose can be gradually increased to 900 mg/day according to the following scheme:

Day 1 – 300 mg of the drug once a day;

Day 2 – 300 mg twice a day;

Day 3 – 300 mg three times a day.

For partial seizures in adults and children over 12 years of age, the effective dose is from 900 mg to 3.6 g/day. Therapy can be started with a dose of 300 mg 3 times a day on the first day or increased gradually to 900 mg according to the scheme described above. Subsequently, the dose can be increased to a maximum of 3.6 g/day (divided into 3 equal doses). Good tolerability of the drug at doses up to 4.8 g/day has been noted. The maximum interval between doses when taking the drug three times a day should not exceed 12 hours to avoid recurrence of seizures.

For children aged 3-12 years, the initial dose of the drug varies from 10 to 15 mg/kg/day, frequency of administration – 3 times a day in equal doses, increasing to the effective dose is carried out over approximately 3 days. The effective dose in children aged 5 years and older is 25-35 mg/kg/day in equal doses in 3 divided doses. The effective dose of Gapentek^® in children aged 3 to 5 years is 40 mg/kg/day in equal doses in 3 divided doses. Good tolerability of the drug at doses up to 50 mg/kg/day with long-term use has been noted. The maximum interval between doses of the drug should not exceed 12 hours to avoid recurrence of seizures.

There is no need to monitor the plasma concentration of gabapentin. Gapentek^® can be used in combination with other anticonvulsant drugs without taking into account changes in its plasma concentration or the concentration of other anticonvulsant drugs in the serum.

For patients with renal impairment, a reduction in the dose of Gapentek^® is recommended according to the table:

*The daily dose should be prescribed in three divided doses.

**Prescribed as 300 mg every other day.

For patients on hemodialysis who have not previously taken Gapentek^®, it is recommended to prescribe it at a loading dose of 300-400 mg, and then apply 200-300 mg every 4 hours of hemodialysis.

Adverse Reactions

When treating neuropathic pain

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

From the CNS gait disturbance, amnesia, ataxia, confusion, dizziness, hypesthesia, drowsiness, thinking impairment, tremor, amblyopia.

From the respiratory system dyspnea, pharyngitis.

Dermatological reactions skin rash.

Other accidental injuries, asthenia, back pain, flu-like syndrome, headache, infection, pain of various localization, peripheral edema, weight gain.

When treating partial seizures

Gapentek^® is most often used in combination with other anticonvulsants, so it was impossible to determine which drug caused the side effects (if there was such a connection at all).

From the cardiovascular system symptoms of vasodilation or increased blood pressure.

From the digestive system flatulence, anorexia, gingivitis, abdominal pain, constipation, dental diseases, diarrhea, dyspepsia, increased appetite, dry mouth or throat, nausea and/or vomiting.

From the hematopoietic system purpura (most often described as bruising that occurred with physical trauma), leukopenia.

From the musculoskeletal system arthralgia, back pain, fractures, myalgia.

From the CNS and peripheral nervous system dizziness, hyperkinesis, increased, decreased or absent reflexes, paresthesia, anxiety, hostility, amnesia, ataxia, confusion, impaired coordination, depression, dysarthria, emotional lability, insomnia, nervousness, nystagmus, drowsiness, thinking impairment, tremor, muscle twitching, visual impairment, amblyopia, diplopia.

From the respiratory system pneumonia, cough, pharyngitis, rhinitis.

Dermatological reactions abrasions, acne, itchy skin, skin rash.

From the urinary system urinary tract infection.

From the reproductive system impotence.

Other asthenia, general malaise, facial edema, fatigue, fever, headache, viral infection, peripheral edema, weight gain.

The indicated side effects were mild or moderate. A dose dependence of such phenomena as dizziness, ataxia, drowsiness, paresthesia and nystagmus was noted.

When used in children, the following were noted

From the digestive system nausea and/or vomiting, anorexia, diarrhea.

From the CNS and peripheral nervous system drowsiness, hostility, emotional lability, dizziness, hyperkinesia, seizures, headache.

From the respiratory system bronchitis, respiratory infection, pharyngitis, rhinitis, cough.

Other viral infection, fever, weight gain, fatigue, otitis.

Side effects that most often required discontinuation of the drug used as adjunctive therapy: drowsiness, ataxia, dizziness, fatigue, nausea and/or vomiting; as monotherapy – dizziness, nervousness, weight gain, nausea and/or vomiting, drowsiness.

Adverse events that most often led to discontinuation of the drug in children: drowsiness, hyperkinesia and hostility.

After abrupt withdrawal of Gapentek^® therapy, anxiety, insomnia, nausea, pain of various localization and sweating were most often observed.

There are also reports of the development of acute renal failure, allergic reactions, fluctuations in glucose levels in patients with diabetes, chest pain, increased liver function tests, multiforme exudative erythema (including Stevens-Johnson syndrome), hallucinations, choreoathetosis, muscle dyskinesia and dystonia, palpitations, pancreatitis, thrombocytopenia, tinnitus, urinary incontinence, hepatitis and jaundice.

Contraindications

• Children under 3 years of age (this dosage form is not intended for use in children under 3 years of age);
• Hypersensitivity to gabapentin and other components of the drug.

With caution the drug should be used in renal failure.

Use in Pregnancy and Lactation

Gapentek^® should be used during pregnancy only if the intended benefit to the mother justifies the potential risk to the fetus, as there are no data on the use of the drug in pregnant women.

Gabapentin is excreted in breast milk, its effect on the breastfed infant is unknown, therefore, during lactation, Gapentek^® should be prescribed only if the benefit to the mother clearly outweighs the risk to the infant.

Use in Renal Impairment

With caution the drug should be used in renal failure.

For patients with renal impairment, a reduction in the dose of Gapentek^® is recommended according to the table:

*The daily dose should be prescribed in three divided doses.

**Prescribed as 300 mg every other day.

For patients on hemodialysis who have not previously taken Gapentek^®, it is recommended to prescribe it at a loading dose of 300-400 mg, and then apply 200-300 mg every 4 hours of hemodialysis.

Pediatric Use

The efficacy and safety of the drug in the treatment of neuropathic pain in children and adolescents under 18 years of age have not been established.

The efficacy and safety of the drug in monotherapy of partial seizures with and without secondary generalization in children under 12 years of age have not been established.

The safety and efficacy of the drug when used as an adjunct in the treatment of partial seizures with secondary generalization in children under 3 years of age have not been established.

Special Precautions

Although no withdrawal syndrome with the development of seizures has been noted with the use of Gapentek^®, nevertheless, abrupt discontinuation of anticonvulsant therapy in patients with partial seizures may provoke the development of seizures.

Gapentek^® is generally not considered an effective treatment for absence epilepsy.

During combination therapy with morphine, an increase in the dose of Gapentek^® may be required. In this case, it is necessary to ensure careful monitoring of patients for the development of such a sign of CNS depression as drowsiness. In this case, the dose of Gapentek^® or morphine should be adequately reduced.

When adding Gapentek^® to other anticonvulsant drugs, false-positive results were recorded when determining protein in urine using test strips. To determine protein in urine, it is recommended to use the more specific sulfosalicylic acid precipitation method.

Use in pediatrics

The efficacy and safety of the drug in the treatment of neuropathic pain in children and adolescents under 18 years of age have not been established.

The efficacy and safety of the drug in monotherapy of partial seizures with and without secondary generalization in children under 12 years of age have not been established.

The safety and efficacy of the drug when used as an adjunct in the treatment of partial seizures with secondary generalization in children under 3 years of age have not been established.

Effect on ability to drive vehicles and machinery

Patients should be advised not to engage in activities requiring increased attention and speed of psychomotor reactions until the individual reaction of the patient to the drug has been determined.

Overdose

Symptoms with a single dose of 49 g of gabapentin, dizziness, double vision, speech impairment, drowsiness, lethargy, mild diarrhea were observed.

Treatment symptomatic therapy. Hemodialysis may be indicated for patients with severe renal impairment.

Drug Interactions

With simultaneous use of Gapentek^® and morphine (when morphine was taken 2 hours before taking gabapentin), an increase in the mean AUC of gabapentin by 44% was observed compared with monotherapy with Gapentek^®, which was accompanied by an increase in the pain threshold (cold pressor test). The clinical significance of this change has not been established, and the pharmacokinetic characteristics of morphine did not change. The side effects of morphine when taken together with Gapentek^® did not differ from those when taking morphine together with placebo.

No interactions between Gapentek^® and phenobarbital, phenytoin, valproic acid and carbamazepine were noted.

The pharmacokinetics of gabapentin at steady state are the same in healthy individuals and patients receiving other anticonvulsants.

Concomitant use of Gapentek^® with oral contraceptives containing norethindrone and/or ethinyl estradiol was not accompanied by changes in the pharmacokinetics of both components.

Concomitant use of Gapentek^® with antacids containing aluminum and magnesium is accompanied by a decrease in the bioavailability of gabapentin by approximately 20%. Gapentek^® is recommended to be taken approximately 2 hours after taking the antacid.

Probenecid does not affect the renal excretion of gabapentin.

A slight decrease in the renal excretion of gabapentin with simultaneous administration of cimetidine is probably not of clinical significance.

Storage Conditions

The drug should be stored out of the reach of children at a temperature not exceeding 30°C (86°F).

Shelf Life

The shelf life is 3 years.

Dispensing Status

The drug is dispensed by prescription.

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.