Epigaba

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT EPIGABA (EPIGABA)

Composition:

Active ingredient: 1 capsule contains 300 mg of gabapentin;

Excipients: anhydrous lactose, maize starch, talc;

capsule composition: gelatin, titanium dioxide (E 171).

Pharmaceutical form. Hard capsules.

Main physicochemical characteristics: hard gelatin capsules of cylindrical shape, white in color, filled with a white powder.

Pharmacotherapeutic group. Agents acting on the nervous system. Antiepileptic agents. Gabapentin.

ATC code N03AX12.

Pharmacological Properties.

Pharmacodynamics.

The precise mechanism of action of gabapentin is unknown.

Gabapentin is structurally similar to the neurotransmitter GABA (gamma-aminobutyric acid), but its mechanism of action differs from that of other agents acting on GABA receptors, such as valproate, barbiturates, benzodiazepines, GABA-transaminase inhibitors, GABA reuptake inhibitors, GABA agonists, and GABA precursors. In vitro studies with radiolabeled gabapentin in rat brain tissue, including the neocortex and hippocampus, have identified a novel peptide-binding fragment that may be related to the anticonvulsant and analgesic activity of gabapentin and its structural analogs. The binding site for gabapentin is the alpha2-delta subunit of voltage-dependent calcium channels.

Gabapentin, at therapeutic concentrations, does not bind to receptors of other common drugs or to neurotransmitter receptors in the brain, including GABAA, GABAB, benzodiazepine, glutamate, glycine, or N-methyl-D-aspartate (NMDA) receptors.

Gabapentin did not interact in vitro with sodium channels, thereby differing from phenytoin and carbamazepine. In some in vitro test systems, gabapentin partially reduced the effects of the glutamate agonist N-methyl-D-aspartate (NMDA). This effect was observed only at drug concentrations exceeding 100 µmol, which are unattainable in vivo. Gabapentin slightly reduces the release of monoamine neurotransmitters in vitro. Administration of gabapentin to rats increases GABA turnover in certain areas of the brain; a similar effect has been described for sodium valproate, but in other brain regions. The significance of these effects of gabapentin with respect to anticonvulsant activity has not yet been established. In animals, gabapentin rapidly penetrates into the brain and prevents seizures induced by maximal electroshock, chemical convulsants, including inhibitors of GABA synthesis.

Pharmacokinetics.

Absorption.

After oral administration, maximum plasma concentration of gabapentin is reached within 2–3 hours. There is a tendency toward decreased bioavailability of gabapentin (fraction of the drug absorbed) with increasing dose. Absolute bioavailability of gabapentin following administration of 300 mg capsules is approximately 60%. Food intake, including high-fat meals, does not have a clinically significant effect on the pharmacokinetics of gabapentin.

Repeated administration does not affect the pharmacokinetics of gabapentin. Although plasma concentrations of the drug varied between 2 µg/mL and 20 µg/mL within clinical studies, this parameter did not determine the efficacy and safety of the drug.

Distribution.

Gabapentin does not bind to plasma proteins. The volume of distribution of the drug is 57.7 L. The concentration of gabapentin in cerebrospinal fluid (CSF) in patients with epilepsy is approximately 20% of the equilibrium minimum plasma concentration. Gabapentin passes into breast milk.

Metabolism.

No data on gabapentin metabolism in humans have been obtained. The drug does not induce hepatic oxidative enzymes involved in drug metabolism.

Elimination.

Gabapentin is excreted exclusively by the kidneys in unchanged form. The elimination half-life of gabapentin is independent of dose and averages 5–7 hours.

In adult patients and patients with impaired renal function, plasma clearance of gabapentin is reduced. The elimination rate constant, plasma clearance, and renal clearance are directly proportional to creatinine clearance.

Gabapentin is removed from plasma during hemodialysis. Dose adjustment is recommended for patients with impaired renal function and/or patients undergoing hemodialysis (see section "Dosage and Administration").

Linearity/Non-linearity.

The bioavailability of gabapentin (fraction absorbed) decreases with increasing dose, indicating non-linear pharmacokinetics of the drug, specifically parameters of bioavailability (F): Ae%, CL/F, Vd/F. The pharmacokinetics of elimination (parameters not including F, such as CLr and T1/2) follow a linear pattern. The steady-state plasma concentration of gabapentin is predictable based on data from single-dose administration.

Clinical characteristics.

Indications.

Epilepsy.

Gabapentin is used as an adjunctive therapy in the treatment of partial seizures with or without secondary generalization in adults and children aged 6 years and older (see section "Pharmacodynamics").

Gabapentin is used as monotherapy in the treatment of partial seizures with or without secondary generalization in adults and children aged 12 years and older.

Neuropathic pain.

Gabapentin is indicated for the treatment of peripheral neuropathic pain, e.g., painful diabetic neuropathy and postherpetic neuralgia in adults.

Contraindications.

Hypersensitivity to the active substance or to any of the excipients.

Interaction with other medicinal products and other forms of interaction.

Antiepileptic drugs. Pharmacokinetic studies have shown no significant changes in plasma concentrations of phenytoin, carbamazepine, valproic acid, or phenobarbital when used as background therapy concomitantly with gabapentin. In these same studies, no changes in the pharmacokinetics of gabapentin were observed.

Oral contraceptives. Concomitant administration of gabapentin and oral contraceptives containing norethisterone and/or ethinylestradiol does not affect the steady-state concentrations of these agents.

Antacids. Concomitant administration of gabapentin with antacids containing aluminium or magnesium reduces the bioavailability of gabapentin by up to 24%. Gabapentin should therefore be administered no earlier than 2 hours after taking antacids.

Cimetidine. A slight reduction in renal clearance of gabapentin has been observed when co-administered with cimetidine; however, this effect is not expected to be clinically significant.

Alcohol and misuse of other CNS-active drugs: possible enhancement of central nervous system (CNS) side effects of gabapentin (e.g., somnolence, ataxia).

Morphine. In a study involving healthy volunteers (N = 12) who received 60 mg controlled-release morphine capsules 2 hours prior to gabapentin (600 mg capsule), a 44% increase in mean AUC of gabapentin was observed compared to when morphine was not administered. Therefore, careful monitoring of patients is required when morphine and gabapentin are used concomitantly to promptly identify symptoms of CNS depression such as somnolence, and appropriate dose reductions of gabapentin or morphine should be considered.

Probenecid does not interfere with renal elimination of gabapentin.

Special precautions.

Severe skin adverse reactions (SSAR)

Severe skin adverse reactions (SSAR), including Stevens–Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and drug reaction with eosinophilia and systemic symptoms (DRESS), which may be life-threatening or lead to fatal outcomes, have been reported in association with gabapentin therapy. Patients should be informed about the signs and symptoms, and closely monitored for skin reactions. If signs or symptoms indicating these reactions occur, gabapentin should be discontinued immediately, and alternative treatment (if necessary) should be considered.

If a serious reaction such as SJS, TEN, or DRESS syndrome develops during gabapentin treatment, re-administration of gabapentin is contraindicated.

Anaphylaxis.

Gabapentin may cause anaphylaxis. Reported cases included symptoms such as difficulty breathing, swelling of lips, throat, and tongue, and hypotension requiring emergency treatment. Patients should be instructed to immediately discontinue gabapentin and seek emergency medical help if symptoms of anaphylaxis occur (see section "Adverse reactions").

Suicidal thoughts and behavior.

Suicidal thoughts and behavior have been observed in patients treated with antiepileptic drugs for various indications. A meta-analysis of randomized, placebo-controlled antiepileptic drug trials also showed a small increased risk of suicidal thoughts and behavior, the mechanism of which is unknown; however, available data do not exclude a potential effect of gabapentin.

Therefore, signs of suicidal thoughts and behavior should be monitored, and appropriate therapy considered. Patients (and caregivers) should be advised to contact their physician if signs of suicidal thoughts or behavior occur.

An increased risk of suicidal thoughts or behavior was observed as early as one week after initiation of antiepileptic drug therapy and persisted throughout the treatment period. Since most studies included in the analysis lasted no more than 24 weeks, the risk of suicidal thoughts or behavior beyond 24 weeks could not be assessed.

Patients and caregivers should be informed that antiepileptic drugs increase the risk of suicidal thoughts and behavior, and they should be alert to the emergence or worsening of symptoms of depression, any unusual changes in mood or behavior, or the occurrence of suicidal thoughts, behavior, or self-harming thoughts. Any concerning problems should be reported to healthcare professionals immediately.

Neuropsychiatric adverse reactions (children aged 3 to 12 years).

The use of gabapentin in pediatric patients with epilepsy aged 3 to 12 years is associated with central nervous system (CNS)-related adverse reactions. The most significant of these can be classified into the following categories:

1. emotional lability (primarily behavioral problems);
2. hostility, including aggressive behavior;
3. cognitive disturbance, including difficulty concentrating and changes in academic performance;
4. hyperkinesia (primarily restlessness and hyperactivity).

Among patients receiving gabapentin, most reactions were mild.

The long-term impact (beyond 36 weeks) of gabapentin therapy on learning ability, intelligence, and development in children and adolescents has not been adequately studied. Therefore, the benefits of long-term therapy should be weighed against its potential risks.

Acute pancreatitis.

Gabapentin should be discontinued if acute pancreatitis occurs during treatment (see section "Adverse reactions").

Seizures.

Although there is no evidence of rebound seizures with gabapentin, abrupt discontinuation of antiepileptic drugs in patients with epilepsy may precipitate status epilepticus (see section "Dosage and administration").

As with other antiepileptic drugs, in some patients, the frequency of seizures may increase or new types of seizures may occur during gabapentin treatment.

As with other antiepileptic drugs, attempts to discontinue concomitant antiepileptic drugs to switch to gabapentin monotherapy in refractory patients receiving multiple antiepileptic drugs have rarely been successful.

Gabapentin is not considered effective in treating primary generalized seizures such as absence seizures and may exacerbate these seizures in some patients. For this reason, gabapentin should be used with caution in patients with mixed seizure types that include absence seizures.

Dose reduction, discontinuation, or substitution with another (alternative) drug should be performed gradually over at least one week. Sudden discontinuation of antiepileptic drugs in patients with epilepsy may provoke seizures.

Dizziness, somnolence, loss of consciousness, confusion, and cognitive impairment.

Gabapentin treatment has been associated with dizziness and somnolence, which may lead to accidental injuries (due to falls). Post-marketing surveillance has reported cases of confusion, loss of consciousness, and cognitive impairment. Therefore, patients should be advised to exercise caution until they are familiar with all potential effects of the drug.

Patients should be carefully monitored for signs of central nervous system (CNS) depression, such as somnolence and sedation, when the drug is used concomitantly with other agents possessing sedative properties.

Concomitant use with opioids.

Patients requiring concomitant opioid therapy should be closely monitored for signs of central nervous system (CNS) depression, such as somnolence, sedation, and respiratory depression. Increased gabapentin concentrations may occur in patients receiving gabapentin and morphine concomitantly. The dose of gabapentin or opioids should be reduced accordingly (see section "Interaction with other medicinal products and other forms of interaction").

Respiratory depression.

Gabapentin use has been associated with severe respiratory depression. Patients with impaired respiratory function, respiratory or neurological disorders, renal impairment, patients receiving concomitant CNS depressant drugs, and elderly patients are at increased risk of severe respiratory depression. These patients may require dose adjustment.

Elderly patients (aged 65 years and older).

Systematic studies of gabapentin use in patients aged 65 years and older have not been conducted. In one double-blind study involving patients with neuropathic pain, somnolence, peripheral edema, and weakness occurred more frequently in patients aged 65 years and older than in younger patients. Except for these findings, clinical studies did not reveal differences in the adverse event profile between elderly and younger patients.

Misuse, abuse, and dependence.

Gabapentin may cause drug dependence, which may occur with therapeutic doses. Cases of abuse have been reported. Patients with a history of substance abuse may have an increased risk of gabapentin misuse, abuse, and dependence; therefore, gabapentin should be used with caution in such patients. The risk of misuse, abuse, or dependence should be carefully assessed before prescribing gabapentin.

Patients receiving gabapentin therapy should be monitored for symptoms of misuse, abuse, or dependence, such as tolerance development, dose escalation, and drug-seeking behavior.

Withdrawal symptoms.

Withdrawal symptoms have been observed after discontinuation of both short-term and long-term gabapentin therapy. Withdrawal symptoms may occur shortly after stopping treatment, usually within 48 hours. The most commonly reported symptoms include anxiety, insomnia, nausea, pain, sweating, tremor, headache, depression, abnormal feelings, dizziness, and malaise. The possible occurrence of withdrawal symptoms after gabapentin discontinuation may indicate drug dependence (see section "Adverse reactions"). Patients should be informed about this at the beginning of treatment. If gabapentin needs to be discontinued, it is recommended to do so gradually over at least one week, regardless of the indication (see section "Dosage and administration").

Laboratory tests.

Semi-quantitative urine protein tests using test strips may yield false-positive results. Therefore, if necessary, additional analyses using other methods (biuret method, turbidimetric method, dye-binding tests) are recommended, or these methods should be used initially.

Excipients.

The medicinal product contains lactose. The product should not be administered to patients with rare hereditary conditions such as lactose intolerance, total lactase deficiency, or glucose-galactose malabsorption.

Tumorigenic potential.

In a carcinogenicity study, oral gabapentin increased the incidence of pancreatic acinar cell tumors in rats. The clinical significance of this finding is unknown. Clinical experience during pre-marketing development of gabapentin does not provide direct data to assess its potential to induce tumors in humans. In clinical adjunctive epilepsy trials involving 2085 patients aged >12 years, 10 patients developed new tumors (2 breast, 3 brain, 2 lung, 1 adrenal gland, 1 non-Hodgkin's lymphoma, 1 in situ endometrial carcinoma). Pre-existing tumors worsened in 11 patients (9 brain, 1 breast, 1 prostate) during or within 2 years after discontinuation of the drug. Without knowledge of the background incidence and recurrence rates in a similar population not receiving the drug, it is not possible to assess the impact of treatment on such conditions.

Use during pregnancy or breastfeeding.

Pregnancy.

General risks of epilepsy and antiepileptic therapy.

The risk of congenital abnormalities in offspring of women receiving antiepileptic drugs is increased 2–3 times. Most frequently reported are cleft lip, cardiovascular system anomalies, and neural tube defects. Combination antiepileptic therapy, compared to monotherapy, is associated with a higher risk of developmental abnormalities; therefore, monotherapy is recommended. All pregnant women and women of reproductive age requiring antiepileptic therapy should consult a specialist before starting treatment. The need for antiepileptic therapy should be re-evaluated before planning pregnancy. Abrupt discontinuation of antiepileptic drugs is not acceptable, as it may lead to seizures and significantly worsen the condition of both mother and child. Developmental delay in offspring of women with epilepsy is rare. It is not possible to determine whether developmental delay is a consequence of genetic disorders, social factors, maternal epilepsy, or antiepileptic drug exposure.

Risk associated with gabapentin therapy.

Gabapentin crosses the human placenta.

Data on gabapentin use in pregnant women are lacking or limited. Animal studies have shown reproductive toxicity. The potential risk to humans is unknown. Gabapentin should not be used during pregnancy unless the potential benefit to the mother clearly outweighs the potential risk to the fetus.

There is no definitive conclusion on whether gabapentin, used by women during pregnancy for epilepsy, may increase the risk of congenital abnormalities in offspring, either due to epilepsy itself or due to concomitant use of other antiepileptic drugs.

Neonatal withdrawal syndrome has been reported in newborns exposed to gabapentin in utero.

Concomitant use of gabapentin and opioids during pregnancy may increase the risk of neonatal withdrawal syndrome in newborns. Newborns should be closely monitored.

Breastfeeding.

Gabapentin passes into breast milk. Since the effect of the drug on breastfed infants is not studied, gabapentin should be used with caution in breastfeeding women. Gabapentin use in breastfeeding women is justified only if the benefit to the mother outweighs the potential risk to the infant.

Fertility.

No effects on fertility were observed in animal studies.

Ability to influence reaction speed when driving or operating machinery.

Gabapentin affects the central nervous system and may cause somnolence, dizziness, or other similar symptoms. These adverse effects, even if mild or moderate, may be potentially hazardous for patients when driving vehicles or operating machinery, especially at the beginning of therapy and after dose escalation.

Method of administration and dosage.

The medicinal product is intended for oral administration.

Gabapentin may be taken with or without food. The product should be taken with sufficient liquid (e.g., a glass of water).

For all indications, the titration regimen described in Table 1 is recommended at the beginning of therapy. This regimen is recommended for adults and children aged 12 years and older. Dosage titration instructions for children aged 12 years are provided in a separate section.

Table 1.

Dosage calculation for initial dose titration.
Day 1	Day 2	Day 3
300 mg once daily	300 mg twice daily	300 mg three times daily

Discontinuation of gabapentin

According to current clinical guidelines, gabapentin should be discontinued gradually over a minimum of 1 week, regardless of the indication.

Epilepsy

In epilepsy, long-term therapy is usually required. The dose is determined by the physician according to individual tolerability and efficacy.

Adults and children aged 12 years and older: effective doses in epilepsy range from 900 to 3600 mg/day. Treatment is initiated with dose titration as described in Table 1, or with a starting dose of 300 mg three times daily on Day 1. Subsequently, depending on individual tolerability and efficacy, the dose may be increased by 300 mg/day every 2–3 days up to the maximum dose of 3600 mg/day. For some patients, a slower titration of gabapentin may be necessary. The shortest time to reach a dose of 1800 mg/day is 1 week, 2400 mg/day is 2 weeks, and 3600 mg/day is 3 weeks.

In long-term open-label clinical studies, a dose of 4800 mg/day was well tolerated by patients. The daily dose should be divided into three administrations. The maximum interval between doses should not exceed 12 hours to avoid interruptions in anticonvulsant therapy and prevent the occurrence of seizure attacks.

Children aged 6 to 12 years

The initial dose should be 10–15 mg/kg/day. The effective dose should be achieved by titrating the drug over approximately 3 days. The effective dose of gabapentin in children aged 6 years and older is 25–35 mg/kg/day. A dose of 50 mg/kg/day was shown to be well tolerated in long-term clinical studies. The total daily dose should be divided into equal parts (administered three times daily); the maximum interval between doses should not exceed 12 hours.

Monitoring serum gabapentin levels is not required. Furthermore, gabapentin can be used in combination with other antiepileptic drugs, as it does not alter the plasma concentration of gabapentin or the serum concentrations of other antiepileptic drugs.

Peripheral neuropathic pain

Adults

Treatment is initiated with dose titration as described in Table 1; otherwise, the starting dose of 900 mg/day should be divided into three doses. Subsequently, depending on individual tolerability and efficacy, the dose may be increased by 300 mg/day every 2–3 days up to the maximum dose of 3600 mg/day. For some patients, a slower titration of gabapentin may be necessary. The shortest time to reach a dose of 1800 mg/day is 1 week, 2400 mg/day is 2 weeks, and 3600 mg/day is 3 weeks.

The efficacy and safety of gabapentin in the treatment of peripheral neuropathic pain (e.g., painful diabetic neuropathy or postherpetic neuralgia) have not been studied in long-term clinical trials lasting more than 5 months. If a patient requires longer-term treatment (more than 5 months) with gabapentin for neuropathic pain, the physician should evaluate the patient's clinical status and determine the need for continued therapy before proceeding.

Instructions for all indications.

For patients with poor general condition or certain complicating factors, such as low body weight or post-transplant status, titration should be performed more slowly, either by reducing the incremental dose or by extending the intervals between dose increases.

Use in elderly patients (aged 65 years and older).

Elderly patients may sometimes require individual dose adjustment due to possible reduced renal function (see Table 2). In elderly patients, somnolence, peripheral edema, and weakness are more frequently observed.

Use in patients with renal impairment.

Patients with severe renal impairment and/or patients on hemodialysis require individual dose adjustment of the drug (see Table 2). For these patients, gabapentin 100 mg capsules are recommended.

Table 2.

Dosing in renal impairment.

Creatinine clearance (mL/min)	Total daily dose of gabapentin* mg/day
>80 (normal creatinine clearance)	900–3600
50–79	600–1800
30–49	300–900
15–29	150**–600
<15***	150**–300

* The total daily dose should be divided into 3 doses. Reduced doses should be used in patients with renal impairment (creatinine clearance <79 mL/min).

** Administer 3 × 100 mg every other day.

*** For patients with creatinine clearance <15 mL/min, the daily dose should be reduced according to creatinine clearance (e.g., patients with creatinine clearance of 7.5 mL/min should receive half the daily dose of patients with creatinine clearance of 15 mL/min).

Dosing for patients undergoing hemodialysis.

For anuric patients undergoing hemodialysis who have never previously received gabapentin, the recommended initial loading dose is 300–400 mg, followed by 200–300 mg of gabapentin after each 4-hour hemodialysis session. Gabapentin should not be administered on days without hemodialysis.

The maintenance dose of gabapentin for patients on hemodialysis should be determined according to the recommendations specified in Table 2. In addition to the maintenance dose, patients undergoing hemodialysis should receive 200–300 mg of gabapentin after each 4-hour hemodialysis session.

Children.

Gabapentin is indicated for the treatment of epilepsy in children: as adjunctive therapy in children aged 6 years and older, and as monotherapy in children aged 12 years and older.

The long-term (more than 36 weeks) effects of gabapentin on learning ability, intelligence, and development in children and adolescents have not been adequately studied. Therefore, when determining the need for prolonged therapy, potential risks should be considered.

Overdose.

Acute, life-threatening toxic reactions have not been observed following gabapentin doses of up to 49 g/day.

Symptoms of overdose included dizziness, double vision, slurred speech, somnolence, loss of consciousness, lethargy, and mild diarrhea. All patients fully recovered with supportive treatment. Reduced absorption of gabapentin at high doses may limit drug absorption and reduce toxic effects of overdose.

Gabapentin overdose, particularly when combined with other CNS depressants, may lead to the development of coma.

Although gabapentin can be removed by hemodialysis, clinical experience suggests that this is usually not necessary. However, hemodialysis may be indicated in patients with severe renal impairment.

In studies in mice and rats, the lethal dose of gabapentin could not be determined, even with doses as high as 8000 mg/kg. Symptoms of acute toxicity in animals included ataxia, labored breathing, ptosis, decreased activity, or, conversely, increased excitability.

Adverse Reactions

Listed below are adverse reactions observed during clinical studies of gabapentin use in the treatment of epilepsy (adjunctive therapy or monotherapy) and neuropathic pain.

Frequency is defined as follows: very common (≥ 1/10), common (≥ 1/100 to <1/10), uncommon (≥ 1/1000 to ≤1/100), rare (≥ 1/10000 to ≤1/1000), very rare (<1/10000). If the frequency of adverse effects varied across different studies, the highest reported frequency was included in the report.

Additional adverse events identified from post-marketing surveillance are included in the list under the category "frequency unknown" (cannot be estimated based on available data) and are presented in italics.

Within each frequency group, adverse effects are listed in descending order of severity.

Infectious and parasitic diseases
Very common	Viral infection
Common	Pneumonia, respiratory infection, urinary tract infection, infection, otitis media
Blood and lymphatic system disorders
Common	Leukopenia
Frequency unknown	Thrombocytopenia
Immune system disorders
Uncommon	Allergic reactions (e.g., urticaria)
Frequency unknown	Hypersensitivity syndrome (systemic reaction with various manifestations, including fever, rash, hepatitis, lymphadenopathy, eosinophilia, sometimes with other signs and symptoms), anaphylaxis (see section "Special precautions for use")
Metabolism and nutrition disorders
Common	Anorexia, increased appetite
Uncommon	Hyperglycemia (most frequently in patients with diabetes mellitus)
Rare	Hypoglycemia (most frequently in patients with diabetes mellitus)
Frequency unknown	Hypnatremia
Psychiatric disorders
Common	Hostility, confusion and emotional lability, depression, anxiety, nervousness, abnormal thinking
Uncommon	Psychomotor hyperactivity
Frequency unknown	Hallucinations, drug dependence
Nervous system disorders
Very common	Somnolence, dizziness, ataxia
Common	Seizures, hyperkinesia, dysarthria, amnesia, tremor, insomnia, headache, sensory disturbances (paresthesia, hypesthesia), coordination disturbances, nystagmus, increased, decreased or absent reflexes
Uncommon	Hypokinesia, cognitive disturbances
Rare	Loss of consciousness
Frequency unknown	Other movement disorders (including choreoathetosis, dyskinesia, dystonia)
Eye disorders
Common	Visual disturbances, e.g., amblyopia or diplopia
Ear and labyrinth disorders
Common	Systemic dizziness
Frequency unknown	Tinnitus
Cardiac disorders
Uncommon	Palpitations
Vascular disorders
Common	Increased blood pressure, vasodilation
Respiratory, thoracic and mediastinal disorders
Common	Dyspnea, bronchitis, pharyngitis, cough, rhinitis
Rare	Respiratory depression
Gastrointestinal disorders
Common	Vomiting, nausea, dental abnormalities, gingivitis, diarrhea, abdominal pain, dyspepsia, constipation, dry mouth or throat, abdominal distension
Uncommon	Dysphagia
Frequency unknown	Pancreatitis
Hepatobiliary disorders
Frequency unknown	Hepatitis, jaundice
Skin and subcutaneous tissue disorders
Common	Facial edema, purpura (most frequently described as bruises after trauma), rash, pruritus, acne
Frequency unknown	Stevens-Johnson syndrome, toxic epidermal necrolysis, eosinophilia with systemic symptoms (see section "Special precautions for use"), angioneurotic edema, erythema multiforme, alopecia
Musculoskeletal and connective tissue disorders
Common	Arthralgia, myalgia, back pain, muscle spasms
Frequency unknown	Rhabdomyolysis, myoclonic seizures
Renal and urinary disorders
Frequency unknown	Acute renal failure, urinary incontinence
Reproductive system and breast disorders
Common	Erectile dysfunction
Frequency unknown	Galactorrhea, gynecomastia, sexual dysfunction (including libido changes, ejaculation disorders, anorgasmia)
General disorders and administration site conditions
Very common	Increased fatigue, fever
Common	Peripheral edema, gait disturbance, weakness, pain, discomfort, influenza-like syndrome
Uncommon	Generalized edema
Frequency unknown	Withdrawal reactions*
Investigations
Common	Decreased white blood cell count, increased body weight
Uncommon	Increased liver function tests [aspartate aminotransferase (AST), alanine aminotransferase (ALT)] and bilirubin levels
Frequency unknown	Elevated blood creatine phosphokinase levels
Injury, poisoning and procedural complications
Common	Accidental injuries, fractures, lacerations
Uncommon	Falls

*After discontinuation of both short-term and long-term treatment with gabapentin, withdrawal symptoms have been observed. Withdrawal symptoms may occur shortly after stopping treatment, usually within 48 hours. The most commonly reported symptoms include anxiety, insomnia, nausea, pain, sweating, tremor, headache, depression, abnormal feeling, dizziness, and malaise (see section “Special precautions for use”). The occurrence of withdrawal symptoms after discontinuation of gabapentin may indicate drug dependence (see section “Adverse reactions”). Patients should be informed about this at the beginning of treatment. If discontinuation of gabapentin is necessary, it is recommended to do so gradually over at least 1 week, regardless of the indication (see section “Dosage and administration”).

Cases of acute pancreatitis during gabapentin treatment have been reported. The relationship to gabapentin has not been established (see section “Special precautions for use”).

Cases of myopathy with elevated creatine kinase levels have been reported in patients with end-stage renal disease undergoing hemodialysis.

Cases of respiratory tract infections, otitis media, seizures, and bronchitis have been reported only in clinical studies involving children. In addition, aggressive behavior and hyperkinesia were frequently observed during studies in children.

Reporting of suspected adverse reactions.

Reporting suspected adverse reactions after medicinal product registration is important. It allows continuous monitoring of the benefit-risk balance of the medicinal product. Healthcare and pharmacy professionals, as well as patients or their legal representatives, should report all suspected adverse reactions and lack of efficacy of the medicinal product via the Automated Information System for Pharmacovigilance at the following link: https://aisf.dec.gov.ua .

Shelf life. 2 years.

Storage conditions.

Store at a temperature not exceeding 25°C.

Keep out of reach of children.

Packaging.

10 capsules in a blister; 2 or 10 blisters in a cardboard box.

Prescription status. Prescription only.

Manufacturer.

JSC “Tekhnolohiya”.

Manufacturer’s location and address of place of business.

8, Stara Prorina Street, Uman, Cherkasy region, 20300, Ukraine.