Gabalept

INSTRUCTION FOR MEDICAL USE OF THE MEDICINAL PRODUCT GABALEPT (GABALEPT)

Composition:

Active substance: gabapentin;

1 capsule contains 300 mg of gabapentin;

Excipients: maize starch, talc, gelatin, sodium lauryl sulfate, yellow iron oxide (E 172), titanium dioxide (E 171).

Pharmaceutical form. Hard gelatin capsules.

Main physicochemical properties: hard gelatin capsules, size 0, yellow in color, containing a white crystalline powder freely moving within the capsule.

Pharmacotherapeutic group. Antiepileptic drugs. ATC code N03AX12.

Pharmacological Properties

Pharmacodynamics

Mechanism of Action

Gabapentin readily crosses into the brain and prevented seizures in a number of animal models of epilepsy. Gabapentin does not alter the metabolism of gamma-aminobutyric acid (GABA) and has no affinity for GABA_A or GABA_B receptors. It does not bind to other neurotransmitter receptors in the brain and does not interact with sodium channels. Gabapentin binds with high affinity to the alpha2-delta (α2-δ) subunit of voltage-dependent calcium channels, which is hypothesized to produce its antiseizure effect in animals. Broad-spectrum screening studies have not identified any other targets for gabapentin besides α2-δ.

Data from several preclinical studies suggest that the pharmacological activity of gabapentin may be mediated through binding to the α2-δ subunit, resulting in reduced release of excitatory neurotransmitters in various regions of the central nervous system (CNS). This activity may underlie the antiseizure effect of gabapentin; however, its role in achieving this effect in humans has not been established.

Gabapentin has also demonstrated efficacy in a number of preclinical animal models of pain. It is hypothesized that the specific binding of gabapentin to the α2-δ subunit produces several different effects that may contribute to its analgesic action in animal pain models. Gabapentin may exert analgesic effects both at the spinal cord level and in higher brain centers by interacting with descending inhibitory pathways of pain sensitivity. The contribution of these properties to the clinical efficacy of the drug in humans has not been studied.

Clinical Efficacy and Safety

Clinical studies of adjunctive therapy for partial seizures in children aged 3 to 12 years showed a numerically greater, but statistically non-significant, difference in the proportion of patients achieving a 50% response rate with gabapentin compared to placebo. An additional post-hoc analysis of responder rates by age did not show a significant age effect, whether using continuous or binary variables (age groups 3–5 years and 6–12 years). The results of this analysis are presented in Table 1.

Table 1

*MITT (modified intent-to-treat population, including all patients who received at least one dose of either study drug) includes all randomized patients who were able to adequately complete seizure diaries during the 28-day period of the baseline and double-blind phase.

Pharmacokinetics

Absorption

Following oral administration of gabapentin, maximum plasma concentration (Cmax) is achieved within 2–3 hours. There is a trend toward decreasing bioavailability (fraction of drug absorbed) of gabapentin with increasing dose. The absolute bioavailability of gabapentin following administration of 300 mg capsules is approximately 60%. Co-administration with food, including high-fat meals, has no 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 and 20 mcg/mL in clinical trials, this range did not determine the efficacy and safety of the drug. Pharmacokinetic parameters are presented in Table 2.

Table 2

Summary of mean (%CV) steady-state pharmacokinetic parameters after dosing every 8 hours

Cmax ‒ maximum steady-state plasma concentration;

tmax ‒ time to reach Cmax;

T1/2 ‒ elimination half-life;

AUC (0–8) ‒ steady-state area under the plasma concentration-time curve from time 0 to 8 hours after drug administration;

Ae% ‒ percentage of the dose excreted unchanged in urine from time 0 to 8 hours after drug administration;

ND ‒ not available.

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) of patients with epilepsy is approximately 20% of the steady-state minimum plasma concentration. Gabapentin penetrates into breast milk.

Biotransformation

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

Elimination

Gabapentin is excreted exclusively by the kidneys in unchanged form. The T1/2 of gabapentin is independent of dose and averages 5–7 hours.

In elderly patients and patients with impaired renal function, the 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 or those undergoing hemodialysis (see section "Dosage and administration").

The pharmacokinetics of gabapentin in children were evaluated in 50 healthy volunteers aged 1 month to 12 years. Overall, when dosing was normalized per kilogram of body weight (mg/kg), plasma concentrations of gabapentin in children aged 5 years and older did not differ from those in adults.

In a pharmacokinetic study of 24 healthy children aged 1 to 48 months, AUC was approximately 30% lower, Cmax was lower, and clearance per unit of body weight was higher compared to data obtained in children aged 5 years and older.

Linearity/Non-linearity

The bioavailability of gabapentin (fraction of drug absorbed) decreases with increasing dose, indicating non-linear pharmacokinetics of the drug, specifically bioavailability parameters (F): Ae%, CL/F, Vd/F. The pharmacokinetics of elimination (pharmacokinetic 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

Gabalept is used as adjunctive therapy in the treatment of partial seizures with or without secondary generalization in adults and children aged 6 years and older.

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

Peripheral Neuropathic Pain

Gabalept is indicated for the treatment of peripheral neuropathic pain, such as 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

There are spontaneous reports and literature data on cases of respiratory depression and/or sedation associated with concomitant use of gabapentin and opioids. In some of these reports, authors have highlighted particular concern regarding the use of gabapentin-opioid combinations, especially in elderly patients.

In a study involving healthy volunteers who received controlled-release capsules containing 60 mg morphine 2 hours prior to gabapentin (600 mg), a 44% increase in mean AUC of gabapentin was observed compared to cases when morphine was not administered. Therefore, careful monitoring of patients is required when morphine and gabapentin are used concomitantly, in order to promptly recognize symptoms of CNS depression such as somnolence, sedation, and respiratory depression, and to adjust the dose of gabapentin or morphine accordingly.

No interaction was observed between gabapentin and phenytoin, carbamazepine, valproic acid, or phenobarbital. The pharmacokinetics of gabapentin at steady state are similar in healthy volunteers and epileptic patients receiving these antiepileptic drugs. Concomitant administration of gabapentin and oral contraceptives containing norethisterone and/or ethinylestradiol does not affect the steady-state concentrations of these contraceptive agents.

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

Renal excretion of gabapentin is not altered by probenecid.

A slight decrease in renal clearance of gabapentin has been observed when co-administered with cimetidine; however, this effect is not expected to be of clinical significance.

Special precautions for use

Anaphylaxis

Gabapentin may cause anaphylaxis. Symptoms reported in documented cases include difficulty breathing, swelling of the lips, throat and tongue, and hypotension requiring emergency treatment. Patients should immediately discontinue gabapentin and seek medical help if they experience any signs of anaphylaxis (see section "Adverse reactions").

Severe skin adverse reactions

Severe skin adverse reactions (SSARs), including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and drug reaction with eosinophilia and systemic symptoms (DRESS), which may be life-threatening or fatal, have been reported in association with gabapentin therapy. When prescribing this medicinal product, patients should be informed about these signs and symptoms, and closely monitored for the development of skin reactions. If signs or symptoms suggestive of these reactions occur, gabapentin should be immediately discontinued and alternative therapy considered (if necessary).

If a serious reaction such as SJS, TEN, or DRESS syndrome develops during gabapentin treatment, re-administration of gabapentin must never be attempted.

Suicidal thoughts and behavior

Suicidal thoughts and behavior have been observed in patients receiving antiepileptic drugs for various indications. Data from randomized, placebo-controlled trials of antiepileptic drugs show a small but increased risk of suicidal thoughts and behavior. The mechanism of this risk is unknown, and available data do not exclude an increased risk associated with gabapentin use.

Therefore, patients should be closely monitored for suicidal thoughts and behavior, and appropriate therapy considered. Patients and caregivers should be advised to consult a physician if signs of suicidal ideation or behavior emerge.

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 discontinuation, abrupt withdrawal of anticonvulsant drugs in patients with epilepsy may precipitate status epilepticus (see section "Dosage and administration").

As with other antiepileptic drugs, gabapentin may increase the frequency of seizures or lead to the emergence of new types of seizures in some patients.

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

Gabapentin is not considered effective in treating primary generalized seizures such as absence seizures. Gabapentin may exacerbate these seizures in some patients. Therefore, gabapentin should be used with caution in patients with mixed seizure types, including absence seizures.

Gabapentin treatment is associated with dizziness and somnolence, which may increase the risk of injury (e.g., falls). Confusion, loss of consciousness, and psychiatric disturbances have also been reported in the post-marketing period; therefore, patients should exercise caution until they become familiar with the potential effects of the drug.

Concomitant use with opioids

Patients requiring concomitant use of opioids and gabapentin require careful monitoring for early signs of central nervous system (CNS) depression, such as somnolence, sedation, and respiratory depression.

Concomitant administration of morphine and gabapentin may increase gabapentin concentrations; therefore, the dose of gabapentin or opioids should be reduced (see section "Interaction with other medicinal products and other forms of interaction").

Respiratory depression

Gabapentin use has been associated with cases of severe respiratory depression. Patients with impaired respiratory function, respiratory or neurological disorders, renal impairment, concomitant use of CNS depressants, and elderly patients may be at increased risk of this serious adverse reaction. Dose adjustment may be necessary in these patients.

Elderly patients

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 compared to younger patients. Except for these findings, clinical trials in this age group have not provided evidence of differences in the adverse reaction profile compared to younger patients.

Pediatric population

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

Abuse, misuse, and dependence

Gabapentin may cause drug dependence, which may occur when the drug is used at therapeutic doses. Cases of abuse have been reported. Patients with a history of substance abuse may be at 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 the development of tolerance, dose escalation, and drug-seeking behavior.

Withdrawal symptoms

Withdrawal symptoms have been observed following discontinuation of both short- and long-term gabapentin treatment. 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 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 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 alternative methods (e.g., biuret method, turbidimetric method, dye-binding tests) should be performed, or such methods should be used from the start of treatment.

Use during pregnancy or breastfeeding

Pregnancy

General risks associated with epilepsy and antiepileptic drugs

The risk of congenital malformations in children whose mothers took antiepileptic drugs during pregnancy is increased by 2–3 times. The most commonly reported malformations include cleft lip, cardiovascular anomalies, and neural tube defects. Combination antiepileptic therapy may be associated with a higher risk of developmental abnormalities compared to monotherapy; therefore, monotherapy is recommended whenever possible. All pregnant women and women of childbearing potential requiring antiepileptic therapy should consult a specialist before starting treatment. The need for antiepileptic therapy should be re-evaluated when planning pregnancy. Abrupt discontinuation of antiepileptic drugs is unacceptable, as it may lead to seizures and significantly worsen the condition of both mother and child. Developmental delay has been rarely observed in children whose mothers had epilepsy. It is not possible to differentiate whether developmental delay is due to genetic disorders, social factors, maternal epilepsy, or antiepileptic drug exposure.

Risk associated with gabapentin therapy

Gabapentin crosses the placenta. Data on gabapentin use in pregnant women are limited or absent. Animal studies have shown reproductive toxicity. The potential risk to humans is unknown.

It has not been established whether gabapentin use during pregnancy increases the risk of congenital abnormalities in children due to maternal epilepsy itself, gabapentin use, or concomitant use of other antiepileptic drugs.

Gabapentin should not be used during pregnancy unless the potential benefit to the mother clearly outweighs the possible risk to the fetus.

There is no definitive conclusion on whether gabapentin use during pregnancy for epilepsy increases 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. Newborns should be closely monitored.

Breastfeeding period

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

Fertility

In animal studies, gabapentin did not affect fertility.

Ability to influence reaction speed when driving or operating machinery

Gabapentin may have a slight or moderate influence on the ability to drive or operate machinery. Gabapentin affects the central nervous system and may cause somnolence, dizziness, or other similar symptoms. These adverse reactions, even if mild or moderate, may be potentially hazardous when driving vehicles or operating other machinery, especially at the beginning of therapy and after dose escalation.

Method of Administration and Dosage

For all indications, the dose titration scheme described in Table 3 should be used at the beginning of therapy. The scheme provided is recommended for adults and children aged 12 years and older. Dosage titration instructions for children under 12 years of age are provided in a separate subsection of this section.

Table 3

Discontinuation of gabapentin

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

Epilepsy

Epilepsy usually requires long-term therapy. The dose is determined by the physician according to individual tolerability and response to treatment.

Adults and children aged 12 years and older: effective doses in epilepsy range from 900 to 3600 mg/day. Treatment should be initiated with dose titration as described in Table 3, or with a starting dose of 300 mg three times daily on Day 1. Subsequently, depending on individual tolerability and response, the dose may be increased by 300 mg/day every 2–3 days up to the maximum dose of 3600 mg/day. Some patients may require slower titration of gabapentin. 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 total daily dose should be divided into three doses, with no interval between doses exceeding 12 hours, to avoid interruptions in anticonvulsant therapy and prevent the occurrence of seizures.

Children aged 6 years and older: 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 has been shown to be well tolerated in long-term clinical studies. The total daily dose should be divided into equal parts (administered three times daily), and the maximum interval between doses should not exceed 12 hours.

There is no need to monitor serum gabapentin levels. 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 should be initiated with dose titration as described in Table 3; otherwise, the starting dose of 900 mg/day should be divided into three equal 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. Some patients may require slower titration of gabapentin. 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 evaluated in long-term clinical studies lasting more than 5 months. If a patient requires longer-term treatment (more than 5 months) with gabapentin for neuropathic pain, the physician should assess the patient's clinical status and determine the need for continued therapy before proceeding.

Dosing instructions for all indications

Patients with poor general condition or specific risk factors, such as low body weight or post-transplant status, may require slower titration, reduced dose increments, or longer intervals between dose increases.

Use in elderly patients (aged 65 years and older)

Elderly patients may occasionally require individual dose adjustment due to possible reduced renal function (see Table 4). Elderly patients more frequently experience somnolence, peripheral edema, and weakness.

Use in patients with renal impairment

Patients with marked renal impairment and/or patients on hemodialysis require individual dose adjustment (see Table 4). For these patients, gabapentin 100 mg capsules are recommended.

Table 4

* 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 at a dose of 300 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 of the daily dose recommended for patients with creatinine clearance of 15 mL/min).

Dosing in patients undergoing hemodialysis

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

Maintenance doses of gabapentin in patients with impaired renal function undergoing hemodialysis should be based on the recommendations provided in Table 4. In addition to the maintenance dose, patients undergoing hemodialysis should be administered 200*–300 mg of gabapentin after every 4 hours of hemodialysis.

Gabapentin is intended for oral administration.

Gabapentin may be taken independently of food intake. The medication should be taken with sufficient fluid (e.g., a glass of water).

*Use gabapentin formulations at appropriate dosages.

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.

Overdose

Acute, life-threatening toxic reactions have not been reported following gabapentin overdoses of up to 49 g. Symptoms of overdose included dizziness, double vision, slurred speech, somnolence, loss of consciousness, lethargy, and mild diarrhea. With supportive treatment, all patients fully recovered.

Reduced absorption of gabapentin at high doses may limit systemic absorption and reduce toxic effects in overdose.

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

Although gabapentin can be removed by hemodialysis, based on previous experience, this is generally 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 up to 8000 mg/kg. Signs of acute toxicity in animals included ataxia, labored breathing, ptosis, decreased activity, or conversely, increased excitability.

Adverse Reactions

During epilepsy (adjunctive or monotherapy) and neuropathic pain studies, the following adverse reactions have been observed (listed according to their frequency): very common (>1/10), common (>1/100 – <1/10), uncommon (>1/1000 – <1/100), rare (>1/10000 – <1/1000). If the frequency of adverse reactions varied across different studies, the highest reported frequency was included in the report.

Additional adverse reactions identified during the post-marketing period are categorized as "frequency unknown" (cannot be estimated based on available data).

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

Infections 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 reactions with various manifestations that may include fever, rash, hepatitis, lymphadenopathy, eosinophilia, and sometimes other signs and symptoms), anaphylaxis (see section "Special precautions").

Metabolism and nutrition disorders

Common: Anorexia, increased appetite.

Uncommon: Hyperglycemia (most frequently observed in patients with diabetes).

Rare: Hypoglycemia (most frequently observed in patients with diabetes).

Frequency unknown: Hyponatremia.

Psychiatric disorders

Common: Hostility, confusion and emotional lability, depression, anxiety, nervousness, pathological thinking.

Uncommon: Agitation.

Frequency unknown: Hallucinations, drug dependence.

Nervous system disorders

Very common: Somnolence, dizziness, ataxia.

Common: Seizures, hyperkinesia, dysarthria, amnesia, tremor, insomnia, headache, sensory disturbances (paresthesia, hypoesthesia), coordination disturbances, nystagmus, increased, decreased or absent reflexes.

Uncommon: Hypokinesia, cognitive disturbances.

Rare: Loss of consciousness.

Frequency unknown: Other movement disorders (e.g., choreoathetosis, dyskinesia, dystonia).

Eye disorders

Common: Vision disorders such as amblyopia, diplopia.

Ear and labyrinth disorders

Common: Vertigo.

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 often described as bruises following trauma), rash, pruritus, acne.

Frequency unknown: Stevens-Johnson syndrome, toxic epidermal necrolysis, eosinophilia with systemic symptoms (see section "Special precautions"), erythema multiforme, angioneurotic edema, alopecia.

Musculoskeletal and connective tissue disorders

Common: Arthralgia, myalgia, back pain, muscle twitching.

Frequency unknown: Rhabdomyolysis, myoclonic seizures.

Renal and urinary disorders

Frequency unknown: Acute renal failure, urinary incontinence.

Reproductive system and breast disorders

Common: Impotence.

Frequency unknown: Breast enlargement, gynecomastia, sexual dysfunction (including changes in libido, ejaculation disorders, and anorgasmia).

General disorders and administration site conditions

Very common: Fatigue, fever.

Common: Peripheral edema, gait disturbance, weakness, pain, malaise, influenza-like syndrome.

Uncommon: Generalized edema.

Frequency unknown: Withdrawal reactions (mainly anxiety, insomnia, nausea, pain, increased sweating), chest pain. Cases of sudden death have been reported; however, a clear causal relationship with gabapentin use has not been established.

Investigations

Common: Decreased leukocyte count, weight gain.

Uncommon: Increased liver function tests (AST, ALT) and bilirubin.

Frequency unknown: Increased blood creatine phosphokinase levels.

Injury and poisoning

Common: Accidental injury, fractures, lacerations.

Uncommon: Falls.

Cases of acute pancreatitis have been reported during gabapentin treatment. A causal relationship with gabapentin has not been established (see section "Special precautions").

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

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

Withdrawal symptoms have been observed after discontinuation of both short- and long-term gabapentin treatment. Withdrawal symptoms may appear 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 (see section "Special precautions"). 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 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").

Reporting of adverse reactions

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

Shelf life. 3 years.

Storage conditions. Store in the original packaging at a temperature not exceeding 25 °C. Keep out of reach of children.

Packaging. 10 capsules in a blister, 3 blisters in a cardboard box.

Prescription status. Prescription only.

Manufacturer. Micro Labs Limited.

Manufacturer's address and location of operations

Plot No. S.155 – S.159 and N1, Verna Industrial Estate, Phase III and Phase IV, Verna Salcette, In-403 722, India.