Pregalin hard capsules 75 mg No. 20

Instructions for Pregalica hard capsules 75 mg No. 20

Composition

active ingredient: pregabalin;

1 capsule contains 75 mg or 150 mg or 300 mg of pregabalin;

excipients: pregelatinized starch, mannitol (E 421), talc.

Dosage form

The capsules are hard.

Main physicochemical properties:

75 mg capsules: white powder in a hard gelatin capsule with a white body and a red-orange cap, imprinted with “75” on the body;

150 mg capsules: white powder in a hard gelatin capsule with a white body and white cap, imprinted with “150” on the body;

300 mg capsules: white powder in a hard gelatin capsule with a white body and a red-orange cap, imprinted with “300” on the body.

Pharmacotherapeutic group

Antiepileptics. Other antiepileptics. ATX code N03A X16.

Pharmacological properties

Pharmacodynamics.

The active substance is pregabalin, which is an analogue of gamma-aminobutyric acid [(S)-3-(aminomethyl)-5-methylhexanoic acid].

Mechanism of action.

Pregabalin binds to the auxiliary subunit (a2–d protein) of voltage-gated calcium channels in the central nervous system (CNS).

Clinical efficacy and safety.

Neuropathic pain.

Studies have shown the drug to be effective in treating diabetic neuropathy, postherpetic neuralgia, and spinal cord injury. The drug's effectiveness in other types of neuropathic pain has not been studied.

Pregabalin has been studied in 10 controlled clinical trials of up to 13 weeks duration with twice daily dosing and in trials of up to 8 weeks duration with three times daily dosing. Overall, the safety and efficacy profiles for the twice and three times daily dosing regimens were similar.

In clinical studies of up to 12 weeks duration in which the drug was used to treat neuropathic pain, a reduction in peripheral and central pain was observed after the first week and was maintained throughout the treatment period.

In controlled clinical trials of peripheral neuropathic pain, 35% of patients treated with pregabalin and 18% of patients treated with placebo achieved a 50% improvement in pain scores. Among patients who did not experience somnolence, this improvement was observed in 33% of patients treated with pregabalin and 18% of patients treated with placebo. Among patients who experienced somnolence, the proportion of patients who responded to treatment was 48% in the pregabalin group and 16% in the placebo group.

In a controlled clinical trial of central neuropathic pain, 22% of patients treated with pregabalin and 7% of patients treated with placebo had a 50% improvement in pain scores.

Epilepsy.

Adjunctive therapy: Pregabalin was studied in three 12-week controlled clinical trials with twice- or three-times-daily dosing regimens. Overall, the safety and efficacy profiles for the twice- and three-times-daily dosing regimens were similar. A reduction in seizure frequency was observed as early as the first week.

Children: The efficacy and safety of pregabalin as an adjunctive therapy in epilepsy in children under 12 years of age and adolescents have not been established. Adverse reactions observed in a pharmacokinetic and tolerability study in patients aged 3 months to 16 years (n=65) with partial onset seizures were similar to those seen in adults. Results from a 12-week placebo-controlled study in 295 children aged 4 to 16 years to evaluate the efficacy and safety of pregabalin as adjunctive therapy for partial onset seizures and a 1-year open-label safety study in 54 children aged 3 months to 16 years with epilepsy indicate that adverse reactions such as pyrexia and upper respiratory tract infections are more common in children than in adult patients with epilepsy (see sections 4.2, 4.8 and 5.2). In the 12-week placebo-controlled study, children were treated with pregabalin 2.5 mg/kg/day (maximum 150 mg/day), pregabalin 10 mg/kg/day (maximum 600 mg/day) or placebo. At least a 50% reduction in partial onset seizures from baseline was observed in 40.6% of patients receiving pregabalin 10 mg/kg/day (p=0.0068 vs. placebo), 29.1% of patients receiving pregabalin 2.5 mg/kg/day (p=0.2600 vs. placebo), and 22.6% of those receiving placebo.

Monotherapy (in newly diagnosed patients). Pregabalin was studied in 1 controlled clinical trial of 56 weeks duration with twice daily dosing. Pregabalin did not achieve the same level of efficacy as lamotrigine as assessed by the 6-month seizure-free endpoint. Pregabalin and lamotrigine were equally safe and well tolerated.

Pregabalin has been studied in 6 controlled studies of 4–6 weeks duration, one 8-week study in elderly patients, and one long-term relapse prevention study with a double-blind relapse prevention phase of 6 months duration.

Reductions in symptoms of generalized anxiety disorder as measured by the Hamilton Anxiety Inventory (HAM-A) were observed as early as week 1. In controlled clinical trials (4–8 weeks duration), 52% of patients treated with pregabalin and 38% of patients treated with placebo had at least a 50% improvement in HAM-A total score from baseline to endpoint.

In controlled trials, blurred vision was more frequently observed in patients treated with pregabalin than in patients treated with placebo. In most cases, this phenomenon resolved with continued therapy. Ophthalmological examinations (including visual acuity testing, formal visual field testing, and dilated fundus examination) were performed in over 3600 patients in controlled clinical trials. Among these patients, visual acuity deteriorated in 6.5% of patients in the pregabalin group and 4.8% of patients in the placebo group. Visual field changes were observed in 12.4% of patients treated with pregabalin and 11.7% of patients in the placebo group. Fundus changes were observed in 1.7% of patients treated with pregabalin and 2.1% of patients in the placebo group.

Fibromyalgia.

The efficacy of pregabalin was established in one 14-week, double-blind, placebo-controlled, multicenter study (F1) and one 6-week, randomized withdrawal study (F2). These studies enrolled patients diagnosed with fibromyalgia based on the American College of Rheumatology criteria (3-month history of widespread pain and pain present in 11 or more of 18 specific tender points). The studies demonstrated a reduction in pain on a visual analog scale. Improvement was additionally demonstrated on the patient's global assessment and on a fibromyalgia impact questionnaire.

Children: A 15-week placebo-controlled study was conducted in 107 children aged 12 to 17 years with fibromyalgia who received pregabalin at a dose of 75 to 450 mg/day. The primary efficacy endpoint (change in total pain intensity from baseline to week 15; calculated using an 11-point rating scale) demonstrated a numerically greater improvement in patients treated with pregabalin compared to patients treated with placebo, but this improvement did not reach statistical significance. The most common adverse reactions observed in clinical trials were dizziness, nausea, headache, weight gain, and fatigue. The overall safety profile in adolescents was similar to that in adults with fibromyalgia.

Pharmacokinetics.

The steady-state pharmacokinetics of pregabalin were similar in healthy volunteers, patients with epilepsy taking antiepileptic drugs, and patients with chronic pain.

Absorption.

Pregabalin is rapidly absorbed in the fasted state and reaches peak plasma concentrations within 1 hour after single or multiple doses. The estimated oral bioavailability of pregabalin is ≥ 90% and is independent of dose. Steady state is reached after 24–48 hours after multiple doses. The rate of absorption of pregabalin is reduced when taken with food, resulting in a decrease in maximum concentration (Cmax) by approximately 25–30% and a prolongation of tmax to approximately 2.5 hours. However, taking pregabalin with food had no clinically significant effect on the extent of its absorption.

Distribution.

Pregabalin has been shown to cross the blood-brain barrier in mice, rats and monkeys in preclinical studies. Pregabalin has been shown to cross the placenta in rats and to pass into the milk of lactating rats. In humans, the volume of distribution of pregabalin after oral administration is approximately 0.56 l/kg. Pregabalin is not bound to plasma proteins.

Metabolism.

Pregabalin undergoes minimal metabolism in humans. Following a dose of radiolabeled pregabalin, approximately 98% of the radioactivity was excreted in the urine as unchanged pregabalin. The N-methylated derivative of pregabalin, the major metabolite of the drug detected in urine, accounted for 0.9% of the administered dose. In nonclinical studies, there was no racemization of the S-enantiomer of pregabalin to the R-enantiomer.

Breeding.

Pregabalin is eliminated from the systemic circulation unchanged, primarily by the kidneys. The mean elimination half-life of pregabalin is 6.3 hours. The plasma and renal clearance of pregabalin are directly proportional to creatinine clearance (see section "Pharmacokinetics. Renal failure").

Patients with impaired renal function or patients on hemodialysis require dose adjustment of the drug (see section "Method of administration and dosage", table).

The pharmacokinetics of pregabalin are linear over the recommended dose range. The inter-patient variability in pregabalin pharmacokinetics is low (<20%). The pharmacokinetics of multiple doses are predictable from single-dose data. Therefore, routine monitoring of pregabalin plasma concentrations is not required.

Sex.

Results of clinical studies indicate that there is no clinically significant effect of gender on pregabalin plasma concentrations.

Kidney failure.

Pregabalin clearance is directly proportional to creatinine clearance. In addition, pregabalin is effectively removed from plasma by hemodialysis (after 4 hours of hemodialysis, the concentration of pregabalin in plasma decreases by approximately 50%). Since the drug is excreted mainly by the kidneys, patients with renal insufficiency should reduce the dose of the drug, and after hemodialysis - apply an additional dose (see section "Method of administration and dosage", table).

Liver failure.

Specific pharmacokinetic studies have not been conducted in patients with hepatic impairment. Since pregabalin is not extensively metabolized and is excreted primarily unchanged in the urine, hepatic impairment is unlikely to have a significant effect on pregabalin plasma concentrations.

Children.

The pharmacokinetics of pregabalin were evaluated in children with epilepsy (age groups: 1 to 23 months, 2 to 6 years, 7 to 11 years, and 12 to 16 years) at doses of 2.5 mg/kg/day, 5 mg/kg/day, 10 mg/kg/day, and 15 mg/kg/day in a pharmacokinetic and tolerability study.

After oral administration of pregabalin to children in the fasted state, the time to peak plasma concentration was generally similar across age groups and ranged from 0.5 hours to 2 hours post-dose.

Pregabalin Cmax and area under the concentration-time curve (AUC) increased linearly with increasing dose in each age group. In children weighing up to 30 kg, AUC values were 30% lower, due to a 43% increase in weight-adjusted clearance in these patients compared to patients weighing ≥30 kg. The terminal half-life of pregabalin averaged approximately 3–4 hours in children aged <6 years and 4–6 hours in children aged 7 years and older.

In a population pharmacokinetic analysis, creatinine clearance was shown to be a significant covariate for oral pregabalin clearance and body weight was a significant covariate for the apparent volume of distribution of oral pregabalin, and this relationship was similar in pediatric and adult patients.

The pharmacokinetics of pregabalin in patients under 3 months of age have not been studied (see sections 4.2, 4.8, and 4.8).

Elderly patients.

Pregabalin clearance tends to decrease with age. This decrease in oral pregabalin clearance is consistent with the age-related decrease in creatinine clearance. Patients with age-related renal impairment may require a reduction in the pregabalin dose (see Dosage and Administration, Table 1).

Breast-feeding.

The pharmacokinetics of pregabalin administered at a dose of 150 mg every 12 hours (300 mg daily dose) were evaluated in 10 lactating women for at least 12 weeks postpartum. Breastfeeding had no or negligible effect on the pharmacokinetics of pregabalin. Pregabalin was excreted in human milk, with mean steady-state concentrations approximately 76% of maternal plasma concentrations. The estimated dose to the breastfed infant (with a mean milk intake of 150 mL/kg/day) from a woman taking pregabalin at a dose of 300 mg/day or a maximum dose of 600 mg/day is 0.31 or 0.62 mg/kg/day, respectively. These estimated doses represent approximately 7% of the total maternal daily dose on a mg/kg basis.

Indication

Neuropathic pain.

Treatment of neuropathic pain of peripheral or central origin in adults. Epilepsy.

As an adjunctive treatment for partial seizures with or without secondary generalization.

Generalized anxiety disorder.

Treatment of generalized anxiety disorder in adults.

Fibromyalgia.

Contraindication

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

Interaction with other medicinal products and other types of interactions

Since pregabalin is excreted primarily unchanged in the urine, undergoes minimal metabolism in humans (≤2% of the dose is excreted in the urine as metabolites), does not inhibit the metabolism of other drugs in vitro, and is not bound to plasma proteins, it is unlikely that pregabalin could cause or be the target of pharmacokinetic interactions.

Thus, in vivo studies, no clinically significant pharmacokinetic interactions were observed between pregabalin and phenytoin, carbamazepine, valproic acid, lamotrigine, gabapentin, lorazepam, oxycodone or ethanol. Population pharmacokinetic analysis demonstrated that oral antidiabetics, diuretics, insulin, phenobarbital, tiagabine and topiramate had no clinically significant effect on the clearance of pregabalin.

Oral contraceptives, norethisterone and/or ethinyl estradiol.

Co-administration of pregabalin with oral contraceptives, norethisterone and/or ethinyl estradiol does not affect the steady-state pharmacokinetics of either drug.

Drugs that affect the CNS.

Pregabalin may potentiate the effects of ethanol and lorazepam. In controlled clinical trials, multiple oral doses of pregabalin with oxycodone, lorazepam, or ethanol did not produce clinically significant effects on respiratory function. There are reports of respiratory failure, coma, and death in patients taking pregabalin with opioids and other CNS depressants, particularly in patients who abuse such substances. Pregabalin is likely to potentiate the cognitive and gross motor impairments caused by oxycodone.

Interactions in elderly patients.

No specific pharmacodynamic interaction studies have been conducted in elderly volunteers. Drug interaction studies have only been conducted in adult patients.

Application features

Patients with diabetes.

In accordance with current clinical practice, some patients with diabetes mellitus who gain weight during pregabalin therapy may require dose adjustment of their antidiabetic medicinal products.

Hypersensitivity reactions.

There are reports of hypersensitivity reactions, including angioedema, with pregabalin. If symptoms of angioedema such as facial edema, perioral edema, or upper respiratory tract edema occur, pregabalin should be discontinued immediately.

Severe skin reactions.

Severe cutaneous adverse reactions, including Stevens-Johnson syndrome and toxic epidermal necrolysis, which can be life-threatening or fatal, have been reported rarely in association with pregabalin treatment.

When prescribing the medicinal product, patients should be informed about the signs and symptoms and monitored closely for skin reactions. If signs and symptoms suggestive of these reactions occur, pregabalin should be discontinued immediately and alternative treatment should be considered (if necessary).

Dizziness, drowsiness, loss of consciousness, confusion and mental disorders.

Pregabalin has been associated with dizziness and somnolence, which may increase the risk of falls in elderly patients. There are reports of loss of consciousness, confusion and mental impairment with pregabalin. Therefore, patients should be advised to exercise caution until they are aware of the potential effects of this medicinal product. Visual disturbances.

In controlled trials, blurred vision was more frequently observed in patients treated with pregabalin than in patients treated with placebo. In most cases, this phenomenon resolved with continued therapy. In clinical trials in which ophthalmological examinations were performed, the incidence of visual acuity deterioration and visual field changes was higher in patients treated with pregabalin compared to patients in the placebo group; the incidence of fundus changes was higher in patients in the placebo group (see section "Pharmacodynamics").

There are reports of visual adverse reactions with pregabalin, including vision loss, blurred vision, or other changes in visual acuity, many of which were transient. These visual symptoms may resolve or improve after discontinuation of pregabalin.

Kidney failure.

Cases of renal failure have been reported, which were sometimes reversible after discontinuation of pregabalin.

Withdrawal of concomitant antiepileptic medications.

There is currently insufficient data on whether concomitant antiepileptic drugs can be withdrawn once seizure control is achieved with the addition of pregabalin to therapy, in order to switch to pregabalin monotherapy.

Withdrawal symptoms.

Some patients have experienced withdrawal symptoms after discontinuation of short-term or long-term pregabalin therapy. The following events have been reported: insomnia, headache, nausea, anxiety, diarrhea, flu-like syndrome, nervousness, depression, pain, seizures, hyperhidrosis, dizziness, suicidal thoughts, which are indicative of physical dependence. This information should be communicated to the patient before starting therapy.

Data on withdrawal of pregabalin after long-term use indicate that the incidence and severity of withdrawal symptoms may be dose-dependent. Congestive heart failure.

There are reports of congestive heart failure in some patients taking pregabalin. This reaction has been observed mainly during the treatment of neuropathic pain with pregabalin in elderly patients with pre-existing cardiovascular disorders. Pregabalin should be used with caution in such patients. This phenomenon may disappear when pregabalin is discontinued.

Treatment of neuropathic pain of central origin due to spinal cord injury.

During the treatment of central neuropathic pain caused by spinal cord injury, the frequency of adverse reactions in general, as well as adverse reactions from the central nervous system and in particular drowsiness, increased. This may be due to the additive effect of concomitant medications (e.g. antispasticity drugs) required for the treatment of this condition. This should be taken into account when prescribing pregabalin in this condition.

Respiratory depression.

Cases of severe respiratory depression have been reported with pregabalin. Patients with impaired respiratory function, respiratory or neurological disease, renal impairment, concomitant use of CNS depressants, and the elderly may be at higher risk of this serious adverse reaction. These patients may require dose adjustment.

Suicidal thinking and behavior.

Suicidal ideation and behavior have been reported in patients treated with antiepileptic drugs for some indications. A meta-analysis of randomized, placebo-controlled trials of antiepileptic drugs also showed a small increased risk of suicidal ideation and behavior. The mechanism of this risk is unknown, and the available data do not exclude the possibility of an increased risk with pregabalin. Suicidal ideation and behavior have been reported in patients treated with pregabalin (see section 4.8). An epidemiological study using a self-control design (comparing treatment periods with periods without treatment in an individual patient) has shown an increased risk of new suicidal behavior and deaths due to suicide in patients treated with pregabalin.

Therefore, patients should be closely monitored for signs of suicidal ideation and behavior and appropriate treatment should be considered. Patients (and caregivers of patients) should be advised to seek medical advice if signs of suicidal ideation or behavior appear. In the event of suicidal ideation and behavior, discontinuation of pregabalin should be considered.

Deterioration of the function of the lower gastrointestinal tract.

There are reports of events associated with a deterioration in lower gastrointestinal function (such as intestinal obstruction, paralytic ileus, constipation) when pregabalin is used together with medicinal products that can cause constipation, such as opioid analgesics. When pregabalin is used concomitantly with opioids, measures should be taken to prevent constipation (especially in women and elderly patients).

Concomitant use with opioids.

Caution is advised when prescribing pregabalin concomitantly with opioids due to the risk of CNS depression. In a controlled study of opioid users, patients taking pregabalin concomitantly with an opioid were at increased risk of opioid-related death compared with opioids alone. This increased risk was observed at low doses of pregabalin (≤ 300 mg, aOR 1.52 [95% CI, 1.04 - 2.22]), and there was a trend toward a higher risk at high doses of pregabalin (> 300 mg, aOR 2.51 [95% CI 1.24 - 5.06]).

Misuse, abuse or addiction.

Cases of misuse, abuse and dependence have been reported. The drug should be used with caution in patients with a history of substance abuse; the patient should be monitored for signs of misuse, abuse or dependence on pregabalin (cases of addiction, exceeding the prescribed dose, drug-seeking behavior have been reported).

Encephalopathy.

Cases of encephalopathy have been reported, occurring predominantly in patients with underlying conditions that may predispose to encephalopathy.

Excipients.

The drug Pregabalin contains mannitol, which may have a mild laxative effect.

Use during pregnancy or breastfeeding

Women of reproductive age/contraceptives for women and men.

Since the potential risk to humans is unknown, women of reproductive age should use effective contraception.

Pregnancy.

There are no adequate data from the use of pregabalin in pregnant women.

The drug should not be used during pregnancy unless absolutely necessary (when the benefit to the mother clearly outweighs the possible risk to the fetus).

Breast-feeding.

Pregabalin is excreted in human milk. The effects of pregabalin on newborns/infants are unknown. A decision must be made whether to discontinue breast-feeding or to discontinue pregabalin therapy taking into account the benefit of breast-feeding for the child and the benefit of therapy for the woman.

Fertility.

There are no clinical data on the effect of pregabalin on female fertility. In a clinical study of the effect of pregabalin on sperm motility, healthy male volunteers were given pregabalin at a dose of 600 mg/day. No effect on sperm motility was observed after 3 months of treatment.

In a fertility study in female rats, adverse effects on reproductive function were observed. In a fertility study in male rats, adverse effects on reproductive function and development were observed. The clinical relevance of these findings is unknown.

Ability to influence reaction speed when driving vehicles or other mechanisms

Pregalica may have minor or moderate influence on the ability to drive and use machines. Pregalica may cause dizziness and drowsiness and thus affect the ability to drive and use machines. Therefore, patients should be advised to refrain from driving, operating complex machinery, and other potentially hazardous activities until it is known whether this medicine affects their ability to perform such activities.

Method of administration and doses

Pregalica should be taken with or without food. The medicine is intended for oral use only.

Doses.

The dosage range of the drug can vary within 150–600 mg per day. The daily dose should be divided into 2 or 3 doses.

Neuropathic pain.

Pregabalin therapy can be initiated at a dose of 150 mg per day, divided into 2 or 3 doses. Depending on the individual response and tolerability of the drug by the patient, the dose can be increased to 300 mg per day after 3–7 days, and if necessary - to a maximum dose of 600 mg per day after another 7 days.

Epilepsy.

Pregabalin therapy can be initiated at a dose of 150 mg per day, divided into 2 or 3 doses. Depending on the individual response and tolerability of the drug by the patient, the dose can be increased to 300 mg per day after the first week of treatment. After another week, the dose can be increased to a maximum of 600 mg per day.

Generalized anxiety disorder.

The dose, divided into 2 or 3 doses, may vary between 150 and 600 mg per day. The need for continued therapy should be reviewed periodically.

Pregabalin therapy can be initiated at a dose of 150 mg per day. Depending on the individual response and tolerability of the drug by the patient, the dose can be increased to 300 mg per day after the first week of treatment. After another week of treatment, the dose can be increased to 450 mg per day. After another week, the dose can be increased to a maximum of 600 mg per day.

Fibromyalgia.

The recommended dose for the treatment of fibromyalgia is 300 to 450 mg per day. Treatment should be initiated at 75 mg twice daily (150 mg per day). Depending on efficacy and tolerability, the dose may be increased to 150 mg twice daily (300 mg per day) within one week. For patients who are not adequately responsive to 300 mg per day, the dose may be increased to 225 mg twice daily (450 mg per day). Although a study has been conducted with a dose of 600 mg per day, there is no evidence that this dose would provide additional benefit; it was also less well tolerated. Given the dose-related adverse reactions, doses above 450 mg per day are not recommended. Since Pregabalin is primarily excreted by the kidneys, the dose should be adjusted in patients with impaired renal function.

Pregabalin withdrawal.

In accordance with current clinical practice, it is recommended to discontinue pregabalin therapy gradually, over a period of at least one week, regardless of the indication (see sections “Special warnings and precautions for use” and “Adverse reactions”).

Kidney dysfunction.

Pregabalin is eliminated from the systemic circulation unchanged, primarily by the kidneys. Since pregabalin clearance is directly proportional to creatinine clearance (see section 5.2), the dose should be reduced in patients with renal impairment on an individual basis as indicated in the table below, based on creatinine clearance (CLcr), which is determined by the formula:

Pregabalin is effectively removed from plasma by haemodialysis (50% of the drug within 4 hours). For patients undergoing haemodialysis, the daily dose of pregabalin should be adjusted according to renal function. In addition to the daily dose, an additional dose of the drug should be administered immediately after each 4-hour haemodialysis session (see table).

Pregabalin dose adjustment according to renal function.

* The total daily dose (mg/day) should be divided into several doses according to the dosing regimen to obtain a single dose (mg/dose).

+ An additional dose is an additional single dose.

Liver failure.

There is no need for dose adjustment for patients with impaired liver function (see section "Pharmacokinetics").

Elderly patients.

Elderly patients may require a reduction in the dose of pregabalin due to decreased renal function (see section 4.4).

Children.

The safety and efficacy of pregabalin in children (under 18 years of age) have not been established. Currently available information is provided in the section "Adverse reactions", as well as in the sections "Pharmacodynamics" and "Pharmacokinetics", however, based on this information, no dosage recommendations can be made for this category of patients.

Overdose

Symptoms: The most common adverse reactions to date with pregabalin overdose have been somnolence, confusion, agitation and restlessness. Convulsions have also been reported. Coma has been reported rarely.

Treatment: Treatment of pregabalin overdose consists of general supportive measures and may include hemodialysis if necessary (see section 4.2, Dosage and Administration, table).

Side effects

In the clinical trial program of pregabalin, more than 8,900 patients received it, of whom 5,600 were participants in double-blind, placebo-controlled studies. The most frequently reported adverse reactions were dizziness and somnolence. Adverse reactions were usually mild to moderate in severity. In all controlled studies, the rate of discontinuation due to adverse reactions was 12% among patients receiving pregabalin and 5% among patients receiving placebo. The most common adverse reactions leading to discontinuation of study drug in the pregabalin group were dizziness and somnolence.

All adverse reactions that occurred more frequently than placebo and in more than one patient are listed below; these adverse reactions are listed by system organ class and frequency: very common (≥ 1/10); common (≥ 1/100 to < 1/10); uncommon (≥ 1/1,000 to < 1/100); rare (≥ 1/10,000 to < 1/1,000); very rare (< 1/10,000); frequency unknown (cannot be estimated from the available data). Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness.

These adverse reactions may also be associated with the course of the underlying disease and/or concomitant use of other medications.

During the treatment of central neuropathic pain caused by spinal cord injury, the frequency of adverse reactions in general, the frequency of adverse reactions from the CNS and especially drowsiness increased (see section "Special warnings and precautions for use").

Additional adverse reactions reported during post-marketing surveillance are listed below and are in italics.

Infections and invasions.

Common: nasopharyngitis.

From the blood and lymphatic system.

Uncommon: neutropenia.

From the immune system.

Uncommon: hypersensitivity.

Rare: angioedema, allergic reactions, anaphylactoid reactions.

Metabolic disorders, metabolism.

Common: increased