Pregadol capsules 300 mg No. 30

Instructions for Pregadol capsules 300 mg No. 30

Composition

active ingredient: pregabalin;

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

excipients: corn starch, talc;

composition of the 75 mg capsule shell: gelatin, titanium dioxide (E 171), red iron oxide (E 172);

composition of the 150 mg capsule shell: gelatin, titanium dioxide (E 171);

composition of the 300 mg capsule shell: gelatin, titanium dioxide (E 171), red iron oxide (E 172).

Dosage form

Capsules.

Main physicochemical properties:

– 75 mg capsules: hard opaque gelatin capsules with a red-brown cap and a white body. The contents of the capsules are white or almost white powder;

– 150 mg capsules: hard opaque gelatin capsules with a white cap and body. The contents of the capsules are white or almost white powder;

– 300 mg capsules: hard opaque gelatin capsules with a red-brown cap and a white body. The contents of the capsules are white or almost white powder.

Pharmacotherapeutic group

Antiepileptic drugs, other antiepileptic drugs.

ATX code N03A X16.

Pharmacological properties

Pharmacodynamics

The active substance pregabalin is an analogue of gamma-aminobutyric acid [(S)-3-(aminomethyl)-

5-methylhexanoic acid)].

Mechanism of action

Pregabalin binds to the auxiliary subunit (α2-δ protein) of voltage-gated calcium channels in the central nervous system (CNS).

Clinical efficacy and safety.

– Neuropathic pain.

Studies have shown that the drug is 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 a twice-daily dosing regimen and in 8-week trials with a three-times-daily dosing regimen. Overall, the safety profile and efficacy of both regimens were similar.

In clinical studies of up to 12 weeks duration, when pregabalin was used to treat neuropathic pain in peripheral and central nervous system lesions, pain reduction 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 in the placebo group had a 50% improvement in pain scores. Among patients who did not experience somnolence, this improvement was observed in 33% of patients in the pregabalin group and 18% of patients in the placebo group. Among patients who experienced somnolence, the number of patients who responded to treatment was 48% in the pregabalin group and 16% in the placebo group.

In controlled clinical trials in central neuropathic pain, 22% of patients treated with pregabalin and 7% of patients in the placebo group experienced a 50% improvement in pain scores.

– Epilepsy.

Additional treatment.

Pregabalin has been studied in 3 controlled clinical trials of 12 weeks duration with twice- or three-times-daily dosing. Overall, the safety profile and efficacy were similar for the twice- and three-times-daily dosing regimens.

A reduction in seizure frequency was observed in the first week.

Children

The efficacy and safety of pregabalin as an adjunctive therapy in the treatment of 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 5.2, 5.2 and 4.8).

In a 12-week placebo-controlled study, children were given 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 from baseline in partial onset seizures 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.

Pregabalin was studied in one controlled clinical trial of 56 weeks duration with a twice-daily regimen. Pregabalin did not achieve greater efficacy compared to lamotrigine as assessed at 6 months for the seizure-free endpoint. Pregabalin and lamotrigine were equally safe and well tolerated.

– Generalized anxiety disorder.

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

Relief of symptoms of generalized anxiety disorder according to the Hamilton Anxiety Rating Scale (HAM-A) was observed in the first week.

In controlled clinical trials (4-8 weeks duration), 52% of patients treated with pregabalin and 38% of patients in the placebo group had at least a 50% improvement in the total HAM-A score from baseline to endpoint.

In controlled trials, blurred vision was reported more frequently in patients treated with pregabalin than in patients treated with placebo. In most cases, this phenomenon resolved with continued use of the drug. 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 treated with pregabalin 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 12-17 years with fibromyalgia who received pregabalin at a dose of

75-450 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 with 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 and multiple doses. The estimated oral bioavailability of pregabalin is greater than 90% and is independent of dose. After multiple doses, steady state is reached within

24-48 hours. 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 by approximately 2.5 hours. However, taking pregabalin with food had no clinically significant effect on the extent of its absorption.

Distribution.

Preclinical studies have shown that pregabalin crosses the blood-brain barrier in animals. Pregabalin also crosses the placenta in animals and is excreted in the milk of lactating animals. In humans, the apparent 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. After administration of a dose of radiolabeled pregabalin, approximately 98% of the radioactivity is excreted in the urine as unchanged pregabalin. The N-methylated derivative of pregabalin, the major metabolite of the drug, was detected in the urine and accounted for 0.9% of the administered dose. In preclinical studies, there was no racemization of the S-enantiomer of pregabalin to the R-enantiomer.

Breeding.

For patients with impaired renal function and patients on hemodialysis, the dose of the drug must be adjusted (see section "Method of administration and dosage", table 1).

Linearity/nonlinearity.

The pharmacokinetics of pregabalin are linear over the recommended dose range. The inter-patient variability in the pharmacokinetics of pregabalin is low (less than 20%). The pharmacokinetics of multiple doses are predictable based on 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 the blood plasma is reduced by approximately 50%). Since renal excretion is the main route of drug elimination, patients with renal insufficiency should reduce the dose of the drug, and after hemodialysis - take an additional dose (see section "Method of administration and dosage", Table 1).

Liver failure.

No specific pharmacokinetic studies have been conducted in patients with hepatic impairment. Since pregabalin is not extensively metabolized and is excreted primarily unchanged in the urine, it is unlikely that hepatic impairment will significantly affect 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 reach Cmax in plasma 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 <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 t1/2 of pregabalin averaged approximately 3-4 hours in children under 6 years of age and 4-6 hours in children over 7 years of age.

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 5.1, 5.2, and 4.8).

Elderly patients (aged 65 years and over)

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).

Breastfeeding period

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 breast 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.

Pregadol is indicated for the treatment of neuropathic pain of peripheral or central origin in adults.

Epilepsy.

Pregadol is indicated in adults as adjunctive treatment for partial seizures with or without secondary generalization.

Generalized anxiety disorder.

Pregadol is indicated for the treatment of generalized anxiety disorder in adults.

Fibromyalgia.

Contraindication

Hypersensitivity to the active substance or any of the excipients.

Interaction with other medicinal products and other types of interactions

Pregabalin is mainly excreted unchanged in the urine, undergoes little metabolism in humans (less than 2% of the dose is excreted in the urine as metabolites), does not inhibit the metabolism of other drugs in vitro, and does not bind to plasma proteins, so it is unlikely that pregabalin can cause or be the subject of pharmacokinetic interactions.

In vivo studies have not shown any clinically significant pharmacokinetic interactions between pregabalin and phenytoin, carbamazepine, valproic acid, lamotrigine, gabapentin, lorazepam, oxycodone and ethanol. Population pharmacokinetic analysis has shown that oral antidiabetics, diuretics, insulin, phenobarbital, tiagabine and topiramate have 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 did 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 studies, co-administration of multiple oral doses of pregabalin with oxycodone, lorazepam, or ethanol did not cause clinically significant effects on respiratory function. Respiratory failure and coma have been reported in post-marketing experience in patients taking pregabalin with other CNS depressants. Pregabalin is likely to potentiate the cognitive and gross motor impairments associated with oxycodone.

Elderly patients.

Specific pharmacodynamic interaction studies have not been conducted in elderly volunteers. Interaction studies have only been conducted in adults.

Application features

Patients with diabetes

Some patients with diabetes who gain weight during pregabalin therapy may require dose adjustment of their antidiabetic medications.

Hypersensitivity reactions.

Hypersensitivity reactions, including angioedema, have been reported. If symptoms of angioedema such as facial edema, perioral edema, or upper airway edema occur, pregabalin should be discontinued immediately.

Severe cutaneous adverse reactions (SCARs), including Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), which can be life-threatening or fatal, have been reported rarely with pregabalin. Patients should be advised of the signs and symptoms and monitored closely for skin reactions when prescribing the drug. If signs and symptoms suggestive of these reactions occur, pregabalin should be discontinued immediately and alternative treatment should be considered (if appropriate).

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

The use of pregabalin has been associated with dizziness and drowsiness, which may increase the risk of traumatic events (falls) in elderly patients.

Cases of loss of consciousness, confusion, and impaired mental performance and cognitive function have been reported. Therefore, patients should be advised to exercise caution until they are familiar with the potential effects of the drug.

Vision disorders

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 decreased visual acuity and visual field changes was higher in patients treated with pregabalin compared to patients in the placebo group; the incidence of fundoscopic changes was higher in patients treated with placebo (see section "Pharmacodynamics").

Ocular adverse reactions, including vision loss, blurred vision, or other changes in visual acuity, many of which were transient, have been reported. Discontinuation of pregabalin may result in resolution or reduction of these ocular symptoms.

Kidney failure

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

Withdrawal of concomitant antiepileptic drugs

There are currently insufficient data on the withdrawal of concomitant antiepileptic drugs after seizure control has been achieved by adding pregabalin to existing treatment in order to switch to pregabalin monotherapy.

Withdrawal symptoms

Withdrawal symptoms have been reported in some patients 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, and dizziness, which are indicative of physical dependence. This information should be communicated to the patient before initiating therapy.

Convulsions, including status epilepticus and grand mal seizures, may occur during pregabalin therapy or shortly after discontinuation of pregabalin.

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

Congestive heart failure has been reported in some patients taking pregabalin. This reaction has been observed primarily in the treatment of neuropathic pain in elderly patients with pre-existing cardiovascular disease. Pregabalin should be used with caution in such patients. This phenomenon may resolve upon discontinuation of pregabalin.

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

In the treatment of central neuropathic pain due to spinal cord injury, the incidence of adverse reactions in general, adverse reactions from the central nervous system and especially drowsiness was increased. This may be due to the additive effect of concomitant medicinal products (e.g. antispasticity agents) required for the treatment of this condition. These data should be taken into account when prescribing pregabalin to such patients.

Suicidal thinking and behavior.

Suicidal ideation and behavior have been reported in patients treated with antiepileptic drugs for certain indications. A meta-analysis of randomized placebo-controlled trials of antiepileptic drugs showed a small increased risk of suicidal ideation and behavior. The mechanism of this risk is unknown, and the available data do not exclude its existence with pregabalin.

Therefore, patients should be closely monitored for signs of suicidal thinking and behavior and treated appropriately if they develop. Patients (and caregivers of patients) should be advised to seek medical advice if signs of suicidal thinking or behavior appear.

Deterioration of the function of the lower gastrointestinal tract.

Post-marketing reports of lower gastrointestinal dysfunction (intestinal obstruction, paralytic ileus, constipation) have been reported following co-administration of pregabalin with medicinal products that may cause constipation, such as opioid analgesics. Precautions should be taken to prevent constipation when pregabalin is co-administered with opioids (especially in women and the elderly).

Misuse, abuse or addiction

Cases of misuse, abuse and dependence have been reported. Caution should be exercised when prescribing the drug to patients with a history of substance abuse; patients should be monitored for signs of misuse, abuse or dependence on pregabalin (cases of addiction, overdose, drug-seeking behavior have been reported).

Encephalopathy.

Encephalopathy occurred predominantly in patients with comorbidities that could cause encephalopathy.

Respiratory depression

Severe respiratory depression has been reported in association with pregabalin treatment. Patients with respiratory impairment, respiratory or central nervous system disease, renal disease, or those taking other CNS depressant medications, or elderly patients may be at higher risk of developing this severe adverse reaction. Dose adjustment may be necessary in these patients.

Concomitant use with opioids

Caution is advised when prescribing pregabalin concomitantly with opioids due to the risk of CNS depression (see Interactions with Other Medicinal Products and Other Forms of Interaction). In a case-control study of opioid users, patients receiving pregabalin concomitantly with an opioid were at increased risk of opioid-related mortality compared with opioids alone (adjusted odds ratio [aOR], 1.68 [95% CI, 1.19–2.36]). This increased risk was observed at low doses of pregabalin (≤ 300 mg, 1.52 aOR [95% CI, 1.04–2.22]) with a trend toward increased risk at high doses of pregabalin (> 300 mg, 2.55 aOR [95% CI 1.24–5.06]).

Use during pregnancy or breastfeeding

Women of reproductive age/contraceptives for women and men.

Women of reproductive age should use effective contraception.

Pregnancy.

Animal studies have shown reproductive toxicity.

Pregabalin has been shown to cross the placenta in rats.

Pregabalin can cross the human placenta.

Data from a Scandinavian observational study of over 2700 pregnancies exposed to pregabalin in the first trimester showed a higher prevalence of major congenital malformations in the pediatric population (live or stillborn) compared with the unexposed population (5.9% vs. 4.1%). The risk of major congenital malformations in the pediatric population exposed to pregabalin in the first trimester was slightly higher compared with the unexposed population (adjusted prevalence ratio and 95% confidence interval: 1.14 (0.96-1.35)), and compared with the population exposed to lamotrigine (1.29 (1.01-1.65)) or duloxetine (1.39 (1.07-1.82)). Analysis of specific malformations showed a higher risk of malformations of the nervous system, eyes, orofacial clefts, and genitourinary tract, but the numbers were small and the estimates imprecise. Pregabalin should not be used during pregnancy unless clearly necessary (if the benefit to the mother clearly outweighs the potential 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.

Reproductive function

There are no clinical data on the effect of pregabalin on female fertility.

In a clinical study of the effects of pregabalin on sperm motility, healthy male volunteers were administered pregabalin at a dose of 600 mg per day. No effect on sperm motility was observed after 3 months of treatment.

A fertility study showed adverse effects on female reproductive function in rats and adverse effects on male reproductive function and development in rats. The clinical relevance of these findings is unknown.

Ability to influence reaction speed when driving vehicles or other mechanisms

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

Method of administration and doses

Pregadol should be taken regardless of food intake.

This medicine is intended for oral use only.

Doses

The dose range is from 150 to 600 mg per day. The daily dose should be divided into 2 or 3 doses. For convenience of administration, doses of Pregadol, 75 mg capsules, or Pregadol, 150 mg capsules, or drugs with the active ingredient pregabalin in the appropriate dosage.

Neuropathic pain.

Pregabalin treatment should be initiated at a dose of 150 mg per day, divided into 2 or 3 doses. Depending on the efficacy and individual tolerability of the drug, the dose may 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 treatment can be started at a dose of 150 mg per day, divided into 2 or 3 doses. Depending on the effectiveness and individual tolerability of the drug, 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 treatment should be reassessed periodically.

Pregabalin treatment can be started at a dose of 150 mg per day. Depending on the effectiveness and individual tolerability of the drug, the dose can be increased to 300 mg per day after the first week of taking it. After another week of taking pregabalin, 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. In patients for whom 300 mg per day is insufficiently effective, 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. In view of the dose-related adverse reactions, doses above 450 mg per day are not recommended. Since Pregadol is excreted primarily by the kidneys, the dose should be adjusted in patients with impaired renal function.

Discontinuation of pregabalin treatment.

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

Pregabalin is eliminated from the systemic circulation unchanged primarily by renal excretion. Since pregabalin clearance is directly proportional to creatinine clearance (see section 5.2), dose reduction for patients with renal impairment should be individualized based on creatinine clearance (CLcr), which is determined by the following formula:

Pregabalin is effectively removed from plasma by haemodialysis (50% of the drug within 4 hours). For patients on 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 1).

Table 1

Pregabalin dose adjustment according to renal function

* The total daily dose (mg/day) should be divided by the number of doses according to the regimen to obtain the required dose (mg).

** Pregabalin should be used in the appropriate dosage form.

Patients with liver failure.

No dose adjustment is necessary for patients with hepatic insufficiency (see section "Pharmacokinetics").

Use in elderly patients (over 65 years of age).

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 sections 5.1, 5.2, and 5.8; however, no dosage recommendations can be made based on this information.

Overdose

The most common adverse reactions in cases of pregabalin overdose were drowsiness, confusion, agitation and restlessness. Convulsions have also been reported. Coma has been reported rarely.

Treatment of pregabalin overdose consists of general supportive measures and may include haemodialysis if necessary (see section 4.2, Table 1).

Adverse reactions

In the clinical program for pregabalin, more than 8,900 patients received it, of whom 5,600 were participants in double-blind, placebo-controlled studies. The most common adverse reactions were dizziness and somnolence. Adverse reactions were usually mild or moderate.

In all controlled trials, the rate of discontinuation due to adverse reactions was 12% in patients treated with pregabalin and 5% in patients treated with placebo. The most common adverse reactions leading to withdrawal from 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); not known (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 related to the course of the underlying disease and/or concomitant use of other medications.

During the treatment of central neuropathic pain due to spinal cord injury, the incidence of adverse reactions in general, CNS adverse reactions and especially drowsiness was increased (see section "Special warnings and precautions for use").

Additional adverse reactions reported since pregabalin was marketed are indicated in italics in the “Frequency unknown” column.

Infections and infestations

Common: nasopharyngitis.

Blood and lymphatic system

Uncommon: neutropenia.

Immune system

Uncommon: hypersensitivity.

Rare: eng