Neogabin 150 capsules 150 mg blister No. 30

Instructions Neogabin 150 capsules 150 mg blister No. 30

Composition

active ingredient: pregabalin;

1 capsule contains 75 mg or 150 mg of pregabalin;

excipients: microcrystalline cellulose, croscarmellose sodium, magnesium stearate, talc; hard gelatin capsule: gelatin, titanium dioxide (E 171).

Dosage form

Capsules.

Main physical and chemical properties: hard gelatin capsules of white color. The contents of the capsules are white or almost white powder. The presence of compressed columns or lumps that disintegrate when pressed is allowed.

Pharmacotherapeutic group

Analgesics. Other analgesics and antipyretics. Gabapentinoids. Pregabalin.

ATX code N02BF02.

Pharmacological properties

Pharmacodynamics.

The active substance is pregabalin, which is a derivative 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.

It is known that during studies, the drug has been shown 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 both 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.

Additional treatment.

Pregabalin has been studied in 3 controlled clinical trials of 12 weeks duration 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 decrease in the frequency of seizures was observed already in the first week of its use.

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 and a 14-day placebo-controlled study in 175 children aged 1 month to less than 4 years to evaluate the efficacy and safety of pregabalin as adjunctive therapy in partial onset seizures, and two 1-year open-label safety studies in 54 and 431 children aged 3 months to 16 years with epilepsy, respectively, indicate that adverse reactions such as pyrexia and upper respiratory tract infections were observed more frequently 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 (aged 4 to 16 years) 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 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 patients receiving placebo.

In a 12-week placebo-controlled study in patients with primary generalized tonic-clonic (PGTC) seizures, 219 patients aged 5 to 65 years (including 66 patients aged 5 to 16 years) were treated with pregabalin 5 mg/kg/day (maximum 300 mg/day) or 10 mg/kg/day (maximum 600 mg/day) or placebo as adjunctive therapy. At least a 50% reduction in PGTC seizure frequency was observed in 41.3%, 38.9% and 41.7% of patients treated with pregabalin 5 mg/kg/day, pregabalin 10 mg/kg/day and placebo, respectively.

Monotherapy (in newly diagnosed patients). Pregabalin was studied in one controlled clinical trial of 56 weeks duration with a twice daily dosing regimen. Pregabalin did not achieve the same level of efficacy as lamotrigine as assessed by a 6-month comparative assessment of the seizure-free endpoint. Pregabalin and lamotrigine were similarly 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 trial with a double-blind relapse prevention phase of 6 months duration.

A reduction in symptoms of generalized anxiety disorder, as measured by the Hamilton Anxiety Rating Scale (HAM-A), was observed as early as the first week of pregabalin treatment.

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 3,600 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 questionnaire regarding the impact of fibromyalgia on quality of life.

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, as measured by an 11-point rating scale) showed significant improvement in patients receiving pregabalin compared to patients receiving placebo, but this improvement was not statistically significant. The most common adverse reactions observed in the studies were dizziness, nausea, headache, weight gain, and fatigue. The overall safety profile in adolescents was similar to that in adults with fibromyalgia.

Pharmacokinetics.

It is known that the pharmacokinetic parameters of pregabalin at steady state were similar in healthy volunteers, patients with epilepsy using antiepileptic drugs, and patients with chronic pain.

Absorption.

Pregabalin is rapidly absorbed after oral administration in the fasted state, reaching peak plasma concentrations within 1 hour after single and multiple dosing. The estimated oral bioavailability of pregabalin is 90% and is independent of dose. Steady state is reached after 24-48 hours after multiple dosing. 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 delay in time to maximum concentration (tmax) of approximately 2.5 hours. However, administration of pregabalin with food had no clinically significant effect on the extent of its absorption.

Distribution.

It is known that in preclinical studies it was demonstrated that pregabalin readily penetrates the blood-brain barrier, as well as the placenta, and is excreted in milk during lactation. The apparent volume of distribution of pregabalin after oral administration is approximately 0.56 l/kg. Pregabalin does not bind to plasma proteins.

Pregabalin undergoes minimal metabolism in humans. Following 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 pregabalin detected in urine) accounted for 0.9% of the administered dose. There is no racemization of the S-enantiomer to the R-enantiomer.

Breeding.

Pregabalin is eliminated from the systemic circulation primarily by renal excretion of unchanged pregabalin. The mean elimination half-life of pregabalin is 6.3 hours. The plasma and renal clearance of pregabalin are directly proportional to creatinine clearance. Dosage adjustment is required in patients with renal impairment or in patients undergoing hemodialysis (see Dosage and Administration).

Linearity/nonlinearity.

The pharmacokinetics of pregabalin are linear over the recommended dose range. The intersubject pharmacokinetic variability for pregabalin is low (less than 20%). Multiple-dose pharmacokinetics are predicted from single-dose data. Therefore, there is no need to monitor pregabalin plasma concentrations.

Sex.

Existing data indicate that there is no clinically significant effect of gender on pregabalin plasma concentrations.

Kidney dysfunction.

Pregabalin clearance is directly proportional to creatinine clearance. In addition, pregabalin is effectively removed from plasma by hemodialysis (after 4 hours of hemodialysis, pregabalin plasma concentrations are reduced by approximately 50%). Since renal excretion is the primary route of elimination of pregabalin, patients with impaired renal function should have a reduced dose of the drug, and after hemodialysis - an additional dose (see section "Method of administration and dosage").

Liver dysfunction.

Specific pharmacokinetic studies in patients with hepatic impairment have not been conducted. Since pregabalin is not extensively metabolized and is excreted primarily unchanged in the urine, hepatic impairment is unlikely to 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 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 <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 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 younger than 3 months of age have not been studied (see sections 4.2, 4.8, and 4.8).

Elderly patients.

Pregabalin clearance is known to tend 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 dose reduction.

Breastfeeding period.

The pharmacokinetics of pregabalin, when administered at a dose of 150 mg every 12 hours (daily dose of 300 mg), have been evaluated in 10 lactating women for at least 12 weeks postpartum. Breastfeeding has been shown to have little or no effect on the pharmacokinetics of pregabalin. Pregabalin is 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.

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

Epilepsy.

Neogabine is indicated as adjunctive therapy for partial seizures with or without secondary generalization in adults.

Generalized anxiety disorder.

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

Fibromyalgia.

Contraindication

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

Interaction with other medicinal products and other types of interactions

Since pregabalin is predominantly excreted unchanged in the urine, undergoes little 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 blood proteins, it is unlikely that pregabalin could cause or be the target of pharmacokinetic drug interactions.

In vivo studies and population pharmacokinetic analysis.

It is known that 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 showed that oral antidiabetic agents, diuretics, insulin, phenobarbital, tiagabine and topiramate had no clinically significant effect on the clearance of pregabalin.

Oral contraceptives, norethisterone and/or ethinyl estradiol.

Concomitant use of pregabalin and the 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. Respiratory failure, coma, and death have been reported in patients taking pregabalin concomitantly with opioids and/or other CNS depressants, particularly in patients with a history of substance abuse. Pregabalin is likely to potentiate the cognitive and gross motor impairments caused by oxycodone.

Interaction in elderly patients.

Specific pharmacodynamic interaction studies in the elderly have not been conducted. 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 while taking pregabalin may require dose adjustment of their antidiabetic medications.

Hypersensitivity reactions.

Hypersensitivity reactions, including angioedema, have been reported. Pregabalin should be discontinued immediately if symptoms of angioedema such as facial, perioral or upper respiratory tract swelling occur.

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

Pregabalin has been associated with dizziness and somnolence, which may increase the risk of accidental injury (fall) in the elderly. Adverse reactions such as loss of consciousness, confusion, and mental impairment have also been reported. Therefore, patients should be advised to exercise caution until they are aware of the potential effects of the drug.

Vision disorders.

Transient blurred vision and other visual changes were reported in patients treated with pregabalin compared to patients treated with placebo. In most cases, this phenomenon resolved with continued use of pregabalin.

It is known that in studies in which ophthalmological examination was performed, the incidence of deterioration in visual acuity and visual field changes was higher in patients treated with pregabalin than in patients in the placebo group; the incidence of changes in the fundus was higher in patients in the placebo group.

Visual side effects, including vision loss, blurred vision, or other changes in visual acuity, most of which were transient, have also been reported. Discontinuation of pregabalin may help resolve or improve these visual symptoms.

Kidney failure.

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

Withdrawal of concomitant antiepileptic medications.

There are insufficient data on the withdrawal of concomitant antiepileptic drugs after seizure control is achieved when pregabalin is added to existing treatment to switch to pregabalin monotherapy.

Withdrawal symptoms.

Withdrawal symptoms have been reported in some patients after discontinuation of short-term and long-term use of pregabalin. The following events have been reported: insomnia, headache, nausea, anxiety, diarrhea, flu-like syndrome, nervousness, depression, suicidal ideation, pain, seizures, hyperhidrosis, and dizziness, which are indicative of physical dependence. This information should be communicated to the patient before initiating therapy.

If pregabalin needs to be discontinued, it is recommended to do so gradually, over a period of at least 1 week, regardless of the indication (see section 4.2).

Seizures, including status epilepticus and grand mal seizures, may occur during treatment with pregabalin or shortly after discontinuation of pregabalin. Data on withdrawal of pregabalin after long-term use indicate that the incidence and severity of withdrawal symptoms may be dose-dependent.

Cases of congestive heart failure have been reported in patients taking pregabalin. This reaction has been observed mainly during the treatment of neuropathic pain with pregabalin in elderly patients with 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.

It is known that during the treatment of central neuropathic pain due to spinal cord injury, the incidence of adverse reactions in general, CNS adverse reactions and somnolence in particular was increased. This may be explained by the additive effect of concomitant medicinal products (e.g. antispasticity agents) required for the treatment of this condition. This fact should be taken into account when prescribing pregabalin to such patients.

Respiratory depression.

Severe respiratory depression has been reported with pregabalin. Patients with compromised respiratory function, respiratory or neurological disease, renal impairment, concomitant use of CNS depressants, and the elderly may be at greater risk of this serious adverse reaction. These patients may require dose adjustment (see Dosage and Administration).

Suicidal thinking and behavior.

Suicidal ideation and behavior have been reported in patients treated with antiepileptic drugs for certain indications. Available data from 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. Suicidal ideation and behavior have been reported in patients treated with pregabalin in the post-marketing setting (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 initiated if they develop. If a patient develops suicidal ideation and behavior, discontinuation of pregabalin should be considered. Patients (and caregivers of patients) should be informed of the need to seek medical advice if signs of suicidal ideation and behavior appear.

Deterioration of the function of the lower digestive tract.

There have been reports of events associated with deterioration of lower gastrointestinal function (such as intestinal obstruction, paralytic ileus, constipation) following the administration of pregabalin with medicinal products that may cause constipation, such as opioid analgesics. When pregabalin is used in combination with opioids, precautions should be taken to prevent constipation (especially in women and the elderly).

Concomitant use with opioids.

Caution is advised when prescribing pregabalin concomitantly with opioids due to the risk of CNS depression (see section 4.5). It is known that in studies, patients taking pregabalin concomitantly with opioids were at an increased risk of fatal outcomes compared to opioids alone. This increased risk was observed with low doses of pregabalin, and there was a trend towards a higher risk with high doses of pregabalin.

Misuse, abuse or addiction.

Pregabalin use at therapeutic doses may cause drug dependence. Cases of misuse, abuse and dependence have been reported. The drug should be used with caution in patients with a history of substance abuse. Before prescribing pregabalin, the risk of misuse, abuse or dependence should be carefully assessed. Patients 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 occurred predominantly in patients with concomitant diseases that could cause encephalopathy.

Severe skin adverse reactions.

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 in association with pregabalin treatment. Patients should be advised of the signs and symptoms of the above-mentioned SCARs and monitored closely for skin reactions when prescribing the medicinal product. If signs and symptoms suggestive of these reactions occur, pregabalin should be discontinued immediately and alternative treatment should be considered (if appropriate).

Pregabalin use during the first trimester of pregnancy may cause serious birth defects in the fetus. Pregabalin should not be used during pregnancy unless the benefit to the pregnant woman clearly outweighs the potential risk to the fetus. Women of childbearing potential should use effective contraception during treatment (see section “Use during pregnancy or lactation”).

This medicinal product contains less than 1 mmol sodium (23 mg) per capsule, i.e. essentially sodium-free. Patients on a controlled sodium diet may be informed of this.

Use during pregnancy or breastfeeding

Women of reproductive age / contraceptives for women and men.

Women of reproductive age should use effective contraception.

Pregnancy.

Reproductive toxicity has been shown in animal studies.

Pregabalin has been shown to cross the placenta in rats (see Pharmacokinetics). Pregabalin may cross the placenta in humans.

Major birth defects: In an observational study conducted in Scandinavia, which followed over 2700 pregnancies, the prevalence of major birth defects (MBD) among infants (live or stillborn) exposed to pregabalin in the first trimester was higher than in infants not exposed to pregabalin (5.9% vs. 4.1%).

The risk of developing VVD in children whose mothers took pregabalin in the first trimester of pregnancy was slightly higher compared with children who were not exposed in utero [adjusted prevalence ratio and 95% confidence interval: 1.14 (0.96–1.35)], and compared with children 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, urinary tract and genital malformations, but the number of such malformations was small and the estimates were imprecise.

The drug Neogabin 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.

Small amounts of pregabalin have been detected in human milk. Women should be advised that breastfeeding is not recommended while taking pregabalin.

Fertility.

There are no clinical data on the effects of pregabalin on female reproductive function.

There is data on the effect of pregabalin on sperm motility in men who received a dose of pregabalin 600 mg per day: after 3 months of treatment, no effect on sperm motility was detected.

It is known that adverse effects on reproductive function were observed in a fertility study in female rats. Adverse effects on reproductive function and development were observed in a fertility study in male 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. The drug may cause dizziness and drowsiness and may affect the ability to drive or use machines. Therefore, patients should be advised to refrain from driving or operating complex machinery until it is known how the drug affects the ability to perform such activities.

Method of administration and doses

Method of application.

The drug can be taken regardless of food intake. This medicine is intended for oral use only.

Doses.

The drug is prescribed in a dose of 150 to 600 mg/day, divided into 2 or 3 doses.

Neuropathic pain.

The initial dose of pregabalin is 150 mg/day, divided into 2 or 3** doses. Depending on the individual patient response and tolerability, the dose can be increased after 3-7 days to 300 mg/day and, if necessary, increased to the maximum dose of 600 mg/day after another 7 days.

Epilepsy.

The initial dose of pregabalin is 150 mg/day, divided into 2 or 3** doses. Depending on the individual patient response and tolerability, the dose can be increased to 300 mg/day after 1 week. After another week, the dose can be increased to a maximum of 600 mg/day.

Generalized anxiety disorder.

The daily dose varies from 150 to 600 mg, divided into two or three doses. The need for pregabalin treatment should be reviewed regularly.

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

The usual dose for most patients is 300–450 mg/day. The dose should be started at 75 mg twice daily (150 mg/day) and may be increased, depending on efficacy and tolerability, to 150 mg twice daily (300 mg/day) within one week. In patients for whom 300 mg/day is not sufficiently effective, the dose may be increased to 225 mg twice daily (450 mg/day). Although a study of 600 mg/day has been conducted, there is no evidence that this dose provides additional benefit; it was also less well tolerated. Given the dose-related adverse reactions, doses above 450 mg/day are not recommended. Since pregabalin is primarily excreted by the kidneys, the dose should be adjusted in patients with impaired renal function.

Drug withdrawal.

If pregabalin must be discontinued, it is recommended to gradually discontinue the drug over a period of at least 1 week, regardless of the indication (see sections “Special warnings and precautions for use” and “Adverse reactions”).

Patients with renal impairment.

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), dose reduction in patients with renal impairment should be individualized based on creatinine clearance (CLcr) as shown in the table. Creatinine clearance 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 dialysis session.

Pregabalin dose adjustment based on renal function status

* The total daily dose (mg/day) should be divided into several doses to obtain the number of milligrams per dose.

** Use pregabalin at the appropriate dosage.

+ A booster dose is a one-time booster dose.

Patients with liver dysfunction.

No dose adjustment is necessary for patients with hepatic impairment.

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

Elderly patients may need to reduce the dose of pregabalin due to decreased renal function.

Children

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

Overdose

The most frequently reported adverse reactions in cases of pregabalin overdose were somnolence, confusion, agitation and restlessness.

Coma has been reported occasionally. Convulsions have also been reported.

Treatment of pregabalin overdose should include general