Instructions for Pregabalin-Teva 150 mg hard capsules No. 28
Composition
active ingredient: pregabalin;
1 capsule contains 75 or 150 mg of pregabalin;
excipients: mannitol (E 421), pregelatinized corn starch, talc, titanium dioxide (E 171), red iron oxide (E 172) (75 mg capsules), yellow iron oxide (E 172) (75 mg and 150 mg capsules), gelatin.
Dosage form
The capsules are hard.
Main physicochemical properties: 75 mg capsules – opaque capsules with a pink cap and an ivory body with a black stamp 75;
150 mg capsules - opaque ivory capsules with a black stamp of 150 on the body.
Pharmacotherapeutic group
Antiepileptic drugs, other antiepileptic drugs.
ATX code N03A X16.
Pharmacological properties
Pharmacodynamics.
The active substance is pregabalin, 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.
Pregabalin has been shown to be effective in treating diabetic neuropathy, postherpetic neuralgia, and spinal cord injury. Its 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-daily 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 in central neuropathic pain, 22% of patients treated with pregabalin and 7% of patients treated with placebo had a 50% improvement in pain scores.
Adjunctive therapy: 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.
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 and a 14-day placebo-controlled study in 175 children aged 1 month to < 4 years, which were designed 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, respectively, with epilepsy, indicate that adverse reactions such as pyrexia and upper respiratory tract infections are observed more frequently in children than in adult patients with epilepsy (see sections 4.2, 4.8 and 5.1).
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 those 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 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.
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. Reductions in generalized anxiety disorder symptoms 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 receiving pregabalin compared to patients receiving 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 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 within 24–48 hours after repeated dosing. The extent of pregabalin absorption is reduced when administered 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, co-administration of pregabalin with food had no clinically significant effect on the extent of its absorption.
Metabolism: 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. In nonclinical studies, there was no racemization of the S-enantiomer of pregabalin to the R-enantiomer.
Elimination: 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 on hemodialysis.
Linearity/non-linearity. The pharmacokinetics of pregabalin are linear over the recommended dose range. The inter-subject pharmacokinetic variability for pregabalin is low (< 20%). Multiple-dose pharmacokinetics are predictable from single-dose data. Therefore, there is no need for routine monitoring of pregabalin plasma concentrations.
Pharmacokinetics in certain patient groups.
Gender: There is no clinically significant effect of gender on pregabalin plasma concentrations.
Renal impairment. Pregabalin clearance is directly proportional to creatinine clearance. In addition, pregabalin is effectively removed from plasma by haemodialysis (pregabalin plasma concentrations are reduced by approximately 50% after 4 hours of haemodialysis). Since renal excretion is the major route of elimination, patients with renal impairment should have their dose reduced and an additional dose administered after haemodialysis (see section 4.2, Dosage and Administration, table).
Hepatic impairment: No specific pharmacokinetic studies have been conducted in patients with hepatic impairment. Since pregabalin is not significantly metabolized and is excreted primarily unchanged in the urine, hepatic impairment is unlikely to 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 maximum plasma concentration was generally similar across age groups and ranged from 0.5 to 2 hours post-dose. Pregabalin Cmax and 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 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 less than 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 reduced dose of pregabalin (see Dosage and Administration, Table 1).
Breastfeeding. 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.
Pregabalin-Teva is prescribed for the treatment of neuropathic pain of peripheral or central origin in adults.
Epilepsy.
Pregabalin-Teva is prescribed to adults as an adjunctive treatment for partial seizures with or without secondary generalization.
Generalized anxiety disorder.
Pregabalin-Teva is prescribed 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
Since 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 blood proteins, it is unlikely that pregabalin can cause or be the target of pharmacokinetic interactions.
In vivo studies and population pharmacokinetic analysis.
Accordingly, no clinically relevant pharmacokinetic interactions were observed between pregabalin and phenytoin, carbamazepine, valproic acid, lamotrigine, gabapentin, lorazepam, oxycodone or ethanol in in vivo studies. Population pharmacokinetic analysis showed that oral antidiabetic agents, diuretics, insulin, phenobarbital, tiagabine and topiramate had no clinically relevant effect on pregabalin clearance.
Oral contraceptives, norethisterone and/or ethinyl estradiol.
Co-administration 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. In the post-marketing period, cases of respiratory failure, coma and death have been reported in patients taking pregabalin concomitantly with opioids and/or other CNS depressants. Pregabalin is likely to have exacerbated the cognitive and gross motor impairment 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 treatment with pregabalin may require dose adjustment of hypoglycemic drugs.
Hypersensitivity reactions.
Hypersensitivity reactions, including angioedema, have been reported. If symptoms of angioedema such as facial, perioral or upper respiratory tract swelling occur, pregabalin should be discontinued immediately.
Severe skin adverse reactions.
Severe cutaneous adverse reactions, including Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), which can be life-threatening or fatal, have been reported rarely during treatment with pregabalin. When prescribing the drug, patients should be informed of the signs and symptoms and closely monitored for skin reactions. If signs and symptoms suggestive of these reactions occur, pregabalin should be discontinued immediately and alternative treatment should be considered (as appropriate).
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 elderly patients. Cases of loss of consciousness, confusion and mental impairment have been reported in the post-marketing setting. Therefore, patients should be advised to exercise caution until they are aware of the potential effects of this medicinal product.
Vision disorders.
In controlled trials, blurred vision was reported more frequently in patients treated with pregabalin than in patients treated with placebo. In most cases, these effects resolved with continued treatment. 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 treated with placebo; the incidence of fundus changes was higher in patients treated with placebo.
In the post-marketing period, visual adverse reactions, including loss of vision, blurred vision or other changes in visual acuity, have been reported, most of which were transient. These visual symptoms may disappear or improve after discontinuation of pregabalin.
Kidney failure.
Cases of renal failure have been reported. This effect was sometimes reversible after discontinuation of pregabalin.
Withdrawal of concomitant antiepileptic medications.
There is currently insufficient data to determine whether concomitant antiepileptic medicinal products can be withdrawn once seizure control has been achieved with the addition of pregabalin to therapy, in order to switch to pregabalin monotherapy.
Withdrawal symptoms have been observed 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. The occurrence of withdrawal symptoms after discontinuation of pregabalin may indicate drug dependence (see section 4.8). This information should be communicated to the patient before starting treatment. If pregabalin needs to be discontinued, it is recommended that this be done gradually over at least 1 week, regardless of the indication (see section 4.8).
Convulsions, including status epilepticus and grand mal seizures, may occur during treatment with pregabalin or shortly after discontinuation of its use.
Regarding discontinuation of long-term pregabalin treatment, data suggest that the incidence and severity of withdrawal symptoms may be dose-dependent.
Congestive heart failure.
Congestive heart failure has been reported in some patients taking pregabalin in the post-marketing setting. This reaction has occurred predominantly during treatment with pregabalin for 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 caused by spinal cord injury, the incidence of adverse reactions in general, CNS adverse reactions and somnolence in particular was higher. This may be explained by the additive effect of other medicinal products (e.g. antispasticity agents) required for the treatment of this condition. This 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 has shown 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 Adverse Reactions). 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.
Patients (and caregivers of patients) should be advised to seek medical advice if they develop signs of suicidal thinking or behaviour. Patients should be closely monitored for signs of suicidal thinking and behaviour and appropriate treatment should be considered. If suicidal thinking and behaviour emerge, discontinuation of pregabalin should be considered.
Deterioration of the function of the lower gastrointestinal tract.
In the post-marketing period, there have been reports of events associated with the deterioration of lower gastrointestinal function (including intestinal obstruction, paralytic ileus, constipation) when pregabalin was used concomitantly with medicinal products that can cause constipation, such as opioid analgesics. When pregabalin and opioids are used concomitantly, 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 (see section 4.5). 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]).
Misuse, abuse or addiction.
Patients receiving pregabalin should be closely monitored for signs of misuse, abuse, or dependence on pregabalin, such as development of habituation, exceeding the prescribed dose, and drug-seeking behavior.
Encephalopathy.
Cases of encephalopathy have been reported, occurring predominantly in patients with concomitant diseases that may predispose to encephalopathy.
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 higher risk of this serious adverse reaction. These patients may require dose adjustment (see Dosage and Administration).
Women of reproductive age/contraception.
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”).
Use during pregnancy or breastfeeding
Women of reproductive age/contraceptives for women and men.
Women of reproductive age should use effective contraception during treatment (see section "Special warnings and precautions for use").
Pregnancy.
Animal studies have shown reproductive toxicity. Pregabalin has been shown to cross the placenta in rats (see Pharmacokinetics). Pregabalin may cross the placenta in humans.
Significant birth defects
An observational study conducted in Scandinavia, which followed over 2700 pregnancies, demonstrated a higher prevalence of major congenital malformations (MCMs) in the infant population (live or stillborn) exposed to pregabalin in the first trimester compared to the unexposed population (5.9% vs. 4.1%).
The risk of developing VVD in children whose mothers used 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.
Pregabalin should not be used during pregnancy unless clearly necessary (when the benefit to the pregnant woman clearly outweighs the potential risk to the fetus).
Breast-feeding.
Small amounts of pregabalin have been detected in human breast milk. Women should be advised that breastfeeding is not recommended while taking pregabalin.
Fertility.
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/day. After 3 months of treatment with pregabalin, no effect on sperm motility was observed.
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 may 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 medicinal product affects their ability to perform such activities.
Method of administration and doses
The drug is prescribed in a dose of 150 to 600 mg per day, divided into 2 or 3 doses. Pregabalin can be used regardless of meals. The drug is intended for oral use only.
Neuropathic pain.
The initial dose of pregabalin is 150 mg per day, divided into 2 or 3 doses. Depending on the individual patient's response and tolerability, the dose may be increased after 3 to 7 days to 300 mg per day and, if necessary, increased to a maximum dose of 600 mg per day after another 7 days.
The recommended dose for most patients is 300-450 mg per day. The drug should be started at a dose of 75 mg twice a day (150 mg/day), which can be increased, depending on efficacy and tolerability, to 150 mg twice a day (300 mg/day) within one week. In patients for whom the dosage of 300 mg/day is not effective enough, the dose can be increased to 225 mg twice a day (450 mg/day). Although there is a study of the use of a dose of 600 mg per day, there is no evidence that its use will have an additional advantage. In addition, this dose was less well tolerated. Given the dose-dependent adverse reactions, the use of doses above 450 mg per day is not recommended. Since pregabalin is excreted primarily by the kidneys, the dose of the drug should be adjusted in patients with impaired renal function.
Epilepsy.
The initial dose of pregabalin is 150 mg per day, divided into 2 or 3 doses. Depending on the individual patient's response and tolerability, the dose can be increased to 300 mg per day after 1 week. After another week, the dose can be increased to a maximum of 600 mg per day.
Generalized anxiety disorders.
The daily dose varies from 150 to 600 mg, divided into 2 or 3 doses. The need for pregabalin treatment should be reviewed regularly.
Pregabalin treatment can be initiated at a dose of 150 mg per day. Depending on individual response and tolerability, the dose can be increased to 300 mg per day after the first week of treatment. During the following 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.
Pregabalin withdrawal.
According to current clinical practice, 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.
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, dose reduction for patients with renal impairment should be individualized according to creatinine clearance (CLcr) as shown in the table below and 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).
| Creatinine clearance (CLcr) (mL/min) | Total daily dose of pregabalin* | Dosage regimen |
Starting dose (mg per day) | Maximum dose (mg per day) |
| ≥ 60 | 150 | 600 | 2 or 3 times a day |
| ≥ 30−< 60 | 75 | 300 | 2 or 3 times a day |
| ≥ 15−< 30 | 25‒50 | 150 | 1 or 2 times a day |
| < 15 | 25 | 75 | 1 time per day |
| Additional dose after hemodialysis (mg) |
| 25 | 100 | Single dose+ | |
* The total daily dose (mg/day) should be divided by the number of doses to obtain the number of milligrams per dose.
+ A booster dose is a one-time booster dose.
Patients with impaired liver function.
No dose adjustment is necessary for patients with hepatic impairment.
Elderly patients.
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 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
After the drug was marketed, the most common adverse reactions reported in pregabalin overdose were drowsiness, confusion, agitation, and restlessness. Convulsions have also been reported.
WITH
