Ograniya capsules 75 mg blister No. 14

Instructions Ograniya capsules 75 mg blister No. 14

Composition

active ingredient: pregabalin;

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

excipients: lactose monohydrate; corn starch; microcrystalline cellulose; talc;

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

composition of the 150 mg capsule shell: gelatin, azorubine, carmoisine (E 122), black iron oxide (E 172), red iron oxide (E 172), titanium dioxide (E 171);

composition of the 300 mg capsule shell: gelatin, azorubine, carmoisine (E 122), indigo carmine (E 132), titanium dioxide (E 171).

Dosage form

Capsules.

Main physicochemical properties:

75 mg capsules: hard gelatin capsule, cylindrical in shape, cap and capsule body light pink. Capsule contents – white to almost white powder;

150 mg capsules: hard gelatin capsule, cylindrical shape, capsule cap – pink, body – white. Capsule contents – white to almost white powder;

300 mg capsules: hard gelatin capsule, cylindrical shape, capsule cap – brownish-red, body – white. Capsule contents – white to almost white powder.

Pharmacotherapeutic group

Antiepileptics. Other antiepileptics. 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 (a2-d-protein) of voltage-gated calcium channels in the central nervous system.

Clinical efficacy and safety

Neuropathic pain

Pregabalin is effective in the treatment of diabetic neuropathy, postherpetic neuralgia, and spinal cord injury. Its efficacy 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 8-week trials with three times daily dosing. Overall, the safety and efficacy profiles were similar for the twice or three times daily dosing regimens.

In clinical studies lasting up to 12 weeks, when pregabalin was used to treat neuropathic pain in peripheral and central nervous system (CNS) 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 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 number of patients who responded to treatment was 48% in the pregabalin group and 16% in the placebo group.

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

Epilepsy

Additional treatment

Pregabalin has been studied in three controlled clinical trials of 12 weeks duration with twice-daily or three-times-daily dosing regimens. Overall, the safety profile and efficacy were similar for the twice-daily 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 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 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 frequently observed in children than in adult patients with epilepsy (see sections 5.2, 5.2 and 4.8).

In a 14-day placebo-controlled study, children (aged 1 month to <4 years) were treated with pregabalin 7 mg/kg/day, pregabalin 14 mg/kg/day, or placebo. The median daily seizure frequency at baseline and final visit was 4.7 and 3.8 for pregabalin 7 mg/kg/day, 5.4 and 1.4 for pregabalin 14 mg/kg/day, and 2.9 and 2.3 for placebo, respectively. Pregabalin 14 mg/kg/day significantly reduced the log-transformed partial-onset seizure frequency compared with placebo (p=0.0223); pregabalin 7 mg/kg/day showed no improvement compared with placebo.

Monotherapy (for patients with newly diagnosed disease)

Pregabalin was studied in one controlled clinical trial of 56 weeks duration with a twice daily dosing regimen. Pregabalin was not superior 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 six controlled trials of 4–6 weeks duration, one 8-week study in elderly patients, and one long-term relapse prevention trial 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 of treatment.

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 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 in the fasting state and reaches peak plasma concentrations (Cmax) within 1 hour after single and multiple dosing. The estimated oral bioavailability of pregabalin is greater than 90% and is independent of dose. Steady state is reached within 24–48 hours after multiple dosing. The rate of absorption of pregabalin is reduced when administered with food, resulting in a decrease in Cmax of approximately 25–30% and a delay in time to peak concentration (tmax) of approximately 2.5 hours. However, co-administration of pregabalin with food had no clinically significant effect on the extent of absorption.

Distribution

Preclinical studies have shown that pregabalin crosses the blood-brain barrier in rats, mice and monkeys. Pregabalin also crosses the placenta in rats and is excreted in the milk of lactating rats. 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.

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 the drug detected in urine, 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

Pregabalin is eliminated from the systemic circulation unchanged primarily by renal excretion. 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 impairment").

Patients with impaired renal function or patients on hemodialysis require dose adjustment (see section "Method of administration and dosage", Table 1).

Linearity/nonlinearity

The pharmacokinetics of pregabalin are linear over the recommended dose range. The interpatient variability in the pharmacokinetics of pregabalin is low (less than 20%). The pharmacokinetics of multiple doses are predictable based on data obtained with the administration of a single dose. Therefore, there is no need for routine monitoring of pregabalin plasma concentrations.

Sex

The 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 is reduced by approximately 50%). Since renal excretion is the main route of drug elimination, patients with renal insufficiency should be given a reduced dose and an additional dose should be given after hemodialysis (see section "Dosage and administration", Table 1).

Liver failure

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, 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 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 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

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).

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 the maternal plasma concentration. 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

The drug Ograniya® is prescribed for the treatment of neuropathic pain in adults with damage to the peripheral and central nervous system.

Epilepsy

Ograniya® is prescribed as an adjunctive therapy for partial seizures with or without secondary generalization in adults.

Ograniya® is prescribed 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 excreted primarily unchanged in the urine, undergoes minimal 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, it is unlikely that pregabalin could cause or be the target of pharmacokinetic interactions.

In vivo studies and population pharmacokinetic analysis

In vivo studies have not shown any clinically significant pharmacokinetic interactions between pregabalin and phenytoin, carbamazepine, valproic acid, lamotrigine, gabapentin, lorazepam, oxycodone or 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 trials, co-administration of multiple oral doses of pregabalin with oxycodone, lorazepam, or ethanol did not result in clinically significant effects on respiratory function. Respiratory failure, coma, and fatalities have been reported in post-marketing experience in patients taking pregabalin with other CNS depressants, particularly in patients who have abused such drugs. Pregabalin is likely to potentiate the cognitive and gross motor impairments associated with oxycodone.

Interaction in 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

Patients with diabetes mellitus whose body weight has increased while taking pregabalin may require dose adjustment of hypoglycemic drugs.

Hypersensitivity reactions

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

Severe skin adverse 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. Patients should be informed of the characteristic signs and symptoms when prescribing the drug and should be closely monitored for skin reactions. If 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 drowsiness, which may lead to falls in elderly patients. Loss of consciousness, confusion, and mental impairment have been reported. Therefore, patients should be advised to exercise caution until they are aware of the effects of the drug.

Vision disorders

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. The incidence of visual acuity deterioration and visual field changes was higher in patients treated with pregabalin than in patients treated with placebo; the incidence of fundus changes was higher in patients treated with placebo (see section 5.1).

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 visual symptoms.

Kidney failure

Cases of renal failure have been reported. This effect was sometimes reversible after discontinuation of pregabalin.

Withdrawal of concomitant antiepileptic drugs

Data on the withdrawal of concomitant antiepileptic drugs after seizure control is achieved with the addition of pregabalin are insufficient to switch to pregabalin monotherapy.

Some patients have experienced withdrawal symptoms after discontinuation of short- or long-term treatment with pregabalin. 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 starting treatment.

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. This reaction has been observed primarily 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 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, CNS adverse reactions, especially somnolence, was increased. This may be due to the additive effect of concomitant medications (e.g. antispasticity agents) required for the treatment of this condition. This should be taken into account when prescribing pregabalin to such patients.

Respiratory depression

Cases of severe respiratory depression have 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. Dose adjustment may be necessary for these patients (see Dosage and Administration).

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 also showed a small increased risk of suicidal ideation and behavior. The mechanism of this risk is unknown. Suicidal ideation and behavior have been observed in patients treated with pregabalin in the post-marketing period (see section "Adverse reactions"). An epidemiological study using a self-controlled study design (comparing treatment periods with periods without treatment within an individual) has shown an increased risk of new suicidal behavior and deaths due to suicide in patients treated with pregabalin.

Patients (and caregivers) should seek medical attention if they develop signs of suicidal thinking or behavior.

Therefore, patients should be closely monitored for signs of suicidal ideation and behavior and appropriate treatment should be initiated if they occur. Discontinuation of pregabalin should be considered if suicidal ideation and behavior occur.

Lower gastrointestinal dysfunction

There have been reports of lower gastrointestinal events (intestinal obstruction, paralytic ileus, constipation) following the concomitant use of pregabalin with medicinal products that may cause constipation, such as opioid analgesics. Precautions should be taken to prevent constipation when pregabalin is used concomitantly with opioids (especially in elderly patients and women).

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, patients taking pregabalin concomitantly with opioids had an increased risk of opioid-related death 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, aOR 1.52 [95% CI, 1.04-2.22]), and there was a trend towards an increased 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. 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

Cases of encephalopathy occurred predominantly in patients with concomitant diseases that could cause encephalopathy.

Pregabalin use during the first trimester of pregnancy may cause serious birth defects (BDD) in the unborn child. Ograniya® should not be used during pregnancy unless the benefit to the mother clearly outweighs the potential risk to the fetus. Women of childbearing potential should use effective contraception during treatment with pregabalin (see section “Use during pregnancy or breastfeeding”).

Excipients

Ograniya® contains lactose monohydrate. If you have been told by your doctor that you have an intolerance to some sugars, contact your doctor before taking this medicine.

The medicinal product in dosages of 150 mg and 300 mg contains azorubine and carmoisine (E 122), which may cause allergic reactions.

Use during pregnancy or breastfeeding

Women of reproductive age

Women of reproductive age should use effective contraception during treatment.

Pregnancy

Animal studies have shown reproductive toxicity. Pregabalin crosses the placenta in rats.

Pregabalin can cross the human placenta.

Serious birth defects (SBD)

Data from a Scandinavian observational study of more than 2,700 pregnant women exposed to pregabalin in the first trimester showed a higher prevalence of serious VVR among children (live or stillborn) exposed to pregabalin in utero compared with a population of children not exposed (5.9% vs. 4.1%).

The risk of developing serious VVD among children exposed to pregabalin in utero in the first trimester of pregnancy was slightly higher compared with the population of children not exposed to such exposure (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 the specificity of VVR demonstrated a higher risk for orofascial nonunions and defects of the eye, nervous or genitourinary system, but the rates were small and the estimates imprecise.

The drug Ogrania® should not be used during pregnancy, except in exceptional cases when the benefit to the pregnant woman clearly outweighs the possible risk to the fetus.

Breastfeeding period

Pregabalin is excreted in human milk (see section 5.1). 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 effects of pregabalin on female reproductive function.

In a clinical study of the effects of pregabalin on sperm motility, healthy male volunteers received a dose of pregabalin 600 mg per day. After 3 months of treatment, 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

Ograniya® may have minor or moderate influence on the ability to drive and use machines. The drug may also cause dizziness and drowsiness, which 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 drug affects their ability to perform such activities.

Method of administration and doses

Method of application

Ogrania® can be taken regardless of food intake.

The drug Ogrania® is intended for oral use only.

Doses

The dose range may vary from 150 to 600 mg per day. The daily dose should be divided into 2 or 3 doses.

Neuropathic pain

Pregabalin treatment can be initiated at a dose of 150 mg/day in 2 divided doses. Depending on the efficacy and tolerability of the drug in individual patients, the dose can be increased to 300 mg/day after an interval of 3 to 7 days, and if necessary, to a maximum dose of 600 mg/day after an additional 7-day interval.

Epilepsy

Pregabalin treatment can be initiated at a dose of 150 mg per day, divided into 2 doses. Depending on the efficacy and tolerability of the drug in the individual 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

Pregabalin treatment can be started at a dose of 150 mg per day. Depending on the effectiveness and tolerability of the drug in individual patients, 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.

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 warnings and precautions for use” and “Adverse reactions”).

Patients with renal insufficiency

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 in patients with renal impairment should be individualized as shown in Table 1, based on creatinine clearance (CLcr), 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 dosing regimen to obtain mg/dose.

Fibromyalgia

The usual dose for most patients is 300–450 mg/day. The drug should be started at a dose of 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 the dosage of 300 mg/day is insufficient, the dose may be increased to 225 mg twice daily (450 mg/day). If necessary, the dose may be increased after another week to a maximum of 600 mg/day. There is no evidence that this dose will have an additional advantage; it was also less well tolerated. Given the dose-related adverse reactions, doses above 450 mg/day are not recommended. Since pregabalin is excreted primarily by the kidneys, the dose of the drug should be adjusted in patients with impaired renal function.

Patients with hepatic insufficiency

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

Use in elderly patients (aged 65 years and over)

Elderly patients may require a reduction in the dose of pregabalin due to impaired renal function (see section "Special warnings and precautions for use").

Children.

The safety and efficacy of Ogrania® in children (under 18 years of age) have not been established. Currently available information is provided in the Adverse Reactions section, as well as in the Pharmacodynamics and Pharmacokinetics sections, but no dosage recommendations can be made for this patient population.

Overdose

The most frequently reported side effects