Neuroz

Neuroz

pregabalin

Manufacturer:

Lloyd

Distributor:

Zydus Healthcare Phils
Full Prescribing Info
Contents
Pregabalin.
Description
Each capsule contains: Pregabalin 75 mg.
Pregabalin is an antiepileptic drug chemically related to gabapentin. Pregabalin binds to calcium channels on nerves and may modify the release of neurotransmitters (chemicals that nerves use to communicate with each other). Reducing communication between nerves may contribute to pregabalin's effect on pain and seizures.
Action
Pharmacology: Pharmacokinetics: Pregabalin steady-state pharmacokinetics are similar in healthy volunteers, patients with epilepsy receiving anti-epileptic drugs and patients with chronic pain.
Absorption: Pregabalin is rapidly absorbed when administered in the fasted state, with peak plasma concentrations occurring within l hour following both single and multiple dose administration. Pregabalin oral bioavailability is estimated to be ≥90% and is independent of dose. Following repeated administration, steady state is achieved within 24 to 48 hours. The rate of Pregabalin absorption is decreased when given with food resulting in a decrease in Cmax by approximately 25-30% and a delay in tmax to approximately 2.5 hours. However, administration of Pregabalin with food has no clinically significant effect on the extent of Pregabalin absorption.
Distribution: In preclinical studies, Pregabalin has been shown to cross the blood brain barrier in mice, rats, and monkeys. Pregabalin has been shown to cross the placenta in rats and is present in the milk of lactating rats. In human, the apparent volume of distribution of Pregabalin following oral administration is approximately 0.56 L/kg. Pregabalin is not bound to plasma proteins.
Biotransformation: Pregabalin undergoes negligible metabolism in humans. Following a dose of radiolabeled Pregabalin, approximately 98% of the radioactivity recovered in the urine was unchanged Pregabalin. The N-methylated derivative of Pregabalin, the major metabolite of Pregabalin found in urine, accounted for 0.9% of the dose. In preclinical studies, there was no indication of racemization of Pregabalin S-enantiomer to the R-enantiomer.
Elimination: Pregabalin is eliminated from the systemic circulation primarily by renal excretion as unchanged drug. Pregabalin mean elimination half-life is 6.3 hours.
Pregabalin plasma clearance and renal clearance are directly proportional to creatinine clearance. Dose adjustment in patients with reduced renal function or undergoing hemodialysis is necessary.
Linearity/non-linearity: Pregabalin pharmacokinetics are linear over the recommended daily dose range. 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 plasma concentrations of Pregabalin.
Gender: Clinical trials indicate that gender does not have a clinically significant influence on the plasma concentrations of Pregabalin.
Renal impairment: Pregabalin clearance is directly proportional to creatinine clearance. In addition, Pregabalin is effectively removed from plasma by hemodialysis (following a 4 hour hemodialysis treatment plasma Pregabalin concentrations are reduced by approximately 50%). Because renal elimination is the major elimination pathway, dose reduction in patients with renal impairment and dose supplementation following haemodialysis is necessary.
Hepatic impairment: No specific pharmacokinetic studies were carried out in patients with impaired liver function. Since Pregabalin does not undergo significant metabolism and is excreted predominantly as unchanged drug in the urine, impaired liver function would not be expected to significantly alter Pregabalin plasma concentrations.
Pediatric population: Pregabalin pharmacokinetics were evaluated in pediatric patients with epilepsy (age groups: 1 to 23 months, 2 to 6 years, 7 to 11 years and 12 to 16 years) at dose levels of 2.5, 5, 10 and 15mg/kg/day in a pharmacokinetic and tolerability study.
After oral administration of Pregabalin in pediatric patients in the fasted state, in general, time to reach peak plasma concentration was similar across the entire age group and occurred 0.5 hours to 2 hours post-dose.
Pregabalin Cmax and AUC parameters increased in a linear manner with increasing dose within each age group. The AUC was lower by 30% in pediatric patients below a weight of 30 kg due to an increased body weight adjusted clearance of 43% for these patients in comparison to patients weighing ≥30 kg.
Pregabalin terminal half-life averaged about 3 to 4 hours in pediatric patients up to 6 years of age, and 4 to 6 hours in those 7 years of age and older.
Population pharmacokinetic analysis showed that creatinine clearance was a significant covariate of Pregabalin oral clearance, body weight was a significant covariate of Pregabalin apparent oral volume of distribution, and these relationships were similar in pediatric and adult patients.
Pregabalin pharmacokinetics in patients younger than 3 months old have not been studied.
Elderly (over 65 years of age): Pregabalin clearance tends to decrease with increasing age. This decrease in Pregabalin oral clearance is consistent with decreases in creatinine clearance associated with increasing age. Reduction of Pregabalin dose may be required in patients who have age related compromised renal function.
Breast-feeding mothers: The pharmacokinetics of 150 mg Pregabalin given every 12 hours (300 mg daily dose) was evaluated in 10 lactating women who were at least 12 weeks postpartum. Lactation had little to no influence on Pregabalin pharmacokinetics. Pregabalin was excreted into breast milk with average steady-state concentrations approximately 76% of those in maternal plasma. The estimated infant dose from breast milk (assuming mean milk consumption of 150 mL/kg/day) of women receiving 300 mg/day or the maximum dose of 600 mg/ day would be 0.31 or 0.62 mg/kg/day, respectively. These estimated doses are approximately 7% of the total daily maternal dose on a mg/kg basis.
Indications/Uses
Epilepsy: Pregabalin is indicated as adjunctive therapy in adults with partial seizures with or without secondary generalization.
Generalized Anxiety Disorder: Pregabalin is indicated for the treatment of Generalized Anxiety Disorder (GAO) in adults.
Dosage/Direction for Use
The dose range is 150 to 600 mg per day given in either two or three divided doses.
Epilepsy: Pregabalin treatment can be started with a dose of 150 mg per day given as two or three divided doses. Based on individual patient response and tolerability, the dose may be increased to 300 mg per day after 1 week. The maximum dose of 600 mg per day may be achieved after an additional week.
Generalized Anxiety Disorder: The dose range is 150 to 600 mg per day as two or three divided doses. The need for treatment should be reassessed regularly.
Pregabalin treatment can be started with a dose of 150 mg per day. Based on individual patient response and tolerability, the dose may be increased to 300 mg per day after 1 week. Following an addition week the dose may be increased to 450 mg per day. The maximum dose of 600 mg per day may be achieved after an additional week.
Discontinuation of Pregabalin: In accordance with current clinical practice, if Pregabalin has to be discontinued it is recommended this should be done gradually over a minimum of 1 week independent of the indication.
Patients with renal impairment: Pregabalin is eliminated from the systemic circulation primarily by renal excretion as unchanged drug. As Pregabalin clearance is directly proportional to creatinine clearance, dose reduction in patients with compromised renal function must be individualized according to creatinine clearance (Clcr), as indicated in Table 1 determined using the following formula: See Equation.

Click on icon to see table/diagram/image

Pregabalin is removed effectively from plasma by hemodialysis (50% of drug in 4 hours). For patients receiving hemodialysis, the Pregabalin daily dose should be adjusted based on renal function. In additional to the daily dose, a supplementary dose should be given immediately following every 4 hour hemodialysis treatment.
Pregabalin dose adjustment based on renal function: See Table 1.

Click on icon to see table/diagram/image

Patients with hepatic impairment: No dose adjustment is required for patients with hepatic impairment.
Pediatric population: The safety and efficacy of Pregabalin in children below the age of 12 years and in adolescents (12-17 years of age) have not been established. No data are available.
Elderly (over 65 years of age) population: Elderly patients may require a dose reduction of Pregabalin due to decreased renal function.
Method of Administration: Pregabalin may be taken with or without food. Pregabalin is for oral use only.
Contraindications
Hypersensitivity to the active substance or to any of the excipients.
Special Precautions
Diabetic patients: In accordance with current clinical practice, some diabetic patients who gain weight on Pregabalin treatment may need to adjust hypoglycemic medicinal products.
Hypersensitivity reactions: There have been reports in the post-marketing experience of hypersensitivity reactions, including cases of angioedema. Pregabalin should be discontinued immediately if symptoms of angioedema, such as facial, perioral, or upper airway swelling occur.
Dizziness, somnolence, loss of consciousness, confusion and mental impairment: Pregabalin treatment has been associated with dizziness and somnolence, which could increase the occurrence of accidental injury (fall) in the elderly population. There have also been post-marketing reports of loss of consciousness, confusion and mental impairment. Therefore, patients should be advised to exercise caution until they are familiar with the potential effects of the medicinal product.
Vision-related effects: In controlled trials, a higher proportion of patients treated with Pregabalin reported blurred vision than did patients treated with placebo which resolved in a majority of cases with continued dosing. In the clinical studies where ophthalmologic testing was conducted, the incidence of visual acuity reduction and visual field changes was greater in Pregabalin-treated patients than in placebo-treated patients; the incidence of fundoscopic changes was greater in placebo-treated patients.
In the post-marketing experience, visual adverse reactions have also been reported, including loss of vision, visual blurring or other changes of visual acuity, many of which were transient. Discontinuation of Pregabalin may result in resolution or improvement of these visual symptoms.
Renal failure: Cases of renal failure have been reported and in some cases discontinuation of Pregabalin did show reversibility of this adverse reaction.
Withdrawal of concomitant antiepileptic medicinal products: There are insufficient data for the withdrawal of concomitant antiepileptic medicinal products, once seizure control with Pregabalin in the add-on situation has been reached, in order to reach monotherapy on Pregabalin.
Withdrawal symptoms: After discontinuation of short-term and long-term treatment with Pregabalin withdrawal symptoms have been observed in some patients. The following events have been mentioned: Insomnia, headache, nausea, anxiety, diarrhea, flu syndrome, nervousness, depression, pain, convulsion, hyperhidrosis and dizziness, suggestive of physical dependence. The patient should be informed about this at the start of the treatment.
Convulsions, including status epilepticus and grand mal convulsions, may occur during Pregabalin use or shortly after discontinuing Pregabalin.
Concerning discontinuation of long-term treatment of Pregabalin, data suggest that the incidence and severity of withdrawal symptoms may be dose-related.
Congestive Heart Failure: There have been post-marketing reports of congestive heart failure in some patients receiving Pregabalin. These reactions are mostly seen in elderly cardiovascular compromised patients during Pregabalin treatment for a neuropathic indication. Pregabalin should be used with caution in these patients. Discontinuation of Pregabalin may resolve the reaction.
Treatment of central neuropathic pain due to spinal cord injury: In the treatment of central neuropathic pain due to spinal cord injury the incidence of adverse reactions in general, central nervous system adverse reactions and especially somnolence was increased. This maybe attributed to an additive effect due to concomitant medicinal products (e.g. anti-spasticity agents) needed for this condition. This should be considered when prescribing Pregabalin in this condition.
Suicidal ideation and behavior: Suicidal ideation and behavior have been reported in patients treated with anti-epileptic agents in several indications. A meta-analysis of randomized placebo controlled studies of anti-epileptic drugs has also shown a small increased risk of suicidal ideation and behavior. The mechanism of this risk is not known and the available data do not exclude the possibility of an increased risk of Pregabalin.
Therefore patients should be monitored for signs of suicidal ideation and behaviors and appropriate treatment should be considered. Patients (and caregivers of patients) should be advised to seek medical advice should signs suicidal ideation or behavior emerge.
Reduced lower gastrointestinal tract function: There are post-marketing reports of events related to reduced lower gastrointestinal tract function (e.g. intestinal obstruction, paralytic ileus, constipation) when Pregabalin was co-administered with medications that have the potential to produce constipation, such as opioid analgesics. When Pregabalin and opioids will be used in combination, measures to prevent constipation may be considered (especially in female patients and elderly).
Misuse, abuse potential or dependence: Cases of misuse, abuse and dependence have been reported. Caution should be exercised in patients with a history of substance abuse and the patient should be monitored for symptoms of Pregabalin misuse, abuse or dependence (development of tolerance, dose escalation, drug-seeking behavior have been reported).
Encephalopathy: Cases of encephalopathy have been reported, mostly in patients with underlying conditions that may precipitate encephalopathy.
Adverse Reactions
In the table as follows all adverse reactions, which occurred at an incidence greater than placebo and in more than one patient are listed by 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, undesirable effects are presented in order of decreasing seriousness.
The adverse reactions listed may also be associated with the underlying disease and/or concomitant medicinal products.
Additional reactions reported from post-marketing experience are included in italics in the list as follows. See Table 2.

Click on icon to see table/diagram/image

After discontinuation of short-term and long-term treatment with Pregabalin withdrawal symptoms have been observed in some patients. The following reactions have been mentioned: insomnia, headache, nausea, anxiety, diarrhea, flu syndrome, convulsions, nervousness, depression, pain, hyperhidrosis and dizziness, suggestive of physical dependence. The patient should be informed about this at the start of the treatment.
Concerning discontinuation of long-term treatment of Pregabalin, data suggest that the incidence and severity of withdrawal symptoms may be dose-related.
Drug Interactions
Since Pregabalin is predominantly excreted unchanged in the urine, undergoes negligible metabolism in humans (<2% of a dose recovered in urine as metabolites), does not inhibit drug metabolism in vitro, and is not bound to plasma proteins, it is unlikely to produce, or be subject to, pharmacokinetic interactions.
In vivo studies and population pharmacokinetic analysis: Accordingly, in vivo studies no clinically relevant pharmacokinetic interactions were observed between Pregabalin and phenytoin, carbamazepine, valproic acid, lamotrigine, gabapentin, lorazepam, oxycodone or ethanol. Population pharmacokinetic analysis indicated that oral antidiabetics, diuretics, insulin, phenobarbital, tiagabine and topiramate had no clinically significant effect on Pregabalin clearance.
Oral contraceptives, norethisterone and/or ethinylestradiol: Co-administration of Pregabalin with the oral contraceptives norethisterone and/or ethinylestradiol does not influence the steady-state pharmacokinetics of either substance.
CNS influencing medical products: Pregabalin may potentiate the effects of ethanol and lorazepam. In controlled clinical trials, multiple oral doses of Pregabalin co-administered with oxycodone, lorazepam, or ethanol did not result in clinically important effects on respiration. In the post-marketing experience, there are reports of respiratory failure and coma in patients taking Pregabalin and other CNS depressant medicinal products. Pregabalin appears to be additive in the impairment of cognitive and gross motor function caused by oxycodone.
Interactions and the elderly: No specific pharmacodynamic interaction studies were conducted in elderly volunteers. Interaction studies have only been performed in adults.
Storage
Store at temperatures not exceeding 30°C.
MIMS Class
ATC Classification
N03AX16 - pregabalin ; Belongs to the class of other antiepileptics.
Presentation/Packing
Cap 75 mg x 20's.
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