Pebarin

PEBARIN (25 MG CAPSULE): Each capsule contains Pregabalin 25 mg.
PEBARIN (75 MG CAPSULE): Each capsule contains Pregabalin 75 mg.
PEBARIN (150 MG CAPSULE): Each capsule contains Pregabalin 150 mg.

Pharmacology: Pharmacodynamics: Pregabalin binds with high affinity to the alpha-2-delta site, an auxiliary subunit of voltage-gated calcium channels in CNS tissues. Binding to the alpha-2-delta may be involved in analgesic and anticonvulsant effects. In vitro, Pregabalin reduces the calcium-dependent release of several neurotransmitters, possibly by modulation of calcium channel function.
Pregabalin is structurally related to the gamma–aminobutyric acid (GABA). However, it does not bind to GABA_A, GABA_B or benzodiazepine receptors.
Pharmacokinetics: Absorption: Pregabalin is well absorbed after oral administration. Following oral administration of Pregabalin capsules under fasting conditions, peak plasma concentrations occur within 1.5 hours. Pregabalin bioavailability is about 90% or more and is independent of dose. Following single dose of 25 to 300 mg and multiple dose of 75 to 900 mg/day administration, maximum plasma concentration (C_max) and area under the curve (AUC) values increase linearly. 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 C_max of approximately 25% to 30% and an increase in time of maximal concentration (T_max) to approximately 3 hours. However, administration of Pregabalin with food has no clinically relevant effect on the total absorption of Pregabalin. Therefore, Pregabalin can be taken with or without food.
Distribution: Pregabalin does not bind to plasma proteins. The apparent volume distribution of Pregabalin following oral administration is approximately 0.5 L/kg. Pregabalin is a substrate for system L transporter, which is responsible for the transport of large amino acids across the blood brain barrier. Although there are no data in humans, Pregabalin crossed the blood brain barrier in mice, rats, and monkeys. In addition, Pregabalin crosses placenta in rats and was present in the milk of lactating rats.
Metabolism: Pregabalin undergoes negligible metabolism in humans. Following a dose of radiolabeled Pregabalin, approximately 90% of the administered dose 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, Pregabalin (S-enantiomer) did not undergo racemization to the R-enantiomer in mice, rats, rabbits, or monkeys.
Excretion: Pregabalin is eliminated from the systemic circulation primarily by renal excretion as unchanged drug, with a mean elimination half-life of 6.3 hours in subjects with healthy renal function. Mean renal clearance was estimated to be 67 to 80.9 mL/min in young, healthy subjects. Because Pregabalin is not bound to plasma proteins, this clearance rate indicates that renal tubular reabsorption is involved.

Neuropathic pain: Pregabalin is indicated for the treatment of central and peripheral neuropathic pain in adults which includes diabetic peripheral neuropathy and postherpetic neuralgia.
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 in adults.
Fibromyalgia: Pregabalin is indicated for the management of fibromyalgia.

Pregabalin is administered in 2 or 3 divided doses. It may be taken with or without food. If Pregabalin is discontinued, dosage should be tapered gradually over at least 1 week.
Epilepsy: The effective dosage of Pregabalin is 150-600 mg daily administered in 2 or 3 divided doses. Therapy is initiated at a dosage of 75 mg twice daily or 50 mg 3 times daily (150 mg daily). Based on individual response and tolerability, dosage may be increased to a maximum of 600 mg daily.
Neuropathic pain: Postherpetic neuralgia: The recommended dosage of Pregabalin is 150-300 mg daily administered in 2 or 3 divided doses. Therapy is initiated at a dosage of 75 mg twice daily or 50 mg 3 times daily (150 mg daily). Dosage may be increased to 300 mg daily within 1 week based on efficacy and tolerability.
Patient who tolerate the drug but do not experience adequate pain relief following 2-4 weeks of treatment with Pregabalin 300 mg daily may receive dosages of up to 600 mg daily administered in 2 or 3 divided doses.
Diabetic peripheral neuropathy: The initial dosage of Pregabalin is 150 mg daily administered in 3 divided doses. The maximum recommended dosage may be increased up to a maximum of 300 mg daily administered in 3 divided doses within 1 week, based on efficacy and tolerability.
Fibromyalgia: The recommended dosage of Pregabalin is 300-450 mg daily. Therapy is initiated at a dosage of 75 mg twice daily (150 mg daily). Dosage may be increased to 300 mg daily (150 mg twice daily) within 1 week based on efficacy and tolerability.
Patients who do not experience adequate benefit with Pregabalin 300 mg daily may have dosage further increased to the maximum recommended dosage of 450 mg daily (225 mg twice daily).
Generalized anxiety disorder: The recommended dosage of Pregabalin is 150-600 mg daily administered in 2 or 3 divided doses. The need for treatment should be reassessed regularly. Therapy is initiated at a dosage of 150 mg daily in 2 or 3 divided doses. Dosage may be increased to 300 mg daily after 1 week based on individual response and tolerability. Following an additional week the dose may be increased to 450 mg per day. The maximum dosage of 600 mg daily may be achieved after an additional week.
Dosage in special populations: Dosage in renal impairment: Pregabalin is mainly excreted by the kidneys. The dosage should be reduced based on creatinine clearance (CrCl) by using the Cockcroft and Gault formula: see Equation.

Click on icon to see table/diagram/image

In patients with creatinine clearance of less than 60 mL/min, the dosage of Pregabalin should be modified based on creatinine clearance (see table.)

Click on icon to see table/diagram/image

Hemodialysis: In patient with hemodialysis, the Pregabalin daily dose should be adjusted based on renal function. In addition to the daily dosage adjustment, supplemental dosage should be administered immediately following every 4 hours hemodialysis treatment.
Posthemodialysis supplementary dosage: Patients on the 25 mg single daily dose: Take single supplementary dose of 25 mg or 50 mg.
Patients on the 25-50 mg single daily dose: Take single supplementary dose of 50 mg or 75 mg.
Patients on the 50-75 mg single daily dose: Take single supplementary dose of 75 mg or 100 mg.
Patients on the 75 mg single daily dose: Take single supplementary dose of 100 mg or 150 mg.
Dosage in hepatic impairment: No dosage adjustment is required for patients with hepatic impairment.
Dosage in elderly: Elderly patients may require a dose reduction of Pregabalin due to a decreased renal function.
Dosage in children: There are no adequate and well-controlled studies in children younger than 18 years of age.

Overdose and Treatment: There is no specific antidote for overdose with Pregabalin. Treatment of Pregabalin overdose should include general supportive measures and may include hemodialysis if necessary.

Hypersensitivity to Pregabalin or any components in the formulation.

(Based on the Ministry of Public Health Announcement): This medicine may cause drowsiness. Do not drive vehicles or work on equipment. Do not take alcohol or alcohol-containing products while using this medication.
This drug can cause blood disorders.
This drug should be used with caution in patients with liver and kidney disease.
Use in Pregnancy: This drug should not be taken during pregnancy due to risk of congenital anomalies in the fetus.

There have been reports in the postmarketing experience of angioedema, such as swelling of the face, mouth and neck, including cases of hypersensitivity reactions. If symptoms occur, Pregabalin should be discontinued immediately. Use with caution in patients with a history of angioedema and concurrent use with other drugs known to cause angioedema e.g. angiotensin-converting enzyme inhibitors (ACEI).
Antiepileptic drugs (AED), including Pregabalin, should not be abruptly discontinued because of the possibility of increasing seizure frequency. Therefore, if Pregabalin is discontinued, dosage should be tapered gradually over at least 1 week.
Antiepileptic drugs (AED), including Pregabalin, increase the risk of suicidal thoughts or behavior in patients taking these drugs for any indication. Monitor patients treated with any AED for any indication for the emergence or worsening of depression, suicidal thoughts or behavior, and/or any unusual changes in mood or behavior.
Pregabalin may cause peripheral edema. Concomitant use of Pregabalin with a thiazolidinedione antidiabetic agent has been associated with a greater risk of developing weight gain and peripheral edema than either drug alone. Therefore use caution when coadministering Pregabalin and these agents.
Because there are limited data regarding use of Pregabalin in patients with New York Heart Association (NYHA) class III or IV congestive heart failure, the drug should be used with caution in these patients.
Pregabalin may cause weight gain. Pregabalin-associated weight gain was related to dose and duration of exposure. However, weight gain did not appear to be associated with baseline body mass index (BMI), gender, or age.
Pregabalin may cause visual disturbance e.g. blurred vision, decreased visual acuity and visual field changes. Patients should be instructed to notify their physician if these effects are noted.
Pregabalin has been associated with increases in creatine kinase. Rhabdomyolysis has been reported in premarketing clinical trials. However, the relationship between this event and Pregabalin is not completely understood. Therefore, patients should be instructed to notify their physician if unexplained muscle pain, tenderness, or weakness, particularly if fever and/or malaise are associated with these symptoms.
Pregabalin is associated with a decrease in platelet count and prolonged PR interval.

Use in pregnancy: Pregnancy category C.
Adverse events have been observed in animal reproduction studies of pregabalin. Male-mediated teratogenicity and impaired male and female fertility have been observed in animal studies.
There are no adequate and well-controlled studies in pregnant women. Use during pregnancy only if the potential benefit justifies the potential risk to the fetus.
Use in lactation: Pregabalin is present in breast milk. A decision should be made whether to discontinue nursing or the drug, taking into account the importance of the drug to the mother.

Adverse effects reported in 2% or more of patients receiving Pregabalin in combination with other anticonvulsant agents in the management of partial seizures include dizziness, somnolence, ataxia, abnormal thinking, tremor, confusion, twitching, myoclonus, amnesia speech disorder, incoordination, abnormal gait, dry mouth, constipation, increased appetite, weight gain, peripheral edema, blurred vision, diplopia, abnormal vision, accidental injury, and pain.
Adverse effects reported in 2% or more of patients receiving Pregabalin for the management of postherpetic neuralgia include dizziness, somnolence, headache, confusion, abnormal thinking, ataxia, incoordination, amnesia, abnormal gait, dry mouth, constipation, flatulence, vomiting, weight gain, peripheral edema, edema, facial edema, blurry vision, diplopia, abnormal vision, infection, flu syndrome, accidental injury, and pain.
Adverse effects reported in 2% or more of patients receiving Pregabalin for the management of pain associated with diabetic neuropathy include dizziness, somnolence, asthenia, neuropathy, ataxia, vertigo, abnormal thinking, confusion, euphoria, incoordination, dry mouth, constipation, flatulence, weight gain, peripheral edema, edema, hypoglycemia, accidental injury, back pain, chest pain, blurry vision, and dyspnea.
Adverse effects reported in 2% or more of patients receiving Pregabalin for the management of fibromyalgia include dizziness, somnolence, headache, euphoric mood, attention disturbance, balance disorder, memory impairment, hypoaesthesia, lethargy, tremor, anxiety, disorientation, depression, dry mouth, constipation, vomiting, flatulence, weight gain, fatigue, peripheral edema, chest pain, abnormal feeling, edema, fluid retention, drunk feeling, increased appetite, blurry vision, sinusitis, vertigo, pharyngolaryngeal pain, arthralgia, muscle spasms, and back pain

Because Pregabalin is not bound to plasma proteins, a pharmacokinetic interaction with drugs that are highly protein bound is unlikely.
Concomitant use of Pregabalin and angiotensin-converting enzyme inhibitors (ACEI) may increase the risk of developing angioedema.
Concomitant use of Pregabalin and CNS depressants (e.g. ethanol, lorazepam, oxycodone) may lead to an additive effect in the impairment of cognitive and gross motor function. No clinically important effects on respiration have been noted.
Concomitant use of Pregabalin and thiazolidinedione antidiabetic agents may increase the risk of edema, weight gain and/or fluid retention. Use with caution.
Concomitant use of Pregabalin and anticonvulsants (e.g. phenytoin, carbamazepine, valproate, lamotrigine, phenobarbital, topiramate) is unlikely to lead to pharmacokinetic interactions.

Store below 30°C.

Anticonvulsants / Anxiolytics / Drugs for Neuropathic Pain

N02BF02 - pregabalin ; Belongs to the class of gabapentinoids. Used to relieve pain and other conditions.

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