Pregabur-75

Pregabalin.

Each hard gelatin capsule contains: Pregabalin 75 mg.
Pregabalin is an anticonvulsant drug used for neuropathic pain and as an adjunct therapy for partial seizures with or without secondary generalization in adults. Its chemical name is (S)-3-(aminomethyl)-5-methylhexanoic acid. Its empirical formula is C₈H₁₇NO₂ and its molecular weight is 159.23.

Pharmacology: Pharmacodynamics: Mechanism of Action: Pregabalin binds to an auxiliary subunit (α2-δ protein) of voltage-gated calcium channels in the central nervous system tissues. Although the mechanism of action of pregabalin has not been fully elucidated, results with genetically modified mice and with compounds structurally related to pregabalin (such as gabapentin) suggest that binding to the alpha2-delta subunit may be involved in pregabalin's antinociceptive and antiseizure effects in animals. In animal models of nerve damage, pregabalin has been shown to reduce calcium dependent release of pronociceptive neurotransmitters in the spinal cord, possibly by disrupting alpha2-delta containing calcium channel trafficking and/or reducing currents. Evidence from other animal models of nerve damage and persistent pain suggest the antinociceptive activities of pregabalin may also be mediated through interactions with descending noradrenergic and serotonergic pathways originating from the brainstem that modulate pain transmission in the spinal cord.
While pregabalin is a structural derivative of the inhibitory neurotransmitter gammaaminobutyric acid (GABA), it does not bind directly to GABA_A, GABA_B, or benzodiazepine receptors, does not augment GABAA responses in cultured neurons, does not alter rat brain GABA concentration or have acute effects on GABA uptake or degradation. However, in cultured neurons prolonged application of pregabalin increases the density of GABA transporter protein and increases the rate of functional GABA transport. Pregabalin does not block sodium channels, is not active at opiate receptors, and does not alter cyclooxygenase enzyme activity. It is inactive at serotonin and dopamine receptors and does not inhibit dopamine, serotonin, or noradrenaline reuptake.
Pharmacokinetics: Oral bioavailability of Pregabalin is estimated to be ≥90% and is independent of dose. In humans, the apparent volume of distribution of pregabalin following oral administration is approximately 0.56 L/kg. Pregabalin is not bound to plasma proteins. Following a dose ratio labeled pregabalin approximately 98% of the administered dose recovered in the urine was unchanged pregabalin. Its mean elimination half-life is 6.3 hours

Pregabalin is indicated for the management of neuropathic pain with diabetic peripheral neuropathy, management of postherpetic neuralgia, adjunctive therapy for adult patients with partial onset seizures, management of fibromyalgia, and management of neuropathic pain associated with spinal cord injury.

Pregabalin is given orally without food.
Neuropathic Pain Associated with Diabetic peripheral Neuropathy: The maximum recommended dose of Pregabalin is 100 mg three times a day (9300 mg/day). In patients with creatinine clearance of at least 60 mL/min, begin dosing at 50 mg three times a day (9150 mg/day). The dose may be increased to 300 mg/day within 1 week based on efficacy and tolerability because Pregabalin is eliminated primarily by renal excretion. Adjust the dose in patients with reduced renal function.
Postherpetic Neuralgia: The recommended dose of Pregabalin is 75 to 150 mg two times a day, or 50 to 100 mg three times a day (150 to 300 mg/day). In patients with creatinine clearance of at least 60 mL/min, begin dosing at 75 mg two times a day, or 50 mg three times a day (150 mg/day). The dose may be increased to 300 mg/day within 1 week based on efficacy and tolerability, because Pregabalin is eliminated primarily by renal excretion, adjust the dose in patients with reduced renal function.
Patients who do not experience sufficient pain relief following 2 to 4 weeks of treatment with 300 mg/day, and who are able to tolerate Pregabalin, may be treated with up to 300 mg two times a day, or 200 mg three times a day (600 mg/day). In view of the dose-dependent adverse reactions and the higher rate of treatment discontinuation due to adverse reactions, reserve dosing above 300 mg/day for those patients who have on-going pain are tolerating 300 mg daily.
Adjunctive Therapy for Adult Patients with Partial Onset Seizures: Pregabalin at doses of 150 to 600 mg/day has been shown to be effective as adjunctive therapy in the treatment of partial onset seizures in adults. Administer the total daily dose in two or three divided doses. In general, it is recommended that patients be started on a total daily dose no greater than 150 mg/day (75 mg two times a day, or 50 mg three times a day). Based on individual patient response and tolerability, the dose may be increased to a maximum dose of 600 mg/day, because Pregabalin is eliminated primarily by renal excretion. Adjust the dose in patients with reduced renal function. The effect of dose escalation rate on the tolerability of Pregabalin has not been formally studied. The efficacy of add-on Pregabalin in patients taking gabapentin has not been evaluated in controlled trials. Consequently, the dosing recommendations for the use of Pregabalin with gabapentin cannot be offered.
Management of Fibromyalgia: The recommended dose of Pregabalin for fibromyalgia is 300 to 450 mg/day. Begin dosing at 75 mg two times a day (150 mg/day). The dose may be increased to 150 mg two times a day (300 mg/day) within 1 week based on efficacy and tolerability. Patients who do not experience sufficient benefit with 300 mg/day may be further increased to 225 mg two times a day (450 mg/day). Although Pregabalin was also studied at 600 mg/day, there is no evidence that this dose confers additional benefit and this dose is less well-tolerated. In view of the dose-dependent adverse reactions, treatment with doses above 450 mg/day is not recommended, because Pregabalin is eliminated primarily by renal excretion. Adjust the dose in patients with reduced renal function.
Neuropathic Pain Associated with Spinal Cord Injury: The recommended dose range of Pregabalin for the treatment of neuropathic pain associated with spinal cord injury is 150 to 600 mg/day. The recommended starting dose is 75 mg two times a day (150 mg/day). The dose may be increased to 150 mg two times a day (300 mg/day) within 1 week based on efficacy and tolerability. Patients who do not experience sufficient pain relief after 2 to 3 weeks of treatment with 150 mg two times a day and who tolerate Pregabalin may be treated with up to 300 mg two times a day because Pregabalin is eliminated primarily by renal excretion. Adjust the dose in patients with reduced renal function.
Patients with Renal Impairment: In view of dose-dependent adverse reactions and since Pregabalin is eliminated primarily by renal excretion, adjust the dose in patients with reduced renal function. Base the dose adjustment in patients with renal impairment on creatinine clearance (CrCl), as indicated in the table. Next, refer to Dosage & Administration to determine the recommended total daily dose based on indication, for a patient with normal renal function (CrCl ≥60 mL/min). Then refer to the table to determine the corresponding renal adjusted dose.
For patients undergoing hemodialysis, adjust the pregabalin daily dose based on renal function. In addition to the daily dose adjustment, administer a supplemental dose immediately following every 4-hour hemodialysis treatment (see table).

Click on icon to see table/diagram/image

Symptoms include somnolence, confusional state, agitation, and restlessness. Treatment of pregabalin overdose should include general supportive measures and may include haemodialysis, if necessary.

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

Angioedema: There have been postmarketing reports of angioedema in patients during initial and chronic treatment with Pregabalin. Specific symptoms included swelling of the face, mouth (tongue, lips, and gums), and neck (throat and larynx). There were reports of life-threatening angioedema with respiratory compromise requiring emergency treatment. Discontinue Pregabalin immediately in patients with these symptoms.
Exercise caution when prescribing Pregabalin to patients who have had a previous episode of angioedema. In addition, patients who are taking other drugs associated with angioedema (e.g. angiotensin converting enzyme inhibitors [ACE-inhibitors]) may be at increased risk of developing angioedema.
Hypersensitivity: There have been postmarketing reports of hypersensitivity in patients shortly after initial of treatment with Pregabalin. Adverse reactions included skin redness, hives, rash, dyspnea, and wheezing. Discontinue Pregabalin immediately in patients with these symptoms.
Withdrawal of Antiepileptic Drugs (AEDs): As with all AEDs, withdraw Pregabalin gradually to minimize the potential of increased seizure frequency in patients with seizure disorders. If pregabalin is discontinued, taper the drug gradually over a minimum of 1 week.
Suicidal Behavior and Ideation: Antiepileptic drugs (AEDs), including Pregabalin, increase the risk of suicidal thoughts or behavior in patients taking drugs for any indication. Monitor patients treated with AEDs for any indication of the emergence or worsening of depression, suicidal thoughts or behavior, and/or any unusual changes in mood or behavior.

Hypersensitivity, angioedema, allergic reaction, increased appetite, euphoric mood, confusion, irritability, decreased libido, disorientation and insomnia.

In vivo studies and population pharmacokinetic analysis show that no pharmacokinetic interactions were observed between pregabalin and phenytoin, carbamazepine, valproic acid, lamotrigine, gabapentin, lorazepam, oxycodone or ethanol and oral contraceptives, such as norethisterone and/or ethinyl oestradiol.

Store at temperatures not exceeding 30°C.

Anticonvulsants / Drugs for Neuropathic Pain

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

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