Meigabalin

Pregabalin.

MEIGABALIN 25 MG: Capsule no. 4 opaque white with black imprinted MS P-51 on cap and body contains white to off-white powder.
MEIGABALIN 75 MG: Capsule no. 4 scarlet/opaque white with black imprinted MS P-52 on cap and body contains white to off-white powder.
Each hard capsule contains 25 mg and 75 mg of pregabalin.

Pharmacology: Pharmacodynamics: Mechanism of Action: The active substance, pregabalin, is a gamma-aminobutyric acid analogue ((S)-3-(aminomethyl)-5-methylhexanoic acid). Pregabalin binds to an auxillary subunit (α₂-δ protein) of voltage-gated calcium channels in the central nervous system.
Evidence from animal models with nerve damage has shown that pregabalin reduces calcium dependent release of pronociceptive neurotransmitters in the spinal cord possibly by disrupting calcium trafficking and/or reducing calcium currents. Evidence from other animal models of nerve damage suggest the antinociceptive activities of pregabalin may also be mediated through interactions with the descending noradrenergic and serotonergic pathways.
Pharmacokinetics: Absorption: Bioavailability: ≥90%.
Distribution: V_d: 0.56 L/kg.
Protein binding: Pregabalin is not bound to plasma proteins.
Metabolism: Negligible.
Half-life elimination: 6.3 hours.
Time to peak, plasma: within 1 hour (2.5 hours with food).
Excretion: Urine (98% as unchanged pregabalin, The N-methylated derivative of pregabalin, the major metabolite of pregabalin found in urine for 0.9% of the dose).
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.
Pharmacokinetics in special patient groups: 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, dosage reduction in patients with renal impairment and dosage supplement following hemodialysis 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.
Elderly (over 65 years of age): Pregabalin clearance tends to decrease with increasing age. This decrease in pregabalin oral clearance is consistent with decrease 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 woman 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 average daily infant dose of pregabalin from breast milk (assuming mean milk consumption of 150 mL/kg/day) was 0.31 mg/kg/day, which on a mg/kg basis would be approximately 7% of the maternal dose.

Neuropathic pain: Pregabalin is indicated for the treatment of central and peripheral neuropathic pain in adults which includes diabetic peripheral neuropathy and post-herpetic 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 (GAD) in adults.
Fibromyalgia: Pregabalin is indicated for the management of fibromyalgia.

Recommended Dose: The dose range is 150 to 600 mg per day given in either two or three divided doses. Pregabalin may be taken with or without food.
Neuropathic pain: Pregabalin treatment can be started at a dose of 150 mg per day. Based on individual patient response and tolerability, the dosage may be increased to 300 mg per day after an interval of 3 to 7 days, and if needed, to a maximum dose of 600 mg per day after an additional 7-day interval.
Epilepsy: Pregabalin treatment can be started with a dose of 150 mg per day. Based on individual patient response and tolerability, the dosage may be increased to 300 mg per day after 1 week. The maximum dosage of 600 mg per day may be achieved after an additional work.
Generalized Anxiety Disorder: The dose range is 150 to 600 mg per day given as two or three divided doses. The need of 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 dosage may be increased to 300 mg per day after 1 week. Following an additional week the dosage may be increased to 450 mg per day. The maximum dosage of 600 mg per day may be achieved an additional week.
Fibromyalgia: The usual dose range for most patients is 300 to 450 mg per day given in two divided doses. Some patients may derive additional benefit at 600 mg per day. Dosing should begin at 75 mg two times a day (150 mg/day) and 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). If needed, in some patient, based on individual response and tolerability, the dose may be increased to maximum dosage of 600 mg/day after an additional week.
Discontinuation of pregabalin: If pregabalin has to be discontinued, it is recommended this should be done gradually over a minimum of 1 week.
Patients with renal impairment: Dosage reduction in patients with compromised renal function must be individualized according to creatinine clearance (CLcr), as indicated in table as follows determined using the following formula: See equation.

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For patients receiving hemodialysis, the pregabalin daily dose should be adjusted based on renal function. In addition to the daily dose a supplementary dose should be given immediately following every 4-hour hemodialysis treatment.
Pregabalin Renal Impairment Dosing: See Table 1.

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Use in patients with hepatic impairment: No dosage adjustment is required for patients with hepatic impairment properties.
Use in children and adolescents (12 to 17 years of age): The safety and effectiveness of pregabalin in pediatric patients below the age of 12 years and adolescents has not been established. The use in children is not recommended.
Use in the elderly (over 65 years of age): Elderly patients may require a dose reduction of pregabalin due to a decreased renal function.
Mode of Administration: Pregabalin capsules is administered orally with or without food. If pregabalin is discontinued, dosage should be tapered gradually over at least 1 week. When discontinuing, taper off gradually over at least 1 week.

Overdose and Treatment: In overdoses up to 15 g, no unexpected adverse reactions were reported.
In the post-marketing experience, the most commonly reported adverse events observed when pregabalin was taken in overdose included affective disorder, somnolence, confusional state, depression, agitation, and restlessness. Seizures were also reported.
Treatment of pregabalin overdose should include general supportive measures and may include hemodialysis if necessary.

Known hypersensitivity to pregabalin or any ingredient in the formulation (pregelanitized starch and talcum).

1. The drug may cause drowsiness, do not drive a car operate machinery, or drink alcoholic beverages while taking the drug.
2. The drug may cause hematologic disorder.
3. Do not use the drug while pregnant because it may cause teratogenesis.
4. Use the drug with caution in patients with liver and kidney disease.

Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.
Some diabetic patients who gain weight on pregabalin treatment may need to adjust hypoglycemic medications.
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.
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 medication.
In the post-marketing experience, transient visual blurring and other changes in visual acuity have been reported in patients treated with pregabalin. Discontinuation of pregabalin may result in resolution or improvement of these visual symptoms.
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.
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, hyperhidrosis and diarrhea.
Pregabalin is not known to be active at receptor sites associated with drugs of abuse. Cases of misuse and abuse have been reported in the post-marketing database. As with any CNS active drug, carefully evaluate patients for history of drug abuse and observe them for signs of pregabalin misuse or abuse (e.g., development of tolerance, dose escalation, drug-seeking behavior).
Although the effects on the reversibility of renal failure have not been systematically studied, improved renal function following discontinuation or dose reduction of pregabalin has been reported.
Although there has been no causal relationship identified between exposure to pregabalin and congestive heart failure. There have been post-marketing reports of congestive heart failure in some patients receiving pregabalin. In short-term trials of patients without clinically significant heart or peripheral vascular disease, there was no apparent association between peripheral edema and cardiovascular complications such as hypertension such as hypertension or congestive heart failure. Because there are limited data on severe congestive heart failure patients, pregabalin should be used with caution in these patients.

Pregnancy: There are no adequate data on the use of pregabalin in pregnant women. Studies in animals have shown reproductive toxicity. The potential risk to humans is unknown. Therefore, pregabalin should not be used during pregnancy unless the benefit to the mother clearly outweighs the potential risk to the fetus. Effective contraception must be used in women of child-bearing potential.
Lactation: Pregabalin is excreted in the milk of lactating women. As the safety of pregabalin in infants is not known, breast-feeding is not recommended during treatment with pregabalin. A decision must be made whether to discontinue breast-feeding or to discontinue from pregabalin therapy taking into account the benefit of breast-feeding for the child and the benefit of therapy for the woman.

The most common adverse reactions resulting in discontinuation from pregabalin treatment groups were dizziness and somnolence.
Selected adverse drug reactions that were treatment related in the pooled analysis of clinical trials are listed in the table as follows by System Organ Class (SOC). The frequency of these terms has been based on all-causality adverse drug reactions in the clinical trial data set (very common (≥1/10), common (≥1/100, <1/100) and rare (<1/1,000)).
The adverse reactions listed may also be associated with the underlying and/or concomitant medications. (See Table 2.)

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The following adverse drug reactions were reported during POST-MARKETING SURVEILLANCE: See Table 3.

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Since pregabalin is predominantly excreted unchanged in the urine, undergoes negligible metabolism in human (<2% of a dose recovered in urine as metabolites), dose not inhibit drug metabolism in vitro, and is not bound to plasma proteins, it is unlikely to produce, or be subject to, pharmacokinetic interactions.
Accordingly, in in vivo studies no clinical 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.
Co-administration of pregabalin with the oral contraceptive norethisterone and/or thinly estradiol dose not influence the steady-state pharmacokinetics of either substance. Pregabalin may potentiate the effects of ethanol and lorazepam. In controlled clinical trials, multiple oral dosed of pregabalin co-administered with oxycodone, lorazepam or ethanol did not result in clinically important effects on respiration. Pregabalin appears to be additive in the impairment of cognitive and gross motor function caused by oxycodone.
In the post-marketing experience, there are reports of respiratory failure and coma in patients taking pregabalin and other CNS depressant medications. There are post-marketing reports of even related to reduced lower gastrointestinal tract function (e.g. intestinal obstruction, paralytic ileus, constipation) when pregabalin was co-administrated with medications that have the potential to produce constipation, such as opioid analgesics.
No specific pharmacodynamics interaction studies were conducted in elderly volunteers.

Store below 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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