Gablin Plus

Maroon opaque cap and pink opaque body, hard gelatin capsule filled with light pink to pink colored, free flowing powder.
Each capsule contains: Pregabalin 75 mg, Mecobalamin (as Mecobalamin 5% in Mannitol) 750 mcg.

Antiepileptic/Vitamin.
Pharmacology: Pharmacodynamics: Pregabalin: Pregabalin binds with high affinity to the alpha-2-delta site (an auxiliary subunit of voltage-gated calcium channels) in central nervous system tissues.
While pregabalin is a structural derivative of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA), it does not bind directly to GABA_A, GABA_B, or benzodiazepine receptors, does not augment GABA_A 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 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.
Methylcobalamin: Methylcobalamin (Mecobalamin, MeCbl), is one of the two biologically active vitamin B₁₂. Mecobalamin acts as an important cofactor in the reaction of one class of the B₁₂ enzymes, the methyltransferases. The B₁₂-dependent methyltransferases play an important role in amino acid metabolism in many organisms as well as in one-carbon metabolism and CO₂ fixation in anaerobic microbes. Among them, methionine synthase is the most extensively studied B₁₂-dependent methyltransferase in humans. As the cofactor of the enzyme methionine synthase, mecobalamin functions to catalyse the transfer of the methyl group from methylene tetrahydrofolate to homocysteine (Hcy) to form methionine and tetrahydrofolate.
Deficiency of vitamin B₁₂ results in the lack of mecobalamin and has been associated with significant neurological pathology, especially peripheral neuropathy.
Pharmacokinetics: Pregabalin: Pregabalin is well absorbed after oral administration, is eliminated largely by renal excretion, and has an elimination half-life of about 6 hours.
Absorption and Distribution: Following oral administration of pregabalin capsules under fasting conditions, peak plasma concentrations occur within 1.5 hours. Pregabalin oral bioavailability is greater than or equal to 90% and is independent of dose. Following single- (25 to 300 mg) and multiple-dose (75 to 900 mg/day) administration, maximum plasma concentrations (C_max) and area under the plasma concentration-time curve (AUC) values increase linearly. Following repeated administration, steady state is achieved within 24 to 48 hours. Multiple-dose pharmacokinetics can be predicted from single-dose data.
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 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.
Pregabalin does not bind to plasma proteins. The apparent volume of distribution of pregabalin following oral administration is approximately 0.5 L/kg. Pregabalin is a substrate for the system L transporter which is responsible for the transport of large amino acids across the blood-brain barrier.
Metabolism and Elimination: Pregabalin undergoes negligible metabolism in humans. Following a dose of radiolabeled pregabalin, approximately 90% of the administered dose was recovered in the urine as unchanged pregabalin. The N-methylated derivative of pregabalin, the major metabolite of pregabalin found in urine, accounted for 0.9% of the dose.
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 normal renal function. Mean renal clearance was estimated to be 67.0 to 80.9 mL/min in young healthy subjects.
Special populations: Age: Geriatrics: Pregabalin oral clearance tended to decrease with increasing age. This decrease in pregabalin oral clearance is consistent with age-related decreases in CLcr_. Reduction of pregabalin dose may be required in patients who have age-related compromised renal function.
Renal impairment and haemodialysis: Pregabalin clearance is nearly proportional to creatinine clearance (CLcr). Dosage reduction in patients with renal dysfunction is necessary. Pregabalin is effectively removed from plasma by haemodialysis. Following a 4-hour haemodialysis treatment, plasma pregabalin concentrations are reduced by approximately 50%. For patients on haemodialysis, dosing must be modified.
Methylcobalamin: Absorption: Evidence indicates methylcobalamin is utilized more efficiently than cyanocobalamin to increase levels of one of the coenzyme forms of vitamin B₁₂. Experiments have demonstrated similar absorption of methylcobalamin following oral administration. The quantity of cobalamin detected following a small oral dose of mecobalamin is similar to the amount detected following the administration of cyanocobalamin, but significantly more cobalamin accumulates in liver tissue, which is associated with mecobalamin intake.
Distribution and Metabolism: Cobalamin circulates in plasma bound to two carrier proteins: transcobalamin (TC) and haptocorrin. TC is a 43-kDa non-glycoprotein that transfers cobalamin from the intestine into the bloodstream and then into all the cells of the body. Cobalamin-saturated transcobalamin (holoTC) constitutes 6-20% of total plasma cobalamin. The unsaturated TC is called apotranscobalamin, which constitutes the major part of TC. Additionally, total homocysteine (Hcy) and methylmalonic acid are considered to be two functional markers of vitamin B₁₂ status in adults.
Excretion: Human urinary excretion of methylcobalamin is about one-third that of a similar dose of cyanocobalamin, indicating substantially greater tissue retention.

Indicated for the treatment of neuropathic pain in patients with diabetic peripheral neuropathy and post herpetic neuralgia.

For Diabetic Peripheral Neuropathy, the maximum recommended dose of pregabalin is 300 mg/day in patients with creatinine clearance of at least 60 mL/min. Begin dosing at 150 mg/day. The dose may be increased to 300 mg/day within 1 week based on efficacy and tolerability. Although pregabalin was also studied at 600 mg/day, there is no evidence that this dose confers additional significant benefit and this dose was less well tolerated. In view of the dose-dependent adverse reactions, treatment with doses above 300 mg/day is not recommended.
For the patient with Postherpetic Neuralgia, the recommended dose of pregabalin is 75 to 150 mg two times a day, or 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 150 mg/day. The dose may be increased to 300 mg/day within 1 week based on efficacy and tolerability.
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 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 ongoing pain and are tolerating 300 mg daily.
For the management of Fibromyalgia, the recommended dose of pregabalin is 300 to 450 mg/day. Begin dosing at 75 mg two times a day (150 mg/day). The dose may be increased to 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 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 was less well tolerated. In view of the dose-dependent adverse reactions, treatment with doses above 450 mg/day is not recommended.
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 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.
The dosage range for methylcobalamin for clinical effectiveness is 0.5-6 mg/day, and no significant therapeutic advantage is observed beyond this range. However, the most commonly used dose was 0.5-1.5 mg/day administered orally.
FDC of Pregabalin and Mecobalamin treatment can be started at dose of two capsules b.i.d. based on individual patient response and tolerability.
When discontinuing FDC of Pregabalin and Mecobalamin, taper gradually over a minimum of 1 week.
Because pregabalin is eliminated primarily by renal excretion, adjust the dose in adult patients with reduced renal function.
Patients with Renal Impairment: In view of dose-dependent adverse reactions and because pregabalin is eliminated primarily by renal excretion, adjust the dose in patients with reduced renal function. The use of pregabalin in pediatric patients with compromised renal function has not been studied.
Base the dose adjustment in patients with renal impairment on CLcr as indicated in the table. To use the dosing table, an estimate of the patient's CLcr in mL/min is needed. CLcr in mL/min may be estimated from serum creatinine (mg/dL) determination using the Cockcroft and Gault equation: See equation.

Click on icon to see table/diagram/image

See table.

Click on icon to see table/diagram/image

Paediatric use: Safety and effectiveness in paediatric patients have not been established.
Geriatric use: Pregabalin is known to be substantially excreted by the kidney, and the risk of toxic reactions to pregabalin may be greater in patients with impaired renal function. Because pregabalin is eliminated primarily by renal excretion, adjust the dose for elderly patients with renal impairment.
FDC of Pregabalin and Mecobalamin capsules is given orally with or without food.

The most commonly reported symptoms observed with Pregabalin overdose included somnolence, confusional state, agitation, and restlessness. In rare occasions, cases of coma have been reported.
Treatment of overdose should include general supportive measures and may include hemodialysis if necessary.

Contraindicated in patients with hypersensitivity to the active substance or to any of the excipients.

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. Some diabetic patients who gain weight on Pregabalin treatment may need to adjust hypoglycemic medicinal products.
Pregabalin should be discontinued immediately if symptoms of hypersensitivity such as 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. Therefore, patients should be advised to exercise caution until they are familiar with the potential effects of the medicinal product.
Pregabalin may cause blurred vision in some patients. Discontinuation of Pregabalin may result in resolution or improvement of these visual symptoms.
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 may be 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.
Dose adjustment in patients with reduced renal function or undergoing hemodialysis is necessary. Vitamin B₁₂ supplementation can mask folate deficiency. In such patients, folate supplementation may be needed.
Effects on ability to drive and use machines: Pregabalin may cause dizziness and somnolence and therefore may influence the ability to drive or use machines. Patients are advised not to drive, operate complex machinery or engage in other potentially hazardous activities until it is known whether Pregabalin + Methylcobalamin capsule affects their ability to perform these activities.
Use in Children: Safety of Pregabalin + Methylcobalamin has not been established in children.

Safety and efficacy have not been evaluated in pregnancy and lactation hence Pregabalin + Methylcobalamin should not be given to pregnant and lactating women.

The most commonly reported adverse reactions with Pregabalin are dizziness and somnolence. Adverse reactions are usually mild to moderate in intensity. Hypersensitivity, increase in appetite, euphoric mood, confusion, irritability, disorientation, insomnia may occur. Methylcobalamin may rarely cause itching and allergic reactions.

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.
Pregabalin may potentiate the effects of ethanol and lorazepam. 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.

Instructions and Special Precautions for Handling and Disposal: Any unused medicinal product or waste material should be disposed of in accordance with local requirements.

Store at temperatures not exceeding 30°C.

Drugs for Neuropathic Pain

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

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