Preg-M

Reddish white to pink powder encapsulated in soft to slightly brittle empty gelatin capsule size #3 with medium orange opaque cap and white opaque body.
Each capsule contains: Pregabalin 75 mg, Mecobalamin 750 mcg.

Pharmacology: Pharmacokinetics: Pregabalin: Absorption: Pregabalin is rapidly absorbed when administered in the fasted state, with peak plasma concentrations occurring within 1 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 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 humans, the apparent volume of distribution of pregabalin following oral administration is approximately 0.56 L/kg. Pregabalin is not bound to plasma proteins.
Metabolism: Pregabalin undergoes negligible metabolism in humans. Following a dose of radiolabelled 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.
Dosage 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 date. Therefore, there is no need for routine monitoring of plasma concentrations of pregabalin.
Mecobalamin: Substances bind to intrinsic factor; a glycoprotein, secreted by the gastric mucosa and are then actively absorbed from the gastrointestinal tract. Absorption is impaired in patients with an absence of intrinsic factor, with a malabsorption syndrome or with disease or abnormality of the gut, or after gastrectomy. Absorption from the gastrointestinal tract can also occur by passive diffusion; little of the vitamin present in food absorbed in this manner although the process becomes increasingly important with larger amounts such as those used therapeutically. After intranasal dosage, peak plasma concentrations of cyanocobalamin have been reached in 1 to 2 hours. The bioavailability preparation is about 7 to 11% of that by intramuscular injection.
Vitamin B₁₂ is extensively bound to specific plasma proteins called transcobalamins; transcobalamin II appears to be involved in the rapid transport of the cobalamins into tissues. Vitamin B₁₂ is stored in the liver, excreted in the bile, and undergoes extensive enterohepatic recycling; part of however, accounts for only a small fraction in the reduction of total body stores acquired by dietary means. Vitamin B₁₂ diffuses across the placenta and also appears in breast milk.

Indicated in the management of peripheral neuropathy.
Pregabalin is an anticonvulsant.
Mecobalamin is a form of Vit. B₁₂. It is given to people suffering from nerve pain, because such condition can be caused or aggravated by a deficiency in this vital nutrient.

Starting dose: 1 capsule twice daily.
Patients previously on gabapentin will have a wash-out of one (1 week) prior to start of dosing with pregabalin.

Pregabalin: In overdose up to 15 g, no unexpected adverse reactions were reported.
Treatment of pregabalin overdose should include general supportive measures and may include hemodialysis if necessary.

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

Pregabalin: 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 the hypersensitivity reactions, including cases of angioedema. Pregabalin should be discontinued immediately if symptoms of angioedema, such as facial, peroral, 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 potential effects of the medication.
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 behaviour).
Although the effects of discontinuation 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 or congestive heart failure. Because there are limited data on severe congestive heart failure patients, pregabalin should be used with caution in these patients.
Mecobalamin: Not to be given in patients with suspected Vitamin B₁₂ deficiency without first confirming diagnosis. Monitor blood regularly. Dose >10 mcg daily may produce haematological response in patients w/ folate deficiency, Leber's disease or tobacco amblyopia.

Pregabalin: 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 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 pregabalin therapy taking into account the benefit of breast-feeding for the child and the benefit therapy for the women.
There are no adequate data on the use of mecobalamin in pregnant women.

Pregabalin: 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.
Accordingly, in 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. Co-administration of pregabalin with the oral contraceptives norethisterone and/or ethinyl estradiol does not influence the steady-state pharmacokinetics of either substance. 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. Pregabalin appears to be additive in the impairment of cognitive and gross motor function caused by oxycodone.
Mecobalamin: Absorption of vitamin B₁₂ from the gastrointestinal tract may be reduced by neomycin, aminosalicylic acid, histamine H₂-antagonists, omeprazole, and colchicines. Serum concentrations may be decreased by used of oral contraceptives. Many of these interactions are unlikely to be of clinical significance but should be taken into account when performing assays for blood concentrations. Parenteral chloramphenicol may attenuate the effect of vitamin B₁₂ in anemia.
Allergic hypersensitivity reactions have occurred rarely after parenteral doses of the vitamin B₁₂ compounds cyanocobalamin and hydroxocobalamin. Antibodies to hydroxocobalamin-transcobalamin II complex have developed during hydroxocobalamin therapy. Arrhythmias secondary to hypokalemia have occurred at the beginning of parenteral treatment with hydroxocobalamin. Intranasal cyanocobalamin may cause rhinitis, nausea and headache.
Cyanocobalamin or hydroxocobalamin should, if possible, not be given to patients with suspected vitamin B₁₂ deficiency without first confirming the diagnosis. Regular monitoring of the blood is advisable. Use of doses greater than 10 micrograms daily may produce haematological response in patients with folate deficiency; indiscriminate use may mask the precise diagnosis. Conversely, folate may mask vitamin B₁₂ deficiency cyanocobalamin should not be used for Leber's disease or tobacco amblyopia since these optic neuropathies may degenerate further.

Store at temperatures not exceeding 30°C.

Drugs for Neuropathic Pain / Anticonvulsants

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

Rx