Nevirin

Indications

Nevirin is indicated for the treatment of neuropathic pain

Adverse Effects

Pregabalin Most common adverse reactions (greater than or equal to 5% and twice placebo) in adults are dizziness, somnolence, dry mouth, edema, blurred vision, weight gain, and thinking abnormal (primarily difficulty with concentration/attention).

Drug Interactions

Pregabalin:Specifically, there are no pharmacokinetic interactions between pregabalin and the following antiepileptic drugs: carbamazepine, valproic acid, lamotrigine, phenytoin, phenobarbital, and topiramate. Important pharmacokinetic interactions would also not be expected to occur between Pregabalin and commonly used antiepileptic drugs

Mechanism of Action

Methylcobalamin: Methylcobalamin helps in the production of a compound called myelin Methylcobalamin rejuvenates the damaged neuron Elevated plasma levels of homocysteine, known as hyper-homocysteinemia (above 15 µmol/L), is associated with osteoporosis. Vitamin B6, B12 and Folic acid help in reducing hyper-homocysteinemia. L-Methylfolate Calcium , Pyridoxal -5 Phosphate , Methylcobalamin are the active form of Folic acid, Vitamin B6 and B12 respectively. Pregabalin: Pregabalin binds with high affinity to the alpha2-delta site (an auxiliary subunit ofvoltage-gated calcium channels) in 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 anti-nociceptive and antiseizure effects in animals. In animal models of nerve damage, pregabalin has been shown to reduce calcium-dependent release of pro-nociceptive neurotransmitters in the spinal cord, possibly by disrupting alpha2-delta containing-calcium channel trafficking and/or reducing calcium currents. Evidence from other animal models of nerve damage and persistent pain suggest the anti-nociceptive 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.

Absorption, Distribution, Metabolism & Excretion

Pregabalin Pregabalin steady-state pharmacokinetics are similar in healthy volunteers, patients with chronic pain. 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 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. Pregabalin is not bound to plasma proteins. Biotransformation 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. Elimination Pregabalin is eliminated from the systemic circulation primarily by renal excretion as unchanged drug. Pregabalin mean elimination half-life is 6.3 hours.

Drug Use in Pregnancy

Pregabalin: Pregnancy: May cause fetal harm. Advise of potential risk to the fetus. Lactation: Breastfeeding is not recommended Safety and efficacy of Nevirin have not been evaluated in pregnancy and lactation hence it should not be given to pregnant and lactating women

Drug Use in Renal Impairment

Renal Impairement:Dose adjustment in patients with reduced renal function or undergoing haemodialysis is necessary

Drug Use in Pediatric Population

Safety has not been established in children

Drug Use in Geriatric Population

Pregabalin: Reduction of pregabalin dose may be required in patients who have age-related compromised renal function. 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