BG NOR NP

- Diabetic Peripheral Neuropathy, Low Back Pain, Post Herpetic Neuralgia, Fibromyalgia, Spinal Cord Injury

Bgnor NP Tablets is contraindicated in patient with hypersensitivity to any component of tablets and history of urinary retention – BPH

a. Mechanism of Actions

Nortriptyline: It is believed that nortriptyline either inhibits the reuptake of the neurotransmitter serotonin at the neuronal membrane or acts at beta-adrenergic receptors. It displays a more selective reuptake inhibition for noradrenaline, which may explain the relief and improvement of biological symptoms with nortriptyline therapy. Tricyclic antidepressants do not inhibit monoamine oxidase nor do they affect dopamine reuptake. As with other TCAs, nortriptyline displays affinity for other receptors including mACh receptors, histamine receptors and 5-HT receptors. Antimuscarinic effects upon binding to mAChR are responsible for various side effects of TCAs.

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Pregabalin: By binding presynaptically to the alpha2-delta subunit of voltage-gated calcium channels in the central nervous system, Pregabalin modulates the release of several excitatory neurotransmitters including glutamate, substance-P, norepinephrine, and calcitonin gene related peptide. In addition, Pregabalin prevents the alpha2-delta subunit from being trafficked from the dorsal root ganglia to the spinal dorsal horn, which may also contribute to the mechanism of action. Although Pregabalin is a structural derivative of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA), it does not bind directly to GABA or benzodiazepine receptors.

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b. Pharmacodynamic properties

Nortriptyline is a tricyclic antidepressant of the dibenzocycloheptene type and is the active metabolite of amitriptyline. It is an inhibitor of pre-synaptic noradrenaline reuptake than of serotonin, and is less anticholinergic than amitriptyline whilst having stronger antihistaminergic effects. Nortriptyline has been observed to increase the pressor effect of norepinephrine but blocks the pressor response of phenethylamine. Although the structure of pregabalin is similar to gamma-aminobutyric acid (GABA), it does not bind to GABA receptors. Instead, it binds the alpha2-delta subunit of presynaptic voltage-gated calcium channels in the central nervous system. Pregabalin does not modulate dopamine receptors, serotonin receptors, opiate receptors, sodium channels or cyclooxygenase activity

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c. Pharmacokinetic properties

Nortriptyline

• Absorption As with other TCAs, nortriptyline is well absorbed from the GI tract. Peak plasma concentrations occur within 4-8.8 hours following oral administration, with the mean time of 5.5 hours. The mean oral bioavailability is 51%
• Protein binding Plasma protein binding is approximately 93%
• Metabolism Nortriptyline undergoes hepatic metabolism via the same pathway as other TCAs, where it is metabolized via demethylation and hydroxylation followed by conjugation with glucuronic acid. The metabolism is subject to genetic polymorphism (CYP2D6). The main active metabolite is 10-hydroxynortriptyline exists in a cis and a trans form, where the trans form is dominant and more pharmacologically potent. Ndemethylnortriptyline is also formed to some extent. The metabolites have the same pharmacological profile as nortiptyline, but are weaker. 10-hydroxynortriptyline dominates in the plasma, but most of the metabolites are conjugated Excretion Nortriptyline and its metabolites are mainly excreted in the urine, where only small amounts (2%) of the total drug is recovered as unchanged parent compound. Approximately one-third of a single orally administered dose is excreted in urine within 24 hours. Small amounts are excreted in faces via biliary elimination.
Pregabalin
• Absorption After oral dosing administered in the fasted state, pregabalin absorption is rapid, and extensive. Pregabalin oral bioavailability is reported to be ≥90% regardless of the dose. Cmax is attained within 1.5 hours after single or multiple doses, and steady state is attained within 24-48 hours with repeated administration. Both Cmax and AUC appear to be dose proportional.
• Protein binding Pregabalin is not plasma protein bound.
• Metabolism Less than 2% of pregabalin is metabolized and it is excreted virtually unchanged in the urine
• Excretion Pregabalin is almost exclusively eliminated in the urine

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• Do not drink alcohol while taking Bgnor NP Tablets. It can increase the effects of alcohol, which could be dangerous.
• Grapefruit and grapefruit juice may also interact with this medicine and cause unwanted side effects.
• Use of Bgnor NP tablets can make patient more prone to sunburns. Hence avoid exposure to sunlight or tanning beds. Wear protective clothing and use sunscreen when outdoors during daytime.

Analgesic

Nortriptyline

• Some products that may interact with Nortriptyline include: arbutamine, "blood thinners" (such as warfarin), disulfiram, thyroid supplements, anticholinergic drugs (such as benztropine, belladonna alkaloids), certain drugs for high blood pressure (drugs that work in the brain such as clonidine, guanabenz).
• Some products that may interact with Nortriptyline include: arbutamine, "blood thinners" (such as warfarin), disulfiram, thyroid supplements, anticholinergic drugs (such as benztropine, belladonna alkaloids), certain drugs for high blood pressure (drugs that work in the brain such as clonidine, guanabenz).
• The risk of serotonin syndrome/toxicity increases if taken with other drugs that increase serotonin. Examples include street drugs such as MDMA/"ecstasy," St. John's wort, certain antidepressants (including SSRIs such asfluoxetine/paroxetine, SNRIs such as duloxetine/venlafaxine), among others.
• Other medications can affect the removal of nortriptyline from body, thereby affecting how nortriptyline works. These drugs include cimetidine, terbinafine, drugs to treat irregular heart rate (such as quinidine/propafenone/flecainide). This is not a complete list

Pregabalin

• Pregabalin has no known severe interactions with other drugs. Serious interactions of Pregabalin include: Benazepril, Captopril, Enalapril, Everolimus, Fosinopril, Imidapril, Lisinopril, Moexipril, Perindopril, Quinapril, Ramipril, Sirolimus, Temsirolimus, Trandolapril
• Moderate interactions of Pregabalin include: Clobazam, Deutetrabenazine, Lurasidone, Orlista

• Sedation, Drowsiness and Dizziness
• Weight Gain
• Dry mouth, blurred vision, increased intraocular pressure, constipation
• Hypotension, Syncope, Palpitations, Myocardial Infarction & Arrhythmias

OD and BID as directed by doctor. It is advised to consult doctor for the dosage, as the frequency also depends on the patient's condition.

• Shelf life – 24 months
• Keep the product out of the reach of children and away from light and moisture.
• Use the product before its expiration date.

NA

NA

• Paediatric: safety and efficacy has not been evaluated in children
• Geriatric: safety and efficacy has not been evaluated in old patients.
• Liver impairment: Not recommended.
• Renal failure:Use with caution.
• Pregnancy and lactation:Category C: Animal reproduction studies have shown an adverse effect on the foetus and there are no adequate and well controlled studies in humans, but potential benefits may warrant use of the drug in pregnant women despite potential risks.
• Effects on ability to drive and use machine:Bgnor NP Tablets may impair thinking or reactions. Patients should be cautioned against engaging in activities requiring complete mental alertness, and motor coordination such as operating machinery until their response to Bgnor NP Tablets is known.