APO-NORTRIPTYLINE CAPSULE 10mg FOR ORAL USE

Product Information

Registration Status: Active

APO-NORTRIPTYLINE CAPSULE 10mg is approved to be sold in Singapore with effective from 1997-03-18. It is marketed by PHARMAFORTE SINGAPORE PTE LTD, with the registration number of SIN09255P.

This product contains Nortriptyline 10mg in the form of CAPSULE. It is approved for ORAL use.

This product is manufactured by APOTEX INC in CANADA.

It is a Prescription Only Medicine that can only be obtained from a doctor or a dentist, or a pharmacist with a prescription from a Singapore-registered doctor or dentist.

Description

Nortriptyline hydrochloride, the N-demethylated active metabolite of amitriptyline, is a dibenzocycloheptene-derivative tricyclic antidepressant (TCA). TCAs are structurally similar to phenothiazines. They contain a tricyclic ring system with an alkyl amine substituent on the central ring. In non-depressed individuals, nortriptyline does not affect mood or arousal, but may cause sedation. In depressed individuals, nortriptyline exerts a positive effect on mood. TCAs are potent inhibitors of serotonin and norepinephrine reuptake. Secondary amine TCAs, such as nortriptyline, are more potent inhibitors of norepinephrine reuptake than tertiary amine TCAs, such as amitriptyline. TCAs also down-regulate cerebral cortical β-adrenergic receptors and sensitize post-synaptic serotonergic receptors with chronic use. The antidepressant effects of TCAs are thought to be due to an overall increase in serotonergic neurotransmission. TCAs also block histamine-H₁ receptors, α₁-adrenergic receptors and muscarinic receptors, which accounts for their sedative, hypotensive and anticholinergic effects (e.g. blurred vision, dry mouth, constipation, urinary retention), respectively. Compared to other TCAs, nortriptyline is less toxic and displays less drug interactions [A6584]. As a more selective noadrenaline reuptake inhibitor, nortriptyline is less likely associated with the hypertensive ‘cheese reaction' [A6584]. Nortriptyline exerts less anticholinergic and sedative side effects compared to the tertiary amine TCAs, amitriptyline and clomipramine. Apart from its indication to treat depression, nortriptyline has been investigated in chronic neuropathic pain (unlabeled use), fibromyalgia [A31911], irritable bowel syndrome (unlabeled use), diabetic neuropathy (unlabeled use) [A31912], post-traumatic stress disorder (unlabeled use), and migraine prophylaxis (unlabeled use).

Indication

Primarily indicated for the relief of symptoms of depression.

Mechanism of Action

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 [T28]. 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 [T28]. Antimuscarinic effects upon binding to mAChR are responsible for various side effects of TCAs.

Pharmacokinetics

Absorption: As with other TCAs, notriptyline 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 [L1354]. The mean oral bioavailability is 51% [L1354].
Distribution: The apparent volume of distribution (Vd)β, estimated after intravenous administration is 1633 ± 268 l with the range from 1460 to 2030 (21 ± 4 l/kg). Nortriptyline may cross the placental barrier [L1354].
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. N-demethylnortriptyline 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 [L1354].
Elimination

Clearance

The mean systemic clearance (Cls) is 30.6 ± 6.9 L/h, ranging from 18.6 to 39.6 L/hour [L1354].

Toxicity

Symptoms of overdose include cardiac dysrhythmias, severe hypotension, shock, congestive heart failure, pulmonary edema, convulsions, and CNS depression, including coma. Changes in the electrocardiogram, particularly in QRS axis or width, are clinically significant indicators of tricyclic antidepressant toxicity. Side effects include: sedation, hypotension, blurred vision, dry mouth, constipation, urinary retention, postural hypotension, tachycardia, hypertension, ECG changes, heart failure, impaired memory and delirium, and precipitation of hypomanic or manic episodes in bipolar depression. Withdrawal symptoms include gastrointestinal disturbances, anxiety, and insomnia. Oral LD50 in rat is 405 mg/kg [MSDS].

Active Ingredient/Synonyms

Source of information: Drugbank (External Link). Last updated on: 3^rd July 18. *Trade Name used in the content below may not be the same as the HSA-registered product.