Norip

Uses

Norip is used for the treatment of depression and nocturnal enuresis.

Norip is also used to associated treatment for these conditions: Irritable Bowel Syndrome (IBS), Major Depressive Disorder (MDD), Myofascial Pain Syndrome, Orofacial Pain, Pain, Chronic, Post-Herpetic Neuralgia (PHN)

How Norip works

Though prescribing information does not identify a specific mechanism of action for nortriptyline, is believed that nortriptyline either inhibits the reuptake of the neurotransmitter serotonin at the neuronal membrane or acts at the level of the beta-adrenergic receptors. It displays a more selective reuptake inhibition for noradrenaline, which may explain increased symptom improvement after nortriptyline therapy. Tricyclic antidepressants do not inhibit monoamine oxidase nor do they affect dopamine reuptake. As with other tricyclics, nortriptyline displays affinity for other receptors including mACh receptors, histamine receptors, 5-HT receptors, in addition to other receptors.

Dosage

Norip dosage

Depression:

• Adult: Low dose initially increased as necessary to 75-100 mg daily in divided doses or as a single dose (max. 150 mg daily)
• Adolescent & Elderly: 30-50 mg daily in divided doses; Child not recommended for depression

Nocturnal enuresis:

• Child 7 years: 10 mg
• 8-11 years: 10-20 mg
• Over 11 years: 25-35 mg, 30 minutes before bedtime; max period of treatment (including gradual withdrawal) 3 months- full physical examination and ECG before further course.

Side Effects

The most common side effects include dry mouth, sedation, constipation and increased appetite, mild blurred vision, tinnitus, often euphoria and mania. An occasional side effect is a rapid or irregular heartbeat. Alcohol may exacerbate some of its side effects and should be avoided.

Toxicity

The oral LD50 of nortriptyline in the rat is 405 mg/kg.Symptoms of overdose with nortriptyline include cardiac arrhythmias, severe hypotension, shock, congestive heart failure, pulmonary edema, convulsions, coma, and CNS depression. Changes in the electrocardiogram, particularly in QRS segment, may be indicative of tricyclic antidepressant toxicity.

Precaution

Not intended for treatment of bipolar depression. Avoid abrupt withdrawal. Patient at risk of seizures, with DM, narrow angle glaucoma, urinary retention, prostatic hyperplasia, chronic constipation, history of CV disease. Renal and hepatic impairment. Elderly, childn. Pregnancy and lactation.

Interaction

Norip should not be given with adrenaline, ephedrine, isoprenaline, noradrenaline, phenylephrine, phenylpropanolamine, drugs that are metabolized by CYP4502D6, MAOIs, guanethidine, debrisoquine, bethanidine, clonidine and reserpine etc. Barbiturates may increase the rate of metabolism of nortriptyline.

Food Interaction

• Avoid alcohol.
• Take with or without food. Food decreases gastrointestinal irritation.

Norip Alcohol interaction

[Moderate] GENERALLY AVOID:

Concomitant use of ethanol and a tricyclic antidepressant (TCA) may result altered TCA plasma levels and efficacy, and additive impairment of motor skills, especially driving skills.

Acute ethanol ingestion may inhibit TCA metabolism, while chronic ingestion of large amounts of ethanol may induce hepatic TCA metabolism.

Patients should be advised to avoid alcohol during TCA therapy.

Alcoholics who have undergone detoxification should be monitored for decreased TCA efficacy.

Dosage adjustments may be required.

Norip Drug Interaction

Major: duloxetine, cyclobenzaprine, escitalopram, topiramate, ondansetron, sertralineModerate: zolpidem, diphenhydramine, pregabalin, acetaminophen / hydrocodone, levothyroxine, alprazolam, cetirizineUnknown: aspirin, omega-3 polyunsaturated fatty acids, esomeprazole, acetaminophen, cyanocobalamin, ascorbic acid, cholecalciferol

Norip Disease Interaction

Major: anticholinergic effects, cardiovascular disease, pheochromocytoma, acute myocardial infarction recovery, cardiovascular disease, depression, seizure disordersModerate: bone marrow suppression, diabetes, renal/liver disease, schizophrenia/bipolar disorder, tardive dyskinesia, acute alcohol intoxication, bipolar disorder screening, glaucoma, hyper/hypoglycemia, liver/renal disease, neutropenia, schizophrenia, thyroid disorders, urinary retention

Volume of Distribution

The apparent volume of distribution (Vd)β, estimated after intravenous administration is 1633 ± 268 L within the range of 1460 to 2030 (21 ± 4 L/kg). Norip crosses the placenta and is found in the breast milk. It distributes to the heart, lungs, brain, and the liver.

Elimination Route

Norip is readily absorbed in the gastrointestinal tract with extensive variation in plasma levels, depending on the patient. This drug undergoes first-pass metabolism and its plasma concentrations are attained within 7 to 8.5 hours after oral administration. The bioavailability of nortriptyline varies considerably and ranges from 45 to 85%.

Half Life

The average plasma half-life of nortriptyline in healthy volunteers is about 26 hours, but is said to range from 16 to 38 hours. One study mentions a mean half-life of about 39 hours.

Clearance

The average plasma clearance of nortriptyline in a study of healthy volunteers was 54 L/h. The average systemic clearance of nortriptyline is 30.6 ± 6.9 L / h, within the range of 18.6 to 39.6 L/hour.

Elimination Route

Norip 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 feces via biliary elimination.

Pregnancy & Breastfeeding use

The safety of nortriptyline for use in pregnancy has not been established. Norip should only be given during pregnancy when there are no alternatives and benefit outweighs risk.

Contraindication

Norip is contraindicated in patients with hypersensitivity to nortriptyline. Concomitant administration with MAOI is contraindicated. Do not use with or within 2 weeks of stopping an MAOI. Norip is contraindicated during the acute recovery period after myocardial infarction.

Acute Overdose

Symptoms: Severe hypotension, cardiac dysrhythmias, shock, CHF, pulmonary oedema, convulsions, and CNS depression, including coma; changes in ECG.

Management: Symptomatic and supportive treatment. Admin IV Na bicarbonate, benzodiazepines. Admin activated charcoal to reduce absorption. Emesis is contraindicated. Initiate cardiac monitoring and observe for signs of CNS or resp depression, hypotension, cardiac dysrhythmias and/or conduction blocks, and seizures.

Storage Condition

Store at 15-30° C. Protect from light and moisture.

Innovators Monograph

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