Brand name
- Pamelor®
- Aventyl®
Drug Class
- Tricyclic antidepressant
Preparations
- Capsules: 10 mg, 25 mg, 50 mg, and 75 mg
- Oral solution: 10 mg, 5 mg
- Tablets: 10mg, 25 mg
Indications
- Depression: Mostly effective on endogenous depression
- Smoking Cessation
- Post-Herpetic Neurolgia
- Migraine Headache = Maintenance Therapy
Metabolism
- Absorption: Oral administration results in maximum plasma concentrations in approximately 5 hours.
- Distribution: 93% bins to plasma proteins.
- Metabolism: Drugs Metabolized by P450 2D6 (debrisoquin hydroxylase). Demethylation and hydroxylation followed by conjugation with glucuronic acid.
- Elimination:
- The half-life: 26 hours
- Excreted 98% through kidneys
- Note: Renal failure: no significant effect on Nortriptyline kinetics.
Dosing
- Usual adult dose: 25 mg 3 or 4 times daily (Gradual Increase)
- MAX dose: 100mg/day
- Elderly patients: 25 mg- 50 mg /day in divided doses.
- Adolescent depression: Not recommended in 13-18 years of age
Drug Interactions
Drug inhibition effect: (Concomitant use will increase the plasma level of Nortriptylin HCL):
- Quinidine
- Cimetidine
- Phenothiazines
- SSRIs
- Type 1C Antiarrhythmics :
- Propafenone
- Flecainide
Drug Inducer effect: (Concomitant use will decrease the plasma level of Nortriptylin HCL):
- Guanethidine
- Debrisoquine
- Bethanidine
- Methyldopa
- Clonidine
- Barbiturates
Reserpine (kind of alkaloid agent in pharmaceutics) + Tricyclic antidepressant (TCA) has “stimulating” effect in depressed patients.
Monoamine oxidase inhibitor (MAOI):
- Increased risk of Serotonin syndrome
Antihistamines: such as Astemizole and Terfenadine
Some antipsychotics mainly Pimozide and Sertindole
Cisapride
Halofrantine
Sotalol
antiarrhythmics class 1
Beta-receptor blockers
Calcium channel blockers: Especially Verapamil
Tramadol: TCAs increase the risk of seizure in patients using Tramadol
Adverse Effects
Cardiovascular:
- Hypotension
- Hypertension
- Tachycardia
- Palpitation
- Myocardial infarction
- Arrhythmias (QT interval Prolongation)
- Heart block
- Stroke
Psychiatric:
- Confusional states (especially in the elderly) with hallucinations
- Disorientation
- Delusions
- Anxiety
- Restlessness
- Agitation
- Insomnia
- Panic
- Nightmares
- Hypomania
- Exacerbation of psychosis
Neurologic:
- Tinnitus
- Numbness
- Paresthesias of extremities
- Incoordination
- Ataxia
- Tremors
- Peripheral neuropathy
- Extrapyramidal symptoms
- Seizures
- Alteration in EEG patterns
Anticholinergic:
- Dry mouth
- Blurred vision
- Disturbance of accommodation
- Mydriasis
- Constipation
- Paralytic ileus
- Urinary retention
- Delayed micturitio
Allergic:
- Skin rash
- Petechiae
- Urticarial
- Itching
- Photosensitization (avoid excessive exposure to sunlight)
- Edema (general or of face and tongue)
Hematologic:
- Bone marrow depression
- Agranulocytosis
- Eosinophilia
- Purpura
Gastrointestinal:
- Nausea and vomiting
- Anorexia
- Epigastric distress
- Diarrhea,
- peculiar taste
- Abdominal cramps
Endocrine:
- Gynecomastia in the male
- Breast enlargement and galactorrhea in the female
- Sexual dysfunction (increased or decreased libido, impotence)
- Testicular swelling
- Elevation or depression of blood sugar levels
- Syndrome of inappropriate ADH (antidiuretic hormone) secretion.
Contraindications
- Patients <= 12 Years of age
- Nocturnal enuresis
- Concurrent use of nortriptyline hydrochloride or other tricyclic antidepressants with a monoamine oxidase inhibitor (MAOI) .
- Hypersensitivity:
- During the acute recovery period after myocardial infarction.
Pregnancy and Breastfeeding
- Pregnancy: D – category
- Lactation: Do Not Nurse
Precautions
- Clinical Worsening and Suicide Risk:
- Adult and paediatric with major depressive disorder (MDD) may experience worsening of their depression and/or the emergence of suicidal ideation and behaviour or unusual changes in behaviour. This risk may persist until significant remission occurs. Observe very carefully during this period!
- Physicians, Family members and caregivers= All ought to monitor patient during the initiation of Nortriptylinr HCL for any unusual behavioral change.
- Concomitant use with Alcohol may have a potentiating effect = Increase suicidal ideation.
- Patients with Bipolar Disorder:
- Warning: Use of Nortriptyline HCL alone can increase the likelihood of increase in precipitation of manic episode.
- Determine patients with bipolar disorder prior to initiation of Nortriptyline HCL!
- Patients with Seizure disorders: Use with caution!
- Patients with Cardiovascular diseases: only under close supervision:
- Q-T interval Prolongation, Sinus tachycardia, Myocardial infarction, and/or ventricular arrhythmia, and strokes have occurred, especially in concurrent use with:
- Quinidine
- Antihistamines (such as Astemizole and Terfenadine)
- Some antipsychotics (mainly Pimozide and Sertindole)
- Cisapride
- Halofrantine
- Sotalol
- antiarrhythmics class 1
- Beta-receptor blockers
- Calcium antagonists (Especially Verapamil)
- Anticholinergic activity: Caution in concomitant use with anti-cholinergics/ sympathomimetics
- Patients with Hyperthyroidism: Great care needed due to risk of cardiac arrhythmias.
- In hypothyroidism: levothyroxine combine with antidepressants can give rise to hyperthyroidism and
- Levothyroxine may strengthen the antidepressant effect!
- May impair the mental and/or physical abilities required for the performance of hazardous tasks:
- Caution is indicated in the co-administration of TCAs with any of the SSRIs and also in switching from one class to the other.
- Safety and effectiveness in the pediatric population have not been established.
- Caution in use in patients > 65 years of age.
- Withdrawal Symptoms: Abrupt cessation: After prolonged therapy, may produce nausea, headache, and malaise.
- Do not prescribe simultaneously with monoamine oxidase inhibitor (MAOI): Risk of Serotonine Syndrom:
- If surgery is necessary: Discontinue Nortriptyline HCL, if possible, for several days prior to the procedure. Anaesthetics given during tricyclic antidepressant therapy may increase the risk of arrhythmias and hypotension.
- Caution in parkinsonism patients who are on Levodopa: The metabolism of levodopa in the intestine may be accelerated, possibly through delay of peristalsis.
- TCAs increase the risk of seizure in patients using Tramadol
- Do not use with serotonin enhancing medications. Risk of Serotonin Syndrome.
- Moderate to severe liver disease: Reducees hepatic clearance resulting in higher plasma levels.
- Renal failure: no significant effect on Nortriptyline kinetics.
Section
This document is prepared by the “Mental Health for All” team. This document is provided for information purposes only and does not necessarily represent endorsement by or an official position of the Essentials of Medicine. Advice on the treatment or care of an individual patient should be obtained through consultation with a physician who has examined that patient or is familiar with that patient’s medical history.