nortriptyline hydrochloride
Aventyl HCl, Pamelor

Available forms
Available by prescription only
Capsules: 10 mg, 25 mg, 50 mg, 75 mg
Solution: 10 mg/5 ml (4% alcohol)

Indications and dosages
 Depression; panic disorder ◇. Adults: 25 mg P.O. t.i.d. or q.i.d., gradually increasing to a maximum of 150 mg daily. Or, entire dosage may be given h.s.
Elderly patients or adolescents: 30 to 50 mg P.O. daily or in divided doses.

Pharmacodynamics
Antidepressant action: Drug is thought to exert antidepressant effects by inhibiting reuptake of norepinephrine and serotonin in CNS nerve terminals (presynaptic neurons), which results in increased levels and enhanced activity of these neurotransmitters in the synaptic cleft. Nortriptyline inhibits reuptake of serotonin more actively than norepinephrine; it’s less likely than other tricyclic antidepressants to cause orthostatic hypotension.

Pharmacokinetics
Absorption: Absorbed rapidly from the GI tract after oral administration.
Distribution: Distributed widely into the body, including the CNS and breast milk, and is 95% protein-bound. Steady state serum levels occur in 2 to 4 weeks. Therapeutic serum level ranges from 50 to 150 ng/ml.
Metabolism: Metabolized by the liver; a significant first-pass effect may account for variability of serum levels in different patients taking the same dosage.
Excretion: Mostly excreted in urine; some in feces, via the biliary tract.

Contraindications and precautions
Contraindicated in patients hypersensitive to drug, patients in acute recovery phase of MI, and patients who have taken an MAO inhibitor within 14 days. Use cautiously in patients receiving thyroid medication and those with glaucoma, suicidal tendencies, CV disease, hyperthyroidism, or a history of urine retention or seizures.

Interactions
Drug-drug. Antiarrhythmics (such as disopyramide, procainamide, and quinidine), pimozide, thyroid medications: May increase risk of arrhythmias and conduction defects. Use together cautiously.
Anticholinergics, including antihistamines, antiparkinsonians, atropine, meperidine, and phenothiazines: Causes oversedation, paralytic ileus, visual changes, and severe constipation. Use together cautiously.
Barbiturates: Induces nortriptyline metabolism and decreases therapeutic efficacy. Monitor patient closely.
Beta blockers, cimetidine, hormonal contraceptives, methylphenidate, propoxyphene: May inhibit nortriptyline metabolism, increasing plasma levels. Monitor patient for toxicity.
Centrally acting antihypertensives, such as clonidine, guanabenz, guanadrel, guanethidine, methyldopa, and reserpine: Decreases hypotensive effects. Monitor blood pressure.
CNS depressants, including analgesics, anesthetics, barbiturates, narcotics, and tranquilizers: Causes additive effects (oversedation). Use together cautiously.
Disulfiram, ethchlorvynol: May cause delirium and tachycardia. Avoid use together.
Haloperidol, phenothiazines: Decreases nortriptyline metabolism. Monitor patient closely.
Metrizamide: Increases risk of seizures. Avoid use together, if possible.
Sympathomimetics, including epinephrine, phenylephrine, and ephedrine (often found in nasal sprays): May increase blood pressure. Use together cautiously.
Warfarin: May increase PT and cause bleeding. Monitor PT and INR. Monitor patient for increased bruising and bleeding.
Drug-herb. Evening primrose oil: May cause additive or synergistic effect resulting in decreased seizure threshold and increased risk of seizures. Discourage use together.
St. John’s wort: Decreases nortriptyline levels. Discourage use together.
Yohimbe: May cause additive or synergistic effects on blood pressure. Discourage use together.
Drug-lifestyle. Alcohol use: Causes additive effects. Discourage alcohol use.
Heavy smoking: Induces nortriptyline metabolism and decreases therapeutic efficacy. Discourage smoking.

Adverse reactions
CNS: drowsiness, dizziness,seizures, tremor, weakness, confusion, headache, nervousness, EEG changes, extrapyramidal reactions, CVA, insomnia, nightmares, hallucinations, paresthesia, ataxia, agitation.
CV: tachycardia, hypertension, hypotension, MI, heart block, prolonged conduction time (elongation of QT and PR intervals, flattened T waves on ECG).
EENT: blurred vision, tinnitus, mydriasis.
GI: dry mouth, constipation, nausea, vomiting, anorexia, paralytic ileus.
GU: urine retention.
Hematologic: bone marrow depression, agranulocytosis, eosinophilia, thrombocytopenia.
Skin: rash, urticaria, photosensitivity, diaphoresis.
Other: hypersensitivity reaction.
After abrupt withdrawal of long-term therapy: nausea, headache, malaise (doesn’t indicate addiction).

Effects on lab test results
• May increase or decrease glucose levels.
• May increase eosinophil count and liver function test values. May decrease granulocyte and platelet counts.

Overdose and treatment
The first 12 hours after acute ingestion are a stimulatory phase characterized by excessive anticholinergic activity, including agitation, irritation, confusion, hallucinations, hyperthermia, parkinsonian symptoms, seizures, urine retention, dry mucous membranes, pupillary dilation, constipation, and ileus. This is followed by CNS depressant effects, including hypothermia; decreased or absent reflexes; sedation; hypotension; cyanosis; and cardiac irregularities, including tachycardia, conduction disturbances, and quinidine-like effects on the ECG.
 Severity of overdose is best indicated by prolonging QRS complex beyond 100 milliseconds, which usually indicates a serum level greater than 1,000 ng/ml. Metabolic acidosis may follow hypotension, hypoventilation, and seizures.
 Treatment is symptomatic and supportive, including maintaining a patent airway, stable body temperature, and fluid and electrolyte balance. Induce emesis with ipecac syrup if patient is conscious; follow with gastric lavage and activated charcoal to prevent further absorption. Dialysis is usually ineffective. Consider use of cardiac glycosides or physostigmine if serious CV abnormalities or cardiac failure occurs. Treat seizures with parenteral diazepam or phenytoin; arrhythmias with parenteral phenytoin or lidocaine; and acidosis with sodium bicarbonate. Don’t use quinidine, procainamide, or disopyramide to treat arrhythmias, since these agents can further depress myocardial conduction and contractility. Don’t give barbiturates; these may enhance CNS and respiratory depressant effects.

Special considerations
• Drug may be given at bedtime to reduce daytime sedation. Tolerance to sedative effects usually develops in early weeks of therapy.
• Withdraw drug gradually over a few weeks and at least 48 hours before surgical procedures.
• Drug is available in liquid form.
• In patients with bipolar disorders, drug may cause symptoms of the manic phase to emerge.
• Monitor nortriptyline level if dose is over 100 mg daily.
Breast-feeding patients
• Nortriptyline appears in breast milk in low levels. Potential benefit to woman should outweigh potential harm to infant.
Pediatric patients
• Drug isn’t recommended for children. Lower dosages may be indicated for adolescents.
Geriatric patients
• Lower dosages may be indicated. These patients have an increased risk for adverse cardiac effects. Nortriptyline is less likely to cause hypotension than other tricyclic antidepressants.

Patient education
• Explain that patient may not see full effects of drug therapy for up to 4 weeks after start of therapy.
• Warn patient about sedative effects.
• Recommend taking full daily dose at bedtime to prevent daytime sedation.
• Instruct patient to avoid drinking alcoholic beverages, doubling doses after missing one, or discontinuing drug abruptly, unless instructed.
• Caution about possible dizziness. Tell patient to lie down for about 30 minutes after each dose at start of therapy and to avoid sudden position changes, to prevent dizziness. Orthostatic hypotension is usually less severe than with amitriptyline.
• Urge patient to report unusual reactions promptly, such as confusion, movement disorders, fainting, rapid heartbeat, or difficulty urinating.
• Tell patient to store drug away from children.
• Suggest relieving dry mouth with sugarless chewing gum or candy.
• Advise patient to avoid activities that require physical and mental alertness, such as driving a car or operating machinery.

Reactions may be common, uncommon, life-threatening, or COMMON AND LIFE THREATENING.
◆ Canada only
◇ Unlabeled clinical use