nortriptyline

Absorption: Well absorbed after oral administration.

Distribution: Widely distributed to tissues.

Protein Binding: 92%.

Metabolism/Excretion: Mostly metabolized by the liver by the CYP2D6 isoenzyme; the CYP2D6 enzyme system exhibits genetic polymorphism; ∼7% of population may be poor metabolizers and may have significantly ↑ nortriptyline concentrations and an ↑ risk of adverse effects.

Half-Life: 18–28 hr.

Time/Action Profile ⬆ ⬇

(antidepressant effect)

ROUTE	ONSET	PEAK	DURATION
PO	2–3 wk	6 wk	unknown

Contraind./Precautions ⬆ ⬇

Contraindicated in:

Hypersensitivity;
Angle-closure glaucoma;
Alcohol intolerance (solution only);
Brugada syndrome;
Concurrent use of MAO inhibitors or MAO-like drugs (linezolid or methylene blue);
Lactation: Lactation.

Use Cautiously in:

Pre-existing cardiovascular disease;
History of seizures;
Asthma;
May ↑ risk of suicide attempt/ideation especially during early treatment or dose adjustment; risk may be greater in children or adolescents
;
OB: Use during pregnancy only if potential maternal benefit justifies potential fetal risk;
Pedi: Safety and effectiveness not established in children;
Geri: Appears on Beers list. ↑ risk of adverse reactions in older adults, including falls secondary to sedative and anticholinergic effects and orthostatic hypotension. Avoid use in older adults.

Adv. Reactions/Side Effects ⬆ ⬇

CV: hypotension, ARRHYTHMIAS, ECG changes

Derm: photosensitivity

EENT: blurred vision, dry eyes

Endo: gynecomastia

GI: constipation, dry mouth, nausea, paralytic ileus, unpleasant taste

GU: urinary retention

Hemat: blood dyscrasias

Metab: weight gain

Neuro: drowsiness, fatigue, lethargy, agitation, confusion, extrapyramidal reactions, hallucinations, headache, insomnia, SUICIDAL THOUGHTS/BEHAVIORS

Interactions ⬆ ⬇

Drug-drug:

MAO inhibitors may result in serious potentially fatal reactions (MAO inhibitors should be stopped ≥14 days before nortriptyline therapy; nortriptyline should be stopped ≥14 days before MAO inhibitor therapy).
MAO-inhibitor-like drugs, such as linezolid or methylene blue, may ↑ risk of serotonin syndrome; concurrent use contraindicated; do not start therapy in patients receiving linezolid or methylene blue; if linezolid or methylene blue need to be started in a patient receiving nortriptyline, immediately discontinue nortriptyline and monitor for signs/symptoms of serotonin syndrome for 2 wk or until 24 hr after last dose of linezolid or methylene blue, whichever comes 1st (may resume nortriptyline therapy 24 hr after last dose of linezolid or methylene blue).
May prevent the therapeutic response to most antihypertensives.
Hypertensive crisis may occur with clonidine.
↑CNS depression with other CNS depressants, including alcohol, antihistamines, opioids, and sedative/hypnotics.
Adrenergic effects may be ↑ with other adrenergic agents, including vasoconstrictors and decongestants.
↑anticholinergic effects with other anticholinergic drugs, including antihistamines, antidepressants, atropine, haloperidol, phenothiazines, quinidine, and disopyramide.
Cimetidine, fluoxetine, or hormonal contraceptives may ↑ levels and risk of toxicity.
↑risk of agranulocytosis with antithyroid agents.
Drugs that affect serotonergic neurotransmitter systems, including SSRIs, SNRIs, fentanyl, buspirone, tramadol, and triptans, may ↑ risk of serotonin syndrome.

Drug-Natural Products:

Kava-kava, valerian, or chamomile can ↑ risk of CNS depression.
St. John's wort may ↑ risk of serotonin syndrome.
↑anticholinergic effects with jimson weed and scopolia.

Route/Dosage ⬆ ⬇

PO (Adults ): 25 mg 3–4 times daily, up to 150 mg/day.
PO Geriatric Patients ): 30–50 mg/day in divided doses or as a single dose.

Availability ⬆ ⬇

(Generic available)

Capsules: 10 mg; 25 mg; 50 mg; 75 mg
Oral solution: 10 mg/5 mL

Assessment ⬆ ⬇

Monitor mental status (orientation, mood, behavior).
- Assess weight and BMI initially and throughout treatment. For overweight/obese individuals, monitor fasting blood glucose and cholesterol levels.
- Monitor BP and HR before and during initial therapy. Report significant ↓ in BP or a sudden ↑ in HR.
- Monitor baseline and periodic ECGs in older adults or patients with heart disease. May cause prolonged PR and QT intervals and may flatten T waves.
Assess for suicidal tendencies, especially during early therapy. Restrict amount of drug available to patient. Risk may be ↑ in adults ≤24 yr. After starting therapy, young adults should be seen by health care provider face-to-face at least weekly for 4 wk, then every other wk for next 4 wk, then at 12 wk, and then on advice of health care provider thereafter.
Pain: Assess type, location, and severity of pain before and periodically during therapy. Use pain scale to monitor effectiveness of medication.

Lab Test Considerations:

Assess WBC with differential, liver function, and serum glucose periodically. May ↑ serum bilirubin and alkaline phosphatase. May cause bone marrow depression. May ↑ or ↓ serum glucose.
- Serum levels may be monitored in patients who fail to respond to usual therapeutic dose. Therapeutic plasma concentration range is 50–150 ng/mL.

Toxicity and Overdose:

Symptoms of acute overdose include disturbed concentration, confusion, restlessness, agitation, seizures, drowsiness, mydriasis, arrhythmias, fever, hallucinations, vomiting, and dyspnea.
- Treatment of overdose includes gastric lavage, activated charcoal, and a stimulant cathartic. Maintain respiratory and cardiac function (monitor ECG for ≥5 days) and temperature. Medications may include digoxin for HF, antiarrhythmics, and anticonvulsants.

Implementation ⬆ ⬇

Taper to avoid withdrawal effects. ↓ dose 50% for 3 days, then by 50% for 3 more days, and then discontinue.
PO: Administer with meals to minimize gastric irritation.
- May be given as a single dose at bedtime to minimize sedation during the day. Dose ↑ should be made at bedtime because of sedation.

Patient/Family Teaching ⬆ ⬇

Explain purpose and side effects of medication to patient. Advise patient to read Patient Information before starting therapy. Advise to take as directed. Take missed doses as soon as possible unless almost time for next dose; if regimen is a single dose at bedtime, do not take in the morning because of side effects. Advise patient that drug effects may not be noticed for ≥2 wk. Abrupt discontinuation may cause nausea, vomiting, diarrhea, headache, trouble sleeping with vivid dreams, and irritability.
Advise patient to notify health care provider of all Rx or OTC medications, vitamins, or herbal products being taken and to consult with health care provider before taking other medications.
May cause drowsiness and blurred vision. Advise patient to avoid driving and other activities requiring alertness until response to drug is known.
Advise patient to notify health care provider if visual changes occur. Inform patient that periodic glaucoma testing may be required during long-term therapy.
Advise patient to make position changes slowly to minimize orthostatic hypotension. This side effect is less pronounced with this medication than with other tricyclic antidepressants.
Advise patient, family, and caregivers to look for suicidality, especially during early therapy or dose changes. Notify health care provider immediately if thoughts about suicide or dying, attempts to commit suicide, new or worse depression or anxiety, agitation or restlessness, panic attacks, insomnia, new or worse irritability, aggressiveness, acting on dangerous impulses, mania, or other changes in mood or behavior occur.
Advise patient to avoid alcohol or other CNS depressant drugs, including opioids, during therapy and for ≥3–7 days after therapy has been discontinued.
Advise patient to notify health care provider if urinary retention occurs or if dry mouth or constipation persists. Sugarless candy or gum may diminish dry mouth, and an ↑ in fluid intake or fiber may prevent constipation. If symptoms persist, dose ↓ or discontinuation may be necessary. Consult health care provider if dry mouth persists for >2 wk.
Advise patient to use sunscreen and protective clothing to prevent photosensitivity reactions.
Alert patient that urine may turn blue-green in color.
Advise patient of need to monitor dietary intake. ↑ in appetite may lead to undesired weight gain. Refer as appropriate for nutritional, weight, or medical management.
Advise patient to notify health care provider of medication regimen before treatment or surgery.
Therapy for depression is usually prolonged. Emphasize the importance of follow-up exams.
Rep: May cause fetal harm. Advise women of reproductive potential to use effective contraception during therapy and for ≥5 mo after last dose and to avoid breastfeeding during therapy. Advise patient to notify health care provider immediately if pregnancy is planned or suspected.

section name header

Pronunciation ⬇

Classifications ⬆ ⬇

Indications ⬆ ⬇

Action ⬆ ⬇

Pharmacokinetics ⬆ ⬇