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;
OB: Use during pregnancy only if potential maternal benefit justifies potential fetal risk;
Pedi: Suicide risk may be greater in children or adolescents. 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

Interactions ⬆ ⬇

Drug-drug:

Concurrent use with MAO inhibitors may result in serious potentially fatal reactions (MAO inhibitors should be stopped at least 14 days before nortriptyline therapy. Nortriptyline should be stopped at least 14 days before MAO inhibitor therapy).
Concurrent use with 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 first (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 drugs possessing anticholinergic properties, including antihistamines, antidepressants, atropine, haloperidol, phenothiazines, quinidine, and disopyramide.
Cimetidine, fluoxetine, or hormonal contraceptives↑ blood 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, ↑ risk of serotonin syndrome.

Drug-Natural Products:

Concomitant use of kava-kava, valerian, or chamomile can ↑ CNS depression.
Use with St. John's wort↑ 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 or Adolescents): 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 pulse rate before and during initial therapy. Report significant decreases in BP or a sudden increase in pulse rate.
- Monitor baseline and periodic ECGs in geriatric patients 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 increased in children, adolescents, and adults ≤24 yrs. After starting therapy, children, adolescents, and young adults should be seen by health care professional 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 professional 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 leukocyte and differential blood counts, liver function, and serum glucose periodically. May cause ↑ serum bilirubin and alkaline phosphatase. May cause bone marrow depression. Serum glucose may be ↑ or ↓.
- Serum levels may be monitored in patients who fail to respond to usual therapeutic dose. Therapeutic plasma concentration range is 50–150 ng/mL.
- May cause alterations in blood glucose levels.

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 at least 5 days) and temperature. Medications may include digoxin for HF, antiarrhythmics, and anticonvulsants.

Implementation ⬆ ⬇

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

Patient/Family Teaching ⬆ ⬇

Instruct patient to take medication 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 at least 2 wk. Abrupt discontinuation may cause nausea, vomiting, diarrhea, headache, trouble sleeping with vivid dreams, and irritability.
May cause drowsiness and blurred vision. Caution patient to avoid driving and other activities requiring alertness until response to drug is known.
Instruct patient to notify health care professional if visual changes occur. Inform patient that periodic glaucoma testing may be required during long-term therapy.
Caution 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 professional 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 or if symptoms of serotonin syndrome occur.
Advise patient to avoid alcohol or other CNS depressant drugs, including opioids, during therapy and for at least 3–7 days after therapy has been discontinued.
Instruct patient to notify health care professional if urinary retention occurs or if dry mouth or constipation persists. Sugarless candy or gum may diminish dry mouth, and an increase in fluid intake or bulk may prevent constipation. If symptoms persist, dose reduction or discontinuation may be necessary. Consult health care professional if dry mouth persists for more than 2 wk.
Caution patient to use sunscreen and protective clothing to prevent photosensitivity reactions.
Alert patient that urine may turn blue-green in color.
Inform patient of need to monitor dietary intake. Increase in appetite may lead to undesired weight gain. Refer as appropriate for nutritional, weight, or medical management.
Advise patient to notify health care professional of medication regimen before treatment or surgery.
Rep: May cause fetal harm. Advise females of reproductive potential to use effective contraception during and for at least 5 mo after last dose and to avoid breastfeeding during therapy. Advise patient to notify health care professional immediately if pregnancy is planned or suspected.
Therapy for depression is usually prolonged. Emphasize the importance of follow-up exams.

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Pronunciation ⬇

Classifications ⬆ ⬇

Indications ⬆ ⬇

Action ⬆ ⬇

Pharmacokinetics ⬆ ⬇