General

Pronunciation
a-mee-TRIP-ti-leen

Trade Name(s)

• Apo-Amitriptyline [Canada]

• Elavil

• Levate [Canada]

• Novotriptyn [Canada]

Pregnancy Category
Category C

Ther. class.
antidepressants

Pharm. class.
tricyclic antidepressants

Indications

Depression

Unlabelled Use(s):

• Anxiety, insomnia, treatment-resistant depression

• Chronic pain syndromes (i.e, fibromyalgia, neuropathic pain/chronic pain, headache, low back pain)

Action

• Potentiates the effect of serotonin and norepinephrine in the CNS

• Has significant anticholinergic properties

Therapeutic Effect(s):
Antidepressant action

Pharmacokinetics

Absorption: Well absorbed from the GI tract

Distribution: Widely distributed

Protein Binding: 95% bound to plasma proteins

Metabolism and Excretion: Extensively metabolized by the liver. Some metabolites have antidepressant activity. Undergoes enterohepatic recirculation and secretion into gastric juices. Probably crosses the placenta and enters breast milk

Half-life: 10–50 hr

TIME/ACTION PROFILE (antidepressant effect)

ROUTE	ONSET	PEAK	DURATION
PO	2–3 wk (up to 30 days)	2–6 wk	days–wks
IM	2–3 wk	2–6 wk	days–wks

Contraindication/Precautions

Contraindicated in:

• Angle-closure glaucoma

• Known history of QTc prolongation, recent MI, heart failure

Use Cautiously in:

• May risk of suicide attempt/ideation especially during dose early treatment or dose adjustment; risk may be greater in children or adolescents

• Patients with pre-existing cardiovascular disease

• Prostatic hyperplasia (increased risk of urinary retention)

• History of seizures (threshold may be )

• OB: Use only if clearly needed and maternal benefits outweigh risk to fetusLactation: May cause sedation in infant

• Pedi: Safety not established in children <12 yr

• Geri: Appears on Beers list. Geriatric patients are at increased risk of adverse reactions including falls secondary to sedative and anticholinergic effects

Adverse Reactions/Side Effects

CNS: lethargy, sedation.

EENT: blurred vision, dry eyes, dry mouth.

CV: ARRHYTHMIAS, hypotension, ECG changes.

GI: constipation, hepatitis, paralytic ileus, increased appetite, weight gain.

GU: urinary retention, libido.

Derm: photosensitivity.

Endo: changes in blood glucose, gynecomastia.

Hemat: blood dyscrasias.

*CAPITALS indicates life-threatening.
*italic indicates most frequent.

Interactions

Drug-Drug

• Amitriptyline is metabolized in the liver by the cytochrome P450 2D6 enzyme, and its action may be affected by drugs that compete for metabolism by this enzyme, including other antidepressants, phenothiazines, carbamazepine, class 1C antiarrhythmics including propafenone, and flecainide; when these drugs are used concurrently with amitriptyline, dosage of one or the other or both may be necessary. Concurrent use of other drugs that inhibit the activity of the enzyme, including cimetidine, quinidine, amiodarone, and ritonavir, may result in effects of amitriptyline

• May cause hypotension, tachycardia, and potentially fatal reactions when used with MAO inhibitors (avoid concurrent use—discontinue 2 wk before starting amitriptyline)

• Concurrent use with SSRI antidepressants may result in toxicity and should be avoided (fluoxetine should be stopped 5 wk before starting amitriptyline)

• Concurrent use with clonidine may result in hypertensive crisis and should be avoided

• Concurrent use with levodopa may result in delayed or absorption of levodopa or hypertension

• Blood levels and effects may be by rifamycins (rifampin, rifapentine, and rifabutin)

• Concurrent use with moxifloxacin risk of adverse cardiovascular reactions

• CNS depression with other CNS depressants including alcohol, antihistamines, clonidine, opioids, and sedative/hypnotics

• Barbiturates may alter blood levels and effects

• Adrenergic and anticholinergic side effects may be with other agents having anticholinergic properties

• Phenothiazines or oral contraceptives levels and may cause toxicity

• Nicotine may metabolism and alter effects

Drug-Natural Products

• St. John's wort may decrease serum concentrations and efficacy

• Concomitant use of kava-kava, valerian, or chamomile can increase CNS depression

• Increased anticholinergic effects with jimson weed and scopolia

Route/Dosage

• PO (Adults): 75 mg/day in divided doses; may be increased up to 150 mg/day
or 50–100 mg at bedtime, may increase by 25–50 mg up to 150 mg (in hospitalized patients, may initiate with 100 mg/day, increasing total daily dose up to 300 mg).

• PO (Geriatric Patients and Adolescents): 10 mg tid and 20 mg at bedtime
or 25 mg at bedtime initially, slowly increased to 100 mg/day as a single bedtime dose or divided doses.

Availability

• Tablets: 10 mg, 25 mg, 50 mg, 75 mg, 100 mg, 150 mg

» Cost:
Generic: 10 mg $13.32/100, 25 mg $12.22/100, 50 mg $14.20/100, 75 mg $12.21/100, 100 mg $12.21/100, 150 mg $24.42/100.

• Syrup: 10 mg/5 ml

Assessment

• Obtain weight and BMI initially and periodically throughout treatment

• Assess fasting glucose and cholesterol levels in overweight/obese individuals

• Monitor blood pressure and pulse before and during initial therapy. Notify physician or other health care professional of decreases in blood pressure (10–20 mmHg) or sudden increase in pulse rate. Patients taking high doses or with a history of cardiovascular disease should have ECG monitored before and periodically during therapy

Depression

• Monitor mental status (orientation, mood behavior) frequently. Assess for suicidal tendencies, especially during early therapy. Restrict amount of drug available to patient

Pain

• Assess intensity, quality, and location of pain periodically during therapy. May require several weeks for effects to be seen. Use pain scale to monitor effectiveness of medication. Assess for sexual dysfunction (decreased libido; erectile dysfunction). Geri: Geriatric patients started on amitriptyline may be at an increased risk for falls; start with low dose and monitor closely. Assess for anticholinergic effects (weakness and sedation).

Lab Test Considerations

• Assess leukocyte and differential blood counts, liver function, and serum glucose before and periodically during therapy. May cause an serum bilirubin and alkaline phosphatase. May cause bone marrow depression. Serum glucose may be or

Potential Nursing Diagnoses

• Ineffective coping (Indications)

• Chronic pain (Indications)

• Risk for injury (Side Effects)

Implementation

• Do not confuse Elavil (amitriptyline) with Oruvail (ketoprofen)

» Dose increases should be made at bedtime because of sedation. Dose titration is a slow process; may take weeks to months. May give entire dose at bedtime. Sedative effect may be apparent before antidepressant effect is noted. May require tapering to avoid withdrawal effects

• PO: Administer medication with or immediately after a meal to minimize gastric upset. Tablet may be crushed and given with food or fluids

Patient/Family Teaching

• Instruct patient to take medication exactly as directed. If a dose is missed, take 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

• Orthostatic hypotension, sedation, and confusion are common during early therapy, especially in geriatric patients. Protect patient from falls and advise patient to make position changes slowly. Institute fall precautions. Advise patient to make position changes slowly. Refer as appropriate for nutrition/weight management and medical management

• Advise patient to avoid alcohol or other CNS depressant drugs during and for 3–7 days after therapy has been discontinued

• Instruct patient to notify health care professional if urinary retention, 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 >2 wk

• Caution patient to use sunscreen and protective clothing to prevent photosensitivity reactions. Alert patient that medication may turn urine blue-green in color

• Inform patient of need to monitor dietary intake. Increase in appetite may lead to undesired weight gain

• Advise patient to notify health care professional if pregnancy is planned or suspected or if breastfeeding

• Advise patient to notify health care professional of medication regimen before treatment or surgery. Medication should be discontinued as long as possible before surgery

• Therapy for depression is usually prolonged and should be continued for at least 3 months to prevent relapse. Emphasize the importance of follow-up exams to monitor effectiveness, side effects, and improve coping skills. Advise patient and family that treatment is not a cure and symptoms can recur after discontinuation of medication. Refer patient to local support group

Evaluation/Desired Outcomes

• Increased sense of well-being

» Renewed interest in surroundings

» Increased appetite

» Improved energy level

» Improved sleep

• Decrease in chronic pain symptoms

• Full therapeutic effects may be seen 2–6 wk after initiating therapy

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