amitriptyline, Elavil, Levate

 Indications

Depression. Unlabeled Use: 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 Effects: 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–wk

Contraindications/Precautions

Contraindicated in: Angle-closure glaucoma;

Known history of QTc interval prolongation, recent MI,

or heart failure.

Use Cautiously in: Mayqrisk 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 (qrisk of urinary retention); History

of seizures (threshold may bep); OB: Use only if

clearly needed and maternal benefits outweigh risk to

fetus; Lactation: May cause sedation in infant; Pedi:

Children 12 yr (safety not established); Geri: Appears

on Beers list.qrisk of adverse reactions including falls

secondary to sedative and anticholinergic effects.

Adverse Reactions/Side Effects

CNS: SUICIDAL THOUGHTS, lethargy, sedation. EENT:

blurred vision, dry eyes, dry mouth. CV: ARRHYTHMIAS,

TORSADE DE POINTES, hypotension, ECG changes, QT interval

prolongation. GI: constipation, hepatitis, paralytic ileus,qappetite, weight gain. GU: urinary retention,

plibido. Derm: photosensitivity. Endo: changes

in blood glucose, gynecomastia. Hemat: blood dyscrasias.

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,

dosagepof 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 inqeffects 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 inqtoxicity 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

pabsorption of levodopa or hypertension. Blood levels

and effects may bepby rifampin, rifapentine, and

rifabutin. Concurrent use with moxifloxacinqrisk of

adverse cardiovascular reactions.qCNS 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 beqwith other agents having anticholinergic

properties. Phenothiazines or oral contraceptives

qlevels and may cause toxicity. Nicotine mayqmetabolism

and alter effects.

Drug-Natural Products: St. John’s wort mayp

serum concentrations and efficacy. Concomitant use of

kava-kava, valerian, or chamomile canqCNS depression.

qanticholinergic effects with jimson weed

and scopolia.

Route/Dosage

PO (Adults): 75 mg/day in divided doses; may bequp

to 150 mg/day or 50–100 mg at bedtime, mayqby

25–50 mg up to 150 mg (in hospitalized patients, may

initiate with 100 mg/day, andqtotal daily dose up to

300 mg).

PO (Geriatric Patients): 10–25 mg at bedtime; may

qby 10–25 mg weekly if tolerated (usual dose range

25–150 mg/day).

Availability (generic available)

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

mg. Cost: Generic—25 mg $9.33/100, 75 mg $9.83/

100.