AMITRIPTYLINE HYDROCHLORIDE

AMITRIPTYLINE HYDROCHLORIDe
(a-mee-trip'ti-leen)
Amitril, Apo-Amitriptyline

, Emitrip, Endep, Enovil, Levate

, Meravil, Novotriptyn

, SK-Amitriptyline
Classifications: psychotherapeutic; tricyclic antidepressant;
Therapeutic: antidepressant
Prototype: Imipramine
Pregnancy Category: C

Availability

10 mg, 25 mg, 50 mg, 75 mg, 100 mg, 150 mg tablets; 10 mg/mL injection

Action

A tricyclic antidepressant (TCA) that inhibits the reuptake of serotonin (5-HT) and norepinephrine from the synaptic gap; also inhibits norepinephrine reuptake to a moderate degree. Restoration of the levels of these neurotransmitters is a proposed mechanism of its antidepressant action.

Therapeutic Effect

Interference with the reuptake of serotonin and norepinephrine results in the antidepressant activity of amitriptyline.

Uses

Endogenous depression.

Unlabeled Uses

Prophylaxis for cluster, migraine, and chronic tension headaches; intractable pain, peptic ulcer disease, to increase muscle strength in myotonic dystrophy, to treat pathologic weeping and laughing secondary to forebrain disease, for eating disorders associated with depression (anorexia or bulimia), and as sedative for nondepressed patients.

Contraindications

TCA hypersensitivity; acute recovery period after MI, cardiac arrhythmias, AV block, long-QT prolongation; suicidal ideation; history of seizure disorders, pregnancy (category C); lactation, children <12 y.

Cautious Use

Prostatic hypertrophy, history of urinary retention or obstruction; angle-closure glaucoma; diabetes mellitus; history of hematologic disorders; history of alcoholism; GERD, BPH; hyperthyroidism; patient with cardiovascular, hepatic, or renal dysfunction; patient with suicidal tendency, electroshock therapy; elective surgery; schizophrenia; respiratory disorders; Parkinson's disease; seizure disorders; older adults, adolescents.

Route & Dosage

Antidepressant
Adult: PO 75–100 mg/d, may gradually increase to 150–300 mg/d (use lower doses in outpatients) IM 20–30 mg q.i.d. until patient can take PO
Adolescent: PO 25–50 mg/d in divided doses, may gradually increase to 100 mg/d (max: 200 mg/d)
Geriatric: PO 10–25 mg h.s., may gradually increase to 25–150 mg/d

Administration

Oral

Give with or immediately after food to reduce possibility of GI irritation. Tablet may be crushed if patient is unable to take it whole; administer with food or fluid.
Give increased doses preferably in late afternoon or at bedtime due to sedative action that precedes antidepressant effect.
Give as single dose at bedtime to promote sleep or for patients with dizziness or when daytime sedation interferes with work productivity.
Note that dose is usually tapered over 2 wk at discontinuation to prevent withdrawal symptoms (headache, nausea, malaise, musculoskeletal pain, panic attack, weakness).

Intramuscular

Reserve IM injections for patients unable or unwilling to take oral drug.
Inject deep IM into a large muscle.
Store drug at 15°–30° C (59°–86° F) and protect from light unless otherwise directed by manufacturer.

Adverse Effects (≥1%)

CNS: Drowsiness, sedation, dizziness, nervousness, restlessness, fatigue, headache, insomnia, abnormal movements (extrapyramidal symptoms), seizures. CV: Orthostatic hypotension, tachycardia, palpitation, ECG changes. Special Senses: Blurred vision, mydriasis. GI: Dry mouth, increased appetite especially for sweets, constipation, weight gain, sour or metallic taste, nausea, vomiting. Urogenital: Urinary retention. Other: (Rare) Bone marrow depression.

Interactions

Drug: antihypertensives may decrease some antihypertensive response; cns depressants, alcohol, hypnotics, barbiturates, sedatives potentiate CNS depression; anticoagulants, oral, may increase hypoprothrombinemic effect; ethchlorvynol, transient delirium; levodopa, sympathomimetics (e.g., epinephrine, norepinephrine), possibility of sympathetic hyperactivity with hypertension and hyperpyrexia; mao inhibitors, possibility of severe reactions, toxic psychosis, cardiovascular instability; methylphenidate increases plasma TCA levels; thyroid drugs may increase possibility of arrhythmias; cimetidine may increase plasma TCA levels. Herbal: Ginkgo may decrease seizure threshold, St. John's wort may cause serotonin syndrome.

Pharmacokinetics

Absorption: Rapidly from GI and injection sites. Peak: 2–12 h. Distribution: Crosses placenta. Metabolism: In liver to active metabolite; by CYP2D6. Elimination: Primarily in urine; enters breast milk. Half-Life: 10–50 h.

Nursing Implications

Assessment & Drug Effects

Monitor therapeutic effectiveness. It may take 1–6 wk to reduce attacks when used for migraine prophylaxis.
Monitor for S&S of drowsiness and dizziness (initial stages of therapy); institute measures to prevent falling. Also monitor for overdose or suicide ideation in patients who use excessive amounts of alcohol.
Lab tests: Baseline and periodic leukocyte and differential counts; renal and hepatic function tests; eye examinations (including glaucoma testing); recommended particularly for older adults, adolescents, and patients receiving high doses/prolonged therapy.
Monitor BP and pulse rate in patients with preexisting cardiovascular disease. Assess for orthostatic hypotension especially in older adults. Withhold drug if there is a rise or fall in systolic BP (by 10–20 mm Hg), or a sudden increase or a significant change in pulse rate or rhythm. Notify physician.
Monitor I&O, including bowel elimination pattern.

Patient & Family Education

Monitor weight; drug may increase appetite or a craving for sweets.
Understand that tolerance/adaptation to anticholinergic actions (see Appendix F) usually develops with maintenance regimen. Keep physician informed.
Relieve dry mouth by taking frequent sips of water and increasing total fluid intake.
Make position change slowly and in stages to prevent dizziness.
Do not drive or engage in potentially hazardous activities until response to drug is known.
Do not use OTC drugs without consulting physician while on TCA therapy; many preparations contain sympathomimetic amines.
Note: Amitriptyline may turn urine blue-green.

Common adverse effects in italic, life-threatening effects underlined; generic names in bold; classifications in SMALL CAPS; Canadian drug name; Prototype drug

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