amitriptyline hydrochloride

amitriptyline hydrochloride

(a mee trip' ti leen)

Endep (CAN), Tryptanol (CAN)

Pregnancy Category D

Drug class

TCA; tertiary amine

Therapeutic actions

Mechanism of action unknown; TCAs inhibit the reuptake of the neurotransmitters norepinephrine and serotonin, leading to an increase in their effects; anticholinergic at CNS and peripheral receptors; sedative.

Indications

·        Relief of symptoms of depression (endogenous most responsive); sedative effects may help when depression is associated with anxiety and sleep disturbance.

·        Unlabeled uses: Control of chronic pain (eg, intractable pain of cancer, central pain syndromes, peripheral neuropathies, postherpetic neuralgia, tic douloureux); prevention of onset of cluster and migraine headaches; treatment of pathologic weeping and laughing secondary to forebrain disease (due to MS), insomnia.

Contraindications and cautions

·        Contraindicated with hypersensitivity to any tricyclic drug; concomitant therapy with an MAOI; recent MI; myelography within previous 24 hr or scheduled within 48 hr; lactation.

·        Use cautiously with electroshock therapy; preexisting CV disorders (severe coronary heart disease, progressive heart failure, angina pectoris, paroxysmal tachycardia); angle-closure glaucoma, increased IOP, urinary retention, ureteral or urethral spasm; seizure disorders; hyperthyroidism; impaired hepatic, renal function; psychiatric patients (schizophrenic or paranoid patients may exhibit a worsening of psychosis with TCA therapy); manic-depressive patients; elective surgery (discontinue as long as possible before surgery).

Available forms

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

Dosages

May be given IM if patients are unable or unwilling to take oral drug. Switch to oral drug as soon as possible.

ADULTS

·        Depression, hospitalized patients: Initially, 100 mg/day PO in divided doses: gradually increase to 200–300 mg/day as required. May be given IM 20–30 mg qid, initially only in patients unable or unwilling to take drug PO. Replace with oral medication as soon as possible.

·        Depression, outpatients: Initially, 75 mg/day PO, in divided doses; may increase to 150 mg/day. Increases should be made in late afternoon or hs. Total daily dosage may be administered hs. Initiate single daily dose therapy with 50–100 mg hs; increase by 25–50 mg as necessary to a total of 150 mg/day. Maintenance dose is 40–100 mg/day, which may be given as a single bedtime dose. After satisfactory response, reduce to lowest effective dosage. Continue therapy for 3 mo or longer to lessen possibility of relapse.

·        Chronic pain: 75–150 mg/day PO.

·        Prevention of cluster or migraine headaches: 50–150 mg/day PO.

·        Prevention of weeping in MS patients with forebrain disease: 25–75 mg PO.

PEDIATRIC PATIENTS > 12 YR

10 mg tid PO and then 20 mg hs.

PEDIATRIC PATIENTS < 12 YR

Not recommended.

GERIATRIC PATIENTS

10 mg tid PO with 20 mg hs

Pharmacokinetics

Route	Onset	Peak	Duration
Oral	Varies	2–4 hr	2–4 wk

Metabolism: Hepatic; T_1/2: 10–50 hr

Distribution: Crosses placenta; enters breast milk

Excretion: Urine

Adverse effects

·        CNS: Disturbed concentration, sedation and anticholinergic (atropine-like) effects, confusion (especially in elderly), hallucinations, disorientation, decreased memory, feelings of unreality, delusions, anxiety, nervousness, restlessness, agitation, panic, insomnia, nightmares, hypomania, mania, exacerbation of psychosis, drowsiness, weakness, fatigue, headache, numbness, tingling, paresthesias of extremities, incoordination, motor hyperactivity, akathisia, ataxia, tremors, peripheral neuropathy, extrapyramidal symptoms, seizures, speech blockage, dysarthria, tinnitus, altered EEG

·        CV: Orthostatic hypotension, hypertension, syncope, tachycardia, palpitations, MI, arrhythmias, heart block, precipitation of CHF, CVA

·        Endocrine: Elevated or depressed blood sugar, elevated prolactin levels, inappropriate ADH secretion

·        GI: Dry mouth, constipation, paralytic ileus, nausea, vomiting, anorexia, epigastric distress, diarrhea, flatulence, dysphagia, peculiar taste, increased salivation, stomatitis, glossitis, parotid swelling, abdominal cramps, black tongue, hepatitis, jaundice (rare), elevated transaminase, altered alkaline phosphatase

·        GU: Urinary retention, delayed micturition, dilation of the urinary tract, gynecomastia, testicular swelling; breast enlargement, menstrual irregularity and galactorrhea; increased or decreased libido; impotence

·        Hematologic: Bone marrow depression, including agranulocytosis; eosinophilia, purpura, thrombocytopenia, leukopenia

·        Hypersensitivity: Rash, pruritus, vasculitis, petechiae, photosensitization, edema (generalized, face, tongue), drug fever

·        Withdrawal: Symptoms on abrupt discontinuation of prolonged therapy: nausea, headache, vertigo, nightmares, malaise

·        Other: Nasal congestion, excessive appetite, weight change; sweating, alopecia, lacrimation, hyperthermia, flushing, chills

Interactions

Drug-drug

·        Increased TCA levels and pharmacologic (especially anticholinergic) effects with cimetidine, fluoxetine

·        Increased TCA levels with methylphenidate, phenothiazines, hormonal contraceptives, disulfiram

·        Hyperpyretic crises, severe seizures, hypertensive episodes and deaths with MAOIs, furazolidone

·        Increased antidepressant response and cardiac arrhythmias with thyroid medication

·        Increased or decreased effects with estrogens

·        Delirium with disulfiram

·        Sympathetic hyperactivity, sinus tachycardia, hypertension, agitation with levodopa

·        Increased biotransformation of TCAs in patients who smoke cigarettes

·        Increased sympathomimetic (especially beta-adrenergic) effects of direct-acting sympathomimetic drugs (norepinephrine, epinephrine)

·        Increased anticholinergic effects of anticholinergic drugs (including anticholinergic antiparkisonians)

·        Increased response (especially CNS depression) to barbiturates

·        Decreased antihypertensive effect of guanethidine, clonidine, other antihypertensives

·        Decreased effects of indirect-acting sympathomimetic drugs (ephedrine)

Nursing considerations

Assessment

·        History: Hypersensitivity to any tricyclic drug; concomitant therapy with an MAOI; recent MI; myelography within previous 24 hr or scheduled within 48 hr; lactation; EST; preexisting CV disorders; angle-closure glaucoma, increased IOP, urinary retention, ureteral or urethral spasm; seizure disorders; hyperthyroidism; impaired hepatic, renal function; psychiatric patients; manic-depressive patients; elective surgery

·        Physical: Weight; T; skin color, lesions; orientation, affect, reflexes, vision and hearing; P, BP, orthostatic BP, perfusion; bowel sounds, normal output, liver evaluation; urine flow, normal output; usual sexual function, frequency of menses, breast and scrotal examination; LFTs, urinalysis, CBC, ECG

Interventions

·        Restrict drug access for depressed and potentially suicidal patients.

·        Give IM only when oral therapy is impossible.

·        Do not administer IV.

·        Administer major portion of dose at bedtime if drowsiness, severe anticholinergic effects occur (note that the elderly may not tolerate single daily dose therapy).

·        Reduce dosage if minor side effects develop; discontinue if serious side effects occur.

·        Arrange for CBC if patient develops fever, sore throat, or other sign of infection.

Teaching points

·        Take drug exactly as prescribed; do not stop abruptly or without consulting health care provider.

·        Avoid using alcohol, other sleep-inducing drugs, over-the-counter drugs.

·        Avoid prolonged exposure to sunlight or sunlamps; use a sunscreen or protective garments.

·        You may experience these side effects: Headache, dizziness, drowsiness, weakness, blurred vision (reversible; if severe, avoid driving and tasks requiring alertness while these persist); nausea, vomiting, loss of appetite, dry mouth (eat frequent small meals; use frequent mouth care and suck on sugarless candies); nightmares, inability to concentrate, confusion; changes in sexual function.

·        Report dry mouth, difficulty in urination, excessive sedation.

Adverse effects in Italic are most common; those in Bold are life-threatening.