No

Antidepressant, Tricyclic (Secondary Amine)

Treatment of symptoms of depression

D

Hypersensitivity to this drug and similar chemical class; use of monoamine oxidase inhibitors within 14 days; use in a patient during the acute recovery phase of MI

May cause sedation, resulting in impaired performance of tasks requiring alertness (ie, operating machinery or driving). Sedative effects may be additive with other CNS depressants and/or ethanol. The degree of sedation is low-moderate relative to other antidepressants. May worsen psychosis in some patients or precipitate a shift to mania or hypomania in patients with bipolar disease. May increase the risks associated with electroconvulsive therapy. This agent should be discontinued, when possible, prior to elective surgery. Therapy should not be abruptly discontinued in patients receiving high doses for prolonged periods. May alter glucose regulation - use caution in patients with diabetes.

Use caution in patients with depression, particularly if suicidal risk may be present. Use with caution in patients with a history of cardiovascular disease (including previous MI, stroke, tachycardia, or conduction abnormalities). The risk of conduction abnormalities with this agent is moderate relative to other antidepressants. Use caution in patients with a previous seizure disorder or condition predisposing to seizures such as brain damage, alcoholism, or concurrent therapy with other drugs which lower the seizure threshold. Use with caution in hyperthyroid patients or those receiving thyroid supplementation. Use with caution in patients with hepatic or renal dysfunction and in elderly patients.

Cardiovascular: Postural hypotension, arrhythmias, hypertension, heart block, tachycardia, palpitations, myocardial infarction

Central nervous system: Confusion, delirium, hallucinations, restlessness, insomnia, disorientation, delusions, anxiety, agitation, panic, nightmares, hypomania, exacerbation of psychosis, incoordination, ataxia, extrapyramidal symptoms, seizures

Dermatologic: Alopecia, photosensitivity, rash, petechiae, urticaria, itching

Endocrine & metabolic: Sexual dysfunction, gynecomastia, breast enlargement, galactorrhea, increase or decrease in libido, increase in blood sugar, SIADH

Gastrointestinal: Xerostomia, constipation, vomiting, anorexia, diarrhea, abdominal cramps, black tongue, nausea, unpleasant taste, weight gain or loss

Genitourinary: Urinary retention, delayed micturition, impotence, testicular edema

Hematologic: Rarely agranulocytosis, eosinophilia, purpura, thrombocytopenia

Hepatic: Increased liver enzymes, cholestatic jaundice

Neuromuscular & skeletal: Tremor, numbness, tingling, paresthesias, peripheral neuropathy

Ocular: Blurred vision, eye pain, disturbances in accommodation, mydriasis

Otic: Tinnitus

Miscellaneous: Diaphoresis (excessive), allergic reactions

Symptoms of overdose include agitation, confusion, hallucinations, urinary retention, hypothermia, hypotension, seizures, ventricular tachycardia

Following initiation of essential overdose management, toxic symptoms should be treated. Sodium bicarbonate is indicated when QRS interval is >0.10 seconds or QT_c >0.42 seconds. Ventricular arrhythmias and EKG changes (QRS widening) often respond to phenytoin 15-20 mg/kg (adults) with concurrent systemic alkalinization (sodium bicarbonate 0.5-2 mEq/kg I.V.). Arrhythmias unresponsive to this therapy may respond to lidocaine 1 mg/kg I.V. followed by a titrated infusion. Physostigmine (1-2 mg I.V. slowly for adults or 0.5 mg I.V. slowly for children) may be indicated in reversing cardiac arrhythmias that are life-threatening. Seizures usually respond to diazepam I.V. boluses (5-10 mg for adults up to 30 mg or 0.25-0.4 mg/kg/dose for children up to 10 mg/dose). If seizures are unresponsive or recur, phenytoin or phenobarbital may be required.

CYP1A2 and 2D6 enzyme substrate

Nortriptyline inhibits the antihypertensive response to bethanidine, clonidine, debrisoquin, guanadrel, guanethidine, guanabenz, guanfacine; monitor BP; consider alternate antihypertensive agent

Abrupt discontinuation of clonidine may cause hypertensive crisis, nortriptyline may enhance the response

Use with altretamine may cause orthostatic hypertension

Nortriptyline may be additive with or may potentiate the action of other CNS depressants (sedatives, hypnotics, or ethanol); with MAO inhibitors, hyperpyrexia, hypertension, tachycardia, confusion, seizures, and deaths have been reported (serotonin syndrome), this combination should be avoided

Nortriptyline may increase the prothrombin time in patients stabilized on warfarin

Cimetidine and methylphenidate may decrease the metabolism of nortriptyline

Additive anticholinergic effects seen with other anticholinergic agents

The SSRIs, to varying degrees, inhibit the metabolism of TCAs and clinical toxicity may result

Use of lithium with a TCA may increase the risk for neurotoxicity

Phenothiazines may increase concentration of some TCAs and TCAs may increase concentration of phenothiazines; monitor for altered clinical response

TCAs may enhance the hypoglycemic effects of tolazamide, chlorpropamide, or insulin; monitor for changes in blood glucose levels

Cholestyramine and colestipol may bind TCAs and reduce their absorption; monitor for altered response

TCAs may enhance the effect of amphetamines; monitor for adverse CV effects

Verapamil and diltiazem appear to decrease the metabolism of imipramine and potentially other TCAs; monitor for increased TCA concentrations. The pressor response to I.V. epinephrine, norepinephrine, and phenylephrine may be enhanced in patients receiving TCAs, this combination is best avoided.

Grapefruit juice, amprenavir, indinavir, ritonavir may inhibit the metabolism of clomipramine and potentially other TCAs; monitor for altered effects; a decrease in TCA dosage may be required

Quinidine may inhibit the metabolism of TCAs; monitor for altered effect

Combined use of anticholinergics with TCAs may produce additive anticholinergic effects; combined use of beta-agonists with TCAs may predispose patients to cardiac arrhythmias

Protect from light

Traditionally believed to increase the synaptic concentration of serotonin and/or norepinephrine in the central nervous system by inhibition of their reuptake by the presynaptic neuronal membrane. However, additional receptor effects have been found including desensitization of adenyl cyclase, down regulation of beta-adrenergic receptors, and down regulation of serotonin receptors.

Onset of action: 1-3 weeks before therapeutic effects are seen

Distribution: V_d: 21 L/kg

Protein binding: 93% to 95%

Metabolism: Undergoes significant first-pass metabolism; primarily detoxified in the liver

Half-life: 28-31 hours

Time to peak serum concentration: Oral: Within 7-8.5 hours

Elimination: As metabolites and small amounts of unchanged drug in urine; small amounts of biliary elimination occur

Oral:

Children:

6-7 years (20-25 kg): 10 mg/day

8-11 years (25-35 kg): 10-20 mg/day

>11 years (35-54 kg): 25-35 mg/day

Depression:

Adolescents: 30-50 mg/day in divided doses

Adults: 25 mg 3-4 times/day up to 150 mg/day

Elderly ( Note: Nortriptyline is one of the best tolerated TCAs in the elderly)

Initial: 10-25 mg at bedtime

Dosage can be increased by 25 mg every 3 days for inpatients and weekly for outpatients if tolerated

Usual maintenance dose: 75 mg as a single bedtime dose, however, lower or higher doses may be required to stay within the therapeutic window

Dosing adjustment in hepatic impairment: Lower doses and slower titration dependent on individualization of dosage is recommended

Alcohol: Additive CNS effect, avoid use

Monitor blood pressure and pulse rate prior to and during initial therapy; evaluate mental status; monitor weight

Plasma levels do not always correlate with clinical effectiveness

Therapeutic: 50-150 ng/mL (SI: 190-570 nmol/L)

Toxic: >500 ng/mL (SI: >1900 nmol/L)

glucose

Use with caution; epinephrine, norepinephrine and levonordefrin have been shown to have an increased pressor response in combination with TCAs

>10% of patients experience dry mouth; long-term treatment with TCAs such as nortriptyline increases the risk of caries by reducing salivation and salivary buffer capacity

Oral: Take exactly as directed (do not increase dose or frequency); may take 2-3 weeks to achieve desired results; may cause physical and/or psychological dependence. Take once-a-day dose at bedtime. Avoid excessive alcohol, caffeine, and other prescription or OTC medications not approved by prescriber. Maintain adequate hydration (2-3 L/day of fluids unless instructed to restrict fluid intake). You may experience drowsiness, lightheadedness, impaired coordination, dizziness, or blurred vision (use caution when driving or engaging in tasks requiring alertness until response to drug is known); nausea, vomiting, altered taste, dry mouth (small frequent meals, frequent mouth care, chewing gum, sucking lozenges may help); constipation (increased exercise, fluids, or dietary fruit and fiber may help); diarrhea (buttermilk, yogurt, or boiled milk may help); increased appetite (monitor dietary intake to avoid excess weight gain); postural hypotension (use caution when climbing stairs or changing position from lying or sitting to standing); urinary retention (void before taking medication); or sexual dysfunction (reversible). Report persistent CNS effects (eg, insomnia, nervousness, restlessness, hallucinations, daytime sedation, impaired cognitive function); muscle cramping or tremors; chest pain, palpitations, rapid heartbeat, swelling of extremities, or severe dizziness; blurred vision or eye pain; yellowing of eyes or skin; pale stools/dark urine; or worsening of condition. Pregnancy/breast-feeding precautions: Do not get pregnant while taking this medication; use appropriate barrier contraceptive measures. Do not breast-feed.

May increase appetite and possibly a craving for sweets

Capsule, as hydrochloride: 10 mg, 25 mg, 50 mg, 75 mg

Solution, as hydrochloride: 10 mg/5 mL (473 mL)

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