No

Antidepressant, Tricyclic (Secondary Amine)

Treatment of depression

C

Hypersensitivity to protriptyline (cross-reactivity to other cyclic antidepressants may occur); 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 relative to other antidepressants. May worsen psychosis in some patients or precipitate a shift to mania or hypomania in patients with bipolar disease. In addition, may aggravate aggressive behavior. 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 with 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-high 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: Arrhythmias, hypotension, myocardial infarction, stroke, heart block, hypertension, tachycardia, palpitations

Central nervous system: Dizziness, drowsiness, headache, confusion, delirium, hallucinations, restlessness, insomnia, nightmares, fatigue, delusions, anxiety, agitation, hypomania, exacerbation of psychosis, panic, seizures, incoordination, ataxia, EPS

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

Endocrine & metabolic: Breast enlargement, galactorrhea, SIADH, gynecomastia, increased or decreased libido

Gastrointestinal: Xerostomia, constipation, unpleasant taste, weight gain, increased appetite, nausea, diarrhea, heartburn, vomiting, anorexia, weight loss, trouble with gums, decreased lower esophageal sphincter tone may cause GE reflux

Genitourinary: Difficult urination, impotence, testicular edema

Hematologic: Agranulocytosis, leukopenia, eosinophilia, thrombocytopenia, purpura

Hepatic: Cholestatic jaundice, increased liver enzymes

Neuromuscular & skeletal: Fine muscle tremors, weakness, tremor, numbness, tingling

Ocular: Blurred vision, eye pain, increased intraocular pressure

Otic: Tinnitus

Miscellaneous: Diaphoresis (excessive), allergic reactions

Symptoms of overdose include confusion, hallucinations, urinary retention, hypotension, tachycardia, seizures, hyperthermia

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 often respond to 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.

Carbamazepine, phenobarbital, and rifampin may increase the metabolism of protriptyline resulting in decreased effect of protriptyline

Protriptyline 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, protriptyline may enhance the response

Use with altretamine may cause orthostatic hypertension

Protriptyline 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

Protriptyline may increase the prothrombin time in patients stabilized on warfarin

Cimetidine and methylphenidate may decrease the metabolism of protriptyline

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

Increases the synaptic concentration of serotonin and/or norepinephrine in the central nervous system by inhibition of their reuptake by the presynaptic neuronal membrane

Maximum antidepressant effect: 2 weeks of continuous therapy is commonly required

Distribution: Crosses the placenta

Protein binding: 92%

Metabolism: Undergoes first-pass metabolism (10% to 25%); extensively metabolized in the liver by N-oxidation, hydroxylation and glucuronidation

Half-life: 54-92 hours, averaging 74 hours

Time to peak serum concentration: Oral: Within 24-30 hours

Elimination: In urine

Oral:

Adults: 15-60 mg in 3-4 divided doses

Elderly: 15-20 mg/day

May be administered with food to decrease GI distress

Make any dosage increase in the morning dose

Therapeutic: 70-250 ng/mL (SI: 266-950 nmol/L); Toxic: >500 ng/mL (SI: >1900 nmol/L)

glucose

No information available to require special precautions

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

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. 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, or 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: Inform prescriber if you are or intend to be pregnant. Breast-feeding is not recommended.

Offer patient sugarless hard candy or gum for dry mouth

Tablet, as hydrochloride: 5 mg, 10 mg

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Larochelle P, Hamet P, and Enjalbert M, "Responses to Tyramine and Norepinephrine After Imipramine and Trazodone," Clin Pharmacol Ther, 1979, 26(1):24-30.

Mitchell JR, "Guanethidine and Related Agents. III Antagonism by Drugs Which Inhibit the Norepinephrine Pump in Man," J Clin Invest, 1970, 49(8):1596-604.

Roose SP, Glassman AH, Attia E, et al, "Comparative Efficacy of Selective Serotonin Reuptake Inhibitors and Tricyclics in the Treatment of Melancholia," Am J Psychiatry, 1994, 151(12):1735-9.

Rundegren J, van Dijken J, Mörnstad H, et al, "Oral Conditions in Patients Receiving Long-Term Treatment With Cyclic Antidepressant Drugs," Swed Dent J, 1985, 9(2):55-64.

Svedmyr N, "The Influence of a Tricyclic Antidepressive Agent (Protriptyline) on Some of the Circulatory Effects of Noradrenaline and Adrenalin in Man," Life Sci, 1968, 7(1):77-84.