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Protriptyline Hydrochloride

Pronunciation: proe-TRIP-ti-leen HYE-droe-KLOR-ide
Class: Tricyclic compound

Trade Names

- Tablets 5 mg
- Tablets 10 mg


Inhibits reuptake of norepinephrine and serotonin in CNS.

Slideshow: Depression, the Risk of Suicide, and Treatment Options



Well absorbed from GI tract and rapidly sequestered into tissues. T max is 8 to 12 h. Steady state is 14 to 19 days.


Widely distributed into tissues, including CNS. Penetrates into the brain rapidly. Small amounts are found in breast milk. Protein binding is 90% in plasma and tissues. Vd is 22 L/kg.


Metabolized in the liver by demethylation of secondary amine moiety.


In the urine (small amounts unchanged). The t ½ is 67 to 89 h.


2 to 3 wk (antidepressant effect).

Indications and Usage

Relief of symptoms of mental depression in patients who are under close medical supervision.

Unlabeled Uses

Obstructive sleep apnea; panic disorder.


Hypersensitivity to tricyclic antidepressants; generally not to be given in combination with an MAOI or within 14 days of treatment with MAOIs; during acute recovery phase of MI; coadministration with cisapride.

Dosage and Administration


PO 15 to 60 mg/day in divided doses. The maintenance dose may be given as a single dose.

Elderly and Adolescents

PO Initial dosage is 5 mg 3 times daily. Increase slowly if needed (max, 20 mg/day).

General Advice

  • Administer without regard to meals; administer with food if GI upset occurs.


Store at 68° to 77°F in tightly closed, light-resistant container.

Drug Interactions

Anticholinergic agents, neuroleptic agents

Risk of hyperpyrexia may be increased, especially during hot weather.

Cimetidine, fluoxetine

Increased protriptyline blood levels and effects.

Cisapride, sparfloxacin

Contraindicated in patients receiving tricyclic antidepressants.


Hypertensive crisis.

CNS depressants

Additive depressant effects.

Drugs inhibiting CYP2D6 (eg, amiodarone, fluoxetine, quinidine)

Protriptyline plasma levels may be elevated, increasing the risk of adverse reactions.


Inhibition of hypotensive action by guanethidine.


Death, hyperexcitability, hyperthermia, and seizures may occur.

Sympathomimetics, direct-acting (eg, norepinephrine, phenylephrine)

Increased pressor response.

Sympathomimetics, indirect-acting (eg, dopamine, ephedrine)

Decreased pressor response.


Risk of seizures may be increased.

Laboratory Test Interactions

None well documented.

Adverse Reactions


Arrhythmias, CHF, ECG changes, heart block, hypertension, MI, orthostatic hypotension, palpitations, stroke, tachycardia.


Agitation, anxiety, ataxia, confusion, delusions, disorientation, dizziness, drowsiness, emotional lability, exacerbation of psychosis, extrapyramidal symptoms, fatigue, hallucinations, headache, incoordination, increased and decreased libido, insomnia, mania, nervousness, nightmares, numbness, panic, paresthesia, peripheral neuropathy, restlessness, seizures, stinging, tremors, weakness.


Acne, alopecia, dry skin, flushing, itching, perspiration, petechiae, photosensitivity reaction, pruritus, rash, urticaria.


Blurred vision, increased IOP, mydriasis, peculiar taste, tinnitus.


Abdominal cramps, anorexia, black tongue, constipation, diarrhea, dry mouth, flatulence, GI distress, nausea, paralytic ileus, peculiar taste, stomatitis, vomiting.


Amenorrhea, breast enlargement and galactorrhea in women, dilatation of the urinary tract, dysmenorrhea, gynecomastia in men, impotence, nocturia, sexual dysfunction, testicular swelling, urinary frequency, urinary retention and hesitancy.


Bone marrow depression (including agranulocytosis), eosinophilia, leukopenia, purpura, thrombocytopenia.


Altered LFTs, jaundice.


Edema, elevation or depression of blood glucose, SIADH, weight gain or loss.


Cough, laryngitis, pharyngitis, rhinitis, sinusitis.


Drug fever, hyperpyrexia, parotid swelling.



Antidepressants increased the risk of suicidal thinking and behavior in short-term studies in children and adolescents with major depressive disorder and other psychiatric disorders. Closely observe patients who are started on therapy for clinical worsening, suicidality, or unusual changes in behavior.




Excreted in breast milk.


Safety and efficacy not established.

Special Risk Patients

Use with caution in patients with history of seizures, urinary retention, urethral or ureteral spasm, angle-closure glaucoma or increased IOP, CV disorders, hyperthyroidism or those receiving thyroid medication, hepatic or renal function impairment, or schizophrenia or paranoia.

Anticholinergic effects

Additive with other medications with anticholinergic effects.


Psychotic symptoms may be aggravated.


Observe adults and children treated with antidepressants for clinical worsening, suicidality, and unusual changes in behavior. Prescribe the smallest quantity consistent with good patient management to reduce the risk of overdose.

Tachycardia/Postural hypotension

May occur more frequently with protriptyline.



Cardiac arrhythmias, CNS stimulation (eg, agitation, delirium, irritability) followed by depression (eg, drowsiness to coma), hyperpyrexia followed by hypothermia, hypertension followed by hypotension, seizures.

Patient Information

  • Advise patient to read the Medication Guide before using product the first time and with each refill.
  • Explain that therapeutic effect of drug may be seen within 2 to 5 days, but full effectiveness of drug may not occur for 2 to 3 wk.
  • Tell patient that dosage will be tapered slowly before stopping to prevent withdrawal symptoms.
  • Warn patient to monitor food intake; weight gain can occur because of increased appetite.
  • Instruct patient to report the following symptoms to health care provider: mental status changes (especially increase in depression or panic); urinary retention and extrapyramidal symptoms (frequently noted in elderly patients), such as rigidity or fine hand tremors; or visual disturbances.
  • Advise patient and caregiver to be alert for abnormal changes in mood or thinking. The following symptoms should be reported immediately to the health care provider: agitation, anxiety, hostility or aggression, impulsivity, irritability, panic attacks, suicidal thoughts and behavior.
  • Advise patient to take sips of water frequently, to suck on ice chips or sugarless hard candy, or chew sugarless gum to relieve dry mouth.
  • Caution patient to avoid sudden position changes to avoid dizziness.
  • Instruct patient to avoid alcoholic beverages or other CNS depressants while taking this medicine.
  • Advise patient that drug may cause drowsiness and to use caution while driving or performing other activities requiring mental alertness.
  • Caution patient to avoid exposure to sunlight and to use sunscreen or wear protective clothing to avoid photosensitivity reaction.

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