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Desipramine Hydrochloride

Pronouncation: (des-IP-ra-meen HYE-droe-KLOR-ide)
Class: Tricyclic compound

Trade Names:
Norpramin
- Tablets 10 mg
- Tablets 25 mg
- Tablets 50 mg
- Tablets 75 mg
- Tablets 100 mg
- Tablets 150 mg

Apo-Desipramine (Canada)
PMS-Desipramine (Canada)
ratio-Desipramine (Canada)

Pharmacology

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Inhibits reuptake of norepinephrine and serotonin in CNS.

Pharmacokinetics

Absorption

Rapidly absorbed.

Metabolism

Metabolized in the liver.

Elimination

Approximately 70% excreted in the urine. The t _½ is 12 to 24 h.

Onset

2 to 5 days.

Peak

2 to 3 wk.

Special Populations

Elderly

Rate of metabolism is slower. Dosage adjustment is recommended.

Indications and Usage

Relief of symptoms of depression.

Unlabeled Uses

Alcohol dependence and major secondary depression, anxiety, attention deficit hyperactivity disorder, bulimia nervosa, enuresis, diabetic neuropathy, Tourette syndrome.

Contraindications

Hypersensitivity to any tricyclic antidepressant; in combination with or within 14 days of treatment with an MAOI (cross-sensitivity may occur across the dibenzazepines); during acute recovery phases of MI.

Dosage and Administration

Adults

PO 100 to 300 mg/day. May be given in divided doses or once daily at bedtime.

Elderly and Adolescent Patients

PO 25 to 150 mg/day.

General Advice

Initiate therapy at a low dose level and increase the dose according to tolerance and clinical response.
Initial therapy may be given in divided doses or as a single daily dose.
Maintenance therapy may be given on a once-daily schedule for convenience and compliance.

Storage/Stability

Store at room temperature, preferably below 30°C (86°F). Protect from excessive heat. Dispense in tight container.

Drug Interactions

Barbiturates, carbamazepine, charcoal

May decrease desipramine effects.

Cisapride, sparfloxacin

These agents are contraindicated in patients receiving desipramine because of the increased risk of life-threatening cardiac arrhythmias resulting from prolongation of the QT interval.

Clonidine

May result in hypertensive crisis.

CNS depressants

CNS and respiratory effects may be increased.

Drugs that inhibit CYP2D6 (eg, cimetidine, flecainide, fluoxetine, haloperidol, hormonal contraceptives, paroxetine, phenothiazines, propafenone, quinidine, sertraline, terbinafine, venlafaxine)

Desipramine plasma levels may be elevated, increasing the pharmacologic effects and adverse reactions.

Guanethidine

The hypotensive action of guanethidine may be inhibited.

Gatifloxacin, levofloxacin, moxifloxacin

Coadministration of desipramine and levofloxacin should be avoided, while gatifloxacin and moxifloxacin should be used with caution. The risk of life-threatening cardiac arrhythmias may be increased.

MAOIs

Hyperpyretic crises, severe convulsions, and death may occur if administered together or within 14 days of each other.

Sympathomimetics (eg, epinephrine)

The pressor response to direct- and indirect-acting sympathomimetics may be increased or decreased, respectively.

Valproic acid

Desipramine plasma levels may be elevated, increasing the pharmacologic effects and adverse reactions.

Laboratory Test Interactions

None well documented.

Adverse Reactions

Cardiovascular

Arrhythmias; flushing; heart block; hypertension; hypotension; MI; palpitations; PVCs; stroke; sudden death; tachycardia; ventricular fibrillation.

CNS

Agitation; alterations in EEG patterns; anxiety; ataxia; confusion; delusions; disorientation; drowsiness; exacerbation of psychosis; extrapyramidal symptoms; fatigue; hallucinations; headache; hypomania; incoordination; insomnia; nightmares; NMS symptoms; numbness; paresthesias of extremities; peripheral nephropathy; restlessness, seizures; tingling; tremors; weakness.

Dermatologic

Alopecia; itching; petechiae; photosensitization; skin rash; urticaria.

EENT

Blurred vision; disturbances in accommodation; increased intraocular pressure; mydriasis; tinnitus.

GI

Abdominal cramps; anorexia; black tongue; constipation; diarrhea; dry mouth; epigastric distress; increased pancreatic enzymes; nausea; paralytic ileus; peculiar taste; stomatitis; sublingual adenitis; vomiting.

Genitourinary

Breast enlargement and galactorrhea in women; decreased or increased libido; delayed micturition; dilation of the urinary tract; gynecomastia in men; impotence; nocturia; painful ejaculation; testicular swelling; urinary frequency; urinary retention.

Hematologic-Lymphatic

Bone marrow depression, including agranulocytosis; eosinophilia; purpura; thrombocytopenia.

Hepatic

Altered hepatic function; hepatitis; jaundice.

Lab Tests

Elevated alkaline phosphatase; elevated liver function tests.

Metabolic-Nutritional

Elevation or depression of blood glucose levels; SIADH; weight gain or loss.

Miscellaneous

Acute collapse; drug fever; edema; fever; parotid swelling; proneness to falling; sudden death; sweating; withdrawal symptoms, including headache, malaise, and nausea.

Precautions

Warnings

Increased risk of suicidal thinking and behavior has been observed in children, adolescents, and young adults taking antidepressants for major depressive disorders and other psychiatric disorders. Monitor patients of all ages who are started on antidepressant therapy appropriately and observe them closely for clinical worsening, suicidality, or unusual changes in behavior. Advise families and caregivers of the need for close observation and communication with the health care provider.

Monitor

Monitor renal function in elderly patients.

Pregnancy

Category C .

Lactation

Excreted in breast milk.

Children

Safety and efficacy not established. Sudden death has been reported in children taking desipramine.

Elderly

Use with caution because of the greater incidence of renal function impairment in elderly patients.

Special Risk Patients

Use drug with caution in patients with history of seizures, urinary retention, urethral or ureteral spasm, angle-closure glaucoma, increased intraocular pressure, or CV disorders; in patients receiving thyroid medication; and in patients who have hepatic or renal function impairment, schizophrenia, or paranoia.

Elective surgery

Because of CV effects, discontinue desipramine as soon as possible prior to elective surgery.

Glucose levels

Both increased and decreased blood sugar levels may occur.

Overdose consideration

Prescribe the smallest quantity consistent with good patient management in order to reduce the risk of overdose.

Psychosis

May be exacerbated.

Schizophrenia

May be exacerbated.

Overdosage

Symptoms

Agitation, cardiac arrhythmias, choreoathetosis, clonus, coma, confusion, dilated pupils, dry mouth, flushing, hallucinations, hyperactive reflexes, hyperpyrexia, positive Babinski signs, renal failure, seizures, status epilepticus.

Patient Information

Warn patient of risk of seizure.
Instruct patient to keep weekly record of weight.
Teach patient how to take BP and heart rate.
Explain missed medication procedure: less than 2 h, take medication; longer than 2 h, wait until next scheduled dose. Instruct patients not to double doses.
Teach proper techniques for oral hygiene to help prevent/treat dry mucous membranes.
Tell patient to increase fluid intake.
Inform men of possible sexual dysfunction.
Tell patient of possible difficult urination.
Instruct patient to avoid intake of alcoholic beverages or other CNS depressants.
Advise patient that drug may cause drowsiness and to use caution while driving or performing other tasks requiring mental alertness.
Advise patient to complete full course of therapy; may take 4 to 6 wk to see full benefits.
Advise patient that medication may cause photosensitization and to avoid unnecessary exposure to sunlight or tanning lamps, and to use sunscreens and wear protective clothing to avoid photosensitivity reactions.