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Desipramine Hydrochloride

Pronunciation

Class: Tricyclics and Other Norepinephrine-reuptake Inhibitors
VA Class: CN601
CAS Number: 58-28-6
Brands: Norpramin

Warning(s)

  • Suicidality
  • Antidepressants may increase risk of suicidal thinking and behavior (suicidality) in children, adolescents, and young adults (18–24 years of age) with major depressive disorder and other psychiatric disorders; balance this risk with clinical need.108 109 Desipramine is not approved for use in pediatric patients.104 (See Pediatric Use under Cautions.)

  • In pooled data analyses, risk of suicidality was not increased in adults >24 years of age and apparently was reduced in adults ≥65 years of age with antidepressant therapy compared with placebo.108 109

  • Depression and certain other psychiatric disorders are themselves associated with an increased risk of suicide.108 109 110

  • Appropriately monitor and closely observe all patients who are started on desipramine therapy for clinical worsening, suicidality, or unusual changes in behavior; involve family members and/or caregivers in this process. 108 109 110 (See Worsening of Depression and Suicidality Risk under Cautions.)

Introduction

Tricyclic antidepressant (TCA);104 active metabolite of imipramine.a c e

Uses for Desipramine Hydrochloride

Major Depressive Disorder

Management of major depressive disorder.104

Results of several studies of TCAs in preadolescent and adolescent patients with major depression indicate lack of overall efficacy in this age group.

Panic Disorder

Has been used for the management of panic disorder with or without agoraphobia.a

Eating Disorders

Has been used for the management of eating disorders (e.g., bulimia, anorexia nervosa) with equivocal results; avoid use in underweight individuals and in those exhibiting suicidal ideation.a

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

Bipolar Disorder

Has been used for the short-term management of acute depressive episodes in bipolar disorder.a b

TCAs associated with a greater risk of precipitating hypomania or manic episodes than other classes of antidepressants;a b should always be used in combination with a mood stabilizer (e.g., lithium).b

Schizophrenia

Has been used for the management of acute depressive episodes (in combination with an antipsychotic) in patients with schizophrenia.a

Postherpetic Neuralgia

Among the drugs of choice for the symptomatic treatment of postherpetic neuralgia.a

Insomnia

Less effective for insomnia and associated with more serious adverse reactions than conventional hypnotics.a

Attention Deficit Hyperactivity Disorder (ADHD)

Not recommended for use in children with ADHD.101 102 103 (See Pediatric Use under Cautions.)

Desipramine Hydrochloride Dosage and Administration

General

  • Allow at least 2 weeks to elapse between discontinuance of therapy with an MAO inhibitor and initiation of desipramine and vice versa.104 Also allow at least 5 weeks to elapse when switching from fluoxetine.104

  • Monitor for possible worsening of depression, suicidality, or unusual changes in behavior, especially at the beginning of therapy or during periods of dosage adjustments.108 109 110 (See Worsening of Depression and Suicidality Risk under Cautions.)

  • Sustained therapy may be required; administer lowest effective dosage and monitor periodically for need for continued therapy.104

  • Avoid abrupt discontinuance in patients receiving high dosages for prolonged periods.104 a To avoid withdrawal reactions, taper dosage gradually.104 a

Administration

Oral Administration

Initially, administer in up to 3 divided doses or as a single daily dose at bedtime (to avoid daytime sedation) or in the morning (to avoid insomnia and/or stimulation from the drug); for maintenance therapy, may be given as a single daily dose for patient compliance and convenience.112 c

Administer desipramine hydrochloride dosages of 300 mg daily in a hospital setting, where regular visits by the physician, skilled nursing care, and frequent ECGs are available.104

Dosage

Available as desipramine hydrochloride; dosage is expressed in terms of the salt.c

Pediatric Patients

Major Depressive Disorder
Oral

Adolescents ≥12 years of age: Initially, 25–50 mg daily.c Increase dosage gradually until maximal therapeutic effect with minimal toxicity is achieved or up to a maximum dosage of 100 mg daily.104 (See Pediatric Use under Cautions.)

Usual dosage: 25–100 mg daily.104 Dosage may be further increased to 150 mg daily, if necessary, in more seriously ill patients.104

After symptoms are controlled, gradually reduce dosage to the lowest level that will maintain relief of symptoms.c

Adults

Major Depressive Disorder
Oral

Initially, 75–150 mg daily, depending on the severity of the condition being treated.c Increase dosage gradually until maximal therapeutic effect with minimal toxicity is achieved.c

Usual dosage: 100–200 mg daily.104 Dosage may be further increased to 300 mg daily, if necessary, in more seriously ill patients.104

After symptoms are controlled, gradually reduce dosage to the lowest level that will maintain relief of symptoms.c

Prescribing Limits

Pediatric Patients

Major Depressive Disorder
Oral

Adolescents ≥12 years of age: Maximum 150 mg daily.104

Adults

Major Depressive Disorder
Oral

Maximum 300 mg daily.104

Special Populations

Geriatric Patients

Initially, 25–50 mg daily.c Increase dosage gradually until maximal therapeutic effect with minimal toxicity is achieved or up to a usual maximum dosage of 100 mg daily.104

Usual dosage: 25–100 mg daily.104 Dosage may be further increased to 150 mg daily, if necessary, in more seriously ill patients.104

After symptoms are controlled, gradually reduce dosage to the lowest level that will maintain relief of symptoms.c

Cautions for Desipramine Hydrochloride

Contraindications

  • Concurrent or recent (i.e., within 2 weeks) therapy with an MAO inhibitor.104 (See Specific Drugs under Interactions.)

  • During the acute recovery phase following MI.104

  • Known hypersensitivity to desipramine.104 (See Cross-Hypersensitivity under Cautions.)

Warnings/Precautions

Warnings

Worsening of Depression and Suicidality Risk

Possible worsening of depression and/or emergence of suicidal ideation and behavior (suicidality) or unusual changes in behavior in both adult and pediatric patients with major depressive disorder, whether or not they are taking antidepressants; may persist until clinically important remission occurs.108 109 110 111 However, suicide is a known risk of depression and certain other psychiatric disorders, and these disorders themselves are the strongest predictors of suicide.108 109 110

Appropriately monitor and closely observe patients receiving desipramine for any reason, particularly during initiation of therapy (i.e., the first few months) and during periods of dosage adjustments.108 109 110 (See Boxed Warning and also see Pediatric Use under Cautions.)

Anxiety, agitation, panic attacks, insomnia, irritability, hostility, aggressiveness, impulsivity, akathisia, hypomania, and/or mania may be precursors to emerging suicidality.109 110 Consider changing or discontinuing therapy in patients whose depression is persistently worse or in those with emerging suicidality or symptoms that might be precursors to worsening depression or suicidality, particularly if severe, abrupt in onset, or not part of patient’s presenting symptoms.108 109 110 (See General under Dosage and Administration.)

Prescribe in smallest quantity consistent with good patient management to reduce risk of overdosage.104 109

Observe these precautions for patients with psychiatric (e.g., major depressive disorder, obsessive-compulsive disorder [OCD]) or nonpsychiatric disorders.109

Bipolar Disorder

May unmask bipolar disorder.109 (See Activation of Mania or Hypomania under Cautions.) Desipramine is not approved for use in treating bipolar depression.104

Screen for risk of bipolar disorder by obtaining detailed psychiatric history (e.g., family history of suicide, bipolar disorder, depression) prior to initiating therapy.109

Cardiovascular Effects

Possible conduction defects, arrhythmias, tachycardia, strokes, and acute MI; use with extreme caution in patients with preexisting cardiovascular disease.112 Monitor such patients closely (e.g., perform ECG at baseline and as appropriate during therapy).a Also use with extreme caution in patients with a family history of sudden death, cardiac dysrhythmias, or cardiac conduction disturbances.112 113 114

Use with caution in patients with disturbed eating behaviors (e.g., purging) that result in inadequate hydration and/or compromised cardiac status.a

Toxicity in Overdosage

Overdosage of desipramine has resulted in a higher death rate compared with overdosages of other tricyclic antidepressants.112 113 114 115

Interactions

May block hypotensive actions of guanethidine and similar agents.104

May enhance effects of alcohol, sedative/hypnotics, and other CNS depressants.104 Use with caution in patients with a history of excessive alcohol consumption.104

Anticholinergic Effects

Use with extreme caution in patients for whom excess anticholinergic activity could be harmful (e.g., history of urinary retention, increased intraocular pressure, angle-closure glaucoma).104

Seizures

Risk of seizures; use with extreme caution in patients with a history of seizure disorder.112 In some patients, seizures precede cardiac dysrhythmias and death.112 113 114

Hyperthyroidism

Possible cardiovascular toxicity (e.g., arrhythmias); use with extreme caution in patients with thyroid disease or patients receiving thyroid agents.112

Cognitive/Physical Impairment

Performance of activities requiring mental alertness and physical coordination may be impaired.104

Sensitivity Reactions

Cross-Hypersensitivity

Possible cross sensitivity to other dibenzazepine-derivative TCAs (e.g., clomipramine, imipramine, trimipramine).104

Photosensitivity

Avoid excessive exposure to sunlight.104

General Precautions

Activation of Mania or Hypomania

Possible activation of hypomania in patients with bipolar disorder.104

Psychosis

Possible exacerbation of psychosis in patients with schizophrenia.104

Hematologic Effects

Perform leukocyte and differential counts in any patient who develops symptoms of blood dyscrasias (e.g., fever, sore throat).104 If evidence of pathologic neutrophil depression is found, discontinue the drug.104

Electroconvulsive Therapy (ECT)

Possible increased ECT risks.104

Elective Surgery

Discontinue therapy several days prior to surgery whenever possible.104 Hypertensive episodes have occurred during surgery in patients receiving desipramine.104

Blood Glucose Effects

Possible alterations in blood glucose concentrations.104

Storage

Keep out of reach of children.104 If possible, dispense in containers with child-resistant safety closures.104

Specific Populations

Pregnancy

Category C.e

Lactation

Distributes into milk;100 e discontinue nursing or the drug.104 e

Pediatric Use

Not effective in management of depression in children or adolescents in clinical studies.

Collapse and/or sudden death reported in children, some of whom received the drug for the treatment of ADHD;101 102 103 104 not recommended for use in children.101 102 103 104 105

FDA warns that a greater risk of suicidal thinking or behavior (suicidality) occurred during first few months of antidepressant treatment (4%) compared with placebo (2%) in children and adolescents with major depressive disorder, obsessive-compulsive disorder (OCD), or other psychiatric disorders based on pooled analyses of 24 short-term, placebo-controlled trials of 9 antidepressant drugs (SSRIs and others).109 However, a more recent meta-analysis of 27 placebo-controlled trials of 9 antidepressants (SSRIs and others) in patients <19 years of age with major depressive disorder, OCD, or non-OCD anxiety disorders suggests that the benefits of antidepressant therapy in treating these conditions may outweigh the risks of suicidal behavior or suicidal ideation.111 No suicides occurred in these pediatric trials.109 111

Carefully consider these findings when assessing potential benefits and risks of desipramine in a child or adolescent for any clinical use.108 109 110 111 (See Worsening of Depression and Suicidality Risk under Cautions.)

Geriatric Use

In pooled data analyses, a reduced risk of suicidality was observed in adults ≥65 years of age with antidepressant therapy compared with placebo.108 109 (See Boxed Warning and also see Worsening of Depression and Suicidality Risk under Cautions.)

Possible increased sensitivity to anticholinergic (e.g., dry mouth, constipation, vision disturbance), cardiovascular, orthostatic hypotension, and sedative effects of TCAs and increased risk for falls and/or other desipramine-induced toxicity.104 Monitor renal function.104

Titrate dosage carefully.104 (See Geriatric Patients under Dosage and Administration.)

Renal Impairment

Use with caution.104

Common Adverse Effects

Anticholinergic effects (e.g., dry mouth,104 a constipation,104 a vision disturbance),104 a orthostatic hypotension, sedation, weakness, lethargy, fatigue.a

Interactions for Desipramine Hydrochloride

Metabolized in the liver by various CYP isoenzymes (e.g., CYP1A2, CYP2C, CYP2D6, CYP3A4).a

Drugs Affecting Hepatic Microsomal Enzymes

Inhibitors of CYP2D6: potential pharmacokinetic interaction (increased plasma desipramine concentrations).a Adjust desipramine dosage whenever a CYP2D6 inhibitor is added or discontinued.a

Specific Drugs

Drug

Interaction

Comments

Alcohol

Potentiates CNS depressant effects of alcohol104

Increased risks if overdose or suicide attempt occurs104

Antiarrhythmics: class 1C (e.g., flecainide, propafenone); quinidine

Potential for decreased desipramine metabolism104

Monitor for TCA toxicity104

Anticholinergic agents

Hyperthermia, particularly during hot weather, and paralytic ileusa

Use with caution; dosage adjustment may be needed104

Antipsychotics (e.g., phenothiazines)

Potential for decreased desipramine metabolism104

Use with caution104

Benzodiazepines (e.g., chlordiazepoxide, diazepam)

Additive sedative effects104

Use with caution104

Cimetidine

Potential for decreased desipramine metabolism104

CNS depressants

Potentiates the effects of CNS depressants104

Use with caution104

Guanethidine

Antagonizes the antihypertensive effects of guanethidine104

Levodopa

May interfere with levodopa absorptiona

Monitor levodopa dosage carefullya

MAO inhibitors

Potentially life-threatening serotonin syndrome104

Concomitant use contraindicated104

Allow at least 14 days to elapse when switching to or from these drugs104

Methylphenidate

Potential for decreased desipramine metabolism104

SSRIs (e.g., citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine, sertraline)

Possible serotonin syndrome104

Potential for decreased desipramine metabolism104

Use with caution; monitor for TCA toxicity104

Allow at least 5 weeks to elapse when switching from fluoxetine104

Sympathomimetic agents (e.g., amphetamines, epinephrine, isoproterenol, norepinephrine, phenylephrine)

Increased vasopressor, cardiac effectsa

Use with caution; dosage adjustment may be requireda

Thyroid agents

Possible cardiovascular toxicity, including arrhythmias112

Use with extreme caution and under close supervision112

Desipramine Hydrochloride Pharmacokinetics

Absorption

Bioavailability

Well absorbed from the GI tract following oral administration, with peak plasma concentration usually attained within 4–6 hours.c

Onset

Antidepressant effects may occasionally be seen in 2–5 days, but full therapeutic effect may not be evident for up to 3 weeks.104

Distribution

Extent

Distributed into milk; concentrations in milk may be greater than or equal to those in maternal serum.100 e

Elimination

Metabolism

Extensively metabolized in the liver via oxidation to pharmacologically active metabolite, 2-hydroxydesipramine,104 106 107 by various CYP isoenzymes (e.g., CYP1A2, CYP2D6, CYP3A4, and CYP2C).114 a

Elimination Route

Excreted principally in urine (70%).104

Half-life

Plasma half-life of desipramine ranges from 7 to >60 hours.c

Special Populations

In geriatric patients, the ratio of the principal metabolite, 2-hydroxydesipramine, to desipramine appears to be increased, most likely because of decreased renal elimination that occurs with aging.104

Stability

Storage

Oral

Tablets

Tight containers at room temperature, preferably <30°C.104 Protect from excessive heat.104

Actions

  • Mechanism of action in the management of depression unknown but may involve inhibition of reuptake of norepinephrine and/or serotonin.104

  • Associated with more frequent anticholinergic, sedative, and cardiovascular effects and weight gain than SSRIs.a

Advice to Patients

  • Risk of suicidality; importance of patients, family, and caregivers being alert to and immediately reporting emergence of suicidality, worsening depression, or unusual changes in behavior, especially during the first few months of therapy or during periods of dosage adjustment.108 109 110 112 FDA recommends providing written patient information (medication guide) explaining risks of suicidality each time the drug is dispensed.108 109 110

  • Importance of considering possible impaired ability to perform hazardous activities (e.g., operating machinery, driving a motor vehicle).104

  • Importance of patients understanding that it may take up to 3 weeks before the full effects are apparent.104

  • Importance of avoiding alcohol-containing beverages or products.104

  • Importance of patients or caregivers supervising storage of the drug in the home and of keeping it out of reach of children.104

  • Importance of women informing their clinician if they are or plan to become pregnant or plan to breast-feed.104

  • Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant illnesses or planned surgery.112

  • Importance of informing patients of other important precautionary information.104 (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Desipramine Hydrochloride

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Tablets

10 mg*

Desipramine Hydrochloride Tablets

25 mg*

Desipramine Hydrochloride Tablets

50 mg*

Desipramine Hydrochloride Tablets

75 mg*

Desipramine Hydrochloride Tablets

100 mg*

Desipramine Hydrochloride Tablets

150 mg*

Desipramine Hydrochloride Tablets

Tablets, film-coated

10 mg

Norpramin

Sanofi-Aventis

25 mg

Norpramin

Sanofi-Aventis

50 mg

Norpramin

Sanofi-Aventis

75 mg

Norpramin

Sanofi-Aventis

100 mg

Norpramin

Sanofi-Aventis

150 mg

Norpramin

Sanofi-Aventis

Comparative Pricing

This pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information was updated 02/2014. Actual costs to patients will vary depending on the use of specific retail or mail-order locations and health insurance copays.

Desipramine HCl 10MG Tablets (ACTAVIS): 60/$60.46 or 120/$113.38

Desipramine HCl 100MG Tablets (ACTAVIS): 30/$100.99 or 90/$266.97

Desipramine HCl 25MG Tablets (SANDOZ): 60/$74.99 or 120/$142.97

Desipramine HCl 50MG Tablets (ACTAVIS): 60/$124.99 or 180/$340.96

Desipramine HCl 75MG Tablets (ACTAVIS): 60/$166.00 or 180/$465.95

Norpramin 10MG Tablets (SANOFI-AVENTIS U.S.): 60/$71.27 or 180/$205.18

Norpramin 100MG Tablets (SANOFI-AVENTIS U.S.): 30/$134.99 or 90/$377.97

Norpramin 150MG Tablets (SANOFI-AVENTIS U.S.): 30/$194.40 or 90/$572.37

Norpramin 25MG Tablets (SANOFI-AVENTIS U.S.): 60/$86.39 or 180/$237.57

Norpramin 50MG Tablets (SANOFI-AVENTIS U.S.): 60/$161.99 or 180/$464.36

Norpramin 75MG Tablets (SANOFI-AVENTIS U.S.): 60/$205.18 or 180/$600.46

AHFS DI Essentials. © Copyright, 2004-2014, Selected Revisions February 1, 2011. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

† Use is not currently included in the labeling approved by the US Food and Drug Administration.

References

Only references cited for selected revisions after 1984 are available electronically.

100. Sovner R, Orsulak PJ. Excretion of imipramine and desipramine in human breast milk. Am J Psychiatry. 1979; 136:451-2. [PubMed 426114]

101. Popper CW. Antidepressants in the treatment of attention-deficit/hypersensitivity disorder. J Clin Psychiatry. 1997; 58(Supp 14):14-29. [IDIS 398614] [PubMed 9418743]

102. Dulcan M. Practice parameters for the assessment and treatment of children, adolescents, and adults with attention-deficit/hyperactivity disorder. J Am Acad Child Adolesc Psychiatry. 1997; 36(Supp 10):85S-121S. [IDIS 395904] [PubMed 9334567]

103. Carrey NJ, Wiggins DM, Milin RP. Pharmacological treatment of psychiatric disorders in children and adolescents. Focus on guidelines for the primary care practitioner. Drugs. 1996; 51:750-9. [PubMed 8861545]

104. Aventis Pharmaceuticals, Inc. Norpramin (desipramine hydrochloride) tablets prescribing information (dated 2000 Jul). In: Physicians’ desk reference, 56th ed. Montvale, NJ: Medical Economics Company, Inc; 2002:755-6.

105. American Academy of Pediatrics Committee on Quality Improvement and Subcommittee on Attention-Deficit/Hyperactivity Disorder. Clinical treatment guideline: treatment of the school-aged child with attention-deficit/hyperactivity disorder. Pediatrics. 2001; 108:1033-44. [IDIS 470916] [PubMed 11581465]

106. Baldessarini RJ. Drugs and the treatment of psychiatric disorders: depression and anxiety disorders. In: Hardman JG, Limbird LE, Molinoff PB et al, eds. Goodman and Gilman’s the pharmacological basis of therapeutics. 10th ed. New York: McGraw-Hill; 2001:463.

107. Cyclic antidepressants. In: Ellenhorn MJ, Schonwald S, Ordog G et al, eds. Ellenhorn’s medical toxicology: diagnosis and treatment of human poisoning. 2nd ed. Baltimore: Williams & Wilkins; 1997:625.

108. Food and Drug Administration. FDA news: FDA proposes new warnings about suicidal thinking, behavior in young adults who take antidepressant medications. Rockville, MD; 2007 May 2. From the FDA web site.

109. Food and Drug Administration. Antidepressant use in children, adolescents, and adults: class revisions to product labeling. Rockville, MD; 2007 May 2. From the FDA web site.

110. Food and Drug Administration. Revisions to medication guide: antidepressant medicines, depression and other serious mental illnesses and suicidal thoughts or actions. Rockville, MD; 2007 May 2. From the FDA web site.

111. Bridge JA, Iyengar S, Salary CB. Clinical response and risk for reported suicidal ideation and suicide attempts in pediatric antidepressant treatment: a meta-analysis of randomized controlled trials. JAMA. 2007; 297:1683-96. [PubMed 17440145]

112. Sanofi-Aventis U.S. LLC. Norparmin (desipramine hydrochloride) tablets prescribing information. Bridgewater, NJ; 2009 Oct.

113. Mirski D. Dear healthcare professional letter regarding an update to Norpramin (desipramine hydrochloride tablets USP) prescribing information. Bridgewater, NJ; 2009 Dec.

114. Food and Drug Administration. Norpramin (desipramine hydrochloride) tablets. Detailed view: Safety labeling changes approved by FDA Center for Drug Evaluation and Research (CDER) -- October 2009. Rockville, MD; 2009 Oct. From the FDA web site.

115. Sandoz Inc. Desipramine hydrochloride tablets, USP prescribing information. Princeton, NJ; 2010 Jan.

a. AHFS drug information 2004. McEvoy GK, ed. Tricyclic antidepressants general statement. Bethesda, MD: American Society of Health-System Pharmacists; 200:2234-41.

b. American Psychiatric Association. Practice guideline for the treatment of patients with bipolar disorder (revised). Am J Psychiatry. 2002; 159(suppl):1-49.

c. AHFS drug information 2004. McEvoy GK, ed. Desipramine hydrochloride. Bethesda, MD: American Society of Health-System Pharmacists; 2004:2252-4.

e. Briggs GG, Freeman RK, Yaffe SJ. Drugs in pregnancy and lactation. 6th ed. Baltimore, MD: Williams & Wilkins; 2002:377-8.

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