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Desipramine Hydrochloride
Pronunciation: 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
PMS-Desipramine (Canada)
ratio-Desipramine (Canada)
Pharmacology
Inhibits reuptake of norepinephrine and serotonin in CNS.
Pharmacokinetics
Absorption
Rapidly absorbed.
Metabolism
Metabolized in the liver.
Elimination
Approximately 70% excreted in the urine.
Onset
2 to 5 days.
Peak
2 to 3 wk.
Special Populations
Renal Function ImpairmentNo data available.
Hepatic Function ImpairmentNo data available.
ElderlyRate of metabolism is slower. Dosage adjustment is recommended.
SmokersTobacco smoke can induce liver enzyme activity, thereby reducing desipramine plasma levels.
Indications and Usage
For the treatment of depression.
Unlabeled Uses
Alcohol dependence and major secondary depression, alcoholism, anxiety, attention deficit hyperactivity disorder (ADHD), bulimia nervosa, enuresis, diabetic neuropathy, postherpetic neuralgia, Tourette syndrome with comorbid ADHD, traumatic brain injury.
Contraindications
Hypersensitivity to desipramine; in combination with or within 14 days of treatment with an MAOI; during acute recovery phases of MI.
Dosage and Administration
AdultsPO 100 to 200 mg/day (max, 300 mg/day).
Elderly and Adolescent PatientsPO 25 to 100 mg/day (max, 150 mg/day).
General Advice
- Initiate therapy at a low dose level and increase the dose according to tolerance and clinical response.
- Lower dosages are recommended for outpatients compared with hospitalized patients, who are closely supervised.
- 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.
- If serious adverse reactions occur, reduce dosage or alter treatment.
- Following remission, maintenance medication may be required for a period of time and should be given at the lowest dose that will maintain remission.
Storage/Stability
Store between 59° and 86°F, preferably below 86°F. Protect from excessive heat.
Drug Interactions
AlcoholAlcohol may induce liver enzyme activity, thereby reducing desipramine levels. Response to alcohol may be exaggerated with coadministration. Caution patients that mental and physical abilities required for hazardous tasks may be impaired.
Anticholinergics (eg, diphenhydramine, scopolamine)Anticholinergic effects may be enhanced. Closely monitor clinical response and adjust treatment as needed.
Bupropion, mibefradilDesipramine plasma concentrations may be elevated, increasing the pharmacologic effects and the risk of adverse reactions. Monitor plasma concentrations and for signs and symptoms of adverse reactions. Adjust the desipramine dose as needed.
CarbamazepineSerum carbamazepine levels may be elevated, while desipramine levels may be decreased. Monitor plasma levels of both drugs and the clinical response when concurrent use of either drug is started or stopped. Adjust treatment as needed.
CholestyramineCholestyramine may reduce the GI absorption of desipramine, decreasing the pharmacologic effect. Separate the administration times by as much as possible. However, separating the administration times by 6 h may still interfere with desipramine absorption. Monitor the clinical response. If an interaction is suspected, be prepared to increase the desipramine dose as needed.
CisaprideCisapride is contraindicated in patients receiving desipramine because of the increased risk of life-threatening cardiac arrhythmias resulting from prolongation of the QT interval.
ClonidineMay result in hypertensive crisis. Avoid coadministration.
CNS depressantsCNS and respiratory effects may be increased. Coadminister with caution. Warn patients that mental and physical abilities required for hazardous tasks may be impaired.
DisulfiramPharmacologic effects of desipramine may be increased. Concurrent use may also be associated with a high frequency of acute organic brain syndrome. Monitor the clinical response. If an interaction is suspected, stop or decrease the dosage of desipramine.
Drugs that inhibit CYP2D6 (eg, cimetidine, cinacalcet, duloxetine, flecainide, phenothiazines, propafenone, protease inhibitors [eg, ritonavir], quinidine, terbinafine, venlafaxine)Desipramine plasma levels may be elevated, increasing the pharmacologic effects and adverse reactions. Monitor desipramine plasma levels. Dosage reduction of desipramine may be necessary.
FluconazoleDesipramine plasma concentrations and risk of adverse reactions may be increased. Monitor desipramine plasma concentrations and the clinical response when starting or stopping fluconazole. Adjust the desipramine dose as needed.
FoodA high-fiber diet may decrease desipramine absorption, decreasing its therapeutic effects. Observe the patient's response to desipramine during ingestion of a high-fiber diet. Adjust the diet as needed.
Gatifloxacin, levofloxacin, moxifloxacinAvoid concurrent use with levofloxacin. Administer desipramine with gatifloxacin or moxifloxacin with caution. The risk of life-threatening cardiac arrhythmias may be increased.
Guanethidine, guanfacineThe hypotensive action of these agents may be inhibited. If coadministration cannot be avoided, monitor BP and adjust the dose of these agents as needed.
IobenguaneDesipramine may reduce uptake and diagnostic efficacy of iobenguane. False-negative iobenguane imaging tests may result. It is recommended that desipramine be discontinued for at least 5 biological half-lives (approximately 48 h) prior to iobenguane administration.
LithiumThe risk of adverse reactions (eg, neurotoxicity, psychotic symptoms) may be increased. Monitor the clinical response. If an interaction is suspected, it may be necessary to discontinue one of the agents and adjust treatment as needed.
MAOIs (eg, phenelzine)Hyperpyretic crises, severe convulsions, and death may occur if desipramine is administered together or within 14 days of MAOI treatment.
Psychotropic agents (eg, hypnotics, sedatives, tranquilizers)Coadministration may enhance the sedative effects of both drugs. Use with caution. Warn patients that mental and physical abilities required for hazardous tasks may be impaired.
Rasagiline, tramadolMay act synergistically to precipitate serotonin syndrome. Closely monitor the clinical response. Serotonin syndrome requires immediate medical attention, including withdrawal of the serotonergic agent and supportive care.
SSRIs (eg, fluoxetine, paroxetine, sertraline)The pharmacologic and toxic effects of desipramine may be increased. Serotonin syndrome has been reported. Dosage reduction may be necessary. Allow sufficient time before initiating desipramine in a patient being withdrawn from fluoxetine because of fluoxetine's long half-life (ie, at least 5 wk may be necessary).
Sympathomimetics (eg, epinephrine)The pressor response to direct- and indirect-acting sympathomimetics may be increased or decreased, respectively. Dosage adjustment of the sympathomimetic may be necessary. Closely monitor for dysrhythmias and hypertension.
Thyroid hormones (eg, levothyroxine)The risk of CV toxicity, including arrhythmias, may be increased. Use with extreme caution and closely monitor cardiac function.
Valproic acidDesipramine plasma levels may be elevated, increasing the pharmacologic effects and adverse reactions. Monitor plasma desipramine concentrations and adjust the dose as needed.
Adverse Reactions
Cardiovascular
Arrhythmias, heart block, hypertension, hypotension, MI, palpitations, PVCs, stroke, tachycardia, ventricular fibrillation, ventricular tachycardia.
CNS
Alterations in EEG patterns; anxiety; ataxia; confusional states with hallucinations, delusions, disorientation, agitation, and restlessness; dizziness; drowsiness; exacerbation of psychosis; extrapyramidal symptoms; fatigue; headache; hypomania; incoordination; insomnia; nightmares; NMS symptoms; numbness; paresthesias of extremities; peripheral nephropathy; seizures; tingling; tremors; weakness.
Dermatologic
Alopecia, perspiration.
EENT
Blurred vision, disturbances in accommodation, increased IOP, mydriasis, tinnitus.
GI
Abdominal cramps, anorexia, black tongue, constipation, diarrhea, dry mouth rarely associated with sublingual adenitis, epigastric distress, nausea, paralytic ileus, peculiar taste, stomatitis, 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, elevated alkaline phosphatase, elevated LFTs, hepatitis, increased pancreatic enzymes, jaundice.
Hypersensitivity
Cross-sensitivity with other tricyclic drugs, drug fever, edema (general or of the face and tongue), itching, petechiae, photosensitization, skin rash, urticaria.
Metabolic-Nutritional
Elevation or depression of blood glucose levels, SIADH, weight gain or loss.
Miscellaneous
Acute collapse; fever; flushing; parotid swelling; proneness to falling; sudden death; withdrawal symptoms, including headache, malaise, and nausea.
Precautions
WarningsAntidepressants increased the risk of suicidal thinking and behavior (suicidality) in children, adolescents, and young adults in short-term studies of major depressive disorder (MDD) and other psychiatric disorders compared with placebo. Anyone considering the use of desipramine or any other antidepressant in a child, adolescent, or young adult must balance this risk with the clinical need. Closely observe and appropriately monitor patients of all ages who are started on antidepressant therapy for clinical worsening, suicidality, or unusual changes in behavior. Advise families and caregivers of the need for close observation and communication with the prescribing health care provider. Desipramine is not approved for use in children. |
MonitorPrior to initiating treatment, adequately screen patients with depressive symptoms to determine if they are at risk for bipolar disorder. Closely observe and appropriately monitor all patients being treated with antidepressants for any indication for clinical worsening, suicidality, and unusual changes in behavior, especially during the initial few months of a course of drug therapy or at times of dose changes (increases or decreases). Perform leukocytes and differential counts in any patient who develops fever and sore throat during therapy; discontinue the drug if there is evidence of pathologic neutrophil depression. |
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 impairment in elderly patients; lower dosages are recommended.
Renal Function
The risk of toxic reactions to this drug may be greater in patients with impaired renal function.
Special Risk Patients
Use drug with caution in patients with history of seizures, urinary retention, and glaucoma, and in patients with thyroid disease or patients receiving thyroid medication.
Hazardous Tasks
May impair the mental and/or physical abilities required for the performance of potentially hazardous tasks such as driving a car or operating machinery.
Bipolar disorder
Not approved for treating bipolar depression.
Cardiovascular effects
Use extreme caution in CV disorder because of the possibility of conduction defects, arrhythmias, tachycardias, strokes, and MI; also use with extreme caution in patients who have a family history of sudden death, cardiac dysrhythmias, or cardiac conduction disturbances.
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.
Mania/Hypomania
Therapy in patients with manic-depressive illness may induce a hypomanic state after the depressive phase terminates.
Schizophrenia
Psychosis may be exacerbated.
Overdosage
Symptoms
Agitation, cardiac arrhythmias, CNS depression, coma, confusion, dilated pupils, disturbed concentration, drowsiness, ECG changes, hyperactive reflexes, hyperpyrexia, hypothermia, muscle rigidity, seizures, severe hypotension, stupor, transient visual hallucinations, vomiting.
Patient Information
- Inform patients, families, and caregivers about the benefits and risks associated with desipramine treatment; counsel them in its appropriate use. Instruct patients, families, and caregivers to read the Medication Guide and assist them in understanding its contents. Give patients the opportunity to discuss the contents of the Medication Guide and to obtain answers to any questions they may have.
- Encourage patients, families, and caregivers to be alert to the emergence of anxiety, agitation, panic attacks, insomnia, irritability, hostility, aggressiveness, impulsivity, akathisia (psychomotor restlessness), hypomania, mania, other unusual changes in behavior, worsening of depression, and suicidal ideation, especially early during antidepressant treatment and when the dose is increased or decreased. Advise families and caregivers to watch for the emergence of such symptoms on a day-to-day basis because changes may be abrupt. Report such symptoms to the patient's health care provider, especially if they are severe, abrupt in onset, or were not part of the patient's presenting symptoms. Symptoms such as these may be associated with an increased risk for suicidal thinking and behavior and may indicate a need for very close monitoring and, possibly, changes in the medication.
- Warn patients that while taking this drug their response to alcoholic beverages may be exaggerated.
- Caution the patient that this drug may impair the mental or physical abilities required for the performance of potentially hazardous tasks such as driving a car or operating machinery.
- Advise patients undergoing elective surgery to discontinue desipramine as soon as possible prior to surgery date.
- 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.
- Advise patients with diabetes that desipramine may raise or lower blood glucose.
Copyright © 2009 Wolters Kluwer Health.
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