Desipramine
Desipramine is a generic medication for the drug Norpramin:
Desipramine medication comes in several different strengths; click on the strength you need to view prices from pharmacies competing to earn your business.
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Desipramine 10 mg
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Desipramine 25 mg
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Desipramine 50 mg
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Desipramine 75 mg
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Desipramine 100 mg
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Desipramine 150 mg
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Drug Interactions
Drug-Herb Interactions
Concurrent use of valerian or St. John’s wort with desipramine should be avoided as it may result in additive serotonergic effects and/or sedation; St. John’s wort can also increase the metabolism and decrease the effectiveness of desipramine, possibly through hepatic enzyme induction.
Drug-Food Interactions
A high-fibre diet may decrease desipramine absorption, resulting in reduced serum levels.
Desipramine
Drug-Drug Interactions
| Interacting Drug | Effect | Clinical Comment |
|---|---|---|
| CNS depressants (e.g., benzodiazepines, ethanol, opioids) | Additive CNS depressant effects (e.g., sedation) | Caution patients about potential effects and monitor appropriately. |
| Drugs that prolong the QTc-interval (e.g., amiodarone, chlorpromazine, clarithromycin, domperidone, erythromycin, haloperidol, methadone, pimozide, quinidine, quinine, sotalol, ziprasidone) | Increased risk of QTc prolongation | Consider therapy modification; obtain ECG early in therapy. |
| Direct-acting alpha/beta agonists (e.g., epinephrine, norepinephrine) | Concurrent use of desipramine and these agents may enhance their vasopressor effect | Consider therapy modification. |
| Serotonergic drugs (e.g., buspirone, irreversible MAOIs such as phenelzine and tranylcypromine, reversible MAOIs such as moclobemide and selegiline, sibutramine, SSRIs, tramadol) | Increased risk of serotonin syndrome | Avoid combination. |
| Strong inhibitors of CYP2D6 (e.g., chlorpromazine, fluoxetine, haloperidol, paroxetine, quinidine, terbinafine) | Increased toxicity of desipramine | Consider therapy modification or lower dose of desipramine. |
Overview
Desipramine is hepatically metabolized by the cytochrome (CYP) isozymes system. The major metabolic pathway is CYP2D6, with minor involvement of CYP1A2. Desipramine may also inhibit CYP2D6, CYP2C19 and CYP2E1 activity. Any drug that is a substrate, inducer or inhibitor of these CYP isozymes may interact with desipramine.
Dosage and Administration
Dose in Dialysis
No dosage supplementation is required following hemodialysis.
Recommended Dose and Dosage Adjustment
Desipramine
Dose in Adult Patients
| Indication | Initial Dose | Dose Titration | Usual Dose | Maximum Dose |
|---|---|---|---|---|
| Depression or anxietya | 75 mg/day in divided doses | Increase gradually; dose can be increased every 3 to 7 days | 100–200 mg/day | 300 mg/day |
| Irritable bowel syndromea | 10 to 50 mg QHS | Start low and titrate as needed; dose can be increased every 3 to 7 days | 10 to 150 mg QHS | |
| Neuropathic paina | 25 mg QHS | Increase by 25 mg daily every 3 to 7 days as tolerated | 50–150 mg/day | 150 mg/day |
| Urge incontinencea | 10 mg QHS | Increase gradually as needed; dose can be increased every 3 to 7 days | 10–100 mg QHS | 100 mg/day |
Dosing Considerations
Administration of the entire daily dose at bedtime may reduce daytime sedation.
Patients who experience insomnia and stimulation from the drug may find it optimal to take the entire daily dose in the morning.
Desipramine therapy should not be terminated abruptly in patients who have received high doses for prolonged periods (see Warnings and Precautions, Withdrawal).
Desipramine
Dose in Geriatric Patients
| Indication | Initial Dose | Dose Titration | Usual Dose | Maximum Dose |
|---|---|---|---|---|
| Depression or anxietya | 10 to 25 mg/day | Increase by 10 to 25 mg every 3 to 7 days if tolerated | 75 to 100 mg/day | 150 mg/day |
Desipramine
Dose in Pediatric Patients
| Indication | Age/Weight | Initial Dose | Dose Titration | Usual Dose | Maximum Dose |
|---|---|---|---|---|---|
| ADHDa | 6 to 12 years | 10–20 mg/day in 3–4 divided doses | 6–12 y: gradually increase every 3 to 7 days up to 20–30 mg/day in divided doses if needed | 20–30 mg/day in divided doses | 150 mg/day |
| Adolescents >12 y | 30 to 50 mg/day in 3 to 4 divided doses | Gradually increase (every 3 to 7 days) up to 100 mg/day in single or divided doses as needed | 50–100 mg/day | 150 mg/day |
Dose in Adult Patients with Renal Impairment
Dosage adjustments are generally not required for patients with renal impairment.
Adverse Reactions
Hepatic/Biliary/Pancreatic
altered liver function, cholestatic jaundice, hepatitis, elevated liver function tests, increased pancreatic enzymes.
Genitourinary
dysuria, polyuria, urinary retention.
Gastrointestinal
anorexia; black tongue; decreased lower esophageal sphincter tone may cause GE reflux/heartburn; diarrhea, stomatitis, unpleasant taste.
Hematologic
agranulocytosis, eosinophilia, purpura, thrombocytopenia.
Less Common Adverse Drug Reactions (<1%)
Endocrine and Metabolism
breast enlargement and galactorrhea in women, gynecomastia in men, hyperglycemia, and syndrome of inappropriate antidiuretic hormone (SIADH).
Central Nervous System
agitation, anxiety, ataxia, confusion, delirium, disorientation, drug fever, hallucinations, incoordination, nervousness, numbness, paresthesias of the extremities, parkinsonian syndrome, restlessness, seizures.
Ophthalmologic
increased intraocular pressure, loss of focusing ability of eye.
Dermatologic
alopecia, itching, petechiae, photosensitivity, urticaria, skin pigmentation.
Desipramine
More Common Adverse Drug Reactions (≥1%)
| Body System | Effect |
|---|---|
| Anticholinergic | Dry mouth and/or eyes Blurred vision Constipation Mild tremors Urinary retention Sweating |
| Cardiovascular | Tachycardia Orthostatic hypotension Arrhythmias |
| CNS | Asthenia Drowsiness Excitement Fatigue Hypomania Insomnia Sedation Weakness Headache Lethargy |
| Dermatologic | Dermatitis Rash |
| Endocrine and Metabolism | Weight gain |
| Gastrointestinal | Abdominal cramps Nausea Vomiting |
| Genitourinary | Sexual dysfunction (e.g., decreased libido, erectile or ejaculatory dysfunction, anorgasmia) |
Cardiovascular
edema, flushing, heart block, myocardial infarction, stroke.
Ear/Nose/Throat
tinnitus.
Indications and Clinical Use
Desipramine is indicated for:
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treatment of major depressive disorder.
Desipramine has also been used:
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as an atypical analgesic agent in the management of chronic peripheral neuropathic pain or other chronic pain conditions.
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in the management of abdominal pain associated with diarrhea-predominant irritable bowel syndrome (IBS). In constipation-predominant IBS, use of desipramine may exacerbate symptoms.
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as a second-line agent in the management of anxiety disorders (e.g., panic disorder, generalized anxiety disorder).
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as a second- or third-line agent in the treatment of attention deficit hyperactivity disorder (ADHD).
Overdosage
Recommended Management
All cases of accidental pediatric exposure or adult overdose should be monitored at a health care facility. Asymptomatic cases without ECG abnormalities should be monitored for a minimum of 6 hours. Plasma concentrations of desipramine are of little use and should not guide management of the patient. In managing overdose, consider the possibility of multiple drug overdose, interactions among drugs and altered pharmacokinetics, including delayed absorption. Protect the patient’s airway and support ventilation and perfusion. Closely monitor and maintain patient’s vital signs, ECG, blood gases, serum electrolytes, and acid-base balance. Minimize external stimulation to reduce the risk of seizures.
Consultation with a regional poison centre is advisable in all patients with TCA overdose. Activated charcoal (1 gram per kilogram) may reduce absorption of drug from the gastrointestinal tract, and should be considered in patients who present within 2 hours of ingestion. This can be given through nasogastric tube if necessary. Although it should not be routinely performed, gastric lavage may be considered in the unusual case where a patient presents within 30 to 60 minutes of massive TCA overdose, but only on the advice of a Poison Control Centre. If performed, gastric lavage should be followed by administration of activated charcoal. If the patient has a decreased level of consciousness, consideration should be given to placement of endotracheal tube with cuff inflated before beginning the lavage procedure, to lessen the likelihood of aspiration of gastric contents.
Hypotension should be promptly corrected. If hypotension does not respond to a rapid isotonic fluid bolus and the patient has a widened QRS interval (>0.1 seconds), sodium bicarbonate boluses should be administered at a dose of 1 to 2 mmol/kg (an average adult would typically receive 1 to 3 ampoules of 50 mmol/50 mL). If hypotension still hasn’t responded, vasopressors should be employed, with a direct-acting agonist such as norepinephrine being the drug of choice.
Widened QRS intervals (>0.14 seconds) and ventricular arrhythmias should be treated with iv sodium bicarbonate. An iv bolus of 1 to 2 mmol/kg (one or two 50 mmol ampoules) should be administered and repeated if necessary to achieve a serum pH of 7.45 to 7.55. Maintain the pH between 7.45 and 7.55. Do not exceed pH 7.6. Monitor for hypokalemia and fluid overload. Hyperventilation may also be used to maintain alkalemia.
Ventricular arrhythmias refractory to sodium bicarbonate may respond to lidocaine. Quinidine, procainamide and other type IA or IC antiarrhythmics should not be used because they may exacerbate arrhythmias and conduction slowing due to the overdosage. Overdrive pacing should be considered in patients whose arrhythmias are not responsive to drug therapy.
In patients with severe/refractory toxicity, consideration should be given to the use of intravenous lipid emulsion. Consult a toxicologist.
Seizures should be aggressively treated with iv benzodiazepines such as lorazepam or diazepam. If this is unsuccessful, barbiturates and other measures should be employed as for status epilepticus. However, phenytoin is no longer recommended in the treatment of TCA-induced seizures.
Diuresis, hemoperfusion and dialysis are not helpful in TCA overdose.
Flumazenil is contraindicated in any patient with an altered level of consciousness who has or may have taken a TCA or any drug that can cause seizures or arrhythmias, as it may precipitate seizures or even cardiac arrest. This is true even in cases of mixed overdose where the patient is known to have coingested benzodiazepines.
Signs and Symptoms
Desipramine and other TCAs are extremely toxic in overdose. Consultation with a Poison Control Centre is recommended. See the CPS Directory for contact numbers.
Cardiac arrhythmias and CNS involvement pose the greatest threat and may occur suddenly even when initial symptoms appear to be mild. The toxic dose is variable but, in general, acute ingestion of 10 to 20 mg/kg may result in serious toxicity and may be lethal. TCA overdose has one of the highest mortality rates of any type of ingestion. Toxicity most commonly begins within 2 hours of ingestion. The onset of symptoms is frequently precipitous, with patients progressing from wakeful, interactive state to having severe CNS and cardiac involvement within a matter of minutes.
Peripheral anticholinergic symptoms may include urinary retention, dry mucous membranes, mydriasis, constipation and occasionally adynamic ileus (diminished or absent peristalsis/bowel sounds). Patients may also be hyperpyrexic. CNS signs and symptoms can be highly variable and may range from somnolence to agitation, irritability, confusion, delirium, and hallucinations. In severe cases, patients may display extreme drowsiness, areflexia, respiratory depression and coma. Patients may occasionally become hypothermic. Seizures are common and may precipitate cardiac toxicity.
Cardiac irregularities are frequent and generally dose-dependent. Sinus tachycardia is common; its presence is not a reliable predictor of serious toxicity, and its absence does not ensure a benign clinical course. An effect on cardiac conduction similar to that of quinidine may be seen with slowing of conduction, widening of QRS complex, rightward shift in the axis of the terminal 40 milliseconds of the QRS complex, prolongation of the PR and QT intervals, right bundle branch and AV block, ventricular tachyarrhythmias (including torsades de pointes and fibrillation), and death. Prolongation of the QRS duration to more than 0.1 seconds is generally associated with more severe toxicity. Bradycardia may be seen in severely poisoned patients. Hypotension is common and may be severe, resulting from vasodilation, central and peripheral alpha-adrenergic blockade, and myocardial depression. Metabolic and/or respiratory acidosis may occur secondary to seizures, poor tissue perfusion, respiratory depression or poor gas exchange. In an otherwise healthy young person, prolonged resuscitation may be required.
Warnings and Precautions
Gastrointestinal
Use with caution in patients with decreased gastrointestinal motility and paralytic ileus due to the potential anticholinergic effects of desipramine.
Peri-Operative Considerations
Perioperative use of desipramine may increase the risk of cardiovascular events, including hypertensive episodes. Discontinue therapy several days prior to elective surgery whenever possible.
Periprocedural Considerations
Concurrent use of desipramine may increase risks associated with electroconvulsive therapy.
Withdrawal
Desipramine should not be abruptly discontinued in patients receiving high doses for prolonged periods, as doing so may result in withdrawal symptoms such as insomnia, gastrointestinal symptoms (anorexia, nausea or vomiting), flu-like symptoms (e.g., fever, malaise, fatigue, myalgias or weakness), anxiety, agitation, hypomania, mania, akathisia, delirium, dizziness, tremor, muscle twitching, and rarely, dyskinesia. Rebound depression has been reported and may occur in patients who take antidepressants for indications other than depression. These usually occur within 1 to 3 days of discontinuation, are mild and self-limiting and resolve within 2 weeks. Very rarely, cardiac disturbances have also occurred.
Self Harm
The potential for suicidality must always be considered in depressed patients. Use of antidepressants, especially during periods of therapy initiation and dosage adjustment, may result in behavioural and/or emotional changes that place patients at increased risk of suicidal ideation and attempt. Patients should be monitored closely for any signs of worsening condition.
Ophthalmologic
Use with caution in patients with angle closure glaucoma as the condition may be exacerbated by potential anticholinergic effects of desipramine.
Pediatrics
Cases of collapse and/or sudden death have been reported in children receiving desipramine for the treatment of ADHD and depression, but a causal relationship has not been established. Desipramine should be used in children and adolescents only by physicians experienced in the use of such agents in the pediatric population and with full consideration of the associated risks and potential benefits.
Pregnant Women
There is insufficient evidence to draw definite conclusions about the safety of desipramine use during pregnancy. Though no reports link desipramine to teratogenicity, tricyclic antidepressants do cross the placenta. Transient withdrawal symptoms such as cyanosis, tachycardia, diaphoresis, weight loss, colic and irritability have been reported in neonates whose mothers took desipramine during pregnancy. The potential risks to the fetus should be weighed against the risks to mother and fetus of untreated maternal depression. Among tricyclic antidepressants, desipramine may be more favorable during pregnancy because of its lower propensity to cause anticholinergic effects and orthostatic hypotension.
Psychiatric
Use of desipramine may unmask bipolar disorder and may increase the risk of rapid cycling or precipitate a shift to mania/hypomania in patients with bipolar disorder.
Geriatrics
Use with caution in elderly patients as they are more susceptible to sedative and anticholinergic effects and which can increase the risk of falls and confusion/cognitive impairment. See Table 4 for dosing recommendations.
Hepatic/Biliary/Pancreatic
Use with caution in patients with hepatic impairment as desipramine is metabolized in the liver by cytochrome P450 isozymes.
Genitourinary
Use with caution in patients with urinary retention, benign prostatic hyperplasia as potential anticholinergic effects of desipramine may aggravate symptoms.
Special Populations
Hematologic
Desipramine has been rarely associated with bone marrow suppression, which may be of concern if a patient presents with signs of serious infection.
Neurologic
Use with caution in patients with a history of seizure disorder as desipramine may lower seizure threshold.
Endocrine and Metabolism
Use with caution in patients with diabetes mellitus as desipramine may decrease insulin sensitivity and cause hyperglycemia. Use of desipramine in patients who are hyperthyroid may result in cardiovascular toxicity including arrhythmias.
Occupational Hazards
Patients should be cautioned regarding potential impairment of their mental and/or physical acuity which may affect their ability to safely operate a vehicle or perform other potentially hazardous tasks.
Nursing Women
Despite the detection of low levels of desipramine in breast milk, there have been no reports of adverse events. When levels were measured, there was no evidence of drug in infants’ serum or any clinical signs of toxicity, especially in infants older than 2 months. Observe infants for any changes in behavior such as drowsiness or difficulty breast feeding.
Cardiovascular
Use with caution in patients with cardiovascular disease; desipramine has been associated with conduction defects, arrhythmia, stroke and acute myocardial infarction. Desipramine may also cause orthostatic hypotension.
Storage and Stability
Desipramine should be stored in airtight containers at room temperature (preferably at less than 30°C), and protected from excessive heat.
Action and Clinical Pharmacology
Geriatrics
The half-life of desipramine was slightly prolonged in studies of elderly males.
Distribution
Desipramine is 73 to 92% bound to plasma protein.
Pharmacokinetics
Special Populations
Absorption
Desipramine is well absorbed from the GI tract, and undergoes extensive first-pass metabolism. Peak plasma concentrations occur 4-6 hours after oral administration.
Mechanism of Action
Desipramine is a secondary amine tricyclic antidepressant. Desipramine blocks the reuptake of and prolongs the synaptic effects of norepinephrine, with a high degree of neurotransmitter selectivity. It has some effect on serotonin reuptake as well.
Excretion
The elimination half-life of desipramine is 7 to 60 hours, with 70% of excretion occurring renally. The elimination half life is prolonged in the elderly and slow metabolizers. Desipramine is not removed by hemodialysis.
Metabolism
Desipramine is hepatically metabolized by CYP2D6 (major) and CYP1A2 (minor) to its pharmacologically active metabolite, 2-hydroxydesipramine. Desipramine may also inhibit CYP2D6, CYP2C19 and CYP2E1 activity.
Adults
Contraindications
Patients who are hypersensitive to desipramine or to any ingredient in the formulation or component of the container.
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Cross-sensitivity between desipramine and other tricyclic antidepressants (TCAs) is possible.
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Desipramine should not be used in conjunction with or within 14 days after monoamine oxidase inhibitor use.
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Desipramine is contraindicated for use in heart block or during the acute recovery period following myocardial infarction.
