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Pronunciation |
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(des
IP ra
meen) |

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U.S. Brand
Names |
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Norpramin® |

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Generic
Available |
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Yes: Tablet |

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Canadian Brand
Names |
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PMS-Desipramine |

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Synonyms |
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Desipramine Hydrochloride; Desmethylimipramine Hydrochloride |

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Pharmacological Index |
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Antidepressant, Tricyclic (Secondary Amine) |

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Use |
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Treatment of depression |

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Pregnancy Risk
Factor |
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C |

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Contraindications |
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Hypersensitivity to this drug and similar chemical class; use of monoamine
oxidase inhibitors within 14 days; use in a patient during the acute recovery
phase of MI |

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Warnings/Precautions |
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May cause sedation, resulting in impaired performance of tasks requiring
alertness (ie, operating machinery or driving). Sedative effects may be additive
with other CNS depressants and/or ethanol. The degree of sedation is
low-moderate relative to other antidepressants. May worsen psychosis in some
patients or precipitate a shift to mania or hypomania in patients with bipolar
disease. May cause hyponatremia/SIADH. May increase the risks associated with
electroconvulsive therapy. This agent should be discontinued, when possible,
prior to elective surgery. Therapy should not be abruptly discontinued in
patients receiving high doses for prolonged periods.
Use caution in patients with depression, particularly if suicidal risk may be
present. Use with caution in patients with a history of cardiovascular disease
(including previous MI, stroke, tachycardia, or conduction abnormalities). The
risk of conduction abnormalities with this agent is moderate relative to other
antidepressants. Use caution in patients with a previous seizure disorder or
condition predisposing to seizures such as brain damage, alcoholism, or
concurrent therapy with other drugs which lower the seizure threshold. Use with
caution in hyperthyroid patients or those receiving thyroid supplementation. Use
with caution in patients with hepatic or renal dysfunction and in elderly
patients. |

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Adverse
Reactions |
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Cardiovascular: Arrhythmias, hypotension, hypertension, palpitations, heart
block, tachycardia
Central nervous system: Dizziness, drowsiness, headache, confusion, delirium,
hallucinations, nervousness, restlessness, parkinsonian syndrome, insomnia,
disorientation, anxiety, agitation, hypomania, exacerbation of psychosis,
incoordination, seizures, extrapyramidal symptoms
Dermatologic: Alopecia, photosensitivity, skin rash, urticaria
Endocrine & metabolic: Breast enlargement, galactorrhea, SIADH
Gastrointestinal: Xerostomia, decreased lower esophageal sphincter tone may
cause GE reflux, constipation, nausea, unpleasant taste, weight gain, anorexia,
abdominal cramps, weight loss, diarrhea, heartburn
Genitourinary: Difficult urination, sexual dysfunction, testicular edema
Hematologic: Agranulocytosis, eosinophilia, purpura, thrombocytopenia
Hepatic: Cholestatic jaundice, increased liver enzyme
Neuromuscular & skeletal: Fine muscle tremors, weakness, numbness,
tingling, paresthesia of extremities, ataxia
Ocular: Blurred vision, disturbances of accommodation, mydriasis, increased
intraocular pressure
Miscellaneous: Diaphoresis (excessive), allergic reactions
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Overdosage/Toxicology |
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Symptoms of overdose include severe hypotension, agitation, confusion,
hyperthermia, urinary retention, CNS depression (including coma), cyanosis, dry
mucous membranes, cardiac arrhythmias, seizures, changes in EKG (particularly in
QRS axis and width), transient visual hallucinations, stupor, muscle rigidity
Following GI decontamination, treatment is supportive. Sodium bicarbonate is
indicated when QRS interval is greater than or equal to 0.10 seconds or
QTc >0.42 seconds. Ventricular arrhythmias and EKG changes (eg,
QRS widening) often respond with concurrent systemic alkalinization (sodium
bicarbonate 0.5-2 mEq/kg I.V.). Arrhythmias unresponsive to phenytoin 15-20
mg/kg (adults) may respond to lidocaine 1 mg/kg I.V. followed by a titrated
infusion. Physostigmine (1-2 mg I.V. slowly for adults or 0.5 mg I.V. slowly for
children) may be indicated in reversing cardiac arrhythmias that are
life-threatening. Seizures usually respond to diazepam I.V. boluses (5-10 mg for
adults up to 30 mg or 0.25-0.4 mg/kg/dose for children up to 10 mg/dose). If
seizures are unresponsive or recur, phenytoin or phenobarbital may be required.
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Drug
Interactions |
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CYP1A2 and 2D6 enzyme substrate; CYP2D6 inhibitor CYP1A2, 2C9, 2C19, 2D6, and
3A3/4 enzyme substrate
Desipramine inhibits the antihypertensive response to bethanidine, clonidine,
debrisoquin, guanadrel, guanethidine, guanabenz, guanfacine; monitor BP;
consider alternate antihypertensive agent
Abrupt discontinuation of clonidine may cause hypertensive crisis,
desipramine may enhance the response
Use with altretamine may cause orthostatic hypertension
Desipramine may be additive with or may potentiate the action of other CNS
depressants (sedatives, hypnotics, or ethanol)
With MAO inhibitors, hyperpyrexia, hypertension, tachycardia, confusion,
seizures, and deaths have been reported (serotonin syndrome); this
combination should be avoided
Desipramine may increase the prothrombin time in patients stabilized on
warfarin
Cimetidine and methylphenidate may decrease the metabolism of desipramine
Additive anticholinergic effects seen with other anticholinergic agents
The SSRIs, to varying degrees, inhibit the metabolism of TCAs and clinical
toxicity may result
Use of lithium with a TCA may increase the risk for neurotoxicity
Phenothiazines may increase concentration of some TCAs and TCAs may increase
concentration of phenothiazines; monitor for altered clinical response
TCAs may enhance the hypoglycemic effects of tolazamide, chlorpropamide, or
insulin; monitor for changes in blood glucose levels
Cholestyramine and colestipol may bind TCAs and reduce their absorption;
monitor for altered response
TCAs may enhance the effect of amphetamines; monitor for adverse CV effects
Verapamil and diltiazem appear to decrease the metabolism of imipramine and
potentially other TCAs; monitor for increased TCA concentrations. The pressor
response to I.V. epinephrine, norepinephrine, and phenylephrine may be enhanced
in patients receiving TCAs, this combination is best avoided.
Grapefruit juice,amprenavir, indinavir, ritonavir may inhibit the metabolism
of clomipramine and potentially other TCAs; monitor for altered effects; a
decrease in TCA dosage may be required
Quinidine may inhibit the metabolism of TCAs, monitor for altered effect
Combined use of anticholinergics with TCAs may produce additive
anticholinergic effects; combined use of beta-agonists with TCAs may predispose
patients to cardiac arrhythmias |

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Mechanism of
Action |
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Traditionally believed to increase the synaptic concentration of
norepinephrine (and to a lesser extent, serotonin) in the central nervous system
by inhibition of its reuptake by the presynaptic neuronal membrane. However,
additional receptor effects have been found including desensitization of adenyl
cyclase, down regulation of beta-adrenergic receptors, and down regulation of
serotonin receptors. |

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Pharmacodynamics/Kinetics |
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Onset of action: 1-3 weeks (maximum antidepressant effects: after >2
weeks)
Absorption: Well absorbed from GI tract
Metabolism: In the liver
Half-life: Adults: 7-60 hours
Peak plasma levels occur within 4-6 hours
Elimination: 70% excreted in urine |

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Usual Dosage |
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Oral:
Adolescents: Initial: 25-50 mg/day; gradually increase to 100 mg/day in
single or divided doses; maximum: 150 mg/day
Adults: Initial: 75 mg/day in divided doses; increase gradually to 150-200
mg/day in divided or single dose; maximum: 300 mg/day
Elderly: Initial dose: 10-25 mg/day; increase by 10-25 mg every 3 days for
inpatients and every week for outpatients if tolerated; usual maintenance dose:
75-100 mg/day, but doses up to 150 mg/day may be necessary
Hemodialysis/peritoneal dialysis: Supplemental dose is not necessary
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Dietary
Considerations |
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Alcohol: Additive CNS effects, avoid use |

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Monitoring
Parameters |
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Monitor blood pressure and pulse rate prior to and during initial therapy;
evaluate mental status; monitor weight |

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Reference Range |
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Plasma levels do not always correlate with clinical effectiveness
Timing of serum samples: Draw trough just before next dose
Therapeutic: 50-300 ng/mL
In elderly patients the response rate is greatest with steady-state plasma
concentrations >115 ng/mL
Possible toxicity: >300 ng/mL
Toxic: >1000 ng/mL |

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Dental Health: Local
Anesthetic/Vasoconstrictor
Precautions |
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Use with caution; epinephrine, norepinephrine and levonordefrin have been
shown to have an increased pressor response in combination
TCAs |

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Dental Health:
Effects on Dental Treatment |
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>10% of patients experience dry mouth; long-term treatment with TCAs
increases the risk of caries by reducing salivation and salivary buffer
capacity |

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Patient
Information |
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Take exactly as directed (do not increase dose or frequency); may take
several weeks to achieve desired results; may cause physical and/or
psychological dependence. Avoid excessive alcohol, excess caffeine, and other
prescription or OTC medications not approved by prescriber. Maintain adequate
hydration (2-3 L/day of fluids unless instructed to restrict fluid intake). You
may experience drowsiness, lightheadedness, impaired coordination, dizziness, or
blurred vision (use caution when driving or engaging in tasks requiring
alertness until response to drug is known); constipation (increased exercise,
fluids, or dietary fruit and fiber may help); urinary retention (void before
taking medication); postural hypotension (use caution climbing stairs or when
changing position from lying or sitting to standing); altered sexual drive or
ability (reversible); or photosensitivity (use sunscreen, wear protective
clothing and eyewear, and avoid direct sunlight). Report persistent CNS effects
(eg, nervousness, restlessness, insomnia, anxiety, excitation, headache,
agitation, impaired coordination, changes in cognition); muscle cramping,
weakness, tremors, or rigidity; chest pain, palpitations, or irregular
heartbeat; blurred vision or eye pain; yellowing of skin or eyes; or worsening
of condition. Pregnancy/breast-feeding precautions: Inform prescriber if
you are or intend to be pregnant; contraceptives may be recommended.
Breast-feeding is not recommended. |

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Nursing
Implications |
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May increase appetite
Monitor blood pressure and pulse rate prior to and during initial therapy;
evaluate mental status; monitor weight |

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Dosage Forms |
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Tablet, as hydrochloride: 10 mg, 25 mg, 50 mg, 75 mg, 100 mg, 150
mg |

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References |
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Biederman J, Thisted RA, Greenhill LL, et al,
"Estimation of the Association Between Desipramine and the Risk for Sudden Death in 5-14 Year-Old Children,"
J Clin Psychiatry, 1995, 56(3):87-93.
Boakes AJ, Laurence DR, Teoh PC, et al,
"Interactions Between Sympathomimetic Amines and Antidepressant Agents in Man,"
Br Med J, 1973, 1(849):311-5.
Goodwin DA, Lally KP, and Null DM Jr,
"Extracorporeal Membrane Oxygenation Support for Cardiac Dysfunction From Tricyclic Antidepressant Overdose,"
Crit Care Med, 1993, 21(4):625-7.
Jastak JT and Yagiela JA,
"Vasoconstrictors and Local Anesthesia: A Review and Rationale for Use," J Am
Dent Assoc, 1983, 107(4):623-30.
Larochelle P, Hamet P, and Enjalbert M,
"Responses to Tyramine and Norepinephrine After Imipramine and Trazodone,"
Clin Pharmacol Ther, 1979, 26(1):24-30.
Levy HB, Harper CR, and Weinberg WA,
"A Practical Approach to Children Failing in School," Pediatr Clin North
Am, 1992, 39(4):895-928.
Mitchell JR,
"Guanethidine and Related Agents. III Antagonism by Drugs Which Inhibit the Norepinephrine Pump in Man,"
J Clin Invest, 1970, 49(8):1596-604.
Nelson JC, Jatlow PI, and Mazure C,
"Desipramine Plasma Levels and Response in Elderly Melancholic Patients," J
Clin Psychopharmacol, 1985, 5(4):217-20.
Nies A, Robinson DS, Friedman MS, et al,
"Relationship Between Age and Tricyclic Antidepressant Plasma Levels," Am J
Psychiatry, 1977, 134:790-3.
Pentel PR, Scarlett W, Ross CA, et al,
"Reduction of Desipramine Cardiotoxicity and Prolongation of Survival in Rats With the Use of Polyclonal Drug-Specific Antibody Fab Fragments,"
Ann Emerg Med, 1995, 26(3):334-41.
Pentel PR, Scarlett W, Ross CA, et al,
"Reduction of Desipramine Cardiotoxicity and Prolongation of Survival in Rats With the Use of Polyclonal Drug-Specific Antibody Fab Fragments,"
Ann Emerg Med, 1995, 26(3):334-41.
Riddle MA, Geller B, and Ryan N,
"Another Sudden Death in a Child Treated With Desipramine," J Am Acad Child
Adolesc Psychiatry, 1993, 32(4):792-7.
Roose SP, Glassman AH, Attia E, et al,
"Comparative Efficacy of Selective Serotonin Reuptake Inhibitors and Tricyclics in the Treatment of Melancholia,"
Am J Psychiatry, 1994, 151(12):1735-9.
Rundegren J, van Dijken J, Mörnstad H, et al,
"Oral Conditions in Patients Receiving Long-Term Treatment With Cyclic Antidepressant Drugs,"
Swed Dent J, 1985, 9(2):55-64.
Svedmyr N,
"The Influence of a Tricyclic Antidepressive Agent (Protriptyline) on Some of
the Circulatory Effects of Noradrenaline and Adrenalin®
in Man," Life Sci, 1968, 7(1):77-84.
Ware MR, "Tricyclic Antidepressant Overdose: Pharmacology and Treatment,"
South Med J, 1987, 80(11):1410-5. |

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