Desipramine

What are the side effects of Norpramin (Desipramine) ?

• Cardiovascular: Hypotension, hypertension, palpitations, heart block, myocardial infarction, stroke, arrhythmias, premature ventricular contractions, tachycardia, ventricular tachycardia, ventricular fibrillation, sudden death
• There has been a report of an “acute collapse” and “sudden death” in an 8-year-old (18 kg) male, treated for 2 years for hyperactivity.
• There have been additional reports of sudden death in children. (See PRECAUTIONS-Pediatric Use)
• Psychiatric: Confusional states (especially in the elderly) with hallucinations, disorientation, delusions; anxiety, restlessness, agitation; insomnia and nightmares; hypomania; exacerbation of psychosis
• Neurologic: Numbness, tingling, paresthesias of extremities; incoordination, ataxia, tremors; peripheral neuropathy; extrapyramidal symptoms; seizures; alterations in EEG patterns; tinnitus Symptoms attributed to Neuroleptic Malignant Syndrome have been reported during desipramine use with and without concomitant neuroleptic therapy.
• Anticholinergic: Dry mouth, and rarely associated sublingual adenitis; blurred vision, disturbance of accommodation, mydriasis, increased intraocular pressure; constipation, paralytic ileus; urinary retention, delayed micturition, dilation of urinary tract
• Allergic: Skin rash, petechiae, urticaria, itching, photosensitization (avoid excessive exposure to sunlight), edema (of face and tongue or general), drug fever, cross-sensitivity with other tricyclic drugs
• Hematologic: Bone marrow depressions including agranulocytosis, eosinophilia, purpura, thrombocytopenia

• Drugs Metabolized by P450 2D6. The biochemical activity of the drug metabolizing isozyme cytochrome P450 2D6 (debrisoquin hydroxylase) is reduced in a subset of the Caucasian population (about 7% to 10% of Caucasians are so called “poor metabolizers”); reliable estimates of the prevalence of reduced P450 2D6 isozyme activity among Asian, African and other populations are not yet available.
• Poor metabolizers have higher than expected plasma concentrations of tricyclic antidepressants (TCAs) when given usual doses.
• Depending on the fraction of drug metabolized by P450 2D6, the increase in plasma concentration may be small, or quite large (8 fold increase in plasma AUC of the TCA).

• Clinical Worsening and Suicide Risk: Patients, their families, and their caregivers should be encouraged 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 adjusted up or down. Families and caregivers of patients should be advised to observe for the emergence of such symptoms on a day-to-day basis, since changes may be abrupt. Such symptoms should be reported to the patient’s prescriber or health professional, 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 indicate a need for very close monitoring and possibly changes in the medication.