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desipramine (Norpramin, Pertofrane)

Tradenames: Norpramin, Pertofrane. Indications: 1) treatment of depression 2) analgesic adjunct in neurogenic pain & peripheral neuropathy, & urticaria 3) management of anxiety/panic attacks 4) bulimia nervosa [7] 5) attention-deficit hyperactivity disorder (ADHD) 6) cataplexy [7] Contraindications: - within 2 weeks of administration of MAO inhibitor Caution: 1) avoid ingestion of alcohol 2) do not discontinue medication abruptly Dosage: 1) start 25-200 mg PO QHS or in divided doses 2) usual maintenance dose is 75-150 mg/day 3) max 300 mg/day Tabs: 10, 25, 50, 75, 100, 150 mg. Pharmacokinetics: 1) may take 1-3 weeks for onset of action 2) metabolized in liver by cyt P450 2D6 to active metabolite 2-OH-desipramine 3) therapeutic range: 100-300 ng/mL 4) 1/2life 12-57 hours [2] 5) 70% eliminated in the urine Adverse effects: 1) common (> 10%) - dizziness, drowsiness, dry mouth, constipation, headache, increased appetite, nausea, weakness, unpleasant taste, weight gain 2) not common (1-10%) - blurred vision, confusion, delirium, hallucinations, difficulty urinating, eye pain, arrhythmias, tremor (fine), hypotension, nervousness, restlessness, parkinsonism, impotence, diarrhea, excessive sweating, heartburn, insomnia 3) uncommon (< 1%) - agranulocytosis, alopecia, anxiety, breast enlargement, galactorrhea, cholestatic jaundice, seizures, SIADH, tinnitus, testicular swelling, gingivitis, GERD, diminished lower esophageal sphincter tone, leukopenia, eosinophilia, abnormal liver function test (LFTs), increased intraocular pressure, allergic reactions, photosensitivity 4) other - low incidence of sedation - low incidence of orthostatic hypotension - lower incidence of anticholinergic side effects than other tricyclic antidepressants (TCA) - may cause urine to turn blue-green - seizures may precede cardiac arrhythmia & sudden death [6] Drug interactions: 1) coadministration enhances metabolism of desipramine a) barbiturates b) carbamazepine c) smoking 2) coadministration decreases protein binding of desipramine a) phenytoin b) phenylbutazone c) aspirin d) scopolamine e) phenothiazines 3) coadministration inhibits metabolism of desipramine a) fluoxetine b) methylphenidate c) oral contraceptives d) haloperidol e) cimetidine f) chloramphenicol g) phenothiazines 4) decreased effect of clonidine, barbiturates, guanethidine, carbamazepine & phenytoin 5) increased CNS effects of benzodiazepines, sympathomimetics 6) increased toxicity when used concurrently with: a) anticholinergic agents b) alcohol c) CNS depressants d) MAO inhibitors 7) agents which prolong the QT interval a) astemizole b) terfenadine c) cisapride 8) any pharmaceutical agent that inhibits cyt P450 2D6 may increase levels of desipramine Laboratory: 1) desipramine in serum a) serum, plasma (EDTA) b) collect at steady state trough; > 12 hours after dose c) separate from cells d) stable for 4 months at -20 degrees C 2) methods: HPLC, GLC, GC-MS 3) interferences: a) iminodibenzyl & imipramine may contaminate dosage forms & contribute to metabolite concentrations b) desipramine may be displaced from protein-binding sites by plasticizers in collecting devices 4) other labs with Loincs - desipramine in specimen - desipramine in gastric fluid - desipramine in urine Mechanism of action: 1) tricyclic antidepressant (TCA) 2) secondary amine metabolite of imipramine 3) inhibits re-uptake of norepinephrine & to a lesser extent serotonin by pre-synaptic neuronal terminals 4) desensitization of adenyl cyclase 5) down-regulation of beta adrenergic & serotonin receptors

Interactions

drug interactions drug adverse effects (more general classes)

Related

cytochrome P450 2D6 (cytochrome P450 2D, cytochrome P450 DB1, debrisoquine-4-hydroxylase, CYP2D6)

General

tricyclic antidepressant (TCA)

Properties

MISC-INFO: elimination route LIVER 1/2life 20-90 HOURS therapeutic-range 75-300 NG/ML toxic-range >400 NG/ML protein-binding 73-92% elimination by hemodialysis - hemoperfusion - peritoneal dialysis - pregnancy-category C safety in lactation ?

Database Correlations

PUBCHEM correlations

References

  1. The Pharmacological Basis of Therapeutics, 9th ed. Gilman et al, eds. Permagon Press/McGraw Hill, 1996
  2. Drug Information & Medication Formulary, Veterans Affairs, Central California Health Care System, 1st ed., Ravnan et al eds, 1998
  3. Kaiser Permanente Northern California Regional Drug Formulary, 1998
  4. Clinical Guide to Laboratory Tests, 3rd ed. Teitz ed., W.B. Saunders, 1995
  5. Harrison's Principles of Internal Medicine, 14th ed. Fauci et al (eds), McGraw-Hill Inc. NY, 1998, pg 56
  6. FDA MedWatch Norpramin (desipramine hydrochloride) - Dear Healthcare Professional Letter http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm192655.htm
  7. Deprecated Reference