desipramine (Norpramin, Pertofrane)
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Introduction
Tradenames: Norpramin, Pertofrane.
Indications
- treatment of depression
- analgesic adjunct in neurogenic pain & peripheral neuropathy, & urticaria
- management of anxiety/panic attacks
- bulimia nervosa[7]
- attention-deficit hyperactivity disorder (ADHD)
- cataplexy[7]
Contraindications
- within 2 weeks of administration of MAO inhibitor
Caution:
- avoid ingestion of alcohol
- do not discontinue medication abruptly
Dosage
Tabs: 10, 25, 50, 75, 100, 150 mg.
Pharmacokinetics
- may take 1-3 weeks for onset of action
- metabolized in liver by cyt P450 2D6 to active metabolite 2-OH-desipramine
- therapeutic range: 100-300 ng/mL
- 1/2life 12-57 hours[2]
- 70% eliminated in the urine
elimination via liver
1/2life = 20-90 hours
protein binding = 73-92 %
elimination by hemodialysis = -
elimination by hemoperfusion = -
elimination by peritoneal dialysis = -
Adverse effects
- common (> 10%)
- dizziness, drowsiness, dry mouth, constipation, headache, increased appetite, nausea, weakness, unpleasant taste, weight gain
- not common (1-10%)
- 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
- 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 adverse effects of tricyclic antidepressants
- drug adverse effects of antidepressants
- drug adverse effects of psychotropic agents
Drug interactions
- coadministration enhances metabolism of desipramine
- coadministration decreases protein binding of desipramine
- coadministration inhibits metabolism of desipramine
- decreased effect of clonidine, barbiturates, guanethidine, carbamazepine & phenytoin
- increased CNS effects of benzodiazepines, sympathomimetics
- increased toxicity when used concurrently with:
- agents which prolong the QT interval
- any pharmaceutical agent that inhibits cyt P450 2D6 may increase levels of desipramine
- drug interaction(s) of tricyclic antidepressants with physostigmine
- drug interaction(s) of antidepressant in combination with GLP1-agonist
- drug interaction(s) of benzodiazepines with antidepressants
- drug interaction(s) of antidepressants with benzodiazepines
- drug interaction(s) of NSAIDs with antidepressants
- drug interaction(s) of antidepressant with opiates
Laboratory
- desipramine in serum
- methods: HPLC, GLC, GC-MS
- interferences:
- iminodibenzyl & imipramine may contaminate dosage forms & contribute to metabolite concentrations
- desipramine may be displaced from protein-binding sites by plasticizers in collecting devices
- other labs with Loincs
Mechanism of action
- tricyclic antidepressant (TCA)
- secondary amine metabolite of imipramine
- inhibits re-uptake of norepinephrine & to a lesser extent serotonin by pre-synaptic neuronal terminals
- desensitization of adenyl cyclase
- down-regulation of beta adrenergic & serotonin receptors
More general terms
Additional terms
References
- ↑ The Pharmacological Basis of Therapeutics, 9th ed. Gilman et al, eds. Permagon Press/McGraw Hill, 1996
- ↑ 2.0 2.1 Drug Information & Medication Formulary, Veterans Affairs, Central California Health Care System, 1st ed., Ravnan et al eds, 1998
- ↑ Kaiser Permanente Northern California Regional Drug Formulary, 1998
- ↑ Clinical Guide to Laboratory Tests, 3rd ed. Teitz ed., W.B. Saunders, 1995
- ↑ Harrison's Principles of Internal Medicine, 14th ed. Fauci et al (eds), McGraw-Hill Inc. NY, 1998, pg 56
- ↑ 6.0 6.1 FDA MedWatch Norpramin (desipramine hydrochloride) - Dear Healthcare Professional Letter http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm192655.htm
- ↑ 7.0 7.1 7.2 Deprecated Reference