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nortriptyline (Aventyl, Pamelor)

Tradenames: Aventyl, Pamelor. Indications: - treatment of depression - enuresis in children - analgesic for chronic pain - management of anxiety/panic attacks - smoking cessation [7] - attention-deficit hyperactivity disorder [7] Contraindications: 1) patients with narrow-angle glaucoma 2) concurrent administration of MAO inhibitor Dosage: - Start 25 mg PO TID/QID, max 150 mg/day. Tabs: 10, 25, 50, 75 mg. Solution: 10 mg/5 mL. Pharmacokinetics: 1) peak effect may take more than 2 weeks 2) metabolized in liver by cyt P450 2D6 to active metabolite 10-OH-nortriptyline 3) metabolites are eliminated in the urine 4) 1/2life of 28-31 hours 5) nortriptyline is the active metabolite of amitriptyline 6) therapeutic range: 50-175 ng/mL. Adverse effects: 1) common (> 10%) - dizziness, drowsiness, dry mouth, constipation, headache, increased appetite, nausea, weakness, unpleasant taste, weight gain 2) less common (1-10%) - blurred vision, confusion, delirium, hallucinations, difficult urination, eye pain, arrhythmias, fine muscle tremors, hypotension, nervousness, restlessness, parkinsonism, sexual dysfunction, diarrhea, excessive sweating, heartburn, insomnia 3) uncommon (< 1%) - agranulocytosis, alopecia, anxiety, breast enlargement, galactorrhea, cholestatic jaundice, seizures, SIADH, tinnitus, testicular swelling, gum disorder, decreased lower esophageal sphincter tone, GERD, leukopenia, eosinophilia, abnormal liver function tests, increased intraocular pressure, allergic reactions, photosensitivity 4) cardiovascular: hypotension, hypertension, tachycardia, arrhythmias, heart block, myocardial infarction, stroke 5) psychiatric: confusional states especially in the elderly, hallucinations, disorientation, delusion, anxiety, restlessness, agitation, insomnia, panic, nightmares, hypomania, exacerbation of psychosis 6) neurologic: paresthesias, numbness, ataxia, peripheral neuropathy, extrapyramidal symptoms, seizures, tinnitus 7) allergic: skin rash, petechiae, urticaria, photosensitivity, edema, drug fever 8) hematologic: bone marrow depression 9) gastrointestinal: nausea/vomiting, diarrhea, stomatitis 10) endocrine: gynecomastia, impotence, testicular swelling, SIADH 11) moderate anticholinergic effects 12) other: jaundice, alopecia, urinary frequency 13) low sedation 14) low incidence of orthostatic hypotension compared with amitriptyline Drug interactions: 1) coadministration enhances metabolism of nortriptyline a) barbiturates b) carbamazepine c) smoking 2) coadministration decreases protein binding of nortriptyline a) phenytoin b) phenylbutazone c) aspirin d) scopolamine e) phenothiazines 3) coadministration inhibits metabolism of nortriptyline a) fluoxetine b) methylphenidate c) oral contraceptives d) haloperidol e) cimetidine f) chloramphenicol g) phenothiazines 4) monoamine oxidase (MAO) inhibitors: hyperpyrexia, seizures 5) alcohol may potentiate effects 6) nortriptyline may reduce hypotensive effects of clonidine & guanethidine 7) nortriptyline may potentiate CNS effects of CNS depressants & sympathomimetics 8) additive side effects in combination with anti-cholinergic agents 9) nortriptyline may enhance anticoagulant effects of warfarin 10) astemizole & terfenadine should be avoided 11) any pharmaceutical agent that inhibits cyt P450 2D6 may increase levels of nortriptyline Laboratory: 1) nortriptyline in serum a) serum, plasma (EDTA) b) collect at steady state trough; > 12 hours after dose 2) methods: HPLC, GLC, GC-MS, RIA 3) interferences: -> nortriptyline may be displaced from protein-binding sites by plasticizers in collecting devices 4) other laboratory measurements with Loincs - nortriptyline in dried blood spot - nortriptyline in gastric fluid - nortriptyline in urine Mechanism of action: 1) increases serotonin & norepinephrine in at synapses by inhibiting re-uptake 2) tricyclic antidepressant activity

Interactions

drug interactions drug adverse effects (more general classes)

Related

amitriptyline (Elavil, Endep) cytochrome P450 2D6 (cytochrome P450 2D, cytochrome P450 DB1, debrisoquine-4-hydroxylase, CYP2D6) depression enuresis

General

tricyclic antidepressant (TCA)

Properties

MISC-INFO: elimination route LIVER 1/2life 18-90 HOURS therapeutic-range 50-150 NG/ML toxic-range >500 NG/ML protein-binding 93-95% elimination by hemodialysis - elimination by hemodialysis - pregnancy-category D 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. 1997 PDR
  3. Drug Information & Medication Formulary, Veterans Affairs, Central California Health Care System, 1st ed., Ravnan et al eds, 1998
  4. Kaiser Permanente Northern California Regional Drug Formulary, 1998
  5. Clinical Guide to Laboratory Tests, 3rd ed. Teitz ed., W.B. Saunders, 1995
  6. Harrison's Principles of Internal Medicine, 14th ed. Fauci et al (eds), McGraw-Hill Inc. NY, 1998, pg 56
  7. Deprecated Reference