Contents

Search

nefazodone (Serzone, Dutonin, Nefador, Nefirel, Rezeril)

Tradename: Serzone. Britol-Myers to discontinue# 06/14/04 [8] Generics to remain on the market. [9] Indications: - depression, major depression - with & without sleep disorder - premenstrual syndrome - anxiety - sleep disorders - mania [11] Dosage: 1) start 100 mg PO BID 2) max 600 mg/day 3) after meal dosing may decrease lightheadedness & orthostatic hypotension, but may also decrease absorption Tabs: 100, 150, 200, 250 mg. Pharmacokinetics: 1) absolute bioavailability is 20% due to 1st pass metabolism 2) food delays absorption & may reduce bioavailability 3) metabolized by cyt P450 3A4 to 3 active metabolites 4) 1/2life depends upon dosage a) parent compound: 2-8 hours b) parent plus active metabolites: 11-24 hours 5) < 1% of the drug is excreted unchanged in the urine 6) hepatic impairment decreases clearance of parent compound 7) renal insufficiency decreases clearance of active metabolites Monitor: - serum ALT or serum AST within 180 days - discontinue if serum AST or serum ALT > 3X upper limit of normal or if signs or symptoms of liver dysfunction develop [10] Adverse effects: 1) common (> 10%) - headache, drowsiness, insomnia, agitation, dizziness (17%), lightheadedness (10%), confusion, dry mouth (8%), nausea (5-22%), tremor 2) less common (1-10%) - orthostatic hypotension, constipation, vomiting, weakness, blurred vision, amblyopia, somnolence (6%) 3) uncommon (< 1%) - diarrhea, priapism, hepatic failure (< 0.001%) [5] 4) other - moderate sedation - moderate orthostatic hypotension - very low anticholinergic effects - dry mouth - blurred vision - headache - somnolence - less likely to cause priapism than trazodone 5) adverse effects are dose-related & occur mainly with doses > 300 mg/day 6) liver failure 0.00025% (removed from market in Europe) [7] (at least 20 deaths) [8] Drug interactions: 1) MAO inhibitors in combination may result in serious, even fatal reactions - allow a 2 week washout period 2) astemizole, terfenadine, cisapride in combination may result in QT prolongation 3) nefazodone increases serum levels of alprazolam, triazolam, midazolam & possibly phenytoin 4) nefazodone increases serum levels of digoxin 5) nefazodone decreases effect of: a) clonidine b) methyldopa c) diuretics d) oral hypoglycemic agents e) anticoagulants 6) carbamazepine 7) decreased effect of beta-blockers 8) any drug that inhibits cyt P450 3A4 may increase levels of nefazodone 9) any drug that induces cyt P450 3A4 may diminish levels of nefazodone 10) nefazodone inhibits cyt P450 3A4, thus inhibits its own metabolism & metabolism of other cyt P450 3A4 substrates Mechanism of action: 1) postsynaptic 5-HT receptor 2A antagonist 2) some presynaptic serotonin re-uptake inhibition 3) does not suppress REM sleep 4) 5-HT 2A inhibits 5-HT 1A, thus inhibition of 5-HT 2A enhances action of 5-HT 1A 5) weak alpha-1 adrenergic receptor antagonist [5] 6) inhibits cyt P450 3A4 & cyt P450 2D6

Interactions

drug interactions drug adverse effects (more general classes)

Related

cytochrome P450 3A4 (cytochrome P450 C3, nifedipine oxidase, P450-PCN1, NF-25, CYP3A4) serotonin [5HT]-2A receptor; 5-hydroxytryptamine receptor 2A; 5-HT-2A; 5-HT-2; serotonin receptor 2A (HTR2A, HTR2)

General

atypical antidepressant receptor antagonist

Properties

INHIBITS: serotonin-2A-receptor MISC-INFO: elimination route LIVER 1/2life 2-8 HOURS 11-24 HOURS 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. Prescriber's Letter 13(3): 2006 Cytochrome P450 drug interactions Detail-Document#: 220233 (subscription needed) http://www.prescribersletter.com
  5. UCLA Intensive Course in Geriatric Medicine & Board Review, Marina Del Ray, CA, Sept 12-15, 2001
  6. Prescriber's Letter 9(1):3 2002
  7. Prescriber's Letter 10(2):8 2003
  8. Netscape, Associated Press 05/14/04
  9. Serzone Off the Market Prescriber's Letter 11(6):35 2004 Detail-Document#: 200616 (subscription needed) http://www.prescribersletter.com
  10. Prescriber's Letter 17(7): 2010 Recommended Lab Monitoring for Common Medications Liver Function Test Scheduling Detail-Document#: 260704 (subscription needed) http://www.prescribersletter.com
  11. Deprecated Reference