nefazodone

Absorption: Well absorbed but undergoes extensive and variable first-pass hepatic metabolism (bioavailability about 20%).

Distribution: Widely distributed; enters the CNS.

Protein Binding: ≥99%.

Metabolism/Excretion: Extensively metabolized. One metabolite (hydroxynefazodone) has antidepressant activity.

Half-Life: Nefazodone: 2–4 hr; hydroxynefazodone: 1.5–4 hr.

Time/Action Profile ⬆ ⬇

(antidepressant action)

ROUTE	ONSET	PEAK	DURATION
PO	days–wk	several wk	unknown

Contraind./Precautions ⬆ ⬇

Contraindicated in:

Hypersensitivity;
Concurrent MAO inhibitor therapy;
Active liver disease or baseline ↑ serum transaminases.

Use Cautiously in:

May ↑ risk of suicide attempt/ideation especially during dose early treatment or dose adjustment;
History of suicide attempt or drug abuse;
Underlying cardiovascular or cerebrovascular disease;
History of mania;
OB: Use during pregnancy only if potential maternal benefit justifies potential fetal risk;
Lactation: Use while breastfeeding only if potential maternal benefit justifies potential risk to infant;
Pedi: Safety and effectiveness not established in children; suicide risk may be greater in children and adolescents ;
Geri: Initiate therapy at lower doses.

Adv. Reactions/Side Effects ⬆ ⬇

CV: bradycardia, hypotension

Derm: rash

EENT: abnormal vision, blurred vision, eye pain, tinnitus

GI: constipation, dry mouth, nausea, gastroenteritis, HEPATOTOXICITY

GU: erectile dysfunction

Hemat: ↓hematocrit

Neuro: dizziness, insomnia, somnolence, agitation, confusion, SUICIDAL THOUGHTS, weakness

Resp: dyspnea

Interactions ⬆ ⬇

Drug-drug:

Serious, potentially fatal reactions may occur during concurrent use withMAO inhibitors(do not use concurrently or within 2 wk of MAO inhibitors; discontinue nefazodone at least 14 days before starting MAO inhibitor therapy).
↑CNS depression with other CNS depressants including alcohol, antihistamines, opioid analgesics, and sedative/hypnotics.
May ↑ levels and effects of alprazolam or triazolam.
May ↑ serum digoxin levels.
Additive hypotension may occur with antihypertensives, nitrates, or acute ingestion of alcohol.
May ↑ risk of myopathy with HMG-CoA reductase inhibitors.
↓antidepressant action with concomitant use of carbamazepine.
May ↓ clearance of haloperidol, so haloperidol dose may need to be ↓.

Drug-Natural Products:

↑risk of serotonin syndrome with St. John’s wort and SAMe.
Kava-kava, valerian, or chamomile can ↑ CNS depression.

Route/Dosage ⬆ ⬇

PO (Adults ): 100 mg twice daily initially; may ↑ weekly up to 600 mg/day in 2 divided doses.
PO Geriatric Patients ): 50 mg twice daily initially; may ↑ weekly as tolerated.

Availability ⬆ ⬇

(Generic available)

Tablets: 50 mg; 100 mg; 150 mg; 200 mg; 250 mg

Assessment ⬆ ⬇

Assess mental status (orientation, mood, behavior) frequently. Inform health care professional if patient demonstrates significant increase in anxiety, nervousness, or insomnia.
Assess suicidal tendencies, especially in early therapy. Restrict amount of drug available to patient.
Monitor BP and pulse before and periodically during therapy.
Monitor liver function tests prior to and routinely during therapy. Obtain LFTs at first sign of hepatic dysfunction (nausea, vomiting, abdominal pain, fatigue, anorexia, dark urine).
Assess for sexual dysfunction throughout treatment.

Lab Test Considerations:

May cause decrease in hematocrit and leukopenia.
- Monitor liver function periodically. If serum AST or ALT levels are >3 times the upper limit of normal discontinue nefazodone.
- May also cause hypercholesterolemia and hypoglycemia.

Implementation ⬆ ⬇

Discontinue nefazodone prior to elective surgery to prevent potential interactions with general anesthesia.
PO: Administer doses twice daily.

Patient/Family Teaching ⬆ ⬇

Instruct patient to take medication as directed. Several wk may be required to obtain a full antidepressant response. Once response is obtained, therapy should be continued for at least 6 mo. If a dose is missed, take as soon as possible unless almost time for next dose. Do not double doses.
May cause drowsiness or dizziness. Caution patient to avoid driving or other activities requiring alertness until response to the drug is known.
Advise patient to make position changes slowly to minimize orthostatic hypotension.
Encourage patient and family to be alert for emergence of anxiety, agitation, panic attacks, insomnia, irritability, hostility, impulsivity, akathisia, hypomania, mania, worsening of depression and suicidal ideation, especially during early antidepressant therapy. Assess symptoms on a day-to-day basis as changes may be abrupt. If these symptoms occur, notify health care professional.
Caution patient to avoid taking alcohol or other CNS depressant drugs during therapy and not to take other prescription, OTC medications, or herbal products without consulting health care professional.
Advise patient to notify health care professional immediately if signs of liver dysfunction (jaundice, anorexia, GI complaints, malaise, dark urine) occur.
Inform patient that frequent mouth rinses, good oral hygiene, and sugarless gum or candy may minimize dry mouth. If dry mouth persists for more than 2 wk, consult health care professional regarding use of saliva substitute.
Instruct patient to notify health care professional of signs of allergy (rash, hives) or if agitation, blurred or other changes in vision, confusion, dizziness, unsteadiness, difficult or frequent urination, difficulty concentrating, or memory problems occur.
Instruct females of reproductive potential to notify health care professional if pregnancy is planned or suspected or if breastfeeding.
Emphasize the importance of follow-up examinations to monitor progress.

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Pronunciation ⬇

Classifications ⬆ ⬇

Indications ⬆ ⬇

Action ⬆ ⬇

Pharmacokinetics ⬆ ⬇