Trade Names:Nefazodone Hydrochloride- Tablets 50 mg- Tablets 100 mg- Tablets 150 mg- Tablets 200 mg- Tablets 250 mg
Undetermined; inhibits neuronal uptake of serotonin and norepinephrine; antagonizes alpha-1 adrenergic receptors.
Absorption is rapid and complete. Absolute bioavailability is approximately 20%, T max is about 1 h, and steady state is 4 to 5 days (parent and metabolite). Food delays absorption and decreases bioavailability.
Nefazodone is widely distributed in body tissues, including CNS, and exhibits nonlinear kinetics for dose and time. Nefazodone Vd is 0.22 to 0.87 L/kg and plasma protein binding is more than 99%.
Nefazodone is extensively metabolized in the liver by n-dealkylation and aliphatic and aromatic hydroxylation. Three active metabolites are hydroxynefazodone (HO-NEF), meta-chlorophenylpiperazine (mCPP), and triazole-dione.
Nefazodone is eliminated in urine (less than 1% excreted as unchanged) and feces. The t ½ is 2 to 4 h (parent compound), 1.5 to 4 h (HO-NEF), 4 to 8 h (mCPP), and 18 h (triazole-dione).
C max and AUC for nefazodone and HO-NEF were twice as high. Initiate at half the dose, especially in elderly women.Gender
Nefazodone has a higher C max and AUC in women in single dose, but no difference after multiple doses.Liver Cirrhosis
AUC for nefazodone and HO-NEF at steady state were approximately 25% greater.
Treatment of depression.
Coadministration with carbamazepine, cisapride, or pimozide; hypersensitivity to nefazodone or other phenylpiperazine antidepressants (eg, trazodone).
PO 100 mg twice daily initially; increase by 100 to 200 mg increments every wk (max, 600 mg/day).Elderly and Debilitated Patients
PO 50 mg twice daily initially; increase by 100 mg increments every wk (max, 600 mg/day).
Store tablets at controlled room temperature (59° to 86°F).
Increased plasma concentrations and effects of alprazolam and triazolam.Buspirone
Elevated buspirone concentrations and decreased buspirone metabolite plasma concentrations.Carbamazepine
Elevated serum carbamazepine concentrations with possible increase in adverse reactions may occur.Cisapride
Increased cisapride plasma concentrations with cardiotoxicity may occur.Digoxin
Increased plasma levels of digoxin.Haloperidol
Decreased haloperidol Cl; may need to adjust haloperidol dose.HMG-CoA reductase inhibitors (eg, simvastatin)
The risk of rhabdomyolysis occurrence may be increased.MAOIs
Do not use nefazodone concurrently or within 14 days of discontinuing an MAOI; do not start MAOIs within 1 wk of stopping nefazodone.Pimozide
Increased plasma concentrations of pimozide may occur associated with QT prolongation and rare cases of serious CV adverse reactions, including death, principally caused by ventricular tachycardia of the torsades de pointes type.Propranolol
Nefazodone may decrease propranolol serum concentration; propranolol may interfere with nefazodone metabolism.St. John's wort
Increased sedative-hypnotic effects may occur.Sibutramine, sumatriptan, trazodone
Serotonin syndrome, including irritability, increased muscle tone, shivering, myoclonus, and altered consciousness may occur.
None well documented.
Postural hypotension, vasodilation (4%); hypotension (2%); sinus bradycardia (1.5%).
Headache (36%); somnolence (28%); dizziness (22%); asthenia, insomnia (11%); lightheadedness (10%); confusion (8%); memory impairment, paresthesia (4%); abnormal dreams, decreased concentration (3%); ataxia, incoordination, psychomotor retardation, tremor (2%); hypertonia, decreased libido (1%); convulsions (postmarketing).
Pruritus, rash (2%); Stevens-Johnson syndrome (postmarketing).
Abnormal vision (10%); blurred vision (9%); pharyngitis (6%); tinnitus (3%); taste perversion, visual field defect (2%).
Dry mouth (25%); nausea (23%); constipation (17%); dyspepsia (9%); diarrhea (8%); increased appetite (5%); nausea and vomiting (2%); gastroenteritis (at least 1%).
Urinary frequency, UTI, urinary retention, vaginitis (2%); breast pain (1%); impotence (at least 1%); gynecomastia (male), priapism (postmarketing).
Liver necrosis, liver failure (postmarketing).
Decreased hematocrit (3%).
Peripheral edema (3%); thirst (1%); galactorrhea, hyponatremia, increased prolactin (postmarketing).
Increased cough (3%); dyspnea, bronchitis (at least 1%).
Infection (8%); flu-like syndrome (3%); chills, fever (2%); neck rigidity (1%); anaphylactic reactions, angioedema, serotonin syndrome (postmarketing).
Life-threatening cases of hepatic failure have been reported. Counsel patient about and immediately report signs of liver dysfunction. Do not initiate therapy in patients with active liver disease or elevated baseline serum transaminases. There is no evidence that preexisting liver disease increases risk of liver failure, but it can complicate patient monitoring. Withdraw therapy and do not consider retreatment if serum AST or ALT is 3 times ULN or more.
Category C .
Safety and efficacy not established.
Initiate treatment at half the usual dose. Dosage range same as younger patients.
Sinus bradycardia reported in 1.5% of patients; use with caution in patients with recent MI or unstable heart disease.
May activate mania/hypomania; use with caution in patients with history of mania.
Use with caution in patients with known CV or cerebrovascular disease that could be exacerbated by hypotension (eg, history of MI, angina, ischemic stroke) and conditions that would predispose to hypotension (eg, dehydration, hypovolemia, treatment with antihypertensive medications).
Priapism (eg, prolonged, painful, inappropriate penile erection) has been reported with closely related antidepressants. Discontinuation of therapy is necessary.
Rare cases of petit mal and grand mal seizures reported.
Closely monitor patients at risk, and do not give them access to excessive quantities.
Visual disturbances, including blurred vision, scotoma, and visual trails reported.
Nausea, vomiting, somnolence.
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