Indications Treatment of depression.

 Contraindications Coadministration with carbamazepine, cisapride, or pimozide; hypersensitivity to nefazodone or other phenylpiperazine antidepressants (eg, trazodone).

 Route/Dosage

ADULTS: PO 100 mg bid initially, increase by 100 to 200 mg increments q wk (max, 600 mg/day).

Elderly/Debilitated patients: PO 50 mg bid initially, increase by 100 mg increments q wk (max, 600 mg/day).

 Interactions

Benzodiazepines: Increased plasma concentrations and effects of alprazolam and triazolam.

Buspirone: Elevated buspirone concentrations, decreased buspirone metabolite plasma concentrations.

Carbamazepine: Elevated serum carbamazepine concentrations with possible increase in side effects may occur.

Cisapride: Increased cisapride plasma concentrations with cardiotoxicity may occur.

Digoxin: Increased plasma levels of digoxin.

Haloperidol: Decreased haloperidol clearance; may need to adjust haloperidol dose.

HMG-CoA Reductase Inhibitors (eg, Simvastatin): The risk of rhabdomyolysis occurrence may be increased.

MAOI: Do not use nefazodone concurrently or within 14 days of discontinuing a MAOI; do not start MAOI within 1 wk of stopping nefazodone.

Pimozide: Increased plasma concentrations of pimozide may occur associated with QT prolongation and rare cases of serious cardiovascular adverse events, 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: A “serotonin syndrome” including irritability, increased muscle tone, shivering, myoclonus, and altered consciousness may occur.

 Lab Test Interferences None well documented.

 Adverse Reactions

CARDIOVASCULAR: Hypotension; orthostatic hypotension; peripheral edema; sinus bradycardia; postural hypotension. CNS: Headache; somnolence; dizziness; insomnia; lightheadedness; confusion; memory impairment; paresthesia; abnormal dreams; decreased concentration; ataxia; incoordination; psychomotor retardation; tremor; hypertonia; decreased libido; vasodilation. DERMATOLOGIC: Pruritus; rash. EENT: Blurred vision; abnormal vision; visual field defects; eye pain; tinnitus; abnormal taste. GI: Dry mouth; nausea; constipation; dyspepsia; diarrhea; increased appetite; vomiting. GU: Urinary frequency; urinary tract infection; urinary retention; vaginitis; breast pain; impotence. HEMATOLOGIC: Decreased hematocrit. RESPIRATORY: Pharyngitis; cough. OTHER: Asthenia; flu syndrome; chills; fever; neck rigidity; arthralgia; thirst.

 Precautions

Pregnancy: Category C. Lactation: Undetermined. Children: Safety and efficacy in children less than 18 yr not established. Elderly: Initiate treatment at half the usual dose. Dosage range same as younger patients. Bradycardia: Sinus bradycardia reported in 1.5% of patients; use with caution in patients with recent MI or unstable heart disease. Hepatotoxicity: Life-threatening hepatic failure may occur; do not initiate nefazodone therapy in patients with active liver disease or elevated baseline transaminases. Mania/Hypomania: May activate mania/hypomania; use with caution in patients with history of mania. Postural Hypotension: Use with caution in patients with known cardiovascular 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). Seizures: Rare cases of petit mal and grand mal seizures reported. Suicide: Closely monitor patients at risk, and do not give them access to excessive quantities. Priapism: Priapism (prolonged, painful, inappropriate penile erection) has been reported with closely related antidepressants. Discontinuation of therapy is necessary. Visual Disturbances: Visual disturbances, including blurred vision, scotoma, and visual trails reported.

 Administration/Storage

• Cautiously administer to the elderly and patients with suicidal behavior, mania, heart disease, or dysrhythmias.
• Administer with caution to patients with known cardiac conditions that could be exacerbated by hypotension (eg, history of MI, angina, ischemic stroke).
• Store at room temperature in a tightly closed container.

 Assessment/Interventions

• Obtain patient history.
• Advise patient to avoid use of alcohol and otc medications without consulting health care provider.
• Evaluate mental and neurological status, mood changes, and suicidal tendencies.
• Assess debilitated or elderly patients for signs of overdose or adverse reactions.
• Determine whether suicide precautions are advisable and implement them as necessary.
• Monitor patient for postural hypotension and cardiac dysrhythmias. Monitor blood pressure and pulse at periodic intervals throughout therapy.

 Patient/Family Education

• Instruct patient to take exactly as directed by health care provider.
• Inform patient or family that several weeks of treatment may be required to obtain the full therapeutic antidepressant effect.
• Instruct patient to inform health care provider of all prescription and otc drugs presently taking or planning to take.
• Instruct patient to avoid alcohol or other CNS depressant drugs during therapy.
• Caution patient not to drive or operate hazardous machinery until certain that therapy does not adversely affect ability to perform these activities.
• Instruct patient to notify health care provider if developing a rash, hives, or any signs of an allergic reaction.
• Instruct women to notify health care provider if pregnant, planning to become pregnant, or nursing an infant.
• Advise patient to take sips of water, suck on ice chips or sugarless hard candy, or chew sugarless gum if dry mouth occurs.
• Instruct men to immediately notify health care provider should symptoms of priapism occur.
• Reinforce the necessity of follow-up examinations and continued therapy.
• Advise patients to avoid sunlight and sunlamps or to wear protective clothing; photosensitivity may occur.
• Advise patient to notify health care provider if symptoms of visual disturbances occur.
• Advise patient to be alert for signs and symptoms of liver dysfunction, including jaundice, anorexia, GI complaints, and malaise, and to report the symptoms to health care provider immediately.

Indications for Drugs ::

 Action Undetermined; inhibits neuronal uptake of serotonin and norepinephrine; antagonizes alpha₁-adrenergic receptors.

 Indications Treatment of depression.

 Contraindications Coadministration with carbamazepine, cisapride, or pimozide; hypersensitivity to nefazodone or other phenylpiperazine antidepressants (eg, trazodone).

 Route/Dosage

ADULTS: PO 100 mg bid initially, increase by 100 to 200 mg increments q wk (max, 600 mg/day).

Elderly/Debilitated patients: PO 50 mg bid initially, increase by 100 mg increments q wk (max, 600 mg/day).

 Interactions

Benzodiazepines: Increased plasma concentrations and effects of alprazolam and triazolam.

Buspirone: Elevated buspirone concentrations, decreased buspirone metabolite plasma concentrations.

Carbamazepine: Elevated serum carbamazepine concentrations with possible increase in side effects may occur.

Cisapride: Increased cisapride plasma concentrations with cardiotoxicity may occur.

Digoxin: Increased plasma levels of digoxin.

Haloperidol: Decreased haloperidol clearance; may need to adjust haloperidol dose.

HMG-CoA Reductase Inhibitors (eg, Simvastatin): The risk of rhabdomyolysis occurrence may be increased.

MAOI: Do not use nefazodone concurrently or within 14 days of discontinuing a MAOI; do not start MAOI within 1 wk of stopping nefazodone.

Pimozide: Increased plasma concentrations of pimozide may occur associated with QT prolongation and rare cases of serious cardiovascular adverse events, 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: A “serotonin syndrome” including irritability, increased muscle tone, shivering, myoclonus, and altered consciousness may occur.

 Lab Test Interferences None well documented.

 Adverse Reactions

CARDIOVASCULAR: Hypotension; orthostatic hypotension; peripheral edema; sinus bradycardia; postural hypotension. CNS: Headache; somnolence; dizziness; insomnia; lightheadedness; confusion; memory impairment; paresthesia; abnormal dreams; decreased concentration; ataxia; incoordination; psychomotor retardation; tremor; hypertonia; decreased libido; vasodilation. DERMATOLOGIC: Pruritus; rash. EENT: Blurred vision; abnormal vision; visual field defects; eye pain; tinnitus; abnormal taste. GI: Dry mouth; nausea; constipation; dyspepsia; diarrhea; increased appetite; vomiting. GU: Urinary frequency; urinary tract infection; urinary retention; vaginitis; breast pain; impotence. HEMATOLOGIC: Decreased hematocrit. RESPIRATORY: Pharyngitis; cough. OTHER: Asthenia; flu syndrome; chills; fever; neck rigidity; arthralgia; thirst.

 Precautions

Pregnancy: Category C. Lactation: Undetermined. Children: Safety and efficacy in children less than 18 yr not established. Elderly: Initiate treatment at half the usual dose. Dosage range same as younger patients. Bradycardia: Sinus bradycardia reported in 1.5% of patients; use with caution in patients with recent MI or unstable heart disease. Hepatotoxicity: Life-threatening hepatic failure may occur; do not initiate nefazodone therapy in patients with active liver disease or elevated baseline transaminases. Mania/Hypomania: May activate mania/hypomania; use with caution in patients with history of mania. Postural Hypotension: Use with caution in patients with known cardiovascular 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). Seizures: Rare cases of petit mal and grand mal seizures reported. Suicide: Closely monitor patients at risk, and do not give them access to excessive quantities. Priapism: Priapism (prolonged, painful, inappropriate penile erection) has been reported with closely related antidepressants. Discontinuation of therapy is necessary. Visual Disturbances: Visual disturbances, including blurred vision, scotoma, and visual trails reported.

 Administration/Storage

• Cautiously administer to the elderly and patients with suicidal behavior, mania, heart disease, or dysrhythmias.
• Administer with caution to patients with known cardiac conditions that could be exacerbated by hypotension (eg, history of MI, angina, ischemic stroke).
• Store at room temperature in a tightly closed container.

 Assessment/Interventions

• Obtain patient history.
• Advise patient to avoid use of alcohol and otc medications without consulting health care provider.
• Evaluate mental and neurological status, mood changes, and suicidal tendencies.
• Assess debilitated or elderly patients for signs of overdose or adverse reactions.
• Determine whether suicide precautions are advisable and implement them as necessary.
• Monitor patient for postural hypotension and cardiac dysrhythmias. Monitor blood pressure and pulse at periodic intervals throughout therapy.

 Patient/Family Education

• Instruct patient to take exactly as directed by health care provider.
• Inform patient or family that several weeks of treatment may be required to obtain the full therapeutic antidepressant effect.
• Instruct patient to inform health care provider of all prescription and otc drugs presently taking or planning to take.
• Instruct patient to avoid alcohol or other CNS depressant drugs during therapy.
• Caution patient not to drive or operate hazardous machinery until certain that therapy does not adversely affect ability to perform these activities.
• Instruct patient to notify health care provider if developing a rash, hives, or any signs of an allergic reaction.
• Instruct women to notify health care provider if pregnant, planning to become pregnant, or nursing an infant.
• Advise patient to take sips of water, suck on ice chips or sugarless hard candy, or chew sugarless gum if dry mouth occurs.
• Instruct men to immediately notify health care provider should symptoms of priapism occur.
• Reinforce the necessity of follow-up examinations and continued therapy.
• Advise patients to avoid sunlight and sunlamps or to wear protective clothing; photosensitivity may occur.
• Advise patient to notify health care provider if symptoms of visual disturbances occur.
• Advise patient to be alert for signs and symptoms of liver dysfunction, including jaundice, anorexia, GI complaints, and malaise, and to report the symptoms to health care provider immediately.

Drug Dose ::

 Action Undetermined; inhibits neuronal uptake of serotonin and norepinephrine; antagonizes alpha₁-adrenergic receptors.

 Indications Treatment of depression.

 Contraindications Coadministration with carbamazepine, cisapride, or pimozide; hypersensitivity to nefazodone or other phenylpiperazine antidepressants (eg, trazodone).

 Route/Dosage

ADULTS: PO 100 mg bid initially, increase by 100 to 200 mg increments q wk (max, 600 mg/day).

Elderly/Debilitated patients: PO 50 mg bid initially, increase by 100 mg increments q wk (max, 600 mg/day).

 Interactions

Benzodiazepines: Increased plasma concentrations and effects of alprazolam and triazolam.

Buspirone: Elevated buspirone concentrations, decreased buspirone metabolite plasma concentrations.

Carbamazepine: Elevated serum carbamazepine concentrations with possible increase in side effects may occur.

Cisapride: Increased cisapride plasma concentrations with cardiotoxicity may occur.

Digoxin: Increased plasma levels of digoxin.

Haloperidol: Decreased haloperidol clearance; may need to adjust haloperidol dose.

HMG-CoA Reductase Inhibitors (eg, Simvastatin): The risk of rhabdomyolysis occurrence may be increased.

MAOI: Do not use nefazodone concurrently or within 14 days of discontinuing a MAOI; do not start MAOI within 1 wk of stopping nefazodone.

Pimozide: Increased plasma concentrations of pimozide may occur associated with QT prolongation and rare cases of serious cardiovascular adverse events, 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: A “serotonin syndrome” including irritability, increased muscle tone, shivering, myoclonus, and altered consciousness may occur.

 Lab Test Interferences None well documented.

 Adverse Reactions

CARDIOVASCULAR: Hypotension; orthostatic hypotension; peripheral edema; sinus bradycardia; postural hypotension. CNS: Headache; somnolence; dizziness; insomnia; lightheadedness; confusion; memory impairment; paresthesia; abnormal dreams; decreased concentration; ataxia; incoordination; psychomotor retardation; tremor; hypertonia; decreased libido; vasodilation. DERMATOLOGIC: Pruritus; rash. EENT: Blurred vision; abnormal vision; visual field defects; eye pain; tinnitus; abnormal taste. GI: Dry mouth; nausea; constipation; dyspepsia; diarrhea; increased appetite; vomiting. GU: Urinary frequency; urinary tract infection; urinary retention; vaginitis; breast pain; impotence. HEMATOLOGIC: Decreased hematocrit. RESPIRATORY: Pharyngitis; cough. OTHER: Asthenia; flu syndrome; chills; fever; neck rigidity; arthralgia; thirst.

 Precautions

Pregnancy: Category C. Lactation: Undetermined. Children: Safety and efficacy in children less than 18 yr not established. Elderly: Initiate treatment at half the usual dose. Dosage range same as younger patients. Bradycardia: Sinus bradycardia reported in 1.5% of patients; use with caution in patients with recent MI or unstable heart disease. Hepatotoxicity: Life-threatening hepatic failure may occur; do not initiate nefazodone therapy in patients with active liver disease or elevated baseline transaminases. Mania/Hypomania: May activate mania/hypomania; use with caution in patients with history of mania. Postural Hypotension: Use with caution in patients with known cardiovascular 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). Seizures: Rare cases of petit mal and grand mal seizures reported. Suicide: Closely monitor patients at risk, and do not give them access to excessive quantities. Priapism: Priapism (prolonged, painful, inappropriate penile erection) has been reported with closely related antidepressants. Discontinuation of therapy is necessary. Visual Disturbances: Visual disturbances, including blurred vision, scotoma, and visual trails reported.

 Administration/Storage

• Cautiously administer to the elderly and patients with suicidal behavior, mania, heart disease, or dysrhythmias.
• Administer with caution to patients with known cardiac conditions that could be exacerbated by hypotension (eg, history of MI, angina, ischemic stroke).
• Store at room temperature in a tightly closed container.

 Assessment/Interventions

• Obtain patient history.
• Advise patient to avoid use of alcohol and otc medications without consulting health care provider.
• Evaluate mental and neurological status, mood changes, and suicidal tendencies.
• Assess debilitated or elderly patients for signs of overdose or adverse reactions.
• Determine whether suicide precautions are advisable and implement them as necessary.
• Monitor patient for postural hypotension and cardiac dysrhythmias. Monitor blood pressure and pulse at periodic intervals throughout therapy.

 Patient/Family Education

• Instruct patient to take exactly as directed by health care provider.
• Inform patient or family that several weeks of treatment may be required to obtain the full therapeutic antidepressant effect.
• Instruct patient to inform health care provider of all prescription and otc drugs presently taking or planning to take.
• Instruct patient to avoid alcohol or other CNS depressant drugs during therapy.
• Caution patient not to drive or operate hazardous machinery until certain that therapy does not adversely affect ability to perform these activities.
• Instruct patient to notify health care provider if developing a rash, hives, or any signs of an allergic reaction.
• Instruct women to notify health care provider if pregnant, planning to become pregnant, or nursing an infant.
• Advise patient to take sips of water, suck on ice chips or sugarless hard candy, or chew sugarless gum if dry mouth occurs.
• Instruct men to immediately notify health care provider should symptoms of priapism occur.
• Reinforce the necessity of follow-up examinations and continued therapy.
• Advise patients to avoid sunlight and sunlamps or to wear protective clothing; photosensitivity may occur.
• Advise patient to notify health care provider if symptoms of visual disturbances occur.
• Advise patient to be alert for signs and symptoms of liver dysfunction, including jaundice, anorexia, GI complaints, and malaise, and to report the symptoms to health care provider immediately.

Contraindication ::

 Action Undetermined; inhibits neuronal uptake of serotonin and norepinephrine; antagonizes alpha₁-adrenergic receptors.

 Indications Treatment of depression.

 Contraindications Coadministration with carbamazepine, cisapride, or pimozide; hypersensitivity to nefazodone or other phenylpiperazine antidepressants (eg, trazodone).

 Route/Dosage

ADULTS: PO 100 mg bid initially, increase by 100 to 200 mg increments q wk (max, 600 mg/day).

Elderly/Debilitated patients: PO 50 mg bid initially, increase by 100 mg increments q wk (max, 600 mg/day).

 Interactions

Benzodiazepines: Increased plasma concentrations and effects of alprazolam and triazolam.

Buspirone: Elevated buspirone concentrations, decreased buspirone metabolite plasma concentrations.

Carbamazepine: Elevated serum carbamazepine concentrations with possible increase in side effects may occur.

Cisapride: Increased cisapride plasma concentrations with cardiotoxicity may occur.

Digoxin: Increased plasma levels of digoxin.

Haloperidol: Decreased haloperidol clearance; may need to adjust haloperidol dose.

HMG-CoA Reductase Inhibitors (eg, Simvastatin): The risk of rhabdomyolysis occurrence may be increased.

MAOI: Do not use nefazodone concurrently or within 14 days of discontinuing a MAOI; do not start MAOI within 1 wk of stopping nefazodone.

Pimozide: Increased plasma concentrations of pimozide may occur associated with QT prolongation and rare cases of serious cardiovascular adverse events, 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: A “serotonin syndrome” including irritability, increased muscle tone, shivering, myoclonus, and altered consciousness may occur.

 Lab Test Interferences None well documented.

 Adverse Reactions

CARDIOVASCULAR: Hypotension; orthostatic hypotension; peripheral edema; sinus bradycardia; postural hypotension. CNS: Headache; somnolence; dizziness; insomnia; lightheadedness; confusion; memory impairment; paresthesia; abnormal dreams; decreased concentration; ataxia; incoordination; psychomotor retardation; tremor; hypertonia; decreased libido; vasodilation. DERMATOLOGIC: Pruritus; rash. EENT: Blurred vision; abnormal vision; visual field defects; eye pain; tinnitus; abnormal taste. GI: Dry mouth; nausea; constipation; dyspepsia; diarrhea; increased appetite; vomiting. GU: Urinary frequency; urinary tract infection; urinary retention; vaginitis; breast pain; impotence. HEMATOLOGIC: Decreased hematocrit. RESPIRATORY: Pharyngitis; cough. OTHER: Asthenia; flu syndrome; chills; fever; neck rigidity; arthralgia; thirst.

 Precautions

Pregnancy: Category C. Lactation: Undetermined. Children: Safety and efficacy in children less than 18 yr not established. Elderly: Initiate treatment at half the usual dose. Dosage range same as younger patients. Bradycardia: Sinus bradycardia reported in 1.5% of patients; use with caution in patients with recent MI or unstable heart disease. Hepatotoxicity: Life-threatening hepatic failure may occur; do not initiate nefazodone therapy in patients with active liver disease or elevated baseline transaminases. Mania/Hypomania: May activate mania/hypomania; use with caution in patients with history of mania. Postural Hypotension: Use with caution in patients with known cardiovascular 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). Seizures: Rare cases of petit mal and grand mal seizures reported. Suicide: Closely monitor patients at risk, and do not give them access to excessive quantities. Priapism: Priapism (prolonged, painful, inappropriate penile erection) has been reported with closely related antidepressants. Discontinuation of therapy is necessary. Visual Disturbances: Visual disturbances, including blurred vision, scotoma, and visual trails reported.

 Administration/Storage

• Cautiously administer to the elderly and patients with suicidal behavior, mania, heart disease, or dysrhythmias.
• Administer with caution to patients with known cardiac conditions that could be exacerbated by hypotension (eg, history of MI, angina, ischemic stroke).
• Store at room temperature in a tightly closed container.

 Assessment/Interventions

• Obtain patient history.
• Advise patient to avoid use of alcohol and otc medications without consulting health care provider.
• Evaluate mental and neurological status, mood changes, and suicidal tendencies.
• Assess debilitated or elderly patients for signs of overdose or adverse reactions.
• Determine whether suicide precautions are advisable and implement them as necessary.
• Monitor patient for postural hypotension and cardiac dysrhythmias. Monitor blood pressure and pulse at periodic intervals throughout therapy.

 Patient/Family Education

• Instruct patient to take exactly as directed by health care provider.
• Inform patient or family that several weeks of treatment may be required to obtain the full therapeutic antidepressant effect.
• Instruct patient to inform health care provider of all prescription and otc drugs presently taking or planning to take.
• Instruct patient to avoid alcohol or other CNS depressant drugs during therapy.
• Caution patient not to drive or operate hazardous machinery until certain that therapy does not adversely affect ability to perform these activities.
• Instruct patient to notify health care provider if developing a rash, hives, or any signs of an allergic reaction.
• Instruct women to notify health care provider if pregnant, planning to become pregnant, or nursing an infant.
• Advise patient to take sips of water, suck on ice chips or sugarless hard candy, or chew sugarless gum if dry mouth occurs.
• Instruct men to immediately notify health care provider should symptoms of priapism occur.
• Reinforce the necessity of follow-up examinations and continued therapy.
• Advise patients to avoid sunlight and sunlamps or to wear protective clothing; photosensitivity may occur.
• Advise patient to notify health care provider if symptoms of visual disturbances occur.
• Advise patient to be alert for signs and symptoms of liver dysfunction, including jaundice, anorexia, GI complaints, and malaise, and to report the symptoms to health care provider immediately.

Drug Precautions ::

 Action Undetermined; inhibits neuronal uptake of serotonin and norepinephrine; antagonizes alpha₁-adrenergic receptors.

 Indications Treatment of depression.

 Contraindications Coadministration with carbamazepine, cisapride, or pimozide; hypersensitivity to nefazodone or other phenylpiperazine antidepressants (eg, trazodone).

 Route/Dosage

ADULTS: PO 100 mg bid initially, increase by 100 to 200 mg increments q wk (max, 600 mg/day).

Elderly/Debilitated patients: PO 50 mg bid initially, increase by 100 mg increments q wk (max, 600 mg/day).

 Interactions

Benzodiazepines: Increased plasma concentrations and effects of alprazolam and triazolam.

Buspirone: Elevated buspirone concentrations, decreased buspirone metabolite plasma concentrations.

Carbamazepine: Elevated serum carbamazepine concentrations with possible increase in side effects may occur.

Cisapride: Increased cisapride plasma concentrations with cardiotoxicity may occur.

Digoxin: Increased plasma levels of digoxin.

Haloperidol: Decreased haloperidol clearance; may need to adjust haloperidol dose.

HMG-CoA Reductase Inhibitors (eg, Simvastatin): The risk of rhabdomyolysis occurrence may be increased.

MAOI: Do not use nefazodone concurrently or within 14 days of discontinuing a MAOI; do not start MAOI within 1 wk of stopping nefazodone.

Pimozide: Increased plasma concentrations of pimozide may occur associated with QT prolongation and rare cases of serious cardiovascular adverse events, 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: A “serotonin syndrome” including irritability, increased muscle tone, shivering, myoclonus, and altered consciousness may occur.

 Lab Test Interferences None well documented.

 Adverse Reactions

CARDIOVASCULAR: Hypotension; orthostatic hypotension; peripheral edema; sinus bradycardia; postural hypotension. CNS: Headache; somnolence; dizziness; insomnia; lightheadedness; confusion; memory impairment; paresthesia; abnormal dreams; decreased concentration; ataxia; incoordination; psychomotor retardation; tremor; hypertonia; decreased libido; vasodilation. DERMATOLOGIC: Pruritus; rash. EENT: Blurred vision; abnormal vision; visual field defects; eye pain; tinnitus; abnormal taste. GI: Dry mouth; nausea; constipation; dyspepsia; diarrhea; increased appetite; vomiting. GU: Urinary frequency; urinary tract infection; urinary retention; vaginitis; breast pain; impotence. HEMATOLOGIC: Decreased hematocrit. RESPIRATORY: Pharyngitis; cough. OTHER: Asthenia; flu syndrome; chills; fever; neck rigidity; arthralgia; thirst.

 Precautions

Pregnancy: Category C. Lactation: Undetermined. Children: Safety and efficacy in children less than 18 yr not established. Elderly: Initiate treatment at half the usual dose. Dosage range same as younger patients. Bradycardia: Sinus bradycardia reported in 1.5% of patients; use with caution in patients with recent MI or unstable heart disease. Hepatotoxicity: Life-threatening hepatic failure may occur; do not initiate nefazodone therapy in patients with active liver disease or elevated baseline transaminases. Mania/Hypomania: May activate mania/hypomania; use with caution in patients with history of mania. Postural Hypotension: Use with caution in patients with known cardiovascular 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). Seizures: Rare cases of petit mal and grand mal seizures reported. Suicide: Closely monitor patients at risk, and do not give them access to excessive quantities. Priapism: Priapism (prolonged, painful, inappropriate penile erection) has been reported with closely related antidepressants. Discontinuation of therapy is necessary. Visual Disturbances: Visual disturbances, including blurred vision, scotoma, and visual trails reported.

 Administration/Storage

• Cautiously administer to the elderly and patients with suicidal behavior, mania, heart disease, or dysrhythmias.
• Administer with caution to patients with known cardiac conditions that could be exacerbated by hypotension (eg, history of MI, angina, ischemic stroke).
• Store at room temperature in a tightly closed container.

 Assessment/Interventions

• Obtain patient history.
• Advise patient to avoid use of alcohol and otc medications without consulting health care provider.
• Evaluate mental and neurological status, mood changes, and suicidal tendencies.
• Assess debilitated or elderly patients for signs of overdose or adverse reactions.
• Determine whether suicide precautions are advisable and implement them as necessary.
• Monitor patient for postural hypotension and cardiac dysrhythmias. Monitor blood pressure and pulse at periodic intervals throughout therapy.

 Patient/Family Education

• Instruct patient to take exactly as directed by health care provider.
• Inform patient or family that several weeks of treatment may be required to obtain the full therapeutic antidepressant effect.
• Instruct patient to inform health care provider of all prescription and otc drugs presently taking or planning to take.
• Instruct patient to avoid alcohol or other CNS depressant drugs during therapy.
• Caution patient not to drive or operate hazardous machinery until certain that therapy does not adversely affect ability to perform these activities.
• Instruct patient to notify health care provider if developing a rash, hives, or any signs of an allergic reaction.
• Instruct women to notify health care provider if pregnant, planning to become pregnant, or nursing an infant.
• Advise patient to take sips of water, suck on ice chips or sugarless hard candy, or chew sugarless gum if dry mouth occurs.
• Instruct men to immediately notify health care provider should symptoms of priapism occur.
• Reinforce the necessity of follow-up examinations and continued therapy.
• Advise patients to avoid sunlight and sunlamps or to wear protective clothing; photosensitivity may occur.
• Advise patient to notify health care provider if symptoms of visual disturbances occur.
• Advise patient to be alert for signs and symptoms of liver dysfunction, including jaundice, anorexia, GI complaints, and malaise, and to report the symptoms to health care provider immediately.

Drug Side Effects ::

 Action Undetermined; inhibits neuronal uptake of serotonin and norepinephrine; antagonizes alpha₁-adrenergic receptors.

 Indications Treatment of depression.

 Contraindications Coadministration with carbamazepine, cisapride, or pimozide; hypersensitivity to nefazodone or other phenylpiperazine antidepressants (eg, trazodone).

 Route/Dosage

ADULTS: PO 100 mg bid initially, increase by 100 to 200 mg increments q wk (max, 600 mg/day).

Elderly/Debilitated patients: PO 50 mg bid initially, increase by 100 mg increments q wk (max, 600 mg/day).

 Interactions

Benzodiazepines: Increased plasma concentrations and effects of alprazolam and triazolam.

Buspirone: Elevated buspirone concentrations, decreased buspirone metabolite plasma concentrations.

Carbamazepine: Elevated serum carbamazepine concentrations with possible increase in side effects may occur.

Cisapride: Increased cisapride plasma concentrations with cardiotoxicity may occur.

Digoxin: Increased plasma levels of digoxin.

Haloperidol: Decreased haloperidol clearance; may need to adjust haloperidol dose.

HMG-CoA Reductase Inhibitors (eg, Simvastatin): The risk of rhabdomyolysis occurrence may be increased.

MAOI: Do not use nefazodone concurrently or within 14 days of discontinuing a MAOI; do not start MAOI within 1 wk of stopping nefazodone.

Pimozide: Increased plasma concentrations of pimozide may occur associated with QT prolongation and rare cases of serious cardiovascular adverse events, 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: A “serotonin syndrome” including irritability, increased muscle tone, shivering, myoclonus, and altered consciousness may occur.

 Lab Test Interferences None well documented.

 Adverse Reactions

CARDIOVASCULAR: Hypotension; orthostatic hypotension; peripheral edema; sinus bradycardia; postural hypotension. CNS: Headache; somnolence; dizziness; insomnia; lightheadedness; confusion; memory impairment; paresthesia; abnormal dreams; decreased concentration; ataxia; incoordination; psychomotor retardation; tremor; hypertonia; decreased libido; vasodilation. DERMATOLOGIC: Pruritus; rash. EENT: Blurred vision; abnormal vision; visual field defects; eye pain; tinnitus; abnormal taste. GI: Dry mouth; nausea; constipation; dyspepsia; diarrhea; increased appetite; vomiting. GU: Urinary frequency; urinary tract infection; urinary retention; vaginitis; breast pain; impotence. HEMATOLOGIC: Decreased hematocrit. RESPIRATORY: Pharyngitis; cough. OTHER: Asthenia; flu syndrome; chills; fever; neck rigidity; arthralgia; thirst.

 Precautions

Pregnancy: Category C. Lactation: Undetermined. Children: Safety and efficacy in children less than 18 yr not established. Elderly: Initiate treatment at half the usual dose. Dosage range same as younger patients. Bradycardia: Sinus bradycardia reported in 1.5% of patients; use with caution in patients with recent MI or unstable heart disease. Hepatotoxicity: Life-threatening hepatic failure may occur; do not initiate nefazodone therapy in patients with active liver disease or elevated baseline transaminases. Mania/Hypomania: May activate mania/hypomania; use with caution in patients with history of mania. Postural Hypotension: Use with caution in patients with known cardiovascular 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). Seizures: Rare cases of petit mal and grand mal seizures reported. Suicide: Closely monitor patients at risk, and do not give them access to excessive quantities. Priapism: Priapism (prolonged, painful, inappropriate penile erection) has been reported with closely related antidepressants. Discontinuation of therapy is necessary. Visual Disturbances: Visual disturbances, including blurred vision, scotoma, and visual trails reported.

 Administration/Storage

• Cautiously administer to the elderly and patients with suicidal behavior, mania, heart disease, or dysrhythmias.
• Administer with caution to patients with known cardiac conditions that could be exacerbated by hypotension (eg, history of MI, angina, ischemic stroke).
• Store at room temperature in a tightly closed container.

 Assessment/Interventions

• Obtain patient history.
• Advise patient to avoid use of alcohol and otc medications without consulting health care provider.
• Evaluate mental and neurological status, mood changes, and suicidal tendencies.
• Assess debilitated or elderly patients for signs of overdose or adverse reactions.
• Determine whether suicide precautions are advisable and implement them as necessary.
• Monitor patient for postural hypotension and cardiac dysrhythmias. Monitor blood pressure and pulse at periodic intervals throughout therapy.

 Patient/Family Education

• Instruct patient to take exactly as directed by health care provider.
• Inform patient or family that several weeks of treatment may be required to obtain the full therapeutic antidepressant effect.
• Instruct patient to inform health care provider of all prescription and otc drugs presently taking or planning to take.
• Instruct patient to avoid alcohol or other CNS depressant drugs during therapy.
• Caution patient not to drive or operate hazardous machinery until certain that therapy does not adversely affect ability to perform these activities.
• Instruct patient to notify health care provider if developing a rash, hives, or any signs of an allergic reaction.
• Instruct women to notify health care provider if pregnant, planning to become pregnant, or nursing an infant.
• Advise patient to take sips of water, suck on ice chips or sugarless hard candy, or chew sugarless gum if dry mouth occurs.
• Instruct men to immediately notify health care provider should symptoms of priapism occur.
• Reinforce the necessity of follow-up examinations and continued therapy.
• Advise patients to avoid sunlight and sunlamps or to wear protective clothing; photosensitivity may occur.
• Advise patient to notify health care provider if symptoms of visual disturbances occur.
• Advise patient to be alert for signs and symptoms of liver dysfunction, including jaundice, anorexia, GI complaints, and malaise, and to report the symptoms to health care provider immediately.

Drug Mode of Action ::  

 Action Undetermined; inhibits neuronal uptake of serotonin and norepinephrine; antagonizes alpha₁-adrenergic receptors.