Trazodone Hydrochloride Prescribing Information
- Antidepresants increased the risk of suicidal thoughts and behaviors in pediatric and young adult patients ()5.1 Suicidal Thoughts and Behaviors in Pediatric and Young Adult Patients
In pooled analyses of placebo-controlled trials of antidepressant drugs (SSRIs and other antidepressant classes) that included approximately 77,000 adult patients and over 4,400 pediatric patients, the incidence of suicidal thoughts and behaviors in pediatric and young adult patients was greater in antidepressant-treated patients than in placebo-treated patients. The drug-placebo differences in the number of cases of suicidal thoughts and behaviors per 1,000 patients treated are provided in Table 1.
No suicides occurred in any of the pediatric studies. There were suicides in the adult studies, but the number was not sufficient to reach any conclusion about antidepressant drug effect on suicide.
Table 1: Risk Differences of the Number of Cases of Suicidal Thoughts or Behaviors in the Pooled Placebo-Controlled Trials of Antidepressants in Pediatric and Adult PatientsAge Range(years)Drug-Placebo Difference in Number of Patients of Suicidal Thoughts or Behaviors per 1,000 Patients TreatedIncreases Compared to Placebo < 18 14 additional patients 18 - 24 5 additional patients Decreases Compared to Placebo 25 - 64 1 fewer patient ≥ 65 6 fewer patients It is unknown whether the risk of suicidal thoughts and behaviors in pediatric and young adult patients extends to longer-term use, i.e., beyond four months. However, there is substantial evidence from placebo-controlled maintenance trials in adults with MDD that antidepressants delay the recurrence of depression.
Monitor all antidepressant-treated patients for clinical worsening and emergence of suicidal thoughts and behaviors, especially during the initial few months of drug therapy and at times of dosage changes. Counsel family members or caregivers of patients to monitor for changes in behavior and to alert the healthcare provider. Consider changing the therapeutic regimen, including possibly discontinuing trazodone hydrochloride tablets, in patients whose depression is persistently worse, or who are experiencing emergent suicidal thoughts or behaviors.
- Closely monitor for clinical worsening and emergence of suicidal thoughts and behaviors ()5.1 Suicidal Thoughts and Behaviors in Pediatric and Young Adult Patients
In pooled analyses of placebo-controlled trials of antidepressant drugs (SSRIs and other antidepressant classes) that included approximately 77,000 adult patients and over 4,400 pediatric patients, the incidence of suicidal thoughts and behaviors in pediatric and young adult patients was greater in antidepressant-treated patients than in placebo-treated patients. The drug-placebo differences in the number of cases of suicidal thoughts and behaviors per 1,000 patients treated are provided in Table 1.
No suicides occurred in any of the pediatric studies. There were suicides in the adult studies, but the number was not sufficient to reach any conclusion about antidepressant drug effect on suicide.
Table 1: Risk Differences of the Number of Cases of Suicidal Thoughts or Behaviors in the Pooled Placebo-Controlled Trials of Antidepressants in Pediatric and Adult PatientsAge Range(years)Drug-Placebo Difference in Number of Patients of Suicidal Thoughts or Behaviors per 1,000 Patients TreatedIncreases Compared to Placebo < 18 14 additional patients 18 - 24 5 additional patients Decreases Compared to Placebo 25 - 64 1 fewer patient ≥ 65 6 fewer patients It is unknown whether the risk of suicidal thoughts and behaviors in pediatric and young adult patients extends to longer-term use, i.e., beyond four months. However, there is substantial evidence from placebo-controlled maintenance trials in adults with MDD that antidepressants delay the recurrence of depression.
Monitor all antidepressant-treated patients for clinical worsening and emergence of suicidal thoughts and behaviors, especially during the initial few months of drug therapy and at times of dosage changes. Counsel family members or caregivers of patients to monitor for changes in behavior and to alert the healthcare provider. Consider changing the therapeutic regimen, including possibly discontinuing trazodone hydrochloride tablets, in patients whose depression is persistently worse, or who are experiencing emergent suicidal thoughts or behaviors.
- Trazodone hydrochloride tablets are not approved for use in pediatric patients ()8.4 Pediatric Use
Safety and effectiveness in the pediatric population have not been established. Antidepressants increased the risk of suicidal thoughts and behaviors in pediatric patients
[see Boxed Warning, Warnings and Precautions ].
Trazodone hydrochloride tablets are a selective serotonin reuptake inhibitor indicated for the treatment of major depressive disorder (MDD) (
Trazodone hydrochloride tablets are a selective serotonin reuptake inhibitor indicated for the treatment of major depressive disorder (MDD) .
Trazodone hydrochloride tablets are indicated for the treatment of major depressive disorder (MDD) in adults.
- Starting dose: 150 mg in divided doses daily. May be increased by 50 mg per day every three to four days. Maximum dose: 400 mg per day in divided doses ().
2 DOSAGE AND ADMINISTRATION- Starting dose: 150 mg in divided doses daily. May be increased by 50 mg per day every three to four days. Maximum dose: 400 mg per day in divided doses .
- Trazodone hydrochloride tablets should be taken shortly after a meal or light snack .
- Tablets should be swallowed whole or broken in half along the score line, and should not be chewed or crushed .
- When discontinued, gradual dose reduction is recommended .
2.1 Dose SelectionAn initial dose of 150 mg/day in divided doses is suggested. The dosage should be initiated at a low-dose and increased gradually, noting the clinical response and any evidence of intolerance. Occurrence of drowsiness may require the administration of a major portion of the daily dose at bedtime or a reduction of dosage.
The dose may be increased by 50 mg/day every 3 to 4 days. The maximum dose for outpatients usually should not exceed 400 mg/day in divided doses. Inpatients (i.e., more severely depressed patients) may be given up to but not in excess of 600 mg/day in divided doses.
Once an adequate response has been achieved, dosage may be gradually reduced, with subsequent adjustment depending on therapeutic response.
2.2 Important Administration InstructionsTrazodone hydrochloride tablets can be swallowed whole or administered as a half tablet by breaking the tablet along the score line.
Trazodone hydrochloride tablets should be taken shortly after a meal or light snack.
2.3 Screen for Bipolar Disorder Prior to Starting Trazodone Hydrochloride TabletsPrior to initiating treatment with trazodone hydrochloride tablets or another antidepressant, screen patients for a personal or family history of bipolar disorder, mania, or hypomania
[see Warnings and Precautions ].2.4 Switching to or from Monoamine Oxidase Inhibitor AntidepressantAt least 14 days must elapse between discontinuation of a monoamine oxidase inhibitor (MAOI) antidepressant and initiation of trazodone hydrochloride tablets. In addition, at least 14 days must elapse after stopping trazodone hydrochloride tablets before starting an MAOI antidepressant
[see Contraindications , Warnings and Precautions ].2.5 Dosage Recommendations for Concomitant Use with Strong CYP3A4 Inhibitors or InducersCoadministration with Strong CYP3A4 InhibitorsConsider reducing trazodone dose based on tolerability when trazodone is coadministered with a strong CYP3A4 inhibitor
[see Drug Interactions ].Coadministration with Strong CYP3A4 InducersConsider increasing trazodone dose based on therapeutic response when trazodone is coadministered with a strong CYP3A4 inducer
[see Drug Interactions ].2.6 Discontinuation of Treatment with Trazodone Hydrochloride TabletsAdverse reactions may occur upon discontinuation of trazodone hydrochloride tablets
[See Warnings and Precautions ]. Gradually reduce the dosage rather than stopping trazodone hydrochloride tablets abruptly whenever possible. - Trazodone hydrochloride tablets should be taken shortly after a meal or light snack ().
2 DOSAGE AND ADMINISTRATION- Starting dose: 150 mg in divided doses daily. May be increased by 50 mg per day every three to four days. Maximum dose: 400 mg per day in divided doses .
- Trazodone hydrochloride tablets should be taken shortly after a meal or light snack .
- Tablets should be swallowed whole or broken in half along the score line, and should not be chewed or crushed .
- When discontinued, gradual dose reduction is recommended .
2.1 Dose SelectionAn initial dose of 150 mg/day in divided doses is suggested. The dosage should be initiated at a low-dose and increased gradually, noting the clinical response and any evidence of intolerance. Occurrence of drowsiness may require the administration of a major portion of the daily dose at bedtime or a reduction of dosage.
The dose may be increased by 50 mg/day every 3 to 4 days. The maximum dose for outpatients usually should not exceed 400 mg/day in divided doses. Inpatients (i.e., more severely depressed patients) may be given up to but not in excess of 600 mg/day in divided doses.
Once an adequate response has been achieved, dosage may be gradually reduced, with subsequent adjustment depending on therapeutic response.
2.2 Important Administration InstructionsTrazodone hydrochloride tablets can be swallowed whole or administered as a half tablet by breaking the tablet along the score line.
Trazodone hydrochloride tablets should be taken shortly after a meal or light snack.
2.3 Screen for Bipolar Disorder Prior to Starting Trazodone Hydrochloride TabletsPrior to initiating treatment with trazodone hydrochloride tablets or another antidepressant, screen patients for a personal or family history of bipolar disorder, mania, or hypomania
[see Warnings and Precautions ].2.4 Switching to or from Monoamine Oxidase Inhibitor AntidepressantAt least 14 days must elapse between discontinuation of a monoamine oxidase inhibitor (MAOI) antidepressant and initiation of trazodone hydrochloride tablets. In addition, at least 14 days must elapse after stopping trazodone hydrochloride tablets before starting an MAOI antidepressant
[see Contraindications , Warnings and Precautions ].2.5 Dosage Recommendations for Concomitant Use with Strong CYP3A4 Inhibitors or InducersCoadministration with Strong CYP3A4 InhibitorsConsider reducing trazodone dose based on tolerability when trazodone is coadministered with a strong CYP3A4 inhibitor
[see Drug Interactions ].Coadministration with Strong CYP3A4 InducersConsider increasing trazodone dose based on therapeutic response when trazodone is coadministered with a strong CYP3A4 inducer
[see Drug Interactions ].2.6 Discontinuation of Treatment with Trazodone Hydrochloride TabletsAdverse reactions may occur upon discontinuation of trazodone hydrochloride tablets
[See Warnings and Precautions ]. Gradually reduce the dosage rather than stopping trazodone hydrochloride tablets abruptly whenever possible. - Tablets should be swallowed whole or broken in half along the score line, and should not be chewed or crushed ().
2 DOSAGE AND ADMINISTRATION- Starting dose: 150 mg in divided doses daily. May be increased by 50 mg per day every three to four days. Maximum dose: 400 mg per day in divided doses .
- Trazodone hydrochloride tablets should be taken shortly after a meal or light snack .
- Tablets should be swallowed whole or broken in half along the score line, and should not be chewed or crushed .
- When discontinued, gradual dose reduction is recommended .
2.1 Dose SelectionAn initial dose of 150 mg/day in divided doses is suggested. The dosage should be initiated at a low-dose and increased gradually, noting the clinical response and any evidence of intolerance. Occurrence of drowsiness may require the administration of a major portion of the daily dose at bedtime or a reduction of dosage.
The dose may be increased by 50 mg/day every 3 to 4 days. The maximum dose for outpatients usually should not exceed 400 mg/day in divided doses. Inpatients (i.e., more severely depressed patients) may be given up to but not in excess of 600 mg/day in divided doses.
Once an adequate response has been achieved, dosage may be gradually reduced, with subsequent adjustment depending on therapeutic response.
2.2 Important Administration InstructionsTrazodone hydrochloride tablets can be swallowed whole or administered as a half tablet by breaking the tablet along the score line.
Trazodone hydrochloride tablets should be taken shortly after a meal or light snack.
2.3 Screen for Bipolar Disorder Prior to Starting Trazodone Hydrochloride TabletsPrior to initiating treatment with trazodone hydrochloride tablets or another antidepressant, screen patients for a personal or family history of bipolar disorder, mania, or hypomania
[see Warnings and Precautions ].2.4 Switching to or from Monoamine Oxidase Inhibitor AntidepressantAt least 14 days must elapse between discontinuation of a monoamine oxidase inhibitor (MAOI) antidepressant and initiation of trazodone hydrochloride tablets. In addition, at least 14 days must elapse after stopping trazodone hydrochloride tablets before starting an MAOI antidepressant
[see Contraindications , Warnings and Precautions ].2.5 Dosage Recommendations for Concomitant Use with Strong CYP3A4 Inhibitors or InducersCoadministration with Strong CYP3A4 InhibitorsConsider reducing trazodone dose based on tolerability when trazodone is coadministered with a strong CYP3A4 inhibitor
[see Drug Interactions ].Coadministration with Strong CYP3A4 InducersConsider increasing trazodone dose based on therapeutic response when trazodone is coadministered with a strong CYP3A4 inducer
[see Drug Interactions ].2.6 Discontinuation of Treatment with Trazodone Hydrochloride TabletsAdverse reactions may occur upon discontinuation of trazodone hydrochloride tablets
[See Warnings and Precautions ]. Gradually reduce the dosage rather than stopping trazodone hydrochloride tablets abruptly whenever possible. - When discontinued, gradual dose reduction is recommended ().
2 DOSAGE AND ADMINISTRATION- Starting dose: 150 mg in divided doses daily. May be increased by 50 mg per day every three to four days. Maximum dose: 400 mg per day in divided doses .
- Trazodone hydrochloride tablets should be taken shortly after a meal or light snack .
- Tablets should be swallowed whole or broken in half along the score line, and should not be chewed or crushed .
- When discontinued, gradual dose reduction is recommended .
2.1 Dose SelectionAn initial dose of 150 mg/day in divided doses is suggested. The dosage should be initiated at a low-dose and increased gradually, noting the clinical response and any evidence of intolerance. Occurrence of drowsiness may require the administration of a major portion of the daily dose at bedtime or a reduction of dosage.
The dose may be increased by 50 mg/day every 3 to 4 days. The maximum dose for outpatients usually should not exceed 400 mg/day in divided doses. Inpatients (i.e., more severely depressed patients) may be given up to but not in excess of 600 mg/day in divided doses.
Once an adequate response has been achieved, dosage may be gradually reduced, with subsequent adjustment depending on therapeutic response.
2.2 Important Administration InstructionsTrazodone hydrochloride tablets can be swallowed whole or administered as a half tablet by breaking the tablet along the score line.
Trazodone hydrochloride tablets should be taken shortly after a meal or light snack.
2.3 Screen for Bipolar Disorder Prior to Starting Trazodone Hydrochloride TabletsPrior to initiating treatment with trazodone hydrochloride tablets or another antidepressant, screen patients for a personal or family history of bipolar disorder, mania, or hypomania
[see Warnings and Precautions ].2.4 Switching to or from Monoamine Oxidase Inhibitor AntidepressantAt least 14 days must elapse between discontinuation of a monoamine oxidase inhibitor (MAOI) antidepressant and initiation of trazodone hydrochloride tablets. In addition, at least 14 days must elapse after stopping trazodone hydrochloride tablets before starting an MAOI antidepressant
[see Contraindications , Warnings and Precautions ].2.5 Dosage Recommendations for Concomitant Use with Strong CYP3A4 Inhibitors or InducersCoadministration with Strong CYP3A4 InhibitorsConsider reducing trazodone dose based on tolerability when trazodone is coadministered with a strong CYP3A4 inhibitor
[see Drug Interactions ].Coadministration with Strong CYP3A4 InducersConsider increasing trazodone dose based on therapeutic response when trazodone is coadministered with a strong CYP3A4 inducer
[see Drug Interactions ].2.6 Discontinuation of Treatment with Trazodone Hydrochloride TabletsAdverse reactions may occur upon discontinuation of trazodone hydrochloride tablets
[See Warnings and Precautions ]. Gradually reduce the dosage rather than stopping trazodone hydrochloride tablets abruptly whenever possible.
- Scored tablets: 50 mg, 100 mg, 150 mg and 300 mg ().
3 DOSAGE FORMS AND STRENGTHS- Scored tablets: 50 mg, 100 mg, 150 mg and 300 mg .
50 mg Tablets, white to off white, round, biconvex, uncoated tablets debossed with "13" bisect "30" on one side and plain on other side.
100 mg Tablets, white to off white, round, biconvex, uncoated tablets debossed with "13" bisect "31" on one side and plain on other side.
150 mg Tablets, white to off white, oval, flat faced beveled edge uncoated tablets with a full bisect and two partial trisects. Debossed "13" bisect "32" on one side and "50 50 50" on other side.
300 mg white to off white, oval, flat faced beveled edge uncoated tablets with a full bisect and two partial trisects. Debossed "13" bisect "33" on one side and "100 100 100" on other side with middle "100" perpendicular to others.
There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to antidepressants during pregnancy. Healthcare providers are encouraged to register patients by calling the National Pregnancy Registry for Antidepressants at 1-844-405-6185 or visiting online at https://womensmentalhealth.org/clinical-and-research-programs/pregnancyregistry/antidepressants/
Published prospective cohort studies, case series, and case reports over several decades with trazodone use in pregnant women have not identified any drug-associated risks of major birth defects, miscarriage, or adverse maternal or fetal outcomes
The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively.
A prospective, longitudinal study followed 201 pregnant women with a history of major depressive disorder who were euthymic and taking antidepressants at the beginning of pregnancy. The women who discontinued antidepressants during pregnancy were more likely to experience a relapse of major depression that women who continued antidepressants. Consider the risk of untreated depression when discontinuing or changing treatment with antidepressant medication during pregnancy and postpartum.
While available studies cannot definitively establish the absence of risk, published data from prospective cohort studies, case series, and case reports over several decades have not identified an association with trazodone use during pregnancy and major birth defects, miscarriage, or other adverse maternal or fetal outcomes. All available studies have methodological limitations, including small sample size and inconsistent comparator groups.
No teratogenic effects were observed when trazodone was given to pregnant rats and rabbits during the period of organogenesis at oral doses up to 450 mg/kg/day. This dose is 11 and 22 times, in rats and rabbits, respectively, the maximum recommended human dose (MRHD) of 400 mg/day in adults on a mg/m2 basis. Increased fetal resorption and other adverse effects on the fetus in rats at 7.3 to 11 times the MRHD and increase in congenital anomalies in rabbits at 7.3 to 22 times the MRHD on a mg/m2 basis were observed. No further details on these studies are available.
- Concomitant use of monoamine oxidase inhibitors (MAOIs), or use within 14 days of stopping MAOIs ().
4 CONTRAINDICATIONS- Concomitant use of monoamine oxidase inhibitors (MAOIs), or use within 14 days of stopping MAOIs .
Trazodone hydrochloride tablets are contraindicated in:
- Patients taking, or within 14 days of stopping, monoamine oxidase inhibitors (MAOIs), including MAOIs such as linezolid or intravenous methylene blue, because of an increased risk of serotonin syndrome[see Warnings and Precautions , Drug Interactions ].