MEDICATION GUIDE Trazodone Hydrochloride

432 mm 36 mm 13422

FULL PRESCRIBING INFORMATION in patients whose depression is persistently worse, or who are experiencing 5.10 Angle-Closure Glaucoma WARNING: SUICIDAL THOUGHTS AND BEHAVIORS emergent suicidal thoughts or behaviors. The pupillary dilation that occurs following use of many antidepressant MEDICATION GUIDE • Antidepressant medicines can interact with Antidepressants increased the risk of suicidal thoughts and behaviors 5.2 Serotonin Syndrome drugs including trazodone hydrochloride tablets may trigger an angle Trazodone Hydrochloride other medicines. Know all of the medicines in pediatric and young adult patients in short-term studies. Closely Serotonin-norepinephrine reuptake inhibitors (SNRIs) and SSRIs, including closure attack in a patient with anatomically narrow angles who does HIGHLIGHTS OF PRESCRIBING • Orthostatic Hypotension and monitor all antidepressant-treated patients for clinical worsening, and trazodone hydrochloride tablets, can precipitate serotonin syndrome, not have a patent iridectomy. Avoid use of antidepressants, including (traz' oh done hye" droe klor' ide) that you take. Keep a list of all medicines to INFORMATION Syncope: Warn patients of risk for emergence of suicidal thoughts and behaviors [see Warnings and a potentially life-threatening condition. The risk is increased with trazodone hydrochloride tablets, in patients with untreated anatomically Tablets, USP for oral use show your healthcare provider. Do not start These highlights do not include and symptoms of hypotension Precautions (5.1)]. Trazodone hydrochloride tablets are not approved concomitant use of other serotonergic drugs (including triptans, tricyclic narrow angles. (5.4). all the information needed to use for use in pediatric patients [see Use in Specific Populations (8.4)]. antidepressants, fentanyl, lithium, tramadol, tryptophan, buspirone, and 5.11 Hyponatremia new medicines without first checking with your TRAZODONE HYDROCHLORIDE • Increased Risk of Bleeding: What is the most important information I should 1 INDICATIONS AND USAGE St. John’s Wort) and with drugs that impair metabolism of serotonin, i.e., Hyponatremia may occur as a result of treatment with SNRIs and SSRIs, TABLETS safely and effectively. Concomitant use of aspirin, MAOIs [see Contraindications (4), Drug Interactions (7.1)]. Serotonin including trazodone hydrochloride tablets. Cases with serum sodium know about trazodone hydrochloride tablets? healthcare provider. See full prescribing information nonsteroidal anti-inflammatory Trazodone hydrochloride tablets are indicated for the treatment of major depressive disorder (MDD) in adults. syndrome can also occur when these drugs are used alone. lower than 110 mmol/L have been reported. Signs and symptoms for TRAZODONE HYDROCHLORIDE drugs (NSAIDs), other antiplatelet of hyponatremia include headache, difficulty concentrating, memory Antidepressant medicines, depression or other It is not known if trazodone hydrochloride tablets TABLETS. drugs, warfarin, and other 2 DOSAGE AND ADMINISTRATION Serotonin syndrome signs and symptoms may include mental status changes (e.g., agitation, hallucinations, delirium, and coma), autonomic impairment, confusion, weakness, and unsteadiness, which can lead to serious mental illnesses, and suicidal thoughts or are safe and effective in children. TRAZODONE HYDROCHLORIDE anticoagulants may increase this 2.1 Dose Selection falls. Signs and symptoms associated with more severe and/or acute cases risk (5.5). An initial dose of 150 mg/day in divided doses is suggested. The instability (e.g., tachycardia, labile blood pressure, dizziness, diaphoresis, actions: Talk to your healthcare provider about: tablets, for oral use Initial U.S. flushing, hyperthermia), neuromuscular symptoms (e.g., tremor, rigidity, have included hallucination, syncope, seizure, coma, respiratory arrest, What are trazodone hydrochloride tablets? Approval: 1981 • Priapism: Cases of painful and dosage should be initiated at a low-dose and increased gradually, noting and death. In many cases, this hyponatremia appears to be the result of the clinical response and any evidence of intolerance. Occurrence of myoclonus, hyperreflexia, incoordination), seizures, and gastrointestinal • All risks and benefits of treatment with Trazodone hydrochloride tablets are a WARNING: SUICIDAL THOUGHTS prolonged penile erections and the syndrome of inappropriate antidiuretic hormone secretion (SIADH). drowsiness may require the administration of a major portion of the daily symptoms (e.g., nausea, vomiting, diarrhea). AND BEHAVIORS priapism have been reported. In patients with symptomatic hyponatremia, discontinue trazodone antidepressant medicines prescription medicine used in adults to treat Immediate medical attention dose at bedtime or a reduction of dosage. The concomitant use of trazodone hydrochloride tablets with MAOIs is See full prescribing information contraindicated. In addition, do not initiate trazodone hydrochloride tablets hydrochloride tablets and institute appropriate medical intervention. Elderly for complete boxed warning. should be sought if signs and The dose may be increased by 50 mg/day every 3 to 4 days. The patients, patients taking diuretics, and those who are volume-depleted may • All treatment choices for depression or other major depressive disorder (MDD). Trazodone symptoms of prolonged penile maximum dose for outpatients usually should not exceed 400 mg/day in in a patient being treated with MAOIs such as linezolid or intravenous • Antidepresants increased the methylene blue. No reports involved the administration of methylene blue by be at greater risk of developing hyponatremia with SSRIs and SNRIs [see serious mental illnesses hydrochloride tablets belong to a class of risk of suicidal thoughts and erections or priapism are divided doses. Inpatients (i.e., more severely depressed patients) may be observed (5.6). other routes (such as oral tablets or local tissue injection). If it is necessary Use in Specific Populations (8.5)]. behaviors in pediatric and given up to but not in excess of 600 mg/day in divided doses. 1. Antidepressant medicines may increase medicines known as SSRIs (or selective • Activation of Mania or to initiate treatment with an MAOI such as linezolid or intravenous methylene 6 ADVERSE REACTIONS young adult patients (5.1) Once an adequate response has been achieved, dosage may be gradually blue in a patient taking trazodone hydrochloride tablets, discontinue The following serious adverse reactions are described elsewhere in the serotonin reuptake inhibitors). Hypomania: Screen for bipolar reduced, with subsequent adjustment depending on therapeutic response. suicidal thoughts or actions in some • Closely monitor for clinical disorder and monitor for mania trazodone hydrochloride tablets before initiating treatment with the MAOI labeling: children, teenagers, and young adults worsening and emergence of or hypomania (5.7). 2.2 Important Administration Instructions [see Contraindications (4), Drug Interactions (7.1)]. • Suicidal Thoughts and Behavior in Children, Adolescents and Young Do not take trazodone hydrochloride tablets: suicidal thoughts and behaviors Trazodone hydrochloride tablets can be swallowed whole or administered Monitor all patients taking trazodone hydrochloride tablets for the Adults [see Boxed Warning and Warnings and Precautions (5.1)] within the first few months of treatment. (5.1) • Potential for Cognitive and Motor as a half tablet by breaking the tablet along the score line. • If you take a monoamine oxidase inhibitor Impairment: Has potential to emergence of serotonin syndrome. Discontinue treatment with trazodone • Serotonin Syndrome [see Warnings and Precautions (5.2)] • Trazodone is not approved for hydrochloride tablets and any concomitant serotonergic agents immediately 2. Depression and other serious mental (MAOI). Ask your healthcare provider or impair judgment, thinking, and Trazodone hydrochloride tablets should be taken shortly after a meal • Cardiac Arrythmias (see Warnings and Precautions (5.3)] use in pediatric patients (8.4) motor skills. Advise patients or light snack. if the above symptoms occur, and initiate supportive symptomatic • Orthostatic Hypotension and Syncope [see Warnings and Precautions (5.4)] illnesses are the most important causes pharmacist if you are not sure if you take an to use caution when operating 2.3 Screen for Bipolar Disorder Prior to Starting Trazodone treatment. If concomitant use of trazodone hydrochloride tablets with other INDICATIONS AND USAGE • Increased Risk of Bleeding [see Warnings and Precautions (5.5)] machinery (5.9). Hydrochloride Tablets serotonergic drugs is clinically warranted, inform patients of the increased of suicidal thoughts and actions. Some MAOI, including the antibiotic linezolid, and Trazodone hydrochloride tablets are a risk for serotonin syndrome and monitor for symptoms. selective serotonin reuptake inhibitor • Angle-Closure Glaucoma: Avoid Prior to initiating treatment with trazodone hydrochloride tablets or • Priapism [see Warnings and Precautions (5.6)] people may have a higher risk of having intravenous methylene blue. indicated for the treatment of major use of antidepressants, including another antidepressant, screen patients for a personal or family history 5.3 Cardiac Arrhythmias • Activation of Mania or Hypomania [see Warnings and Precautions (5.7)] suicidal thoughts or actions. These depressive disorder (MDD) (1). trazodone hydrochloride tablets, of bipolar disorder, mania, or hypomania [see Warnings and Precautions Clinical studies indicate that trazodone hydrochloride may be arrhythmogenic • Discontinuation Syndrome [see Warnings and Precautions (5.8)] • Do not take an MAOI within 2 weeks of stopping in patients with preexisting cardiac disease. Arrhythmias identified include DOSAGE AND ADMINISTRATION in patients with untreated (5.7)]. • Potential for Cognitive and Motor Impairment [see Warnings and include people who have or have a family anatomically narrow angles. isolated PVCs, ventricular couplets, tachycardia with syncope, and torsade trazodone hydrochloride tablets unless directed • Starting dose: 150 mg in divided 2.4 Switching to or from Monoamine Oxidase Inhibitor Precautions (5.9)] (5.10). de pointes. Postmarketing events, including torsade de pointes have been history of bipolar illness (also called doses daily. May be increased by Antidepressant • Angle-Closure Glaucoma [see Warnings and Precautions (5.10)] to do so by your healthcare provider. 50 mg per day every three to four ADVERSE REACTIONS At least 14 days must elapse between discontinuation of a monoamine reported at doses of 100 mg or less with the immediate-release form of manic-depressive illness) or suicidal Most common adverse reactions trazodone hydrochloride. Trazodone hydrochloride should also be avoided in • Hyponatremia [see Warnings and Precautions (5.11)] 288 mm days. Maximum dose: 400 mg per oxidase inhibitor (MAOI) antidepressant and initiation of trazodone thoughts or actions. • Do not start trazodone hydrochloride tablets if you day in divided doses (2). (incidence ≥ 5% and twice that of hydrochloride tablets. In addition, at least 14 days must elapse after stopping patients with a history of cardiac arrhythmias, as well as other circumstances 6.1 Clinical Trials Experience placebo) are: edema, blurred vision, trazodone hydrochloride tablets before starting an MAOI antidepressant [see that may increase the risk of the occurrence of torsade de pointes Because clinical trials are conducted under widely varying conditions, stopped taking an MAOI in the last 2 weeks unless • Trazodone hydrochloride tablets and/or sudden death, including symptomatic bradycardia, hypokalemia or 3. How can I watch for and try to prevent should be taken shortly after a meal syncope, drowsiness, fatigue, Contraindications (4), Warnings and Precautions (5.2)]. adverse reaction rates observed in the clinical trials of a drug cannot be directed to do so by your healthcare provider. diarrhea, nasal congestion, weight hypomagnesemia, and the presence of congenital prolongation of the QT directly compared to rates in the clinical trials of another drug and may or light snack (2). 2.5 Dosage Recommendations for Concomitant Use with Strong suicidal thoughts and actions? loss (6). interval. Trazodone hydrochloride is not recommended for use during the not reflect the rates observed in practice. • Tablets should be swallowed whole CYP3A4 Inhibitors or Inducers initial recovery phase of myocardial infarction. Caution should be used when • Pay close attention to any changes, especially Before you take trazodone hydrochloride tablets or broken in half along the score To report SUSPECTED Coadministration with Strong CYP3A4 Inhibitors Table 2: Common Adverse Reactions Occurring in ≥ 2% of Trazodone ADVERSE REACTIONS, contact administering trazodone hydrochloride to patients with cardiac disease and tell your healthcare provider about all of your line, and should not be chewed or Consider reducing trazodone hydrochloride tablets dose based on such patients should be closely monitored, since antidepressant drugs Hydrochloride Tablets-treated Patients and Greater than the sudden changes in mood, behaviors, thoughts, Teva Pharmaceuticals USA, Inc. Rate of Placebo-Treated Patients as Observed in Controlled 36 mm 36 crushed (2). tolerability when trazodone hydrochloride tablets are coadministered with at 1-888-838-2872 or FDA (including trazodone hydrochloride ) may cause cardiac arrhythmias [see or feelings. This is very important when an medical conditions, including if you: a strong CYP3A4 inhibitor [see Drug Interactions (7.1)]. Clinical Studies • When discontinued, gradual dose at 1-800-FDA-1088 or Adverse Reactions (6.2)]. Inpatients Outpatients antidepressant medicine is started or when the • have heart problems, including QT prolongation reduction is recommended (2). www.fda.gov/medwatch. Coadministration with Strong CYP3A4 Inducers Trazodone hydrochloride prolongs the QT/QTc interval. The use of trazodone DOSAGE FORMS AND STRENGTHS Consider increasing trazodone hydrochloride tablets dose based on therapeutic hydrochloride should be avoided in patients with known QT prolongation Trazodone Placebo Trazodone Placebo dose is changed. or a family history of it DRUG INTERACTIONS Hydrochloride Hydrochloride • Bisectable tablets of 50 mg, 100 mg • CNS Depressants: Trazodone response when trazodone hydrochloride tablets are coadministered with a or in combination with other drugs that are inhibitors of CYP3A4 (e.g., Tablets Tablets • have ever had a heart attack and 150 mg (3). hydrochloride tablets may enhance strong CYP3A4 inducer [see Drug Interactions (7.1)]. itraconazole, clarithromycin, voriconazole), or known to prolong QT interval • Call your healthcare provider right away to report CONTRAINDICATIONS effects of alcohol, barbiturates, or 2.6 Discontinuation of Treatment with Trazodone Hydrochloride including Class 1A antiarrhythmics (e.g., quinidine, procainamide) or Class 3 N =142 N=95 N =157 N=158 new or sudden changes in mood, behavior, • have bipolar disorder • Concomitant use of monoamine other CNS depressants (7). Tablets antiarrhythmics (e.g., amiodarone, sotalol), certain antipsychotic medications Allergic thoughts or feelings. oxidase inhibitors (MAOIs), or • CYP3A4 Inhibitors: Consider Adverse reactions may occur upon discontinuation of trazodone (e.g., ziprasidone, chlorpromazine, thioridazine), and certain antibiotics (e.g., 3% 1% 7% 1% • have liver or kidney problems gatifloxacin). Concomitant administration of drugs may increase the risk of

use within 14 days of stopping trazodone hydrochloride tablets hydrochloride tablets [See Warnings and Precautions (5.8)]. Gradually Skin

Rev. I 7/2020 I Rev. • Keep all follow-up visits with your healthcare Rx only Rx MAOIs (4). reduce the dosage rather than stopping trazodone hydrochloride tablets cardiac arrhythmia [see Drug Interactions (7.1)]. 39 mm 39 dose reduction based on tolerability Condition/Edema • have other serious medical conditions abruptly whenever possible. WARNINGS AND PRECAUTIONS (2.5, 7). 5.4 Orthostatic Hypotension and Syncope Autonomic provider as scheduled. Call your healthcare • Serotonin Syndrome: Increased • CYP3A4 Inducers: Increase in 3 DOSAGE FORMS AND STRENGTHS Hypotension, including orthostatic hypotension and syncope has been provider between visits as needed, especially if • are pregnant or plan to become pregnant. It is risk when co-administered Trazodone hydrochloride tablets, USP are available in the following reported in patients receiving trazodone hydrochloride. Concomitant Blurred Vision 6% 4% 15% 4% 2mm trazodone hydrochloride tablets not known if trazodone hydrochloride tablets will with other serotonergic agents dosage may be necessary (2.5, 7). strengths: use with an antihypertensive may require a reduction in the dose of the Constipation 7% 4% 8% 6% you are worried about symptoms.

(e.g., SSRI, SNRI, triptans), antihypertensive drug. Dry Mouth 15% 8% 34% 20% harm your unborn baby. Talk to your healthcare 13422 50 mg: White, round, compressed tablet, debossed “PLIVA 433” on one but also when taken alone. If it • Digoxin or Phenytoin: Monitor for increased digoxin or phenytoin side and scored on the other side. 5.5 Increased Risk of Bleeding Cardiovascular Call a healthcare provider right away if you have provider about the risk to your unborn baby if occurs, discontinue trazodone Drugs that interfere with serotonin reuptake inhibition, including trazodone

hydrochloride tablets and initiate serum levels (7). 100 mg: White, round, compressed tablet, debossed “PLIVA 434” on one Hypertension 20% 1% 1% * any of the following symptoms, especially if they

hydrochloride, increase the risk of bleeding events. Concomitant use of you take trazodone hydrochloride tablets.

2mm USP Tablets, supportive treatment (5.2). • Warfarin: Monitor for increased or side and scored on the other side. Hypotension 7% 1% 4% 0

aspirin, nonsteroidal anti-inflammatory drugs (NSAIDS), other antiplatelet are new, worse, or worry you: TraZODONE Hydrochloride Hydrochloride TraZODONE decreased prothrombin time (7). • Cardiac Arrhythmias: Increases the 150 mg: White, oval, flat-faced, beveled edge tablet, scored and debossed drugs, warfarin, and other anticoagulants may add to this risk. Case Syncope 3% 2% 5% 1% • If you become pregnant during treatment QT interval. Avoid use with drugs See 17 for PATIENT COUNSELING as “PLIVA” bisect “441” on one side and tri-scored and debossed as “50” reports and epidemiological studies (case-control and cohort design) CNS • Thoughts about • New or worse with trazodone hydrochloride tablets, that also increase the QT interval INFORMATION and Medication in each section on the other side. have demonstrated an association between use of drugs that interfere Confusion 5% 0 6% 8% suicide or dying irritability and in patients with risk factors for Guide. 4 CONTRAINDICATIONS with serotonin reuptake and the occurrence of gastrointestinal bleeding. talk to your healthcare provider about prolonged QT interval (5.3) Decreased 3% 2% 1% 0 Revised: 7/2020 Trazodone hydrochloride tablets are contraindicated in: Bleeding events related to drugs that interfere with serotonin reuptake Concentration • Attempts to commit • Acting aggressive, registering with the National Pregnancy • Patients taking, or within 14 days of stopping, monoamine oxidase have ranged from ecchymosis, hematoma, epistaxis, and petechiae to Disorientation 2% 0 * 0 life-threatening hemorrhages. suicide being angry or Registry for Antidepressants. You can inhibitors (MAOIs), including MAOIs such as linezolid or intravenous Dizziness/Light- 20% 5% 28% 15% FULL PRESCRIBING INFORMATION: 5.11 Hyponatremia methylene blue, because of an increased risk of serotonin syndrome Inform patients about the risk of bleeding associated with the concomitant Headedness violent register by calling 1-844-405-6185. CONTENTS* 6 ADVERSE REACTIONS use of trazodone hydrochloride and antiplatelet agents or anticoagulants. • New or worse [see Warnings and Precautions (5.2), Drug Interactions (7.1)]. Drowsiness 24% 6% 41% 20% WARNING: SUICIDAL THOUGHTS 6.1 Clinical Trials Experience For patients taking warfarin, carefully monitor coagulation indices when depression • Acting on dangerous • are breastfeeding or plan to breastfeed. 6.2 Postmarketing Experience 5 WARNINGS AND PRECAUTIONS Fatigue 11% 4% 6% 3% AND BEHAVIORS 5.1 Suicidal Thoughts and Behaviors in Pediatric and Young initiating, titrating, or discontinuing trazodone hydrochloride. 1 INDICATIONS AND USAGE 7 DRUG INTERACTIONS Headache 10% 5% 20% 16% • New or worse impulses Trazodone hydrochloride passes into your 7.1 Drugs Having Clinically Adult Patients 5.6 Priapism 2 DOSAGE AND ADMINISTRATION In pooled analyses of placebo-controlled trials of antidepressant drugs Cases of priapism (painful erections greater than 6 hours in duration) have Nervousness 15% 11% 6% 8% breast milk. Talk to your healthcare provider 2.1 Dose Selection Important Interactions with anxiety • An extreme increase Trazodone Hydrochloride (SSRIs and other antidepressant classes) that included approximately been reported in men receiving trazodone hydrochloride tablets. Priapism, if Gastrointestinal about the best way to feed your baby if you 2.2 Important Administration 77,000 adult patients and over 4,400 pediatric patients, the incidence of not treated promptly, can result in irreversible damage to the erectile tissue. in activity and Instructions Tablets Abdominal/Gastric 4% 4% 6% 4% • Feeling very agitated suicidal thoughts and behaviors in pediatric and young adult patients was Men who have an erection lasting greater than 4 hours, whether painful or take trazodone hydrochloride. 2.3 Screen for Bipolar Disorder 8 USE IN SPECIFIC POPULATIONS Disorder greater in antidepressant-treated patients than in placebo-treated patients. not, should immediately discontinue the drug and seek emergency medical or restless talking (mania) Prior to Starting Trazodone 8.1 Pregnancy Diarrhea 0 1% 5% 1% The drug-placebo differences in the number of cases of suicidal thoughts attention [see Adverse Reactions (6.2), Overdosage (10)]. • have taken a Monoamine Oxidase Inhibitor Hydrochloride Tablets 8.2 Lactation and behaviors per 1000 patients treated are provided in Table 1. Nausea/Vomiting 10% 1% 13% 10% • Panic attacks • Other unusual 2.4 Switching to or from 8.4 Pediatric Use Trazodone hydrochloride tablets should be used with caution in men (MAOI) or if you have stopped taking an MAOI Musculoskeletal changes in behavior Monoamine Oxidase 8.5 Geriatric Use No suicides occurred in any of the pediatric studies. There were suicides who have conditions that might predispose them to priapism (e.g., sickle • Trouble sleeping in the last 2 weeks. Inhibitor Antidepressant 8.6 Renal Impairment in the adult studies, but the number was not sufficient to reach any cell anemia, multiple myeloma, or leukemia), or in men with anatomical Aches/Pains 6% 3% 5% 3% or mood 2.5 Dosage Recommendations 8.7 Hepatic Impairment conclusion about antidepressant drug effect on suicide. deformation of the penis (e.g., angulation, cavernosal fibrosis, or Peyronie’s Neurological (insomnia) 9 DRUG ABUSE AND for Concomitant Use with Table 1: Risk Differences of the Number of Cases of Suicidal Thoughts disease). Incoordination 5% 0 2% * Tell your healthcare provider about all the DEPENDENCE Strong CYP3A4 Inhibitors or Behaviors in the Pooled Placebo-Controlled Trials of 5.7 Activation of Mania or Hypomania Tremors 3% 1% 5% 4% What else do I need to know about antidepressant medicines you take, including prescription and or Inducers 9.1 Controlled Substance Antidepressants in Pediatric and Adult Patients In patients with bipolar disorder, treating a depressive episode with Other 2.6 Discontinuation of 9.2 Abuse trazodone hydrochloride tablets or another antidepressant may precipitate medicines? over-the-counter medicines, vitamins, and herbal 108 mm 108 10 OVERDOSAGE Drug-Placebo Difference in Number of Treatment with Trazodone Age Range a mixed/manic episode. Activation of mania/hypomania has been reported Eyes 3% 0 0 0 11 DESCRIPTION Patients of Suicidal Thoughts or Behaviors • Never stop an antidepressant medicine supplements. Using trazodone hydrochloride Hydrochloride Tablets (years) in a small proportion of patients with major affective disorder who were Red/Tired/Itching 12 CLINICAL PHARMACOLOGY per 1000 Patients Treated 3 DOSAGE FORMS AND treated with antidepressants. Prior to initiating treatment with trazodone Head Full-Heavy 3% 0 0 0 without first talking to a healthcare provider. tablets with certain other medicines can affect 12.1 Mechanism of Action Increases Compared to Placebo STRENGTHS hydrochloride tablets, screen patients for any personal or family history Malaise 3% 0 0 0 12.2 Pharmacodynamics Stopping an antidepressant medicine suddenly 4 CONTRAINDICATIONS <18 of bipolar disorder, mania, or hypomania each other causing serious side effects. 12.3 Pharmacokinetics 14 additional patients [see Dosage and Administration Nasal/Sinus 3% 0 6% 3% 5 WARNINGS AND PRECAUTIONS (2.3)]. can cause other symptoms. 5.1 Suicidal Thoughts and 13 NONCLINICAL TOXICOLOGY 18 to 24 5 additional patients Congestion Especially tell your healthcare provider if you take: Behaviors in Pediatric and 13.1 Carcinogenesis, 5.8 Discontinuation Syndrome Weight Gain 1% 0 5% 2% • Antidepressants are medicines used to Young Adult Patients Mutagenesis, Impairment Decreases Compared to Placebo Adverse reactions after discontinuation of serotonergic antidepressants, Weight Loss * 3% 6% 3% • triptans used to treat migraine headache particularly after abrupt discontinuation, include: nausea, sweating, treat depression and other illnesses. It is 5.2 Serotonin Syndrome of Fertility 25 to 64 1 fewer patient 5.3 Cardiac Arrhythmias 14 CLINICAL STUDIES dysphoric mood, irritability, agitation, dizziness, sensory disturbances important to discuss all the risks of treating • medicines used to treat mood, anxiety, 5.4 Orthostatic Hypotension 16 HOW SUPPLIED/STORAGE AND ≥65 6 fewer patients (e.g., paresthesia, such as electric shock sensations), tremor, anxiety, psychotic or thought disorders, including and Syncope HANDLING confusion, headache, lethargy, emotional lability, insomnia, hypomania, depression and also the risks of not treating it. 17 PATIENT COUNSELING It is unknown whether the risk of suicidal thoughts and behaviors in tinnitus, and seizures. A gradual reduction in dosage rather than 5.5 Increased Risk of Bleeding pediatric and young adult patients extends to longer-term use, i.e., beyond You should discuss all treatment choices with tricyclics, lithium, SSRIs, SNRIs, buspirone, or 5.6 Priapism INFORMATION abrupt cessation is recommended whenever possible [See Dosage and four months. However, there is substantial evidence from placebo- Administration (2.6)]. your healthcare provider, not just the use of antipsychotics 5.7 Activation of Mania or * Sections or subsections controlled maintenance trials in adults with MDD that antidepressants Hypomania omitted from the full prescribing delay the recurrence of depression. 5.9 Potential for Cognitive and Motor Impairment antidepressants. • tramadol 5.8 Discontinuation Syndrome information are not listed. Trazodone hydrochloride tablets may cause somnolence or sedation and 5.9 Potential for Cognitive and Monitor all antidepressant-treated patients for clinical worsening and may impair the mental and/or physical ability required for the performance • Antidepressant medicines have other side • over-the-counter supplements such as Motor Impairment emergence of suicidal thoughts and behaviors, especially during the initial of potentially hazardous tasks. Patients should be cautioned about 5.10 Angle-Closure Glaucoma few months of drug therapy and at times of dosage changes. Counsel operating hazardous machinery, including automobiles, until they are effects. Talk to your healthcare provider about tryptophan or St. John’s Wort family members or caregivers of patients to monitor for changes in behavior reasonably certain that the drug treatment does not affect them adversely. the side effects of your medicines. and to alert the healthcare provider. Consider changing the therapeutic • nonsteroidal anti-inflammatory drugs (NSAIDS) regimen, including possibly discontinuing trazodone hydrochloride tablets,

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Other adverse reactions occurring at an incidence of <2% with the use Table 3: Clinically Important Drug Interactions with Trazodone 9 DRUG ABUSE AND DEPENDENCE Directions for using the correct score when breaking the tablet please refer • Withdrawal symptoms. Symptoms of of trazodone hydrochloride in the controlled clinical studies: akathisia, Hydrochloride Tablets 9.1 Controlled Substance to the following: withdrawal can include anxiety, agitation, allergic reaction, anemia, chest pain, delayed urine flow, early menses, Digoxin and Phenytoin Trazodone hydrochloride tablets are not a controlled substance. - For 50 mg, break the score on either the left or right side of the tablet flatulence, hallucinations/delusions, hematuria, hypersalivation, hypomania, 9.2 Abuse (one-third of a tablet). impaired memory, impaired speech, impotence, increased appetite, increased Clinical Digoxin and phenytoin are narrow therapeutic index and sleep problems. Do not stop taking Impact: drugs. Concomitant use of trazodone hydrochloride Although trazodone hydrochloride has not been systematically studied • aspirin libido, increased urinary frequency, missed periods, muscle twitches, in preclinical or clinical studies for its potential for abuse, no indication trazodone hydrochloride tablets without numbness, paresthesia, retrograde ejaculation, shortness of breath, and tablets can increase digoxin or phenytoin concentrations. of drug-seeking behavior was seen in the clinical studies with trazodone • warfarin (Coumadin, Jantoven) talking to your healthcare provider. tachycardia/palpitations. Occasional sinus bradycardia has occurred in hydrochloride. - For 75 mg, break the score down the middle of the tablet (one-half of long-term studies. Intervention: Measure serum digoxin or phenytoin concentrations a tablet). before initiating concomitant use of trazodone 10 OVERDOSAGE • phenytoin (Mesantoin) 6.2 Postmarketing Experience • Visual problems. hydrochloride tablets. Continue monitoring and reduce Death from overdose has occurred in patients ingesting trazodone The following adverse reactions have been identified during post-approval digoxin or phenytoin dose as necessary. hydrochloride and other CNS depressant drugs concurrently (alcohol; • diuretics • eye pain use of trazodone hydrochloride tablets. Because these reactions are reported Examples: digoxin, phenytoin alcohol and chloral hydrate and diazepam; amobarbital; chlordiazepoxide; - For 100 mg, break the score on either the left or right side of the tablet voluntarily from a population of uncertain size, it is not always possible to or meprobamate). (two-thirds of a tablet). Know the medicines you take. Keep a list of them • changes in vision estimate their frequency or establish a causal relationship to drug exposure: Central Nervous System (CNS) Depressants The most severe reactions reported to have occurred with overdose Clinical Trazodone hydrochloride tablets may enhance the and show it to your healthcare provider and Blood and lymphatic system disorders: hemolytic anemia, leukocytosis of trazodone hydrochloride alone have been priapism, respiratory • swelling or redness in or around the eye Impact: response CNS depressants. Cardiac disorders: cardiospasm, congestive heart failure, conduction arrest, seizures, and ECG changes, including QT prolongation. The pharmacist when you get a new medicine. - For 150 mg, use the entire tablet. Only some people are at risk for these problems. block, orthostatic hypotension and syncope, palpitations, bradycardia, atrial Intervention: Patients should be counseled that trazodone reactions reported most frequently have been drowsiness and vomiting. How should I take trazodone hydrochloride fibrillation, myocardial infarction, cardiac arrest, arrhythmia, ventricular hydrochloride tablets may enhance the response to Overdosage may cause an increase in incidence or severity of any of the tablets? You may want to undergo an eye examination ectopic activity, including ventricular tachycardia and QT prolongation. alcohol, barbiturates, and other CNS depressants. reported adverse reactions. to see if you are at risk and receive preventative Prolonged QT interval, torsade de pointes, and ventricular tachycardia Examples: alcohol, barbiturates There is no specific antidote for trazodone hydrochloride overdose. Store at 20°C to 25°C (68°F to 77°F) [see USP Controlled Room • Take trazodone hydrochloride tablets exactly as have been reported at doses of 100 mg per day or less [see Warnings and QT Interval Prolongation In managing overdosage, consider the possibility of multiple drug Temperature]. Precautions (5.3)]. treatment if you are. Clinical Concomitant use of drugs that prolong the QT interval involvement. For current information on the management of poisoning Dispense in a tight, light-resistant container as defined in the USP. your healthcare provider tells you. Endocrine disorders: inappropriate ADH syndrome Impact: may add to the QT effects of trazodone hydrochloride or overdose, contact a poison control center (1-800-222-1222 or • Low sodium in your blood (hyponatremia). KEEP THIS AND ALL MEDICATIONS OUT OF THE REACH OF CHILDREN. Eye disorders: diplopia tablets and increase the risk of cardiac arrhythmia. www.poison.org). • Trazodone hydrochloride tablets should be 17 PATIENT COUNSELING INFORMATION Symptoms of hyponatremia include: headache, Intervention: Avoid the use of trazodone hydrochloride tablets in 11 DESCRIPTION Gastrointestinal disorders: increased salivation, nausea/vomiting Advise the patient to read the FDA-approved patient labeling (Medication taken shortly after a meal or light snack. combination with other drugs known to prolong QTc Trazodone hydrochloride tablets, USP for oral administration contain feeling weak, feeling confused, trouble General disorders and administration site conditions: chills, edema, Guide). • If you feel drowsy after taking trazodone unexplained death, weakness [see Warnings and Precautions (5.3)]. trazodone hydrochloride, USP a selective serotonin reuptake inhibitor and concentrating, memory problems and feeling Examples: Class 1A antiarrhythmics: quinidine, procainamide, 5HT2 receptor antagonist. Trazodone hydrochloride, USP is a triazolopyridine Suicidal Thoughts and Behaviors Hepatobiliary disorders: cholestasis, jaundice, hyperbilirubinemia, liver derivative designated as 2-[3-[4-(3-chlorophenyl)-1-piperazinyl]propyl] Advise patients and caregivers to look for the emergence of suicidality, hydrochloride tablets, talk to your healthcare unsteady when you walk. enzyme alterations disopyramide; Class 3 antiarrhythmics: amiodarone, sotalol; Antipsychotics: ziprasidone, chlorpromazine, -1,2,4-triazolo[4, 3-a]pyridin-3(2H)-one hydrochloride. It is a white, odorless especially early during treatment and when the dosage is adjusted up provider. Your healthcare provider may change Get medical help right away, if you have any of the Investigations: increased amylase thioridazine; Antibiotics: gatifloxacin crystalline powder which is freely soluble in water. The structural formula is or down and instruct them to report such symptoms to the healthcare Metabolism and nutrition disorders: methemoglobinemia represented as follows: provider [see Box Warning and Warnings and Precautions (5.1)]. your dose or the time of day you take your symptoms listed above. 8 USE IN SPECIFIC POPULATIONS trazodone hydrochloride tablets. Nervous system disorders: aphasia, ataxia, cerebrovascular accident, 8.1 Pregnancy Dosage and Administration extrapyramidal symptoms, grand mal seizures, paresthesia, tardive Pregnancy Exposure Registry Advise patients that trazodone hydrochloride tablets should be taken The most common side effects of trazodone dyskinesia, vertigo There is a pregnancy exposure registry that monitors pregnancy outcomes shortly after a meal or light snack. Advise patients regarding the • Do not stop taking trazodone hydrochloride N N Cl • HCI hydrochloride tablets include: Psychiatric disorders: abnormal dreams, agitation, anxiety, hallucinations, in women exposed to antidepressants during pregnancy. Healthcare N importance of following dosage titration instructions [see Dosage and tablets without talking to your healthcare provider. insomnia, paranoid reaction, psychosis, stupor N N Administration (2)]. • swelling • tiredness providers are encouraged to register patients by calling the National • Trazodone hydrochloride tablets should be Renal and urinary disorders: urinary incontinence, urinary retention Pregnancy Registry for Antidepressants at 1-844-405-6185 or visiting Serotonin Syndrome Reproductive system and breast disorders: breast enlargement online at https://womensmentalhealth.org/clinical-and-research-programs/ O Caution patients about the risk of serotonin syndrome, particularly

288 mm • blurred vision • diarrhea or engorgement, clitorism, lactation, priapism [see Warnings and pregnancyregistry/antidepressants/ with the concomitant use of trazodone hydrochloride tablets with swallowed whole or broken in half along the C19H22CIN5O • HCl M.W. 408.32 Precautions (5.6)] Risk Summary other serotonergic drugs including triptans, tricyclic antidepressants, score line. Do not chew or crush trazodone • dizziness • stuffy nose Each tablet, for oral administration, contains 50 mg, 100 mg or 150 mg of fentanyl, lithium, tramadol, tryptophan, buspirone, St. John’s Wort, and Respiratory, thoracic and mediastinal disorders: apnea Published prospective cohort studies, case series, and case reports over trazodone hydrochloride, USP. In addition, each tablet contains colloidal several decades with trazodone hydrochloride use in pregnant women with drugs that impair metabolism of serotonin (in particular, MAOIs, hydrochloride tablets. Tell your healthcare • sleepiness • weight loss Skin and subcutaneous tissue disorders: alopecia, hirsutism, silicon dioxide, lactose anhydrous, magnesium stearate, microcrystalline have not identified any drug-associated risks of major birth defects, both those intended to treat psychiatric disorders and also others, leukonychia, pruritus, psoriasis, rash, urticaria cellulose and sodium starch glycolate. provider if you cannot swallow trazodone either These are not all the possible side effects of miscarriage, or adverse maternal or fetal outcomes (see Data). Trazodone such as linezolid). Patients should contact their health care provider or whole or as a half tablet. Vascular disorders: vasodilation hydrochloride has been shown to cause increased fetal resorption and 12 CLINICAL PHARMACOLOGY report to the emergency room if they experience signs or symptoms trazodone hydrochloride tablets. Call your doctor 7 DRUG INTERACTIONS other adverse effects on the fetus in the rat when given at dose levels 12.1 Mechanism of Action of serotonin syndrome [see Warnings and Precautions (5.2) and Drug • If you take too many trazodone hydrochloride 7.1 Drugs Having Clinically Important Interactions with Trazodone approximately 7.3 to 11 times the maximum recommended human dose The mechanism of trazodone’s antidepressant action is not fully Interactions (7)]. for medical advice about side effects. You may Hydrochloride Tablets (MRHD) of 400 mg/day in adults on a mg/m2 basis. There was also an understood, but is thought to be related to its enhancement of Activation of Mania/Hypomania serotonergic activity in the CNS. Trazodone is both a selective serotonin tablets, call your healthcare provider, your report side effects to FDA at 1-800-FDA-1088. Table 3: Clinically Important Drug Interactions with Trazodone increase in congenital anomalies in the rabbit at approximately 7.3 to 22 Advise patients and their caregivers to observe for signs of activation times the MRHD on a mg/m2 basis (see Data). reuptake inhibitor (SSRI) and a 5HT2 receptor antagonist and the of mania/hypomania and instruct them to report such symptoms to the Poison Control Center at 1-800-222-1222, or Hydrochloride Tablets net result of this action on serotonergic transmission and its role in How should I store trazodone hydrochloride The estimated background risk of major birth defects and miscarriage for healthcare provider [see Warnings and Precautions (5.7)]. go to the nearest emergency room right away. Monoamine Oxidase Inhibitors (MAOIs) trazodone’s antidepressant effect is unknown. Clinical The concomitant use of MAOIs and serotonergic the indicated population is unknown. All pregnancies have a background Increased Risk of Bleeding tablets? risk of birth defect, loss, or other adverse outcomes. In the U.S. general 12.2 Pharmacodynamics Inform patients about the concomitant use of trazodone hydrochloride What should I avoid while taking trazodone Impact: drugs including trazodone hydrochloride tablets Preclinical studies have shown that trazodone selectively inhibits neuronal • Store trazodone hydrochloride tablets at increases the risk of serotonin syndrome. population, the estimated background risk of major birth defects and tablets with aspirin, NSAIDs, other antiplatelet drugs, warfarin, or other hydrochloride tablets? miscarriage in clinically recognized pregnancies is 2% to 4% and 15% reuptake of serotonin (Ki = 367 nM) and acts as an antagonist at 5-HT-2A anticoagulants because the combined use of drugs that interfere with room temperature between 68°F to 77°F Intervention: Trazodone hydrochloride tablets are contraindicated to 20%, respectively. (Ki = 35.6 nM) serotonin receptors. Trazodone is also an antagonist at serotonin reuptake and these medications has been associated with in patients taking MAOIs, including MAOIs such several other monoaminergic receptors including 5-HT2B (Ki = 78.4 nM), • Do not drive, operate heavy machinery, or do (20°C to 25°C). Clinical Considerations an increased risk of bleeding. Advise them to inform their health care as linezolid or intravenous methylene blue [see 5-HT2C (Ki = 224 nM), α1A (Ki = 153 nM), α2C (Ki = 155 nM) receptors providers if they are taking or planning to take any prescription or over- other dangerous activities until you know how Contraindications (4), Dosage and Administration Disease-associated maternal and/or embryofetal risk and it is a partial agonist at 5- HT1A (Ki = 118 nM) receptor. • Keep in tight container A prospective, longitudinal study followed 201 pregnant women with the-counter medications that increase the risk of bleeding [see Warnings (2.3, 2.4), and Warnings and Precautions (5.2)]. Trazodone antagonizes alpha 1-adrenergic receptors, a property which trazodone hydrochloride tablets affects you. a history of major depressive disorder who were euthymic and taking and Precautions (5.5)]. may be associated with postural hypotension. Trazodone hydrochloride tablets can slow your • Keep out of the light Examples: isocarboxazid, moclobemide, phenelzine, selegiline, antidepressants at the beginning of pregnancy. The women who Discontinuation Syndrome tranylcypromine discontinued antidepressants during pregnancy were more likely to 12.3 Pharmacokinetics Advise patients not to abruptly discontinue trazodone hydrochloride thinking and motor skills. • Safely throw away medicine that is out of date Other Serotonergic Drugs experience a relapse of major depression that women who continued Absorption tablets and to discuss any tapering regimen with their healthcare provider. or no longer needed. Clinical The concomitant use of serotonergic drugs antidepressants. Consider the risk of untreated depression when In humans, trazodone hydrochloride is absorbed after oral administration Adverse reactions can occur when trazodone hydrochloride tablets is • Do not drink alcohol or take other medicines that Impact: including trazodone hydrochloride tablets and other discontinuing or changing treatment with antidepressant medication without selective localization in any tissue. When trazodone hydrochloride discontinued [see Warnings and Precautions (5.8)]. is taken shortly after ingestion of food, there may be an increase in the make you sleepy or dizzy while taking trazodone serotonergic drugs increases the risk of serotonin during pregnancy and postpartum. Concomitant Medications Keep trazodone hydrochloride tablets and all syndrome. amount of drug absorbed, a decrease in maximum concentration and a Data lengthening in the time to maximum concentration. Peak plasma levels Advise patients to inform their health care providers if they are taking, or hydrochloride tablets until you talk with your medicines out of the reach of children. Intervention: Monitor patients for signs and symptoms of serotonin Human Data occur approximately one hour after dosing when trazodone hydrochloride plan to take any prescription or over-the-counter medications since there syndrome, particularly during trazodone hydrochloride healthcare provider. Trazodone hydrochloride While available studies cannot definitively establish the absence of risk, is taken on an empty stomach or 2 hours after dosing when taken with is a potential for interactions [see Drug Interactions (7.1)]. tablets initiation. If serotonin syndrome occurs, General information about the safe and effective published data from prospective cohort studies, case series, and case food. Pregnancy tablets may make your sleepiness or dizziness consider discontinuation of trazodone hydrochloride use of trazodone hydrochloride tablets. reports over several decades have not identified an association with Advise patients to notify their healthcare provider if they become tablets and/or concomitant serotonergic drugs [see trazodone use during pregnancy and major birth defects, miscarriage, Metabolism worse if you take it with alcohol or other In vitro studies in human liver microsomes show that trazodone pregnant or intend to become pregnant during therapy with trazodone Medicines are sometimes prescribed for purposes Warnings and Precautions (5.2)]. or other adverse maternal or fetal outcomes. All available studies have hydrochloride tablets. Advise patients that there is a pregnancy exposure medicines that cause sleepiness or dizziness. Examples: triptans, antidepressants (tricyclic and serotonin methodological limitations, including small sample size and inconsistent is metabolized, via oxidative cleavage, to an active metabolite, m-chlorophenylpiperazine (mCPP) by CYP3A4. Other metabolic pathways registry that monitors pregnancy outcomes in women exposed to other than those listed in a Medication Guide. Do uptake inhibitors), fentanyl, lithium, tramadol, comparator groups. that may be involved in the metabolism of trazodone have not been well trazodone hydrochloride tablets during pregnancy [see Use in Special tryptophan, buspirone, and St. John’s Wort What are the possible side effects of trazodone not use trazodone hydrochloride tablets for a Animal Data characterized. Trazodone is extensively metabolized; less than 1% of an Populations (8.1)]. condition for which it was not prescribed. Do Antiplatelet Agents and Anticoagulants No teratogenic effects were observed when trazodone was given to oral dose is excreted unchanged in the urine. Manufactured In Croatia By: hydrochloride tablets? Clinical Serotonin release by platelets plays an important role pregnant rats and rabbits during the period of organogenesis at oral Pliva Hrvatska d.o.o. not give trazodone hydrochloride tablets to other doses up to 450 mg/kg/day. This dose is 11 and 22 times, in rats and Elimination Trazodone hydrochloride tablets can cause Impact: in hemostasis. The concurrent use of an antiplatelet In some patients trazodone may accumulate in the plasma. Zagreb, Croatia agent or anticoagulant with trazodone hydrochloride rabbits, respectively, the maximum recommended human dose (MRHD) people, even if they have the same symptoms that 2 Manufactured For: serious side effects or death, including: tablets may potentiate the risk of bleeding. of 400 mg/day in adults on a mg/m basis. Increased fetal resorption and Protein Binding you have. It may harm them. You can ask your other adverse effects on the fetus in rats at 7.3 to 11 times the MRHD Trazodone is 89 to 95% protein bound in vitro at concentrations attained Teva Pharmaceuticals USA, Inc. • See “What is the most important information Intervention: Inform patients of the increased risk of bleeding with therapeutic doses in humans. Parsippany, NJ 07054 with the concomitant use of trazodone hydrochloride and increase in congenital anomalies in rabbits at 7.3 to 22 times the pharmacist or healthcare provider for information 2 I should know about trazodone hydrochloride tablets and antiplatelet agents and anticoagulants. MRHD on a mg/m basis were observed. No further details on these 13 NONCLINICAL TOXICOLOGY Rev. I 7/2020 tablets?” about trazodone hydrochloride tablets that is For patients taking warfarin, carefully monitor the studies are available. 13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility written for health professionals. international normalized ratio (INR) when initiating or 8.2 Lactation Carcinogenesis • Serotonin syndrome. Symptoms of serotonin discontinuing trazodone hydrochloride tablets [see Risk Summary No drug- or dose-related occurrence of carcinogenesis was evident in Warnings and Precautions (5.5)]. Data from published literature report the transfer of trazodone into human rats receiving trazodone in daily oral doses up to 7.3 times the maximum recommended human dose (MRHD) of 400 mg/day in adults on a mg/m2 syndrome include: agitation, hallucinations, What are the ingredients in trazodone hydrochloride Examples: warfarin, rivaroxaban, dabigatran, clopidogrel milk. There are no data on the effect of trazodone on milk production. Limited data from postmarketing reports have not identified and basis. Strong CYP3A4 Inhibitors problems with coordination, fast heartbeat, tablets? association of adverse effects on the breastfed child. The developmental Mutagenesis Clinical The concomitant use of trazodone hydrochloride and health benefits of breastfeeding should be considered along with No genotoxicity studies were conducted with trazodone. tight muscles, trouble walking, sweating, fever, Active ingredient: trazodone hydrochloride, USP Impact: tablets and strong CYP3A4 inhibitors increased the mother’s clinical need for trazodone hydrochloride and any potential Impairment of Fertility nausea, vomiting, and diarrhea. Inactive ingredients: colloidal silicon dioxide, the exposure of trazodone compared to the use of adverse effects on the breastfed child from trazodone hydrochloride or trazodone hydrochloride tablets alone. Trazodone has no effect on fertility in rats at doses up to 7.3 times the lactose anhydrous, magnesium stearate, from the underlying maternal condition. MRHD in adults on a mg/m2 basis. • Irregular or fast heartbeat or faint (QT Intervention: If trazodone hydrochloride tablets is used with a 8.4 Pediatric Use potent CYP3A4 inhibitor, the risk of adverse reactions, 14 CLINICAL STUDIES prolongation) microcrystalline cellulose and sodium starch Safety and effectiveness in the pediatric population have not been The efficacy and safety of trazodone hydrochloride were established including cardiac arrhythmias, may be increased and a established. Antidepressants increased the risk of suicidal thoughts glycolate. lower dose of trazodone hydrochloride tablets should from inpatient and outpatient trials of the trazodone immediate release • Low blood pressure. You feel dizzy or faint and behaviors in pediatric patients [see Boxed Warning, Warnings and formulation in the treatment of major depressive disorder. be considered [see Dosage and Administration (2.5), Precautions (5.1)]. when you change positions (go from sitting to All brand names listed are the registered Warnings and Precautions (5.3)]. 16 HOW SUPPLIED/STORAGE AND HANDLING 8.5 Geriatric Use Examples: itraconazole, ketoconazole, clarithromycin, indinavir Trazodone hydrochloride tablets, USP are available as follows: trademarks of their respective owners and are not Reported clinical literature and experience with trazodone has not identified standing) 50 mg: White, round, compressed tablet, debossed “PLIVA 433” on Strong CYP3A4 Inducers differences in responses between elderly and younger patients. However, as trademarks of Teva Pharmaceuticals USA. one side and scored on the other side. Available in bottles of 100 tablets • Unusual bruising or bleeding Clinical The concomitant use of trazodone hydrochloride experience in the elderly with trazodone hydrochloride is limited, it should (50111-560-01), 500 tablets (NDC 50111-560-02) and 1000 tablets Manufactured In Croatia By: Pliva Hrvatska d.o.o., Impact: tablets and strong CYP3A4 inducers decreased be used with caution in geriatric patients. (50111-560-03). • Erection lasting for more than 6 hours Zagreb, Croatia the exposure of trazodone compared to the use of Serotonergic antidepressants have been associated with cases of clinically trazodone hydrochloride tablets alone. 100 mg: White, round, compressed tablet, debossed “PLIVA 434” on (priapism) Manufactured For: Teva Pharmaceuticals USA, Inc., significant hyponatremia in elderly patients, who may be at greater risk for one side and scored on the other side. Available in bottles of 100 tablets Parsippany, NJ 07054 Intervention: Patients should be closely monitored to see if this adverse reaction [see Warnings and Precautions (5.11)]. • Feeling high or in a very good mood, then there is a need for an increased dose of trazodone (50111-561-01), 500 tablets (NDC 50111-561-02) and 1000 tablets hydrochloride tablets when taking CYP3A4 inducers 8.6 Renal Impairment (NDC 50111-561-03). This Medication Guide has been approved by the U.S. Food Trazodone has not been studied in patients with renal impairment. becoming irritable, or having too much [see Dosage and Administration (2.5)]. 150 mg: White, oval, flat-faced, beveled edge tablet, scored and debossed and Drug Administration Rev. E 7/2020 Trazodone should be used with caution in this population. Examples: rifampin, carbamazepine, phenytoin, St. John’s wort as “PLIVA” bisect “441” on one side and tri-scored and debossed as energy, feeling like you have to keep talking 8.7 Hepatic Impairment “50” in each section on the other side. Available in bottles of 100 tablets or do not sleep (mania). Trazodone has not been studied in patients with hepatic impairment. (NDC 50111-450-01) and 500 tablets (50111-450-02). Trazodone should be used with caution in this population.

65899_TrazTabs_PiMG_I7_20.indd 2 7/23/20 3:51 PM

Mat# 70065899 Filename: 65899_TrazTabs_PiMG_I7_20.indd Proof# 2 Artist Name/Date: Richard Barthelemy 7/23/2020 AMT Version: 22 Jul 2020 Vault# VV-207674 Approvals:* NDA/ANDA# 071523 Black

Approval: Date: 071524, 071525