tial increases in trazodone plasma concentrations with the potential for adverse effects. if trazodone is used with a potent cyp3a4 inhibitor, the risk of cardiac arrhythmia may be increased [see warnings andprecautions ( 5.4 )] and a lower dose of trazodone should be considered. cytochrome p450 inducers (e.g., carbamazepine) carbamazepine induces cyp3a4. following coadministration of carbamazepine 400 mg per day with trazodone 100 mg to 300 mg daily, carbamazepine reduced plasma concentrations of trazodone and m-chlorophenlypiperazine (an active metabolite) by 76% and 60% respectively, compared to pre-carbamazepine values. patients should be closely monitored to see if there is a need for an increased dose of trazodone when taking both drugs. digoxin and phenytoin increased serum digoxin or phenytoin levels have been reported in patients receiving trazodone concurrently with either of these drugs. monitor serum levels and adjust dosages as needed. serotonergic drugs based on the mechanism of action of trazodone and the potential for serotonin syndrome, caution is advised when trazodone is coadministered with other drugs that may affect the neurotransmitter systems [ see warnings and precautions ( 5.2 ) ]. nsaids, aspirin, or other drugs affecting coagulation or bleeding due to a possible association between serotonin modulating drugs and gastrointestinal bleeding, patients should be monitored for and cautioned about the potential risk of bleeding associated with the concomitant use of trazodone and nsaids, aspirin, or other drugs that affect coagulation or bleeding [s eewarnings and precautions ( 5.7 ) ]. warfarin there have been reports of altered (either increased or decreased) prothrombin times in taking both warfarin and trazodone. • cns depressants: trazodone may enhance effects of alcohol, barbiturates, or other cns depressants ( 7 ). • cyp3a4 inhibitors: may necessitate lower dose of trazodone hydrochloride tablets ( 7 ). • cyp3a4 inducers (e.g., carbamazepine): may necessitate higher dose of trazodone hydrochloride tablets ( 7 ). • digoxin or phenytoin: monitor for increased serum levels ( 7 ). • warfarin: monitor for increased or decreased prothrombin time ( 7 ).

k ( 5.7 , 7 ). • interaction with maois: do not use concomitantly or within 14 days of monoamine oxidase inhibitors ( 5.8 , 7 ). • priapism: has occurred. warn male patients of this risk and how/when to seek medical attention ( 5.9 ). • hyponatremia: can occur in association with siadh ( 5.10 ). • potential for cognitive and motor impairment: has potential to impair judgment, thinking, and motor skills. advise patients to use caution when operating machinery ( 5.11 ). • discontinuation symptoms: may occur with abrupt discontinuation and include anxiety and sleep disturbance. upon discontinuation, taper trazodone hydrochloride tablets and monitor for symptoms ( 5.12 ). 5.1 clinical worsening and suicide risk patients with major depressive disorder (mdd), both adult and pediatric, may experience worsening of their depression and/or the emergence of suicidal ideation and behavior (suicidality) or unusual changes in behavior, whether or not they are taking antidepressant medications, and this risk may persist until significant remission occurs. suicide is a known risk of depression and certain other psychiatric disorders and these disorders themselves are the strongest predictors of suicide. there has been a long standing concern, however, that antidepressants may have a role in inducing worsening of depression and the emergence of suicidality in certain patients during the early phases of treatment. pooled analyses of short-term placebo-controlled trials of antidepressant drugs (ssris and others) showed that these drugs increase the risk of suicidal thinking and behavior (suicidality) in children, adolescents, and young adults (ages 18 to 24) with mdd and other psychiatric disorders. short-term studies did not show an increase in the risk of suicidality with antidepressants compared to placebo in adults beyond age 24; there was a reduction with antidepressants compared to placebo in adults aged 65 and older. the pooled analyses of placebo-controlled trials in children and adolescents with mdd, obsessive compulsive disorder (ocd), or other psychiatric disorders included a total of 24 short-term trials of 9 antidepressant drugs in over 4,400 patients. the pooled analyses of placebo-controlled trials in adults with mdd or other psychiatric disorders included a total of 295 short-term trials (median duration of 2 months) of 11 antidepressant drugs in over 77,000 patients. there was considerable variation in risk of suicidality among drugs, but a tendency toward an increase in the younger patients for almost all drugs studied. there were differences in absolute risk of suicidality across the different indications, with the highest incidence in mdd. the risk differences (drug vs. placebo), however, were relatively stable within age strata and across indications. these risk differences (drug-placebo difference in the number of cases of suicidality per 1,000 patients treated) are provided in table 1 . table 1 age range drug-placebo difference in number of cases of suicidality per 1,000 patients treated increases compared to placebo < 18 14 additional cases 18 to 24 5 additional cases decreases compared to placebo 25 to 64 1 fewer case ≥ 65 6 fewer cases no suicides occurred in any of the pediatric trials. there were suicides in the adult trials, but the number was not sufficient to reach any conclusion about drug effect on suicide. it is unknown whether the suicidality risk extends to longer-term use, i.e., beyond several months. however, there is substantial evidence from placebo-controlled maintenance trials in adults with depression that the use of antidepressants can delay the recurrence of depression. all patients being treated with antidepressants for any indication should be monitored appropriately and observed closely for clinical worsening, suicidality, and unusual changes in behavior, especially during the initial few months of a course of drug therapy, or at times of dose changes, either increases or decreases . the following symptoms, anxiety, agitation, panic attacks, insomnia, irritability, hostility, aggressiveness, impulsivity, akathisia (psychomotor restlessness), hypomania, and mania, have been reported in adult and pediatric patients being treated with antidepressants for major depressive disorder as well as for other indications, both psychiatric and nonpsychiatric. although a causal link between the emergence of such symptoms and either the worsening of depression and/or the emergence of suicidal impulses has not been established, there is concern that such symptoms may represent precursors to emerging suicidality. consideration should be given to changing the therapeutic regimen, including possibly discontinuing the medication, in patients whose depression is persistently worse, or who are experiencing emergent suicidality or symptoms that might be precursors to worsening depression or suicidality, especially if these symptoms are severe, abrupt in onset, or were not part of the patient's presenting symptoms. families and caregivers of patients being treated with antidepressants for major depressive disorder or other indications, both psychiatric and nonpsychiatric, should be alerted about the need to monitor patients for the emergence of agitation, irritability, unusual changes in behavior, and the other symptoms described above, as well as the emergence of suicidality, and to report such symptoms immediately to healthcare providers . such monitoring should include daily observation by families and caregivers . prescriptions for trazodone should be written for the smallest quantity of tablets consistent with good patient management, in order to reduce the risk of overdose. 5.2 serotonin syndrome or neuroleptic malignant syndrome (nms)-like reactions the development of a potentially life-threatening serotonin syndrome or neuroleptic malignant syndrome (nms)-like reactions have been reported with antidepressants alone and may occur with trazodone treatment, but particularly with concomitant use of other serotoninergic drugs (including ssris, snris and triptans) and with drugs that impair metabolism of serotonin (including monoamine oxidase inhibitors [maois]), or with antipsychotics or other dopamine antagonists. serotonin syndrome symptoms may include mental status changes (e.g., agitation, hallucinations, and coma), autonomic instability (e.g., tachycardia, labile blood pressure, and hyperthermia), neuromuscular aberrations (e.g., hyperreflexia, incoordination) and/or gastrointestinal symptoms (e.g., nausea, vomiting, and diarrhea). serotonin syndrome, in its most severe form, can resemble neuroleptic malignant syndrome, which includes hyperthermia, muscle rigidity, autonomic instability with possible rapid fluctuation of vital signs, and mental status changes. treatment with trazodone hydrochloride tablets and any concomitant serotonergic or antidopaminergic agents, including antipsychotics, should be discontinued immediately if the above reactions occur and supportive symptomatic treatment should be initiated. trazodone hydrochloride tablets should not be used within 14 days of an maoi [see warnings and precautions ( 5.8 ) and drug interactions ( 7 )]. if concomitant treatment with trazodone hydrochloride tablets and an ssri, snri or a 5-hydroxytryptamine receptor agonist (triptan) is clinically warranted, careful observation of the patient is advised, particularly during treatment initiation and dose increases. the concomitant use of trazodone hydrochloride tablets with serotonin precursors (such as tryptophan) is not recommended. 5.3 screening patients for bipolar disorder and monitoring for mania/hypomania a major depressive episode may be the initial presentation of bipolar disorder. it is generally believed (though not established in controlled trials) that treating such an episode with an antidepressant alone may increase the likelihood of precipitation of a mixed/manic episode in patients at risk for bipolar disorder. whether any of the symptoms described for clinical worsening and suicide risk represent such a conversion is unknown. however, prior to initiating treatment with an antidepressant, patients with depressive symptoms should be adequately screened to determine if they are at risk for bipolar disorder; such screening should include a detailed psychiatric history, including a family history of suicide, bipolar disorder, and depression. it should be noted that trazodone hydrochloride tablets are not approved for use in treating bipolar depression. 5.4 qt prolongation and risk of sudden death trazodone is known to prolong the qt/qt c interval. some drugs that prolong the qt/qt c interval can cause torsade de pointes with sudden, unexplained death. the relationship of qt prolongation is clearest for larger increases (20 msec and greater), but it is possible that smaller qt/qt c prolongations may also increase risk, especially in susceptible individuals, such as those with hypokalemia, hypomagnesemia, or a genetic predisposition to prolonged qt/qt c . although torsade de pointes has not been observed with the use of trazodone hydrochloride tablets at recommended doses in premarketing trials, experience is too limited to rule out an increased risk. however, there have been postmarketing reports of torsade de pointes with the immediate-release form of trazodone (in the presence of multiple confounding factors), even at doses of 100 mg per day or less. 5.5 use in patients with heart disease trazodone hydrochloride is not recommended for use during the initial recovery phase of myocardial infarction. caution should be used when administering trazodone hydrochloride tablets to patients with cardiac disease and such patients should be closely monitored, since antidepressant drugs (including trazodone hydrochloride) may cause cardiac arrhythmias. qt prolongation has been reported with trazodone therapy [see warnings and precautions (5.4)] . clinical studies in patients with preexisting cardiac disease indicate that trazodone hydrochloride may be arrhythmogenic in some patients in that population. arrhythmias identified include isolated pvcs, ventricular couplets, tachycardia with syncope, and torsade de pointes. postmarketing events have been reported at doses of 100 mg or less with the immediate-release form of trazodone. concomitant administration of drugs that prolong the qt interval or that are inhibitors of cyp3a4 may increase the risk of cardiac arrhythmia. 5.6 orthostatic hypotension and syncope hypotension, including orthostatic hypotension and syncope has been reported in patients receiving trazodone hydrochloride. concomitant use with an antihypertensive may require a reduction in the dose of the antihypertensive drug. 5.7 abnormal bleeding postmarketing data have shown an association between use of drugs that interfere with serotonin reuptake and the occurrence of gastrointestinal (gi) bleeding. while no association between trazodone and bleeding events, in particular gi bleeding, was shown, patients should be cautioned about potential risk of bleeding associated with the concomitant use of trazodone and nsaids, aspirin, or other drugs that affect coagulation or bleeding. other bleeding events related to ssris and snris have ranged from ecchymosis, hematoma, epistaxis, and petechiae to life-threatening hemorrhages. 5.8 interaction with maois in patients receiving serotonergic drugs in combination with a monoamine oxidase inhibitor (maoi), there have been reports of serious, sometimes fatal reactions including hyperthermia, rigidity, myoclonus, autonomic instability with rapid fluctuation in vital signs, and mental status changes that include extreme agitation progressing to delirium and coma. these reactions have also been reported in patients who have recently discontinued antidepressant treatment and have been started on an maoi. some cases presented with features resembling neuroleptic malignant syndrome. furthermore, limited animal data on the effects of combined use of serotonergic antidepressants and maois suggest that these drugs may act synergistically to elevate blood pressure and evoke behavioral excitation. therefore, it is recommended that trazodone hydrochloride tablets should not be used in combination with an maoi or within 14 days of discontinuing treatment with an maoi. similarly, at least 14 days should be allowed after stopping trazodone hydrochloride tablets before starting an maoi. 5.9 priapism rare cases of priapism (painful erections greater than 6 hours in duration) were reported in men receiving trazodone. priapism, if not treated promptly, can result in irreversible damage to the erectile tissue. men who have an erection lasting greater than 6 hours, whether painful or not, should immediately discontinue the drug and seek emergency medical attention [see adverse reactions ( 6.2 ) and overdosage ( 10 )]. trazodone should be used with caution in men who have conditions that might predispose them to priapism (e.g., sickle cell anemia, multiple myeloma, or leukemia), or in men with anatomical deformation of the penis (e.g., angulation, cavernosal fibrosis, or peyronie's disease). 5.10 hyponatremia hyponatremia may occur as a result of treatment with antidepressants. in many cases, this hyponatremia appears to be the result of the syndrome of inappropriate antidiuretic hormone secretion (siadh). cases with serum sodium lower than 110 mmol/l have been reported. elderly patients may be at greater risk of developing hyponatremia with antidepressants. also, patients taking diuretics or who are otherwise volume-depleted can be at greater risk. discontinuation of trazodone hydrochloride tablets should be considered in patients with symptomatic hyponatremia and appropriate medical intervention should be instituted. signs and symptoms of hyponatremia include headache, difficulty concentrating, memory impairment, confusion, weakness, and unsteadiness, which can lead to falls. signs and symptoms associated with more severe and/or acute cases have included hallucination, syncope, seizure, coma, respiratory arrest, and death. 5.11 potential for cognitive and motor impairment trazodone hydrochloride tablets may cause somnolence or sedation and may impair the mental and/or physical ability required for the performance of potentially hazardous tasks. patients should be cautioned about operating hazardous machinery, including automobiles, until they are reasonably certain that the drug treatment does not affect them adversely. 5.12 discontinuation symptoms withdrawal symptoms including anxiety, agitation and sleep disturbances, have been reported with trazodone. clinical experience suggests that the dose should be gradually reduced before complete discontinuation of the treatment.

should be gradually reduced whenever possible [see warnings andprecautions ( 5.12 )] . maintenance treatment the efficacy of trazodone hydrochloride tablets for the maintenance treatment of mdd has not been evaluated. while there is no body of evidence available to answer the question of how long a patient treated with trazodone hydrochloride tablets should continue the drug, it is generally recommended that treatment be continued for several months after an initial response. patients should be maintained on the lowest effective dose and be periodically reassessed to determine the continued need for maintenance treatment. important administration instructions trazodone hydrochloride tablets are scored to provide flexibility in dosing. trazodone hydrochloride tablets can be swallowed whole or administered as a half tablet by breaking the tablet along the score line. • 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 ). • trazodone hydrochloride tablets should be taken shortly after a meal or light snack ( 2 ). • tablets should be swallowed whole or broken in half along the score line, and should not be chewed or crushed ( 2 ). • when discontinued, gradual dose reduction is recommended ( 2 ).

to discontinuation of trazodone hydrochloride tablets treatment with an incidence of at least 1% and at least twice that for placebo. table 2: adverse reactions with discontinuation as action taken (≥ 1%) incidence and incidence 2x placebo trazodone n = 202 somnolence/sedation 8 (4%) dizziness 7 (3.5%) confusional state 2 (1%) coordination abnormal 2 (1%) headache 2 (1%) nausea 2 (1%) balance disorder/gait disturbance 2 (1%) most common adverse reactions (incidence ≥ 5% and twice that of placebo) are: somnolence/sedation, dizziness, constipation, vision blurred ( 6 ). to report suspected adverse reactions, contact teva usa, pharmacovigilance at 1-866-832-8537 or drug.safety@tevapharm.com ; or fda at 1-800-fda-1088 or www.fda.gov/medwatch 6.1 clinical studies experience the table below is presented solely to indicate the relative frequency of adverse events reported in representative controlled clinical studies conducted to evaluate the safety and efficacy of trazodone hydrochloride. the figures cited cannot be used to predict concisely the incidence of untoward events in the course of usual medical practice where patient characteristics and other factors often differ from those which prevailed in the clinical trials. these incidence figures, also, cannot be compared with those obtained from other clinical studies involving related drug products and placebo as each group of drug trials is conducted under a different set of conditions. table 3: adverse reactions: percentage of patients (> 2%) as observed in controlled clinical studies inpatientsoutpatients trazodone placebo trazodone placebo number of patients 142 95 157 158 % of patients reporting allergic skin condition/edema 2.8 1.1 7 1.3 autonomic blurred vision 6.3 4.2 14.7 3.8 constipation 7 4.2 7.6 5.7 dry mouth 14.8 8.4 33.8 20.3 cardiovascular hypertension 2.1 1.1 1.3 incidence less than 1% hypotension 7 1.1 3.8 0 shortness of breath 1.1 1.3 0 syncope 2.8 2.1 4.5 1.3 tachycardia/palpitations 0 0 7 7 cns anger/hostility 3.5 6.3 1.3 2.5 confusion 4.9 0 5.7 7.6 decreased concentration 2.8 2.1 1.3 0 disorientation 2.1 0 0 dizziness/light-headedness 19.7 5.3 28 15.2 drowsiness 23.9 6.3 40.8 19.6 excitement 1.1 1.1 5.1 5.7 fatigue 11.3 4.2 5.7 2.5 headache 9.9 5.3 19.8 15.8 insomnia 9.9 10.5 6.4 12 impaired memory 1.4 0 nervousness 14.8 10.5 6.4 8.2 gastrointestinal abdominal/gastric disorder 3.5 4.2 5.7 4.4 bad taste in mouth 1.4 0 0 0 diarrhea 0 1.1 4.5 1.9 nausea/vomiting 9.9 1.1 12.7 9.5 musculoskeletal musculoskeletal aches/pains 5.6 3.2 5.1 2.5 neurological incoordination 4.9 0 1.9 0 paresthesia 1.4 0 0 tremors 2.8 1.1 5.1 3.8 sexual function decreased libido 1.1 1.3 other decreased appetite 3.5 5.3 0 eyes red/tired/itching 2.8 0 0 0 head full-heavy 2.8 0 0 0 malaise 2.8 0 0 0 nasal/sinus congestion 2.8 0 5.7 3.2 nightmares/vivid dreams 1.1 5.1 5.7 sweating/clamminess 1.4 1.1 tinnitus 1.4 0 0 weight gain 1.4 0 4.5 1.9 weight loss 3.2 5.7 2.5 occasional sinus bradycardia has occurred in long-term studies. in addition to the relatively common (i.e., greater than 1%) untoward events enumerated above, the following adverse events have been reported to occur in association with the use of trazodone hydrochloride in the controlled clinical studies: akathisia, allergic reaction, anemia, chest pain, delayed urine flow, early menses, flatulence, hallucinations/delusions, hematuria, hyper-salivation, hypomania, impaired speech, impotence, increased appetite, increased libido, increased urinary frequency, missed periods, muscle twitches, numbness, and retrograde ejaculation. 6.2 postmarketing experience spontaneous reports regarding trazodone hydrochloride received from postmarketing experience include the following: abnormal dreams, agitation, alopecia, anxiety, aphasia, apnea, ataxia, breast enlargement or engorgement, cardiospasm, cerebrovascular accident, chills, cholestasis, clitorism, congestive heart failure, diplopia, edema, extrapyramidal symptoms, grand mal seizures, hallucinations, hemolytic anemia, hirsutism, hyperbilirubinemia, increased amylase, increased salivation, insomnia, leukocytosis, leukonychia, jaundice, lactation, liver enzyme alterations, methemoglobinemia, nausea/vomiting (most frequently), paresthesia, paranoid reaction, priapism [see warnings and precautions ( 5.9 ) and patient counseling information ( 17.1 )] , pruritus, psoriasis, psychosis, rash, stupor, inappropriate adh syndrome, tardive dyskinesia, unexplained death, urinary incontinence, urinary retention, urticaria, vasodilation, vertigo, and weakness. cardiovascular system effects which have been reported include the following: conduction block, orthostatic hypotension and syncope, palpitations, bradycardia, atrial fibrillation, myocardial infarction, cardiac arrest, arrhythmia, ventricular ectopic activity, including ventricular tachycardia and qt prolongation. in postmarketing surveillance, prolonged qt interval, torsade de pointes, and ventricular tachycardia have been reported with the immediate-release form of trazodone at doses of 100 mg per day or less [see warnings and precautions ( 5.4 )] .

tial increases in trazodone plasma concentrations with the potential for adverse effects. if trazodone is used with a potent cyp3a4 inhibitor, the risk of cardiac arrhythmia may be increased [see warnings andprecautions ( 5.4 )] and a lower dose of trazodone should be considered. cytochrome p450 inducers (e.g., carbamazepine) carbamazepine induces cyp3a4. following coadministration of carbamazepine 400 mg per day with trazodone 100 mg to 300 mg daily, carbamazepine reduced plasma concentrations of trazodone and m-chlorophenlypiperazine (an active metabolite) by 76% and 60% respectively, compared to pre-carbamazepine values. patients should be closely monitored to see if there is a need for an increased dose of trazodone when taking both drugs. digoxin and phenytoin increased serum digoxin or phenytoin levels have been reported in patients receiving trazodone concurrently with either of these drugs. monitor serum levels and adjust dosages as needed. serotonergic drugs based on the mechanism of action of trazodone and the potential for serotonin syndrome, caution is advised when trazodone is coadministered with other drugs that may affect the neurotransmitter systems [ see warnings and precautions ( 5.2 ) ]. nsaids, aspirin, or other drugs affecting coagulation or bleeding due to a possible association between serotonin modulating drugs and gastrointestinal bleeding, patients should be monitored for and cautioned about the potential risk of bleeding associated with the concomitant use of trazodone and nsaids, aspirin, or other drugs that affect coagulation or bleeding [s eewarnings and precautions ( 5.7 ) ]. warfarin there have been reports of altered (either increased or decreased) prothrombin times in taking both warfarin and trazodone. • cns depressants: trazodone may enhance effects of alcohol, barbiturates, or other cns depressants ( 7 ). • cyp3a4 inhibitors: may necessitate lower dose of trazodone hydrochloride tablets ( 7 ). • cyp3a4 inducers (e.g., carbamazepine): may necessitate higher dose of trazodone hydrochloride tablets ( 7 ). • digoxin or phenytoin: monitor for increased serum levels ( 7 ). • warfarin: monitor for increased or decreased prothrombin time ( 7 ).

have been found in the milk of lactating rats, suggesting that the drug may be secreted in human milk. caution should be exercised when trazodone is administered to a nursing woman. 8.4 pediatric use safety and effectiveness in the pediatric population have not been established [ see boxed warning and warnings and precautions ( 5.1 ) ]. trazodone hydrochloride should not be used in children or adolescents. 8.5 geriatric use reported clinical literature and experience with trazodone has not identified differences in responses between elderly and younger patients. however, as experience in the elderly with trazodone hydrochloride is limited, it should be used with caution in geriatric patients. antidepressants have been associated with cases of clinically significant hyponatremia in elderly patients who may be at greater risk for this adverse reaction [ see warnings and precautions ( 5.10 ) ]. 8.6 renal impairment trazodone has not been studied in patients with renal impairment. trazodone should be used with caution in this population. 8.7 hepatic impairment trazodone has not been studied in patients with hepatic impairment. trazodone should be used with caution in this population.

mum concentration. peak plasma levels occur approximately one hour after dosing when trazodone hydrochloride is taken on an empty stomach or 2 hours after dosing when taken with food. metabolism in vitro studies in human liver microsomes show that trazodone is metabolized, via oxidative cleavage, to an active metabolite, m-chlorophenylpiperazine (mcpp) by cyp3a4. other metabolic pathways that may be involved in the metabolism of trazodone have not been well characterized. trazodone is extensively metabolized; less than 1% of an oral dose is excreted unchanged in the urine. elimination in some patients trazodone may accumulate in the plasma protein binding trazodone is 89 to 95% protein bound in vitro at concentrations attained with therapeutic doses in humans.

lasma protein binding trazodone is 89 to 95% protein bound in vitro at concentrations attained with therapeutic doses in humans.

ressure, and hyperthermia), neuromuscular aberrations (e.g., hyperreflexia, incoordination) and/or gastrointestinal symptoms (e.g., nausea, vomiting, and diarrhea). • trazodone hydrochloride has been associated with the occurrence of priapism. • there is a potential for hypotension, including orthostatic hypotension and syncope. • there is a potential risk of bleeding (including life-threatening hemorrhages) and bleeding related events (including ecchymosis, hematoma, epistaxis, and petechiae) with the concomitant use of trazodone hydrochloride and nsaids, aspirin, or other drugs that affect coagulation or bleeding. • withdrawal symptoms including anxiety, agitation and sleep disturbances, have been reported with trazodone. clinical experience suggests that the dose should be gradually reduced. patients should be counseled that: • trazodone may cause somnolence or sedation and may impair the mental and/or physical ability required for the performance of potentially hazardous tasks. patients should be cautioned about operating hazardous machinery, including automobiles until they are reasonably certain that the drug treatment does not affect them. • trazodone may enhance the response to alcohol, barbiturates, and other cns depressants. • women who intend to become pregnant or who are breastfeeding should discuss with a physician whether they should continue to use trazodone, since use in pregnant and nursing women is not recommended. important administration instructions: • trazodone hydrochloride tablets should be swallowed whole or broken in half along the score line. • trazodone hydrochloride tablets should be taken shortly after a meal or light snack. manufactured in croatia by: pliva hrvatska d.o.o. zagreb, croatia manufactured for: teva pharmaceuticals usa sellersville, pa 18960 rev. d 1/2014 repackaged by: proficient rx lp thousand oaks, ca 91320