DRUGS & SUPPLEMENTS
WARNING: SUICIDALITY AND ANTIDEPRESSANT DRUGS
Antidepressants increased the risk compared to placebo of suicidal thinking and behavior (suicidality) in children, adolescents, and young adults in short-term studies of major depressive disorder (MDD) and other psychiatric disorders. Anyone considering the use of Trazodone tablets or any other antidepressant in a child, adolescent, or young adult must balance this risk with the clinical need. 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 in risk with antidepressants compared to placebo in adults aged 65 and older. Depression and certain other psychiatric disorders are themselves associated with increases in the risk of suicide. Patients of all ages who are started on antidepressant therapy should be monitored appropriately and observed closely for clinical worsening, suicidality, or unusual changes in behavior. Families and caregivers should be advised of the need for close observation and communication with the prescriber. Trazodone tablets are not approved for use in pediatric patients .
WARNING: SUICIDALITY AND ANTIDEPRESSANT DRUGS
See full prescribing information for complete boxed warning.
Increased risk of suicidal thinking and behavior in children, adolescents and young adults taking antidepressants for major depressive disorder (MDD) and other psychiatric disorders. Trazodone is not approved for use in pediatric patients (5.1).
1 INDICATIONS AND USAGE
Trazodone tablets are indicated for the treatment of major depressive disorder (MDD) in adults. The efficacy of Trazodone tablets has been established in trials with the immediate release formulation of trazodone .
Trazodone tablets are indicated for the treatment of major depressive disorder (1).
2 DOSAGE AND ADMINISTRATION
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. Trazodone tablets should be taken shortly after a meal or light snack.
An initial dose of 150 mg/day in divided doses is suggested. 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.
The efficacy of Trazodone 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 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 tablets are scored to provide flexibility in dosing.
Trazodone tablets can be swallowed whole or administered as a half tablet by breaking the tablet along the score line.
3 DOSAGE FORMS AND STRENGTHS
Trazodone Tablets USP are available in the following strength:
300 mg: White, oval, flat-faced, beveled-edge tablet with one side scored with a full bisect and having two partial trisects. Debossed with stylized barr/733 on one side and 100 100 100 on the other side with the middle 100 perpendicular to the others.
Bisectable tablet of 300 mg (3).
5 WARNINGS AND PRECAUTIONS
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.
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 -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 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 tablets should not be used within 14 days of an MAOI .
If concomitant treatment with Trazodone 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 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 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 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/QTc interval. Some drugs that prolong the QT/QTc 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/QTc prolongations may also increase risk, especially in susceptible individuals, such as those with hypokalemia, hypomagnesemia, or a genetic predisposition to prolonged QT/QTc.
Although torsade de pointes has not been observed with the use of Trazodone 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 is not recommended for use during the initial recovery phase of myocardial infarction.
Caution should be used when administering Trazodone tablets to patients with cardiac disease and such patients should be closely monitored, since antidepressant drugs may cause cardiac arrhythmias.
QT prolongation has been reported with trazodone therapy . Clinical studies in patients with preexisting cardiac disease indicate that Trazodone 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. 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 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 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 tablets before starting an MAOI.
Rare cases of priapism 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 .
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).
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 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 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 Angle-Closure Glaucoma
The pupillary dilation that occurs following use of many antidepressant drugs including Trazodone may trigger an angle closure attack in a patient with anatomically narrow angles who does not have a patent iridectomy.
5.13 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.
6 ADVERSE REACTIONS
The following serious adverse reactions are described elsewhere in the labeling:
The most common adverse reactions (reported in ≥ 5% and at twice the rate of placebo) are:
Somnolence/sedation, dizziness, constipation, vision blurred.
Table 2 presents the summary of adverse events (AEs) leading to discontinuation of Trazodone tablets treatment with an incidence of at least 1% and at least twice that for placebo.
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.safetyTrazodonetevapharm.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.
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.
*Incidence less than 1%
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 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 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 , 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 .
7 DRUG INTERACTIONS
MAOIs should not be used within 14 days of trazodone .
Central Nervous System (CNS) Depressants
Trazodone may enhance the response to alcohol, barbiturates, and other CNS depressants.
Cytochrome P450 3A4 Inhibitors
In vitro drug metabolism studies suggest that there is a potential for drug interactions when trazodone is given with cytochrome P450 3A4 (CYP3A4) inhibitors. The effect of short-term administration of ritonavir (200 mg twice daily, 4 doses) on the pharmacokinetics of a single dose of trazodone (50 mg) has been studied in 10 healthy subjects. The Cmax of trazodone increased by 34%, the AUC increased 2.4 fold, the half-life increased by 2.2 fold, and the clearance decreased by 52%. Adverse effects including nausea, hypotension, and syncope were observed when ritonavir and trazodone were coadministered. It is likely that ketoconazole, indinavir, and other CYP3A4 inhibitors such as itraconazole may lead to substantial 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 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.
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 [see Warnings and Precautions (5.7)].
There have been reports of altered (either increased or decreased) prothrombin times in taking both warfarin and trazodone.
8 USE IN SPECIFIC POPULATIONS
Pregnancy Category C
Trazodone has been shown to cause increased fetal resorption and other adverse effects on the fetus in two studies using the rat when given at dose levels approximately 30 to 50 times the proposed maximum human dose. There was also an increase in congenital anomalies in one of three rabbit studies at approximately 15 to 50 times the maximum human dose. There are no adequate and well-controlled studies in pregnant women. Trazodone should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
8.3 Nursing Mothers
Trazodone and/or its metabolites 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 ]. Trazodone 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 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.
9 DRUG ABUSE AND DEPENDENCE
9.1 Controlled Substance
Trazodone tablets are not a controlled substance.
Although Trazodone has not been systematically studied in preclinical or clinical studies for its potential for abuse, no indication of drug-seeking behavior was seen in the clinical studies with Trazodone. However, it is difficult to predict the extent to which a CNS-active drug will be misused, diverted, and abused. Consequently, physicians should carefully evaluate patients for a history of drug abuse and follow such patients closely, observing them for signs of misuse or abuse of Trazodone (e.g., development of tolerance, incrementation of dose, drug-seeking behavior).
10.1 Human Experience
Death from overdose has occurred in patients ingesting trazodone and other CNS depressant drugs concurrently.
The most severe reactions reported to have occurred with overdose of trazodone alone have been priapism, respiratory arrest, seizures, and ECG changes, including QT prolongation. The reactions reported most frequently have been drowsiness and vomiting. Overdosage may cause an increase in incidence or severity of any of the reported adverse reactions.
10.2 Management of Overdose
There is no specific antidote for Trazodone overdose.
Treatment should consist of those general measures employed in the management of overdosage with any drug effective in the treatment of major depressive disorder.
Ensure an adequate airway, oxygenation and ventilation. Monitor cardiac rhythm and vital signs.
General supportive and symptomatic measures are also recommended. Induction of emesis is not recommended. Gastric lavage with a large bore orogastric tube with appropriate airway protection, if needed, may be indicated if performed soon after ingestion, or in symptomatic patients. Activated charcoal should be administered. Forced diuresis may be useful in facilitating elimination of the drug.
In managing overdosage, consider the possibility of multiple drug involvement. The physician should consider contacting a poison control center for additional information on the treatment of any overdose.
Trazodone, USP is an antidepressant chemically unrelated to tricyclic, tetracyclic, or other known antidepressant agents. Trazodone, USP is a triazolopyridine derivative designated as 2-[3-[4-(3-chlorophenyl)-1-piperazinyl]propyl]-1,2,4-triazolo[4, 3-a]pyridin-3(2H)-one hydrochloride. It is a white, odorless crystalline powder which is freely soluble in water. The structural formula is represented as follows:
C19H22ClN5O - HCl M. W. 408.33
Each tablet, for oral administration, contains 300 mg of Trazodone, USP. In addition, each tablet contains the following inactive ingredients: colloidal silicon dioxide, magnesium stearate, microcrystalline cellulose, pregelatinized corn starch, sodium lauryl sulfate and sodium starch glycolate.
12 CLINICAL PHARMACOLOGY
12.1 Mechanism of Action
The mechanism of trazodone’s antidepressant action is not fully understood, but is thought to be related to its potentiation of serotonergic activity in the CNS.
Preclinical studies have shown that trazodone selectively inhibits neuronal reuptake of serotonin and acts as an antagonist at 5-HT-2A/2C serotonin receptors.
Trazodone is not a monoamine oxidase inhibitor and, unlike amphetamine-type drugs, does not stimulate the central nervous system.
Trazodone antagonizes alpha 1-adrenergic receptors, a property which may be associated with postural hypotension.
In humans, Trazodone is well absorbed after oral administration without selective localization in any tissue. When Trazodone is taken shortly after ingestion of food, there may be an increase in the amount of drug absorbed, a decrease in maximum concentration and a lengthening in the time to maximum concentration. Peak plasma levels occur approximately one hour after dosing when Trazodone is taken on an empty stomach or 2 hours after dosing when taken with food.
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.
In some patients trazodone may accumulate in the plasma.
Trazodone is 89 to 95% protein bound in vitro at concentrations attained with therapeutic doses in humans.
13 NONCLINICAL TOXICOLOGY
13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility
No drug- or dose-related occurrence of carcinogenesis was evident in rats receiving trazodone in daily oral doses up to 300 mg/kg for 18 months.
14 CLINICAL STUDIES
The efficacy and safety of Trazodone was established from both inpatient and outpatient trials of the trazodone immediate release formulation in the treatment of major depressive disorder.
16 HOW SUPPLIED/STORAGE AND HANDLING
Trazodone Tablets USP are available as follows:
300 mg: White, oval, flat-faced, beveled-edge tablet with one side scored with a full bisect and having two partial trisects. Debossed with stylized barr/733 on one side and 100 100 100 on the other side with the middle 100 perpendicular to the others. Available in bottles of 100 tablets (0555-0733-02).
Directions for using the correct score when breaking the tablet, please refer to the following:
-For 100 mg, break the score on either the left or right side of the tablet (one-third of a tablet).
-For 150 mg, break the score down the middle of the tablet (one-half of a tablet).
-For 200 mg, break the score on either the left or right side of the tablet (two-thirds of a tablet).
-For 300 mg, use the entire tablet.
Store at 20° to 25°C (68° to 77°F).
Dispense in a tight, light-resistant container as defined in the USP, with a child-resistant closure (as required).
KEEP THIS AND ALL MEDICATIONS OUT OF THE REACH OF CHILDREN.
17 PATIENT COUNSELING INFORMATION
See FDA-approved Medication Guide
17.1 Information for Patients
Prescribers or other health professionals should inform patients, their families, and their caregivers about the benefits and risks associated with treatment with Trazodone and should counsel them in its appropriate use.
Patients should be warned that:
Patients should be counseled that:
Important Administration Instructions:
TEVA PHARMACEUTICALS USA, INC.
North Wales, PA 19454
Rev. E 3/2016
Trazodone (traz' oh done hye'' droe klor' ide) Tablets USP
Read the Medication Guide that comes with Trazodone tablets before you start taking it and each time you get a refill. There may be new information. This information does not take the place of talking to your healthcare provider about your medical condition or treatment. Talk to your healthcare provider or pharmacist if there is something you do not understand or you want to learn about Trazodone tablets.
What is the most important information I should know about Trazodone tablets?
Antidepressant medicines, depression or other serious mental illnesses, and suicidal thoughts or actions: Talk to your healthcare provider about:
4. Visual problems:
Only some people are at risk for these problems. You may want to undergo an eye examination to see if you are at risk and receive preventative treatment if you are.
5. What else do I need to know about antidepressant medicines?
Never stop an antidepressant medicine without first talking to a healthcare provider. Stopping an antidepressant medicine suddenly can cause other symptoms.
Antidepressants are medicines used to treat depression and other illnesses. It is important to discuss all the risks of treating depression and also the risks of not treating it. You should discuss all treatment choices with your healthcare provider, not just the use of antidepressants.
Antidepressant medicines have other side effects. Talk to your healthcare provider about the side effects of your medicines.
Antidepressant medicines can interact with other medicines. Know all of the medicines that you take. Keep a list of all medicines to show your healthcare provider. Do not start new medicines without first checking with your healthcare provider.
6. Trazodone tablets are not approved for use in children. Talk to your healthcare provider for more information.
What are Trazodone tablets?
Trazodone tablets are a prescription medicine used to treat major depressive disorder in adults.
What should I tell my healthcare provider before taking Trazodone tablets?
Before you take Trazodone tablets tell your healthcare provider if you:
Tell your healthcare provider about all the medicines you take, including prescription and non-prescription medicines, vitamins, and herbal supplements.
Using Trazodone tablets with certain other medicines can affect each other causing serious side effects.
Know the medicines you take. Keep a list of them and show it to your healthcare provider and pharmacist when you get a new medicine.
How should I take Trazodone tablets?
What should I avoid while taking Trazodone tablets?
What are the possible side effects of Trazodone tablets?
Trazodone tablets can cause serious side effects or death. See “What is the most important information I should know about Trazodone tablets?”
Serious side effects include:
Get medical help right away, if you have any of the symptoms listed above.
The most common side effects of Trazodone tablets include:
Tell your healthcare provider if you have any side effect that bothers you or that does not go away.
These are not all the possible side effects of Trazodone tablets. For more information, ask your healthcare provider or pharmacist.
Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.
How should I store Trazodone tablets?
Keep Trazodone tablets and all medicines out of the reach of children.
General information about the safe and effective use of Trazodone tablets.
Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not use Trazodone tablets for a condition for which it was not prescribed. Do not give Trazodone tablets to other people, even if they have the same symptoms that you have. It may harm them.
This Medication Guide summarizes the most important information about Trazodone tablets. If you would like more information, talk with your healthcare provider. You can ask your pharmacist or healthcare provider for information about Trazodone tablets that is written for health professionals.
For more information, call 1-888-838-2872.
What are the ingredients in Trazodone tablets?
Active ingredient: Trazodone
Inactive ingredients: colloidal silicon dioxide, magnesium stearate, microcrystalline cellulose, pregelatinized corn starch, sodium lauryl sulfate and sodium starch glycolate.
This Medication Guide has been approved by the U.S. Food and Drug Administration.
TEVA PHARMACEUTICALS USA, INC.
North Wales, PA 19454
Rev. D 3/2016
PHARMACIST: Dispense the accompanying
Medication Guide to each patient.
Trazodone pharmaceutical active ingredients containing related brand and generic drugs:
Active ingredient is the part of the drug or medicine which is biologically active. This portion of the drug is responsible for the main action of the drug which is intended to cure or reduce the symptom or disease. The other portions of the drug which are inactive are called excipients; there role is to act as vehicle or binder. In contrast to active ingredient, the inactive ingredient's role is not significant in the cure or treatment of the disease. There can be one or more active ingredients in a drug.
Trazodone available forms, composition, doses:
Form of the medicine is the form in which the medicine is marketed in the market, for example, a medicine X can be in the form of capsule or the form of chewable tablet or the form of tablet. Sometimes same medicine can be available as injection form. Each medicine cannot be in all forms but can be marketed in 1, 2, or 3 forms which the pharmaceutical company decided based on various background research results.
Composition is the list of ingredients which combinedly form a medicine. Both active ingredients and inactive ingredients form the composition. The active ingredient gives the desired therapeutic effect whereas the inactive ingredient helps in making the medicine stable.
Doses are various strengths of the medicine like 10mg, 20mg, 30mg and so on. Each medicine comes in various doses which is decided by the manufacturer, that is, pharmaceutical company. The dose is decided on the severity of the symptom or disease.
Trazodone destination | category:
Destination is defined as the organism to which the drug or medicine is targeted. For most of the drugs what we discuss, human is the drug destination.
Drug category can be defined as major classification of the drug. For example, an antihistaminic or an antipyretic or anti anginal or pain killer, anti-inflammatory or so.
Trazodone Anatomical Therapeutic Chemical codes:
A medicine is classified depending on the organ or system it acts [Anatomical], based on what result it gives on what disease, symptom [Therapeutical], based on chemical composition [Chemical]. It is called as ATC code. The code is based on Active ingredients of the medicine. A medicine can have different codes as sometimes it acts on different organs for different indications. Same way, different brands with same active ingredients and same indications can have same ATC code.
Trazodone pharmaceutical companies:
Pharmaceutical companies are drug manufacturing companies that help in complete development of the drug from the background research to formation, clinical trials, release of the drug into the market and marketing of the drug.
Researchers are the persons who are responsible for the scientific research and is responsible for all the background clinical trials that resulted in the development of the drug.
Frequently asked QuestionsCan i drive or operate heavy machine after consuming Trazodone?
Depending on the reaction of the Trazodone after taken, if you are feeling dizziness, drowsiness or any weakness as a reaction on your body, Then consider Trazodone not safe to drive or operate heavy machine after consumption. Meaning that, do not drive or operate heavy duty machines after taking the capsule if the capsule has a strange reaction on your body like dizziness, drowsiness. As prescribed by a pharmacist, it is dangerous to take alcohol while taking medicines as it exposed patients to drowsiness and health risk. Please take note of such effect most especially when taking Primosa capsule. It's advisable to consult your doctor on time for a proper recommendation and medical consultations.Is Trazodone addictive or habit forming?
Medicines are not designed with the mind of creating an addiction or abuse on the health of the users. Addictive Medicine is categorically called Controlled substances by the government. For instance, Schedule H or X in India and schedule II-V in the US are controlled substances.
Please consult the medicine instruction manual on how to use and ensure it is not a controlled substance.In conclusion, self medication is a killer to your health. Consult your doctor for a proper prescription, recommendation, and guidiance.
ReviewsDrugs.com conducted a study on Trazodone, and the result of the survey is set out below. It is noteworthy that the product of the survey is based on the perception and impressions of the visitors of the website as well as the views of Trazodone consumers. We, as a result of this, advice that you do not base your therapeutic or medical decisions on this result, but rather consult your certified medical experts for their recommendations.
One visitor reported frequency of useHow often in a day do you take the medicine?
Are you taking the Trazodone drug as prescribed by the doctor?
Few medications can be taken Once in a day more than prescribed when the doctor's advice mentions the medicine can be taken according to frequency or severity of symptoms. Most times, be very careful and clear about the number of times you are taking the medication. The report of sDrugs.com website users about the frequency of taking the drug Trazodone is mentioned below.
Two visitors reported dosesWhat is the dose of Trazodone drug you are taking?
According to the survey conducted among sDrugs.com website users, the maximum number of people are using the following dose 101-200mg. Few medications come in only one or two doses. Few are specific for adult dose and child dose. The dose of the medicine given to the patient depends on the severity of the symptom/disease. There can be dose adjustments made by the doctor, based on the progression of the disease. Follow-up is important.
The information was verified by Dr. Arunabha Ray, MD Pharmacology