TRAZODONE HYDROCHLORIDE tablet

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Active ingredient:
TRAZODONE HYDROCHLORIDE (UNII: 6E8ZO8LRNM) (TRAZODONE - UNII:YBK48BXK30)
Available from:
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Administration route:
ORAL
Prescription type:
PRESCRIPTION DRUG
Therapeutic indications:
Trazodone hydrochloride tablets are indicated for the treatment of major depressive disorder (MDD) in adults. Trazodone hydrochloride tablets are contraindicated in: Patients taking, or within 14 days of stopping, monoamine oxidase inhibitors (MAOIs), including MAOIs such as linezolid or intravenous methylene blue, because of an increased risk of serotonin syndrome [see Warnings and Precautions (5.2), Drug Interactions (7.1)]. 8.1 Pregnancy Pregnancy Exposure Registry There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to antidepressants during pregnancy. Healthcare providers are encouraged to register patients by calling the National Pregnancy Registry for Antidepressants at 1-844-405-6185 or visiting online at https://womensmentalhealth.org/clinical-and-research-programs/pregnancyregistry/antidepressants/ Risk Summary Published prospective cohort studies, case series, and case reports over several decades with trazodone hydrochloride tablets use in pregnant women have no
Product summary:
Trazodone Hydrochloride Tablets USP, 50 mg are white to off-white, round-shape, biconvex beveled tablets, bisect on one side and plain on other side. The bisected side of tablet is debossed with '8' on upper side of bisect and '05' on lower side of bisect and are supplied as follows: in bottle of 30 tablets in bottle of 90 tablets in bottle of 100 tablets in bottle of 500 tablets in bottle of 1000 tablets in unit-dose blister cartons of 100 (10 x 10) unit-dose tablets Trazodone Hydrochloride Tablets USP, 100 mg are white to off-white, round-shape, biconvex beveled tablets, bisect on one side and plain on other side. The bisected side of tablet is debossed with '8' on upper side of bisect and '06' on lower side of bisect and are supplied as follows: in bottle of 30 tablets in bottle of 90 tablets in bottle of 100 tablets in bottle of 500 tablets in bottle of 1000 tablets in unit-dose blister cartons of 100 (10 x 10) unit-dose tablets Trazodone Hydrochloride Tablets USP, 150 mg are white to off-white, oval-shape, flat faced beveled tablets having one full bisect and two trisect notches on one side and two trisects on other side. The full bisected side of tablet is debossed with '8' on one side of bisect and '07' on other bisect segments and are supplied as follows: in bottle of 30 tablets in bottle of 90 tablets in bottle of 100 tablets in bottle of 500 tablets in bottle of 1000 tablets in unit-dose blister cartons of 100 (10 x 10) unit-dose tablets Directions for using the correct score when breaking the tablet, please refer to the following: -For 50 mg, break the score on either the left or right side of the tablet (one-third of a tablet). [Trazodone Hydrochloride Tablets USP] -For 75 mg, break the score down the middle of the tablet (one-half of a tablet). [Trazodone Hydrochloride Tablets USP] -For 100 mg, break the score on either the left or right side of the tablet (two-thirds of a tablet). [Trazodone Hydrochloride Tablets USP] -For 150 mg, use the entire tablet. [Trazodone Hydrochloride Tablets USP] Trazodone Hydrochloride Tablets USP, 300 mg are white to off-white, oval-shape, flat faced beveled tablets having one full bisect and two trisect notches on one side and two trisects on other side. The full bisected side of tablet is debossed with '8' on one side of bisect and '08' on other bisect segment and are supplied as follows: in bottle of 30 tablets in bottle of 90 tablets in bottle of 100 tablets in bottle of 500 tablets in bottle of 1000 tablets in unit-dose blister cartons of 100 (10 x 10) unit-dose tablets 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). [Trazodone Hydrochloride Tablets USP] -For 150 mg, break the score down the middle of the tablet (one-half of a tablet). [Trazodone Hydrochloride Tablets USP] -For 200 mg, break the score on either the left or right side of the tablet (two-thirds of a tablet). [Trazodone Hydrochloride Tablets USP] -For 300 mg, use the entire tablet. [Trazodone Hydrochloride Tablets USP] Store at 20° to 25°C (68° to 77°F) [See USP Controlled Room Temperature]. Dispense with a child-resistant closure in a tight, light-resistant container.
Authorization status:
Abbreviated New Drug Application
Authorization number:
61919-631-30, 61919-631-90

TRAZODONE HYDROCHLORIDE- trazodone hydrochloride tablet

Direct_Rx

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TRAZODONE HYDROCHLORIDE

WARNING: SUICIDAL THOUGHTS and BEHAVIORS

Antidepressants increased the risk of suicidal thoughts and behaviors in pediatric and young adult

patients in short-term studies. Closely monitor all antidepressant-treated patients for clinical

worsening, and for emergence of suicidal thoughts and behaviors [see Warnings and Precautions

(5.1)]. Trazodone is not approved for use in pediatric patients [see Use in Specific Populations

(8.4)].

Trazodone hydrochloride tablets are indicated for the treatment of major depressive disorder (MDD) in

adults.

2.1 Dose Selection

An initial dose of 150 mg/day in divided doses is suggested. The dosage should be initiated at a low-

dose and increased gradually, noting the clinical response and any evidence of intolerance. Occurrence

of drowsiness may require the administration of a major portion of the daily dose at bedtime or a

reduction of dosage.

The dose may be increased by 50 mg/day every 3 to 4 days. The maximum dose for outpatients usually

should not exceed 400 mg/day in divided doses. Inpatients (i.e., more severely depressed patients) may

be given up to but not in excess of 600 mg/day in divided doses.

Once an adequate response has been achieved, dosage may be gradually reduced, with subsequent

adjustment depending on therapeutic response.

2.2 Improtant Administration Instructions

Trazodone hydrochloride tablets can be swallowed whole or administered as a half tablet by breaking

the tablet along the score line.

Trazodone hydrochloride tablets should be taken shortly after a meal or light snack.

2.3 Screen for Bipolar Disorder Prior to Starting Trazodone

Prior to initiating treatment with trazodone hydrochloride tablets or another antidepressant, screen

patients for a personal or family history of bipolar disorder, mania, or hypomania [see Warnings and

Precautions (5.7)].

2.4 Switchning to or from Monoamine Oxidase Inhibitor Antidepressant

At least 14 days must elapse between discontinuation of a monoamine oxidase inhibitor (MAOI)

antidepressant and initiation of trazodone hydrochloride tablets. In addition, at least 14 days must elapse

after stopping trazodone hydrochloride tablets before starting an MAOI antidepressant [see

Contraindications (4), Warnings and Precautions (5.2)].

2.5 Dosage Recommendations for Concomitant Use with Strong CYP3A4 Inhibitors or Inducers

Coadministration with Strong CYP3A4 Inhibitors

Consider reducing trazodone dose based on tolerability when trazodone is coadministered with a strong

CYP3A4 inhibitor [see Drug Interactions (7.1)].

Coadministration with Strong CYP3A4 Inducers

Consider increasing trazodone dose based on therapeutic response when trazodone is coadministered

with a strong CYP3A4 inducer [see Drug Interactions (7.1)].

2.6 Discontinuation of Treatment with Trazodone

Adverse reactions may occur upon discontinuation of trazodone [See Warnings and Precautions (5.8)].

Gradually reduce the dosage rather than stopping trazodone abruptly whenever possible.

Trazodone hydrochloride tablets, USP are available in the following strengths:

Trazodone hydrochloride tablets USP, 50 mg are white to off-white, round-shape, biconvex beveled

tablets, bisect on one side and plain on other side. The bisected side oftablet is debossed with '8' on

upper side of bisect and '05' on lower side of bisect.

Trazodone hydrochloride tablets USP, 100 mg are white to off-white, round-shape, biconvex beveled

tablets, bisect on one side and plain on other side. The bisected side of tablet is debossed with '8' on

upper side of bisect and '06' on lower side of bisect.

Trazodone hydrochloride tablets USP, 150 mg are white to off-white, oval-shape, flat faced beveled

tablets having one full bisect and two trisect notches on one side and two trisects on other side. The full

bisected side of tablet is debossed with '8' on one side of bisect and '07' on other bisect segments.

Trazodone hydrochloride tablets USP, 300 mg are white to off-white, oval-shape, flat faced beveled

tablets having one full bisect and two trisect notches on one side and two trisects on other side. The full

bisected side of tablet is debossed with '8' on one side of bisect and '08' on other bisect segment.

Trazodone hydrochloride tablets are contraindicated in:

Patients taking, or within 14 days of stopping, monoamine oxidase inhibitors (MAOIs), including MAOIs

such as linezolid or intravenous methylene blue, because of an increased risk of serotonin syndrome

[see Warnings and Precautions (5.2), Drug Interactions (7.1)].

5.1 Suicidal Thoughts and Behaviors in Pediatric and Young Adult Patients

In pooled analyses of placebo-controlled trials of antidepressant drugs (SSRIs and other antidepressant

classes) that included approximately 77,000 adult patients and over 4,400 pediatric patients, the

incidence of suicidal thoughts and behaviors in pediatric and young adult patients was greater in

antidepressant-treated patients than in placebo-treated patients. The drug-placebo differences in the

number of cases of suicidal thoughts and behaviors per 1,000 patients treated are provided in Table 1.

No suicides occurred in any of the pediatric studies. There were suicides in the adult studies, but the

number was not sufficient to reach any conclusion about antidepressant drug effect on suicide.

Table 1 Risk Differences of the Number of Cases of Suicidal Thoughts or Behaviors in the Pooled

Placebo-Controlled Trials of Antidepressants in Pediatric and Adult Patients

Age Range

(years)

Drug-Placebo Difference in Number of Patients of

Suicidal Thoughts or Behaviors per 1,000 Patients Treated

Increases Compared to Placebo

< 18

14 additional patients

18 to 24

5 additional patients

Decreases Compared to Placebo

25 to 64

1 fewer patient

≥ 65

6 fewer patients

It is unknown whether the risk of suicidal thoughts and behaviors in pediatric and young adult patients

extends to longer-term use, i.e., beyond four months. However, there is substantial evidence from

placebo-controlled maintenance trials in adults with MDD that antidepressants delay the recurrence of

depression.

Monitor all antidepressant-treated patients for clinical worsening and emergence of suicidal thoughts

and behaviors, especially during the initial few months of drug therapy and at times of dosage changes.

Counsel family members or caregivers of patients to monitor for changes in behavior and to alert the

healthcare provider. Consider changing the therapeutic regimen, including possibly discontinuing

trazodone, in patients whose depression is persistently worse, or who are experiencing emergent

suicidal thoughts or behaviors.

5.2 Serotonin Syndrome

Serotonin-norepinephrine reuptake inhibitors (SNRIs) and SSRIs, including trazodone, can precipitate

serotonin syndrome, a potentially life-threatening condition. The risk is increased with concomitant use

of other serotonergic drugs (including triptans, tricyclic antidepressants, fentanyl, lithium, tramadol,

tryptophan, buspirone, and St. John's Wort) and with drugs that impair metabolism of serotonin, i.e.,

MAOIs [see Contraindications (4), Drug Interactions (7.1)]. Serotonin syndrome can also occur when

these drugs are used alone.

Serotonin syndrome signs and symptoms may include mental status changes (e.g., agitation,

hallucinations, delirium, and coma), autonomic instability (e.g., tachycardia, labile blood pressure,

dizziness, diaphoresis, flushing, hyperthermia), neuromuscular symptoms (e.g., tremor, rigidity,

myoclonus, hyperreflexia, incoordination), seizures, and gastrointestinal symptoms (e.g., nausea,

vomiting, diarrhea).

The concomitant use of trazodone with MAOIs is contraindicated. In addition, do not initiate trazodone

in a patient being treated with MAOIs such as linezolid or intravenous methylene blue. No reports

involved the administration of methylene blue by other routes (such as oral tablets or local tissue

injection). If it is necessary to initiate treatment with an MAOI such as linezolid or intravenous

methylene blue in a patient taking trazodone, discontinue trazodone before initiating treatment with the

MAOI [see Contraindications (4), Drug Interactions (7.1)].

Monitor all patients taking trazodone for the emergence of serotonin syndrome. Discontinue treatment

with trazodone and any concomitant serotonergic agents immediately if the above symptoms occur, and

initiate supportive symptomatic treatment. If concomitant use of trazodone with other serotonergic drugs

is clinically warranted, inform patients of the increased risk for serotonin syndrome and monitor for

symptoms.

5.3 Cardiac Arrhythmias

Clinical studies indicate that trazodone hydrochloride may be arrhythmogenic in patients with

preexisting cardiac disease. Arrhythmias identified include isolated PVCs, ventricular couplets,

tachycardia with syncope, and torsade de pointes. Postmarketing events, including torsade de pointes

have been reported at doses of 100 mg or less with the immediate-release form of trazodone.

Trazodone should also be avoided in patients with a history of cardiac arrhythmias, as well as other

circumstances that may increase the risk of the occurrence of torsade de pointes and/or sudden death,

including symptomatic bradycardia, hypokalemia or hypomagnesemia, and the presence of congenital

prolongation of the QT interval. Trazodone is not recommended for use during the initial recovery

phase of myocardial infarction. Caution should be used when administering trazodone to patients with

cardiac disease and such patients should be closely monitored, since antidepressant drugs (including

trazodone) may cause cardiac arrhythmias [see Adverse Reactions (6.2)].

Trazodone prolongs the QT/QTc interval. The use of trazodone should be avoided in patients with

known QT prolongation or in combination with other drugs that are inhibitors of CYP3A4 (e.g.,

itraconazole, clarithromycin, voriconazole), or known to prolong QT interval including Class 1A

antiarrhythmics (e.g., quinidine, procainamide) or Class 3 antiarrhythmics (e.g., amiodarone, sotalol),

certain antipsychotic medications (e.g., ziprasidone, chlorpromazine, thioridazine), and certain

antibiotics (e.g., gatifloxacin). Concomitant administration of drugs may increase the risk of cardiac

arrhythmia [see Drug Interactions (7.1)].

5.4 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.

5.5 Increased Risk of Bleeding

Drugs that interfere with serotonin reuptake inhibition, including trazodone, increase the risk of

bleeding events. Concomitant use of aspirin, nonsteroidal anti-inflammatory drugs (NSAIDS), other

antiplatelet drugs, warfarin, and other anticoagulants may add to this risk. Case reports and

epidemiological studies (case-control and cohort design) have demonstrated an association between use

of drugs that interfere with serotonin reuptake and the occurrence of gastrointestinal bleeding. Bleeding

events related to drugs that interfere with serotonin reuptake have ranged from ecchymosis, hematoma,

epistaxis, and petechiae to life-threatening hemorrhages.

Inform patients about the risk of bleeding associated with the concomitant use of trazodone and

antiplatelet agents or anticoagulants. For patients taking warfarin, carefully monitor coagulation indices

when initiating, titrating, or discontinuing trazodone.

5.6 Priapism

Cases of priapism (painful erections greater than 6 hours in duration) have been 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 4 hours, whether painful or not, should

immediately discontinue the drug and seek emergency medical attention [see Adverse Reactions (6.2),

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).

5.7 Activation of Mania or Hypomania

In patients with bipolar disorder, treating a depressive episode with trazodone or another antidepressant

may precipitate a mixed/manic episode. Activation of mania/hypomania has been reported in a small

proportion of patients with major affective disorder who were treated with antidepressants. Prior to

initiating treatment with trazodone, screen patients for any personal or family history of bipolar

disorder, mania, or hypomania [see Dosage and Administration (2.3)].

5.8 Discontinuation Syndrome

Adverse reactions after discontinuation of serotonergic antidepressants, particularly after abrupt

discontinuation, include: nausea, sweating, dysphoric mood, irritability, agitation, dizziness, sensory

disturbances (e.g., paresthesia, such as electric shock sensations), tremor, anxiety, confusion, headache,

lethargy, emotional lability, insomnia, hypomania, tinnitus, and seizures. A gradual reduction in dosage

rather than abrupt cessation is recommended whenever possible [See Dosage and Administration (2.6)].

5.9 Potential for Cognitive and Motor Impairment

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 adversely.

5.10 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. Avoid use of antidepressants, including trazodone, in patients with untreated anatomically

narrow angles.

5.11 Hyponatremia

Hyponatremia may occur as a result of treatment with SNRIs and SSRIs, including trazodone. Cases with

serum sodium lower than 110 mmol/L have been reported. 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. In many cases, this hyponatremia

appears to be the result of the syndrome of inappropriate antidiuretic hormone secretion (SIADH).

In patients with symptomatic hyponatremia, discontinue trazodone and institute appropriate medical

intervention. Elderly patients, patients taking diuretics, and those who are volume-depleted may be at

greater risk of developing hyponatremia with SSRIs and SNRIs [see Use in Specific Populations (8.5)].

The following serious adverse reactions are described elsewhere in the labeling:

Suicidal Thoughts and Behavior in Children, Adolescents and Young Adults [see Boxed Warning and

Warnings and Precautions (5.1)]

Serotonin Syndrome [see Warnings and Precautions (5.2)]

Cardiac Arrythmias (see Warnings and Precautions (5.3)]

Orthostatic Hypotension and Syncope [see Warnings and Precautions (5.4)]

Increased Risk of Bleeding [see Warnings and Precautions (5.5)]

Priapism [see Warnings and Precautions (5.6)]

Activation of Mania or Hypomania [see Warnings and Precautions (5.7)]

Discontinuation Syndrome [see Warnings and Precautions (5.8)]

Potential for Cognitive and Motor Impairment [see Warnings and Precautions (5.9)]

Angle-Closure Glaucoma [see Warnings and Precautions (5.10)]

Hyponatremia [see Warnings and Precautions (5.11)]

6.1 Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed

in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug

and may not reflect the rates observed in practice.

Table 2 Common Adverse Reactions Occurring in ≥ 2% of Trazodone-treated Patients and Greater than

the Rate of Placebo-Treated Patients as Observed in Controlled Clinical Studies

Inpatients

Outpatients

Trazodone

Placebo

Trazodone

Placebo

Allergic

Skin Condition/Edema

Autonomic

Blurred Vision

Constipation

Dry Mouth

Cardiovascular

Hypertension

Hypotension

Syncope

Confusion

Decreased Concentration

Disorientation

Dizziness/Light-Headedness

Drowsiness

Fatigue

Headache

Nervousness

Gastrointestinal

Abdominal/Gastric Disorder

Diarrhea

Nausea/Vomiting

Musculoskeletal

Aches/Pains

Neurological

Incoordination

Tremors

Other

Eyes Red/Tired/Itching

Head Full-Heavy

Malaise

Nasal/Sinus Congestion

Weight Gain

Weight Loss

Other adverse reactions occurring at an incidence of <2% 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, hypersalivation, hypomania, impaired memory,

impaired speech, impotence, increased appetite, increased libido, increased urinary frequency, missed

periods, muscle twitches, numbness, paresthesia, retrograde ejaculation, shortness of breath, and

tachycardia/palpitations. Occasional sinus bradycardia has occurred in long-term studies.

6.2 Postmarketing Experience

The following adverse reactions have been identified during post-approval use of trazodone. Because

these reactions are reported voluntarily from a population of uncertain size, it is not always possible to

estimate their frequency or establish a causal relationship to drug exposure:

Blood and lymphatic system disorders: hemolytic anemia, leukocytosis

Cardiac disorders: cardiospasm, congestive heart failure, conduction block, orthostatic hypotension and

syncope, palpitations, bradycardia, atrial fibrillation, myocardial infarction, cardiac arrest, arrhythmia,

ventricular ectopic activity, including ventricular tachycardia and QT prolongation. Prolonged QT

interval, torsade de pointes, and ventricular tachycardia have been reported at doses of 100 mg per day

or less [see Warnings and Precautions (5.3)].

Endocrine disorders: inappropriate ADH syndrome

Eye disorders: diplopia

Gastrointestinal disorders: increased salivation, nausea/vomiting

General disorders and administration site conditions: chills, edema, unexplained death, weakness

Hepatobiliary disorders: cholestasis, jaundice, hyperbilirubinemia, liver enzyme alterations

Investigations: increased amylase

Metabolism and nutrition disorders: methemoglobinemia

Nervous system disorders: aphasia, ataxia, cerebrovascular accident, extrapyramidal symptoms, grand

mal seizures, paresthesia, tardive dyskinesia, vertigo

Psychiatric disorders: abnormal dreams, agitation, anxiety, hallucinations, insomnia, paranoid reaction,

psychosis, stupor

Renal and urinary disorders: urinary incontinence, urinary retention

Reproductive system and breast disorders: breast enlargement or engorgement, clitorism, lactation,

priapism [see Warnings and Precautions (5.6)]

Respiratory, thoracic and mediastinal disorders: apnea

Skin and subcutaneous tissue disorders: alopecia, hirsutism, leukonychia, pruritus, psoriasis, rash,

urticaria

Vascular disorders: vasodilation

MAOIs

MAOIs should not be used within 14 days of trazodone [see Warnings and Precautions (5.8)].

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 [see Warnings and Precautions (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

[see Warnings and Precautions (5.7)].

Warfarin

There have been reports of altered (either increased or decreased) prothrombin times in taking both

warfarin and trazodone.

7.1 Drugs Having Clinically Important Interactions with Trazodone

Table 3 Clinically Important Drug Interactions with Trazodone

Monoamine Oxidase Inhibitors (MAOIs)

Clinical Impact:

The concomitant use of MAOIs and serotonergic drugs including trazodone increases the risk of

serotonin syndrome.

Intervention:

Trazodone is contraindicated in patients taking MAOIs, including MAOIs such as linezolid or

intravenous methylene blue [see Contraindications (4), Dosage and Administration (2.3, 2.4), and

Warnings and Precautions (5.2)].

Examples:

isocarboxazid, moclobemide, phenelzine, selegiline, tranylcypromine

Other Serotonergic Drugs

Clinical Impact:

The concomitant use of serotonergic drugs including trazodone and other serotonergic drugs increases

the risk of serotonin syndrome.

Intervention:

Monitor patients for signs and symptoms of serotonin syndrome, particularly during trazodone initiation.

If serotonin syndrome occurs, consider discontinuation of trazodone and/or concomitant serotonergic

drugs [see Warnings and Precautions (5.2)].

Examples:

triptans, antidepressants (tricyclic and serotonin uptake inhibitors), fentanyl, lithium, tramadol,

tryptophan, buspirone, and St. John's Wort

Antiplatelet Agents and Anticoagulants

Clinical Impact:

Serotonin release by platelets plays an important role in hemostasis. The concurrent use of an

antiplatelet agent or anticoagulant with trazodone may potentiate the risk of bleeding.

Intervention:

Inform patients of the increased risk of bleeding with the concomitant use of trazodone and antiplatelet

agents and anticoagulants. For patients taking warfarin, carefully monitor the international normalized

ratio (INR) when initiating or discontinuing trazodone [see Warnings and Precautions (5.5)].

Examples:

warfarin, rivaroxaban, dabigatran, clopidogrel

Strong CYP3A4 Inhibitors

Clinical Impact:

The concomitant use of trazodone and strong CYP3A4 inhibitors increased the exposure of trazodone

compared to the use of trazodone alone.

Intervention:

If trazodone is used with a potent CYP3A4 inhibitor, the risk of adverse reactions, including cardiac

arrhythmias, may be increased and a lower dose of trazodone should be considered [see Dosage and

Administration (2.5), Warnings and Precautions (5.3)].

Examples:

itraconazole, ketoconazole, clarithromycin, indinavir

Strong CYP3A4 Inducers

Clinical Impact:

The concomitant use of trazodone and strong CYP3A4 inducers decreased the exposure of trazodone

compared to the use of trazodone alone.

Intervention:

Patients should be closely monitored to see if there is a need for an increased dose of trazodone when

taking CYP3A4 inducers [see Dosage and Administration (2.5)].

Examples:

rifampin, carbamazepine, phenytoin, St. John's wort

Digoxin and Phenytoin

Clinical Impact:

Digoxin and phenytoin are narrow therapeutic index drugs. Concomitant use of trazodone can increase

digoxin or phenytoin concentrations.

Intervention:

Measure serum digoxin or phenytoin concentrations before initiating concomitant use of trazodone.

Continue monitoring and reduce digoxin or phenytoin dose as necessary.

Examples:

digoxin, phenytoin

Central Nervous System (CNS) Depressants

Clinical Impact:

Trazodone may enhance the response CNS depressants.

Intervention:

Patients should be counseled that trazodone may enhance the response to alcohol, barbiturates, and other

CNS depressants.

Examples:

alcohol, barbiturates

QT Interval Prolongation

Clinical Impact:

Concomitant use of drugs that prolong the QT interval may add to the QT effects of trazodone and

increase the risk of cardiac arrhythmia.

Intervention:

Avoid the use of trazodone in combination with other drugs known to prolong QTc [see Warnings and

Precautions (5.3)] .

Examples:

Class 1A antiarrhythmics: quinidine, procainamide, disopyramide; Class 3 antiarrhythmics: amiodarone,

sotalol;

Antipsychotics: ziprasidone, chlorpromazine, thioridazine; Antibiotics: gatifloxacin

8.1 Pregnancy

Pregnancy Exposure Registry

There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to

antidepressants during pregnancy. Healthcare providers are encouraged to register patients by calling

the National Pregnancy Registry for Antidepressants at 1-844-405-6185 or visiting online at

https://womensmentalhealth.org/clinical-and-research-programs/pregnancyregistry/antidepressants/

Risk Summary

Published prospective cohort studies, case series, and case reports over several decades with

trazodone hydrochloride tablets use in pregnant women have not identified any drug-associated risks of

major birth defects, miscarriage, or adverse maternal or fetal outcomes (see Data). Trazodone

hydrochloride has been shown to cause increased fetal resorption and other adverse effects on the fetus

in the rat when given at dose levels approximately 7.3 to 11 times the maximum recommended human

dose (MRHD) of 400 mg/day in adults on a mg/m2 basis. There was also an increase in congenital

anomalies in the rabbit at approximately 7.3 to 22 times the MRHD on a mg/m2 basis (see Data).

The estimated background risk of major birth defects and miscarriage for the indicated population is

unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In

the U.S. general population, the estimated background risk of major birth defects and miscarriage in

clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively.

Clinical Considerations

Disease-associated maternal and/or embryofetal risk

A prospective, longitudinal study followed 201 pregnant women with a history of major depressive

disorder who were euthymic and taking antidepressants at the beginning of pregnancy. The women who

discontinued antidepressants during pregnancy were more likely to experience a relapse of major

depression that women who continued antidepressants. Consider the risk of untreated depression when

discontinuing or changing treatment with antidepressant medication during pregnancy and postpartum.

Data

Human Data

While available studies cannot definitively establish the absence of risk, published data from

prospective cohort studies, case series, and case reports over several decades have not identified an

association with trazodone use during pregnancy and major birth defects, miscarriage, or other adverse

maternal or fetal outcomes. All available studies have methodological limitations, including small

sample size and inconsistent comparator groups.

Animal Data

No teratogenic effects were observed when trazodone was given to pregnant rats and rabbits during the

period of organogenesis at oral doses up to 450 mg/kg/day. This dose is 11 and 22 times, in rats and

rabbits, respectively, the maximum recommended human dose (MRHD) of 400 mg/day in adults on a

mg/m2 basis. Increased fetal resorption and other adverse effects on the fetus in rats at 7.3 to 11 times

the MRHD and increase in congenital anomalies in rabbits at 7.3 to 22 times the MRHD on a mg/m2 basis

were observed. No further details on these studies are available.

8.2 Lactation

Risk Summary

Data from published literature report the transfer of trazodone into human milk. There are no data on the

effect of trazodone on milk production. Limited data from postmarketing reports have not identified and

association of adverse effects on the breastfed child. The developmental and health benefits of

breastfeeding should be considered along with the mother's clinical need for trazodone hydrochloride

tablets and any potential adverse effects on the breastfed child from trazodone hydrochloride tablets or

from the underlying maternal condition.

8.4 Pediatric Use

Safety and effectiveness in the pediatric population have not been established. Antidepressants

increased the risk of suicidal thoughts and behaviors in pediatric patients [see Boxed Warning,

Warnings and Precautions (5.1)].

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.

Serotonergic 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

(5.11)].

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.

9.1 Controlled Substance

Trazodone hydrochloride tablets are not a controlled substance.

9.2 Abuse

Although trazodone hydrochloride 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 hydrochloride.

Death from overdose has occurred in patients ingesting trazodone and other CNS depressant drugs

concurrently (alcohol; alcohol and chloral hydrate and diazepam; amobarbital; chlordiazepoxide; or

meprobamate).

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.

There is no specific antidote for trazodone hydrochloride overdose. In managing overdosage, consider

the possibility of multiple drug involvement. For current information on the management of poisoning or

overdose, contact a poison control center (1-800-222-1222 or www.poison.org).

Trazodone hydrochloride is a selective serotonin reuptake inhibitor and 5HT2 receptor antagonist.

Trazodone hydrochloride, 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 to off-white,

crystalline powder which is sparingly soluble in chloroform and in water. The structural formula is

represented as follows:

[Trazodone Hydrochloride Tablets USP]

Molecular Formula: C19H22ClN5OHCl

Molecular Weight: 408.33

Each trazodone hydrochloride tablet, USP for oral administration contains 50 mg, 100 mg, 150 mg or

300 mg of trazodone hydrochloride, USP. In addition, each tablet contains the following inactive

ingredients: colloidal silicon dioxide, magnesium stearate, microcrystalline cellulose, pregelatinized

starch, sodium lauryl sulfate, and sodium starch glycolate.

The USP Dissolution Test is pending.

12.1 Mechanism of Action

The mechanism of trazodone's antidepressant action is not fully understood, but is thought to be related

to its enhancement of serotonergic activity in the CNS. Trazodone is both a selective serotonin reuptake

inhibitor (SSRI) and a 5HT2 receptor antagonist and the net result of this action on serotonergic

transmission and its role in trazodone's antidepressant effect is unknown.

12.2 Pharmacodynamics

Preclinical studies have shown that trazodone selectively inhibits neuronal reuptake of serotonin (Ki =

367 nM) and acts as an antagonist at 5-HT-2A (Ki = 35.6 nM) serotonin receptors. Trazodone is also an

antagonist at several other monoaminergic receptors including 5-HT2B (Ki = 78.4 nM), 5-HT2C (Ki =

224 nM), α1A (Ki = 153 nM), α2C (Ki = 155 nM) receptors and it is a partial agonist at 5HT1A (Ki = 118

nM) receptor.

Trazodone antagonizes alpha 1-adrenergic receptors, a property which may be associated with postural

hypotension.

12.3 Pharmacokinetics

Absorption

In humans, trazodone hydrochloride is absorbed after oral administration without selective localization

in any tissue. When trazodone hydrochloride 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 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.

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

Carcinogenesis

No drug- or dose-related occurrence of carcinogenesis was evident in 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/m2basis.

Mutagenesis

No genotoxicity studies were conducted with trazodone.

Impairment of Fertility

Trazodone has no effect on fertility in rats at doses up to 7.3 times the MRHD in adults on a mg/m2

basis.

The efficacy and safety of trazodone hydrochloride were established from inpatient and outpatient trials

of the trazodone immediate release formulation in the treatment of major depressive disorder.

Trazodone Hydrochloride Tablets USP, 50 mg are white to off-white, round-shape, biconvex beveled

tablets, bisect on one side and plain on other side. The bisected side of tablet is debossed with '8' on

upper side of bisect and '05' on lower side of bisect and are supplied as follows:

in bottle of 30 tablets

in bottle of 90 tablets

in bottle of 100 tablets

in bottle of 500 tablets

in bottle of 1000 tablets

in unit-dose blister cartons of 100 (10 x 10) unit-dose tablets

Trazodone Hydrochloride Tablets USP, 100 mg are white to off-white, round-shape, biconvex beveled

tablets, bisect on one side and plain on other side. The bisected side of tablet is debossed with '8' on

upper side of bisect and '06' on lower side of bisect and are supplied as follows:

in bottle of 30 tablets

in bottle of 90 tablets

in bottle of 100 tablets

in bottle of 500 tablets

in bottle of 1000 tablets

in unit-dose blister cartons of 100 (10 x 10) unit-dose tablets

Trazodone Hydrochloride Tablets USP, 150 mg are white to off-white, oval-shape, flat faced beveled

tablets having one full bisect and two trisect notches on one side and two trisects on other side. The full

bisected side of tablet is debossed with '8' on one side of bisect and '07' on other bisect segments and

are supplied as follows:

in bottle of 30 tablets

in bottle of 90 tablets

in bottle of 100 tablets

in bottle of 500 tablets

in bottle of 1000 tablets

in unit-dose blister cartons of 100 (10 x 10) unit-dose tablets

Directions for using the correct score when breaking the tablet, please refer to the

following:

-For 50 mg, break the score on either the left or right side of the tablet (one-third of a

tablet).

[Trazodone Hydrochloride Tablets USP]

-For 75 mg, break the score down the middle of the tablet (one-half of a tablet).

[Trazodone Hydrochloride Tablets USP]

-For 100 mg, break the score on either the left or right side of the tablet (two-thirds of a

tablet).

[Trazodone Hydrochloride Tablets USP]

-For 150 mg, use the entire tablet.

[Trazodone Hydrochloride Tablets USP]

Trazodone Hydrochloride Tablets USP, 300 mg are white to off-white, oval-shape, flat

faced beveled tablets having one full bisect and two trisect notches on one side and two

trisects on other side. The full bisected side of tablet is debossed with '8' on one side of

bisect and '08' on other bisect segment and are supplied as follows:

in bottle of 30 tablets

in bottle of 90 tablets

in bottle of 100 tablets

in bottle of 500 tablets

in bottle of 1000 tablets

in unit-dose blister cartons of 100 (10 x 10) unit-dose tablets

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).

[Trazodone Hydrochloride Tablets USP]

-For 150 mg, break the score down the middle of the tablet (one-half of a tablet).

[Trazodone Hydrochloride Tablets USP]

-For 200 mg, break the score on either the left or right side of the tablet (two-thirds of a

tablet).

[Trazodone Hydrochloride Tablets USP]

-For 300 mg, use the entire tablet.

[Trazodone Hydrochloride Tablets USP]

Store at 20° to 25°C (68° to 77°F) [See USP Controlled Room Temperature].

Dispense with a child-resistant closure in a tight, light-resistant container.

Advise the patient to read the FDA-approved patient labeling (Medication Guide).

Suicidal Thoughts and Behaviors

Advise patients and caregivers to look for the emergence of suicidality, especially early during

treatment and when the dosage is adjusted up or down and instruct them to report such symptoms to the

healthcare provider [see Box Warning and Warnings and Precautions (5.1)].

Dosage and Administration

Advise patients that trazodone hydrochloride tablets should be taken shortly after a meal or light snack.

Advise patients regarding the importance of following dosage titration instructions [see Dosage and

Administration (2)].

Serotonin Syndrome

Caution patients about the risk of serotonin syndrome, particularly with the concomitant use of trazodone

hydrochloride tablets with other serotonergic drugs including triptans, tricyclic antidepressants,

fentanyl, lithium, tramadol, tryptophan, buspirone, St. John's Wort, and with drugs that impair metabolism

of serotonin (in particular, MAOIs, both those intended to treat psychiatric disorders and also others,

such as linezolid). Patients should contact their health care provider or report to the emergency room if

they experience signs or symptoms of serotonin syndrome [see Warnings and Precautions (5.2) and

Drug Interactions (7)].

Activation of Mania/Hypomania

Advise patients and their caregivers to observe for signs of activation of mania/hypomania and instruct

them to report such symptoms to the healthcare provider [see Warnings and Precautions (5.7)].

Increased Risk of Bleeding

Inform patients about the concomitant use of trazodone hydrochloride tablets with aspirin, NSAIDs,

other antiplatelet drugs, warfarin, or other anticoagulants because the combined use of drugs that

interfere with serotonin reuptake and these medications has been associated with an increased risk of

bleeding. Advise them to inform their health care providers if they are taking or planning to take any

prescription or over-the-counter medications that increase the risk of bleeding [see Warnings and

Precautions (5.5)].

Discontinuation Syndrome

Advise patients not to abruptly discontinue trazodone hydrochloride tablets and to discuss any tapering

regimen with their healthcare provider. Adverse reactions can occur when trazodone hydrochloride

tablets are discontinued [see Warnings and Precautions (5.8)].

Concomitant Medications

Advise patients to inform their health care providers if they are taking, or plan to take any prescription

or over-the-counter medications since there is a potential for interactions [see Drug Interactions (7.1)].

Pregnancy

Advise patients to notify their healthcare provider if they become pregnant or intend to become pregnant

during therapy with trazodone hydrochloride tablets. Advise patients that there is a pregnancy exposure

registry that monitors pregnancy outcomes in women exposed to trazodone hydrochloride tablets during

pregnancy [see Use in Special Populations (8.1)].

MEDICATION GUIDE

Trazodone Hydrochloride (traz' oh done hye'' droe klor' ide) Tablets, USP

What is the most important information I should know about trazodone hydrochloride tablets?

Antidepressant medicines, depression or other serious mental illnesses, and suicidal thoughts or

actions: Talk to your healthcare provider about:

All risks and benefits of treatment with antidepressant medicines

All treatment choices for depression or other serious mental illnesses

Antidepressant medicines may increase suicidal thoughts or actions in some children, teenagers, and

young adults within the first few months of treatment.

Depression and other serious mental illnesses are the most important causes of suicidal thoughts and

actions. Some people may have a higher risk of having suicidal thoughts or actions. These include

people who have or have a family history of bipolar illness (also called manic- depressive illness) or

suicidal thoughts or actions.

How can I watch for and try to prevent suicidal thoughts and actions?

Pay close attention to any changes, especially sudden changes in mood, behaviors, thoughts, or

feelings. This is very important when an antidepressant medicine is started or when the dose is changed.

Call your healthcare provider right away to report new or sudden changes in mood, behavior, thoughts

or feelings.

Keep all follow-up visits with your healthcare provider as scheduled. Call your healthcare provider

between visits as needed, especially if you are worried about symptoms.

Call a healthcare provider right away if you have any of the following symptoms, especially if they are

new, worse, or worry you:

Thoughts about suicide or dying

Attempts to commit suicide

New or worse depression

New or worse anxiety

Feeling very agitated or restless

Panic attacks

Trouble sleeping (insomnia)

New or worse irritability

Acting aggressive, being angry or violent

Acting on dangerous impulses

An extreme increase in activity and talking (mania)

Other unusual changes in behavior or mood

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.

It is not known if trazodone hydrochloride tablets are safe and effective in children.

What are trazodone hydrochloride tablets?

Trazodone hydrochloride tablets are prescription medicine used in adults to treat major depressive

disorder (MDD). Trazodone hydrochloride tablets belong to a class of medicines known as SSRIs (or

selective serotonin reuptake inhibitors).

Do not take trazodone hydrochloride tablets:

If you take a monoamine oxidase inhibitor (MAOI). Ask your healthcare provider or pharmacist if you

are not sure if you take an MAOI, including the antibiotic linezolid, and intravenous methylene blue.

Do not take an MAOI within 2 weeks of stopping trazodone hydrochloride tablets unless directed to do

so by your healthcare provider.

Do not start trazodone hydrochloride tablets if you stopped taking an MAOI in the last 2 weeks unless

directed to do so by your healthcare provider.

Before you take trazodone hydrochloride tablets tell your healthcare provider about all of your medical

conditions, including if you:

have heart problems, including QT prolongation or a family history of it

have ever had a heart attack

have bipolar disorder

have liver or kidney problems

have other serious medical conditions

are pregnant or plan to become pregnant. It is not known if trazodone hydrochloride tablets will harm

your unborn baby. Talk to your healthcare provider about the risk to your unborn baby if you take

trazodone hydrochloride tablets.

If you become pregnant during treatment with trazodone hydrochloride tablets, talk to your healthcare

provider about registering with the National Pregnancy Registry for Antidepressants. You can register

by calling 1-844-405-6185.

are breastfeeding or plan to breastfeed. Trazodone hydrochloride passes into your breast milk. Talk to

your healthcare provider about the best way to feed your baby if you take trazodone hydrochloride

tablets.

have taken a Monoamine Oxidase Inhibitor (MAOI) or if you have stopped taking an MAOI in the last 2

weeks.

Tell your healthcare provider about all the medicines you take, including prescription and over-the-

counter medicines, vitamins, and herbal supplements. Using trazodone hydrochloride tablets with certain

other medicines can affect each other causing serious side effects.

Especially tell your healthcare provider if you take:

triptans used to treat migraine headache

medicines used to treat mood, anxiety, psychotic or thought disorders, including tricyclics, lithium,

SSRIs, SNRIs, buspirone, or antipsychotics

tramadol

over-the-counter supplements such as tryptophan or St. John's Wort

nonsteroidal anti-inflammatory drugs (NSAIDS)

aspirin

warfarin (Coumadin, Jantoven)

phenytoin (Mesantoin)

diuretics

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 hydrochloride tablets?

Take trazodone hydrochloride tablets exactly as your healthcare provider tells you.

Trazodone hydrochloride tablets should be taken shortly after a meal or light snack.

If you feel drowsy after taking trazodone hydrochloride tablets, talk to your healthcare provider. Your

healthcare provider may change your dose or the time of day you take your trazodone hydrochloride

tablets.

Do not stop taking trazodone hydrochloride tablets without talking to your healthcare provider.

Trazodone hydrochloride tablets should be swallowed whole or broken in half along the score line. Do

not chew or crush trazodone hydrochloride tablets. Tell your healthcare provider if you cannot

swallow trazodone either whole or as a half tablet.

If you take too much trazodone hydrochloride tablets, call your healthcare provider, your Poison

Control Center at 1-800-222-1222, or go to the nearest emergency room right away.

What should I avoid while taking trazodone hydrochloride tablets?

Do not drive, operate heavy machinery, or do other dangerous activities until you know how trazodone

hydrochloride tablets affect you. Trazodone hydrochloride tablets can slow your thinking and motor

skills.

Do not drink alcohol or take other medicines that make you sleepy or dizzy while taking trazodone

hydrochloride tablets until you talk with your healthcare provider. Trazodone hydrochloride tablets

may make your sleepiness or dizziness worse if you take it with alcohol or other medicines that cause

sleepiness or dizziness.

What are the possible side effects of trazodone hydrochloride tablets?

Trazodone hydrochloride tablets can cause serious side effects or death, including:

See "What is the most important information I should know about Trazodone?"

Serotonin syndrome. Symptoms of serotonin syndrome include: agitation, hallucinations, problems with

coordination, fast heartbeat, tight muscles, trouble walking, sweating, fever, nausea, vomiting, and

diarrhea.

Irregular or fast heartbeat or faint (QT prolongation)

Low blood pressure. You feel dizzy or faint when you change positions (go from sitting to standing)

Unusual bruising or bleeding

Erection lasting for more than 6 hours (priapism)

Feeling high or in a very good mood, then becoming irritable, or having too much energy, feeling like

you have to keep talking or do not sleep (mania ).

Withdrawal symptoms. Symptoms of withdrawal can include anxiety, agitation, and sleep problems. Do

not stop taking trazodone without talking to your healthcare provider.

Visual problems.

eye pain

changes in vision

swelling or redness in or around the eye

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.

Low sodium in your blood (hyponatremia). Symptoms of hyponatremia include: headache, feeling weak,

feeling confused, trouble concentrating, memory problems and feeling unsteady when you walk.

Get medical help right away, if you have any of the symptoms listed above.

The most common side effects of trazodone hydrochloride tablets include:

swelling

blurred vision

dizziness

sleepiness

tiredness

diarrhea

stuffy nose

weight loss

These are not all the possible side effects of trazodone hydrochloride tablets. 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 hydrochloride tablets?

Store trazodone hydrochloride tablets between 20° to 25°C (68° to 77°F).

Keep in tight container

Keep out of the light

Safely throw away medicine that is out of date or no longer needed.

Keep trazodone hydrochloride tablets and all medicines out of the reach of children.

General information about the safe and effective use of trazodone hydrochloride tablets.

Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not

use trazodone hydrochloride tablets for a condition for which it was not prescribed. Do not give

trazodone hydrochloride tablets to other people, even if they have the same symptoms that you have. It

may harm them.

You can ask your pharmacist or healthcare provider for information about trazodone hydrochloride

tablets that is written for health professionals.

Please address medical inquiries to, MedicalAffairs@zydususa.com Tel.: 1-877-993-8779.

What are the ingredients in trazodone hydrochloride tablets?

Active ingredient: trazodone hydrochloride, USP

Inactive ingredients: colloidal silicon dioxide, magnesium stearate, microcrystalline cellulose,

pregelatinized starch, sodium lauryl sulfate, and sodium starch glycolate.

This Medication Guide has been approved by the U.S. Food and Drug Administration.

Manufactured by:

Cadila Healthcare Limited

Ahmedabad, India.

Distributed by:

Zydus Pharmaceuticals (USA) Inc.

Pennington, NJ 08534

Rev.: 11/18

Manufactured by:

Cadila Healthcare Limited

Ahmedabad, India.

Distributed by:

Zydus Pharmaceuticals (USA) Inc.

Pennington, NJ 08534

Rev.: 11/18

TRAZODONE HYDROCHLORIDE

trazodone hydrochloride tablet

Product Information

Product T ype

HUMAN PRESCRIPTION DRUG

Ite m Code (Source )

NDC:6 19 19 -6 31(NDC:6 8 38 2-8 0 6 )

Route of Administration

ORAL

Active Ingredient/Active Moiety

Ingredient Name

Basis of Strength

Stre ng th

TRAZO DO NE HYDRO CHLO RIDE (UNII: 6 E8 ZO8 LRNM) (TRAZODONE -

UNII:YBK48 BXK30 )

TRAZODONE

HYDROCHLORIDE

10 0 mg

Inactive Ingredients

Ingredient Name

Stre ng th

SILICO N DIO XIDE (UNII: ETJ7Z6 XBU4)

CELLULO SE, MICRO CRYSTALLINE (UNII: OP1R32D6 1U)

STARCH, CO RN (UNII: O8 232NY3SJ)

SO DIUM LAURYL SULFATE (UNII: 36 8 GB5141J)

MAGNESIUM STEARATE (UNII: 70 0 9 7M6 I30 )

SO DIUM STARCH GLYCO LATE TYPE A PO TATO (UNII: 58 56 J3G2A2)

Product Characteristics

Color

white ((WHITE TO OFF-WHITE))

S core

2 pieces

S hap e

ROUND ((ROUND))

S iz e

10 mm

Flavor

Imprint Code

8 ;0 6

Contains

Packag ing

#

Item Code

Package Description

Marketing Start Date

Marketing End Date

1

NDC:6 19 19 -6 31-30

30 in 1 BOTTLE; Type 0 : No t a Co mbinatio n Pro duct

0 8 /19 /20 19

2

NDC:6 19 19 -6 31-9 0

9 0 in 1 BOTTLE; Type 0 : No t a Co mbinatio n Pro duct

0 8 /19 /20 19

Marketing Information

Marke ting Cate gory

Application Numbe r or Monograph Citation

Marke ting Start Date

Marke ting End Date

ANDA

ANDA20 5253

0 8 /19 /20 19

Labeler -

Direct_Rx (079254320)

Registrant -

Direct_Rx (079254320)

Establishment

Name

Ad d re s s

ID/FEI

Busine ss Ope rations

Dire c t_Rx

0 79 254320

re pa c k(6 19 19 -6 31)

Dire ct_Rx

Revised: 10/2019

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