Trazodone Hydrochloride (Page 4 of 6)

6.2 Postmarketing Experience

Spontaneous reports regarding trazodone hydrochloride received from postmarketing experience include the following: abnormal dreams, agitation, alopecia, anxiety, aphasia, apnea, ataxia, breast enlargement or engorgement, cardiospasm, cerebrovascular accident, chills, cholestasis, clitorism, congestive heart failure, diplopia, edema, extrapyramidal symptoms, grand mal seizures, hallucinations, hemolytic anemia, hirsutism, hyperbilirubinemia, increased amylase, increased salivation, insomnia, leukocytosis, leukonychia, jaundice, lactation, liver enzyme alterations, methemoglobinemia, nausea/vomiting (most frequently), paresthesia, paranoid reaction, priapism [see Warnings and Precautions (5.9) and Patient Counseling Information (17.1)], pruritus, psoriasis, psychosis, rash, stupor, inappropriate ADH syndrome, tardive dyskinesia, unexplained death, urinary incontinence, urinary retention, urticaria, vasodilation, vertigo, and weakness.

Cardiovascular system effects which have been reported include the following: conduction block, orthostatic hypotension and syncope, palpitations, bradycardia, atrial fibrillation, myocardial infarction, cardiac arrest, arrhythmia, ventricular ectopic activity, including ventricular tachycardia and QT prolongation. In postmarketing surveillance, prolonged QT interval, Torsades de Pointes, and ventricular tachycardia have been reported with the immediate-release form of trazodone at doses of 100 mg per day or less [see Warnings and Precautions (5.4)].

7 DRUG INTERACTIONS

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 co-administered. 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 co-administration of carbamazepine 400 mg per day with trazodone 100 mg to 300 mg daily, carbamazepine reduced plasma concentrations of trazodone and m-chlorophenylpiperazine (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 co-administered 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.

8 USE IN SPECIFIC POPULATIONS

8.1 Pregnancy

Pregnancy Category C

Trazodone hydrochloride 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 – 50 times the proposed maximum human dose. There was also an increase in congenital anomalies in one of three rabbit studies at approximately 15 – 50 times the maximum human dose. There are no adequate and well-controlled studies in pregnant women. Trazodone hydrochloride 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 (5.1)]. Trazodone hydrochloride should not be used in children or adolescents.

8.5 Geriatric Use

Reported clinical literature and experience with trazodone has not identified differences in responses between elderly and younger patients. However, as experience in the elderly with trazodone hydrochloride is limited, it should be used with caution in geriatric patients.

Antidepressants have been associated with cases of clinically significant hyponatremia in elderly patients who may be at greater risk for this adverse reaction [see Warnings and Precautions (5.10)].

8.6 Renal Impairment

Trazodone has not been studied in patients with renal impairment. Trazodone should be used with caution in this population.

8.7 Hepatic Impairment

Trazodone has not been studied in patients with hepatic impairment. Trazodone should be used with caution in this population.

9 DRUG ABUSE AND DEPENDENCE

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. 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 hydrochloride (e.g., development of tolerance, incrementation of dose, drug-seeking behavior).

10 OVERDOSAGE

10.1 Human Experience

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.

All MedLibrary.org resources are included in as near-original form as possible, meaning that the information from the original provider has been rendered here with only typographical or stylistic modifications and not with any substantive alterations of content, meaning or intent.

This site is provided for educational and informational purposes only, in accordance with our Terms of Use, and is not intended as a substitute for the advice of a medical doctor, nurse, nurse practitioner or other qualified health professional.

Privacy Policy | Copyright © 2022. All Rights Reserved.