Trazodone Hydrochloride (Page 5 of 6)

10.2 Management of Overdose

There is no specific antidote for trazodone hydrochloride 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.

11 DESCRIPTION

Trazodone hydrochloride is a triazolopyridine. It is a white, odorless crystalline powder which is freely soluble in water.

Chemical Name:

2-[3-[4-(3-chlorophenyl)-1-piperazinyl]propyl]-1,2,4-triazolo [4,3-a]pyridin-3(2H)-one hydrochloride

Structural Formula:

Chemical Structure
(click image for full-size original)

Molecular Formula:

C19 H22 ClN5 O • HCl

Molecular Weight:

408.32

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

Trazodone hydrochloride tablets, 50 mg and 100 mg, contain the following inactive ingredients: anhydrous lactose, carnauba wax, colloidal silicon dioxide, crospovidone, hypromellose, magnesium stearate, microcrystalline cellulose, polyethylene glycol, polysorbate 80, and titanium dioxide.

Trazodone hydrochloride tablets, 150 mg, contain the following inactive ingredients: anhydrous lactose, colloidal silicon dioxide, crospovidone, magnesium stearate, and microcrystalline cellulose.

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.

12.2 Pharmacodynamics

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.

12.3 Pharmacokinetics

Absorption

In humans, trazodone hydrochloride is well 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 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 hydrochloride 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 hydrochloride tablets, USP are available as follows:

Trazodone hydrochloride tablets 50 mg are scored, white, film coated, round, debossed MP 118

Bottles of 30

NDC 53489-510-07

Bottles of 100

NDC 53489-510-01

Trazodone hydrochloride tablets 100 mg are scored, white, film coated, round, debossed MP 114

Bottles of 30

NDC 53489-511-07

Bottles of 100

NDC 53489-511-01

Trazodone hydrochloride tablets 150 mg are scored in the divided dose design, white, round, debossed figure on one side and MP 168 on the reverse side.

Bottles of 30

NDC 53489-517-07

Bottles of 100

NDC 53489-517-01

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

DISPENSE IN TIGHT, LIGHT-RESISTANT CONTAINER.

17 PATIENT COUNSELING INFORMATION

See Medication Guide (17.2).

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 hydrochloride and should counsel them in its appropriate use.

Patients should be warned that:

There is a potential for increased risk of suicidal thoughts especially in children, teenagers and young adults.
The following symptoms should be reported to the physician: anxiety, agitation, panic attacks, insomnia, irritability, hostility, aggressiveness, impulsivity, akathisia, hypomania and mania.
They should inform their physician if they have a history of bipolar disorder, cardiac disease or myocardial infarction.
Serotonin syndrome could occur and symptoms may include changes in mental status (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).
Trazodone hydrochloride has been associated with the occurrence of priapism.
There is a potential for hypotension, including orthostatic hypotension and syncope.
There is a potential risk of bleeding (including life-threatening hemorrhages) and bleeding related events (including ecchymosis, hematoma, epistaxis, and petechiae) with the concomitant use of trazodone hydrochloride and NSAIDs, aspirin, or other drugs that affect coagulation or bleeding.
Withdrawal symptoms including anxiety, agitation and sleep disturbances, have been reported with trazodone. Clinical experience suggests that the dose should be gradually reduced.

Patients should be counseled that:

Trazodone may cause somnolence or sedation and may impair the mental and/or physical ability required for the performance of potentially hazardous tasks. Patients should be cautioned about operating hazardous machinery, including automobiles until they are reasonably certain that the drug treatment does not affect them.
Trazodone may enhance the response to alcohol, barbiturates, and other CNS depressants.
Women who intend to become pregnant or who are breastfeeding should discuss with a physician whether they should continue to use trazodone, since use in pregnant and nursing women is not recommended.

Important Administration Instructions:

Trazodone hydrochloride tablets should be swallowed whole or broken along the score lines.
Trazodone hydrochloride tablets should be taken shortly after a meal or light snack.

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