Trimethobenzamide

For Intramuscular Use Only

NOT FOR USE IN PEDIATRIC PATIENTS

Rx only

Trimethobenzamide Description

Trimethobenzamide hydrochloride is a sterile solution for intramuscular injection. Each 1 mL contains 100 mg Trimethobenzamide hydrochloride compounded with 0.45% phenol as preservative, 0.5 mg sodium citrate anhydrous and 0.2 mg citric acid anhydrous as buffers, and 0.1 mg edetate disodium as stabilizer in Water for Injection. pH is adjusted with sodium hydroxide or hydrochloric acid.

Trimethobenzamide hydrochloride is an antiemetic agent which is known chemically as N-[p-[2-(Dimethylamino)ethoxy] benzyl]-3,4,5,-trimethoxybenzamide monohydrochloride. It has a molecular weight of 424.92, and has the following structural formula:

Trimethobenzamide - Clinical Pharmacology

Mechanism of Action

The mechanism of action of Trimethobenzamide hydrochloride as determined in animals is obscure, but may involve the chemoreceptor trigger zone (CTZ), an area in the medulla oblongata through which emetic impulses are conveyed to the vomiting center; direct impulses to the vomiting center apparently are not similarly inhibited. In dogs pretreated with Trimethobenzamide hydrochloride, the emetic response to apomorphine is inhibited, while little or no protection is afforded against emesis induced by intragastric copper sulfate.

PHARMACOKINETICS

The pharmacokinetics of Trimethobenzamide have been studied in healthy adult subjects. Following administration of 200 mg (100 mg/mL) Trimethobenzamide I.M. injection, the time to reach maximum plasma concentration (TMAX) was about half an hour, about 15 minutes longer for Trimethobenzamide 300 mg oral capsule than an I.M. injection. A single dose of Trimethobenzamide 300 mg oral capsule provided a plasma concentration profile of Trimethobenzamide similar to Trimethobenzamide 200 mg I.M. The relative bioavailability of the capsule formulation compared to the solution is 100%. The mean elimination half-life of Trimethobenzamide is 7 to 9 hours.

Special Populations

Gender

Systemic exposure to Trimethobenzamide was similar between men (N=40) and women (N=28).

Race

Pharmacokinetics appeared to be similar for Caucasians (N=53) and African Americans (N=12).

Indications and Usage for Trimethobenzamide

For the treatment of postoperative nausea and vomiting and nausea associated with gastroenteritis.

Contraindications

The injectable form of Trimethobenzamide hydrochloride is contraindicated in pediatric patients, and in patients with known hypersensitivity to Trimethobenzamide.

Warnings

Caution should be exercised when administering Trimethobenzamide hydrochloride to pediatric patients for the treatment of vomiting. Antiemetics are not recommended for treatment of uncomplicated vomiting in pediatric patients and their use should be limited to prolonged vomiting of known etiology. There are two principal reasons for caution:

1. The extrapyramidal symptoms which can occur secondary to Trimethobenzamide hydrochloride may be confused with the central nervous system signs of an undiagnosed primary disease responsible for the vomiting, e.g., Reye’s syndrome or other encephalopathy.

2. It has been suspected that drugs with hepatotoxic potential, such as Trimethobenzamide hydrochloride, may unfavorably alter the course of Reye’s syndrome. Such drugs should therefore be avoided in pediatric patients whose signs and symptoms (vomiting) could represent Reye’s syndrome.

Trimethobenzamide hydrochloride may produce drowsiness. Patients should not operate motor vehicles or other dangerous machinery until their individual responses have been determined.

Usage in Pregnancy

Trimethobenzamide hydrochloride was studied in reproduction experiments in rats and rabbits and no teratogenicity was suggested. The only effects observed were an increased percentage of embryonic resorptions or stillborn pups in rats administered 20 mg and 100 mg/kg and increased resorptions in rabbits receiving 100 mg/kg. In each study these adverse effects were attributed to one or two dams. The relevance to humans is not known. Since there is no adequate experience in pregnant or lactating women who have received this drug, safety in pregnancy or in nursing mothers has not been established.

Usage with Alcohol

Concomitant use of alcohol with Trimethobenzamide hydrochloride may result in an adverse drug interaction.

Precautions

During the course of acute febrile illness, encephalitides, gastroenteritis, dehydration and electrolyte imbalance, especially in pediatrics and the elderly or debilitated, CNS reactions such as opisthotonos, convulsions, coma and extrapyramidal symptoms have been reported with and without use of Trimethobenzamide hydrochloride or other antiemetic agents. In such disorders caution should be exercised in administering Trimethobenzamide, particularly to patients who have recently received other CNS-acting agents (phenothiazines, barbiturates, belladonna derivatives). Primary emphasis should be directed toward the restoration of body fluids and electrolyte balance, the relief of fever and relief of the causative disease process. Overhydration should be avoided since it may result in cerebral edema.

The antiemetic effects of Trimethobenzamide may render diagnosis more difficult in such conditions as appendicitis and obscure signs of toxicity due to overdosage of other drugs.

Adverse Reactions

There have been reports of hypersensitivity reactions and Parkinson-like symptoms. There have been instances of hypotension reported following parenteral administration to surgical patients. There have been reports of blood dyscrasias, blurring of vision, coma, convulsions, depression of mood, disorientation, dizziness, drowsiness, headache, jaundice, muscle cramps and opisthotonos. If these occur, the administration of the drug should be discontinued. Allergic-type skin reactions have been observed; therefore, the drug should be discontinued at the first sign of sensitization. While these symptoms will usually disappear spontaneously, symptomatic treatment may be indicated in some cases.

Trimethobenzamide Dosage and Administration

(See WARNINGS and PRECAUTIONS.)

Dosage should be adjusted according to the indication for therapy, severity of symptoms, and the response of the patient.

Injectable — 100 mg/mL (Not for use in pediatric patients.)

Usual Adult Dosage. 2 mL (200 mg) t.i.d. or q.i.d. intramuscularly.

Intramuscular administration may cause pain, stinging, burning, redness, and swelling at the site of injection. Such effects may be minimized by deep injection into the upper outer quadrant of the gluteal region, and by avoiding the escape of solution along the route.

Note: The injectable form is intended for intramuscular administration only; it is not recommended for intravenous use.

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.

How is Trimethobenzamide Supplied

To prevent needle-stick injuries, needles should not be recapped, purposely bent or broken by hand.

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

Revised: January, 2008

Revised: 06/2008

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Nausea/Vomiting

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