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Trimethobenzamide

Class: Antihistamines
VA Class: GA700
Chemical Name: N-(p-[2-(Dimethylamino)ethoxy]benzyl)-3,4,5,-trimethoxybenzamide monohydrochloride
CAS Number: 554-92-7
Brands: Tigan

Medically reviewed by Drugs.com on Jan 24, 2022. Written by ASHP.

Introduction

Antiemetic agent.

Uses for Trimethobenzamide

Nausea and Vomiting

Control of nausea and vomiting, including treatment of postoperative nausea and vomiting.

Treatment of nausea associated with gastroenteritis.

Less effective than phenothiazines, but may be associated with fewer adverse effects.

Trimethobenzamide Dosage and Administration

Administration

Administer orally or by IM injection.

Not recommendedfor IV administration.

Preparation for rectal administration is no longer commercially available in the US; FDA has withdrawn approval of the new drug application (NDA) for the rectal suppositories because of lack of substantial evidence of efficacy. (See Preparations.)

IM Administration

Minimize local adverse effects by injecting deep into the upper outer quadrant of the gluteus maximus; avoid local infiltration of the solution along the needle track.

Dosage

Available as trimethobenzamide hydrochloride; dosage expressed in terms of the salt.

Pediatric Patients

Nausea and Vomiting
Oral

Children weighing 13.6–45 kg: 100 or 200 mg 3 or 4 times daily; alternatively, children may receive 15–20 mg/kg daily given in 3 or 4 divided doses. However, suitable oral dosage forms are no longer commercially available in the US.

Adults

Nausea and Vomiting
Oral

Usual dosage: 300 mg 3 or 4 times daily. Adjust dosage according to indication for use, severity of symptoms, and patient response.

IM

Usual dosage: 200 mg 3 or 4 times daily. Adjust dosage according to indication for use, severity of symptoms, and patient response.

Special Populations

No special population dosage recommendations at this time.

Cautions for Trimethobenzamide

Contraindications

  • Known hypersensitivity to trimethobenzamide.

  • Injection contraindicated in children.

Warnings/Precautions

Warnings

CNS Depression

May impair ability to perform activities requiring mental alertness or physical coordination (e.g., operating machinery, driving a motor vehicle); avoid concomitant use with alcohol.

Neurologic Effects

Possible neurologic reactions (e.g., opisthotonos, seizures, coma, extrapyramidal reactions); may be similar to CNS signs and symptoms accompanying certain disorders (e.g., acute febrile illness, encephalitis, Reye’s syndrome, encephalopathy, gastroenteritis, dehydration, electrolyte imbalance), especially in children and in geriatric or debilitated patients. Diagnosis of these disorders may be obscured or the disease-associated signs and symptoms may be incorrectly diagnosed as drug induced.

Use with caution in patients with such disorders, particularly in those who have recently received other CNS drugs (e.g., phenothiazines, barbiturates, belladonna derivatives). (See Specific Drugs under Interactions.)

Avoid use in pediatric patients with signs and symptoms suggestive of Reye’s syndrome. (See Pediatric Use under Cautions.)

Discontinue drug if CNS symptoms occur.

Sensitivity Reactions

Hypersensitivity Reactions

Hypersensitivity reactions including allergic skin reactions have been reported; discontinue at the first sign of sensitization.

General Precautions

Hepatic Effects

Jaundice reported; discontinue drug if jaundice occurs.

Potential hepatotoxic effects may unfavorably alter the course of Reye’s syndrome. (See Pediatric Use under Cautions.)

Hematologic Effects

Blood dyscrasias reported; discontinue drug if blood dyscrasia occurs.

GI Effects

Antiemetic effect may mask signs of overdosage of other drugs or may obscure the cause of vomiting in various disorders (e.g., appendicitis).

Discontinue drug if exaggeration of preexisting nausea occurs.

Specific Populations

Pregnancy

Category C.

Lactation

Not known whether trimethobenzamide is distributed into milk. Safety not established.

Pediatric Use

Injection contraindicated in children. Suitable oral dosage forms and rectal suppositories for pediatric use no longer are commercially available in the US. (See Preparations.)

Use trimethobenzamide with caution in children. Not recommended for treatment of uncomplicated vomiting in children; limit use to treatment of prolonged vomiting of known etiology. Avoid use in pediatric patients with signs and symptoms suggestive of Reye’s syndrome.

Extrapyramidal effects of trimethobenzamide may obscure the diagnosis of or be confused with CNS manifestations of Reye’s syndrome or other encephalopathies. (See Neurologic Effects under Cautions.)

Potential hepatotoxic effects of trimethobenzamide may unfavorably alter the course of Reye’s syndrome.

Children with acute febrile illnesses, encephalitides, gastroenteritis, dehydration, or electrolyte imbalance may be at increased risk for adverse CNS effects (e.g., extrapyramidal reactions, opisthotonos, seizures, coma). Use with caution in such children, especially those who recently have received other CNS agents.

Geriatric Use

Geriatric and debilitated patients with acute febrile illnesses, encephalitides, gastroenteritis, dehydration, or electrolyte imbalance may be at increased risk for adverse CNS effects (e.g., extrapyramidal reactions, opisthotonos, seizures, coma). Use with caution in such individuals, especially those who recently have received other CNS agents.

Common Adverse Effects

Adverse effects may include blurred vision, depression, disorientation, dizziness, drowsiness, headache, extrapyramidal symptoms, diarrhea, opisthotonos, and muscle cramps. In addition, injection site reactions (pain, stinging, redness, swelling ) and hypotension may occur following IM injection.

Interactions for Trimethobenzamide

Specific Drugs

Drug

Interaction

Comments

Alcohol

Impaired mental alertness/physical coordination

Avoid concomitant use

CNS drugs (e.g., barbiturates, belladonna derivatives, phenothiazines)

Possible increased risk of CNS reactions

Use with caution

Trimethobenzamide Pharmacokinetics

Absorption

Bioavailability

Relative bioavailability of oral capsule compared with IM injection is 100%. Peak plasma concentration attained within 30 minutes after IM injection or 45 minutes after oral dose.

Onset

10–40 minutes after oral administration; 15–35 minutes after IM injection.

Duration

3–4 hours after oral administration; 2–3 hours after IM injection.

Plasma Concentrations

300-mg oral dose equivalent to a 200-mg IM dose.

Distribution

Extent

Distribution into human body tissues and fluids has not been determined. Drug and metabolites are distributed mainly into liver, kidneys, and lungs in animals.

Elimination

Elimination Route

30–50% of a single dose excreted in urine as unchanged drug within 48–72 hours following administration.

Half-life

7–9 hours.

Stability

Storage

Oral

Capsules

25°C (may be exposed to 15–30°C).

Parenteral

Injection

20–25°C.

Actions

  • Appears to directly affect the medullary chemoreceptor trigger zone (CTZ) by inhibiting stimuli at the CTZ.

  • Inhibits the emetic effect of apomorphine in animals; however, does not appear to inhibit direct impulses to the vomiting center in the lateral reticular formation and does not act peripherally to decrease the sensitivity of visceral nerves that transmit afferent impulses from the GI tract to the vomiting center.

  • Structurally related to the substituted ethanolamine antihistamines (e.g., diphenhydramine) but exhibits only weak antihistaminic activity.

Advice to Patients

  • Potential for drug to impair mental alertness or physical coordination; use caution when driving or operating machinery until effects on individual are known. Avoid concomitant use of alcohol.

  • Importance of informing clinician of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant illnesses.

  • Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.

  • Importance of informing patients of other important precautionary information. (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

In April 2007, FDA announced that the agency was withdrawing approval of the NDA for trimethobenzamide hydrochloride (Tigan) suppositories because of lack of substantial evidence of efficacy. FDA also announced that it would take enforcement action against all firms attempting to manufacture or distribute trimethobenzamide-containing suppositories after May 9, 2007, without an approved application. Any firm seeking to market this formulation must obtain an approved NDA prior to marketing.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Trimethobenzamide Hydrochloride

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Capsules

300 mg*

Tigan

Monarch

Trimethobenzamide Hydrochloride Capsules

Amide

Parenteral

Injection, for IM use only

100 mg/mL*

Tigan (with phenol in multiple-dose vials and preservative-free in single-dose vials)

Monarch

Trimethobenzamide Hydrochloride Injection Carpuject (with phenol)

Hospira

AHFS DI Essentials™. © Copyright 2022, Selected Revisions February 1, 2008. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.

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