ATC Class:A04AD
Trimethobenzamide hydrochloride, which is structurally related to ethanolamine-derivative antihistamines, is an antiemetic.
Trimethobenzamide is used for the control of nausea and vomiting, including the treatment of postoperative nausea and vomiting, and also is used for the treatment of nausea associated with gastroenteritis. The drug is less effective as an antiemetic than phenothiazines, but may be associated with fewer adverse effects than phenothiazine therapy. When vomiting is severe and potentially hazardous and may likely be of short duration, phenothiazine antiemetics may be preferred. When long-term antiemetic therapy is anticipated, non-phenothiazine antiemetics such as trimethobenzamide hydrochloride should be considered. The cause of vomiting should be established, if possible, and primary emphasis should be directed toward restoration of body fluids and electrolyte balance, relief of fever, and treatment of the causative disease process. Overhydration should be avoided since it may result in cerebral edema.
Trimethobenzamide hydrochloride is administered orally or by IM injection. The drug is not recommended for IV administration. The preparation for rectal administration is no longer commercially available in the US;102, 103 the US Food and Drug Administration (FDA) has withdrawn approval of the new drug application (NDA) for the rectal suppositories because of lack of substantial evidence of efficacy.102, 103 (See Preparations.)
Local adverse effects associated with IM administration of trimethobenzamide hydrochloride may be minimized by injecting the drug deep into the upper outer quadrant of the gluteus maximus and avoiding local infiltration of the solution along the needle track.
For the control of nausea and vomiting, the usual adult oral dosage of trimethobenzamide hydrochloride is 300 mg 3 or 4 times daily. For the treatment of postoperative nausea and vomiting or for the treatment of nausea associated with gastroenteritis, the usual adult oral dosage of trimethobenzamide hydrochloride is 300 mg 3 or 4 times daily. In children weighing 13.6-45 kg, an oral dosage of 100 or 200 mg 3 or 4 times daily has been recommended; however, suitable oral dosage forms are no longer commercially available in the US. Dosage should be adjusted according to indication for use, severity of symptoms, and patient response.100, 101
The usual adult IM dosage is 200 mg 3 or 4 times daily. Dosage should be adjusted according to indication for use, severity of symptoms, and patient response.100, 101
Adverse effects occur infrequently in patients receiving usual dosages of trimethobenzamide and seldom require discontinuance of the drug. Occasionally, parkinsonian symptoms and hypersensitivity reactions including allergic skin reactions have been reported. The drug should be discontinued at the first sign of sensitization. Hypotension has been reported occasionally following IM administration of trimethobenzamide in surgical patients. Pain, stinging, burning, redness, and swelling may occur at the site of IM injection.
Blurred vision, coma, seizures, depression of mood, disorientation, vertigo, dizziness, drowsiness, and headache have been reported rarely. Such CNS symptoms as opisthotonus, seizures, coma, and extrapyramidal symptoms have been reported both with and without trimethobenzamide hydrochloride administration in patients with acute febrile illness, encephalitides, gastroenteritis, dehydration, and electrolyte imbalance, especially in children and elderly or debilitated patients. Trimethobenzamide hydrochloride should be administered with caution to patients with these disorders, especially in those patients who have received other drugs which act on the CNS such as phenothiazines, barbiturates, and belladonna derivatives.
Blood dyscrasias, jaundice, muscle cramps, opisthotonos, and exaggeration of preexisting nausea have also occurred in some patients receiving trimethobenzamide. If any of these effects occur or if CNS symptoms occur, the drug should be discontinued. Diarrhea also has occurred in some patients receiving trimethobenzamide.
Precautions and Contraindications
Patients should be warned that trimethobenzamide may impair their ability to perform activities requiring mental alertness or physical coordination (e.g., operating machinery, driving a motor vehicle); concomitant use with alcohol should be avoided.
Because neurologic reactions (e.g., opisthotonos, seizures, coma, extrapyramidal reactions) resulting from trimethobenzamide therapy may be similar to CNS signs and symptoms accompanying certain disorders such as acute febrile illness, encephalitis, Reye's syndrome, encephalopathy, gastroenteritis, dehydration, and electrolyte imbalance, especially in children and in geriatric or debilitated patients, the diagnosis of these disorders may be obscured or the disease-associated signs and symptoms may be incorrectly diagnosed as drug induced. Trimethobenzamide should be used with caution in patients with such disorders, particularly in those who have recently received other drugs which act on the CNS (e.g., phenothiazines, barbiturates, belladonna derivatives).
It should be kept in mind that the antiemetic effect of trimethobenzamide may mask the signs of overdosage of other drugs or may obscure the cause of vomiting in various disorders such as appendicitis.
Trimethobenzamide is contraindicated in patients who are hypersensitive to the drug.
Trimethobenzamide should be used with caution for the treatment of vomiting in children. Antiemetics are not recommended for treatment of uncomplicated vomiting in children, and their use should be limited to treatment of prolonged vomiting of known etiology.100, 101 Since it has been suspected that drugs which are potentially hepatotoxic, including trimethobenzamide, may unfavorably alter the course of Reye's syndrome, such drugs should not be used in children with signs and symptoms (e.g., vomiting) that could represent Reye's syndrome.
Trimethobenzamide injection is contraindicated in children.
Reproduction studies in rats and rabbits using trimethobenzamide dosages up to 100 mg/kg have not revealed evidence of teratogenicity; however, there was an increased incidence of fetal resorption and stillbirths in these animals. There are no adequate and controlled studies to date using trimethobenzamide in pregnant women, and safety of the drug during pregnancy has not been established.
Safety of trimethobenzamide in nursing women has not been established.
The precise mechanism of antiemetic action of trimethobenzamide is unclear, but the drug appears to directly affect the medullary chemoreceptor trigger zone (CTZ) by inhibiting stimuli at the CTZ. The drug inhibits the emetic effect of apomorphine in animals. Trimethobenzamide 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 which transmit afferent impulses from the GI tract to the vomiting center.
Although trimethobenzamide is structurally related to the substituted ethanolamine antihistamines (e.g., diphenhydramine), trimethobenzamide exhibits only weak antihistaminic activity.
Following oral administration of trimethobenzamide hydrochloride in a limited number of patients, the onset of antiemetic action occurred within 10-40 minutes and persisted for approximately 3-4 hours. Following IM administration of the drug, the onset of antiemetic action reportedly occurs within 15-35 minutes and persists for 2-3 hours. Following oral or rectal administration of a single 500-mg dose of trimethobenzamide in adults, average peak blood trimethobenzamide concentrations have been reported to be 1-2 mcg/mL; in addition, an unidentified metabolite has been demonstrated. Plasma concentrations of the drug attained after a 300-mg oral dose are approximately equivalent to those attained after a 200-mg IM dose, and the relative bioavailability of the oral capsule compared with the IM injection is 100%. Peak plasma concentrations are reached about 45 minutes after a 300-mg oral dose and about 30 minutes after a 200-mg IM dose of trimethobenzamide hydrochloride.
Distribution of trimethobenzamide into human body tissues and fluids has not been determined. Following administration of trimethobenzamide in animals, the drug and its metabolites are distributed mainly into the liver, kidneys, and lungs.
The mean elimination half-life of trimethobenzamide reportedly is 7-9 hours. The exact metabolic fate of trimethobenzamide in humans is not clearly established. In animals, trimethobenzamide is metabolized principally in the liver to the N -desmethyl and N -oxide derivatives of the drug.
In animals, trimethobenzamide and its metabolites are excreted in urine and feces; the drug and its metabolites are excreted in feces via biliary elimination. In humans, approximately 30-50% of a single dose of trimethobenzamide is excreted in urine as unchanged drug within 48-72 hours following administration; 20% of an administered dose is excreted within 24 hours.
Trimethobenzamide hydrochloride is an antiemetic. The drug is structurally related to the substituted ethanolamine antihistamines. Trimethobenzamide hydrochloride occurs as a white, crystalline powder with a slight phenolic odor and is soluble in water and in warm alcohol. Trimethobenzamide hydrochloride injection is a sterile solution of the drug in water for injection. The commercially available injection is adjusted to pH 4.8-5.2 with sodium hydroxide and also contains parabens or phenol as preservatives.
Commercially available trimethobenzamide hydrochloride capsules should be stored at controlled room temperature of 25°C, but may be exposed to temperatures ranging from 15-30°C.100
Trimethobenzamide hydrochloride injection should be stored at 20-25°C;100, 101 freezing of the injection should be avoided. The injection reportedly is stable for up to 3 months when a solution containing 100 mg/mL is drawn into Tubex® cartridges and stored at room temperature.
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.
Routes | Dosage Forms | Strengths | Brand Names | Manufacturer |
|---|---|---|---|---|
Oral | Capsules | 300 mg* | ||
Trimethobenzamide Hydrochloride Capsules | ||||
Parenteral | Injection, for IM use only | 100 mg/mL* | Tigan® | Monarch |
Trimethobenzamide Hydrochloride Injection Carpuject® |
* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name
AHFS® Drug Information. © Copyright, 1959-2025, Selected Revisions January 1, 2009. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, MD 20814.
Only references cited for selected revisions after 1984 are available electronically.
100. Monarch Pharmaceuticals, Inc. Tigan® (trimethobenzamide hydrochloride) capsules and injection prescribing information. Bristol, TN; 2006 Jul.
101. Hospira, Inc. Trimethobenzamide hydrochloride injection prescribing information. Lake Forest, IL; 2004 Oct.
102. US Food and Drug Administration. FDA announces that companies must stop marketing suppository products containing trimethobenzamide. Rockville, MD; 2007 Apr 6. Press release No. P07-58.
103. Food and Drug Administration. Trimethobenzamide hydrochloride suppositories; withdrawal of approval. Notice. [Docket No. 1978N-0224 (formerly Docket No. 78N-0224); DESI 11853]. Fed Regist . 2007; 72:17556-8.