Trimethobenzamide (injection)

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# Overview
Trimethobenzamide (injection) is an antiemetic that is FDA approved for the treatment of postoperative nausea and vomiting and for nausea associated with gastroenteritis.   Common adverse reactions include hypotension, anticholinergic reactions, and somnolence.

# Adult Indications and Dosage

## FDA-Labeled Indications and Dosage (Adult)

## Indications
- Trimethobenzamide hydrochloride is indicated for the treatment of postoperative nausea and vomiting and for nausea associated with gastroenteritis.

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

### Geriatric Patients
- Dose adjustments such as reducing the total dose administered at each dosing or increasing the dosing interval should be considered in elderly patients with renal impairment (creatinine clearance  70 mL/min/1.73m2). Final dose adjustment should be based upon integration of clinical efficacy and safety considerations.

### Patients with Renal Impairment
- In subjects with renal impairment (creatinine clearance  70 mL/min/1.73m2), dose adjustment such as reducing the total dose administered at each dosing or increasing the dosing interval should be considered.
- 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.
- NOTE: The injectable form is intended for intramuscular administration only; it is not recommended for intravenous use.
- 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.

## Off-Label Use and Dosage (Adult)

### Guideline-Supported Use
- There is limited information regarding Off-Label Guideline-Supported Use of Trimethobenzamide (injection) in adult patients.

### NonGuideline-Supported Use
- There is limited information regarding Off-Label NonGuideline-Supported Use of Trimethobenzamide (injection) in adult patients.

# Pediatric Indications and Dosage

## FDA-Labeled Indications and Dosage (Pediatric)
- The injectable form of trimethobenzamide hydrochloride is contraindicated in pediatric patients.

## Off-Label Use and Dosage (Pediatric)

### Guideline-Supported Use
- There is limited information regarding Off-Label Guideline-Supported Use of Trimethobenzamide (injection) in pediatric patients.

### NonGuideline-Supported Use
- There is limited information regarding Off-Label NonGuideline-Supported Use of Trimethobenzamide (injection) in pediatric patients.

# Contraindications
- The injectable form of trimethobenzamide hydrochloride is contraindicated in pediatric patients and in patients with known hypersensitivity to trimethobenzamide.

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

## Precautions
- During the course of acute febrile illness, encephalitides, gastroenteritis, dehydration and electrolyte imbalance, especially in children 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 hydrochloride, 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 hydrochloride may render diagnosis more difficult in such conditions as appendicitis and obscure signs of toxicity due to overdosage of other drugs.

# Adverse Reactions

## Clinical Trials Experience
- 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, diarrhea, 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.

## Postmarketing Experience
- There is limited information regarding postmarketing experience.

# Drug Interactions
- Concomitant use of alcohol with trimethobenzamide hydrochloride may result in an adverse drug interaction.

# Use in Specific Populations

### Pregnancy
Pregnancy Category (FDA):
- 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.
Pregnancy Category (AUS): 
There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Trimethobenzamide (injection) in women who are pregnant.

### Labor and Delivery
There is no FDA guidance on use of Trimethobenzamide (injection) during labor and delivery.

### Nursing Mothers
There is no FDA guidance on the use of Trimethobenzamide (injection) in women who are nursing.

### Pediatric Use
There is no FDA guidance on the use of Trimethobenzamide (injection) in pediatric settings.

### Geriatic Use
- Clinical studies of trimethobenzamide hydrochloride did not include sufficient numbers of patients aged 65 and over to determine whether they respond differently from younger patients. Although there are studies reported in the literature that include elderly patients >65 years old with younger patients, it is not known if there are differences in efficacy or safety parameters for elderly and non-elderly patients treated with trimethobenzamide. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.
- This drug is known to be substantially excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function.

### Gender
There is no FDA guidance on the use of Trimethobenzamide (injection) with respect to specific gender populations.

### Race
There is no FDA guidance on the use of Trimethobenzamide (injection) with respect to specific racial populations.

### Renal Impairment
- A substantial route of elimination of unchanged trimethobenzamide is via the kidney. Dosage adjustment should be considered in patients with reduced renal function including some elderly patients.

### Hepatic Impairment
There is no FDA guidance on the use of Trimethobenzamide (injection) in patients with hepatic impairment.

### Females of Reproductive Potential and Males
There is no FDA guidance on the use of Trimethobenzamide (injection) in women of reproductive potentials and males.

### Immunocompromised Patients
There is no FDA guidance one the use of Trimethobenzamide (injection) in patients who are immunocompromised.

# Administration and Monitoring

### Administration
- Intramuscular.

### Monitoring
- Monitor renal function in elderly patient who is taking the medication.

# IV Compatibility
- There is limited information regarding IV Compatibility.

# Overdosage
- There is limited information regarding Overdose.

# 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 HCl, the emetic response to apomorphine is inhibited, while little or no protection is afforded against emesis induced by intragastric copper sulfate.

## Structure
- Chemically, trimethobenzamide hydrochloride (HCl) is N-benzyl]-3,4,5-trimethoxybenzamide monohydrochloride. It has a molecular weight of 424.93 and the following structural formula:

### Single Dose Vials:
- Each 2-mL single-dose vial contains 200 mg trimethobenzamide hydrochloride compounded with 1 mg sodium citrate and 0.4 mg citric acid as buffers and pH adjusted to approximately 5.0 with sodium hydroxide.

### Multi-Dose Vials:
- Each mL contains 100 mg trimethobenzamide hydrochloride compounded with 0.45% phenol as preservative, 0.5 mg sodium citrate and 0.2 mg citric acid as buffers and pH adjusted to approximately 5.0 with sodium hydroxide.

## Pharmacodynamics
- There is limited information regarding pharmacodynamics.

## Pharmacokinetics
- The pharmacokinetics of trimethobenzamide have been studied in healthy adult subjects. Following administration of 200 mg (100 mg/mL) trimethobenzamide hydrochloride IM injection, the time to reach maximum plasma concentration (Tmax) was about half an hour, about 15 minutes longer for trimethobenzamide hydrochloride 300 mg oral capsule than an IM injection. A single dose of trimethobenzamide hydrochloride 300 mg oral capsule provided a plasma concentration profile of trimethobenzamide similar to trimethobenzamide hydrochloride 200 mg IM. 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. Between 30  50% of a single dose in humans is excreted unchanged in the urine within 48  72 hours. The metabolic disposition of trimethobenzamide in humans is not known. Specifically, it is not known if active metabolites are generated in humans.

## Nonclinical Toxicology
- There is limited information regarding nonclinical toxicology.

# Clinical Studies
- There is limited information regarding Clinical Studies.

# How Supplied
- Single Dose Vials, 2 mL, trays of 25
- NDC 42023-143-25 100 mg/mL in 2 mL Single Dose Vials
- Multi-Dose Vials, 20 mL
- NDC 42023-142-01 100 mg/mL in 20 mL Multi-Dose Vials

## Storage
- Store between 20 to 25C (68 to 77F).
- (See USP Controlled Room Temperature.)

# Images

## Drug Images

## Package and Label Display Panel

# Patient Counseling Information
- There is limited information regarding Patient Counseling Information.

# Precautions with Alcohol
- Concomitant use of alcohol with trimethobenzamide hydrochloride may result in an adverse drug interaction.

# Brand Names
- TRIMETHOBENZAMIDE HYDROCHLORIDE

# Look-Alike Drug Names
- There is limited information regarding Look-Alike Drug Names.

# Drug Shortage Status

# Price