Limitation of Use:

Tigan is not recommended for use in pediatric patients due to the risk of extrapyramidal signs and symptoms and other serious central nervous system (CNS) effects, and the risk of exacerbation of the underlying disease in pediatric patients with Reye's syndrome or other hepatic impairment.

2.1 Recommended Adult Dosage

The recommended adult dosage is 300 mg orally three or four times daily. Select the lowest effective daily dosage and adjust as needed based upon therapeutic response and tolerability.

2.2 Dosage Adjustment for Geriatric Patients and/or Patients with Renal Impairment

In geriatric patients and/or in patients with renal impairment (creatinine clearance 70 mL/min/1.73m2 or less), reduce the daily dosage of Tigan by increasing the dosing interval and adjust as needed based upon therapeutic response and tolerability. Monitor renal function [see Use in Specific Populations (8.5, 8.6)].

5.1 Acute Dystonic Reactions and Other Extrapyramidal Symptoms (EPS)

Extrapyramidal symptoms (EPS), manifested primarily as acute dystonic reactions, may occur with Tigan. Dystonic reactions may include sudden onset of muscular spasms, especially in the head and neck or opisthotonos. Other EPS include laryngospasm, dysphagia, and oculogyric crisis. Involuntary spasms of the tongue and mouth may lead to difficulty in speaking and swallowing. Anticholinergic drugs can be used to treat acute dystonic reactions.

EPS may also include akathisia, restlessness, akinesia, and other parkinsonian-like symptoms (e.g., tremor). Depending on the severity of symptoms, reduce the daily dosage of Tigan by increasing the dosing interval or discontinue Tigan [see Dosage and Administration (2.1)].

Avoid Tigan in patients receiving other drugs that are likely to cause EPS (e.g. antipsychotics) [see Drug Interactions (7.2)].

5.2 Masking of Other Serious Disorders

EPS and other CNS symptoms which can occur in patients treated with Tigan may be confused with CNS signs of undiagnosed primary disease (e.g., encephalopathy, metabolic imbalance, Reye's syndrome) [see Warnings and Precautions (5.1, 5.3)]. If CNS symptoms occur, evaluate the risks and benefits of continuing Tigan for each patient.

5.3 Other CNS Reactions

Other serious CNS adverse reactions such as coma, depression of mood, disorientation, and seizures have been reported with Tigan administration. The recent use of other drugs that cause CNS depression or EPS symptoms (e.g., alcohol, sedatives, hypnotics, opiates, anxiolytics, antipsychotics, and anticholinergics) may also increase the risk for these serious CNS reactions [see Warnings and Precautions (5.1, 5.5)]. Consider reducing the daily dosage of Tigan by increasing the dosing interval or discontinuing the drug [see Dosage and Administration (2.1), Drug Interactions (7.1, 7.2)].

5.4 Hepatotoxicity

Tigan is potentially hepatotoxic [see Adverse Reactions (6)]. Avoid use of Tigan in patients whose signs and symptoms suggest the presence of hepatic impairment. Discontinue Tigan in patients who develop impaired liver function while taking Tigan.

5.5 Effects on the Ability to Drive or Operate Machinery

Tigan can cause drowsiness and may impair the mental and/or physical abilities required for the performance of hazardous tasks such as driving a motor vehicle or operating machinery [see Warnings and Precautions (5.1, 5.3)]. Concomitant use of other drugs that cause CNS depression or EPS symptoms (e.g., alcohol, sedatives, hypnotics, opiates, anxiolytics, antipsychotics, and anticholinergics) may increase this effect. Either Tigan or the other interacting drug should be chosen, depending on the importance of the drug to the patient [Drug Interactions (7.1, 7.2)]. Inform patients not to operate motor vehicles or other dangerous machinery until they are reasonably certain that Tigan does not affect them adversely.

7.1 Alcohol

Alcohol may increase the CNS depressant effects of Tigan and may cause drowsiness [see Warnings and Precautions (5.3, 5.5)]. Avoid concomitant use of Tigan with alcohol.

7.2 Other Drugs that Cause CNS Depression or EPS

The concurrent use of Tigan with other drugs that cause CNS depression or EPS (e.g., sedatives, hypnotics, opiates, anxiolytics, antipsychotics, and anticholinergics, may potentiate the effects of Tigan [see Warnings and Precautions (5.1, 5.2, 5.3, 5.5)]. Either Tigan or the other interacting drug should be chosen, depending on the importance of the drug to the patient. If CNS-acting drugs cannot be avoided, monitor patients for CNS adverse reactions.

8.1 Pregnancy

8.2 Lactation

8.4 Pediatric Use

The safety and effectiveness of Tigan in pediatric patients has not been established.

Tigan is not recommended for use in pediatric patients due to the risk of EPS and other serious CNS effects, and the risk of exacerbation of underlying disease in pediatric patients with Reye's Syndrome, or other hepatic impairment [see Warnings and Precautions (5.1, 5.2, 5.3, 5.4)].

8.5 Geriatric Use

Clinical studies of trimethobenzamide did not include sufficient numbers of patients aged 65 years and over to determine whether they respond differently from younger patients. Although there are studies reported in the literature that included geriatric patients 65 years and older with younger patients, it is not known if there are differences in efficacy or safety parameters for geriatric and non-geriatric patients treated with Tigan. Trimethobenzamide is excreted by the kidney, and the risk of adverse reactions to this drug may be greater in patients with impaired renal function.

Because geriatric patients are more likely to have decreased renal function, reduce the daily dosage of Tigan by increasing the dosing interval and adjust as needed based upon therapeutic response and tolerability. Monitor renal function [see Dosage and Administration (2.2), Use in Specific Populations (8.6)].

8.6 Renal Impairment

Trimethobenzamide is eliminated by renal excretion [see Clinical Pharmacology (12.3)]. In patients with renal impairment (creatinine clearance 70 mL/min/1.73m2 or less), reduce the daily dosage by increasing the dosing interval and adjust as needed based upon therapeutic response and tolerability. Monitor renal function [see Dosage and Administration (2.2)].

8.7 Hepatic Impairment

Avoid Tigan in patients whose signs and symptoms suggest the presence of hepatic impairment due to the risk of hepatotoxicity [see Warnings and Precautions (5.4)]. Discontinue Tigan in patients who develop impaired liver function while taking Tigan.

12.1 Mechanism of Action

The mechanism of action of trimethobenzamide 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.

12.3 Pharmacokinetics

Store at 25°C (77°F).

Excursions permitted to 15–30°C (59–86°F).

[See USP Controlled Room Temperature]

Effects on the Ability to Drive or Operate Machinery

Advise patients that Tigan can cause drowsiness and may impair their judgment, thinking, or motor skills required for tasks such as driving a motor vehicle or operating machinery. Inform patients not to operate motor vehicles or other dangerous machinery until they are reasonably certain that Tigan does not affect them adversely [see Warnings and Precautions (5.5)].

Drug Interactions

Inform patients that use of alcohol or concomitant treatment with other CNS-acting drugs can precipitate or worsen CNS depression and/or EPS [see Drug Interactions (7.1, 7.2)]. Instruct patients to avoid alcohol and to tell their health care providers when they start taking any concomitant medication.