Chemically, trimethobenzamide HCl is N-[p-[2-(dimethylamino)ethoxy]benzyl]-3,4,5- trimethoxybenzamide monohydrochloride. It has a molecular weight of 424.93 and the following structural formula:

Capsules: Each 300-mg Tigan®capsule for oral use contains trimethobenzamide hydrochloride equivalent to 300 mg. The capsule has an opaque purple cap marked "Tigan" and an opaque purple body marked "M079".

Inactive Ingredients: D&C Red No. 28, FD&C Blue No. 1, lactose, magnesium stearate, starch and titanium dioxide.

Tigan® is indicated for the treatment of postoperative nausea and vomiting and for nausea associated with gastroenteritis.

(See WARNINGS and PRECAUTIONS.)

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

Geriatric Patients

Dose adjustment 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. (See CLINICAL PHARMACOLOGY and PRECAUTIONS).

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. (See CLINICAL PHARMACOLOGY and DOSAGE AND ADMINISTRATION).

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.

Storage

Store at 25°C (77°F).

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

[See USP Controlled Room Temperature]

Single-Dose Vials, 2 mL, trays of 25

NDC 42023-119-25 100 mg/mL in 2 mL Single-Dose Vials

Multi-Dose Vials, 20 mL

NDC 42023-118-01 100 mg/mL in 20 mL Multi-Dose Vials

Prescribing Information as of January 2008. Manufactured and Distributed by: JHP Pharmaceuticals, LLC Rochester, MI 48307. FDA Rev date: 04/18/08

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.

No information provided.

Caution should be exercised when administering Tigan® to children for the treatment of vomiting. Antiemetics are not recommended for treatment of uncomplicated vomiting in children 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 Tigan® 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 Tigan®, may unfavorably alter the course of Reye's syndrome. Such drugs should therefore be avoided in children whose signs and symptoms (vomiting) could represent Reye's syndrome.

Tigan® 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 Tigan® may result in an adverse drug interaction.

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 Tigan® (trimethobenzamide hydrochloride) or other antiemetic agents. In such disorders caution should be exercised in administering Tigan®, 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 Tigan® may render diagnosis more difficult in such conditions as appendicitis and obscure signs of toxicity due to overdosage of other drugs.

General

Adjustment of Dose in Renal Failure

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. (See CLINICAL PHARMACOLOGY and DOSAGE AND ADMINISTRATION).

Geriatric 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 included 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. (See CLINICAL PHARMACOLOGY and DOSAGE AND ADMINISTRATION).

No information provided.

Use of any dosage form in patients with known hypersensitivity to trimethobenzamide is contraindicated.

Mechanism of Action

The mechanism of action of Tigan® 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.

Pharmacokinetics

The pharmacokinetics of trimethobenzamide have been studied in healthy adult subjects. Following administration of 200 mg (100 mg/mL) Tigan I.M. injection, the time to reach maximum plasma concentration (Tmax) was about half an hour, about 15 minutes longer for Tigan 300 mg oral capsule than an I.M. injection. A single dose of Tigan 300 mg oral capsule provided a plasma concentration profile of trimethobenzamide similar to Tigan 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. 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.

Special Populations

Age

The clearance of trimethobenzamide is not known in patients with renal impairment. However, it may be advisable to consider reduction in the dosing of trimethobenzamide in elderly patients with renal impairment considering that a substantial amount of excretion and elimination of trimethobenzamide occurs via the kidney and that elderly patients may have various degrees of renal impairment. (See PRECAUTIONS: General and DOSAGE AND ADMINISTRATION).

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).

Renal Impairment

The clearance of trimethobenzamide is not known in patients with renal impairment. However, it may be advisable to consider reduction in the dosing of trimethobenzamide in patients with renal impairment considering that a substantial amount of excretion and elimination of trimethobenzamide occurs via the kidney. (See PRECAUTIONS: General and DOSAGE AND ADMINISTRATION).

No information provided. Please refer to the WARNINGS and PRECAUTIONS sections.

IMPORTANT NOTE: This is a summary and does not contain all possible information about this product. For complete information about this product or your specific health needs, ask your health care professional. Always seek the advice of your health care professional if you have any questions about this product or your medical condition. This information is not intended as individual medical advice and does not substitute for the knowledge and judgment of your health care professional. This information does not contain any assurances that this product is safe, effective, or appropriate for you.

TRIMETHOBENZAMIDE - ORAL

(try-meth-oh-BENZ-uh-mide)

COMMON BRAND NAME(S): Tigan

WARNING: Do not give children trimethobenzamide to treat vomiting when the cause of vomiting is unknown. Trimethobenzamide may worsen Reye's syndrome, a rare but serious illness. Do not give trimethobenzamide (or aspirin or acetaminophen) to a child with symptoms of Reye's syndrome (sudden/severe/persistent vomiting, drowsiness or stupor, unusual behavior, seizures). Call the doctor immediately if these symptoms are present.

USES: This medication is used to treat nausea and vomiting that can occur following surgery or with certain stomach/intestinal problems (e.g., gastroenteritis). Treating vomiting quickly can prevent a serious loss of body water (dehydration). Trimethobenzamide belongs to a class of drugs known as antiemetics. It works by decreasing the signals in the brain that lead to vomiting.

HOW TO USE: Take this medication by mouth, usually 3-4 times daily as needed or as directed by your doctor.

Dosage is based on your medical condition and response to therapy. Take this medication exactly as directed to get the most benefit from it. Do not take more medication or take it more often than prescribed. Ask your doctor or pharmacist if you have questions.

Inform your doctor if your condition persists or worsens.

SIDE EFFECTS: Diarrhea, headache, dizziness, drowsiness, blurred vision, or muscle cramps may occur. If any of these effects persist or worsen, tell your doctor or pharmacist promptly.

Remember that your doctor has prescribed this medication because he or she has judged that the benefit to you is greater than the risk of side effects. Many people using this medication do not have serious side effects.

Tell your doctor immediately if any of these unlikely but serious side effects occur: confusion, muscle spasms, unusual uncontrolled movements (especially of the face, mouth, tongue, arms, or legs), shaking (tremor), restlessness, drooling.

Tell your doctor immediately if any of these rare but very serious side effects occur: severe arching of the back, mouth sores, unusual bleeding/bruising, seizures, mental/mood changes (e.g., depression), yellowing eyes/skin, dark urine.

A very serious allergic reaction to this drug is rare. However, seek immediate medical attention if you notice any symptoms of a serious allergic reaction, including: rash, itching, swelling, severe dizziness, trouble breathing.

This is not a complete list of possible side effects. If you notice other effects not listed above, contact your doctor or pharmacist.

Contact your doctor for medical advice about side effects. The following numbers do not provide medical advice, but in the US you may report side effects to the Food and Drug Administration (FDA) at 1-800-FDA-1088. In Canada, you may call Health Canada at 1-866-234-2345.

PRECAUTIONS: See also Warning section.

Before taking trimethobenzamide, tell your doctor or pharmacist if you are allergic to it; or if you have any other allergies.

Before using this medication, tell your doctor or pharmacist your medical history, especially of: high fever, kidney problems, stomach/intestinal problems (e.g., appendicitis), swelling/disease of the brain (encephalitis/encephalopathy), a serious loss of body water (dehydration), mineral (electrolyte) imbalance.

This drug may make you dizzy or drowsy or cause blurred vision. Use caution while driving, using machinery, or doing any activity that requires alertness or clear vision. Limit alcoholic beverages because it can increase the risk of dizziness or drowsiness.

Kidney function declines as you grow older. This medication is removed by the kidneys. Therefore, older adults may be more sensitive to the effects of this drug.

Children and teenagers should not use this drug if they have chickenpox, flu, or any undiagnosed illness without first consulting a doctor about Reye's syndrome.

During pregnancy, this medication should be used only when clearly needed. Discuss the risks and benefits with your doctor.

It is not known whether this drug passes into breast milk. Consult your doctor before breast-feeding.

DRUG INTERACTIONS: Your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor or pharmacist first.

Before using this medication, tell your doctor or pharmacist of all prescription and nonprescription/herbal products you may use.

Tell your doctor or pharmacist if you also take drugs that cause drowsiness such as: certain antihistamines (e.g., diphenhydramine), anti-seizure drugs (e.g., carbamazepine), medicine for sleep or anxiety (e.g., alprazolam, diazepam, zolpidem), muscle relaxants, narcotic pain relievers (e.g., codeine), psychiatric medicines (e.g., chlorpromazine, risperidone, amitriptyline, trazodone).

Check the labels on all your medicines (e.g., cough-and-cold products) because they may contain drowsiness-causing ingredients. Ask your pharmacist about the safe use of those products.

This document does not contain all possible interactions. Therefore, before using this product, tell your doctor or pharmacist of all the products you use. Keep a list of all your medications with you, and share the list with your doctor and pharmacist.

OVERDOSE: If overdose is suspected, contact your local poison control center or emergency room immediately. US residents should call the US National Poison Hotline at 1-800-222-1222. Canada residents should call a provincial poison control center.

NOTES: If vomiting occurs just after a capsule is taken, the medication may not have had a chance to be absorbed. In these cases, use of the suppositories is recommended. Discuss this with your doctor or pharmacist.

Do not share this medication with others.

Laboratory and/or medical tests (e.g., complete blood counts, liver function) should be performed periodically to monitor your progress or check for side effects. Consult your doctor for more details.

MISSED DOSE: If you take this medication regularly and miss a dose, take it as soon as you remember. If it is near the time of the next dose, skip the missed dose and resume your usual dosing schedule. Do not double the dose to catch up.

STORAGE: Store at room temperature at 77 degrees F (25 degrees C) away from light and moisture. Brief storage between 59-86 degrees F (15-30 degrees C) is permitted. Do not store in the bathroom. Keep all medicines away from children and pets.

Do not flush medications down the toilet or pour them into a drain unless instructed to do so. Properly discard this product when it is expired or no longer needed. Consult your pharmacist or local waste disposal company for more details about how to safely discard your product.

Information last revised July 2008 Copyright(c) 2008 First DataBank, Inc.