CONTRAINDICATIONS

This product is contraindicated in patients with hypersensitivity to guaifenesin, dextromethorphan, or phenylephrine, or in patients receiving monoamine oxidase inhibitor (MAOI) therapy and for 14 days after stopping MAOI therapy. Risk-benefit should be considered when any of the following medical conditions exist:

Cardiovascular disease - pressor effects and increased heart rate may be exacerbated due to sympathomimetic amine - induced cardiovascular effects; Diabetes mellitus - sympathomimetics may increase risk of developing cardiovascular disease; Hypertension - vasoconstrictive properties of sympathomimetics may exacerbate condition; Hyperthyroidism - which is characterized by tachycardia, may be increased due to cardiac stimulant properties of sympathomimetics.

WARNINGS

A persistent cough may be a sign of a more serious condition. If cough persists for more than one week, tends to recur, or is accompanied by fever, rash or persistent headache, consult a physician. Sympathomimetic amines should be used with caution in patients with hypertension, ischemic heart disease, diabetes mellitus, increased intraocular pressure, hyperthyroidism, or prostatic hypertrophy. Sympathomimetics may produce central nervous system stimulation with convulsions or cardiovascular collapse with accompanying hypotension. Dextromethorphan in overdosage may cause respiratory depression, toxic psychosis, confusion, drowsiness or dizziness, nausea or vomiting, or excitation. Do not exceed recommended dosage.

PRECAUTIONS
General: Use phenylephrine with caution in patients with hypoxia, acidosis, or a history of arteriosclerosis, bradycardia, partial heart block, hypertension, myocardial disease, thrombosis, or ventricular tachycardia. Caution in use with the elderly (see "Geriatric Use" section). Dextromethorphan should be used with caution in sedated or debilitated patients, and in patients confined to the supine position. Administration of dextromethorphan may be accompanied by histamine release and should be used with caution in atopic children. Phenylketonurics: Contains Phenylalanine 25.26 mg per 5 ml.

Information for Patients:
Patient consultation should include the following information regarding the proper use of this medication:
. Do not take more medication than the amount recommended.
. Take medication with food, water, or milk to minimize gastric irritation.
. Do not drive or operate machinery if drowsiness or dizziness occurs.
. Do not ingest alcoholic beverages, monoamine oxidase inhibitor, or CNS depression- producing medications (hypnotics, sedatives, tranquilizers) while taking this medication.
. If a dose is missed, the medication should be taken as soon as possible unless it is almost time for the next dose: not doubling doses.
. This medication should be stored in a tight, light resistant container at temperatures 20°-25°C (68°- 77°F), see USP Controlled Room Temperature.
. Keep all medications out of the reach of children. In case of accidental overdose, seek professional assistance or contact a poison control center immediately.
. Asthma patients should be under the supervision of a physician.
- Shake well prior to pouring from bottle for each dosage.

Drug Interactions:
Do not take this product if you are presently taking a prescription MAOI (certain drugs for depression, psychiatric or emotional conditions, or Parkinson's disease), or for 14 days after stopping the MAOI drug therapy. Combinations containing any of the following medications, depending on the amount present, may also interact with this medication:
. a- adrenergic blocking agents - Concurrent use may block the pressor response to phenylephrine, possibly resulting in severe hypotension.
. ß- adrenergic blocking agents - Concurrent use with phenylephrine may result in significant hypertension and excessive bradycardia with possible heart block.
. Anesthetics, hydrocarbon inhalation (chloroform, cyclopropane, halothane, trichloroethylene) - may increase the risk of severe ventricular arrhythmias.
. Digitalis - cardiac arrhythmias may occur when phenylephrine is used prior to anesthesia or concurrently with digitalis glycosides, since these medications may sensitize the myocardium to the effects of the sympathomimetic amines.
. Diuretics used as antihypertensives - effects may be reduced when these medications are used concurrently with sympathomimetic amines.
. CNS depression-producing medications - Concurrent use may potentiate the CNS depressant effects of these medications or dextromethorphan.

Drug / Laboratory Test Interactions:
Guaifenesin may increase renal clearance for urate and thereby lower serum uric acid levels. Guaifenesin may produce an increase in urinary 5-hydroxyindoleacetic acid and may therefore interfere with the interpretation of this test for diagnosis of carcinoid syndrome. It may also falsely elevate VMA test for catechols. Administration of this product should be discontinued 48 hours prior to the collection of urine specimens for such tests.

Carcinogenesis, Mutagenesis, Impairment of Fertility:
No data are available on the long term potential of the components of this product for carcinogenesis, mutagenesis, or impairment of fertility in animals or humans.

Pregnancy Category C:
Animal reproduction studies have not been conducted with this product. TUSSOT-XR Tannate Suspension should be given to a pregnant woman only if clearly needed.

Labor and Delivery:
Use of phenylephrine during late pregnancy or during labor may cause fetal anoxia and bradycardia by increasing contractility of the uterus and decreasing uterine blood flow.

Nursing Mothers:
Small amounts of phenylephrine may be excreted in breast milk. Use is not recommended because of the risk of adverse effects, such as unusual excitement or irritability in infants.

Pediatric Use:
Appropriate studies on the relationship of age to the effects of guaifenesin, dextromethorphan, or phenylephrine have not been performed. However, no pediatric specific problems have been documented to date.

Geriatric Use:
(60 years of age and older) Confusion, hallucinations, seizures, and CNS depression may be more likely to occur in geriatric patients taking sympathomimetic amines. Geriatric patients also may be more sensitive to the effects, especially the vasopressor effects, of sympathomimetic amines. If these side effects occur and continue, or are severe, medication should probably be discontinued.

ADVERSE REACTIONS

DRUG ABUSE AND DEPENDENCE

Signs and symptoms:
This product is comprised of pharmacologically different components (guaifenesin, dextromethorphan, and phenylephrine). Therefore, it is difficult to predict the exact manifestation of symptoms in a given individual. A description of symptoms which are likely to appear after ingestion of an excess of individual components follows: Overdosage with guaifenesin is unlikely to produce toxic effects since its toxicity is low. Guaifenesin, when administered by stomach tube to test animals in doses up to 5gm/ kg, produced no signs of toxicity. One case of toxic psychosis (hyperactivity, visual and auditory hallucinations) has been reported after ingestion of 300 mg of dextromethorphan. Respiratory depression has been reported to occur with high doses. Other symptoms of dextromethorphan overdose include mild to severe confusion, drowsiness or dizziness, severe nausea or vomiting, unusual excitement, nervousness, restlessness or irritability. Overdosage with sympathomimetic amines can cause cardiac arrhythmias, cerebral hemorrhage and pulmonary edema. It can also cause palpitations, tremor, dizziness, tingling in hands or feet, vomiting, labored breathing, headache, dryness of mouth, pallor, weakness, panic, fear, anxiety, confusion, and hallucination. Other effects may include hyperpyrexia, hypertension, mydriasis, hyperglycemia, and urinary retention. Arrhythmias (including ventricular fibrillation) may lead to hypotension and circulatory collapse. Severe hypokalemia can occur, probably due to a compartmental shift rather than a depletion of potassium. No organ damage or significant metabolic derangement is associated with overdosage.For additional information about overdose treatment, call a poison control center at (1-800-222-1222)

Recommended Treatment:
Treatment of acute overdose of TUSSOT-XR Tannate Suspension would probably be based upon treating the patient for phenylephrine toxicity. Treatment is symptomatic and supportive with possible utilization of the following:
. Induction of emesis (Syrup of Ipecac recommended); however, precaution against aspiration is necessary, especially in infants, children, or if the patient is convulsing, comatose, or has lost the gag reflex, in which case perform gastric lavage using a large bore tube. If indicated follow with activated charcoal and a saline cathartic.
. Gastric lavage (isotonic or 0.45% sodium chloride solution) if patient is unable to vomit within three hours of ingestion.
. Saline cathartics (Citrate of Magnesia) are sometimes used.
. Vasopressors to treat hypotension, however, epinephrine should not be used since it may further lower blood pressure.
. Oxygen and intravenous fluids.
. Precaution against use of stimulants (analeptic agents) is recommended because they may cause seizures.
. For reflex bradycardia accompanying the pressor response to phenylephrine, Atropine may be used.
. For excessive hypertensive effect, an alpha-adrenergic blocker, such as phentolamine, may be administered. In severe cases of overdosage, it is essential to monitor both the heart (by electrocardiograph) and plasma electrolytes, and give intravenous potassium as indicated.
Excessive CNS stimulation may be counteracted with parenteral diazepam. Hyperpyrexia, especially in children, may require treatment with tepid sponge baths or a hyperthermic blanket. Apnea is treated with ventilatory support.

DOSAGE AND ADMINISTRATION

HOW SUPPLIED

TUSSOT-XR Tannate Suspension is purple, grape flavored, and supplied in 16 fl. Oz (473ml) bottles; NDC # 0642-0616-16.

KEEP THIS AND ALL MEDICATIONS OUT OF THE REACH OF CHILDREN. IN CASE OF ACCIDENTAL OVERDOSE, SEEK PROFESSIONAL ASSISTANCE OR CONTACT A POISON CONTROL CENTER IMMEDIATELY.

Dispense in tight, light-resistant and child-resistant containers as described in the USP/NF. Shake well.
Store at controlled room temperature 20°-25°C (68°-77°F), see USP Controlled Room Temperature.

Manufactured for:
Everett Laboratories, Inc.
West Orange, NJ 07052 USA

Utilizing

	U.S. Patent No. 6,869,618 U.S. Patent No. 7,094,429 U.S. Patent Pending
	Iss. 06/2006 546-68416-0

TUSSOT-XR Tannate Suspension is available for oral administration. Each 10ml dose of purple grape flavored suspension contains:

Guaifenesin .... .......200 mg
Phenylephrine HCl (USP) .....20 mg
Dextromethorphan HBr (USP).40 mg

Plus tannic acid yielding a tannate suspension.

Inactive ingredients include:

Aspartame, acesulfame, glycerin, neusilin, xanthan gum, sodium citrate dehydrate, citric acid, methylparaben, sodium benzoate, bitter mask, FD&C blue #1, FD&C red #40, artificial grape flavor, purified water, hydrochloric acid, sodium hydroxide.

CLINICAL PHARMACOLOGY

Guaifenesin is an expectorant which increases respiratory tract fluid secretions and helps loosen phlegm and bronchial secretions. By reducing the viscosity of secretions, guaifenesin increases the efficiency of the cough reflex and of ciliary action in removing accumulated secretions from the trachea and bronchi. This changes a dry, unproductive cough to a cough that is more productive and less frequent. Guaifenesin is readily absorbed from the gastrointestinal tract and is rapidly metabolized and excreted in the urine. Guaifenesin has a plasma half life of one hour. The major urinary metabolite is ß-(2- methoxyphenoxy) lactic acid.

Phenylephrine Hydrochloride is a direct-acting sympathomimetic amine that acts on alpha-adrenergic receptors in the mucosa of the respiratory tract to produce vasoconstriction. This temporarily reduces the swelling associated with inflammation of the mucous membranes lining the nasal passages and upper respiratory tract tissues.

Dextromethorphan Hydrobromide is a salt of the methyl ether of the dextrorotatory isomer of levorphanol, a narcotic analgesic. It is a non-narcotic antitussive with effectiveness equal to codeine. It acts in the medulla oblongata to elevate the cough threshold. Dextromethorphan does not produce analgesia or induce tolerance, and has no potential for addiction. The onset of antitussive action occurs within 15 to 30 minutes after administration and is of long duration. At usual doses, it will not depress respiration nor inhibit ciliary activity. Dextromethorphan Hydrobromide is rapidly metabolized with trace amounts of the parent compound in blood and urine. About one-half of the administered dose is excreted in the urine as conjugated metabolites..

INDICATIONS AND USAGE

TUSSOT-XR Tannate Suspension is indicated for the temporary relief of dry, nonproductive coughs associated with upper and lower respiratory tract infections and related conditions such as the common cold, sinusitis, pharyngitis, asthma and bronchitis, particularly when these conditions are complicated by tenacious mucus.