Axcel Tridine

This product is indicated for temporary relief of symptoms due to upper respiratory tract disorders such as nasal congestion, sinusitis, vasomotor rhinitis and hay fever; as well as for the temporary relief of coughs associated with respiratory tract infections and related conditions such as sinusitis, pharyngitis, bronchitis, and asthma, when these conditions are complicated by tenacious mucus and/or mucus plugs and congestion. This product is effective in a productive as well as a nonproductive cough, but is of particular value in a dry, nonproductive cough which tends to injure themucous membrane of the air passages.

Adults and children 12 years of age and older:

One capsule every 12 hours, not to exceed 2 capsules in 24 hours.

This product is contraindicated in patients with hypersensitivity to guaifenesin or with hypersensitivity or idiosyncrasy to sympathomimetic amines which may be manifested by insomnia, dizziness, weakness, tremor, or arrhythmias. Patients known to be hypersensitive to other sympathomimetic amines may exhibit cross sensitivity with Axcel Tridinedoephedrine.

Axcel Tridinedoephedrine is contraindicated in patients with hypertension, ventricular tachycardia, narrow-angle glaucoma or urinary retention and should be employed only with extreme caution in elderly patients or in patients with hyperthyroidism, bradycardia, partial heart block, myocardial disease, or severe arteriosclerosis.

Axcel Tridinedoephedrine is contraindicated in patients on monoamine oxidase inhibitor (MAOI) therapy and for 14 days after stopping MAOI therapy (see PRECAUTIONS: DRUG INTERACTIONS).

WARNINGS

Sympathomimetic amines should be used judiciously and sparingly in patients with hypertension, diabetes mellitus, ischemic heart disease, peripheral vascular disease, renal impairment, increased intraocular pressure, hyperthyroidism or prostatic hypertrophy (see CONTRAINDICATIONS). Sympathomimetics may produce central nervous system stimulation with convulsions or cardiovascular collapse with accompanying hypotension. Do not exceed recommended dosage.

Hypertensive crisis can occur with concurrent use of Axcel Tridinedoephedrine and MAO inhibitors (and for 14 days after stopping MAOI therapy), indomethacin, or with beta- blockers and methyldopa. If a hypertensive crisis occurs, these drugs should be discontinued immediately and therapy to lower blood pressure should be instituted. Fever should be managed by means of external cooling.

Before prescribing medication to suppress or modify a cough, it is important that the underlying cause of the cough is identified, that modification of the cough does not increase the risk of clinical or physiological complications, and that appropriate therapy for the primary disease is instituted.

PRECAUTIONS

General

Check with physician if cough persists after medication has been used for 7 days or if high fever, skin rash, or continued headache, or sore throat is present with cough. Hypertensive patients should use Axcel Tridinedovent™ 400 (Axcel Tridinedoephedrine hcl extended-release and guaifenesin) Capsules only with medical advice, as they may experience a change in blood pressure due to added vasoconstriction.

Carcinogenesis, Mutagenesis, Impairment of Fertility

There are no animal or in vitro studies on the combination product Axcel Tridinedoephedrine hydrochloride and guaifenesin to evaluate carcinogenesis, mutagenesis, and impairment of fertility.

Pregnancy Pregnancy Category C

Animal reproduction studies have not been conducted with this product. It is also not known whether this product can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. This product should be given to a pregnant woman only if the potential benefit justifies risk to the fetus.

Nursing Mothers

Small amounts of Axcel Tridinedoephedrine are excreted in breast milk. Use of this product by nursing mothers is contraindicated because of the higher than usual risk for infants from sympathomimetic amines. It is not known if guaifenesin is excreted in breast milk.

Pediatric Use

Safety and effectiveness of Axcel Tridinedovent™ 400 (Axcel Tridinedoephedrine hcl extended-release and guaifenesin) in pediatric patients below the age of 12 years have not been established.

Axcel Tridinedovent™ 400 (Axcel Tridinedoephedrine hcl extended-release and guaifenesin) contains a fixed dose of Axcel Tridinedoephedrine hydrochloride in an extended release formulation. Very young children may be more sensitive to the effects, especially the vasopressor effects, of sympathomimetic amines like Axcel Tridinedoephedrine. Demonstrate safe use of a short-acting sympathomimetic amine before use of an extended-action formulation in pediatric patients. Appropriate studies on the relationship of age to the effects of guaifenesin have not been performed in the pediatric population.

Geriatric Use

Patients aged 60 and older are more likely to experience adverse reactions to sympathomimetics. Overdosage of sympathomimetics in this age group may cause hallucinations, convulsions, CNS depression, and death. Demonstrate safe use of a short-acting sympathomimetic amine before use of an extended-action formulation in geriatric patients. 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 drug therapy.

Hyperreactive individuals may display ephedrine-like reactions such as tachycardia, palpitations, headache, dizziness, or nausea. Sympathomimetic amines have been associated with certain untoward reactions including fear, anxiety, nervousness, restlessness, tremor, weakness, pallor, respiratory difficulty, dysuria, insomnia, hallucinations, convulsions, CNS depression, arrhythmias, and cardiovascular collapse with hypotension.

Guaifenesin is well tolerated and has a wide margin of safety. Side effects are generally mild and infrequent. Nausea and vomiting are the most frequently occurring side effects.

Drug Abuse And Dependence

Central nervous system stimulants have been abused. At high doses, subjects commonly experience an elevation of mood, a sense of increased energy and alertness, and decreased appetite. Some individuals become anxious, irritable and loquacious. In addition to the marked euphoria, the user experiences a sense of markedly enhanced physical strength and mental capacity. With continued use, tolerance develops, the user increases the dose, and toxic signs and symptoms appear. Depression may follow rapid withdrawal.

This product is comprised of pharmacologically different compounds (Axcel Tridinedoephedrine and guaifenesin). 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:

Signs and symptoms: Overdosage with sympathomimetic amines can cause cardiac arrhythmias, cerebral hemorrhage and pulmonary edema. It can also cause palpitation, tremor, dizziness, vomiting, fear, labored breathing, headache, dryness of mouth, pallor, weakness, panic, anxiety, confusion, hallucinations, and delirium.

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 5 gm/kg, produced no signs of toxicity.

Treatment: The treatment described below is for Axcel Tridinedoephedrine overdose.

The treatment of overdosage should provide symptomatic and supportive care. If the amount ingested is considered dangerous or excessive, induce vomiting with ipecac syrup, unless 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. Ammonium chloride may acidify the urine to increase urinary excretion of Axcel Tridinedoephedrine.