Prescription Drugs

CLINICAL PHARMACOLOGY Pseudoephedrine hydrochloride is an oral sympathomimetic amine which acts predominantly by a direct action on alpha(a)-adrenergic receptors. Clinically, pseudoephedrine shrinks swollen mucus membranes, reduces tissue hyperemia, edema, and nasal congestion; and increases nasal airway patency. Pseudoepherine has been shown to have a mean elimination half-life of 4-6 hours, which is dependent on urine pH. Guaifenesin is an expectorant which increases respiratory tract fluid secretions and helps to 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. 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 β - (2 - methoxyphenoxy) lactic acid. As a result of these drugs, sinus and bronchial drainage is improved, and dry, nonproductive coughs become more productive and less frequent.

Pseudovent™ 400 (pseudoephedrine hcl extended-release and guaifenesin) (pseudoephedrine HCl [extended-release]/ guaifenesin) Capsules DESCRIPTION Each Pseudovent™ 400 (pseudoephedrine hcl extended-release and guaifenesin) 12-hour Capsule contains in combination: Pseudoephedrine hydrochloride .......... 120 mg (extended-release) Guaifenesin ........................ 400 mg (immediate-release to provide rapid action) in a formula to provide a prolonged and immediate release therapeutic effect Pseudovent™ 400 (pseudoephedrine hcl extended-release and guaifenesin) also contains the following inactive ingredients: Black iron oxide, calcium stearate, D&C yellow #10 aluminum lake, dibutyl sebacate, ethylcellulose, FD&C blue #1 aluminum lake, FD&C blue #2 aluminum lake, FD&C red #3 aluminum lake, FD&C red #40 aluminum lake, gelatin, hypromellose, oleic acid, pharmaceutical glaze, polyethylene glycol, propylene glycol, red iron oxide, silica, sucrose, starch, talc and titanium dioxide. Pseudoephedrine hydrochloride is an adrenergic (vasoconstrictor) agent having the chemical name benzenemethanol, α-[1-(methylamino)ethyl]-, [S - (R*, R*)] -, hydrochloride. Guaifenesin is an expectorant. Chemically, it is 3-(2- methoxyphenoxy)-1, 2-propanediol.

INDICATIONS 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. DOSAGE AND ADMINISTRATION Adults and children 12 years of age and older: One capsule every 12 hours, not to exceed 2 capsules in 24 hours. HOW SUPPLIED Pseudovent™ 400 (pseudoephedrine hcl extended-release and guaifenesin) is an opaque light blue/opaque maroon capsule, filled with white to off-white beads, imprinted "ETHEX" (cap) and "096" (body) in black ink, in bottles of 100, NDC 58177-096-04 Dispense in a tight, light-resistant container as defined in USP/NF with a child-resistant closure. Store at controlled room temperature 25°C (77°F); excursions permitted to 15°C-30°C (59°F-86° F). [See USP Controlled Room Temperature.] Avoid excessive heat and humidity. KEEP THIS AND ALL DRUGS OUT OF THE REACH OF CHILDREN. IN CASE OF ACCIDENTAL OVERDOSE, SEEK PROFESSIONAL ASSISTANCE OR CONTACT A POISON CONTROL CENTER IMMEDIATELY. Manufactured by KV Pharmaceutical Co. for ETHEX Corporation St. Louis, MO 63044. Rev. 08/04. FDA Rev date: n/a

OVERDOSE This product is comprised of pharmacologically different compounds (pseudoephedrine 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 pseudoephedrine 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 pseudoephedrine. CONTRAINDICATIONS 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 pseudoephedrine. Pseudoephedrine 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. Pseudoephedrine is contraindicated in patients on monoamine oxidase inhibitor (MAOI) therapy and for 14 days after stopping MAOI therapy (see PRECAUTIONS: DRUG INTERACTIONS).

SIDE EFFECTS 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. DRUG INTERACTIONS Beta-adrenergic blockers and MAO inhibitors may potentiate the pressor effect of pseudoephedrine. Concurrent use of digitalis glycosides may increase the possibility of cardiac arrhythmias. Sympathomimetics may reduce the hypotensive effects of guanethidine, mecamylamine, methyldopa, reserpine and veratrum alkaloids. Concurrent use of tricyclic antidepressants may antagonize the effects of pseudoephedrine. Use of other vasopressor drugs during halothane anesthesia may cause serious cardiac arrhythmias. Drug/Laboratory Test Interactions Guaifenesin interferes with the colorimetric determination of 5-hydroxyindoleacetic acid (5-HIAA) and vanilylmandelic acid (VMA). Administration of the drug should be discontinued 48 hours prior to the collection of urine specimens for such tests.

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 pseudoephedrine 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 Pseudovent™ 400 (pseudoephedrine 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 pseudoephedrine 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 pseudoephedrine 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 Pseudovent™ 400 (pseudoephedrine hcl extended-release and guaifenesin) in pediatric patients below the age of 12 years have not been established. Pseudovent™ 400 (pseudoephedrine hcl extended-release and guaifenesin) contains a fixed dose of pseudoephedrine hydrochloride in an extended release formulation. Very young children may be more sensitive to the effects, especially the vasopressor effects, of sympathomimetic amines like pseudoephedrine. 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.