Prescription Drugs

CLINICAL PHARMACOLOGY Pseudoephedrine hydrochloride is an orally indirect acting sympathomimetic amine and exerts a decongestant action on the nasal mucosa. It does this by vasocon-striction which results in reduction of tissue hyperemia, edema, nasal congestion, and an increase in nasal airway patency. The vasoconstriction action of pseudoephedrine is similar to that of ephedrine. In the usual dose it has minimal vasopressor effects. Pseudoephedrine is rapidly and almost completely absorbed from the gastrointestinal tract. It has a plasma half-life of 6 to 8 hours. Acidic urine is associated with faster elimination of the drug. The drug is distributed to body tissues and fluids, including the fetal tissue, breast milk and the central nervous system (CNS). Approximately 50% to 75% of the administered dose is excreted unchanged in the urine; the remainder is apparently metabolized in the liver to inactive compounds by N-demethylation, parahydroxylation and oxidative deamination. 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.

Guaifenex® PSE 60 (guaifenesin/pseudoephedrine) Extended-release Tablets Expectorant/Nasal Decongestant DESCRIPTION Each bisected, blue Guaifenex® PSE 60 (guaifenesin pseudoephedrine extended-release tablets) capsule shaped extended-release tablet provides 60 mg pseudoephedrine hydrochloride and 600 mg guaifenesin in an extended-release formulation intended for oral administration. Inactive ingredients: calcium phosphate dibasic, hydroxypropyl methylcellulose, lactose, lake blue No. 1 FD&C, magnesium stearate, povidone, silicon dioxide colloidal, and stearic acid. Guaifenesin is an expectorant. Chemically, it is 3-(2-methoxyphe-noxy)-1, 2-propanediol and has the following structural formula: Pseudoephedrine hydrochloride is a nasal decongestant. Chemically, it is [S-(R*,R*)]-α-[1-(methylamino)ethyl] benzen-emethanol hydrochloride and has the following structural formula:

INDICATIONS Guaifenex® PSE 60 Extended-release Tablets are indicated for the temporary relief of nasal congestion and cough associated with respiratory tract infections and related conditions such as sinusitis, pharyngitis, bronchitis, and asthma, when these conditions are complicated by tenacious mucous and/or mucous plugs and congestion. The product is effective in productive as well as non-productive cough, but is of particular value in dry, non-productive cough which tends to injure the mucous membrane of the air passages. DOSAGE AND ADMINISTRATION Adults and pediatric patients over 12 years of age: One or two tablets every 12 hours not to exceed 4 tablets in 24 hours. Pediatric patients 6 to 12 years: 1 tablet every 12 hours not to exceed 2 tablets in 24 hours. Pediatric patients 2 to 6 years: ½ tablet every 12 hours not to exceed 1 tablet in 24 hours. HOW SUPPLIED Guaifenex® PSE 60 Extended-release Tablets are available as bisected, capsule shaped blue tablets, debossed “ETHEX/214”. Bottles of 100 tablets (NDC 58177-214-04). Store at controlled room temperature, 15°-30°C (59°-86°F). Dispense in tight, light-resistant containers as defined in the USP . 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 63043-2413. 8/98. FDA revision date: n/a

PATIENT INFORMATION Patients should be instructed to check with physician if symptoms do not improve within 5 days or if fever is present.

OVERDOSE Since Guaifenex® PSE 60 (guaifenesin pseudoephedrine extended-release tablets) Extended-release Tablets contain two pharmacologically different compounds, treatment of overdosage should be based upon the symptomatology of the patient as it relates to the individual ingredients. Treatment of acute overdosage would probably be based upon treating the patient for pseudoephedrine toxicity which may manifest itself as excessive CNS stimulation resulting in excitement, tremor, restlessness, and insomnia. Other effects may include tachycardia, hypertension, pallor, mydriasis, hyperglycemia and urinary retention. Severe overdosage may cause tachypnea or hyperpnea, hallucinations, convulsions or delirium, but in some individuals there may be CNS depression with somnolence, stupor or respiratory depression. 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 pseudoephedrine overdosage. Overdosage with guaifenesin is unlikely to produce toxic effects since its toxicity is much lower than that of pseudoephedrine. The LD50 of pseudoephedrine (single oral dose) has been reported to be 726 mg/kg in the mouse, 2206 mg/kg in the rat and 1177 mg/kg in the rabbit. The toxic and lethal concentrations in human biologic fluids are not known. Urinary excretion increases with acidification and decreases with alkalinization of the urine. There are few published reports of toxicity due to pseudoephedrine and no case of fatal overdosage has been reported. Guaifenesin, when administered by stomach tube to test animals in doses up to 5 grams/kg, produced no signs of toxicity. Since the action of extended-release products may continue for as long as 12 hours, treatment of overdosage should be directed toward reducing further absorption and supporting the patient for at least that length of time. Gastric emptying (Syrup of Ipecac) and/or lavage is recommended as soon as possible after ingestion, even if the patient has vomited spontaneously. Either isotonic or half-isotonic saline may be used for lavage. Administration of an activated charcoal slurry is beneficial after lavage and/or emesis if less than 4 hours have passed since ingestion. Saline cathartics, such as Milk of Magnesia, are useful for hastening the evacuation of unreleased medication. Adrenergic receptor blocking agents are antidotes to pseudoephedrine. In practice, the most useful is the beta-blocker propranolol which is indicated when there are signs of cardiac toxicity. Theoretically, pseudoephedrine is dialyzable but procedures have not been clinically established. In severe cases of overdosage, it is essential to monitor both the heart (by electrocardiograph) and plasma electrolytes, and to give intravenous potassium as indicated. Vasopressors may be used to treat hypotension. Excessive CNS stimulation may be counteracted with parenteral diazepam. Stimulants should not be used. 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. Sympathomimetic amines are contraindicated in patients with severe hypertension, severe coronary artery disease and patients on monoamine oxidase (MAO) inhibitor therapy (see DRUG INTERACTIONS section).

SIDE EFFECTS Hyper-reactive individuals may display ephedrine-like reactions such as tachycardia, palpitations, headache, dizziness, or nausea. Sympathomimetics 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. No serious side effects have been reported with the use of guaifenesin. DRUG INTERACTIONS Do not prescribe this product for use in patients that are now 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. Beta-adrenergic blockers and MAOI 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. 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-hydroxy-indoleacetic acid and may therefore interfere with the interpretation of this test for the diagnosis of carcinoid syndrome. It may also falsely elevate the VMA test for catechols. Administration of this drug should be discontinued 48 hours prior to the collection of urine specimens for such tests.

WARNINGS 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. Do not exceed recommended dosage. Hypertensive crisis can occur with concurrent use of pseudoephedrine or phenylephrine and monoamine oxidase (MAO) inhibitors, indomethacin, or with beta-blockers and methyl-dopa. 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. PRECAUTIONS General: Use with caution in patients with diabetes, hypertension, cardiovascular disease and hyper-reactivity to ephedrine. Before prescribing medication to suppress or modify cough, it is important to ascertain that the underlying cause of cough is identified, that modification of cough does not increase the risk of clinical or physiologic complications, and that appropriate therapy for the primary disease is instituted. Pediatric Use: Safety and effectiveness in pediatric patients below the age of 2 years has not been established. This product is not recommended for use in pediatric patients under 2 years of age. Geriatric Use: The elderly (60 years 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. Clinical studies of Guaifenex® PSE 60 (guaifenesin pseudoephedrine extended-release tablets) Extended-release Tablets did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger 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 other drug therapy. 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: Teratogenic Effects: Pregnancy Category C. Animal reproduction studies have not been conducted with the components of this product. It is also not known whether these drugs can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. Accordingly, this product should be given to a pregnant woman only if clearly needed. Nursing Mothers: Pseudoephedrine is excreted in breast milk. Use of this product by nursing mothers is not recommended because of the higher than usual risk for infants from sympathomimetic amines.