Prescription Drugs

CLINICAL PHARMACOLOGY Brompheniramine maleate is a histamine antagonist, specifically an H1-receptor-blocking agent belonging to the alkylamine class of antihistamines. Antihistamines appear to compete with histamine for receptor sites on effector cells. Brompheniramine also has anticholinergic (drying) and sedative effects. Among the antihistaminic effects, it antagonizes the allergic response (vasodilation, increased vascular permeability, increased mucus secretion) of nasal tissue. Brompheniramine is well absorbed from the gastrointestinal tract with peak plasma concentration after a single oral dose of 4 mg reached in 5 hours; urinary excretion is the major route of elimination, mostly as products of biodegradation; the liver is assumed to be the main site of metabolic transformation. Phenylpropanolamine HCl is a sympathomimetic drug which is readily absorbed from the gastrointestinal tract and produces nasal vasoconstriction (decongestion). Phenylpropanolamine stimulates both A and B-adrenergic receptors, similar to ephedrine. Part of its peripheral action is indirect and is due to the displacement of norepinephrine from storage sites, but it also has direct effect on the adrenergic receptors. Codeine is an opiate analgesic and antitussive. Codeine calms the cough control center.

Dimetane (brompheniramine, phenylpropanolamine, codeine) DESCRIPTION The product is a bluish pink to pink syrup with a raspberry flavor. Each 5 mL (1 teaspoonful) contains: Brompheniramine Maleate, USP ........................................2 mg Phenylpropanolamine Hydrochloride, USP .........................12.5 mg *Codeine Phosphate, USP .................................................10 mg *(WARNING: May be habit forming) Alcohol ..................................................................... 1.2% In a palatable aromatic vehicle Brompheniramine Maleate, USP: 2-Pyridinepropanamine,r-(4-bromophenyl)N, N-dimethyl-,(Z)-butenedioate(l:l). Phenylpropanolamine Hydrochloride, USP: Benzenemethanol, a-(1-aminoethyl)-hydrochloride, (R*,S*)-( + ). Codeine Phosphate, USP: Morphinan-6-01, 7,8,-didehydro-4,5-epoxy-3-methoxy-17- methyl-&,6a)-,phosphate (1:l) (salt), hemihydrate. Antihistamine/Nasal Decongestan/Antitussive syrup for oral administratton. INACTIVE INGREDIENTS: Citric Acid, USP; FD&C Blue No. 1; FD&C Red No. 40; Flavor; Glycerin, USP; Menthol, USP; Methylparaben, NF; Propylene Glycol, USP; Purified Water, USP; Sodium Benzoate, NF; Sodium Citrate, USP and Sorbitol Solution, USP.

INDICATIONS For relief of coughs and upper respiratory symptoms, including nasal congestion, associated with allergy or the common cold. DOSAGE AND ADMINISTRATION Adults and children 12 years of age and over: 2 teaspoonfuls every 4 hours. Children 6 to under 12 years: 1 teaspoonful every 4 hours. Children 2 to under 6 years: 1/2 teaspoonful every 4 hours. Children 6 months to under 2 years: Dosage to be established by physician. Do not exceed 6 doses during a 24-hour period. HOW SUPPLIED This product is a bluish pink to pink syrup containing in each 5 mL (1 teaspoonful): brompheniramine maleate 2 mg, phenylpropanolamine hydrochloride 12.5 mg and codeine phosphate 10 mg; available in the following sizes: 4 fl oz (118 mL) 16 fl oz (473 mL) 128 fl oz (3785 mL) RECOMMENDED STORAGE Store at controlled room temperature, 15°-30° C (59°-86° F). Dispense in tight, light-resistant containers as defined in the USP. CAUTION: federal law prohibits dispensing without prescription.

PATIENT INFORMATION Patients should be warned about engaging in activities requiring mental alertness, such as driving a car or operating dangerous machinery.

OVERDOSE Signs and Symptoms Serious overdose with codeine is characterized by respiratory depression, extreme somnolence progressing to stupor or coma. In severe overdosage, apnea, circulatory collapse, cardiac arrest and death may occur. The central nervous system effects from overdosage of brompheniramine may vary from depression to stimulation. Anticholinergic effects may also occur. Overdosage of phenylpropanolamine may be associated with tachycardia, hypertension and cardiac arrhythmias. Toxic Doses Doses of 800 mg or more of codeine have caused partial loss of consciousness, delirium, restlessness, excitement, tremors, convulsions and collapse, or respiratory paralysis with such sequelae as mydriasis, marked vasodilatation, and finally death. A 2.5 year old child survived a dose of 300-900 mg of brompheniramine; the lethal dose of phenylpropanolamine is in the range of 50 mg/kg. Treatment Respiratory depression should be treated promptly. Oxygen, intravenous fluids, vasopressors and other supportive measures should be employed as indicated. If necessary, reestablishment of adequate respiratory exchange through provision of a patent airway and the institution of assisted or controlled ventilation must be provided. The narcotic antagonist, naloxone, is a specific antidote to codeine-induced respiratory depression, and should be administered by intravenous route if appropriate (see package insert for naloxone). Since the duration of action of codeine may exceed that of the antagonist, the patient should be kept under constant surveillance. Gastric emptying may be useful in removing unabsorbed drug, either by inducing emesis or lavage; precautions against aspiration must be taken. Stimulants or depressants should be used cautiously and only when specifically indicated. If marked excitement is present, one of the short-acting barbiturates or chloral hydrate may be used. CONTRAINDICATIONS Hypersensitivity to any of the ingredients. Do not use in the newborn, in premature infants, in nursing mothers, in patients with severe hypertension or severe coronary artery disease, or in those receiving monoamine oxidase (MAO) inhibitors. Antihistamines should not be used to treat lower respiratory tract conditions including asthma.

SIDE EFFECTS The most frequent adverse reactions to this product are: sedation; dryness of mouth, nose and throat; thickening of bronchial secretions; dizziness. Other adverse reactions may include: Dermatologic: Urticaria, drug rash, photosensitivity, pruritus. Cardiovascular System: Hypotension, hypertension, cardiac arrhythmias. CNS: Disturbed coordination, tremor, irritability, insomnia, visual disturbances, weakness, nervousness, convulsions, headache, euphoria and dysphoria. G.U. System: Urinary frequency, difficult urination. G.I. System: Epigastric discomfort, anorexia, nausea, vomiting, diarrhea, constipation. Respiratory System: Tightness of chest and wheezing, shortness of breath. At higher doses, codeine has most of the disadvantages of morphine including respiratory depression. Hematologic System: Hemolytic anemia, thrombocytopenia, agranulocytosis. DRUG ABUSE AND DEPENDENCE Codeine can produce a drug dependence of the morphine type, and therefore has the potential for being abused. Psychic dependence, physical dependence, physical dependence and tolerance may develop upon repeated administration of this drug and it should be prescribed and administered with the same degree of caution appropriate to the use of other oral narcotic medications. The product is subject to the Federal Controlled Substances Act (Schedule V). DRUG INTERACTIONS Antihistamines have additive effects with alcohol and other CNS depressants (hypnotics, sedatives, tranquilizers, antianxiety agents, etc.). MAO inhibitors prolong and intensify the anticholinergic (drying) effects of antihistamines. MAO inhibitors may enhance the effect of phenylpropanolamine. Sympathomimetics may reduce the effects of antihypertensive drugs.

WARNINGS Especially in infants and small children, antihistamines in overdosage may cause hallucinations, convulsions, death. Codeine may cause or aggravate constipation. Antihistamines may diminish mental alertness. In the young child, they may produce excitation. PRECAUTIONS General Because of its antihistamine component, this product should be used with caution in patients with a history of bronchial asthma, narrow angle glaucoma, gastrointestinal obstruction, or urinary bladder neck obstruction. Because of its sympathomimetic component, this product should be used with caution in patients with diabetes, hypertension, heart disease or thyroid disease. Informatlon for Patients Patients should be warned about engaging in activities requiring mental alertness, such as driving a car or operating dangerous machinery. Drug Interactions Antihistamines have additive effects with alcohol and other CNS depressants (hypnotics, sedatives, tranquilizers, antianxiety agents, etc.). MAO inhibitors prolong and intensify the anticholinergic (drying) effects of antihistamines. MAO inhibitors may enhance the effect of phenylpropanolamine. Sympathomimetics may reduce the effects of antihypertensive drugs. Carcinogenesis, Mutagenesis Long-term studies in animals to evaluate carcinogenic and mutagenic potential have not been performed. 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 clearly needed. Reproduction studies of brompheniramine maleate (one of the components of this product) in rats and mice at doses up to 16 times the maximum human dose have revealed no evidence of impaired fertility or harm to the fetus. Nursing Mothers Because of the higher risk of intolerance of antihistamines in small infants generally, and in newborns and prematures in particular, and the fact that codeine appears in human milk, this product is contraindicated in nursing mothers.