Promethazine Hydrochloride and Dextromethorphan Hydrobromide Oral Solution

INDICATIONS AND USAGE Promethazine hydrochloride and dextromethorphan hydrobromide oral solution is indicated for the temporary relief of coughs and upper respiratory symptoms associated with allergy or the common cold.

DOSAGE AND ADMINISTRATION Promethazine hydrochloride and dextromethorphan hydrobromide oral solution is contraindicated for children under 2 years of age (see WARNINGS – Black Box Warning and Use In Pediatric Patients ). The average effective dose is given in the following table: Adults 1 teaspoonful (5 mL) every 4 to 6 hours, not to exceed 30 mL in 24 hours. Children 6 Years To Under 12 Years 1⁄2 to 1 teaspoonful (2.5 to 5 mL) every 4 to 6 hours, not to exceed 20 mL in 24 hours. Children 2 Years To Under 6 Years 1⁄4 to 1⁄2 teaspoonful (1.25 to 2.5 mL) every 4 to 6 hours, not to exceed 10 mL in 24 hours.

CONTRAINDICATIONS Dextromethorphan should not be used in patients receiving a monoamine oxidase inhibitor (MAOI) (see PRECAUTIONS , Drug Interactions ). Promethazine is contraindicated in comatose states, and in individuals known to be hypersensitive or to have had an idiosyncratic reaction to promethazine or to other phenothiazines. Antihistamines are contraindicated for use in the treatment of lower respiratory tract symptoms, including asthma.

ADVERSE REACTIONS Dextromethorphan: Dextromethorphan hydrobromide occasionally causes slight drowsiness, dizziness, and gastrointestinal disturbances. Promethazine: Central Nervous System – Drowsiness is the most prominent CNS effect of this drug. Sedation, somnolence, blurred vision, dizziness; confusion, disorientation, and extrapyramidal symptoms such as oculogyric crisis, torticollis, and tongue protrusion; lassitude, tinnitus, incoordination, fatigue, euphoria, nervousness, diplopia, insomnia, tremors, convulsive seizures, excitation, catatonic-like states, hysteria. Hallucinations have also been reported. Cardiovascular – Increased or decreased blood pressure, tachycardia, bradycardia, faintness. Dermatologic – Dermatitis, photosensitivity, urticaria. Hematologic – Leukopenia, thrombocytopenia, thrombocytopenic purpura, agranulocytosis. Gastrointestinal – Dry mouth, nausea, vomiting, jaundice. Respiratory – Asthma, nasal stuffiness, respiratory depression (potentially fatal) and apnea (potentially fatal). (See WARNINGS – Promethazine ; Respiratory Depression .) Other – Angioneurotic edema. Neuroleptic malignant syndrome (potentially fatal) has also been reported. (See WARNINGS – Promethazine ; Neuroleptic Malignant Syndrome .) Paradoxical Reactions – Hyperexcitability and abnormal movements have been reported in patients following a single administration of promethazine HCl. Consideration should be given to the discontinuation of promethazine HCl and to the use of other drugs if these reactions occur. Respiratory depression, nightmares, delirium, and agitated behavior have also been reported in some of these patients.

Drug Interactions Dextromethorphan: Hyperpyrexia, hypotension, and death have been reported coincident with the coadministration of monoamine oxidase (MAO) inhibitors and products containing dextromethorphan. Thus, concomitant administration of promethazine with dextromethorphan and MAO inhibitors should be avoided (see CONTRAINDICATIONS ). Promethazine: CNS Depressants – Promethazine may increase, prolong, or intensify the sedative action of other central nervous system depressants, such as alcohol, sedatives/hypnotics (including barbiturates), narcotics, narcotic analgesics, general anesthetics, tricyclic antidepressants, and tranquilizers; therefore, such agents should be avoided or administered in reduced dosage to patients receiving promethazine HCl. When given concomitantly with promethazine, the dose of barbiturates should be reduced by at least one-half, and the dose of narcotics should be reduced by one-quarter to one-half. Dosage must be individualized. Excessive amounts of promethazine HCl relative to a narcotic may lead to restlessness and motor hyperactivity in the patient with pain; these symptoms usually disappear with adequate control of the pain. Epinephrine – Because of the potential for promethazine to reverse epinephrine's vasopressor effect, epinephrine should NOT be used to treat hypotension associated with promethazine overdose. Anticholinergics – Concomitant use of other agents with anticholinergic properties should be undertaken with caution. Monoamine Oxidase Inhibitors (MAOI) – Drug interactions, including an increased incidence of extrapyramidal effects, have been reported when some MAOI and phenothiazines are used concomitantly.

DESCRIPTION Each 5 mL (one teaspoonful), for oral administration contains: Dextromethorphan hydrobromide 15 mg; promethazine hydrochloride 6.25 mg. Alcohol 7%. Inactive Ingredients: Ascorbic acid, citric acid, D&C yellow #10, FD&C yellow #6, menthol, methylparaben, orange pineapple flavor, propylene glycol, propylparaben, purified water, saccharin sodium, sodium benzoate, sodium citrate and sucrose. Dextromethorphan hydrobromide is a salt of the methyl ether of the dextrorotatory isomer of levorphanol, a narcotic analgesic. It is chemically designated as 3-methoxy-17-methyl-9α, 13α, 14α-morphinan hydrobromide monohydrate. Dextromethorphan hydrobromide occurs as white crystals sparingly soluble in water and freely soluble in alcohol. It has a molecular weight of 370.32, a molecular formula of C 18 H 25 NO•HBr•H 2 O, and the following structural formula: Promethazine is a racemic compound. Promethazine hydrochloride, a phenothiazine derivative, is chemically designated as 10 H -Phenothiazine-10-ethanamine, N , N , α-trimethyl-monohydrochloride. Promethazine hydrochloride occurs as a white to faint yellow, practically odorless, crystalline powder which slowly oxidizes and turns blue on prolonged exposure to air. It is soluble in water and freely soluble in alcohol. It has a molecular weight of 320.88, a molecular formula of C 17 H 20 N 2 S•HCI, and the following structural formula: dextromethorphan-struc-form promethazine-struc-form

OVERDOSAGE Dextromethorphan: Dextromethorphan may produce central excitement and mental confusion. Very high doses may produce respiratory depression. One case of toxic psychosis (hyperactivity, marked visual and auditory hallucinations) after ingestion of a single dose of 20 tablets (300 mg) of dextromethorphan has been reported. Promethazine: Signs and symptoms of overdosage with promethazine HCl range from mild depression of the central nervous system and cardiovascular system to profound hypotension, respiratory depression, unconsciousness, and sudden death. Other reported reactions include hyperreflexia, hypertonia, ataxia, athetosis, and extensor-plantar reflexes (Babinski reflex). Stimulation may be evident, especially in children and geriatric patients. Convulsions may rarely occur. A paradoxical reaction has been reported in children receiving single doses of 75 mg to 125 mg orally, characterized by hyperexcitability and nightmares. Atropine-like signs and symptoms – dry mouth, fixed dilated pupils, flushing, as well as gastrointestinal symptoms, may occur. Treatment: The treatment of overdosage with promethazine and dextromethorphan is essentially symptomatic and supportive. Only in cases of extreme overdosage or individual sensitivity do vital signs including respiration, pulse, blood pressure, temperature, and EKG need to be monitored. Activated charcoal orally or by lavage may be given, or sodium or magnesium sulfate orally as a cathartic. Attention should be given to the re-establishment of adequate respiratory exchange through provision of a patent airway and institution of assisted or controlled ventilation. Diazepam may be used to control convulsions. Acidosis and electrolyte losses should be corrected. The antidotal efficacy of narcotic antagonists to dextromethorphan has not been established; note that any of the depressant effects of promethazine are not reversed by naloxone. Avoid analeptics, which may cause convulsions. Severe hypotension usually responds to the administration of norepinephrine or phenylephrine. EPINEPHRINE SHOULD NOT BE USED, since its use in a patient with partial adrenergic blockage may further lower the blood pressure. Limited experience with dialysis indicates that it is not helpful.

HOW SUPPLIED This preparation is a clear oral solution with yellow color and pineapple menthol odor, containing promethazine hydrochloride 6.25 mg/5 mL, dextromethorphan hydrobromide 15 mg/5 mL and alcohol 7 percent, and is available in 4 fluid ounce (118 mL) NDC 71205-654-04. Keep tightly closed. Protect from light. Store at 20° to 25°C (68° to 77°F) [see USP Controlled Room Temperature]. Dispense in a tight, light-resistant container with a child-resistant closure as defined in the USP. Distributed by: Slate Run Pharmaceuticals, LLC Columbus, Ohio 43215 Relabeled by: Proficient Rx LP Thousand Oaks, CA 91320 10000197/01 Revised: 03/2020