Promethazine Hydrochloride

INDICATIONS AND USAGE Promethazine hydrochloride tablets are useful for: • Perennial and seasonal allergic rhinitis. • Vasomotor rhinitis. • Allergic conjunctivitis due to inhalant allergens and foods. • Mild, uncomplicated allergic skin manifestations of urticaria and angioedema. • Amelioration of allergic reactions to blood or plasma. • Dermographism. • Anaphylactic reactions as adjunctive therapy to epinephrine and other standard measures after the acute manifestations have been controlled. • Preoperative, postoperative and obstetric sedation. • Prevention and control of nausea and vomiting associated with certain types of anesthesia and surgery. • Therapy adjunctive to meperidine or other analgesics for control of postoperative pain. • Sedation in both children and adults as well as relief of apprehension and production of light sleep from which the patient can be easily aroused. • Active and prophylactic treatment of motion sickness. • Antiemetic therapy in postoperative patients.

DOSAGE AND ADMINISTRATION Promethazine hydrochloride tablets are contraindicated for children under 2 years of age (see WARNINGS: Black Box Warning and Use in Pediatric Patients ). Allergy The average oral dose is 25 mg taken before retiring; however, 12.5 mg may be taken before meals and on retiring, if necessary. Single 25 mg doses at bedtime or 6.25 mg to 12.5 mg taken three times daily will usually suffice. After initiation of treatment, in children or adults, dosage should be adjusted to the smallest amount adequate to relieve symptoms. The administration of promethazine hydrochloride in 25 mg doses will control minor transfusion reactions of an allergic nature. Motion Sickness The average adult dose is 25 mg taken twice daily. The initial dose should be taken one-half to one hour before anticipated travel and be repeated eight to twelve hours later if necessary. On succeeding days of travel, it is recommended that 25 mg be given on arising and again before the evening meal. For children, promethazine hydrochloride tablets, syrup, or rectal suppositories, 12.5 mg to 25 mg, twice daily, may be administered. Nausea and Vomiting Antiemetics should not be used in vomiting of unknown etiology in children and adolescents (see WARNINGS: Use in Pediatric Patients ). The average effective dose of promethazine hydrochloride for the active therapy of nausea and vomiting in children or adults is 25 mg. When oral medication cannot be tolerated, the dose should be given parenterally or by rectal suppository. 12.5 mg to 25 mg doses may be repeated, as necessary, at four- to six-hour intervals. For nausea and vomiting in children, the usual dose is 0.5 mg per pound of body weight, and the dose should be adjusted to the age and weight of the patient and the severity of the condition being treated. For prophylaxis of nausea and vomiting, as during surgery and the post-operative period, the average dose is 25 mg repeated at four- to six-hour intervals, as necessary. Sedation This product relieves apprehension and induces a quiet sleep from which the patient can be easily aroused. Administration of 12.5 mg to 25 mg promethazine hydrochloride by the oral route or by rectal suppository at bedtime will provide sedation in children. Adults usually require 25 mg to 50 mg for nighttime, pre-surgical, or obstetrical sedation. Pre- and Post-operative Use Promethazine hydrochloride in 12.5 mg to 25 mg doses for children and 50 mg doses for adults the night before surgery relieves apprehension and produces a quiet sleep. For pre-operative medication, children require doses of 0.5 mg per pound of body weight in combination with an appropriately reduced dose of narcotic or barbiturate and the appropriate dose of an atropine-like drug. Usual adult dosage is 50 mg promethazine hydrochloride with an appropriately reduced dose of narcotic or barbiturate and the required amount of a belladonna alkaloid. Post-operative sedation and adjunctive use with analgesics may be obtained by the administration of 12.5 mg to 25 mg in children and 25 mg to 50 mg doses in adults. Promethazine hydrochloride tablets are contraindicated for children under 2 years of age.

CONTRAINDICATIONS Promethazine hydrochloride tablets, USP are contraindicated for use in pediatric patients less than two years of age. Promethazine hydrochloride tablets, USP are 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 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: Respiratory Depression). Other: Angioneurotic edema. Neuroleptic malignant syndrome (potentially fatal) has also been reported. (See WARNINGS: Neuroleptic Malignant Syndrome). Paradoxical Reactions: Hyperexcitability and abnormal movements have been reported in patients following a single administration of promethazine hydrochloride. Consideration should be given to the discontinuation of promethazine hydrochloride 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. To report SUSPECTED ADVERSE REACTIONS, contact KVK-Tech, Inc. at 1-800-862-3895 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

Drug Interactions CNS Depressants – Promethazine hydrochloride tablets, USP 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 hydrochloride. When given concomitantly with promethazine hydrochloride tablets, USP, 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 hydrochloride 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 hydrochloride tablets, USP to reverse epinephrine’s vasopressor effect, epinephrine should NOT be used to treat hypotension associated with promethazine hydrochloride tablets, USP 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. This possibility should be considered with promethazine hydrochloride tablets, USP.

DESCRIPTION Each 12.5 mg promethazine hydrochloride tablet for oral administration contains 12.5 mg promethazine hydrochloride. Each 25 mg promethazine hydrochloride tablet for oral administration contains 25 mg promethazine hydrochloride. Each 50 mg promethazine hydrochloride tablet for oral administration contains 50 mg promethazine hydrochloride. Each tablet contains the following inactive ingredients: lactose monohydrate, magnesium stearate, and methylcellulose. In addition, 50 mg tablet contains FD&C Red #40 and 12.5 mg tablet contains FD&C Yellow #6. Promethazine hydrochloride is a racemic compound; the empirical formula is C 17 H 20 N 2 S•HCl and its molecular weight is 320.88. Promethazine hydrochloride, a phenothiazine derivative, is designated chemically as 10 H -Phenothiazine-10-ethanamine, N,N ,α-trimethyl-, monohydrochloride, (±)- with the following structural formula: 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 freely soluble in water and soluble in alcohol. chemical-structure

OVERDOSAGE Signs and symptoms of overdosage with promethazine hydrochloride 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-type 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 Treatment of overdosage 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 reestablishment 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. Note that any depressant effects of promethazine hydrochloride are not reversed by naloxone. Avoid analeptics which may cause convulsions. The treatment of choice for resulting hypotension is administration of intravenous fluids, accompanied by repositioning if indicated. In the event that vasopressors are considered for the management of severe hypotension which does not respond to intravenous fluids and repositioning, the administration of norepinephrine or phenylephrine should be considered. EPINEPHRINE SHOULD NOT BE USED, since its use in patients with partial adrenergic blockade may further lower the blood pressure. Extrapyramidal reactions may be treated with anticholinergic antiparkinsonian agents, diphenhydramine, or barbiturates. Oxygen may also be administered. Limited experience with dialysis indicates that it is not helpful.

HOW SUPPLIED Promethazine hydrochloride tablets USP, 12.5 mg are white to off-white, round shape, biconvex, uncoated tablets debossed with the logo of "ZC", "01" and bisect on one side and plain on the other side and are supplied as follows: Bottle of 10 tablets NDC 87063-014-10 (repackaged from NDC 68382-040-XX) Bottle of 20 tablets NDC 87063-014-20 (repackaged from NDC 68382-040-XX) Bottle of 30 tablets NDC 87063-014-30 (repackaged from NDC 68382-040-XX) Bottle of 60 tablets NDC 87063-014-60 (repackaged from NDC 68382-040-XX) Bottle of 90 tablets NDC 87063-014-90 (repackaged from NDC 68382-040-XX) Bottle of 100 tablets NDC 87063-014-01 (relabeled from NDC 68382-040-01) Bottle of 500 tablets NDC 87063-014-05 (relabeled from NDC 68382-040-05) Bottle of 1000 tablets NDC 87063-014-00 (relabeled from NDC 68382-040-10) Promethazine hydrochloride tablets USP, 25 mg are white to off-white, round shape, biconvex, uncoated tablets debossed with the quadrisect and the logo of "Z", "C", "0" and "2" on one side and plain on the other side and are supplied as follows: Bottle of 10 tablets NDC 87063-015-10 (repackaged from NDC 68382-041-XX) Bottle of 12 tablets NDC 87063-015-12 (repackaged from NDC 68382-041-XX) Bottle of 20 tablets NDC 87063-015-20 (repackaged from NDC 68382-041-XX) Bottle of 30 tablets NDC 87063-015-30 (repackaged from NDC 68382-041-XX) Bottle of 60 tablets NDC 87063-015-60 (repackaged from NDC 68382-041-XX) Bottle of 90 tablets NDC 87063-015-90 (repackaged from NDC 68382-041-XX) Bottle of 100 tablets NDC 87063-015-01 (relabeled from NDC 68382-041-01) Bottle of 500 tablets NDC 87063-015-05 (relabeled from NDC 68382-041-05) Bottle of 1000 tablets NDC 87063-015-00 (relabeled from NDC 68382-041-10) Promethazine hydrochloride tablets USP, 50 mg are white to off-white, round shape, biconvex, uncoated tablets debossed with the logo of "ZC03" on one side and plain on the other side and are supplied as follows: Bottle of 10 tablets NDC 87063-016-10 (repackaged from NDC 68382-042-XX) Bottle of 20 tablets NDC 87063-016-20 (repackaged from NDC 68382-042-XX) Bottle of 30 tablets NDC 87063-016-30 (repackaged from NDC 68382-042-XX) Bottle of 60 tablets NDC 87063-016-60 (repackaged from NDC 68382-042-XX) Bottle of 90 tablets NDC 87063-016-90 (repackaged from NDC 68382-042-XX) Bottle of 100 tablets NDC 87063-016-01 (relabeled from NDC 68382-042-01) Bottle of 500 tablets NDC 87063-016-05 (relabeled from NDC 68382-042-05) Bottle of 1000 tablets NDC 87063-016-00 (relabeled from NDC 68382-042-10) Keep tightly closed. Store at 20°C to 25°C (68°F to 77°F) [See USP Controlled Room Temperature]. Protect from light. Dispense in light-resistant, tight container.