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, USP 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 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 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 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 postoperative 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 to 25 mg promethazine hydrochloride by the oral route or by rectal suppository at bedtime will provide sedation in children. Adults usually require 25 to 50 mg for nighttime, presurgical, or obstetrical sedation.
Pre- and Postoperative Use: Promethazine hydrochloride in 12.5 to 25 mg doses for children and 50 mg doses for adults the night before surgery relieves apprehension and produces a quiet sleep.
For preoperative 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.
Postoperative sedation and adjunctive use with analgesics may be obtained by the administration of 12.5 to 25 mg in children and 25 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 is contraindicated in comatose state, and in individuals known to be hypersensitive or to have had an idiosyncratic reaction to promethazine or to other phenthiazines.
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.
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.
Description
Promethazine hydrochloride, a phenothiazine derivative, is designated chemically as 10- [2-(Dimethylamino)propyl]phenothiazine monohydrochloride and has the following structural formula:
Promethazine hydrochloride is a racemic compound; the empirical formula is C17H20N2S HCl and its molecular weight is 320.88.
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.
Each tablet for oral administration contains 12.5 mg, 25 mg or 50 mg promethazine hydrochloride, USP. The inactive ingredients include: lactose anhydrous, magnesium stearate, and microcrystalline cellulose. The 50 mg also contains D&C Red # 27 Lake.
StructureClinical Pharmacology
Promethazine is a phenothiazine derivative which differs structurally from the antipsychotic phenothiazines by the presence of a branched side chain and no ring substitution. It is thought that this configuration is responsible for its relative lack (1/10 that of chlorpromazine) of dopamine antagonist properties.
Promethazine is an H1 receptor blocking agent. In addition to its antihistaminic action, it provides clinically useful sedative and antiemetic effects.
Promethazine is well absorbed from the gastrointestinal tract. Clinical effects are apparent within 20 minutes after oral administration and generally last four to six hours, although they may persist as long as 12 hours. Promethazine is metabolized by the liver to a variety of compounds; the sulfoxides of promethazine and N-demethylpromethazine are the predominant metabolites appearing in the urine.
How Supplied / Storage and Handling
Promethazine Hydrochloride Tablets, USP for oral administration are available as:
12.5 mg: White to off-white, biconvex, round uncoated tablets, debossed with “AN” and bisect on one side and “745” on the other side are supplied as:
Bottles of 100: NDC 65162-745-10
Bottles of 500: NDC 65162-745-50
25 mg: White to off-white, flat-faced, beveled edge, round, uncoated tablets, debossed with “AN” above “521” with single line bisect separating them on one side and plain on the other side are supplied as:
Bottles of 100: NDC 65162-521-10
Bottles of 500: NDC 65162-521-50
Bottles of 1000: NDC 65162-521-11
50 mg: Pink color, biconvex, round tablets, debossed with “AN” above “522” on one side and plain on the other side are supplied as:
Bottles of 100: NDC 65162-522-10
Bottles of 500: NDC 65162-522-50
Store at 20º to 25°C (68° to 77ºF) [See USP Controlled Room Temperature].
Dispense in a tight, light-resistant container.
Distributed by:
Amneal Pharmaceuticals
Bridgewater, NJ 08807
Rev. 10-2015-00