Promethazine Hydrochloride

INDICATIONS AND USAGE Promethazine hydrochloride injection is indicated for the following conditions: • Amelioration of allergic reactions to blood or plasma. • In anaphylaxis as an adjunct to epinephrine and other standard measures after the acute symptoms have been controlled. • For other uncomplicated allergic conditions of the immediate type when oral therapy is impossible or contraindicated. • For sedation and relief of apprehension and to produce light sleep from which the patient can be easily aroused. • Active treatment of motion sickness. • Prevention and control of nausea and vomiting associated with certain types of anesthesia and surgery. • As an adjunct to analgesics for the control of postoperative pain. • Preoperative, postoperative, and obstetric (during labor) sedation. • Intravenously in special surgical situations, such as repeated bronchoscopy, ophthalmic surgery, and poor-risk patients, with reduced amounts of meperidine or other narcotic analgesic as an adjunct to anesthesia and analgesia.

DOSAGE AND ADMINISTRATION Important Administration Information for Adult and Pediatric Patients 2 Years of Age and Older • The preferred route of administration of promethazine hydrochloride injection is by deep intramuscular administration (see WARNINGS - Severe Tissue Injury, Including Gangrene ). • Promethazine hydrochloride injection may be administered intravenously after dilution as recommended below (see Preparation and Administration ). If pain occurs at the injection site during intravenous infusion, immediately discontinue the infusion, and evaluate for possible arterial injection or perivascular extravasation. Allergic Conditions The average adult dose is 25 mg. This dose may be repeated within two hours if necessary, but continued therapy, if indicated, should be via the oral route as soon as existing circumstances permit. After initiation of treatment, dosage should be adjusted to the smallest amount adequate to relieve symptoms. The average adult dose for amelioration of allergic reactions to blood or plasma is 25 mg. Sedation In hospitalized adult patients, nighttime sedation may be achieved by a dose of 25 to 50 mg of promethazine hydrochloride injection. Nausea and Vomiting For control of nausea and vomiting, the usual adult dose is 12.5 to 25 mg, not to be repeated more frequently than every four hours. When used for control of postoperative nausea and vomiting, the dosage of analgesics and barbiturates should be reduced accordingly (see PRECAUTIONS - Drug Interactions ). Antiemetics should not be used in vomiting of unknown etiology in children and adolescents (see PRECAUTIONS - Pediatric Use ). Preoperative and Postoperative Use As an adjunct to preoperative or postoperative medication, 25 to 50 mg of promethazine hydrochloride injection in adults may be combined with appropriately reduced doses of analgesics and atropine-like drugs as desired. Dosage of concomitant analgesic or hypnotic medication should be reduced accordingly (see PRECAUTIONS - Drug Interactions ). Promethazine hydrochloride is contraindicated for use in pediatric patients less than two years of age. Obstetrics Promethazine hydrochloride injection in doses of 50 mg will provide sedation and relieve apprehension in the early stages of labor. When labor is definitely established, 25 to 75 mg (average dose, 50 mg) promethazine hydrochloride injection may be given with an appropriately reduced dose of any desired narcotic (see PRECAUTIONS - Drug Interactions ). If necessary, promethazine hydrochloride injection with a reduced dose of analgesic may be repeated once or twice at four-hour intervals in the course of a normal labor. A maximum total dose of 100 mg of promethazine hydrochloride injection may be administered during a 24-hour period to patients in labor. Pediatric Patients Promethazine hydrochloride injection is contraindicated for use in pediatric patients less than 2 years of age (see WARNINGS - Respiratory Depression ). Caution should be exercised when administering promethazine hydrochloride to pediatric patients 2 years of age or older. It is recommended that the lowest effective dose of promethazine hydrochloride be used in pediatric patients 2 years of age and older and concomitant administration of other drugs with respiratory depressant effects be avoided (see WARNINGS - Respiratory Depression ). In pediatric patients 2 years of age and older, the dosage should not exceed half that of the suggested adult dose. As an adjunct to premedication, the suggested dose is 1.1 mg per kg of body weight in combination with an appropriately reduced dose of narcotic or barbiturate and the appropriate dose of an atropine-like drug (see PRECAUTIONS - Drug Interactions ). Antiemetics should not be used in vomiting of unknown etiology in pediatric patients. Preparation and Administration Instructions for Diluted Intravenous Infusion in Adults Inspect the solution for particulate matter and discoloration, before dilution, after dilution, and be …

CONTRAINDICATIONS Children Less Than 2 Years of Age Promethazine hydrochloride injection is contraindicated for use in pediatric patients less than two years of age due to the risk of respiratory depression ( see WARNINGS - Respiratory Depression ) . Comatose State Promethazine hydrochloride injection is contraindicated in comatose states. Intra-Arterial Injection Under no circumstances should promethazine hydrochloride injection be given by intra-arterial injection due to the likelihood of severe arteriospasm and the possibility of resultant gangrene (see WARNINGS - Severe Tissue Injury, Including Gangrene ). Subcutaneous Injection Promethazine hydrochloride injection should not be given by the subcutaneous route because evidence of chemical irritation has been noted, and necrotic lesions have resulted following subcutaneous injection. The preferred parenteral route of administration is by deep intramuscular injection. Idiosyncratic Reaction or Hypersensitivity Promethazine hydrochloride injection is contraindicated in patients who have demonstrated an idiosyncratic reaction or hypersensitivity to promethazine or other phenothiazines.

ADVERSE REACTIONS Respiratory Depression Promethazine hydrochloride injection is contraindicated in pediatric patients less than 2 years of age, because of the potential for fatal respiratory depression. Promethazine hydrochloride injection should be used with caution in pediatric patients 2 years of age and older (see WARNINGS - Respiratory Depression ). Severe Tissue Injury, Including Gangrene Promethazine hydrochloride injection can cause severe chemical irritation and damage to tissues regardless of the route of administration . Irritation and damage can result from perivascular extravasation, unintentional intra-arterial injection and intraneuronal or perineuronal infiltration. Adverse reactions include burning, pain, erythema, swelling, sensory loss, palsies, paralysis, severe spasm of distal vessels, thrombophlebitis, venous thrombosis, phlebitis, abscesses, tissue necrosis, and gangrene. In some cases, surgical intervention, including fasciotomy, skin graft, and/or amputation have been required (see WARNINGS - Severe Tissue Injury, Including Gangrene ; and DOSAGE AND ADMINISTRATION ). 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 injection. Consideration should be given to the discontinuation of promethazine hydrochloride injection 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 CNS Depressants Promethazine hydrochloride injection may increase, prolong, or intensify the sedative action of central-nervous-system depressants, such as alcohol, sedative/hypnotics (including barbiturates), general anesthetics, narcotics, narcotic analgesics, 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 injection, 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 injection 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 to reverse epinephrine’s vasopressor effect, epinephrine should NOT be used to treat hypotension associated with promethazine hydrochloride injection overdose. Anticholinergics Concomitant use of other agents with anticholinergic properties should be undertaken with caution. Monoamine Oxidase (MAO) Inhibitors Drug interactions, including an increased incidence of extrapyramidal effects, have been reported when some MAO Inhibitors and phenothiazines are used concomitantly. This possibility should be considered with promethazine hydrochloride injection.

DESCRIPTION Promethazine hydrochloride injection, USP is a sterile, pyrogen-free solution for deep intramuscular or intravenous administration. Promethazine hydrochloride (10 H -Phenothiazine-10-ethanamine, N,N,α -trimethyl-, monohydrochloride, (±)-) is a racemic compound and has the following structural formula: C 17 H 21 ClN 2 S MW 320.88 Each mL contains promethazine hydrochloride, either 25 mg or 50 mg, edetate disodium 0.1 mg, calcium chloride 0.04 mg, sodium metabisulfite 0.25 mg and phenol 5 mg in Water for Injection. pH 4.0 to 5.5; buffered with acetic acid-sodium acetate. Promethazine hydrochloride injection is a clear, colorless solution. The product is light sensitive. It should be inspected before use and discarded if either color or particulate is observed. Promethazine Structural Formula

OVERDOSAGE Signs and symptoms of overdosage 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 pediatric patients and geriatric patients. Convulsions may rarely occur. A paradoxical-type reaction has been reported in pediatric patients 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; etc., 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. 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 injection 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 a patient with partial adrenergic blockade may further lower the blood pressure. Extrapyramidal reactions may be treated with anticholinergic antiparkinson agents, diphenhydramine, or barbiturates. Oxygen may also be administered. Limited experience with dialysis indicates that it is not helpful.

HOW SUPPLIED Promethazine Hydrochloride Injection, USP is available as follows: 25 mg/mL 1 mL ampuls packaged in 25s (NDC 0641-1495-35) 50 mg/mL 1 mL ampuls packaged in 25s (NDC 0641-1496-35) Storage Store at 20°-25°C (68°-77°F) [see USP Controlled Room Temperature] . Protect from light. Keep covered in carton until time of use. Do not use if solution has developed color or contains a precipitate. To report SUSPECTED ADVERSE REACTIONS, contact West-Ward Pharmaceutical Corp. at 1-877-845-0689, or the FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. For Product Inquiry call 1-877-845-0689. Product repackaged by: Henry Schein, Inc., Bastian, VA 24314 From Original Manufacturer/Distributor's NDC and Unit of Sale To Henry Schein Repackaged Product NDC and Unit of Sale Total Strength/Total Volume (Concentration) per unit NDC 0641-1495-35 1 mL ampuls packaged in 25s NDC 0404-9941-01 1 1 mL ampuls vial in a bag (Ampul bears NDC 0641-1495-31) 25 mg/mL NDC 0641-1496-35 1 mL ampuls packaged in 25s NDC 0404-9942-01 1 1 mL ampuls vial in a bag (Ampul bears NDC 0641-1496-31) 50 mg/mL Manufactured by: HIKMA FARMACEUTICA (PORTUGAL), S.A. Estrada do Rio da Mo, 8, 8A e 8B - Fervenca - 2705-906 Terrugem SNT, PORTUGAL Distributed by: Hikma Pharmaceuticals USA Inc. Berkeley Heights, NJ 07922 Revised September 2020 462-638-02 PIN292-WES/3