FDA label a64134d5-e6b8-3b61-e053-2a95a90a7013

WARNING: RESPIRATORY DEPRESSION IN CHILDREN; DEATH RELATED TO ULTRA RAPID METABOLISM OF CODEINE TO MORPHINE and RISKS FROM CONCOMITANT USE WITH BENZODIAZEPINES OR OTHER CNS DEPRESSANTS Respiratory Depression in Children The combination of promethazine hydrochloride and codeine phosphate is contraindicated in pediatric patients less than 6 years of age. Concomitant administration of promethazine products with other respiratory depressants has an association with respiratory depression, and sometimes death, in pediatric patients. Postmarketing cases of respiratory depression, including fatalities, have been reported with use of promethazine hydrochloride in pediatric patients less than 2 years of age. A wide range of weight-based doses of promethazine hydrochloride have resulted in respiratory depression in these patients. Death Related to Ultra-Rapid Metabolism of Codeine to Morphine Respiratory depression and death have occurred in children who received codeine following tonsillectomy and/or adenoidectomy and had evidence of being ultra-rapid metabolizers of codeine due to a CYP2D6 polymorphism. Risks from Concomitant Use with Benzodiazepines or Other CNS Depressants Concomitant use of opioids with benzodiazepines or other central nervous system (CNS) depressants, including alcohol, may result in profound sedation, respiratory depression, coma, and death (see WARNINGS , PRECAUTIONS - Drug Interactions ). Avoid use of opioid cough medications in patients taking benzodiazepines, other CNS depressants, or alcohol.

Other Considerations Administration of promethazine has been associated with reported cholestatic jaundice.

ADVERSE REACTIONS Codeine Central Nervous System: CNS depression, particularly respiratory depression, and to a lesser extent circulatory depression; light-headedness, dizziness, sedation, euphoria, dysphoria, headache, transient hallucination, disorientation, visual disturbances, and convulsions. Cardiovascular: Tachycardia, bradycardia, palpitation, faintness, syncope, orthostatic hypotension (common to narcotic analgesics). Gastrointestinal: Nausea, vomiting, constipation, and biliary tract spasm. Patients with chronic ulcerative colitis may experience increased colonic motility; in patients with acute ulcerative colitis, toxic dilation has been reported. Genitourinary: Oliguria, urinary retention, antidiuretic effect has been reported (common to narcotic analgesics). Allergic: Infrequent pruritus, giant urticaria, angioneurotic edema, and laryngeal edema. Other: Flushing of the face, sweating and pruritus (due to opiate-induced histamine release); weakness. 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 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.