⛔ FDA Black Box Warning
WARNING : ADDICTION, ABUSE, AND MISUSE; LIFE-THREATENING RESPIRATORY DEPRESSION; ACCIDENTAL INGESTION; ULTRA-RAPID METABOLISM OF CODEINE AND OTHER RISK FACTORS FOR LIFE-THREATENING RESPIRATORY DEPRESSION IN CHILDREN; PROMETHAZINE AND RESPIRATORY DEPRESSION IN CHILDREN; MEDICATION ERRORS; INTERACTIONS WITH DRUGS AFFECTING CYTOCHROME P450 ISOENZYMES; CONCOMITANT USE WITH BENZODIAZEPINES OR OTHER CNS DEPRESSANTS; NEONATAL OPIOID WITHDRAWAL SYNDROME Addiction, Abuse, and Misuse Promethazine HCl and Codeine Phosphate Oral Solution exposes patients and other users to the risks of opioid addiction, abuse, and misuse, which can lead to overdose and death. Reserve Promethazine HCl and Codeine Phosphate Oral Solution for use in adult patients for whom the benefits of cough suppression are expected to outweigh the risks, and in whom an adequate assessment of the etiology of the cough has been made. Assess each patient’s risk prior to prescribing Promethazine HCl and Codeine Phosphate Oral Solution, prescribe Promethazine HCl and Codeine Phosphate Oral Solution for the shortest duration that is consistent with individual patient treatment goals, monitor all patients regularly for the development of addiction or abuse, and refill only after reevaluation of the need for continued treatment. [ see Warnings and Precautions (5.1) ] Life-Threatening Respiratory Depression Serious, life-threatening, or fatal respiratory depression may occur with use of Promethazine HCl and Codeine Phosphate Oral Solution. Monitor for respiratory depression, especially during initiation of Promethazine HCl and Codeine Phosphate Oral Solution therapy or when used in patients at higher risk [ see Warnings and Precautions (5.2) ]. Accidental Ingestion Accidental ingestion of even one dose of Promethazine HCl and Codeine Phosphate Oral Solution, especially by children, can result in a fatal overdose of codeine [ see Warnings and Precautions (5.2) ]. Ultra-Rapid Metabolism of Codeine and Other Risk Factors
Contraindications
4 CONTRAINDICATIONS Promethazine HCl and Codeine Phosphate Oral Solution is contraindicated for: All children younger than 12 years of age [ see Warnings and Precautions (5.2 , 5.3 , 5.5) , Use in Specific Populations (8.4) ]. Postoperative pain management in children younger than 18 years of age following tonsillectomy and/or adenoidectomy [ see Warnings and Precautions (5.2 , 5.3) ]. Promethazine HCl and Codeine Phosphate Oral Solution is also contraindicated in patients with: Significant respiratory depression [ see Warnings and Precautions (5.2) ]. Acute or severe bronchial asthma in an unmonitored setting or in the absence of resuscitative equipment [ see Warnings and Precautions (5.6) ]. Known or suspected gastrointestinal obstruction, including paralytic ileus [ see Warnings and Precautions (5.11) ]. A history of an idiosyncratic reaction to promethazine or to other phenothiazines [ see Warnings and Precautions (5.14) ]. Concurrent use of monoamine oxidase inhibitors (MAOIs) or use of MAOIs within 14 days [ see Warnings and Precautions (5.16) , Drug Interactions (7.6) ]. Hypersensitivity to codeine, promethazine, or any of the inactive ingredients in Promethazine HCl and Codeine Phosphate Oral Solution [ see Adverse Reactions (6) ]. Persons known to be hypersensitive to certain other opioids may exhibit cross-reactivity to codeine. Children younger than 12 years of age. ( 4 ) Significant respiratory depression. ( 4 ) Acute or severe bronchial asthma in an unmonitored setting or in absence of resuscitative equipment. ( 4 ) Known or suspected gastrointestinal obstruction, including paralytic ileus. ( 4 ) Concurrent use of monoamine oxidase inhibitor (MAOI) therapy or within the last 14 days. ( 4 ) History of an idiosyncratic reaction to promethazine or to other phenothiazines. ( 4 ) Hypersensitivity to codeine or other opiates, promethazine, or any of the inactive ingredients in Promethazine HCl and Codeine Phosphate Oral Solution. ( 4 )
Pregnancy & Breastfeeding
8.1 Pregnancy Risk Summary Promethazine HCl and Codeine Phosphate Oral Solution is not recommended for use in pregnant women, including during or immediately prior to labor. Prolonged use of opioids during pregnancy may cause neonatal opioid withdrawal syndrome [ see Warnings and Precautions (5.19) , Clinical Considerations ]. There are no available data with Promethazine HCl and Codeine Phosphate Oral Solution use in pregnant women to inform a drug-associated risk for adverse developmental outcomes. Published studies with codeine have reported inconsistent findings and have important methodological limitations ( see Data ). There are reports of respiratory depression when codeine is used during labor and delivery ( see Clinical Considerations ). Reproductive toxicity studies have not been conducted with Promethazine HCl and Codeine Phosphate Oral Solution; however, studies are available with individual active ingredients ( see Data ). In animal reproduction studies, codeine administered by the oral route to pregnant rats during the period of organogenesis increased resorptions and decreased fetal weights at a dose approximately 25 times the maximum recommended human dose (MRHD) in the presence of maternal toxicity (see Data). For pregnant mice and rats that received promethazine at doses 0.2 and 3-6 times the MRHD, during various periods of gestation, there were findings of increased fetal resorptions and skeletal fragility, decreased pup weight, and developmental delays of pups ( see Data ). Based on the animal data, advise pregnant women of the potential risk to a fetus. The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. Clinical Consideration