Promethazine Hydrochloride And Codeine Phosphate
FDA Drug Information • Also known as: Promethazine Hydrochloride And Codeine Phosphate
- Brand Names
- Promethazine Hydrochloride And Codeine Phosphate
- Route
- ORAL
- Dosage Form
- SOLUTION
- Product Type
- HUMAN PRESCRIPTION DRUG
⚠ Boxed Warning (Black Box)
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 addition 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 for Life-Threatening Respiratory Depression in Children Life-threatening respiratory depression and death have occurred in children who received codeine. Most of the reported cases occurred following tonsillectomy and/or adenoidectomy, and many of the children had evidence of being an ultra-rapid metabolizer of codeine due to a CYP2D6 polymorphism [see Warnings and Precautions (5.3) ]. Promethazine HCl and Codeine Phosphate Oral Solution is contraindicated in children younger than 12 years of age and in children younger than 18 years of age following tonsillectomy and/or adenoidectomy [see Contraindications (4) ]. Avoid the use of Promethazine HCl and Codeine Phosphate Oral Solution in adolescents 12 to 18 years of age who have other risk factors that may increase their sensitivity to the respiratory depressant effects of codeine. Promethazine and Respiratory Depression in Children Postmarketing cases of respiratory depression, including fatalities have been reported with use of promethazine in pediatric patients. Children may be particularly sensitive to the additive respiratory depressant effects when promethazine is combined with other respiratory depressants, including codeine. [see Warnings and Precautions (5.4) ]. Risk of Medication Errors Ensure accuracy when prescribing, dispensing, and administering Promethazine HCl and Codeine Phosphate Oral Solution. Dosing errors can result in accidental overdose and death. Always use an accurate milliliter measuring device when measuring and administering Promethazine HCl and Codeine Phosphate Oral Solution [see Dosage and Administration (2.1) , Warnings and Precautions (5.7) ]. Interactions with Drugs Affecting Cytochrome P450 Isoenzymes The effects of concomitant use or discontinuation of cytochrome P450 3A4 inducers, 3A4 inhibitors, or 2D6 inhibitors with codeine are complex, requiring careful consideration of the effects on the parent drug, codeine, and the active metabolite, morphine. Avoid the use of Promethazine HCl and Codeine Phosphate Oral Solution in patients who are taking a CYP3A4 inhibitor, CYP3A4 inducer, or 2D6 inhibitor [see Warnings and Precautions (5.9) , Drug Interactions (7.1 , 7.2 , 7.3 ) ]. 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. Avoid the use of Promethazine HCl and Codeine Phosphate Oral Solution in patients taking benzodiazepines, other CNS depressants, or alcohol. [see Warnings and Precautions (5.10) , Drug Interactions (7.4) ] Neonatal Opioid Withdrawal Syndrome Promethazine HCl and Codeine Phosphate Oral Solution is not recommended for use in pregnant women [see Use in Specific Populations (8.1) ]. Prolonged use of Promethazine HCl and Codeine Phosphate Oral Solution during pregnancy can result in neonatal opioid withdrawal syndrome, which may be life-threatening if not recognized and treated, and requires management according to protocols developed by neonatology experts. If Promethazine HCl and Codeine Phosphate Oral Solution is used for a prolonged period in a pregnant woman, advise the patient of the risk of neonatal opioid withdrawal syndrome and ensure that appropriate treatment will be available [see Warnings and Precautions (5.20) ]. 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 See full prescribing information for complete boxed warning. Promethazine HCl and Codeine Phosphate Oral Solution exposes users to risks of addiction, abuse, and misuse, which can lead to overdose and death. Assess patient’s risk before prescribing and monitor closely for these behaviors and conditions. ( 5.1 ) Serious, life-threatening, or fatal respiratory depression may occur. Monitor closely, especially upon initiation or when used in patients at higher risk. ( 5.2 ) Accidental ingestion of Promethazine HCl and Codeine Phosphate Oral Solution, especially by children, can result in a fatal overdose of codeine. ( 5.2 ) Life-threatening respiratory depression and death have occurred in children who received codeine; most cases followed tonsillectomy and/or adenoidectomy, and many of the children had evidence of being an ultra-rapid metabolizer of codeine due to a CYP2D6 polymorphism. ( 5.3 ) Promethazine HCl and Codeine Phosphate Oral Solution is contraindicated in children younger than 12 years of age and in children younger than 18 years of age following tonsillectomy and/or adenoidectomy. ( 4 ) Avoid the use of Promethazine HCl and Codeine Phosphate Oral Solution in adolescents 12 to 18 years of age who have other risk factors that may increase their sensitivity to the respiratory depressant effects of codeine. Postmarketing cases of respiratory depression, including fatalities have been reported with use of promethazine in pediatric patients. Children may be particularly sensitive to the additive respiratory depressant effects when promethazine is combined with other respiratory depressants, including codeine. ( 5.4 ). Ensure accuracy when prescribing, dispensing, and administering Promethazine HCl and Codeine Phosphate Oral Solution. Dosing errors can result in accidental overdose and death. ( 2.1 , 5.7 ) The effects of concomitant use or discontinuation of cytochrome P450 3A4 inducers, 3A4 inhibitors, or 2D6 inhibitors with codeine are complex, requiring careful consideration of the effects on the parent drug, codeine, and the active metabolite, morphine. Avoid the use of Promethazine HCl and Codeine Phosphate Oral Solution in patients who are taking a CYP3A4 inhibitor, CYP3A4 inducer, or 2D6 inhibitor. ( 5.9 , 7.1 , 7.2 , 7.3 ) 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. Avoid the use of Promethazine HCl and Codeine Phosphate Oral Solution in patients taking benzodiazepines, other CNS depressants, or alcohol. ( 5.10 , 7.4 ) Promethazine HCl and Codeine Phosphate Oral Solution is not recommended for use in pregnant women. Prolonged use of Promethazine HCl and Codeine Phosphate Oral Solution during pregnancy can result in neonatal opioid withdrawal syndrome, which may be life-threatening if not recognized and treated. If Promethazine HCl and Codeine Phosphate Oral Solution is used for a prolonged period in a pregnant woman, advise the patient of the risk of neonatal opioid withdrawal syndrome and ensure that appropriate treatment will be available. ( 5.19 , 8.1 )
Description
11 DESCRIPTION Promethazine HCl and Codeine Phosphate Oral Solution contains codeine, an opioid agonist, and promethazine, a phenothiazine. Each 5 mL of Promethazine HCl and Codeine Phosphate Oral Solution contains 10 mg of codeine phosphate and 6.25 mg of promethazine hydrochloride for oral administration. Promethazine HCl and Codeine Phosphate Oral Solution has a pH between 4.4 and 5.4 and contains alcohol 7%. Promethazine HCl and Codeine Phosphate Oral Solution also contains the following inactive ingredients: artificial and natural raspberry flavor, ascorbic acid, citric acid, D&C Red 33, dehydrated alcohol, edetate disodium, FD&C Blue 1, glycerin, methylparaben, propylparaben, saccharin sodium, sodium benzoate, sodium citrate, sucrose and water. Codeine Phosphate The chemical name for codeine phosphate is 7,8-Didehydro-4, 5α-epoxy-3-methoxy-17-methylmorphinan-6α-ol phosphate (1:1) (salt) hemihydrate. Codeine is one of the naturally occurring phenanthrene alkaloids of opium derived from the opium poppy, it is classified pharmacologically as a narcotic analgesic. The phosphate salt of codeine occurs as white, needle-shaped crystals or white crystalline powder. Codeine phosphate is freely soluble in water and slightly soluble in alcohol. The molecular weight is 406.37. Its molecular formula is C 18 H 21 NO 3
What Is Promethazine Hydrochloride And Codeine Phosphate Used For?
1 INDICATIONS AND USAGE Promethazine HCl and Codeine Phosphate Oral Solution is indicated for the temporary relief of coughs and upper respiratory symptoms associated with allergy or the common cold in patients 18 years of age and older. Important Limitations of Use Not indicated for pediatric patients under 18 years of age [see Use in Specific Populations (8.4) ]. Contraindicated in pediatric patients under 12 years of age [see Contraindications (4) , Use in Specific Populations (8.4) ]. Contraindicated in pediatric patients 12 to 18 years of age after tonsillectomy or adenoidectomy [see Contraindications (4) , Use in Specific Populations (8.4) ]. Because of the risks of addiction, abuse, and misuse with opioids, even at recommended doses [see Warnings and Precautions (5.1) ], 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. Promethazine HCl and Codeine Phosphate Oral Solution is a combination of codeine, an opioid agonist; and promethazine, a phenothiazine, indicated for the temporary relief of cough and upper respiratory symptoms associated with allergy or the common cold in patients 18 years of age and older. ( 1 ) Important Limitations of Use ( 1 ) Not indicated for pediatric patients under 18 years of age. Because of the risks of addiction, abuse, and misuse with opioids, even at recommended doses, 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.
Dosage and Administration
2 DOSAGE AND ADMINISTRATION Adults 18 years of age and older : 5 mL every 4 to 6 hours as needed, not to exceed 6 doses (30 mL) in 24 hours. ( 2.2 ) Measure Promethazine HCl and Codeine Phosphate Oral Solution with an accurate milliliter measuring device. ( 2.1 , 5.7 ) Do not increase the dose or dosing frequency. ( 2.1 ) Prescribe for the shortest duration consistent with treatment goals. ( 2.3 ) Reevaluate patients with unresponsive cough in 5 days or sooner for possible underlying pathology. ( 2.3 ) Reevaluate patient prior to refilling. (2.3) 2.1 Important Dosage and Administration Instructions Administer Promethazine HCl and Codeine Phosphate Oral Solution by the oral route only. Always use an accurate milliliter measuring device when administering Promethazine HCl and Codeine Phosphate Oral Solution to ensure that the dose is measured and administered accurately. A household teaspoon is not an accurate measuring device and could lead to overdosage [see Warnings and Precautions (5.7) ] . For prescriptions where a measuring device is not provided, a pharmacist can provide an appropriate measuring device and can provide instructions for measuring the correct dose. Do not overfill. Rinse the measuring device with water after each use. Advise patients not to increase the dose or dosing frequency of Promethazine HCl and Codeine Phosphate Oral Solution because serious adverse events such as respiratory depression may occur with overdosage [see Warnings and Precautions (5.1) , Overdosage (10) ] . The dosage of Promethazine HCl and Codeine Phosphate Oral Solution should not be increased if cough fails to respond; an unresponsive cough should be reevaluated for possible underlying pathology [see Dosage and Administration (2.3) , Warnings and Precautions (5.6) ]. 2.2 Recommended Dosage Adults 18 years of age and older : 5 mL every 4 to 6 hours as needed, not to exceed 6 doses (30 mL) in 24 hours. 2.3 Monitoring, Maintenance, and Discontinuation of Therapy Prescribe Promethazine HCl and Codeine Phosphate Oral Solution for the shortest duration that is consistent with individual patient treatment goals [see Warnings and Precautions (5.1) ]. Monitor patients closely for respiratory depression, especially within the first 24-72 hours of initiating therapy [see Warnings and Precautions (5.2) ]. Reevaluate patients with unresponsive cough in 5 days or sooner for possible underlying pathology, such as foreign body or lower respiratory tract disease [see Warnings and Precautions (5.6) ]. If a patient requires a refill, reevaluate the cause of the cough and assess the need for continued treatment with Promethazine HCl and Codeine Phosphate Oral Solution, the relative incidence of adverse reactions, and the development of addiction, abuse, or misuse [see Warnings and Precautions (5.1) ]. Do not abruptly discontinue Promethazine HCl and Codeine Phosphate Oral Solution in a physically-dependent patient [see Drug Abuse and Dependence (9.3) ]. When a patient who...
Side Effects (Adverse Reactions)
6 ADVERSE REACTIONS The following serious adverse reactions are described, or described in greater detail, in other sections: Addiction, abuse, and misuse [see Warnings and Precautions (5.1), Drug Abuse and Dependence (9.3) ] Life-threatening respiratory depression [see Warnings and Precautions (5.2, 5.3, 5.4, 5.5, 5.6 ), Overdosage (10) ] Ultra-rapid metabolism of codeine and other risk factors for life-threatening respiratory depression in children [see Warnings and Precautions (5.3) ] Accidental overdose and death due to medication errors [see Warnings and Precautions (5.7) ] Decreased mental alertness with impaired mental and/or physical abilities [see Warnings and Precautions (5.8) ] Interactions with benzodiazepines and other CNS depressants [see Warnings and Precautions (5.10) ] Paralytic ileus, gastrointestinal adverse reactions [see Warnings and Precautions (5.11) ] Increased intracranial pressure [see Warnings and Precautions (5.12) ] Obscured clinical course in patients with head injuries [see Warnings and Precautions (5.12) ] Neuroleptic Malignant Syndrome [see Warnings and Precautions (5.13) ] Paradoxical reactions, including dystonias [see Warnings and Precautions (5.14) ] Seizures [see Warnings and Precautions (5.15) ] Interactions with MAOI [see Warnings and Precautions (5.16) ] Bone marrow suppression [see Warnings and Precautions (5.17) ] Severe hypotension [see Warnings and Precautions (5.18) ] Neonatal Opioid Withdrawal Syndrome [see Warnings and Precautions (5.19) ] Adrenal insufficiency [see Warnings and Precautions (5.20) ] The following adverse reactions have been identified during clinical studies, in the literature, or during post-approval use of codeine and/or promethazine. Because these reactions may be reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. The most common adverse reactions to Promethazine HCl and Codeine Phosphate Oral Solution include: Sedation (somnolence, mental clouding, lethargy), impaired mental and physical performance, lightheadedness, dizziness, headache, dry mouth, nausea, vomiting, constipation, shortness of breath, sweating. Other reactions include: Anaphylaxis : Anaphylaxis has been reported with codeine, one of the ingredients in Promethazine HCl and Codeine Phosphate Oral Solution. Body as a whole : Coma, death, fatigue, falling injuries, lethargy. Cardiovascular : Peripheral edema, increased blood pressure, decreased blood pressure, tachycardia, chest pain, palpitation, syncope, orthostatic hypotension, prolonged QT interval, hot flush. Central Nervous System : Ataxia, diplopia, facial dyskinesia, insomnia, migraine, increased intracranial pressure, seizure, tinnitus, tremor, vertigo. Dermatologic : Flushing, hyperhidrosis, photosensitivity, pruritus, rash, urticaria. Endocrine/Metabolic : Cases of serotonin syndrome, a potentially life-threatening condition, have been reported during concomitant use of opioids with serotonergic drugs. Cases of adrenal insufficiency have been reported with opioid use, more often following greater than one month of use. Cases of androgen deficiency have occurred with chronic use of opioids [see Clinical Pharmacology (12.2) ]. Gastrointestinal : Abdominal pain, bowel obstruction, decreased appetite, diarrhea, difficulty swallowing, dry mouth, GERD, indigestion, jaundice, pancreatitis, paralytic ileus, biliary tract spasm (spasm of the sphincter of Oddi). Genitourinary : Urinary tract infection, ureteral spasm, spasm of vesicle sphincters, urinary retention. Hematologic : Bone marrow suppression, agranulocytosis, aplastic anemia, and thrombocytopenia have been reported. Laboratory : Increases in serum amylase. Musculoskeletal : Arthralgia, backache, muscle spasm. Ophthalmic : Blurred vision, miosis (constricted pupils), visual disturbances. Paradoxical Reactions : Dystonias, torticollis, tongue protrusion,...
Drug Interactions
7 DRUG INTERACTIONS No specific drug interaction studies have been conducted with Promethazine HCl and Codeine Phosphate Oral Solution. Serotonergic Drugs : Concomitant use may result in serotonin syndrome. Discontinue if serotonin syndrome is suspected. ( 7.5 ) Muscle relaxants : Avoid concomitant use. ( 7.7 ) Diuretics : Codeine may reduce the efficacy of diuretics. Monitor for reduced effect. ( 7.8 ) Anticholinergic drugs : Concurrent use may cause paralytic ileus. ( 5.11 , 7.9 ) 7.1 Inhibitors of CYP3A4 The concomitant use of Promethazine HCl and Codeine Phosphate Oral Solution with CYP3A4 inhibitors, such as macrolide antibiotics (e.g., erythromycin), azole-antifungal agents (e.g. ketoconazole), or protease inhibitors (e.g., ritonavir), may result in an increase in codeine plasma concentrations with subsequently greater metabolism by cytochrome CYP2D6, resulting in greater morphine levels, which could increase or prolong adverse reactions and may cause potentially fatal respiratory depression, particularly when an inhibitor is added after a stable dose of Promethazine HCl and Codeine Phosphate Oral Solution is achieved [see Warnings and Precautions (5.9) ]. After stopping a CYP3A4 inhibitor, as the effects of the inhibitor decline, it may result in lower codeine levels, greater norcodeine levels, and less metabolism via CYP2D6 with resultant lower morphine levels [see Clinical Pharmacology (12.3) ], resulting in decreased opioid efficacy or a withdrawal syndrome in patients who had developed physical dependence to codeine. Avoid the use of Promethazine HCl and Codeine Phosphate Oral Solution while taking a CYP3A4 inhibitor. If concomitant use is necessary, monitor patients for respiratory depression and sedation at frequent intervals. 7.2 CYP3A4 Inducers The concomitant use of Promethazine HCl and Codeine Phosphate Oral Solution and CYP3A4 inducers, such as rifampin, carbamazepine, or phenytoin, can result in lower codeine levels, greater norcodeine levels, and less metabolism via 2D6 with resultant lower morphine levels [see Clinical Pharmacology (12.3) ], resulting in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence [see Warnings and Precautions (5.9) ]. After stopping a CYP3A4 inducer, as the effects of the inducer decline, codeine plasma concentrations may increase with subsequently greater metabolism by cytochrome CYP2D6, resulting in greater morphine levels [see Clinical Pharmacology (12.3) ], which could increase or prolong both the therapeutic effects and adverse reactions, and may cause serious respiratory depression. Avoid the use of Promethazine HCl and Codeine Phosphate Oral Solution in patients who are taking CYP3A4 inducers. If concomitant use of a CYP3A4 inducer is necessary, follow the patient for reduced efficacy. 7.3 Inhibitors of CYP2D6 Codeine is metabolized by CYP2D6 to form morphine. The concomitant use of Promethazine HCl and Codeine Phosphate Oral Solution and...
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 and 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 Considerations...
Overdosage
10 OVERDOSAGE Clinical Presentation Codeine Acute overdose with codeine is characterized by respiratory depression (a decrease in respiratory rate and/or tidal volume, Cheyne-Stokes respiration, cyanosis), extreme somnolence progressing to stupor or coma, skeletal muscle flaccidity, cold and clammy skin, constricted pupils, and, in some cases, pulmonary edema, bradycardia, partial or complete airway obstruction, atypical snoring, hypotension, circulatory collapse, cardiac arrest, and death. Codeine may cause miosis, even in total darkness. Pinpoint pupils are a sign of opioid overdose but are not pathognomonic (e.g., pontine lesions of hemorrhagic or ischemic origin may produce similar findings). Marked mydriasis rather than miosis may be seen with hypoxia in overdose situations [see Clinical Pharmacology (12.2) ]. Promethazine Signs and symptoms of overdosage with promethazine 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 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, tachycardia, hallucinations, gastrointestinal symptoms, convulsions, urinary retention, cardiac arrhythmias and coma) may be observed. Impaired secretion from sweat glands following toxic doses of drugs with anticholinergic side effects may predispose to hyperthermia. Treatment of Overdose Treatment of overdosage is driven by the overall clinical presentation, and consists of discontinuation of Promethazine HCl and Codeine Phosphate Oral Solution together with institution of...
How Supplied
16 HOW SUPPLIED/STORAGE AND HANDLING Promethazine HCl and Codeine Phosphate Oral Solution, 6.25 mg and 10 mg per 5 mL, is a clear, purple solution, supplied as: NDC Number Size 70752-139-06 4 fl. oz. (118 mL) bottle 70752-139-12 16 fl. oz. (473 mL) bottle Keep bottles tightly closed. Store at 20° to 25°C (68° to 77°F). [See USP Controlled Room Temperature.] Protect from light. Dispense in tight, light-resistant container (USP/NF) with a child-resistant closure. Ensure that patients have an oral dosing dispenser that measures the appropriate volume in milliliters. Counsel patients on how to utilize an oral dosing dispenser and correctly measure the oral suspension as prescribed.
About This Information
This drug information is sourced from FDA-approved labeling via the openFDA database. It is intended for educational and reference purposes only. This is not medical advice. Always consult your healthcare provider before making decisions about medication. Drug information may be updated by the FDA; check with your pharmacist for the most current information.
What are side effects?
Side effects are unwanted reactions that can occur when taking a medication. They range from mild (headache, nausea) to severe (allergic reactions, organ damage). Not everyone experiences side effects, and severity varies. Report any concerning side effects to your doctor.
What are drug interactions?
Drug interactions occur when a medication is affected by another drug, food, or supplement. Interactions can make medications less effective or cause dangerous side effects. Always tell your doctor about all medications and supplements you take.