Promethazine hydrochloride and codeine phosphate

What Promethazine hydrochloride and codeine phosphate is used for

Quoted from the “Indications and Usage” section of the FDA-approved label.

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 […]. Contraindicated in pediatric patients under 12 years of age […]. …

— FDA label: Promethazine Hydrochloride and Codeine Phosphate, Cosette Pharmaceuticals, Inc., effective December 18, 2025. Read the full label on DailyMed →

Label quoted: the one for the most common form (solution, oral), Promethazine Hydrochloride and Codeine Phosphate, Cosette Pharmaceuticals, Inc.; it covers 1 product in the FDA NDC Directory. The side effects, interactions, dosage and pregnancy quotes below come from this same label.

The FDA has 5 labels for products of this medicine (different makers and forms); uses can differ between them. Check the label that comes with your own medicine.

This page is not medical advice. Talk to your doctor or pharmacist before you start, stop or change any medicine.

Boxed warning

A boxed warning (“black box”) is the FDA’s strongest warning on a drug label, for serious or life-threatening risks.

This label has a boxed warning. Read it on the full label →

5 of 5 FDA labels for this medicine have a boxed warning.

Promethazine hydrochloride and codeine phosphate boxed warning: what the label says

Quoted from the boxed warning of the FDA-approved label.

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.

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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 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.

— FDA label: Promethazine Hydrochloride and Codeine Phosphate, Cosette Pharmaceuticals, Inc., effective December 18, 2025. This is part of the section. Read the full label on DailyMed →

Promethazine hydrochloride and codeine phosphate side effects

Quoted from the “Adverse Reactions” section of the FDA-approved label. Tell your doctor about any side effect that worries you.

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 …

— FDA label: Promethazine Hydrochloride and Codeine Phosphate, Cosette Pharmaceuticals, Inc., effective December 18, 2025. This is part of the section. Read the full label on DailyMed →

Promethazine hydrochloride and codeine phosphate drug interactions

Quoted from the “Drug Interactions” section of the FDA-approved label. Tell your pharmacist about every medicine, vitamin and herbal product you take.

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.

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(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 CYP2D6 inhibitors, such as paroxetine, fluoxetine, bupropion, or quinidine, can increase the plasma concentration of codeine, but can decrease the plasma concentration of active metabolite morphine, which could result in reduced efficacy [see Clinical Pharmacology (12.3)].

— FDA label: Promethazine Hydrochloride and Codeine Phosphate, Cosette Pharmaceuticals, Inc., effective December 18, 2025. This is part of the section. Read the full label on DailyMed →

Promethazine hydrochloride and codeine phosphate dosage

Quoted from the “Dosage and Administration” section of the FDA-approved label. Your own dose is the one your doctor prescribes: do not change it on your own.

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.

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(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)].

— FDA label: Promethazine Hydrochloride and Codeine Phosphate, Cosette Pharmaceuticals, Inc., effective December 18, 2025. This is part of the section. Read the full label on DailyMed →

Promethazine hydrochloride and codeine phosphate in pregnancy

Quoted from the pregnancy part of the FDA-approved label. Ask your doctor before you take any medicine while pregnant or planning a 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].

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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 Fetal/Neonatal Adverse Reactions Prolonged use of opioid analgesics during pregnancy for medical or nonmedical purposes can result in physical dependence in the neonate and neonatal opioid withdrawal syndrome shortly after birth. Neonatal opioid withdrawal syndrome presents as irritability, hyperactivity and abnormal sleep pattern, high pitched cry, tremor, vomiting, diarrhea and failure to gain weight. The onset, duration, and severity of neonatal opioid withdrawal syndrome vary based on the specific opioid used, duration of use, timing and amount of last maternal use, and rate of elimination of the drug by the newborn. Observe newborns for symptoms of neonatal opioid withdrawal syndrome and manage accordingly [see Warnings and Precautions (5.19)]. Labor or Delivery Opioids cross the placenta and may produce respiratory depression and psycho-physiologic effects in neonates. An opioid antagonist, such as naloxone, must be available for reversal of opioid-induced respiratory depression in the neonate.

— FDA label: Promethazine Hydrochloride and Codeine Phosphate, Cosette Pharmaceuticals, Inc., effective December 18, 2025. This is part of the section. Read the full label on DailyMed →

When Promethazine hydrochloride and codeine phosphate should not be used

Quoted from the “Contraindications” section of the FDA-approved label.

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)].

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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)

— FDA label: Promethazine Hydrochloride and Codeine Phosphate, Cosette Pharmaceuticals, Inc., effective December 18, 2025. Read the full label on DailyMed →

Promethazine hydrochloride and codeine phosphate overdose

Quoted from the “Overdosage” section of the FDA-approved label. If someone may have taken too much, call Poison Help at 1-800-222-1222 (or 911 in an emergency).

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, hypoglycemia, circulatory collapse, cardiac arrest, and death.

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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 appropriate therapy. Give primary attention to the reestablishment of adequate respiratory exchange through provision of a patent and protected airway and the institution of assisted or controlled ventilation. Employ other supportive measures (including oxygen and vasopressors) in the management of circulatory shock and pulmonary edema as indicated. Cardiac arrest or arrhythmias will require advanced life-support techniques. Gastric emptying may be useful in removing unabsorbed drug. The opioid antagonists, naloxone and nalmefene, are specific antidotes for respiratory depression resulting from opioid overdose. For clinically significant respiratory or circulatory depression secondary to codeine overdose, administer an opioid antagonist. An antagonist should not be administered in the absence of clinically significant respiratory depression. Because the duration of opioid reversal is expected to be less than the duration of action of codeine in Promethazine HCl and Codeine Phosphate Oral Solution, carefully monitor the patient until spontaneous respiration is reliably reestablished. If the response to an opioid antagonist is suboptimal or only brief in nature, administer additional antagonist as directed by the product’s prescribing information.

— FDA label: Promethazine Hydrochloride and Codeine Phosphate, Cosette Pharmaceuticals, Inc., effective December 18, 2025. This is part of the section. Read the full label on DailyMed →

Forms and how it is given

Same medicine, other forms and combinations

Prescription medicine pages on this site that share an active ingredient with this one, from the FDA NDC Directory. A combination is a different medicine: ask your pharmacist before you switch.

Other medicines with one of these active ingredients

• Promethazine, phenylephrine, codeine1 product
• Promethazine hydrochloridePhenergan, Promethegan · 129 products
• Acetaminophen and codeine phosphate74 products
• Promethazine hydrochloride and dextromethorphan hydrobromidePromethazine Dm · 18 products
• Butalbital, acetaminophen, caffeine and codeine phosphate8 products
• Codeine sulfate6 products
• Butalbital, aspirin, caffeine and codeine phosphateAscomp with Codeine · 4 products
• Promethazine hydrochloride and phenylephrine hydrochloride2 products
• Codeine phosphate and chlorpheniramine maleateTuxarin · 1 product

Companies that list this medicine

Labelers in the FDA NDC Directory: the company named on the package (maker or distributor), with the number of prescription products.

• Quagen Pharmaceuticals LLC1 product
• Cosette Pharmaceuticals, Inc.1 product
• Cranbury Pharmaceuticals, LLC1 product
• Bryant Ranch Prepack1 product
• Atlantic Biologicals Corp.1 product

FDA approval history

• ANDA: Abbreviated New Drug Application: how a generic version is approved.

Generic approvals (2)

• ANDA200386Cosette Pharms Nc · June 29, 2012
• ANDA214238Quagen · October 8, 2020

Shortage status

The FDA drug shortage list does not show these products.

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Recalls

No recall linked to these products (by their NDC code) appears in the FDA enforcement reports.

Official identifiers

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• Cosette Pharmaceuticals, Inc.Maker or distributor
• Cranbury Pharmaceuticals, LLCMaker or distributor
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Sources

1. FDA-approved label on DailyMed (National Library of Medicine) — Promethazine Hydrochloride and Codeine Phosphate, Cosette Pharmaceuticals, Inc., effective December 18, 2025; via openFDA, FDA data exported October 30, 2026, retrieved October 31, 2026
2. NDC Directory (openFDA) — U.S. Food and Drug Administration (FDA), FDA data exported October 30, 2026, retrieved October 31, 2026
3. Drugs@FDA (openFDA) — U.S. Food and Drug Administration (FDA), FDA data exported October 30, 2026, retrieved October 31, 2026
4. Drug recall enforcement reports (openFDA) — U.S. Food and Drug Administration (FDA), FDA data exported October 27, 2026, retrieved October 31, 2026
5. Drug shortages (openFDA) — U.S. Food and Drug Administration (FDA), FDA data exported October 30, 2026, retrieved October 31, 2026

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