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Promethazine with Codeine: Uses, Dosage, and Side Effects
Oct
Written by: David W., PharmD
Medically reviewed by: Microdose Vault, MD
Last medically reviewed: October, 2026]
Last updated: [October, 2026]
Promethazine with codeine is a prescription cough medication that combines promethazine, a sedating antihistamine, with codeine, an opioid cough suppressant. It provides temporary relief of cough and upper respiratory symptoms associated with allergies or the common cold in adults 18 and older. It is federally classified as a Schedule V controlled substance and carries serious risks of respiratory depression and addiction.
Key Medical Facts About Promethazine with Codeine
Promethazine with codeine is an FDA-approved prescription cough medication for adults 18 and older. It combines codeine phosphate, an opioid cough suppressant, with promethazine hydrochloride, a sedating antihistamine, to relieve cough and upper respiratory symptoms associated with allergies or the common cold.
Classified as a Schedule V controlled substance under the Controlled Substances Act, the medication carries serious risks, including respiratory depression, addiction, overdose, and dangerous interactions with alcohol or benzodiazepines. People who are CYP2D6 ultra-rapid metabolizers face an increased risk of opioid toxicity. Common side effects include drowsiness, dizziness, nausea, and constipation. Non-opioid alternatives include dextromethorphan and benzonatate. Use of the medication requires a medical evaluation and a valid prescription.
This article is based on current FDA prescribing information and guidance from recognized medical and regulatory authorities, including the FDA, the DEA, the CDC, and the Clinical Pharmacogenetics Implementation Consortium. It is intended for general educational purposes and does not replace individualized medical advice from a licensed healthcare provider.
What Is Promethazine with Codeine?
Promethazine with codeine oral solution is a combination prescription medication sold under generic labeling and historically marketed under brand names such as Phenergan with Codeine. Each dose contains two active ingredients with different mechanisms of action.
Promethazine hydrochloride belongs to the phenothiazine class of drugs and works primarily by blocking H1 histamine receptors. It produces sedation, reduces allergy symptoms, and causes anticholinergic effects such as dry mouth and drowsiness. It is also used independently as an antiemetic and sedative in other clinical settings.
Codeine phosphate is an opioid agonist that suppresses the cough reflex through action on the central nervous system. A portion of each codeine dose is metabolized by the liver enzyme CYP2D6 into morphine, which contributes to opioid exposure and toxicity risk. Genetic differences in CYP2D6 activity can substantially affect how an individual responds to codeine. Current FDA-approved labeling for this combination product is available through the National Library of Medicine’s DailyMed database.
Promethazine with Codeine Uses
Promethazine with codeine is indicated for temporary relief of cough and upper respiratory symptoms associated with allergies or the common cold in adults 18 and older. It is not approved for treating cough related to lower respiratory conditions such as asthma or emphysema, and the plain promethazine-codeine formulation does not contain a decongestant.
The medication does not treat the underlying cause of a respiratory infection. It is intended for short-term symptomatic relief rather than long-term management of chronic cough.
What Are the Different Types of Promethazine Syrup?
Promethazine is formulated into several distinct products, and confusing them can lead to unintended opioid exposure or missed therapeutic effect. Syrup color is not a reliable way to identify which ingredients a product contains.
| Medication | Ingredients | Contains an Opioid | Typical Purpose |
|---|---|---|---|
| Plain promethazine | Promethazine | No | Allergy symptoms, nausea, and other labeled uses |
| Promethazine DM | Promethazine and dextromethorphan | No | Cough relief |
| Promethazine with codeine | Promethazine and codeine | Yes | Cough and upper respiratory symptoms |
| Promethazine VC with codeine | Promethazine, codeine, and phenylephrine | Yes | Cough with selected nasal congestion |
Patients should confirm the exact ingredients of any promethazine product with a pharmacist before use, particularly when refilling a prescription from a different manufacturer.
Promethazine with Codeine Dosage and Administration
The prescribing clinician determines whether promethazine with codeine is appropriate and provides individualized dosing instructions based on the patient’s clinical condition, medication history, and risk factors. Patients should use the calibrated measuring device provided with the prescription rather than household spoons, since inaccurate dosing increases the risk of overdose.
The medication should be taken exactly as prescribed. Patients should not exceed the recommended dose or frequency, and they should avoid combining it with other sedating drugs, muscle relaxants, or alcohol, since all of these substances depress the central nervous system.
How Long Does Promethazine with Codeine Take to Work?
Promethazine with codeine typically begins relieving cough symptoms within 30 to 60 minutes of oral administration, and effects generally last 4 to 6 hours. Onset and duration vary based on an individual’s metabolism, liver function, and other medications. Patients should follow their prescribed dosing schedule rather than adjusting timing or amount based on symptom severity.
Promethazine Codeine Side Effects
Common side effects include drowsiness, dizziness, sedation, nausea, vomiting, constipation, dry mouth, and impaired coordination. These effects can impair the ability to drive or operate machinery, and patients are typically advised to avoid these activities until they understand how the medication affects them.
More serious adverse effects include respiratory depression, severe sedation, low blood pressure, and paradoxical excitation in some patients, particularly children. Anticholinergic effects from promethazine, such as blurred vision and urinary retention, can also occur.
Anyone experiencing slowed or difficult breathing, extreme drowsiness, confusion, or an inability to be awakened should receive emergency medical attention immediately, since these signs can indicate a potentially life-threatening overdose.
Promethazine with Codeine FDA Boxed Warnings
The U.S. Food and Drug Administration has issued safety communications addressing opioid-containing prescription cough and cold medications, including formulations combined with promethazine. In 2018, the FDA required labeling changes restricting these products to adults 18 and older because of the risk of slowed or difficult breathing in children, a risk that can be fatal. Details are available directly from the FDA’s drug safety communication on prescription opioid cough and cold medicines.
Boxed warning language on opioid-containing products generally addresses several areas of risk, including addiction and misuse, life-threatening respiratory depression, accidental exposure in children, increased toxicity in CYP2D6 ultra-rapid metabolizers, dangerous interactions with other central nervous system depressants, and neonatal opioid withdrawal syndrome following prolonged use during pregnancy. The precise warning language depends on the current FDA-approved label for the specific formulation dispensed, which can be confirmed through DailyMed.
Promethazine with Codeine Contraindications
Promethazine with codeine is not approved for use in patients younger than 18 years. It is also contraindicated in certain patients with significant respiratory depression, acute or severe bronchial asthma in an unmonitored setting, gastrointestinal obstruction, or known hypersensitivity to either active ingredient. Additional precautions may apply to patients with obstructive sleep apnea, impaired liver or kidney function, or a history of substance use disorder.
Patients should review their full medical history with a prescribing clinician, since individual contraindications and precautions depend on the current product label and the patient’s specific health conditions.
How CYP2D6 Affects Codeine Metabolism
Codeine itself is a relatively weak opioid. The liver enzyme CYP2D6 converts a portion of each dose into morphine, which is primarily responsible for codeine’s opioid effects. The rate of this conversion varies significantly between individuals based on genetic differences in CYP2D6 activity, and a smaller portion of codeine metabolism also occurs through the CYP3A4 pathway.
People classified as CYP2D6 ultra-rapid metabolizers convert codeine into morphine more quickly and in greater amounts than typical metabolizers, which increases the risk of opioid toxicity and potentially fatal respiratory depression, even at standard doses. This risk has been documented most clearly in children and in breastfeeding infants whose mothers are ultra-rapid metabolizers. The Clinical Pharmacogenetics Implementation Consortium publishes clinical guidelines recommending that codeine be avoided in patients with known CYP2D6 ultra-rapid metabolizer status.
Promethazine with Codeine Drug Interactions
Promethazine with codeine can interact with a range of other medications and substances. Combining it with alcohol, benzodiazepines, sedative-hypnotics, muscle relaxants, or other opioids substantially increases the risk of profound sedation, respiratory depression, coma, and death.
Monoamine oxidase inhibitors can interact seriously with opioid-containing medications, and patients must inform their prescriber about current or recent MAOI use. Certain antidepressants may also alter codeine metabolism or contribute to adverse effects, including an increased risk of serotonin-related symptoms when combined with other serotonergic drugs. The precise interaction warnings and restrictions depend on the product’s current FDA-approved labeling, and patients should provide their healthcare provider and pharmacist with a complete list of current medications and supplements before starting treatment.
Promethazine DM vs. Promethazine with Codeine
| Feature | Promethazine DM | Promethazine with Codeine |
|---|---|---|
| Cough suppressant ingredient | Dextromethorphan | Codeine phosphate |
| Controlled substance status | Not federally controlled | Schedule V controlled substance |
| Opioid dependence risk | No | Yes |
| Respiratory depression risk | Lower | Higher, particularly with other CNS depressants |
| Typical prescribing restriction | Available by prescription | Restricted to adults 18 and older |
Promethazine DM contains dextromethorphan, a non-opioid cough suppressant, while promethazine with codeine contains an opioid. Both formulations share the same antihistamine component and similar sedative effects, but they differ substantially in dependence risk, adverse effect profile, and controlled substance status.
Is Promethazine with Codeine a Controlled Substance?
Promethazine with codeine oral solution is federally classified as a Schedule V controlled substance under the Controlled Substances Act when it meets specific formulation and concentration requirements. The Drug Enforcement Administration maintains the federal drug scheduling system, which categorizes controlled substances based on accepted medical use and potential for abuse.
Schedule V is the least restrictive category for controlled substances, but it still reflects recognized risks of misuse, dependence, and diversion associated with codeine. State laws governing prescribing, dispensing, and monitoring of this medication may be more restrictive than federal requirements, and many states track prescriptions through a Prescription Drug Monitoring Program.
Prescription Requirements and Telehealth
Promethazine with codeine requires a valid prescription and must be dispensed according to applicable federal and state controlled-substance laws. Telehealth prescribing of controlled substances is subject to federal rules, including requirements established under the Ryan Haight Act, as well as current DEA regulations and individual state requirements, which can change over time. Patients should obtain the medication only through a licensed prescriber and a legitimate, licensed pharmacy.
Addiction, Dependence, and Withdrawal
Because promethazine with codeine contains an opioid, repeated use can lead to physical dependence, tolerance, and in some cases opioid use disorder. Physical dependence can develop even when the medication is taken as prescribed, and it is distinct from addiction, which involves compulsive use despite harmful consequences.
Withdrawal symptoms after stopping codeine use can include anxiety, irritability, muscle aches, sweating, nausea, and insomnia. Patients who have taken the medication for an extended period should not stop abruptly without consulting a healthcare provider, since a gradual, medically supervised taper can reduce the severity of withdrawal.
Promethazine with codeine has also been associated with recreational misuse, sometimes referred to by street terms such as lean, purple drank, or sizzurp, which typically involves combining the syrup with soda and sometimes candy. This practice carries substantial risks of overdose and death, particularly when combined with alcohol or other depressants.
Anyone experiencing cravings, loss of control over use, or withdrawal symptoms should consult a healthcare professional for evaluation. The Substance Abuse and Mental Health Services Administration provides resources for individuals seeking treatment for opioid use disorder.
Signs of Promethazine with Codeine Overdose
An overdose involving promethazine with codeine can cause life-threatening respiratory depression. Warning signs include extremely slow or shallow breathing, bluish or gray lips or fingernails, pinpoint pupils, severe drowsiness or unresponsiveness, and loss of consciousness.
Anyone who suspects an overdose should call 911 immediately. Naloxone, available under the brand name Narcan, can temporarily reverse the opioid component’s effects and should be administered if available while waiting for emergency responders. Naloxone does not reverse the sedative effects of promethazine, so continued medical monitoring is necessary even after naloxone is given. The Centers for Disease Control and Prevention provides public information on recognizing and responding to opioid overdose.
Is Promethazine with Codeine Safe During Pregnancy or Breastfeeding?
Promethazine with codeine can expose a fetus or a breastfed infant to opioid-related risks. Prolonged use during pregnancy may cause neonatal opioid withdrawal syndrome, a condition requiring medical treatment in the newborn. Breastfeeding is generally not recommended during treatment because codeine and its metabolites may cause excessive sedation and respiratory depression in infants, particularly if the mother is a CYP2D6 ultra-rapid metabolizer.
Patients who are pregnant, planning a pregnancy, or breastfeeding should discuss the risks and alternatives with a healthcare provider before starting this medication.
How Long Does Promethazine with Codeine Stay in Your System?
Codeine generally has an elimination half-life of approximately three hours, while promethazine remains in the body somewhat longer. Detection times in urine, blood, or other testing depend on the dose taken, frequency of use, individual metabolism, and kidney or liver function. The presence of a drug in a test does not necessarily indicate current impairment.
Non-Opioid Alternatives to Promethazine with Codeine
Because of the risks associated with opioid-containing cough medications, many patients are prescribed non-opioid alternatives for cough and cold symptoms. Dextromethorphan is a widely used non-opioid antitussive found in many over-the-counter products. Benzonatate is a prescription non-opioid cough suppressant that works by numbing stretch receptors in the lungs and airways. Guaifenesin, an expectorant, is sometimes used alongside these medications to help thin mucus. Patients should discuss the most appropriate option for their symptoms and medical history with a healthcare provider.
Frequently Asked Questions
What is promethazine with codeine used for?
Promethazine with codeine is prescribed for temporary relief of cough and upper respiratory symptoms associated with allergies or the common cold in adults 18 and older. It combines an opioid cough suppressant with a sedating antihistamine and does not treat the underlying cause of a respiratory infection.
Is promethazine with codeine a controlled substance?
Yes. Promethazine with codeine oral solution is federally classified as a Schedule V controlled substance when it meets applicable formulation requirements. Schedule V medications have accepted medical uses but remain regulated because of their potential for misuse and dependence. State prescribing and dispensing rules may be stricter than federal law.
What are the most common side effects of promethazine with codeine?
Common side effects include drowsiness, dizziness, nausea, vomiting, constipation, dry mouth, and impaired coordination. Serious complications include respiratory depression, severe sedation, low blood pressure, and overdose. Slow breathing, unconsciousness, or an inability to wake the person requires immediate emergency medical attention.
What is the difference between promethazine DM and promethazine with codeine?
Promethazine DM contains promethazine and dextromethorphan, a non-opioid cough suppressant. Promethazine with codeine contains promethazine and codeine, an opioid. Both suppress coughing, but the codeine formulation carries additional risks of opioid dependence, respiratory depression, and overdose.
How long does promethazine with codeine take to work?
Promethazine with codeine typically begins relieving cough symptoms within 30 to 60 minutes of oral administration, and effects generally last 4 to 6 hours. Response time varies based on metabolism, underlying health conditions, and other medications. Patients should follow their prescribed dosing instructions.
Why is promethazine with codeine not recommended for children?
FDA-approved prescription opioid cough medications containing codeine are restricted to adults 18 and older because children can metabolize codeine unpredictably, which can lead to potentially fatal respiratory depression. Certain CYP2D6 genetic variations increase the rate of morphine formation, making codeine exposure particularly dangerous in children.
Can you take promethazine with codeine and alcohol?
No. Alcohol should be avoided while taking promethazine with codeine. Both substances depress the central nervous system, and combining them increases the risk of extreme sedation, impaired consciousness, respiratory depression, overdose, and death. Combining codeine with benzodiazepines or other sedatives poses similar dangers.
Can promethazine with codeine cause addiction?
Yes. Promethazine with codeine contains an opioid that can cause physical dependence, tolerance, misuse, and addiction, and repeated use increases these risks. Anyone experiencing cravings, loss of control over use, or withdrawal symptoms should consult a healthcare professional for evaluation and appropriate treatment.
How long does promethazine with codeine stay in your system?
Codeine has an elimination half-life of approximately three hours, while promethazine remains in the body somewhat longer. Detection time depends on the dose, frequency of use, individual metabolism, and kidney or liver function, and a positive drug test does not necessarily indicate current impairment.
Can promethazine with codeine be prescribed online?
Telehealth prescribing of controlled substances, including promethazine with codeine, is subject to federal requirements such as those established under the Ryan Haight Act, along with current DEA regulations and state laws. Patients should obtain the medication only through a licensed prescriber and a legitimate, licensed pharmacy.
Is promethazine with codeine safe during pregnancy or breastfeeding?
Promethazine with codeine is generally not recommended during pregnancy or breastfeeding because of opioid-related risks to the fetus or infant, including neonatal opioid withdrawal syndrome and infant sedation. Patients who are pregnant or breastfeeding should consult a healthcare provider before using this medication.
Conclusion
Promethazine with codeine is an FDA-approved prescription medication for temporary relief of cough and upper respiratory symptoms associated with allergies or the common cold in adults. Its potential benefits must be weighed against serious risks, including respiratory depression, overdose, drug interactions, and dependence. Understanding its FDA warnings, controlled substance status, contraindications, and potential for misuse allows patients and caregivers to use it safely and to recognize when a non-opioid alternative or professional medical evaluation may be more appropriate.
About this article
This article was written by [Author Name], PharmD, and medically reviewed by [Reviewer Name], MD, for accuracy and alignment with current FDA prescribing information. Sources referenced include the U.S. Food and Drug Administration, the Drug Enforcement Administration, the Centers for Disease Control and Prevention, the Substance Abuse and Mental Health Services Administration, and the Clinical Pharmacogenetics Implementation Consortium. Content is reviewed periodically and updated to reflect changes in FDA labeling, DEA scheduling, or clinical guidance. This article is for informational purposes only and is not a substitute for professional medical advice, diagnosis, or treatment. Always consult a licensed healthcare provider regarding any medical condition or before starting, stopping, or changing a medication.
