Acetaminophen and Codeine
Generic name: acetaminophen and codeine phosphate · Brand names: Tylenol with Codeine (#3, #4), Capital & Codeine, Codrix, Empracet, Papa-deine, Phenaphen with Codeine, Proval #3 (all marked no longer on the market)
Quick facts
Drug class
The tablet combines acetaminophen, a non-opiate, non-salicylate analgesic and antipyretic, with codeine phosphate, a narcotic (opioid) analgesic.
Section
DESCRIPTION (Eywa label)
Source text (exact source wording)
Codeine phosphate, ... a white crystalline powder, is a narcotic analgesic and antitussive. | Acetaminophen, 4'-hydroxyacetanilide, ... is a non-opiate, non-salicylate analgesic and antipyretic.
Rx or otc
Rx (opioid analgesic; tablets carry the CIII designation on the SpecGx label title)
Controlled schedule
Section
WARNINGS, Addiction, Abuse, and Misuse (Eywa label); the SpecGx label page title also shows CIII
Value
Schedule III (tablets)
Source text (exact source wording)
Acetaminophen and codeine phosphate tablets contain codeine. Codeine in combination with acetaminophen, is a Schedule III controlled substance.
Forms and strengths
- Tablets: acetaminophen 300 mg / codeine phosphate 15 mg
- Tablets: acetaminophen 300 mg / codeine phosphate 30 mg
- Tablets: acetaminophen 300 mg / codeine phosphate 60 mg
Generic available
Value
yes
Source
DailyMed Eywa Pharma label, Marketing Category ANDA (ANDA211610)
Common use one line
Opioid-plus-acetaminophen pain reliever for mild to moderate pain when an opioid is appropriate and other treatments are inadequate.
What it is used for
These tablets are for managing mild to moderate pain when treatment with an opioid is appropriate and other treatments are inadequate. Because of the risks of addiction, abuse, misuse, overdose and death, opioids are reserved for people for whom other options are ineffective, not tolerated or inadequate.
Section
INDICATIONS AND USAGE
Medlineplus section
Why is this medication prescribed?
Source text (exact source wording)
Acetaminophen and codeine phosphate tablets are indicated for the management of mild to moderate pain, where treatment with an opioid is appropriate and for which alternative treatments are inadequate.
Limitations of Use
Because of the risks of addiction, abuse, misuse, overdose, and death, which can occur at any dosage or duration and persist over the course of therapy, (see WARNINGS), reserve opioid analgesics, including codeine phosphate for use in patients for whom alternative treatment options are ineffective, not tolerated, or would be otherwise inadequate to provide sufficient management of pain.
Limitations of Use
Because of the risks of addiction, abuse, misuse, overdose, and death, which can occur at any dosage or duration and persist over the course of therapy, (see WARNINGS), reserve opioid analgesics, including codeine phosphate for use in patients for whom alternative treatment options are ineffective, not tolerated, or would be otherwise inadequate to provide sufficient management of pain.
Medlineplus source text (exact source wording)
The combination of acetaminophen and codeine is used to relieve pain.
How it works
Codeine is an opioid that acts on the mu-opioid receptor, with a much weaker affinity than morphine. Its pain-relieving effect is speculated to come from its conversion to morphine, but the exact mechanism remains unknown. The precise mechanism of acetaminophen's pain relief is not established but is thought to involve central actions.
Section
CLINICAL PHARMACOLOGY, Mechanism of Action
Source text (exact source wording)
Codeine is an opioid agonist relatively selective for the mu-opioid receptor, but with a much weaker affinity than morphine. The analgesic properties of codeine have been speculated to come from its conversion to morphine, although the exact mechanism of analgesic action remains unknown.
The precise mechanism of the analgesic properties of acetaminophen is not established but is thought to involve central actions.
The precise mechanism of the analgesic properties of acetaminophen is not established but is thought to involve central actions.
Dosage: adults
Treatment starts at 300 mg to 600 mg of acetaminophen and 30 mg to 60 mg of codeine phosphate every 4 hours as needed for pain, at the lowest dose that works. The usual adult dose is 1 to 2 tablets every 4 hours as needed for the 15 mg and 30 mg codeine strengths, and one tablet every 4 hours as needed for the 60 mg strength. The maximum 24-hour dose is 360 mg of codeine phosphate and 4,000 mg of acetaminophen. The prescriber decides the number of tablets.
Source text (exact source wording)
Initiate treatment with acetaminophen and codeine phosphate tablets in a dosing range of 300 mg to 600 mg of acetaminophen and 30 mg to 60 mg of codeine phosphate every 4 hours as needed for pain, at the lowest dose necessary to achieve adequate analgesia. Titrate the dose based upon the individual patient’s response to their initial dose of acetaminophen and codeine phosphate tablets. The usual adult dosage is: Acetaminophen and codeine phosphate tablets (codeine 15 mg and acetaminophen 300 mg): Take 1 to 2 tablets every 4 hours as needed for pain. Acetaminophen and codeine phosphate tablets (codeine 30 mg and acetaminophen 300 mg): Take 1 to 2 tablets every 4 hours as needed for pain. Acetaminophen and codeine phosphate tablets (codeine 60 mg and acetaminophen 300 mg): Take one tablet every 4 hours as needed for pain. Single Doses (Range) Maximum 24-Hour Dose Codeine Phosphate 15 mg to 60 mg 360 mg Acetaminophen 300 mg to 1,000 mg 4,000 mg The prescriber must determine the number of tablets per dose, and the maximum number of tablets per24 hours, based upon the above dosage guidance. This information should be conveyed in the prescription.
Dosage: children
Source text (exact source wording)
Acetaminophen and codeine phosphate tablets are contraindicated for:
• All children younger than 12 years of age (see WARNINGS)
• Post-operative management in children younger than 18 years of age following tonsillectomy and/or adenoidectomy (see WARNINGS).
• All children younger than 12 years of age (see WARNINGS)
• Post-operative management in children younger than 18 years of age following tonsillectomy and/or adenoidectomy (see WARNINGS).
Dosage adjustments
Drug interaction caps
If a CYP3A4 inhibitor must be used, or a CYP3A4 inducer is stopped, a lower dose may be considered, with frequent checks for respiratory depression and sedation. If a CYP3A4 inducer must be used, or an inhibitor is stopped, a higher dose may be considered, with checks for withdrawal.
Section
WARNINGS, CYP3A4 Interaction
Source text (exact source wording)
If concomitant use of a CYP3A4 inhibitor is necessary or if a CYP3A4 inducer is discontinued, consider dosage reduction of acetaminophen and codeine phosphate tablets until stable drug effects are achieved. Evaluate patients at frequent intervals for respiratory depression and sedation.
If concomitant use of a CYP3A4 inducer is necessary or if a CYP3A4 inhibitor is discontinued, consider increasing the acetaminophen and codeine phosphate tablets dosage until stable drug effects are achieved. Evaluate for signs of opioid withdrawal (see PRECAUTIONS,Drug Interactions).
If concomitant use of a CYP3A4 inducer is necessary or if a CYP3A4 inhibitor is discontinued, consider increasing the acetaminophen and codeine phosphate tablets dosage until stable drug effects are achieved. Evaluate for signs of opioid withdrawal (see PRECAUTIONS,Drug Interactions).
Elderly
Life-threatening respiratory depression is more likely in elderly, cachectic or debilitated patients.
Section
WARNINGS, Elderly, Cachectic, or Debilitated Patients
Source text (exact source wording)
Life-threatening respiratory depression is more likely to occur in elderly, cachectic, or debilitated patients because they may have altered pharmacokinetics, including clearance, compared to younger, healthier patients (see WARNINGS; Life-Threatening Respiratory Depression).
Missed dose
This medicine is usually taken as needed. If your doctor told you to take it regularly, take the missed dose as soon as you remember. If it is almost time for the next dose, skip it. Do not take a double dose.
Source
MedlinePlus a601005 (the label has no missed-dose section in the captured text)
Source text (exact source wording)
This medication usually is taken as needed. If your doctor has told you to take acetaminophen and codeine regularly, take the missed dose as soon as you remember it. However, if it is almost time for the next dose, skip the missed dose and continue your regular dosing schedule. Do not take a double dose to make up for a missed one.
Overdose
In an overdose, call poison control at 1-800-222-1222, or 911 if the person has collapsed, had a seizure, has trouble breathing, or can't be awakened. Get medical help right away if someone takes more than the recommended dose, even with no symptoms. Symptoms may include nausea, vomiting, loss of appetite, sweating, unusual bleeding or bruising, pain in the upper right part of the stomach, yellowing of the skin or eyes, slow or shallow breathing, and not being able to wake up.
Section
MedlinePlus a601005, In case of emergency/overdose
Medlineplus source text (exact source wording)
In case of overdose, call the poison control helpline at 1-800-222-1222. Information is also available online at https://www.poisonhelp.org/help. If the victim has collapsed, had a seizure, has trouble breathing, or can't be awakened, immediately call emergency services at 911.
If someone takes more than the recommended dose of acetaminophen and codeine, get medical help immediately, even if the person does not have any symptoms. Symptoms of overdose may include the following:
nausea, vomiting
loss of appetite
sweating
unusual bleeding or bruising
pain in upper right part of the stomach
yellowing of skin or eyes
slow or shallow breathing, difficulty breathing
unable to respond or wake up
loss of muscle tone
increase or decrease in pupil (dark circle in the eye) size
cold and clammy skin
slow heartbeat
If someone takes more than the recommended dose of acetaminophen and codeine, get medical help immediately, even if the person does not have any symptoms. Symptoms of overdose may include the following:
nausea, vomiting
loss of appetite
sweating
unusual bleeding or bruising
pain in upper right part of the stomach
yellowing of skin or eyes
slow or shallow breathing, difficulty breathing
unable to respond or wake up
loss of muscle tone
increase or decrease in pupil (dark circle in the eye) size
cold and clammy skin
slow heartbeat
Storage
Store at 20° to 25°C (68° to 77°F), securely, out of reach of children, away from excess heat and moisture (not in the bathroom), and dispose of unneeded tablets properly.
Section
HOW SUPPLIED (Eywa label; storage details are labeler-specific; sentence ends at the point my extraction stopped)
Source text (exact source wording)
Store Acetaminophen and Codeine Phosphate Tablets, USP at 20° to 25°C (68° to 77°F). [See USP Controlled Room Temperature.] Dispense in tight, light-resistant container as defined in the USP. Store acetaminophen and codeine phosphate tablets securely and dispose of properly
Medlineplus source text (exact source wording)
Keep this medication in the container it came in, tightly closed, and out of reach of children. Store it at room temperature and away from excess heat and moisture (not in the bathroom).
Boxed warning
Section
BOXED WARNING (Eywa Pharma label, copied exactly as returned by the page)
Source text (exact source wording)
WARNING: SERIOUS AND LIFE-THREATENING RISKS FROM USE OF ACETAMINOPHEN AND CODEINE PHOSPHATE TABLETS, USP
Addiction, Abuse, and Misuse
Because the use of acetaminophen and codeine phosphate tablets exposes patients and other users to the risks of opioid addiction, abuse, and misuse, which can lead to overdose and death, assess each patient’s risk prior to prescribing and reassess all patients regularly for the development of these behaviors and conditions [see Warnings].
Life-Threatening Respiratory Depression
Serious, life-threatening, or fatal respiratory depression may occur with use of acetaminophen and codeine phosphate tablets, especially during initiation or following a dosage increase. To reduce the risk of respiratory depression, proper dosing and titration of acetaminophen and codeine phosphate tablets are essential [see Warnings].
Accidental Ingestion
Accidental ingestion of even one dose of acetaminophen and codeine phosphate tablets, especially by children, can result in a fatal overdose of acetaminophen and codeine phosphate [see Warnings].
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. Reserve concomitant prescribing of acetaminophen and codeine phosphate tablets and benzodiazepines or other CNS depressants for use in patients for whom alternative treatment options are inadequate [see Warnings, Drug Interactions].
Neonatal Opioid Withdrawal Syndrome (NOWS)
Advise pregnant women using opioids for an extended period of time of the risk of Neonatal Opioid Withdrawal Syndrome, which may be life-threatening if not recognized and treated. Ensure that management by neonatology experts will be available at delivery [see Warnings].
Opioid Analgesic Risk Evaluation and Mitigation Strategy (REMS)
Healthcare providers are strongly encouraged to complete a REMS-compliant education program and to counsel patients and caregivers on serious risks, safe use, and the importance of reading the Medication Guide with each prescription [see Warnings].
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 ultra-rapid metabolizers of codeine due to a cytochrome P450 (CYP) 2D6 polymorphism (see WARNINGS, PRECAUTIONS; Information for Patients /Caregivers,Nursing Mothers). Acetaminophen and codeine phosphate tablets are contraindicated in children younger than 12 years of age and in children younger than 18 years of age following tonsillectomy and/or adenoidectomy (seeCONTRAINDICATIONS). Avoid the use of acetaminophen and codeine phosphate tablets 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 (see WARNINGS,PRECAUTIONS).
Interactions with Drugs Affecting Cytochrome P450 Isoenzymes
The effects of concomitant use or discontinuation of CYP3A4 inducers, CYP3A4inhibitors, or CYP2D6 inhibitors with codeine are complex. Use of CYP3A4inducers, CYP3A4 inhibitors, or CYP2D6 inhibitors with acetaminophen and codeine phosphate tablets requires careful consideration of the effects on the parent drug, codeine, and the active metabolite, morphine (see WARNINGS, PRECAUTIONS: DRUG INTERACTIONS).
Hepatotoxicity
Acetaminophen has been associated with cases of acute liver failure, at times resulting in liver transplant and death. Most of the cases of liver injury are associated with the use of acetaminophen at doses that exceed 4,000 milligrams per day, and often involve more than one acetaminophen-containing product (see WARNINGS).
Addiction, Abuse, and Misuse
Because the use of acetaminophen and codeine phosphate tablets exposes patients and other users to the risks of opioid addiction, abuse, and misuse, which can lead to overdose and death, assess each patient’s risk prior to prescribing and reassess all patients regularly for the development of these behaviors and conditions [see Warnings].
Life-Threatening Respiratory Depression
Serious, life-threatening, or fatal respiratory depression may occur with use of acetaminophen and codeine phosphate tablets, especially during initiation or following a dosage increase. To reduce the risk of respiratory depression, proper dosing and titration of acetaminophen and codeine phosphate tablets are essential [see Warnings].
Accidental Ingestion
Accidental ingestion of even one dose of acetaminophen and codeine phosphate tablets, especially by children, can result in a fatal overdose of acetaminophen and codeine phosphate [see Warnings].
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. Reserve concomitant prescribing of acetaminophen and codeine phosphate tablets and benzodiazepines or other CNS depressants for use in patients for whom alternative treatment options are inadequate [see Warnings, Drug Interactions].
Neonatal Opioid Withdrawal Syndrome (NOWS)
Advise pregnant women using opioids for an extended period of time of the risk of Neonatal Opioid Withdrawal Syndrome, which may be life-threatening if not recognized and treated. Ensure that management by neonatology experts will be available at delivery [see Warnings].
Opioid Analgesic Risk Evaluation and Mitigation Strategy (REMS)
Healthcare providers are strongly encouraged to complete a REMS-compliant education program and to counsel patients and caregivers on serious risks, safe use, and the importance of reading the Medication Guide with each prescription [see Warnings].
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 ultra-rapid metabolizers of codeine due to a cytochrome P450 (CYP) 2D6 polymorphism (see WARNINGS, PRECAUTIONS; Information for Patients /Caregivers,Nursing Mothers). Acetaminophen and codeine phosphate tablets are contraindicated in children younger than 12 years of age and in children younger than 18 years of age following tonsillectomy and/or adenoidectomy (seeCONTRAINDICATIONS). Avoid the use of acetaminophen and codeine phosphate tablets 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 (see WARNINGS,PRECAUTIONS).
Interactions with Drugs Affecting Cytochrome P450 Isoenzymes
The effects of concomitant use or discontinuation of CYP3A4 inducers, CYP3A4inhibitors, or CYP2D6 inhibitors with codeine are complex. Use of CYP3A4inducers, CYP3A4 inhibitors, or CYP2D6 inhibitors with acetaminophen and codeine phosphate tablets requires careful consideration of the effects on the parent drug, codeine, and the active metabolite, morphine (see WARNINGS, PRECAUTIONS: DRUG INTERACTIONS).
Hepatotoxicity
Acetaminophen has been associated with cases of acute liver failure, at times resulting in liver transplant and death. Most of the cases of liver injury are associated with the use of acetaminophen at doses that exceed 4,000 milligrams per day, and often involve more than one acetaminophen-containing product (see WARNINGS).
Contraindications
Do not use these tablets in children younger than 12 years, or in children younger than 18 years after tonsillectomy and/or adenoidectomy. Do not use them with significant respiratory depression, acute or severe asthma in an unmonitored setting, MAOI use now or within the last 14 days, known or suspected gastrointestinal obstruction including paralytic ileus, or an allergy to codeine, acetaminophen or any ingredient.
Section
CONTRAINDICATIONS
Source text (exact source wording)
Acetaminophen and codeine phosphate tablets are contraindicated for:
• All children younger than 12 years of age (see WARNINGS)
• Post-operative management in children younger than 18 years of age following tonsillectomy and/or adenoidectomy (see WARNINGS).
Acetaminophen and codeine phosphate tablets are contraindicated in patients with:
• Significant respiratory depression (see WARNINGS).
• Acute or severe bronchial asthma in an unmonitored setting or in the absence of resuscitative equipment (see WARNINGS).
• Concurrent use of monoamine oxidase inhibitors (MAOIs) or use of MAOIs within the last 14 days (see WARNINGS).
• Known or suspected gastrointestinal obstruction, including paralytic ileus (see WARNINGS).
• Hypersensitivity to codeine, acetaminophen, or any of the ingredients (e.g., anaphylaxis) (see WARNINGS).
• All children younger than 12 years of age (see WARNINGS)
• Post-operative management in children younger than 18 years of age following tonsillectomy and/or adenoidectomy (see WARNINGS).
Acetaminophen and codeine phosphate tablets are contraindicated in patients with:
• Significant respiratory depression (see WARNINGS).
• Acute or severe bronchial asthma in an unmonitored setting or in the absence of resuscitative equipment (see WARNINGS).
• Concurrent use of monoamine oxidase inhibitors (MAOIs) or use of MAOIs within the last 14 days (see WARNINGS).
• Known or suspected gastrointestinal obstruction, including paralytic ileus (see WARNINGS).
• Hypersensitivity to codeine, acetaminophen, or any of the ingredients (e.g., anaphylaxis) (see WARNINGS).
Warnings and precautions
These tablets contain codeine, a Schedule III controlled substance. As an opioid, they carry risks of addiction, abuse and misuse, and addiction can occur at recommended dosages.
Heading
Addiction, Abuse, and Misuse
Source text (exact source wording)
Acetaminophen and codeine phosphate tablets contain codeine. Codeine in combination with acetaminophen, is a Schedule III controlled substance. As an opioid, acetaminophen and codeine phosphate tablets expose users to the risks of addiction, abuse, and misuse (seeDRUG ABUSE and DEPENDENCE).
Although the risk of addiction in any individual is unknown, it can occur in patients appropriately prescribed acetaminophen and codeine phosphate tablets. Addiction can occur at recommended dosages and if the drug is misused or abused.
Although the risk of addiction in any individual is unknown, it can occur in patients appropriately prescribed acetaminophen and codeine phosphate tablets. Addiction can occur at recommended dosages and if the drug is misused or abused.
Serious, life-threatening or fatal breathing problems can happen even when used as recommended, and the risk is greatest when starting or after a dose increase.
Heading
Life-Threatening Respiratory Depression
Source text (exact source wording)
Serious, life-threatening, or fatal respiratory depression has been reported with the use of opioids, even when used as recommended. Respiratory depression, if not immediately recognized and treated, may lead to respiratory arrest and death.
While serious, life-threatening, or fatal respiratory depression can occur at any time during the use of acetaminophen and codeine phosphate tablets, the risk is greatest during the initiation of therapy or following a dosage increase of acetaminophen and codeine phosphate tablets.
While serious, life-threatening, or fatal respiratory depression can occur at any time during the use of acetaminophen and codeine phosphate tablets, the risk is greatest during the initiation of therapy or following a dosage increase of acetaminophen and codeine phosphate tablets.
Using these tablets with benzodiazepines or other CNS depressants, including alcohol, can cause profound sedation, breathing problems, coma and death.
Heading
Risks from Concomitant Use with Benzodiazepines and Other CNS Depressants
Source text (exact source wording)
Profound sedation, respiratory depression, coma, and death may result from the concomitant use of acetaminophen and codeine phosphate tablets with benzodiazepines and/or other CNS depressants, including alcohol (e.g., non-benzodiazepine sedatives/hypnotics, anxiolytics, tranquilizers, muscle relaxants, general anesthetics, antipsychotics, gabapentinoids [gabapentin or pregabalin], and other opioids).
People who are ultra-rapid metabolizers of codeine because of a specific CYP2D6 genotype can have life-threatening or fatal respiratory depression at labeled doses and should not use these tablets.
Heading
Ultra-Rapid Metabolism of Codeine
Source text (exact source wording)
Some individuals may be ultra-rapid metabolizers because of a specific CYP2D6 genotype (e.g., gene duplications denoted as *1/*1×N or *1/*2×N). ... Even at labeled dosage regimens, individuals who are ultra-rapid metabolizers may have life-threatening or fatal respiratory depression or experience signs of overdose (such as extreme sleepiness, confusion, or shallow breathing) (see OVERDOSAGE). Therefore, individuals who are ultra-rapid metabolizers should not use acetaminophen and codeine phosphate tablets.
Acetaminophen has been linked to acute liver failure, mostly at doses that exceed 4,000 milligrams per day and often involving more than one acetaminophen-containing product. Look for acetaminophen or APAP on labels and do not use more than one such product. Seek medical attention immediately after taking more than 4,000 milligrams in a day, even if you feel well.
Heading
Hepatotoxicity
Source text (exact source wording)
Acetaminophen has been associated with cases of acute liver failure, at times resulting in liver transplant and death. Most of the cases of liver injury are associated with the use of acetaminophen at doses that exceed 4,000 milligrams per day, and often involve more than one acetaminophen-containing product. ... Instruct patients to look for acetaminophen or APAP on package labels and not to use more than one product that contains acetaminophen. Instruct patients to seek medical attention immediately upon ingestion of more than 4,000 milligrams of acetaminophen per day, even if they feel well.
MAOIs may increase the effects of morphine, including respiratory depression, coma and confusion. Do not use these tablets while taking MAOIs or within 14 days of stopping them.
Heading
Interaction with Monoamine Oxidase Inhibitors
Source text (exact source wording)
Monoamine oxidase inhibitors (MAOIs) may potentiate the effects of morphine, codeine's active metabolite, including respiratory depression, coma, and confusion. Acetaminophen and codeine phosphate tablets should not be used in patients taking MAOIs or within 14 days of stopping such treatment.
Rarely, acetaminophen may cause serious, sometimes fatal skin reactions. Stop the drug at the first sign of skin rash or any other sign of hypersensitivity.
Heading
Serious Skin Reactions
Source text (exact source wording)
Rarely, acetaminophen may cause serious skin reactions such as acute generalized exanthematous pustulosis (AGEP), Stevens-Johnson Syndrome (SJS), and toxic epidermal necrolysis (TEN), which can be fatal. Patients should be informed about the signs of serious skin reactions, and use of the drug should be discontinued at the first appearance of skin rash or any other sign of hypersensitivity.
Do not rapidly reduce or abruptly stop these tablets in a person physically dependent on opioids, because this may lead to a withdrawal syndrome and return of pain.
Heading
Withdrawal
Source text (exact source wording)
Do not rapidly reduce or abruptly discontinue acetaminophen and codeine phosphate tablets in a patient physically dependent on opioids. Rapid tapering of acetaminophen and codeine phosphate tablets in a patient physically dependent on opioids may lead to a withdrawal syndrome and return of pain
Pregnancy and breastfeeding
Using these tablets for an extended time during pregnancy can cause withdrawal in the newborn, which may be life-threatening. Breastfeeding is not recommended during treatment, because at least one death was reported in a nursing infant exposed to high levels of morphine in breast milk. Tell your doctor if you are pregnant or plan to become pregnant.
Source text (exact source wording)
Advise pregnant women using opioids for an extended period of time of the risk of Neonatal Opioid Withdrawal Syndrome, which may be life-threatening if not recognized and treated. Ensure that management by neonatology experts will be available at delivery [see Warnings]. | Neonatal Opioid Withdrawal Syndrome: Use of acetaminophen and codeine phosphate tablets for an extended period of time during pregnancy can result in withdrawal in the neonate. | Nursing Mothers: At least one death was reported in a nursing infant who was exposed to high levels of morphine in breast milk because the mother was an ultra-rapid metabolizer of codeine. Breastfeeding is not recommended during treatment with acetaminophen and codeine phosphate tablets.
Medlineplus source text (exact source wording)
Tell your doctor if you are pregnant or plan to become pregnant. If you take acetaminophen and codeine regularly during your pregnancy, your baby may experience life-threatening withdrawal symptoms after birth.
Side effects
Common
The most frequently observed reactions with codeine include drowsiness, lightheadedness, dizziness, sedation, shortness of breath, nausea, vomiting, sweating and constipation. The label does not give percentages.
Section
ADVERSE REACTIONS (post-approval use; frequency cannot be reliably estimated per the label)
Source text (exact source wording)
The most frequently observed adverse reactions with codeine administration include drowsiness, lightheadedness, dizziness, sedation, shortness of breath, nausea, vomiting, sweating, and constipation.
Less common
Other reactions include allergic reactions, euphoria, dysphoria, abdominal pain, itching, rash, low platelet counts and agranulocytosis.
Section
ADVERSE REACTIONS (the label has no placebo-controlled table in captured text)
Source text (exact source wording)
Other adverse reactions include allergic reactions, euphoria, dysphoria, abdominal pain, pruritus, rash, thrombocytopenia, and agranulocytosis.
Serious
Serious reactions associated with codeine are respiratory depression and, to a lesser degree, circulatory depression, respiratory arrest, shock and cardiac arrest. MedlinePlus says to call your doctor right away or get emergency help for symptoms such as agitation, hallucinations, fever, fast heartbeat, severe muscle stiffness, rash, hives, trouble breathing or swallowing, chest pain, seizures, extreme drowsiness, new or worse pain, or long pauses in breathing during sleep.
Label section
ADVERSE REACTIONS
Medlineplus section
What side effects can this medication cause?
Label source text (exact source wording)
Serious adverse reactions associated with codeine are respiratory depression and, to a lesser degree, circulatory depression, respiratory arrest, shock, and cardiac arrest.
Medlineplus source text (exact source wording)
Some side effects can be serious. If you experience any of these symptoms or those mentioned in the IMPORTANT WARNING section, call your doctor immediately or get emergency medical help:
nausea, vomiting, loss of appetite, weakness, or dizziness
agitation, hallucinations (seeing things or hearing voices that do not exist), fever, sweating, confusion, fast heartbeat, shivering, severe muscle stiffness or twitching, loss of coordination, nausea, vomiting, or diarrhea
rash; hives; itching; red, peeling or blistering skin; difficulty breathing or swallowing; swelling of the face, throat, tongue, lips, eyes, hands, feet, ankles, or lower legs
chest pain, changes in heartbeat
seizures
extreme drowsiness
new pain or pain from touch or doing ordinary tasks such as combing your hair
difficulty swallowing, regurgitation (bringing up swallowed food into throat and mouth), pain in the chest area
unusual snoring or long pauses during breaths during sleep
nausea, vomiting, loss of appetite, weakness, or dizziness
agitation, hallucinations (seeing things or hearing voices that do not exist), fever, sweating, confusion, fast heartbeat, shivering, severe muscle stiffness or twitching, loss of coordination, nausea, vomiting, or diarrhea
rash; hives; itching; red, peeling or blistering skin; difficulty breathing or swallowing; swelling of the face, throat, tongue, lips, eyes, hands, feet, ankles, or lower legs
chest pain, changes in heartbeat
seizures
extreme drowsiness
new pain or pain from touch or doing ordinary tasks such as combing your hair
difficulty swallowing, regurgitation (bringing up swallowed food into throat and mouth), pain in the chest area
unusual snoring or long pauses during breaths during sleep
Medlineplus mild
Section
MedlinePlus a601005
Source text (exact source wording)
Acetaminophen and codeine may cause side effects. Tell your doctor if any of these symptoms or those in the SPECIAL PRECAUTIONS section are severe or do not go away:
nausea, vomiting
sweating
decreased sexual desire, inability to get or keep an erection
nausea, vomiting
sweating
decreased sexual desire, inability to get or keep an erection
Interactions
Drugs
Using opioids with benzodiazepines or other CNS depressants, including alcohol, may cause profound sedation, respiratory depression, coma and death.
Name
Benzodiazepines and other CNS depressants (including other opioids, gabapentinoids)
Section
BOXED WARNING; WARNINGS
Source text (exact source wording)
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.
CYP3A4 inhibitors such as erythromycin, ketoconazole and ritonavir, or stopping an inducer such as rifampin, carbamazepine or phenytoin, can raise codeine and morphine levels and may cause potentially fatal respiratory depression.
Name
CYP3A4 inhibitors (e.g., erythromycin, ketoconazole, ritonavir) and inducers (rifampin, carbamazepine, phenytoin)
Section
WARNINGS, CYP3A4 Interaction
Source text (exact source wording)
The concomitant use of acetaminophen and codeine phosphate tablets with all CYP3A4 inhibitors, such as macrolide antibiotics (e.g., erythromycin), azole-antifungal agents (e.g., ketoconazole), and protease inhibitors (e.g., ritonavir) or discontinuation of a CYP3A4 inducer such as rifampin, carbamazepine, and phenytoin, may result in an increase in codeine plasma concentrations with subsequently greater metabolism by CYP2D6, resulting in greater morphine levels, which could increase or prolong adverse reactions and may cause potentially fatal respiratory depression.
CYP2D6 inhibitors such as amiodarone and quinidine may reduce pain relief or cause opioid withdrawal symptoms.
Name
CYP2D6 inhibitors (e.g., amiodarone, quinidine)
Section
WARNINGS, Risks of Concomitant Use or Discontinuation of CYP2D6 Inhibitors
Source text (exact source wording)
The concomitant use of acetaminophen and codeine phosphate tablets with all CYP2D6 inhibitors (e.g., amiodarone, quinidine) may result in an increase in codeine plasma concentrations and a decrease in active metabolite morphine plasma concentration which could result in an analgesic efficacy reduction or symptoms of opioid withdrawal.
Do not use with MAOIs or within 14 days of stopping them.
Name
MAOIs
Section
WARNINGS
Source text (exact source wording)
Acetaminophen and codeine phosphate tablets should not be used in patients taking MAOIs or within 14 days of stopping such treatment.
Avoid pentazocine, nalbuphine, butorphanol and buprenorphine in people receiving these tablets.
Name
Mixed agonist/antagonist and partial agonist opioids
Section
WARNINGS, Withdrawal
Source text (exact source wording)
avoid the use of mixed agonist/antagonist (e.g., pentazocine, nalbuphine, and butorphanol) or partial agonist (e.g., buprenorphine) analgesics in patients who are receiving a full opioid agonist analgesic, including acetaminophen and codeine phosphate tablets.
Do not use more than one product that contains acetaminophen.
Name
Other acetaminophen-containing products
Section
WARNINGS, Hepatotoxicity
Source text (exact source wording)
Instruct patients to look for acetaminophen or APAP on package labels and not to use more than one product that contains acetaminophen.
Food and alcohol
Do not drink alcohol while taking acetaminophen and codeine. Alcohol can make side effects worse and, with opioids, can cause profound sedation, breathing problems, coma and death.
Name
Alcohol
Section
BOXED WARNING; MedlinePlus
Source text (exact source wording)
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. | you should know to not drink alcoholic beverages while you are taking acetaminophen and codeine. Alcohol can make the side effects from acetaminophen and codeine worse.
Name
Grapefruit
Other
MedlinePlus lists St. John's wort and tryptophan as nonprescription products that may interact.
Name
St. John's wort and tryptophan (MedlinePlus)
Section
MedlinePlus a601005
Source text (exact source wording)
the following nonprescription products may interact with acetaminophen and codeine: St. John's wort and tryptophan.
Patient tips
Take it exactly as directed, and do not stop suddenly after taking it for several weeks or longer without talking to your doctor. Do not take more than 4,000 mg of acetaminophen per day from all products. Store the tablets securely where others cannot get them, and do not share them. Ask about a rescue medicine such as naloxone or nalmefene. The tablets may make you drowsy, so do not drive or operate machinery until you know how they affect you. Call 911 for a suspected overdose.
Label
Source text (exact source wording)
Storage and Disposal:
Because of the risks associated with accidental ingestion, misuse, and abuse, advise patients to store acetaminophen and codeine phosphate tablets securely, out of sight and reach of children, and in a location not accessible by others, including visitors to the home. Inform patients that leaving acetaminophen and codeine phosphate tablets unsecured can pose a deadly risk to others in the home.
Instruct patients not to share acetaminophen and codeine phosphate tablets with others and to take steps to protect acetaminophen and codeine phosphate tablets from theft or misuse.
Acetaminophen and codeine phosphate tablets may impair the mental or physical abilities needed to perform potentially hazardous activities such as driving a car or operating machinery.
Because of the risks associated with accidental ingestion, misuse, and abuse, advise patients to store acetaminophen and codeine phosphate tablets securely, out of sight and reach of children, and in a location not accessible by others, including visitors to the home. Inform patients that leaving acetaminophen and codeine phosphate tablets unsecured can pose a deadly risk to others in the home.
Instruct patients not to share acetaminophen and codeine phosphate tablets with others and to take steps to protect acetaminophen and codeine phosphate tablets from theft or misuse.
Acetaminophen and codeine phosphate tablets may impair the mental or physical abilities needed to perform potentially hazardous activities such as driving a car or operating machinery.
Medlineplus
Section
MedlinePlus a601005 (sentences from several paragraphs)
Source text (exact source wording)
Take acetaminophen and codeine exactly as directed. Do not take more or less of it, take it more often, stop taking it suddenly, or take it in a different way than directed by your doctor.
Do not take more than 4,000 mg of acetaminophen per day.
If you have taken acetaminophen and codeine for several weeks or longer, do not stop taking the medication without talking to your doctor.
Talk to your doctor or pharmacist about access to rescue medicines, naloxone or nalmefene, while taking acetaminophen and codeine.
you should know that this medication may make you drowsy. Do not drive a car or operate machinery until you know how this medication affects you.
Do not take more than 4,000 mg of acetaminophen per day.
If you have taken acetaminophen and codeine for several weeks or longer, do not stop taking the medication without talking to your doctor.
Talk to your doctor or pharmacist about access to rescue medicines, naloxone or nalmefene, while taking acetaminophen and codeine.
you should know that this medication may make you drowsy. Do not drive a car or operate machinery until you know how this medication affects you.
Alternatives
Class statement
Source text (exact source wording)
Codeine belongs to a class of medications called opiate (narcotic) analgesics. | Acetaminophen is in a class of medications called analgesics (pain relievers) and antipyretics (fever reducers).
Recommendation
none (not ranked)
Frequently asked questions
Question
What is acetaminophen and codeine used for?
Answer
It is used to manage mild to moderate pain when treatment with an opioid is appropriate and other treatments are inadequate.
Source section
INDICATIONS AND USAGE
Source
DailyMed Eywa Pharma label
Question
Is acetaminophen and codeine a controlled substance?
Answer
Yes. Codeine in combination with acetaminophen is a Schedule III controlled substance, and the tablets carry a boxed warning about addiction, abuse and misuse.
Source section
WARNINGS, Addiction, Abuse, and Misuse; BOXED WARNING
Source
DailyMed Eywa Pharma label
Question
How often can I take it?
Answer
The usual adult dose for the 15 mg and 30 mg codeine strengths is 1 to 2 tablets every 4 hours as needed for pain, and for the 60 mg strength it is one tablet every 4 hours as needed. The maximum 24-hour dose is 360 mg of codeine phosphate and 4,000 mg of acetaminophen. Your prescriber sets the number of tablets.
Source section
DOSAGE AND ADMINISTRATION, Initial Dosage
Source
DailyMed Eywa Pharma label
Question
What if I miss a dose?
Answer
It is usually taken as needed. If you were told to take it regularly, take the missed dose as soon as you remember, unless it is almost time for the next dose. Do not take a double dose.
Source section
What should I do if I forget a dose?
Source
MedlinePlus a601005
Question
Can I drink alcohol with acetaminophen and codeine?
Answer
No. MedlinePlus says not to drink alcoholic beverages while taking it because alcohol can make the side effects worse. The label warns that using opioids with alcohol may cause profound sedation, breathing problems, coma and death.
Source section
BOXED WARNING; MedlinePlus special precautions
Source
DailyMed Eywa Pharma label; MedlinePlus a601005
Question
What are the most common side effects?
Answer
The most frequently observed reactions with codeine include drowsiness, lightheadedness, dizziness, sedation, shortness of breath, nausea, vomiting, sweating and constipation. The label does not give percentages.
Source section
ADVERSE REACTIONS
Source
DailyMed Eywa Pharma label
Question
Is it safe during pregnancy or breastfeeding?
Answer
Using it for an extended time during pregnancy can cause withdrawal in the newborn, which may be life-threatening. Breastfeeding is not recommended during treatment. Tell your doctor if you are pregnant or plan to become pregnant.
Source section
WARNINGS, Neonatal Opioid Withdrawal Syndrome; Nursing Mothers
Source
DailyMed Eywa Pharma label; MedlinePlus a601005
Question
How much acetaminophen is too much?
Answer
Most cases of liver injury involve doses that exceed 4,000 milligrams of acetaminophen per day, and often more than one acetaminophen-containing product. Do not take more than 4,000 mg per day, and do not use more than one product that contains acetaminophen.
Source section
WARNINGS, Hepatotoxicity
Source
DailyMed Eywa Pharma label; MedlinePlus a601005
Sources
- DailyMed acetaminophen and codeine phosphate tablets (primary)
Set id: 79377617-686b-4640-b2b8-e1358cf82358 · Label effective or revised date: Revised: 9/2026 (the label text also contains 'Revised: 12/2025' twice) · Dailymed version date: DailyMed list API published_date Sep 23, 2026 · Fetched at: 2026-11-02 · Sections used: Boxed warning, Description, Clinical Pharmacology, Indications, Contraindications, Warnings, Precautions (first 50,000 characters) plus short slices of Dosage and Administration, Adverse Reactions and How Supplied - Alternate 1 (opened, compared)
Set id: eadc80fa-13c3-471a-a22f-6fe7e1ab290f · Label effective or revised date: Revised: 6/2026 · Dailymed version date: published Jun 18, 2026 (list API) · Fetched at: 2026-11-02 - Alternate 2 (not opened, revised date NOT READ)
Set id: 02386806-02d4-47e3-9c8b-7810146ee795 · Label effective or revised date: NOT READ · Dailymed version date: published Dec 25, 2025 (list API) - MedlinePlus Acetaminophen and Codeine
Label effective or revised date: Last Revised - 10/15/2025 · Fetched at: 2026-11-02 - Drugs@FDA
- openFDA
Information is taken from the cited sources and is for general reference only. It is not medical advice. Report side effects to FDA MedWatch at 1-800-FDA-1088. For a poison emergency call 1-800-222-1222. See prices for this drug