Acetaminophen With Codeine

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Acetaminophen With Codeine

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Medically reviewed

Marina Burgos

Last updated on 10/01/2026

This page provides general, reference-level information compiled from official medical sources. It is not a substitute for professional medical advice, diagnosis, or treatment. For decisions about your health, please consult a qualified healthcare professional.

Overview of Acetaminophen With Codeine

Acetaminophen with Codeine is a pharmaceutical combination product that functions as an oral prescription analgesic, clinically recognized for its ability to manage pain through combined pathways. It is classified as both a Non-Opioid Analgesic and a Narcotic Opioid Analgesic, targeting the Central Nervous System (CNS) to modulate pain perception.


Quick Facts: Acetaminophen With Codeine

Property Description
Active Ingredients Acetaminophen, Codeine Phosphate
Common Forms Tablet, Oral Solution, Elixir
Pharmacological Class Opioid Analgesic, CNS Agent
General Purpose Pain relief, fever reduction, cough suppression
Origin Synthetic (Acetaminophen), Natural Opioid Base (Codeine)

What Type of Medicine is Acetaminophen With Codeine?

The medication is formally classified within the Opioid Analgesics therapeutic category, a designation it earns due to the presence of Codeine, which acts on opioid receptors in the brain. This strategic combination utilizes the synergistic effect of two distinct mechanisms, providing a broader strategy for discomfort management than single-agent analgesics. This formulation is notably featured in popular preparations such as Tylenol-Codeine and generic equivalents, which utilize the same dual active ingredients.

What is the Composition and Origin of the Drug?

The two active ingredients are Acetaminophen (chemically identical to Paracetamol), a synthetic compound that also acts as an antipyretic, and Codeine Phosphate. Codeine itself is a natural opioid base, derived from the opium poppy, although it is commonly prepared semi-synthetically for commercial use. The combination product is available in multiple common dosage forms, including the Tablet, Oral Solution, and Elixir. The Oral Solution form is a distinctive feature of this INN combination, specifically positioning it for patients who may have difficulty swallowing solid medication.

What is the General Therapeutic Purpose?

The general therapeutic purpose of this medication is to deliver comprehensive pain relief by simultaneously targeting different pain pathways in the body. The opioid component (Codeine) primarily works to diminish the perception of moderate pain, while the Acetaminophen component contributes to pain modulation and helps to lower a fever. Additionally, Codeine is categorized as an antitussive (cough suppressant), meaning the formulation carries the general benefit of suppressing the cough reflex in adults.

Regulatory References

  1. NIH, MedlinePlus Drug Information

What side effects are possible with Acetaminophen With Codeine?

Possible Side Effects and Safety Information

The safety profile of this combination product is defined by the known risks associated with its two active components. Adverse reactions are formally classified by frequency and grouped according to the System-Organ Classes (SOC) affected, as documented in regulatory sources.


Frequency-Classified Adverse Reactions

The most commonly listed adverse reactions relate to the Central Nervous System (CNS) and the gastrointestinal system.

  • Common: Adverse events that may affect up to 1 in 10 people include nausea, vomiting, constipation, dizziness, and sedation (drowsiness).
  • Rare: Reactions that may affect up to 1 in 1,000 people include thrombocytopenia (low platelet count), hepatitis, and severe allergic reactions such as anaphylaxis.

Serious Adverse Reactions and Safety Constraints

Regulatory documents highlight several potentially life-threatening risks. The Acetaminophen component carries a specific risk of severe hepatotoxicity, which can lead to acute liver failure. The Codeine component is associated with the risk of respiratory depression, which is potentially fatal. Additionally, serious skin reactions, including Stevens-Johnson Syndrome (SJS), are documented safety risks.

Safety is also addressed via constraints specific to certain populations. Ultra-rapid metabolizers of codeine, an enzyme variation leading to rapid conversion into morphine, are at a significantly increased risk of respiratory depression, a condition also increased in older adults. Furthermore, the risk of developing physical dependence and tolerance is associated with long-term exposure to the codeine component. The medication is officially contraindicated in patients with known severe respiratory depression or certain gastrointestinal obstructions.

Overdose and Emergency Response

Overdose of Acetaminophen with Codeine carries distinct risks from both active components and requires immediate medical attention as mandated by regulatory authorities. Overdose manifestations related to Acetaminophen may initially present with non-specific symptoms such as nausea, vomiting, and diaphoresis, but can progress to severe, potentially fatal hepatic necrosis and liver failure. Clinical signs like jaundice and elevated serum aminotransferase levels are documented, highlighting the time-critical nature of the toxicity due to delayed hepatic damage.

Overdose due to the Codeine component primarily manifests as acute opioid intoxication, including severe respiratory depression leading to respiratory arrest. Other documented signs are profound somnolence, stupor, coma, and pinpoint pupils (miosis). Cardiovascular effects like hypotension and circulatory collapse may also occur. Seek immediate medical attention for any suspected overdose event. Emergency services must be contacted immediately if severe signs like difficult breathing or confusion are present.

Treatment is defined as symptomatic and supportive. Specific antidotes are available: N-acetylcysteine (NAC) is used for Acetaminophen toxicity, and Naloxone is used to reverse acute opioid effects. Furthermore, regulatory documents note that overdose in pediatric patients, particularly ultra-rapid metabolizers of Codeine, can be life-threatening and requires vigilant medical management.

Therapeutic Uses of Acetaminophen With Codeine

Quick Facts: Uses of Acetaminophen with Codeine

  • Utilized to address mild to moderately severe pain.
  • Intended for use when non-opioid options are not suitable or adequate.
  • Assists in managing acute discomfort.

Acetaminophen with Codeine is a therapeutic option indicated for the management of mild to moderately severe pain in individuals. It is generally reserved for situations where the relief achieved with non-opioid analgesics, such as acetaminophen or ibuprofen alone, is not considered sufficient or when other alternatives are not tolerated. This combination compound is utilized to help modify the body's response to discomfort.

The component acetaminophen in the formulation may also provide assistance in addressing fever. The use of this medication is typically for short-term management of acute discomfort.

Eligibility and Restrictions for Use

Who Can and Cannot Use Acetaminophen With Codeine?

The official regulatory profile strictly defines which populations are eligible for this prescription analgesic. Use is absolutely forbidden for several patient groups, a status defined by formal contraindications in regulatory labeling.

Absolute Contraindications

The medicine is strictly forbidden for all children younger than 12 years of age. Use is also contraindicated for adolescents under 18 years when managing pain post-tonsillectomy or adenoidectomy. Individuals known to be CYP2D6 ultra-rapid metabolizers must not use this product due to the severe risk of toxicity. Further absolute contraindications include women who are breastfeeding, patients with known hypersensitivity to the components, significant respiratory depression, or known gastrointestinal obstruction.

Age and Condition Restrictions

Adults are the primary approved population. Eligibility is restricted by age in the pediatric population and by organ function in all patients. The medication requires caution and potential dose adjustment for patients with severe hepatic or renal impairment. During pregnancy, long-term use is not recommended due to the risk of Neonatal Opioid Withdrawal Syndrome. Adolescents 12 to 18 years of age with compromised respiratory function are generally advised to avoid use.

What should I know about interactions with other medicines?

The official interaction profile for Acetaminophen With Codeine is primarily determined by its metabolic pathways and pharmacodynamic effects. Co-administration with Central Nervous System (CNS) Depressants, including sedatives, hypnotics, and other opioids, may result in additive CNS depression, leading to a risk of profound sedation and severe respiratory depression. This interaction is also documented with alcohol (ethanol). Concomitant use with Serotonergic Drugs is documented with a risk of Serotonin Syndrome.

Pharmacokinetic interactions involve the CYP2D6 enzyme. Co-administration with CYP2D6 inhibitors is documented to decrease the plasma concentration of codeine’s active metabolite, which may result in reduced analgesic efficacy. Conversely, CYP3A4 inhibitors may increase codeine plasma concentrations, raising the potential for prolonged adverse reactions. The acetaminophen component may also increase the anticoagulant effect of warfarin and coumarin derivatives, increasing the risk of bleeding.

Regulatory documentation defines several restrictions. The medicine is contraindicated in children younger than 12 years of age and in children younger than 18 years following tonsillectomy or adenoidectomy. It is also contraindicated in patients who are known CYP2D6 ultra-rapid metabolizers. Furthermore, the combination must not be co-administered with other products containing acetaminophen or with Monoamine Oxidase Inhibitors (MAOIs) or within 14 days of stopping MAOI therapy.

Mechanism of Action

Codeine, an opioid agonist, produces its effect by binding to mu-opioid receptors located throughout the central nervous system (CNS). This receptor occupancy modulates ascending nociceptive pathways, thereby altering the transmission of signals related to pain.

Acetaminophen exerts its action through the non-covalent, reversible inhibition of cyclooxygenase (COX) enzymes, primarily COX-2, leading to limited prostaglandin synthesis in the CNS. Prostaglandins function as localized mediators in inflammatory signaling, and their resulting decrease modulates overall nociceptive input.

The combination of both compounds acts upon distinct, yet related, molecular targets—opioid receptors and the COX pathway—to exert a combined modulation of nociceptive processing across the CNS and periphery.

Dosage and Administration Information

How to Use Acetaminophen With Codeine

The usage of the Acetaminophen with Codeine combination product is intended for short-term use.

Official Administration and Dosing

Instruction Domain Official Requirement (Adults)
Route of Administration Exclusively Oral (by mouth).
Dosing Frequency Taken every 4 to 6 hours as needed (PRN).
Codeine Dose Range Typically 15 mg to 60 mg of Codeine per dose.

Administration is required to utilize the lowest effective dosage for the shortest duration consistent with individual treatment goals. The usual adult dose is individualized, often starting with one or two tablets of a given strength or the equivalent volume of oral solution, and should not exceed 60 mg of Codeine in a single dose.

Maximum Limits and Special Forms

Two critical restrictions govern the use of this medicine:

  1. Acetaminophen Maximum: The total daily dose of acetaminophen from all sources (including this product) must not exceed 4,000 mg (4 g) in any 24-hour period.
  2. Oral Solution: Liquid forms must be shaken well before each use and measured with a specifically marked measuring device to ensure dosage accuracy.

Population-Specific Rules

There are specific age-related rules for administration. The medicine is contraindicated in all children younger than 12 years of age. Furthermore, caution must be exercised in older adults or in patients with severe hepatic or renal impairment, where the dose should be chosen cautiously, often starting at the low end of the dosing range.

Recent Clinical Evidence

Research Evidence / Overview of Studies for Acetaminophen With Codeine


Evidence for Management of Acute Pain (Mild to Moderately Severe)

Research has primarily studied the use of this combination product in adults experiencing acute, short-term discomfort. The foundational evidence largely comes from Randomized Controlled Trials (RCTs), where the medicine was evaluated in settings like post-operative pain, such as following dental or minor surgical procedures. These studies monitored outcomes related to physical discomfort, including overall pain measurements over short observation periods.

Findings from this research describe patterns observed in the studies regarding the combination product's pain measurement changes when compared to a placebo. Long-term effects are not fully established based on these foundational studies, as most research focuses on the immediate, single-dose response. The results apply only to the populations studied and offer limited information for long-term outcomes.


Research Comparing the Combination to Non-Opioid Treatments

Studies explored the use of this combination product in clinical scenarios where non-opioid pain relievers alone may have been deemed inadequate. Trials examined the combination product's pain measurements against those of the non-opioid component (acetaminophen) when used alone. The data show patterns related to pain measurements, but findings were mixed when assessing the added contribution of the codeine component against the maximum allowed dose of a non-opioid component in all types of acute pain.


Evidence in Special Populations

Data for certain groups remain insufficient, especially for pediatric patients (children and adolescents). Regulators have reviewed reports and findings where children may process codeine too quickly, leading to unpredictable levels of the active metabolite. This variability is the reason evidence quality varies across studies when evaluating children and adolescents. For other groups, such as older adults, subgroup findings are uncertain, and limited information for long-term outcomes is available across all special populations.

Key Studies & References Safety and efficacy of codeine for pain and cough in children: Systematic review

Frequently Asked Questions (FAQ)

Common questions about Acetaminophen With Codeine (FAQ)

Q: Is Acetaminophen With Codeine considered a strong pain reliever?

A: Official information indicates that this combination medication is typically prescribed for the relief of mild to moderately severe pain. It is intended for use when an opioid analgesic is considered appropriate for pain management. The indication is for pain relief when the use of an opioid analgesic is considered appropriate.


Q: Is it normal to feel drowsy or dizzy when taking Acetaminophen With Codeine?

A: Yes, regulatory documents list drowsiness, dizziness, and lightheadedness as common adverse effects associated with this medication. These effects are related to the codeine component working within the central nervous system. These effects can impact a person's ability to safely perform activities that require mental alertness.


Q: What are the possible signs of physical dependence after taking the medication for a while?

A: If physical dependence has developed after a period of use, stopping the medication abruptly can lead to withdrawal symptoms. These symptoms, described in official patient resources, may include anxiety, body aches, increased sweating, nausea, vomiting, or diarrhea. Concerns regarding dependence should be addressed by a healthcare professional.


Q: Is there an interaction risk between Acetaminophen With Codeine and common over-the-counter cold medicines?

A: Yes, there is a potential interaction risk. Many over-the-counter cold and flu medicines contain ingredients, such as certain antihistamines, that can cause additive Central Nervous System (CNS) depression when taken with this medication. Using both together could lead to excessive sedation or breathing issues. Reviewing the ingredients of all non-prescription drugs is necessary to manage interaction risks.


Q: Why do some people report a lack of pain relief even after taking the prescribed dose?

A: Lack of pain relief may be related to how an individual’s body processes the codeine component. According to official labeling, if a person takes certain CYP2D6 inhibitor drugs or is a poor metabolizer due to genetics, the body may convert codeine to its active form (morphine) too slowly, resulting in a reduced analgesic effect.


Q: Can Acetaminophen With Codeine cause mental changes like confusion or hallucinations?

A: Yes, adverse reactions reported in official sources associated with the codeine component include mental status changes. These can specifically involve feelings of confusion and, in rare instances, reports of hallucinations or agitation. Unexpected changes in thinking or behavior are documented adverse effects that require evaluation by a healthcare professional.


Q: Can Acetaminophen With Codeine be used for pain that is not severe?

A: The official indication for this medicine is the relief of mild to moderately severe pain. The use of an opioid analgesic, even for mild pain, requires clinical evaluation to determine appropriateness. Appropriate use is determined based on clinical evaluation.


Q: Are there any skin reactions, like a severe rash, associated with the acetaminophen component?

A: Yes, the acetaminophen component is associated with the risk of rare but serious skin reactions. Official warnings highlight conditions such as Stevens-Johnson Syndrome (SJS), Toxic Epidermal Necrolysis (TEN), and Acute Generalized Exanthematous Pustulosis (AGEP). These conditions can begin with flu-like symptoms and a painful, spreading rash.


Q: What should be done if pain gets worse or new pain develops while on this medicine?

A: If the pain worsens, or if new pain or increased sensitivity to pain develops (a phenomenon known as hyperalgesia), it may indicate that the current treatment is insufficient or that the underlying condition is changing. Regulatory guidance suggests that a healthcare professional should be consulted for evaluation if this occurs.


Q: What are the signs of liver problems that require immediate medical attention?

A: Due to the risk of liver damage (hepatotoxicity), recognizing the signs of potential liver problems is important. Official warnings list symptoms such as yellowing of the skin or eyes (jaundice), dark urine, loss of appetite, persistent nausea and vomiting, or pain in the upper right abdomen. The appearance of these signs indicates a need for immediate medical evaluation.


Q: Is it possible for this drug to cause an increase in urination or difficulty urinating?

A: Yes, urinary adverse reactions have been reported in official documents. The codeine component has been associated with issues like urinary retention and difficulty or pain when urinating (urinary hesitancy). These are listed among the known adverse effects of opioid analgesics.


Q: Can taking Acetaminophen With Codeine cause problems with sleep?

A: The medication can affect sleep due to its action on the central nervous system. The official list of adverse reactions includes both drowsiness and somnolence (sleepiness). Conversely, official reports have also noted insomnia (difficulty falling or staying asleep) as a less common adverse event.


Q: Are there any specific concerns for people with a history of head injury or seizures?

A: Yes, regulatory warnings advise caution for patients with head injuries, increased intracranial pressure, or brain tumors. The codeine component may obscure signs of worsening neurological status. The risks associated with use in patients with a history of seizure disorders should be addressed by a healthcare professional.


Q: Is it true that this drug can cause a rare but serious adrenal gland problem?

A: Official warnings note that chronic opioid use, which includes the codeine component, has been linked to Adrenal Insufficiency. This is a rare but serious condition where the adrenal glands do not produce sufficient amounts of important hormones. If this condition occurs, it requires appropriate medical management.


Q: What should a user know about serotonin syndrome in relation to codeine?

A: Serotonin Syndrome is a known risk when codeine is combined with certain other medicines that affect serotonin levels, such as antidepressants. Regulatory information states symptoms can include mental changes, elevated heart rate, lack of coordination, and high fever.


Q: Why is it advised not to take this drug more often or for longer than prescribed?

A: Regulatory guidance strictly advises against taking the medication more often or for longer than prescribed due to severe risks. This includes an increased potential for addiction, abuse, and misuse, as well as the risk of life-threatening respiratory depression and serious acetaminophen hepatotoxicity (liver damage).


Q: Does the medication have a known effect on blood pressure?

A: Yes, official adverse event reports indicate that the codeine component can cause hypotension (low blood pressure) and, in rare instances, circulatory depression. Due to the potential for low blood pressure, monitoring for symptoms like dizziness or feeling faint is relevant for the safe use of this medicine.


Q: Is it normal to feel a dry mouth when taking this medication?

A: Yes, dry mouth (xerostomia) is a reported adverse reaction associated with the use of this combination product. This is a common anticholinergic-like effect seen with many medications that act on the central nervous system, including opioids.


Q: What is the process for safely stopping Acetaminophen With Codeine after taking it long-term?

A: If the medication has been taken long-term, official guidance generally recommends that the dose be gradually reduced over time rather than stopped suddenly. This tapering process is intended to minimize the potential for withdrawal symptoms. A plan for discontinuation requires the supervision of a healthcare professional.

How should Acetaminophen With Codeine be stored and disposed of?

Storage and Disposal

Official regulatory guidelines mandate that Acetaminophen with Codeine be stored at controlled room temperature, typically 20 C to 25 C, protected from excessive heat, moisture, and light. The medicine must be kept securely in a closed container and out of the reach of children to prevent accidental ingestion, misuse, or theft of the controlled substance (codeine). Do not freeze the product.

Disposal of unused medication must be done according to official regulations. The preferred method is using a drug take-back program. If this is not immediately available, the product should be disposed of in the household trash by mixing it with an undesirable substance (e.g., dirt, cat litter) and sealing it in a plastic bag before discarding.

Attention! Always consult to a doctor or pharmacist before using pills or medicines.

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