Acetaminophen and Codeine Phosphate
Tablet · Oral
Uses
Acetaminophen and codeine phosphate oral solution is 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 acetaminophen and codeine phosphate oral solution, for use in patients for whom alternative treatment options are ineffective, not tolerated, or would be otherwise inadequate to provide sufficient management of pain.
Dosage and administration
Important Dosage and Administration Instructions Ensure accuracy when prescribing, dispensing, and administering acetaminophen and codeine phosphate oral solution to avoid dosing errors due to confusion between mg and mL, and with other acetaminophen and codeine phosphate solutions of different concentrations, which could result in accidental overdose and death. Ensure the proper dose is communicated and dispensed. When writing prescriptions, include both the total dose in mg and the total dose in volume. Instruct patients and caregivers on how to accurately measure and take or administer the correct dose of acetaminophen and codeine phosphate oral solution. Strongly advise patients and caregivers to always use a graduated oral syringe or measuring cup, with metric units of measurements (i.e., mL), to correctly measure the prescribed amount of medication. Inform patients and caregivers that oral dosing devises may be obtained from their pharmacy and to never use household teaspoons or tablespoons to measure acetaminophen and codeine phosphate oral solution. Acetaminophen and codeine phosphate oral solution should be prescribed only by healthcare professionals who are knowledgeable about the use of opioids and how to mitigate the associated risks. Use the lowest effective dosage for the shortest duration of time consistent with individual patient treatment goals [see WARNINGS ]. Because the risk of overdose increases as opioid doses increase, reserve titration to higher doses of acetaminophen and codeine phosphate oral solution for patients in whom lower doses are insufficiently effective and in whom the expected benefits of using a higher dose opioid clearly outweigh the substantial risks. Many acute pain conditions (e.g., the pain that occurs with a number of surgical procedures or acute musculoskeletal injuries) require no more than a few days of an opioid analgesic. Clinical guidelines on opioid prescribing for some acute pain conditions are available. There is variability in the opioid analgesic dose and duration needed to adequately manage pain due both to the cause of pain and to individual patient factors. Initiate the dosing regimen for each patient individually, taking into account the patient’s underlying cause and severity of pain, prior analgesic treatment and response, and risk factors for addiction, abuse, and misuse [see WARNINGS ]. Respiratory depression can occur at any time during opioid therapy, especially when initiating and following dosage increases with acetaminophen and codeine phosphate oral solution. Consider this risk when selecting an initial dose and when making dose adjustments [see WARNINGS ]. Patient Access to an Opioid Overdose Reversal Agent for the Emergency Treatment of Opioid Overdose Inform patients and caregivers about opioid overdose reversal agents (e.g., naloxone, nalmefene). Discuss the importance of having access to an opioid overdose reversal agent, especially if the patient has risk factors for overdose (e.g., concomitant use of CNS depressants, a history of opioid use disorder, or prior opioid overdose) or if there are household members (including children) or other close contacts at risk for accidental ingestion or opioid overdose. The presence of risk factors for overdose should not prevent the management of pain in any patient [see WARNINGS ; Addiction, Abuse, and Misuse ; Life-Threatening Respiratory Depression ; Risks from Concomitant Use with Benzodiazepines or Other CNS Depressants ]. Discuss the options for obtaining an opioid overdose reversal agent (e.g., prescription, over-the-counter, or as part of a community-based program). There are important differences among the opioid overdose reversal agents, such as route of administration, product strength, approved patient age range, and pharmacokinetics. Be familiar with these differences, as outlined in the approved labeling for those products, prior to recommending or prescribing such an agent. Initial Dosage Use of Acetaminophen and Codeine Phosphate Oral Solution as the First Opioid Analgesic Initiate treatment with acetaminophen and codeine phosphate oral solution at a dose of 15 mL (1 tablespoonful every 4 hours as needed for pain. Titrate the dose based upon the individual patient’s response to their initial dose of acetaminophen and codeine phosphate oral solution. Dosage should be adjusted according to severity of pain and response of the patient. However, it should be kept in mind that tolerance to codeine can develop with continued use and that the incidence of untoward effects is dose related. Adult doses of codeine higher than 60 mg are associated with an increased incidence of adverse reactions and are not associated with greater efficacy. Acetaminophen and codeine phosphate oral solution contains 120 mg of acetaminophen and 12 mg of codeine phosphate per 5 mL (teaspoonful) and is given orally. Adults 15 mL (1 tablespoonful) every 4 hours as needed. Conversion from Other Opioids to Acetaminophen and Codeine Phosphate Oral Solution There is inter-patient variability in the potency of opioid drugs and opioid formulations. Therefore, a conservative approach is advised when determining the total daily dosage of acetaminophen and codeine phosphate oral solution. It is safer to underestimate a patient’s 24-hour acetaminophen and codeine phosphate oral solution dosage than to overestimate the 24-hour acetaminophen and codeine phosphate oral solution dosage and manage an adverse reaction due to overdose. Titration and Maintenance of Therapy Individually titrate acetaminophen and codeine phosphate oral solution to a dose that provides adequate analgesia and minimizes adverse reactions. Continually reevaluate patients receiving acetaminophen and codeine phosphate oral solution to assess the maintenance of pain control, signs and symptoms of opioid withdrawal, and other adverse reactions, as well as reassess for the development of addiction, abuse, or misuse [see WARNINGS ].
Contraindications
Acetaminophen and codeine phosphate oral solution is 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 oral solution is 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 ] . Patients with known or suspected gastrointestinal obstruction, including paralytic ileus [see WARNINGS ]. Patients with hypersensitivity to codeine, acetaminophen, or any of the formulation excipients (e.g., anaphylaxis) [see WARNINGS ].
Warnings
Risk of Accidental Overdose and Death due to Medication Errors Dosing errors can result in accidental overdose and death. Avoid dosing errors that may result from confusion between mg and mL and confusion with acetaminophen and codeine phosphate solutions of different concentrations, when prescribing, dispensing, and administering acetaminophen and codeine phosphate oral solution. Ensure that the dose is communicated clearly and dispensed accurately. Instruct patients and caregivers on how to measure and take or administer the correct dose of acetaminophen and codeine phosphate oral solution and to use extreme caution when measuring the dose. Strongly advise patients to obtain and always use a graduated device that can measure and deliver the prescribed dose accurately, and to never use household teaspoons or tablespoons to measure a dose because these are not accurate measuring devices. Addiction, Abuse, and Misuse Acetaminophen and codeine phosphate oral solution contains codeine, a Schedule II controlled substance. As an opioid, acetaminophen and codeine phosphate oral solution exposes users to the risks of addiction, abuse, and misuse [see DRUG ABUSE AND DEPENDENCE ]. Although the risk of addiction in any individual is unknown, it can occur in patients appropriately prescribed acetaminophen and codeine phosphate oral solution. Addiction can occur at recommended dosages and if the drug is misused or abused. The risk of opioid-related overdose or overdose-related death is increased with higher opioid doses, and this risk persists over the course of therapy. In postmarketing studies, addiction, abuse, misuse, and fatal and non-fatal opioid overdose were observed in patients with long-term opioid use [see ADVERSE REACTIONS ]. Assess each patient’s risk for opioid addiction, abuse, or misuse prior to prescribing acetaminophen and codeine phosphate oral solution, and reassess all patients receiving acetaminophen and codeine phosphate oral solution for the development of these behaviors and conditions. Risks are increased in patients with a personal or family history of substance abuse (including drug or alcohol abuse or addiction) or mental illness (e.g., major depression). The potential for these risks should not, however, prevent the proper management of pain in any given patient. Patients at increased risk may be prescribed opioids such as acetaminophen and codeine phosphate oral solution, but use in such patients necessitates intensive counseling about the risks and proper use of acetaminophen and codeine phosphate oral solution along with frequent reevaluation for signs of addiction, abuse, and misuse. Consider recommending or prescribing an opioid overdose reversal agent [ WARNINGS , DOSAGE AND ADMINISTRATION ] Opioids are sought for nonmedical use and are subject to diversion from legitimate prescribed use. Consider these risks when prescribing or dispensing acetaminophen and codeine phosphate oral solution. Strategies to reduce these risks include prescribing the drug in the smallest appropriate quantity and advising the patient on the proper disposal of unused drug. Contact local state professional licensing board or state-controlled substances authority for information on how to prevent and detect abuse or diversion of this product. Life-Threatening Respiratory Depression 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. Management of respiratory depression may include close observation, supportive measures, and use of opioid overdose reversal agents, depending on the patient's clinical status [see OVERDOSAGE ]. Carbon dioxide (CO 2 ) retention from opioid-induced respiratory depression can exacerbate the sedating effects of opioids. While serious, life-threatening, or fatal respiratory depression can occur at any time during the use of acetaminophen and codeine phosphate oral solution, the risk is greatest during the initiation of therapy or following a dosage increase. Monitor patients closely for respiratory depression, especially within the first 24-72 hours of initiating therapy with and following dosage increases of acetaminophen and codeine phosphate oral solution. To reduce the risk of respiratory depression, proper dosing and titration of acetaminophen and codeine phosphate oral solution is essential [see DOSAGE AND ADMINISTRATION ]. Overestimating the acetaminophen and codeine phosphate oral solution dosage when converting patients from another opioid product can result in a fatal overdose with the first dose. Accidental ingestion of even one dose of acetaminophen and codeine phosphate oral solution, especially by children, can result in respiratory depression and death due to an overdose of codeine. Educate patients and caregivers on how to recognize respiratory depression and emphasize the importance of calling 911 or getting emergency medical help right away in the event of a known or suspected overdose [see PRECAUTIONS , Information for Patients ]. Opioids can cause sleep-related breathing disorders including central sleep apnea (CSA) and sleep related hypoxemia. Opioid use increases the risk of CSA in a dose-dependent fashion. In patients who present with CSA, consider decreasing the opioid dosage using best practices for opioid taper [see DOSAGE AND ADMINISTRATION ]. Patient Access to an Opioid Overdose Reversal Agent for the Emergency Treatment of Opioid Overdose Inform patients and caregivers about opioid overdose reversal agents (e.g., naloxone, nalmefene).
Precautions
Risks of Driving and Operating Machinery Acetaminophen and codeine phosphate oral solution may impair the mental or physical abilities needed to perform potentially hazardous activities such as driving a car or operating machinery. Warn patients not to drive or operate dangerous machinery unless they are tolerant to the effects of acetaminophen and codeine phosphate oral solution and know how they will react to the medication [see PRECAUTIONS ; Information for Patients/Caregivers ]. Information for Patients/Caregivers Advise the patient to read the FDA-approved patient labeling (Medication Guide). Storage and Disposal: Because of the risks associated with accidental ingestion, misuse, and abuse, advise patients to store acetaminophen and codeine phosphate oral solution 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 oral solution unsecured can pose a deadly risk to others in the home [see WARNINGS , DRUG ABUSE AND DEPENDENCE ]. Advise patients and caregivers that when medicines are no longer needed, they should be disposed of promptly. Inform patients that medicine take-back options are the preferred way to safely dispose of most types of unneeded medicines. If no take-back programs or DEA-registered collectors are available, instruct patients to dispose of acetaminophen and codeine phosphate oral solution by following these four steps: Mix acetaminophen and codeine phosphate oral solution with an unpalatable substance such as dirt, cat litter, or used coffee grounds; Place the mixture in a container such as a sealed plastic bag; Throw the container in the household trash; Delete all personal information on the prescription label of the empty bottle Inform patients that they can visit www.fda.gov/drugdisposal for additional information on disposal of unused medicines. Advise the patient to read the FDA-approved patient labeling (Medication Guide). Medication Errors Strongly advise patients and caregivers to always use a graduated oral syringe or measuring cup, with metric units of measurements (i.e., mL), to correctly measure the prescribed amount of medication. Inform patients and caregivers that oral dosing devices may be obtained from their pharmacy and to never use household teaspoons or tablespoons to measure acetaminophen and codeine phosphate oral solution [see WARNINGS ; PRECAUTIONS ]. Instruct patients how to measure and take the correct dose of acetaminophen and codeine phosphate oral solution and ensure that the dose is communicated clearly and dispensed accurately. A household teaspoon is not an adequate measuring device. Given the inexactitude of the household spoon measure and the risk of using a tablespoon instead of a teaspoon, which could lead to overdosage, it is strongly recommended that caregivers obtain and use a calibrated measuring device. Healthcare providers should recommend a calibrated device that can measure and deliver the prescribed dose accurately, and instruct caregivers to use extreme caution in measuring the dosage and when administering acetaminophen and codeine phosphate oral solution to ensure the dose is measured and administered accurately [see WARNINGS ]. If the prescribed concentration is changed, instruct patients on how to correctly measure the new dose to avoid errors which could result in accidental overdose and death. Addiction, Abuse, and Misuse Inform patients that the use of acetaminophen and codeine phosphate oral solution, even when taken as recommended, can result in addiction, abuse, and misuse, which can lead to overdose and death [see WARNINGS ]. Instruct patients not to share acetaminophen and codeine phosphate oral solution with others and to take steps to protect acetaminophen and codeine phosphate oral solution from theft or misuse. Life-Threatening Respiratory Depression Inform patients of the risk of life-threatening respiratory depression, including information that the risk is greatest when starting acetaminophen and codeine phosphate oral solution or when the dosage is increased, and that it can occur even at recommended dosages. Educate patients and caregivers on how to recognize respiratory depression and emphasize the importance of calling 911 or getting emergency medical help right away in the event of a known or suspected overdose [see WARNINGS , Life Threatening Respiratory Depression ]. Accidental Ingestion Inform patients that accidental ingestion, especially by children, may result in respiratory depression or death [see WARNINGS ]. Interactions with Benzodiazepines and Other CNS Depressants Inform patients and caregivers that potentially fatal additive effects may occur if acetaminophen and codeine phosphate oral solution is used with benzodiazepines or other CNS depressants, (e.g., alcohol, non-benzodiazepine, sedative/hypnotics, anxiolytics, tranquilizers, muscle relaxants, general anesthetics, antipsychotics, gabapentinoids [gabapentin or pregabalin], and other opioids), and not to use these concomitantly unless supervised by a healthcare provider [see WARNINGS , PRECAUTIONS ; Drug Interactions ] . Patient Access to an Opioid Overdose Reversal Agent for the Emergency Treatment of Opioid Overdose Inform patients and caregivers about opioid overdose reversal agents (e.g., naloxone, nalmefene). Discuss the importance of having access to an opioid overdose reversal agent, especially if the patient has risk factors for overdose (e.g., concomitant use of CNS depressants, a history of opioid use disorder, or prior opioid overdose) or if there are household members (including children) or other close contacts at risk for accidental ingestion or opioid overdose. Discuss with the patient the options for obtaining an opioid overdose reversal agent (e.g., prescription, over-the-counter, or as part of a community-based program) [see WARNINGS , DOSAGE AND ADMINISTRATION ].
Side effects
The following serious adverse reactions are described, or described in greater detail, in other sections: Addiction, Abuse, and Misuse [see WARNINGS ] Life-Threatening Respiratory Depression [see WARNINGS ] Ultra-Rapid Metabolism of Codeine and Other Risk Factors for Life-Threatening Respiratory Depression in Children [see WARNINGS ] Neonatal Opioid Withdrawal Syndrome [see WARNINGS ] Interactions with CNS Depressants [see WARNINGS ] Severe Hypotension [see WARNINGS ] Gastrointestinal Adverse Reactions [see WARNINGS ] Seizures [see WARNINGS ] Withdrawal [see WARNINGS ] The following adverse reactions associated with the use of codeine were identified in postmarketing reports. Because some of these reactions were reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Serious adverse reactions associated with codeine are respiratory depression and, to a lesser degree, circulatory depression, respiratory arrest, shock, and cardiac arrest. The most frequently observed adverse reactions with codeine administration include drowsiness, lightheadedness, dizziness, sedation, shortness of breath, nausea, vomiting, sweating, and constipation. Other adverse reactions include allergic reactions, euphoria, dysphoria, abdominal pain, pruritis, rash, thrombocytopenia, and agranulocytosis. Other less frequently observed adverse reactions expected from opioid analgesics, including acetaminophen and codeine phosphate oral solution: Cardiovascular system : faintness, flushing, hypotension, palpitations, syncope Digestive System : abdominal cramps, anorexia, diarrhea, dry mouth, gastrointestinal distress, pancreatitis Nervous system : anxiety, drowsiness, fatigue, headache, insomnia, nervousness, shakiness, somnolence, vertigo, visual disturbances, weakness Skin and Appendages : rash, sweating, urticarial Serotonin syndrome : Cases of serotonin syndrome, a potentially life-threatening condition, have been reported during concomitant use of opioids with serotonergic drugs. Adrenal insufficiency : Cases of adrenal insufficiency have been reported with opioid use, more often following greater than one month of use. Anaphylaxis : Anaphylaxis has been reported with ingredients contained in acetaminophen and codeine phosphate oral solution. Androgen deficienc y: Cases of androgen deficiency have occurred with chronic use of opioids [see CLINICAL PHARMACOLOGY ]. Hyperalgesia and Allodynia : Cases of hyperalgesia and allodynia have been reported with opioid therapy of any duration [see WARNINGS ] Hypoglycemia: Cases of hypoglycemia have been reported in patients taking opioids. Most reports were in patients with at least one predisposing risk factor (e.g., diabetes). Opioid –induced esophageal dysfunction (OIED): Cases of OIED have been reported in patients taking opioids, and may occur more frequently in patients taking higher doses of opioids, and/or in patients taking opioids longer term [see WARNINGS ]. Adverse Reactions from Observation Studies A prospective, observational cohort study estimated the risks of addiction, abuse, and misuse in patients initiating long-term use of Schedule II opioid analgesics between 2017 and 2021. Study participants included in one or more analyses had been enrolled in selected insurance plans or health systems for at least one year, were free of at least one outcome at baseline, completed a minimum number of follow-up assessments, and either: 1) filled multiple extended-release/long-acting opioid analgesic prescriptions during a 90 day period (n=978); or 2) filled any Schedule II opioid analgesic prescriptions covering at least 70 of 90 days (n=1,244). Those included also had no dispensing of the qualifying opioids in the previous 6 months. Over 12 months: approximately 1% to 6% of participants across the two cohorts newly met criteria for addiction, as assessed with two validated interview-based measures of moderate-to- severe opioid use disorder based on Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) criteria, and approximately 9% and 22% of participants across the two cohorts newly met criteria for prescription opioid abuse and misuse [defined in DRUG ABUSE AND DEPENDENCE ], respectively, as measured with a validated self-reported instrument. A retrospective, observational cohort study estimated the risk of opioid-involved overdose or opioid overdose-related death in patients with new long-term use of Schedule II opioid analgesics from 2006 through 2016 (n=220,249). Included patients had been enrolled in either one of two commercial insurance programs, one managed care program, or one Medicaid program for at least 9 months. New long-term use was defined as having Schedule II opioid analgesic prescriptions covering at least 70 days’ supply over the 3 months prior to study entry and none during the preceding 6 months. Patients were excluded if they had an opioid-involved overdose in the 9 months prior to study entry. Overdose was measured using a validated medical code-based algorithm with linkage to the National Death Index database. The 5-year cumulative incidence estimates for opioid-involved overdose or opioid overdose-related death ranged from approximately 1.5% to 4% across study sites, counting only the first event during follow-up. Approximately 17% of first opioid overdoses observed over the entire study period (5-11 years, depending on the study site) were fatal. Higher baseline opioid dose was the strongest and most consistent predictor of opioid-involvedoverdose or opioid overdose-related death. Study exclusion criteria may have selected patients at lower risk of overdose, and substantial loss to follow-up (approximately 80%) also may have biased estimates.
Overdosage
Following an acute overdosage, toxicity may result from codeine or acetaminophen. Clinical Presentation Codeine Acute overdose with codeine can be manifested by respiratory depression, somnolence progressing to stupor or coma, skeletal muscle flaccidity, cold and clammy skin, constricted pupils, and, in some cases, pulmonary edema, bradycardia, hypotension, hypoglycemia, partial or complete airway obstruction, atypical snoring, and death. Marked mydriasis rather than miosis may be seen with hypoxia in overdose situations [see CLINICAL PHARMACOLOGY ]. Toxic leukoencephalopathy has been reported after opioid overdose and can present hours, days, or weeks after apparent recovery from the initial intoxication. Acetaminophen Dose-dependent, potentially fatal hepatic necrosis is the most serious adverse effect of acetaminophen. Renal tubular necrosis, hypoglycemic coma, and coagulation defects may also occur. Early symptoms following a potentially hepatotoxic overdose may include; anorexia, nausea, vomiting, diaphoresis, pallor and general malaise. Clinical and laboratory evidence of hepatic toxicity may not be apparent until 48 to 72 hours post-ingestion. Treatment of Overdose Codeine In case of overdose, priorities are the reestablishment of a patent and protected airway and institution of assisted or controlled ventilation, if needed. Employ other supportive measures (including oxygen and vasopressors) in the management of circulatory shock and pulmonary edema as indicated. Cardiac arrest or serious arrhythmias will require advanced life-support measures. For clinically significant respiratory or circulatory depression secondary to opioid overdose, administer an opioid overdose reversal agent such as naloxone or nalmefene. Because the duration of opioid reversal is expected to be less than the duration of action of acetaminophen and codeine phosphate oral solution, carefully monitor the patient until spontaneous respiration is reliably reestablished. If the response to an opioid overdose reversal agent is suboptimal or only brief in nature, administer additional reversal agent as directed by the product’s prescribing information. In an individual physically dependent on opioids, administration of the recommended dosage of the opioid overdose reversal agent will precipitate an acute withdrawal syndrome. The severity of the withdrawal symptoms experienced will depend on the degree of physical dependence and the dose of the reversal agent administered. If a decision is made to treat serious respiratory depression in the physically dependent patient, administration of the reversal agent should be begun with care and by titration with smaller than usual doses of the reversal agent. Acetaminophen Gastric decontamination with activated charcoal should be administered just prior to N-acetylcysteine (NAC) to decrease systemic absorption if acetaminophen ingestion is known or suspected to have occurred within a few hours of presentation. Serum acetaminophen levels should be obtained immediately if the patient presents 4 hours or more after ingestion to assess potential risk of hepatotoxicity; acetaminophen levels drawn less than 4 hours post-ingestion may be misleading. To obtain the best possible outcome, NAC should be administered as soon as possible where impending or evolving liver injury is suspected. Intravenous NAC may be administered when circumstances preclude oral administration.
Description
Acetaminophen and Codeine Phosphate Oral Solution is pharmacologically classified as an analgesic. Acetaminophen, 4'-hydroxyacetanilide, a slightly bitter, white, odorless, crystalline powder, is a non-opioid, non-salicylate analgesic and antipyretic. It has the following structural formula: C 8 H g NO 2 N.W. 151.16 Codeine phosphate, 7,8-didehydro-4,5α-epoxy-3-methoxy-17-methylmorphinan-6α-ol phosphate (1:1) (salt) hemihydrate, a white crystalline powder, is an opioid agonist. It has the following structural formula: C 18 H 21 NO 3∙ H 3 PO 4∙ 1/2H 2 O M.W. 406.37 Each Acetaminophen and Codeine Phosphate Oral Solution, USP 120 mg/12 mg per 5 mL, for oral administration, contains: Acetaminophen 120 mg Codeine Phosphate 12 mg Alcohol 7% Acetaminophen Chemical Structure Codeine Phosphate structure INACTIVE INGREDIENTS FD&C Red No. 40, FD&C Yellow No. 6 (Sunset Yellow), flavoring, glycerin, propylene glycol, purified water, saccharin sodium, and sucrose.
Mechanism of action
Mechanism of Action 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.
How supplied
Acetaminophen and Codeine Phosphate Oral Solution USP (orange-yellow color, cherry flavor) is supplied in the following oral dosage forms: NDC 0121-0504-05: 5 mL unit dose cup. Case contains 40 unit-dose cups of 5 mL (NDC 0121-0504-40), packaged in 4 trays of 10 unit-dose cups each. NDC 0121-1008-12: 12.5 mL unit dose cup. Case contains 40 unit-dose cups of 12.5 mL (NDC 0121-1008-40), packaged in 4 trays of 10 unit-dose cups each.
Storage
Store at 20° to 25°C (68° to 77°F) [See USP Controlled Room Temperature]. Dispense in a tight, light-resistant container with a child-resistant closure. Store acetaminophen and codeine phosphate oral solution securely and dispose of properly [see PRECAUTIONS / Information for Patients ].
Label text from the FDA structured product label by PAI Holdings, LLC dba PAI Pharma (revised Aug 6, 2026). Long sections are shortened; the complete label is on DailyMed.
Active ingredients
- Acetaminophen in 69 products
- Codeine Phosphate in 69 products
Acetaminophen and Codeine Phosphate NDC products (69)
| NDC | Strength & form | Labeler | Type |
|---|---|---|---|
| 50090-4611 | Acetaminophen 300 mg/1; Codeine Phosphate 30 mg/1 Tablet | A-S Medication Solutions | ANDA · DEA CIII |
| 50090-4610 | Acetaminophen 300 mg/1; Codeine Phosphate 30 mg/1 Tablet | A-S Medication Solutions | ANDA · DEA CIII |
| 50090-3011 | Acetaminophen 300 mg/1; Codeine Phosphate 60 mg/1 Tablet | A-S Medication Solutions | ANDA · DEA CIII |
| 80425-0530 | Acetaminophen 300 mg/1; Codeine Phosphate 60 mg/1 Tablet | Advanced Rx of Tennessee, LLC | ANDA · DEA CIII |
| 80425-0527 | Acetaminophen 300 mg/1; Codeine Phosphate 30 mg/1 Tablet | Advanced Rx of Tennessee, LLC | ANDA · DEA CIII |
| 80425-0528 | Acetaminophen 300 mg/1; Codeine Phosphate 60 mg/1 Tablet | Advanced Rx of Tennessee, LLC | ANDA · DEA CIII |
| 80425-0529 | Acetaminophen 300 mg/1; Codeine Phosphate 30 mg/1 Tablet | Advanced Rx of Tennessee, LLC | ANDA · DEA CIII |
| 67544-003 | Acetaminophen 300 mg/1; Codeine Phosphate 60 mg/1 Tablet | Aphena Pharma Solutions - Tennessee, LLC | ANDA · DEA CIII |
| 67544-002 | Acetaminophen 300 mg/1; Codeine Phosphate 30 mg/1 Tablet | Aphena Pharma Solutions - Tennessee, LLC | ANDA · DEA CIII |
| 76420-821 | Acetaminophen 300 mg/1; Codeine Phosphate 30 mg/1 Tablet | Asclemed USA, Inc. | ANDA · DEA CIII |
| 13107-058 | Acetaminophen 300 mg/1; Codeine Phosphate 15 mg/1 Tablet | Aurolife Pharma, LLC | ANDA · DEA CIII |
| 13107-059 | Acetaminophen 300 mg/1; Codeine Phosphate 30 mg/1 Tablet | Aurolife Pharma, LLC | ANDA · DEA CIII |
| 13107-060 | Acetaminophen 300 mg/1; Codeine Phosphate 60 mg/1 Tablet | Aurolife Pharma, LLC | ANDA · DEA CIII |
| 71335-0256 | Acetaminophen 300 mg/1; Codeine Phosphate 30 mg/1 Tablet | Bryant Ranch Prepack | ANDA · DEA CIII |
| 71335-0336 | Acetaminophen 300 mg/1; Codeine Phosphate 60 mg/1 Tablet | Bryant Ranch Prepack | ANDA · DEA CIII |
| 71335-1522 | Acetaminophen 300 mg/1; Codeine Phosphate 30 mg/1 Tablet | Bryant Ranch Prepack | ANDA · DEA CIII |
| 71335-1818 | Acetaminophen 300 mg/1; Codeine Phosphate 30 mg/1 Tablet | Bryant Ranch Prepack | ANDA · DEA CIII |
| 71335-1846 | Acetaminophen 300 mg/1; Codeine Phosphate 60 mg/1 Tablet | Bryant Ranch Prepack | ANDA · DEA CIII |
| 71335-2818 | Acetaminophen 300 mg/1; Codeine Phosphate 60 mg/1 Tablet | Bryant Ranch Prepack | ANDA · DEA CIII |
| 71335-2916 | Acetaminophen 300 mg/1; Codeine Phosphate 30 mg/1 Tablet | Bryant Ranch Prepack | ANDA · DEA CIII |
| 63629-3031 | Acetaminophen 300 mg/1; Codeine Phosphate 60 mg/1 Tablet | Bryant Ranch Prepack | ANDA · DEA CIII |
| 63629-1190 | Acetaminophen 300 mg/1; Codeine Phosphate 60 mg/1 Tablet | Bryant Ranch Prepack | ANDA · DEA CIII |
| 72162-2001 | Acetaminophen 300 mg/1; Codeine Phosphate 30 mg/1 Tablet | Bryant Ranch Prepack | ANDA · DEA CIII |
| 63629-5666 | Acetaminophen 300 mg/1; Codeine Phosphate 30 mg/1 Tablet | Bryant Ranch Prepack | ANDA · DEA CIII |
| 72162-2002 | Acetaminophen 300 mg/1; Codeine Phosphate 60 mg/1 Tablet | Bryant Ranch Prepack | ANDA · DEA CIII |
| 58118-0485 | Acetaminophen 300 mg/1; Codeine Phosphate 60 mg/1 Tablet | Clinical Solutions Wholesale, LLC | ANDA · DEA CIII |
| 58118-4484 | Acetaminophen 300 mg/1; Codeine Phosphate 30 mg/1 Tablet | Clinical Solutions Wholesale, LLC | ANDA · DEA CIII |
| 72189-376 | Acetaminophen 300 mg/1; Codeine Phosphate 60 mg/1 Tablet | Direct_Rx | ANDA · DEA CIII |
| 64850-641 | Acetaminophen 300 mg/1; Codeine Phosphate 15 mg/1 Tablet | Elite Laboratories, Inc. | ANDA · DEA CII |
| 64850-642 | Acetaminophen 300 mg/1; Codeine Phosphate 30 mg/1 Tablet | Elite Laboratories, Inc. | ANDA · DEA CIII |
| 64850-643 | Acetaminophen 300 mg/1; Codeine Phosphate 60 mg/1 Tablet | Elite Laboratories, Inc. | ANDA · DEA CIII |
| 71930-055 | Acetaminophen 300 mg/1; Codeine Phosphate 30 mg/1 Tablet | Eywa Pharma Inc | ANDA · DEA CIII |
| 71930-054 | Acetaminophen 300 mg/1; Codeine Phosphate 15 mg/1 Tablet | Eywa Pharma Inc | ANDA · DEA CIII |
| 71930-056 | Acetaminophen 300 mg/1; Codeine Phosphate 60 mg/1 Tablet | Eywa Pharma Inc | ANDA · DEA CIII |
| 64950-374 | Acetaminophen 120 mg/5mL; Codeine Phosphate 12 mg/5mL Solution | Genus Lifesciences Inc. | ANDA · DEA CV |
| 68071-3658 | Acetaminophen 300 mg/1; Codeine Phosphate 30 mg/1 Tablet | NuCare Pharmaceuticals, Inc. | ANDA · DEA CIII |
| 68071-3824 | Acetaminophen 300 mg/1; Codeine Phosphate 30 mg/1 Tablet | NuCare Pharmaceuticals, Inc. | ANDA · DEA CIII |
| 68071-3798 | Acetaminophen 300 mg/1; Codeine Phosphate 30 mg/1 Tablet | NuCare Pharmaceuticals, Inc. | ANDA · DEA CIII |
| 68071-3651 | Acetaminophen 300 mg/1; Codeine Phosphate 30 mg/1 Tablet | NuCare Pharmaceuticals, Inc. | ANDA · DEA CIII |
| 68071-4533 | Acetaminophen 300 mg/1; Codeine Phosphate 30 mg/1 Tablet | NuCare Pharmaceuticals,Inc. | ANDA · DEA CIII |
| 68071-4673 | Acetaminophen 300 mg/1; Codeine Phosphate 30 mg/1 Tablet | NuCare Pharmaceuticals,Inc. | ANDA · DEA CIII |
| 68071-4749 | Acetaminophen 300 mg/1; Codeine Phosphate 60 mg/1 Tablet | NuCare Pharmaceuticals,Inc. | ANDA · DEA CIII |
| 68071-5010 | Acetaminophen 300 mg/1; Codeine Phosphate 30 mg/1 Tablet | NuCare Pharmaceuticals,Inc. | ANDA · DEA CIII |
| 68071-4475 | Acetaminophen 300 mg/1; Codeine Phosphate 30 mg/1 Tablet | NuCare Pharmaceuticals,Inc. | ANDA · DEA CIII |
| 0121-1008 | Acetaminophen 300 mg/12.5mL; Codeine Phosphate 30 mg/12.5mL Solution | PAI Holdings, LLC dba PAI Pharma | ANDA · DEA CV |
| 0121-0504 | Acetaminophen 120 mg/5mL; Codeine Phosphate 12 mg/5mL Solution | PAI Holdings, LLC dba PAI Pharma | ANDA · DEA CV |
| 68788-8882 | Acetaminophen 300 mg/1; Codeine Phosphate 60 mg/1 Tablet | Preferred Pharmaceuticals Inc. | ANDA · DEA CIII |
| 68788-8881 | Acetaminophen 300 mg/1; Codeine Phosphate 60 mg/1 Tablet | Preferred Pharmaceuticals Inc. | ANDA · DEA CIII |
| 68788-7859 | Acetaminophen 300 mg/1; Codeine Phosphate 60 mg/1 Tablet | Preferred Pharmaceuticals Inc. | ANDA · DEA CIII |
| 68788-7835 | Acetaminophen 300 mg/1; Codeine Phosphate 30 mg/1 Tablet | Preferred Pharmaceuticals Inc. | ANDA · DEA CIII |
| 82804-283 | Acetaminophen 300 mg/1; Codeine Phosphate 30 mg/1 Tablet | Proficient Rx LP | ANDA · DEA CIII |
| 82804-181 | Acetaminophen 300 mg/1; Codeine Phosphate 30 mg/1 Tablet | Proficient Rx LP | ANDA · DEA CIII |
| 63187-106 | Acetaminophen 300 mg/1; Codeine Phosphate 30 mg/1 Tablet | Proficient Rx LP | ANDA · DEA CIII |
| 63187-815 | Acetaminophen 300 mg/1; Codeine Phosphate 30 mg/1 Tablet | Proficient Rx LP | ANDA · DEA CIII |
| 49999-060 | Acetaminophen 300 mg/1; Codeine Phosphate 30 mg/1 Tablet | Quality Care Products, LLC | ANDA · DEA CIII |
| 67296-2239 | Acetaminophen 300 mg/1; Codeine Phosphate 30 mg/1 Tablet | Redpharm Drug | ANDA · DEA CIII |
| 70518-3705 | Acetaminophen 300 mg/1; Codeine Phosphate 30 mg/1 Tablet | REMEDYREPACK INC. | ANDA · DEA CIII |
| 70518-2628 | Acetaminophen 300 mg/1; Codeine Phosphate 30 mg/1 Tablet | REMEDYREPACK INC. | ANDA · DEA CIII |
| 70518-4104 | Acetaminophen 300 mg/1; Codeine Phosphate 30 mg/1 Tablet | REMEDYREPACK INC. | ANDA · DEA CIII |
| 70518-2764 | Acetaminophen 300 mg/1; Codeine Phosphate 60 mg/1 Tablet | REMEDYREPACK INC. | ANDA · DEA CIII |
| 0406-0485 | Acetaminophen 300 mg/1; Codeine Phosphate 60 mg/1 Tablet | SpecGx LLC | ANDA · DEA CIII |
| 0406-0484 | Acetaminophen 300 mg/1; Codeine Phosphate 30 mg/1 Tablet | SpecGx LLC | ANDA · DEA CIII |
| 0406-0483 | Acetaminophen 300 mg/1; Codeine Phosphate 15 mg/1 Tablet | SpecGx LLC | ANDA · DEA CIII |
| 60760-938 | Acetaminophen 300 mg/1; Codeine Phosphate 30 mg/1 Tablet | ST. MARY'S MEDICAL PARK PHARMACY | ANDA · DEA CIII |
| 60760-581 | Acetaminophen 300 mg/1; Codeine Phosphate 30 mg/1 Tablet | St. Mary's Medical Park Pharmacy | ANDA · DEA CIII |
| 64380-446 | Acetaminophen 300 mg/1; Codeine Phosphate 30 mg/1 Tablet | Strides Pharma Science Limited | ANDA · DEA CIII |
| 64380-447 | Acetaminophen 300 mg/1; Codeine Phosphate 60 mg/1 Tablet | Strides Pharma Science Limited | ANDA · DEA CIII |
| 64380-448 | Acetaminophen 300 mg/1; Codeine Phosphate 15 mg/1 Tablet | Strides Pharma Science Limited | ANDA · DEA CII |
| 87441-009 | Acetaminophen 300 mg/1; Codeine Phosphate 30 mg/1 Tablet | Unit Dose Solutions, Inc. | ANDA · DEA CIII |
Acetaminophen and Codeine Phosphate recalls
- D-1229-2020 Apr 22, 2020 · Class II · Terminated
CGMP Deviations: Products were manufactured in a processing area in which water leakage was observed - D-1230-2020 Apr 22, 2020 · Class II · Terminated
CGMP Deviations: Products were manufactured in a processing area in which water leakage was observed - D-1231-2020 Apr 22, 2020 · Class II · Terminated
CGMP Deviations: Products were manufactured in a processing area in which water leakage was observed - D-0806-2018 May 23, 2018 · Class II · Terminated
Labeling: Not Elsewhere Classified: due to a labeled declaration of; Store at 15¿C to 30¿C (59¿F to 86¿F) which differs from the original manufacturer declaration of; Store at 20¿C to 25¿C (68¿F to 77¿F).
Frequently asked questions
What is Acetaminophen and Codeine Phosphate used for?
Acetaminophen and codeine phosphate oral solution is 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 ],…
What are the side effects of Acetaminophen and Codeine Phosphate?
The following serious adverse reactions are described, or described in greater detail, in other sections: Addiction, Abuse, and Misuse [see WARNINGS ] Life-Threatening Respiratory Depression [see WARNINGS ] Ultra-Rapid Metabolism of Codeine and Other Risk Factors for Life-Threatening Respiratory Depression in Children [see WARNINGS ] Neonatal Opioid Withdrawal Syndrome [see WARNINGS ]… See the full label for the complete list.
Who makes Acetaminophen and Codeine Phosphate?
Acetaminophen and Codeine Phosphate is listed by 24 labelers in the FDA NDC directory, including A-S Medication Solutions, Advanced Rx of Tennessee, LLC, Aphena Pharma Solutions - Tennessee, LLC, Asclemed USA, Inc..
Has Acetaminophen and Codeine Phosphate been recalled?
The FDA enforcement database lists 4 recalls for Acetaminophen and Codeine Phosphate, most recently D-1229-2020 (class ii): CGMP Deviations: Products were manufactured in a processing area in which water leakage was observed