FDA label 7acaaa54-3d76-6ef3-e053-2a91aa0a384f

WARNING: ADDICTION, ABUSE, AND MISUSE; LIFE-THREATENING RESPIRATORY DEPRESSION; ACCIDENTAL INGESTION; ULTRA-RAPID METABOLISM OF CODEINE AND OTHER RISK FACTORS FOR LIFE- THREATENING RESPIRATORY DEPRESSION IN CHILDREN; NEONATAL OPIOID WITHDRAWAL SYNDROME; INTERACTIONS WITH DRUGS AFFECTING CYTOCHROME P450 ISOENZYMES; HEPATOTOXICITY; and RISKS FROM CONCOMITANT USE WITH BENZODIAZEPINES OR OTHER CNS DEPRESSANTS Addiction, Abuse and Misuse Acetaminophen and codeine phosphate tablets expose 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 acetaminophen and codeine phosphate tablets, and monitor all patients regularly for the development of these behaviors and conditions [see WARNINGS ]. L ife-Threatening Respiratory Depression S er ious, life-threatening, or fatal respiratory depression may occur with use of acetaminophen and codeine phosphate tablets. Monitor for respiratory depression, especially during initiation of acetaminophen and codeine phosphate tablets or following a dose increase [see WARNINGS ]. Accidental Ingestion Accidental ingestion of acetaminophen and codeine phosphate tablets, especially by children, can result in a fatal overdose of acetaminophen and codeine phosphate tablets [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 CYP2D6 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 (see CONTRAINDICATIONS ). 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. Neonatal Opioid Withdrawal Syndrome P r olonged use of acetaminophen and codeine phosphate tablets during pregnancy can result in neonatal opioid withdrawal syndrome, which may be life-threatening if not recognized and treated, and requires management according to protocols developed by neonatology experts. If opioid use is required for a prolonged period in a pregnant woman, advise the patient of the risk of neonatal opioid withdrawal syndrome and ensure that appropriate treatment will be available [see WARNINGS ]. Interactions with Drugs Affecting Cytochrome P450 Isoenzymes Th e effects of concomitant use or discontinuation of cytochrome P450 3A4 inducers, 3A4 inhibitors, or 2D6 inhibitors with codeine are complex. Use of cytochrome P450 3A4 inducers, 3A4 inhibitors, or 2D6 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 ]. 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 [see WARNINGS , Drug Interactions ]. 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. Limit dosages and durations to the minimum required. Follow patients for signs and symptoms of respiratory depression and sedation.

Sulfite Sensitivity Acetaminophen and codeine phosphate tablets contain sodium metabisulfite, a sulfite that may cause allergic-type reactions including anaphylactic symptoms and life-threatening or less severe asthmatic episodes in certain susceptible people. The overall prevalence of sulfite sensitivity in the general population is unknown and probably low. Sulfite sensitivity is seen more frequently in asthmatic than in nonasthmatic people.

Increased Risk of Seizures in Patients with Seizure Disorders The codeine in acetaminophen and codeine phosphate tablets may increase the frequency of seizures in patients with seizure disorders, and may increase the risk of seizures occurring in other clinical settings associated with seizures. Monitor patients with a history of seizure disorders for worsened seizure control during acetaminophen and codeine phosphate tablets therapy.

Withdrawal 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. In these patients, mixed agonist/antagonist and partial analgesics may reduce the analgesic effect and/or precipitate withdrawal symptoms. When discontinuing acetaminophen and codeine phosphate tablets, gradually taper the dosage [see DOSAGE AND ADMINISTRATION ]. Do not abruptly discontinue acetaminophen and codeine phosphate tablets [see DRUG ABUSE AND DEPENDENCE ].

ADVERSE REACTIONS 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, pruritus, rash, thrombocytopenia, and agranulocytosis. Other less frequently observed adverse reactions expected from opioid analgesics, including Acetaminophen and Codeine phosphate Tablets: 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 tablets. Androgen deficiency : Cases of androgen deficiency have occurred with chronic use of opioids [see CLINICAL PHARMACOLOGY ] .