Last reviewed 2026-04-20 · How we verify

CODEINE PHOSPHATE

At a glance

Approved indications

No approved indications tracked.

Boxed warnings

• WARNING: ADDICTION, ABUSE, AND MISUSE: RISK EVALUATION AND MITIGATION STRATEGY (REMS), 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 WARNING: SERIOUS AND LIFE-THREATENING RISKS FROM USE OF ACETAMINOPHEN AND CODEINE PHOSPHATE TABLETS 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 acetaminophen and codeine phosphate tablets and monitor 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 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 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. Interactions with Drugs Affecting Cytochrome P450 Isoenzymes The 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 ].

Common side effects

• Nausea
• Drowsiness
• Dizziness
• Headache
• Vomiting
• Dry mouth
• Hyperhidrosis
• Shaky feeling
• Tingling
• Agitation
• Fatigue
• Heavy eyelids

Serious adverse events

• Fainting
• Numbness
• Diuresis
• Fever
• Earache
• Tinnitus
• High energy
• Hot spells

Key clinical trials

• E7 TCR T Cells for Human Papillomavirus-Associated Cancers (PHASE1, PHASE2)
• Evaluation of the Analgesic Efficacy of the Combination of Dexketoprofen + Paracetamol and the Combination of Naproxen Sodium + Codeine in Patients With Acute Dental Pain (PHASE4)
• PK of Codeine and Metabolites in Human Fingerprint Sweat, Oral Fluid, Blood and Urine
• Colonic Motor Patterns in Healthy Volunteers (PHASE4)
• An Randomized Control Trial Comparing Two Drug Combinations for Pain Management After Third Molars Surgery (NA)
• COMPARISON OF EFFICACY OF DIFFERENT DRUG COMBINATIONS IN ACUTE SCIATICA (PHASE3)
• Efficacy of Naproxen-codeine, Naproxen+Dexamethasone, and Naproxen on Myofascial Pain (PHASE4)
• A Prospective Trial to Assess Cost and Clinical Outcomes of a Clinical Pharmacogenomic Program (NA)

Primary sources

Every claim on this page is sourced from regulatory or scientific primary sources. See our editorial policy for full methodology.

Competitive intelligence

For the full competitive landscape — auto-detected comparators, recent regulatory actions across the set, upcoming PDUFA, patent timeline, sponsor landscape:

• CODEINE PHOSPHATE CI brief — competitive landscape report
• CODEINE PHOSPHATE updates RSS · CI watch RSS