Acetaminophen-Codeine Risks, Warnings, and Complications

MISUSE, ABUSE, AND DRUG ADDICTION: Acetaminophen-codeine is habit-forming and can lead to misuse, abuse, and psychological and physical dependence (opioid addiction) even when you take it at the recommended doses. Taking this medication without a doctor’s prescription or at higher doses can put you at risk of opioid overdose and death. Your doctor will prescribe the lowest effective dose of acetaminophen-codeine for the shortest period of time possible.

Before starting acetaminophen and codeine, tell your doctor if you have a personal or family history of mental illness or alcohol or drug abuse. Do not take a higher dose of this medicine or take it more frequently or for a longer duration than prescribed. 

The FDA mandates a Risk Evaluation and Mitigation Strategy (REMS) program for people receiving medical treatment with acetaminophen-codeine because of the potential for misuse, abuse, and dependence. Licensed healthcare practitioners are required to explain how to use this medicine properly as well as its risks and how to ensure safety with proper storage and disposal of this combination medicine.

SERIOUS BREATHING PROBLEMS: Acetaminophen-codeine can cause dangerously slow breathing, which can be fatal. The risk of this happening is highest in the first few days after starting the medication or after an increase in the dose. People with chronic breathing disorders like asthma, COPD, and obstructive sleep apnea; older adults; and children under 12 years of age are at a higher risk of this occurring. Drinking alcohol or taking certain medications such as benzodiazepines, anxiety medications, sedatives, and certain muscle relaxants, which can also slow down breathing, increases the risk of serious breathing problems. 

Give your provider a full list of all your medications to prevent potential interactions between your medications. Talk to your doctor about having naloxone (Narcan) available in case of an accidental overdose of acetaminophen and codeine. Seek emergency medical attention if you or a loved one develops difficulty breathing or bluish discoloration of the lips, fingers, or toes.

NEONATAL OPIOID WITHDRAWAL SYNDROME: If a pregnant woman takes acetaminophen-codeine, the medicine can be passed on to the unborn baby, causing a dependence on opioids. After birth, the baby can experience life-threatening withdrawal symptoms. This condition is called neonatal opioid withdrawal syndrome. Seek immediate medical attention if you took acetaminophen and codeine during pregnancy and your baby develops poor feeding, high-pitched crying, irritability, poor sleep, or seizures after birth.

DRUG INTERACTIONS: Acetaminophen-codeine can interact with many commonly prescribed medications, including antibiotics such as erythromycin, antiviral drugs like ritonavir, and antifungal medicines like ketoconazole. These interactions can lead to high plasma concentrations of acetaminophen-codeine in the body, increasing the risk of severe side effects and life-threatening slowed breathing. Other medications such as the TB medicine rifampin or a seizure medication such as phenytoin or carbamazepine can lower the plasma concentration of acetaminophen-codeine in the body and cause withdrawal symptoms or make it less effective in treating pain. Taking acetaminophen and codeine with alcohol, benzodiazepines, sedatives, and other CNS depressants can lead to life-threatening breathing problems. Tell your doctor or pharmacist about all the other medications you're taking before starting acetaminophen-codeine to avoid potentially dangerous interactions.

ADRENAL INSUFFICIENCY: Use of acetaminophen-codeine for more than one month can cause a fall in adrenal hormone levels with symptoms such as nausea, vomiting, lack of appetite, dizziness, and tiredness. Tell your doctor without delay if you experience these symptoms. You may need to stop acetaminophen-codeine and require treatment with corticosteroids.

SEVERE HYPOTENSION: Acetaminophen-codeine can cause dangerously low blood pressure (hypotension), dizziness, and fainting, especially when going from a sitting or lying position to standing. To lower your risk of falls, get up slowly from a sitting or lying position. Tell your doctor if you take a blood pressure medication or experience dizziness or lightheadedness that does not go away.

SERIOUS LIVER DAMAGE: High doses of acetaminophen can cause hepatotoxicity (permanent and serious liver damage) that can be life-threatening. The maximum dose of acetaminophen in adults is 3,000 to 4,000 mg per day. Before starting acetaminophen-codeine, tell your doctor if you have liver problems since this medicine can cause further damage to your liver. Avoid drinking alcohol while on this medicine since alcohol can damage the liver as well. Call your doctor if you develop signs of liver damage, such as upper stomach pain, yellowing of the skin or eyes, dark urine, and tiredness.

SEVERE SKIN REACTION AND ALLERGIC REACTION: Severe allergic reactions to acetaminophen-codeine can cause swelling of the face, anaphylaxis (closing of the throat), and difficulty breathing. Seek emergency medical help if you develop these signs and symptoms. Serious skin reactions can also occur with skin rash, hives, itching, blistering, and peeling. Stop taking acetaminophen and codeine and call your provider right away if you notice any skin changes. People with a sulfite or opioid allergy are at a higher risk.

RISK IN PEOPLE WITH CERTAIN MEDICAL CONDITIONS: People with certain health conditions, such as increased intracranial pressure (pressure inside the head) due to brain tumors or head injuries, gastrointestinal conditions such as paralytic ileus, and seizure disorders are at increased risk of complications from acetaminophen-codeine use. Give your healthcare professional a complete medical history before starting this medication.

WITHDRAWAL: Stopping acetaminophen and codeine suddenly after taking it for a long time can lead to life-threatening withdrawal symptoms. Do not abruptly stop this medicine without talking to your doctor. Call your doctor right away if you develop restlessness, irritability, anxiety, enlarged pupils, runny nose, sleep problems, sweating, chills, fast breathing, fast heartbeat, stomach cramps, nausea, vomiting, diarrhea, loss of appetite, or muscle aches.

OVERDOSE: Taking higher doses or more frequent doses of acetaminophen-codeine can lead to an overdose which can be fatal. Keep this medication out of reach of children to prevent accidental ingestion. Even one tablet of acetaminophen and codeine can cause an overdose in children. Make sure you and the people in your household know how to recognize the signs of an opioid overdose, such as extreme drowsiness, unresponsiveness, slowed breathing, slow heartbeat, and cold or clammy skin.

Talk to your provider about having naloxone (Narcan) available in case of an accidental opioid overdose. Call 911 or emergency medical services in case of a known or suspected overdose.

EXTREME SLEEPINESS AND DIFFICULTY CONCENTRATING: Taking opioid medicine such as acetaminophen-codeine can make you sleepy and affect your ability to focus and react. The risk is higher if you're taking other medications that also cause drowsiness, such as sedatives, benzodiazepines, muscle relaxants, and sleep aids. Older adults (age 65 years and above) are at a higher risk of these side effects. Alcohol can make these symptoms worse. Tell your doctor if acetaminophen-codeine makes you very sleepy.