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Acetaminophen Side Effects

Acetaminophen is one of the most common medications used to treat mild to moderate pain and fever. It has a long record of safety and effectiveness when taken as directed. Like all drugs, it has side effects. Some are more common than others.

Last Modified: September 5, 2023
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Common Side Effects

Common acetaminophen side effects such as headaches and nausea tend to be mild and happen the most frequently, according to studies and clinical trials. Most of the time common side effects don’t pose a serious risk.

Acetaminophen may cause different side effects depending on the way it is administered. For example, acetaminophen administered through an IV may cause vomiting and constipation, which is less likely to occur with oral versions of the drug. Check with your doctor or pharmacist for additional potential side effects if you are using acetaminophen in IV or suppository form.

Common acetaminophen side effects include:
  • Agitation
  • Constipation
  • Headaches
  • Insomnia
  • Itchy skin
  • Stomach pain
  • Vomiting

Most people using acetaminophen do not experience side effects at all and even fewer people experience serious side effects. If any of these common side effects persist for more than a day or if you vomit or experience severe agitation, you should contact your doctor.

More serious side effects, although rare, can occur. These include jaundice, fever, allergic reactions, blistering or peeling skin, fever and blood in the stool. Severe skin reactions and acute liver damage are the most serious side effects of acetaminophen.

Overdose Signs and Risk of Liver Failure

The first signs of an acetaminophen overdose include abdominal pain, vomiting, clamminess, lack of appetite and unexplained fatigue. An overdose of acetaminophen causes the most serious side effect associated with the drug – liver damage or liver failure.

After a person takes acetaminophen, the liver metabolizes the drug. A percentage of it converts into a compound that, in large amounts, harms liver cells. If a person consumes more than three alcoholic drinks each day and takes acetaminophen, it can also cause liver damage.

There are four phases of an overdose of acetaminophen:
Phase 1:
The initial phase comes within the first 24 hours following an overdose. You may feel sick to your stomach, vomit and feel overly tired. You also may feel clammy and sweaty and have little or no appetite.
Phase 2:
The progression of the overdose involves your abdomen and happens between 18 and 72 hours after taking the medication. You will likely experience cramping, nausea and vomiting. You may also have a more rapid heartbeat or low blood pressure.
Phase 3:
This is the most serious stage of an acetaminophen overdose, and it occurs 72 to 96 hours after the overdose. Signs of liver failure develop, including jaundice, bleeding, low blood sugar and loss of brain function. Multiple organ failure can lead to death during this phase.
Phase 4:
This is the recovery stage. Symptoms start to resolve, though they can last between four days and three weeks.

Acetaminophen toxicity is linked to about 500 deaths and 50,000 emergency room visits annually in the U.S. It’s also the most common cause of drug-related liver failure, according to an article published on StatPearls in the National Library of Medicine.

People who have signs of an overdose should seek medical attention immediately. If you are around someone who is showing signs of acetaminophen toxicity, call 911 or a poison control center immediately.

Symptoms of Acetaminophen Liver Damage

Symptoms of acetaminophen liver damage, including weakness, fatigue, nausea and jaundice, may take up to 12 hours to appear. Most people who take acetaminophen as directed and don’t have preexisting liver issues shouldn’t experience liver damage.

Signs of liver damage include:
  • Yellowing of eyes and skin
  • Abdominal pain
  • Nausea and vomiting
  • Lack of appetite
  • Fatigue
  • Dark/cloudy urine and stools
  • Pale skin color
  • Excessive sweating
  • Gastrointestinal bleeding

The U.S. Food and Drug Administration has asked health care providers not to prescribe acetaminophen or medications that contain acetaminophen in doses larger than 325 mg. The medication has not proven to be any more effective in doses larger than 325 mg, and the risk of liver damage overrides any need for a larger dose.

People shouldn’t take more than 4,000 mg in 24 hours, according to drug labels.

Treatment of Acetaminophen Liver Damage

Following diagnosis, the treatment options for acetaminophen liver damage include intravenous fluids, activated charcoal, N-acetylcysteine and anti-nausea medication. You shouldn’t try to treat an acetaminophen overdose at home. Treatments should be administered at a medical center or clinic by medical professionals.

Because an acetaminophen overdose causes acute liver damage or failure, doctors prefer to start treatment within eight hours of an overdose. It’s important to seek medical attention immediately because the sooner treatment can be administered, the better the outcome.

Serious Acetaminophen Skin Reactions

Acetaminophen’s other significant side effects are serious skin reactions, some of which are fatal. They include Stevens-Johnson syndrome, toxic epidermal necrolysis and acute generalized exanthematous pustulosis. These reactions can happen on the first use of the medication and demand immediate medical attention in addition to stopping the use of the drug.

In 2013, the FDA issued a warning about pain relievers and fever reducers producing significant adverse skin reactions. It noted that if acetaminophen or a medication that has it as an ingredient triggers any major skin reaction, it should never be taken again.

Stevens-Johnson Syndrome (SJS)

Stevens-Johnson syndrome is a severe, potentially fatal skin reaction that causes skin to die and fall off. It is usually triggered by a medication. SJS can also affect mucus membranes in the mouth, eyes and genitals. The mortality rate is about 10%.

Medications most closely associated with SJS are pain relievers such as acetaminophen, allopurinol (for gout), anti-epileptic drugs, antibiotics and cancer medications. Severe infections such as hepatitis A, pneumonia and herpes can also trigger Stevens-Johnson syndrome.

Early signs of the condition include flu-like symptoms (sore throat, cough, weariness and body aches) followed by a purple or red rash. Red and purple blisters and peeling skin come next.

Someone must experience a loss of at least 10% of their body’s skin to be classified as having Stevens-Johnson syndrome. SJS is closely related to toxic epidermal necrolysis and can recur.

Toxic Epidermal Necrolysis (TEN)

Toxic epidermal necrolysis is included in the same spectrum of disease as SJS. It is also life-threatening but is more severe and rare. All the medications that cause SJS also cause TEN, including acetaminophen.

Symptoms of toxic epidermal necrolysis are identical to those of Stevens-Johnson syndrome.What separates TEN from SJS is the amount of skin damage. Someone must have damage to 30% of their skin to have TEN. People who have between 10% and 30% damage are diagnosed with SJS/TEN overlap.

The mortality rate of TEN is just over 30%.

Acute Generalized Exanthematous Pustulosis (AGEP)

Acute generalized exanthematous pustulosis is a rare, severe skin reaction also closely related to medications, including acetaminophen. About 90% of cases are linked to adverse reactions to drugs, usually antibiotics. The condition is not as serious as SJS or TEN.

AGEP presents as sudden skin eruptions, or pustules, that usually appear within two to three days after taking the medication. Other signs include fever and an elevated white blood cell count. Treatment involves stopping the offending medication and caring for the peeling skin with topical ointments.

AGEP usually runs its course in two to three weeks and does not recur.

Please seek the advice of a medical professional before making health care decisions.