PainSAFE
Acetaminophen and Pain
By: Richard L. Stieg, MD, MHS
The drug acetaminophen has been used for decades as a pain reliever and fever reducer. It is available in pure form and in combination with many other medications in both over-the-counter (OTC) and prescription preparations. An estimated 50 million Americans take acetaminophen containing products in the Unites States each week (see list below). When taken at recommended doses, acetaminophen can be used safely by children, adults and the elderly, even in the face of chronic kidney or chronic stable liver disease.
The precise way that acetaminophen works as a pain reliever, fever reducer and weak anti-inflammatory drug is not entirely known. Safe levels of dosing, however, have been established through years of careful testing. In adults, 1 g per dose and 4 g per day (24 hours) appears to be the most useful level of intake. Lower doses do not work as well and higher doses may be harmful (see discussion below).
In children, the recommended dose is 5 mg to 7 mg per pound taken every four to six hours, with a maximum of five doses per day. Acetaminophen for infants and children are packaged over-the-counter as a concentrated liquid with a dropper for infants or liquid for older children. Small sized chewable tablets of 80 mg are useful for older children. It is important that you – the health care provider - calculate the proper dose for your pediatric patients (e.g., a 10-lb infant would receive 50 mg to 70 mg per dose and a 20-lb toddler would receive 100 mg to 140 mg per dose). The safest way to administer medicine to infants is in milliliters, and only infants should receive the infant formulations as they are more concentrated than the doses for older children. Use of acetaminophen is generally recommended for infants and children with fever and gastrointestinal symptoms. Aspirin is never recommended for children because of the possibility of Reye’s syndrome, a very serious disorder that can be fatal.
As a health care provider, it’s important that you educate the parent or guardian about the risks of giving children medications that may interact with acetaminophen or formulations that may contain additional doses of acetaminophen. For example, if a child has a cold, warn parents or guardians that many cold medicines may already contain acetaminophen. A single dose of 140 mg/kg (body weight) of acetaminophen can result in liver injury in children so parents and guardians should be cautioned. Parents and guardians should be informed that the safest formulations for children are single active ingredient medicines. They should also be reminded to follow medication instructions and to use only the dosing devices provided with the medications.
If you prescribe hydrocodone with acetaminophen or any other prescription medications containing acetaminophen (often labeled APAP), warn parents that they should never give their child more than one acetaminophen-containing product. Remind them that they should always read the label of all prescription and over-the-counter medication because they may contain acetaminophen.
Serious side effects: Although the exact number of cases is unknown and probably uncommon, serious damage to the liver may occur when acetaminophen is used at higher doses than recommended. This is more likely to occur with very high single doses, as might occur when children have access to unprotected bottles or with accidental or intentional overdoses in adults. Remind parents and guardians to always store medications out of reach of children, The incidence of liver disease with chronic daily use at higher than recommended doses is unknown but probably also occurs.
If the correct dosing guidelines for adults and children are followed, acetaminophen is safe and carries little to no risk of liver injury. Liver injury from acetaminophen may occur when a healthy patient takes more than more than 4 g per 24-hour period. Patients who drink two or more alcoholic beverages per day should take no more than 2 g per 24-hour period, as alcohol increases acetaminophen’s toxic effect. The higher the dose ingested, the greater the likelihood of liver damage. Acetaminophen overdose can result in liver failure and death and is the leading cause of acute liver failure in the United States. If you recommend a patient take acetaminophen for longer than a two-week period, liver enzyme levels should be monitored.
Patients with mild to moderate liver disease do not appear to be at increased risk for further liver injury from taking acetaminophen, regardless of the cause of the liver disease and provided the patient does not drink alcohol regularly. For example, patients with acute or chronic hepatitis can take acetaminophen safely if they follow the recommended doses and do not drink alcohol. Acetaminophen, however, should be used with extreme caution or not at all in patients with severe liver disease, such as advanced cirrhosis or liver failure.
Acetaminophen is often used with narcotic (opioid) agents because the mechanism of action is different for those two classes of drugs, potentially allowing for better pain relief than either the acetaminophen or opioid taken alone at the same dose may offer. When you prescribe a combination medication, make sure your patient understands that the abbreviation APAP indicates the medication contains acetaminophen and warn him or her about the maximum daily dose of acetaminophen should never exceed 4 g.
The precise way that acetaminophen works as a pain reliever, fever reducer and weak anti-inflammatory drug is not entirely known. Safe levels of dosing, however, have been established through years of careful testing. In adults, 1 g per dose and 4 g per day (24 hours) appears to be the most useful level of intake. Lower doses do not work as well and higher doses may be harmful (see discussion below).
Acetaminophen for Children
In children, the recommended dose is 5 mg to 7 mg per pound taken every four to six hours, with a maximum of five doses per day. Acetaminophen for infants and children are packaged over-the-counter as a concentrated liquid with a dropper for infants or liquid for older children. Small sized chewable tablets of 80 mg are useful for older children. It is important that you – the health care provider - calculate the proper dose for your pediatric patients (e.g., a 10-lb infant would receive 50 mg to 70 mg per dose and a 20-lb toddler would receive 100 mg to 140 mg per dose). The safest way to administer medicine to infants is in milliliters, and only infants should receive the infant formulations as they are more concentrated than the doses for older children. Use of acetaminophen is generally recommended for infants and children with fever and gastrointestinal symptoms. Aspirin is never recommended for children because of the possibility of Reye’s syndrome, a very serious disorder that can be fatal.
As a health care provider, it’s important that you educate the parent or guardian about the risks of giving children medications that may interact with acetaminophen or formulations that may contain additional doses of acetaminophen. For example, if a child has a cold, warn parents or guardians that many cold medicines may already contain acetaminophen. A single dose of 140 mg/kg (body weight) of acetaminophen can result in liver injury in children so parents and guardians should be cautioned. Parents and guardians should be informed that the safest formulations for children are single active ingredient medicines. They should also be reminded to follow medication instructions and to use only the dosing devices provided with the medications.
If you prescribe hydrocodone with acetaminophen or any other prescription medications containing acetaminophen (often labeled APAP), warn parents that they should never give their child more than one acetaminophen-containing product. Remind them that they should always read the label of all prescription and over-the-counter medication because they may contain acetaminophen.
Serious side effects: Although the exact number of cases is unknown and probably uncommon, serious damage to the liver may occur when acetaminophen is used at higher doses than recommended. This is more likely to occur with very high single doses, as might occur when children have access to unprotected bottles or with accidental or intentional overdoses in adults. Remind parents and guardians to always store medications out of reach of children, The incidence of liver disease with chronic daily use at higher than recommended doses is unknown but probably also occurs.
Acetaminophen and Liver Injury in Adults
If the correct dosing guidelines for adults and children are followed, acetaminophen is safe and carries little to no risk of liver injury. Liver injury from acetaminophen may occur when a healthy patient takes more than more than 4 g per 24-hour period. Patients who drink two or more alcoholic beverages per day should take no more than 2 g per 24-hour period, as alcohol increases acetaminophen’s toxic effect. The higher the dose ingested, the greater the likelihood of liver damage. Acetaminophen overdose can result in liver failure and death and is the leading cause of acute liver failure in the United States. If you recommend a patient take acetaminophen for longer than a two-week period, liver enzyme levels should be monitored.
Patients with mild to moderate liver disease do not appear to be at increased risk for further liver injury from taking acetaminophen, regardless of the cause of the liver disease and provided the patient does not drink alcohol regularly. For example, patients with acute or chronic hepatitis can take acetaminophen safely if they follow the recommended doses and do not drink alcohol. Acetaminophen, however, should be used with extreme caution or not at all in patients with severe liver disease, such as advanced cirrhosis or liver failure.
Acetaminophen and Narcotic Medication Combinations
Acetaminophen is often used with narcotic (opioid) agents because the mechanism of action is different for those two classes of drugs, potentially allowing for better pain relief than either the acetaminophen or opioid taken alone at the same dose may offer. When you prescribe a combination medication, make sure your patient understands that the abbreviation APAP indicates the medication contains acetaminophen and warn him or her about the maximum daily dose of acetaminophen should never exceed 4 g.
| Over-the-Counter Acetaminophen-only Products | Over-the-Counter Acetaminophen Containing Products | Prescription Narcotic (opioid)/Acetaminophen Combination Products |
| Adenol | Actifed | Anexsia |
| Atasol | Anacin | Capital with codeine |
| Panadol | Benadryl | Darvocet |
| Paracetamol | Comtrex | Endocet |
| Pediatrix | Contac | Fioricet |
| Tempra | Coricidin | Lortab |
| Tylenol | Dimetapp | Magnacet |
| Excedrin | Maxidone | |
| Feverall | Mersyndol with codeine | |
| Goody's Powder | Norco | |
| Midol | Percocet | |
| NyQuil/DayQuil | Roxicet | |
| Pamprin | Talacen | |
| Robitussin | Tylenol with codeine (#2 or #3) | |
| Sinus Alka-Seltzer Plus | Tylox | |
| Sinutab | Ultracet | |
| Tavist | Vicodin | |
| TheraFlu | Wygesic | |
| Triaminic | Xodol | |
| Vanguish | Zydone | |
| Vicks | ||
| Women's Tylenol Menstrual Relief |
Five Reminders for Patients – Using Acetaminophen and Acetaminophen Containing Products Safely:
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Do not exceed the recommended single dose and total daily dose of acetaminophen.
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Be aware that many over-the-counter (OTC) and prescription drugs contain acetaminophen and that the label “APAP” on prescriptions is shorthand for acetaminophen.
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It is up to patients to calculate how much acetaminophen they are taking, especially if both OTC and prescription drugs are being used at the same time. Be especially careful in calculating doses for infants and children.
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Keep acetaminophen products safely away from children and adults with impaired thinking (e.g., dementia).
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If the patient has chronic kidney or liver disease, remind patients to discuss using acetaminophen with you.