acetaminophen/ibuprofen

Action and Spectrum

Actions and Spectrum: 

acetaminophen and ibuprofen are both common over-the-counter pain relievers, but they work in slightly different ways. acetaminophen, generally a pain reliever and fever reducer. It acts by blocking the production of certain chemicals in the brain that cause pain and fever.

acetaminophen is often used for mild to moderate pain relief and to reduce fever. It is not a nonsteroidal anti-inflammatory drug (NSAID) and does not have anti-inflammatory properties. 

ibuprofen, on the other hand, is an NSAID that reduces pain, fever, and inflammation. It acts by blocking the production of prostaglandins, which are chemicals that promote inflammation, pain, and fever. ibuprofen is often used for mild to moderate pain relief, such as headaches, menstrual cramps, and joint pain. 

Drug Interaction

Adverse Reaction

Frequency defined 

>10% 

Nausea (15%) 

1-10% 

Vomiting (7%) 

Headache (5%) 

Dizziness (3%) 

Facial swelling (2%) 

Constipation (1%) 

Somnolence (2%) 

Post-procedural hemorrhage (2%) 

<1% 

Pruritus (0.4%) 

Dyspepsia (0.4%) 

Black Box Warning

Black Box Warning: 

acetaminophen and ibuprofen are generally safe when used as directed, but they do carry some risks and have black box warnings associated with their use. 

acetaminophen has a black box warning regarding the potential for liver damage, especially when taken in high doses or in combination with alcohol. The warning advises that people should not take more than the recommended dose and should not take acetaminophen for more than 10 days without consulting a healthcare provider. 

ibuprofen also has a black box warning regarding the potential for cardiovascular and gastrointestinal risks, such as heart attack, stroke, and stomach bleeding. The warning advises that people with a history of heart disease, high blood pressure, or stomach ulcers should use ibuprofen with caution and only under the guidance of a healthcare provider. 

It is important to read the labels and follow the recommended dosages when using acetaminophen or ibuprofen, and to talk to a healthcare provider. 

Contraindication / Caution

Contraindication/Caution: 

Contraindication 

acetaminophen and ibuprofen are generally safe when used as directed, but there are some contraindications that people should be aware of before using them. 

Contraindications for acetaminophen use include: 

• Hypersensitivity or allergy to acetaminophen 
• Severe liver disease 
• Alcoholism or chronic alcohol use 
• Pregnancy (if taken in high doses or for extended periods of time) 

Contraindications for ibuprofen use include: 

• Hypersensitivity or allergy to ibuprofen or other NSAIDs 
• Asthma or other respiratory conditions 
• Severe liver or kidney disease 
• Active gastrointestinal bleeding or ulcers 
• Pregnancy (especially in the third trimester) 

Caution 

acetaminophen and ibuprofen are generally safe when used as directed, but there are some cautions that people should be aware of before using them. 

Cautions for acetaminophen use include: 

• Taking other medications that contain acetaminophen, as it can lead to an overdose. 
• Chronic use or high doses, which can lead to liver damage. 
• Drinking alcohol while taking acetaminophen, which can increase the risk of liver damage. 
• People with liver disease or kidney disease should use acetaminophen with caution and only under the guidance of a healthcare provider. 

Cautions for ibuprofen use include: 

• Taking other NSAIDs or aspirin, which can increase the risk of stomach ulcers and bleeding. 
• Chronic use or high doses, which can lead to stomach ulcers and bleeding, kidney damage, and other health problems. 
• Drinking alcohol while taking ibuprofen, which can increase the risk of stomach bleeding and other complications. 
• People with heart disease or high bp should use ibuprofen with caution and only under the guidance of a healthcare provider. 

Pregnancy / Lactation

Pregnancy consideration:  

US FDA pregnancy category: Not assigned. 

Lactation:   

Excreted into human milk is Not known. 

Pregnancy category: 

• Category A: well-controlled and Satisfactory studies do not show risk to the fetus in the first/later trimester.        
• Category B: there was no evidence of risk to the fetus in animal studies, and there were not enough studies on pregnant women        
• Category C: there was evidence of risk of adverse effects in animal reproduction studies, and no adequate evidence in human studies must take care of potential risks in pregnant women.       
• Category D: adequate data available with sufficient evidence of human fetal risk from various platforms, but despite the potential risk, and used only in emergency cases for potential benefits.        
• Category X: Drugs listed in this category outweigh the risks over benefits. Hence these categories of drugs need to be avoided by pregnant women.        
• Category N: There is no data available for the drug under this category 

Pharmacology

Pharmacology: 

acetaminophen and ibuprofen have different pharmacological mechanisms of action: 

acetaminophen: 

• Acts primarily in the central nervous system to inhibit the production of prostaglandins, which are chemicals that contribute to pain and fever. 
• Has little to no effect on inflammation. 

ibuprofen: 

• It belongs to a class of drugs i.e nonsteroidal anti-inflammatory drugs (NSAIDs). 
• It acts by inhibiting the production of prostaglandins, which are chemicals that contribute to pain, fever, and inflammation. 
• Blocks the action of two forms of cyclooxygenase (COX) enzymes, COX-1 and COX-2, which are responsible for the production of prostaglandins. 

Pharmacodynamics: 

Mechanism of Action 

acetaminophen 

This medication acts primarily on the hypothalamus to produce antipyresis, which helps to lower fever. Additionally, it may work peripherally to block the generation of pain impulses, providing pain relief. The drug may also inhibit prostaglandin synthesis in the central nervous system, further contributing to its pain-relieving properties. 

ibuprofen 

This medication elicits anti-inflammatory, analgesic, and antipyretic activity by inhibiting the synthesis of prostaglandins in body tissues. It does this by inhibiting at least two cyclooxygenase (COX) isoenzymes, COX-1 and COX-2.  

Pharmacokinetics: 

Absorption 

The peak plasma time for these medications are 0.75-1.25 hours. The peak plasma concentration for acetaminophen is 14.88 mcg/mL, and for ibuprofen is 25.58 mcg/mL. The AUC (area under the curve) for acetaminophen is 47.44 mcg⋅hr/mL, and for ibuprofen is 95.62 mcg⋅hr/mL. When taken with food, the peak plasma concentration for acetaminophen is delayed by approximately 30 minutes and reduced by approximately 30%, while the extent of absorption remains the same. However, the peak plasma time and concentration for ibuprofen are not affected by food. 

Distribution 

ibuprofen is highly bound to plasma proteins, mainly albumin, and has a volume of distribution of approximately 0.1-0.2 L/kg. 

acetaminophen is approximately 20% protein bound. Its volume of distribution (Vd) is 0.9 L/kg, which indicates that it is widely distributed throughout most tissues except fat. 

Metabolism 

ibuprofen is metabolized in the liver by oxidation and conjugation to inactive metabolites, primarily by CYP2C9 and to a lesser extent by CYP2C19. It is eliminated in the urine and feces, with the majority (80%) being excreted in the urine as metabolites. 

acetaminophen is mainly metabolized in the liver by conjugation with glucuronide and sulfate and to a lesser extent by oxidation via CYP450-dependent mixed-function oxidase enzymes, particularly CYP2E1. The reactive intermediate metabolite formed by CYP2E1 can lead to hepatotoxicity in high doses or in individuals with impaired liver function. The metabolites are excreted in the urine, with a small fraction excreted in the feces. 

Elimination and Excretion 

For acetaminophen, the half-life is generally 2-3 hours in healthy adults, but it can be shorter in children and longer in neonates and patients with liver cirrhosis. 

For ibuprofen half-life is 1.9-2.2 hr. 

Excretion: For acetaminophen, less than 9% of the administered dose is excreted unchanged in urine, while the majority is excreted as metabolites via urine (mainly glucuronidation and sulfation) and a smaller portion via feces. 

For ibuprofen 45-79% excreted through urine and 14% as conjugated. 

Adminstartion

Administration: 

Oral administration 

acetaminophen is available in various forms, including tablets, capsules, liquids, and suppositories. Here are some general guidelines for administering acetaminophen: 

• acetaminophen can be generally taken with or without food, but it is suggested to take it with food if you have a sensitive stomach. 
• It is important to not exceed the recommended dosage and to avoid taking acetaminophen for more than 10 days without consulting a healthcare provider. 
• acetaminophen is available in various strengths, so it is important to read the label carefully. 

ibuprofen is available in various forms, including tablets, capsules, liquids, and suppositories. Here are some general guidelines for administering ibuprofen: 

• ibuprofen should be taken with food or milk to reduce the risk of stomach upset. 
• It is important to not exceed the recommended dosage and to avoid taking ibuprofen for more than 10 days without consulting a healthcare provider. 
• ibuprofen is available in various strengths, so it is important to read the label carefully. 

Patient Information Leaflet

Patient information leaflet 

Generic Name: acetaminophen/ibuprofen 

Pronounced: [ a-SEET-a-MIN-oh-fen-and-EYE-bue-PROE-fen ] 

Why do we use acetaminophen/ibuprofen? 

acetaminophen and ibuprofen are both commonly used over-the-counter pain relievers and fever reducers. Here are some specific uses for each medication: 

acetaminophen: 

• Relief of mild-moderate pains such as toothache, headache, menstrual cramps, or arthritis pain. 
• Reduction of fever. 

ibuprofen: 

• Relief of mild-moderate pains such as headache, toothache, menstrual cramps, or arthritis pain. 
• Reduction of fever. 
• Reduction of inflammation, such as swelling and redness associated with sprains, strains, or other injuries. 

Both acetaminophen and ibuprofen can be used for a variety of conditions, but it is important to use them only as directed and to talk to a physician if you have any questions or concerns about their use. It is also key to note that these medications may interact with other medications, so it is important to check with a healthcare provider before taking them if you are taking other medications or have any underlying health conditions.