Acetaminophen

WARNING: RISK OF MEDICATION ERRORS AND •

 Use caution when administering acetaminophen in patients with the HEPATOTOXICITY following conditions: hepatic impairment or active hepatic disease, in See full prescribing information for complete boxed warning cases of alcoholism, chronic malnutrition, severe hypovolemia, or severe renal impairment (creatinine clearance ≤ 30 mL/min). (5.1) Take care when prescribing, preparing, and administering Acetaminophen • Discontinue acetaminophen immediately at the first appearance of skin Injection to avoid dosing errors which could result in accidental overdose rash and if symptoms associated with allergy or hypersensitivity occur. and death. (5.3) Do not use in patients with acetaminophen allergy. (5.2, 5.4) -----------------------------



ADVERSE REACTIONS--

­ The most common adverse reactions in patients treated with acetaminophen been associated with cases of acute liver failure, at times resulting in liver were nausea, vomiting, headache, and insomnia in adult patients and nausea, transplant and death. Most of the cases of liver injury are associated with vomiting, constipation, pruritus, agitation, and atelectasis in pediatric patients. the use of acetaminophen at doses that exceed the recommended maximum (6.1) daily limits, and often involve more than one acetaminophen-containing product. (5.1).





Acetaminophen is a centrally acting analgesic and antipyretic with minimal anti-inflammatory properties. The mechanism of action of acetaminophen in reducing pain is unknown but may be due to an inhibition of central prostaglandin synthesis (specifically cyclooxygenase (COX)-2) and an elevation of the pain threshold. Acetaminophen reduces fever by inhibiting the formulation and release of prostaglandins in the CNS and by inhibition endogenous pyrogens at the hypothalamic thermoregulator center [4]

Fever

• 650 mg orally every 4 to 6 hours as needed; MAX: 3250 mg/24 hours [2]
• (Extra-strength) 1000 mg orally every 6 hours as needed; MAX: 3000 mg/24 hour [3]
• (Extended-release) 1300 mg orally every 8 hours as needed; MAX: 3900 mg/24 hours [4]
• (IV, 50 kg or greater) 1000 mg IV every 6 hours, or 650 mg IV every 4 hours; may be administered as a single or repeated dose; minimum dosing interval, 4 hours; MAX single dose 1000 mg; MAX total daily dosage by all routes 4000 mg/24 hours [5]
• (IV, less than 50 kg) 15 mg/kg IV every 6 hours or 12.5 mg/kg IV every 4 hours; may be administered as a single or repeated dose; minimum dosing interval, 4 hours; MAX single dose 15 mg/kg or 750 mg; MAX total daily dosage by all routes 75 mg/kg/day or 3750 mg/24 hours [5]
• (Rectal) 650 mg rectally every 4 to 6 hours; MAX: 6 suppositories/24 hours [6]

Osteoarthritis

• 1000 mg orally 4 times daily for four weeks, total 4000 mg/day (off-label dosage) [7]

Pain (Mild to Moderate)

• 650 mg orally every 4 to 6 hours as needed, MAX: 3250 mg/24 hours [2][4]
• (Extra-strength) 1000 mg orally every 6 hours as needed; MAX: 3000 mg/24 hours [3]
• (Extended-release) 1300 mg orally every 8 hours as needed: MAX: 3900 mg/24 hours [4]
• (IV, less than 50 kg) 15 mg/kg IV every 6 hours or 12.5 mg/kg IV every 4 hours; may be administered as a single or repeated dose; minimum dosing interval, 4 hours; MAX single dose 15 mg/kg or 750 mg; MAX daily dosage 75 mg/kg/day or 3750 mg/24 hours [8]
• (IV, 50 kg or greater) 1000 mg IV every 6 hours or 650 mg IV every 4 hours; may be administered as a single or repeated dose; minimum dosing interval, 4 hours; MAX single dose 1000 mg; MAX daily dosage 4000 mg/24 hours [8]
• (Rectal) 650 mg rectally every 4 to 6 hours; MAX: 6 suppositories/24 hours [6]

Pain (Moderate to Severe), In combination with opioid medications

• (50 kg or greater) 1000 mg IV every 6 hours or 650 mg IV every 4 hours; may be administered as a single or repeated dose; minimum dosing interval, 4 hours; MAX single dose 1000 mg; MAX daily dosage 4000 mg/24 hours [8]
• (Less than 50 kg) 15 mg/kg IV every 6 hours or 12.5 mg/kg IV every 4 hours; may be administered as a single or repeated dose; minimum dosing interval, 4 hours; MAX single dose 15 mg/kg or 750 mg; MAX daily dosage 75 mg/kg/day or 3750 mg/24 hours [8]

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Dosing/Administration

FDA Uses

See 'In-Depth Answers' for detailed results.

• Fever
• Pain (Mild to Moderate)
• Pain (Moderate to Severe), In combination with opioid medications

Contraindications

See 'In-Depth Answers' for detailed results.

Active and severe hepatic disease [8]

Hypersensitivity to acetaminophen or any other components of the product [8]

Severe hepatic impairment [8

[8] Product Information: OFIRMEV(R) intravenous injection, acetaminophen intravenous injection. Cadence Pharmaceuticals, Inc. (per FDA), San Diego, CA, 2013.

Black box warning: 

Intravenous (Solution)

• Prevent acetaminophen injection dosing errors, which may result in accidental overdose and death, by confirming that doses in milligrams (mg) are not confused with doses in milliliters (mL); that patients under 50 kg receive weight-based doses; that infusion pumps are programmed correctly; and that the total dose of acetaminophen from all routes and from all sources does not exceed daily limits. Life-threatening cases of acute hepatic failure leading to liver transplant or death have been linked with acetaminophen use. In most cases of hepatic injury, acetaminophen doses exceeded maximum daily limits and often involved the use of more than 1 acetaminophen-containing product [8]

Pregnancy Category

Fetal risk cannot be ruled out. (TH)

Breast Feeding

AAP: Maternal medication usually compatible with breastfeeding.[38]

WHO: Compatible with breastfeeding.[39]

Micromedex: Infant risk is minimal.

Common

• Dermatologic: Pruritus (5% or greater )
• Gastrointestinal: Constipation (5% or greater ), Nausea (adult, 34%; pediatric, 5% or greater ), Vomiting (adult, 15%; pediatric, 5% or greater )
• Neurologic: Headache (1% to 10% ), Insomnia (1% to 7% )
• Psychiatric: Agitation (5% or greater )
• Respiratory: Atelectasis (5% or greater )

Serious

• Dermatologic: Generalized exanthematous pustulosis, acute, Stevens-Johnson syndrome, Toxic epidermal necrolysis
• Hepatic: Liver failure
• Respiratory: Pneumonitis

Alcoholism: Increases risk of hepatic injury [8]

Dermatologic: Serious and potentially fatal skin reactions (including Stevens-Johnson syndrome, toxic epidermal necrolysis, and acute generalized exanthematous pustulosis) have been reported; discontinue at first appearance of rash or other sign of hypersensitivity [8]

Hepatic: Active hepatic disease or hepatic impairment increases risk of hepatic injury; dose reductions may be required [8]

Hypovolemia: Severe hypovolemia, due to dehydration or blood loss, increases risk of hepatic injury [8]

Immunologic: Anaphylaxis and hypersensitivity reactions, some cases life-threatening, have been reported; immediately discontinue if suspected [8]

Malnutrition: Chronic malnutrition increases risk of hepatic injury [8]

Renal: Severe renal impairment (CrCl of 30 mL/min or less) increases risk of hepatic injury; dose reductions may be required [8]

Drug-Drug  Interactions (19)
Drugs:	Severity:	Documentation:	Summary:
ISONIAZID [Systemic] -- ACETAMINOPHEN [Systemic]	Major	Excellent	Concurrent use of ACETAMINOPHEN and ISONIAZID may result in an increased risk of hepatotoxicity.
ACETAMINOPHEN [Systemic] -- PNEUMOCOCCAL 13-VALENT VACCINE, DIPHTHERIA CONJUGATE [Systemic]	Major	Good	Concurrent use of ACETAMINOPHEN and PNEUMOCOCCAL 13-VALENT VACCINE, DIPHTHERIA CONJUGATE may result in an inadequate immunologic response to the vaccine.
ACETAMINOPHEN [Systemic] -- IMATINIB [Systemic]	Major	Fair	Concurrent use of ACETAMINOPHEN and IMATINIB may result in increased acetaminophen levels.
PIXANTRONE -- CYP1A2 SUBSTRATES	Major	Fair	Concurrent use of PIXANTRONE and CYP1A2 SUBSTRATES may result in increased exposure of CYP1A2 substrates.
WARFARIN [Systemic] -- ACETAMINOPHEN [Systemic]	Moderate	Excellent	Concurrent use of ACETAMINOPHEN and WARFARIN may result in an increased risk of bleeding.
ACETAMINOPHEN [Systemic] -- LIXISENATIDE [Systemic]	Moderate	Good	Concurrent use of ACETAMINOPHEN and LIXISENATIDE may result in slowed absorption of acetaminophen.
ACETAMINOPHEN -- PHENYTOIN Acetaminophen interact(s) with:Interacting substances	Moderate	Good	Concurrent use of ACETAMINOPHEN and PHENYTOIN may result in decreased acetaminophen effectiveness and an increased risk of hepatotoxicity.
CARBAMAZEPINE [Systemic] -- ACETAMINOPHEN [Systemic]	Moderate	Good	Concurrent use of ACETAMINOPHEN and CARBAMAZEPINE may result in an increased risk of acetaminophen hepatotoxicity.
ACETAMINOPHEN [Systemic] -- ACENOCOUMAROL [Systemic]	Moderate	Good	Concurrent use of ACENOCOUMAROL and ACETAMINOPHEN may result in potentiation of anticoagulant effect.
ACETAMINOPHEN [Systemic] -- ZIDOVUDINE [Systemic]	Moderate	Good