Acetaminophen

• the dose in milligrams (mg) and milliliters (mL) is not confused;
• the dosing is based on weight for patients under 50 kg;
• infusion pumps are properly programmed; and
• the total daily dose of acetaminophen from all sources does not exceed maximum daily limits.

Acetaminophen Injection is indicated for

• the management of mild to moderate pain in adult and pediatric patients 2 years and older
• the management of moderate to severe pain with adjunctive opioid analgesics in adult and pediatric patients 2 years and older
• the reduction of fever in adult and pediatric patients 2 years and older.

• Acetaminophen Injection may be given as a single or repeated dose. (
  2.1 General Dosing Information

  Acetaminophen Injection, for intravenous use, may be given as a single or repeated dose for the treatment of acute pain or fever. No dose adjustment is required when converting between oral acetaminophen and acetaminophen injection dosing in adults and adolescents who weigh 50 kg and above. Calculated maximum daily dose of acetaminophen is based on all routes of administration (i.e., intravenous, oral, and rectal) and all products containing acetaminophen. Exceeding the maximum mg/kg daily dose of acetaminophen as described in Tables 1and 2may result in hepatic injury, including the risk of liver failure and death.

  To avoid the risk of overdose, ensure that the total amount of acetaminophen from all routes and from all sources does not exceed the maximum recommended dose.
  )
• Acetaminophen Injection should be administered only as a 15-minute intravenous infusion. (
  2.4 Instructions for Intravenous Administration

  For adult and adolescent patients weighing ≥ 50 kg requiring 1,000 mg doses of acetaminophen injection, administer the dose by inserting an intravenous set through the administration spike port of the 100 mL bag. Acetaminophen Injection may be administered without further dilution. Examine the flexible bag contents before dose preparation or administering. DO NOT USE if particulate matter or discoloration is observed. Administer the contents of the flexible bag intravenously over 15 minutes. Use aseptic technique when preparing acetaminophen injection for intravenous infusion. Do not add other medications to the acetaminophen injection flexible bag.

  For doses less than 1,000 mg, the appropriate dose must be withdrawn from the acetaminophen injection flexible bag and placed into a separate container prior to administration

  . Using aseptic technique, withdraw the appropriate dose (650 mg or weight-based) from an intact sealed acetaminophen injection flexible bag using a spike adaptor with an external spike diameter between 5.5 mm to 5.7 mm and 27 mm to 29 mm in length in accordance with ISO 8536-4. Place the measured dose in a separate empty, sterile container (e.g., glass bottle, plastic intravenous container, or syringe) for intravenous infusion to avoid the inadvertent delivery and administration of the total volume of the commercially available container. The entire 100 mL flexible bag of acetaminophen injection is not intended for use in patients weighing less than 50 kg.

  Acetaminophen Injection is supplied in a single-dose flexible bag and the unused portion must be discarded.

  Place small volume pediatric doses up to 60 mL in volume in a syringe and administer over 15 minutes using a syringe pump.

  Monitor the end of the infusion in order to prevent the possibility of an air embolism, especially in cases where the Acetaminophen Injection infusion is the primary infusion.

  Once the seal of the flexible bag has been penetrated, or the contents transferred to another container, administer the dose of acetaminophen injection within 6 hours.

  For bags, refrain from applying excessive pressure causing distortion to the bag, such as wringing or twisting, since such handling could result in breakage of the bag.

  Do not add other medications to the acetaminophen injection solution. Diazepam and chlorpromazine hydrochloride are physically incompatible with acetaminophen injection, therefore do not administer simultaneously.
  )

• 1,000 mg every 6 hours or 650 mg every 4 hours to a maximum of 4,000 mg per day. Minimum dosing interval of 4 hours. (
  2.2 Recommended Dosage: Adults and Adolescents

  Adults and adolescents weighing 50 kg and over: the recommended dosage of acetaminophen injection is 1,000 mg every 6 hours or 650 mg every 4 hours, with a maximum single dose of acetaminophen injection of 1,000 mg, a minimum dosing interval of 4 hours, and a maximum daily dose of acetaminophen of 4,000 mg per day (includes all routes of administration and all acetaminophen-containing products including combination products).

  Adults and adolescents weighing under 50 kg: the recommended dosage of acetaminophen injection is 15 mg/kg every 6 hours or 12.5 mg/kg every 4 hours, with a maximum single dose of acetaminophen injection of 15 mg/kg, a minimum dosing interval of 4 hours, and a maximum daily dose of acetaminophen of 75 mg/kg per day (includes all routes of administration and all acetaminophen-containing products including combination products).

  Table 1. Dosing for Adults and Adolescents

  Age group	Dose given every 4 hours	Dose given every 6 hours	Maximum single dose	Maximum total daily dose of acetaminophen (by all routes)
  Adults and adolescents (13 years and older) weighing ≥ 50 kg	650 mg	1,000 mg	1,000 mg	4,000 mg in 24 hours
  Adults and adolescents (13 years and older) weighing < 50 kg	12.5 mg/kg	15 mg/kg	15 mg/kg (up to 750 mg)	75 mg/kg in 24 hours (up to 3,750 mg)
  )

• 15 mg/kg every 6 hours or 12.5 mg/kg every 4 hours to a maximum of 75 mg/kg per day. Minimum dosing interval of 4 hours. (
  2.2 Recommended Dosage: Adults and Adolescents

  Adults and adolescents weighing 50 kg and over: the recommended dosage of acetaminophen injection is 1,000 mg every 6 hours or 650 mg every 4 hours, with a maximum single dose of acetaminophen injection of 1,000 mg, a minimum dosing interval of 4 hours, and a maximum daily dose of acetaminophen of 4,000 mg per day (includes all routes of administration and all acetaminophen-containing products including combination products).

  Adults and adolescents weighing under 50 kg: the recommended dosage of acetaminophen injection is 15 mg/kg every 6 hours or 12.5 mg/kg every 4 hours, with a maximum single dose of acetaminophen injection of 15 mg/kg, a minimum dosing interval of 4 hours, and a maximum daily dose of acetaminophen of 75 mg/kg per day (includes all routes of administration and all acetaminophen-containing products including combination products).

  Table 1. Dosing for Adults and Adolescents

  Age group	Dose given every 4 hours	Dose given every 6 hours	Maximum single dose	Maximum total daily dose of acetaminophen (by all routes)
  Adults and adolescents (13 years and older) weighing ≥ 50 kg	650 mg	1,000 mg	1,000 mg	4,000 mg in 24 hours
  Adults and adolescents (13 years and older) weighing < 50 kg	12.5 mg/kg	15 mg/kg	15 mg/kg (up to 750 mg)	75 mg/kg in 24 hours (up to 3,750 mg)
  )

• Children 2 to 12 years of age: 15 mg/kg every 6 hours or 12.5 mg/kg every 4 hours to a maximum of 75 mg/kg per day. Minimum dosing interval of 4 hours. (
  2.3 Recommended Dosage: Children

  Children 2 to 12 years of age: the recommended dosage of acetaminophen injection is 15 mg/kg every 6 hours or 12.5 mg/kg every 4 hours, with a maximum single dose of acetaminophen injection of 15 mg/kg, a minimum dosing interval of 4 hours, and a maximum daily dose of acetaminophen of 75 mg/kg per day.

  Table 2. Dosing for Children

  Age group	Dose given every 4 hours	Dose given every 6 hours	Maximum single dose	Maximum total daily dose of acetaminophen (by all routes)
  Children 2 to 12 years of age	12.5 mg/kg	15 mg/kg	15 mg/kg (up to 750 mg)	75 mg/kg in 24 hours (up to 3,750 mg)
  )

Acetaminophen Injection is a sterile, clear, colorless, non-pyrogenic, preservative free, isotonic formulation of acetaminophen intended for intravenous infusion. Each 100 mL single-dose flexible bag contains 1,000 mg acetaminophen (10 mg/mL).

• Pediatric Use: The effectiveness of acetaminophen for the treatment of acute pain in pediatric patients younger than 2 years of age has not been established. The safety and effectiveness of acetaminophen in pediatric patients older than 2 years of age is supported by evidence from adequate and well-controlled studies in adults with additional safety and pharmacokinetic data for this age group. (
  8.4 Pediatric Use

  Treatment of Acute Pain

  The safety and effectiveness of acetaminophen for the treatment of acute pain in pediatric patients ages 2 years and older is supported by evidence from adequate and well- controlled studies of acetaminophen in adults and safety and pharmacokinetic data from adult and 355 pediatric patients across all age groups

  [see Dosage and Administration and Pharmacokinetics ]

  .

  The effectiveness of acetaminophen for the treatment of acute pain in pediatric patients younger than 2 years of age has not been established.

  Treatment of Fever

  The safety and effectiveness of acetaminophen injection for the treatment of fever in pediatric patients is supported by adequate and well-controlled studies of acetaminophen injection in adults and clinical studies in 244 pediatric patients 2 years and older.
  )
• Geriatric Use: No overall differences in safety or effectiveness were observed between geriatric and younger subjects. (
  8.5 Geriatric Use

  Of the total number of subjects in clinical studies of acetaminophen, 15% were age 65 and over, while 5% were age 75 and over. No overall differences in safety or effectiveness were observed between these subjects and younger subjects, and other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out.
  )
• Hepatic Impairment: Acetaminophen is contraindicated in patients with severe hepatic impairment or severe active liver disease and should be used with caution in patients with hepatic impairment or active liver disease. (
  4 CONTRAINDICATIONS

  Acetaminophen is contraindicated:

  • in patients with known hypersensitivity to acetaminophen or to any of the excipients in the intravenous formulation.
  • in patients with severe hepatic impairment or severe active liver disease [see Warnings and Precautions ].

  Acetaminophen is contraindicated:

  • In patients with known hypersensitivity to acetaminophen or to any of the excipients in the IV formulation.
  • In patients with severe hepatic impairment or severe active liver disease.
  ,
  5.1 Hepatic Injury

  Administration of acetaminophen in doses higher than recommended may result in hepatic injury, including the risk of liver failure and death

  [see Overdosage ]

  . Do not exceed the maximum recommended daily dose of acetaminophen

  [see Dosage and Administration ]

  . The maximum recommended daily dose of acetaminophen includes all routes of administration and all acetaminophen-containing products administered, including combination products.

  Use caution when administering acetaminophen in patients with the following conditions: hepatic impairment or active hepatic disease, alcoholism, chronic malnutrition, severe hypovolemia (e.g., due to dehydration or blood loss), or severe renal impairment (creatinine clearance ≤ 30 mL/min)

  [see Use in Specific Populations ]

  .
  ,
  8.6 Patients with Hepatic Impairment

  Acetaminophen is contraindicated in patients with severe hepatic impairment or severe active liver disease and should be used with caution in patients with hepatic impairment or active liver disease

  [see Warnings and Precautions and Clinical Pharmacology ]

  . A reduced total daily dose of acetaminophen may be warranted.
  )
• Renal Impairment: In cases of severe renal impairment, longer dosing intervals and a reduced total daily dose of acetaminophen may be warranted. (
  5.1 Hepatic Injury

  Administration of acetaminophen in doses higher than recommended may result in hepatic injury, including the risk of liver failure and death

  [see Overdosage ]

  . Do not exceed the maximum recommended daily dose of acetaminophen

  [see Dosage and Administration ]

  . The maximum recommended daily dose of acetaminophen includes all routes of administration and all acetaminophen-containing products administered, including combination products.

  Use caution when administering acetaminophen in patients with the following conditions: hepatic impairment or active hepatic disease, alcoholism, chronic malnutrition, severe hypovolemia (e.g., due to dehydration or blood loss), or severe renal impairment (creatinine clearance ≤ 30 mL/min)

  [see Use in Specific Populations ]

  .
  ,
  8.7 Patients with Renal Impairment

  In cases of severe renal impairment (creatinine clearance ≤ 30 mL/min), longer dosing intervals and a reduced total daily dose of acetaminophen may be warranted.
  )