Acetaminophen Injection

Adult Population

A total of 1020 adult patients have received acetaminophen in clinical trials, including 37.3% (n=380) who received 5 or more doses, and 17.0% (n=173) who received more than 10 doses. Most patients were treated with acetaminophen 1000 mg every 6 hours. A total of 13.1% (n=134) received another dosage of acetaminophen injection.

All adverse reactions that occurred in adult patients treated with either acetaminophen or placebo in repeated dose, placebo-controlled clinical trials at an incidence ≥ 3% and at a greater frequency than placebo are listed in Table 4. The most common adverse events in adult patients treated with acetaminophen (incidence ≥ 5% and greater than placebo) were nausea, vomiting, headache, and insomnia.

Acetaminophen is a non-salicylate antipyretic and non-opioid analgesic agent. Its chemical name is N-acetyl-p-aminophenol. Acetaminophen has a molecular weight of 151.16. Its structural formula is:

Acetaminophen Injection is a sterile, clear, colorless, nonpyrogenic, isotonic formulation of acetaminophen intended for intravenous infusion. It has a pH of approximately 5.5 and an osmolality of approximately 290 mOsm/kg. Each 100 mL contains 1000 mg acetaminophen, USP, 3850 mg mannitol, USP, 25 mg cysteine hydrochloride, monohydrate, USP, and 10.4 mg dibasic sodium phosphate, USP. pH is adjusted with hydrochloric acid and/or sodium hydroxide.

The efficacy of acetaminophen 1000 mg in the treatment of adult fever was evaluated in one randomized, double-blind, placebo-controlled clinical trial. The study was a 6-hour, single-dose, endotoxin-induced fever study in 60 healthy adult males. A statistically significant antipyretic effect of acetaminophen was demonstrated through 6 hours in comparison to placebo. The mean temperature over time is shown in Figure 1.

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.

Administration of acetaminophen in doses higher than recommended may result in hepatic injury, including the risk of liver failure and death [see Overdosage (10)]. Do not exceed the maximum recommended daily dose of acetaminophen [see Dosage and Administration (2)]. The maximum recommended daily dose of acetaminophen includes all routes of acetaminophen 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, 8.7)].

Chronic oral acetaminophen use at a dose of 4000 mg/day has been shown to cause an increase in international normalized ratio (INR) in some patients who have been stabilized on sodium warfarin as an anticoagulant. As no studies have been performed evaluating the short-term use of acetaminophen in patients on oral anticoagulants, more frequent assessment of INR may be appropriate in such circumstances.

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 (5.1)].

The following serious adverse reactions are discussed elsewhere in the labeling:

• •
  Hepatic Injury [see Warnings and Precautions (5.1)]
• •
  Serious Skin Reactions [see Warnings and Precautions (5.2)]
• •
  Allergy and Hypersensitivity [see Warnings and Precautions (5.4)]

• •
  Substances that induce or regulate hepatic cytochrome enzyme CYP2E1 may alter the metabolism of acetaminophen and increase its hepatotoxic potential. (7.1)
• •
  Chronic oral acetaminophen use at a dose of 4000 mg/day has been shown to cause an increase in international normalized ratio (INR) in some patients who have been stabilized on sodium warfarin as an anticoagulant. (7.2)

Acetaminophen has been shown to have analgesic and antipyretic activities in animal and human studies.

Single doses of acetaminophen up to 3000 mg and repeated doses of 1000 mg every 6 hours for 48 hours have not been shown to cause a significant effect on platelet aggregation. Acetaminophen does not have any immediate or delayed effects on small-vessel hemostasis. Clinical studies of both healthy subjects and patients with hemophilia showed no significant changes in bleeding time after receiving multiple doses of oral acetaminophen.

The efficacy of acetaminophen in the treatment of acute pain in adults was evaluated in two randomized, double-blind, placebo-controlled clinical trials in patients with postoperative pain.

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.

The precise mechanism of the analgesic and antipyretic properties of acetaminophen is not established but is thought to primarily involve central actions.

• •
  Administration of acetaminophen in doses higher than recommended (by all routes of administration and from all acetaminophen-containing products including combination products) may result in hepatic injury, including the risk of liver failure and death. (5.1)
• •
  Use caution when administering acetaminophen in patients with the following conditions: hepatic impairment or active hepatic disease, in cases of alcoholism, chronic malnutrition, severe hypovolemia, or severe renal impairment (creatinine clearance ≤ 30 mL/min). (5.1)
• •
  Discontinue acetaminophen immediately at the first appearance of skin rash and if symptoms associated with allergy or hypersensitivity occur. Do not use in patients with acetaminophen allergy. (5.2, 5.4)
• •
  Take care when prescribing, preparing, and administering Acetaminophen Injection to avoid dosing errors which could result in accidental overdose and death. (5.3)

Rarely, acetaminophen may cause serious skin reactions such as acute generalized exanthematous pustulosis (AGEP), Stevens-Johnson Syndrome (SJS), and toxic epidermal necrolysis (TEN), which can be fatal. Patients should be informed about the signs of serious skin reactions, and use of the drug should be discontinued at the first appearance of skin rash or any other sign of hypersensitivity.

• •
  Acetaminophen Injection may be given as a single or repeated dose. (2.1)
• •
  Acetaminophen Injection should be administered only as a 15-minute intravenous infusion. (2.4)

Adults and Adolescents Weighing 50 kg and Over:

• •
  1000 mg every 6 hours to a maximum of 4000 mg per day. Minimum dosing interval of 4 hours. (2.2)

Adults and Adolescents Weighing Under 50 kg:

• •
  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)

Children:

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

Neonates and Infants:

• •
  Neonates including premature neonates born at ≥ 32 weeks gestational age to 28 days chronological age, 12.5 mg/kg every 6 hours to a maximum of 50 mg/kg per day. Minimum dosing interval of 6 hours. (2.4)
• •
  Infants (29 days to 2 years of age): 15 mg/kg every 6 hours to a maximum of 60 mg/kg per day. Minimum dosing interval of 6 hours. (2.4)

Acetaminophen Injection is a sterile, clear, colorless to slightly yellow colored, non-pyrogenic, preservative free, isotonic formulation of acetaminophen intended for intravenous infusion. Each 100 mL single-dose bag contains 1000 mg acetaminophen (10 mg/mL).

Take care when prescribing, preparing, and administering Acetaminophen Injection in order to avoid dosing errors which could result in accidental overdose and death. In particular, be careful to ensure that:

• •
  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 [see Dosage and Administration (2)].

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed cannot be directly compared to rates in other clinical trials and may not reflect the rates observed in practice.

• •
  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 is supported by evidence from adequate and well controlled studies in adults with additional safety and pharmacokinetic data for this age group. (8.4)
• •
  Geriatric Use: No overall differences in safety or effectiveness were observed between geriatric and younger subjects. (8.5)
• •
  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, 5.1, 8.6)
• •
  Renal Impairment: In cases of severe renal impairment, longer dosing intervals and a reduced total daily dose of acetaminophen may be warranted. (5.1, 8.7)

Acetaminophen Injection 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 1-3 may 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.

Children 2 to 12 years of age: the recommended dosage of Acetaminophen Injection is 15 mg/kg every 6 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.

There have been post-marketing reports of hypersensitivity and anaphylaxis associated with the use of acetaminophen. Clinical signs included swelling of the face, mouth, and throat, respiratory distress, urticaria, rash, and pruritus. There were infrequent reports of life-threatening anaphylaxis requiring emergent medical attention. Discontinue acetaminophen immediately if symptoms associated with allergy or hypersensitivity occur. Do not use acetaminophen in patients with acetaminophen allergy.

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.

Acetaminophen was studied in pediatric patients in three active-controlled trials and three open-label safety and pharmacokinetic trials [see Use in Specific Populations (8.4)].

NDC 44567-340-10 - Acetaminophen Injection is supplied in 100 mL single-dose bags (NDC 44567-340-01) containing 1000 mg acetaminophen (10 mg/mL) in cartons of 10 bags, with each overwrap containing an oxygen absorber and oxygen indicator.

Do not remove unit from overwrap until ready for use.

To open, tear outer wrap at the notch and remove solution bag. After removing the outer wrap, check the container for minute leaks by squeezing the solution bag firmly. If leaks are found, discard the solution because the sterility may be impaired. A small amount of moisture may be present inside the outer wrap.

Acetaminophen Injection should be stored at 20°C to 25°C (68°F to 77°F) [see USP Controlled Room Temperature].

For single-dose only. The product should be used within 6 hours after the container seal has been penetrated and within 28 days of removal from the aluminum overwrap. The indicator must be yellow when opening the overwrap since the oxygen indicator will turn blue if the oxygen has exceeded acceptable levels. Do not refrigerate. Protect from freezing.

Rx only.

Manufactured for:

WG Critical Care, LLC

Paramus, NJ 07652

Made in Switzerland

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 (5.1) and Clinical Pharmacology (12)]. A reduced total daily dose of acetaminophen may be warranted.

Adults and adolescents weighing 50 kg and over: the recommended dosage of Acetaminophen Injection is 1000 mg every 6 hours, with a maximum single dose of Acetaminophen Injection of 1000 mg, a minimum dosing interval of 4 hours, and a maximum daily dose of acetaminophen of 4000 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).

•  
  For adult and adolescent patients weighing ≥ 50 kg requiring 1000 mg doses of Acetaminophen Injection, administer the dose by inserting a non-vented intravenous set through the administration spike port of the 100 mL bag. Acetaminophen Injection may be administered without further dilution. Examine the container contents before dose preparation or administering. DO NOT USE if particulate matter or discoloration is observed. Administer the contents of the container intravenously over 15 minutes. Use aseptic technique when preparing Acetaminophen Injection for intravenous infusion. Do not add other medications to the Acetaminophen Injection infusion device.

For doses less than 1000 mg, the appropriate dose must be withdrawn from the container and placed into a separate container prior to administration. Using aseptic technique, withdraw the appropriate dose (another dosage or weight-based) from an intact sealed Acetaminophen Injection container and 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 container of Acetaminophen Injection is not intended for use in patients weighing less than 50 kg. Acetaminophen Injection is supplied in a single-dose container 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 container seal 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.

Based on animal data use of acetaminophen may cause reduced fertility in males and females of reproductive potential. It is not known whether these effects on fertility are reversible. Published animal studies reported that oral acetaminophen treatment of male animals at doses that are 1.2 times the MHDD and greater (based on a body surface area comparison) result in decreased testicular weights, reduced spermatogenesis, and reduced fertility. In female animals given the same doses, reduced implantation sites were reported. Additional published animal studies indicate that acetaminophen exposure in utero adversely impacts reproductive capacity of both male and female offspring at clinically relevant exposures [see Nonclinical Toxicology (13.1)].

Substances that induce or regulate hepatic cytochrome enzyme CYP2E1 may alter the metabolism of acetaminophen and increase its hepatotoxic potential. The clinical consequences of these effects have not been established. Effects of ethanol are complex, because excessive alcohol usage can induce hepatic cytochromes, but ethanol also acts as a competitive inhibitor of the metabolism of acetaminophen.

Take care when prescribing, preparing, and administering Acetaminophen Injection to avoid dosing errors which could result in accidental overdose and death. In particular, be careful to ensure that:

• •
  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 contains acetaminophen. Acetaminophen has been associated with cases of acute liver failure, at times resulting in liver transplant and death. Most of the cases of liver injury are associated with the use of acetaminophen at doses that exceed the maximum daily limits, and often involve more than one acetaminophen-containing product [see Warnings and Precautions (5.1)].

•  
  Neonates, including premature neonates born at ≥ 32 weeks gestational age, up to 28 days chronological age: the recommended dosage of Acetaminophen Injection is 12.5 mg/kg every 6 hours, to a maximum daily dose of acetaminophen of 50 mg/kg per day, with a minimum dosing interval of 6 hours.

Infants 29 days to 2 years of age: the recommended dosage of Acetaminophen Injection is 15 mg/kg every 6 hours, to a maximum daily dose of acetaminophen of 60 mg/kg per day, with a minimum dosing interval of 6 hours.

Adult Population

A total of 1020 adult patients have received acetaminophen in clinical trials, including 37.3% (n=380) who received 5 or more doses, and 17.0% (n=173) who received more than 10 doses. Most patients were treated with acetaminophen 1000 mg every 6 hours. A total of 13.1% (n=134) received another dosage of acetaminophen injection.

All adverse reactions that occurred in adult patients treated with either acetaminophen or placebo in repeated dose, placebo-controlled clinical trials at an incidence ≥ 3% and at a greater frequency than placebo are listed in Table 4. The most common adverse events in adult patients treated with acetaminophen (incidence ≥ 5% and greater than placebo) were nausea, vomiting, headache, and insomnia.

Acetaminophen is a non-salicylate antipyretic and non-opioid analgesic agent. Its chemical name is N-acetyl-p-aminophenol. Acetaminophen has a molecular weight of 151.16. Its structural formula is:

Acetaminophen Injection is a sterile, clear, colorless, nonpyrogenic, isotonic formulation of acetaminophen intended for intravenous infusion. It has a pH of approximately 5.5 and an osmolality of approximately 290 mOsm/kg. Each 100 mL contains 1000 mg acetaminophen, USP, 3850 mg mannitol, USP, 25 mg cysteine hydrochloride, monohydrate, USP, and 10.4 mg dibasic sodium phosphate, USP. pH is adjusted with hydrochloric acid and/or sodium hydroxide.

The efficacy of acetaminophen 1000 mg in the treatment of adult fever was evaluated in one randomized, double-blind, placebo-controlled clinical trial. The study was a 6-hour, single-dose, endotoxin-induced fever study in 60 healthy adult males. A statistically significant antipyretic effect of acetaminophen was demonstrated through 6 hours in comparison to placebo. The mean temperature over time is shown in Figure 1.

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.

Administration of acetaminophen in doses higher than recommended may result in hepatic injury, including the risk of liver failure and death [see Overdosage (10)]. Do not exceed the maximum recommended daily dose of acetaminophen [see Dosage and Administration (2)]. The maximum recommended daily dose of acetaminophen includes all routes of acetaminophen 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, 8.7)].

Chronic oral acetaminophen use at a dose of 4000 mg/day has been shown to cause an increase in international normalized ratio (INR) in some patients who have been stabilized on sodium warfarin as an anticoagulant. As no studies have been performed evaluating the short-term use of acetaminophen in patients on oral anticoagulants, more frequent assessment of INR may be appropriate in such circumstances.

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 (5.1)].

The following serious adverse reactions are discussed elsewhere in the labeling:

• •
  Hepatic Injury [see Warnings and Precautions (5.1)]
• •
  Serious Skin Reactions [see Warnings and Precautions (5.2)]
• •
  Allergy and Hypersensitivity [see Warnings and Precautions (5.4)]

• •
  Substances that induce or regulate hepatic cytochrome enzyme CYP2E1 may alter the metabolism of acetaminophen and increase its hepatotoxic potential. (7.1)
• •
  Chronic oral acetaminophen use at a dose of 4000 mg/day has been shown to cause an increase in international normalized ratio (INR) in some patients who have been stabilized on sodium warfarin as an anticoagulant. (7.2)

Acetaminophen has been shown to have analgesic and antipyretic activities in animal and human studies.

Single doses of acetaminophen up to 3000 mg and repeated doses of 1000 mg every 6 hours for 48 hours have not been shown to cause a significant effect on platelet aggregation. Acetaminophen does not have any immediate or delayed effects on small-vessel hemostasis. Clinical studies of both healthy subjects and patients with hemophilia showed no significant changes in bleeding time after receiving multiple doses of oral acetaminophen.

The efficacy of acetaminophen in the treatment of acute pain in adults was evaluated in two randomized, double-blind, placebo-controlled clinical trials in patients with postoperative pain.

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.

The precise mechanism of the analgesic and antipyretic properties of acetaminophen is not established but is thought to primarily involve central actions.

• •
  Administration of acetaminophen in doses higher than recommended (by all routes of administration and from all acetaminophen-containing products including combination products) may result in hepatic injury, including the risk of liver failure and death. (5.1)
• •
  Use caution when administering acetaminophen in patients with the following conditions: hepatic impairment or active hepatic disease, in cases of alcoholism, chronic malnutrition, severe hypovolemia, or severe renal impairment (creatinine clearance ≤ 30 mL/min). (5.1)
• •
  Discontinue acetaminophen immediately at the first appearance of skin rash and if symptoms associated with allergy or hypersensitivity occur. Do not use in patients with acetaminophen allergy. (5.2, 5.4)
• •
  Take care when prescribing, preparing, and administering Acetaminophen Injection to avoid dosing errors which could result in accidental overdose and death. (5.3)

Rarely, acetaminophen may cause serious skin reactions such as acute generalized exanthematous pustulosis (AGEP), Stevens-Johnson Syndrome (SJS), and toxic epidermal necrolysis (TEN), which can be fatal. Patients should be informed about the signs of serious skin reactions, and use of the drug should be discontinued at the first appearance of skin rash or any other sign of hypersensitivity.

• •
  Acetaminophen Injection may be given as a single or repeated dose. (2.1)
• •
  Acetaminophen Injection should be administered only as a 15-minute intravenous infusion. (2.4)

Adults and Adolescents Weighing 50 kg and Over:

• •
  1000 mg every 6 hours to a maximum of 4000 mg per day. Minimum dosing interval of 4 hours. (2.2)

Adults and Adolescents Weighing Under 50 kg:

• •
  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)

Children:

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

Neonates and Infants:

• •
  Neonates including premature neonates born at ≥ 32 weeks gestational age to 28 days chronological age, 12.5 mg/kg every 6 hours to a maximum of 50 mg/kg per day. Minimum dosing interval of 6 hours. (2.4)
• •
  Infants (29 days to 2 years of age): 15 mg/kg every 6 hours to a maximum of 60 mg/kg per day. Minimum dosing interval of 6 hours. (2.4)

Acetaminophen Injection is a sterile, clear, colorless to slightly yellow colored, non-pyrogenic, preservative free, isotonic formulation of acetaminophen intended for intravenous infusion. Each 100 mL single-dose bag contains 1000 mg acetaminophen (10 mg/mL).

Take care when prescribing, preparing, and administering Acetaminophen Injection in order to avoid dosing errors which could result in accidental overdose and death. In particular, be careful to ensure that:

• •
  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 [see Dosage and Administration (2)].

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed cannot be directly compared to rates in other clinical trials and may not reflect the rates observed in practice.

• •
  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 is supported by evidence from adequate and well controlled studies in adults with additional safety and pharmacokinetic data for this age group. (8.4)
• •
  Geriatric Use: No overall differences in safety or effectiveness were observed between geriatric and younger subjects. (8.5)
• •
  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, 5.1, 8.6)
• •
  Renal Impairment: In cases of severe renal impairment, longer dosing intervals and a reduced total daily dose of acetaminophen may be warranted. (5.1, 8.7)

Acetaminophen Injection 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 1-3 may 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.

Children 2 to 12 years of age: the recommended dosage of Acetaminophen Injection is 15 mg/kg every 6 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.

There have been post-marketing reports of hypersensitivity and anaphylaxis associated with the use of acetaminophen. Clinical signs included swelling of the face, mouth, and throat, respiratory distress, urticaria, rash, and pruritus. There were infrequent reports of life-threatening anaphylaxis requiring emergent medical attention. Discontinue acetaminophen immediately if symptoms associated with allergy or hypersensitivity occur. Do not use acetaminophen in patients with acetaminophen allergy.

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.

Acetaminophen was studied in pediatric patients in three active-controlled trials and three open-label safety and pharmacokinetic trials [see Use in Specific Populations (8.4)].

NDC 44567-340-10 - Acetaminophen Injection is supplied in 100 mL single-dose bags (NDC 44567-340-01) containing 1000 mg acetaminophen (10 mg/mL) in cartons of 10 bags, with each overwrap containing an oxygen absorber and oxygen indicator.

Do not remove unit from overwrap until ready for use.

To open, tear outer wrap at the notch and remove solution bag. After removing the outer wrap, check the container for minute leaks by squeezing the solution bag firmly. If leaks are found, discard the solution because the sterility may be impaired. A small amount of moisture may be present inside the outer wrap.

Acetaminophen Injection should be stored at 20°C to 25°C (68°F to 77°F) [see USP Controlled Room Temperature].

For single-dose only. The product should be used within 6 hours after the container seal has been penetrated and within 28 days of removal from the aluminum overwrap. The indicator must be yellow when opening the overwrap since the oxygen indicator will turn blue if the oxygen has exceeded acceptable levels. Do not refrigerate. Protect from freezing.

Rx only.

Manufactured for:

WG Critical Care, LLC

Paramus, NJ 07652

Made in Switzerland

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 (5.1) and Clinical Pharmacology (12)]. A reduced total daily dose of acetaminophen may be warranted.

Adults and adolescents weighing 50 kg and over: the recommended dosage of Acetaminophen Injection is 1000 mg every 6 hours, with a maximum single dose of Acetaminophen Injection of 1000 mg, a minimum dosing interval of 4 hours, and a maximum daily dose of acetaminophen of 4000 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).

•  
  For adult and adolescent patients weighing ≥ 50 kg requiring 1000 mg doses of Acetaminophen Injection, administer the dose by inserting a non-vented intravenous set through the administration spike port of the 100 mL bag. Acetaminophen Injection may be administered without further dilution. Examine the container contents before dose preparation or administering. DO NOT USE if particulate matter or discoloration is observed. Administer the contents of the container intravenously over 15 minutes. Use aseptic technique when preparing Acetaminophen Injection for intravenous infusion. Do not add other medications to the Acetaminophen Injection infusion device.

For doses less than 1000 mg, the appropriate dose must be withdrawn from the container and placed into a separate container prior to administration. Using aseptic technique, withdraw the appropriate dose (another dosage or weight-based) from an intact sealed Acetaminophen Injection container and 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 container of Acetaminophen Injection is not intended for use in patients weighing less than 50 kg. Acetaminophen Injection is supplied in a single-dose container 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 container seal 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.

Based on animal data use of acetaminophen may cause reduced fertility in males and females of reproductive potential. It is not known whether these effects on fertility are reversible. Published animal studies reported that oral acetaminophen treatment of male animals at doses that are 1.2 times the MHDD and greater (based on a body surface area comparison) result in decreased testicular weights, reduced spermatogenesis, and reduced fertility. In female animals given the same doses, reduced implantation sites were reported. Additional published animal studies indicate that acetaminophen exposure in utero adversely impacts reproductive capacity of both male and female offspring at clinically relevant exposures [see Nonclinical Toxicology (13.1)].

Substances that induce or regulate hepatic cytochrome enzyme CYP2E1 may alter the metabolism of acetaminophen and increase its hepatotoxic potential. The clinical consequences of these effects have not been established. Effects of ethanol are complex, because excessive alcohol usage can induce hepatic cytochromes, but ethanol also acts as a competitive inhibitor of the metabolism of acetaminophen.

Take care when prescribing, preparing, and administering Acetaminophen Injection to avoid dosing errors which could result in accidental overdose and death. In particular, be careful to ensure that:

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

Acetaminophen Injection contains acetaminophen. Acetaminophen has been associated with cases of acute liver failure, at times resulting in liver transplant and death. Most of the cases of liver injury are associated with the use of acetaminophen at doses that exceed the maximum daily limits, and often involve more than one acetaminophen-containing product [see Warnings and Precautions (5.1)].

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  Neonates, including premature neonates born at ≥ 32 weeks gestational age, up to 28 days chronological age: the recommended dosage of Acetaminophen Injection is 12.5 mg/kg every 6 hours, to a maximum daily dose of acetaminophen of 50 mg/kg per day, with a minimum dosing interval of 6 hours.

Infants 29 days to 2 years of age: the recommended dosage of Acetaminophen Injection is 15 mg/kg every 6 hours, to a maximum daily dose of acetaminophen of 60 mg/kg per day, with a minimum dosing interval of 6 hours.