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HIGHLIGHTS OF PRESCRIBING INFORMATIONThese highlights do not include all the information needed to useAcetaminophen Injection safely and effectively. See full prescribinginformation for Acetaminophen Injection. Acetaminophen Injection, for intravenous useInitial U.S. Approval: 1951products including combination products) may result in hepatic injury,including the risk of liver failure and death. (5.1)Do not exceed the maximum recommended daily dose of acetaminophen(by all routes of administration and all acetaminophen-containingproducts including combination products). (5.1)Take care when prescribing, preparing, and administeringacetaminophen injection to avoid dosing errors which could result inaccidental overdose and death. (5.3)Use caution when administering acetaminophen in patients with thefollowing conditions: hepatic impairment or active hepatic disease, incases of alcoholism, chronic malnutrition, severe hypovolemia, or severerenal impairment (creatinine clearance 30 mL/min). (5.1)Discontinue acetaminophen immediately at the first appearance of skinrash and if symptoms associated with allergy or hypersensitivity occur.Do not use in patients with acetaminophen allergy. (5.2, 5.4)WARNING: RISK OF MEDICATION ERRORS ANDHEPATOTOXICITYSee full prescribing information for complete boxed warning Take care when prescribing, preparing, and administering AcetaminophenInjection to avoid dosing errors which could result in accidental overdoseand death. (5.3) Acetaminophen Injection contains acetaminophen. Acetaminophen hasbeen associated with cases of acute liver failure, at times resulting in livertransplant and death. Most of the cases of liver injury are associated withthe use of acetaminophen at doses that exceed the recommended maximumdaily limits, and often involve more than one acetaminophen-containingproduct. (5.1).------------------------------ADVERSE REACTIONS------------------------------ The most common adverse reactions in patients treated with acetaminophenwere nausea, vomiting, headache, and insomnia in adult patients and nausea,vomiting, constipation, pruritus, agitation, and atelectasis in pediatric patients.(6.1)To report SUSPECTED ADVERSE REACTIONS, contactFresenius Kabi USA, LLC, Vigilance & Medical Affairs at 1-800-551 7176 or FDA at 1-800-FDA-1088 or NDICATIONS AND USAGE--------------------------Acetaminophen injection is indicated for the: Management of mild to moderate pain. (1) Management of moderate to severe pain with adjunctive opioidanalgesics. (1) Reduction of fever. (1)------------------------------DRUG INTERACTIONS------------------------------ Substances that induce or regulate hepatic cytochrome enzyme CYP2E1may alter the metabolism of acetaminophen and increase its hepatotoxicpotential. (7.1) Chronic oral acetaminophen use at a dose of 4,000 mg/day has beenshown to cause an increase in international normalized ratio (INR) insome patients who have been stabilized on sodium warfarin as ananticoagulant. (7.2)----------------------DOSAGE AND ADMINISTRATION---------------------- Acetaminophen injection may be given as a single or repeated dose.(2.1) Acetaminophen injection should be administered only as a 15 minuteintravenous infusion. (2.4)-----------------------USE IN SPECIFIC POPULATIONS----------------------- Pregnancy: Category C. There are no studies of intravenousacetaminophen in pregnant women. Use only if clearly needed. (8.1) Nursing Mothers: Caution should be exercised when administered to anursing woman. (8.3) Pediatric Use: The effectiveness of acetaminophen for the treatment ofacute pain and fever has not been studied in pediatric patients less than 2years of age. The safety and effectiveness of acetaminophen in pediatricpatients older than 2 years is supported by evidence from adequate andwell-controlled studies in adults with additional safety andpharmacokinetic data for this age group. (8.4) Geriatric Use: No overall differences in safety or effectiveness wereobserved between geriatric and younger subjects. (8.5) Hepatic Impairment: Acetaminophen is contraindicated in patients withsevere hepatic impairment or severe active liver disease and should beused with caution in patients with hepatic impairment or active liverdisease. (4, 5.1, 8.6) Renal Impairment: In cases of severe renal impairment, longer dosingintervals and a reduced total daily dose of acetaminophen may bewarranted. (5.1, 8.7)Adults and Adolescents Weighing 50 kg and Over: 1,000 mg every 6 hours or 650 mg every 4 hours to a maximum of4,000 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 of75 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 or 12.5 mg/kgevery 4 hours to a maximum of 75 mg/kg per day. Minimum dosinginterval of 4 hours. (2.3)---------------------DOSAGE FORMS AND STRENGTHS--------------------- Injection for intravenous infusion. Each 100 mL flexible plastic container has 1,000 mg acetaminophen (10mg/mL). S----------------------------- Acetaminophen is contraindicated: In patients with known hypersensitivity to acetaminophen or to any ofthe excipients in the IV formulation. (4) In patients with severe hepatic impairment or severe active liver disease.(4)Revised: 10/2015-----------------------WARNINGS AND PRECAUTIONS----------------------- Administration of acetaminophen in doses higher than recommended (byall routes of administration and from all acetaminophen-containingFULL PRESCRIBING INFORMATION: CONTENTS*WARNING: RISK OF MEDICATION ERRORS AND HEPATOTOXICITY1 INDICATIONS AND USAGE2 DOSAGE AND ADMINISTRATION2.1 General Dosing Information2.2 Recommended Dosage: Adults and Adolescents2.3 Recommended Dosage: Children2.4 Instructions for Intravenous Administration3 DOSAGE FORMS AND STRENGTHS4 CONTRAINDICATIONS5 WARNINGS AND PRECAUTIONS5.1 Hepatic Injury5.2 Serious Skin Reactions5.3 Risk of Medication Errors6781Reference ID: 38393185.4 Allergy and HypersensitivityADVERSE REACTIONS6.1 Clinical Trial ExperienceDRUG INTERACTIONS7.1 Effects of Other Substances on Acetaminophen7.2 AnticoagulantsUSE IN SPECIFIC POPULATIONS8.1 Pregnancy8.2 Labor and Delivery8.3 Nursing Mothers8.4 Pediatric Use8.5 Geriatric Use8.6 Patients with Hepatic Impairment8.7 Patients with Renal Impairment

14.3 Pediatric Acute Pain and Fever16 HOW SUPPLIED/STORAGE AND HANDLING10 OVERDOSAGE11 DESCRIPTION12 CLINICAL PHARMACOLOGY12.1 Mechanism of Action12.2 Pharmacodynamics12.3 Pharmacokinetics13 NONCLINICAL TOXICOLOGY13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility14 CLINICAL STUDIES14.1 Adult Acute Pain14.2 Adult Fever*Sections or subsections omitted from the full prescribing information are notlisted.FULL PRESCRIBING INFORMATIONWARNING: Risk of Medication Errors and HepatotoxicityTake care when prescribing, preparing, and administering Acetaminophen Injection toavoid dosing errors which could result in accidental overdose and death. In particular, becareful 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 maximumdaily limits [see Warnings and Precautions (5.3)].Acetaminophen injection contains acetaminophen. Acetaminophen has been associatedwith cases of acute liver failure, at times resulting in liver transplant and death. Most of thecases of liver injury are associated with the use of acetaminophen at doses that exceed themaximum daily limits, and often involve more than one acetaminophen-containing product[see Warnings and Precautions (5.1)].1INDICATIONS AND USAGEAcetaminophen injection is indicated for: the management of mild to moderate pain the management of moderate to severe pain with adjunctive opioid analgesics the reduction of fever2DOSAGE AND ADMINISTRATION2.1General Dosing InformationAcetaminophen injection, for intravenous use, may be given as a single or repeated dose forthe treatment of acute pain or fever. No dose adjustment is required when converting2Reference ID: 3839318

between oral acetaminophen and acetaminophen injection dosing in adults and adolescentswho weigh 50 kg and above. Calculated maximum daily dose of acetaminophen is based onall routes of administration (i.e. intravenous, oral, and rectal) and all products containingacetaminophen. Exceeding the maximum mg/kg daily dose of acetaminophen as describedin Tables 1 and 2 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 routesand from all sources does not exceed the maximum recommended dose.2.2Recommended Dosage: Adults and AdolescentsAdults and adolescents weighing 50 kg and over: the recommended dosage ofacetaminophen injection is 1,000 mg every 6 hours or 650 mg every 4 hours, with amaximum single dose of acetaminophen injection of 1,000 mg, a minimum dosing intervalof 4 hours, and a maximum daily dose of acetaminophen of 4,000 mg per day (includes allroutes of administration and all acetaminophen-containing products including combinationproducts).Adults and adolescents weighing under 50 kg: the recommended dosage of acetaminopheninjection is 15 mg/kg every 6 hours or 12.5 mg/kg every 4 hours, with a maximum singledose of acetaminophen injection of 15 mg/kg, a minimum dosing interval of 4 hours, and amaximum daily dose of acetaminophen of 75 mg/kg per day (includes all routes ofadministration and all acetaminophen-containing products including combination products).Table 1. Dosing for Adults and AdolescentsAge GroupAdults and adolescents(13 years and older)weighing 50 kgAdults and adolescents(13 years and older)weighing 50 kg2.3Dose givenevery 4 hoursDose givenevery 6 hoursMaximumsingle doseMaximum total dailydose ofacetaminophen(by any routes)650 mg1,000 mg1,000 mg4,000 mg in 24 hours12.5 mg/kg15 mg/kg15 mg/kg(up to 750 mg)75 mg/kg in 24hours(up to 3,750 mg)Recommended Dosage: ChildrenChildren 2 to 12 years of age: the recommended dosage of acetaminophen injection is 15mg/kg every 6 hours or 12.5 mg/kg every 4 hours, with a maximum single dose of3Reference ID: 3839318

acetaminophen injection of 15 mg/kg, a minimum dosing interval of 4 hours, and amaximum daily dose of acetaminophen of 75 mg/kg per day.Table 2. Dosing for ChildrenAge GroupChildren 2 to 12 yearsof age2.4Dose givenevery 4 hoursDose givenevery 6 hours12.5 mg/kg15 mg/kgMaximumsingle dose15 mg/kg(up to 750 mg)Maximum total dailydose ofacetaminophen(by any routes)75 mg/kg in 24hours(up to 3,750 mg)Instructions for Intravenous AdministrationFor adult and adolescent patients weighing 50 kg requiring 1,000 mg doses ofacetaminophen injection, acetaminophen injection may be administered withoutfurther dilution. Examine the flexible plastic container contents before dose preparation oradministering. DO NOT USE if particulate matter or discoloration is observed. Administerthe contents of the flexible plastic container intravenously over 15minutes. Use aseptictechnique when preparing acetaminophen injection for intravenous infusion. Do not addother medications to the acetaminophen injection flexible plastic container.For doses less than 1,000 mg, the appropriate dose must be withdrawn from theacetaminophen injection flexible plastic container and placed into a separate containerprior to administration. Using aseptic technique, withdraw the appropriate dose (650 mgor weight-based) from an intact sealed acetaminophen injection flexible plastic containerand place the measured dose in a separate empty, sterile container (e.g. glass bottle, plasticintravenous container, or syringe) for intravenous infusion to avoid the inadvertent deliveryand administration of the total volume of the commercially available container. The entire100 mL flexible plastic container of acetaminophen injection is not intended for use inpatients weighing less than 50 kg. Acetaminophen injection is provided in a single-useflexible plastic container and the unused portion must be discarded.Place small volume pediatric doses up to 60 mL in volume in a syringe and administer over15 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.4Reference ID: 3839318

Once the seal of the flexible plastic container has been penetrated, or the contents transferredto another container, administer the dose of acetaminophen injection within 6 hours.Do not add other medications to the acetaminophen injection solution. Diazepam andchlorpromazine hydrochloride are physically incompatible with acetaminophen injection,therefore do not administer simultaneously.3DOSAGE FORMS AND STRENGTHSAcetaminophen injection is a sterile, clear, colorless, non-pyrogenic, preservative free,isotonic formulation of acetaminophen intended for intravenous infusion. Each 100 mLflexible plastic container has 1,000 mg acetaminophen (10 mg/mL).4CONTRAINDICATIONSAcetaminophen is contraindicated: in patients with known hypersensitivity to acetaminophen or to any of the excipients in theintravenous formulation. in patients with severe hepatic impairment or severe active liver disease [see Warningsand Precautions (5.1)].5WARNINGS AND PRECAUTIONS5.1Hepatic InjuryAdministration of acetaminophen in doses higher than recommended may result in hepaticinjury, including the risk of liver failure and death [see Overdosage (10)]. Do not exceedthe maximum recommended daily dose of acetaminophen [see Dosage and Administration(2)]. The maximum recommended daily dose of acetaminophen includes all routes ofadministration and all