Effective pain management begins with OFIRMEV (acetaminophen) injection FIRST Proven efficacy with rapid reduction in pain 1

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1 Effective pain management begins with OFIRMEV (acetaminophen) injection FIRST Proven efficacy with rapid reduction in pain 1 Fast onset of pain relief with 7% reduction in visual analog scale (VAS) scores in 1 minutes was demonstrated in a renal colic study 1 Significant mean differences in pain intensity reductions were observed for IV acetaminophen (P=.) and IV morphine (P=.) when compared with placebo. 1 IV acetaminophen 1 g rapidly reduced pain intensity scores in patients with acute renal colic VAS score reductions were not significantly different between OFIRMEV and morphine arms (P=.7). 1 This study was not designed as a head-to-head, noninferiority trial comparing the efficacy of OFIRMEV to morphine. Bektas et al. Randomized, prospective, double-blind, placebo-controlled, single-center, single-dose trial with 3 parallel groups. Patients received a single dose of IV acetaminophen 1 g, IV morphine.1 mg/kg, or placebo upon presenting to the emergency department with suspected renal colic. IV fentanyl was available to patients with inadequate pain relief at 3 minutes. Primary endpoint: change in pain intensity, based on VAS score, from baseline, at 1 and 3 minutes. 1 Median pain intensity (VAS 1 mm) Time (min) OFIRMEV 1 g (n=6) P =. vs placebo INDICATIONS AND USAGE OFIRMEV (acetaminophen) injection is indicated for the management of mild to moderate pain, management of moderate to severe pain with adjunctive opioid analgesics, and reduction of fever. WARNING: RISK OF MEDICATION ERRORS AND HEPATOTOXICITY Take care when prescribing, preparing, and administering OFIRMEV 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 kg; infusion pumps are properly programmed; and the total daily dose of acetaminophen from all sources does not exceed maximum daily limits. OFIRMEV 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 recommended maximum daily limits, and often involve more than one acetaminophen-containing product. OFIRMEV should be administered only as a 1-minute intravenous infusion Serious adverse reactions may include hepatic injury, serious skin reactions, hypersensitivity, and anaphylaxis Common adverse reactions in adults include nausea, vomiting, headache, and insomnia Please see the back cover for additional Important Risk Information, including boxed warning, and in the accompanying Full Prescribing Information.

2 Why OFIRMEV? OFIRMEV (acetaminophen) injection provides 7% more drug available in the cerebrospinal fluid (CSF), the believed site of action, than oral acetaminophen 2 More acetaminophen reaches the CSF with IV administration Overall CSF levels were 7% higher than oral acetaminophen (P<.1) and 12% higher than rectal acetaminophen (P<.1). 2 Mean CSF concentration (μg/ml) OFIRMEV 1 g (n=6) Oral acetaminophen 1 g (n=6) Rectal acetaminophen 1 g*(n=6) Efficacy was not assessed in this study. Singla et al. Three-way, crossover, single-center, single-dose pharmacokinetic study of 6 healthy adult males. Each received 3 single-dose treatments of IV, oral, and rectal acetaminophen, separated by a washout period of 2 h. Treatment dosage was 1 g IV and oral acetaminophen, and 13 mg rectal. IV acetaminophen was administered over 1 minutes commencing at h. CSF and blood draws were performed prior to study medication administration and at 8 additional time points for 6 h in each treatment period Time (h) * Rectal acetaminophen data reflect standardization of the 13-mg dose to 1 g (linear kinetics). Unlike oral acetaminophen, OFIRMEV bypasses first-pass liver metabolism. 2 OFIRMEV does not result in transfer constant delay issues 3 OFIRMEV provides: Early and high C max Higher peak CSF concentration No transfer constant delay issues 2,3 No first-pass hepatic exposure 1% bioavailability Administration of acetaminophen in doses higher than recommended may result in hepatic injury, including the risk of liver failure and death Do not exceed the maximum recommended daily dose of acetaminophen by all routes The maximum total daily dose of OFIRMEV for adults kg is mg 2 Please see the back cover for additional Important Risk Information, including boxed warning, and in the accompanying Full Prescribing Information.

3 Effective pain relief that can help eliminate the need for foundational opioid therapy Proven efficacy with rapid reduction in pain 6 Pain relief Rapid, sustained pain relief with IV acetaminophen and PCA morphine in hip and knee replacement surgery.2..7 Significant improvement over placebo + PCA morphine Time (h) OFIRMEV 1 g + PCA morphine (n=9) Placebo + PCA morphine (n=2) P<. at every time point 6 In an orthopedic surgery study, time to first rescue medication was significantly improved for OFIRMEV 1 g vs placebo (3 hours vs.8 hours, P.1). 6 In this repeated-dose study over 2 hours, OFIRMEV maintained a significant reduction of pain intensity compared with placebo throughout the 2-hour study period (sum-of-pain-intensity difference, based on VAS score, at to 2 h; P<.1). 6,7 Sinatra et al. (Pain Study 1) Randomized, double-blind, placebo-controlled, single- and repeated-dose 2-h study (n=11). Patients received OFIRMEV 1 g + PCA morphine or placebo + PCA morphine the morning following total hip or knee replacement surgery. Primary endpoint: pain relief measured on a -point verbal scale over 6 h. Morphine rescue was administered as needed. 7 PCA=patient-controlled analgesia. Starting OFIRMEV earlier helps maximize pain control 8 Mean pain intensity (VAS 1 cm) Earlier administration of OFIRMEV produced better control of postoperative pain IV acetaminophen 1 g given 3 min prior to induction (n=28) IV acetaminophen 1 g prior to skin closure (n=27) Placebo (n=27) P< Time (h) In an abdominal hysterectomy study, preoperative administration of OFIRMEV produced the greatest reduction in mean pain intensity scores compared with placebo (P<.). Intraoperative administration also resulted in statistically significant reduction in pain intensity at all time points (P<.). 8 Arici et al. Randomized, placebo-controlled, parallel-group, single-site study. Patients scheduled for total abdominal hysterectomy received IV acetaminophen 1 g 3 minutes prior to induction (pre-op), IV acetaminophen 1 g prior to skin closure (intra-op), or placebo. PCA morphine was available to all patients. Pain intensity, based on VAS, at rest and with movement, sedation, and total morphine consumption was measured at 1 and 3 minutes and at 1, 2,, 8, 12, and 2 hours. 8 INDICATIONS AND USAGE OFIRMEV (acetaminophen) injection is indicated for the management of mild to moderate pain, management of moderate to severe pain with adjunctive opioid analgesics, and reduction of fever. Acetaminophen is contraindicated in patients with: - known hypersensitivity to acetaminophen or to any of the excipients in the intravenous (IV) formulation - severe hepatic impairment or severe active liver disease 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 3 ml/min) 3

4 OFIRMEV reduced opioids and improved patient satisfaction 6,9 Reduced opioid consumption 6 6 Reduction in morphine consumption (Total hip or knee replacement surgery) OFIRMEV 1 g + PCA morphine (n=9) Placebo + PCA morphine (n=2) 33 % In an orthopedic surgery study, time to first rescue medication was significantly improved for OFIRMEV (acetaminophen) injection 1 g vs placebo (3 hours vs.8 hours, P.1). 6 The clinical benefit of reduced opioid consumption was not evaluated or demonstrated. Morphine (mg) Over 6 h P<.1 6 % 17.8 mg 9.7 mg 7. mg 38.3 mg Over 2 h P<.1 Sinatra et al. (Pain Study 1) Randomized, double-blind, placebo-controlled, single- and repeated-dose 2-h study (n=11). Patients received OFIRMEV 1 g + PCA morphine or placebo + PCA morphine the morning following total hip or knee replacement surgery. Primary endpoint: pain relief measured on a -point verbal scale over 6 h. Morphine rescue was administered as needed. 6 Improved patient satisfaction 9 Percentage of patients, after total hip replacement, rating satisfaction as good or excellent at bedtime improved OFIRMEV + rescue (n=3) Placebo + rescue (n=31) P= % 8.7% In an orthopedic surgery study, 8.7% of patients receiving OFIRMEV reported good to excellent satisfaction with their pain management versus 39.3% of patients receiving opioid standard of care (SOC). 9 Viscusi et al. Randomized, double-blind, placebo-controlled, single-dose, 6-h study (n=69). Patients received OFIRMEV 1 g + PCA morphine or placebo + PCA morphine the morning following total hip arthroplasty. Primary endpoint: pain intensity differences measured over 6 h. Morphine rescue was administered as needed. 9 This study was terminated early due to the detection of particulates in some placebo vials. WARNING: RISK OF MEDICATION ERRORS AND HEPATOTOXICITY Take care when prescribing, preparing, and administering OFIRMEV Injection to avoid dosing errors which could result in accidental overdose and death. OFIRMEV 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 recommended maximum daily limits, and often involve more than one acetaminophen-containing product. Please see the back cover for additional Important Risk Information, including boxed warning, and in the accompanying Full Prescribing Information.

5 Well-established safety profile 1,,6,8,1 Most common adverse events (AEs) associated with various analgesics according to prescribing information and clinical trials* Adverse event ( 3% incidence ) OFIRMEV (acetaminophen) Ketorolac (NSAID) 11 Morphine (opioid) 8,12 Constipation Dizziness Drowsiness/sedation Dyspepsia GI pain Headaches Insomnia Light-headedness Nausea Postoperative ileus Pruritus Sweating Urinary retention Vomiting Serious AEs associated with various analgesics according to prescribing information* Serious adverse event OFIRMEV (acetaminophen) * AEs described in these tables were not derived from head-to-head trials in comparable patient populations. Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed cannot be directly compared with rates in other clinical trials and may not reflect the rates observed in practice. Those AEs presented here have occurred at 3% incidence as described in the prescribing information or clinical trials. Ketorolac (NSAID) 11 Morphine (opioid) 12 Acute renal failure Allergy and hypersensitivity Apnea Cardiac arrest Cardiovascular thrombotic events Circulatory depression Congestive heart failure GI ulceration, bleeding, and perforation Hemorrhage Hepatic injury Hypertension Postoperative bleeding Pregnancy: fetal cardiovascular system abnormalities Renal effects Respiratory arrest Respiratory depression Serious skin reactions Shock Serious adverse reactions may include hepatic injury, serious skin reactions, hypersensitivity, and anaphylaxis Common adverse reactions in adults include nausea, vomiting, headache, and insomnia 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

6 Less pain. Less opioids. From the start. Effective pain management begins with OFIRMEV (acetaminophen) injection first 1 Well-established safety profile 1,,6,8,1 Significantly improved patient satisfaction vs opioid SOC 9 Effective pain relief that can help eliminate the need for foundational opioid therapy OFIRMEV provides 7% more drug available in the CSF, the believed site of action, than oral acetaminophen 2 INDICATIONS AND USAGE OFIRMEV (acetaminophen) injection is indicated for the management of mild to moderate pain, management of moderate to severe pain with adjunctive opioid analgesics, and reduction of fever. WARNING: RISK OF MEDICATION ERRORS AND HEPATOTOXICITY Take care when prescribing, preparing, and administering OFIRMEV 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 kg; infusion pumps are properly programmed; and the total daily dose of acetaminophen from all sources does not exceed maximum daily limits. OFIRMEV 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 recommended maximum daily limits, and often involve more than one acetaminophen-containing product. CONTRAINDICATIONS Acetaminophen is contraindicated in patients with: known hypersensitivity to acetaminophen or to any of the excipients in the intravenous (IV) formulation. severe hepatic impairment or severe active liver disease. WARNINGS AND PRECAUTIONS Administration of acetaminophen in doses higher than recommended may result in hepatic injury, including the risk of liver failure and death. Do not exceed the maximum recommended daily dose of acetaminophen. The maximum recommended daily dose of acetaminophen includes all routes of acetaminophen administration and all acetaminophen-containing products administered, including combination products. Dosing errors could result in accidental overdose and death. 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 3 ml/min). 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. Hypersensitivity and anaphylaxis associated with the use of acetaminophen have been reported. Clinical signs included swelling of the face, mouth, and throat, respiratory distress, urticaria, rash, and pruritus. The antipyretic effects of OFIRMEV may mask fever. ADVERSE REACTIONS Serious adverse reactions may include hepatic injury, serious skin reactions, hypersensitivity, and anaphylaxis. Common adverse reactions in adults include nausea, vomiting, headache, and insomnia. Common adverse reactions in pediatric patients include nausea, vomiting, constipation, pruritus, agitation, and atelectasis. USE IN SPECIFIC POPULATIONS Pregnancy Category C. OFIRMEV should be given to a pregnant woman only if clearly needed. Breastfeeding: While studies with OFIRMEV have not been conducted, acetaminophen is secreted in human milk in small quantities after oral administration. Pediatric Use: The effectiveness of OFIRMEV for the treatment of acute pain and fever has not been studied in pediatric patients < 2 years of age. To report SUSPECTED ADVERSE REACTIONS, contact Mallinckrodt Hospital Products, Inc. at or the FDA at 1-8-FDA-188 or Please see Important Risk Information, including complete boxed warning, in the accompanying Full Prescribing Information. References: 1. Bektas F et al. Ann Emerg Med. 29;(): Singla NK et al. Pain Pract. 212;12(7): Jahr JS et al. Anesthesiol Clin. 21;28(): OFIRMEV [package insert]. Hazelwood, MO: Mallinckrodt Hospital Products, Inc; 21.. Data on file. Mallinckrodt Hospital Products, Inc. 6. Sinatra RS et al. Anesthesiology. 2;12(): Sinatra RS et al. Pain Pract. 212;12(): Arici S et al. Agri. 29;21(2): Viscusi E et al. Poster #21 presented at: The American Academy of Pain Medicine s 2th Annual Meeting; February 13-16, 28; Orlando, FL. 1. Wininger SJ et al. Clin Ther. 21;32(1): Toradol [package insert]. Cromer NSW 299, Australia: Roche Products Pty Limited; Morphine sulfate [package insert]. Lake Forest, IL: Hospira, Inc.; 211. Mallinckrodt, the M brand mark and the Mallinckrodt Pharmaceuticals logo are trademarks of a Mallinckrodt company. Other brands are trademarks of a Mallinckrodt company or their respective owners. 21 Mallinckrodt. OFV179 6/1 OFIRMEV.com