Less Pain1-5 Less Opioids2,3 Improved Patient Satisfaction2,4

Clinical studies

The efficacy of OFIRMEV has been studied in multiple clinical settings1-6

ORTHOPEDIC SURGERY Sinatra et al (pain study 1)

STUDY DESIGN2: The primary endpoint of this study was pain relief measured on a 5-point verbal scale over 6 hours. This was a randomized, double-blind, placebo-controlled, single- and repeated-dose 24-hour study (n=101). Patients received OFIRMEV 1 g with patient-controlled analgesia (PCA) morphine or placebo with PCA morphine the morning following total hip or knee replacement surgery. Morphine rescue was administered as needed.

Thirty-two patients in the OFIRMEV group and thirty-two patients in the placebo group experienced at least one adverse event after the first administration of the study medication. The most common adverse events reported in this study included constipation, nausea, injection site pain, anemia, pruritus, and vomiting.

Highly efficacious with proven rapid reduction in pain

OFIRMEV with PCA morphine demonstrated significant pain relief vs placebo with PCA morphine2

Mean pain relief scores, single dose2

Mean pain relief scores, single dose PCA, patient-controlled analgesia.
  • In this repeated-dose study over 24 hours, OFIRMEV maintained a significant reduction of pain intensity when compared with placebo throughout the 24-hour study period (sum of pain intensity differences from 0 to 24 hours, based on visual analog scale score;
    P<0.001; data not shown)5

Significantly less opioids

OFIRMEV with PCA morphine significantly reduced morphine consumption vs placebo with PCA morphine2

Reduction in morphine consumption2

Reduction in morphine consumption PCA, patient-controlled analgesia.
  • Patient satisfaction with study treatment (patients reporting “good” or “excellent” satisfaction) was also significantly higher with OFIRMEV vs placebo (40.8% vs 23.1%, P=0.004)2,33
  • The clinical benefit of reduced opioid consumption was not evaluated or demonstrated

Longer time to rescue analgesia

Significantly increased time to first rescue medication with OFIRMEV vs placebo2

Longer time to first rescue medication2

Time to first rescue medication
  • Time to first rescue medication was significantly increased for patients receiving OFIRMEV when compared with patients receiving placebo (3 hours vs 0.8 hours, P<0.001)2
  • The clinical benefit of reduced opioid consumption was not evaluated or demonstrated

Adverse events reported in this study

Thirty-two patients in the OFIRMEV group and thirty-two patients in the placebo group experienced at least one adverse event after the first administration of the study medication. The most common adverse events reported in this study included constipation, nausea, injection site pain, anemia, pruritus, and vomiting.

Safety Considerations

  • 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
Back to top ^

ABDOMINAL LAPAROSCOPIC SURGERYWininger et al (pain study 2)

STUDY DESIGN4: The primary endpoint of this study was the sum of pain intensity differences from 0 to 24 hours (SPID24) from baseline visual analog scale (VAS) score. This was a randomized, double-blind, placebo-controlled, multicenter, parallel-group study. The morning following abdominal laparoscopic surgery, patients received OFIRMEV 1 g (n=92) or placebo (n=42) every 6 hours (q6h) or OFIRMEV 650 mg (n=41) or placebo (n=66) every 4 hours. IV or oral rescue medication was available to all patients. Results from the OFIRMEV 1 g q6h and combined placebo groups are shown below.

The most common overall adverse events reported in this study were constipation, flatulence, nausea, and headache. The frequency of treatment-emergent adverse events across the treatment groups was not statistically significant.

Significant improvement in pain intensity4

OFIRMEV with rescue significantly reduced pain intensity vs placebo with rescue

Sum of pain intensity differences from baseline over 24 hoursa

Sum of pain intensity differences from baseline over 24 hours q6h, every 6 hours; SPID24, sum of pain intensity differences from 0 to 24 hours; VAS, visual analog scale. aSPID24 values represent reductions from baseline.

Pain intensity scores4,33

OFIRMEV pain intensity scores at each dosing interval over 24 hours

Mean pain intensity scores at 6-hour intervals

Mean pain intensity scores at 6-hour intervals q6h, every 6 hours; VAS, visual analog scale.

Improved patient satisfaction at 24 hours4

Significantly more patients reported "good" or "excellent" satisfaction compared with placebo

Patient-reported satisfaction of "good" or "excellent" with study treatment at 24 hours

Patient-reported satisfaction of 'good' or 'excellent' with study treatment at 24 hours q6h, every 6 hours. aOverall P value derived from a statistical analysis of a 4-point global categorical scale.
  • Patients were asked to evaluate the study treatments overall, using a 4-point categorical scale
  • Study encompassed laparoscopic OB-GYN and laparoscopic general surgical procedures
    • Cholecystectomy
    • Hernia repair
    • Hysterectomy
    • Prostatectomy

Adverse events reported in this study

The most common overall adverse events reported in this study were constipation, flatulence, nausea, and headache. The frequency of treatment-emergent adverse events across the treatment groups was not statistically significant.

Indications and Usage

OFIRMEV® (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, and the reduction of fever in adult and pediatric patients.

Safety Considerations

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 50 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.

Back to top ^

ADULT FEVERKett et al6

STUDY DESIGN: The primary endpoint of this study was the weighted sum of temperature differences from baseline through 6 hours. This was a randomized, double-blind, placebo-controlled, single-dose, single-center US study evaluating the efficacy and safety of OFIRMEV 1 g in the treatment of endotoxin-induced fever in healthy adult males. Subjects experienced elevated body temperatures following administration of reference standard endotoxin and received either OFIRMEV (n=31) or placebo (n=29).

No clinically relevant differences were observed in frequency of overall or severe treatment-emergent adverse events reported in this study.

Rapid and significant fever reduction

OFIRMEV 1 g significantly reduced fever at 30 minutes (15 minutes after completion of administration)

Significant reduction in mean temperature (mITT population)

Reduction in mean temperature (mITT population) mITT, modified intention-to-treat. aOverall P value from an analysis of covariance of the weighted sum of temperature differences through 6 hours.
  • Statistically significant reductions in temperature at each time point from 30 minutes through 5.5 hours with OFIRMEV compared with placebo
  • The primary endpoint, the weighted sum of temperature differences from baseline through 6 hours, was significantly in favor of OFIRMEV compared with placebo (P<0.001)

Adverse events reported in this study

No clinically relevant differences were observed in frequency of overall or severe treatment-emergent adverse events reported in this study.

Safety Considerations

  • The antipyretic effects of OFIRMEV may mask fever
  • 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. Discontinue OFIRMEV immediately at the first sign of skin rash
Back to top ^

SUPPORTING DATA FROM AN ACUTE RENAL COLIC STUDYBektas et al1

STUDY DESIGN: The primary endpoint of this study was change in pain intensity from baseline visual analog scale (VAS) score at 15 and 30 minutes. This was a 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 at 0.1 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 30 minutes. Results for the IV acetaminophen 1 g and placebo groups are shown below.

At least 1 adverse event was experienced by 11 (24%) receiving IV acetaminophen, 16 (33%) receiving morphine, and 8 (16%) receiving placebo (P=0.14). The most common adverse events reported in this study were nausea and vomiting, dry mouth, and nonspecific symptoms.

Rapid reduction in pain intensity

Fast, reliable pain relief in 15 minutes

Median pain intensity scores, single dose

Median pain intensity scores, single dose VAS, visual analog scale.
  • Significant mean differences in pain intensity reductions were observed for both IV acetaminophen (P=0.005) and IV morphine (P=0.045) when compared with placebo
  • IV acetaminophen and morphine demonstrated similar reductions in VAS scores (P=0.74)
  • This study was not designed as a head-to-head, noninferiority trial comparing the efficacy of IV acetaminophen to morphine

Adverse events reported in this study

At least 1 adverse event was experienced by 11 (24%) receiving IV acetaminophen, 16 (33%) receiving morphine, and 8 (16%) receiving placebo (P=0.14). The most common adverse events reported in this study were nausea and vomiting, dry mouth, and nonspecific symptoms.

Safety Considerations

  • Take care when prescribing, preparing, and administering OFIRMEV Injection to avoid dosing errors, which could result in accidental overdose and death
Back to top ^

SUPPORTING DATA FROM AN ABDOMINAL LAPAROSCOPIC HYSTERECTOMY STUDYArici et al3

STUDY DESIGN: This was a randomized, placebo-controlled, parallel-group study. Patients scheduled for total hysterectomy by laparotomy received IV acetaminophen 1 g 30 minutes prior to induction (pre-op), IV acetaminophen 1 g prior to skin closure (intra-op), or placebo. Patient-controlled analgesia (PCA) morphine was available to all patients. Pain intensity, based on visual analog scale score at rest and with movement, sedation, and total morphine consumption were measured at 15 and 30 minutes and 1, 2, 4, 8, 12, and 24 hours.

The most common adverse events reported in this study were nausea, vomiting, and itching and were significantly more frequent in the placebo group than in either IV acetaminophen group (P<0.05). Of the 90 patients involved in the study, 2 patients in the pre-op IV acetaminophen group and 3 patients each in the intra-op IV acetaminophen and placebo groups were excluded.

Impact of IV acetaminophen on opioid consumption

Mean morphine consumption over 24 hours

Mean morphine consumption over 24 hours
  • Total morphine consumption was significantly lower in each IV acetaminophen group compared with the placebo group (P<0.05)
  • Additionally, administering IV acetaminophen 1 g pre-op demonstrated a significantly greater reduction in morphine consumption compared with administering the same dose intra-op (P<0.05)
  • The clinical benefit of reduced opioid consumption was not evaluated or demonstrated

Impact of IV acetaminophen on pain intensity

Pain intensity scores

Pain intensity scores VAS, visual analog scale. aP<0.05 compared with each IV acetaminophen group.
  • Pre-op and intra-op administration of IV acetaminophen produced statistically significant reductions in pain intensity at all time points compared with placebo (P<0.05)

Adverse events reported in this study

The most common adverse events reported in this study were nausea, vomiting, and itching and were significantly more frequent in the placebo group than in either IV acetaminophen group (P<0.05). Of the 90 patients involved in the study, 2 patients in the pre-op IV acetaminophen group and 3 patients each in the intra-op IV acetaminophen and placebo groups were excluded.

Safety Considerations

  • 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. Discontinue OFIRMEV immediately upon occurrence of signs or symptoms associated with allergy or hypersensitivity. Do not use OFIRMEV in patients with acetaminophen allergy
  • Acetaminophen is contraindicated in patients with
    • known hypersensitivity to acetaminophen or to any of the excipients in the intravenous formulation
    • severe hepatic impairment or severe active liver disease
Back to top ^
Scroll down for additional important safety information

Indications and Usage

OFIRMEV® (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, and the reduction of fever in adult and pediatric patients.

Important Safety Information

WARNING: RISK OF MEDICATION ERRORS AND HEPATOTOXICITY

Take care when prescribing, preparing, and administering OFIRMEV® (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.

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 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, or severe renal impairment (creatinine clearance ≤ 30 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. Discontinue OFIRMEV immediately at the first sign of skin rash.
  • Take care when prescribing, preparing, and administering OFIRMEV Injection to avoid dosing errors, which could result in accidental overdose and death.
  • 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. Discontinue OFIRMEV immediately upon occurrence of signs or symptoms associated with allergy or hypersensitivity. Do not use OFIRMEV in patients with acetaminophen allergy.
  • The antipyretic effects of OFIRMEV may mask fever.

Adverse Reactions

  • Serious adverse reactions may include hepatic injury, serious skin reactions, allergy, and hypersensitivity.
  • The most common adverse reactions in patients treated with OFIRMEV were nausea, vomiting, headache, and insomnia in adult patients and nausea, vomiting, constipation, and pruritus in pediatric patients.

To report SUSPECTED ADVERSE REACTIONS, contact Mallinckrodt Hospital Products, Inc. at 1-800-778-7898 or the FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

Please see additional Important Safety Information, including Boxed Warning, in the Full Prescribing Information.