/publications/health-system-edition/2012/Jan-2012/-IV-Acetaminophen-Ofirmev-

IV Acetaminophen (Ofirmev)

Author: Ashley N. Lewis PharmD, BCPS

Background

Intravenous (IV) acetaminophen (Ofirmev), manufactured by Cadence Pharmaceuticals, is FDA approved for use in management of mild-to-moderate pain, moderate-to-severe pain with adjunctive opioid analgesics, and reduction of fever in patients 2 years and older.1,2 Acetaminophen is one of the most widely used, well-known analgesic agents available in a wide variety of dosage forms, including the IV formulation which was approved for use in the United States in November 2010.

With so many formulations available, the place in therapy for Ofirmev is often unclear. However, IV administration of analgesics is often preferred immediately postoperatively when a faster onset of pain relief is desired, or when oral or rectal routes of administration are not options. This, as well as shortterm, postoperative opioid augmentation, may be 2 practice areas where IV acetaminophen can play a role.

Pharmacokinetics

The mechanism by which Ofirmev exerts its antipyretic and analgesic effects is not precisely known; however, it is thought to be centrally mediated. The onset of action of Ofirmev occurs at approximately 15 minutes for analgesia and within 30 minutes for antipyresis. The peak analgesic effect is reached at approximately 1 hour.1,3,4 The duration of action of Ofirmev for analgesia is 4 to 6 hours, and 6 or more hours for antipyresis. The maximum blood concentration (Cmax) of Ofirmev is higher than with oral or rectal administration; however, it is important to note that the Cmax with Ofirmev (29 mcg/mL) remains far below the 150 mcg/ mL concentration considered potentially hepatotoxic.

Despite the difference in Cmax, overall volume of distribution and area under the curve (AUC) values remain similar for all acetaminophen formulations. Due to the avoidance of first-pass metabolism, Ofirmev exposes the liver to approximately 50% less acetaminophen compared with equivalent doses of oral acetaminophen.3,5 This lack of first-pass metabolism and resultant decrease in liver exposure likely play a role in the low incidence of hepatic damage reported with Ofirmev thus far.3,5

Dosing

The dose of Ofirmev is similar to acetaminophen formulations in both children (≥2 years) and adults. Each dose of Ofirmev should be infused over 15 minutes.1-4

Clinical Efficacy

Macario and colleagues published a metaanalysis reviewing randomized clinical trials of IV acetaminophen for acute postoperative pain. A total of 22 studies were included, 8 of which compared IV acetaminophen with an active comparator, and 14 of which compared IV acetaminophen with placebo. In 7 of the 8 active comparator studies, IV acetaminophen was reported to have analgesic outcomes similar to the active comparator, and 12 of the 14 placebo-controlled trials showed an improvement in analgesia with the use of the IV acetaminophen.6 Additionally, 10 of the 14 studies reported less opioid consumption, and a lower percentage of patients requiring rescue medications. The authors concluded that these data indicate that IV acetaminophen is effective as an analgesic agent across a range of surgical procedures.6

Medication Safety

Administering IV acetaminophen in higher- than-recommended doses may result in hepatic injury. In adults, adverse events reported in clinical trials with an incidence of at least 5% were headache, insomnia, nausea, and vomiting. In the pediatric population, the most common adverse effects (incidence of at least 5%) were agitation, atelectasis, constipation, pruritus, vomiting, and nausea. As Ofirmev is metabolized primarily by the liver, including CYP2E1, substances that alter the metabolism of acetaminophen can potentially result in hepatotoxicity. Drug/substance interactions of note with IV acetaminophen include warfarin (Coumadin), alcohol, barbiturates, carbamazepine (Tegretol), phenytoin (Dilantin), and known CYP2E1 inducers/inhibitors. Patients in the hospital can oftentimes be receiving several different sources of acetaminophen (eg, combination pain products, oral, rectal, PRN for pain/fever); therefore, it is very important that all sources are taken into consideration so as to not exceed the maximum amount of acetaminophen recommended per day.1-4

Availability and Cost Considerations

Ofirmev is supplied in a 100-mL glass vial containing 1 g of acetaminophen (10 mg/ mL), and should be administered without further dilution. Ofirmev should be stored at room temperature and each vial is intended for single use only. Once opened, the product should be used within 6 hours, after which time it should be discarded. For doses less than 1 g, the appropriate dose must be withdrawn from the vial and placed into a separate container prior to administration. Compatibility of Ofirmev with other medications has not been studied and therefore it should not be infused with any other medications.1,2 The average wholesale price of Ofirmev is $13 per 1-g vial, which is significantly more expensive than a dose of oral or rectal acetaminophen.

McNeil Consumer Healthcare announced that the maximum daily dose of singleingredient acetaminophen Extra Strength Tylenol OTC products were lowered from 4 g per day to 3 g per day as of fall 2011. According to Cadence Pharmaceuticals, the sole manufacturer of Ofirmev, the maximum dose of Ofirmev will remain 4 g per day for adults and children weighing at least 50 kg. More information, including complete prescribing information, is available at www.ofirmev.com. PTHS


Dr. Lewis is a drug information specialist at University of North Carolina Hospitals (UNCH). She completed her pharmacy training at Virginia Commonwealth University and went on to complete a general pharmacy practice residency followed by a drug information specialty residency at the Medical University of South Carolina. She is currently the pharmacy and therapeutics secretary at UNCH, and manages the day-to-day operations of the Drug Information Center and serves as a clinical assistant professor at the UNC Eshelman School of Pharmacy.