The combination of ibuprofen and acetaminophen works better than the combination of an opioid drug and acetaminophen for the relief of pain from dental operations, according to results from a new analysis of published data. The analysis also showed that the ibuprofen and acetaminophen combination was safer than combinations that include opioids.

Most dentists and oral surgeons frequently prescribe a combination of hydrocodone and acetaminophen for severe postoperative pain, first author Paul A. Moore, DMD, PhD, MPH, told Medscape Medical News. However, this combination, marketed as Vicodin (Abbott Laboratories) among other brand names, poses a risk for abuse and adverse reactions. "This [analysis] gives them an alternative," said Dr. Moore, chair of dental anesthesiology at the University of Pittsburgh in Pennsylvania.

Dr. Moore and Elliot V. Hersh, DMD, PhD, a professor of pharmacology at the University of Pennsylvania in Philadelphia, published their findings in the August issue of the Journal of the American Dental Association.

Previous research has shown that combining analgesics that work differently provides more pain relief than a single analgesic can provide on its own.

Nonsteroidal anti-inflammatory drugs (NSAIDs), such as ibuprofen, work by blocking the synthesis of prostaglandins, suppressing both inflammation and pain, the researchers note. In contrast, acetaminophen does not suppress inflammation and appears to suppress pain through multiple other mechanisms. Increasing doses of these drugs can increase their effectiveness only up to a point, and high doses can be toxic, but the 2 together can suppress pain better than either alone, the authors write.

In addition to ibuprofen, other NSAIDs also appear to work well with acetaminophen, said Dr. Moore, but ibuprofen is commonly used in the United States, and recent clinical trials have lent support to its use. Therefore, Dr. Moore and Dr. Hersh searched for systemic reviews of clinical trials of the combination of ibuprofen and acetaminophen.

They found consistent evidence for the effectiveness of the combination. As a measurement for comparing the various treatments, they used number needed to treat (NNT), defined as "the number of patients needed to be treated to obtain one additional patient achieving at least 50 percent maximum pain relief over four to six hours compared with placebo." The lower the NNT, the more potent the pain relief.

Zeroing in on studies for controlling the pain of third molar extractions, they found that 200 mg ibuprofen combined with 500 mg acetaminophen had the lowest NNT of the treatments tested in the studies they analyzed. The NNT for this combination was of 1.6 (95% confidence interval [CI], 1.4 - 1.8) compared with a 2.2 NNT (95% CI, 1.8 - 2.9) for 60 mg codeine with 1000 mg acetaminophen.

The authors also found a 2.3 NNT (95% CI, 2.0 - 6.4) for 10 mg oxycodone with 650 mg acetaminophen. For 200 mg ibuprofen alone, they found an NNT of 2.7 (95% CI, 2.5 - 3.0), and for 1000 mg acetaminophen alone, they found an NNT of 3.2 (95% CI, 2.9 - 3.6).

In addition, they cited a study by Daniels et al comparing various combinations of ibuprofen, codeine, and acetaminophen for treating the pain of third molar extraction. Not only did the patients receiving the ibuprofen/acetaminophen combination experience less pain than those receiving codeine and acetaminophen but they also had fewer adverse reactions such as nausea, vomiting, headache, and dizziness.

Among patients who took 200 mg ibuprofen with 500 mg acetaminophen, 18.5% had treatment-emergent adverse reactions compared with 24.9% of those who took 400 mg ibuprofen with 1000 mg acetaminophen and 34.9% of those who took a combination of ibuprofen and codeine.

An additional advantage of choosing ibuprofen and acetaminophen over opioid drugs is that opioid drugs are often abused, Dr. Moore said. Teenagers frequently steal opioids from the medicine cabinets of their friends and family, he said.

Stepwise Treatment Guideline

On the basis of their analysis, the researchers devised stepwise guidelines for treating postoperative pain in dentistry based on the pain the clinician estimates their patients will feel once local anesthesia wears off.

For mild pain, the guidelines call for clinicians to prescribe 200 to 400 mg ibuprofen to be taken every 4 to 6 hours as needed. For mild to moderate pain, the guidelines call for 400 to 600 mg ibuprofen every 6 hours for 24 hours, followed by 400 mg ibuprofen every 4 to 6 hours as needed. For moderate to severe pain, the guidelines call for 400 to 600 mg ibuprofen with 500 mg acetaminophen every 6 hours for 24 hours, and then 400 mg ibuprofen with 500 mg acetaminophen every 6 hours as needed. Finally, for severe pain, the guidelines call for 400 to 600 mg ibuprofen with 650 mg acetaminophen and 10 mg hydrocodone every 6 hours for 24 to 48 hours, followed by 400 to 600 mg ibuprofen with 500 mg acetaminophen every 6 hours as needed.

It is important to avoid daily doses of more than 3000 mg acetaminophen or 2400 mg ibuprofen, the guidelines state. Therefore, clinicians should be aware of what other medications patients might be using that contain these drugs and should warn patients about the maximum safe daily dose.

In addition, NSAIDS may work best when administered preemptively. The guidelines add that a perioperative corticosteroid such as dexamethasone may limit swelling and decrease postoperative discomfort after third molar extractions.

Many oral surgeons are already taking a similar approach, J. David Johnson, Jr, DDS, an associate professor of oral and maxillofacial surgery at the University of Tennessee in Memphis and a spokesperson for the American Dental Association, told Medscape Medical News.

The work of Don Melisch, DDS, MD, from Palm Desert, California, highlighted the effectiveness of ibuprofen and acetaminophen combinations many years ago, said Dr. Johnson, who was not involved in the current study.

"For oral and maxillofacial surgeons, this article will come as no surprise," he said. However, he praised the stepwise guidelines.

Dr. Johnson said he typically writes patients prescriptions for both prescription-strength ibuprofen and hydrocodone with acetaminophen, advising them to use the second prescription only if the first one fails to control their pain.

Dr. Moore and Dr. Johnson have disclosed no relevant financial interests.

JADA. 2013;144(8):898-908. Abstract