RxPRODUCT NEWS: PROFILE: Combunox (oxycodone 5 mg and ibuprofen 400 mg)

APRIL 01, 2005
Monica Holmberg, PharmD

Each year, nearly 25 million Americans seek medical treatment for acute pain following medical or dental surgery or injury subsequent to accidents, sports, or overexertion. Untreated pain has been linked to longer hospital stays, higher rehospitalization rates, and more outpatient visits. It also can cause anxiety, but it tends to respond to analgesics better than chronic pain does. With pain that is probably the result of multiple mechanisms, combining analgesics with different mechanisms of action (sometimes called "cross-firing") often is recommended and is in fact necessary for optimal relief.1

Combunox (oxycodone 5 mg and ibuprofen 400 mg), the first fixed-dose nonsteroidal anti-inflammatory drug (NSAID) and opioid in tablet formulation, has been approved by the FDA for short-term treatment of moderate-tosevere pain. Whereas the active agents in Combunox have been used independently, Forest Pharmaceuticals is promoting Combunox as offering a new option for physicians treating short-term postsurgical or postinjury pain. Combunox became available in pharmacies in March 2005.2


Oxycodone is an opioid analgesic; it produces analgesia by binding to opiate receptors in the central nervous system (CNS). As with other opiate medications, oxycodone may produce respiratory depression and sedation.3 Oxycodone is 1.5 times stronger than hydrocodone and almost 10 times stronger than codeine.2

The exact mechanism of action of ibuprofen is not known. Like other NSAIDs, however, ibuprofen inhibits cyclooxygenase-1 and cyclooxygenase- 2 activity and prostaglandin synthesis without exerting an effect on the opiate receptors, thus inhibiting both inflammation and pain.3

Clinical Studies

Combunox was evaluated in 3 double- blind, placebo-controlled clinical studies. Two of the studies, involving a total of 949 patients, examined patients after dental surgery. The remaining study examined 456 patients after abdominal or pelvic surgery. Each study compared Combunox as a single dose with ibuprofen alone, oxycodone alone, or placebo. In each study, Combunox was shown to be more effective than ibuprofen, oxycodone, or placebo alone. The measurement of pain relief was based on the magnitude of pain and the reduction in pain intensity.3


Combunox is dosed as 1 tablet as needed for pain, with a daily maximum of 4 tablets. Multiple doses of Combunox have not yet been studied. The maximum length of treatment is 1 week. Combunox has not yet been studied in patients under 14 years old.3

Warnings and Contraindications

Patients with a history of ibuprofen or oxycodone allergy should not receive Combunox. Additionally, patients with respiratory depression, hypercarbia, severe bronchial asthma, or paralytic ileus should not take Combunox. Caution should be used in patients with a history of allergic reaction to other opiate medications.

Potential drug interactions may occur with anticholinergic medications, CNS depressants, mixed agonist/antagonist opioid analgesics, monoamine oxidase inhibitors, neuromuscular blocking agents, other NSAIDs, diuretics, lithium, methotrexate, and warfarin.3

Combunox is in Pregnancy Category C and should be avoided altogether in the third trimester because ibuprofen has the potential to inhibit labor via the inhibition of prostaglandin synthesis. Additionally, oxycodone use immediately prior to delivery may result in respiratory depression in the infant.3

Adverse Effects

In clinical studies, the most commonly reported adverse effects were nausea (8.8%), vomiting (5.3%), flatulence (1.0%), somnolence (7.3%), dizziness (5.1%), and sweating (1.6%).

Drug Abuse

Combunox is a Schedule II medication, and health care providers should be aware of its potential for abuse or diversion. Appropriate vigilance should be exercised.

Patient Counseling

When dispensing Combunox or any combination product that contains an OTC analgesic, the pharmacist should take a few moments to remind patients that they should not take any other OTC analgesics without consulting their prescribers. The pharmacist should mention that Combunox contains ibuprofen, and list several brands of OTC ibuprofen. Should a prescriber instruct patients to treat breakthrough pain with additional ibuprofen, the pharmacist should keep in mind that the absolute maximum recommended daily dose of ibuprofen is 3.2 g in healthy adults.

Dr. Holmberg is a pharmacist at Phoenix Children's Hospital, Phoenix, Ariz.

For a list of references, send a stamped, self-addressed envelope to: References Department, Attn. A. Stahl, Pharmacy Times, 241 Forsgate Drive, Jamesburg, NJ 08831; or send an e-mail request to: astahl@ascendmedia.com.

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