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

Each year, nearly 25 million Americansseek medical treatment foracute pain following medical ordental surgery or injury subsequent toaccidents, sports, or overexertion.Untreated pain has been linked tolonger hospital stays, higher rehospitalizationrates, and more outpatientvisits. It also can cause anxiety, but ittends to respond to analgesics betterthan chronic pain does. With pain thatis probably the result of multiple mechanisms,combining analgesics with differentmechanisms of action (sometimescalled "cross-firing") often isrecommended and is in fact necessaryfor optimal relief.¹

Combunox (oxycodone 5 mg andibuprofen 400 mg), the first fixed-dosenonsteroidal anti-inflammatory drug(NSAID) and opioid in tablet formulation,has been approved by the FDA forshort-term treatment of moderate-toseverepain. Whereas the active agentsin Combunox have been used independently,Forest Pharmaceuticals ispromoting Combunox as offering anew option for physicians treatingshort-term postsurgical or postinjurypain. Combunox became available inpharmacies in March 2005.²

Pharmacology

Oxycodone is an opioid analgesic; itproduces analgesia by binding to opiatereceptors in the central nervoussystem (CNS). As with other opiatemedications, oxycodone may producerespiratory depression and sedation.³Oxycodone is 1.5 times stronger thanhydrocodone and almost 10 timesstronger than codeine.²

The exact mechanism of action ofibuprofen is not known. Like otherNSAIDs, however, ibuprofen inhibitscyclooxygenase-1 and cyclooxygenase-2 activity and prostaglandin synthesiswithout exerting an effect onthe opiate receptors, thus inhibitingboth inflammation and pain.³

Clinical Studies

Combunox was evaluated in 3 double-blind, placebo-controlled clinicalstudies. Two of the studies, involving atotal of 949 patients, examined patientsafter dental surgery. The remainingstudy examined 456 patients afterabdominal or pelvic surgery. Each studycompared Combunox as a single dosewith ibuprofen alone, oxycodone alone,or placebo. In each study, Combunoxwas shown to be more effective thanibuprofen, oxycodone, or placeboalone. The measurement of pain reliefwas based on the magnitude of painand the reduction in pain intensity.³

Dosing

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

Warnings and Contraindications

Patients with a history of ibuprofenor oxycodone allergy should notreceive Combunox. Additionally,patients with respiratory depression,hypercarbia, severe bronchial asthma,or paralytic ileus should not take Combunox.Caution should be used inpatients with a history of allergic reactionto other opiate medications.

Potential drug interactions may occurwith anticholinergic medications, CNSdepressants, mixed agonist/antagonistopioid analgesics, monoamine oxidaseinhibitors, neuromuscular blockingagents, other NSAIDs, diuretics, lithium,methotrexate, and warfarin.³

Combunox is in Pregnancy CategoryC and should be avoided altogether inthe third trimester because ibuprofenhas the potential to inhibit labor via theinhibition of prostaglandin synthesis.Additionally, oxycodone use immediatelyprior to delivery may result in respiratorydepression in the infant.³

Adverse Effects

In clinical studies, the most commonlyreported adverse effects werenausea (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 shouldbe aware of its potential for abuse ordiversion. Appropriate vigilance shouldbe exercised.

Patient Counseling

When dispensing Combunox or anycombination product that contains anOTC analgesic, the pharmacist shouldtake a few moments to remind patientsthat they should not take any otherOTC analgesics without consultingtheir prescribers. The pharmacistshould mention that Combunox containsibuprofen, and list several brandsof OTC ibuprofen. Should a prescriberinstruct patients to treat breakthroughpain with additional ibuprofen, thepharmacist should keep in mind thatthe absolute maximum recommendeddaily dose of ibuprofen is 3.2 g inhealthy adults.

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

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