Acetaminophen and Ibuprofen

COMBOGESIC is indicated in adults for the short-term management of mild to moderate acute pain. COMBOGESIC is a combination of acetaminophen and ibuprofen, a non-steroidal anti-inflammatory drug (NSAID), and is indicated in adults for the short term management of mild to moderate acute pain.

Analgesia COMBOGESIC contains acetaminophen and ibuprofen. Acetaminophen is a non-opiate, non-salicylate analgesic. The precise mechanism of the analgesic properties of acetaminophen is not established but is thought to primarily involve central actions. Ibuprofen is a nonsteroidal anti-inflammatory drug (NSAID). Its mechanism of action for analgesia, like that of other NSAIDs, is not completely understood, but involves inhibition of cyclooxygenase (COX-1 and COX-2). Ibuprofen is a potent inhibitor of prostaglandin synthesis in vitro. Prostaglandins sensitize afferent nerves and potentiate the action of bradykinin in inducing pain in animal models. Prostaglandins are mediators of inflammation. Because ibuprofen is an inhibitor of prostaglandin synthesis, its mode of action may be due to a decrease of prostaglandins in peripheral tissues.

Use the lowest effective dosage for the shortest duration consistent with individual patient treatment goals. Do not exceed the recommended dose of COMBOGESIC in 24 hours. Do not co-administer COMBOGESIC with other acetaminophen- or NSAID-containing products. The recommended dose of COMBOGESIC is 3 tablets every 6 hours as needed for pain relief, up to a maximum of 12 tablets per day. Use the lowest effective dosage for shortest duration consistent with individual patient treatment goals. Do not administer with other acetaminophen-containing products. Three tablets every 6 hours as needed for pain relief, up to a maximum of 12 tablets per day.

COMBOGESIC is contraindicated in: patients with a known hypersensitivity (e.g., anaphylactic reactions, serious skin reactions) to acetaminophen, ibuprofen, other NSAIDs, or to any of the excipients in this product. patients with a history of asthma, urticaria, or other allergic-type reactions after taking aspirin or other NSAIDS. the setting of coronary artery bypass graft (CABG) surgery. COMBOGESIC is contraindicated in: patients with known hypersensitivity to acetaminophen, ibuprofen, other NSAIDs, or to any of the excipients in this product. patients with a history of asthma, urticaria, or other allergic-type reactions after taking aspirin or other NSAIDs.

Boxed warning: contains acetaminophen, which 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 doses of acetaminophen that exceed 4,000 milligrams per day, and often involve more than one acetaminophen containing product. Hypertension: Patients taking some antihypertensive medications may have impaired response to these therapies when taking NSAIDs. Monitor blood pressure. Heart Failure and Edema: Avoid use of COMBOGESIC in patients with severe heart failure unless benefits are expected to outweigh risk of worsening heart failure. Renal Toxicity: Long-term administration of NSAIDs, including the ibuprofen component of COMBOGESIC, has resulted in renal papillary necrosis and other renal injury. Anaphylactic Reactions: Seek emergency help if an anaphylactic reaction occurs.

The following clinically significant adverse reactions to ibuprofen or acetaminophen are described elsewhere in other sections of the labelling. Hepatotoxicity Cardiovascular Thrombotic Events Gastrointestinal Bleeding, Ulceration, and Perforation Hypertension Heart Failure and Edema Renal Toxicity and Hyperkalemia Anaphylaxis and Other Hypersensitivity Reactions Serious Skin Reactions Hematologic Toxicity The most common adverse reactions (incidence of ≥ 2% for patients receiving COMBOGESIC) are: nausea, vomiting, headache, dizziness, somnolence, post-procedural hemorrhage, and swelling of the face (Table 1). The most common adverse reactions (greater than or equal to 2%) are nausea, vomiting, headache, dizziness, somnolence, post-procedural hemorrhage, and swelling of the face.

Table 2: Clinically Significant Drug Interactions with COMBOGESIC Drugs That Interfere with Hemostasis Clinical Impact: Ibuprofen and anticoagulants such as warfarin have a synergistic effect on bleeding. The concomitant use of ibuprofen and anticoagulants have an increased risk of serious bleeding compared to the use of either drug alone. Serotonin release by platelets plays an important role in hemostasis. Case-control and cohort epidemiological studies showed that concomitant use of drugs that interfere with serotonin reuptake and an NSAID may potentiate the risk of bleeding more than an NSAID alone. Intervention: Monitor patients with concomitant use of COMBOGESIC with anticoagulants (e.g., warfarin), antiplatelet agents (e.g., aspirin), selective serotonin reuptake inhibitors (SSRIs), and serotonin norepinephrine reuptake inhibitors (SNRIs) for signs of bleeding.

Store at 20°C to 25°C (68°F to 77°F) with excursions permitted within USP controlled room temperature of 15°C to 30°C (59°F to 86°F). Protect from moisture and light.