Offers health care providers a new multimodal approach to adult pain management COMBOGESIC® IV is an intravenous, opioid-free pain relief medicine that is a combination of 1,000 mg of acetaminophen and 300 mg of ibuprofen, a nonsteroidal anti-inflammatory drug (NSAID). It was approved by the US FDA in October 2023 for use in adults where an intravenous route of administration is considered clinically necessary for: (i) the relief of mild to moderate pain; and (ii) the management of moderate to severe pain as an adjunct to opioid analgesics.1 The American Society of Anesthesiology's (ASA) evidence-based recommendations emphasize the importance of a multimodal approach to pain management using multiple interventions with different mechanisms of action that may offer additive or synergistic effects to optimize pain relief.2 COMBOGESIC® IV offers health care providers a new, non-opioid approach to pain management by combining active drug substances with different mechanisms of action in a single formulation, providing: Shorter onset to analgesia3
Superior analgesia efficacy and comparable safety in common adverse events3
Sustained pain-management results3
"The approval of COMBOGESIC® IV is an important step in providing hospitals and health care providers in the US with an alternative treatment option for managing patients' pain," said Dr. Bill Larkins, President of Injectables, Hikma. "This is another example of how we continue to expand our portfolio of critical medicines and we are pleased to make this important new treatment option available for patients, helping to put better health within reach, every day." In 2021, Hikma signed an exclusive license and distribution agreement with AFT Pharmaceuticals (AFT) for the commercialization of COMBOGESIC® IV in the US. Under the trade name of MAXIGESIC® IV outside of the United States, COMBOGESIC® IV is licensed in over 100 countries and marketed in over 20 countries. COMBOGESIC® IV is the only IV analgesic therapy formulated with 1,000 mg of acetaminophen and 300 mg of ibuprofen, utilizing the synergistic effect of both medicines for optimal pain relief.1 It offers health care providers a new approach to multimodal analgesia by combining active drug substances with different mechanisms of action that harness additive or synergistic effects to provide more effective pain relief compared with individual components used as single-modality interventions.1-3 COMBOGESIC® IV is supplied as a readily available solution with no mixing required for administration.1 It is administered as a 15-minute IV infusion, every 6 hours as needed, not to exceed the maximum total daily dose of 4,000 mg acetaminophen and 1,200 mg of ibuprofen in 24 hours.1 (LSE: HIK) (NASDAQ Dubai: HIK) (OTC: HKMPY) (rated BBB-/stable S&P and BBB-/positive Fitch)
Hikma helps put better health within reach every day for millions of people around the world. For more than 40 years, we've been creating high-quality medicines and making them accessible to the people who need them. Headquartered in the UK, we are a global company with a local presence across the North America, the Middle East and North Africa (MENA) and Europe, and we use our unique insight and expertise to transform cutting-edge science into innovative solutions that transform people's lives. We're committed to our customers, and the people they care for, and by thinking creatively and acting practically, we provide them with a broad range of branded and non-branded generic medicines. Together, our 8,800 colleagues are helping to shape a healthier world that enriches all our communities. We are a leading licensing partner, and through our venture capital arm, are helping bring innovative health technologies to people around the world. For more information, please visit: www.hikma.com
This product has been approved for marketing in the United States by the US FDA. This product approval does not confer the right on Hikma, or any other party, to market this product outside the United States. IMPORTANT SAFETY INFORMATION
The treatment of peri-operative pain in the setting of coronary artery bypass graft (CABG) surgery. Risk of Medication Errors. Take care when prescribing, preparing, and administering COMBOGESIC® IV in order to avoid dosing errors which could result in accidental overdose and death. In particular, be careful to ensure that the dose in milligrams (mg) and milliliters (mL) is not confused, the dosing is based on weight for patients under 50 kg, infusion pumps are properly programmed, and the total daily dose of acetaminophen from all sources does not exceed maximum daily limits. (ii) COMBOGESIC® IV contains ibuprofen. Elevations of ALT or AST (three or more times the upper limit of normal [ULN]) have been reported in approximately 1% of NSAID-treated patients in clinical trials. In addition, rare, sometimes fatal, cases of severe hepatic injury, including fulminant hepatitis, liver necrosis, and hepatic failure have been reported. Elevations of ALT or AST (less than three times ULN) may occur in up to 15% of patients treated with NSAIDs. Cardiovascular Thrombotic Events. Trials suggest that NSAIDs, taken for up to 3 years, elevate the risk of serious cardiovascular events like myocardial infarction and stroke. To minimize these risks, the lowest effective dose for the shortest duration possible should be used in these patients. Gastrointestinal Bleeding, Ulceration, and Perforation. NSAIDs cause serious gastrointestinal (GI) adverse events including inflammation, bleeding, ulceration, and perforation of the esophagus, stomach, small or large intestine, which can be fatal. These adverse events can occur at any time, with or without warning symptoms. Avoid use in patients at higher risk. In concomitant use with low-dose aspirin for cardiac prophylaxis, monitor patients more closely for evidence of GI bleeding. Heart Failure and Edema. Studies have demonstrated an increase in hospitalizations for heart failure in NSAID-treated patients compared to placebo-treated patients. Additionally, in a study of patients with heart failure, NSAID use increased the risk of MI, hospitalization for heart failure, and death. Additionally, fluid retention and edema have been observed in some patients treated with NSAIDs. Use of ibuprofen may blunt the CV effects of several therapeutic agents used to treat these medical conditions. Fetal Toxicity: Premature Closure of Fetal Ductus Arteriosus. Avoid use of COMBOGESIC® IV in pregnant women at about 30 weeks gestation and later. COMBOGESIC® IV increases the risk of premature closure of the fetal ductus arteriosus at approximately this gestational age. Hematologic Toxicity. Anemia has occurred in NSAID-treated patients. This may be due to occult or gross GI blood loss, fluid retention, or an incompletely described effect on erythropoiesis. NSAIDs included in COMBOGESIC® IV may increase the risk of bleeding events. Ophthalmological Effects. If a patient develops ophthalmological complaints while receiving COMBOGESIC® IV, the drug should be discontinued, and the patient should have an ophthalmologic examination. Increased Risk of Hepatotoxicity with Concomitant Use of Other Acetaminophen-containing Products. COMBOGESIC® IV should not be used concomitantly with other acetaminophen containing products. Use with Alcohol. COMBOGESIC® IV should not be used concomitantly with alcoholic beverages. Laboratory Monitoring. Consider monitoring patients on NSAID treatment with a CBC and a chemistry profile as clinically indicated.
A number of known or potential interactions between COMBOGESIC® IV and other drugs/drug classes exist. Please refer to the Drug Interactions in the Prescribing Information for further information. Drugs That Interfere with Hemostasis. 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. Concomitant use of drugs that interfere with serotonin reuptake and an NSAID may potentiate the risk of bleeding more than an NSAID alone. Aspirin. There is no consistent evidence that concurrent use of aspirin mitigates the increased risk of serious CV thrombotic events associated with NSAID use. The concurrent use of aspirin and an NSAID increases the risk of serious gastrointestinal (GI) events. ACE Inhibitors, Angiotensin Receptor Blockers, and Beta-Blockers. NSAIDs may diminish the antihypertensive effect of ACE inhibitors, ARBs, or Beta-Blockers. Diuretics. NSAIDs can reduce the natriuretic effect of loop diuretics and thiazides in some patients.
Lithium. NSAIDs produced an elevation of plasma lithium levels and a reduction in renal lithium clearance. Monitor patients for signs of lithium toxicity.
USE IN SPECIFIC POPULATIONS
Females and Males of Reproductive Potential. Use of acetaminophen may cause reduced fertility in males and females of reproductive potential. It is not known whether these effects on fertility are reversible. The use of NSAIDs may delay or prevent rupture of ovarian follicles. Consider withdrawal of NSAID-containing products in women who have difficulties conceiving or who are undergoing investigation of infertility. Geriatric Use. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function. Elderly patients (65 years and older) are at greater risk for NSAID-associated serious cardiovascular, gastrointestinal, and/or renal adverse reactions. If the anticipated benefit for the elderly patient outweighs these potential risks, start dosing at the low end of the dosing range, and monitor patients for adverse effects.
Hepatic Impairment. Use of COMBOGESIC® IV in patients with hepatic impairment is not recommended. COMBOGESIC® IV is indicated in adults (over age 18) where an intravenous route of administration is considered clinically necessary for: The relief of mild to moderate pain. The management of moderate to severe pain as an adjunct to opioid analgesics. COMBOGESIC® IV is indicated for short-term use of five days or less. Patient counseling information should be shared with the patient prior to administration. For additional information, please refer to the Package Insert for full Prescribing Information, available on www.hikma.com.
To report an adverse event or product complaint, please contact us at [email protected] or call 1-877-845-0689 or 1-800-962-8364. Adverse events may also be reported to the FDA directly at 1-800-FDA-1088 or www.fda.gov/medwatch.
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Document identification number: HK-2471-v3
2 Chou R, Gordon DB, de Leon-Casasola OA, et al. Management of post operative pain: a clinical practice guideline from the American pain society, the American society of regional anesthesia and pain medicine, and the American society of anesthesiologists' committee on regional anesthesia, executive committee, and administrative council. J Pain. 2016;17:131-157. 3 Daniels SE, Playne R, Stanescu I, Zhang J, Gottlieb IJ, Atkinson HC. Efficacy and safety of an intravenous acetaminophen/ibuprofen fixed-dose combination after bunionectomy: A randomized, double-blind, factorial, placebo-controlled trial. Clinical Therapeutics. 2019;41(10).