preloader

COMBOGESIC® IV

This site is intended for U.S. residents age 18 and over

Prescribing Information

Connect With Hikma

Order Product Today
Menu

THE COMBOGESIC® IV PAIN MODEL©

COMBOGESIC® IV (acetaminophen and ibuprofen) delivers the advantages of multimodal,
non-opioid analgesia while offering an advanced approach to adult pain management1

The clinical benefits of COMBOGESIC® IV are featured in the Pain Model©:

*A superior analgesic effect of COMBOGESIC® IV was observed during a single dosing interval (SPID6 and TOTPAR6) and at most scheduled time points.1
AE=adverse event; SPID6=Sum of Pain Intensity Differences over 6 hours; TOTPAR6=Total Pain Relief over 6 hours.

Shorter Onset to Analgesia

  • Time to meaningful pain relief and onset time to analgesia were shorter in the COMBOGESIC® IV group than in the ibuprofen IV and placebo groups1
  • Time to perceptible pain relief was shorter in the COMBOGESIC® IV group than in the acetaminophen IV and placebo groups1
  • COMBOGESIC® IV provided a more rapid, statistically significant analgesic effect compared with either individual constituent alone or placebo1

COMBOGESIC® IV is studied as a more effective pain management tool1,2

Superior Analgesia Efficacy. Comparable Safety in Common AEs

  • COMBOGESIC® IV allows for superior analgesic efficacy and comparable safety in common AEs versus ibuprofen IV or acetaminophen IV alone3‡

Primary Endpoint: Time-adjusted SPID48 With Pre-Rescue VAS Score Carried Forward Up to 2 Hours (P<0.001)

  • COMBOGESIC® IV offered the greatest reduction in pain over the 48-hour study period compared with the individual components and placebo3‡
  • MORE THAN DOUBLE pain relief than that of acetaminophen IV and ibuprofen IV alone1‡
  • The superior analgesic effect was maintained in subgroup analyses according to sex, age, race, and American Society of Anesthesiology Physical Status Classification1

Comparable Safety

  • The incidence of common AEs was largely comparable between the COMBOGESIC® IV group and the other active treatment groups1
  • There was no difference in the rate of nausea or dizziness between the COMBOGESIC® IV group and the comparators1

‡Based on time-adjusted Sum of Pain Intensity Differences over 48 hours (SPID48), calculated from Visual Analogue Scale (VAS) pain intensity scores recorded up until the time of consumption of the first dose of rescue.

Sustained Pain Management Results

  • Superior analgesic effect over a single dosing interval and multiple dosing periods1§

Secondary Endpoint: VAS Pain Intensity Scores Over the 48-Hour Treatment Period

  • COMBOGESIC® IV provided greater pain relief than all 3 comparative treatment groups at the majority of scheduled time points1§
  • More patients treated with COMBOGESIC® IV achieved at least a 50% reduction in baseline pain without rescue medication than patients receiving ibuprofen or placebo1||
  • COMBOGESIC® IV delayed the time to first request for rescue medication and reduced the usage rates and consumption of rescue medication over 24 and 48 hours1||
  • Usage rates of supplementary analgesia were lower with COMBOGESIC® IV (75%) compared to ibuprofen (92%), acetaminophen (93%), and placebo (96%) (P<0.005)1

COMBOGESIC® IV offers an advanced strategy to provide multimodal analgesia to patients when an intravenous route of administration is clinically necessary1

§According to VAS Pain Intensity, Pain Intensity Differences, and Pain Relief scores.
||Rescue medication was available on request as primary oral oxycodone 5-10 mg or secondary IV morphine sulfate 2-4 mg.

Study Design

  • COMBOGESIC® IV was studied in a Phase 3, placebo-controlled, prospective, randomized, double-blind, factorial design trial comparing the analgesic efficacy and safety of COMBOGESIC® IV (n=75/276) with acetaminophen alone (n=75/276), ibuprofen alone (n=76/276), and placebo (n=50/276) after bunionectomy surgery1
  • The primary efficacy endpoint was the time-adjusted Sum of Pain Intensity Differences over 48 hours (SPID48) and analyzed with each pre-rescue Visual Analogue Scale (VAS) carried forward up to 2 hours1
  • All study medicines were administered to patients as intravenous infusions over 15 minutes every 6 hours over a 48-hour period1

Open Access Bunionectomy Study

  • The bunionectomy study conducted with COMBOGESIC® IV is an open access document available to download

View Study

COMBOGESIC® IV is already being used in 36 countries4

ORDER PRODUCT TODAY

Ordering COMBOGESIC® IV is simple

Order Product today

Important Safety Information

WARNING: HEPATOTOXICITY, CARDIOVASCULAR RISK, and GASTROINTESTINAL RISK

  • RISK OF MEDICATION ERRORS: Take care when prescribing, preparing, and administering COMBOGESIC® IV to avoid dosing errors which could result in accidental overdose and death.
  • HEPATOTOXICITY: COMBOGESIC® IV contains acetaminophen which has been associated with cases of acute liver failure, at times resulting in liver transplant and death. Most cases of liver injury are associated with doses exceeding 4,000 mg per day and often involve more than one acetaminophen-containing product.
  • CARDIOVASCULAR RISK: COMBOGESIC® IV contains ibuprofen, a nonsteroidal anti-inflammatory drug (NSAID). NSAIDs cause an increased risk of serious cardiovascular (CV) thrombotic events, including myocardial infarction and stroke, which can be fatal. This risk may occur early in treatment and may increase with duration of use.
  • COMBOGESIC® IV is contraindicated for treatment of peri-operative pain in the setting of coronary artery bypass graft (CABG) surgery.
  • GASTROINTESTINAL RISK: NSAIDs cause an increased risk of serious gastrointestinal (GI) adverse events including bleeding, ulceration, and perforation of the stomach or intestines, which can be fatal. These events can occur at any time during use and without warning symptoms. Elderly patients are at greater risk.

CONTRAINDICATIONS

COMBOGESIC® IV is contraindicated in:

  • Patients with known hypersensitivity to acetaminophen, ibuprofen, other NSAIDs or to any components of this product.
  • Patients who have experienced asthma, urticaria, or allergic-type reactions after taking aspirin or other NSAIDs.
  • Patients with severe hepatic impairment or severe active liver disease.

WARNINGS & PRECAUTIONS

  • Hepatotoxicity. COMBOGESIC® IV contains acetaminophen and ibuprofen. Acetaminophen has been associated with cases of acute liver failure; the risk is higher in those with underlying liver disease and in those who ingest alcohol. Use in patients with hepatic impairment is not recommended. Elevations of ALT or AST have been reported in NSAID-treated patients.
  • Cardiovascular Thrombotic Events. To minimize the risks of CV events, use the lowest effective dose for the shortest duration possible.
  • Gastrointestinal Bleeding, Ulceration, and Perforation. NSAIDs may cause serious and sometimes fatal GI adverse events at any time and without warning. Avoid use in patients at higher risk. In concomitant use with low-dose aspirin, monitor patients more closely for evidence of GI bleeding.
  • Hypertension. NSAIDs can lead to onset of new hypertension or worsening of pre-existing hypertension, which may contribute to the increased incidence of CV events.
  • Heart Failure and Edema. Avoid use in patients with severe heart failure unless benefits outweigh risk.
  • Renal Toxicity and Hyperkalemia. Use in patients with renal impairment is not recommended. Long-term administration of NSAIDs has resulted in renal papillary necrosis and other renal injury. Increases in serum potassium concentration, including hyperkalemia, have been reported.
  • Hypersensitivity and Anaphylactic Reactions. Hypersensitivity and anaphylaxis associated with ibuprofen and acetaminophen have been reported, including life-threatening anaphylaxis associated with acetaminophen.
  • Exacerbation of Asthma Related to Aspirin Sensitivity. Patients with asthma may have intolerance to aspirin and other NSAIDs.
  • Serious Skin Reactions. Acetaminophen or NSAIDs may cause serious skin reactions such as exfoliative dermatitis, acute generalized exanthematous pustulosis (AGEP), Stevens-Johnson Syndrome (SJS), and toxic epidermal necrolysis (TEN), which can be fatal and may occur without warning. Discontinue the use of COMBOGESIC® IV at the first appearance of skin rash or any other sign of hypersensitivity.
  • Drug Rash with Eosinophilia and Systemic Symptoms (DRESS). DRESS that may be life-threatening or fatal has been reported in patients taking NSAIDs.
  • 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 and NSAID-treatment may increase the risk of bleeding events.
  • Ophthalmological Effects. Blurred or diminished vision, scotomata, and/or changes in color vision have been reported with oral ibuprofen.
  • Aseptic Meningitis. Aseptic meningitis with fever and coma has been observed in patients on oral ibuprofen.
  • Masking of Inflammation and Fever. Activity of COMBOGESIC® IV in reducing inflammation, and possibly fever, may diminish signs of infections.
  • Laboratory Monitoring. Monitor patients on NSAID treatment with a CBC and a chemistry profile as clinically indicated.

ADVERSE REACTIONS

The most common adverse reactions (≥ 3%) were infusion site pain, nausea, constipation, dizziness, infusion site extravasation, vomiting, headache, and somnolence.

DRUG INTERACTIONS

  • Drugs That Interfere with Hemostasis. Ibuprofen and anticoagulants have a synergistic effect on bleeding. Concomitant use increases the risk of serious bleeding. Concomitant use of drugs that interfere with serotonin reuptake and an NSAID may increase the risk of bleeding.
  • ACE Inhibitors, Angiotensin Receptor Blockers, and Beta-Blockers. NSAIDs may diminish the antihypertensive effect of ACE inhibitors, ARBs, or Beta-Blockers. In the elderly, volume depleted, or those that have renal impairment, concomitant use with ACE inhibitors or ARBs may result in deterioration of renal function, including possible acute renal failure.
  • Diuretics. NSAIDs can reduce the natriuretic effect of loop diuretics and thiazides in some patients.
  • Digoxin. Concomitant use of ibuprofen with digoxin has been reported to increase the serum concentration and prolong the half-life of digoxin.
  • Lithium. NSAIDs produced an elevation of plasma lithium levels and a reduction in renal lithium clearance.
  • Methotrexate. Concomitant use of NSAIDs and methotrexate may increase the risk for methotrexate toxicity.
  • Cyclosporine. Concomitant use of NSAIDS and cyclosporine may increase cyclosporine’s nephrotoxicity.
  • NSAIDs and Salicylates. Concomitant use with other NSAIDs or salicylates increases the risk of GI toxicity.
  • Pemetrexed. Concomitant use of NSAIDS and pemetrexed may increase the risk of pemetrexed-associated myelosuppression, renal, and GI toxicity.

INDICATIONS AND USAGE

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.

LIMITATIONS OF USE

COMBOGESIC® IV is indicated for short-term use of five days or less.

For more information, please see the full Prescribing Information , available at 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 .
References:
  1. Daniels SE, Playne R, Stanescu I, et al. 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).
  2. Daniels SE, Atkinson HC, Stanescu I, et al. Analgesic efficacy of an acetaminophen/ibuprofen fixed-dose combination in moderate to severe postoperative dental pain: a randomized, double-blind, parallel-group, placebo-controlled trial. Clinical Therapeutics. 2018;40(10).
  3. COMBOGESIC® IV (acetaminophen 1000 mg and ibuprofen 300 mg) [package insert]. Hikma Pharmaceuticals USA Inc.
  4. Data on File. AFT Pharmaceuticals. 2023.

Important Safety Information

WARNING: HEPATOTOXICITY, CARDIOVASCULAR RISK, and GASTROINTESTINAL RISK

  • RISK OF MEDICATION ERRORS: Take care when prescribing, preparing, and administering COMBOGESIC® IV to avoid dosing errors which could result in accidental overdose and death.
  • HEPATOTOXICITY: COMBOGESIC® IV contains acetaminophen which has been associated with cases of acute liver failure, at times resulting in liver transplant and death. Most cases of liver injury are associated with doses exceeding 4,000 mg per day and often involve more than one acetaminophen-containing product.
  • CARDIOVASCULAR RISK: COMBOGESIC® IV contains ibuprofen, a nonsteroidal anti-inflammatory drug (NSAID). NSAIDs cause an increased risk of serious cardiovascular (CV) thrombotic events, including myocardial infarction and stroke, which can be fatal. This risk may occur early in treatment and may increase with duration of use.
  • COMBOGESIC® IV is contraindicated for treatment of peri-operative pain in the setting of coronary artery bypass graft (CABG) surgery.
  • GASTROINTESTINAL RISK: NSAIDs cause an increased risk of serious gastrointestinal (GI) adverse events including bleeding, ulceration, and perforation of the stomach or intestines, which can be fatal. These events can occur at any time during use and without warning symptoms. Elderly patients are at greater risk.
Scroll to Top