Acute Generalized Exanthematous Pustulosis

DEERFIELD, Ill.--( BUSINESS WIRE )--Baxter International Inc. (NYSE:BAX), a global leader in injectables, anesthesia and drug compounding, today announced five new injectable pharmaceutical product launches in the U.S., joining the previous five launches announced in April of this year and marking a total of 10 U.S. injectable product launches in 2024. “ Our Pharmaceuticals teams are relentlessly focused on bringing differentiated products to market that support our customers in helping to address vital patient needs,” said Alok Sonig, executive vice president and group president, Pharmaceuticals, at Baxter. “ We look forward to further accelerating our impact with a robust innovation pipeline across our key therapeutic areas, including critical care, anti-infectives, pain and oncology.” The five recent product launches within Baxter’s Pharmaceuticals portfolio in the U.S. include the following. For all products, please see full Indications, including Limitations of Use, Important Risk Information and links to full Prescribing Information below. Micafungin in 0.9% Sodium Chloride Injection single-dose container is indicated for use in adult and pediatric patients to treat Candida infections and for prophylaxis of Candida infections in patients undergoing hematopoietic stem cell transplantation for whom appropriate dosing with this formulation can be achieved. Micafungin uses Baxter’s proprietary container technology. Baxter offers Micafungin in 50 mg/50 mL, 100 mg/100 mL and 150 mg/150 mL strengths. Cyclophosphamide Injection is an alkylating drug indicated for treatment of adults and pediatric patients with various malignant diseases and is frequently used in combination with other oncology medications. This liquid cyclophosphamide product requires further dilution before use. Baxter offers Cyclophosphamide Injection in 500 mg/2.5 mL and 1000 mg/5 mL strengths in Multiple-Dose Vials. Pantoprazole Sodium in 0.9% Sodium Chloride Injection is a proton pump inhibitor indicated in adults for the short-term treatment (seven to 10 days) of gastroesophageal reflux disease (GERD) associated with a history of erosive esophagitis (EE) and pathological hypersecretion conditions including Zollinger-Ellison (ZE) Syndrome. Pantoprazole uses Baxter’s proprietary container technology. Baxter offers Pantoprazole in 40 mg/50 mL, 40 mg/100 mL and 80 mg/100 mL strengths. Cefazolin in Dextrose Injection, USP now available in a new 3 g/150 mL strength, is a single-dose, first generation cephalosporin antibacterial indicated for adults and pediatric patients to treat various infections caused by susceptible organisms and for perioperative prophylaxis. Cefazolin uses Baxter’s proprietary container technology. Baxter offers Cefazolin in 1 g/50 mL, 2 g/100 mL and 3 g/150 mL strengths. Levetiracetam in Sodium Chloride Injection is an anti-epileptic drug indicated for adjunct therapy in adult patients for partial onset seizures, myoclonic seizures, and tonic-clonic seizures. Levetiracetam uses Baxter’s proprietary container technology and is now offered in 500 mg/100 mL, 1000 mg/100 mL and 1500 mg/100 mL strengths. Ready-to-use formats of standard concentrations of commonly prescribed drugs may offer operational efficiencies for healthcare providers. Compounding a drug for patient use is a multi-step, manual process that requires oversight by pharmacy staff. A ready-to-use product can simplify the preparation process and support patient safety by reducing the chance of contamination 2 and avoiding potential errors that may occur when medications are compounded. 3 These five newly launched products are now available for use in the U.S. About Baxter Pharmaceuticals Baxter is a global leader in specialty injectables, drug compounding and anesthesia that addresses unmet patient needs in the therapeutic areas of pain, critical care, anti-infectives and oncology. Baxter’s comprehensive pharmaceuticals portfolio contains injectables (including ready-to-use products), inhaled gases and compounded medications, and is designed to expand access to products that simplify medication preparation and support patient safety. Pharmaceuticals employees across the globe are focused on driving customer-centered innovation, bringing new and differentiated products and delivery platforms to market, and helping patients receive the medications they need. About Baxter Every day, millions of patients, caregivers and healthcare providers rely on Baxter’s leading portfolio of diagnostic, critical care, kidney care, nutrition, hospital and surgical products used across patient homes, hospitals, physician offices and other sites of care. For more than 90 years, we’ve been operating at the critical intersection where innovations that save and sustain lives meet the healthcare providers who make it happen. With products, digital health solutions and therapies available in more than 100 countries, Baxter’s employees worldwide are now building upon the company’s rich heritage of medical breakthroughs to advance the next generation of transformative healthcare innovations. To learn more, visit www.baxter.com and follow us on X , LinkedIn and Facebook . Micafungin in 0.9% Sodium Chloride Injection Indications Micafungin in Sodium Chloride Injection is an echinocandin indicated in adult and pediatric patients for: Treatment of Candidemia, Acute Disseminated Candidiasis, Candida Peritonitis and Abscesses in adult and pediatric patients 4 months of age and older for whom appropriate dosing with this formulation can be achieved. Treatment of Candidemia, Acute Disseminated Candidiasis, Candida Peritonitis and Abscesses without meningoencephalitis and/or ocular dissemination in pediatric patients younger than 4 months of age for whom appropriate dosing with this formulation can be achieved. Treatment of Esophageal Candidiasis in adult and pediatric patients 4 months of age and older for whom appropriate dosing with this formulation can be achieved. Prophylaxis of Candida Infections in adult and pediatric patients 4 months of age and older undergoing Hematopoietic Stem Cell Transplantation (HSCT) for whom appropriate dosing with this formulation can be achieved. Limitations of Use: The safety and effectiveness of Micafungin in Sodium Chloride Injection have not been established for the treatment of candidemia with meningoencephalitis and/or ocular dissemination in pediatric patients younger than 4 months of age as a higher dose may be needed. Micafungin in Sodium Chloride Injection has not been adequately studied in patients with endocarditis, osteomyelitis or meningoencephalitis due to Candida. The efficacy of Micafungin in Sodium Chloride Injection against infections caused by fungi other than Candida has not been established. Important Risk Information Contraindications: Micafungin in Sodium Chloride Injection is contraindicated in persons with known hypersensitivity to micafungin sodium, any component of Micafungin in Sodium Chloride Injection, or other echinocandins. Hypersensitivity Reactions: Anaphylaxis and anaphylactoid reactions (including shock) have been observed. Discontinue Micafungin in Sodium Chloride Injection and administer appropriate treatment. Hematological Effects: Acute intravascular hemolysis and hemoglobinuria was seen in a healthy volunteer during infusion of Micafungin for Injection (200 mg) and oral prednisolone (20 mg). Cases of significant hemolysis and hemolytic anemia have also been reported in patients treated with Micafungin for Injection. Patients who develop clinical or laboratory evidence of hemolysis or hemolytic anemia during therapy should be monitored closely for evidence of worsening of these conditions and evaluated for the risk/benefit of continuing therapy. Hepatic Effects: Laboratory abnormalities in liver function tests have been seen in healthy volunteers and patients treated with Micafungin. In some patients with serious underlying conditions who were receiving Micafungin along with multiple concomitant medications, clinical hepatic abnormalities have occurred, and isolated cases of significant hepatic impairment, hepatitis, and hepatic failure have been reported. Monitor hepatic function. Discontinue if severe dysfunction occurs. Renal Effects: Elevations in BUN and creatinine; isolated cases of renal impairment or acute renal failure have been reported. Monitor renal function. Infusion and Injection Site Reactions: Possible histamine-mediated symptoms have been reported with Micafungin for Injection, including rash, pruritus, facial swelling, and vasodilatation. Slow the infusion rate if infusion reaction occurs. Injection site reactions, including phlebitis and thrombophlebitis have been reported, at Micafungin for Injection doses of 50 to 150 mg/day. These reactions tended to occur more often in patients receiving Micafungin for Injection via peripheral intravenous administration. High Sodium Load: Each 50, 100, and 150 mL Galaxy container contains 200, 400, and 600 mg of sodium, respectively. Avoid use in patients with congestive heart failure, elderly patients, and patients requiring restricted sodium intake. Adverse Reactions: Most common adverse reactions across adult and pediatric clinical trials for all indications include diarrhea, nausea, vomiting, abdominal pain, pyrexia, thrombocytopenia, neutropenia, and headache. In pediatric patients younger than 4 months of age, the following additional common adverse reactions were reported at an incidence rate of ≥15%: hypokalemia, acidosis, sepsis, anemia, and oxygen saturation decreased. Drug Interactions: Monitor for sirolimus, itraconazole or nifedipine toxicity, and dosage of sirolimus, itraconazole or nifedipine should be reduced, if necessary. Pregnancy: Based on animal data, Micafungin in Sodium Chloride Injection may cause fetal harm. Advise pregnant women of the risk to the fetus. Please see accompanying full Prescribing Information for Micafungin in 0.9% Sodium Chloride Injection . Cyclophosphamide Injection Indications Cyclophosphamide Injection is an alkylating drug indicated for treatment of adult and pediatric patients with: Malignant Diseases: malignant lymphomas: Hodgkin's disease, lymphocytic lymphoma, mixed-cell type lymphoma, histiocytic lymphoma, Burkitt's lymphoma; multiple myeloma, leukemias, mycosis fungoides, neuroblastoma, adenocarcinoma of ovary, retinoblastoma, breast carcinoma. Important Risk Information Contraindications Hypersensitivity: Cyclophosphamide is contraindicated in patients who have a history of severe hypersensitivity reactions to it, any of its metabolites, or to other components of the product. Anaphylactic reactions including death have been reported. Possible cross-sensitivity with other alkylating agents can occur. Urinary outflow obstruction Myelosuppression, Immunosuppression, Bone Marrow Failure and Infections: Cyclophosphamide can cause myelosuppression, bone marrow failure, and severe immunosuppression which may lead to serious and sometimes fatal infections, including sepsis and septic shock. Latent infections can be reactivated. Monitoring of complete blood counts is essential during cyclophosphamide treatment so that the dose can be adjusted, if needed. Urinary Tract and Renal Toxicity: Hemorrhagic cystitis, pyelitis, ureteritis, and hematuria have been reported with cyclophosphamide. Discontinue cyclophosphamide therapy in case of severe hemorrhagic cystitis. Urotoxicity may require interruption of cyclophosphamide treatment or cystectomy. Urotoxicity can be fatal. Before starting treatment, exclude or correct any urinary tract obstructions. Urinary sediment should be checked regularly for the presence of erythrocytes and other signs of urotoxicity and/or nephrotoxicity. Cyclophosphamide Injection should be used with caution, if at all, in patients with active urinary tract infections. Aggressive hydration with forced diuresis and frequent bladder emptying can reduce the frequency and severity of bladder toxicity. Mesna has been used to prevent severe bladder toxicity. Cardiotoxicity: Myocarditis, myopericarditis, pericardial effusion including cardiac tamponade, and congestive heart failure, which may be fatal, have been reported with cyclophosphamide therapy. Supraventricular arrhythmias and ventricular arrhythmias have been reported after treatment with regimens that included cyclophosphamide. The risk of cardiotoxicity may be increased with high doses of cyclophosphamide, in patients with advanced age, and in patients with previous radiation treatment to the cardiac region and/or previous or concomitant treatment with other cardiotoxic agents. Monitor patients, especially those with risk factors for cardio toxicity or pre-existing cardiac disease. Pulmonary Toxicity: Pneumonitis, pulmonary fibrosis, pulmonary veno-occlusive disease and other forms of pulmonary toxicity leading to respiratory failure have been reported during and following treatment with cyclophosphamide. Late onset pneumonitis appears to be associated with increased mortality. Monitor patients for signs and symptoms of pulmonary toxicity. Secondary Malignancies: Cyclophosphamide is genotoxic. Secondary malignancies have been reported in patients treated with cyclophosphamide-containing regimens. The risk of bladder cancer may be reduced by prevention of hemorrhagic cystitis. Veno-occlusive Liver Disease (VOD): VOD including fatal outcome has been reported in patients receiving cyclophosphamide-containing regimens. A cytoreductive regimen in preparation for bone marrow transplantation that consists of cyclophosphamide in combination with whole-body irradiation, busulfan, or other agents has been identified as a major risk factor. VOD has also been reported to develop gradually in patients receiving long-term low-dose immunosuppressive doses of cyclophosphamide. Alcohol Content: The alcohol content in a dose of Cyclophosphamide Injection may affect the central nervous system. Consideration should be given to the alcohol content on the ability to drive or use machines immediately after the infusion. Embryo-Fetal Toxicity: Cyclophosphamide Injection can cause fetal harm when administered to a pregnant woman. Exposure to cyclophosphamide during pregnancy may cause birth defects, miscarriage, fetal growth retardation, and fetotoxic effects in the newborn. Advise females of reproductive potential to use effective contraception during treatment and for up to 1 year after completion of therapy. Advise male patients with female partners of reproductive potential to use effective contraception during treatment and for 4 months after completion of therapy. Infertility: Male and female reproductive function and fertility may be impaired in patients being treated with Cyclophosphamide Injection. Cyclophosphamide interferes with oogenesis and spermatogenesis. It may cause sterility in both sexes. Cyclophosphamide-induced sterility may be irreversible in some patients. Adverse Reactions: Most common adverse reactions reported are neutropenia, febrile neutropenia, fever, alopecia, nausea, vomiting, and diarrhea. Lactation: Advise not to breastfeed. Renal Patients: Monitor for toxicity in patients with moderate and severe renal impairment. Please see accompanying full Prescribing Information for Cyclophosphamide Injection . Pantoprazole Sodium in 0.9% Sodium Chloride Injection Indications Pantoprazole Sodium in 0.9% Sodium Chloride Injection is a proton pump inhibitor (PPI) indicated in adults for the following: Short-term treatment (7 to 10 days) of gastroesophageal reflux disease (GERD) associated with a history of erosive esophagitis (EE). Pathological hypersecretion conditions including Zollinger-Ellison (ZE) Syndrome. Important Risk Information Contraindications Patients with a known hypersensitivity to any component of the formulation or to substituted benzimidazoles. Hypersensitivity reactions may include anaphylaxis, anaphylactic shock, angioedema, bronchospasm, acute tubulointerstitial nephritis, and urticaria. Patients receiving rilpivirine-containing products. Presence of Gastric Malignancy: In adults, symptomatic response to therapy does not preclude the presence of gastric malignancy. Consider additional follow-up and diagnostic testing in adult patients who have a suboptimal response or an early symptomatic relapse after completing treatment with a PPI. In older patients, also consider an endoscopy. Injection Site Reactions: Thrombophlebitis was reported in association with the administration of another intravenous pantoprazole sodium product. Potential for Exacerbation of Zinc Deficiency: Pantoprazole Sodium in 0.9% Sodium Chloride Injection contains edetate disodium (the salt form of EDTA), a chelator of metal ions including zinc. Therefore, zinc supplementation should be considered in patients who are prone to zinc deficiency. Caution should be used when other EDTA containing products are also co-administered intravenously. Acute Tubulointerstitial Nephritis (TIN): Has been observed in patients taking PPIs and may occur at any point during PPI therapy. Patients may present with varying signs and symptoms from symptomatic hypersensitivity reactions to non-specific symptoms of decreased renal function. Discontinue Pantoprazole Sodium in 0.9% Sodium Chloride Injection and evaluate patients with suspected acute TIN. Clostridioides difficile -associated diarrhea: Published observational studies suggest that PPI therapy may be associated with an increased risk of Clostridioides difficile -associated diarrhea, especially in hospitalized patients. This diagnosis should be considered for diarrhea that does not improve. Patients should use the lowest dose and shortest duration of PPI therapy appropriate to the condition being treated. Bone Fracture: Several published observational studies suggest that PPI therapy may be associated with an increased risk for osteoporosis-related fractures of the hip, wrist, or spine. The risk of fracture was increased in patients who received high-dose, defined as multiple daily doses, and long-term PPI therapy (a year or longer). Patients should use the lowest dose and shortest duration of PPI therapy appropriate to the condition being treated. Patients at risk for osteoporosis-related fractures should be managed according to established treatment guidelines. Severe Cutaneous Adverse Reactions: Including erythema multiforme, Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), drug reaction with eosinophilia and systemic symptoms (DRESS), and acute generalized exanthematous pustulosis (AGEP) have been reported in association with the use of PPIs. Discontinue Pantoprazole Sodium in 0.9% Sodium Chloride Injection at the first signs or symptoms of severe cutaneous adverse reactions or other signs of hypersensitivity and consider further evaluation. Cutaneous Lupus Erythematosus (CLE) and Systemic Lupus Erythematosus (SLE): Have been reported in patients taking PPIs, including pantoprazole sodium. These events have occurred as both new onset and an exacerbation of existing autoimmune disease. The majority of PPI-induced lupus erythematous cases were CLE. Avoid administration of PPIs for longer than medically indicated. If signs or symptoms consistent with CLE or SLE are noted in patients, discontinue the drug and refer the patient to the appropriate specialist for evaluation. Most patients improve with discontinuation of the PPI alone in 4 to 12 weeks. Hepatic Effects: Mild, transient transaminase elevations have been observed in clinical studies with another intravenous pantoprazole sodium product. The clinical significance of this finding in a large population of subjects is unknown. Hypomagnesemia and Mineral Metabolism: Hypomagnesemia, symptomatic and asymptomatic, has been reported rarely in patients treated with PPIs for at least three months, and in most cases after a year of therapy. Serious adverse events include tetany, arrhythmias, and seizures. Hypomagnesemia may lead to hypocalcemia and/or hypokalemia and may exacerbate underlying hypocalcemia in at-risk patients. In most patients, treatment of hypomagnesemia required magnesium replacement and discontinuation of the PPI. Fundic Gland Polyps: PPI use is associated with an increased risk of fundic gland polyps that increases with long-term use, especially beyond one year. Most PPI users who developed fundic gland polyps were asymptomatic. Use the shortest duration of PPI therapy appropriate to the condition being treated. Adverse Reactions: Most common adverse reactions (incidence > 2%) are headache, diarrhea, nausea, abdominal pain, vomiting, flatulence, dizziness, and arthralgia. Drug Interactions: See the full prescribing information for a list of clinically important drug interactions. Pregnancy: Based on animal data, may cause fetal harm. Please see accompanying full Prescribing Information for Pantoprazole Sodium in 0.9% Sodium Chloride Injection . Cefazolin in Dextrose Injection, USP Indications Cefazolin in Dextrose Injection is a cephalosporin antibacterial indicated for: Treatment of respiratory tract infections in adults and pediatric patients for whom appropriate dosing with this formulation can be achieved. Limitations of Use : Injectable benzathine penicillin is considered the drug of choice in treatment and prevention of streptococcal infections, including the prophylaxis of rheumatic fever. Treatment of the following infections caused by susceptible isolates of the designated microorganisms in adult and pediatric patients for whom appropriate dosing with this formulation can be achieved: Urinary tract infections; Skin and skin structure infections; Biliary tract infections; Bone and joint infections; Genital infections; Septicemia; Endocarditis. Perioperative prophylaxis in adults and pediatric patients aged 10 – 17 years old for whom appropriate dosing with this formulation can be achieved. To reduce the development of drug-resistant bacteria and maintain the effectiveness of Cefazolin in Dextrose Injection and other antibacterial drugs, Cefazolin in Dextrose Injection should be used only to treat or prevent infections that are proven or strongly suspected to be caused by bacteria. Important Risk Information Contraindications: Hypersensitivity to Cefazolin or other cephalosporin class antibacterial drugs, penicillins, or other beta-lactams. Hypersensitivity Reactions to Cefazolin, Cephalosporins, Penicillins, or Other Beta-lactams: Serious and occasionally fatal hypersensitivity (anaphylactic) reactions have been reported in patients receiving beta-lactam antibacterial drugs. Before therapy with Cefazolin in Dextrose Injection, careful inquiry should be made to determine whether the patient has had previous immediate hypersensitivity reactions to cefazolin, cephalosporins, penicillins, or carbapenems. Exercise caution if this product is to be given to penicillin-sensitive patients because cross-hypersensitivity among betalactam antibacterial drugs may occur in up to 10% of patients with a history of penicillin allergy. If an allergic reaction occurs, discontinue the drug. Seizures in Patients with Renal Impairment: Seizures may occur particularly in patients with renal impairment when the dosage is not reduced appropriately. Discontinue Cefazolin in Dextrose Injection if seizures occur or make appropriate dosage adjustments in patients with renal impairment. Anticonvulsant therapy should be continued in patients with known seizure disorders Clostridioides difficile -associated Diarrhea (CDAD): May range in severity from mild diarrhea to fatal colitis. CDAD must be considered in all patients who present with diarrhea following antibiotic use. If CDAD is suspected or confirmed, ongoing antibiotic use not directed against C. difficile may need to be discontinued. Appropriate fluid and electrolyte management, protein supplementation, antibiotic treatment of C. difficile , and surgical evaluation should be instituted as clinically indicated. Prothrombin Activity: Cefazolin in Dextrose Injection may be associated with a fall in prothrombin activity. Those at risk include patients with renal or hepatic impairment or poor nutritional state, as well as patients receiving a protracted course of antimicrobial therapy, and patients previously stabilized on anticoagulant therapy. Prothrombin time should be monitored in patients at risk and exogenous vitamin K administered as indicated. Adverse Reactions: Adult and Pediatric Patients : Most common adverse reactions: gastrointestinal (nausea, vomiting, diarrhea), and allergic reactions (anaphylaxis, urticaria, skin rash). Pediatric Patients with Perioperative Prophylaxis : The most frequently reported adverse reactions (incidence ≥ 5%) were nausea, infusion site pain, and headache. Drug Interactions: Probenecid: The renal excretion of cefazolin is inhibited by probenecid. Co-administration of probenecid with Cefazolin in Dextrose Injection is not recommended. Please see accompanying full Prescribing Information for Cefazolin in Dextrose Injection, USP . Levetiracetam in Sodium Chloride Injection Indications Levetiracetam in Sodium Chloride Injection is indicated for adjunct therapy in adults (≥16 years of age) with the following seizure types when oral administration is temporarily not feasible: Partial-onset seizures Myoclonic seizures in patients with juvenile myoclonic epilepsy Primary generalized tonic-clonic seizures Important Risk Information Contraindications: Levetiracetam in Sodium Chloride Injection is contraindicated in patients with a hypersensitivity to levetiracetam. Reactions have included anaphylaxis and angioedema. Psychiatric Reactions: Behavioral abnormalities including psychotic symptoms, suicidal ideation, irritability, and aggressive behavior have been observed. Monitor patients for psychiatric signs and symptoms. Somnolence and Fatigue: Monitor patients for these symptoms and advise patients not to drive or operate machinery until they have gained sufficient experience on levetiracetam. Anaphylaxis and Angioedema: Levetiracetam can cause anaphylaxis or angioedema. In some reported cases, reactions were life-threatening and required emergency treatment. If a patient develops signs or symptoms of anaphylaxis or angioedema, levetiracetam should be discontinued and the patient should seek immediate medical attention. Serious Dermatological Reactions: Serious reactions, including Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), have been reported in patients treated with levetiracetam. Recurrence of the serious skin reactions following rechallenge has also been reported. Levetiracetam should be discontinued at the first sign of a rash, unless the rash is clearly not drug-related. If signs or symptoms suggest SJS/TEN, use of this drug should not be resumed, and alternative therapy should be considered. Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS)/Multiorgan Hypersensitivity: This has been reported in patients taking antiepileptic drugs, including levetiracetam. These events can be fatal or life-threatening, particularly if diagnosis and treatment do not occur as early as possible. DRESS typically, although not exclusively, presents with fever, rash, lymphadenopathy, and/or facial swelling, in association with other organ system involvement, sometimes resembling an acute viral infection. If such signs or symptoms are present, the patient should be evaluated immediately. Levetiracetam should be discontinued if an alternative etiology for the signs or symptoms cannot be established. Coordination Difficulties: Monitor for ataxia, abnormal gait, and incoordination. Patients should be monitored for these signs and symptoms and advised not to drive or operate machinery until they have gained sufficient experience on levetiracetam. Withdrawal Seizures: Levetiracetam must be gradually withdrawn. But if withdrawal is needed because of a serious adverse reaction, rapid discontinuation can be considered. Hematologic Abnormalities: Hematologic abnormalities occurred in clinical trials and included decreases in white blood cell, neutrophil, and red blood cells counts; decreases in hemoglobin and hematocrit; and increases in eosinophil counts. Cases of agranulocytosis, pancytopenia, and thrombocytopenia have been reported in the post-marketing setting. A complete blood count is recommended in patients experiencing significant weakness, pyrexia, recurrent infections, or coagulation disorders. Adverse Reactions: Most common adverse reactions (incidence in levetiracetam-treated patients is ≥5% more than in placebo-treated patients) include: somnolence, asthenia, infection, and dizziness. Pregnancy: Plasma levels of levetiracetam may be decreased; monitor closely during pregnancy. Based on animal data, may cause fetal harm. Encourage women who are taking levetiracetam injection during pregnancy to enroll in the North American Antiepileptic Drug (NAAED) pregnancy registry. Renal Impairment: Dosage adjustment is recommended for patients with impaired renal function and supplemental doses should be given to patients after dialysis. Please see accompanying full Prescribing Information for Levetiracetam in Sodium Chloride Injection . This release includes forward-looking statements concerning Micafungin in 0.9% Sodium Chloride Injection, Cyclophosphamide Injection, Pantoprazole Sodium in 0.9% Sodium Chloride Injection, Cefazolin in Dextrose Injection, USP and Levetiracetam in Sodium Chloride Injection, including potential benefits associated with the use of these products. The statements are based on assumptions about many important factors, including the following, which could cause actual results to differ materially from those in the forward-looking statements: demand for and market acceptance for new and existing products; product development risks; inability to create additional production capacity in a timely manner or the occurrence of other manufacturing or supply difficulties (including as a result of natural disasters, public health crises and epidemics/pandemics, regulatory actions or otherwise); satisfaction of regulatory and other requirements; actions of regulatory bodies and other governmental authorities; product quality, manufacturing or supply, or patient safety issues; changes in law and regulations; and other risks identified in Baxter's most recent filing on Form 10-K and Form 10-Q and other SEC filings, all of which are available on Baxter's website. Baxter does not undertake to update its forward-looking statements. Baxter is a registered trademark of Baxter International Inc. 1 Includes line extensions. 2 Mercaldi CJ, Lanes S, Bradt J. Comparative risk of bloodstream infection in hospitalized patients receiving intravenous medication by open, point-of-care, or closed delivery systems. Am J Health-Syst Pharm. 2013;70:957-965. 3 Billstein-Leber M, Carrillo CJD, Cassano AT, Moline K, Robertson JJ. ASHP Guidelines on Preventing Medication Errors in Hospitals. Am J Health Syst Pharm. 2018;75(19):1493-1517. US-PH121-240011 (v3.0) 12/2024

Five new launches reinforce Baxter’s focus on differentiated products and enhance the company’s Pharmaceuticals portfolio in critical therapeutic areas Products feature ready-to-use formulations to help support patient safety and offer added convenience for healthcare professionals DEERFIELD, Ill.--(BUSINESS WIRE)-- Baxter International Inc. (NYSE:BAX), a global leader in injectables, anesthesia and drug compounding, announced the continued expansion of its Pharmaceuticals portfolio with five injectable product launches in the U.S. “These launches demonstrate Baxter’s focus on differentiated products that address unmet patient needs in key therapeutic areas, including anti-infective and anti-hypotensive medications,” said Alok Sonig, executive vice president and group president, Pharmaceuticals, at Baxter. “We are proud to offer important new options for our customers and look forward to continuing to bring new innovations to the market.” Product launches within Baxter’s Pharmaceuticals portfolio in the U.S. include the following. For all products, please see full Indications, Important Risk Information and links to full Prescribing Information below. Norepinephrine Bitartrate in 5% Dextrose Injection in a new 16 mg/250 mL strength, which is indicated to raise blood pressure in adult patients with severe, acute hypotension. Baxter offers the first and only FDA-approved ready-to-use Norepinephrine in Dextrose, and now provides Norepinephrine in 4 mg/250 mL, 8 mg/250 mL and 16 mg/250 mL strengths. Vasopressin in 0.9% Sodium Chloride Injection, the first and only FDA-approved ready-to-use Vasopressin in a flexible container. Vasopressin uses Baxter’s proprietary sterile, closed system container, which is collapsible and does not require a vented intravenous set.1 Manufactured closed drug-delivery systems decrease the need for manual admixture and reduce the possibility of contamination.2 Vasopressin is indicated to increase blood pressure in adults with vasodilatory shock who remain hypotensive despite fluids and catecholamines. Baxter offers Vasopressin in 20 units/100 mL and 40 units/100 mL strengths. Vancomycin Injection, USP in 5% Dextrose in new 1.25 g/250 mL and 1.5 g/300 mL strengths. These launches are Baxter’s first frozen ready-to-use offerings in 250 mL and 300 mL volumes. Vancomycin is indicated for serious or severe infections caused by susceptible strains of methicillin-resistant (β-lactam-resistant) staphylococci. Baxter now offers Vancomycin in 500 mg/100 mL, 750 mg/150 mL, 1 g/200 mL, 1.25 g/250 mL and 1.5 g/300 mL strengths. Ropivacaine Hydrochloride Injection, USP in a ready-to-use, single-dose infusion bag. Ropivacaine is indicated in adults to produce local or regional anesthesia for surgery and for acute pain management. Baxter offers Ropivacaine in 200 mg/100 mL and 400 mg/200 mL strengths. Regadenoson Injection pre-filled syringe, a coronary vasodilator that is commonly used in pharmacologic stress testing. Baxter offers Regadenoson in a 0.4 mg/5 mL strength. Ready-to-use formats of standard concentrations of commonly prescribed drugs may offer operational efficiencies for healthcare providers. Compounding a drug for patient use is a multi-step, manual process that requires oversight by pharmacy staff. A ready-to-use product can simplify the preparation process and support patient safety by reducing the chance of contamination2 and avoiding potential errors that may occur when medications are compounded.3 These newly launched products are now available for use in the U.S. About Baxter Every day, millions of patients, caregivers and healthcare providers rely on Baxter’s leading portfolio of diagnostic, critical care, kidney care, nutrition, hospital and surgical products used across patient homes, hospitals, physician offices and other sites of care. For more than 90 years, we’ve been operating at the critical intersection where innovations that save and sustain lives meet the healthcare providers who make it happen. With products, digital health solutions and therapies available in more than 100 countries, Baxter’s employees worldwide are now building upon the company’s rich heritage of medical breakthroughs to advance the next generation of transformative healthcare innovations. To learn more, visit and follow us on X/Twitter, LinkedIn and Facebook. Norepinephrine Bitartrate in 5% Dextrose Injection Indications Norepinephrine Bitartrate in Dextrose Injection is indicated to raise blood pressure in adult patients with severe, acute hypotension. Important Risk Information Contraindications: None. Tissue Ischemia: Administration of Norepinephrine Bitartrate in Dextrose Injection to patients who are hypotensive from hypovolemia can result in severe peripheral and visceral vasoconstriction, decreased renal perfusion and reduced urine output, tissue hypoxia, lactic acidosis, and reduced systemic blood flow despite “normal” blood pressure. Address hypovolemia prior to initiating Norepinephrine Bitartrate in Dextrose Injection. Avoid use in patients with mesenteric or peripheral vascular thrombosis, as this may increase ischemia and extend the area of infarction. Gangrene of the extremities has occurred in patients with occlusive or thrombotic vascular disease or who received prolonged or high dose infusions. Monitor for changes to the skin of the extremities in susceptible patients. Extravasation of Norepinephrine Bitartrate in Dextrose Injection may cause necrosis and sloughing of surrounding tissue. To reduce the risk of extravasation, infuse into a large vein, check the infusion site frequently for free flow, and monitor for signs of extravasation. Avoid administration into the veins in the leg in elderly patients. Emergency Treatment of Extravasation: Infiltrate the ischemic area as soon as possible, using a syringe with a fine hypodermic needle with 5 to 10 mg of phentolamine mesylate in 10 to 15 mL of 0.9% Sodium Chloride Injection in adults. Hypotension after Abrupt Discontinuation: Sudden cessation of the infusion rate may result in marked hypotension. When discontinuing the infusion, gradually reduce the infusion rate while expanding blood volume with intravenous fluids. Cardiac Arrhythmias: Norepinephrine Bitartrate in Dextrose Injection elevates intracellular calcium concentrations and may cause arrhythmias, particularly in the setting of hypoxia or hypercarbia. Perform continuous cardiac monitoring of patients with arrhythmias. Elderly Patients: May be at a greater risk of developing adverse reactions. Adverse Reactions: Most common adverse reactions are hypertension and bradycardia. Drug Interactions: Co-administration of Norepinephrine Bitartrate in Dextrose Injection with monoamine oxidase (MAO) inhibitors or other drugs with MAO-inhibiting properties (e.g., linezolid) or with tricyclic antidepressants can cause severe, prolonged hypertension. Anti-diabetics: Norepinephrine Bitartrate in Dextrose Injection can decrease insulin sensitivity and raise blood glucose. Concomitant use of Norepinephrine Bitartrate in Dextrose Injection with halogenated anesthetics may lead to ventricular tachycardia or ventricular fibrillation. Monitor cardiac rhythm in patients receiving concomitant halogenated anesthetics. Please see accompanying full Prescribing Information for Norepinephrine Bitartrate in 5% Dextrose Injection. Vasopressin in 0.9% Sodium Chloride Injection Indications Vasopressin in Sodium Chloride Injection is indicated to increase blood pressure in adults with vasodilatory shock who remain hypotensive despite fluids and catecholamines. Important Risk Information Contraindications: Vasopressin in Sodium Chloride Injection is contraindicated in patients with a known allergy or hypersensitivity to 8-L-arginine vasopressin. Worsening Cardiac Function: A decrease in cardiac index may be observed with the use of vasopressin. Reversible Diabetes Insipidus: Patients may experience reversible diabetes insipidus, manifested by the development of polyuria, a dilute urine, and hypernatremia, after cessation of treatment with vasopressin. Monitor serum electrolytes, fluid status and urine output after vasopressin discontinuation. Some patients may require readministration of vasopressin or administration of desmopressin to correct fluid and electrolyte shifts. Adverse Reactions: The most common adverse reactions include decreased cardiac output, bradycardia, tachyarrhythmias, hyponatremia and ischemia (coronary, mesenteric, skin, digital). Drug Interactions: Pressor effects of catecholamines and Vasopressin in Sodium Chloride Injection are expected to be additive. Indomethacin may prolong effects of Vasopressin in Sodium Chloride Injection. Co-administration of ganglionic blockers or drugs causing SIADH (syndrome of inappropriate antidiuretic hormone secretion) may increase the pressor response. Co-administration of drugs causing diabetes insipidus may decrease the pressor response. Pregnancy: May induce tonic uterine contractions that could threaten the continuation of pregnancy. Please see accompanying full Prescribing Information for Vasopressin in 0.9% Sodium Chloride Injection. Vancomycin Injection, USP in 5% Dextrose Indications Vancomycin is indicated for the treatment of serious or severe infections caused by susceptible strains of methicillin-resistant (beta-lactam-resistant) staphylococci. It is indicated for penicillin-allergic patients, for patients who cannot receive or who have failed to respond to other drugs, and for infections caused by vancomycin-susceptible organisms that are resistant to other antimicrobial drugs. Vancomycin is effective in the treatment of: Infective Endocarditis (staphylococcal endocarditis; endocarditis caused by Streptococcus viridans or S. bovis, alone or in combination with an aminoglycoside; endocarditis caused by enterococci (e.g., E. faecalis), only in combination with an aminoglycoside; diphtheroid endocarditis; early-onset prosthetic valve endocarditis caused by S. epidermidis or diphtheroids in combination with either rifampin, an aminoglycoside, or both) Septicemia Skin and Skin Structure Infections Bone Infections Lower Respiratory Tract Infections To reduce the development of drug-resistant bacteria and maintain the effectiveness of vancomycin and other antibacterial drugs, vancomycin should be used only to treat or prevent infections that are proven or strongly suspected to be caused by susceptible bacteria. Important Risk Information Contraindications: Vancomycin is contraindicated in patients with known hypersensitivity to this antibiotic. Solutions containing dextrose may be contraindicated in patients with known allergy to corn or corn products. Infusion Reactions: Rapid bolus administration (e.g., over several minutes) may be associated with exaggerated hypotension, including shock, and, rarely, cardiac arrest. During or soon after rapid infusion of vancomycin, patients may develop anaphylactoid reactions, including hypotension, wheezing, dyspnea, urticaria, or pruritus. Rapid infusion may also cause flushing of the upper body (“vancomycin infusion reaction”) or pain and muscle spasm of the chest and back. Vancomycin should be administered over a period of not less than 60 minutes. Stopping the infusion usually results in prompt cessation of these reactions. Nephrotoxicity: Systemic vancomycin exposure may result in acute kidney injury (AKI). The risk of AKI increases as systemic exposure/serum levels increase. Monitor renal function in all patients; especially with underlying renal impairment, with co-morbidities, and receiving concomitant therapy with a known nephrotoxic drug. Ototoxicity: It may be transient or permanent. It has been reported mostly in patients who have been given excessive doses, who have an underlying hearing loss, or who are receiving concomitant therapy with another ototoxic agent, such as an aminoglycoside. Vancomycin should be used with caution in patients with renal insufficiency. Severe Dermatologic Reactions: Toxic epidermal necrolysis (TEN), Stevens-Johnson syndrome (SJS), drug reaction with eosinophilia and systemic symptoms (DRESS), acute generalized exanthematous pustulosis (AGEP), and linear IgA bullous dermatosis (LABD) have been reported. Cutaneous signs or symptoms reported include skin rashes, mucosal lesions, and blisters. Discontinue vancomycin Injection at the first appearance of signs and symptoms of TEN, SJS, DRESS, AGEP, or LABD. Dosage of vancomycin must be adjusted for patients with renal dysfunction. Clostridioides difficile associated diarrhea (CDAD): May range in severity from mild diarrhea to fatal colitis. CDAD must be considered in all patients who present with diarrhea following antibiotic use. If CDAD is suspected or confirmed, ongoing antibiotic use not directed against C. difficile may need to be discontinued. Appropriate fluid and electrolyte management, protein supplementation, antibiotic treatment of C. difficile, and surgical evaluation should be instituted as clinically indicated. Hemorrhagic Occlusive Retinal Vasculitis: Including permanent loss of vision, occurred in patients receiving intracameral or intravitreal administration of vancomycin during or after cataract surgery. The safety and efficacy of vancomycin administered by the intracameral or the intravitreal route have not been established. Adverse Reactions: Not already mentioned above, patients have been reported to have neutropenia, phlebitis, drug fever, nausea, chills, and vasculitis in association with administration of vancomycin. Drug Interactions: Anesthetic Agents: Concomitant administration of vancomycin and anesthetic agents has been associated with erythema and histamine-like flushing and anaphylactoid reactions. Monitor renal function in patients receiving vancomycin and concurrent and/or sequential systemic or topical use of other potentially neurotoxic and/or nephrotoxic drugs, such as amphotericin B, aminoglycosides, bacitracin, polymyxin B, colistin, viomycin, or cisplatin. Please see accompanying full Prescribing Information for Vancomycin Injection, USP. Ropivacaine Hydrochloride Injection, USP Indications Ropivacaine Hydrochloride Injection is an amide local anesthetic indicated in adults for the production of local or regional anesthesia for surgery and for acute pain management. Surgical Anesthesia: epidural block for surgery including cesarean section; major nerve block; local infiltration. Acute Pain Management: epidural continuous infusion or intermittent bolus, e.g., postoperative or labor; local infiltration. Important Risk Information Contraindications: Ropivacaine Hydrochloride Injection is contraindicated in patients with a known hypersensitivity to ropivacaine or to any local anesthetic agent of the amide type. General Warning: Delay in proper management of dose-related toxicity, underventilation, and/or altered sensitivity may lead to the development of acidosis, cardiac arrest and, possibly, death. The safe and effective use of local anesthetics depends on proper dosage, correct technique, adequate precautions, and readiness for emergencies. It is essential that aspiration for blood, or cerebrospinal fluid (where applicable), be done prior to injecting any local anesthetic, both the original dose and all subsequent doses, to avoid intravascular or subarachnoid injection. Unintended Intravenous Injection: In performing Ropivacaine Hydrochloride Injection blocks, unintended intravenous injection is possible and may result in cardiac arrhythmia or cardiac arrest. Ropivacaine hydrochloride injection should be administered in incremental doses. It is not recommended for emergency situations, where a fast onset of surgical anesthesia is necessary. Intra-Articular Infusions and Risk of Chondrolysis: Intra-articular infusions of local anesthetics may cause chondrolysis. Ropivacaine Hydrochloride Injection is not approved for this use. Risk of Methemoglobinemia: Patients with glucose-6-phosphate dehydrogenase deficiency, congenital or idiopathic methemoglobinemia, cardiac or pulmonary compromise, infants under 6 months of age, and concurrent exposure to oxidizing agents or their metabolites are more susceptible to developing clinical manifestations of the condition. If local anesthetics must be used in these patients, close monitoring for symptoms and signs of methemoglobinemia is recommended. Signs of methemoglobinemia may occur immediately or may be delayed some hours after exposure. Immediate treatment is required to avert more serious central nervous system and cardiovascular adverse effects, including seizures, coma, arrhythmias, and death. Discontinue ropivacaine hydrochloride injection and any other oxidizing agents. Central Nervous System Toxicity: Careful and constant monitoring of cardiovascular and respiratory vital signs and the patient's state of consciousness should be performed after each local anesthetic injection. Hepatic Disease: Because amide-type local anesthetics such as ropivacaine are metabolized by the liver, these drugs, especially repeat doses, should be used cautiously in patients with hepatic disease. Patients with severe hepatic disease are at a greater risk of developing toxic plasma concentrations. Adverse Reactions: Most common adverse reactions (incidence ≥ 5%) are hypotension, nausea, vomiting, bradycardia, fever, pain, postoperative complications, anemia, paresthesia, headache, pruritus, and back pain. Drug Interactions: Agents structurally related to amide-type local anesthetics: Concurrent use may cause additive effects. Please see accompanying full Prescribing Information for Ropivacaine Hydrochloride Injection, USP. Regadenoson Injection Indications Regadenoson injection is a pharmacologic stress agent indicated for radionuclide myocardial perfusion imaging (MPI) in patients unable to undergo adequate exercise stress. Important Risk Information Contraindications: Do not administer regadenoson injection to patients with: Second- or third-degree AV block, or Sinus node dysfunction, unless these patients have a functioning artificial pacemaker. Myocardial Ischemia: Fatal cardiac events have occurred. Avoid use in patients with symptoms or signs of acute myocardial ischemia, for example unstable angina or cardiovascular instability, who may be at greater risk. Cardiac resuscitation equipment and trained staff should be available before administration. Sinoatrial (SA) and Atrioventricular (AV) Nodal Block: Adenosine receptor agonists, including regadenoson injection, can depress the SA and AV nodes and may cause first-, second- or third-degree AV block, or sinus bradycardia. Atrial Fibrillation/Atrial Flutter: New-onset or recurrent atrial fibrillation with rapid ventricular response and atrial flutter have been reported. Hypersensitivity, Including Anaphylaxis: Anaphylaxis, angioedema, cardiac or respiratory arrest, respiratory distress, decreased oxygen saturation, hypotension, throat tightness, urticaria and rashes have occurred. Have personnel and resuscitative equipment immediately available. Hypotension: Adenosine receptor agonists, including regadenoson injection, induce vasodilation and hypotension. The risk of serious hypotension may be higher in patients with autonomic dysfunction, stenotic valvular heart disease, pericarditis or pericardial effusions, stenotic carotid artery disease with cerebrovascular insufficiency, or hypovolemia. Hypertension: Adenosine receptor agonists, including regadenoson injection, may induce clinically significant increases in blood pressure particularly in patients with a history of hypertension and when the MPI includes low level exercise. Bronchoconstriction: Adenosine receptor agonists, including regadenoson injection, may induce dyspnea, bronchoconstriction and respiratory compromise, especially in patients with chronic obstructive pulmonary disease (COPD) or asthma. Resuscitative measures should be available. Seizure: Regadenoson injection may lower the seizure threshold. New onset or recurrence of convulsive seizures has occurred. Some seizures are prolonged and require urgent anticonvulsive management. Methylxanthine use is not recommended in patients who experience a seizure in association with regadenoson injection. Cerebrovascular Accident (Stroke): Hemorrhagic and ischemic cerebrovascular accidents have occurred. Adverse Reactions: The most common (incidence ≥ 5%) adverse reactions to regadenoson injection are dyspnea, headache, flushing, chest discomfort, dizziness, angina pectoris, chest pain, and nausea. Drug Interactions: Methylxanthines, e.g., caffeine, aminophylline and theophylline, interfere with the activity of regadenoson injection. Aminophylline may be used to attenuate severe and/or persistent adverse reactions to regadenoson injection. Dipyridamole may increase the activity of regadenoson injection. When possible, withhold dipyridamole for at least two days prior to regadenoson injection administration. Please see accompanying full Prescribing Information for Regadenoson Injection. This release includes forward-looking statements concerning Norepinephrine Bitartrate in 5% Dextrose Injection, Vasopressin in 0.9% Sodium Chloride Injection, Vancomycin Injection, USP in 5% Dextrose, Ropivacaine Hydrochloride Injection, USP and Regadenoson Injection pre-filled syringe, including potential benefits associated with the use of these products. The statements are based on assumptions about many important factors, including the following, which could cause actual results to differ materially from those in the forward-looking statements: demand for and market acceptance for new and existing products; product development risks; inability to create additional production capacity in a timely manner or the occurrence of other manufacturing or supply difficulties (including as a result of natural disasters, public health crises and epidemics/pandemics, regulatory actions or otherwise); satisfaction of regulatory and other requirements; actions of regulatory bodies and other governmental authorities; product quality, manufacturing or supply, or patient safety issues; changes in law and regulations; and other risks identified in Baxter's most recent filing on Form 10-K and Form 10-Q and other SEC filings, all of which are available on Baxter's website. Baxter does not undertake to update its forward-looking statements. Baxter is a registered trademark of Baxter International Inc. 1 Baxter data on > 2 Mercaldi CJ, Lanes S, Bradt J. Comparative risk of bloodstream infection in hospitalized patients receiving intravenous medication by open, point-of-care, or closed delivery systems. Am J Health-Syst Pharm. 2013;70:957-965. 3 Billstein-Leber M, Carrillo CJD, Cassano AT, Moline K, Robertson JJ. ASHP Guidelines on Preventing Medication Errors in Hospitals. Am J Health Syst Pharm. 2018;75(19):1493-1517. US-PH57-240005 (v1.0) 04/2024 View source version on businesswire.com: Contacts Media Contact Andrea Johnson, (224) 948-5353 media@baxter.com Investor Contact Clare Trachtman, (224) 948-3020 Source: Baxter International Inc. View this news release online at:

Offers health care providers a new multimodal approach to adult pain management LONDON, Feb. 5, 2024 /PRNewswire/ -- Hikma Pharmaceuticals PLC (Hikma), the multinational pharmaceutical company, announces the launch of COMBOGESIC® IV (acetaminophen and ibuprofen) injection in the US. 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 In a Phase 3 clinical trial, COMBOGESIC® IV provided more than double the pain relief than that of acetaminophen IV and ibuprofen IV alone.3 Time to meaningful pain relief was shorter in the COMBOGESIC® IV group than that in the Ibuprofen IV or placebo groups.3 COMBOGESIC® IV also allows for superior analgesia efficacy.3 "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. About COMBOGESIC® IV 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 About Hikma (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: 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 CONTRAINDICATIONS COMBOGESIC® IV is contraindicated in: Patients with previous demonstrated hypersensitivity to acetaminophen, ibuprofen, other NSAIDs or to any of the excipients/components of this product. Patients who have experienced asthma, urticaria, or allergic-type reactions after taking aspirin or other NSAIDs. Severe, sometimes fatal, anaphylactic reactions to NSAIDs have been reported in such patients. The treatment of peri-operative pain in the setting of coronary artery bypass graft (CABG) surgery. Patients with severe hepatic impairment or severe active liver disease. WARNINGS & PRECAUTIONS 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. Hepatotoxicity. (i) COMBOGESIC® IV contains acetaminophen which has been associated with cases of acute liver failure, at times resulting in liver transplant and death. The risk of acute liver failure is higher in individuals with underlying liver disease and in individuals who ingest alcohol while taking acetaminophen. The use of COMBOGESIC® IV in patients with hepatic impairment is not recommended. (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. 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. These serious events may occur without warning. Inform patients about the signs and symptoms and discontinue the use of the drug at the first appearance of skin rash or any other sign of hypersensitivity. COMBOGESIC® IV is contraindicated in patients with previous serious skin reactions to acetaminophen or NSAIDs. Drug Rash with Eosinophilia and Systemic Symptoms (DRESS). Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) has been reported in patients taking NSAIDs such as COMBOGESIC® IV. Some of these events have been fatal or life-threatening. Hypersensitivity and Anaphylactic Reactions. There have been post marketing reports of hypersensitivity and anaphylaxis, including life-threatening anaphylaxis associated with the use of acetaminophen. Hypertension. NSAIDs can lead to onset of new hypertension or worsening of pre-existing hypertension, either of which may contribute to the increased incidence of CV events. 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. Renal Toxicity and Hyperkalemia. Long-term administration of NSAIDs has resulted in renal papillary necrosis and other renal injury. Renal toxicity has also been seen in patients in whom renal prostaglandins have a compensatory role in the maintenance of renal perfusion. Increases in serum potassium concentration, including hyperkalemia, have been reported with use of NSAIDs, even in some patients without renal impairment. No information is available regarding the use of COMBOGESIC® IV in patients with advanced renal disease. Exacerbation of Asthma Related to Aspirin Sensitivity. Patients with asthma may have aspirin-sensitive asthma which may include chronic rhinosinusitis complicated by nasal polyps; severe bronchospasm, which can be fatal and/or intolerance to aspirin and other NSAIDs. Because cross-reactivity between aspirin and other NSAIDs has been reported in such aspirin-sensitive patients, COMBOGESIC® IV is contraindicated in patients with this form of aspirin sensitivity. 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. Fetal Toxicity: Oligohydramnios/Neonatal Renal Impairment. Use of COMBOGESIC® IV at about 20 weeks gestation or later in pregnancy may cause fetal renal dysfunction leading to oligohydramnios and, in some cases, neonatal renal impairment. 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. Masking of Inflammation and Fever. Activity of COMBOGESIC® IV in reducing inflammation, and possibly fever, may diminish the utility of diagnostic signs in detecting infections. 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. ADVERSE REACTIONS The most common TEAEs (occurring in ≥ 3% of COMBOGESIC® IV -treated participants) were related to the infusion site (infusion site pain, infusion site extravasation), or affected the gastrointestinal (nausea, vomiting, constipation) or nervous (dizziness, headache, somnolence) systems. Other skin and subcutaneous-related TEAEs (pruritis, hyperhidrosis) also affected around 2 to 3% of the study population, as did procedural nausea and polyuria. DRUG INTERACTIONS 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. Methotrexate. Concomitant use of NSAIDs and methotrexate may increase the risk for methotrexate toxicity (e.g., neutropenia, thrombocytopenia, renal dysfunction). Monitor patients for methotrexate 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. Renal Impairment. The use of COMBOGESIC® IV in these patients is not recommended as it may hasten the progression of renal dysfunction in patients with pre-existing renal disease. 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. 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 . 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 . Manufactured by: S.M. Farmaceutici SRL Zona Industriale, 85050 Tito (PZ), Italy Distributed by: Hikma Pharmaceuticals USA Inc. Berkeley Heights, NJ 07922 USA COMBOGESIC® is a registered trademark of AFT Pharmaceuticals Limited. © 2024 Hikma Pharmaceuticals USA Inc. All rights reserved. Document identification number: HK-2471-v3 1 COMBOGESIC® IV (acetaminophen 1000 mg and ibuprofen 300 mg) [package insert]. 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). SOURCE Hikma Pharmaceuticals USA Inc.