Ditiazem Hydrochloride

Indian drugmakers Aurobindo, Glenmark and Zydus have issued separate drug recalls linked to issues with impurities and labeling. Indian drugmakers Aurobindo, Glenmark and Zydus have issued separate sweeping drug recalls over issues pertaining to impurities and labeling.The product pulls were reported in a recent edition of the U.S. FDA's weekly enforcement report, which catalogs recalls after they've been properly classified by the regulator.In the case of Aurobindo, the company issued a recall of more than 100,000 bottles of cinacalcet at the 30 mg dose and more than 3,300 bottles at the 60 mg dose.  The company also recalled an undisclosed number of 90 mg bottles.The drug is used to treat hyperparathyroidism in patients with chronic kidney disease who are on dialysis.The recall for cinacalcet, which was manufactured in India, was attributed to the presence of N-nitroso Cinacalcet impurity levels that exceeded recommended limits set by the FDA. N-nitroso compounds are considered potentially carcinogenic. The drugs in question were distributed nationwide in the U.S., and the recall has been classified as Class II, which means there is a low chance of serious injuries or death. Aurobindo also recalled an undisclosed amount of nebivolol 2.5 mg tablets in 30-count bottles due to the presence of excess levels of the nitrosamine drug substance-related impurity N-Nitroso Nebivolol. The recall of nebivolol, which is used to treat high blood pressure, is also classified as Class II. The tablets were shipped out across the U.S., though Aurobindo didn’t specify where the products were manufactured.Glenmark Pharmaceuticals, for its part, issued voluntary recalls for 90,528 bottles of the high blood pressure drug diltiazem hydrochloride in tablet and extended-release forms due to unacceptable levels of another N-nitroso compound, N-nitroso-Desmethyl-Diltiazem.  The suspect diltiazem lots were manufactured by Glenmark in India for multiple different customers. As with the other recalls listed in the enforcement report, Glenmark’s medicine withdrawal falls under Class II.Meanwhile, Zydus Pharmaceuticals recalled 4,404 40 mg single-dose packets of the acid reflux treatment esomeprazole magnesium due to a labeling issue. The product, which was produced in India, was distributed nationwide in the U.S. The recall has been classified as Class III, which is the least severe of the FDA’s recall rankings. N-nitroso compounds, and in particular nitrosamines, crop up in countless products, including cured meats, beer and medicine. Some nitrosamines cause cancer in laboratory animals and may increase the risk of certain types of cancer in humans, according to the National Cancer Institute. Notably, the discovery of N-nitrosodimethylamine (NDMA) in Zantac led to mass product pulls and lawsuits over the popular heartburn med around the start of the decade. More recently, Dr. Reddy’s Laboratories in November said it was yanking 331,590 bottles of cinacalcet—the same drug covered in Aurobindo's recall—after uncovering traces of a nitrosamine-related impurity in certain batches of the product. 

PRINCETON, N.J.--( BUSINESS WIRE )-- Bristol Myers Squibb (NYSE: BMY) today announced the presentation of data across its cardiovascular portfolio at the American Heart Association (AHA) Annual Scientific Sessions, taking place November 16-18, 2024, in Chicago, Illinois. New analyses include updated results from the nearly two-year post-launch evaluation of the CAMZYOS ® (mavacamten) Risk Evaluation and Mitigation Strategy (REMS) Program and real-world and long-term extension data reinforcing the efficacy and safety profile of CAMZYOS, as well as data on behalf of the BMS-Pfizer Alliance on ELIQUIS ® (apixaban) and the BMS-Johnson & Johnson Collaboration on milvexian. “We look forward to AHA where we will share data that build on our 70-year legacy of pioneering cardiovascular research and delivering paradigm-changing medicines to address the growing burden of cardiovascular disease,” said Roland Chen, MD , senior vice president and head of Immunology, Cardiovascular & Neuroscience (ICN) Development at Bristol Myers Squibb. “Data to be presented at the meeting highlight our commitment to improving clinical outcomes for patients around the world by delivering transformational therapies, like CAMZYOS, the first and only approved cardiac myosin inhibitor.” With inclusion in both the ESC and AHA/ACC clinical guidelines as a recommended option for when symptoms persist after first-line therapy, CAMZYOS is a standard of care for NYHA class II-III symptomatic obstructive hypertrophic cardiomyopathy (oHCM). Research to be presented at the meeting supports the growing body of evidence of CAMZYOS, including compliance with the REMS Program. These data include: An updated analysis of results from the post-launch evaluation of the CAMZYOS REMS Program spanning nearly 2-years (22-months). A featured science presentation of the 128-week analysis (nearly 2.5 years) of the VALOR-HCM long-term study analyzing the efficacy and safety profile of CAMZYOS in reducing patient eligibility and/or decision to proceed with septal reduction therapy (SRT) in patients with symptomatic oHCM. New real-world evidence on CAMZYOS’ long-term effectiveness and safety profile, including data from MARVEL-HCM—the largest observational study on CAMZYOS’ effectiveness—and from COLLIGO-HCM, a real-world study examining racially diverse patients and those with higher disease burden than typically seen in clinical trials. Abstracts sponsored by Bristol Myers Squibb, the BMS-Pfizer Alliance and the BMS-Johnson & Johnson Collaboration to be presented at AHA Scientific Sessions 2024 can be found below. Complete abstracts may be accessed online here . Visit this page on BMS.com for more information on Bristol Myers Squibb’s scientific approach and resources on cardiovascular diseases. Abstract Title Primary Author Type Session Title Date/Time (CST) CAMZYOS (mavacamten) Investigating the natural history and risk factors underlying deterioration in early-stage hypertrophic cardiomyopathy: Findings from SOLENOID Bradlow, W. Moderated Poster Bulking Up: The Latest in Hypertrophic Cardiomyopathy Saturday, Nov. 16, 3:10 PM – 3:15 PM Beta blockers and calcium channel blockers in asymptomatic patients with hypertrophic cardiomyopathy: Prevalence, discontinuation, and effectiveness Bradlow, W. Moderated Poster Data to Discovery: Novel Methods in Cardiovascular Outcomes Research Saturday, Nov. 16, 3:50 PM – 3:55 PM Identification of obstructive and non-obstructive hypertrophic cardiomyopathy patients using natural language processing in a large integrated healthcare system Solomon, M. Moderated Poster Advances in Identification and Management of Hypertrophic Cardiomyopathy – MDP964 Sunday, Nov. 17, 9:30 AM – 9:35 AM Real-world treatment patterns of mavacamten and associated background therapies in patients with obstructive hypertrophic cardiomyopathy (HCM) in the United States Han, X. Traditional Poster Emerging Interventions for Heart Failure – Su2191 Sunday, Nov. 17, 3:15 PM – 4:15 PM Mavacamten: Real-world experience from 22 months of the Risk Evaluation and Mitigation Strategy (REMS) Program Desai, M. Oral Presentation From Bench to Bedside in Heart Failure Monday, Nov. 18, 9:00 AM – 9:10 AM Mavacamten treatment in patients with obstructive HCM referred for septal reduction therapy: 128-week results from VALOR-HCM trial Desai, M. Oral Featured Science Presentation Featured Science: Amyloid, Hypertrophic, and Danon Cardiomyopathies: Targeted Therapies and Specific Populations Monday, Nov. 18, 9:57 AM – 10:05 AM Long-term effectiveness and safety of mavacamten in a real-world, multi-center, global study: Preliminary results of COLLIGO-HCM from a diverse cohort in the United States MacNamara, J. Moderated Poster Hypertrophy and Heart Failure – MDP1368 Monday, Nov. 18, 11:50 AM – 11:55 AM Early insights on mavacamten usage in Canada: A retrospective cohort of the patient support program Ong, K. Moderated Poster Hypertrophy and Heart Failure – MDP1369 Monday, Nov. 18, 12:00 PM – 12:05 PM Real-world long-term effectiveness of mavacamten in patients with symptomatic obstructive hypertrophic cardiomyopathy: A multicenter observational study (MARVEL-HCM) Abraham, T. Moderated Poster Hypertrophy and Heart Failure – MDP1370 Monday, Nov. 18, 12:10 PM – 12:15 PM Integrated safety and tolerability of mavacamten treatment over 5 years in patients with obstructive hypertrophic cardiomyopathy Owens, A. Moderated Poster Hypertrophy and Heart Failure – MDP1371 Monday, Nov. 18, 12:20 PM – 12:25 PM Mavacamten in adolescent patients with symptomatic obstructive hypertrophic cardiomyopathy: Design of the Phase 3 SCOUT-HCM trial Rossano, J. Traditional Poster Pediatric Heart Failure, Transplantation, and Long-Term Outcomes – Mo2025 Monday, Nov. 18, 1:30 PM – 2:30 PM ELIQUIS (apixaban) – Sponsored by the Bristol Myers Squibb-Pfizer Alliance Understanding medication adherence to oral anticoagulants in atrial fibrillation management: Patient and provider perspectives in a mixed methods study Wendt, S. Moderated Poster Data to Discovery: Novel Methods in Cardiovascular Outcomes Research Monday, Nov. 18, 10:30 AM – 11:30 AM Milvexian – Sponsored by the Bristol Myers Squibb-Johnson & Johnson Collaboration Current oral anticoagulation use among patients with atrial fibrillation and risk factors associated with inadequate treatments: A report from a UK population cohort study Kang, A. Poster presentation Medications in Motion: Innovating Pharmacotherapy for Enhanced Treatment Outcomes Monday, Nov. 18, 1:30 PM – 2:30 PM About CAMZYOS ® (mavacamten) CAMZYOS ® (mavacamten) is the first and only cardiac myosin inhibitor approved in the U.S., indicated for the treatment of adults with symptomatic New York Heart Association (NYHA) class II-III obstructive hypertrophic cardiomyopathy (HCM) to improve functional capacity and symptoms, and in the European Union, indicated for the treatment of symptomatic (NYHA, class II-III) obstructive HCM in adult patients. It has also received regulatory approvals in countries and regions across five continents. CAMZYOS is an allosteric and reversible inhibitor selective for cardiac myosin. CAMZYOS modulates the number of myosin heads that can enter “on actin” (power-generating) states, thus reducing the probability of force-producing (systolic) and residual (diastolic) cross-bridge formation. Excess myosin actin cross-bridge formation and dysregulation of the super-relaxed state are mechanistic hallmarks of HCM. CAMZYOS shifts the overall myosin population towards an energy-sparing, recruitable, super-relaxed state. In HCM patients, myosin inhibition with CAMZYOS reduces dynamic left ventricular outflow tract (LVOT) obstruction and improves cardiac filling pressures. IMPORTANT SAFETY INFORMATION WARNING: RISK OF HEART FAILURE CAMZYOS reduces left ventricular ejection fraction (LVEF) and can cause heart failure due to systolic dysfunction. Echocardiogram assessments of LVEF are required prior to and during treatment with CAMZYOS. Initiation of CAMZYOS in patients with LVEF <55% is not recommended. Interrupt CAMZYOS if LVEF is <50% at any visit or if the patient experiences heart failure symptoms or worsening clinical status. Concomitant use of CAMZYOS with certain cytochrome P450 inhibitors or discontinuation of certain cytochrome P450 inducers may increase the risk of heart failure due to systolic dysfunction; therefore, the use of CAMZYOS is contraindicated with the following: Moderate to strong CYP2C19 inhibitors or strong CYP3A4 inhibitors Moderate to strong CYP2C19 inducers or moderate to strong CYP3A4 inducers Because of the risk of heart failure due to systolic dysfunction, CAMZYOS is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the CAMZYOS REMS PROGRAM. CONTRAINDICATIONS CAMZYOS is contraindicated with concomitant use of: Moderate to strong CYP2C19 inhibitors or strong CYP3A4 inhibitors Moderate to strong CYP2C19 inducers or moderate to strong CYP3A4 inducers WARNINGS AND PRECAUTIONS Heart Failure CAMZYOS reduces systolic contraction and can cause heart failure or totally block ventricular function. Patients who experience a serious intercurrent illness (e.g., serious infection) or arrhythmia (e.g., atrial fibrillation or other uncontrolled tachyarrhythmia) are at greater risk of developing systolic dysfunction and heart failure. Assess the patient’s clinical status and LVEF prior to and regularly during treatment and adjust the CAMZYOS dose accordingly. New or worsening arrhythmia, dyspnea, chest pain, fatigue, palpitations, leg edema, or elevations in N-terminal pro-B-type natriuretic peptide (NT-proBNP) may be signs and symptoms of heart failure and should also prompt an evaluation of cardiac function. Asymptomatic LVEF reduction, intercurrent illnesses, and arrhythmias require additional dosing considerations. Initiation of CAMZYOS in patients with LVEF <55% is not recommended. Avoid concomitant use of CAMZYOS in patients on disopyramide, ranolazine, verapamil with a beta blocker, or diltiazem with a beta blocker as these medications and combinations increase the risk of left ventricular systolic dysfunction and heart failure symptoms and clinical experience is limited. CYP 450 Drug Interactions Leading to Heart Failure or Loss of Effectiveness CAMZYOS is primarily metabolized by CYP2C19 and CYP3A4 enzymes. Concomitant use of CAMZYOS and drugs that interact with these enzymes may lead to life-threatening drug interactions such as heart failure or loss of effectiveness. Advise patients of the potential for drug interactions, including with over-the-counter medications (such as omeprazole, esomeprazole, or cimetidine). Advise patients to inform their healthcare provider of all concomitant products prior to and during CAMZYOS treatment. CAMZYOS Risk Evaluation and Mitigation Strategy (REMS) Program CAMZYOS is only available through a restricted program called the CAMZYOS REMS Program because of the risk of heart failure due to systolic dysfunction. Notable requirements of the CAMZYOS REMS Program include the following: Prescribers must be certified by enrolling in the REMS Program. Patients must enroll in the REMS Program and comply with ongoing monitoring requirements. Pharmacies must be certified by enrolling in the REMS Program and must only dispense to patients who are authorized to receive CAMZYOS. Wholesalers and distributors must only distribute to certified pharmacies. Further information is available at www.CAMZYOSREMS.com or by telephone at 1-833-628-7367. Embryo-Fetal Toxicity CAMZYOS may cause fetal toxicity when administered to a pregnant female, based on animal studies. Confirm absence of pregnancy in females of reproductive potential prior to treatment and advise patients to use effective contraception during treatment with CAMZYOS and for 4 months after the last dose. CHCs containing a combination of ethinyl estradiol and norethindrone may be used with CAMZYOS. However, CAMZYOS may reduce the effectiveness of combined hormonal contraceptives (CHC). If these CHCs are used, advise patients to add nonhormonal contraception (such as condoms) during concomitant use and for 4 months after the last dose of CAMZYOS. ADVERSE REACTIONS In the EXPLORER-HCM trial, adverse reactions occurring in >5% of patients and more commonly in the CAMZYOS group than in the placebo group were dizziness (27% vs 18%) and syncope (6% vs 2%). There were no new adverse reactions identified in VALOR-HCM. Effects on Systolic Function In the EXPLORER-HCM trial, mean (SD) resting LVEF was 74% (6) at baseline in both treatment groups. Mean (SD) absolute change from baseline in LVEF was -4% (8) in the CAMZYOS group and 0% (7) in the placebo group over the 30-week treatment period. At Week 38, following an 8-week interruption of trial drug, mean LVEF was similar to baseline for both treatment groups. In the EXPLORER-HCM trial, 7 (6%) patients in the CAMZYOS group and 2 (2%) patients in the placebo group experienced reversible reductions in LVEF <50% (median 48%: range 35-49%) while on treatment. In all 7 patients treated with CAMZYOS, LVEF recovered following interruption of CAMZYOS. DRUG INTERACTIONS Potential for Other Drugs to Affect Plasma Concentrations of CAMZYOS CAMZYOS is primarily metabolized by CYP2C19 and to a lesser extent by CYP3A4 and CYP2C9. Inducers and inhibitors of CYP2C19 and moderate to strong inhibitors or inducers of CYP3A4 may affect the exposures of CAMZYOS. Impact of Other Drugs on CAMZYOS: Moderate to Strong CYP2C19 Inhibitors or Strong CYP3A4 Inhibitors : Concomitant use increases CAMZYOS exposure, which may increase the risk of heart failure due to systolic dysfunction. Concomitant use is contraindicated. Moderate to Strong CYP2C19 Inducers or Moderate to Strong CYP3A4 Inducers : Concomitant use decreases CAMZYOS exposure, which may reduce CAMZYOS’ efficacy. The risk of heart failure due to systolic dysfunction may increase with discontinuation of these inducers as the levels of induced enzyme normalizes. Concomitant use is contraindicated. Weak CYP2C19 Inhibitors or Moderate CYP3A4 Inhibitors : Concomitant use with a weak CYP2C19 inhibitor or a moderate CYP3A4 inhibitor increases CAMZYOS exposure, which may increase the risk of adverse drug reactions. Initiate CAMZYOS at the recommended starting dose of 5 mg orally once daily in patients who are on stable therapy with a weak CYP2C19 inhibitor or a moderate CYP3A4 inhibitor. Reduce dose of CAMZYOS by one level (i.e., 15 to 10 mg, 10 to 5 mg, or 5 to 2.5 mg) in patients who are on CAMZYOS treatment and intend to initiate a weak CYP2C19 inhibitor or a moderate CYP3A4 inhibitor. Schedule clinical and echocardiographic assessment 4 weeks after inhibitor initiation, and do not up-titrate CAMZYOS until 12 weeks after inhibitor initiation. Avoid initiation of concomitant weak CYP2C19 and moderate CYP3A4 inhibitors in patients who are on stable treatment with 2.5 mg of CAMZYOS because a lower dose is not available. Potential for CAMZYOS to Affect Plasma Concentrations of Other Drugs CAMZYOS is an inducer of CYP3A4, CYP2C9, and CYP2C19. Concomitant use with CYP3A4, CYP2C19, or CYP2C9 substrates may reduce plasma concentration of these drugs. Closely monitor when CAMZYOS is used in combination with CYP3A4, CYP2C19, or CYP2C9 substrates unless otherwise recommended in the Prescribing Information. Certain Combined Hormonal Contraceptives (CHC): Progestin and ethinyl estradiol are CYP3A4 substrates. Concomitant use of CAMZYOS may decrease exposures of certain progestins, which may lead to contraceptive failure. CHCs containing a combination of ethinyl estradiol and norethindrone may be used with CAMZYOS, but if other CHCs are used, advise patients to add nonhormonal contraception (such as condoms) during concomitant use and for 4 months after the last dose of CAMZYOS. Drugs That Reduce Cardiac Contractility Expect additive negative inotropic effects of CAMZYOS and other drugs that reduce cardiac contractility. Avoid concomitant use of CAMZYOS in patients on disopyramide, ranolazine, verapamil with a beta blocker, or diltiazem with a beta blocker as these medications and combinations increase the risk of left ventricular systolic dysfunction and heart failure symptoms and clinical experience is limited. If concomitant therapy with a negative inotrope is initiated, or if the dose of a negative inotrope is increased, monitor LVEF closely until stable doses and clinical response have been achieved. SPECIFIC POPULATIONS Pregnancy CAMZYOS may cause fetal harm when administered to a pregnant female. Advise pregnant females about the potential risk to the fetus with maternal exposure to CAMZYOS during pregnancy. There is a pregnancy safety study for CAMZYOS. If CAMZYOS is administered during pregnancy, or if a patient becomes pregnant while receiving CAMZYOS or within 4 months after the last dose of CAMZYOS, healthcare providers should report CAMZYOS exposure by contacting Bristol Myers Squibb at 1-800-721-5072 or www.bms.com . Lactation The presence of CAMZYOS in human or animal milk, the drug’s effects on the breastfed infant, or the effects on milk production are unknown. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for CAMZYOS and any potential adverse effects on the breastfed child from CAMZYOS or from the underlying maternal condition. Females and Males of Reproductive Potential Confirm absence of pregnancy in females of reproductive potential prior to initiation of CAMZYOS. Advise females of reproductive potential to use effective contraception during treatment with CAMZYOS and for 4 months after the last dose. CHCs containing a combination of ethinyl estradiol and norethindrone may be used with CAMZYOS. However, CAMZYOS may reduce the effectiveness of certain other combined hormonal contraceptives (CHC). If these CHCs are used, advise patients to add nonhormonal contraception (such as condoms) during concomitant use and for 4 months after the last dose of CAMZYOS. Please see U.S. Full Prescribing Information , including Boxed WARNING and Medication Guide . About ELIQUIS ® (apixaban) ELIQUIS ® is an oral selective Factor Xa inhibitor. By inhibiting Factor Xa, a key blood clotting protein, ELIQUIS decreases thrombin generation and blood clot formation. ELIQUIS is approved for multiple indications in the U.S. based on efficacy and safety data from multiple Phase 3 clinical trials. ELIQUIS is a prescription medicine indicated to reduce the risk of stroke and systemic embolism in patients with non-valvular atrial fibrillation (NVAF); for the prophylaxis of deep vein thrombosis (DVT), which may lead to pulmonary embolism (PE), in patients who have undergone hip or knee replacement surgery; for the treatment of DVT and PE; and to reduce the risk of recurrent DVT and PE, following initial therapy. ELIQUIS continues to be developed and commercialized by The Bristol Myers Squibb-Pfizer Alliance. ELIQUIS Important Safety Information Indications ELIQUIS is indicated to reduce the risk of stroke and systemic embolism in patients with nonvalvular atrial fibrillation. ELIQUIS is indicated for the prophylaxis of deep vein thrombosis (DVT), which may lead to pulmonary embolism (PE), in patients who have undergone hip or knee replacement surgery. ELIQUIS is indicated for the treatment of DVT and PE, and to reduce the risk of recurrent DVT and PE following initial therapy. Important Safety Information WARNING: (A) PREMATURE DISCONTINUATION OF ELIQUIS INCREASES THE RISK OF THROMBOTIC EVENTS, (B) SPINAL/EPIDURAL HEMATOMA (A) Premature discontinuation of any oral anticoagulant, including ELIQUIS, increases the risk of thrombotic events. If anticoagulation with ELIQUIS is discontinued for a reason other than pathological bleeding or completion of a course of therapy, consider coverage with another anticoagulant. (B) Epidural or spinal hematomas may occur in patients treated with ELIQUIS who are receiving neuraxial anesthesia or undergoing spinal puncture. These hematomas may result in long-term or permanent paralysis. Consider these risks when scheduling patients for spinal procedures. Factors that can increase the risk of developing epidural or spinal hematomas in these patients include: use of indwelling epidural catheters concomitant use of other drugs that affect hemostasis, such as nonsteroidal anti-inflammatory drugs (NSAIDs), platelet inhibitors, other anticoagulants a history of traumatic or repeated epidural or spinal punctures a history of spinal deformity or spinal surgery optimal timing between the administration of ELIQUIS and neuraxial procedures is not known Monitor patients frequently for signs and symptoms of neurological impairment. If neurological compromise is noted, urgent treatment is necessary. Consider the benefits and risks before neuraxial intervention in patients anticoagulated or to be anticoagulated. CONTRAINDICATIONS Active pathological bleeding Severe hypersensitivity reaction to ELIQUIS (e.g., anaphylactic reactions) WARNINGS AND PRECAUTIONS Increased Risk of Thrombotic Events after Premature Discontinuation: Premature discontinuation of any oral anticoagulant, including ELIQUIS, in the absence of adequate alternative anticoagulation increases the risk of thrombotic events. An increased rate of stroke was observed during the transition from ELIQUIS to warfarin in clinical trials in atrial fibrillation patients. If ELIQUIS is discontinued for a reason other than pathological bleeding or completion of a course of therapy, consider coverage with another anticoagulant. Bleeding Risk: ELIQUIS increases the risk of bleeding and can cause serious, potentially fatal, bleeding. Concomitant use of drugs affecting hemostasis increases the risk of bleeding, including aspirin and other antiplatelet agents, other anticoagulants, heparin, thrombolytic agents, SSRIs, SNRIs, and NSAIDs. Advise patients of signs and symptoms of blood loss and to report them immediately or go to an emergency room. Discontinue ELIQUIS in patients with active pathological hemorrhage. The anticoagulant effect of apixaban can be expected to persist for at least 24 hours after the last dose (i.e., about two half-lives). An agent to reverse the anti-factor Xa activity of apixaban is available. Please visit www.andexxa.com for more information on availability of a specific reversal agent. Spinal/Epidural Anesthesia or Puncture: Patients treated with ELIQUIS undergoing spinal/epidural anesthesia or puncture may develop an epidural or spinal hematoma which can result in long-term or permanent paralysis. The risk of these events may be increased by the postoperative use of indwelling epidural catheters or the concomitant use of medicinal products affecting hemostasis. Indwelling epidural or intrathecal catheters should not be removed earlier than 24 hours after the last administration of ELIQUIS. The next dose of ELIQUIS should not be administered earlier than 5 hours after the removal of the catheter. The risk may also be increased by traumatic or repeated epidural or spinal puncture. If traumatic puncture occurs, delay the administration of ELIQUIS for 48 hours. Monitor patients frequently and if neurological compromise is noted, urgent diagnosis and treatment is necessary. Physicians should consider the potential benefit versus the risk of neuraxial intervention in ELIQUIS patients. Prosthetic Heart Valves: The safety and efficacy of ELIQUIS have not been studied in patients with prosthetic heart valves and is not recommended in these patients. Acute PE in Hemodynamically Unstable Patients or Patients who Require Thrombolysis or Pulmonary Embolectomy : Initiation of ELIQUIS is not recommended as an alternative to unfractionated heparin for the initial treatment of patients with PE who present with hemodynamic instability or who may receive thrombolysis or pulmonary embolectomy. Increased Risk of Thrombosis in Patients with Triple Positive Antiphospholipid Syndrome (APS): Direct-acting oral anticoagulants (DOACs), including ELIQUIS, are not recommended for use in patients with triple-positive APS. For patients with APS (especially those who are triple positive [positive for lupus anticoagulant, anticardiolipin, and anti–beta 2-glycoprotein I antibodies]), treatment with DOACs has been associated with increased rates of recurrent thrombotic events compared with vitamin K antagonist therapy. ADVERSE REACTIONS The most common and most serious adverse reactions reported with ELIQUIS were related to bleeding. TEMPORARY INTERRUPTION FOR SURGERY AND OTHER INTERVENTIONS ELIQUIS should be discontinued at least 48 hours prior to elective surgery or invasive procedures with a moderate or high risk of unacceptable or clinically significant bleeding. ELIQUIS should be discontinued at least 24 hours prior to elective surgery or invasive procedures with a low risk of bleeding or where the bleeding would be noncritical in location and easily controlled. Bridging anticoagulation during the 24 to 48 hours after stopping ELIQUIS and prior to the intervention is not generally required. ELIQUIS should be restarted after the surgical or other procedures as soon as adequate hemostasis has been established. DRUG INTERACTIONS Combined P-gp and Strong CYP3A4 Inhibitors: Inhibitors of P-glycoprotein (P-gp) and cytochrome P450 3A4 (CYP3A4) increase exposure to apixaban and increase the risk of bleeding. For patients receiving ELIQUIS doses of 5 mg or 10 mg twice daily, reduce the dose of ELIQUIS by 50% when ELIQUIS is coadministered with drugs that are combined P-gp and strong CYP3A4 inhibitors (e.g., ketoconazole, itraconazole, or ritonavir). In patients already taking 2.5 mg twice daily, avoid coadministration of ELIQUIS with combined P-gp and strong CYP3A4 inhibitors. Clarithromycin Although clarithromycin is a combined P-gp and strong CYP3A4 inhibitor, pharmacokinetic data suggest that no dose adjustment is necessary with concomitant administration with ELIQUIS. Combined P-gp and Strong CYP3A4 Inducers: Avoid concomitant use of ELIQUIS with combined P-gp and strong CYP3A4 inducers (e.g., rifampin, carbamazepine, phenytoin, St. John’s wort) because such drugs will decrease exposure to apixaban. Anticoagulants and Antiplatelet Agents: Coadministration of antiplatelet agents, fibrinolytics, heparin, aspirin, and chronic NSAID use increases the risk of bleeding. APPRAISE-2, a placebo-controlled clinical trial of apixaban in high-risk post-acute coronary syndrome patients treated with aspirin or the combination of aspirin and clopidogrel, was terminated early due to a higher rate of bleeding with apixaban compared to placebo. PREGNANCY The limited available data on ELIQUIS use in pregnant women are insufficient to inform drug-associated risks of major birth defects, miscarriage, or adverse developmental outcomes. Treatment may increase the risk of bleeding during pregnancy and delivery, and in the fetus and neonate. Labor or delivery: ELIQUIS use during labor or delivery in women who are receiving neuraxial anesthesia may result in epidural or spinal hematomas. Consider use of a shorter acting anticoagulant as delivery approaches. LACTATION Breastfeeding is not recommended during treatment with ELIQUIS. FEMALES AND MALES OF REPRODUCTIVE POTENTIAL Females of reproductive potential requiring anticoagulation should discuss pregnancy planning with their physician. The risk of clinically significant uterine bleeding, potentially requiring gynecological surgical interventions, identified with oral anticoagulants including ELIQUIS should be assessed in these patients and those with abnormal uterine bleeding. Please see U.S. Full Prescribing Information , including Boxed WARNINGS , available at BMS.com . About the Bristol Myers Squibb-Pfizer Collaboration The Bristol Myers Squibb-Pfizer Alliance (the Alliance) is committed to driving education and awareness about atrial fibrillation and deep vein thrombosis (DVT) and/or pulmonary embolism (PE). With long-standing cardiovascular leadership, global scale and expertise in this field, the Alliance strives to implement global, research-driven approaches to illuminate and address the unmet needs around strokes related to non-valvular atrial fibrillation, which are often fatal or debilitating. Through collaborations with non-profit organizations, the Alliance aims to provide patients, healthcare professionals and decision makers with the information they need to understand and take appropriate action on risk factors associated with stroke and other cardiovascular conditions. About Milvexian * Milvexian is an investigational oral, highly selective Factor XIa (FXIa) inhibitor, part of a new class of anticoagulants in development aimed at preventing harmful clotting that restricts blood flow (thrombosis) while preserving the normal clotting process (hemostasis). As a result, milvexian could potentially reduce major cardiovascular events due to harmful clotting without significantly increasing the risk of bleeding. It is currently being studied in the Phase 3 Librexia program, the most comprehensive FXIa clinical development program to date, for the prevention and treatment of major thrombotic conditions. * Milvexian is an investigational agent and has not been approved for use in any country, for any indication. About the Bristol Myers Squibb-Johnson & Johnson Collaboration Bristol Myers Squibb and Johnson & Johnson, two unsurpassed leaders in cardiovascular care, are determined to close the gap in unmet needs in thrombosis management by overcoming the limits of today’s treatments. The collaboration to develop and commercialize milvexian aims to leverage the combined scientific expertise and world-class commercial capabilities of each company, to improve patient outcomes. The alliance is uniquely equipped to deliver on the promise of FXIa inhibitors and is working diligently to ensure cutting-edge safe and effective treatment options are available for patients. About Bristol Myers Squibb Bristol Myers Squibb is a global biopharmaceutical company whose mission is to discover, develop and deliver innovative medicines that help patients prevail over serious diseases. For more information about Bristol Myers Squibb, visit us at BMS.com or follow us on LinkedIn , X , YouTube , Facebook and Instagram . Cautionary Statement Regarding Forward-Looking Statements This press release contains “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995 regarding, among other things, the research, development and commercialization of pharmaceutical products. All statements that are not statements of historical facts are, or may be deemed to be, forward-looking statements. Such forward-looking statements are based on current expectations and projections about our future financial results, goals, plans and objectives and involve inherent risks, assumptions and uncertainties, including internal or external factors that could delay, divert or change any of them in the next several years, that are difficult to predict, may be beyond our control and could cause our future financial results, goals, plans and objectives to differ materially from those expressed in, or implied by, the statements. These risks, assumptions, uncertainties and other factors include, among others, that future study results may not be consistent with the results to date, that milvexian may not receive regulatory approval for the indications described in this release, any marketing approvals, if granted, may have significant limitations on their use, and, whether CAMZYOS (mavacamten), ELIQUIS (apixaban) or milvexian, if approved, for such indications described in this release will be commercially successful. No forward-looking statement can be guaranteed. Forward-looking statements in this press release should be evaluated together with the many risks and uncertainties that affect Bristol Myers Squibb’s business and market, particularly those identified in the cautionary statement and risk factors discussion in Bristol Myers Squibb’s Annual Report on Form 10-K for the year ended December 31, 2023, as updated by our subsequent Quarterly Reports on Form 10-Q, Current Reports on Form 8-K and other filings with the Securities and Exchange Commission. The forward-looking statements included in this document are made only as of the date of this document and except as otherwise required by applicable law, Bristol Myers Squibb undertakes no obligation to publicly update or revise any forward-looking statement, whether as a result of new information, future events, changed circumstances or otherwise. corporatefinancial-news