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Expanded indication for this one-time infusion will provide more patients with a potential period away from their multiple myeloma treatment as early as first relapse Approval is based on results from the Phase 3 CARTITUDE-4 study, in which treatment with CARVYKTI® in 1-3 prior lines of therapy reduced the risk of disease progression or death by 59 percent compared to standard therapies HORSHAM, Pa., April 5, 2024 /PRNewswire/ -- Johnson & Johnson (NYSE: JNJ) announced today that the U.S. Food and Drug Administration (FDA) has approved CARVYKTI® (ciltacabtagene autoleucel; cilta-cel) for the treatment of adult patients with relapsed or refractory multiple myeloma who have received at least one prior line of therapy, including a proteasome inhibitor and an immunomodulatory agent, and are refractory to lenalidomide.1 With this approval, CARVYKTI® becomes the first and only B-cell maturation antigen (BCMA)-targeted therapy approved for the treatment of patients with multiple myeloma as early as first relapse. FDA approval is based on positive results from the Phase 3 CARTITUDE-4 study, which demonstrated that the earlier use of CARVYKTI® reduced the risk of disease progression or death by 59 percent compared to standard therapies—pomalidomide, bortezomib and dexamethasone (PVd) or daratumumab, pomalidomide and dexamethasone (DPd)—in adults with relapsed and lenalidomide-refractory multiple myeloma who received one to three prior lines of therapy.1 The study, which was presented at the 2023 American Society of Clinical Oncology (ASCO) Annual Meeting and published in The New England Journal of Medicine, also included and reported key secondary results such as overall response (OR) and overall survival (OS).1 "CARVYKTI demonstrated remarkable efficacy as a personalized, one-time infusion in the earlier treatment of relapsed/refractory multiple myeloma as shown through the CARTITUDE-4 study results," said Binod Dhakal, M.D., Associate Professor, Medical College of Wisconsin, Division of Hematology and Oncology.* "With this approval, I'm excited for patients who may have the opportunity for a treatment-free period for their multiple myeloma as early as first relapse, with the hope of eliminating the burden of having to be on continuous treatment while living with this challenging disease." More than 35,000 estimated new cases of multiple myeloma, an incurable blood cancer, will be diagnosed in 2024 in the United States.2 Real-world studies show that only an estimated 15 percent of patients initially diagnosed with multiple myeloma are able to start a 5th line of therapy.3 With this new indication, more patients will be able to access this innovative treatment. "This milestone underscores our commitment to improve outcomes for patients and transform the treatment of multiple myeloma with CARVYKTI," said Jordan Schecter, M.D., Vice President, Disease Area Leader, Multiple Myeloma, Johnson & Johnson Innovative Medicine. "We are proud to bring an important, highly effective immunotherapy that has demonstrated a favorable benefit/risk profile to physicians and patients for the earlier treatment of relapsed/refractory multiple myeloma, and we look forward to building on this latest milestone as we continue to focus on our ultimate goal of delivering a cure for multiple myeloma." CARVYKTI® is a cell therapy that works by harnessing a patient's immune system, or T cells, to fight the disease. Treatment requires extensive training, preparation, and certification to ensure a positive experience for patients. Since initial approval in February 2022, Johnson & Johnson has made significant advances in manufacturing to rapidly scale CARVYKTI® production. "We understand the urgency for patients in need of CARVYKTI, and we have been making considerable progress in increasing supply and availability in anticipation of this milestone approval," said Tyrone Brewer, President, U.S. Hematology, Johnson & Johnson Innovative Medicine. "We more than doubled manufacturing of CARVYKTI in 2023, we are striving to double again in 2024, and we will continue to invest in our capacity so we can provide this critical therapy to as many patients as possible." The safety profile for CARVYKTI® includes a boxed warning for Cytokine Release Syndrome (CRS), Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS), Parkinsonism and Guillain-Barre syndrome and their associated complications, Hemophagocytic Lymphohistiocytosis/Macrophage Activation Syndrome (HLH/MAS), Prolonged and Recurrent Cytopenias and Secondary Malignancies including myelodysplastic syndrome, acute myeloid leukemia and T-cell malignancies.1 Warnings and Precautions include Increased Early Mortality, Hypogammaglobulinemia, Infections, Hypersensitivity Reactions and Effects on Ability to Drive and Use Machines.1 The most common nonlaboratory adverse reactions (incidence greater than 20 percent) are pyrexia, cytokine release syndrome, hypogammaglobulinemia, hypotension, musculoskeletal pain, fatigue, infections-pathogen unspecified, cough, chills, diarrhea, nausea, encephalopathy, decreased appetite, upper respiratory tract infection, headache, tachycardia, dizziness, dyspnea, edema, viral infections, coagulopathy, constipation, and vomiting.1The most common Grade 3 or 4 laboratory adverse reactions (incidence greater than or equal to 50 percent) include lymphopenia, neutropenia, white blood cell decreased, thrombocytopenia, and anemia.1 About CARTITUDE-4 CARTITUDE-4 (NCT04181827) is the first international, randomized, open-label Phase 3 study evaluating the efficacy and safety of cilta-cel versus pomalidomide, bortezomib and dexamethasone (PVd) or daratumumab, pomalidomide and dexamethasone (DPd) in adult patients with relapsed and lenalidomide-refractory multiple myeloma who received one to three prior lines of therapy.4 Results were presented at the 2023 American Society of Clinical Oncology (ASCO) Annual Meeting and published in The New England Journal of Medicine. About CARVYKTI ® (ciltacabtagene autoleucel; cilta-cel) CARVYKTI® (cilta-cel) received U.S. Food and Drug Administration approval in February 2022 for the treatment of adults with relapsed or refractory multiple myeloma after four or more prior lines of therapy, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody.1 CARVYKTI® is now approved in the U.S. for the second-line treatment of adult patients with relapsed or refractory myeloma who have received at least one prior line of therapy including a proteasome inhibitor, an immunomodulatory agent, and who are refractory to lenalidomide. In addition to a unanimous (11 to 0) FDA Oncologic Drugs Advisory Committee (ODAC) recommendation in support of this new indication, in March 2024, the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) recommended the approval of a Type II variation for CARVYKTI® for the treatment of adults with relapsed and refractory multiple myeloma who have received at least one prior therapy, including an immunomodulatory agent and a proteasome inhibitor, have demonstrated disease progression on the last therapy, and are refractory to lenalidomide. In September 2022, Japan's Ministry of Health, Labour and Welfare (MHLW) approved CARVYKTI® for the treatment of adults with relapsed or refractory multiple myeloma in patients that have no history of CAR-positive T cell infusion therapy targeting BCMA and who have received three or more lines of therapies, including an immunomodulatory agent, a proteasome inhibitor and an anti-CD38 monoclonal antibody, and in whom multiple myeloma has not responded to or has relapsed following the most recent therapy. CARVYKTI® is a BCMA-directed, genetically modified autologous T-cell immunotherapy, which involves reprogramming a patient's own T-cells with a transgene encoding chimeric antigen receptor (CAR) that directs the CAR positive T cells to eliminate cells that express BCMA. BCMA is primarily expressed on the surface of malignant multiple myeloma B-lineage cells, as well as late-stage B cells and plasma cells. The CARVYKTI® CAR protein features two BCMA-targeting single domains designed to confer high avidity against human BCMA. Upon binding to BCMA-expressing cells, the CAR promotes T-cell activation, expansion, and elimination of target cells. In December 2017, Janssen Biotech, Inc., a Johnson & Johnson company, entered into an exclusive worldwide license and collaboration agreement with Legend Biotech USA, Inc. to develop and commercialize CARVYKTI®. For more information, visit . About Multiple Myeloma Multiple myeloma is an incurable blood cancer that affects a type of white blood cell called plasma cells, which are found in the bone marrow.5 In multiple myeloma, these plasma cells change, spread rapidly and replace normal cells in the bone marrow with tumors.6 In 2024, it is estimated that more than 35,000 people will be diagnosed with multiple myeloma, and more than 12,000 people will die from the disease in the U.S.2 While some people diagnosed with multiple myeloma initially have no symptoms, most patients are diagnosed due to symptoms that can include bone fracture or pain, low red blood cell counts, tiredness, high calcium levels, kidney problems, or infections.7,8 INDICATIONS AND USAGE CARVYKTI® (ciltacabtagene autoleucel) is a B-cell maturation antigen (BCMA)-directed genetically modified autologous T cell immunotherapy indicated for the treatment of adult patients with relapsed or refractory multiple myeloma, who have received at least 1 prior line of therapy, including a proteasome inhibitor and an immunomodulatory agent, and are refractory to lenalidomide. IMPORTANT SAFETY INFORMATION WARNINGS AND PRECAUTIONS Increased early mortality - In CARTITUDE-4, a (1:1) randomized controlled trial, there was a numerically higher percentage of early deaths in patients randomized to the CARVYKTI® treatment arm compared to the control arm. Among patients with deaths occurring within the first 10 months from randomization, a greater proportion (29/208; 14%) occurred in the CARVYKTI® arm compared to (25/211; 12%) in the control arm. Of the 29 deaths that occurred in the CARVYKTI® arm within the first 10 months of randomization, 10 deaths occurred prior to CARVYKTI® infusion, and 19 deaths occurred after CARVYKTI® infusion. Of the 10 deaths that occurred prior to CARVYKTI® infusion, all occurred due to disease progression, and none occurred due to adverse events. Of the 19 deaths that occurred after CARVYKTI® infusion, 3 occurred due to disease progression, and 16 occurred due to adverse events. The most common adverse events were due to infection (n=12). Cytokine release syndrome (CRS), including fatal or life-threatening reactions, occurred following treatment with CARVYKTI®. Among patients receiving CARVYKTI® for RRMM in the CARTITUDE-1 & 4 studies (N=285), CRS occurred in 84% (238/285), including ≥Grade 3 CRS (ASCT 2019) in 4% (11/285) of patients. Median time to onset of CRS, any grade, was 7 days (range: 1 to 23 days). CRS resolved in 82% with a median duration of 4 days (range: 1 to 97 days). The most common manifestations of CRS in all patients combined (≥10%) included fever (84%), hypotension (29%) and aspartate aminotransferase increased (11%). Serious events that may be associated with CRS include pyrexia, hemophagocytic lymphohistiocytosis, respiratory failure, disseminated intravascular coagulation, capillary leak syndrome, and supraventricular and ventricular tachycardia. CRS occurred in 78% of patients in CARTITUDE-4 (3% Grade 3 to 4) and in 95% of patients in CARTITUDE-1 (4% Grade 3 to 4). Identify CRS based on clinical presentation. Evaluate for and treat other causes of fever, hypoxia, and hypotension. CRS has been reported to be associated with findings of HLH/MAS, and the physiology of the syndromes may overlap. HLH/MAS is a potentially life-threatening condition. In patients with progressive symptoms of CRS or refractory CRS despite treatment, evaluate for evidence of HLH/MAS. Ensure that a minimum of two doses of tocilizumab are available prior to infusion of CARVYKTI®. Of the 285 patients who received CARVYKTI® in clinical trials, 53% (150/285) patients received tocilizumab; 35% (100/285) received a single dose, while 18% (50/285) received more than 1 dose of tocilizumab. Overall, 14% (39/285) of patients received at least one dose of corticosteroids for treatment of CRS. Monitor patients at least daily for 10 days following CARVYKTI® infusion at a REMS-certified healthcare facility for signs and symptoms of CRS. Monitor patients for signs or symptoms of CRS for at least 4 weeks after infusion. At the first sign of CRS, immediately institute treatment with supportive care, tocilizumab, or tocilizumab and corticosteroids. Counsel patients to seek immediate medical attention should signs or symptoms of CRS occur at any time. Neurologic toxicities, which may be severe, life-threatening, or fatal, occurred following treatment with CARVYKTI®. Neurologic toxicities included ICANS, neurologic toxicity with signs and symptoms of parkinsonism, GBS, immune mediated myelitis, peripheral neuropathies, and cranial nerve palsies. Counsel patients on the signs and symptoms of these neurologic toxicities, and on the delayed nature of onset of some of these toxicities. Instruct patients to seek immediate medical attention for further assessment and management if signs or symptoms of any of these neurologic toxicities occur at any time. Among patients receiving CARVYKTI® in the CARTITUDE-1 & 4 studies for RRMM, one or more neurologic toxicities occurred in 24% (69/285), including ≥Grade 3 cases in 7% (19/285) of patients. Median time to onset was 10 days (range: 1 to 101) with 63/69 (91%) of cases developing by 30 days. Neurologic toxicities resolved in 72% (50/69) of patients with a median duration to resolution of 23 days (range: 1 to 544). Of patients developing neurotoxicity, 96% (66/69) also developed CRS. Subtypes of neurologic toxicities included ICANS in 13%, peripheral neuropathy in 7%, cranial nerve palsy in 7%, parkinsonism in 3%, and immune mediated myelitis in 0.4% of the patients. Immune Effector Cell-associated Neurotoxicity Syndrome (ICANS): Patients receiving CARVYKTI® may experience fatal or life-threatening ICANS following treatment with CARVYKTI®, including before CRS onset, concurrently with CRS, after CRS resolution, or in the absence of CRS. Among patients receiving CARVYKTI® in the CARTITUDE-1 & 4 studies, ICANS occurred in 13% (36/285), including Grade ≥3 in 2% (6/285) of the patients. Median time to onset of ICANS was 8 days (range: 1 to 28 days). ICANS resolved in 30 of 36 (83%) of patients with a median time to resolution of 3 days (range: 1 to 143 days). Median duration of ICANS was 6 days (range: 1 to 1229 days) in all patients including those with ongoing neurologic events at the time of death or data cut off. Of patients with ICANS 97% (35/36) had CRS. The onset of ICANS occurred during CRS in 69% of patients, before and after the onset of CRS in 14% of patients respectively. Immune Effector Cell-associated Neurotoxicity Syndrome occurred in 7% of patients in CARTITUDE-4 (0.5% Grade 3) and in 23% of patients in CARTITUDE-1 (3% Grade 3). The most frequent ≥2% manifestations of ICANS included encephalopathy (12%), aphasia (4%), headache (3%), motor dysfunction (3%), ataxia (2%) and sleep disorder (2%). Monitor patients at least daily for 10 days following CARVYKTI® infusion at the REMS-certified healthcare facility for signs and symptoms of ICANS. Rule out other causes of ICANS symptoms. Monitor patients for signs or symptoms of ICANS for at least 4 weeks after infusion and treat promptly. Neurologic toxicity should be managed with supportive care and/or corticosteroids as needed. Parkinsonism: Neurologic toxicity with parkinsonism has been reported in clinical trials of CARVYKTI®. Among patients receiving CARVYKTI® in the CARTITUDE-1 & 4 studies, parkinsonism occurred in 3% (8/285), including Grade ≥ 3 in 2% (5/285) of the patients. Median time to onset of parkinsonism was 56 days (range: 14 to 914 days). Parkinsonism resolved in 1 of 8 (13%) of patients with a median time to resolution of 523 days. Median duration of parkinsonism was 243.5 days (range: 62 to 720 days) in all patients including those with ongoing neurologic events at the time of death or data cut off. The onset of parkinsonism occurred after CRS for all patients and after ICANS for 6 patients. Parkinsonism occurred in 1% of patients in CARTITUDE-4 (no Grade 3 to 4) and in 6% of patients in CARTITUDE-1 (4% Grade 3 to 4). Manifestations of parkinsonism included movement disorders, cognitive impairment, and personality changes. Monitor patients for signs and symptoms of parkinsonism that may be delayed in onset and managed with supportive care measures. There is limited efficacy information with medications used for the treatment of Parkinson's disease for the improvement or resolution of parkinsonism symptoms following CARVYKTI® treatment. Guillain-Barré syndrome: A fatal outcome following GBS occurred following treatment with CARVYKTI® despite treatment with intravenous immunoglobulins. Symptoms reported include those consistent with Miller-Fisher variant of GBS, encephalopathy, motor weakness, speech disturbances, and polyradiculoneuritis. Monitor for GBS. Evaluate patients presenting with peripheral neuropathy for GBS. Consider treatment of GBS with supportive care measures and in conjunction with immunoglobulins and plasma exchange, depending on severity of GBS. Immune mediated myelitis: Grade 3 myelitis occurred 25 days following treatment with CARVYKTI® in CARTITUDE-4 in a patient who received CARVYKTI® as subsequent therapy. Symptoms reported included hypoesthesia of the lower extremities and the lower abdomen with impaired sphincter control. Symptoms improved with the use of corticosteroids and intravenous immune globulin. Myelitis was ongoing at the time of death from other cause. Peripheral neuropathy occurred following treatment with CARVYKTI®. Among patients receiving CARVYKTI® in the CARTITUDE-1 & 4 studies, peripheral neuropathy occurred in 7% (21/285), including Grade ≥3 in 1% (3/285) of the patients. Median time to onset of peripheral neuropathy was 57 days (range: 1 to 914 days). Peripheral neuropathy resolved in 11 of 21 (52%) of patients with a median time to resolution of 58 days (range: 1 to 215 days). Median duration of peripheral neuropathy was 149.5 days (range: 1 to 692 days) in all patients including those with ongoing neurologic events at the time of death or data cut off. Peripheral neuropathies occurred in 7% of patients in CARTITUDE-4 (0.5% Grade 3 to 4) and in 7% of patients in CARTITUDE-1 (2% Grade 3 to 4). Monitor patients for signs and symptoms of peripheral neuropathies. Patients who experience peripheral neuropathy may also experience cranial nerve palsies or GBS. Cranial nerve palsies occurred following treatment with CARVYKTI®. Among patients receiving CARVYKTI® in the CARTITUDE-1 & 4 studies, cranial nerve palsies occurred in 7% (19/285), including Grade ≥3 in 1% (1/285) of the patients. Median time to onset of cranial nerve palsies was 21 days (range: 17 to 101 days). Cranial nerve palsies resolved in 17 of 19 (89%) of patients with a median time to resolution of 66 days (range: 1 to 209 days). Median duration of cranial nerve palsies was 70 days (range: 1 to 262 days) in all patients including those with ongoing neurologic events at the time of death or data cut off. Cranial nerve palsies occurred in 9% of patients in CARTITUDE-4 (1% Grade 3 to 4) and in 3% of patients in CARTITUDE-1 (1% Grade 3 to 4). The most frequent cranial nerve affected was the 7th cranial nerve. Additionally, cranial nerves III, V, and VI have been reported to be affected. Monitor patients for signs and symptoms of cranial nerve palsies. Consider management with systemic corticosteroids, depending on the severity and progression of signs and symptoms. Hemophagocytic Lymphohistiocytosis (HLH)/Macrophage Activation Syndrome (MAS): Among patients receiving CARVYKTI® in the CARTITUDE-1 & 4 studies, HLH/MAS occurred in 1% (3/285) of patients. All events of HLH/MAS had onset within 99 days of receiving CARVYKTI®, with a median onset of 10 days (range: 8 to 99 days) and all occurred in the setting of ongoing or worsening CRS. The manifestations of HLH/MAS included hyperferritinemia, hypotension, hypoxia with diffuse alveolar damage, coagulopathy and hemorrhage, cytopenia and multi-organ dysfunction, including renal dysfunction and respiratory failure. Patients who develop HLH/MAS have an increased risk of severe bleeding. Monitor hematologic parameters in patients with HLH/MAS and transfuse per institutional guidelines. Fatal cases of HLH/MAS occurred following treatment with CARVYKTI®. HLH is a life-threatening condition with a high mortality rate if not recognized and treated early. Treatment of HLH/MAS should be administered per institutional standards. CARVYKTI® REMS: Because of the risk of CRS and neurologic toxicities, CARVYKTI® is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the CARVYKTI® REMS. Further information is available at or 1-844-672-0067. Prolonged and Recurrent Cytopenias: Patients may exhibit prolonged and recurrent cytopenias following lymphodepleting chemotherapy and CARVYKTI® infusion. Among patients receiving CARVYKTI® in the CARTITUDE-1 & 4 studies, Grade 3 or higher cytopenias not resolved by day 30 following CARVYKTI® infusion occurred in 62% (176/285) of the patients and included thrombocytopenia 33% (94/285), neutropenia 27% (76/285), lymphopenia 24% (67/285) and anemia 2% (6/285). After Day 60 following CARVYKTI® infusion 22%, 20%, 5%, and 6% of patients had a recurrence of Grade 3 or 4 lymphopenia, neutropenia, thrombocytopenia, and anemia respectively, after initial recovery of their Grade 3 or 4 cytopenia. Seventy-seven percent (219/285) of patients had one, two or three or more recurrences of Grade 3 or 4 cytopenias after initial recovery of Grade 3 or 4 cytopenia. Sixteen and 25 patients had Grade 3 or 4 neutropenia and thrombocytopenia, respectively, at the time of death. Monitor blood counts prior to and after CARVYKTI® infusion. Manage cytopenias with growth factors and blood product transfusion support according to local institutional guidelines. Infections: CARVYKTI® should not be administered to patients with active infection or inflammatory disorders. Severe, life-threatening, or fatal infections, occurred in patients after CARVYKTI® infusion. Among patients receiving CARVYKTI® in the CARTITUDE-1 & 4 studies, infections occurred in 57% (163/285), including ≥Grade 3 in 24% (69/285) of patients. Grade 3 or 4 infections with an unspecified pathogen occurred in 12%, viral infections in 6%, bacterial infections in 5%, and fungal infections in 1% of patients. Overall, 5% (13/285) of patients had Grade 5 infections, 2.5% of which were due to COVID-19. Patients treated with CARVYKTI® had an increased rate of fatal COVID-19 infections compared to the standard therapy arm. Monitor patients for signs and symptoms of infection before and after CARVYKTI® infusion and treat patients appropriately. Administer prophylactic, pre-emptive and/or therapeutic antimicrobials according to the standard institutional guidelines. Febrile neutropenia was observed in 5% of patients after CARVYKTI® infusion and may be concurrent with CRS. In the event of febrile neutropenia, evaluate for infection and manage with broad-spectrum antibiotics, fluids and other supportive care, as medically indicated. Counsel patients on the importance of prevention measures. Follow institutional guidelines for the vaccination and management of immunocompromised patients with COVID-19. Viral Reactivation: Hepatitis B virus (HBV) reactivation, in some cases resulting in fulminant hepatitis, hepatic failure and death, can occur in patients with hypogammaglobulinemia. Perform screening for Cytomegalovirus (CMV), HBV, hepatitis C virus (HCV), and human immunodeficiency virus (HIV) or any other infectious agents if clinically indicated in accordance with clinical guidelines before collection of cells for manufacturing. Consider antiviral therapy to prevent viral reactivation per local institutional guidelines/clinical practice. Hypogammaglobulinemia: can occur in patients receiving treatment with CARVYKTI®. Among patients receiving CARVYKTI® in the CARTITUDE-1 & 4 studies, hypogammaglobulinemia adverse event was reported in 36% (102/285) of patients; laboratory IgG levels fell below 500mg/dl after infusion in 93% (265/285) of patients. Hypogammaglobulinemia either as an adverse reaction or laboratory IgG level below 500mg/dl, after infusion occurred in 94% (267/285) of patients treated. Fifty six percent (161/285) of patients received intravenous immunoglobulin (IVIG) post CARVYKTI® for either an adverse reaction or prophylaxis. Monitor immunoglobulin levels after treatment with CARVYKTI® and administer IVIG for IgG <400 mg/dL. Manage per local institutional guidelines, including infection precautions and antibiotic or antiviral prophylaxis. Use of Live Vaccines: The safety of immunization with live viral vaccines during or following CARVYKTI® treatment has not been studied. Vaccination with live virus vaccines is not recommended for at least 6 weeks prior to the start of lymphodepleting chemotherapy, during CARVYKTI® treatment, and until immune recovery following treatment with CARVYKTI®. Hypersensitivity Reactions occurred following treatment with CARVYKTI®. Among patients receiving CARVYKTI® in the CARTITUDE-1 & 4 studies, hypersensitivity reactions occurred in 5% (13/285), all of which were ≤Grade 2. Manifestations of hypersensitivity reactions included flushing, chest discomfort, tachycardia, wheezing, tremor, burning sensation, non-cardiac chest pain, and pyrexia. Serious hypersensitivity reactions, including anaphylaxis, may be due to the dimethyl sulfoxide (DMSO) in CARVYKTI®. Patients should be carefully monitored for 2 hours after infusion for signs and symptoms of severe reaction. Treat promptly and manage patients appropriately according to the severity of the hypersensitivity reaction. Secondary Malignancies: Patients treated with CARVYKTI® may develop secondary malignancies. Among patients receiving CARVYKTI® in the CARTITUDE-1 & 4 studies, myeloid neoplasms occurred in 5% (13/285) of patients (9 cases of myelodysplastic syndrome, 3 cases of acute myeloid leukemia, and 1 case of myelodysplastic syndrome followed by acute myeloid leukemia). The median time to onset of myeloid neoplasms was 447 days (range: 56 to 870 days) after treatment with CARVYKTI®. Ten of these 13 patients died following the development of myeloid neoplasms; 2 of the 13 cases of myeloid neoplasm occurred after initiation of subsequent antimyeloma therapy. Cases of myelodysplastic syndrome and acute myeloid leukemia have also been reported in the post marketing setting. T-cell malignancies have occurred following treatment of hematologic malignancies with BCMA- and CD19-directed genetically modified autologous T-cell immunotherapies, including CARVYKTI®. Mature T-cell malignancies, including CAR-positive tumors, may present as soon as weeks following infusions, and may include fatal outcomes. Monitor life-long for secondary malignancies. In the event that a secondary malignancy occurs, contact Janssen Biotech, Inc. at 1-800-526-7736 for reporting and to obtain instructions on collection of patient samples. Effects on Ability to Drive and Use Machines: Due to the potential for neurologic events, including altered mental status, seizures, neurocognitive decline or neuropathy, patients receiving CARVYKTI® are at risk for altered or decreased consciousness or coordination in the 8 weeks following CARVYKTI® infusion. Advise patients to refrain from driving and engaging in hazardous occupations or activities, such as operating heavy or potentially dangerous machinery during this initial period, and in the event of new onset of any neurologic toxicities. ADVERSE REACTIONS The most common nonlaboratory adverse reactions (incidence greater than 20%) are pyrexia, cytokine release syndrome, hypogammaglobulinemia, hypotension, musculoskeletal pain, fatigue, infections-pathogen unspecified, cough, chills, diarrhea, nausea, encephalopathy, decreased appetite, upper respiratory tract infection, headache, tachycardia, dizziness, dyspnea, edema, viral infections, coagulopathy, constipation, and vomiting. The most common Grade 3 or 4 laboratory adverse reactions (incidence greater than or equal to 50%) include lymphopenia, neutropenia, white blood cell decreased, thrombocytopenia, and anemia. Please read full Prescribing Information, including Boxed Warning, for CARVYKTI®. About Johnson & Johnson At Johnson & Johnson, we believe health is everything. Our strength in healthcare innovation empowers us to build a world where complex diseases are prevented, treated, and cured, where treatments are smarter and less invasive, and solutions are personal. Through our expertise in Innovative Medicine and MedTech, we are uniquely positioned to innovate across the full spectrum of healthcare solutions today to deliver the breakthroughs of tomorrow, and profoundly impact health for humanity. Learn more at or at . Follow us at @JanssenUS and @JNJInnovMed. Janssen Research & Development, LLC, and Janssen Biotech, Inc., are both Johnson & Johnson companies. Cautions Concerning Forward-Looking Statements This press release contains "forward-looking statements" as defined in the Private Securities Litigation Reform Act of 1995 regarding product development of CARVYKTI®. The reader is cautioned not to rely on these forward-looking statements. These statements are based on current expectations of future events. If underlying assumptions prove inaccurate or known or unknown risks or uncertainties materialize, actual results could vary materially from the expectations and projections of Janssen Research & Development, LLC, Janssen Biotech, Inc., and/or Johnson & Johnson. Risks and uncertainties include, but are not limited to: challenges and uncertainties inherent in product research and development, including the uncertainty of clinical success and of obtaining regulatory approvals; uncertainty of commercial success; manufacturing difficulties and delays; competition, including technological advances, new products and patents attained by competitors; challenges to patents; product efficacy or safety concerns resulting in product recalls or regulatory actions; changes in behavior and spending patterns of purchasers of health care products and services; changes to applicable laws and regulations, including global health care reforms; and trends toward health care cost containment. A further list and descriptions of these risks, uncertainties and other factors can be found in Johnson & Johnson's Annual Report on Form 10-K for the fiscal year ended December 31, 2023, including in the sections captioned "Cautionary Note Regarding Forward-Looking Statements" and "Item 1A. Risk Factors," and in Johnson & Johnson's subsequent Quarterly Reports on Form 10-Q and other filings with the Securities and Exchange Commission. Copies of these filings are available online at , or on request from Johnson & Johnson. None of Janssen Research & Development, LLC, Janssen Biotech, Inc. nor Johnson & Johnson undertakes to update any forward-looking statement as a result of new information or future events or developments. * Dr. Dhakal has provided consulting, advisory, and speaking services to Johnson & Johnson; he has not been paid for any media work. CARVYKTI® [Prescribing Information]. Horsham, PA: Janssen Biotech Inc. American Cancer Society. Key statistics about multiple myeloma. Accessed March 2024. Fonseca R, Usmani S, Mehra M, et al. Frontline treatment patterns and attrition rates by subsequent lines of therapy in patients with newly diagnosed multiple myeloma. 2020. Accessed March 2024. . ClinicalTrials.Gov. A study comparing JNJ-68284528, a CAR-T therapy directed against B-cell maturation antigen (BCMA), versus pomalidomide, bortezomib and dexamethasone (PVd) or daratumumab, pomalidomide and dexamethasone (DPd) in participants with relapsed and lenalidomide-refractory multiple myeloma (CARTITUDE-4). Accessed March 2024. Gandhi U, Cornell R, Lakshman A, et al. Outcomes of patients with multiple myeloma refractory to CD38-targeted monoclonal antibody therapy. Leukemia. 2019;33(9). Accessed March 2024. National Cancer Institute. Plasma Cell Neoplasms. . Accessed March 2024. American Cancer Society. What is Multiple Myeloma? . Accessed March 2024. American Cancer Society. Multiple Myeloma Early Detection, Diagnosis, and Staging. . Accessed March 2024. SOURCE Johnson & Johnson

来源：国家药监局   编辑：wangxinglai2004 2024年034月01日，国家药监局发布公告，根据药品不良反应评估结果，国家药监局决定对西沙必利口服制剂（包括西沙必利片和西沙必利胶囊）、替硝唑注射剂（包括替硝唑氯化钠注射液、替硝唑葡萄糖注射液、注射用替硝唑）说明书内容进行统一修订，要求MAH于2024年6月21日前完成完成修订后说明书备案，备案后9个月内对已出厂的药品说明书及标签予以更换。01 西沙必利口服制剂根据药品不良反应评估结果，为进一步保障公众用药安全，国家药监局决定对西沙必利口服制剂（包括西沙必利片和西沙必利胶囊）说明书内容进行统一修订。现将有关事项公告如下：  一、所有上述药品的上市许可持有人均应当依据《药品注册管理办法》等有关规定，按照附件要求修订说明书，于2024年6月21日前报省级药品监督管理部门备案。  修订内容涉及药品标签的，应当一并进行修订；说明书及标签其他内容应当与原批准内容一致。在备案之日起生产的药品，不得继续使用原药品说明书。药品上市许可持有人应当在备案后9个月内对已出厂的药品说明书及标签予以更换。  二、药品上市许可持有人应当对新增不良反应发生机制开展深入研究，采取有效措施做好药品使用和安全性问题的宣传培训，指导医师、药师合理用药。  三、临床医师、药师应当仔细阅读上述药品说明书的修订内容，在选择用药时，应当根据新修订说明书进行充分的获益/风险分析。  四、患者用药前应当仔细阅读药品说明书，使用处方药的，应当严格遵医嘱用药。  五、省级药品监督管理部门应当督促行政区域内上述药品的上市许可持有人按要求做好相应说明书修订和标签、说明书更换工作，对违法违规行为依法严厉查处。    西沙必利片、西沙必利胶囊说明书  修订要求  一、【警示语】项增加以下内容  西沙必利有引起QT间期延长和严重或致命的心律失常的潜在风险，临床使用前应权衡利弊。  二、【不良反应】项增加以下内容  在国内上市的西沙必利口服制剂监测到如下不良反应/事件，由于这些不良反应/事件是在无法确定总数的人群中自发报告的，因此不能准确估算其发生率：  心血管系统：心悸、胸部不适、QT间期延长、心动过速、心律失常。  胃肠系统：口干、恶心、呕吐、消化不良、肠胃胀气、腹痛、便秘。  皮肤及皮下组织：红斑性皮疹、斑丘疹、多汗、面部水肿。  神经系统：嗜睡、失眠、感觉减退、眩晕。  全身性反应：发热、乏力、胸部不适、疼痛。  其他：呼吸困难、过敏样反应。  三、【注意事项】项增加以下内容  具有以下心律失常危险因素的患者，应慎重使用。  严重心脏病史，包括严重室性心律失常、二度或三度房室传导阻滞、窦房结功能障碍、充血性心力衰竭、缺血性心脏病；  猝死家庭史；  肾衰竭，尤其是进行长期透析的患者；  慢性阻塞性肺疾病和呼吸衰竭；  电解质紊乱的危险因素，如服用排钾利尿药；  胰岛素用量的剧烈调整；  持续性呕吐和/或腹泻。  （注：如原批准说明书的安全性内容较本修订要求更全面或更严格的，应保留原批准内容。说明书其他内容如与上述修订要求不一致的，应当一并进行修订。）02 替硝唑注射剂  根据药品不良反应评估结果，为进一步保障公众用药安全，国家药监局决定对替硝唑注射剂（包括替硝唑氯化钠注射液、替硝唑葡萄糖注射液、注射用替硝唑）说明书内容进行统一修订。现将有关事项公告如下：  一、所有上述药品的上市许可持有人均应当依据《药品注册管理办法》等有关规定，按照附件要求修订说明书，于2024年6月21日前报省级药品监督管理部门备案。  修订内容涉及药品标签的，应当一并进行修订；说明书及标签其他内容应当与原批准内容一致。在备案之日起生产的药品，不得继续使用原药品说明书。药品上市许可持有人应当在备案后9个月内对已出厂的药品说明书及标签予以更换。  二、药品上市许可持有人应当对新增不良反应发生机制开展深入研究，采取有效措施做好药品使用和安全性问题的宣传培训，指导医师、药师合理用药。  三、临床医师、药师应当仔细阅读上述药品说明书的修订内容，在选择用药时，应当根据新修订说明书进行充分的获益/风险分析。  四、患者用药前应当仔细阅读药品说明书，使用处方药的，应当严格遵医嘱用药。  五、省级药品监督管理部门应当督促行政区域内上述药品的上市许可持有人按要求做好相应说明书修订和标签、说明书更换工作，对违法违规行为依法严厉查处。   替硝唑注射剂说明书修订要求  一、增加黑框警告  二、【不良反应】项下修订为以下内容  在本品治疗期间报道过以下不良反应：  胃肠系统：恶心、呕吐、腹痛、腹部不适、腹胀、腹泻、反酸或食物反流、呃逆、消化不良、食欲减退、便秘、口唇麻木、口腔异味、口干、口腔炎。  皮肤及皮下组织：皮疹（如红斑、斑丘疹、水疱疹等）、瘙痒、皮肤肿胀、皮肤潮红、多汗、荨麻疹、血管性水肿、过敏性紫癜、多形性红斑、剥脱性皮炎、急性全身性发疹性脓疱病、史蒂文斯-约翰逊综合征。  精神及神经系统：头晕、头痛、味觉倒错、感觉减退、周围神经病变、烧灼感、抽搐、震颤、惊厥发作、意识丧失、晕厥、共济失调、言语障碍、嗜睡、困倦、失眠、烦躁不安、意识模糊状态、躁动、谵妄、幻觉。  全身性及给药部位反应：胸部不适、胸痛、寒战、发热、水肿、乏力、不适、疲劳、注射部位反应（静脉炎、疼痛、肿胀、皮疹、瘙痒等）。  免疫系统：过敏反应、过敏性休克，有死亡病例报告。  心血管系统：心悸、心动过速、血管性疼痛、血压降低、血压升高。  呼吸系统：呼吸困难、呼吸急促、窒息感、喉水肿、咳嗽、鼻塞、咽干、口咽疼痛。  眼部：视觉损害、视物模糊、眼睑水肿、眼睑瘙痒、眼眶周围水肿、结膜充血。  骨骼肌肉系统：肌无力、肌痛、肌痉挛、关节痛。  肝胆系统：肝功能异常、肝酶升高。  泌尿系统：尿频、血尿、尿液发黑。  血液系统：白细胞减少、粒细胞减少症、血小板减少症。  其他：眩晕、耳鸣、听觉减退、双硫仑样反应、念珠菌感染、外阴阴道瘙痒、肿胀。  三、【禁忌】项下修订为以下内容：  1.对替硝唑或吡咯类药物过敏者、对本品中其他成份过敏者以及器质性中枢神经疾病患者禁用。  2.与其他结构相似药物一样，有血液不调或恶病质史的患者禁用。尽管目前的动物和临床研究中尚未发现导致长期血液病的例子。  3.妊娠早期（妊娠前3个月）的孕妇禁用。  4.哺乳期妇女禁用。除非在替硝唑治疗期间及停药后3天内暂停母乳喂养。  四、【注意事项】项下应包含以下内容  1.在接受替硝唑治疗的患者中，有惊厥发作和周围神经病变的报道，后者主要症状有四肢麻木或感觉异常。如果出现任何异常精神症状或神经系统症状/体征，如共济失调、头晕、意识混乱等，应立即停用替硝唑。  2.在替硝唑治疗之前、期间和之后72小时内不应饮用酒精饮料或含酒精产品，因为可能出现腹部绞痛、恶心、呕吐、头痛、心动过速、面部潮红等。  3.念珠菌感染者应用本品，其症状会加重，需同时给予抗真菌治疗。治疗阴道滴虫病时需同时治疗其性伙伴。  4.据报道，在科克因（Cockayne）综合征患者中，使用与替硝唑结构相似的甲硝唑后，出现了严重的不可逆的肝毒性/急性肝衰竭，并伴有致命后果。  五、【药物相互作用】项下修订为以下内容  以下是关于甲硝唑的药物相互作用的报道，甲硝唑是一种与替硝唑有化学相关性的硝基咪唑类药物，因此以下报道可能也会发生于替硝唑中。  1.替硝唑对其他药物的潜在影响  华法林和其他口服香豆素抗凝血药：鉴于甲硝唑的相关报道，替硝唑可以增强华法林及其他香豆素抗凝血剂的药效，从而导致凝血酶原时间延长。在替硝唑治疗期间及其停药后8天内，抗凝血剂用量可能需要调整。  酒精、双硫仑：在替硝唑治疗期间及停药后3天内应避免饮用酒精饮料以及任何含有酒精或丙二醇的制剂，否则可能出现腹部绞痛、恶心、呕吐、头痛、潮红的反应。据报道，酗酒患者同时服用甲硝唑和双硫仑会出现精神病反应。虽然替硝唑未见类似报道，但仍不应给近两周内服用过双硫仑的患者使用替硝唑。  锂：据报道，甲硝唑提高血清锂的水平。目前尚未知替硝唑是否也有相同的性质，但是建议同时使用锂和替硝唑的患者在治疗几天后做血清锂和肌酸酐的检查，以监测潜在的锂中毒危险。  环孢菌素、他克莫司：据一些报道显示，甲硝唑有可能提高环孢菌素和他克莫司的水平。在替硝唑与此任意一种联合给药时，应监测这些患者免疫抑制药物的毒性反应。  氟尿嘧啶：研究显示甲硝唑会降低氟尿嘧啶的清除率从而导致对治疗效果无益反而增加其副作用，如果不可避免的要将替硝唑与氟尿嘧啶联合用药，应监测患者的氟尿嘧啶相关的毒性反应。  2.其他药物对替硝唑的潜在影响  CYP3A4诱导剂/抑制剂：替硝唑与诱导肝微粒体酶的药物联合给药，即CYP3A4诱导剂，如苯巴比妥、利福平、苯妥英、磷苯妥英（一种苯妥英的前体药物），可能加速替硝唑的消除，降低血浆中替硝唑的水平。替硝唑与抑制肝微粒体酶活性的药物联合给药，即CYP3A4抑制剂如西咪替丁和酮康唑，可能会延长替硝唑的半衰期并降低其血浆清除率，从而增加替硝唑在血浆中的浓度。  土霉素：据报道，土霉素会拮抗甲硝唑的治疗效果。  3.实验室试验的药物相互作用  与甲硝唑类似，替硝唑也可能干扰某些特定血清生化指标的测定，如谷氨酸氨基转移酶（AST）、丙氨酸氨基转移酶（ALT）、乳酸脱氢酶（LDH）、甘油三酯和葡萄糖己糖激酶。可能观测到零值。所有有干扰现象报道的含量测定试验，都涉及到了烟酰胺腺嘌呤二核苷酸的氧化还原反应过程中（NAD+NADH）酶的耦合。潜在的干扰是由于NADH和替硝唑的吸收峰具有相似性。  与甲硝唑类似，替硝唑也可能会产生短暂的白细胞和中性粒细胞减少，然而在临床试验中没有观测到由替硝唑引起的持续的血液学异常现象。如果有必要重复治疗，建议进行白细胞总数和分类计数。  六、【药物过量】项下修订为以下内容  未进行此项实验且无可靠参考文献。  替硝唑过量无特异性解毒药。本品过量时，应给予对症治疗，本品大部分随尿液排泄，可增加尿量以加快清除速率。血液透析也可以考虑，因为大约43%的体内药物可以在血液透析6小时内消除。  （注：如原批准说明书的安全性内容较本修订要求内容更全面或更严格的，应保留原批准内容。说明书其他内容如与上述修订要求不一致的，应当一并进行修订。）

今日（4月1日），NMPA发布通知，决定对替硝唑注射剂（包括替硝唑氯化钠注射液、替硝唑葡萄糖注射液、注射用替硝唑）、西沙必利口服制剂（包括西沙必利片和西沙必利胶囊）说明书内容进行统一修订。其中，替硝唑注射剂说明书增加黑框警告。根据药品不良反应评估结果，为进一步保障公众用药安全，国家药监局决定对替硝唑注射剂（包括替硝唑氯化钠注射液、替硝唑葡萄糖注射液、注射用替硝唑）说明书内容进行统一修订。现将有关事项公告如下： 一、所有上述药品的上市许可持有人均应当依据《药品注册管理办法》等有关规定，按照附件要求修订说明书，于2024年6月21日前报省级药品监督管理部门备案。 修订内容涉及药品标签的，应当一并进行修订；说明书及标签其他内容应当与原批准内容一致。在备案之日起生产的药品，不得继续使用原药品说明书。药品上市许可持有人应当在备案后9个月内对已出厂的药品说明书及标签予以更换。 二、药品上市许可持有人应当对新增不良反应发生机制开展深入研究，采取有效措施做好药品使用和安全性问题的宣传培训，指导医师、药师合理用药。 三、临床医师、药师应当仔细阅读上述药品说明书的修订内容，在选择用药时，应当根据新修订说明书进行充分的获益/风险分析。 四、患者用药前应当仔细阅读药品说明书，使用处方药的，应当严格遵医嘱用药。 五、省级药品监督管理部门应当督促行政区域内上述药品的上市许可持有人按要求做好相应说明书修订和标签、说明书更换工作，对违法违规行为依法严厉查处。 特此公告。 附件：替硝唑注射剂说明书修订要求 国家药监局 2024年3月21日附件替硝唑注射剂说明书修订要求 一、增加黑框警告二、【不良反应】项下修订为以下内容在本品治疗期间报道过以下不良反应：胃肠系统：恶心、呕吐、腹痛、腹部不适、腹胀、腹泻、反酸或食物反流、呃逆、消化不良、食欲减退、便秘、口唇麻木、口腔异味、口干、口腔炎。皮肤及皮下组织：皮疹（如红斑、斑丘疹、水疱疹等）、瘙痒、皮肤肿胀、皮肤潮红、多汗、荨麻疹、血管性水肿、过敏性紫癜、多形性红斑、剥脱性皮炎、急性全身性发疹性脓疱病、史蒂文斯-约翰逊综合征。精神及神经系统：头晕、头痛、味觉倒错、感觉减退、周围神经病变、烧灼感、抽搐、震颤、惊厥发作、意识丧失、晕厥、共济失调、言语障碍、嗜睡、困倦、失眠、烦躁不安、意识模糊状态、躁动、谵妄、幻觉。全身性及给药部位反应：胸部不适、胸痛、寒战、发热、水肿、乏力、不适、疲劳、注射部位反应（静脉炎、疼痛、肿胀、皮疹、瘙痒等）。免疫系统：过敏反应、过敏性休克，有死亡病例报告。心血管系统：心悸、心动过速、血管性疼痛、血压降低、血压升高。呼吸系统：呼吸困难、呼吸急促、窒息感、喉水肿、咳嗽、鼻塞、咽干、口咽疼痛。眼部：视觉损害、视物模糊、眼睑水肿、眼睑瘙痒、眼眶周围水肿、结膜充血。骨骼肌肉系统：肌无力、肌痛、肌痉挛、关节痛。肝胆系统：肝功能异常、肝酶升高。泌尿系统：尿频、血尿、尿液发黑。血液系统：白细胞减少、粒细胞减少症、血小板减少症。其他：眩晕、耳鸣、听觉减退、双硫仑样反应、念珠菌感染、外阴阴道瘙痒、肿胀。三、【禁忌】项下修订为以下内容：1.对替硝唑或吡咯类药物过敏者、对本品中其他成份过敏者以及器质性中枢神经疾病患者禁用。2.与其他结构相似药物一样，有血液不调或恶病质史的患者禁用。尽管目前的动物和临床研究中尚未发现导致长期血液病的例子。3.妊娠早期（妊娠前3个月）的孕妇禁用。4.哺乳期妇女禁用。除非在替硝唑治疗期间及停药后3天内暂停母乳喂养。四、【注意事项】项下应包含以下内容1.在接受替硝唑治疗的患者中，有惊厥发作和周围神经病变的报道，后者主要症状有四肢麻木或感觉异常。如果出现任何异常精神症状或神经系统症状/体征，如共济失调、头晕、意识混乱等，应立即停用替硝唑。2.在替硝唑治疗之前、期间和之后72小时内不应饮用酒精饮料或含酒精产品，因为可能出现腹部绞痛、恶心、呕吐、头痛、心动过速、面部潮红等。3.念珠菌感染者应用本品，其症状会加重，需同时给予抗真菌治疗。治疗阴道滴虫病时需同时治疗其性伙伴。4.据报道，在科克因（Cockayne）综合征患者中，使用与替硝唑结构相似的甲硝唑后，出现了严重的不可逆的肝毒性/急性肝衰竭，并伴有致命后果。五、【药物相互作用】项下修订为以下内容以下是关于甲硝唑的药物相互作用的报道，甲硝唑是一种与替硝唑有化学相关性的硝基咪唑类药物，因此以下报道可能也会发生于替硝唑中。1.替硝唑对其他药物的潜在影响华法林和其他口服香豆素抗凝血药：鉴于甲硝唑的相关报道，替硝唑可以增强华法林及其他香豆素抗凝血剂的药效，从而导致凝血酶原时间延长。在替硝唑治疗期间及其停药后8天内，抗凝血剂用量可能需要调整。酒精、双硫仑：在替硝唑治疗期间及停药后3天内应避免饮用酒精饮料以及任何含有酒精或丙二醇的制剂，否则可能出现腹部绞痛、恶心、呕吐、头痛、潮红的反应。据报道，酗酒患者同时服用甲硝唑和双硫仑会出现精神病反应。虽然替硝唑未见类似报道，但仍不应给近两周内服用过双硫仑的患者使用替硝唑。锂：据报道，甲硝唑提高血清锂的水平。目前尚未知替硝唑是否也有相同的性质，但是建议同时使用锂和替硝唑的患者在治疗几天后做血清锂和肌酸酐的检查，以监测潜在的锂中毒危险。环孢菌素、他克莫司：据一些报道显示，甲硝唑有可能提高环孢菌素和他克莫司的水平。在替硝唑与此任意一种联合给药时，应监测这些患者免疫抑制药物的毒性反应。氟尿嘧啶：研究显示甲硝唑会降低氟尿嘧啶的清除率从而导致对治疗效果无益反而增加其副作用，如果不可避免的要将替硝唑与氟尿嘧啶联合用药，应监测患者的氟尿嘧啶相关的毒性反应。2.其他药物对替硝唑的潜在影响CYP3A4诱导剂/抑制剂：替硝唑与诱导肝微粒体酶的药物联合给药，即CYP3A4诱导剂，如苯巴比妥、利福平、苯妥英、磷苯妥英（一种苯妥英的前体药物），可能加速替硝唑的消除，降低血浆中替硝唑的水平。替硝唑与抑制肝微粒体酶活性的药物联合给药，即CYP3A4抑制剂如西咪替丁和酮康唑，可能会延长替硝唑的半衰期并降低其血浆清除率，从而增加替硝唑在血浆中的浓度。土霉素：据报道，土霉素会拮抗甲硝唑的治疗效果。3.实验室试验的药物相互作用与甲硝唑类似，替硝唑也可能干扰某些特定血清生化指标的测定，如谷氨酸氨基转移酶（AST）、丙氨酸氨基转移酶（ALT）、乳酸脱氢酶（LDH）、甘油三酯和葡萄糖己糖激酶。可能观测到零值。所有有干扰现象报道的含量测定试验，都涉及到了烟酰胺腺嘌呤二核苷酸的氧化还原反应过程中（NAD +NADH）酶的耦合。潜在的干扰是由于NADH和替硝唑的吸收峰具有相似性。与甲硝唑类似，替硝唑也可能会产生短暂的白细胞和中性粒细胞减少，然而在临床试验中没有观测到由替硝唑引起的持续的血液学异常现象。如果有必要重复治疗，建议进行白细胞总数和分类计数。六、【药物过量】项下修订为以下内容未进行此项实验且无可靠参考文献。替硝唑过量无特异性解毒药。本品过量时，应给予对症治疗，本品大部分随尿液排泄，可增加尿量以加快清除速率。血液透析也可以考虑，因为大约43%的体内药物可以在血液透析6小时内消除。（注：如原批准说明书的安全性内容较本修订要求内容更全面或更严格的，应保留原批准内容。说明书其他内容如与上述修订要求不一致的，应当一并进行修订。）根据药品不良反应评估结果，为进一步保障公众用药安全，国家药监局决定对西沙必利口服制剂（包括西沙必利片和西沙必利胶囊）说明书内容进行统一修订。现将有关事项公告如下： 一、所有上述药品的上市许可持有人均应当依据《药品注册管理办法》等有关规定，按照附件要求修订说明书，于2024年6月21日前报省级药品监督管理部门备案。 修订内容涉及药品标签的，应当一并进行修订；说明书及标签其他内容应当与原批准内容一致。在备案之日起生产的药品，不得继续使用原药品说明书。药品上市许可持有人应当在备案后9个月内对已出厂的药品说明书及标签予以更换。 二、药品上市许可持有人应当对新增不良反应发生机制开展深入研究，采取有效措施做好药品使用和安全性问题的宣传培训，指导医师、药师合理用药。 三、临床医师、药师应当仔细阅读上述药品说明书的修订内容，在选择用药时，应当根据新修订说明书进行充分的获益/风险分析。 四、患者用药前应当仔细阅读药品说明书，使用处方药的，应当严格遵医嘱用药。 五、省级药品监督管理部门应当督促行政区域内上述药品的上市许可持有人按要求做好相应说明书修订和标签、说明书更换工作，对违法违规行为依法严厉查处。 特此公告。 附件：西沙必利片、西沙必利胶囊说明书修订要求 国家药监局 2024年3月22日附件西沙必利片、西沙必利胶囊说明书修订要求一、【警示语】项增加以下内容西沙必利有引起QT间期延长和严重或致命的心律失常的潜在风险，临床使用前应权衡利弊。二、【不良反应】项增加以下内容在国内上市的西沙必利口服制剂监测到如下不良反应/事件，由于这些不良反应/事件是在无法确定总数的人群中自发报告的，因此不能准确估算其发生率：心血管系统：心悸、胸部不适、QT间期延长、心动过速、心律失常。胃肠系统：口干、恶心、呕吐、消化不良、肠胃胀气、腹痛、便秘。皮肤及皮下组织：红斑性皮疹、斑丘疹、多汗、面部水肿。神经系统：嗜睡、失眠、感觉减退、眩晕。全身性反应：发热、乏力、胸部不适、疼痛。其他：呼吸困难、过敏样反应。三、【注意事项】项增加以下内容具有以下心律失常危险因素的患者，应慎重使用。严重心脏病史，包括严重室性心律失常、二度或三度房室传导阻滞、窦房结功能障碍、充血性心力衰竭、缺血性心脏病；猝死家庭史；肾衰竭，尤其是进行长期透析的患者；慢性阻塞性肺疾病和呼吸衰竭；电解质紊乱的危险因素，如服用排钾利尿药；胰岛素用量的剧烈调整；持续性呕吐和/或腹泻。（注：如原批准说明书的安全性内容较本修订要求更全面或更严格的，应保留原批准内容。说明书其他内容如与上述修订要求不一致的，应当一并进行修订。）