Take a deeper look at advanced SM       View this as a Web page             Prescribing Information Important Safety Information         IT'S TIME TO TAKE A DEEPER LOOK AT ADVANCED SM*           *Aggressive systemic mastocytosis (ASM), systemic mastocytosis with an associated hematological neoplasm (SM-AHN), and mast cell leukemia (MCL) are collectively referred to as advanced systemic mastocytosis (SM)         ADVANCED SM IS A RARE GROUP OF MYELOID NEOPLASMS THAT CAN BE HARD TO IDENTIFY1-3       • Some patients require 2 to 10+ years to receive an accurate diagnosis4         Learn about how prompt identification of advanced SM can help make a critical difference         • Skin-related symptoms include itching (pruritus), flushing (usually triggered by temperature changes, fever, exercise, and friction), hives (urticaria), and swelling (angioedema)5   • Constitutional symptoms include fatigue, chills, sweats, anaphylaxis, osteopenia/osteoporosis, bone pain, back pain, joint pains (arthralgia), muscle pains (myalgia), and weakness6   • Gastrointestinal symptoms include nausea, vomiting, abdominal pain, and diarrhea5   • Organ-related symptoms include cytopenias, hepatomegaly, ascites, lymphadenopathy, malabsorption or protein-losing enteropathy with weight loss, osteolysis with pathologic fracture, splenomegaly, and hypersplenism6       Symptoms are not limited to only those listed.         WHO, World Health Organization.       It is crucial to identify advanced SM as soon as it is suspected to help your patients and provide them with effective treatment options2,8         Click here to learn about RYDAPT® (midostaurin) capsules, the only FDA‑approved treatment for advanced SM, including adult patients with the KIT D816V mutation9         INDICATION RYDAPT is indicated for the treatment of adult patients with aggressive systemic mastocytosis (ASM), systemic mastocytosis with associated hematological neoplasm (SM-AHN), or mast cell leukemia (MCL).       IMPORTANT SAFETY INFORMATION for RYDAPT® (midostaurin) capsules CONTRAINDICATIONS     • Do not use in patients with hypersensitivity to midostaurin or its excipients. Hypersensitivity reactions have included anaphylactic shock, dyspnea, flushing, chest pain, and angioedema       WARNINGS AND PRECAUTIONS Embryofetal Toxicity     • Do not use during pregnancy. Midostaurin caused severe embryofetal abnormalities and death in animal studies     • Verify pregnancy status of females of reproductive potential within 7 days prior to initiating RYDAPT     • Advise females of reproductive potential to use effective contraception during treatment and for at least 4 months after the last dose     • Males taking RYDAPT should use effective contraception with females of reproductive potential and pregnant women and for at least 4 months after the last dose     • Pregnancy exposure registry to monitor pregnancy outcomes: Females who may have been exposed to RYDAPT during pregnancy, directly or through a male partner receiving RYDAPT, should contact Novartis Pharmaceuticals Corporation at 1-8‍88-6‍69-66‍82 and/or at ht‍tps://p‍si.nov‍artis.c‍om       Pulmonary Toxicity     • Cases of interstitial lung disease and pneumonitis, some fatal, have occurred in patients treated with RYDAPT as monotherapy or with chemotherapy     • Monitor patients for pulmonary symptoms. Discontinue RYDAPT in patients who experience signs or symptoms of interstitial lung disease or pneumonitis without an infectious etiology       ADDITIONAL CONSIDERATIONS Lactation     • Because of the potential for serious adverse reactions in breastfed infants from RYDAPT, advise women not to breastfeed during treatment with RYDAPT and for at least 4 months after the last dose       Infertility     • Based on findings in animals, RYDAPT may impair fertility in females and males of reproductive potential. It is unknown whether these effects on fertility are reversible       Drug Interactions     • Strong CYP3A4 Inducers: Avoid concomitant use as strong CYP3A4 inducers decrease exposure to midostaurin and may reduce efficacy     • Strong CYP3A4 Inhibitors: Coadministration with strong CYP3A4 inhibitors may increase midostaurin concentrations and may increase the risk of toxicity. Monitor patients for increased risk of adverse reactions, especially during the first week of RYDAPT use in each chemotherapy cycle and the first week of consecutive RYDAPT administration. Consider alternative therapies that do not strongly inhibit CYP3A4 activity       ADVERSE REACTIONS Aggressive Systemic Mastocytosis (SM), SM With Associated Hematological Neoplasm, Mast Cell Leukemia   ‍ • Most common adverse reactions (≥20%) excluding lab terms were nausea (‍8‍2‍%‍), vomiting (‍6‍8‍%‍), diarrhea (‍5‍4‍%‍), edema (‍4‍0‍%‍), musculoskeletal pain (‍3‍5‍%‍), abdominal pain (‍3‍4‍%‍), fatigue (‍3‍4‍%‍), upper respiratory tract infection (‍3‍0‍%‍), constipation (‍2‍9‍%‍), pyrexia (‍2‍7‍%‍), headache (‍2‍6‍%‍), and dyspnea (‍2‍3‍%‍)     • Grade ≥3 adverse reactions (≥5%) excluding lab terms were fatigue (‍9‍%‍), sepsis (‍9‍%‍), gastrointestinal hemorrhage ‍(9‍%‍), pneumonia (‍8‍%‍), diarrhea (‍8‍%‍), febrile neutropenia (‍7‍%‍), edema (‍7‍%‍), dyspnea (‍7‍%‍), nausea (‍6‍%‍), vomiting (‍6‍%‍), abdominal pain (‍6‍%‍), and renal insufficiency (‍5‍%‍)     • Most common (≥10%) nonhematologic grade ≥3 lab abnormalities were hyperglycemia (‍nonfasting‍) (‍1‍8‍%‍), lipase increase (‍1‍8‍%‍), and hyperuricemia (‍1‍1‍%‍)     • Most common (≥20%) hematologic grade ≥3 lab abnormalities were thrombocytopenia (‍2‍7‍%‍), neutropenia (‍2‍2‍%‍), anemia (‍3‍8‍%‍) and lymphopenia (‍2‍7‍%‍)       Please see full Prescribing Information for RYDAPT® (midostaurin) capsules.       References: 1. Gotlib J, Kluin-Nelemans HC, George TI, et al. Efficacy and safety of midostaurin in advanced systemic mastocytosis. N Engl J Med. 2016;374(26):25‍30-25‍41. 2. Gülen T, Hägglund H, Dahlén B, Nilsson G. Mastocytosis: the puzzling clinical spectrum and challenging diagnostic aspects of an enigmatic disease. J Intern Med. 2016;279(3):211-228. 3. Horny HP, Sotlar K, Valent P. Differential diagnoses of systemic mastocytosis in routinely processed bone marrow biopsy specimens: a review. Pathobiology. 2010;77(4):169-180. 4. Sev'er A, Sibbald RG, D'Arville C. Thousand faces of mastocytosis: mistaken medical diagnoses, patient suffering & gender implications. Women's Health & Urban Life. 2009;8(2):84-112. 5. Arock M, Akin C, Hermine O, Valent P. Current treatment options in patients with mastocytosis: status in 2015 and future perspectives. Eur J Haematol. 2015;94(6):474-490. 6. Pardanani A. Systemic mastocytosis in adults: 2017 update on diagnosis, risk stratification and management. Am J Hematol. 2016;91(11):1146-1159. 7. Gotlib J, Kluin-Nelemans HC, George TI, et al. Efficacy and safety of midostaurin in advanced systemic mastocytosis [supplementary appendix]. N Engl J Med. 2016;374(26):25‍30-25‍41. 8. Broesby-Olsen S, Dybedal I, Gülen T, et al. Multidisciplinary management of mastocytosis: Nordic Expert Group Consensus. Acta Derm Venereol. 2016;96(5):602-612. 9. Rydapt [prescribing information]. East Hanover, NJ: Novartis Pharmaceuticals Corp; 2018.       This is a sponsored message from DMD on behalf of Novartis Pharmaceuticals Corporation. DMD provides sponsored health care–related messages from trusted third parties. This material is intended specifically and exclusively for US health care professionals. You are receiving this email because you have subscribed and agreed to receive information from the DMD email list.       If you prefer not to receive further messages from DMD, please click here and confirm your request.       DMD 10‍255 W. 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