Interaksi Tofasitinib

Additionally, concomitant use of ORENCIA with other biologic RA/PsA therapy or JAK inhibitors is not recommended. (label Abatasept, Peringatan dan perhatian)

MALIGNANCIES Malignancies, including lymphomas and solid tumors, have occurred in patients treated with XELJANZ and other Janus kinase inhibitors used to treat inflammatory conditions. (label Tofasitinib, Peringatan kotak hitam)

• Higher rate of all-cause mortality, including sudden cardiovascular (CV) death with XELJANZ vs. TNF blockers in rheumatoid arthritis (RA) patients. (label Tofasitinib, Peringatan kotak hitam)

…of or reduced clinical response Intervention Concomitant use with XELJANZ/XELJANZ XR is not recommended [see Clinical Pharmacology, Figure 3 (12.3) ] Immunosuppressive Drugs (e.g., azathioprine, tacrolimus, cyclosporine) Clinical Impact Risk of added immunosuppression; concomitant use of XELJANZ/XELJANZ XR with biologic DMARDs or potent immunosuppressants has… (label Tofasitinib, Interaksi obat)

Most patients who developed these infections were taking concomitant immunosuppressants such as methotrexate or corticosteroids. (label Tofasitinib, Peringatan kotak hitam)

MALIGNANCIES Malignancies, including lymphomas and solid tumors, have occurred in patients treated with XELJANZ and other Janus kinase inhibitors used to treat inflammatory conditions. (label Tofasitinib, Peringatan kotak hitam)

Most patients who developed these infections were taking concomitant immunosuppressants such as methotrexate or corticosteroids. (label Tofasitinib, Peringatan kotak hitam)

Most patients who developed these infections were taking concomitant immunosuppressants such as methotrexate or corticosteroids. (label Tofasitinib, Peringatan kotak hitam)

Most patients who developed these infections were taking concomitant immunosuppressants such as methotrexate or corticosteroids. (label Tofasitinib, Peringatan kotak hitam)

Most patients who developed these infections were taking concomitant immunosuppressants such as methotrexate or corticosteroids. (label Tofasitinib, Peringatan kotak hitam)

Immunosuppressant/neoplastic: everolimus Co-administration of everolimus and PREZISTA/ritonavir is not recommended. irinotecan Discontinue PREZISTA/ritonavir at least 1 week prior to starting irinotecan therapy. (label Darunavir, Interaksi obat)

Most patients who developed these infections were taking concomitant immunosuppressants such as methotrexate or corticosteroids. (label Tofasitinib, Peringatan kotak hitam)

Most patients who developed these infections were taking concomitant immunosuppressants such as methotrexate or corticosteroids. (label Tofasitinib, Peringatan kotak hitam)

Most patients who developed these infections were taking concomitant immunosuppressants such as methotrexate or corticosteroids. (label Tofasitinib, Peringatan kotak hitam)

• Higher rate of all-cause mortality, including sudden cardiovascular (CV) death with XELJANZ vs. TNF blockers in rheumatoid arthritis (RA) patients. (label Tofasitinib, Peringatan kotak hitam)

Most patients who developed these infections were taking concomitant immunosuppressants such as methotrexate or corticosteroids. (label Tofasitinib, Peringatan kotak hitam)

Most patients who developed these infections were taking concomitant immunosuppressants such as methotrexate or corticosteroids. (label Tofasitinib, Peringatan kotak hitam)

Most patients who developed these infections were taking concomitant immunosuppressants such as methotrexate or corticosteroids. (label Tofasitinib, Peringatan kotak hitam)

Most patients who developed these infections were taking concomitant immunosuppressants such as methotrexate or corticosteroids. (label Tofasitinib, Peringatan kotak hitam)

Most patients who developed these infections were taking concomitant immunosuppressants such as methotrexate or corticosteroids. (label Tofasitinib, Peringatan kotak hitam)

Most patients who developed these infections were taking concomitant immunosuppressants such as methotrexate or corticosteroids. (label Tofasitinib, Peringatan kotak hitam)

Most patients who developed these infections were taking concomitant immunosuppressants such as methotrexate or corticosteroids. (label Tofasitinib, Peringatan kotak hitam)

• Higher rate of all-cause mortality, including sudden cardiovascular (CV) death with XELJANZ vs. TNF blockers in rheumatoid arthritis (RA) patients. (label Tofasitinib, Peringatan kotak hitam)

Immunosuppressants Everolimus Sirolimus Temsirolimus (IV) Not recommended during and 2 weeks after TOLSURA treatment. (label Itrakonazol, Interaksi obat)

About 13 percent of the cases of neutropenia have ended fatally, but almost all fatalities were in patients with serious illness, having collagen vascular disease, renal failure, heart failure or immunosuppressant therapy, or a combination of these complicating factors. (label Kaptopril, Peringatan)

Prevention or Management Concomitant use with myelosuppressive or other immunosuppressive drugs is not recommended. (label Kladribin, Interaksi obat)

Most patients who developed these infections were taking concomitant immunosuppressants such as methotrexate or corticosteroids. (label Tofasitinib, Peringatan kotak hitam)

Most patients who developed these infections were taking concomitant immunosuppressants such as methotrexate or corticosteroids. (label Tofasitinib, Peringatan kotak hitam)

Most patients who developed these infections were taking concomitant immunosuppressants such as methotrexate or corticosteroids. (label Tofasitinib, Peringatan kotak hitam)

Most patients who developed these infections were taking concomitant immunosuppressants such as methotrexate or corticosteroids. (label Tofasitinib, Peringatan kotak hitam)

…methylergonovine • HMG-CoA reductase inhibitors: lovastatin, simvastatin (these drugs can be temporarily discontinued to allow PAXLOVID use [see Table 2 , Drug Interactions (7.3) ] ) • Immunosuppressants: voclosporin • Microsomal triglyceride transfer protein inhibitor: lomitapide • Migraine medications: eletriptan, ubrogepant • Mineralocorticoid receptor antagonists:… (label Nirmatrelvir dan ritonavir, Kontraindikasi)

Most patients who developed these infections were taking concomitant immunosuppressants such as methotrexate or corticosteroids. (label Tofasitinib, Peringatan kotak hitam)

Most patients who developed these infections were taking concomitant immunosuppressants such as methotrexate or corticosteroids. (label Tofasitinib, Peringatan kotak hitam)

Most patients who developed these infections were taking concomitant immunosuppressants such as methotrexate or corticosteroids. (label Tofasitinib, Peringatan kotak hitam)

MALIGNANCIES Malignancies, including lymphomas and solid tumors, have occurred in patients treated with XELJANZ and other Janus kinase inhibitors used to treat inflammatory conditions. (label Tofasitinib, Peringatan kotak hitam)

MALIGNANCIES Malignancies, including lymphomas and solid tumors, have occurred in patients treated with XELJANZ and other Janus kinase inhibitors used to treat inflammatory conditions. (label Tofasitinib, Peringatan kotak hitam)

Most patients who developed these infections were taking concomitant immunosuppressants such as methotrexate or corticosteroids. (label Tofasitinib, Peringatan kotak hitam)

In kidney, liver, and heart transplant patients Neoral may be administered with other immunosuppressive agents. (label Siklosporin, Peringatan kotak hitam)

…clinical response Intervention Concomitant use with XELJANZ/XELJANZ XR is not recommended [see Clinical Pharmacology, Figure 3 (12.3) ] Immunosuppressive Drugs (e.g., azathioprine, tacrolimus, cyclosporine) Clinical Impact Risk of added immunosuppression; concomitant use of XELJANZ/XELJANZ XR with biologic DMARDs or potent immunosuppressants has not been studied… (label Tofasitinib, Interaksi obat)

Patients who are current or past smokers are at additional increased risk. (label Tofasitinib, Peringatan kotak hitam)

Most patients who developed these infections were taking concomitant immunosuppressants such as methotrexate or corticosteroids. (label Tofasitinib, Peringatan kotak hitam)

MALIGNANCIES Malignancies, including lymphomas and solid tumors, have occurred in patients treated with XELJANZ and other Janus kinase inhibitors used to treat inflammatory conditions. (label Tofasitinib, Peringatan kotak hitam)

Table 7: Clinically Significant Interactions Affecting XELJANZ/XELJANZ XR When Concomitantly Used with Other Drugs Strong CYP3A4 Inhibitors (e.g., ketoconazole) Clinical Impact Increased exposure to tofacitinib Intervention Dosage modification of XELJANZ/XELJANZ XR is recommended [see Dosage and Administration (2) , Clinical Pharmacology, Figure 3 (12.3) ] Moderate… (label Tofasitinib, Interaksi obat)

Immunosuppressants Amlodipine may increase the systemic exposure of cyclosporine or tacrolimus when co-administered. (label Amlodipin, Interaksi obat)

Impact of Amlodipine on Other Drugs Immunosuppressants Amlodipine may increase the systemic exposure of cyclosporine or tacrolimus when co-administered. (label Amlodipin dan atorvastatin, Interaksi obat)

Immunosuppressants: Amlodipine may increase the systemic exposure of cyclosporine or tacrolimus when co-administered. (label Amlodipin dan olmesartan, Interaksi obat)

Immunosuppressants Amlodipine may increase the systemic exposure of cyclosporine or tacrolimus when coadministered. (label Amlodipin dan valsartan, Interaksi obat)

Table 7: Clinically Significant Interactions Affecting XELJANZ/XELJANZ XR When Concomitantly Used with Other Drugs Strong CYP3A4 Inhibitors (e.g., ketoconazole) Clinical Impact Increased exposure to tofacitinib Intervention Dosage modification of XELJANZ/XELJANZ XR is recommended [see Dosage and Administration (2) , Clinical Pharmacology, Figure 3 (12.3) ] Moderate… (label Tofasitinib, Interaksi obat)

…exposure to tofacitinib Intervention Dosage modification of XELJANZ/XELJANZ XR is recommended [see Dosage and Administration (2) , Clinical Pharmacology, Figure 3 (12.3) ] Strong CYP3A4 Inducers (e.g., rifampin) Clinical Impact Decreased exposure to tofacitinib and may result in loss of or reduced clinical response Intervention Concomitant use with XELJANZ/XELJANZ… (label Tofasitinib, Interaksi obat)

Frequent PT/INR determinations are advisable until it has been definitely determined that the PT/INR has stabilized Immunosuppressants Clinical Impact: Immunosuppressants such as cyclosporine and tacrolimus can produce nephrotoxicity with decreases in creatinine clearance and rises in serum creatinine, and because renal excretion is the primary elimination route… (label Asam fenofibrat, Interaksi obat)

Promptly evaluate patients treated with XELJANZ/XELJANZ XR who may be at increased risk for gastrointestinal perforation (e.g., patients with a history of diverticulitis or taking NSAIDs) and who present with new onset abdominal symptoms for early identification of gastrointestinal perforation [see Adverse Reactions (6.1) ] . (label Tofasitinib, Peringatan dan perhatian)

Promptly evaluate patients treated with XELJANZ/XELJANZ XR who may be at increased risk for gastrointestinal perforation (e.g., patients with a history of diverticulitis or taking NSAIDs) and who present with new onset abdominal symptoms for early identification of gastrointestinal perforation [see Adverse Reactions (6.1) ] . (label Tofasitinib, Peringatan dan perhatian)

Promptly evaluate patients treated with XELJANZ/XELJANZ XR who may be at increased risk for gastrointestinal perforation (e.g., patients with a history of diverticulitis or taking NSAIDs) and who present with new onset abdominal symptoms for early identification of gastrointestinal perforation [see Adverse Reactions (6.1) ] . (label Tofasitinib, Peringatan dan perhatian)

Table 7: Clinically Significant Interactions Affecting XELJANZ/XELJANZ XR When Concomitantly Used with Other Drugs Strong CYP3A4 Inhibitors (e.g., ketoconazole) Clinical Impact Increased exposure to tofacitinib Intervention Dosage modification of XELJANZ/XELJANZ XR is recommended [see Dosage and Administration (2) , Clinical Pharmacology, Figure 3 (12.3) ] Moderate… (label Tofasitinib, Interaksi obat)

Consider discontinuation or reduction of any concomitant chemotherapy or immunosuppressive therapy in patients who develop PML. (label Bendamustin, Peringatan dan perhatian)

…exposure to tofacitinib Intervention Dosage modification of XELJANZ/XELJANZ XR is recommended [see Dosage and Administration (2) , Clinical Pharmacology, Figure 3 (12.3) ] Strong CYP3A4 Inducers (e.g., rifampin) Clinical Impact Decreased exposure to tofacitinib and may result in loss of or reduced clinical response Intervention Concomitant use with XELJANZ/XELJANZ… (label Tofasitinib, Interaksi obat)

Promptly evaluate patients treated with XELJANZ/XELJANZ XR who may be at increased risk for gastrointestinal perforation (e.g., patients with a history of diverticulitis or taking NSAIDs) and who present with new onset abdominal symptoms for early identification of gastrointestinal perforation [see Adverse Reactions (6.1) ] . (label Tofasitinib, Peringatan dan perhatian)

Promptly evaluate patients treated with XELJANZ/XELJANZ XR who may be at increased risk for gastrointestinal perforation (e.g., patients with a history of diverticulitis or taking NSAIDs) and who present with new onset abdominal symptoms for early identification of gastrointestinal perforation [see Adverse Reactions (6.1) ] . (label Tofasitinib, Peringatan dan perhatian)

Table 7: Clinically Significant Interactions Affecting XELJANZ/XELJANZ XR When Concomitantly Used with Other Drugs Strong CYP3A4 Inhibitors (e.g., ketoconazole) Clinical Impact Increased exposure to tofacitinib Intervention Dosage modification of XELJANZ/XELJANZ XR is recommended [see Dosage and Administration (2) , Clinical Pharmacology, Figure 3 (12.3) ] Moderate… (label Tofasitinib, Interaksi obat)

…exposure to tofacitinib Intervention Dosage modification of XELJANZ/XELJANZ XR is recommended [see Dosage and Administration (2) , Clinical Pharmacology, Figure 3 (12.3) ] Strong CYP3A4 Inducers (e.g., rifampin) Clinical Impact Decreased exposure to tofacitinib and may result in loss of or reduced clinical response Intervention Concomitant use with XELJANZ/XELJANZ… (label Tofasitinib, Interaksi obat)

Other risk factors for the development of ONJ include immunosuppressive therapy, treatment with angiogenesis inhibitors, systemic corticosteroids, diabetes, and gingival infections. (label Denosumab, Peringatan dan perhatian)

Promptly evaluate patients treated with XELJANZ/XELJANZ XR who may be at increased risk for gastrointestinal perforation (e.g., patients with a history of diverticulitis or taking NSAIDs) and who present with new onset abdominal symptoms for early identification of gastrointestinal perforation [see Adverse Reactions (6.1) ] . (label Tofasitinib, Peringatan dan perhatian)

Promptly evaluate patients treated with XELJANZ/XELJANZ XR who may be at increased risk for gastrointestinal perforation (e.g., patients with a history of diverticulitis or taking NSAIDs) and who present with new onset abdominal symptoms for early identification of gastrointestinal perforation [see Adverse Reactions (6.1) ] . (label Tofasitinib, Peringatan dan perhatian)

Promptly evaluate patients treated with XELJANZ/XELJANZ XR who may be at increased risk for gastrointestinal perforation (e.g., patients with a history of diverticulitis or taking NSAIDs) and who present with new onset abdominal symptoms for early identification of gastrointestinal perforation [see Adverse Reactions (6.1) ] . (label Tofasitinib, Peringatan dan perhatian)

Table 7: Clinically Significant Interactions Affecting XELJANZ/XELJANZ XR When Concomitantly Used with Other Drugs Strong CYP3A4 Inhibitors (e.g., ketoconazole) Clinical Impact Increased exposure to tofacitinib Intervention Dosage modification of XELJANZ/XELJANZ XR is recommended [see Dosage and Administration (2) , Clinical Pharmacology, Figure 3 (12.3) ] Moderate… (label Tofasitinib, Interaksi obat)

Table 7: Clinically Significant Interactions Affecting XELJANZ/XELJANZ XR When Concomitantly Used with Other Drugs Strong CYP3A4 Inhibitors (e.g., ketoconazole) Clinical Impact Increased exposure to tofacitinib Intervention Dosage modification of XELJANZ/XELJANZ XR is recommended [see Dosage and Administration (2) , Clinical Pharmacology, Figure 3 (12.3) ] Moderate… (label Tofasitinib, Interaksi obat)

…modification of XELJANZ/XELJANZ XR is recommended [see Dosage and Administration (2) , Clinical Pharmacology, Figure 3 (12.3) ] Moderate CYP3A4 Inhibitors Concomitantly Used with Strong CYP2C19 Inhibitors (e.g., fluconazole) Clinical Impact Increased exposure to tofacitinib Intervention Dosage modification of XELJANZ/XELJANZ XR is recommended [see Dosage and Administration… (label Tofasitinib, Interaksi obat)

…modification of XELJANZ/XELJANZ XR is recommended [see Dosage and Administration (2) , Clinical Pharmacology, Figure 3 (12.3) ] Moderate CYP3A4 Inhibitors Concomitantly Used with Strong CYP2C19 Inhibitors (e.g., fluconazole) Clinical Impact Increased exposure to tofacitinib Intervention Dosage modification of XELJANZ/XELJANZ XR is recommended [see Dosage and Administration… (label Tofasitinib, Interaksi obat)

Table 7: Clinically Significant Interactions Affecting XELJANZ/XELJANZ XR When Concomitantly Used with Other Drugs Strong CYP3A4 Inhibitors (e.g., ketoconazole) Clinical Impact Increased exposure to tofacitinib Intervention Dosage modification of XELJANZ/XELJANZ XR is recommended [see Dosage and Administration (2) , Clinical Pharmacology, Figure 3 (12.3) ] Moderate… (label Tofasitinib, Interaksi obat)

Table 7: Clinically Significant Interactions Affecting XELJANZ/XELJANZ XR When Concomitantly Used with Other Drugs Strong CYP3A4 Inhibitors (e.g., ketoconazole) Clinical Impact Increased exposure to tofacitinib Intervention Dosage modification of XELJANZ/XELJANZ XR is recommended [see Dosage and Administration (2) , Clinical Pharmacology, Figure 3 (12.3) ] Moderate… (label Tofasitinib, Interaksi obat)

…exposure to tofacitinib Intervention Dosage modification of XELJANZ/XELJANZ XR is recommended [see Dosage and Administration (2) , Clinical Pharmacology, Figure 3 (12.3) ] Strong CYP3A4 Inducers (e.g., rifampin) Clinical Impact Decreased exposure to tofacitinib and may result in loss of or reduced clinical response Intervention Concomitant use with XELJANZ/XELJANZ… (label Tofasitinib, Interaksi obat)

…modification of XELJANZ/XELJANZ XR is recommended [see Dosage and Administration (2) , Clinical Pharmacology, Figure 3 (12.3) ] Moderate CYP3A4 Inhibitors Concomitantly Used with Strong CYP2C19 Inhibitors (e.g., fluconazole) Clinical Impact Increased exposure to tofacitinib Intervention Dosage modification of XELJANZ/XELJANZ XR is recommended [see Dosage and Administration… (label Tofasitinib, Interaksi obat)

Promptly evaluate patients treated with XELJANZ/XELJANZ XR who may be at increased risk for gastrointestinal perforation (e.g., patients with a history of diverticulitis or taking NSAIDs) and who present with new onset abdominal symptoms for early identification of gastrointestinal perforation [see Adverse Reactions (6.1) ] . (label Tofasitinib, Peringatan dan perhatian)

…modification of XELJANZ/XELJANZ XR is recommended [see Dosage and Administration (2) , Clinical Pharmacology, Figure 3 (12.3) ] Moderate CYP3A4 Inhibitors Concomitantly Used with Strong CYP2C19 Inhibitors (e.g., fluconazole) Clinical Impact Increased exposure to tofacitinib Intervention Dosage modification of XELJANZ/XELJANZ XR is recommended [see Dosage and Administration… (label Tofasitinib, Interaksi obat)

Table 7: Clinically Significant Interactions Affecting XELJANZ/XELJANZ XR When Concomitantly Used with Other Drugs Strong CYP3A4 Inhibitors (e.g., ketoconazole) Clinical Impact Increased exposure to tofacitinib Intervention Dosage modification of XELJANZ/XELJANZ XR is recommended [see Dosage and Administration (2) , Clinical Pharmacology, Figure 3 (12.3) ] Moderate… (label Tofasitinib, Interaksi obat)

…exposure to tofacitinib Intervention Dosage modification of XELJANZ/XELJANZ XR is recommended [see Dosage and Administration (2) , Clinical Pharmacology, Figure 3 (12.3) ] Strong CYP3A4 Inducers (e.g., rifampin) Clinical Impact Decreased exposure to tofacitinib and may result in loss of or reduced clinical response Intervention Concomitant use with XELJANZ/XELJANZ… (label Tofasitinib, Interaksi obat)

…exposure to tofacitinib Intervention Dosage modification of XELJANZ/XELJANZ XR is recommended [see Dosage and Administration (2) , Clinical Pharmacology, Figure 3 (12.3) ] Strong CYP3A4 Inducers (e.g., rifampin) Clinical Impact Decreased exposure to tofacitinib and may result in loss of or reduced clinical response Intervention Concomitant use with XELJANZ/XELJANZ… (label Tofasitinib, Interaksi obat)

Immunosuppressants Clinical Impact: Immunosuppressants such as cyclosporine and tacrolimus can produce nephrotoxicity with decreases in creatinine clearance and rises in serum creatinine, and because renal excretion is the primary elimination route of fibrate drugs including fenofibrate, there is a risk that an interaction will lead to deterioration of renal… (label Fenofibrat, Interaksi obat)

Promptly evaluate patients treated with XELJANZ/XELJANZ XR who may be at increased risk for gastrointestinal perforation (e.g., patients with a history of diverticulitis or taking NSAIDs) and who present with new onset abdominal symptoms for early identification of gastrointestinal perforation [see Adverse Reactions (6.1) ] . (label Tofasitinib, Peringatan dan perhatian)

…modification of XELJANZ/XELJANZ XR is recommended [see Dosage and Administration (2) , Clinical Pharmacology, Figure 3 (12.3) ] Moderate CYP3A4 Inhibitors Concomitantly Used with Strong CYP2C19 Inhibitors (e.g., fluconazole) Clinical Impact Increased exposure to tofacitinib Intervention Dosage modification of XELJANZ/XELJANZ XR is recommended [see Dosage and Administration… (label Tofasitinib, Interaksi obat)

…modification of XELJANZ/XELJANZ XR is recommended [see Dosage and Administration (2) , Clinical Pharmacology, Figure 3 (12.3) ] Moderate CYP3A4 Inhibitors Concomitantly Used with Strong CYP2C19 Inhibitors (e.g., fluconazole) Clinical Impact Increased exposure to tofacitinib Intervention Dosage modification of XELJANZ/XELJANZ XR is recommended [see Dosage and Administration… (label Tofasitinib, Interaksi obat)

Promptly evaluate patients treated with XELJANZ/XELJANZ XR who may be at increased risk for gastrointestinal perforation (e.g., patients with a history of diverticulitis or taking NSAIDs) and who present with new onset abdominal symptoms for early identification of gastrointestinal perforation [see Adverse Reactions (6.1) ] . (label Tofasitinib, Peringatan dan perhatian)

…modification of XELJANZ/XELJANZ XR is recommended [see Dosage and Administration (2) , Clinical Pharmacology, Figure 3 (12.3) ] Moderate CYP3A4 Inhibitors Concomitantly Used with Strong CYP2C19 Inhibitors (e.g., fluconazole) Clinical Impact Increased exposure to tofacitinib Intervention Dosage modification of XELJANZ/XELJANZ XR is recommended [see Dosage and Administration… (label Tofasitinib, Interaksi obat)

Table 7: Clinically Significant Interactions Affecting XELJANZ/XELJANZ XR When Concomitantly Used with Other Drugs Strong CYP3A4 Inhibitors (e.g., ketoconazole) Clinical Impact Increased exposure to tofacitinib Intervention Dosage modification of XELJANZ/XELJANZ XR is recommended [see Dosage and Administration (2) , Clinical Pharmacology, Figure 3 (12.3) ] Moderate… (label Tofasitinib, Interaksi obat)

Table 7: Clinically Significant Interactions Affecting XELJANZ/XELJANZ XR When Concomitantly Used with Other Drugs Strong CYP3A4 Inhibitors (e.g., ketoconazole) Clinical Impact Increased exposure to tofacitinib Intervention Dosage modification of XELJANZ/XELJANZ XR is recommended [see Dosage and Administration (2) , Clinical Pharmacology, Figure 3 (12.3) ] Moderate… (label Tofasitinib, Interaksi obat)

…exposure to tofacitinib Intervention Dosage modification of XELJANZ/XELJANZ XR is recommended [see Dosage and Administration (2) , Clinical Pharmacology, Figure 3 (12.3) ] Strong CYP3A4 Inducers (e.g., rifampin) Clinical Impact Decreased exposure to tofacitinib and may result in loss of or reduced clinical response Intervention Concomitant use with XELJANZ/XELJANZ… (label Tofasitinib, Interaksi obat)

…exposure to tofacitinib Intervention Dosage modification of XELJANZ/XELJANZ XR is recommended [see Dosage and Administration (2) , Clinical Pharmacology, Figure 3 (12.3) ] Strong CYP3A4 Inducers (e.g., rifampin) Clinical Impact Decreased exposure to tofacitinib and may result in loss of or reduced clinical response Intervention Concomitant use with XELJANZ/XELJANZ… (label Tofasitinib, Interaksi obat)

Promptly evaluate patients treated with XELJANZ/XELJANZ XR who may be at increased risk for gastrointestinal perforation (e.g., patients with a history of diverticulitis or taking NSAIDs) and who present with new onset abdominal symptoms for early identification of gastrointestinal perforation [see Adverse Reactions (6.1) ] . (label Tofasitinib, Peringatan dan perhatian)

Promptly evaluate patients treated with XELJANZ/XELJANZ XR who may be at increased risk for gastrointestinal perforation (e.g., patients with a history of diverticulitis or taking NSAIDs) and who present with new onset abdominal symptoms for early identification of gastrointestinal perforation [see Adverse Reactions (6.1) ] . (label Tofasitinib, Peringatan dan perhatian)

Promptly evaluate patients treated with XELJANZ/XELJANZ XR who may be at increased risk for gastrointestinal perforation (e.g., patients with a history of diverticulitis or taking NSAIDs) and who present with new onset abdominal symptoms for early identification of gastrointestinal perforation [see Adverse Reactions (6.1) ] . (label Tofasitinib, Peringatan dan perhatian)

Table 7: Clinically Significant Interactions Affecting XELJANZ/XELJANZ XR When Concomitantly Used with Other Drugs Strong CYP3A4 Inhibitors (e.g., ketoconazole) Clinical Impact Increased exposure to tofacitinib Intervention Dosage modification of XELJANZ/XELJANZ XR is recommended [see Dosage and Administration (2) , Clinical Pharmacology, Figure 3 (12.3) ] Moderate… (label Tofasitinib, Interaksi obat)

Promptly evaluate patients treated with XELJANZ/XELJANZ XR who may be at increased risk for gastrointestinal perforation (e.g., patients with a history of diverticulitis or taking NSAIDs) and who present with new onset abdominal symptoms for early identification of gastrointestinal perforation [see Adverse Reactions (6.1) ] . (label Tofasitinib, Peringatan dan perhatian)

…modification of XELJANZ/XELJANZ XR is recommended [see Dosage and Administration (2) , Clinical Pharmacology, Figure 3 (12.3) ] Moderate CYP3A4 Inhibitors Concomitantly Used with Strong CYP2C19 Inhibitors (e.g., fluconazole) Clinical Impact Increased exposure to tofacitinib Intervention Dosage modification of XELJANZ/XELJANZ XR is recommended [see Dosage and Administration… (label Tofasitinib, Interaksi obat)

Table 7: Clinically Significant Interactions Affecting XELJANZ/XELJANZ XR When Concomitantly Used with Other Drugs Strong CYP3A4 Inhibitors (e.g., ketoconazole) Clinical Impact Increased exposure to tofacitinib Intervention Dosage modification of XELJANZ/XELJANZ XR is recommended [see Dosage and Administration (2) , Clinical Pharmacology, Figure 3 (12.3) ] Moderate… (label Tofasitinib, Interaksi obat)

…modification of XELJANZ/XELJANZ XR is recommended [see Dosage and Administration (2) , Clinical Pharmacology, Figure 3 (12.3) ] Moderate CYP3A4 Inhibitors Concomitantly Used with Strong CYP2C19 Inhibitors (e.g., fluconazole) Clinical Impact Increased exposure to tofacitinib Intervention Dosage modification of XELJANZ/XELJANZ XR is recommended [see Dosage and Administration… (label Tofasitinib, Interaksi obat)

…exposure to tofacitinib Intervention Dosage modification of XELJANZ/XELJANZ XR is recommended [see Dosage and Administration (2) , Clinical Pharmacology, Figure 3 (12.3) ] Strong CYP3A4 Inducers (e.g., rifampin) Clinical Impact Decreased exposure to tofacitinib and may result in loss of or reduced clinical response Intervention Concomitant use with XELJANZ/XELJANZ… (label Tofasitinib, Interaksi obat)

Table 7: Clinically Significant Interactions Affecting XELJANZ/XELJANZ XR When Concomitantly Used with Other Drugs Strong CYP3A4 Inhibitors (e.g., ketoconazole) Clinical Impact Increased exposure to tofacitinib Intervention Dosage modification of XELJANZ/XELJANZ XR is recommended [see Dosage and Administration (2) , Clinical Pharmacology, Figure 3 (12.3) ] Moderate… (label Tofasitinib, Interaksi obat)

Promptly evaluate patients treated with XELJANZ/XELJANZ XR who may be at increased risk for gastrointestinal perforation (e.g., patients with a history of diverticulitis or taking NSAIDs) and who present with new onset abdominal symptoms for early identification of gastrointestinal perforation [see Adverse Reactions (6.1) ] . (label Tofasitinib, Peringatan dan perhatian)

Promptly evaluate patients treated with XELJANZ/XELJANZ XR who may be at increased risk for gastrointestinal perforation (e.g., patients with a history of diverticulitis or taking NSAIDs) and who present with new onset abdominal symptoms for early identification of gastrointestinal perforation [see Adverse Reactions (6.1) ] . (label Tofasitinib, Peringatan dan perhatian)

Table 7: Clinically Significant Interactions Affecting XELJANZ/XELJANZ XR When Concomitantly Used with Other Drugs Strong CYP3A4 Inhibitors (e.g., ketoconazole) Clinical Impact Increased exposure to tofacitinib Intervention Dosage modification of XELJANZ/XELJANZ XR is recommended [see Dosage and Administration (2) , Clinical Pharmacology, Figure 3 (12.3) ] Moderate… (label Tofasitinib, Interaksi obat)

…exposure to tofacitinib Intervention Dosage modification of XELJANZ/XELJANZ XR is recommended [see Dosage and Administration (2) , Clinical Pharmacology, Figure 3 (12.3) ] Strong CYP3A4 Inducers (e.g., rifampin) Clinical Impact Decreased exposure to tofacitinib and may result in loss of or reduced clinical response Intervention Concomitant use with XELJANZ/XELJANZ… (label Tofasitinib, Interaksi obat)

HBV reactivation has also been reported in patients receiving certain immunosuppressants or chemotherapeutic agents; the risk of HBV reactivation associated with treatment with HCV direct-acting antivirals may be increased in these patients. (label Ledipasvir dan sofosbuvir, Peringatan dan perhatian)

If used with concomitant methotrexate and/or other potential immunosuppressive agents, chronic monitoring should be monthly. (label Leflunomid, Peringatan dan perhatian)

Table 7: Clinically Significant Interactions Affecting XELJANZ/XELJANZ XR When Concomitantly Used with Other Drugs Strong CYP3A4 Inhibitors (e.g., ketoconazole) Clinical Impact Increased exposure to tofacitinib Intervention Dosage modification of XELJANZ/XELJANZ XR is recommended [see Dosage and Administration (2) , Clinical Pharmacology, Figure 3 (12.3) ] Moderate… (label Tofasitinib, Interaksi obat)

Table 7: Clinically Significant Interactions Affecting XELJANZ/XELJANZ XR When Concomitantly Used with Other Drugs Strong CYP3A4 Inhibitors (e.g., ketoconazole) Clinical Impact Increased exposure to tofacitinib Intervention Dosage modification of XELJANZ/XELJANZ XR is recommended [see Dosage and Administration (2) , Clinical Pharmacology, Figure 3 (12.3) ] Moderate… (label Tofasitinib, Interaksi obat)

…exposure to tofacitinib Intervention Dosage modification of XELJANZ/XELJANZ XR is recommended [see Dosage and Administration (2) , Clinical Pharmacology, Figure 3 (12.3) ] Strong CYP3A4 Inducers (e.g., rifampin) Clinical Impact Decreased exposure to tofacitinib and may result in loss of or reduced clinical response Intervention Concomitant use with XELJANZ/XELJANZ… (label Tofasitinib, Interaksi obat)

Promptly evaluate patients treated with XELJANZ/XELJANZ XR who may be at increased risk for gastrointestinal perforation (e.g., patients with a history of diverticulitis or taking NSAIDs) and who present with new onset abdominal symptoms for early identification of gastrointestinal perforation [see Adverse Reactions (6.1) ] . (label Tofasitinib, Peringatan dan perhatian)

A treatment regimen containing multiple immunosuppressants (including thiopurines) should therefore be used with caution as this could lead to lymphoproliferative disorders, some with reported fatalities. (label Merkaptopurin, Peringatan dan perhatian)

Table 7: Clinically Significant Interactions Affecting XELJANZ/XELJANZ XR When Concomitantly Used with Other Drugs Strong CYP3A4 Inhibitors (e.g., ketoconazole) Clinical Impact Increased exposure to tofacitinib Intervention Dosage modification of XELJANZ/XELJANZ XR is recommended [see Dosage and Administration (2) , Clinical Pharmacology, Figure 3 (12.3) ] Moderate… (label Tofasitinib, Interaksi obat)

Lymphoma and Other Malignancies Patients receiving immunosuppressants, including mycophenolate mofetil, are at increased risk of developing lymphomas and other malignancies, particularly of the skin [see Adverse Reactions ( 6.1 )]. (label Mikofenolat, Peringatan dan perhatian)

Table 7: Clinically Significant Interactions Affecting XELJANZ/XELJANZ XR When Concomitantly Used with Other Drugs Strong CYP3A4 Inhibitors (e.g., ketoconazole) Clinical Impact Increased exposure to tofacitinib Intervention Dosage modification of XELJANZ/XELJANZ XR is recommended [see Dosage and Administration (2) , Clinical Pharmacology, Figure 3 (12.3) ] Moderate… (label Tofasitinib, Interaksi obat)

…exposure to tofacitinib Intervention Dosage modification of XELJANZ/XELJANZ XR is recommended [see Dosage and Administration (2) , Clinical Pharmacology, Figure 3 (12.3) ] Strong CYP3A4 Inducers (e.g., rifampin) Clinical Impact Decreased exposure to tofacitinib and may result in loss of or reduced clinical response Intervention Concomitant use with XELJANZ/XELJANZ… (label Tofasitinib, Interaksi obat)

…exposure to tofacitinib Intervention Dosage modification of XELJANZ/XELJANZ XR is recommended [see Dosage and Administration (2) , Clinical Pharmacology, Figure 3 (12.3) ] Strong CYP3A4 Inducers (e.g., rifampin) Clinical Impact Decreased exposure to tofacitinib and may result in loss of or reduced clinical response Intervention Concomitant use with XELJANZ/XELJANZ… (label Tofasitinib, Interaksi obat)

…exposure to tofacitinib Intervention Dosage modification of XELJANZ/XELJANZ XR is recommended [see Dosage and Administration (2) , Clinical Pharmacology, Figure 3 (12.3) ] Strong CYP3A4 Inducers (e.g., rifampin) Clinical Impact Decreased exposure to tofacitinib and may result in loss of or reduced clinical response Intervention Concomitant use with XELJANZ/XELJANZ… (label Tofasitinib, Interaksi obat)

Promptly evaluate patients treated with XELJANZ/XELJANZ XR who may be at increased risk for gastrointestinal perforation (e.g., patients with a history of diverticulitis or taking NSAIDs) and who present with new onset abdominal symptoms for early identification of gastrointestinal perforation [see Adverse Reactions (6.1) ] . (label Tofasitinib, Peringatan dan perhatian)

…exposure to tofacitinib Intervention Dosage modification of XELJANZ/XELJANZ XR is recommended [see Dosage and Administration (2) , Clinical Pharmacology, Figure 3 (12.3) ] Strong CYP3A4 Inducers (e.g., rifampin) Clinical Impact Decreased exposure to tofacitinib and may result in loss of or reduced clinical response Intervention Concomitant use with XELJANZ/XELJANZ… (label Tofasitinib, Interaksi obat)

Promptly evaluate patients treated with XELJANZ/XELJANZ XR who may be at increased risk for gastrointestinal perforation (e.g., patients with a history of diverticulitis or taking NSAIDs) and who present with new onset abdominal symptoms for early identification of gastrointestinal perforation [see Adverse Reactions (6.1) ] . (label Tofasitinib, Peringatan dan perhatian)

Promptly evaluate patients treated with XELJANZ/XELJANZ XR who may be at increased risk for gastrointestinal perforation (e.g., patients with a history of diverticulitis or taking NSAIDs) and who present with new onset abdominal symptoms for early identification of gastrointestinal perforation [see Adverse Reactions (6.1) ] . (label Tofasitinib, Peringatan dan perhatian)

Table 7: Clinically Significant Interactions Affecting XELJANZ/XELJANZ XR When Concomitantly Used with Other Drugs Strong CYP3A4 Inhibitors (e.g., ketoconazole) Clinical Impact Increased exposure to tofacitinib Intervention Dosage modification of XELJANZ/XELJANZ XR is recommended [see Dosage and Administration (2) , Clinical Pharmacology, Figure 3 (12.3) ] Moderate… (label Tofasitinib, Interaksi obat)

…exposure to tofacitinib Intervention Dosage modification of XELJANZ/XELJANZ XR is recommended [see Dosage and Administration (2) , Clinical Pharmacology, Figure 3 (12.3) ] Strong CYP3A4 Inducers (e.g., rifampin) Clinical Impact Decreased exposure to tofacitinib and may result in loss of or reduced clinical response Intervention Concomitant use with XELJANZ/XELJANZ… (label Tofasitinib, Interaksi obat)

Promptly evaluate patients treated with XELJANZ/XELJANZ XR who may be at increased risk for gastrointestinal perforation (e.g., patients with a history of diverticulitis or taking NSAIDs) and who present with new onset abdominal symptoms for early identification of gastrointestinal perforation [see Adverse Reactions (6.1) ] . (label Tofasitinib, Peringatan dan perhatian)

…exposure to tofacitinib Intervention Dosage modification of XELJANZ/XELJANZ XR is recommended [see Dosage and Administration (2) , Clinical Pharmacology, Figure 3 (12.3) ] Strong CYP3A4 Inducers (e.g., rifampin) Clinical Impact Decreased exposure to tofacitinib and may result in loss of or reduced clinical response Intervention Concomitant use with XELJANZ/XELJANZ… (label Tofasitinib, Interaksi obat)

Immunosuppressants: Amlodipine may increase the systemic exposure of cyclosporine or tacrolimus when co-administered. (label Olmesartan, amlodipin, dan hidroklorotiazid, Interaksi obat)

…modification of XELJANZ/XELJANZ XR is recommended [see Dosage and Administration (2) , Clinical Pharmacology, Figure 3 (12.3) ] Moderate CYP3A4 Inhibitors Concomitantly Used with Strong CYP2C19 Inhibitors (e.g., fluconazole) Clinical Impact Increased exposure to tofacitinib Intervention Dosage modification of XELJANZ/XELJANZ XR is recommended [see Dosage and Administration… (label Tofasitinib, Interaksi obat)

…modification of XELJANZ/XELJANZ XR is recommended [see Dosage and Administration (2) , Clinical Pharmacology, Figure 3 (12.3) ] Moderate CYP3A4 Inhibitors Concomitantly Used with Strong CYP2C19 Inhibitors (e.g., fluconazole) Clinical Impact Increased exposure to tofacitinib Intervention Dosage modification of XELJANZ/XELJANZ XR is recommended [see Dosage and Administration… (label Tofasitinib, Interaksi obat)

Promptly evaluate patients treated with XELJANZ/XELJANZ XR who may be at increased risk for gastrointestinal perforation (e.g., patients with a history of diverticulitis or taking NSAIDs) and who present with new onset abdominal symptoms for early identification of gastrointestinal perforation [see Adverse Reactions (6.1) ] . (label Tofasitinib, Peringatan dan perhatian)

Table 7: Clinically Significant Interactions Affecting XELJANZ/XELJANZ XR When Concomitantly Used with Other Drugs Strong CYP3A4 Inhibitors (e.g., ketoconazole) Clinical Impact Increased exposure to tofacitinib Intervention Dosage modification of XELJANZ/XELJANZ XR is recommended [see Dosage and Administration (2) , Clinical Pharmacology, Figure 3 (12.3) ] Moderate… (label Tofasitinib, Interaksi obat)

Promptly evaluate patients treated with XELJANZ/XELJANZ XR who may be at increased risk for gastrointestinal perforation (e.g., patients with a history of diverticulitis or taking NSAIDs) and who present with new onset abdominal symptoms for early identification of gastrointestinal perforation [see Adverse Reactions (6.1) ] . (label Tofasitinib, Peringatan dan perhatian)

Treatment has consisted of high doses of corticosteroids alone or, in some cases, concomitantly with an immunosuppressant. (label Penisilamin, Peringatan)

Table 7: Clinically Significant Interactions Affecting XELJANZ/XELJANZ XR When Concomitantly Used with Other Drugs Strong CYP3A4 Inhibitors (e.g., ketoconazole) Clinical Impact Increased exposure to tofacitinib Intervention Dosage modification of XELJANZ/XELJANZ XR is recommended [see Dosage and Administration (2) , Clinical Pharmacology, Figure 3 (12.3) ] Moderate… (label Tofasitinib, Interaksi obat)

Promptly evaluate patients treated with XELJANZ/XELJANZ XR who may be at increased risk for gastrointestinal perforation (e.g., patients with a history of diverticulitis or taking NSAIDs) and who present with new onset abdominal symptoms for early identification of gastrointestinal perforation [see Adverse Reactions (6.1) ] . (label Tofasitinib, Peringatan dan perhatian)

Table 7: Clinically Significant Interactions Affecting XELJANZ/XELJANZ XR When Concomitantly Used with Other Drugs Strong CYP3A4 Inhibitors (e.g., ketoconazole) Clinical Impact Increased exposure to tofacitinib Intervention Dosage modification of XELJANZ/XELJANZ XR is recommended [see Dosage and Administration (2) , Clinical Pharmacology, Figure 3 (12.3) ] Moderate… (label Tofasitinib, Interaksi obat)

…exposure to tofacitinib Intervention Dosage modification of XELJANZ/XELJANZ XR is recommended [see Dosage and Administration (2) , Clinical Pharmacology, Figure 3 (12.3) ] Strong CYP3A4 Inducers (e.g., rifampin) Clinical Impact Decreased exposure to tofacitinib and may result in loss of or reduced clinical response Intervention Concomitant use with XELJANZ/XELJANZ… (label Tofasitinib, Interaksi obat)

Table 7: Clinically Significant Interactions Affecting XELJANZ/XELJANZ XR When Concomitantly Used with Other Drugs Strong CYP3A4 Inhibitors (e.g., ketoconazole) Clinical Impact Increased exposure to tofacitinib Intervention Dosage modification of XELJANZ/XELJANZ XR is recommended [see Dosage and Administration (2) , Clinical Pharmacology, Figure 3 (12.3) ] Moderate… (label Tofasitinib, Interaksi obat)

…exposure to tofacitinib Intervention Dosage modification of XELJANZ/XELJANZ XR is recommended [see Dosage and Administration (2) , Clinical Pharmacology, Figure 3 (12.3) ] Strong CYP3A4 Inducers (e.g., rifampin) Clinical Impact Decreased exposure to tofacitinib and may result in loss of or reduced clinical response Intervention Concomitant use with XELJANZ/XELJANZ… (label Tofasitinib, Interaksi obat)

…exposure to tofacitinib Intervention Dosage modification of XELJANZ/XELJANZ XR is recommended [see Dosage and Administration (2) , Clinical Pharmacology, Figure 3 (12.3) ] Strong CYP3A4 Inducers (e.g., rifampin) Clinical Impact Decreased exposure to tofacitinib and may result in loss of or reduced clinical response Intervention Concomitant use with XELJANZ/XELJANZ… (label Tofasitinib, Interaksi obat)

…exposure to tofacitinib Intervention Dosage modification of XELJANZ/XELJANZ XR is recommended [see Dosage and Administration (2) , Clinical Pharmacology, Figure 3 (12.3) ] Strong CYP3A4 Inducers (e.g., rifampin) Clinical Impact Decreased exposure to tofacitinib and may result in loss of or reduced clinical response Intervention Concomitant use with XELJANZ/XELJANZ… (label Tofasitinib, Interaksi obat)

Table 7: Clinically Significant Interactions Affecting XELJANZ/XELJANZ XR When Concomitantly Used with Other Drugs Strong CYP3A4 Inhibitors (e.g., ketoconazole) Clinical Impact Increased exposure to tofacitinib Intervention Dosage modification of XELJANZ/XELJANZ XR is recommended [see Dosage and Administration (2) , Clinical Pharmacology, Figure 3 (12.3) ] Moderate… (label Tofasitinib, Interaksi obat)

Promptly evaluate patients treated with XELJANZ/XELJANZ XR who may be at increased risk for gastrointestinal perforation (e.g., patients with a history of diverticulitis or taking NSAIDs) and who present with new onset abdominal symptoms for early identification of gastrointestinal perforation [see Adverse Reactions (6.1) ] . (label Tofasitinib, Peringatan dan perhatian)

Promptly evaluate patients treated with XELJANZ/XELJANZ XR who may be at increased risk for gastrointestinal perforation (e.g., patients with a history of diverticulitis or taking NSAIDs) and who present with new onset abdominal symptoms for early identification of gastrointestinal perforation [see Adverse Reactions (6.1) ] . (label Tofasitinib, Peringatan dan perhatian)

…modification of XELJANZ/XELJANZ XR is recommended [see Dosage and Administration (2) , Clinical Pharmacology, Figure 3 (12.3) ] Moderate CYP3A4 Inhibitors Concomitantly Used with Strong CYP2C19 Inhibitors (e.g., fluconazole) Clinical Impact Increased exposure to tofacitinib Intervention Dosage modification of XELJANZ/XELJANZ XR is recommended [see Dosage and Administration… (label Tofasitinib, Interaksi obat)

…modification of XELJANZ/XELJANZ XR is recommended [see Dosage and Administration (2) , Clinical Pharmacology, Figure 3 (12.3) ] Moderate CYP3A4 Inhibitors Concomitantly Used with Strong CYP2C19 Inhibitors (e.g., fluconazole) Clinical Impact Increased exposure to tofacitinib Intervention Dosage modification of XELJANZ/XELJANZ XR is recommended [see Dosage and Administration… (label Tofasitinib, Interaksi obat)

HBV reactivation has also been reported in patients receiving certain immunosuppressant or chemotherapeutic agents; the risk of HBV reactivation associated with treatment with HCV direct-acting antivirals may be increased in these patients. (label Sofosbuvir dan velpatasvir, Peringatan dan perhatian)

Promptly evaluate patients treated with XELJANZ/XELJANZ XR who may be at increased risk for gastrointestinal perforation (e.g., patients with a history of diverticulitis or taking NSAIDs) and who present with new onset abdominal symptoms for early identification of gastrointestinal perforation [see Adverse Reactions (6.1) ] . (label Tofasitinib, Peringatan dan perhatian)

Promptly evaluate patients treated with XELJANZ/XELJANZ XR who may be at increased risk for gastrointestinal perforation (e.g., patients with a history of diverticulitis or taking NSAIDs) and who present with new onset abdominal symptoms for early identification of gastrointestinal perforation [see Adverse Reactions (6.1) ] . (label Tofasitinib, Peringatan dan perhatian)

Table 7: Clinically Significant Interactions Affecting XELJANZ/XELJANZ XR When Concomitantly Used with Other Drugs Strong CYP3A4 Inhibitors (e.g., ketoconazole) Clinical Impact Increased exposure to tofacitinib Intervention Dosage modification of XELJANZ/XELJANZ XR is recommended [see Dosage and Administration (2) , Clinical Pharmacology, Figure 3 (12.3) ] Moderate… (label Tofasitinib, Interaksi obat)

…exposure to tofacitinib Intervention Dosage modification of XELJANZ/XELJANZ XR is recommended [see Dosage and Administration (2) , Clinical Pharmacology, Figure 3 (12.3) ] Strong CYP3A4 Inducers (e.g., rifampin) Clinical Impact Decreased exposure to tofacitinib and may result in loss of or reduced clinical response Intervention Concomitant use with XELJANZ/XELJANZ… (label Tofasitinib, Interaksi obat)

Immunosuppressants: Amlodipine may increase the systemic exposure of cyclosporine or tacrolimus when co-administered. (label Telmisartan dan amlodipin, Interaksi obat)

Prophylaxis of PJP should be considered when concomitant use of corticosteroids or other immunosuppressive agents are required. (label Temsirolimus, Peringatan dan perhatian)

Table 7: Clinically Significant Interactions Affecting XELJANZ/XELJANZ XR When Concomitantly Used with Other Drugs Strong CYP3A4 Inhibitors (e.g., ketoconazole) Clinical Impact Increased exposure to tofacitinib Intervention Dosage modification of XELJANZ/XELJANZ XR is recommended [see Dosage and Administration (2) , Clinical Pharmacology, Figure 3 (12.3) ] Moderate… (label Tofasitinib, Interaksi obat)

Cyclosporine, tacrolimus: Monitor for toxicities of these immunosuppressive drugs ( 7.1 ) (label Tinidazol, Interaksi obat)

Promptly evaluate patients treated with XELJANZ/XELJANZ XR who may be at increased risk for gastrointestinal perforation (e.g., patients with a history of diverticulitis or taking NSAIDs) and who present with new onset abdominal symptoms for early identification of gastrointestinal perforation [see Adverse Reactions (6.1) ] . (label Tofasitinib, Peringatan dan perhatian)

…modification of XELJANZ/XELJANZ XR is recommended [see Dosage and Administration (2) , Clinical Pharmacology, Figure 3 (12.3) ] Moderate CYP3A4 Inhibitors Concomitantly Used with Strong CYP2C19 Inhibitors (e.g., fluconazole) Clinical Impact Increased exposure to tofacitinib Intervention Dosage modification of XELJANZ/XELJANZ XR is recommended [see Dosage and Administration… (label Tofasitinib, Interaksi obat)

Table 7: Clinically Significant Interactions Affecting XELJANZ/XELJANZ XR When Concomitantly Used with Other Drugs Strong CYP3A4 Inhibitors (e.g., ketoconazole) Clinical Impact Increased exposure to tofacitinib Intervention Dosage modification of XELJANZ/XELJANZ XR is recommended [see Dosage and Administration (2) , Clinical Pharmacology, Figure 3 (12.3) ] Moderate… (label Tofasitinib, Interaksi obat)

…modification of XELJANZ/XELJANZ XR is recommended [see Dosage and Administration (2) , Clinical Pharmacology, Figure 3 (12.3) ] Moderate CYP3A4 Inhibitors Concomitantly Used with Strong CYP2C19 Inhibitors (e.g., fluconazole) Clinical Impact Increased exposure to tofacitinib Intervention Dosage modification of XELJANZ/XELJANZ XR is recommended [see Dosage and Administration… (label Tofasitinib, Interaksi obat)

Thirty-four patients were treated with corticosteroids and one patient was treated with a non-steroidal immunosuppressant. (label Aksitinib, Peringatan dan perhatian)

IMNM is characterized by proximal muscle weakness and elevated serum creatine kinase that persists despite discontinuation of statin treatment; positive anti-HMG CoA reductase antibody; muscle biopsy showing necrotizing myopathy; and improvement with immunosuppressive agents. (label Atorvastatin, Peringatan dan perhatian)

IMNM is characterized by proximal muscle weakness and elevated serum creatine kinase that persist despite discontinuation of statin treatment; positive anti-HMG CoA reductase antibody; muscle biopsy showing necrotizing myopathy without significant inflammation; and improvement with immunosuppressive agents. (label Ezetimib dan simvastatin, Peringatan dan perhatian)

IMNM is characterized by proximal muscle weakness and elevated serum CK, which persist despite discontinuation of statin treatment; positive anti-HMG CoA reductase antibody, muscle biopsy showing necrotizing myopathy, and improvement with immunosuppressive agents. (label Fluvastatin, Peringatan dan perhatian)

IMNM is characterized by: proximal muscle weakness and elevated serum creatine kinase, which persist despite discontinuation of statin treatment; positive anti-HMG CoA reductase antibody; muscle biopsy showing necrotizing myopathy; and improvement with immunosuppressive agents. (label Lovastatin, Peringatan)

Immunosuppressive Drugs Tacrolimus: Tacrolimus has been shown to be metabolized via the CYP3A system. (label Nifedipin, Perhatian)

IMNM is characterized by proximal muscle weakness and elevated serum creatine kinase that persist despite discontinuation of statin treatment; positive anti-HMG CoA reductase antibody; muscle biopsy showing necrotizing myopathy; and improvement with immunosuppressive agents. (label Pitavastatin, Peringatan dan perhatian)

IMNM is characterized by proximal muscle weakness and elevated serum creatine kinase that persist despite discontinuation of statin treatment; positive anti-HMG CoA reductase antibody; muscle biopsy showing necrotizing myopathy; and improvement with immunosuppressive agents. (label Pravastatin, Peringatan dan perhatian)

In some cases, vasculitis resolved/improved with drug discontinuation; however, more severe cases required treatment with additional measures including corticosteroids, immunosuppressant therapy, and plasmapheresis. (label Propiltiourasil, Peringatan)

IMNM is characterized by proximal muscle weakness and elevated serum creatine kinase that persist despite discontinuation of statin treatment; positive anti-HMG CoA reductase antibody; muscle biopsy showing necrotizing myopathy; and improvement with immunosuppressive agents. (label Rosuvastatin, Peringatan dan perhatian)

IMNM is characterized by proximal muscle weakness and elevated serum creatine kinase that persist despite discontinuation of statin treatment; positive anti-HMG CoA reductase antibody; muscle biopsy showing necrotizing myopathy without significant inflammation; and improvement with immunosuppressive agents. (label Simvastatin, Peringatan dan perhatian)

In some cases, vasculitis resolved/improved with drug discontinuation; however, more severe cases required treatment with additional measures including corticosteroids, immunosuppressant therapy, and plasmapheresis. (label Tiamazol, Peringatan)