Wechselwirkungen von Tofacitinib

Additionally, concomitant use of ORENCIA with other biologic RA/PsA therapy or JAK inhibitors is not recommended. (Fachinformation zu Abatacept, Warnhinweise und Vorsichtsmaßnahmen)

MALIGNANCIES Malignancies, including lymphomas and solid tumors, have occurred in patients treated with XELJANZ and other Janus kinase inhibitors used to treat inflammatory conditions. (Fachinformation zu Tofacitinib, Boxed Warning (umrahmter Warnhinweis))

• Higher rate of all-cause mortality, including sudden cardiovascular (CV) death with XELJANZ vs. TNF blockers in rheumatoid arthritis (RA) patients. (Fachinformation zu Tofacitinib, Boxed Warning (umrahmter Warnhinweis))

…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… (Fachinformation zu Tofacitinib, Arzneimittelwechselwirkungen)

Most patients who developed these infections were taking concomitant immunosuppressants such as methotrexate or corticosteroids. (Fachinformation zu Tofacitinib, Boxed Warning (umrahmter Warnhinweis))

MALIGNANCIES Malignancies, including lymphomas and solid tumors, have occurred in patients treated with XELJANZ and other Janus kinase inhibitors used to treat inflammatory conditions. (Fachinformation zu Tofacitinib, Boxed Warning (umrahmter Warnhinweis))

Most patients who developed these infections were taking concomitant immunosuppressants such as methotrexate or corticosteroids. (Fachinformation zu Tofacitinib, Boxed Warning (umrahmter Warnhinweis))

Most patients who developed these infections were taking concomitant immunosuppressants such as methotrexate or corticosteroids. (Fachinformation zu Tofacitinib, Boxed Warning (umrahmter Warnhinweis))

Most patients who developed these infections were taking concomitant immunosuppressants such as methotrexate or corticosteroids. (Fachinformation zu Tofacitinib, Boxed Warning (umrahmter Warnhinweis))

Most patients who developed these infections were taking concomitant immunosuppressants such as methotrexate or corticosteroids. (Fachinformation zu Tofacitinib, Boxed Warning (umrahmter Warnhinweis))

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. (Fachinformation zu Captopril, Warnhinweise)

Most patients who developed these infections were taking concomitant immunosuppressants such as methotrexate or corticosteroids. (Fachinformation zu Tofacitinib, Boxed Warning (umrahmter Warnhinweis))

In kidney, liver, and heart transplant patients Neoral may be administered with other immunosuppressive agents. (Fachinformation zu Ciclosporin, Boxed Warning (umrahmter Warnhinweis))

Prevention or Management Concomitant use with myelosuppressive or other immunosuppressive drugs is not recommended. (Fachinformation zu Cladribin, Arzneimittelwechselwirkungen)

Most patients who developed these infections were taking concomitant immunosuppressants such as methotrexate or corticosteroids. (Fachinformation zu Tofacitinib, Boxed Warning (umrahmter Warnhinweis))

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. (Fachinformation zu Darunavir, Arzneimittelwechselwirkungen)

Most patients who developed these infections were taking concomitant immunosuppressants such as methotrexate or corticosteroids. (Fachinformation zu Tofacitinib, Boxed Warning (umrahmter Warnhinweis))

Most patients who developed these infections were taking concomitant immunosuppressants such as methotrexate or corticosteroids. (Fachinformation zu Tofacitinib, Boxed Warning (umrahmter Warnhinweis))

Most patients who developed these infections were taking concomitant immunosuppressants such as methotrexate or corticosteroids. (Fachinformation zu Tofacitinib, Boxed Warning (umrahmter Warnhinweis))

• Higher rate of all-cause mortality, including sudden cardiovascular (CV) death with XELJANZ vs. TNF blockers in rheumatoid arthritis (RA) patients. (Fachinformation zu Tofacitinib, Boxed Warning (umrahmter Warnhinweis))

Most patients who developed these infections were taking concomitant immunosuppressants such as methotrexate or corticosteroids. (Fachinformation zu Tofacitinib, Boxed Warning (umrahmter Warnhinweis))

Most patients who developed these infections were taking concomitant immunosuppressants such as methotrexate or corticosteroids. (Fachinformation zu Tofacitinib, Boxed Warning (umrahmter Warnhinweis))

Most patients who developed these infections were taking concomitant immunosuppressants such as methotrexate or corticosteroids. (Fachinformation zu Tofacitinib, Boxed Warning (umrahmter Warnhinweis))

Most patients who developed these infections were taking concomitant immunosuppressants such as methotrexate or corticosteroids. (Fachinformation zu Tofacitinib, Boxed Warning (umrahmter Warnhinweis))

Most patients who developed these infections were taking concomitant immunosuppressants such as methotrexate or corticosteroids. (Fachinformation zu Tofacitinib, Boxed Warning (umrahmter Warnhinweis))

Most patients who developed these infections were taking concomitant immunosuppressants such as methotrexate or corticosteroids. (Fachinformation zu Tofacitinib, Boxed Warning (umrahmter Warnhinweis))

Most patients who developed these infections were taking concomitant immunosuppressants such as methotrexate or corticosteroids. (Fachinformation zu Tofacitinib, Boxed Warning (umrahmter Warnhinweis))

• Higher rate of all-cause mortality, including sudden cardiovascular (CV) death with XELJANZ vs. TNF blockers in rheumatoid arthritis (RA) patients. (Fachinformation zu Tofacitinib, Boxed Warning (umrahmter Warnhinweis))

Immunosuppressants Everolimus Sirolimus Temsirolimus (IV) Not recommended during and 2 weeks after TOLSURA treatment. (Fachinformation zu Itraconazol, Arzneimittelwechselwirkungen)

Most patients who developed these infections were taking concomitant immunosuppressants such as methotrexate or corticosteroids. (Fachinformation zu Tofacitinib, Boxed Warning (umrahmter Warnhinweis))

Most patients who developed these infections were taking concomitant immunosuppressants such as methotrexate or corticosteroids. (Fachinformation zu Tofacitinib, Boxed Warning (umrahmter Warnhinweis))

Most patients who developed these infections were taking concomitant immunosuppressants such as methotrexate or corticosteroids. (Fachinformation zu Tofacitinib, Boxed Warning (umrahmter Warnhinweis))

…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:… (Fachinformation zu Nirmatrelvir und Ritonavir, Gegenanzeigen)

Most patients who developed these infections were taking concomitant immunosuppressants such as methotrexate or corticosteroids. (Fachinformation zu Tofacitinib, Boxed Warning (umrahmter Warnhinweis))

Most patients who developed these infections were taking concomitant immunosuppressants such as methotrexate or corticosteroids. (Fachinformation zu Tofacitinib, Boxed Warning (umrahmter Warnhinweis))

Most patients who developed these infections were taking concomitant immunosuppressants such as methotrexate or corticosteroids. (Fachinformation zu Tofacitinib, Boxed Warning (umrahmter Warnhinweis))

MALIGNANCIES Malignancies, including lymphomas and solid tumors, have occurred in patients treated with XELJANZ and other Janus kinase inhibitors used to treat inflammatory conditions. (Fachinformation zu Tofacitinib, Boxed Warning (umrahmter Warnhinweis))

MALIGNANCIES Malignancies, including lymphomas and solid tumors, have occurred in patients treated with XELJANZ and other Janus kinase inhibitors used to treat inflammatory conditions. (Fachinformation zu Tofacitinib, Boxed Warning (umrahmter Warnhinweis))

Patients who are current or past smokers are at additional increased risk. (Fachinformation zu Tofacitinib, Boxed Warning (umrahmter Warnhinweis))

…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… (Fachinformation zu Tofacitinib, Arzneimittelwechselwirkungen)

Most patients who developed these infections were taking concomitant immunosuppressants such as methotrexate or corticosteroids. (Fachinformation zu Tofacitinib, Boxed Warning (umrahmter Warnhinweis))

MALIGNANCIES Malignancies, including lymphomas and solid tumors, have occurred in patients treated with XELJANZ and other Janus kinase inhibitors used to treat inflammatory conditions. (Fachinformation zu Tofacitinib, Boxed Warning (umrahmter Warnhinweis))

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) ] . (Fachinformation zu Tofacitinib, Warnhinweise und Vorsichtsmaßnahmen)

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) ] . (Fachinformation zu Tofacitinib, Warnhinweise und Vorsichtsmaßnahmen)

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… (Fachinformation zu Tofacitinib, Arzneimittelwechselwirkungen)

Immunosuppressants Amlodipine may increase the systemic exposure of cyclosporine or tacrolimus when co-administered. (Fachinformation zu Amlodipin, Arzneimittelwechselwirkungen)

Impact of Amlodipine on Other Drugs Immunosuppressants Amlodipine may increase the systemic exposure of cyclosporine or tacrolimus when co-administered. (Fachinformation zu Amlodipin und Atorvastatin, Arzneimittelwechselwirkungen)

Immunosuppressants: Amlodipine may increase the systemic exposure of cyclosporine or tacrolimus when co-administered. (Fachinformation zu Amlodipin und Olmesartan, Arzneimittelwechselwirkungen)

Immunosuppressants Amlodipine may increase the systemic exposure of cyclosporine or tacrolimus when coadministered. (Fachinformation zu Amlodipin und Valsartan, Arzneimittelwechselwirkungen)

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… (Fachinformation zu Tofacitinib, Arzneimittelwechselwirkungen)

…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… (Fachinformation zu Tofacitinib, Arzneimittelwechselwirkungen)

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… (Fachinformation zu Tofacitinib, Arzneimittelwechselwirkungen)

Consider discontinuation or reduction of any concomitant chemotherapy or immunosuppressive therapy in patients who develop PML. (Fachinformation zu Bendamustin, Warnhinweise und Vorsichtsmaßnahmen)

…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… (Fachinformation zu Tofacitinib, Arzneimittelwechselwirkungen)

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) ] . (Fachinformation zu Tofacitinib, Warnhinweise und Vorsichtsmaßnahmen)

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) ] . (Fachinformation zu Tofacitinib, Warnhinweise und Vorsichtsmaßnahmen)

…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… (Fachinformation zu Tofacitinib, Arzneimittelwechselwirkungen)

…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… (Fachinformation zu Tofacitinib, Arzneimittelwechselwirkungen)

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) ] . (Fachinformation zu Tofacitinib, Warnhinweise und Vorsichtsmaßnahmen)

…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… (Fachinformation zu Tofacitinib, Arzneimittelwechselwirkungen)

…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… (Fachinformation zu Tofacitinib, Arzneimittelwechselwirkungen)

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… (Fachinformation zu Tofacitinib, Arzneimittelwechselwirkungen)

…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… (Fachinformation zu Tofacitinib, Arzneimittelwechselwirkungen)

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… (Fachinformation zu Tofacitinib, Arzneimittelwechselwirkungen)

…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… (Fachinformation zu Tofacitinib, Arzneimittelwechselwirkungen)

Other risk factors for the development of ONJ include immunosuppressive therapy, treatment with angiogenesis inhibitors, systemic corticosteroids, diabetes, and gingival infections. (Fachinformation zu Denosumab, Warnhinweise und Vorsichtsmaßnahmen)

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) ] . (Fachinformation zu Tofacitinib, Warnhinweise und Vorsichtsmaßnahmen)

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) ] . (Fachinformation zu Tofacitinib, Warnhinweise und Vorsichtsmaßnahmen)

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) ] . (Fachinformation zu Tofacitinib, Warnhinweise und Vorsichtsmaßnahmen)

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… (Fachinformation zu Tofacitinib, Arzneimittelwechselwirkungen)

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… (Fachinformation zu Tofacitinib, Arzneimittelwechselwirkungen)

…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… (Fachinformation zu Tofacitinib, Arzneimittelwechselwirkungen)

…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… (Fachinformation zu Tofacitinib, Arzneimittelwechselwirkungen)

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… (Fachinformation zu Tofacitinib, Arzneimittelwechselwirkungen)

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… (Fachinformation zu Tofacitinib, Arzneimittelwechselwirkungen)

…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… (Fachinformation zu Tofacitinib, Arzneimittelwechselwirkungen)

…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… (Fachinformation zu Tofacitinib, Arzneimittelwechselwirkungen)

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) ] . (Fachinformation zu Tofacitinib, Warnhinweise und Vorsichtsmaßnahmen)

…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… (Fachinformation zu Tofacitinib, Arzneimittelwechselwirkungen)

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… (Fachinformation zu Tofacitinib, Arzneimittelwechselwirkungen)

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… (Fachinformation zu Fenofibrat, Arzneimittelwechselwirkungen)

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… (Fachinformation zu Fenofibrinsäure, Arzneimittelwechselwirkungen)

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) ] . (Fachinformation zu Tofacitinib, Warnhinweise und Vorsichtsmaßnahmen)

…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… (Fachinformation zu Tofacitinib, Arzneimittelwechselwirkungen)

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) ] . (Fachinformation zu Tofacitinib, Warnhinweise und Vorsichtsmaßnahmen)

…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… (Fachinformation zu Tofacitinib, Arzneimittelwechselwirkungen)

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… (Fachinformation zu Tofacitinib, Arzneimittelwechselwirkungen)

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… (Fachinformation zu Tofacitinib, Arzneimittelwechselwirkungen)

…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… (Fachinformation zu Tofacitinib, Arzneimittelwechselwirkungen)

…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… (Fachinformation zu Tofacitinib, Arzneimittelwechselwirkungen)

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) ] . (Fachinformation zu Tofacitinib, Warnhinweise und Vorsichtsmaßnahmen)

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) ] . (Fachinformation zu Tofacitinib, Warnhinweise und Vorsichtsmaßnahmen)

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) ] . (Fachinformation zu Tofacitinib, Warnhinweise und Vorsichtsmaßnahmen)

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… (Fachinformation zu Tofacitinib, Arzneimittelwechselwirkungen)

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) ] . (Fachinformation zu Tofacitinib, Warnhinweise und Vorsichtsmaßnahmen)

…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… (Fachinformation zu Tofacitinib, Arzneimittelwechselwirkungen)

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… (Fachinformation zu Tofacitinib, Arzneimittelwechselwirkungen)

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… (Fachinformation zu Tofacitinib, Arzneimittelwechselwirkungen)

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) ] . (Fachinformation zu Tofacitinib, Warnhinweise und Vorsichtsmaßnahmen)

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) ] . (Fachinformation zu Tofacitinib, Warnhinweise und Vorsichtsmaßnahmen)

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. (Fachinformation zu Ledipasvir und Sofosbuvir, Warnhinweise und Vorsichtsmaßnahmen)

If used with concomitant methotrexate and/or other potential immunosuppressive agents, chronic monitoring should be monthly. (Fachinformation zu Leflunomid, Warnhinweise und Vorsichtsmaßnahmen)

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… (Fachinformation zu Tofacitinib, Arzneimittelwechselwirkungen)

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… (Fachinformation zu Tofacitinib, Arzneimittelwechselwirkungen)

…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… (Fachinformation zu Tofacitinib, Arzneimittelwechselwirkungen)

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) ] . (Fachinformation zu Tofacitinib, Warnhinweise und Vorsichtsmaßnahmen)

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) ] . (Fachinformation zu Tofacitinib, Warnhinweise und Vorsichtsmaßnahmen)

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. (Fachinformation zu Mercaptopurin, Warnhinweise und Vorsichtsmaßnahmen)

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… (Fachinformation zu Tofacitinib, Arzneimittelwechselwirkungen)

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… (Fachinformation zu Tofacitinib, Arzneimittelwechselwirkungen)

…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… (Fachinformation zu Tofacitinib, Arzneimittelwechselwirkungen)

…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… (Fachinformation zu Tofacitinib, Arzneimittelwechselwirkungen)

…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… (Fachinformation zu Tofacitinib, Arzneimittelwechselwirkungen)

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 )]. (Fachinformation zu Mycophenolat, Warnhinweise und Vorsichtsmaßnahmen)

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) ] . (Fachinformation zu Tofacitinib, Warnhinweise und Vorsichtsmaßnahmen)

…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… (Fachinformation zu Tofacitinib, Arzneimittelwechselwirkungen)

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) ] . (Fachinformation zu Tofacitinib, Warnhinweise und Vorsichtsmaßnahmen)

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) ] . (Fachinformation zu Tofacitinib, Warnhinweise und Vorsichtsmaßnahmen)

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… (Fachinformation zu Tofacitinib, Arzneimittelwechselwirkungen)

…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… (Fachinformation zu Tofacitinib, Arzneimittelwechselwirkungen)

Immunosuppressants: Amlodipine may increase the systemic exposure of cyclosporine or tacrolimus when co-administered. (Fachinformation zu Olmesartan, Amlodipin und Hydrochlorothiazid, Arzneimittelwechselwirkungen)

…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… (Fachinformation zu Tofacitinib, Arzneimittelwechselwirkungen)

…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… (Fachinformation zu Tofacitinib, Arzneimittelwechselwirkungen)

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) ] . (Fachinformation zu Tofacitinib, Warnhinweise und Vorsichtsmaßnahmen)

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) ] . (Fachinformation zu Tofacitinib, Warnhinweise und Vorsichtsmaßnahmen)

…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… (Fachinformation zu Tofacitinib, Arzneimittelwechselwirkungen)

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… (Fachinformation zu Tofacitinib, Arzneimittelwechselwirkungen)

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) ] . (Fachinformation zu Tofacitinib, Warnhinweise und Vorsichtsmaßnahmen)

Treatment has consisted of high doses of corticosteroids alone or, in some cases, concomitantly with an immunosuppressant. (Fachinformation zu Penicillamin, Warnhinweise)

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… (Fachinformation zu Tofacitinib, Arzneimittelwechselwirkungen)

…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… (Fachinformation zu Tofacitinib, Arzneimittelwechselwirkungen)

…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… (Fachinformation zu Tofacitinib, Arzneimittelwechselwirkungen)

…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… (Fachinformation zu Tofacitinib, Arzneimittelwechselwirkungen)

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) ] . (Fachinformation zu Tofacitinib, Warnhinweise und Vorsichtsmaßnahmen)

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… (Fachinformation zu Tofacitinib, Arzneimittelwechselwirkungen)

…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… (Fachinformation zu Tofacitinib, Arzneimittelwechselwirkungen)

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… (Fachinformation zu Tofacitinib, Arzneimittelwechselwirkungen)

…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… (Fachinformation zu Tofacitinib, Arzneimittelwechselwirkungen)

…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… (Fachinformation zu Tofacitinib, Arzneimittelwechselwirkungen)

…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… (Fachinformation zu Tofacitinib, Arzneimittelwechselwirkungen)

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… (Fachinformation zu Tofacitinib, Arzneimittelwechselwirkungen)

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) ] . (Fachinformation zu Tofacitinib, Warnhinweise und Vorsichtsmaßnahmen)

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. (Fachinformation zu Sofosbuvir und Velpatasvir, Warnhinweise und Vorsichtsmaßnahmen)

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) ] . (Fachinformation zu Tofacitinib, Warnhinweise und Vorsichtsmaßnahmen)

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) ] . (Fachinformation zu Tofacitinib, Warnhinweise und Vorsichtsmaßnahmen)

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… (Fachinformation zu Tofacitinib, Arzneimittelwechselwirkungen)

…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… (Fachinformation zu Tofacitinib, Arzneimittelwechselwirkungen)

Immunosuppressants: Amlodipine may increase the systemic exposure of cyclosporine or tacrolimus when co-administered. (Fachinformation zu Telmisartan und Amlodipin, Arzneimittelwechselwirkungen)

Prophylaxis of PJP should be considered when concomitant use of corticosteroids or other immunosuppressive agents are required. (Fachinformation zu Temsirolimus, Warnhinweise und Vorsichtsmaßnahmen)

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… (Fachinformation zu Tofacitinib, Arzneimittelwechselwirkungen)

Cyclosporine, tacrolimus: Monitor for toxicities of these immunosuppressive drugs ( 7.1 ) (Fachinformation zu Tinidazol, Arzneimittelwechselwirkungen)

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) ] . (Fachinformation zu Tofacitinib, Warnhinweise und Vorsichtsmaßnahmen)

…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… (Fachinformation zu Tofacitinib, Arzneimittelwechselwirkungen)

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… (Fachinformation zu Tofacitinib, Arzneimittelwechselwirkungen)

…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… (Fachinformation zu Tofacitinib, Arzneimittelwechselwirkungen)

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. (Fachinformation zu Atorvastatin, Warnhinweise und Vorsichtsmaßnahmen)

Thirty-four patients were treated with corticosteroids and one patient was treated with a non-steroidal immunosuppressant. (Fachinformation zu Axitinib, Warnhinweise und Vorsichtsmaßnahmen)

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. (Fachinformation zu Ezetimib und Simvastatin, Warnhinweise und Vorsichtsmaßnahmen)

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. (Fachinformation zu Fluvastatin, Warnhinweise und Vorsichtsmaßnahmen)

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. (Fachinformation zu Lovastatin, Warnhinweise)

Immunosuppressive Drugs Tacrolimus: Tacrolimus has been shown to be metabolized via the CYP3A system. (Fachinformation zu Nifedipin, Vorsichtsmaßnahmen)

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. (Fachinformation zu Pitavastatin, Warnhinweise und Vorsichtsmaßnahmen)

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. (Fachinformation zu Pravastatin, Warnhinweise und Vorsichtsmaßnahmen)

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

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. (Fachinformation zu Rosuvastatin, Warnhinweise und Vorsichtsmaßnahmen)

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. (Fachinformation zu Simvastatin, Warnhinweise und Vorsichtsmaßnahmen)

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