ABATACEPT Drug Interactions: What You Need to Know

INTERACTIONS

7.1 Immunosuppressants Concomitant administration of a TNF antagonist with ORENCIA has been associated with an increased risk of serious infections and no significant additional efficacy over use of the TNF antagonists alone. Concurrent therapy with ORENCIA and TNF antagonists is not recommended <span class="opacity-50 text-xs">[see Warnings and Precautions (5.1) ]</span>. There is insufficient experience to assess the safety and efficacy of ORENCIA administered concurrently with other biologic RA therapy, such as anakinra, or other biologic PsA therapy, and JAK inhibitors and therefore such use is not recommended. <span class="opacity-50 text-xs">[see Warnings and Precautions (5.1) ]</span> .

7.2 Blood Glucose Testing Parenteral drug products containing maltose can interfere with the readings of blood glucose monitors that use test strips with glucose dehydrogenase pyrroloquinoline quinone (GDH-PQQ). The GDH-PQQ based glucose monitoring systems may react with the maltose present in ORENCIA for intravenous administration, resulting in falsely elevated blood glucose readings on the day of infusion. When receiving intravenous ORENCIA, patients that require blood glucose monitoring should be advised to consider methods that do not react with maltose, such as those based on glucose dehydrogenase nicotine adenine dinucleotide (GDH-NAD), glucose oxidase, or glucose hexokinase test methods. ORENCIA for subcutaneous administration does not contain maltose; therefore, patients do not need to alter their glucose monitoring.

None. None. (4)

AND PRECAUTIONS

• Concomitant use with a TNF antagonist can increase the risk of infections and serious infections. (5.1)
• Hypersensitivity and anaphylaxis have occurred. (5.2)
• Serious infections reported. Patients with a history of recurrent infections or underlying conditions predisposing to infections may experience more infections. Discontinue if a serious infection develops. (5.3)
• Screen for latent TB infection prior to initiating therapy. Patients testing positive should be treated prior to initiating ORENCIA. (5.3)
• Screen for viral hepatitis prior to initiating ORENCIA. (5.3)
• Update vaccinations prior to initiating ORENCIA. Live vaccines should not be given concurrently or within 3 months of discontinuation. ORENCIA may blunt the effectiveness of some immunizations. (5.4)
• COPD patients may develop more frequent respiratory adverse reactions. (5.5)
• Cytomegalovirus (CMV) and Epstein-Barr Virus (EBV) reactivation in patients treated for aGVHD prophylaxis. (5.7)

5.1 Increased Risk of Infection with Concomitant Use of TNF Antagonists, Other Biologic RA/PsA Therapy, or JAK Inhibitors In controlled clinical trials in patients with adult RA, patients receiving concomitant intravenous ORENCIA and TNF antagonist therapy experienced more infections (63% vs. 43%) and serious infections (4.4% vs. 0.8%) compared to patients treated with only TNF antagonists <span class="opacity-50 text-xs">[see Adverse Reactions (6.1) ]</span> . These trials failed to demonstrate an important enhancement of efficacy with concomitant administration of ORENCIA with TNF antagonists; therefore, concurrent therapy with ORENCIA and a TNF antagonist is not recommended. While transitioning from TNF antagonist therapy to ORENCIA therapy, patients should be monitored for signs of infection. Additionally, concomitant use of ORENCIA with other biologic RA/PsA therapy or JAK inhibitors is not recommended.

5.2 Hypersensitivity Reactions In clinical trials of 2688 adult RA patients treated with intravenous ORENCIA, there were two cases (&lt;0.1%) of anaphylaxis reactions. Other reactions potentially associated with drug hypersensitivity, such as hypotension, urticaria, and dyspnea, each occurred in less than 0.9% of ORENCIA-treated patients. Of the 190 ORENCIA-treated patients in pJIA clinical trials, there was one case of a hypersensitivity reaction (0.5%) <span class="opacity-50 text-xs">[see Adverse Reactions (6.1 )]</span> . In postmarketing experience, fatal anaphylaxis following the first infusion of ORENCIA and life-threatening cases of angioedema have been reported. Angioedema has occurred as early as after the first dose of ORENCIA, but also has occurred with subsequent doses. Angioedema reactions have occurred within hours of administration and in some instances had a delayed onset (i.e., days). Appropriate medical support measures for the treatment of hypersensitivity reactions should be available for immediate use in the event of a reaction. If an anaphylactic or other serious allergic reaction occurs, administration of intravenous or subcutaneous ORENCIA should be stopped immediately with appropriate therapy instituted, and the use of ORENCIA should be permanently discontinued.

5.3 Infections Serious infections, including sepsis and pneumonia, have been reported in patients receiving ORENCIA (serious infections were reported in 3% and 1.9% of RA patients treated with intravenous ORENCIA and placebo, respectively) <span class="opacity-50 text-xs">[see Adverse Reactions (6.1) ]</span> . Some of these infections have been fatal. Many of the serious infections have occurred in patients on concomitant immunosuppressive therapy which in addition to their underlying disease, could further predispose them to infection. A higher rate of serious infections has been observed in adult RA patients treated with concurrent TNF antagonists and ORENCIA compared to those treated with ORENCIA alone <span class="opacity-50 text-xs">[see Warnings and Precautions (5.1) ]</span> . Healthcare providers should exercise caution when considering the use of ORENCIA in patients with a history of recurrent infections, underlying conditions which may predispose them to infections, or chronic, latent, or localized infections. Patients who develop a new infection while undergoing treatment with ORENCIA should be monitored closely. Administration of ORENCIA should be discontinued if a patient develops a serious infection. Prior to initiating ORENCIA, patients should be screened for latent tuberculosis (TB) infection according to current TB guidelines. ORENCIA has not been studied in patients with a positive TB screen, and the safety of ORENCIA in individuals with latent TB infection is unknown. Patients testing positive in TB screening should be treated by standard medical practice prior to therapy with ORENCIA. Antirheumatic therapies have been associated with hepatitis B reactivation. Therefore, screening for viral hepatitis should be performed in accordance with published guidelines before starting therapy with ORENCIA. In clinical studies with ORENCIA, patients who screened positive for hepatitis were excluded from study.

5.4 Immunizations Prior to initiating ORENCIA in pediatric and adult patients, update vaccinations in accordance with current vaccination guidelines. ORENCIA-treated patients may receive current non-live vaccines. Live vaccines should not be given concurrently with ORENCIA or within 3 months after discontinuation. No data are available on the secondary transmission of infection from persons receiving live vaccines to patients receiving ORENCIA. In addition, there are clinical considerations for administering live vaccines to infants who were exposed to ORENCIA while in utero <span class="opacity-50 text-xs">[see Use in Specific Populations (8.1) ]</span> . Based on its mechanism of action, ORENCIA may blunt the effectiveness of some immunizations.

5.5 Increased Risk of Adverse Reactions When Used in Patients with Chronic Obstructive Pulmonary Disease (COPD)

In

Study V, adult COPD patients treated with ORENCIA for RA developed adverse reactions more frequently than those treated with placebo, including COPD exacerbations, cough, rhonchi, and dyspnea. A greater percentage of patients treated with ORENCIA developed a serious adverse event compared to patients treated with placebo (27% vs 6%) [see Clinical Studies (14.1) and Adverse Reactions (6.1) ] . Use of ORENCIA in patients with COPD should be undertaken with caution and such patients should be monitored for worsening of their respiratory status.

5.6 Immunosuppression The possibility exists for drugs inhibiting T-cell activation, including ORENCIA, to affect host defenses against infections and malignancies since T cells mediate cellular immune responses. In clinical trials in patients with adult RA, a higher rate of infections was seen in ORENCIA-treated patients compared to placebo-treated patients <span class="opacity-50 text-xs">[see Warnings and Precautions (5.3) and Adverse Reactions (6.1) ]</span> . The impact of treatment with ORENCIA on the development and course of malignancies is not fully understood <span class="opacity-50 text-xs">[see Adverse Reactions (6.1) ]</span> . There have been reports of malignancies, including skin cancer in patients receiving ORENCIA <span class="opacity-50 text-xs">[see Adverse Reactions (6.3) ]</span> . Periodic skin examinations are recommended for all ORENCIA-treated patients, particularly those with risk factors for skin cancer.

5.7 Cytomegalovirus (CMV) and Epstein-Barr Virus (EBV) Reactivation in aGVHD Prophylaxis after Hematopoietic Stem Cell Transplant (HSCT) Post-Transplant Lymphoproliferative Disorder (PTLD) occurred in patients who received ORENCIA for aGVHD prophylaxis during unrelated HSCT.

Of

116 patients who received ORENCIA, 4 patients (3.4%) experienced PTLD. All the PTLD events were associated with Epstein-Barr virus (EBV) infection. Three of the four patients were EBV serology positive at baseline; one patient had negative baseline EBV serology with donor EBV serology unknown. Three of the 4 patients discontinued acyclovir prophylaxis at day 30 post-transplant. The range of time to onset of the events was 49 to 89 days post-transplant. Monitor patients for EBV reactivation in accordance with institutional practices. Provide prophylaxis for EBV infection for 6 months post-transplantation to prevent EBV-associated PTLD [see Dosage and Administration (2.4) ] . Cytomegalovirus (CMV) invasive disease occurred in patients who received ORENCIA for aGVHD prophylaxis during unrelated HSCT.

Of

116 patients who received ORENCIA, 7% experienced CMV invasive diseases up to day 225 post-transplant. All the patients who experienced CMV invasive disease were CMV serology positive at baseline. The median time to onset of the event was 91 days post-transplant. CMV invasive diseases predominantly involved the gastrointestinal tract [see Adverse Reactions (6.1) ] . Monitor patients for CMV infection/reactivation for 6 months post-transplant regardless of the results of donor and recipient pre-transplant CMV serology. Consider prophylaxis for CMV infection/reactivation [see Dosage and Administration (2.4) ] .