RILONACEPT Drug Interactions: What You Need to Know

INTERACTIONS

7.1 TNF-Blocking Agent and IL-1 Blocking Agent Specific drug interaction studies have not been conducted with ARCALYST. Concomitant administration of another drug that blocks IL-1 with a TNF-blocking agent in another patient population has been associated with an increased risk of serious infections and an increased risk of neutropenia. The concomitant administration of ARCALYST with TNF-blocking agents may also result in similar toxicities and is not recommended <span class="opacity-50 text-xs">[see Warnings and Precautions (5.1) ]</span> . The concomitant administration of ARCALYST with other drugs that block IL-1 has not been studied. Based upon the potential for pharmacologic interactions between rilonacept and a recombinant IL-1ra, concomitant administration of ARCALYST and other agents that block IL-1 or its receptors is not recommended.

7.2 Cytochrome P450 Substrates The formation of CYP450 enzymes is suppressed by increased levels of cytokines (e.g., IL-1) during chronic inflammation. Thus it is expected that for a molecule that binds to IL-1, such as rilonacept, the formation of CYP450 enzymes could be normalized. This is clinically relevant for CYP450 substrates with a narrow therapeutic index, where the dose is individually adjusted (e.g., warfarin). Upon initiation of ARCALYST in patients being treated with these types of medicinal products, therapeutic monitoring of the effect or drug concentration should be performed, and the individual dose of the medicinal product may need to be adjusted.

None. None. ( 4 )

AND PRECAUTIONS Serious Infections : Serious, life-threatening infections have been reported in patients taking ARCALYST. Do not initiate treatment with ARCALYST in patients with active or chronic infections. Discontinue treatment if a patient develops a serious infection. ( 5.1 )

Hypersensitivity

Reactions : If a hypersensitivity reaction occurs, discontinue administration of ARCALYST and initiate appropriate therapy. ( 5.3 ) Immunizations : Avoid live vaccines. Update recommended vaccinations prior to initiation of therapy per current guidelines. ( 5.5 )

5.1 Serious Infections Interleukin-1 (IL-1) blockade may interfere with the immune response to infections. Treatment with another medication that works through inhibition of IL-1 has been associated with an increased risk of serious infections, and serious infections have been reported in patients taking ARCALYST <span class="opacity-50 text-xs">[see Clinical Studies (14) ]</span> . There was a greater incidence of infections in CAPS and RP patients on ARCALYST compared with placebo. In the controlled portion of the CAPS study <span class="opacity-50 text-xs">[see Clinical Studies (14.1) ]</span> , severe infection (bronchitis) was reported in one patient receiving ARCALYST. In an open-label extension study in CAPS, one patient developed bacterial meningitis and died <span class="opacity-50 text-xs">[see Adverse Reactions (6.1) ]</span> . In clinical studies, ARCALYST has not been administered concomitantly with tumor necrosis factor (TNF) inhibitors. An increased incidence of serious infections has been associated with administration of an IL-1 blocker in combination with TNF inhibitors. ARCALYST is not recommended for use with TNF inhibitors because this may increase the risk of serious infections. Drugs that affect the immune system by blocking TNF have been associated with an increased risk of reactivation of latent tuberculosis (TB). It is possible that taking drugs such as ARCALYST that block IL-1 increases the risk of TB or other atypical or opportunistic infections. Refer to current practice guidelines for evaluation and treatment of possible latent tuberculosis infections before initiating therapy with ARCALYST. Treatment with ARCALYST should not be initiated in patients with an active or chronic infection. Discontinue ARCALYST if a patient develops a serious infection.

5.2 Risk of Malignancy The impact of treatment with ARCALYST on the development of malignancies is not known. Treatment with immunosuppressants, including ARCALYST, may result in an increase in the risk of malignancies.

5.3 Hypersensitivity Reactions Hypersensitivity reactions associated with ARCALYST occurred in clinical trials. If a hypersensitivity reaction occurs, discontinue ARCALYST and initiate appropriate therapy.

5.4 Lipid Profile Changes Cholesterol and lipid levels may be reduced in patients with chronic inflammation. Increases in non-fasting lipid profile parameters occurred in patients treated with ARCALYST in clinical trials. Monitor patients&apos; lipid profiles and consider lipid-lowering therapies if needed, based on cardiovascular risk factors and current guidelines <span class="opacity-50 text-xs">[see Adverse Reactions (6.1) ]</span> .

5.5 Immunizations Since no data are available on the risks of secondary transmission of infection by live vaccines in patients receiving ARCALYST, avoid administration of live vaccines during treatment with ARCALYST. No data are available on the effectiveness of vaccines in patients receiving ARCALYST. Since ARCALYST may interfere with normal immune response to new antigens, vaccines may not be effective in patients receiving ARCALYST. Because IL-1 blockade may interfere with immune response to infections, it is recommended that prior to initiation of therapy with ARCALYST, adult and pediatric patients receive all recommended vaccinations, as per current immunization guidelines, including pneumococcal vaccine and inactivated influenza vaccine.