ANAKINRA Drug Interactions: What You Need to Know

INTERACTIONS No drug-drug interaction studies in human subjects have been conducted. Toxicologic and toxicokinetic studies in rats did not demonstrate any alterations in the clearance or toxicologic profile of either methotrexate or KINERET when the two agents were administered together. A higher rate of serious infections has been observed in RA patients treated with concurrent KINERET and etanercept therapy than in patients treated with etanercept alone. Use of KINERET in combination with TNF blocking agents is not recommended ( 7 )

7.1 TNF Blocking Agents A higher rate of serious infections has been observed in patients treated with concurrent KINERET and etanercept therapy than in patients treated with etanercept alone <span class="opacity-50 text-xs">[see Warnings and Precautions ( 5.2 )]</span> . Two percent of patients treated concurrently with KINERET and etanercept developed neutropenia (ANC &lt; 1 x 10 9 /L). Use of KINERET in combination with TNF blocking agents is not recommended.

KINERET is contraindicated in patients with known hypersensitivity to E coli -derived proteins, KINERET, or any components of the product [see Hypersensitivity Reactions ( 5.3 )] . Known hypersensitivity to E coli -derived proteins, Kineret, or to any component of the product. ( 4 )

AND PRECAUTIONS In RA, discontinue use if serious infection develops. In KINERET-treated NOMID or DIRA patients, the risk of a disease flare when discontinuing KINERET treatment should be weighed against the potential risk of continued treatment. Do not initiate KINERET in patients with active infections. ( 5.1 ) Use in combination with Tumor Necrosis Factor (TNF) blocking agents is not recommended ( 5.2 ) Hypersensitivity reactions, including anaphylactic reactions and angioedema, and serious cutaneous reactions including Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) can occur; discontinue KINERET, treat promptly, and monitor until reaction resolves. Patients with DIRA may have an increased risk of allergic reactions, particularly in the first several weeks after starting KINERET treatment ( 5.3 ) The impact of treatment with KINERET on active and/or chronic infections and the development of malignancies is not known ( 5.4 ) Recommend patients to rotate injection sites to reduce the risk of injection site amyloid deposits ( 5.5 ) Live vaccines should not be given concurrently with KINERET ( 5.6 ) Neutrophil counts should be assessed prior to initiating KINERET treatment, and while receiving KINERET, monthly for 3 months, and thereafter quarterly for a period up to 1 year ( 5.7 )

5.1 Serious Infections KINERET has been associated with an increased incidence of serious infections (2%) vs. Placebo (&lt; 1%) in clinical trials in RA. Administration of KINERET in RA should be discontinued if a patient develops a serious infection. In KINERET treated NOMID and DIRA patients the risk of a disease flare when discontinuing KINERET treatment should be weighed against the potential risk of continued treatment. Treatment with KINERET should not be initiated in patients with active infections. The safety and efficacy of KINERET in immunosuppressed patients or in patients with chronic infections have not been evaluated. Drugs that affect the immune system by blocking tumor necrosis factor (TNF) have been associated with an increased risk of reactivation of latent tuberculosis (TB). It is possible that taking drugs such as KINERET that blocks IL-1 increases the risk of TB or other atypical or opportunistic infections. Health care providers should follow current CDC guidelines both to evaluate for and to treat possible latent tuberculosis infections before initiating therapy with KINERET.

5.2 Use with TNF Blocking Agents In a 24-week study of concurrent KINERET and etanercept therapy in RA patients, the rate of serious infections in the combination arm (7%) was higher than with etanercept alone (0%). The combination of KINERET and etanercept did not result in higher ACR response rates compared to etanercept alone <span class="opacity-50 text-xs">[see Clinical Studies ( 14 )]</span> . Use of KINERET in combination with TNF blocking agents is not recommended.

5.3 Hypersensitivity Reactions Hypersensitivity reactions, including anaphylactic reactions and angioedema, have been reported with KINERET. Serious cutaneous reactions, including Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS), have been reported in patients with autoinflammatory conditions treated with KINERET. If a severe hypersensitivity reaction occurs, immediately discontinue KINERET; treat promptly and monitor until signs and symptoms resolve. KINERET is the recombinant form of IL-1Ra that DIRA patients are lacking. Patients with DIRA may have an increased risk of allergic reactions, particularly in the first several weeks after starting KINERET treatment. Patients should be closely monitored during this time period. If a severe allergic reaction occurs, appropriate treatment should be initiated and discontinuation of KINERET should be considered.

5.4 Immunosuppression The impact of treatment with KINERET on active and/or chronic infections and the development of malignancies is not known <span class="opacity-50 text-xs">[see Adverse Reactions ( 6 )]</span> .

5.5 Amyloidosis Post-marketing cases of injection site amyloid deposits <span class="opacity-50 text-xs">[see Postmarketing Experience ( 6.4 )]</span> have been reported in NOMID patients after receiving high doses of Kineret injected subcutaneously into the same area of skin over long periods of time. Systemic AIL1RAP (IL-1 receptor antagonist protein) amyloidosis occurred in some of these patients with injection site amyloid deposits; these patients presented with proteinuria. Recommend patients to rotate their injection sites. In patients with confirmed injection site amyloid deposits, monitor proteinuria for systemic amyloidosis.

5.6 Immunizations In a placebo-controlled clinical trial (n = 126), no difference was detected in anti-tetanus antibody response between the KINERET and placebo treatment groups when the tetanus/diphtheria toxoids vaccine was administered concurrently with KINERET. No data are available on the effects of vaccination with other inactivated antigens in patients receiving KINERET. No data are available on either the effects of live vaccination or the secondary transmission of infection by live vaccines in patients receiving KINERET. Therefore, live vaccines should not be given concurrently with KINERET.

5.7 Neutrophil Count Patients receiving KINERET may experience a decrease in neutrophil counts. Neutrophil counts should therefore be assessed prior to initiating KINERET treatment, and while receiving KINERET, monthly for 3 months, and thereafter quarterly for a period up to 1 year. In the placebo-controlled studies, 8% of RA patients receiving KINERET had decreases in neutrophil counts of at least one World Health Organization (WHO) toxicity grade compared with 2% in the placebo control group. Nine KINERET-treated patients (0.4%) experienced neutropenia (ANC &lt; 1 x 10 9 /L). This is discussed in more detail in the Adverse Reactions ( 6 ): Hematologic Events ( 6.1 ) section.

In

43 NOMID patients followed for up to 60 months 2 patients experienced neutropenia that resolved over time during continued KINERET treatment. [see Adverse Reactions ( 6.2 )]