Rilonacept

Rilonacept is used to treat some of the symptoms of rare genetic conditions such as Familial Cold Auto-inflammatory Syndrome (FCAS) or Muckle-Wells Syndrome (MWS).

FCAS and MWS are inflammatory disorders in which the body develops certain symptoms without a known cause (such as virus, bacteria, or illness). These symptoms include fever, chills, fatigue, and joint pain. More serious symptoms may involve the bones and joints, the central nervous system (deafness, vision loss, mental impairment), or major organs such as the kidneys.

Rilonacept may treat or prevent the symptoms of Familial Cold Auto-inflammatory Syndrome (FCAS) or Muckle-Wells Syndrome (MWS). However, this medication is not a cure for these inherited conditions.

Rilonacept may also be used for purposes not listed in this medication guide.

Serious and sometimes fatal infections may occur during treatment with rilonacept. Call your doctor right away if you have signs of infection such as: fever, chills, sore throat, flu symptoms, easy bruising or bleeding (nosebleeds, bleeding gums), loss of appetite, nausea and vomiting, mouth sores, or unusual weakness.

You should not use this medication if you are allergic to rilonacept, or if you have any type of infection.

Before using rilonacept, tell your doctor if you have an active or chronic infection, a history of tuberculosis or recurrent infections, or high cholesterol or triglycerides. Make sure you are current on all vaccines before you start treatment with rilonacept.

Tell your doctor about all other medications you use, especially drugs to treat arthritis, psoriasis, Crohn's disease, or ankylosing spondylitis.

Do not receive a "live" vaccine while using rilonacept. The vaccine may not work as well during this time, and may not fully protect you from disease. Avoid coming into contact with anyone who has recently received a live vaccine. There is a chance that the virus could be passed on to you.

You should not use this medication if you are allergic to rilonacept, or if you have any type of infection.

To make sure rilonacept is safe for you, tell your doctor if you have any of these conditions:

• an active or chronic infection;
• a history of tuberculosis or recurrent infections; or
• high cholesterol or triglycerides (a type of fat in blood).

Make sure you are current on all vaccines before you start treatment with rilonacept.

Using rilonacept may increase your risk of developing certain types of cancer. Talk with your doctor about your specific risk.

FDA pregnancy category C. It is not known whether rilonacept will harm an unborn baby. Tell your doctor if you are pregnant or plan to become pregnant while using this medication.

It is not known whether rilonacept passes into breast milk or if it could harm a nursing baby. Do not use this medication without telling your doctor if you are breast-feeding a baby.

Do not give this medicine to a child younger than 12 years old without medical advice.

Do not receive a "live" vaccine while using rilonacept. The vaccine may not work as well during this time, and may not fully protect you from disease. Avoid coming into contact with anyone who has recently received a live vaccine. There is a chance that the virus could be passed on to you.

Live vaccines include: measles, mumps, rubella (MMR), Bacillus Calmette-Guérin (BCG), oral polio, rotavirus, smallpox, yellow fever, varicella (chickenpox), zoster (shingles), oral typhoid vaccine, and nasal flu (influenza) vaccine.

Tell your doctor about all medications you use, and those you start or stop using during your treatment with rilonacept, especially:

• adalimumab (Humira);
• certolizumab (Cimzia)
• etanercept (Enbrel);
• fingolimod (Gilenya);
• golimumab (Simponi);
• infliximab (Remicade);
• leflunomide (Arava); or
• a blood thinner such as warfarin (Coumadin, Jantoven).

This list is not complete. Other drugs may interact with rilonacept, including prescription, over-the-counter, vitamin, and herbal products. Not all possible interactions are listed in this medication guide.

Dosage Forms And Strengths

ARCALYST is supplied in sterile, single-use, 20-mL, glass vials. Each vial contains 220 mg of rilonacept as a white to off-white, preservative-free, lyophilized powder. Reconstitution with 2.3 mL of preservative-free Sterile Water for Injection is required prior to subcutaneous administration of the drug. The reconstituted ARCALYST is a viscous, clear, colorless to pale yellow, essentially free from particulates, 80-mg/mL solution.

Storage And Handling

Each 20-mL glass vial of ARCALYST contains a sterile, white to off-white, preservative-free, lyophilized powder. ARCALYST is supplied in a carton containing four vials (NDC 61755-001-01).

The lyophilized ARCALYST product is to be stored refrigerated at 2° to 8°C (36° to 46°F) inside the original carton to protect from light. Do not use beyond the date stamped on the label. After reconstitution, ARCALYST may be kept at room temperature, should be kept from light, and should be used within three hours of reconstitution. ARCALYST does not contain preservatives; therefore, unused portions of ARCALYST should be discarded. Discard the vial after a single withdrawal of drug.

Manufactured and distributed by: Regeneron Pharmaceuticals, Inc., 777 Old Saw Mill River Road, Tarrytown, NY 10591-6707, 1-877-REGN-777 (1-877-734-6777). Revised: Sep 2016

Six serious adverse reactions were reported by four patients during the clinical program. These serious adverse reactions were Mycobacterium intracellulare infection; gastrointestinal bleeding and colitis; sinusitis and bronchitis; and Streptococcus pneumoniae meningitis [see Malignancies].

The most commonly reported adverse reaction associated with ARCALYST was injection-site reaction (ISR) [see Injection-Site Reactions]. The next most commonly reported adverse reaction was upper respiratory infection [see Malignancies].

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

The data described herein reflect exposure to ARCALYST in 600 patients, including 85 exposed for at least 6 months and 65 exposed for at least one year. These included patients with CAPS, patients with other diseases, and healthy volunteers. Approximately 60 patients with CAPS have been treated weeklywith 160 mg of ARCALYST. The pivotal trial population included 47 patients with CAPS. These patients were between the ages of 22 and 78 years (average 51 years). Thirty-one patients were female and 16 were male. All of the patients were White/Caucasian. Six pediatric patients (12-17 years) were enrolled directly into the open-label extension phase.

Clinical Trial Experience

Part A of the clinical trial was conducted in patients with CAPS who were na�ve to treatment with ARCALYST. Part A of the study was a randomized, double-blind, placebo-controlled, six-week study comparing ARCALYST to placebo [see Clinical Studies]. Table 1 reflects the frequency of adverse events reported by at least two patients during Part A.

Table 1: Most Frequent Adverse Reactions (Part A, Reported by at Least Two Patients )

Injection-Site Reactions

In patients with CAPS, the most common and consistently reported adverse event associated with ARCALYST was injection-site reaction (ISR). The ISRs included erythema, swelling, pruritus, mass, bruising, inflammation, pain, edema, dermatitis, discomfort, urticaria, vesicles, warmth and hemorrhage. Most injection-site reactions lasted for one to two days. No ISRs were assessed as severe, and no patient discontinued study participation due to an ISR.

Infections

During Part A, the incidence of patients reporting infections was greater with ARCALYST (48%) than with placebo (17%). In Part B, randomized withdrawal, the incidence of infections were similar in the ARCALYST (18%) and the placebo patients (22%). Part A of the trial was initiated in the winter months, while Part B was predominantly performed in the summer months.

In placebo-controlled studies across a variety of patient populations encompassing 360 patients treated with rilonacept and 179 treated with placebo, the incidence of infections was 34% and 27% (2.15 per patient-exposure year and 1.81 per patient-exposure year), respectively, for rilonacept and placebo.

Serious Infections: One patient receiving ARCALYST for an unapproved indication in another study developed an infection in his olecranon bursa with Mycobacterium intracellulare. The patient was on chronic glucocorticoid treatment. The infection occurred after an intraarticular glucocorticoid injection into the bursa with subsequent local exposure to a suspected source of mycobacteria. The patient recovered after the administration of the appropriate antimicrobial therapy. One patient treated for another unapproved indication developed bronchitis/sinusitis, which resulted in hospitalization. One patient died in an open-label study of CAPS from Streptococcus pneumoniae meningitis.

Malignancies

[see WARNINGS AND PRECAUTIONS].

Hematologic Events

One patient in a study in an unapproved indication developed transient neutropenia (ANC < 1 x 109/L) after receiving a large dose (2000 mg intravenously) of ARCALYST. The patient did not experience any infection associated with the neutropenia.

Immunogenicity

Antibodies directed against the receptor domains of rilonacept were detected by an ELISA assay in patients with CAPS after treatment with ARCALYST. Nineteen of 55 patients (35%) who had received ARCALYST for at least 6 weeks tested positive for treatment-emergent binding antibodies on at least one occasion. Of the 19, seven tested positive at the last assessment (Week 18 or 24 of the open-label extension period), and five patients tested positive for neutralizing antibodies on at least one occasion. There was no correlation of antibody activity and either clinical effectiveness or safety.

The data reflect the percentage of patients whose test results were positive for antibodies to the rilonacept receptor domains in specific assays, and are highly dependent on the sensitivity and specificity of the assays. The observed incidence of antibody (including neutralizing antibody) positivity in an assay is highly dependent on several factors including assay sensitivity and specificity, assay methodology, sample handling, timing of sample collection, concomitant medications, and underlying disease. For these reasons, comparison of the incidence of antibodies to rilonacept with the incidence of antibodies to other products may be misleading.

Lipid Profiles

Cholesterol and lipid levels may be reduced in patients with chronic inflammation. Patients with CAPS treated with ARCALYST experienced increases in their mean total cholesterol, HDL cholesterol, LDL cholesterol, and triglycerides. The mean increases from baseline for total cholesterol, HDL cholesterol, LDL cholesterol, and triglycerides were 19 mg/dL, 2 mg/dL, 10 mg/dL, and 57 mg/dL respectively after 6 weeks of open-label therapy. Physicians should monitor the lipid profiles of their patients (for example after 2-3 months) and consider lipid-lowering therapies as needed based upon cardiovascular risk factors and current guidelines.

Read the entire FDA prescribing information for Arcalyst (Rilonacept)

• Store rilonacept in the refrigerator inside the original carton.
• Rilonacept may be kept at room temperature after mixing.
• Rilonacept should be used within 3 hours of mixing.
• Keep this medication away from light.
• If you need to take rilonacept with you when traveling, store the carton in a cool carrier with a cold pack and protect it from light.
• Keep this and all medications out of the reach of children.

Rilonacept is used to treat some of the symptoms of rare genetic conditions such as Familial Cold Auto-inflammatory Syndrome (FCAS) or Muckle-Wells Syndrome (MWS).

FCAS and MWS are inflammatory disorders in which the body develops certain symptoms without a known cause (such as virus, bacteria, or illness). These symptoms include fever, chills, fatigue, and joint pain. More serious symptoms may involve the bones and joints, the central nervous system (deafness, vision loss, mental impairment), or major organs such as the kidneys.

Rilonacept may treat or prevent the symptoms of Familial Cold Auto-inflammatory Syndrome (FCAS) or Muckle-Wells Syndrome (MWS). However, this medication is not a cure for these inherited conditions.

Rilonacept may also be used for purposes not listed in this medication guide.

Follow the directions on your prescription label. Do not use this medicine in larger or smaller amounts or for longer than recommended.

Rilonacept is injected under the skin. You may be shown how to use injections at home. Use exactly as prescribed by your doctor. Do not self inject this medicine if you do not fully understand how to give the injection and properly dispose of used needles and syringes.

Your first dose may be given in two injections at a time, each on a different place on your body.

Rilonacept is a powder medicine that must be mixed with a liquid (diluent) before using it. If you are using the injections at home, be sure you understand how to properly mix and store the medicine.

Use a different place on your stomach, thigh, or upper arm each time you give the injection. Your care provider will show you the best places on your body to inject the medication. Do not inject into the same place two times in a row.

While using rilonacept, you may need frequent blood tests at your doctor's office.

Each single-use vial (bottle) of this medicine is for one use only. Throw away after one use, even if there is still some medicine left in it after injecting your dose.

Use a disposable needle only once. Throw away used needles in a puncture-proof container (ask your pharmacist where you can get one and how to dispose of it). Keep this container out of the reach of children and pets.

Store the unmixed powder medicine in the refrigerator and protected from light. Do not freeze. Keep each vial in the original container until you are ready to mix your medicine.

After mixing rilonacept with a diluent, store at room temperature and use it within 3 hours. Protect from light.

Call your doctor for instructions if you miss an appointment for your rilonacept injection.

Tell your doctor about all medications you use, and those you start or stop using during your treatment with rilonacept, especially:

• adalimumab (Humira);

• certolizumab (Cimzia)

• etanercept (Enbrel);

• fingolimod (Gilenya);

• golimumab (Simponi);

• infliximab (Remicade);

• leflunomide (Arava); or

• a blood thinner such as warfarin (Coumadin, Jantoven).

This list is not complete. Other drugs may interact with rilonacept, including prescription, over-the-counter, vitamin, and herbal products. Not all possible interactions are listed in this medication guide.

• If you have an allergy to rilonacept or any other part of rilonacept.
• If you are allergic to any drugs like this one, any other drugs, foods, or other substances. Tell your doctor about the allergy and what signs you had, like rash; hives; itching; shortness of breath; wheezing; cough; swelling of face, lips, tongue, or throat; or any other signs.
• If you have an infection.
• If you are taking any of these drugs: Adalimumab, certolizumab, etanercept, golimumab, or infliximab.
• If you are taking anakinra.

This is not a list of all drugs or health problems that interact with this medicine.

Tell your doctor and pharmacist about all of your drugs (prescription or OTC, natural products, vitamins) and health problems. You must check to make sure that it is safe for you to take rilonacept with all of your drugs and health problems. Do not start, stop, or change the dose of any drug without checking with your doctor.

• Tell all of your health care providers that you take this medicine. This includes your doctors, nurses, pharmacists, and dentists.
• Have blood work checked as you have been told by the doctor. Talk with the doctor.
• This medicine may cause high cholesterol and triglyceride levels. Talk with the doctor.
• Very bad infections have been reported with use of rilonacept. If you have any infection, are taking antibiotics now or in the recent past, or have many infections, talk with your doctor.
• You may have more of a chance of getting an infection. Wash hands often. Stay away from people with infections, colds, or flu. Some infections have been very bad and even deadly.
• This medicine may add to the chance of getting some types of cancer. Talk with the doctor.
• TB (tuberculosis) has been seen in patients started on this medicine. These patients were exposed to TB in the past, but never got the infection. You will be tested to see if you have been exposed to TB before starting rilonacept.
• Talk with your doctor before getting any vaccines. Use with this medicine may either raise the chance of an infection or make the vaccine not work as well.
• This medicine may affect growth in children and teens in some cases. They may need regular growth checks. Talk with the doctor.
• If you are taking warfarin, talk with your doctor. You may need to have your blood work checked more closely while you are taking it with rilonacept.
• This medicine may cause harm to the unborn baby if you take it while you are pregnant. If you are pregnant or you get pregnant while taking this medicine, call your doctor right away.
• Tell your doctor if you are breast-feeding. You will need to talk about any risks to your baby.

If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Solution Reconstituted, Subcutaneous [preservative free]:

Arcalyst: 220 mg (1 ea) [contains polyethylene glycol]

Cryopyrin-associated periodic syndromes (CAPS) refers to rare genetic syndromes caused by mutations in the nucleotide-binding domain, leucine rich family (NLR), pyrin domain containing 3 (NLRP-3) gene or the cold-induced autoinflammatory syndrome-1 (CIAS1) gene. Cryopyrin, a protein encoded by this gene, regulates interleukin-1 beta (IL-1β) activation. Deficiency of cryopyrin results in excessive inflammation. Rilonacept reduces inflammation by binding to IL-1β (some binding of IL-1α and IL-1 receptor antagonist) and preventing interaction with cell surface receptors.

Cryopyrin-associated periodic syndromes: SubQ:

Children ≥12 years and Adolescents <18 years:

Initial: 4.4 mg/kg (maximum loading dose: 320 mg) given as 1 to 2 separate injections (maximum single injection: 160 mg [2 mL]); if multiple injections are necessary, administer on the same day at 2 different sites

Maintenance: 2.2 mg/kg (maximum dose: 160 mg) once weekly. Note: Begin maintenance dose 1 week following loading dose; do not administer more frequently than once weekly.

Adolescents ≥18 years: Refer to adult dosing.

Reconstitute rilonacept 220 mg powder for injection with 2.3 mL of preservative free SWFI; quickly shake the vial back and forth for 1 minute, then allow solution to sit for 1 minute. If the powder is not completely dissolved, shake the vial for an additional 30 seconds, then allow solution to sit for 1 minute; repeat if necessary until powder is completely dissolved. Each reconstituted vial allows for withdrawal of 2 mL (160 mg) for SubQ administration.

Anti-TNF Agents: May enhance the adverse/toxic effect of Rilonacept. Avoid combination

BCG (Intravesical): Immunosuppressants may diminish the therapeutic effect of BCG (Intravesical). Avoid combination

Canakinumab: Interleukin-1 Inhibitors may enhance the adverse/toxic effect of Canakinumab. Whether such a combination will also alter the therapeutic response to one or both agents is unclear. Avoid combination

Coccidioides immitis Skin Test: Immunosuppressants may diminish the diagnostic effect of Coccidioides immitis Skin Test. Monitor therapy

Denosumab: May enhance the adverse/toxic effect of Immunosuppressants. Specifically, the risk for serious infections may be increased. Monitor therapy

Echinacea: May diminish the therapeutic effect of Immunosuppressants. Consider therapy modification

Fingolimod: Immunosuppressants may enhance the immunosuppressive effect of Fingolimod. Management: Avoid the concomitant use of fingolimod and other immunosuppressants when possible. If combined, monitor patients closely for additive immunosuppressant effects (eg, infections). Consider therapy modification

Leflunomide: Immunosuppressants may enhance the adverse/toxic effect of Leflunomide. Specifically, the risk for hematologic toxicity such as pancytopenia, agranulocytosis, and/or thrombocytopenia may be increased. Management: Consider not using a leflunomide loading dose in patients receiving other immunosuppressants. Patients receiving both leflunomide and another immunosuppressant should be monitored for bone marrow suppression at least monthly. Consider therapy modification

Natalizumab: Immunosuppressants may enhance the adverse/toxic effect of Natalizumab. Specifically, the risk of concurrent infection may be increased. Avoid combination

Nivolumab: Immunosuppressants may diminish the therapeutic effect of Nivolumab. Consider therapy modification

Ocrelizumab: May enhance the immunosuppressive effect of Immunosuppressants. Monitor therapy

Pimecrolimus: May enhance the adverse/toxic effect of Immunosuppressants. Avoid combination

Roflumilast: May enhance the immunosuppressive effect of Immunosuppressants. Consider therapy modification

Sipuleucel-T: Immunosuppressants may diminish the therapeutic effect of Sipuleucel-T. Monitor therapy

Tacrolimus (Topical): May enhance the adverse/toxic effect of Immunosuppressants. Avoid combination

Tertomotide: Immunosuppressants may diminish the therapeutic effect of Tertomotide. Monitor therapy

Tofacitinib: Immunosuppressants may enhance the immunosuppressive effect of Tofacitinib. Management: Concurrent use with antirheumatic doses of methotrexate or nonbiologic disease modifying antirheumatic drugs (DMARDs) is permitted, and this warning seems particularly focused on more potent immunosuppressants. Consider therapy modification

Trastuzumab: May enhance the neutropenic effect of Immunosuppressants. Monitor therapy

Vaccines (Inactivated): Immunosuppressants may diminish the therapeutic effect of Vaccines (Inactivated). Management: Vaccine efficacy may be reduced. Complete all age-appropriate vaccinations at least 2 weeks prior to starting an immunosuppressant. If vaccinated during immunosuppressant therapy, revaccinate at least 3 months after immunosuppressant discontinuation. Consider therapy modification

Vaccines (Live): Immunosuppressants may enhance the adverse/toxic effect of Vaccines (Live). Immunosuppressants may diminish the therapeutic effect of Vaccines (Live). Management: Avoid use of live organism vaccines with immunosuppressants; live-attenuated vaccines should not be given for at least 3 months after immunosuppressants. Avoid combination