Arcalyst

Name: Arcalyst

US Brand Name

  1. Arcalyst

Arcalyst Drug Class

Arcalyst is part of the drug class:

  • Interleukin inhibitors

Side Effects of Arcalyst

Serious side effects have been reported with Arcalyst. See the "Drug Precautions" section.

Common side effects of Arcalyst include the following:

  • Upper respiratory tract infections (such as a sinus infection)
  • Cough
  • Injection site reactions (redness, swelling, itching, or pain, typically lasting one to two days)
  • Increases in cholesterol and lipid levels

This is not a complete list of Arcalyst side effects. Ask your doctor or pharmacist for more information.

Tell your doctor if you have any side effect that bothers you or that does not go away.

Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

Arcalyst Food Interactions

Medications can interact with certain foods. In some cases, this may be harmful and your doctor may advise you to avoid certain foods. In the case of Arcalyst, there are no specific foods that you must exclude from your diet when receiving this medication.

Pharmacology

Mechanism of Action

Blocks interleukin-1beta (IL-1beta) signaling by acting as a soluble decoy receptor that binds IL-1beta and prevents its interaction with cell surface receptors

Inflammation in CAPS is associated with mutations in the NLRP-3 gene which encodes the protein cryopyrin, an important component of the inflammasome; cryopyrin regulates the protease caspase-1 and controls the activation of IL-1beta; mutations in NLRP-3 result in an overactive inflammasome resulting in excessive release of activated IL-1beta that drives inflammation

What is 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.

Rilonacept side effects

Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficult breathing; swelling of your face, lips, tongue, or throat.

Serious and sometimes fatal infections may occur during treatment with rilonacept. Call your doctor right away if you have any new signs of infection such as:

  • fever, chills, sore throat, flu symptoms;

  • easy bruising or bleeding (nosebleeds, bleeding gums);

  • nausea and vomiting, loss of appetite;

  • mouth sores; or

  • unusual weakness.

Call your doctor at once if you have any other serious side effect such as:

  • bloody, black, or tarry stools;

  • coughing up blood or vomit that looks like coffee grounds;

  • wheezing, chest tightness, trouble breathing;

  • pain or burning when you urinate; or

  • headache, neck stiffness, increased sensitivity to light, purple spots on the skin, and/or seizure (convulsions).

Other common side effects may include:

  • cold symptoms such as stuffy nose, sneezing, cough, sore throat;

  • nausea, stomach pain, diarrhea;

  • numbness or tingly feeling; or

  • pain, swelling, redness, itching, warmth, blistering, bleeding, or other irritation where the medicine was injected.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Introduction

Interleukin-1 (IL-1) receptor antagonist (IL-1Ra); dimeric fusion protein.1 2 3 4 5 13

Stability

Storage

Parenteral

Powder for Injection

2–8°C in original carton to protect from light.1

Following reconstitution, store at room temperature, protect from light, and use within 3 hours.1 Discard unused portion of vial after a single withdrawal of drug.1

Actions

  • Dimeric fusion protein consisting of the ligand-binding domains of the extracellular portions of the human IL-1 type I receptor (IL-1RI) and IL-1 receptor accessory protein (IL-1RAcP) linked in-line to the Fc portion of human immunoglobulin G1.1 2 4

  • IL-1 receptor antagonist (IL-1Ra) used for the management of CAPS, including FCAS and MWS.1 2 3 4 5 6 13

  • Blocks IL-1β signaling by acting as a soluble decoy receptor that binds IL-1β and prevents its interaction with cell surface receptors;1 2 also binds IL-1α and IL-1Ra to a lesser extent.1 4 Mutations in the NLRP-3 gene in patients with CAPS result in an overactive inflammasome, causing excessive release of activated IL-1β.1

  • Results in sustained reductions in mean concentrations of SAA and CRP, indicators of inflammatory disease activity.1 Elevated SAA concentrations have been associated with the development of systemic amyloidosis in patients with CAPS.1

Proper Use of Arcalyst

This medicine is given as a shot under your skin. Rilonacept may sometimes be given at home to patients who do not need to be in the hospital. If you are using this medicine at home, your doctor will teach you how to prepare and inject the medicine. Be sure that you understand exactly how the medicine is prepared and injected .

This medicine comes with a patient instructions. Read and follow the instructions in the insert carefully. Ask your doctor if you have any questions .

Use a new needle and syringe each time you inject your medicine .

You will be shown the body areas where this shot can be given. Use a different body area each time you give yourself a shot. Keep track of where you give each shot to make sure you rotate body areas. This will help prevent skin problems from the injections. Do not inject into skin areas that are bruised, red, tender, or hard .

This powder medicine must be mixed with the liquid provided in your dose kit. Mix the medicine only when you are ready to use it. Do not use if it is cloudy or has specks floating in it .

Dosing

The dose of this medicine will be different for different patients. Follow your doctor's orders or the directions on the label. The following information includes only the average doses of this medicine. If your dose is different, do not change it unless your doctor tells you to do so.

The amount of medicine that you take depends on the strength of the medicine. Also, the number of doses you take each day, the time allowed between doses, and the length of time you take the medicine depend on the medical problem for which you are using the medicine.

  • For injection dosage form (vial):
    • For cryopyrin-associated periodic syndromes:
      • Adults—At first, 320 milligrams (mg) given as two, 2-milliliter (mL) doses of 160 mg injected under the skin on the same day at two different sites. Your dose will be adjusted to 160 mg once a week, given as a single, 2 mL injection.
      • Children and teenagers 12 to 17 years of age—At first, 4.4 milligrams (mg) per kilogram (kg) of body weight up to 320 mg given as one or two, 2-milliliter (mL) doses injected under the skin. Your dose will be adjusted to 2.2 mg per kg of body weight up to 160 mg once a week, given as a single, 2 mL injection.
      • Children below 12 years of age—Use and dose must be determined by your doctor .

Missed Dose

If you miss a dose of this medicine, take it as soon as possible. However, if it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not double doses.

Storage

Store in the refrigerator. Do not freeze.

Keep out of the reach of children.

Do not keep outdated medicine or medicine no longer needed.

Ask your healthcare professional how you should dispose of any medicine you do not use.

Once the powder medicine has been mixed with the liquid, this mixture may be stored at room temperature, away from direct light. You must use this mixture within 3 hours. Throw away any leftover mixture .

Throw away used needles in a hard, closed container that the needles cannot poke through. Keep this container away from children and pets .

How do I store and/or throw out Arcalyst?

  • Store unopened vials in a refrigerator. Do not freeze.
  • Store in original container.
  • After mixing, you may store at room temperature for 3 hours.
  • Protect unmixed and mixed product from light.
  • Throw away any part left over after the dose is given.
  • Keep all drugs in a safe place. Keep all drugs out of the reach of children and pets.
  • Check with your pharmacist about how to throw out unused drugs.

Adverse Reactions

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 Adverse Reactions (6.3)].

The most commonly reported adverse reaction associated with Arcalyst was injection-site reaction (ISR) [see Adverse Reactions (6.2)]. The next most commonly reported adverse reaction was upper respiratory infection [see Adverse Reactions (6.3)].

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 weekly with 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 naïve 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 (14)]. 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)
Adverse Event Arcalyst
160 mg
(n = 23)
Placebo
(n= 24)
Any AE 17 (74%) 13 (54%)
Injection-site reactions 11 (48%) 3 (13%)
Upper respiratory tract infection 6 (26%) 1 (4%)
Nausea 1 (4%) 3 (13%)
Diarrhea 1 (4%) 3 (13%)
Sinusitis 2 (9%) 1 (4%)
Abdominal pain upper 0 2 (8%)
Cough 2 (9%) 0
Hypoesthesia 2 (9%) 0
Stomach discomfort 1 (4%) 1 (4%)
Urinary tract infection 1 (4%) 1 (4%)

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 (5.2)].

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.

How supplied/ 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.

Patient Counseling Information

See FDA-approved patient labeling.

The first injection of Arcalyst should be performed under the supervision of a qualified healthcare professional. If a patient or caregiver is to administer Arcalyst, he/she should be instructed on aseptic reconstitution of the lyophilized product and injection technique. The ability to inject subcutaneously should be assessed to ensure proper administration of Arcalyst, including rotation of injection sites. (See Patient Information Leaflet for Arcalyst®). Arcalyst should be reconstituted with preservative-free Sterile Water for Injection to be provided by the pharmacy. A puncture-resistant container for disposal of vials, needles and syringes should be used. Patients or caregivers should be instructed in proper vial, syringe, and needle disposal, and should be cautioned against reuse of these items.

Injection-site Reactions: Physicians should explain to patients that almost half of the patients in the clinical trials experienced a reaction at the injection site. Injection-site reactions may include pain, erythema, swelling, pruritus, bruising, mass, inflammation, dermatitis, edema, urticaria, vesicles, warmth, and hemorrhage. Patients should be cautioned to avoid injecting into an area that is already swollen or red. Any persistent reaction should be brought to the attention of the prescribing physician.

Infections: Patients should be cautioned that Arcalyst has been associated with serious, life-threatening infections, and not to initiate treatment with Arcalyst if they have a chronic or active infection. Patients should be counseled to contact their healthcare professional immediately if they develop an infection after starting Arcalyst. Treatment with Arcalyst should be discontinued if a patient develops a serious infection. Patients should be counseled not to take any IL-1 blocking drug, including Arcalyst, if they are also taking a drug that blocks TNF such as etanercept, infliximab, or adalimumab. Use of Arcalyst with other IL-1 blocking agents, such as anakinra, is not recommended.

Vaccinations: Prior to initiation of therapy with Arcalyst physicians should review with adult and pediatric patients their vaccination history relative to current medical guidelines for vaccine use, including taking into account the potential of increased risk of infection during treatment with Arcalyst.

REGENERON

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)
U.S. License Number 1760
NDC 61755-001-01

© 2016, Regeneron Pharmaceuticals, Inc.
All rights reserved.
V 5.0

Patient Information
Arcalyst® (ARK-a-list)
(rilonacept)
Injection for Subcutaneous Use

Read the patient information that comes with Arcalyst before you start taking it and each time you refill your prescription. There may be new information. The information in this leaflet does not take the place of talking with your healthcare provider about your medical condition and your treatment.

What is the most important information I should know about Arcalyst?

Arcalyst can affect your immune system. Arcalyst can lower the ability of your immune system to fight infections. Serious infections, including life-threatening infections and death have happened in patients taking Arcalyst. Taking Arcalyst can make you more likely to get infections, including life-threatening serious infections, or may make any infection that you have worse.

You should not begin treatment with Arcalyst if you have an infection or have infections that keep coming back (chronic infection).

After starting Arcalyst, if you get an infection, any sign of an infection including a fever, cough, flu-like symptoms, or have any open sores on your body, call your healthcare provider right away. Treatment with Arcalyst should be stopped if you develop a serious infection.

You should not take medicines that block Tumor Necrosis Factor (TNF), such as Enbrel® (etanercept), Humira® (adalimumab), or Remicade® (infliximab), while you are taking Arcalyst. You should also not take other medicines that block Interleukin-1 (IL-1), such as Kineret® (anakinra), while taking Arcalyst. Taking Arcalyst with any of these medicines may increase your risk of getting a serious infection.

Before starting treatment with Arcalyst, tell your healthcare provider if you:

  • think you have an infection
  • are being treated for an infection
  • have signs of an infection, such as fever, cough, or flu-like symptoms
  • have any open sores on your body
  • have a history of infections that keep coming back
  • have asthma. Patients with asthma may have an increased risk of infection.
  • have diabetes or an immune system problem. People with these conditions have a higher chance for infections.
  • have tuberculosis (TB), or if you have been in close contact with someone who has had tuberculosis.
  • have or have had HIV, Hepatitis B, or Hepatitis C
  • take other medicines that affect your immune system

Before you begin treatment with Arcalyst, talk with your healthcare provider about your vaccination history. Ask your healthcare provider whether you should receive any vaccinations, including pneumonia vaccine and flu vaccine, before you begin treatment with Arcalyst.

What is Arcalyst?

Arcalyst is a prescription medicine called an interleukin-1 (IL-1) blocker. Arcalyst is used to treat adults and children 12 years and older with Cryopyrin-Associated Periodic Syndromes (CAPS), including Familial Cold Auto-inflammatory Syndrome (FCAS) and Muckle Wells Syndrome (MWS). Arcalyst can help lessen the signs and symptoms of CAPS, such as rash, joint pain, fever, and tiredness, but it can also lead to serious side effects because of the effects on your immune system.

What should I tell my healthcare provider before taking Arcalyst?

Arcalyst may not be right for you. Before taking Arcalyst, tell your healthcare provider about all of your medical conditions, including if you:

 
  • are scheduled to receive any vaccines. You should not receive live vaccines if you take Arcalyst.
  • are pregnant or planning to become pregnant. It is not known if Arcalyst will harm your unborn child. Tell your healthcare provider right away if you become pregnant while taking Arcalyst.
  • are breast-feeding or planning to breast-feed. It is not known if Arcalyst passes into your breast milk.
See “What is the most important information I should know about Arcalyst?”   Tell your healthcare provider about all the medicines you take, including prescription and non-prescription medicines, vitamins, and herbal supplements. Especially tell your healthcare provider if you take other medicines that affect your immune system, such as:
  • other medicines that block IL-1, such as Kineret® (anakinra).
  • medicines that block Tumor Necrosis Factor (TNF), such as Enbrel® (etanercept), Humira® (adalimumab), or Remicade® (infliximab).
  • corticosteroids.
See “What is the most important information I should know about Arcalyst?”

Know the medicines you take. Keep a list of your medicines and show it to your healthcare provider and pharmacist every time you get a new prescription.

If you are not sure or have any questions about any of this information, ask your healthcare provider.

How should I take Arcalyst?

See the “Patient Instructions for Use” at the end of this leaflet.

  • Take Arcalyst exactly as prescribed by your healthcare provider.
  • Arcalyst is given by injection under the skin (subcutaneous injection) one time each week.
  • Your healthcare provider will tell and show you or your caregiver:
    • how much Arcalyst to inject
    • how to prepare your dose
    • how to give the injection
  • Do not try to give Arcalyst injections until you are sure that you or your caregiver understands how to prepare and inject your dose. Call your healthcare provider or pharmacist if you have any questions about preparing and injecting your dose, or if you or your caregiver would like more training.
  • If you miss a dose of Arcalyst, inject it as soon as you remember, up to the day before your next scheduled dose. The next dose should be taken at the next regularly scheduled time. If you have any questions, contact your healthcare provider.
  • If you accidentally take more Arcalyst than prescribed, call your healthcare provider.

What are the possible side effects of Arcalyst?

Serious side effects may occur while you are taking and after you finish taking Arcalyst including:

  • Serious Infections. See “What is the most important information I should know about taking Arcalyst?” Treatment with Arcalyst should be discontinued if you develop a serious infection.
  • Allergic Reaction. Call your healthcare provider or seek emergency care right away if you get any of the following symptoms of an allergic reaction while taking Arcalyst:
    • rash
    • swollen face
    • trouble breathing

Common side effects with Arcalyst include:

  • Injection-site reaction. This includes: pain, redness, swelling, itching, bruising, lumps, inflammation, skin rash, blisters, warmth, and bleeding at the injection site.
  • Upper respiratory infection.
  • Changes in your blood cholesterol and triglycerides (lipids). Your healthcare provider will check you for this.

These are not all the possible side effects of Arcalyst. Tell your healthcare provider about any side effects that bother you or that do not go away. For more information ask your healthcare provider or pharmacist. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

How should I store Arcalyst?

  • Keep Arcalyst in the carton it comes in.
  • Store Arcalyst in a refrigerator between 36°F to 46°F (2°C to 8°C). Call your pharmacy if you have any questions.
  • Always keep Arcalyst away from light.
  • Refrigerated Arcalyst can be used until the expiration date printed on the vial and carton.
  • Arcalyst may be kept at room temperature after mixing. Arcalyst should be used within three hours of mixing. Keep Arcalyst away from light.
  • If you need to take Arcalyst with you when traveling, store the carton in a cool carrier with a cold pack and protect it from light.

Keep Arcalyst, injection supplies, and all other medicines out of reach of children.

What are the ingredients in Arcalyst?

Active ingredient: rilonacept.

Inactive ingredients: histidine, arginine, polyethylene glycol 3350, sucrose, and glycine.

General Information about Arcalyst

Medicines are sometimes prescribed for conditions other than those listed in patient information leaflets. Do not use Arcalyst for a condition for which it was not prescribed. Do not give Arcalyst to other people even if they have the same condition. It may harm them.

This leaflet summarizes the most important information about Arcalyst. If you would like more information, speak with your healthcare provider. You can ask your healthcare provider or pharmacist for information about Arcalyst that was written for healthcare professionals. For more information about Arcalyst, call 1-877-REGN-777 (1-877-734-6777), or visit www.Arcalyst.com.

Patient Instructions for Use

It is important for you to read, understand and follow the instructions below exactly. Following the instructions correctly will help to make sure that you use, prepare and inject the medicine the right way to prevent infection.

How do I prepare and give an injection of Arcalyst?

STEP 1: Setting up for an injection

  1. Choose a table or other flat surface area to set up the supplies for your injection. Be sure that the area is clean or clean it with an antiseptic or soap and water first.
  2. Wash your hands well with soap and water, and dry with a clean towel.
  3. Put the following items on a table, or other flat surface, for each injection (see Figure 1):

    Figure 1

    • 2 sterile, 3-milliliter (mL) disposable syringes with markings at each 0.1 mL (see Figure 2):
      • one needed for mixing (reconstitution) Arcalyst
      • one needed for injection

    Figure 2

    • 2 sterile disposable needles (27-gauge, ½-inch)
      • one needed for mixing
      • one needed for injection
    • 4 alcohol wipes
    • 1 2x2 gauze pad
    • 1 vial of Arcalyst (powder in vial)
    • 1 vial of preservative-free Sterile Water for Injection
    • 1 puncture-resistant container for disposal of used needles, syringes, and vials

    Note:

    • Do not use Sterile Water for Injection, syringes or needles other than those provided by your pharmacy. Contact your pharmacy if you need replacement syringes or needles.
    • Do not touch the needles or the rubber stoppers on the vials with your hands. If you do touch a stopper, clean it with a fresh alcohol wipe.
    • If you touch a needle or the needle touches any surface, throw away the entire syringe into the puncture-resistant container and start over with a new syringe.
    • Do not reuse needles or syringes.
    • To protect yourself and others from possible needle sticks, it is very important to throw away every syringe, with the needle attached, in the puncture proof container right after use. Do not try to recap the needle.

STEP 2: Preparing Vials

  1. Check the expiration date on the carton of Arcalyst. Do not use the vial if the expiration date has passed. Contact your pharmacy for assistance.
  2. Check the expiration date on the vial of Sterile Water for Injection. Do not use the vial if the expiration date has passed. Contact your pharmacy for assistance.
  3. Remove the protective plastic cap from both vials.
  4. Clean the top of each vial with an alcohol wipe. Use one wipe for each vial and wipe in one direction around the top of the vial (see Figure 3).

    Figure 3

  5. Open the wrapper that contains the 27-gauge needle by pulling apart the tabs and set it aside for later use. Do not remove the needle cover. This needle will be used to mix the water with powder. Open the wrapper that contains the syringe by pulling apart the tabs. Hold the barrel of the syringe with one hand and twist the 27-gauge needle onto the tip of the syringe until it fits snugly with the other hand (see Figure 4).

    Figure 4

  6. Hold the syringe at eye level. With the needle covered pull back the plunger to the 2.3 mL mark, filling the syringe with air (see Figure 5).

    Figure 5

  7. Hold the syringe in one hand, use the other hand to pull the needle cover straight off. Do not twist the needle as you pull off the cover. Place the needle cover aside. Hold the syringe in the hand that you will use to mix (reconstitute) your medicine. Hold the Sterile Water vial on a firm surface with your other hand. Slowly insert the needle straight through the rubber stopper. Do not bend the needle. Push the plunger in all the way to push the air into the vial (see Figure 6).

    Figure 6

  8. Hold the vial in one hand and the syringe in the other hand and carefully turn the vial upside down so that the needle is pointing straight up.
  9. Make sure the tip of the needle is covered by the liquid and slowly pull back on the plunger to the 2.3 mL mark to withdraw the Sterile Water from the vial (see Figure 7).

    Figure 7

  10. Keep the vial upside down and tap or flick the syringe with your fingers until any air bubbles rise to the top of the syringe.
  11. To remove the air bubbles, gently push in the plunger so only the air is pushed out of the syringe and back into the bottle.
  12. After removing the bubbles, check the syringe to be sure that the right amount of Sterile Water has been drawn into the syringe (see Figure 8).

    Figure 8

  13. Carefully remove the syringe with needle from the Sterile Water vial. Do not touch the needle.

STEP 3: Mixing (Reconstituting) Arcalyst

  1. With one hand, hold the Arcalyst vial on a firm surface.
  2. With the other hand, take the syringe with the Sterile Water and the same needle, and slowly insert the needle straight down through the rubber stopper of the Arcalyst vial. Push the plunger in all the way to inject the Sterile Water into the vial.
  3. Direct the water stream to gently go down the side of the vial into the powder (see Figure 9).

    Figure 9

  4. Remove the syringe and needle from the stopper and throw away the needle, syringe, and Sterile Water vial in the puncture-resistant container. Do not try to put the needle cover back on the needle.
  5. Hold the vial containing the Arcalyst and sterile water for injection sideways (not upright) with your thumb and a finger at the top and bottom of the vial, and quickly shake the vial back and forth (side-to-side) for about 1 minute (see Figure 10).

    Figure 10

  6. Put the vial back on the table and let the vial sit for about 1 minute.
  7. Look at the vial for any particles or clumps of powder which have not dissolved.
  8. If the powder has not completely dissolved, shake the vial quickly back and forth for 30 seconds more. Let the vial sit for about 1 minute.
  9. Repeat Step 8 until the powder is completely dissolved and the solution is clear.
  10. The mixed Arcalyst should be thick, clear, and colorless to pale yellow. Do not use the mixed liquid if it is discolored or cloudy, or if small particles are in it (see Figure 11).
    NOTE: Contact your pharmacy to report any mixed Arcalyst that is discolored or contains particles.

    Figure 11

  11. Arcalyst may be kept at room temperature after mixing. Arcalyst should be used within three hours of mixing. Keep Arcalyst away from light.

STEP 4: Preparing the injection

  1. Hold the Arcalyst vial on a firm surface and wipe the top of the Arcalyst vial with a new alcohol wipe (see Figure 12).

    Figure 12

  2. Take a new sterile, disposable needle and attach securely to a new syringe without removing the needle cover (see Figure 13).

    Figure 13

  3. The amount of air you draw into the syringe should equal the amount of mixed Arcalyst that your healthcare provider has prescribed for you to inject.
  4. To draw air into the syringe, hold the syringe at eye level. Do not remove the needle cover. Pull back the plunger on the syringe to the mark that is equal to the amount of mixed Arcalyst that your healthcare provider has prescribed for you to inject (see Figure 14).

    Figure 14

  5. Remove the needle cover and be careful not to touch the needle. Keep the Arcalyst vial on a flat surface and slowly insert the needle straight down through the stopper. Push the plunger down and inject all the air into the vial (see Figure 15).

    Figure 15

  6. Hold the vial in one hand and the syringe in the other hand and carefully turn the vial upside down so that the needle is pointing straight up. Hold the vial at eye level.
  7. Keep the tip of the needle in the liquid and slowly pull back on the plunger to the mark on the syringe that matches the amount of medicine prescribed by your healthcare provider (see Figure 16).

    Figure 16

    NOTE: The maximum adult dose of Arcalyst is 2 mL.

  8. Keep the vial upside down with the needle straight up, and gently tap the syringe until any air bubbles rise to the top of the syringe (see Figure 17).

    It is important to remove air bubbles so that you withdraw up the right amount of medicine from the vial.

    Figure 17

  9. To remove the air bubbles, slowly and gently push in the plunger so only the air is pushed through the needle.
  10. Check to make sure that you have the amount of medicine prescribed by your healthcare provider in the syringe.
  11. Throw away the Arcalyst vial in the puncture-resistant container even if there is any medicine left in the vial (see Figure 18). Do not use any vial of Arcalyst more than one time.

    Figure 18

STEP 5: Giving the Injection

  1. Arcalyst is given by subcutaneous injection, an injection that is given into the tissue directly below the layers of skin. It is not meant to go into any muscle, vein, or artery.

    You should change (rotate) the sites and inject in a different place each time in order to keep your skin healthy.

    Rotating injection sites helps to prevent irritation and allows the medicine to be completely absorbed. Ask your healthcare provider any questions that you have about rotating injection sites.

    • Do not inject into skin that is tender, red, or hard. If an area is tender or feels hardened, choose another site for injection until the tenderness or "hardening" goes away.
    • Tell your healthcare provider about any skin reactions including redness, swelling, or hardening of the skin.
    • Areas where you may inject Arcalyst include the left and right sides of the abdomen, and left and right thighs. If someone else is giving the injection, the upper left and right arms may also be used for injection (see Figure 19):

      (Do not inject within a 2-inch area around the navel)

    Figure 19

  2. Choose the area for the injection. Clean the area in a circular motion with a new alcohol wipe. Begin at the center of the site and move outward. Let the alcohol air dry completely.
  3. Take the cover off the needle and be careful not to touch the needle.
  4. Hold the syringe in one hand like you would hold a pencil.
  5. With the other hand gently pinch a fold of skin at the cleaned site for injection (see Figure 20).

    Figure 20

  6. Use a quick “dart like” motion to insert the needle straight into the skin (90 degree angle) (see Figure 21). Do not push down on the plunger while inserting the needle into the skin.

    For small children or persons with little fat under the skin, you may need to hold the syringe and needle at a 45 degree angle (see Figure 21).

    Figure 21

  7. After the needle is completely in the skin, let go of the skin that you are pinching.
  8. With your free hand hold the syringe near its base. Gently pull back the plunger. If blood comes into the syringe, the needle has entered a blood vessel. Remove the needle, discard the syringe and needle. Start over with “STEP 1: Setting up for an injection” using new supplies (syringes, needles, vials, alcohol swabs and gauze pad).
  9. If no blood appears, inject all the medicine in the syringe at a slow, steady rate, pushing the plunger all the way down. It may take up to 30 seconds to inject the entire dose.
  10. Pull the needle out of the skin, and hold a piece of sterile gauze over the injection site for several seconds (see Figure 22).

    Figure 22

  11. Do not replace the needle cover. Throw away the vials, used syringes and needles in the puncture-resistant container (see Figure 23). Do not recycle the container. DO NOT throw away vials, needles, or syringes in the household trash or recycle.

    Figure 23

  12. Keep the puncture-resistant container out of reach of children. When the container is about two-thirds full, dispose of it as instructed by your healthcare provider. Follow any special state or local laws about the right way to throw away needles and syringes.
  13. Used alcohol wipes can be thrown away in the household trash.

Contact your healthcare provider right away with any questions or concerns about Arcalyst.

Notes: 1. Enbrel®, Humira®, Kineret®, and Remicade®, respectively, are trademarks of Immunex Corporation, AbbVie Biotechnology Ltd., Amgen Inc., and Janssen Biotech, Inc., respectively.

REGENERON

Manufactured and distributed by:
Regeneron Pharmaceuticals, Inc.
777 Old Saw Mill River Road
Tarrytown, NY 10591-6707
U.S. License Number 1760
NDC 61755-001-01

© 2016, Regeneron Pharmaceuticals, Inc.
All rights reserved.
V 4.0

Missed Dose

If you miss a dose of this medicine, take it as soon as possible. However, if it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not double doses.

What is the most important information i should know about rilonacept (arcalyst)?

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.

Before using Arcalyst

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

To make sure Arcalyst 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 Arcalyst.

Using Arcalyst 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 Arcalyst 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 Arcalyst to a child younger than 12 years old without medical advice.

What other drugs will affect Arcalyst?

Tell your doctor about all medications you use, and those you start or stop using during your treatment with Arcalyst, 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 Arcalyst, including prescription, over-the-counter, vitamin, and herbal products. Not all possible interactions are listed in this medication guide.

In Summary

Common side effects of Arcalyst include: upper respiratory tract infection and injection site reaction. See below for a comprehensive list of adverse effects.

For Healthcare Professionals

Applies to rilonacept: subcutaneous powder for injection

Local

In patients with Cryopyrin-Associated Periodic Syndromes (CAPS), the most common and consistently reported adverse event associated with rilonacept (the active ingredient contained in Arcalyst) was injection-site reaction (ISR). The ISRs included erythema, swelling, pruritis, 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.[Ref]

Local side effects including injection-site reactions (48%) have been reported.[Ref]

Immunologic

One subject receiving rilonacept (the active ingredient contained in Arcalyst) for an unapproved indication 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.

A 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.[Ref]

Immunologic side effects including infections (34%) have been reported.[Ref]

Respiratory

Respiratory side effects including upper respiratory tract infection (26%), sinusitis (9%), and cough (9%) have been reported.[Ref]

Nervous system

Nervous system side effects including hypoesthesia (9%) have been reported.[Ref]

Gastrointestinal

Gastrointestinal side effects including nausea (4%) diarrhea (4%) and stomach discomfort (4%) have been reported.[Ref]

Hematologic

Hematologic side effects have been reported including one case of transient neutropenia (ANC less than 1 x 109/L) after receiving a large dose (2000 mg intravenously) of rilonacept (the active ingredient contained in Arcalyst) Patients with CAPS treated with rilonacept 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.[Ref]

The patient did not experience any infection associated with the neutropenia.

Physicians should monitor the lipid profiles of their patients (for example after 2 to 3 months) and consider lipid-lowering therapies as needed based upon cardiovascular risk factors and current guidelines.[Ref]

Genitourinary

Genitourinary side effects including urinary tract infection (4%) have been reported.[Ref]

Some side effects of Arcalyst may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA.

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