• Kevzara is a brand (trade) name for sarilumab which is a biologic that may be used to treat adults with rheumatoid arthritis (RA) or polymyalgia rheumatica (PMR).
• Kevzara (sarilumab) works by blocking the effects of a protein called interleukin-6. IL-6 is a type of inflammatory cytokine and it is involved in several different processes within the body, including inducing the production of C-reactive protein (CRP) by the liver. IL-6 contributes significantly to the symptoms of RA and PMR. It is found in abundance in the synovial fluid and serum of people with RA and levels of IL-6 are higher during periods of increased disease activity and joint destruction. It also contributes to other symptoms of RA, such as anemia, osteoporosis, and fatigue. Levels of IL-6 are elevated in people with PMR, and high levels correlate with disease activity and systemic inflammation.
• Kevzara belongs to the class of medicines known as interleukin-6 (IL-6) receptor antagonists (also called IL-6 inhibitors) and is a type of biologic.

• May be used to treat moderately-to-severely active rheumatoid arthritis (RA) in adults who have not adequately responded to or who cannot tolerate one or more disease-modifying antirheumatic drugs (DMARDs). Examples of DMARDs include methotrexate, sulfasalazine, hydroxychloroquine, and leflunomide.
• In PMR, Kevzara may be used to treat adults who have not responded to corticosteroids or who cannot tolerate a decrease in corticosteroid dose.
• Can be self-administered by subcutaneous injection (under the skin) every 2 weeks.
• May be used alone as monotherapy, or in combination with methotrexate or other conventional DMARDs. In PMR, it may be used alongside a decreasing dose of prednisone.
• Reduces symptoms of RA such as painful, tender, and swollen joints; anemia, osteoporosis, and fatigue.
• Is three times more likely than placebo to induce remission in patients with PMR.
• Also slows the progression of RA, protecting joints from further damage.
• The recommended dosage is 200 mg once every two weeks. The dosage can be reduced from 200 mg to 150 mg once every two weeks, as needed, to help manage certain laboratory abnormalities (neutropenia, thrombocytopenia, and liver enzyme elevations).
• No dosage adjustment is required in patients with mild-to-moderate kidney impairment. Kevzara has not been studied in severe kidney impairment.
• Available as a single-use prefilled syringe or single-use prefilled pen.

If you are between the ages of 18 and 60, take no other medication or have no other medical conditions, side effects you are more likely to experience include:

• Elevated liver enzymes, such as alanine aminotransferase (ALT) (up to 43%), aspartate aminotransferase (AST) (up to 30%), low white blood cells (eg, neutropenia, leukopenia), lipid abnormalities (elevated LDL, HDL, and triglycerides) and injection site reactions (redness, swelling, and itching at the injection site) are the most common side effects reported.
• Kevzara can suppress the immune system. Serious, sometimes fatal, infections caused by bacteria, mycobacteria, fungi, viruses, or other opportunistic pathogens have been reported in up to 10% of people. Kevzara should not be used in patients with an active infection and patients should be closely monitored for signs and symptoms of infection during treatment with Kevzara. If a serious infection develops, Kevzara should be withheld until the infection is controlled. Most patients who developed infections were taking concomitant immunosuppressants such as methotrexate or corticosteroids. Urinary tract infections and upper respiratory tract infections have been reported in up to 10% of people.
• Other side effects reported include black, bloody, or tarry stools, cough, fever, lower back pain, sore throat, tiredness or weakness, ulcers in the mouth, unusual bleeding or bruising, and an increased risk of cancer. Perforation of the gastrointestinal tract has also been reported. This may be associated with concurrent diverticulitis or concomitant use of NSAIDs or corticosteroids. Investigate thoroughly any patients complaining of new-onset abdominal symptoms
• Weight gain is not a reported side effect of Kevzara. However, the symptoms of RA or PMR can make people tired and make it hard for them to move and exercise, which may contribute to weight gain. Other drugs that may also be given for RA or PMR, such as prednisone, are more likely to cause weight gain.
• Kevzara should not be started in people with active infections, an absolute neutrophil count less than 2000 per mm3, platelet count less than 150,000 per mm3, or who have ALT or AST above 1.5 times the upper limit of normal. Test patients for latent tuberculosis prior to administration. Avoid using Kevzara with biological DMARDs because of the possibility of increased immunosuppression and increased risk of infection. Kevzara is not recommended in people with active liver disease or liver impairment.
• Serious hypersensitivity reactions (such as angioedema and urticaria) have been reported in 0.3% of people administered Kevzara. A health professional should always administer the first dose of Kevzara and patients should be advised to seek urgent emergency help if they experience an allergic-type reaction.
• Kevzara is only available as an injection that is administered under the skin.
• Kevzara is only approved for use in adults.
• It is unknown what effect Kevzara has during pregnancy on the unborn child. There is a pregnancy exposure registry (call 1-877-311-8972 to register) that monitors pregnancy outcomes in women exposed to Kevzara during pregnancy. Research so far has found that monoclonal antibodies such as Kevzara are actively transported across the placenta during the third trimester of pregnancy and may affect the immune response in the infant and also the delivery of the baby. There are no data on the effect of Kevzara during lactation.

Note: In general, seniors or children, people with certain medical conditions (such as liver or kidney problems, heart disease, diabetes, seizures) or people who take other medications are more at risk of developing a wider range of side effects. View complete list of side effects

• If you have been shown how to self-inject Kevzara by your health professional, administer yourself a dose once every two weeks, preferably on the same day (such as every second Monday), otherwise see your healthcare provider for a dose. If you forget a dose, schedule it in for as soon as you can, then continue with your regular dosing schedule.
• Immediately before administration remove one Kevzara injection out of the refrigerator and leave it on a flat surface, away from children and pets, to warm up to room temperature for at least 30 minutes for the prefilled syringe (60 minutes for the pen). Do not warm in any other way (such as by putting in hot water). Kevzara at room temperature reduces the risk of stinging. Inspect the injection for any discoloration or particulate matter and do not use if the liquid is cloudy, contains particles, or is discolored. The liquid in Kevzara should be clear, colorless, or have a slightly yellow tinge. Check the expiry date on the side of the injection and do not use Kevzara if it has expired. Do not shake Kevzara.
• Kevzara is best administered into the front of your thighs or the lower part of your abdomen, avoiding the area around your belly button (stay an inch away from your belly button). If somebody else is giving you your injection they can also administer it into the outer area of your upper arm. Change your injection site each month so that you are not injecting into the same spot each time.
• Only inject into clear, healthy skin. Do not inject into any areas that are bruised, tender, red, scaly, or hard. You should also not inject into any scars, stretch marks, or areas of psoriasis.
• If you feel pain when you inject Kevzara, placing an ice pack on the area of skin where you inject Kevzara for a few minutes before and after the injection can help reduce this pain.
• Wash your hands then clean the injection site with an alcohol wipe and let the area dry. Take the needle cap off the syringe and hold the syringe between your thumb and first finger. Pinch up a fold of skin at the cleaned injection site and insert the needle into the fold of skin at a 45-degree angle. Slowly push the plunger down as far as it will go until the syringe is empty. Pull the needle out and throw the syringe away in an approved sharps container.
• For the pre-filled pen, when you are ready to inject, twist off the orange cap, and hold the pen at a 90-degree angle to the cleaned injection site (straight up and down). Make sure you can see the window. Press down and hold the pen firmly against your skin, you should hear a click when the injection starts. The window should turn solid yellow and will take up to 15 seconds to complete. There will be a second click when the injection is complete. If the entire window does not turn solid yellow then you may have not received your full dose. Contact your health provider if this happens. Remove the pen from your skin and dispose of in an approved sharps container. Do not rub the injection site.
• Store Kevzara in the refrigerator at 36°F to 46°F (2°C to 8°C). Once taken out of the refrigerator, use within 14 days. If you have not used it within this time throw it away. Do not put Kevzara back in the refrigerator if it has been out of the refrigerator for more than a few minutes. Do not freeze Kevzara. Protect Kevzara from light.
• Before starting Kevzara, your doctor will ask you if you have been exposed to tuberculosis (TB) in the past. They may need to do some further tests and may require you to undertake a course of antibiotics if their investigations show you have been exposed to TB. If you develop symptoms of TB (such as a persistent cough lasting longer than three weeks, chest pain, coughing up blood or sputum), tell your doctor immediately.
• Seek urgent medical attention if you experience shortness of breath, facial or throat tightness after administering Kevzara. If you feel unwell, or experience other signs of infection, tell your doctor immediately. Also remember to tell your doctor about any other side effects that you may be experiencing, such as dizziness or fainting.
• Kevzara can increase your risk of developing an infection, or worsening infections you currently have. Tell your doctor about any infection you currently have if you are starting Kevzara, and if you have ever had tuberculosis or other significant infections before. See your doctor immediately if you develop any signs of an infection, such as fever, shortness of breath, fatigue, burning when urinating, red or discharging sores on your body, cough, diarrhea, or stomach pain.
• Tell other health professionals that you are being administered Kevzara. Before you start Kevzara, all your vaccinations should be up to date. While you are receiving Kevzara, you should not receive any live vaccines (such as the MMR vaccine or the chickenpox vaccine).
• Kevzara is not recommended during pregnancy unless the benefits outweigh the risks but tell your doctor immediately if you become pregnant while being administered Kevzara.
• Talk to your doctor or pharmacist before taking any other medicines with Kevzara.

• Following a single injection of Kevzara, a rapid reduction in CRP levels was observed within two weeks in most people, although it may take up to 12 weeks (three months) for Kevzara to work in some people with RA.
• Trials have shown that people with RA treated with 200 mg of Kevzara every two weeks + methotrexate (MTX)/DMARD had higher ACR20 (66% Vs 33%), ACR50 (46% Vs 17%), and ACR70 (25% Vs 7%) response rates versus placebo + MTX/DMARD-treated patients at Week 24.
• A Phase 3 RCT found 28% of patients were still in clinical remission after 52 weeks, after first achieving clinical remission within 12 weeks. There was also absence of disease flare, C-reactive protein levels displayed normalization from weeks 12 thru 52, and overall adherence to the corticosteroid taper from weeks 12 to 52.

Medicines that interact with Kevzara may either decrease its effect, affect how long it works for, increase side effects, or have less of an effect when taken with Kevzara. An interaction between two medications does not always mean that you must stop taking one of the medications; however, sometimes it does. Speak to your doctor about how drug interactions should be managed.

Common medications that may interact with Kevzara include:

• aminophylline
• anticonvulsants, such as phenobarbital or phenytoin
• antipsychotics, such as clozapine
• benzodiazepines, such as alprazolam or clonazepam
• corticosteroids (such as prednisone or dexamethasone)
• heart medications such as amiodarone or flecainide
• herbals, such as echinacea or black cohosh
• hormones such as levonorgestrel or norgestrel
• immunosuppressants such as azathioprine, cyclosporine, or tacrolimus
• live vaccines and some other vaccines, such as BCG, cholera, measles, hepatitis b vaccines, yellow fever or live influenza vaccines
• methotrexate
• opioids, such as fentanyl or oxycodone
• other biologics, such as adalimumab, etanercept, golimumab, or infliximab
• probiotics, such as lactobacillus
• statins, such as atorvastatin or simvastatin
• theophylline
• warfarin
• zinc.

There is a potential for any medication that is metabolized by CYP450 enzymes, particularly those with a narrow therapeutic index (such as cyclosporine or warfarin) to interact with Kevzara. This is because the formation of CYP450 enzymes can be altered by increased levels of certain cytokines (such as IL-1, IL-6, IL-10, Il-17) during chronic inflammation. Because Kevzara stops IL-6 from interacting with the IL-6 receptor, this could normalize the formation of CYP450 enzymes. Monitor for any change in effect and consider any dosage modification.

Note that this list is not all-inclusive and includes only common medications that may interact with Kevzara. You should refer to the prescribing information for Kevzara for a complete list of interactions.