Lupkynis

Lupkynis is used to treat active lupus nephritis (LN) in adults in combination with background immunosuppressive therapy.

Lupkynis gained FDA approval on January 22, 2021, and was the first oral prescription treatment approved specifically for LN. There is no generic.

Take Lupkynis exactly as your healthcare provider tells you to take it. Your healthcare provider may change your dose if needed.

• Swallow the Lupkynis capsule whole.
• Do not break, crush, chew, or dissolve the Lupkynis capsules before swallowing. If you cannot swallow Lupkynis capsules whole, tell your healthcare provider.
• Take Lupkynis on an empty stomach, at least 1 hour before or 2 hours after a meal and as close to 12 hours between doses as possible. Do not take your doses of Lupkynis less than 8 hours apart.

Do not take Lupkynis:

• With medicines known as strong CYP3A4 inhibitors, such as ketoconazole, itraconazole, and clarithromycin
• With cyclophosphamide
• If you are allergic to voclosporin, Lupkynis, or any of the inactive ingredients in the medicine.

Before taking Lupkynis, tell your healthcare provider about all your medical conditions, including if you:

• Plan to receive any vaccines. You should not receive any live vaccines during treatment with Lupkynis. Ask your healthcare provider if you are not sure if your vaccine is a live vaccine. Other vaccines may not work as well during treatment with Lupkynis
• Have or have had liver, kidney, or heart problems
• Have high blood pressure
• Are pregnant or plan to become pregnant
• Are breastfeeding or plan to breastfeed.

Pregnancy

Lupkynis may harm your unborn baby. When taking Lupkynis in combination with mycophenolate mofetil, you should also read the Medication Guide for mycophenolate mofetil for important pregnancy information.

Breastfeeding

Lupkynis can pass into breastmilk. You and your healthcare provider should decide if you will take Lupkynis while you are breastfeeding.

Warnings

Lupkynis carries a Boxed Warning for Malignancies and Serious Infections.

Increased Risk of Cancer (Malignancies)

People who take Lupkynis have an increased risk of getting certain kinds of cancer, including skin cancer and cancer of the lymph glands (lymphoma).

Increased Risk of Infection

Lupkynis affects your immune system and can lower the ability of your immune system to fight infections. Serious infections can happen in people receiving Lupkynis that can lead to hospitalizations and death. Call your healthcare provider right away if you have symptoms of an infection, such as:

• Fever
• Sweats or chills
• Cough or flu-like symptoms
• Muscle aches
• Warm, red, or painful areas on your skin.

Common Side Effects

The most common side effects of Lupkynis are:

• Diarrhea
• Headache
• Cough
• Urinary tract infection
• Stomach pain
• Heartburn
• Hair loss (alopecia).

Serious side effects and warnings

Lupkynis can cause other serious side effects.

Kidney Problems

Kidney problems are a common side effect of Lupkynis and may be serious. Your healthcare provider may do certain tests to check your kidney function while you take this medicine. Call your healthcare provider if you develop: little or no urination, swelling in your feet or ankles, feeling tired or short of breath.

High Blood Pressure

High blood pressure is a common side effect of Lupkynis and may be serious. Your healthcare provider will monitor your blood pressure while you take this medicine and may ask you to check your blood pressure at home. Call your healthcare provider if you develop a severe headache, blurred vision, pounding in your neck or ears, or a high blood pressure reading.

Nervous System Problems

Nervous system problems are a common side effect of Lupkynis and may be serious. Call your healthcare provider or go to the nearest hospital emergency room right away if you get any of these symptoms while taking Lupkynis. These could be signs of serious nervous system problems:

• confusion
• numbness and tingling
• seizures
• changes in alertness
• headache
• vision changes
• muscle tremors.

High Potassium Levels in Your Blood

Your healthcare provider may do certain tests to check your potassium levels while you take Lupkynis. Call your healthcare provider if you develop nausea, weakness, a tingly feeling, chest pain, irregular heartbeats, or loss of movement.

A Serious Heart Rhythm Problem (QT Prolongation)

In people at high risk, Lupkynis may cause QT prolongation. Your healthcare provider may monitor your electrolytes and heart rhythm with an electrocardiogram if you are at high risk.

Severe Low Red Blood Cell Count (Anemia)

Lupkynis may cause anemia.

Allergic Reactions

Allergic reactions, including a severe allergic reaction called anaphylaxis, can happen after taking Lupkynis. Stop taking Lupkynis and get emergency medical help right away if you have any of the following symptoms of an allergic reaction:

• swelling on the face, lips, tongue, or throat
• trouble breathing or swallowing
• rash, hives, or itching
• fast heartbeat
• fainting, dizziness, feeling lightheaded
• chest pain
• severe low red blood cell count (anemia).

Notes:

These are not all the possible side effects of Lupkynis. Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

Lupkynis works by blocking the enzyme calcineurin, although exactly how it works is not understood.

• In immune cells: Normally, when T-cells activate, calcium enters the cells and triggers calcineurin, which then activates genes that cause inflammation. Lupkynis blocks this process, preventing T-cells from multiplying and producing inflammatory signals that damage the kidneys.
• In kidney cells: Lupkynis also appears to directly protect specialized kidney cells called podocytes by strengthening their structural framework. This helps maintain the kidney's filtering system and reduces protein leakage into urine.

Lupkynis belongs to the drug class called calcineurin-inhibitor immunosuppressants.

Baseline eGFR: Your healthcare provider will measure your kidney function and assess your blood pressure (BP) before starting Lupkynis.

• Lupkynis is not recommended if your eGFR ≤45 mL/min/1.73 m² unless the benefits to you outweigh the kidney toxicity risks.
• If your BP is >165/105 mmHg, or you are having a hypertensive emergency, Lupkynis will not be started.

Adult Dose of Lupkynis for Lupus Nephritis in Combination with Immunosuppressive Therapy:

• Recommended Starting Dose: 23.7 mg (3 capsules) orally, twice a day. Each capsule of Lupkynis contains 7.9 mg.
• Use in combination with mycophenolate mofetil (MMF) and corticosteroids.

Monitoring

eGFR Monitoring & Dose Adjustments:

• Monitor eGFR: every 2 weeks (month 1), every 4 weeks (year 1), then quarterly
• If eGFR <60 and reduced 20-30% from baseline: decrease dose by 7.9 mg twice daily; reassess in 2 weeks. if eGFR is still reduced from baseline by >20%, reduce the dose again by 7.9 mg twice a day.
• If eGFR <60 and reduced ≥30% from baseline: stop Lupkynis. Reassess eGFR within two weeks; may restart at lower dose (7.9 mg twice daily) only if eGFR returns to ≥80% of baseline
• For patients who had a decrease in dose due to eGFR, consider increasing the dose by 7.9 mg twice a day for each eGFR measurement that is ≥80% of baseline. Do not exceed the starting dose.

Blood Pressure Monitoring:

• Check BP every 2 weeks for the first month, then as needed
• If BP >165/105 mmHg or hypertensive emergency: stop Lupkynis and start antihypertensive treatment.

Treatment Duration:

• Consider discontinuing if no therapeutic benefit by 24 weeks.

While taking Lupkynis, avoid:

• Live vaccines such as the flu vaccine through your nose, measles, mumps, rubella, polio by mouth, BCG (TB vaccine), yellow fever, chicken pox (varicella), or typhoid
• Exposure to sunlight and UV light, such as tanning machines. Wear protective clothing, wear sunglasses, and use sunscreen outside
• Grapefruit or drinking grapefruit juice while taking Lupkynis.

Do not take Lupkynis in combination with cyclophosphamide because its safety and effectiveness have not been established.

If you miss a dose of Lupkynis, and it is less than 4 hours from the time you were supposed to take it, take the dose.

If more than 4 hours have passed, skip the missed dose and take the next dose at the regular time. Do not take 2 doses at the same time.

Aurinia Alliance is the personalized support program for people taking Lupkynis. An Aurinia Alliance Nurse Case Manager can be assigned to you to help you enroll in the program, access Lupkynis, and connect you with other services such as the copay program for eligible commercial patients.

If you take too much Lupkynis, call your healthcare provider or go to the nearest hospital emergency room right away. Overdose symptoms may include headache, weakness, tremors, vomiting, infections, rash, or fast heartbeats.

Many drugs can interact and cause dangerous effects. Some drugs should not be used together with Lupkynis. Your doctor may change your treatment plan if you also use:

• cyclophosphamide;
• nefazodone;
• an antibiotic - clarithromycin, telithromycin;
• antifungal medicine - itraconazole, ketoconazole, posaconazole, voriconazole; or
• antiviral medicine to treat HIV or hepatitis C -boceprevir, cobicistat, dasabuvir, elvitegravir, indinavir, lopinavir/ritonavir, nelfinavir, ombitasvir, paritaprevir saquinavir, telaprevir, tipranavir.

Lupkynis may affect your heart. Your risk may be higher if you also use certain other medicines for infections, asthma, heart problems, high blood pressure, depression, mental illness, cancer, malaria, or HIV.

Lupkynis can interact with medications that are OATP1B1 substrates, such as statins, some heart disease medications, and cancer drugs. Ask your healthcare provider if you take one of these medications.

Tell your healthcare provider about all the medicines you take, including prescription and over-the-countermedicines, vitamins, and herbal supplements. Lupkynis may affect the way other medicines work, and othermedicines may affect how Lupkynis works.

Store at room temperature between 68°F to 77°F (20°C to 25°C).

Do not put Lupkynis in another container. Keep capsules in their original package until you are ready to take them.

Keep out of the reach of children.

Active ingredient: voclosporin 7.9 mgInactive ingredients: alcohol, Vitamin E polyethylene glycol succinate, polysorbate 40, medium-chain triglycerides, gelatin.

Lupkynis is supplied as an oval pink/orange capsule, imprinted on one side with VCS in white ink, packed in aluminum blisters. The Lupkynis capsule strength is 7.9 mg.

Aurinia Pharmaceuticals Inc., manufactures Lupkynis.