Lupkynis

What is Lupkynis?

Lupkynis is a prescription medicine used with other medicines to treat adults with active lupus nephritis. Lupkynis should not be taken with a medicine called cyclophosphamide. Talk with your healthcare provider if you are not sure if you take this medicine.

Description

LUPKYNIS (voclosporin) capsules, a calcineurin-inhibitor immunosuppressant, is available for administration as soft gelatin capsules containing 7.9 mg voclosporin per capsule. Inactive ingredients include alcohol, Vitamin E polyethylene glycol succinate (NF), polysorbate 40 (NF), medium-chain triglycerides (NF), gelatin, sorbitol, glycerin, iron oxide yellow, iron oxide red, titanium dioxide, and water.

Voclosporin (90 to 95% trans-isomer) is the active ingredient in LUPKYNIS. Chemically, voclosporin is named: Cyclo{{(6E)-(2S,3R,4R)-3-hydroxy-4-methyl-2-(methylamino)-6,8-nonadienoyl}-L-2-aminobutyryl-N-methyl-glycyl-N-methyl-L-leucyl-L-valyl-N-methyl-L-leucyl-L-alanyl-D-alanyl-N-methyl-L-leucyl-N-methyl-L-leucyl-N-methyl-L-valyl}. The chemical structure of voclosporin is:

Voclosporin has an empirical formula of C 63H 111N 11O 12 and a molecular weight of 1214.6 g/mole. It appears as white to off-white solid matter. At ambient temperature, voclosporin is freely soluble in acetone, acetonitrile, ethanol, and methanol, and practically insoluble in heptanes (USP). Voclosporin is practically insoluble (less than 0.1 g/L at 20ºC) in water and melts above 144ºC with decomposition.

 Mechanism of Action

LUPKYNIS is a calcineurin-inhibitor immunosuppressant. The mechanism of voclosporin suppression of calcineurin has not been fully established. Activation of lymphocytes involves an increase in intracellular calcium concentrations that bind to the calcineurin regulatory site and activate calmodulin binding catalytic subunit and through dephosphorylation activates the transcription factor, Nuclear Factor of Activated T-Cell Cytoplasmic (NFATc). The immunosuppressant activity results in inhibition of lymphocyte proliferation, T-cell cytokine production, and expression of T-cell activation surface antigens.

Studies in animal models also support a non-immunological role for calcineurin inhibition in kidney function to stabilize actin cytoskeleton and stress fibers in podocytes leading to increased podocyte integrity in glomeruli.

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

Lupkynis can cause serious side effects, including:

• Increased risk of cancer. 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 is a medicine that affects your immune system. Lupkynis 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 can cause death. Call your healthcare provider right away if you have symptoms of an infection such as:
  • fever
  • cough or flu-like symptoms
  • warm, red, or painful areas on your skin
  • sweats or chills
  • muscle aches

See “What are the possible side effects of Lupkynis?” for more information about side effects.

Who should not take Lupkynis?

Do not take Lupkynis:

• with medicines known as strong CYP3A4 inhibitors such as ketoconazole, itraconazole, and clarithromycin.
• if you are allergic to voclosporin or any of the ingredients in Lupkynis. See the end of this Medication Guide for a complete list of ingredients in Lupkynis.

What should I tell my healthcare provider before taking Lupkynis?

Before you take 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 when taking Lupkynis. 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.
• are breastfeeding or plan to breastfeed. You and your healthcare provider should decide if you will take Lupkynis or breastfeed. You should not do both. After you stop your treatment with Lupkynis, do not start breastfeeding again until 7 days after your last dose of Lupkynis.

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

How should I take Lupkynis?

• Take Lupkynis exactly as your healthcare provider tells you to take it.
• Your healthcare provider may change your dose, if needed. Do not stop taking or change your dose of Lupkynis without talking to your healthcare provider.
• Swallow Lupkynis capsules whole. Do not break, crush, chew or dissolve Lupkynis capsules before swallowing. If you cannot swallow Lupkynis capsules whole, tell your healthcare provider.
• Take Lupkynis on an empty stomach, either 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. If a dose is missed, take it as soon as possible within 4 hours after missing the dose. If more than 4 hours has passed, skip the missed dose and take the next dose at the regular time. Do not take 2 doses at the same time.
• If you take too much Lupkynis, call your healthcare provider or go to the nearest hospital emergency room right away.
• Talk with your healthcare provider if you have been taking Lupkynis for close to one year. It is not known if taking Lupkynis is safe or effective beyond a year.

What should I avoid while taking Lupkynis?

• Live vaccines such as 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 and use a sunscreen.
• You should not eat grapefruit or drink grapefruit juice while taking Lupkynis.

What are the possible side effects of Lupkynis?

Lupkynis may cause serious side effects, including:

• See “What is the most important information I should know about Lupkynis?”
• kidney problems. Kidney problems are common side effects of Lupkynis and may be serious. Your healthcare provider may do certain tests to check your kidney function while you take Lupkynis.
• 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 Lupkynis and may ask you to check your blood pressure at home.
• 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 levels of potassium in your blood. Your healthcare provider may do certain tests to check your potassium levels while you take Lupkynis.
• a serious heart rhythm problem (QT prolongation).
• severe low red blood cell count (anemia).

The most common side effects of Lupkynis are:

• diarrhea
• urinary tract infection
• heartburn
• headache
• stomach pain
• loss of hair (alopecia)
• cough

These are not all the possible side effects of Lupkynis.
Call your healthcare provider for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088. You may also report side effects to www.FDA.Gov/Medwatch.

General information about the safe and effective use of Lupkynis

Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not use Lupkynis for a condition for which it was not prescribed. Do not give Lupkynis to other people, even if they have the same symptoms that you have. It may harm them. You can ask your pharmacist or healthcare provider for information about Lupkynis that is written for healthcare professionals.

How should I store Lupkynis?

• Store Lupkynis at room temperature between 68⁰F to 77⁰F (20⁰C to 25⁰C).
• Do not put Lupkynis in another container. Keep capsules in their original package until you are ready to take them.
• Keep Lupkynis and all medicines out of the reach of children.

What are the ingredients in Lupkynis?

Active ingredient: voclosporin

Inactive ingredients: alcohol, Vitamin E polyethylene glycol succinate, polysorbate 40, medium-chain triglycerides, gelatin

Label

PACKAGE LABEL PRINCIPAL DISPLAY PANEL SECTION