Voclosporin

Voclosporin decreases the activity of your immune system. This may increase the risk that you will get a serious infection. If you experience any of the following symptoms, call your doctor immediately: cough; sore throat; fever; chills; flu-like symptoms; warm, red, or painful skin; pain or burning on urination; frequent urination; lower back pain; or other signs of infection.

Taking voclosporin may increase the risk that you will develop cancer, especially lymphoma (cancer of a part of the immune system) or skin cancer. Tell your doctor if you have or have ever had any type of cancer. To reduce your risk of skin cancer, plan to avoid unnecessary or prolonged exposure to sunlight and to wear protective clothing, sunglasses, and sunscreen during your treatment. If you experience any of the following symptoms, call your doctor immediately: new sores or discoloration on the skin; lumps or masses anywhere in your body; night sweats; swollen glands in the neck, armpits, or groin; trouble breathing; chest pain; weakness or tiredness that does not go away; or pain, swelling, or fullness in the stomach.

Your doctor or pharmacist will give you the manufacturer's patient information sheet (Medication Guide) when you begin treatment with voclosporin and each time you refill your prescription. Read the information carefully and ask your doctor or pharmacist if you have any questions. You can also visit the Food and Drug Administration (FDA) website (http://www.fda.gov/Drugs/DrugSafety/ucm085729.htm) to obtain the Medication Guide.

Keep all appointments with your doctor and the laboratory. Your doctor will order certain lab tests to check your body's response to voclosporin.

Voclosporin is used in combination with other mycophenolate mofetil (Cellcept) and corticosteroids like methylprednisolone or prednisone for treatment of lupus nephritis (an autoimmune disease in which the immune system attacks the kidneys) in adults. Voclosporin is in a class of medications called immunosupressants. It works by decreasing the activity of the immune system to prevent it from attacking the transplanted organ.

Voclosporin comes as a capsule to take by mouth. It is usually taken twice a day for up to 1 year. Voclosporin capsules should be taken on an empty stomach 1 hour before or 2 hours after a meal, as close to every 12 hours as possible. There should be at least 8 hours between doses. Take voclosporin at around the same times every day. Follow the directions on your prescription label carefully, and ask your doctor or pharmacist to explain any part you do not understand. Take voclosporin exactly as directed. Do not take more or less of it or take it more often than prescribed by your doctor.

Swallow the capsules whole; do not split, chew, crush, or dissolve them.

Voclosporin controls lupus nephritis but does not cure it. Continue to take voclosporin even if you feel well. Do not stop taking voclosporin without talking to your doctor.

It is not known if taking voclosporin for longer than one year is safe. Talk to your doctor about benefits and risks of continuing to take voclosporin after 1 year.

This medication may be prescribed for other uses; ask your doctor or pharmacist for more information.

Before taking voclosporin,

• tell your doctor and pharmacist if you are allergic to voclosporin, any other medications, or any of the ingredients in voclosporin capsules. Ask your pharmacist or check the Medication Guide for a list of the ingredients.
• tell your doctor if you are taking clarithromycin, itraconazole (Sporanox, Tolsura), ketoconazole or ritonavir (Norvir, in Kaletra). Your doctor may tell you not to take voclosporin if you are taking /one or more of these medications.
• tell your doctor and pharmacist what prescription and nonprescription medications, vitamins, and nutritional supplements you are taking or plan to take. Be sure to mention any of the following: amiloride (Midamor); angiotensin-converting enzyme (ACE) inhibitors such as benazepril (Lotensin), captopril, enalapril (Vasotec), fosinopril (Monopril), lisinopril (Prinivil, Zestril, Qbrelis, in Zestoretic), moexipril, perindopril (in Prestalia), quinapril (Accupril, in Accuretic, in Quinaretic), ramipril (Altace), and trandolapril; angiotensin II receptor antagonists such as candesartan (Atacand), irbesartan (Avapro, in Avalide), losartan (Cozaar, in Hyzaar), olmesartan (Benicar, in Azor, in Tribenzor), telmisartan (Micardis), and valsartan (Diovan, in Entresto, in Exforge); carbamazepine (Carbatrol, Epitol, Equetro, Tegretol, Teril); digoxin (Lanoxin); diltiazem (Cardizem, Cartia XT, Taztia XT, Tiazac); efavirenz (Sustiva; in Atripla, in Symfi); erythromycin (E.E.S., ERY-C, Ery-Tab, Erythrocin); fluconazole (Diflucan); nevirapine (Viramune); oxcarbazepine (Oxtellar XR, Trileptal); phenobarbital; phenytoin (Dilantin, Phenytek); rifabutin (Mycobutin, in Talicia); rifampin (Rifadin, Rimactane); spironolactone (Aldactone, Carospir, in Aldactazide); triamterene (Dyrenium, in Maxzide); and verapamil (Calan, Verelan). Your doctor may need to change the doses of your medications or monitor you carefully for side effects. Many other medications may also interact with voclosporin, so be sure to tell your doctor about all the medications you are taking, even those that do not appear on this list.
• tell your doctor what herbal products you are taking, especially St. John's wort.
• tell your doctor if you have or have ever had any of the conditions mentioned in the IMPORTANT WARNING section or any of the following: long QT syndrome (an inherited condition in which a person is more likely to have QT prolongation); an irregular heartbeat; heart disease; low levels of potassium, calcium, or magnesium in your blood: high blood pressure; or liver or kidney disease.
• tell your doctor if you are pregnant or plan to become pregnant. Voclosporin capsules contain a small amount of alcohol and it is not known what effect it an have on an unborn baby if taken during pregnancy. If you become pregnant while taking voclosporin, call your doctor.
• tell your doctor if you are breastfeeding. Your doctor may tell you not to breastfeed during your treatment and for 7 days after your final dose.
• you should know that voclosporin may cause high blood pressure. Your doctor will monitor your blood pressure carefully, and may prescribe medication to treat high blood pressure if it develops.
• do not have any vaccinations without talking to your doctor.

Do not eat grapefruit or drink grapefruit juice while taking this medication.

Take the missed dose as soon as you remember it. However, if it is more than 4 hours after the time you were supposed to take the dose, skip the missed dose and continue your regular dosing schedule. Do not take a double dose to make up for a missed one.

Voclosporin may cause side effects. Tell your doctor if any of these symptoms are severe or do not go away:

• diarrhea
• headache
• cough
• stomach pain
• upset stomach
• hair loss
• sores in or around the mouth
• shakiness
• loss of appetite

Some side effects can be serious. If you experience any of these symptoms or those listed in the IMPORTANT WARNING section, call your doctor immediately:

• confusion, changes in alertness, muscle tremors, numbness and tingling, headache, vision changes, or seizures
• pale skin, shortness of breath, or dizziness
• decreased urination; swelling in your legs, ankles or feet; or unusual tiredness or weakness
• fast, irregular, or pounding heartbeat; lightheadedness; or fainting

Voclosporin may cause other side effects. Call your doctor if you have any unusual problems while taking this medication.

If you experience a serious side effect, you or your doctor may send a report to the Food and Drug Administration's (FDA) MedWatch Adverse Event Reporting program online (http://www.fda.gov/Safety/MedWatch) or by phone (1-800-332-1088).

Keep this medication in the container it came in, tightly closed, and out of reach of children. Store it at room temperature and away from excess heat and moisture (not in the bathroom).

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

It is important to keep all medication out of sight and reach of children as many containers (such as weekly pill minders and those for eye drops, creams, patches, and inhalers) are not child-resistant and young children can open them easily. To protect young children from poisoning, always lock safety caps and immediately place the medication in a safe location – one that is up and away and out of their sight and reach. http://www.upandaway.org

Unneeded medications should be disposed of in special ways to ensure that pets, children, and other people cannot consume them. However, you should not flush this medication down the toilet. Instead, the best way to dispose of your medication is through a medicine take-back program. Talk to your pharmacist or contact your local garbage/recycling department to learn about take-back programs in your community. See the FDA's Safe Disposal of Medicines website (http://goo.gl/c4Rm4p) for more information if you do not have access to a take-back program.

In case of overdose, call the poison control helpline at 1-800-222-1222. Information is also available online at https://www.poisonhelp.org/help. If the victim has collapsed, had a seizure, has trouble breathing, or can't be awakened, immediately call emergency services at 911.

Symptoms of overdose may include:

• tremor
• headache
• nausea
• vomiting
• fast heart rate or heartbeat
• hives
• itching
• sleepiness

Do not let anyone else take your medication. Ask your pharmacist any questions you have about refilling your prescription.

It is important for you to keep a written list of all of the prescription and nonprescription (over-the-counter) medicines you are taking, as well as any products such as vitamins, minerals, or other dietary supplements. You should bring this list with you each time you visit a doctor or if you are admitted to a hospital. It is also important information to carry with you in case of emergencies.

• Lupkynis^®