Levoketoconazole

IMPORTANT WARNING:

Levoketoconazole may cause liver damage, sometimes serious enough to require liver transplantation or to cause death. Liver damage may occur in people who do not already have liver disease or any other conditions that increase the risk that they will develop liver damage. Tell your doctor if you have or have ever had liver disease; cirrhosis (scarring) of the liver; history of liver disease following use of ketoconazole, other antifungals (e.g. fluconazole, voriconazole, posaconazole), or other drug; or recurrent gall stones. Your doctor may tell you not to take levoketoconazole. Also tell your doctor if you drink or have ever drunk large amounts of alcohol. Avoid heavy use of alcoholic beverages during your treatment with levoketoconazole because drinking alcoholic beverages may increase the risk that you will develop liver damage. If you experience any of the following symptoms, call your doctor immediately: extreme tiredness, pain in the upper right part of the stomach, nausea, yellowing of the skin or eyes, dark yellow urine, pale stools, or unusual bleeding or bruising.

Levoketoconazole may cause QT prolongation (an irregular heart rhythm that can lead to fainting, loss of consciousness, seizures, or sudden death). Tell your doctor if you or anyone in your family has or has ever had long QT syndrome (an inherited condition in which a person is more likely to have QT prolongation). Your doctor may tell you not to take levoketoconazole. Also, tell your doctor if you have or have ever had low levels of potassium or magnesium in your blood, an irregular heartbeat or other heart rhythm problems, heart failure, or a heart attack. Tell your doctor and pharmacist if you are taking bosutinib (Bosulif), cisapride (not available in the U.S.), clarithromycin, cobimetinib (Cotellic), crizotinib (Xalkori), disopyramide (Norpace), dofetilide (Tikosyn), dronedarone (Multaq), eligustat (Cerdelga), ivabradine (Corlanor), methadone (Methadose), midostaurin (Rydapt), nicardipine, pimozide, quinidine, or ranolazine (Aspruzyo sprinkle, Ranexa). If you experience any of the following symptoms, stop taking levoketoconazole and call your doctor immediately or get emergency medical treatment: fast, pounding, or irregular heartbeat; fainting; lightheadedness; or loss of consciousness.

Keep all appointments with your doctor and the laboratory. Your doctor will order certain tests before and during your treatment to check your body's response to levoketoconazole. Your doctor may also order an electrocardiogram (ECG; test that measures the electrical activity in the heart) before and during your treatment.

Your doctor or pharmacist will give you the manufacturer's patient information sheet (Medication Guide) when you begin treatment with levoketoconazole 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 ) or the manufacturer's website to obtain the Medication Guide.

Talk to your doctor about the risks of taking levoketoconazole.

WHY is this medicine prescribed?

Levoketoconazole is used to treat high levels of cortisol (a hormone produced by your adrenal glands) in patients with Cushing's syndrome (a condition in which the body produces too much cortisol) and who have failed surgery or cannot have surgery to treat this condition. Levoketoconazole is in a class of medications called cortisol synthesis inhibitors. It works by stopping the production of cortisol.

Are there OTHER USES for this medicine?

Levoketoconazole is not approved by the Food and Drug Administration (FDA) for treatment of fungal infections.

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

HOW should this medicine be used?

Levoketoconazole comes as a tablet to take by mouth. It is usually taken two times a day with or without food. Take levoketoconazole 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 levoketoconazole exactly as directed. Do not take more or less of it or take it more often than prescribed by your doctor.

Your doctor will probably start you on a low dose of levoketoconazole and gradually increase your dose, not more than once every 2-3 weeks.

Levoketoconazole controls high levels of cortisol secondary to Cushing's syndrome but does not cure it. Continue to take levoketoconazole even if you feel well. Do not stop taking levoketoconazole without talking to your doctor.

Ask your pharmacist or doctor for a copy of the manufacturer's information for the patient.

What SPECIAL PRECAUTIONS should I follow?

Before taking levoketoconazole,

• tell your doctor and pharmacist if you are allergic to levoketoconazole, ketoconazole, any other medications, or any of the ingredients in levoketoconazole tablets. Ask your pharmacist for a list of the ingredients.

• tell your doctor if you are taking avanafil (Stendra), buspirone (Buspar), conivaptan, dabigatran (Pradaxa), darifenacin, darunavir (Prezista, in Prezcobix, Symtuza), digoxin (Lanoxin), everolimus (Afinitor, Zortress), fexofenadine (Allegra), ibrutinib (Imbruvica), lomitapide (Juxtapid), lovastatin (Altoprev), midazolam (Nayzilam), naloxegol (Movantik), nisoldipine (Sular), saquinavir (Invirase), simvastatin (Flolipid, Zocor, in Vytorin), sirolimus (Rapamune), tacrolimus (Astagraf, Envarsus, Prograf), tipranavir (Aptivus), triazolam (Halcion), and vardenafil (Staxyn). Your doctor will probably tell you not to take levoketoconazole if you are taking one or more of these medications or any of the medications listed in the IMPORTANT WARNING section.

• tell your doctor and pharmacist what other prescription and nonprescription medications, vitamins, nutritional supplements, and herbal products you are taking or plan to take. Be sure to mention any of the following: atorvastatin (Lipitor, in Caduet), carbamazepine (Carbatrol, Epitol, Equetro, Tegretol, Teril), efavirenz (Sustiva, in Atripla), fosamprenavir (Lexiva), isoniazid, metformin (Fortamet, Glumetza, Riomet, in Actoplus Met, Invokamet, Janumet, Jentadueto, Kazano, Kombiglyze, Segluromet, Synjardy, Trijardy, Xigduo), mifepristone (Korlym, Mifeprex), mitotane (Lysodren), phenytoin (Dilantin, Phenytek), rifabutin (Mycobutin, in Talicia), nevirapine (Viramune), rifampin (Rifadin, Rimactane), and ritonavir (Norvir, in Kaletra). 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 levoketoconazole, so be sure to tell your doctor about all the medications you are taking, even those that do not appear on this list.

• if you are taking antacids (e.g. aluminum hydroxide, calcium carbonate, magnesium hydroxide) take them 2 hours after levoketoconazole.

• tell your doctor if you are taking a medication for indigestion, heartburn, or ulcers such as cimetidine (Tagamet), dexlansoprazole (Dexilant), esomeprazole (Nexium, in Vimovo), famotidine (Pepcid, in Duexis), lansoprazole (Prevacid), nizatidine (Axid), omeprazole (Prilosec, in Zegerid, Talicia), pantoprazole (Protonix), rabeprazole (AcipHex), ranitidine (Zantac), or sucralafate (Carafate). Your doctor may tell you not to take the medication.

• tell your doctor if you have an infection or if you have or ever had any of the conditions listed in the IMPORTANT WARNINGS section or adrenal insufficiency (condition in which the adrenal glands do not make enough steroid hormones).

• tell your doctor if you are pregnant or plan to become pregnant. If you become pregnant while taking levoketoconazole, call your doctor.

• tell your doctor if you are breast feeding. You should not breastfeed while you are taking levoketoconazole and for 1 day after your final dose.

• you should know that levoketoconazole may cause fertility problems. Talk to your healthcare provider about the risks of receiving this medication if you would like to have children.

• ask your doctor about the safe use of alcoholic beverages while you are taking levoketoconazole.

What SPECIAL DIETARY instructions should I follow?

Talk to your doctor about eating grapefruit and drinking grapefruit juice while taking this medication.

What should I do IF I FORGET to take a dose?

Take the missed dose as soon as you remember it. However, if it is almost time for the next dose, skip the missed dose and continue your regular dosing schedule. Do not take a double dose to make up for a missed one.

What SIDE EFFECTS can this medicine cause?

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

• redness of the skin
• headache
• upset stomach or stomach pain
• decreased appetite
• joint or back pain
• abnormal vaginal bleeding
• difficulty sleeping or falling asleep
• diarrhea
• burning or pain on urination or frequent urination
• difficulty paying attention
• irritability or depressed mood
• dry mouth
• dry skin
• loss of hair

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 or get medical treatment:

• rash; hives; itching; swelling of the eyes, face, lips, or tongue; difficulty breathing or swallowing; or chest pain
• swelling of the arms, hands, feet, ankles, or lower legs
• muscle cramps, weakness, fatigue, and constipation
• nausea, vomiting, tiredness or lack of energy, abdominal pain, loss of appetite, or dizziness
• unusual bruising or bleeding, blood in urine, nose bleeding
• sexual problems in females: decreased sex drive, mood change
• sexual problems in males: decreased sex drive, inability to get or keep an erection
• breast enlargement in males

Levoketoconazole 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).

What should I know about STORAGE and DISPOSAL of this medication?

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).

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.

What should I do in case of OVERDOSE?

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.

What OTHER INFORMATION should I know?

Before having any laboratory test, tell your doctor and the laboratory personnel that you are taking levoketoconazole.

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.