Ocaliva (Obeticholic acid)

Obeticholic Acid (oh be'' i koe' lik) Ocaliva® [Posted 02/01/2018] AUDIENCE: Pharmacy, Hepatology, Gastroenterology ISSUE: FDA is warning that the liver disease medicine obeticholic acid (Ocaliva) has been incorrectly dosed daily instead of weekly in patients with moderate to severe primary biliary cholangitis (PBC), a rare chronic liver disease, increasing the risk of serious liver injury. To ensure correct dosing and reduce the risk of liver problems, FDA is clarifying the current recommendations for screening, dosing, monitoring, and managing PBC patients with moderate to severe liver disease taking obeticholic acid. FDA is adding a new Boxed Warning, FDA's most prominent warning, to highlight this information in the prescribing information of the drug label. FDA is also requiring a Medication Guide for patients to inform them about this issue. As a condition of approval, FDA required the manufacturer of obeticholic acid, Intercept Pharmaceuticals, to continue studying the medicine in patients with advanced PBC. These clinical trials are currently ongoing and FDA expects to receive results in 2023. FDA is adding the additional warnings to the drug label after receiving reports that obeticholic acid is being given to PBC patients with moderate to severe liver impairment more often than is recommended in the prescribing information, resulting in liver decompensation, liver failure, and sometimes death. FDA will continue to monitor this medicine and will update the public if new information becomes available. BACKGROUND: This is an update to the MedWatch safety alert for Ocaliva (obeticholic acid) - Increased Risk of Serious Liver Injury, issued 09-21-2017. RECOMMENDATION: Health care professionals should follow the obeticholic acid dosing regimen in the drug label, which is based on calculating a Child-Pugh score in PBC patients with suspected liver cirrhosis before treatment to determine their specific classification and starting dosage (see Table for the Clarified obeticholic acid Dosage Regimen and more detailed instructions). Dosing higher than recommended in the drug label can increase the risk for liver decompensation, liver failure, and sometimes death. Routinely monitor all patients for biochemical response, tolerability, and PBC progression, and re-evaluate Child-Pugh classification to determine if dosage adjustment is needed. Close monitoring is recommended for patients at an increased risk of liver decompensation, including those with laboratory evidence of worsening liver function (e.g., total bilirubin, INR, albumin) or progression to cirrhosis. Educate patients and caregivers on the symptoms of worsening liver function. Temporarily stop obeticholic acid in those with laboratory or clinical evidence of worsening liver function that may indicate decompensation and monitor the patient's liver function. If a patient's condition returns to baseline, weigh the potential risks and benefits of restarting obeticholic acid. Re-initiate, using the recommended starting dosage based on Child Pugh classification. Consider discontinuing obeticholic acid in patients who have experienced clinically significant liver-related adverse reactions. Patients should be aware that your prescriber should do regular tests to check how well your liver is working while you are taking obeticholic acid. If your liver problems get worse, your dose may need to be changed or stopped. Report new or worsening severe skin itching to your health care professional. See the Drug Safety Communication for additional information. For more information visit the FDA website at: http://www.fda.gov/Safety/MedWatch/SafetyInformation and http://www.fda.gov/Drugs/DrugSafety.

Obeticholic acid is used alone or in combination with ursodiol (Actigall, Urso) to treat primary biliary cholangitis (PBC; a type of liver disease that destroys bile ducts, which allows bile to stay in the liver and cause damage) in people who cannot take ursodiol or in people who were not treated successfully with ursodiol alone. Obeticholic acid is in a class of medications called farnesoid X receptor agonists. It works by decreasing the production of bile in the liver and increasing the removal of bile from the liver.

Obeticholic acid comes as a tablet to take by mouth. It is taken usually once a day with or without food. Take obeticholic acid at around the same time 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 obeticholic acid exactly as directed. Do not take more or less of it or take it more often than prescribed by your doctor. Your doctor may adjust your dose of obeticholic acid or delay your treatment. This will depend on how well the medication works for you or if you experience certain side effects. Continue to take obeticholic acid even if you feel well. Do not stop taking obeticholic acid without talking to your doctor. Ask your pharmacist or doctor for a copy of the manufacturer's information for the patient.

Before taking obeticholic acid, tell your doctor and pharmacist if you are allergic to obeticholic acid, any other medications, or any of the ingredients in obeticholic acid tablets. Ask your pharmacist for a list of the ingredients. 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: caffeine (found in certain medications to treat drowsiness and headaches), theophylline (Elixophyllin, Theo-24, Theochron, others), tizanidine (Zanaflex), or warfarin (Coumadin, Jantoven). 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 obeticholic acid, 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 cholestyramine (Prevalite), colestipol (Colestid), or colesevelam (Welchol), take them at least 4 hours before or 4 hours after obeticholic acid. tell your doctor if you have bile duct obstruction (blockage in the tubes that carry bile from the liver to the gallbladder and small intestine). Your doctor may tell you not to take obeticholic acid. tell your doctor if you have or have ever had liver disease or high cholesterol. tell your doctor if you are pregnant, plan to become pregnant, or are breastfeeding. If you become pregnant while taking obeticholic acid, call your doctor.

Unless your doctor tells you otherwise, continue your normal diet.

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.

Obeticholic acid may cause side effects. Tell your doctor if any of these symptoms are severe or do not go away: mouth or throat pain irregular or pounding heartbeat rash stomach pain dizziness fainting swelling of the hands, feet, ankles, or lower legs tiredness or weakness joint or muscle pain constipation Some side effects can be serious. If you experience any of these symptoms, call your doctor immediately: itching yellowing of the skin or eyes dark colored urine pain in the upper right part of the stomach nausea vomiting fatigue weight loss loss of appetite bloody stools fever pale colored stools anxiety confusion swelling in the area around the stomach Obeticholic acid 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). 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.

Keep all appointments with your doctor and the laboratory. Your doctor will order certain lab tests before and during your treatment to check your body's response to obeticholic acid. Before having any laboratory test, tell your doctor and the laboratory personnel that you are taking obeticholic acid. 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.