AUDIENCE:Patient, Health Professional, Pharmacy
ISSUE: The FDA is restricting the use of the liver disease medicine Ocaliva (obeticholic acid) in patients having primary biliary cholangitis (PBC) with advanced cirrhosis of the liver because it can cause serious harm. Some PBC patients with cirrhosis who took Ocaliva, especially those with evidence of advanced cirrhosis, developed liver failure, sometimes requiring liver transplant. In the five years since Ocaliva's accelerated approval, FDA identified 25 cases of serious liver injury leading to liver decompensation or liver failure associated with Ocaliva in PBC patients with cirrhosis, both in those without clinical signs of cirrhosis (compensated) or in those with clinical signs of cirrhosis (decompensated). Many of these PBC patients had advanced cirrhosis before starting Ocaliva.
FDA added a new Contraindication, FDA's strongest warning, to the Ocaliva prescribing information, available at: https://bit.ly/3gsEhhm,and patient Medication Guide, available at: https://bit.ly/3glMRyE, stating that Ocaliva should not be used in PBC patients with advanced cirrhosis. FDA also revised the Boxed Warning, our most prominent warning, to include this information along with related warnings about this risk.
Based on the original clinical trials, FDA believes the benefits of Ocaliva outweigh the risks for PBC patients who do not have advanced cirrhosis. FDA will continue to monitor and evaluate the clinical benefit and adverse events of Ocaliva and will communicate any new information to the public if it becomes available.
BACKGROUND: PBC is a rare, chronic disease affecting the ducts in the liver that carry bile, which helps with digestion.
- Patients with PBC who have cirrhosis and are taking Ocaliva should talk to your health care professional about these new warnings. Contact your prescriber immediately if you develop any symptoms, which may be signs of worsening liver injury or development of advanced cirrhosis.
Health Care Professionals:
- Health care professionals should determine before starting Ocaliva whether a patient with PBC has advanced cirrhosis as the medicine is contraindicated in these patients. Advanced cirrhosis is defined as cirrhosis with current or prior evidence of hepatic decompensation (e.g., encephalopathy, coagulopathy) or portal hypertension (e.g., ascites, gastroesophageal varices, persistent thrombocytopenia).
- Routinely monitor patients during Ocaliva treatment for progression of PBC with laboratory and clinical assessments to determine whether the medicine needs to be discontinued. Permanently discontinue Ocaliva in patients with cirrhosis who progress to advanced cirrhosis.
- Also monitor patients for clinically significant liver-related adverse reactions that may manifest as development of acute-on-chronic liver disease with nausea, vomiting, diarrhea, jaundice, scleral icterus, and/or dark urine. Permanently discontinue Ocaliva in patients developing these symptoms.
For more information visit the FDA website at: http://www.fda.gov/Safety/MedWatch/SafetyInformation and http://www.fda.gov/Drugs/DrugSafety.
Obeticholic acid can cause serious or life-threatening liver damage, especially if the dose of obeticholic acid is not adjusted when liver disease worsens. If you experience any of the following symptoms while taking obeticholic acid, call your doctor immediately: yellowing of the skin or eyes, dark urine, black tarry stools, coughing up or vomiting blood, nausea, vomiting, abdominal pain, swelling in and around the stomach area, weight loss, loss of appetite, fatigue, diarrhea, confusion, slurred speech, anxiety, mood swings, changes in personality, or less frequent urination.
Keep all appointments with your doctor and the laboratory. Your doctor may order certain tests before and during your treatment to check your liver function and your body's response to obeticholic acid.
Why is this medication prescribed?
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.
How should this medicine be used?
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 need to temporarily or permanently stop your treatment or decrease your dose of obeticholic acid during 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.
Other uses for this medicine
This medication may be prescribed for other uses; ask your doctor or pharmacist for more information.
What special precautions should I follow?
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 high cholesterol or thyroid disease.
- 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.
What special dietary instructions should I follow?
Unless your doctor tells you otherwise, continue your normal diet.
What should I do if I forget 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 medication cause?
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
- fast, irregular, or pounding heartbeat
- swelling of the hands, feet, ankles, or lower legs
- tiredness or weakness
- joint or muscle pain
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:
- severe itching
- fever, chills, or other signs of infection
- dryness, irritation, redness, crusting or drainage of the skin
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).
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.
In case of emergency/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.
Symptoms of overdose may include the following:
- yellowing of the skin or eyes
- dark colored urine
- loss of appetite
- pain in the upper right part of the stomach
- swelling in the area around the stomach
What other information should I know?
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.