Obeticholic acid

Oral Administration

May take with or without food

Concomitant bile-acid binding resin: Separate obeticholic acid dose by at least 4 hr

Storage

Store at 20-25ºC (68-77ºF); excursions permitted to 15-30ºC (59-86ºF)

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).

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.

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

Obeticholic acid is part of the drug class:

• Bile acid preparations

Follow all directions on your medicine label and package. Tell each of your healthcare providers about all your medical conditions, allergies, and all medicines you use.

Follow all directions on your prescription label. Your doctor may occasionally change your dose to make sure you get the best results. Do not use this medicine in larger or smaller amounts or for longer than recommended.

Obeticholic acid is usually taken once per day, with or without food.

To be sure this medicine is helping your condition, you may need frequent blood tests. You may not notice any change in your symptoms, but your blood work will help your doctor determine how best to treat you with obeticholic acid.

You may be given other medications to treat itching that may be caused by obeticholic acid.

If you stop taking obeticholic acid for any reason, you may need to use a lower dose when you start taking it again. Follow your doctor's dosing instructions carefully.

Call your doctor if your symptoms do not improve, or if they get worse. The most common symptoms of PBC is intense itching, especially in your arms, legs, and back.

Store at room temperature away from moisture and heat.

Take the missed dose as soon as you remember. Skip the missed dose if it is almost time for your next scheduled dose. Do not take extra medicine to make up the missed dose.

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222.

• It is used to treat a certain bile duct problem (cholangitis).

Use this medicine as ordered by your doctor. Read all information given to you. Follow all instructions closely.

• Take with or without food.

What do I do if I miss a dose?

• Take a missed dose as soon as you think about it.
• If it is close to the time for your next dose, skip the missed dose and go back to your normal time.
• Do not take 2 doses at the same time or extra doses.

Obeticholic acid is a farnesoid X receptor agonist; activation of FXR suppresses de novo synthesis of bile acids from cholesterol and increases transport of bile acids out of the hepatocytes, limiting the overall size of the circulating bile acid pool while promoting choleresis.

Distribution

618 L

Metabolism

Conjugated in the liver to active metabolites (glyco- and tauro- obeticholic acid; activity similar to parent drug) that undergo enterohepatic recirculation and conversion by intestinal microbiota back to obeticholic acid that is reabsorbed or excreted. A third metabolite, 3-glucuronide, has minimal pharmacologic activity.

Excretion

Feces (~87%); urine (<3%)

Time to Peak

Plasma: Obeticholic acid: ~1.5 hours; glyco- and tauro- obeticholic acid: 10 hours

Protein Binding

>99%

Mean AUC of total obeticholic acid (the sum of obeticholic acid and its 2 active conjugates) increased by 1.1-, 4- and 17-fold in patients with mild, moderate and severe hepatic impairment (Child-Pugh class A, B, and C), respectively.

Concerns related to adverse effects:

• Hepatic effects: Dose-related hepatic adverse reactions (eg, jaundice, worsening ascites, primary biliary cholangitis flare) have been reported, as early as one month after initiating therapy. Monitor LFTs and for signs/symptoms of hepatic adverse reactions; in patients who develop clinically significant hepatic-related adverse reactions, weigh the potential risks against the benefits of continuing treatment. Discontinue use in patients who develop complete biliary obstruction.

• Lipid effects: Dose-dependent reductions in high density lipoprotein-cholesterol (HDL-C) levels have been reported; monitor lipids during treatment. In patients who experience a reduction in HDL-C and do not respond to therapy after 1 year at the maximum dosage, consider the potential risks against the benefits of continuing obeticholic acid.

• Pruritus: Severe pruritus (ie, intense or widespread itching, interfering with activities of daily living, or causing severe sleep disturbance, or intolerable discomfort, typically requiring medical interventions) has been reported. Consider dosage reduction, temporary interruption of dosing, and/or addition of bile acid resins or antihistamines to manage severe pruritus.

Disease-related concerns:

• Hepatic impairment: Use with caution in patients with moderate to severe hepatic impairment (Child-Pugh classes B and C); exposure increases significantly; dosage adjustment recommended.

Concurrent drug therapy issues:

• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

Safety and efficacy have not been established in patients younger than 18 years.

Consult WARNINGS section for additional precautions.

Administration advice:
-This drug may be taken with or without food.
-Patients taking concomitant bile acid binding resins should allow at least 4 hours before or after taking the bile acid resin, or as great an interval as possible.

Storage requirements:
-The manufacturer product information should be consulted.

General:
-This drug is indicated for patients who have not achieved adequate biochemical response to an appropriate response to UDCA for at least 1 year or are intolerant of UDCA.
-Approval of this drug is based on a reduction in ALP levels; improvements in survival/disease-related symptoms have not been established.
-The dose should be increased to 10 mg/day to achieve optimal response.

Monitoring:
-Periodic liver function tests
-Periodic HDL levels

Patient advice:
-Instruct patients to immediately report any signs/symptoms of severe pruritus, hepatitis/jaundice, or hypersensitivity reactions.
-Patients should be advised to speak to a healthcare provider if they become pregnant, intend to become pregnant, or are breastfeeding.
-Patients should be advised to report all concurrent prescription and nonprescription medications or herbal products they are taking.