Obeticholic acid

Name: Obeticholic acid

Dosing & Uses

Dosage Forms & Strengths

tablet

  • 5mg
  • 10mg

Primary Biliary Cholangitis

Indicated for primary biliary cholangitis (PBC) in combination with ursodeoxycholic acid (UDCA) in adults with an inadequate response to UDCA for at least 1 yr or as monotherapy in adults unable to tolerate UDCA

Starting dose: 5 mg PO qDay

Dosage titration: If an adequate response has not been achieved after 3 months at 5 mg/day, and obeticholic acid is being tolerated, increase dose to 10 mg qDay

Not to exceed 10 mg/day

Dosage Modifications

Intolerable pruritus

  • Consider 1 or more of the following options:
  • Add an antihistamine or bile-acid binding resin
  • Temporarily interrupt treatment for up to 2 weeks, followed by restarting at reduced dosage
  • Reduce dose to
    • If intolerant to 5 mg/day, decrease to 5 mg every other day
    • If intolerant to 10 mg/day, decrease to 5 mg/day
  • If possible, gradually increase dose to 10 mg/day, as tolerated, to achieve optimal response
  • Consider discontinuing treatment in patients who continue to experience intolerable pruritus

Hepatic impairment

  • Moderate-to-severe (Child-Pugh class B/C): Initiate dose at 5 mg once weekly
  • If response is inadequate after 3 months, increase the dosage to 5 mg twice weekly (at least 3 days apart) and subsequently 10 mg twice weekly depending on response and tolerability
  • Contraindicated with complete biliary obstruction

Dosing Considerations

Indication is approved under accelerated approval based on a reduction in alkaline phosphatase

Continued approval for this indication may be contingent on verification and description of clinical benefit in confirmatory trials

Safety and efficacy not established

No overall differences in safety or effectiveness were observed between subjects older than 65 yr, but sensitivity in some older individuals cannot be ruled out

Other uses for this medicine

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

What special dietary instructions should I follow?

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

Obeticholic Acid Dosage

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.

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

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.

What is obeticholic acid?

Primary biliary cholangitis (PBC) is a chronic type of liver disease that can gradually destroy bile ducts. These ducts deliver bile from the liver to the small intestines, to help your body digest fats and certain vitamins. When bile ducts are destroyed by PBC, bile stays in the liver and damages liver cells, which can cause cirrhosis (scarring of the liver) and lead to liver failure. PBC is a slow progressive disease that may have no symptoms for many years. Treating PBC to keep the liver functioning normally can allow for a normal life expectancy.

Obeticholic acid is used to treat PBC. This medicine is sometimes used together with another drug called ursodeoxycholic acid (UDCA).

Obeticholic acid was approved by the US Food and Drug Administration (FDA) on an "accelerated" basis. In clinical studies, patients with PBC responded to obeticholic acid. However, further studies are needed to determine if this medicine can improve survival or disease-related symptoms.

Obeticholic acid may also be used for purposes not listed in this medication guide.

Proper Use of obeticholic acid

Take obeticholic acid exactly as directed by your doctor. Do not take more of it, do not take it more often, and do not take it for a longer time than your doctor ordered. To do so may increase the chance of side effects.

Take obeticholic acid with or without food.

If you are taking cholestyramine, colestipol, or colesevelam, take Ocaliva™ at least 4 hours before or 4 hours after these medicines.

Dosing

The dose of obeticholic acid will be different for different patients. Follow your doctor's orders or the directions on the label. The following information includes only the average doses of obeticholic acid. If your dose is different, do not change it unless your doctor tells you to do so.

The amount of medicine that you take depends on the strength of the medicine. Also, the number of doses you take each day, the time allowed between doses, and the length of time you take the medicine depend on the medical problem for which you are using the medicine.

  • For oral dosage form (tablets):
    • For treatment of primary biliary cholangitis:
      • Adults—At first, 5 milligrams (mg) once a day. Your doctor may adjust your dose as needed and tolerated. However, the dose is not more than 10 mg once a day.
      • Children—Use and dose must be determined by your doctor.

Missed Dose

If you miss a dose of obeticholic acid, take it as soon as possible. However, if it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not double doses.

Storage

Store the medicine in a closed container at room temperature, away from heat, moisture, and direct light. Keep from freezing.

Keep out of the reach of children.

Do not keep outdated medicine or medicine no longer needed.

Ask your healthcare professional how you should dispose of any medicine you do not use.

What are some other side effects of Obeticholic Acid?

All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:

  • Itching.
  • Feeling very tired or weak.
  • Stomach pain.
  • Joint pain.
  • Throat pain.
  • Dizziness.
  • Hard stools (constipation).
  • Eczema.

These are not all of the side effects that may occur. If you have questions about side effects, call your doctor. Call your doctor for medical advice about side effects.

You may report side effects to the FDA at 1-800-FDA-1088. You may also report side effects at http://www.fda.gov/medwatch.

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Tablet, Oral:

Ocaliva: 5 mg, 10 mg

Pharmacologic Category

  • Farnesoid X Receptor Agonist

Administration

Oral: Administer with or without food. For patients taking a bile acid binding resin to manage intolerable pruritus, take obeticholic acid ≥4 hours before or 4 hours after taking the bile acid binding resin.

Drug Interactions

Bile Acid Sequestrants: May decrease the serum concentration of Obeticholic Acid. Management: Administer obeticholic acid at least 4 hours before or at least 4 hours after the administration of bile acid sequestrants. Consider therapy modification

CloZAPine: CYP1A2 Inhibitors (Weak) may increase the serum concentration of CloZAPine. Monitor therapy

CYP1A2 Substrates: Obeticholic Acid may increase the serum concentration of CYP1A2 Substrates. Monitor therapy

TiZANidine: CYP1A2 Inhibitors (Weak) may increase the serum concentration of TiZANidine. Management: Avoid these combinations when possible. If combined use is necessary, initiate tizanidine at an adult dose of 2 mg and increase in 2 to 4 mg increments based on patient response. Monitor for increased effects of tizanidine, including adverse reactions. Consider therapy modification

Warfarin: Obeticholic Acid may diminish the anticoagulant effect of Warfarin. Monitor therapy

Renal Dose Adjustments

No adjustment recommended.

Liver Dose Adjustments

Mild liver dysfunction (Child Pugh Class A): No adjustment recommended.
Moderate to severe liver dysfunction (Child Pugh Class B and C):
-Initial dose: 5 mg orally once a week
-Maintenance dose: 5 mg orally once a week; if adequate reduction in ALP and/or total bilirubin is not achieved after 3 months, increase the dosage to 5 mg 2 times a week (at least 3 days apart), and subsequently to 10 mg 2 times a week (at least 3 days apart) depending on response and tolerability
-Maximum dose: 10 mg/day

Comments;
-Patients should be monitored for the occurrence of liver-related adverse reactions
-The potential risks should be weighed against benefits in patients with a history of clinically significant liver-related adverse reactions.

Obeticholic acid Pregnancy Warnings

The manufacturer makes no recommendation regarding use during pregnancy. US FDA pregnancy category: Not assigned. Risk Summary: Limited data available on use of this drug in pregnant women is not sufficient to inform a drug-related risk.

Animal models have failed to show evidence of fetal harm or abnormalities at MRHD 6 to 13 times 10 mg. Lower fetal body weight, increased early/late resorptions and decreased viable fetuses were observed at levels approaching maternal toxicity. There are limited controlled data in human pregnancy. US FDA pregnancy category Not Assigned: The US FDA has amended the pregnancy labeling rule for prescription drug products to require labeling that includes a summary of risk, a discussion of the data supporting that summary, and relevant information to help health care providers make prescribing decisions and counsel women about the use of drugs during pregnancy. Pregnancy categories A, B, C, D, and X are being phased out.

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