obeticholic acid

General

Pronunciation:
oh-bet-i-koe-lik as-id

Trade Name(s)

  • Ocaliva

Ther. Class.
none assigned

Pharm. Class.
temporary class farnesoid X receptor agonists

Indications

Treatment of primary biliary cholangitis (PBC) in patients with an inadequate response to ursodeoxycholic acid (UDCA) (in combination with UDCA) or unable to tolerate UDCA (as monotherapy).

Action

Stimulates farnesoid X receptor (FXR) in the liver and intestine, resulting in decreased synthesis of bile acids from cholesterol and increased transport of bile acids out of the hepatocytes. Overall, the result is a reduction in intracellular hepatocyte concentrations of bile acids.

Therapeutic Effect(s):

Reduction in alkaline phosphatase and total bilirubin concentrations.

Pharmacokinetics

Absorption: Rapidly absorbed following oral administration.

Distribution: Widely distributed to tissues.

Protein Binding: >99%.

Metabolism and Excretion: Conjugated in the liver to glycine and tauro conjugates of obeticholic acid (both are active metabolites) that undergo enterohepatic recirculation and conversion by intestinal microbiota back to obeticholic acid that is reabsorbed or excreted in feces. Minimal excretion in urine.

Half-life: Unknown.

TIME/ACTION PROFILE (plasma concentrations)

ROUTEONSETPEAKDURATION
POunknown1.5 hrunknown

Contraindication/Precautions

Contraindicated in:

  • Complete biliary obstruction.

Use Cautiously in:

  • Decompensated cirrhosis or Child-Pugh Class B or C hepatic impairment;
  • OB: Lactation: Safety not established;
  • Pedi: Safety and effectiveness not established.

Adverse Reactions/Side Effects

CNS: HEPATIC ENCEPHALOPATHY, dizziness

CV: palpitations, peripheral edema

Derm: pruritus, eczema, rash

EENT: oropharyngeal pain

Endo: ↓ high-density lipoprotein cholesterol, hypothyroidism

GI: VARICEAL BLEEDING, abdominal pain, ascites (worsening), constipation, ↑ liver enzymes, jaundice

MS: arthralgia

Misc: fatigue, fever

* CAPITALS indicate life-threatening.
Underline indicate most frequent.

Interactions

Drug-Drug

Route/Dosage

PO (Adults) Non-cirrhotic or compensated Child-Pugh Class A–5 mg once daily for 3 mo; if adequate reduction in alkaline phosphatase and/or total bilirubin not achieved and tolerating medication, ↑ dose to 10 mg once daily; Child-Pugh Class B or C or prior hepatic decompensation event–5 mg once weekly for 3 mo; if adequate reduction in alkaline phosphatase and/or total bilirubin not achieved and tolerating medication, ↑ dose to 5 mg twice weekly (with doses given ≥3 days apart); may further titrate to 10 mg twice weekly (with doses given ≥3 days apart) based on clinical response and tolerability.

Availability

Tablets: 5 mg, 10 mg

Assessment

  • Monitor for severe pruritus (intense or widespread itching, interfering with activities of daily living, or causing severe sleep disturbance, or intolerable discomfort) during therapy. For Non-Cirrhotic or Compensated Cirrhotic Child-Pugh Class A Patients: add and antihistamine or bile acid binding resin. Reduce dose of obeticholic acid. For patients unable to tolerate 5 mg daily, reduce to 5 mg every other day. For patients intolerant to 10 mg daily, reduce to 5 mg daily. Interrupt therapy for 2 wks and resume at reduced dose. For Child-Pugh Class B or C or Patients with a Prior Decompensation Event: add and antihistamine or bile acid binding resin. Interrupt therapy for 2 wks and resume at reduced dose. If persistent, intolerable pruritus continues, consider discontinuing therapy.

Lab Test Considerations: Determine patient's Child-Pugh classification before starting therapy to determine starting dose. Re-evaluate dosing regimen periodically during therapy.

  • Monitor total bilirubin, alkaline phosphatase, INR, and albumin routinely during therapy to determine liver function and response to therapy. Hold therapy if signs of worsening liver function occur. When levels return to baseline, reinitiate therapy using recommended starting dose with adjustment for Child-Pugh classification. If liver function decline is severe, consider discontinuing therapy.
  • Monitor for changes in serum lipid levels during treatment. If patient does not respond to therapy after 1 yr at highest recommended dose tolerated (maximum of 10 mg once daily), and experiences ↓ in HDL-C, consider risks against benefits of therapy.
  • May cause decreased INR. Monitor INR and adjust dose of warfarin, as needed, to maintain target INR range when co-administering obeticholic acid and warfarin.

Potential Diagnoses

Implementation

  • PO Administer without regard to food.
    • For patients taking bile acid binding resin, administer obeticholic acid at least 4 hours before or 4 hours after taking the bile acid binding resin.

Patient/Family Teaching

  • Instruct patient to take medication as directed.
  • Advise patient to notify health care professional if signs and symptoms of disease progression or worsening liver function (stomach-area swelling from build-up of fluid; yellowing of skin or whites of eyes; black, tarry, or bloody stools; coughing up or vomiting blood, or coffee grounds vomit; mental changes such as confusion, sleepier than usual or harder to wake up, slurred speech, mood swings, changes in personality), complete biliary obstruction, severe or persistent signs of impaired health (nausea, vomiting, abdominal pain, diarrhea, weight loss, fever and chills, worsening or new fatigue, weakness, loss of appetite, dehydration) occur.
  • Advise patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and to consult with health care professional before taking other medications.
  • Emphasize need for regular laboratory tests to monitor liver function.
  • Advise female patient to notify health care professional if pregnancy is planned or suspected, or if breast feeding.

Evaluation/Desired Outcomes

Reduction in alkaline phosphatase and total bilirubin concentrations.

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