obeticholic acid

oh-bet-i-KOE-lik AS-id

Therapeutic Classification: none assigned

Pharmacologic Classification: farnesoid X receptor agonists

REMS

Primary biliary cholangitis in patients either without cirrhosis or with compensated cirrhosis and no evidence of portal hypertension (to be used either in combination with ursodeoxycholic acid if experienced an inadequate response to ursodeoxycholic acid or as monotherapy if unable to tolerate ursodeoxycholic acid).

Stimulates farnesoid X receptor 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 effects:

Reduction in alkaline phosphatase and total bilirubin concentrations.

Absorption: Rapidly absorbed following oral administration.

Distribution: Widely distributed to tissues.

Protein Binding: >99%.

Metabolism/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.

(plasma concentrations)

ROUTE	ONSET	PEAK	DURATION
PO	unknown	1.5 hr	unknown

Contraindicated in:

Complete biliary obstruction;
Decompensated cirrhosis or a prior episode of hepatic decompensation;
Compensated cirrhosis with evidence of portal hypertension.

Use Cautiously in:

OB: Safety not established in pregnancy;
Lactation: Safety not established in breastfeeding;
Pedi: Safety and effectiveness not established in children.

CV: palpitations, peripheral edema

Derm: pruritus, eczema, rash

EENT: oropharyngeal pain

Endo: ↓high-density lipoprotein cholesterol, hypothyroidism

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

MS: arthralgia

Neuro: fatigue, dizziness, ENCEPHALOPATHY

Misc: fever

Drug-drug:

Bile acid resins, including cholestyramine, colesevelam, and colestipol may ↓ absorption; give obeticholic acid ≥4 hr before or after bile acid resins.
May ↓ efficacy of warfarin.
May ↑ levels and risk of toxicity of CYP1A2 substrates, including theophylline and tizanidine.
Cyclosporine may exacerbate accumulation of conjugated bile salts; avoid concurrent use.

PO (Adults ): 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.

(Generic available)

Tablets: 5 mg; 10 mg

Monitor patients with compensated cirrhosis, concomitant hepatic disease (autoimmune hepatitis, alcoholic liver disease), and/or with severe intercurrent illness for new evidence of portal hypertension (ascites, gastroesophageal varices, persistent thrombocytopenia) or increases above the upper limit of normal in total bilirubin, direct bilirubin, or prothrombin time. If laboratory or clinical signs of hepatic decompensation (ascites, jaundice, variceal bleeding, hepatic encephalopathy), portal hypertension (ascites, gastroesophageal varices, persistent thrombocytopenia), clinically significant hepatic adverse reactions or complete biliary obstruction develop, permanently discontinue obeticholic acid.
Monitor for severe pruritus (intense or widespread itching, interfering with activities of daily living, or causing severe sleep disturbance, or intolerable discomfort) during therapy. 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 wk and resume at reduced dose.

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 therapy. 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 coadministering obeticholic acid and warfarin.

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

Instruct patient to take medication as directed. Advise patient to read Medication Guide before starting therapy and with each Rx refill in case of changes.
Advise patient to notify health care professional if signs and symptoms of disease progression or worsening liver function (stomach-area swelling from buildup 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.
Inform patient of potential for itching. Advise patient to notify health care professional if severe itching causing discomfort, problems sleeping, or interference with daily activities occurs.
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.
Rep: Advise females of reproductive potential to notify health care professional if pregnancy is planned or suspected or if breastfeeding.
Emphasize need for regular laboratory tests to monitor liver function.

Reduction in alkaline phosphatase and total bilirubin concentrations.

Ocaliva

NDC Code

69516- Intercept Pharmaceuticals Inc
- 69516-005- Ocaliva
  - 69516-005-30- 30 TABLET, FILM COATED in 1 BOTTLE, PLASTIC (69516-005-30)

69516- Intercept Pharmaceuticals Inc
- 69516-010- Ocaliva
  - 69516-010-30- 30 TABLET, FILM COATED in 1 BOTTLE, PLASTIC (69516-010-30)

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