Dosing and uses of Ocaliva (obeticholic acid)
Adult dosage forms and 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
Pediatric dosage forms and strengths
Safety and efficacy not established
Geriatric dosage forms and strengths
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
Ocaliva (obeticholic acid) adverse (side) effects
>10%
Pruritus (56-70%)
Fatigue (19-25%)
Severe pruritus (19-23%)
Reduced HDL-C (9-20%)
Abdominal pain and discomfort (10-19%)
1-10%
Rash (7-10%)
Oropharyngeal pain (7-8%)
Dizziness (7%)
Constipation (7%)
Peripheral edema (3-7%)
Palpitations (3-7%)
Pyrexia (7%)
Thyroid function abnormality (4-6%)
Eczema (3-6%)
Warnings
Contraindications
Complete biliary obstruction
Cautions
Monitor patients with moderate-to-severe hepatic impairment
Dose response relationship observed in clinical trials for liver-related adverse reactions, including jaundice, worsening ascites, and primary biliary cholangitis flare (doses ≥10 mg/day)
Discontinue therapy if complete biliary obstruction occurs (see Contraindications)
Management strategies for severe pruritus include antihistamines, bile acid resins, and temporary treatment interruption (see Dosage modifications); discontinue therapy if persistent intolerable pruritus occurs
Monitor for reduction in HDL-C; for patients who do not respond after 1 yr at the highest recommended dosage that can be tolerated (ie, 10 mg/day), and who experience a reduction in HDL-C, weigh the potential risks against the benefits of continuing treatment
Drug interaction overview
- Bile-acid binding resins may reduce the absorption, systemic exposure, and efficacy of obeticholic acid
- Coadministration of warfarin and obeticholic acid has been shown to decrease the INR; monitor the INR and adjust warfarin dose accordingly
- Coadministration with CYP1A2 substrates (eg, theophylline, tizanidine) may increase exposure of CYP1A2 substrates; monitor CYP1A2 substrates with narrow therapeutic index
Pregnancy
Pregnancy
Limited available human data on the use of obeticholic acid during pregnancy are not sufficient to inform a drug-associated risk
Lactation
Unknown if distributed in human breast milk
Consider the developmental and health benefits of breastfeeding along with the mother’s clinical need for the drug, and any potential adverse effects on the breastfed infant from the drug or from the underlying maternal condition
Pregnancy categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA: Information not available.
Pharmacology of Ocaliva (obeticholic acid)
Mechanism of action
Farnesoid X receptor (FXR) agonist
FXR is a nuclear receptor expressed in the liver, intestine, kidney, and adipose tissue that regulates a wide variety of target genes critically involved in the control of bile acid synthesis and transport, lipid metabolism, and glucose homeostasis
FXR activation suppresses de novo synthesis of bile acids in hepatocytes as well as increasing transport of bile acids out of hepatocytes, thereby reducing exposure of the hepatocytes to bile acid
Absorption
Peak plasma concentration
- Obeticholic acid: 1.5 hr
- Active metabolites: 10 hr
Distribution
Protein bound: >99%
Vd: 618 L
Metabolism
Obeticholic acid is conjugated with glycine or taurine in the liver then secreted into bile
The conjugates are converted back to obeticholic acid and either reabsorbed in the small intestine for enterohepatic recirculation or excreted in feces
Elimination
Excretion: ~87% feces; <3% urine
Administration
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)
