Download Ocaliva

New Drug Introduction: Ocaliva / obeticholic acid
Pharmacology
Manufacturer
Approval Date
Indications
Contraindications
Black Box Warnings
Warnings/Precautions
Pregnancy/Lactation
Pharmacokinetics
Drug Interactions –
Object Drugs
All drug interaction effects
listed at: 10 mg Ocaliva
Drug Interactions –
Precipitant drugs
Adverse Effects
(Treatment%) [Placebo%]
Monitoring Efficacy
Monitoring Toxicity
Dosing - Initial
Dosing - Usual
Dosing - Max
Renal Adjustment
Hepatic Adjustment
Farnesoid X Receptor Agonist
Intercept Pharmaceuticals, Inc
5/27/2016
Treatment of primary biliary cholangitis (PBC) as monotherapy or in
combination with ursodeoxycholic acid (UDCA)
Patients with complete biliary obstruction
None
 Liver – Related Adverse Reactions
 Severe Pruritus
 Reduction in HDL-C
Limited human data available. No fetal harm at exposures at 13 and 6 times
the max amount in rats and rabbits, respectively. No information on drug
transfer in lactation.
A – Cmax occurred ~1.5 hrs and follows linear kinetics. Food did not alter
extent of absorption.
D – Volume is 618 L and binds to >99% of human plasma protein.
M – Conjugated with glycine or taurine in liver and secreted into bile, these
metabolites are pharmaceutically active. Conjugates are absorbed in the
small intestine leading to enterohepatic recirculation.
E – 87% excretion in feces through biliary secretion. <3% was excreted in
urine with no detection of obeticholic acid.
CYP1A2: potential for increased exposure to CYP1A2 substrates.
25 mg warfarin – 13%  systemic exposure
200 mg caffeine – 42%  AUC and 6%  in Cmax
20 mg omeprazole – 32%  AUC and 33%  in Cmax
20 mg rosuvastatin – 22%  AUC and 27%  in Cmax
Not metabolized to significant extent by CYP450
20 mg omeprazole <1.2 fold  exposure. Determined to be not clinically
significant.
Pruritus (70%) [38%]
Fatigue (25%) [15%]
Rash (10%) [8%]
Abdominal pain and discomfort(19%) [14%]
Improvement in lowering ALP, a liver enzyme and biomarker used to track
disease progression in PBC. No current mortality or symptom relief benefits
LFTs, including alkaline phosphatase and bilirubin, lipid profile;
signs/symptoms of hepatic adverse reactions and/or pruritus
5 mg daily
10 mg daily if adequate reduction not achieved in 3 months
10 mg daily
None
In moderate to severe impairment (Child-Pugh B and C):
Initial: 5 mg PO weekly. If inadequate reduction in ALP and/or total
bilirubin after 3 months, increase to 5 mg twice weekly (at least 3 days
apart) and subsequently to 10 mg twice weekly (at least 3 days apart).
Cost: Source: Uptodate. Accessed 09/01/2016
Dose(s)
Brand- generic
5 mg
Ocaliva – obeticholic
10
mg
acid
250 mg (Urso 250)
ursodiol tablets
500
mg (Urso Forte)
dosed:
250
mg generic
13-15mg/kg/day
500 mg generic
in 2-4 doses
$ (30d)
$6840 (30 tabs)
$6840 (30 tabs)
$528 (100 tabs)
$936 (100 tabs)
$268 (100 tabs)
$475 (100 tabs)
Summary
 Ocaliva™ - obeticholic acid is indicated for the treatment of primary biliary cholangitis
(PBC) in combination with ursodiol (ursodeoxycholic acid) in adults with an inadequate
response to ursodiol, or as monotherapy in adults unable to tolerate ursodiol.
 This medication provides an alternative treatment option for PBC through a unique,
novel mechanism of action.
 Obeticholic acid is a farnesoid X receptor agonist.
 Initial dosing for Ocaliva is 5 mg daily, titrated to 10 mg if adequate reduction not
achieved in 3 months.
o Child-Pugh B and C: 5 mg weekly
References:
1. https://ocaliva.com/
2. Ocaliva package insert. Intercept Pharmaceutical. May 2016.
3. Nevens F, Andreone P, Mazzella G, et al. A Placebo-Controlled Trial of Obeticholic
Acid in Primary Biliary Cholangitis. N Engl J Med. 2016;375(7):631-43.
Date Prepared: 09/23/2016
Editor: Peter G. Koval, Pharm.D., BCPS
Author: Han Lin, Pharm.D. Candidate, UNC Eshelman School of Pharmacy