Olic 5

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

May take with or without food Concomitant bile-acid binding resin: Separate obeticholic acid dose by at least 4 hr

Adult Tablet 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 Before initiating obeticholic acid in patients with suspected cirrhosis, determine patient’s Child-Pugh classification (A, B, or C) using nomogram and determine the appropriate starting dosage Starting dose and titration Noncirrhotic or compensated Child-Pugh class A 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 Child-Pugh class B or C, or prior decompensation event Starting dose: 5 mg PO once weekly Dosage titration: If an adequate response has not been achieved after 3 months at 5 mg once weekly, and obeticholic acid is being tolerated, increase dose to 5 mg twice weekly (at least 3 days apart) May titrate to 10 mg twice weekly (at least 3 days apart) based on response and tolerability

Complete biliary obstruction

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

Hepatic decompensation and failure, in some cases fatal, reported in patients with PBC who have decompensated cirrhosis or Child-Pugh Class B or C hepatic impairment when obeticholic acid was dosed more frequently than the recommended starting dosage of 5 mg once weekly Monitor patients for elevations in liver enzymes and risks for hepatic decompensation (eg, worsening renal function, dehydration) 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) 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

>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%)

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 Avoid concomitant use of inhibitors of the bile salt efflux pump (BSEP) (eg, cyclosporine); BSEP inhibitors may exacerbate accumulation of conjugated bile salts in the liver and result in clinical symptoms