Indication

Primary Biliary Cholangitis\r\nIndicated 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

Administration

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

Adult Dose

$4e

Contraindication

Complete biliary obstruction

Mode of Action

Farnesoid X receptor (FXR) agonist\r\n\r\nFXR 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\r\n\r\nFXR 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

Precaution

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\r\n\r\nMonitor patients for elevations in liver enzymes and risks for hepatic decompensation (eg, worsening renal function, dehydration)\r\n\r\nDose response relationship observed in clinical trials for liver-related adverse reactions, including jaundice, worsening ascites, and primary biliary cholangitis flare (doses >10 mg/day)\r\n\r\nLactation\r\nUnknown if distributed in human breast milk\r\n\r\nConsider 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\r\n

Side Effect

>10%\r\nPruritus (56-70%)\r\nFatigue (19-25%)\r\nSevere pruritus (19-23%)\r\nReduced HDL-C (9-20%)\r\nAbdominal pain and discomfort (10-19%)\r\n\r\n1-10%\r\nRash (7-10%)\r\nOropharyngeal pain (7-8%)\r\nDizziness (7%)\r\nConstipation (7%)\r\nPeripheral edema (3-7%)\r\nPalpitations (3-7%)\r\nPyrexia (7%)\r\nThyroid function abnormality (4-6%)\r\nEczema (3-6%)\r\n\r\n

Interaction

Bile-acid binding resins may reduce the absorption, systemic exposure, and efficacy of obeticholic acid\r\nCoadministration of warfarin and obeticholic acid has been shown to decrease the INR; monitor the INR and adjust warfarin dose accordingly\r\nCoadministration with CYP1A2 substrates (eg, theophylline, tizanidine) may increase exposure of CYP1A2 substrates; monitor CYP1A2 substrates with narrow therapeutic index\r\nAvoid 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