奥贝胆酸的用药用量,药物相互作用及禁忌？

(trademark: Ocaliva) is a first-in-class farnesoid X receptor (FXR) agonist, an effective drug for the treatment of primary biliary cirrhosis and non-alcoholic fatty liver disease, and its market value is huge. The recommended starting dose of obeticholic acid is 5 mg orally once daily for adults who have not achieved an adequate response to UDCA at appropriate doses for more than 1 year or cannot tolerate UDCA.

Obeticholic acid dosage

For patients with primary biliary cirrhosis (PBC) without cirrhosis or compensated cirrhosis, without evidence of portal hypertension, who have not achieved an adequate biochemical response to appropriate doses of ursodeoxycholic acid (UDCA) for at least 1 year or who are intolerant to UDCA, obeticholic acid is as follows:

1. The starting dose for the first 3 months is 5 mg once a day.

2. After the first 3 months, in patients with insufficient reduction in ALP and/or total bilirubin and in patients who tolerate obeticholic acid, increase to the maximum dose of 10 mg once daily.

Important Dosage and Administration Instructions for Obeticholic Acid

Before initiating obeticholic acid, healthcare providers should determine whether the patient has decompensated cirrhosis (eg, Child-Pugh class B or C), has had a previous decompensated event, or has compensated cirrhosis with portal hypertension (eg, ascites, gastroesophageal varices, sustained thrombocytopenia), as obeticholic acid is contraindicated in these patients.

Obeticholic acid drug interactions

1. Bile acid binding resin

Bile acid-binding resins, such as cholestyramine, colestipol, or colesevelam, adsorb and reduce bile acid absorption and may reduce obeticholic acid absorption, systemic exposure, and efficacy. If taking a bile acid-binding resin, take obeticholic acid at least 4 hours before or 4 hours after taking the bile acid, or as long as possible.

2. Warfarin

The international normalized ratio (INR) decreases after combined use of warfarin and ocarilin. Monitor NR and adjust warfarin dose as necessary to maintain the target INR range when occapiper and warfarin are coadministered.

3. CYP1A2 substrates with narrow therapeutic index

Cholic acid may increase exposure to concomitant drugs that are CYP1A2 substrates. Treatment monitoring with CYP1A2 substrates with a narrow therapeutic index (such as theophylline and tizanidine) is recommended when coadministered with obeticholic acid.

4. Bile salt efflux pump inhibitors

Avoid concurrent use of bile salt efflux pump (BSEP) inhibitors, such as cyclosporine. Concomitant drugs that inhibit canalicular membrane bile acid transporters (such as BSEP) may exacerbate the accumulation of conjugated bile salts (including taurine conjugates of bile acids) in the liver and lead to clinical symptoms. If concurrent use is deemed necessary, monitor serum aminotransferases and bilirubin.

Contraindications of obeticholic acid

Obeticholic acid is contraindicated in the following patients:

1. Decompensated cirrhosis (such as Child-Pugh class B or C) or previous decompensation events.

2. Compensated cirrhosis with signs of portal hypertension (such as ascites, gastroesophageal varices, sustained thrombocytopenia).

3. Complete biliary obstruction.

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