Description

Livacol tablet is indicated for the treatment of adult patients with primary biliary cholangitis (PBC) without cirrhosis or with compensated cirrhosis who do not have evidence of portal hypertension Either in combination with ursodeoxycholic acid (UDCA) with an inadequate response to UDCA or as monotherapy in patients unable to tolerate UDCA. * রেজিস্টার্ড চিকিৎসকের পরামর্শ মোতাবেক ঔষধ সেবন করুন'

Mechanism of Action: Obeticholic acid is an agonist for Farnesoid X Receptor (FXR), a nuclear receptor expressed in the liver and intestine. FXR is a key regulator of bile acid, inflammatory, fibrotic and metabolic pathways. FXR activation decreases the intracellular hepatocyte concentrations of bile acids by suppressing de novo synthesis from cholesterol as well as by increased transport of bile acids out of the hepatocytes. These mechanisms limit the overall size of the circulating bile acid pool while promoting choleresis, thus reducing hepatic exposure to bile acids. Pharmacodynamics: Pharmacodynamic Markers: In the trial, administration of Obeticholic acid 10 mg once daily was associated with a 173% increase in concentrations of FGF-19 an FXR-inducible enterokine involved in bile acid homeostasis from baseline to Month 12. Concentrations of cholic acid and chenodeoxycholic acid were reduced 2.7 micromolar and 1.4 micromolar respectively from baseline to Month 12. The clinical relevance of these findings is unknown. Cardiac Electrophysiology: At a dose of 10 times the maximum recommended dose Obeticholic acid does not prolong the QT interval to any clinically relevant extent.

Important Dosage and Administration Instructions: Prior to the initiation of Obeticholic acid, healthcare providers should determine whether the patient has decompensated cirrhosis (e.g., Child-Pugh Class B or C) has had a prior decompensation event or has compensated cirrhosis with evidence of portal hypertension (e.g., ascites, gastroesophageal varices, persistent thrombocytopenia) because Obeticholic acid is contraindicated in these patients. Recommended Dosage Regimen: The recommended dosage of Obeticholic acid for PBC patients without cirrhosis or with compensated cirrhosis who do not have evidence of portal hypertension, who have not achieved an adequate biochemical response to an appropriate dosage of UDCA for at least 1 year or are intolerant to UDCA follows below: Start with a dosage of 5 mg once daily for the first 3 months. After the first 3 months, for patients who have not achieved an adequate reduction in ALP and/or total bilirubin and who are tolerating Obeticholic acid increase to a maximum dosage of 10 mg once daily. Monitoring to Assess Safety, Need for Obeticholic acid Discontinuation: Routinely monitor patients during Obeticholic acid treatment for biochemical response, tolerability and progression of PBC. Closely monitor patients with compensated cirrhosis, concomitant hepatic disease (e.g., autoimmune hepatitis, alcoholic liver disease) and/or severe intercurrent illness for new evidence of portal hypertension (e.g., ascites, gastroesophageal varices, persistent thrombocytopenia) or increases above the upper limit of normal in total bilirubin, direct bilirubin or prothrombin time. Permanently discontinue Obeticholic acid in patients who develop laboratory or clinical evidence of hepatic decompensation, have compensated cirrhosis and develop evidence of portal hypertension, experience clinically significant hepatic adverse reactions, or develop complete biliary obstruction. Management of Patients with Intolerable Pruritus on Obeticholic acid: For patients with intolerable pruritus on Obeticholic acid consider one or more of the following management strategies. Add an antihistamine or bile acid-binding resin. Reduce the dosage of Obeticholic acid to: 5 mg every other day, for patients intolerant to 5 mg once daily. 5 mg once daily, for patients intolerant to 10 mg once daily. Temporarily interrupt Obeticholic acid dosing for up to 2 weeks. Restart at a reduced dosage. For patients whose dosage is reduced or interrupted, titrate the dosage based on biochemical response and tolerability. Consider discontinuing Obeticholic acid treatment in patients who continue to experience persistent, intolerable pruritus despite management strategies.

Bile Acid Binding Resins: Bile acid binding resins such as cholestyramine, colestipol or colesevelam adsorb and reduce bile acid absorption and may reduce the absorption, systemic exposure and efficacy of Livacol. If taking a bile acid binding resin, take Livacol at least 4 hours before or 4 hours after taking the bile acid binding resin or at as great an interval as possible. Warfarin: The International Normalized Ratio (INR) decreased following the coadministration of warfarin and Livacol. Monitor INR and adjust the dosage of warfarin as needed to maintain the target INR range when co-administering Livacol and warfarin. CYP1A2 Substrates with Narrow Therapeutic Index: Livacol may increase the exposure to concomitant drugs that are CYP1A2 substrates. Therapeutic monitoring of CYP1A2 substrates with a narrow therapeutic index (e.g., theophylline and tizanidine) is recommended when co-administered with Livacol. Inhibitors of Bile Salt Efflux Pump: Avoid concomitant use of inhibitors of the bile salt efflux pump (BSEP) such as cyclosporine. Concomitant medications that inhibit canalicular membrane bile acid transporters such as the BSEP may exacerbate accumulation of conjugated bile salts including taurine conjugate of Livacol in the liver and result in clinical symptoms. If concomitant use is deemed necessary, monitor serum transaminases and bilirubin.

The most common side effects of Livacol include: Pruritus, Fatigue & Stomach pain and discomfort. Other common side effects include rash, arthralgia (joint pain), oropharyngeal pain (pain in the middle part of the throat), dizziness, constipation, abnormal thyroid function, and eczema (inflammation of the skin).

Pregnancy: The limited available human data on the use of obeticholic acid during pregnancy are not sufficient to inform a drug-associated risk. In animal reproduction studies, no developmental abnormalities or fetal harm was observed when pregnant rats or rabbits were administered obeticholic acid during the period of organogenesis at exposures approximately 13-times and 6-times human exposures, respectively, at the maximum recommended human dose (MRHD) of 10 mg. Lactation: There is no information on the presence of obeticholic acid in human milk, the effects on the breastfed infant or the effects on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for Obeticholic acid and any potential adverse effects on the breastfed infant from Obeticholic acid or from the underlying maternal condition.