Survey
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
Drug interaction wikipedia , lookup
Discovery and development of angiotensin receptor blockers wikipedia , lookup
Discovery and development of neuraminidase inhibitors wikipedia , lookup
Discovery and development of ACE inhibitors wikipedia , lookup
Acetic acid wikipedia , lookup
Hyaluronic acid wikipedia , lookup
Discovery and development of proton pump inhibitors wikipedia , lookup
Ocaliva™ obeticholic acid Manufacturer: Intercept Pharmaceuticals FDA Approval Date: 5/27/2016 Han Lin, PharmD Candidate Ocaliva™ - obeticholic acid Objectives • At the end of this presentation participants will be able to: 1. Appropriately recommend Ocaliva™ - (obeticholic acid) 2. Effectively educate patients on the purpose, proper use and potential adverse effects of Ocaliva™ (obeticholic acid) Ocaliva™ - obeticholic acid Clinical Application • Indications: • Treatment of primary biliary cholangitis (PBC) as monotherapy or in combination with ursodeoxycholic acid (UDCA) • Place in therapy: • Second line therapy in patients that are seeing inadequate response to UDCA Ocaliva [package insert]. Ocaliva™ - obeticholic acid Clinical Application • Contraindications: • Complete biliary obstruction • Black Box warnings: • None listed • Warnings/Precautions: • Liver – Related Adverse Reactions • Severe Pruritus • Reduction in HDL-C Ocaliva [package insert]. Ocaliva™ - obeticholic acid Clinical Application • Pregnancy: • Limited human data • No fetal harm at 13 and 6 times max amount in rats and rabbits • Lactation: • No information on drug transfer Ocaliva [package insert]. Ocaliva™ - obeticholic acid Drug Facts • Pharmacology: • Farnesoid X Receptor Agonist • Expressed in liver and intestine • Suppresses CYP7A1, the rate-limiting enzyme in bile acid synthesis from cholesterol Ocaliva [package insert]. Ocaliva™ - obeticholic acid Drug Facts • Pharmacokinetics: A Cmax ~1.5 hrs. Follows linear kinetics. Food does not alter extent of absorption. D V = 618 L. >99% protein binding M Conjugation with glycine or taurine E 87% excretion in feces Ocaliva [package insert]. Ocaliva™ - obeticholic acid Drug Interactions • Drug Interactions – Object Drugs: • CYP1A2: potential for increased exposure to CYP1A2 substrates. • 25 mg warfarin – 13% systemic exposure • 200 mg caffeine – 42% AUC • 20 mg omeprazole – 32% AUC • 20 mg rosuvastatin – 22% AUC Ocaliva [package insert]. Ocaliva™ - obeticholic acid Drug Interactions • Drug Interactions – Precipitant Drugs: • 20 mg omeprazole – <1.2 fold exposure. Determined to be not clinically significant. Ocaliva [package insert]. Ocaliva™ - obeticholic acid Adverse Effects • Common Adverse Effects: (obeticholic acid%)[placebo%] Pruritus 70% [38%] Fatigue 25% [15%] Abdominal pain and 19% [14%] discomfort Rash 10% [8%] Ocaliva [package insert]. Ocaliva™ - obeticholic acid Monitoring Parameters • Efficacy Monitoring: • Improvement in lowering ALP. No current mortality or symptom relief benefits • Toxicity Monitoring: • LFTs, including alkaline phosphatase and bilirubin • Lipid profile • Pruritus Ocaliva [package insert]. Ocaliva™ - obeticholic acid Prescription Information • Dosing: • Initial: 5 mg daily • Max: 10 mg daily if adequate reduction not achieved in 3 months • Cost: $6840 • Source: Uptodate. Accessed 09/01/2016 Ocaliva [package insert]. Ocaliva™ - obeticholic acid Literature Review Nevens, F. et al. NEJM. 2016;375(7):631-43. Ocaliva™ - obeticholic acid Literature Review Study Design: • 12 month, double-blind, placebo controlled randomized phase 3 trial • Inclusion Criteria: • ≥ 18 YO diagnosed with PBC • Alkaline phosphatase level ≥1.67x UL, or • Abnormal total bilirubin < 2 times UL Nevens, F. et al. NEJM. 2016;375(7):631-43. Ocaliva™ - obeticholic acid Literature Review Interventions: • N=217 who had inadequate response to ursodeoxycholic acid (ursodiol) or unacceptable side effects • Randomization into 1:1:1 • Obeticholic acid 10 mg, • 5 mg (titrating up to 10 mg as need), or • Placebo Nevens, F. et al. NEJM. 2016;375(7):631-43. Ocaliva™ - obeticholic acid Literature Review Primary Endpoint: • Reduction of alkaline phosphatase level <1.67 times the upper limit of normal (reduction of at least 15%) AND • Normal total bilirubin level at 12 months Nevens, F. et al. NEJM. 2016;375(7):631-43. Ocaliva™ - obeticholic acid Literature Review Patient Demographics Characteristic Placebo Ocaliva 510 mg Ocaliva 10 mg Age (years) 56 ± 10 56 ± 11 56 ± 11 Female no. (%) 68 (93%) 65 (93%) 63 (86%) White Race 66 (90%) 67 (96%) 70 (96%) Alk Phos 327 ± 115 326 ± 116 316 ± 104 Tbili 0.69 ± 0.42 0.6 ± 0.33 0.66 ± 0.39 Ursodiol use 68 (93%) 65 (93%) 67 (92%) Pruritus 47 (93%) 37 (53%) 44 (60%) Nevens, F. et al. NEJM. 2016;375(7):631-43. Ocaliva™ - obeticholic acid Literature Review Results: • Primary endpoint • 5-10 mg; 10 mg; placebo • 46% and 47% vs. 10%; p<0.001 • Alkaline phosphatase level • -113 and -130 vs. -14 U/L; p<0.001 • Total bilirubin • -0.3 and -0.9 vs. 0.12 μmol/L; p<0.001 Nevens, F. et al. NEJM. 2016;375(7):631-43. Ocaliva™ - obeticholic acid Literature Review Adverse Effect: Ocaliva Ocaliva Placebo 5-10 mg 10 mg Pruritus Nasopharyngitis 28 (38%) 13 (18%) 39 (56%) 17 (24%) 50 (68%) 13 (18%) Headache Fatigue Arthralgia 13 (18%) 10 (14%) 3 (4%) 12 (17%) 11 (16%) 4 (6%) 6 (8%) 17 (23%) 7 (10%) Nevens, F. et al. NEJM. 2016;375(7):631-43. Ocaliva™ - obeticholic acid Literature Review Conclusion: • Obeticholic acid administered with ursodiol or as monotherapy resulted in significant decreases in alkaline phosphatase and total bilirubin levels • There were more serious adverse events with obeticholic acid Nevens, F. et al. NEJM. 2016;375(7):631-43. Ocaliva™ - obeticholic acid Summary • Ocaliva™ - obeticholic acid is indicated for the treatment of primary biliary cholangitis (PBC) in combination with ursodeoxycholic acid (ursodiol) as monotherapy • 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 • Child-Pugh B and C: 5 mg weekly Ocaliva™ - obeticholic acid References 1. https://ocaliva.com/ocaliva_pi.pdf. 2. Ocaliva [package insert]. New York, NY. Intercept Pharmaceuticals, Inc; 2016. 3. Nevens, F. et al. NEJM. 2016;375(7):631-43.