iqirvo

Before treatment, evaluate for muscle pain or myopathy, and/or verify that females of reproductive potential are not pregnant. ( 2.1 ) The recommended dosage is 80 mg orally once daily with or without food. ( 2.2 ) 2.1 Recommended Evaluation Before Initiating IQIRVO Before initiating IQIRVO: Evaluate for muscle pain or myopathy [see Warnings and Precautions (5.1) ] . Verify that females of reproductive potential are not pregnant prior to initiating treatment with IQIRVO [ see Warnings and Precautions (5.3) , Use in Specific Populations (8.1 , 8.3) ] . 2.2 Recommended Dosage and Administration The recommended dosage of IQIRVO is 80 mg taken orally once daily with or without food [see Clinical Pharmacology (12.3) ] . 2.3 Administration Modification for Bile Acid Sequestrants Administer IQIRVO at least 4 hours before or 4 hours after administering the bile acid sequestrant, or at as great an interval as possible [see Drug Interactions (7.2) ] .

The following clinically significant adverse reactions are described elsewhere in the labeling: Myalgia, Myopathy, and Rhabdomyolysis [see Warnings and Precautions (5.1) ] Fractures [see Warnings and Precautions (5.2) ] Drug-Induced Liver Injury [see Warnings and Precautions (5.4) ] Hypersensitivity Reactions [see Warnings and Precautions (5.5) ] Most common adverse reactions with IQIRVO (reported in ≥ 5% and higher compared to placebo) are weight gain, diarrhea, abdominal pain, nausea, vomiting, arthralgia, constipation, muscle injury, fracture, gastroesophageal reflux disease, dry mouth, weight loss, and rash. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Ipsen Biopharmaceuticals, Inc. at 1-855-463-5127 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The safety of IQIRVO is based on Study 1 consisting of 161 patients who were randomized to receive IQIRVO 80 mg (n=108) or placebo (n=53) once daily with a median duration of exposure during the double-blind period of 62 weeks (inter quartile range: 52, 84) [see Clinical Studies (14) ] . IQIRVO or placebo was administered in…

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Hormonal Contraceptives: Switch to progestin only products containing levonorgestrel/norgestrel, intrauterine systems, or effective non-hormonal contraceptives during treatment and for at least 3 weeks after last dose. ( 5.3 , 7.1 ) HMG-CoA Reductase Inhibitors : Monitor for signs and symptoms of muscle injury. ( 5.1 , 7.1 ) Strong CYP2C8 Inhibitors: Avoid concomitant use with strong CYP2C8 inhibitors (e.g. gemfibrozil). If concomitant use cannot be avoided, monitor patients for adverse reactions. ( 7.2 ) Other Peroxisome Proliferator-Activated Receptor-Alpha (PPAR-alpha) Agonists : Monitor for signs and symptoms of liver injury and muscle injury. (7.2) Other PPAR-gamma Agonists : Monitor for signs and symptoms of liver injury (7.2) Rifampin: Monitor the biochemical response (e.g., ALP and bilirubin) when patients initiate rifampin during IQIRVO treatment. ( 7.2 ) Bile Acid Sequestrants: Administer at least 4 hours before or 4 hours after taking a bile acid binding sequestrant, or at as great an interval as possible. ( 2.3 , 7.2 ) 7.1 Effects of IQIRVO on Other Drugs Table 3 includes clinically significant drug interactions affecting other drugs. Table 3: Clinically Significant Interactions Affecting Other Drugs Hormonal Contraceptives Clinical Impact IQIRVO is a weak CYP3A4 inducer [see Clinical Pharmacology (12.3) ] . A clinical interaction study demonstrated that co-administration of IQIRVO and a combined oral hormonal contraceptive produced a decrease of ethinylestradiol which may lead to contraceptive failure and/or an increase in breakthrough bleeding, while levonorgestrel exposure remained unaffected. Intervention Switch to progestin only product containing levonorgestrel/norgestrel, intrauterine system, or effective non-hormonal contraceptives when using hormonal contraceptives during treatment with IQIRVO and for at least 3 weeks after last dose [see Warnings and Precautions (5.3) , Use in Specific Populations (8.1 , 8.3) ] . HMG-CoA Reductase Inhibitors Clinical Impact CPK elevation and/or myalgia occurred in patients on IQIRVO monotherapy. Co-administration of IQIRVO and HMG-CoA reductase inhibitors (statins) which have a risk of myalgia, can increase the risk of myopathy by a mechanism that has not been fully characterized [see Adverse Reactions (6.1) ] . Intervention Monitor for signs and symptoms of muscle injury. Consider periodic assessment (clinical exam, CPK) during treatment. Interrupt IQIRVO treatment if there is new onset or worsening of muscle pain or myopathy [see Warnings and Precautions (5.1) ] . 7.2 Effects of Other Drugs on IQIRVO Table 4 includes clinically significant drug interactions affecting IQIRVO. Table 4: Clinically Significant Interactions Affecting IQIRVO Strong CYP2C8 Inhibitors Clinical Impact The major active metabolite of elafibranor, GFT1007, is a CYP2C8 substrate. Concomitant use with a strong CYP2C8 inhibitor may increase systemic exposure of GFT1007 [see Clinical Pharmacology (12.3) ] , which may increase the risk of IQIRVO adverse reactions. Intervention Avoid concomitant use of IQIRVO with strong CYP2C8 inhibitors (e.g. gemfibrozil). If concomitant use cannot be avoided, monitor patients for adverse reactions. Other Peroxisome Proliferator-Activated Receptor-Alpha (PPAR-alpha) Agonists Clinical impact Co-administration of IQIRVO with other PPAR-alpha agonists (e.g., fenofibrate, fenofibric acid) may increase risk of liver injury and muscle injury. Intervention Monitor for signs and symptoms of liver injury and muscle injury [see Warnings and Precautions (5.1 , 5.4) ] . Other Peroxisome Proliferator-Activated Receptor-gamma (PPAR-gamma) Agonists Clinical impact Co-administration of IQIRVO with PPAR-gamma agonists (e.g., pioglitazone, rosiglitazone) may increase risk of liver injury. Intervention Monitor for signs and symptoms of liver injury [see Warnings and Precautions (5.4) ]. Rifampin Clinical Impact Co-administration of IQIRVO with rifampin, an inducer of metabolizing enzymes, may reduce the systemic exposure of elafibranor and its active metabolite via increased metabolism and may result in delayed or suboptimal biochemical response [see Clinical Pharmacology (12.3) ] . Intervention Monitor the biochemical response (e.g., ALP and bilirubin) when patients initiate rifampin during treatment with IQIRVO. Bile Acid Binding Sequestrants Clinical Impact Bile acid sequestrants may interfere with the action of IQIRVO by reducing its absorption and systemic exposure, which may reduce IQIRVO efficacy. Intervention Administer IQIRVO at least 4 hours before or 4 hours after taking a bile acid binding sequestrant, or at as great an interval as possible [see Dosage and Administration (2.3) ] .