Elafibranor

Elafibranor is a prescription medication indicated for primary biliary cholangitis (PBC) in combination with ursodeoxycholic acid (UDCA) in adults who have had an inadequate response to UDCA or as monotherapy in patients unable to tolerate UDCA.

• Elafibranor is available under the following different brand names: Iqirvo.

Common side effects of Elafibranor include:

• weight gain 
• constipation 
• dry mouth
• diarrhea 
• muscle problems 
• weight loss
• nausea and vomiting 
• bone fractures 
• rash
• joint pain 
• gastroesophageal reflux disease
• stomach pain

Serious side effects of Elafibranor include:

• muscle problems (myalgia, myopathy, rhabdomyolysis): symptoms include severe muscle pain, unexplained muscle weakness, unexplained soreness, dark, reddish urine
• bone fractures
• liver problems: symptoms include stomach-area (abdomen) pain, weakness, nausea, vomiting, diarrhea, fever and chills, loss of appetite weight loss, light-headedness, new or worsening fatigue, less frequent urination
• allergic reactions: symptoms include rash, itching, trouble breathing, and swelling of the face, lips, tongue, or throat
• blockage of the bile duct: symptoms include pain in the upper right stomach area or yellowing of the skin

Rare side effects of Elafibranor include:

• none 

Seek medical care or call 911 at once if you have the following serious side effects:

• Severe headache, confusion, slurred speech, arm or leg weakness, trouble walking, coordination loss, unsteady, very stiff muscles, high fever, profuse sweating, or tremors.
• Serious eye symptoms include sudden vision loss, blurred vision, tunnel vision, eye pain or swelling, or seeing halos around lights.
• Serious heart symptoms include fast, irregular, or pounding heartbeats; fluttering in the chest; shortness of breath; sudden dizziness, lightheadedness, or passing out.

This is not a complete list of side effects and other serious side effects or health problems that may occur because of the use of this drug. Call your doctor for medical advice about serious side effects or adverse reactions. You may report side effects or health problems to FDA at 1-800-FDA-1088.

Adult dosage

Tablet

• 80 mg

Primary biliary cholangitis

Adult dosage

• 80 mg orally once a day

Dosage Considerations – Should be Given as Follows: 

• See "Dosages"

If your medical doctor is using this medicine to treat your pain, your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor, health care provider, or pharmacist first.

• Elafibranor has severe interactions with no other drugs
• Elafibranor has serious interactions with no other drugs
• Elafibranor has moderate interactions with the following drugs:
  • dienogest/estradiol valerate
  • drospirenone
  • ethinylestradiol
  • levonorgestrel oral
  • levonorgestrel oral/ethinylestradiol/ferrous bisglycinate
  • levonorgestrel transdermal
  • norgestrel
• Elafibranor has minor interactions with no other drugs

This information does not contain all possible interactions or adverse effects. Visit the RxList Drug Interaction Checker for any drug interactions. Therefore, before using this product, tell your doctor or pharmacist about all the products you use. Keep a list of all your medications with you and share this information with your doctor and pharmacist. Check with your healthcare professional or doctor for additional medical advice, health questions, or concerns.

Contraindications

• None

Effects of drug abuse

• None

Short-Term Effects

• See “What Are Side Effects Associated with Using Elafibranor?”

Long-Term Effects

• See “What Are Side Effects Associated with Using Elafibranor?”

Cautions

• Myalgia, myopathy, and rhabdomyolysis
  • Rhabdomyolysis resulting in acute kidney injury occurred in 1 patient treated who had cirrhosis at baseline and was also taking a stable dose of an HMG-CoA reductase inhibitor (statin)
  • Myalgia or myopathy, with or without CPK elevations, occurred in patients treated with Elafibranor alone or with a stable dose of an HMG-CoA reductase inhibitor
  • Assess for myalgia and myopathy before initiating; consider periodic assessment (clinical exam, CPK measurement) during treatment, especially in those who have signs and symptoms of new onset or worsening of muscle pain or myopathy
  • Interrupt treatment if new onset or worsening of muscle pain, myopathy, or rhabdomyolysis occurs
  • Inform patients to report immediately to their healthcare provider any unexplained muscle symptoms such as pain, soreness, or weakness
• Fractures
  • Fractures reported
  • Consider fracture risk in the care of patients and monitor bone health according to the standard of care
  • Instruct patient to inform healthcare provider about any bone fractures, experience pain, or changes in ability to move around
• Embryo-fetal toxicity
  • Based on findings from animal reproduction studies, may cause fetal harm when administered during pregnancy
  • Verify negative pregnancy test before initiating in females of reproductive potential
• Drug-induced liver injury
  • Liver injury reported
  • Median time to onset of elevation in liver tests was 85 days (range: day 57 to 288)
  • Obtain baseline clinical and laboratory assessments at treatment initiation and monitor thereafter according to routine patient management
  • Interrupt if liver tests (ALT, AST, TB, and/or ALP) worsen, or the patient develops signs and symptoms consistent with clinical hepatitis (eg, jaundice, right upper quadrant pain, eosinophilia)
  • Consider permanent discontinuation if liver tests worsen after restarting
  • Instruct patients to report any signs or symptoms of liver injury (eg, loss of appetite, nausea, increased fatigue, lower extremity edema, abdominal swelling, or jaundice/icterus) to their healthcare provider
• Hypersensitivity reactions
  • Hypersensitivity reactions reported
  • If a severe reaction occurs, permanently discontinue
  • If a mild or moderate hypersensitivity reaction occurs, interrupt and treat promptly
  • Monitor until signs and symptoms resolve
  • Permanently discontinue if hypersensitivity reaction recurs after rechallenging
• Biliary obstruction
  • Avoid use with complete biliary obstruction
    • If biliary obstruction is suspected, interrupt and treat as clinically indicated
    • Instruct patients to immediately report any signs or symptoms of biliary obstruction (eg, right upper quadrant pain, jaundice) to the healthcare provider so that treatment can be interrupted while the patient is being evaluated
• Drug interaction overview
• Weak CYP3A4 inducer
• Hormonal contraceptives
  • Modify therapy
    • Switch to effective nonhormonal contraceptives or add a barrier method when using hormonal contraceptives during treatment and for at least 3 weeks after the last dose
    • Coadministration with hormonal contraceptives (eg, oral contraceptives, transdermal contraceptives, implants) may reduce the systemic exposure of progestin and ethinyl estradiol (CYP3A4 substrates), which may lead to contraceptive failure and/or an increase in breakthrough bleeding
• HMG-CoA reductase inhibitors
  • Caution, monitor
    • Additive risk of CPK elevation and/or myalgia if coadministered
    • Monitor for signs and symptoms of muscle injury; consider periodic assessment (clinical exam, CPK) during treatment
    • Interrupt treatment if new onset or worsening of muscle pain or myopathy
• Rifampin
  • Caution, monitor
    • Monitor the biochemical response (eg, ALP and bilirubin)
    • Coadministration with rifampin, an inducer of metabolizing enzymes, may reduce Elafibranor systemic exposure and its active metabolite via increased metabolism and may result in delayed or suboptimal biochemical response
• Bile acid binding sequestrants
  • Modify dose
    • Administer Elafibranor at least 4 hours before after taking a bile acid binding sequestrant, or at as great an interval as possible
    • Bile acid sequestrants may reduce Elafibranor absorption and systemic exposure, which may reduce efficacy

Pregnancy and Lactation

• Based on data from animal reproduction studies, may cause fetal harm when administered during pregnancy
• Data are insufficient on human pregnancies exposed during treatment to allow an assessment of a drug-associated risk of major birth defects, miscarriage, or other adverse maternal or fetal outcomes
• Verify negative pregnancy test before initiating in females of reproductive potential
• Report pregnancies to Ipsen Pharmaceuticals, Inc. at 1-855-463-5127 or https://www.ipsen.com/contact-us/
  • Contraception
  • Elafibranor may decrease the efficacy of hormonal contraceptives
  • Advise women of reproductive potential to use effective contraception (nonhormonal) or add a barrier method of contraception when using hormonal contraceptives during treatment and for 3 weeks after the last dose
• Lactation
  • Data are unavailable on the presence of Elafibranor or its metabolites in human or animal milk, its effects on breastfed infants, or its effects on milk production
  • Owing to the potential for serious adverse reactions in breastfed infants, advise patients not to breastfeed during treatment and for 3 weeks after last dose