Linerixibat

Linerixibat is approved for one indication at this time, under the brand Lynavoy.

• Lynavoy (oral tablet) is indicated for the treatment of cholestatic pruritus — persistent, severe itch caused by bile acid buildup — in adult patients with primary biliary cholangitis (PBC).
• Lynavoy is not appropriate for patients with decompensated cirrhosis or for those who have experienced liver decompensation events such as variceal hemorrhage (bleeding from enlarged veins), ascites (fluid in the abdomen), or hepatic encephalopathy (brain confusion from liver failure).

Linerixibat works by blocking a protein called the ileal bile acid transporter (IBAT), which sits in the lower part of the small intestine. Normally, IBAT recycles bile acids back into the bloodstream, but linerixibat interrupts that cycle. With less reabsorption happening, more bile acids exit the body through stool. In people with PBC, high levels of bile acids in the blood are linked to intense itching — by lowering those levels, linerixibat may reduce the itch. The exact way it relieves pruritus is not fully understood, but reducing bile acid levels in the blood appears to play a key role.

Lynavoy is taken as an oral tablet twice a day. The most important timing rule: swallow each tablet at least 30 minutes before eating or drinking anything other than water. This gives the medicine time to reach the intestine before food triggers bile acid release, which is how it works best.

• Swallow tablets whole — do not crush or chew.
• If you miss a dose, take it as soon as you can, still at least 30 minutes before your next meal. If it has been more than 6 hours since the missed dose, skip it entirely.
• Never take a double dose to make up for one you missed.
• If you take a bile acid binding resin, separate it from Lynavoy by at least 4 hours (either before or after).

The most common side effects of Lynavoy reported in clinical trials include:

• Diarrhea — affects most patients and is the most frequent reason people stop treatment
• Abdominal (belly) pain or discomfort
• Nausea
• Elevated liver enzymes (ALT and AST) on blood tests
• Bleeding or unusual bruising
• Indigestion or acid reflux (GERD)
• Abdominal bloating
• Headache and dizziness
• Joint pain (arthralgia)

More serious concerns include liver enzyme elevations that persist, significant bleeding (possibly related to low vitamin K), fat-soluble vitamin deficiency, and bone fractures. Contact your doctor promptly if you have ongoing diarrhea, signs of dehydration, yellowing skin or eyes, or any unusual bleeding.

• Liver enzyme elevations: Liver tests (ALT, AST, bilirubin, ALP) should be checked before starting Lynavoy and monitored regularly. If levels rise significantly and don't come back down, your doctor may need to stop the medicine.
• Diarrhea: This is the most common side effect. If it's severe or ongoing, watch for dehydration and contact your doctor — a treatment break or stopping may be needed.
• Fat-soluble vitamin (A, D, E, K) deficiency: Lynavoy can reduce absorption of these vitamins. Low vitamin K can cause bleeding; low vitamin D affects bones. Levels should be checked before and during treatment. Supplements may be prescribed.
• Bleeding: Bleeding events occurred more often in Lynavoy-treated patients than placebo patients in trials. If bleeding happens, treatment should be paused and vitamin levels evaluated.
• Bone fractures: Drugs in this class (IBAT inhibitors) have been associated with bone fractures. Monitoring bone health and keeping vitamin levels adequate are important.

There is one key interaction to know about with Lynavoy:

• Bile acid binding resins (e.g., cholestyramine, colesevelam): These medicines can bind to linerixibat in the gut and block it from working. Always take Lynavoy at least 4 hours before or 4 hours after taking a bile acid binding resin.

Not a complete list. The label covers the interactions the manufacturer studied or reported, and our own interaction database does not cover every medicine either. Bring your full medication list, including vitamins and herbal products, to your pharmacist.

• Decompensated cirrhosis or past liver decompensation: Lynavoy should be avoided if you have had variceal bleeding, ascites, or hepatic encephalopathy — tell your doctor your full liver history.
• Pregnancy: There are no human safety data for Lynavoy in pregnancy. The drug is minimally absorbed, but it may reduce fat-soluble vitamin absorption, which is critical for fetal development. Monitoring and supplementation are especially important. Report any pregnancy exposure to the manufacturer's registry.
• Breastfeeding: Because linerixibat is minimally absorbed, infant exposure through breast milk is expected to be very low. However, discuss the benefits and risks with your doctor. Fat-soluble vitamin levels should be monitored during breastfeeding.
• Children: Safety and effectiveness have not been established in pediatric patients. Lynavoy is approved for adults only.
• Adults 65 and older: No dose adjustment is required for older adults based on clinical trial data. However, greater individual sensitivity cannot be ruled out.
• Kidney impairment: No dose change is needed for most patients with kidney disease, since linerixibat is minimally absorbed and barely excreted through urine. The medicine has not been fully studied in severe kidney impairment.
• Liver function monitoring: Baseline liver tests and fat-soluble vitamin levels must be checked before starting treatment.

Taking significantly more Lynavoy than prescribed is likely to cause more intense gastrointestinal side effects — particularly diarrhea and abdominal symptoms. There is no specific antidote. If an overdose is suspected, stop taking the medicine and seek medical attention. You can also contact Poison Control at 1-800-222-1222 for guidance.

Linerixibat measurably reduces total bile acid levels in the blood. In clinical studies, bile acids began falling within the first day of treatment in healthy volunteers, and in patients with PBC and cholestatic pruritus, bile acid levels remained reduced throughout 24 weeks of treatment compared to placebo. This reduction in circulating bile acids is believed to be central to how linerixibat relieves itch.

Linerixibat is designed to act locally in the gut, and very little is absorbed into the bloodstream — its oral bioavailability is only about 0.05%. Because systemic levels are so low, standard pharmacokinetic measurements are difficult to calculate reliably at the recommended dose. The medicine is largely eliminated through the feces rather than through the kidneys. Its half-life (the time for blood levels to drop by half) is roughly 6–7 hours after a single dose, and it is not significantly broken down into active metabolites in the body. Food slightly delays absorption but does not meaningfully change how much drug reaches the gut, where it does its work — though the 30-minute-before-food rule is still important for it to be effective.

Store at 20°C to 25°C (68°F to 77°F); excursions are permitted between 15°C to 30°C (59°F to 86°F) . Store in the original package to protect from moisture.