Seladelpar is an oral prescription medicine that may be used to treat primary biliary cholangitis (PBC) in adults.

Seladelpar is:

Taken in combination with ursodeoxycholic acid (UDCA) in adults who have not responded well to UDCA.

Used alone in patients unable to tolerate UDCA.

It is not known if taking Seladelpar will improve your chance of survival or prevent liver decompensation.

Seladelpar helps manage PBC by activating specific receptors that control key metabolic and liver disease pathways involved in bile acid synthesis, inflammation, and fibrosis, as well as lipid metabolism, storage, and transport. Seladelpar is beneficial for PBC patients because it reduces bile acid production and helps counteract the liver damage caused by the buildup of bile acids.

Seladelpar is used to treat primary biliary cholangitis (PBC) in adults in combination with ursodeoxycholic acid (UDCA) in adults who have not responded well to UDCA or used alone in patients unable to tolerate UDCA.

Seladelpar works by activating specific receptors that control key metabolic and liver disease pathways involved in bile acid synthesis, inflammation, and fibrosis, as well as lipid metabolism, storage, and transport. This reduces bile acid production and helps counteract liver damage caused by bile acid buildup in PBC patients. It is unknown if it improves survival or prevents liver decompensation. Seladelpar belongs to the drug class called peroxisome proliferator-activated receptor (PPAR)-delta agonists.

Pharmacological activity potentially relevant to therapeutic effects includes inhibition of bile acid synthesis through activation of PPARδ, which is a nuclear receptor expressed in most tissues, including the liver.

PPARδ activation by seladelpar reduces bile acid synthesis through fibroblast growth factor 21 (FGF21)-dependent downregulation of CYP7A1 (a key enzyme for bile acid synthesis from cholesterol).

May take with or without food.

Take Seladelpar exactly as your healthcare provider tells you to. Do not take more Seladelpar than your healthcare provider tells you to.

Take Seladelpar by mouth 1 time each day.

Seladelpar may be taken with or without food.

Seladelpar should be taken at least 4 hours before or 4 hours after you take medicines to help lower your cholesterol, called bile acid-binding resins (examples include cholestyramine or colestipol). If this is not possible, space the time between taking seladelpar and your bile acid-binding resin as far apart as possible.

Call your doctor at once if you have:

Sudden or unusual pain

Trouble moving your hip, thigh, wrist, or back

Liver problems—abnormal liver function tests

Swelling around your midsection

Loss of appetite

Nausea

Vomiting

Stomach pain (upper right side)

Tiredness

Itching

Dark urine

Clay-colored stools

Jaundice (yellowing of the skin or eyes)

Your treatment may be delayed or permanently discontinued if you have certain side effects.

Common side effects may include:

Headache, stomach pain;

Nausea, bloating, or dizziness.

Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. Seladelpar can affect the way certain medicines work. Certain other medicines may affect the way this medicine works. Especially tell your healthcare provider if you take:

OAT3 inhibitors, such as probenecid, rifampin, or cabotegravir. Avoid taking together, or monitor ALP and bilirubin for rifampin

Strong CYP2C9 inhibitors, such as cotrimoxazole, fluoxetine, or amiodarone. Avoid taking together

Dual moderate CYP2C9 and moderate-to-strong CYP3A4 inhibitors, such as fluconazole. Monitor closely for side effects

CYP2C9 poor metabolizers using moderate to strong CYP3A4 inhibitors: Monitor more frequently for side effects.

BCRP inhibitors such as rosuvastatin, glyburide, nitrofurantoin, dipyridamole, cimetidine, chlorothiazide, sulfasalazine, and leflunomide. Monitor closely for adverse effects.

Store at 20-25ºC (68-77ºF); excursions permitted to 15-30ºC (59-86ºF).

Inform patients that seladelpar may increase the risk of bone fractures. Advise patients to call their healthcare provider to report any fractures.

Instruct patients to report any signs or symptoms of liver-related adverse reactions (e.g., loss of appetite, nausea, increased fatigue, lower extremity edema, abdominal swelling, or jaundice/icterus) to their healthcare provider.

Instruct patients to immediately report any signs or symptoms of biliary obstruction (e.g., right upper quadrant pain, jaundice) to their healthcare provider so that seladelpar treatment can be interrupted while the patient is being evaluated.

Advise patients to inform their clinician of existing or contemplated concomitant therapy, including prescription and OTC drugs and dietary or herbal supplements, as well as any concomitant illnesses.

Advise patients to inform their clinician if they are or plan to become pregnant or plan to breast-feed.