LIVDELZI
Clinical safety rating: caution
Comprehensive clinical and safety monograph for LIVDELZI (LIVDELZI).
LIVDELZI is a peroxisome proliferator-activated receptor alpha (PPARα) agonist. It binds to and activates PPARα, which regulates the expression of genes involved in lipid metabolism, reducing hepatic fat accumulation and improving steatohepatitis.
| Metabolism | Metabolized primarily via CYP3A4 and also CYP2C8. Following oral administration, it undergoes extensive metabolism to form active and inactive metabolites, with parent drug accounting for approximately 25% of total circulating exposure. |
| Excretion | Primarily biliary excretion (≥70% of absorbed dose) as unchanged drug and metabolites; renal excretion accounts for <5%. |
| Half-life | Terminal elimination half-life approximately 26–32 hours in patients with primary biliary cholangitis; supports once-daily dosing. |
| Protein binding | >99% bound, primarily to albumin and alpha-1-acid glycoprotein. |
| Volume of Distribution | Approximately 18–30 L (0.25–0.43 L/kg in a 70 kg adult); indicates extensive tissue distribution. |
| Bioavailability | Oral bioavailability approximately 30–40% (under fed conditions); food increases exposure by ~2-fold. |
| Onset of Action | Oral: Reduction in alkaline phosphatase (ALP) detectable within 2–4 weeks of starting therapy. |
| Duration of Action | Sustained biochemical response with continued dosing; effect wanes over weeks after discontinuation. |
80 mg intravenously once daily infused over 1 hour.
| Dosage form | CAPSULE |
| Renal impairment | No dosage adjustment required for any degree of renal impairment, including end-stage renal disease. |
| Liver impairment | No dosage adjustment required for mild or moderate hepatic impairment (Child-Pugh A or B). Not studied in severe hepatic impairment (Child-Pugh C). |
| Pediatric use | Not recommended for pediatric patients under 18 years of age due to lack of safety and efficacy data. |
| Geriatric use | No specific dose adjustment recommended; pharmacokinetics not significantly altered in elderly patients aged ≥65 years. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for LIVDELZI (LIVDELZI).
| Breastfeeding | It is unknown whether LIVDELZI is excreted in human milk. In animal studies, lifibrol and its metabolites were detected in milk of lactating rats. The M/P ratio has not been determined in humans. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants, a decision should be made whether to discontinue nursing or discontinue the drug, taking into account the importance of the drug to the mother. |
| Teratogenic Risk | There are no adequate and well-controlled studies in pregnant women. In animal reproduction studies, administration of LIVDELZI (lifibrol) to pregnant rats and rabbits during organogenesis resulted in developmental toxicity at maternal doses equivalent to 0.5 and 1.0 times the maximum recommended human dose (MRHD), respectively. Based on the mechanism of action (PPARα agonist), there is a potential risk of fetal harm. Use during pregnancy only if the potential benefit justifies the potential risk to the fetus. |
■ FDA Black Box Warning
LIVDELZI can cause drug-induced liver injury (DILI), which may be severe and potentially fatal. Liver enzymes and bilirubin must be monitored before and during treatment. Discontinue if ALT ≥5 times upper limit of normal or ALT ≥3 times with bilirubin >2 times upper limit of normal.
| Serious Effects |
LIVDELZI is contraindicated in patients with decompensated cirrhosis (Child-Pugh B or C), acute liver failure, or chronic hepatitis B or C.
| Precautions | ["Drug-induced liver injury (DILI): Monitor liver enzymes and bilirubin. Discontinue if hepatotoxicity occurs.","Gallbladder-related adverse events: Cholelithiasis and cholecystitis have been reported; monitor for symptoms.","Myopathy: Increased risk with concomitant use of statins metabolized by CYP3A4."] |
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| Fetal Monitoring | Monitor liver function tests (ALT, AST, alkaline phosphatase, total bilirubin) periodically during therapy. Assess lipid profile (LDL-C, HDL-C, triglycerides) at baseline and periodically. In pregnant women, monitor fetal growth and development via ultrasound if exposure occurs. Pregnancy testing is recommended prior to initiation in women of reproductive potential. |
| Fertility Effects | In animal studies, lifibrol did not impair fertility in male or female rats at doses up to 2 times the MRHD based on AUC. However, there are no human data on fertility effects. Based on its pharmacological activity as a PPARα agonist, there is a potential for hormonal disruption, though clinical significance is unknown. |