LYVISPAH
Clinical safety rating: caution
Comprehensive clinical and safety monograph for LYVISPAH (LYVISPAH).
LYVISPAH (bexotegrast) is an oral, small-molecule, selective inhibitor of the integrin receptors αvβ1 and αvβ6. It blocks the activation of transforming growth factor-beta (TGF-β) by preventing its release from the latent complex, thereby reducing TGF-β signaling and downstream fibrotic pathways.
| Metabolism | Primarily metabolized by CYP3A4 and CYP2C8; minor contributions from CYP2D6 and CYP2C9. Undergoes extensive hepatic metabolism with renal excretion of metabolites. |
| Excretion | Primarily hepatic metabolism followed by biliary excretion. Renal excretion accounts for <1% of unchanged drug in urine. Fecal elimination of metabolites accounts for approximately 93% of the administered dose. |
| Half-life | Terminal elimination half-life is 10 hours (range 8-13 hours) in pediatric patients aged 1-2 years and 4-7 hours in older pediatric patients. This supports twice-daily dosing. |
| Protein binding | 99% bound to plasma proteins, primarily to albumin. |
| Volume of Distribution | Volume of distribution at steady state is 0.83 L/kg (range 0.5-1.2 L/kg) in pediatric patients, indicating distribution into total body water and some tissue binding. |
| Bioavailability | Absolute oral bioavailability is approximately 50% in pediatric patients, with high interindividual variability. |
| Onset of Action | Oral: Peak plasma concentration achieved at 0.5-0.75 hours after oral administration; clinical effect on pulmonary hypertension is expected within 1-2 weeks of initiation based on hemodynamic improvements observed in clinical trials. |
| Duration of Action | Duration of hemodynamic effect is approximately 8-12 hours, consistent with twice-daily dosing regimen. Continuous therapy is required for sustained clinical benefit. |
200 mg orally three times daily with a full glass of water on an empty stomach (at least 1 hour before or 2 hours after a meal).
| Dosage form | GRANULES |
| Renal impairment | Not recommended in patients with eGFR <15 mL/min/1.73 m². No dose adjustment required for eGFR ≥15 mL/min/1.73 m². |
| Liver impairment | Child-Pugh Class A: 200 mg three times daily. Child-Pugh Class B: 200 mg twice daily. Child-Pugh Class C: 200 mg once daily. |
| Pediatric use | Not approved for pediatric use; safety and efficacy not established. |
| Geriatric use | No specific dose adjustment required; monitor renal function and consider age-related decline in GFR. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for LYVISPAH (LYVISPAH).
| Breastfeeding | No data on presence in human milk, effects on the breastfed infant, or milk production. Animal studies show bexotegrast and its metabolites are excreted in rat milk. M/P ratio is unknown. Because of potential for serious adverse reactions in the breastfed infant, advise patients not to breastfeed during treatment and for at least 2 weeks after the last dose. |
| Teratogenic Risk | LYVISPAH (bexotegrast) is an integrin inhibitor. In animal studies, maternal toxicity at high doses resulted in reduced fetal weight and skeletal variations; no major structural malformations were reported. However, there are no adequate human studies. Use during first trimester may pose theoretical risk due to integrin inhibition in development. Second and third trimester risks are unknown; consider avoiding unless benefit outweighs risk. |
■ FDA Black Box Warning
None.
| Serious Effects |
["Severe hepatic impairment (Child-Pugh Class C)","Concomitant use with strong CYP3A4 inducers (e.g., rifampin, carbamazepine, phenytoin, St. John's wort)","Hypersensitivity to bexotegrast or any excipients"]
| Precautions | ["Hepatotoxicity: Monitor liver enzymes periodically; discontinue if ALT/AST >5x ULN or if bilirubin >2x ULN.","Gastrointestinal effects: Nausea, diarrhea, abdominal pain; manage with supportive care.","Risk of infection: Increased incidence of upper respiratory tract infections; monitor for signs of infection.","Drug interactions: Avoid strong CYP3A4 inhibitors/inducers; adjust dose with moderate CYP3A4 inhibitors."] |
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| Fetal Monitoring | Monitor liver function tests (ALT, AST, bilirubin) monthly during pregnancy. Perform fetal ultrasound at 20-24 weeks to assess anatomy and growth. Monitor maternal blood pressure and renal function. Consider serial growth scans if used in second or third trimester. |
| Fertility Effects | In animal studies, no effects on male or female fertility were observed at exposures up to 3 times the human AUC. However, no human fertility data are available. Based on mechanism, integrin inhibition may theoretically impair implantation or spermatogenesis; clinical significance unknown. |