LOGILIA
Clinical safety rating: caution
Comprehensive clinical and safety monograph for LOGILIA (LOGILIA).
Lorecivivt, the active component of Logilia, is a small interfering RNA (siRNA) that targets the synthesis of transthyretin (TTR) protein. It binds to a genetically conserved sequence in the 3' untranslated region of mutant and wild-type TTR mRNA, leading to its degradation via RNA interference. This reduces TTR protein production and deposition in tissues.
| Metabolism | Lorecivivt is metabolized by nucleases to shorter oligonucleotides. It is not a substrate for cytochrome P450 enzymes or other common metabolic pathways. |
| Excretion | Approximately 60% renal (as unchanged drug), 40% biliary/fecal |
| Half-life | Terminal elimination half-life: 12–15 hours; dose adjustment recommended in renal impairment |
| Protein binding | 97% bound to albumin and alpha-1-acid glycoprotein |
| Volume of Distribution | 0.5–0.8 L/kg, indicating moderate tissue distribution |
| Bioavailability | Oral: 85–90% |
| Onset of Action | Oral: 1–2 hours; Intravenous: 5–10 minutes |
| Duration of Action | Oral: 8–12 hours; Intravenous: 6–8 hours |
100 mg orally once daily.
| Dosage form | TABLET |
| Renal impairment | GFR ≥60 mL/min: no adjustment. GFR 30-59 mL/min: 50 mg once daily. GFR <30 mL/min: not recommended. |
| Liver impairment | Child-Pugh A: no adjustment. Child-Pugh B: 50 mg once daily. Child-Pugh C: not recommended. |
| Pediatric use | ≥12 years: 100 mg once daily. <12 years: not established. |
| Geriatric use | No specific adjustment required, but monitor renal function due to age-related decline. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for LOGILIA (LOGILIA).
| Breastfeeding | Excreted in human milk; M/P ratio not specified. Potential for kernicterus in neonates or infants with G6PD deficiency or hyperbilirubinemia. Not recommended during breastfeeding. |
| Teratogenic Risk | First trimester: Risk of neural tube defects (NTDs) and cardiovascular malformations; association with maternal folate antagonism. Second/third trimester: Risk of preterm birth, low birth weight, and fetal/nconatal hemorrhage due to vitamin K antagonism. Avoid in pregnancy unless benefit outweighs risk. |
| Fetal Monitoring |
■ FDA Black Box Warning
There are no FDA black box warnings for Logilia (lorecivivt).
| Serious Effects |
["Hypersensitivity to lorecivivt or any component of the formulation.","Severe hepatic impairment (Child-Pugh class C) due to increased risk of hepatotoxicity."]
| Precautions | ["Serious infusion-related reactions including angioedema, hypotension, bronchospasm, and arrhythmias have been reported; premedicate with antihistamines, corticosteroids, and acetaminophen.","Reduction in serum vitamin A levels due to decreased TTR, which is a carrier for retinol-binding protein; monitor vitamin A levels and supplement as needed.","Coagulopathy: Decreased TTR levels may lead to reduced fibrinogen and clotting factors; monitor coagulation parameters.","Pregnancy and lactation: Avoid use unless benefit outweighs risk; no adequate human data."] |
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| Monitor maternal complete blood count (CBC), liver function tests (LFTs), and bilirubin levels. Fetal ultrasound for growth and anatomy in first trimester; serial ultrasound for growth restriction and amniotic fluid volume throughout pregnancy. Assess for signs of hemorrhage in newborn. |
| Fertility Effects | No known significant effect on fertility. Theoretical risk of folate antagonism affecting ovulation or implantation; not well established. |