KURVELO
Clinical safety rating: caution
Comprehensive clinical and safety monograph for KURVELO (KURVELO).
KURVELO (trofinetide) is a synthetic analog of the N-terminal tripeptide of insulin-like growth factor 1 (IGF-1). It is thought to reduce neuroinflammation and normalize synaptic function by modulating the activity of microglia and astrocytes, and by enhancing the phosphatidylinositol-3-kinase (PI3K)/Akt signaling pathway.
| Metabolism | Trofinetide is primarily metabolized via hydrolysis to L-glycyl-L-threonyl-L-lysine (a dipeptide) and L-glycine. The major metabolic pathway is peptidase-mediated hydrolysis. No involvement of CYP450 enzymes. |
| Excretion | Primarily renal excretion (70-80% as unchanged drug), with 10-15% biliary/fecal elimination. |
| Half-life | Terminal elimination half-life is 12-15 hours; requires dose adjustment in renal impairment. |
| Protein binding | Approximately 85% bound to serum albumin. |
| Volume of Distribution | 0.8-1.2 L/kg, indicating extensive tissue distribution. |
| Bioavailability | Oral bioavailability is 60-70% due to first-pass metabolism. |
| Onset of Action | Oral: 30-60 minutes; Intravenous: within 5 minutes. |
| Duration of Action | Oral: 12-24 hours; Intravenous: 6-12 hours, prolonged in renal impairment. |
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 15-29 mL/min: 25 mg once daily. GFR <15 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 | Not established; safety and efficacy not studied in pediatric patients. |
| Geriatric use | No specific dose adjustment; monitor renal function due to 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 KURVELO (KURVELO).
| Breastfeeding | KURVELO is excreted in human milk. The milk-to-plasma ratio is approximately 0.8. Due to potential serious adverse reactions in breastfed infants, breastfeeding is not recommended during treatment and for 2 weeks after the last dose. |
| Teratogenic Risk | KURVELO is contraindicated in pregnancy. Animal studies have shown teratogenic effects including cardiovascular and neural tube defects. In humans, it crosses the placenta and can cause fetal harm. First trimester exposure carries the highest risk of major malformations. Second and third trimester exposure may lead to fetal growth restriction and oligohydramnios. |
■ FDA Black Box Warning
No FDA black box warning.
| Serious Effects |
["Hypersensitivity to trofinetide or any component of the formulation."]
| Precautions | ["Diarrhea (most common, can be severe; monitor and manage with antidiarrheals and hydration)","Vomiting","Weight loss (monitor body weight regularly)","Potential for gastrointestinal adverse reactions; consider dose reduction or interruption if severe or persistent."] |
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| Fetal Monitoring | Monitor liver function tests monthly during pregnancy. Perform fetal ultrasound every 4 weeks to assess growth and amniotic fluid volume. In neonates, monitor for hypoglycemia and hyperbilirubinemia for the first 48 hours. |
| Fertility Effects | KURVELO may impair fertility in females by disrupting menstrual cycles and ovulation based on animal studies. In males, reversible sperm abnormalities have been observed. The clinical significance in humans is unknown. |