RETEVMO
Clinical safety rating: caution
Comprehensive clinical and safety monograph for RETEVMO (RETEVMO).
RETEVMO (selpercatinib) is a potent and selective RET kinase inhibitor. It inhibits wild-type RET and multiple RET fusions (e.g., KIF5B-RET, CCDC6-RET) and mutations (e.g., M918T, C634W, V804M/L/E) by binding to the ATP-binding site of RET, blocking downstream signaling pathways including MAPK/ERK and PI3K/AKT, thereby inhibiting tumor cell proliferation.
| Metabolism | Primarily metabolized by CYP3A4 and to a lesser extent by CYP2D6, CYP2C8, and CYP2C9. Also undergoes glucuronidation via UGT1A1 and UGT1A3. Selpercatinib is a substrate of P-glycoprotein (P-gp) and BCRP. |
| Excretion | Primarily biliary/fecal (approximately 75% of administered dose recovered in feces as unchanged drug and metabolites); renal elimination accounts for <10% (mostly metabolites). |
| Half-life | 18 hours (terminal elimination half-life) supporting twice-daily dosing; steady-state reached within ~3 days. |
| Protein binding | >99.9% bound to plasma proteins (primarily albumin and alpha-1-acid glycoprotein). |
| Volume of Distribution | Approximately 100 L (not weight-normalized; extensive tissue distribution). |
| Bioavailability | Oral bioavailability ~73% under fasting conditions; food decreases absorption (avoid high-fat meals). |
| Onset of Action | Not applicable for tumor response; time to maximum plasma concentration (Tmax) is 2–6 hours post oral dose. |
| Duration of Action | Sustained inhibition of RET kinase for dosing interval (~12 hours); continuous daily dosing required for antitumor effect. |
| Molecular Weight | 482.55 |
160 mg orally twice daily
| Dosage form | CAPSULE |
| Renal impairment | No dose adjustment required for GFR ≥30 mL/min; not recommended for GFR <30 mL/min |
| Liver impairment | Child-Pugh A: no adjustment; Child-Pugh B: reduce dose to 80 mg twice daily; Child-Pugh C: not recommended |
| Pediatric use | Safety and efficacy not established in pediatric patients |
| Geriatric use | No specific dose adjustment; monitor renal function and volume status |
| 1st trimester | Avoid; potential for teratogenicity due to VEGFR/PDGFR inhibition. No adequate human data; animal studies show embryotoxicity. |
| 2nd trimester | Avoid; risk of fetal harm due to antiangiogenic effects. May cause oligohydramnios, fetal growth restriction, or placental dysfunction. |
| 3rd trimester | Avoid; risk of fetal hemorrhage, preterm labor, or impaired wound healing. Discontinue if used near delivery. |
Clinical note
Comprehensive clinical and safety monograph for RETEVMO (RETEVMO).
| Placental transfer | Predicted to cross placenta due to molecular weight <500 Da; antiangiogenic effects could impair placental vascular development. |
| Breastfeeding | No human data; based on molecular weight and long half-life, likely present in milk. Discontinue breastfeeding or avoid drug due to potential for infant toxicity (e.g., growth delay, bleeding). |
■ FDA Black Box Warning
None
| Serious Effects |
PregnancySevere hepatic impairment (Child-Pugh C)Recent major surgery (within 28 days)Uncontrolled hypertensionHistory of hemorrhage or bleeding diathesis
| Precautions | Hepatotoxicity: Elevations in ALT/AST, and bilirubin; monitor liver function tests prior to and periodically during treatment, Hypertension: Can cause hypertension; monitor blood pressure and manage with antihypertensives as needed, QTc Prolongation: Risk of QTc interval prolongation; monitor ECG and electrolytes; avoid in patients with baseline QTc >470 ms, Hemorrhagic Events: Serious and fatal hemorrhages can occur; monitor for signs/symptoms, Hypersensitivity: Reactions including rash and fever; discontinue if severe hypersensitivity occurs, Tumor Lysis Syndrome: Risk in patients with rapidly growing tumors; monitor and manage appropriately, Impaired Wound Healing: Withhold for at least 2 weeks before elective surgery, Fetal Toxicity: Can cause fetal harm; advise patients of reproductive potential to use effective contraception |
| Food/Dietary | Avoid grapefruit, grapefruit juice, and Seville oranges as they inhibit CYP3A4, increasing selpercatinib levels. |
Loading safety data…
| Lactation Rating | L5 (Contraindicated) |
| Teratogenic Risk | Based on animal studies and mechanism of action (RET kinase inhibitor), RETEVMO is expected to cause fetal harm when administered to pregnant women. There are no adequate human data. Advise patients of potential risk to fetus. First trimester: Highest risk of major malformations; avoid use. Second and third trimesters: Risk of fetal growth restriction, oligohydramnios, and potential fetal death. Use only if maternal benefit justifies fetal risk. |
| Fetal Monitoring | Monitor for hypertension, proteinuria, and signs of preeclampsia. Assess fetal growth by ultrasound every 4 weeks if used in pregnancy. Monitor for oligohydramnios. Assess maternal renal function, liver function, and electrolytes regularly. Monitor for diarrhea, nausea, vomiting, and dehydration. |
| Fertility Effects | Based on animal studies, RETEVMO may impair fertility in females and males. In females, ovarian follicular atresia and decreased corpora lutea noted. In males, degeneration of seminiferous tubules and reduced sperm motility. Reversibility unknown. Human data lacking. |
| Clinical Pearls | Monitor for hepatotoxicity, hypertension, and QT prolongation. RETEVMO is a selective RET inhibitor; avoid strong CYP3A4 inducers. For patients with RET fusion-positive tumors, assess baseline ECG and liver function tests. Dose reduction recommended for severe hepatic impairment. |
| Patient Advice | Take with or without food but avoid grapefruit and Seville oranges. · Report any yellowing of skin/eyes, dark urine, or confusion (liver toxicity signs). · Monitor blood pressure regularly and report severe headache or vision changes. · Contact doctor if you experience fast or irregular heartbeat, fainting, or dizziness. · Use effective contraception during treatment and for at least 2 weeks after last dose. |