Selpercatinib

Mechanism :

Inhibits wild-type RET, vascular endothelial growth factors (VEGFR1 and VEGFR3), mutated isoforms of RET, fibroblast growth factor receptor ( FGFR 1, 2, 3)

Indication :

• RET mutant thyroid medullary cancer
• RET fusion positive thyroid cancer

Contraindications :

Discontinue in case of life threatening haemorrhage

Do not initiate in patients with uncontrolled high blood pressures

Dosing :

Adverse Effect :

Haemorrhage, Dose-related hepatotoxicity, Hypersensitivity reaction (fever, skin rash, arthralgia), tumor lysis syndrome

Decreased serum calcium, magnesium, sodium, albumin, glucose levels

Increase serum cholesterol, potassium levels,

hypertansion, constipation, cough, dysnea

Interaction :

QT prolonging agents can worsen the QT prolongation

CYP3A4 Inducers can reduce the serum concentration of Selpercatinib

Hypertension associated agents can worsen the hypertensive effect

Lactation :

Not enough data. Females should be on breast feed while on treatment and for a week post their last dose.

Hepatic Dose :

Grade 3 or 4 – Stop the drug and monitor AST and ALT every week till it recovers to grade 1. Continue with reduce dosage by two levels and monitor AST and ALT weekly. Resume back to the original dose after 4 weeks of no recurrence.

If total bilirubin > 3 to 10 times the Upper limit of normal – reduce the dose to 80mg twice daily

Grade 4 hypertension – Discontinue

Pregnanacy :

Females should be on contraception while on treatment and for a week post their last dose. Can cause fetal harm so avoided in pregnancy