Selpercatinib (Retevmo) demonstrates significant efficacy in the treatment of various RET-driven tumors, yet it may also induce a range of adverse reactions.

I. Common Side Effects

1. Common Adverse Reactions in Adults (Incidence ≥ 25%)

(1) Edema (swelling of the extremities, face, or periorbital area), diarrhea, fatigue, dry mouth, hypertension, abdominal pain, constipation, rash, nausea, and headache.

(2) In addition, cough, dyspnea, and hemorrhagic events are also relatively common.

2. Common Adverse Reactions in Pediatric Patients (Aged 2 Years and Older, Incidence ≥ 25%)

Musculoskeletal pain, diarrhea, nausea, hemorrhage, pyrexia, abdominal pain, headache, vomiting, fatigue, cough, rash, COVID-19 infection, upper respiratory tract infection, and edema.

3. Common Grade 3–4 Laboratory Abnormalities in Adults

Lymphopenia, elevated ALT, elevated AST, decreased blood sodium, and decreased blood calcium.

4. Severe Side Effects Requiring Vigilance

Hepatotoxicity, interstitial lung disease/pneumonitis (potentially fatal), hypertension, QT interval prolongation, hemorrhagic events, hypersensitivity reactions, tumor lysis syndrome, and hypothyroidism.

II. Side Effect Management Strategies

1. Hepatotoxicity

(1) Monitor ALT/AST every 2 weeks before treatment and for the first 3 months of treatment, then monthly thereafter.

(2) In the event of Grade 3–4 elevations, withhold treatment. Upon recovery to Grade 1 or baseline, resume treatment at a dose reduced by 2 levels, with weekly monitoring until stabilization.

2. Hypertension

(1) Optimize blood pressure to the normal range prior to treatment initiation.

(2) Monitor blood pressure starting 1 week after treatment initiation, and at least monthly thereafter.

(3) For Grade 3 hypertension uncontrolled by antihypertensive agents, withhold treatment; resume at a reduced dose once blood pressure is controlled.

(4) Permanently discontinue treatment for Grade 4 hypertension.

3. Diarrhea

(1) For mild diarrhea, administer oral rehydration salts and avoid high-fiber and greasy foods.

(2) For severe diarrhea, promptly consult a physician; dose interruption or reduction may be required.

4. Edema

(1) For mild edema, elevate the lower extremities and restrict sodium intake.

(2) If edema impairs mobility or severe facial/periorbital edema occurs, seek medical evaluation; dose reduction or interruption may be necessary.

5. QT Interval Prolongation

(1) Regularly monitor electrocardiogram, electrolytes, and thyroid function before and during treatment.

(2) Correct hypokalemia, hypomagnesemia, and hypocalcemia. Avoid concomitant use with CYP3A inhibitors or drugs known to prolong the QT interval.

(3) Withhold treatment for Grade 3 QT prolongation; resume at a reduced dose or permanently discontinue upon recovery.

6. Hemorrhage and Hypersensitivity

(1) Permanently discontinue treatment for severe or life-threatening hemorrhage.

(2) For hypersensitivity reactions (pyrexia, rash, arthralgia), withhold treatment and administer corticosteroids (prednisone 1 mg/kg). Upon recovery, resume treatment at a dose reduced by 3 levels, with weekly dose escalation by 1 level until the original dose is reached.

7. Hypothyroidism

(1) Regularly monitor thyroid function before and during treatment.

(2) Administer thyroid hormone replacement therapy for hypothyroidism, with dose adjustment as needed.

8. Special Considerations for Pediatric Patients

Monitor for changes in the epiphyseal growth plates and symptoms of slipped capital femoral epiphysis (hip or knee pain, limping). Evaluate the need for treatment interruption or discontinuation if abnormalities occur.

III. Storage Conditions

1. Temperature Requirements

(1) Store at room temperature between 20°C and 25°C.

(2) Short-term fluctuations between 15°C and 30°C are permitted (e.g., during transportation).

2. Additional Precautions

(1) Store in the original bottle, which contains a desiccant.

(2) Protect from light and moisture.

(3) Keep out of reach of children.