Selpercatinib

Selpercatinib is a prescription medication used to treat adult patients with metastatic RET fusion-positive non-small cell lung cancer, adult and pediatric patients aged 12 years and older with advanced or metastatic RET-mutant medullary thyroid cancer who require systemic therapy, and adult and pediatric patients aged 12 years and older with advanced or metastatic RET fusion-positive thyroid cancer who require systemic therapy and who are radioactive iodine-refractory (if radioactive iodine is appropriate).

Common side effects of Selpercatinib include:

• increased aspartate aminotransferase (AST)
• increased alanine aminotransferase (ALT)
• increased blood sugar (glucose)
• decreased leukocytes
• decreased albumin
• decreased calcium
• dry mouth
• diarrhea
• increased creatinine
• increased alkaline phosphatase
• high blood pressure (hypertension)
• fatigue
• fluid retention (edema)
• decreased platelets
• increased total cholesterol
• rash
• decreased sodium
• constipation

Serious side effects of Selpercatinib include:

• hives
• rash
• fever
• joint or muscle pain
• difficult breathing
• swelling of the face, lips, tongue, or throat
• easy bruising or bleeding (nosebleeds, bleeding gums)
• coughing up blood or vomit that looks like coffee grounds
• any wound that will not heal
• fast or pounding heartbeats
• fluttering in the chest
• shortness of breath, and sudden dizziness (like you might pass out)
• chills
• cough with mucus
• chest pain
• feeling short of breath
• liver problems--loss of appetite, stomach pain (upper right side), dark urine, jaundice (yellowing of the skin or eyes)

Rare side effects of Selpercatinib include:

• none

Seek medical care or call 911 at once if you have the following serious side effects:

• Severe headache, confusion, slurred speech, arm or leg weakness, trouble walking, coordination loss, unsteady, very stiff muscles, high fever, profuse sweating, or tremors;
• Serious eye symptoms such as sudden vision loss, blurred vision, tunnel vision, eye pain or swelling, or seeing halos around lights;
• Serious heart symptoms include fast, irregular, or pounding heartbeats; fluttering in the chest; shortness of breath; sudden dizziness, lightheadedness, or passing out.

This is not a complete list of side effects and other serious side effects or health problems that may occur because of the use of this drug. Call your doctor for medical advice about serious side effects or adverse reactions. You may report side effects or health problems to FDA at 1-800-FDA-1088.

Adult and pediatric dosage

Capsule

• 40 mg
• 80 mg

Non-small cell lung cancer

Adult dosage

• Weighing less than 50 kg: 120 mg orally two times a day
• Weighing 50 kg and more: 160 mg orally two times a day
• Continue until disease progression or unacceptable toxicity

Medullary thyroid cancer

Adult dosage

• Weighing less than 50 kg: 120 mg orally two times a day
• Weighing 50 kg and more: 160 mg orally two times a day
• Continue until disease progression or unacceptable toxicity

Pediatric dosage

• Children aged younger than 12 years: Safety and efficacy not established
• Children aged 12 years and older:
• Children weighing less than 50 kg: 120 mg orally two times a day
• Children weighing 50 kg and more: 160 mg orally two times a day
• Continue until disease progression or unacceptable toxicity

Thyroid cancer

Adult dosage

• Weighing less than 50 kg: 120 mg orally two times a day
• Weighing 50 kg and more: 160 mg orally two times a day
• Continue until disease progression or unacceptable toxicity

Pediatric dosage

• Children aged younger than 12 years: Safety and efficacy not established
• Children aged 12 years and older
• Children weighing less than 50 kg: 120 mg orally two times a day
• Children weighing 50 kg and more: 160 mg orally two times a day
• Continue until disease progression or unacceptable toxicity

Other RET fusion-positive solid tumors

Adult dosage

• Weighing less than 50 kg: 120 mg orally two times a day
• Weighing 50 kg and more: 160 mg orally two times a day
• Continue until disease progression or unacceptable toxicity

Dosage Considerations – Should be Given as Follows: 

• See “Dosages”

If your medical doctor is using this medicine to treat your pain, your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor, health care provider, or pharmacist first.

• Selpercatinib has severe interactions with no other drugs
• Selpercatinib has serious interactions with at least 67 other drugs
• Selpercatinib has moderate interactions with at least 127 other drugs
• Selpercatinib has minor interactions with the following drugs
  • acetazolamide
  • anastrozole
  • cyclophosphamide
  • larotrectinib

This information does not contain all possible interactions or adverse effects. Visit the RxList Drug Interaction Checker for any drug interactions. Therefore, before using this product, tell your doctor or pharmacist about all the products you use. Keep a list of all your medications with you and share this information with your doctor and pharmacist. Check with your healthcare professional or doctor for additional medical advice, health questions, or concerns.

Contraindications

• None

Effects of drug abuse

• None

Short-Term Effects

• See “What Are Side Effects Associated with Using Selpercatinib?”

Long-Term Effects

• See “What Are Side Effects Associated with Using Selpercatinib?”

Cautions

• Serious hepatic adverse reactions reported; monitor ALT and AST before initiating, every 2 weeks during first 3 months, then monthly thereafter as clinically indicated; dose adjustment or discontinuation required based on the severity
• Hypertension reported; manage with antihypertension medications; monitor blood pressure after 1 week and at least monthly thereafter as clinically indicated
• Monitor patients at significant risk of developing QTc prolongation; assess QT interval, electrolytes, and TSH at baseline and periodically during treatment
• Serious fatal hemorrhagic events can occur; permanently discontinue severe or life-threatening hemorrhage
• Hypersensitivity reported; signs and symptoms include fever, rash, and arthralgia or myalgia with concurrent decreased platelets or transaminitis; if hypersensitivity occurs, withhold the drug and begin corticosteroids at a dose of 1 mg/kg prednisone
• Impaired wound healing can occur in patients who receive drugs that inhibit the vascular endothelial growth factor signaling pathway; withhold for at least 7 days before elective surgery and do not administer for at least 2 weeks following major surgery and until adequate wound healing
• Tumor lysis syndrome (TLS) occurred in 1% of patients with medullary thyroid carcinoma receiving therapy; patients may be at risk of TLS if they have rapidly growing tumors, a high tumor burden, renal dysfunction, or dehydration; closely monitor patients at risk, consider appropriate prophylaxis including hydration, and treat as clinically indicated
• Monitor growth plates in adolescent patients with open growth plates; consider interrupting or discontinuing therapy based on the severity of any growth plate abnormalities and based on individual risk-benefit assessment
• Severe, life-threatening, and fatal interstitial lung disease/pneumonitis can occur; monitor for pulmonary symptoms indicative of interstitial lung disease (ILD)/pneumonitis; withhold and promptly investigate for ILD in any patient who presents with acute or worsening respiratory symptoms which may be indicative of ILD (e.g., dyspnea, cough, and fever); withhold, reduce the dose or permanently discontinue therapy based on the severity of confirmed ILD
• May cause hypothyroidism; monitor thyroid function before treatment and periodically during treatment; treat with thyroid hormone replacement as clinically indicated; withhold therapy until clinically stable or permanently discontinue based on the severity
• Based on animal reproductive studies and its mechanism of action, can cause fetal harm
• Drug interaction overview
  • Strong or moderate CYP3A inhibitors or inducers
    • Selpercatinib is predominantly metabolized by CYP3A4
    • Avoid coadministration with strong or moderate CYP3A inhibitors or inducers
    • Adjust selpercatinib dose if unable to avoid use with strong or moderate CYP3A4 inhibitors
  • Acid-reducing agents
    • Coadministration with acid-reducing agents decreases selpercatinib plasma concentrations, which may reduce the efficacy
    • Avoid concomitant use of PPIs, H2 receptor antagonists, and locally acting antacids
    • If unable to avoid, take selpercatinib with food (with a PPI) or modify its administration time (with an H2 receptor antagonist or a locally acting antacid)
  • QT prolongation
    • Selpercatinib is associated with QTc interval prolongation
    • Monitor QT interval with ECGs more frequently in patients who require treatment with concomitant medications known to prolong QT interval
  • CYP2C8 or CYP3A substrates
    • Selpercatinib is a moderate CYP2C8 inhibitor and a weak CYP3A inhibitor
    • Avoid coadministration with CYP2C8 or CYP3A substrates where minimal concentration changes may lead to increased adverse reactions
    • If unable to avoid, follow any dose adjustment recommendations for CYP2C8 or CYP3A substrates provided in their product labeling

Pregnancy and Lactation

• Based on findings from animal studies and its mechanism of action, can cause fetal harm when administered to pregnant women
• Data are not available regarding use in pregnant women
• Verify pregnancy status in women of reproductive potential before initiating
• Advise patients of potential risks
• Contraception
  • Use effective contraception during treatment and for 1 week after the final dose in women of reproductive potential and men with women partners of reproductive potential
• Fertility
  • May impair fertility in women’s and men’s reproductive potential
• Lactation
  • Data are not available on the presence of selpercatinib or its metabolites in human milk or on their effects on breastfed children or milk production
  • Advise women not to breastfeed during treatment and for 1 week after the final dose