Repotrectinib

Repotrectinib is a prescription medication indicated for locally advanced or metastatic ROS1-positive non–small cell lung cancer (NSCLC).

• Repotrectinib is available under the following different brand names: Augtyro

Common side effects of Repotrectinib include:

• dizziness
• changes in taste
• numbness and tingling in extremities
• constipation
• shortness of breath
• loss of balance and coordination
• fatigue
• cognitive disorders
• muscular weakness

Serious side effects of Repotrectinib include:

• central nervous system (CNS) effects include dizziness; problems with thinking, such as forgetfulness or confusion; seeing or hearing things that are not real (hallucinations); problems with concentration, attention, memory, and sleep; vertigo; changes in mood, such as anxiety, irritability, and depression; and balance or coordination problems
• lung problems (pneumonitis) include dry cough (without mucus), productive cough (with mucus), wheezing, or trouble breathing
• liver problems include yellowing of the skin or the white part of your eyes, loss of appetite, dark or “tea-colored” urine, nausea or vomiting, light-colored stools (bowel movements), and pain on the upper right side of your stomach area
• muscle problems
• increased uric acid levels in your blood (hyperuricemia)
• bone fractures

Rare side effects of Repotrectinib 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 dosage

Capsule

• 40 mg

Non–small cell lung cancer

Adult dosage

• 160 mg orally once a day for 14 days, then increase to 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, healthcare provider, or pharmacist first.

• Repotrectinib has severe interactions with no other drugs.
• Repotrectinib has serious interactions with at least 171 other drugs.
• Repotrectinib has moderate interactions with no other drugs.
• Repotrectinib has minor interactions with no other drugs.

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 Repotrectinib?”

Long-Term Effects

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

Cautions

• Hyperuricemia may occur; monitor serum uric acid levels before initiating and periodically during treatment; initiate urate-lowering medications as clinically indicated
• Associated with skeletal fractures; promptly evaluate signs or symptoms (eg, pain, changes in mobility, deformity) of fractures; no data are available on the effects of Repotrectinib on the healing of known fractures and risk for future fractures
• Based on studies and its mechanism of action, fetal harm may occur when administered to pregnant women
• Myalgia
  • May cause myalgia with or without creatine phosphokinase (CPK) elevation
  • Monitor serum CPK levels every 2 weeks during the first month of treatment and as needed if unexplained muscle pain, tenderness, or weakness reported
  • Initiate supportive care as clinically indicated
• Hepatoxicity
  • Hepatoxicity reported
  • Monitor liver function tests every 2 weeks during the first month of treatment, then monthly after that and as clinically indicated
  • Withhold and then resume at the same or reduced dose upon improvement, or permanently discontinue based on severity
• Interstitial lung disease (ILD)/pneumonitis
  • May cause ILD/pneumonitis
  • Monitor for new or worsening pulmonary symptoms indicative of ILD/pneumonitis
  • Immediately withhold if ILD/pneumonitis is suspected
  • If confirmed, permanently discontinue
• CNS adverse reactions
  • CNS adverse reactions (eg, dizziness, ataxia, cognitive disorders) may occur
  • Sleep (eg, insomnia, hypersomnia) and mood disorders also reported
  • Reported incidences were similar in patients with or without CNS metastases
  • Advise patients and caregivers of CNS adverse reactions
  • Advise patients not to drive or use machines if CNS adverse reactions occur
  • Withhold and then resume at the same or reduced dose upon improvement, or permanently discontinue based on the severity
• Drug interaction overview
  • Strong and moderate CYP3A inhibitors
    • Avoid coadministration
    • Discontinue CYP3A inhibitors for 3-5 elimination half-lives of CYP3A4 inhibitor before initiating
    • Strong or moderate CYP3A inhibitors may increase repotrectinib exposure and the risk for toxicities
  • P-gp inhibitors
    • Avoid coadministration
    • P-gp inhibitors may increase repotrectinib exposure and the severity of adverse reactions
  • Strong and moderate CYP3A inducers
    • Avoid coadministration
    • Strong or moderate CYP3A inducers may decrease repotrectinib plasma concentrations and its efficacy
  • Sensitive CYP3A substrates
    • Avoid coadministration with CYP3A substrates, where minimal concentration changes can cause reduced efficacy
    • If unavoidable, increase CYP3A4 substrate dosage by approved product labeling
  • Hormonal contraceptives
    • Avoid coadministration
    • Advise women to use effective nonhormonal contraceptives
    • Repotrectinib is a CYP3A4 inducer, which can decrease progestin or estrogen exposure and may reduce the effectiveness of hormonal contraceptives

Pregnancy and Lactation

• Based on studies and the drug’s mechanism of action, fetal harm may occur when repotrectinib is administered to pregnant women
• There are no available data on the drug’s use in pregnant women
• Verify the pregnancy status of women of childbearing potential before initiating repotrectinib
• Contraception
  • Women of childbearing potential: Use effective nonhormonal contraception during treatment and for 2 months after the last dose
  • Repotrectinib renders some hormonal contraceptives ineffective
  • Men with women partners of childbearing potential: Use effective contraception during treatment and for 4 months after the last dose
• Lactation
  • There are no data on the drug’s presence in human milk or its effects on either breastfed children or milk production
  • Advise lactating women to discontinue breastfeeding during treatment and for 10 days after the last dose