Taletrectinib

Taletrectinib is a prescription medication indicated for the treatment of adult patients with locally advanced or metastatic ROS proto-oncogene 1 (ROS1)-positive non-small cell lung cancer (NSCLC).

• Taletrectinib is available under the following different brand names: Ibtrozi.

Common side effects of Taletrectinib include:

• diarrhea  
• nausea 
• vomiting 
• dizziness 
• rash
• constipation 
• tiredness 
• changes in liver function tests 
• decreased white blood cell levels

Serious side effects of Taletrectinib include:

• symptoms of liver problems may include jaundice, loss of appetite, nausea or vomiting, dark or “tea-colored” urine, pain on the upper right side of the stomach, light-colored stools, feeling tired or weak
• lung problems may cause symptoms like cough, trouble breathing or shortness of breath, fever, and wheezing 
• symptoms of QT prolongation may include feeling dizzy, lightheadedness, and irregular heartbeat, 
• symptoms of hyperuricemia may include red, hot, tender or swollen joints, especially in big toe, abdominal pain, nausea or vomiting, pink or brown urine
• myalgia with or without elevation of creatinine phosphokinase (CPK)
• skeletal fractures

Rare side effects of Taletrectinib 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

• 200 mg

Non-Small Cell Lung Cancer

Adult dosage

• 600 mg orally daily until disease progression or unacceptable toxicity

Dosage Considerations – Should be Given as Follows: 

• See “Dosages”

If your doctor has directed you to use this medication, 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.

Drug interaction overview

• Taletrectinib is a moderately sensitive CYP3A4 substrate
• Strong and moderate CYP3A4 inhibitors
  • Avoid coadministration
  • Concomitant use may increase exposure of taletrectinib and increase the risk of adverse effects (e.g., QT prolongation)
• Strong and moderate CYP3A4 inducers
  • Avoid coadministration
  • Concomitant use may decrease exposure of taletrectinib and reduce efficacy
• Gastric acid reducing agents
  • Proton pump inhibitors (PPIs): Avoid coadministration; concomitant use may decrease exposure of taletrectinib and reduce efficacy
  • H2 receptor antagonists: Avoid coadministration
• Locally acting antacids: Separate administration by 2 hours
• Drugs that prolong the QTc interval
  • Avoid coadministration
    • If concomitant use cannot be avoided, increase the frequency of ECG and electrolyte monitoring
    • Concomitant use with other drug(s) with known potential for QTc interval prolongation (e.g., antiarrhythmic drugs) may result in additive prolongation of QTc interval

Contraindications

• None

Effects of drug abuse

• None

Short-Term Effects

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

Long-Term Effects

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

Cautions

• Hepatotoxicity
  • Can cause hepatotoxicity (e.g., drug-induced liver injury); fatal cases reported
  • Median time to AST or ALT elevation onset: 15 days (range, 3 days to 20.8 months)
  • Monitor liver function tests (ie, AST, ALT, and bilirubin levels) before starting therapy, every 2 weeks for the first 2 months, and then monthly thereafter as clinically indicated
  • More frequent monitoring is required in patients who develop transaminase elevations
  • Hold, reduce dose, or permanently discontinue based on severity
• Interstitial lung disease (ILD)/pneumonitis
  • Can cause severe, life-threatening, or fatal ILD or pneumonitis
  • Median time to ILD/pneumonitis onset: 3.8 months (range, 12 days to 11.8 months)
  • Monitor for new or worsening pulmonary symptoms indicative of ILD/pneumonitis
  • Immediately hold therapy in patients with suspected ILD/pneumonitis
  • Hold, reduce dose, or permanently discontinue if Grade greater than 2 ILD/pneumonitis is confirmed
• QTc interval prolongation
  • Can cause concentration-dependent QTc interval prolongation
  • Median time to QT prolongation onset: 22 days (range, 1 day to 38.7 months)
  • May increase risk for ventricular tachyarrhythmias (e.g., TdP) or sudden death
  • Significantly prolonged QTc interval may occur if taken with food; therefore, take Taletrectinib on an empty stomach
  • Monitor ECGs and electrolytes before starting therapy and then periodically thereafter as clinically indicated
  • Adjust monitoring frequency based on risk factors
• Long QT syndromes
  • Clinically significant bradyarrhythmia
  • Severe or uncontrolled heart failure
  • Concomitant medications associated with QTc interval prolongation
  • Hold, reduce dose, or permanently discontinue based on severity
• Hyperuricemia
  • Can cause hyperuricemia
  • Monitor serum uric acid levels before starting and periodically during therapy
  • Initiate treatment with urate-lowering medications as clinically indicated
  • Hold, reduce dose, or permanently discontinue based on severity
• Myalgia with CPK elevation
  • Can cause myalgia; may occur with or without CPK elevation
  • Median time to myalgia onset: 11 days (range, 2 days to 10 months)
  • Monitor serum CPK levels every 2 weeks during the first month of therapy and then as clinically indicated in patients reporting unexplained muscle pain, tenderness, or weakness
  • Hold and resume therapy at the same or reduced dose as required upon improvement
• Skeletal fractures
  • Can increase the risk of fractures; ROS1 inhibitors are associated with skeletal fractures
  • Median time to fracture onset: 10.7 months (range, 26 days to 29.1 months)
  • Promptly evaluate patients with signs or symptoms (e.g., pain, changes in mobility, deformity) of fractures
  • No data regarding taletrectinib effects on the healing of known fractures and the risk of future fractures
• Photosensitivity reactions
  • Can cause photosensitivity reactions
  • Advise patients to minimize sun exposure and use sun protection (e.g., broad-spectrum sunscreen) during and for at least 5 days after therapy
• Embryo-fetal toxicity
  • May cause fetal harm when administered during pregnancy
  • Advise pregnant patients and females of reproductive potential of fetal risk
  • Effective contraception is recommended during and after therapy in females of reproductive potential and male patients with female partners of reproductive potential

Pregnancy and Lactation

• May cause fetal harm when administered during pregnancy, based on literature reports in humans with congenital mutations leading to changes in tropomyosin receptor kinases (TRK) signaling, findings from animal studies, and its mechanism of action
• Limited data from case reports of use in pregnant women are insufficient to inform the drug-associated risk of adverse developmental outcomes
• Advise pregnant patients with potential fetal risk. Verify the pregnancy status of females of reproductive potential before starting therapy
• Human data
  • Published reports of individuals with congenital mutations in TRK pathway proteins suggest that decreases in TRK-mediated signaling are correlated with obesity, developmental delays, cognitive impairment, insensitivity to pain, and anhidrosis
• Contraception requirements
  • Effective contraception is recommended during therapy and for 3 weeks after the last dose in females of reproductive potential and male patients with female partners of reproductive potential
• Infertility
  • May impair fertility in males and females, based on findings in animals
  • Effects on animal fertility were reversible
• Lactation
  • No data on presence in human milk or effects in breastfed children or on milk production
  • Avoid breastfeeding during therapy and for 3 weeks after the last dose due to the potential for adverse reactions in breastfed children