Repotrectinib Dosage

Medically reviewed by Drugs.com. Last updated on Feb 6, 2024.

Usual Adult Dose for Non-Small Cell Lung Cancer

Initial dose: 160 mg orally once a day for 14 days
Maintenance dose: 160 mg orally twice a day

Duration of therapy: Until disease progression or unacceptable toxicity

Comments:

• Patients should be selected based on the presence of ROS proto-oncogene 1, receptor tyrosine kinase (ROS1) rearrangement(s) in tumor specimens. The US FDA-approved test to detect ROS1 rearrangements is currently not available.
• Treatment with strong and moderate CYP450 3A inhibitors should be stopped for 3 to 5 elimination half-lives before starting this drug.

Use: For the treatment of locally advanced or metastatic ROS1-positive non-small cell lung cancer

Renal Dose Adjustments

Mild to moderate renal dysfunction (estimated GFR-Modification of Diet in Renal Disease [eGFR-MDRD] 30 to 90 mL/min): No adjustment recommended
Severe renal dysfunction (eGFR-MDRD less than 30 mL/min): Data not available

Liver Dose Adjustments

Mild liver dysfunction (total bilirubin greater than 1 to 1.5 times the upper limit of normal [1 to 1.5 x ULN] or AST greater than ULN): No adjustment recommended
Moderate (total bilirubin greater than 1.5 to 3 x ULN with any AST) to severe (total bilirubin greater than 3 x ULN with any AST) liver dysfunction: Data not available

If Hepatotoxicity Develops During Therapy:

• Grade 3: Withhold this drug until grade 1 or less or baseline. Resume at the same dose if resolution occurs within 4 weeks or at a reduced dose for recurrent grade 3 events that resolve within 4 weeks.
• Grade 4: Withhold this drug until grade 1 or less or baseline; resume at reduced dose. Permanently discontinue if the adverse reaction does not resolve within 4 weeks or for recurrent grade 4 events.
• ALT or AST greater than 3 x ULN with concurrent total bilirubin greater than 1.5 x ULN (without cholestasis or hemolysis): Permanently discontinue this drug.

Dose Adjustments

Dose Reductions for Adverse Reactions:
If dose is 160 mg once a day:

• First dose reduction: 120 mg orally once a day
• Second dose reduction: 80 mg orally once a day

If dose is 160 mg twice a day:

• First dose reduction: 120 mg orally twice a day
• Second dose reduction: 80 mg orally twice a day

Dosage Modifications for Adverse Reactions:
CNS Effects:

• Intolerable grade 2: Withhold this drug until grade 1 or less or baseline; resume at same or reduced dose, as clinically appropriate.
• Grade 3: Withhold this drug until grade 1 or less or baseline; resume at reduced dose.
• Grade 4: Permanently discontinue this drug.

Interstitial Lung Disease (ILD)/Pneumonitis:

• Any grade: Withhold this drug if ILD/pneumonitis is suspected; permanently discontinue if ILD/pneumonitis is confirmed.

Creatine Phosphokinase (CPK) Elevation:

• CPK elevation greater than 5 x ULN: Withhold until recovery to baseline or to 2.5 x ULN or less, then resume at same dose.
• CPK elevation greater than 10 x ULN or second occurrence of CPK elevation greater than 5 x ULN: Withhold until recovery to baseline or to 2.5 x ULN or less, then resume at reduced dose.

Hyperuricemia:

• Grade 3 or 4: Withhold this drug until improvement of signs/symptoms; resume at same or reduced dose.

Other Clinically Relevant Adverse Reactions:

• Grade 3 or 4 or intolerable grade 2: Withhold this drug until grade 1 or less or baseline; resume at the same or reduced dose if resolution occurs within 4 weeks. Permanently discontinue if adverse reaction does not resolve within 4 weeks or for recurrent grade 4 events.

Precautions

CONTRAINDICATIONS: None

Safety and efficacy have not been established in patients younger than 18 years.

Consult WARNINGS section for additional precautions.

Dialysis

Data not available

Other Comments

Administration advice:

• Before starting this drug, evaluate liver function tests (including bilirubin) and uric acid levels.
• Administer at the same time each day, with or without food.
• Swallow the capsules whole. Do not open, chew, crush, or dissolve the capsule prior to swallowing.
• Do not take any capsules that are broken, cracked, or damaged.
• If a dose is missed or if vomiting occurs at any time after taking a dose, skip the dose and resume this drug at its regularly scheduled time.

Storage requirements:

• Store at 20C to 25C (68F to 77F); excursions are permitted between 15C to 30C (59F to 86F).

Monitoring:

• Hepatic: Liver function tests including ALT, AST, and bilirubin (every 2 weeks during first month of therapy, monthly thereafter, and as clinically indicated)
• Metabolic: Serum uric acid levels (before starting and periodically during therapy)
• Musculoskeletal: Serum CPK levels (during therapy)
• Respiratory: For ILD or pneumonitis

Patient advice:

• Read the US FDA-approved patient labeling (Patient Information).
• Notify your health care provider if new/worsening CNS symptoms develop; do not drive or operate hazardous machinery if you are having CNS adverse reactions.
• Notify your health care provider if new/worsening pulmonary symptoms suggestive of ILD or pneumonitis develop.
• Patients should be informed of the need for laboratory tests to monitor liver function and to immediately report symptoms of hepatotoxicity.
• Notify your doctor if you experience muscle pain or signs or symptoms associated with hyperuricemia.
• Bone fractures may occur with the use of this drug; report symptoms to health care provider.
• Females of reproductive potential should notify their health care provider of a known or suspected pregnancy.
• Inform your health care providers about all concomitant medications, including prescription medicines, over-the-counter drugs, vitamins, and herbal products.
• Avoid grapefruit or grapefruit juice during treatment.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

Medical Disclaimer