Tabrecta (capmatinib) for NSCLC: Side Effects & Interactions

Tabrecta (capmatinib) for NSCLC: Side Effects & Interactions [the_ad id=”28610″]

What is Tabrecta (capmatinib), and what is it used for?

Tabrecta (capmatinib) is a prescription medicine used to treat adults with a kind of lung cancer called non-small cell lung cancer (NSCLC) that:

has spread to other parts of the body or cannot be removed by surgery (metastatic), and
whose tumors have an abnormal mesenchymal epithelial transition (MET) gene

It is not known if Tabrecta is safe and effective in children.

What are the side effects of Tabrecta?

Tabrecta may cause serious side effects, including:

lung or breathing problems. Tabrecta may cause inflammation of the lungs that can cause death. Tell your healthcare provider right away if you develop any new or worsening symptoms, including:

Your healthcare provider may temporarily stop or permanently stop treatment with
Tabrecta if you develop lung or breathing problems during treatment.

liver problems. Tabrecta may cause abnormal liver blood test results. Your healthcare provider will do blood tests to check your liver function before you start treatment and during treatment with
Tabrecta. Tell your healthcare provider right away if you develop any signs and symptoms of liver problems, including:
- your skin or the white part of your eyes turns yellow (jaundice)
- loss of appetite for several days or longer
- dark or &lduqo;tea-colored&rduqo; urine
- nausea and vomiting
- light-colored stools (bowel movements)
- confusion
- pain, aching, or tenderness on the right side of your stomach-area (abdomen)
- tiredness
- weakness
- swelling in your stomach-area

Your healthcare provider may change your dose, temporarily stop, or permanently stop treatment with
Tabrecta if you develop liver problems during treatment.

The most common side effects of Tabrecta include:

swelling of your hands or feet
nausea
tiredness and weakness
vomiting
loss of appetite
changes in certain blood tests

These are not all of the possible side effects of Tabrecta. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Is Tabrecta addictive?

No information provided

What is the dosage for Tabrecta?

Select patients for treatment with Tabrecta based on the presence of a mutation that leads to MET exon 14 skipping in tumor specimens. Information on FDA-approved tests is available at: http://www.fda.gov/CompanionDiagnostics

Recommended Dosage

The recommended dosage of Tabrecta is 400 mg orally twice daily with or without food.

Swallow Tabrecta tablets whole. Do not break, crush or chew the tablets.

If a patient misses or vomits a dose, instruct the patient not to make up the dose, but to take the next dose at its scheduled time.

Dosage Modifications For Adverse Reactions

The recommended dose reductions for the management of adverse reactions are listed in Table 1.

Table 1: Recommended Tabrecta Dose Reductions for Adverse Reactions

Dose Reduction	Dose and Schedule
First	300 mg orally twice daily
Second	200 mg orally twice daily

Permanently discontinue Tabrecta in patients who are unable to tolerate 200 mg orally twice daily.

The recommended dosage modifications of Tabrecta for adverse reactions are provided in Table 2.

Table 2: Recommended Tabrecta Dosage Modifications for Adverse Reactions

Adverse Reaction	Severity	Dosage Modification
Interstitial Lung Disease (ILD)/Pneumonitis	Any grade	Permanently discontinue Tabrecta.
Increased ALT and/or AST without increased total bilirubin	Grade 3	Withhold Tabrecta until recovery to baseline ALT/AST. If recovered to baseline within 7 days, then resume Tabrecta at the same dose; otherwise resume Tabrecta at a reduced dose.
Increased ALT and/or AST without increased total bilirubin	Grade 4	Permanently discontinue Tabrecta.
Increased ALT and/or AST with increased total bilirubin in the absence of cholestasis or hemolysis	ALT and/or AST greater than 3 times ULN with total bilirubin greater than 2 times ULN	Permanently discontinue Tabrecta.
Increased total bilirubin without concurrent increased ALT and/or AST	Grade 2	Withhold Tabrecta until recovery to baseline bilirubin. If recovered to baseline within 7 days, then resume Tabrecta at the same dose; otherwise resume Tabrecta at a reduced dose.
	Grade 3	Withhold Tabrecta until recovery to baseline bilirubin. If recovered to baseline within 7 days, then resume Tabrecta at a reduced dose; otherwise permanently discontinue Tabrecta.
	Grade 4	Permanently discontinue Tabrecta.
Other Adverse Reactions	Grade 2	Maintain dose level. If intolerable, consider withholding Tabrecta until resolved, then resume Tabrecta at a reduced dose.
	Grade 3	Withhold Tabrecta until resolved, then resume Tabrecta at a reduced dose.
	Grade 4	Permanently discontinue Tabrecta.
Abbreviations: ALT, alanine aminotransferase; AST, aspartate aminotransferase; ILD, interstitial lung disease; ULN, upper limit of normal. Grading according to CTCAE Version 4.03 (CTCAE = Common Terminology Criteria for Adverse Events).

QUESTION

Lung cancer is a disease in which lung cells grow abnormally in an uncontrolled way.
See Answer

What drugs interact with Tabrecta?

Effect Of Other Drugs On Tabrecta

Strong CYP3A Inhibitors

Coadministration of Tabrecta with a strong CYP3A inhibitor increased
capmatinib exposure, which may increase the incidence and severity of adverse
reactions of Tabrecta. Closely monitor patients for adverse reactions during coadministration of
Tabrecta with strong CYP3A inhibitors.

Strong And Moderate CYP3A Inducers

Coadministration of Tabrecta with a strong CYP3A inducer decreased capmatinib
exposure. Coadministration of Tabrecta with a moderate CYP3A inducer may also
decrease capmatinib exposure. Decreases in capmatinib exposure may decrease
Tabrecta anti-tumor activity. Avoid coadministration of Tabrecta with strong and moderate CYP3A inducers.

Effect Of Tabrecta On Other Drugs

CYP1A2 Substrates

Coadministration of Tabrecta increased the exposure of a CYP1A2 substrate,
which may increase the adverse reactions of these substrates. If coadministration is unavoidable between
Tabrecta and CYP1A2 substrates where minimal concentration changes may lead to serious adverse reactions, decrease the CYP1A2 substrate dosage in accordance with the approved prescribing information.

P-glycoprotein (P-gp) And Breast Cancer Resistance Protein (BCRP) Substrates

Coadministration of Tabrecta increased the exposure of a P-gp substrate and a
BCRP substrate, which may increase the adverse reactions of these substrates. If coadministration is unavoidable between
Tabrecta and P-gp or BCRP substrates where minimal concentration changes may lead to serious adverse reactions, decrease the P-gp or BCRP substrate dosage in accordance with the approved prescribing information.

MATE1 And MATE2K Substrates

Coadministration of Tabrecta may increase the exposure of MATE1 and MATE2K
substrates, which may increase the adverse reactions of these substrates. If coadministration is unavoidable between
Tabrecta and MATE1 or MATE2K substrates where minimal concentration changes may lead to serious adverse reactions, decrease the MATE1 or MATE2K substrate dosage in accordance with the approved prescribing information.

Tabrecta contraindications, and pregnancy and breastfeeding safety

Before taking Tabrecta, tell your healthcare provider about all of your medical conditions, including if you:

have or have had lung or breathing problems other than your lung cancer
have or have had liver problems
are pregnant or plan to become pregnant. Tabrecta can harm your unborn baby.

Females who are able to become pregnant:

- Your healthcare provider should do a pregnancy test before you start your treatment with
  Tabrecta.
- You should use effective birth control during treatment and for 1 week after your last dose of
  Tabrecta. Talk to your healthcare provider about birth control choices that might be right for you during this time.
- Tell your healthcare provider right away if you become pregnant or think you may be pregnant duriing treatment with
  Tabrecta.

Males who have female partners who can become pregnant:

- You should use effective birth control during treatment and for 1 week after your last dose of
  Tabrecta.
are breastfeeding or plan to breastfeed. It is not known if Tabrecta passes into your breast milk. Do not breastfeed during treatment and for 1 week after your last dose of
Tabrecta.

Tell your healthcare provider about all the medicines you take or start taking, including prescription and over-the-counter medicines, vitamins, and herbal supplements.