Tepmetko (tepotinib)

Tepmetko may cause serious side effects, including:

• Liver problems. Tepmetko 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 Tepmetko. 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
  • dark or “tea colored” urine
  • light-colored stools (bowel movements)
  • confusion
  • tiredness
  • loss of appetite for several days or longer
  • nausea and vomiting
  • pain, aching, or tenderness on the right side of your stomach-area (abdomen)
  • weakness
  • swelling in your stomach-area

The most common side effects of Tepmetko include:

• swelling in your face or other parts of your body
• tiredness
• nausea
• diarrhea
• muscle and joint pain
• shortness of breath

Your healthcare provider may change your dose, temporarily stop, or permanently stop treatment with Tepmetko if you develop serious side effects during treatment.

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

Patient Selection For METex14 Skipping Alterations

• Select patients for treatment with Tepmetko based on the presence of MET exon 14 skipping alterations in plasma or tumor specimens.
• Testing for the presence of MET exon 14 skipping alterations in plasma specimens is recommended only in patients for whom a tumor biopsy cannot be obtained.
• If an alteration is not detected in a plasma specimen, re-evaluate the feasibility of biopsy for tumor tissue testing.
• An FDA-approved test for detection of MET exon 14 skipping alterations in NSCLC for selecting patients for treatment with Tepmetko is not available.

Recommended Dosage

• The recommended dosage of Tepmetko is 450 mg orally once dailywith food until disease progression or unacceptable toxicity.
• Instruct patients to take their dose of Tepmetko at approximately the same time every day and to swallow tablets whole. Do not chew, crush or split tablets.
• Advise patients not to make up a missed dose within 8 hours of the next scheduled dose. If vomiting occurs after taking a dose of Tepmetko, advise patients to take the next dose at the scheduled time.

Dose Modifications For Adverse Reactions

• The recommended dose reduction of Tepmetko for the management of adverse reactions is 225 mg orally once daily.
• Permanently discontinue Tepmetko in patients who are unable to tolerate 225 mg orally once daily.
• The recommended dosage modifications of Tepmetko for adverse reactions are provided in Table 1.

Table 1: Recommended Tepmetko Dosage Modifications for Adverse Reactions

Effects Of Other Drugs On Tepmetko

Dual Strong CYP3A Inhibitors and P-gp Inhibitors

• The effect of strong CYP3A inhibitors or P-gp inhibitors on Tepmetko has not been studied clinically.
• However, metabolism and in vitro data suggest concomitant use of drugs that are strong CYP3A inhibitors and P-gp inhibitors may increase tepotinib exposure, which may increase the incidence and severity of adverse reactions of Tepmetko.
• Avoid concomitant use of Tepmetko with dual strong CYP3A inhibitors and P-gp inhibitors.

Strong CYP3A Inducers

• The effect of strong CYP3A inducers on Tepmetko has not been studied clinically.
• However, metabolism and in vitro data suggest concomitant use may decrease tepotinib exposure, which may reduce Tepmetko efficacy. Avoid concomitant use of Tepmetko with strong CYP3A inducers.

Effects Of Tepmetko On Other Drugs

Certain P-gp Substrates

• Tepotinib is a P-gp inhibitor. Concomitant use of Tepmetko increases the concentration of P-gp substrates, which may increase the incidence and severity of adverse reactions of these substrates.
• Avoid concomitant use of Tepmetko with certain P-gp substrates where minimal concentration changes may lead to serious or life-threatening toxicities.
• If concomitant use is unavoidable, reduce the P-gp substrate dosage if recommended in its approved product labeling.

• Based on findings in animal studies and the mechanism of action, Tepmetko can cause fetal harm when administered to a pregnant woman.
• There are no available data on the use of Tepmetko in pregnant women.
• There are no data regarding the secretion of tepotinib or its metabolites in human milk or its effects on the breastfed infant or milk production.
• Advise women not to breastfeed during treatment with Tepmetko and for one week after the final dose.