TEPOTINIB Drug Interactions: What You Need to Know

INTERACTIONS Certain P-gp substrates : Avoid coadministration of TEPMETKO with P-gp substrates where minimal concentration changes may lead to serious or life-threatening toxicities. ( 7.1 )

7.1 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 <span class="opacity-50 text-xs">[see Clinical Pharmacology (12.3) ]</span>, 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.

None. None. ( 4 )

AND PRECAUTIONS Interstitial Lung Disease (ILD)/Pneumonitis : Immediately withhold TEPMETKO in patients with suspected ILD/pneumonitis. Permanently discontinue TEPMETKO in patients diagnosed with ILD/pneumonitis of any severity. ( 2.4 , 5.1 ) Hepatotoxicity : Monitor liver function tests. Withhold, dose reduce, or permanently discontinue TEPMETKO based on severity. ( 5.2 )

Pancreatic

Toxicity : Monitor amylase and lipase. Withhold, dose reduce, or permanently discontinue TEPMETKO based on severity. ( 5.3 ) Embryo-fetal toxicity : TEPMETKO can cause fetal harm. Advise of potential risk to a fetus and use of effective contraception. ( 5.4 , 8.1 , 8.3 )

5.1 Interstitial Lung Disease (ILD)/Pneumonitis ILD/pneumonitis, which can be fatal, occurred in patients treated with TEPMETKO <span class="opacity-50 text-xs">[see Adverse Reactions (6.1) ]</span>. ILD/pneumonitis occurred in 2% patients treated with TEPMETKO, with one patient experiencing a Grade 3 or higher event; this event resulted in death. Five patients (1%) discontinued TEPMETKO due to ILD/pneumonitis. Monitor patients for new or worsening pulmonary symptoms indicative of ILD/pneumonitis (e.g., dyspnea, cough, fever). Immediately withhold TEPMETKO in patients with suspected ILD/pneumonitis and permanently discontinue if no other potential causes of ILD/pneumonitis are identified <span class="opacity-50 text-xs">[see Dosage and Administration (2.4) ]</span>.

5.2 Hepatotoxicity Hepatotoxicity occurred in patients treated with TEPMETKO <span class="opacity-50 text-xs">[see Adverse Reactions (6.1) ]</span> . Increased alanine aminotransferase (ALT)/increased aspartate aminotransferase (AST) occurred in 18% of patients treated with TEPMETKO.

Grade

3 or 4 increased ALT/AST occurred in 4.7% of patients. A fatal adverse reaction of hepatic failure occurred in one patient (0.2%). Four patients (0.8%) discontinued TEPMETKO due to increased ALT/AST. The median time-to-onset of Grade 3 or higher increased ALT/AST was 47 days (range 1 to 262). Monitor liver function tests (including ALT, AST, and total bilirubin) prior to the start of TEPMETKO, every 2 weeks during the first 3 months of treatment, then once a month or as clinically indicated, with more frequent testing in patients who develop increased transaminases or bilirubin. Based on the severity of the adverse reaction, withhold, dose reduce, or permanently discontinue TEPMETKO [see Dosage and Administration (2.4) ] .

5.3 Pancreatic Toxicity Elevations in amylase and lipase levels occurred in patients treated with TEPMETKO <span class="opacity-50 text-xs">[see Adverse Reactions (6.1) ]</span>. Increased amylase and/or lipase occurred in 13% of patients treated with TEPMETKO.

Grade

3 and 4 increased amylase and/or lipase occurred in 5% and 1.2% of patients, respectively. Monitor amylase and lipase at baseline and regularly during treatment with TEPMETKO. Based on the severity of the adverse drug reaction, temporarily withhold, dose reduce, or permanently discontinue TEPMETKO [see Dosage and Administration (2.4) ].

5.4 Embryo-Fetal Toxicity Based on findings in animal studies and its mechanism of action TEPMETKO can cause fetal harm when administered to a pregnant woman. Oral administration of tepotinib to pregnant rabbits during the period of organogenesis resulted in malformations (teratogenicity) and anomalies at exposures less than the human exposure based on area under the curve (AUC) at the 450 mg daily clinical dose. Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential or males with female partners of reproductive potential to use effective contraception during treatment with TEPMETKO and for one week after the last dose. [See Use in Specific Populations (8.1 , 8.3) ]