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Indications and Dosage
Oral
Advanced non-small cell lung carcinoma with MET exon 14 skipping alterations Adult: 450 mg once daily. Continue treatment until disease progression or unacceptable toxicity. Dosing reduction, interruption, or discontinuation may be required depending on the patient’s experienced adverse drug reaction (refer to specific product guidelines).
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Administration
Should be taken with food. Swallow whole, do not split/crush/chew. Take at the same time each day.
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Contraindications
Pregnancy and lactation.
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Adverse Reactions
Significant: Hepatotoxicity (e.g. increased ALT and AST).
Gastrointestinal disorders: Nausea, vomiting, diarrhoea, abdominal pain, constipation. General disorders and administration site conditions: Oedema, fatigue/asthenia. Infections and infestations: Pneumonia. Investigations: Increased creatinine, lipase, and amylase. Metabolism and nutrition disorders: Hypoalbuminaemia, decreased appetite. Musculoskeletal and connective tissue disorders: Musculoskeletal pain. Respiratory, thoracic and mediastinal disorders: Cough, dyspnoea, pleural effusion. Potentially Fatal: Interstitial pulmonary disease (ILD) or ILD-like adverse reactions (e.g. pneumonitis). |
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PO: Z (Teratogenicity and embryo-foetal death were observed in animal studies. Avoid during pregnancy.)
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Patient Counseling Information
This drug may cause fatigue and asthenia, if affected, do not drive or operate machinery.
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Monitoring Parameters
Before treatment initiation, assess MET exon 14 skipping alterations status via tumour biopsy; plasma specimen may be used only when tumour biopsy cannot be obtained; pregnancy status (in women of childbearing potential). Monitor LFTs (at baseline, every 2 weeks for the 1st 3 months, and as necessary thereafter), CBC, electrolytes, and renal function tests. Assess pulmonary symptoms which may indicate ILD/pneumonitis.
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Drug Interactions
Decreased exposure with strong P-glycoprotein (P-gp) or strong CYP inducers (e.g. carbamazepine, phenytoin, rifampicin). Increased exposure and the risk of adverse reactions with dual strong CYP3A and P-gp inhibitors (e.g. itraconazole). May inhibit the transport of P-gp sensitive substrates (e.g. digoxin) and breast cancer resistance protein substrates. May impair the exposure to metformin.
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Food Interaction
St. John’s wort may decrease tepotinib exposure.
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Lab Interference
Tepotinib or its main metabolite inhibits the renal tubular transporter proteins organic cation transporter (OCT) 2 and multidrug and toxin extrusion transporters (MATE) 1 and 2; interpret renal function tests that rely on serum creatinine with caution.
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Action
Description: Tepotinib is a tyrosine kinase inhibitor which selectively targets mesenchymal-epithelial transition (MET). It inhibits the phosphorylation of hepatocyte growth factor-dependent and-independent MET and the MET-dependent downstream signalling pathways, thereby causing the inhibition of tumour cell proliferation, anchorage-independent growth, and metastases of MET-dependent tumour cells.
Pharmacokinetics: Absorption: Bioavailability: 71.6% (fed state). Time to peak plasma concentration: Median: 8 hours (range: 6-12 hours). Distribution: Volume of distribution: 1,038 L. Plasma protein binding: 98%. Metabolism: Metabolised mainly by the CYP3A4 and CYP2C8 isoenzyme into the major metabolite M506. Excretion: Via faeces (approx 85% [45% as unchanged drug]); urine (approx 14% [7% as unchanged drug]). Elimination half-life: 32 hours. |
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Chemical Structure
 Source: National Center for Biotechnology Information. PubChem Compound Summary for CID 25171648, Tepotinib. https://pubchem.ncbi.nlm.nih.gov/compound/Tepotinib. Accessed Oct. 26, 2022. |
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Storage
Store below 30°C. Protect from moisture. This is a cytotoxic drug. Follow applicable procedures for receiving, handling, administration, and disposal.
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MIMS Class
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ATC Classification
L01EX21 - tepotinib ; Belongs to the class of other protein kinase inhibitors. Used in the treatment of cancer.
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References
Anon. Tepotinib. AHFS Clinical Drug Information [online]. Bethesda, MD. American Society of Health-System Pharmacists, Inc. https://www.ahfscdi.com. Accessed 31/08/2022. Anon. Tepotinib. Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 31/08/2022. Buckingham R (ed). Tepotinib. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 21/09/2022. Joint Formulary Committee. Tepotinib. British National Formulary [online]. London. BMJ Group and Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 31/08/2022. Tepmetko 225 mg Film-coated Tablets (Merck Healthcare KGaA). MIMS Singapore. http://www.mims.com/singapore. Accessed 31/08/2022. Tepmetko 225 mg Film-coated Tablets (Merck Serono Ltd). MHRA. https://products.mhra.gov.uk. Accessed 31/08/2022. Tepmetko Tablet (EMD Serono, Inc.). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed. Accessed 31/08/2022.
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