Tepotinib (TEPMETKO): Complete Dosing, Side-Effect Management, and Discontinuation Guide

　　1.Drug Overview and Standard Dosing Regimen

　　Tepotinib is an oral,highly selective MET tyrosine kinase inhibitor that blocks aberrant MET signaling,thereby suppressing proliferation and survival of non-small cell lung cancer(NSCLC)cells harboring MET exon 14 skipping(METex14)mutations.It is indicated for adult patients with metastatic NSCLC confirmed to carry METex14 mutations by validated molecular testing.

　　The recommended dose is 450 mg taken orally once daily with food to optimize absorption,continued until disease progression or unacceptable toxicity.Patients should take the tablet at the same time each day to maintain steady-state plasma concentrations.Tablets must be swallowed whole and must not be split,crushed,or chewed.If a dose is missed,it may be taken if more than 12 hours remain before the next scheduled dose;otherwise,the missed dose should be skipped and the regular schedule resumed.Doubling up on doses is not advised.

　　2.Proactive Prevention and Lifestyle Management of Adverse Effects

　　Peripheral edema is the most characteristic adverse effect of tepotinib.To mitigate its severity,patients should adopt a low-sodium diet,avoid prolonged standing or sitting,elevate the lower extremities during rest,and wear loose,comfortable footwear.Daily morning weight measurement is recommended;a gain of more than 2 kg within one week suggests worsening fluid retention and warrants prompt communication with the treating physician.

　　Gastrointestinal effects,including nausea and diarrhea,are relatively common.Small,frequent meals and avoidance of greasy,spicy,or extremely hot or cold foods are advisable.Antiemetics may be prescribed for persistent nausea,and antidiarrheal agents may be used short-term for frequent loose stools.

　　Hepatic protection is equally important.Patients should abstain from alcohol throughout treatment and avoid concurrent use of other potentially hepatotoxic medications or herbal supplements to minimize cumulative liver injury risk.

　　3.Dose Modification:Reduction Protocol and Restart Timing

　　When a Grade 3(severe)adverse event occurs,tepotinib should be withheld.Once the toxicity resolves to Grade 1 or baseline,the treating oncologist may consider restarting therapy at a reduced dose—typically stepping down from 450 mg to 300 mg,and if necessary,further to 225 mg.If the same Grade 3 toxicity recurs after dose reduction,further reduction or permanent discontinuation should be considered.

　　A Grade 4(life-threatening)adverse event generally warrants permanent discontinuation of tepotinib.Although interstitial lung disease(ILD)is uncommon,it can be fatal.Any new or worsening respiratory symptoms should prompt immediate drug cessation and initiation of corticosteroid therapy.

　　All dose-modification decisions must be made under the guidance of the treating oncologist.Patients are encouraged to maintain a daily log of adverse events—including type,severity,and duration—to help the clinical team determine the optimal timing for dose adjustment or discontinuation.

　　4.Discontinuation Criteria and Subsequent Treatment Planning

　　The principal indications for discontinuing tepotinib include radiographically confirmed or clinically evident disease progression;intolerable toxicity(persistent Grade 3–4 adverse events despite appropriate dose reduction);and patient-initiated withdrawal.

　　For patients who discontinue due to toxicity,alternative MET inhibitors or other therapeutic options may be discussed once toxicity has fully resolved.For those who discontinue due to disease progression,re-biopsy(tissue or liquid)is strongly recommended to identify resistance mechanisms—such as secondary MET mutations,bypass pathway activation,or histologic transformation—and to guide subsequent precision therapy.Before stopping treatment,patients should have a thorough discussion with their medical team regarding the need for bridging therapy to prevent rapid disease flare.

　　5.Special Populations:Risk Assessment and Individualized Management

　　Elderly patients(aged 65 and older)may have age-related declines in hepatic and renal function,potentially reducing drug clearance and increasing susceptibility to adverse effects.Enhanced monitoring of hematologic and biochemical parameters is recommended during the first treatment cycle,with particular attention to peripheral edema and liver function.

　　For hepatic impairment,patients with mild impairment(Child-Pugh A)do not require starting-dose adjustment;data are limited for moderate-to-severe impairment(Child-Pugh B/C),and use in these patients requires careful benefit-risk assessment.For renal impairment,mild-to-moderate impairment does not necessitate dose adjustment;patients with severe renal impairment or those on dialysis should be managed under close specialist supervision.

　　Patients with a history of interstitial lung disease or pulmonary fibrosis may be at increased risk of drug-related pneumonitis and should be especially vigilant for new respiratory symptoms.Women of childbearing potential should use highly effective contraception during treatment and for at least one week after the last dose.Male patients should use contraception during treatment and for three months after the final dose.

　　6.Drug Interactions:Managing the CYP Enzyme Pathway

　　Tepotinib is primarily metabolized by hepatic CYP3A4 and CYP2C8 enzymes.Co-administration with strong CYP3A4 inhibitors(e.g.,clarithromycin,itraconazole,ketoconazole)may significantly elevate tepotinib plasma concentrations and increase toxicity risk;concomitant use should be avoided or undertaken only with close medical supervision.Co-administration with strong CYP3A4 inducers(e.g.,rifampicin,phenytoin,St.John's wort)may substantially reduce tepotinib exposure and compromise efficacy;such combinations should be avoided.

　　Before initiating tepotinib,patients should provide their treating physician with a complete list of all prescription medications,over-the-counter drugs,vitamins,and herbal supplements to allow comprehensive interaction screening and individualized treatment planning.

　　7.Structured Monitoring Schedule and Efficacy Assessment

　　A systematic monitoring plan is the cornerstone of safe and effective tepotinib therapy.Baseline assessments before treatment initiation should include a comprehensive hepatic function panel,renal function(serum creatinine and estimated glomerular filtration rate),complete blood count,and electrocardiogram.

　　During treatment,hepatic function should be monitored monthly,particularly during the first three months;renal function should be rechecked every two to three months.The first imaging efficacy assessment(contrast-enhanced chest CT)is typically performed 6 to 8 weeks after treatment initiation,with subsequent scans every 8 to 12 weeks to dynamically evaluate tumor response and detect early progression.

　　Patients should also monitor blood pressure at home using a personal electronic sphygmomanometer and keep a daily log.Any new-onset cough,progressive dyspnea on exertion,unexplained fever,or hypoxemia during treatment should prompt immediate medical evaluation with high-resolution chest CT to exclude interstitial pneumonitis or other serious pulmonary complications.