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TEPMETKO is a brand name for Tepotinib, supplied as a tablet. The medicine, its uses, side effects and dosage are the same regardless of brand.
Used for: TEPMETKO (tepotinib) is indicated for the treatment of adult patients with locally advanced unresectable or metastatic non-small cell lung cancer (NSCLC) harbouring mesenchymal- epithelial transition (MET) tyrosine kinase receptor exon 14 skipping alterations. Documentation of MET tyrosine kinase receptor exon 14…
Verbatim from this product's HC label. Tap a section to expand.
2 Recommended Dose and Dosage Adjustment The recommended dose of TEPMETKO is 450 mg (as tepotinib hydrochloride) once daily with food (two tablets). Treatment should continue until disease progression or unacceptable toxicity. Dose Modification The recommended dose reduction of TEPMETKO for the management of adverse reactions is 225 mg orally once daily.
Permanent discontinuation of TEPMETKO is recommended 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 Adverse Reaction Severity Dose Modification Interstitial Lung Disease (ILD) / Pneumonitis (see WARNINGS AND PRECAUTIONS) Any grade Withhold TEPMETKO if ILD is suspected.
Permanently discontinue TEPMETKO if ILD is confirmed. TEPMETKO® Product Monograph Page 6 of 32 Adverse Reaction Severity Dose Modification Increased alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) without increased total bilirubin (see WARNINGS AND PRECAUTIONS) Grade 3 Withhold TEPMETKO until recovery to baseline ALT/AST.
If recovered to baseline within 7 days, then resume TEPMETKO at the same dose; otherwise resume TEPMETKO at a reduced dose. Grade 4 Permanently discontinue TEPMETKO. Increased ALT and/or AST with increased total bilirubin in the absence of cholestasis or hemolysis (see WARNINGS AND PRECAUTIONS) ALT and/or AST greater than 3 times the upper limit of normal (ULN) with total bilirubin greater than 2 times ULN Permanently discontinue TEPMETKO.
Other adverse reactions (see ADVERSE REACTIONS) Grade 2 Maintain dose level. If intolerable, consider withholding TEPMETKO until resolved, then resume TEPMETKO at a reduced dose. Grade 3 Withhold TEPMETKO until resolved, then resume TEPMETKO at a reduced dose.
Grade 4 Permanently discontinue TEPMETKO.
Geriatrics (> 65 years of age):
No dose adjustment is necessary in patients aged 65 years and above (see ACTION AND CLINICAL PHARMACOLOGY, Pharmacokinetics, Special Populations and Conditions).
Hepatic Impairment:
No dose adjustment is recommended in patients with mild (Child Pugh A) or moderate (Child Pugh B) hepatic impairment. The pharmacokinetics and safety of TEPMETKO in patients with severe hepatic impairment (Child Pugh C) have not been studied (see WARNINGS AND PRECAUTIONS, Hepatic and ACTION AND CLINICAL PHARMACOLOGY, Pharmacokinetics, Special Populations and Conditions).
1 Adverse Reaction Overview The pooled safety population reflects exposure to TEPMETKO in 506 patients with various solid tumours enrolled in five open-label, single-arm studies, in which patients received TEPMETKO monotherapy at a dose of 450 mg once daily.
This includes 313 patients with advanced NSCLC harbouring METex14 skipping alterations included in the pivotal clinical study (VISION). 7 weeks (range 0 to 312 weeks), with 44% exposed for 6 months or longer, and 22% exposed for greater than one year.
4 weeks (range 0 to 312 weeks), with 60% exposed for 6 months or longer and 32% exposed for greater than one year. In the VISION study, a treatment-emergent adverse event (TEAE) was reported by 99% of patients who received TEPMETKO in the target indication.
5% of patients); hypoalbuminemia; nausea, increase in creatinine; diarrhea; decreased appetite; and dyspnea (see Clinical Trial Adverse Reactions). 8% of patients who received TEPMETKO. 2%). 1%, respectively. 4%)]. 6%). 3%) due to interstitial lung disease.
3%). 2%). 9% of patients who received TEPMETKO in VISION. 0%). 7% of patients who received TEPMETKO in VISION. The maximum permitted period of continuous treatment interruption was 21 days. 2%). 1% of patients who received TEPMETKO in VISION.
2%). 2 Clinical Trial Adverse Reactions Because clinical trials are conducted under very specific conditions, the adverse reaction rates observed in the clinical trials may not reflect the rates observed in practice and should not be compared to the rates in the clinical trials of another drug.
Adverse reaction information from clinical trials is useful for identifying drug-related adverse events and for approximating rates. The safety of TEPMETKO was evaluated in 313 adult patients with locally advanced (stage IIIb) or metastatic (stage IV) NSCLC harbouring METex14 skipping alterations who received at least one dose of TEPMETKO in the single-arm, open-label Phase II VISION study.
Please see the Serious Warnings and Precautions Box at the beginning of Part 1:
Health Professional Information. Route of Administration Dosage Form / Strength/Composition Non-medicinal Ingredients oral tablets / 225 mg tepotinib (as tepotinib hydrochloride) Colloidal silicon dioxide, crospovidone, hypromellose, lactose monohydrate, magnesium stearate, mannitol, microcrystalline cellulose, polyethylene glycol, red iron oxides (E172), titanium dioxide, triacetin.
TEPMETKO® Product Monograph Page 8 of 32 General Patient selection for METex14 skipping alterations Patients treated with TEPMETKO must have a documented METex14 skipping alteration based on a validated METex14 plasma and/or tissue assay.
Assessment for the presence of METex14 skipping alterations should be performed by laboratories with demonstrated proficiency in the specific technology being utilized (see CLINICAL TRIALS). Driving and Operating Machinery No studies on the effects of TEPMETKO on the ability to drive or use machines have been performed.
Caution should be exercised when operating a vehicle or potentially dangerous machinery until the patient is reasonably certain that TEPMETKO does not affect them adversely. Hepatic Hepatotoxicity Hepatotoxicity occurred in patients with advanced NSCLC with METex14 skipping alterations who received TEPMETKO monotherapy at the recommended dosage regimen (n=313) (see ADVERSE REACTIONS).
8% of patients treated with TEPMETKO. 8%. 3%) treated with TEPMETKO. 6%) had dose reductions due to increase in ALT/AST. 4 weeks). Liver function tests (ALT and AST, and total bilirubin) should be monitored 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.
TEPMETKO is contraindicated in patients who are hypersensitive to this drug or to any ingredient in the formulation, including any non-medicinal ingredient, or component of the container. For a complete listing, see Dosage Forms, Strengths, Composition and Packaging.
Not medical advice. Always read the patient information leaflet and follow your prescriber or pharmacist.
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Renal Impairment:
No dose adjustment is recommended in patients with mild or moderate renal impairment (creatinine clearance 30 to 89 mL/min). The pharmacokinetics and safety of TEPMETKO in patients with severe renal impairment (creatinine clearance below 30 mL/min) have not been studied (see WARNINGS AND PRECAUTIONS, Monitoring and Laboratory Tests and ACTION AND CLINICAL PHARMACOLOGY, Pharmacokinetics, Special Populations and Conditions).
4 Administration TEPMETKO is for oral use. Tablets should be taken once daily with food, at approximately the same time each day. Tablets should be swallowed whole. Tablets should not be chewed, crushed, or split. 5 Missed Dose If a daily dose of TEPMETKO is missed, it should be taken with food as soon as remembered on the same day, unless the next dose is due within 8 hours.
If vomiting occurs after taking a dose of TEPMETKO, patients should be advised to take the next dose at the scheduled time.
TEPMETKO was administered as monotherapy at a dose of 450 mg once daily. 4 weeks (range 0 to 312 weeks). The median age was 72 years TEPMETKO® Product Monograph Page 12 of 32 (range: 41 to 94 years), with 79% of patients ≥ 65 years of age.
Patients with active brain metastases, clinically significant uncontrolled cardiac disease, severe hepatic impairment, and severe renal impairment were excluded from the study. Table 3 summarizes the incidence of adverse reactions that occurred in ≥1% of patients with advanced NSCLC harbouring METex14 skipping alterations.
2) Nervous system disorders […]
Based on the severity of the adverse reaction, TEPMETKO should be withheld, dose reduced, or permanently discontinued. See DOSAGE AND ADMINISTRATION, Dose Modification. Monitoring and Laboratory Tests Interpretation of laboratory tests Increase in creatinine In patients with advanced NSCLC with METex14 skipping alterations who received TEPMETKO monotherapy at the recommended dosage regimen (n=313), a median increase in serum creatinine of 30% was computed 21 days after initiation of treatment with TEPMETKO (see ADVERSE REACTIONS).
In vitro studies suggest that tepotinib or its main metabolite inhibit the renal tubular transporter proteins organic cation transporter (OCT) 2 and multidrug and toxin extrusion (MATE) 2 at clinically relevant concentrations (see DRUG INTERACTIONS, Drug-Drug Interactions).
As TEPMETKO® Product Monograph Page 9 of 32 creatinine is a substrate of these transporters, one component of the observed increases in serum creatinine may be the inhibition of active tubular secretion. Renal function estimates that rely on serum creatinine [creatinine clearance or estimated glomerular filtration rate (GFR)] should be interpreted with caution considering this effect.
If persistent elevations in serum creatinine are observed, a comprehensive evaluation of the patient’s clinical status should be performed, and alternative markers of renal function should be considered in line with local clinical practice.
6%) with advanced NSCLC with METex14 skipping alterations who received TEPMETKO monotherapy at the recommended dosage regimen (n=313). Four of 8 patients had serious adverse reactions. One of 8 patients had an adverse reaction which was Grade ≥ 3, serious, and resulted in death.
6%) permanently discontinued TEPMETKO due to ILD / pneumonitis. (See ADVERSE REACTIONS). , dyspnea, cough, fever). TEPMETKO should be immediately withheld in patients with suspected ILD / pneumonitis. If no other potential causes of ILD / pneumonitis are identified, TEPMETKO must be permanently discontinued and the patient should be treated appropriately.
Sexual Health Reproduction TEPMETKO can cause fetal harm when administered to a pregnant woman (see Special Populations). Women of childbearing potential or male patients with female partners of childbearing potential should be advised of the potential risk to a fetus.
Pregnancy testing Pregnancy testing is recommended in women of childbearing potential prior to initiating treatment with TEPMETKO. Contraception in females and males Women of childbearing potential should use effective contraception during TEPMETKO treatment and for 1 week after the final dose.
Male patients with female partners of childbearing potential should use barrier contraception during TEPMETKO treatment and for 1 week after the final dose. Fertility No clinical data on the effect of TEPMETKO on fertility are available.
See NON-CLINICAL TOXICOLOGY. 1 Pregnant Women There are no clinical data on the use of TEPMETKO in pregnant women or on the transmission of TEPMETKO through the seminal fluid of male patients to their female partners of childbearing potential.
003 times the human exposure based on area […]