Tepmetko

White-pink, oval, biconvex film-coated tablet of approximately 18 mm in length with embossment 'M' on one side and plain on the other side.
Each film-coated tablet contains 225 mg tepotinib (as hydrochloride hydrate).
Excipient with known effect: Each film-coated tablet contains 4.15 mg lactose.
Excipients/Inactive Ingredients: Tablet core: Mannitol, Colloidal anhydrous silica, Crospovidone, Magnesium stearate, Microcystalline cellulose.
Film-coating: Hypromellose, Lactose monohydrate, Macrogol, Triacetin, Red iron oxides (E172), Titanium dioxide.

Pharmacotherapeutic group: Antineoplastic agents, other protein kinase inhibitors, ATC code: L01EX21.
Pharmacology: Pharmacodynamics: Mechanism of action: Tepotinib is a kinase inhibitor that targets MET, including variants with exon 14 skipping alterations. Tepotinib inhibits hepatocyte growth factor (HGF)-dependent and -independent MET phosphorylation and MET-dependent downstream signaling pathways. Tepotinib also inhibited melatonin 2 and imidazoline 1 receptors at clinically achievable concentrations.
In vitro, tepotinib inhibited tumor cell proliferation, anchorage-independent growth, and migration of MET-dependent tumor cells. In mice implanted with tumor cell lines with oncogenic activation of MET, including METex14 skipping alterations, tepotinib inhibited tumor growth, led to sustained inhibition of MET phosphorylation, and, in one model, decreased the formation of metastases.
Pharmacodynamic effects: Cardiac electrophysiology: In an exposure-QTc analysis, the QTcF interval prolongation potential of tepotinib was assessed in 392 patients with various solid tumours following single or multiple daily doses of tepotinib ranging from 27 mg to 1,261 mg. At the recommended dose, no large mean increases in QTc (i.e. >20 ms) were detected. A concentration-dependent increase in QTc interval was observed. The QTc effect of tepotinib at high clinical exposures has not been evaluated.
Clinical efficacy and safety: The efficacy of tepotinib was evaluated in a single-arm, open-label, multicentre study (VISION) in adult patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) harbouring METex14 skipping alterations (n=313). Patients had an Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 to 1 and were either treatment-naïve or had progressed on up to 2 lines prior systemic therapies. Neurologically stable patients with central nervous system metastases were permitted. Patients with epidermal growth factor receptor (EGFR) or anaplastic lymphoma kinase (ALK) activating alterations were excluded. Patients received tepotinib as first-line (52%), second-line (29%) or later line (18%) therapy.
Patients who received tepotinib for second- or later line therapy (n=149) had a median age of 71 years (range 41 to 89), 52% were female and 48% male. The majority of patients were white (56%), followed by Asian patients (38%) and were never (53%) or former smokers (40%). Most patients were ≥65 years of age (75%) and 35% of patients were ≥75 years of age. The majority of patients (95%) had stage IV disease, 81% had adenocarcinoma histology. Thirteen percent of the patients had stable brain metastases. Eighty-four percent of patients had received prior platinum-based cancer therapy and 54% of patients had received immune-based cancer therapy, including 40% of patients who had received immunotherapy as monotherapy. METex14 skipping was prospectively detected by testing from tumour tissue in 65% of patients and by testing from plasma in 56% of patients; 56% of patients tested positive with both methods.
Patients received 450 mg tepotinib once daily until disease progression or unacceptable toxicity. Median treatment duration was 7.5 months (range 0 to 72). The follow-up time was at least 18 and up to 72 months at the time of the data cut-off (cut-off date 20 November 2022).
The primary efficacy outcome measure was confirmed objective response (complete response or partial response) according to Response Evaluation Criteria in Solid Tumors (RECIST v1.1) as evaluated by an Independent Review Committee (IRC). Additional efficacy outcome measures included duration of response and progression-free survival assessed by IRC as well as overall survival. (See Table 1.)

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Efficacy outcome was independent of the testing modality (in plasma or tumour specimens) used to establish the METex14 skipping status. Consistent efficacy results in subgroups by prior therapy, presence of brain metastasis or age were observed.
Pharmacokinetics: Absorption: A mean absolute bioavailability of 71.6% was observed for a single 450 mg dose of tepotinib administered in the fed state in healthy subjects; the median time to C_max was 8 hours (range from 6 to 12 hours).
The presence of food (standard high-fat, high-calorie breakfast) increased the AUC of tepotinib by about 1.6-fold and C_max by 2-fold.
Distribution: In human plasma, tepotinib is highly protein bound (98%). The mean volume of distribution (Vz) of tepotinib after an intravenous tracer dose (geometric mean and geoCV%) was 574 L (14.4%).
In vitro studies indicate that tepotinib is a substrate for P-glycoprotein (P-gp) (see Interactions).
Biotransformation: Metabolism is not the major route of elimination. No metabolic pathway accounted for more than 25% of tepotinib elimination. Only one major circulating plasma metabolite has been identified. There is only a minor contribution of the major circulating metabolite to the overall efficacy of tepotinib in humans.
Elimination: After a single oral administration of a radiolabelled dose of 450 mg tepotinib, approximately 85% of the dose was recovered in faeces (45% unchanged) and 13.6% in urine (7% unchanged). The major circulating metabolite, M506, accounted for about 40.4% of the total radioactivity in plasma.
The elimination half-life for tepotinib is approximately 32 h following oral administration.
Dose and time dependence: Tepotinib exposure increases dose-proportionally over the clinically relevant dose range up to 450 mg. The oral clearance of tepotinib did not change with respect to time. After multiple daily administrations of 450 mg tepotinib, median accumulation was 2.5 fold for C_max and 3.3 fold for AUC_0-24h.
Special populations: A population kinetic analysis did not show any effect of age (range 18 to 89 years), race, gender or body weight, on the pharmacokinetics of tepotinib.
Renal impairment: There was no clinically meaningful change in exposure in patients with mild and moderate renal impairment. Patients with severe renal impairment (creatinine clearance less than 30 mL/min) were not included in clinical trials.
Hepatic impairment: Following a single oral dose of 450 mg, tepotinib exposure was similar in healthy subjects and patients with mild hepatic impairment (Child-Pugh Class A), and was slightly lower (-13% AUC and -29% Cmax) in patients with moderate hepatic impairment (Child-Pugh Class B) compared to healthy subjects. However, the free plasma concentrations of tepotinib were in a similar range in the healthy subjects, patients with mild hepatic impairment and in patients with moderate hepatic impairment. The pharmacokinetics of tepotinib have not been studied in patients with severe (Child Pugh Class C) hepatic impairment.
Pharmacokinetic interaction studies: Clinical studies: Effect of tepotinib on CYP3A4 substrates: Multiple administrations of 450 mg tepotinib orally once daily had no clinically relevant effect on the pharmacokinetics of the sensitive CYP3A4 substrate midazolam. Effect of tepotinib on P-gp substrates: Tepotinib is an inhibitor of P-gp. Multiple administrations of tepotinib 450 mg orally once daily had a mild effect on the pharmacokinetics of the sensitive P-gp substrate dabigatran etexilate, increasing its AUC_t by approximately 50% and C_max by approximately 40%.
Effect of acid-reducing agents on tepotinib: Co-administration of omeprazole under fed conditions had no marked effect on the pharmacokinetic profile of tepotinib and its metabolites.
In-vitro studies: Effects of tepotinib on other transporters: Tepotinib or its major circulating metabolite inhibits BCRP, OCT1 and 2, organic-anion-transporting polypeptide (OATP) 1B1 and MATE1 and 2 at clinically relevant concentrations. At clinically relevant concentrations tepotinib represents a remote risk for bile salt export pump (BSEP) whilst it presents no risk for OATP1B3, organic anion transporter (OAT) 1 and 3.
Effects of tepotinib on UDP-glucuronosyltransferase (UGT): Tepotinib or its major circulating metabolite, M506, do not inhibit UGT1A1, 1A9, 2B17 1A3/4/6 and 2B7/15 at clinically relevant concentrations.
Effect of tepotinib on CYP 450 enzymes: Tepotinib is a substrate of CYP3A4 and CYP2C8. Tepotinib and M506 do not inhibit CYP1A2, CYP2A6, CYP2B6, CYP2C8, CYP2C19, CYP2D6 and CYP2E1.
Toxicology: Preclinical safety data: Oral repeat-dose toxicity studies have been conducted in rats up to 26 weeks and dogs up to 39 weeks.
Increased hepato-biliary parameters concomitant with pronounced cholangitis and pericholangitis were seen in dogs starting at doses of 30 mg tepotinib hydrochloride hydrate per kg per day (approximately 18% the human exposure at the recommended dose of TEPMETKO 450 mg once daily based on AUC). Slightly increased liver enzymes were seen in rats starting at doses 15 mg tepotinib hydrochloride hydrate per kg per day (approximately 3% of the human exposure at the recommended dose of TEPMETKO 450 mg once daily based on AUC). In dogs vomiting and diarrhoea were seen starting at 2.5 mg tepotinib hydrochloride hydrate per kg per day and at exposures approximately 0.3% of the human exposure at the recommended dose of 450 mg TEPMETKO based on AUC. All changes proved to be reversible or showed indications of reversibility or improvements.
A no-observed-adverse-effect-level (NOAEL) was established at 45 mg tepotinib hydrochloride hydrate per kg per day in the 26-week study in rats and at 10 mg tepotinib hydrochloride hydrate per kg per day in the 39-week study in dogs (both equivalent to approximately 4% of the human exposure at the recommended dose of 450 mg TEPMETKO based on AUC).
Genotoxicity: No mutagenic or genotoxic effects of tepotinib were observed in in vitro and in vivo studies. The major circulating metabolite was also shown to be non-mutagenic.
Carcinogenicity: No studies have been performed to evaluate the carcinogenic potential of tepotinib.
Reproduction toxicity: In a first oral embryo-foetal development study, pregnant rabbits received doses of 50, 150, and 450 mg tepotinib hydrochloride hydrate per kg per day during organogenesis. The dose of 450 mg/kg was discontinued due to severe maternal toxic effects. In the 150 mg per kg group, two animals aborted and one animal died prematurely. Mean foetal body weight was decreased at doses of ≥150 mg per kg per day. A dose-dependent increase of skeletal malformations, including malrotations of fore and/or hind paws with concomitant misshapen scapula and/or malpositioned clavicle and/or calcaneous and/or talus, was observed at 50 and 150 mg per kg per day.
In the second embryo-foetal development study, pregnant rabbits received oral doses of 0.5, 5, and 25 mg tepotinib hydrochloride hydrate per kg per day during organogenesis. Two malformed foetuses with malrotated hind limbs were observed (one in the 5 mg/kg group (approximately 0.21% of the human exposure at the recommended dose of TEPMETKO 450 mg once daily based on AUC) and one in the 25 mg/kg group), together with a generally increased incidence of foetuses with hind limb hyperextension.
Fertility studies of tepotinib to evaluate the possible impairment of fertility have not been performed. No morphological changes in male or female reproductive organs were seen in the repeat-dose toxicity studies in rats and dogs.

TEPMETKO is indicated for the treatment of adult patients with metastatic non-small cell lung cancer (NSCLC) harbouring mesenchymal-epithelial transition factor gene (MET) exon 14 (METex14) skipping alterations.

Treatment must be initiated and supervised by a physician experienced in the use of anticancer therapies.
Assessment of METex14 skipping alterations status: Prior to initiation of treatment with TEPMETKO the presence of METex14 skipping alterations should be confirmed by a validated test method using nucleic acids isolated from either tumour or plasma specimens. Testing for the presence of METex14 skipping alterations in tissue specimens is recommended because of higher sensitivity. However, plasma specimes may be used in patients for whom a tumour biopsy cannot be obtained. If an alteration is not detected in a plasma specimen, the feasibility of biopsy for tumour tissue testing should be evaluated.
Posology: The recommended dose is 450 mg tepotinib (2 tablets) taken once daily. Treatment should continue until disease progression or unacceptable toxicity.
If a daily dose is missed, it can be taken as soon as remembered on the same day, unless the next dose is due within 8 hours.
Dose modification for adverse reactions: Dose interruption, dose reduction or discontinuation of treatment with TEPMETKO may be required based on adverse reactions. The recommended dose reduction level for the management of adverse reactions is 225 mg (1 tablet) daily. TEPMETKO should be permanently discontinued if patients are unable to tolerate 225 mg (1 tablet) daily. Detailed recommendations for dose modification are provided in the table as follows. (See Table 2.)

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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) (see Pharmacology: Pharmacokinetics under Actions). The pharmacokinetics and safety of tepotinib in patients with severe renal impairment (creatinine clearance below 30 mL/min) have not been studied.
Hepatic impairment: No dose adjustment is recommended in patients with mild (Child Pugh Class A) or moderate (Child Pugh Class B) hepatic impairment (see Pharmacology: Pharmacokinetics under Actions). The pharmacokinetics and safety of tepotinib in patients with severe hepatic impairment (Child Pugh Class C) have not been studied.
Elderly: No dose adjustment is necessary in patients aged 65 years and above (see Pharmacology: Pharmacokinetics under Actions).
Paediatric population: Safety and efficacy of TEPMETKO in paediatric patients below 18 years of age have not been established.
Method of administration: TEPMETKO is for oral use. The tablet(s) should be taken with food and should be swallowed whole (patients should not crush or chew the tablet before swallowing).

Tepotinib has been investigated at doses up to 1,261 mg. Symptoms of overdose have not been identified. There is no specific treatment in the event of tepotinib overdose. In case of overdose, TEPMETKO should be withheld and symptomatic treatment initiated.

Hypersensitivity to tepotinib or to any of the excipients listed in Description.

Interstitial lung disease: Interstitial lung disease (ILD) or ILD-like adverse reactions (e.g. pneumonitis) have been reported, including a fatal case (see Adverse Reactions).
Patients should be monitored for new or worsening pulmonary symptoms indicative for ILD-like reactions (e.g. dyspnoea, cough, fever). TEPMETKO should be withheld immediately and patients should be promptly investigated for alternative diagnosis or specific aetiology of interstitial lung disease. TEPMETKO must be permanently discontinued if interstitial lung disease is confirmed and the patient be treated according to local clinical practice.
Hepatotoxicity: Increases in ALT and/or AST have been reported (see Adverse Reactions).
Liver enzymes (ALT and AST) and bilirubin should be monitored prior to the start of TEPMETKO, every 2 weeks during the first 3 months of treatment, then once a month. If grade 3 or higher increases occur, dose adjustment is recommended (see Dosage & Administration).
Embryo-foetal toxicity: TEPMETKO can cause foetal harm when administered to pregnant women (see Use in Pregnancy & Lactation).
Women of childbearing potential or male patients with female partners of childbearing potential should be advised of the potential risk to a foetus.
Women of childbearing potential should use effective contraception during TEPMETKO treatment and for at least 1 week after the last dose.
Male patients with female partners of childbearing potential should use barrier contraception during TEPMETKO treatment and for at least 1 week after the last dose.
Interpretation of laboratory tests: Nonclinical studies suggest that 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 (see Pharmacology: Pharmacokinetics under Actions). Creatinine is a substrate of these transporters, and the observed increases in creatinine (see Adverse Reactions) may be the result of inhibition of active tubular secretion rather than renal injury. Renal function estimates that rely on serum creatinine (creatinine clearance or estimated glomerular filtration rate) should be interpreted with caution considering this effect. In case of blood creatinine increase while on treatment, it is recommended that further assessment of the renal function be performed to exclude renal impairment.
Lactose content: TEPMETKO contains lactose. Patients with rare hereditary problems of galactose intolerance, total lactase deficiency or glucose-galactose malabsorption should not take this medicine.
Effects on ability to drive and use machines: TEPMETKO may have minor influence on the ability to drive and use machines. During treatment with tepotinib, fatigue and asthenia have been reported.

Contraception in males and females: Pregnancy testing is recommended in women of childbearing potential prior to initiating treatment with TEPMETKO.
Women of childbearing potential should use effective contraception during TEPMETKO treatment and for at least 1 week after the last dose.
Male patients with female partners of childbearing potential should use barrier contraception during TEPMETKO treatment and for at least 1 week after the last dose.
Pregnancy: There are no clinical data on the use of TEPMETKO in pregnant women. Studies in animals have shown teratogenicity (see Pharmacology: Toxicology: Preclinical safety data under Actions). Based on the mechanism of action and findings in animals, TEPMETKO can cause foetal harm when administered to pregnant women.
TEPMETKO should not be used during pregnancy, unless the clinical condition of the woman requires treatment with tepotinib. Women of childbearing potential or male patients with female partners of childbearing potential should be advised of the potential risk to a foetus.
Breast-feeding: There are no data regarding the secretion of tepotinib or its metabolites in human milk or its effects on the breast-fed infant or milk production. Breast-feeding should be discontinued during treatment with TEPMETKO and for at least 1 week after the last dose.
Fertility: No human data on the effect of TEPMETKO on fertility are available. No morphological changes in male or female reproductive organs were seen in the repeat-dose toxicity studies in rats and dogs (see Pharmacology: Toxicology: Preclinical safety data under Actions).

Summary of the safety profile: The most common adverse reactions in ≥20% of exposed to tepotinib at the recommended dose in the target indication (N=313) are oedema (81.5% of patients), mainly peripheral oedema (72.5%), hypoalbuminaemia (32.9%), nausea (31.0%), increase in creatinine (29.1%) and diarrhoea (28.8%). The most common serious adverse reactions in ≥1% of patients are peripheral oedema (3.2%), generalised oedema (1.9%) and ILD (1.0%).
The percentage of patients who had adverse events leading to permanent treatment discontinuation is 24.9%. The most common adverse reactions leading to permanent discontinuation in ≥1% of patients are peripheral oedema (5.4%), oedema (1.3%), genital oedema (1.0%) and ILD (1.0%).
The percentage of patients who had adverse events leading to temporary treatment discontinuation is 52.7%. The most common adverse reactions leading to temporary discontinuation in ≥2% of patients are peripheral oedema (19.8%), increase in creatinine (5.8%), generalised oedema (4.8%), oedema (3.8%), increase in ALT (2.9%), nausea (3.2%) and increase in amylase (1.6%).
The percentage of patients who had adverse events leading to dose reduction is 36.1%. The most common adverse reactions leading to dose reduction in ≥2% of patients are peripheral oedema (15.7%), increase in creatinine (2.9%), generalised oedema (3.2%) and oedema (2.6%).
List of adverse reactions: Adverse reactions described in the list as follows reflect exposure to tepotinib in 506 patients with various solid tumours enrolled in five open-label studies, in which patients received tepotinib as a single agent at a dose of 450 mg once daily.
The frequencies of adverse reactions are based on all-cause adverse event frequencies identified in 313 patients exposed to tepotinib at the recommended dose in the target indication, whereas frequencies for changes in laboratory parameters are based on worsening from baseline by at least 1 grade and shifts to ≥grade 3. Median duration of treatment was 7.5 months (range 0 to 72).
Frequencies presented may not be fully attributable to tepotinib alone but may contain contributions from the underlying disease or from other medicinal products used concomitantly.
The severity of adverse reactions was assessed based on the Common Terminology Criteria for Adverse Events (CTCAE), defining grade 1 = mild, grade 2 = moderate, grade 3 = severe, grade 4 = life threatening and grade 5 = death.
List of adverse reactions: An asterisk (*) indicates that additional information on the respective adverse reaction is provided after the table.
The following definitions apply to the frequency terminology used hereafter: Very common (≥1/10), Common (≥1/100 to <1/10), Uncommon (≥1/1,000 to <1/100), Rare (≥1/10,000 to <1/1,000), Very rare (<1/10,000), Frequency not known (cannot be estimated from the available data). (See Table 3.)

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Description of selected adverse reactions: Interstitial lung disease: Interstitial lung disease (ILD) or ILD-like reactions have been reported in 8 patients (2.6%), including 1 case of grade 3 or higher; serious cases occurred in 4 patients (1.3%), 1 case was fatal. Treatment was permanently discontinued in 5 patients and temporarily in 3 patients. Median time to onset of ILD was 9.4 weeks. For clinical recommendations, see Dosage & Administration and Precautions.
Increase in liver enzymes: ALT and/or AST increase led to permanent treatment discontinuation in 1 patient and infrequently led to temporary discontinuation (3.2%) or dose reduction (0.3%) of tepotinib. Median time to first onset for ALT and/or AST increase of any grade reported as an adverse event by investigators was 9.1 weeks. The median time to resolution was 3.6 weeks, 86% of events resolved. For clinical recommendations, see Dosage & Administration and Precautions.
ALP increase did not lead to any dose reductions, temporary treatment discontinuation or permanent discontinuation. The observed ALP increase was not associated with cholestasis. Median time to first onset for ALP increase of any grade reported as an adverse event by investigators was 9.1 weeks. The median time to resolution was 9.1 weeks, 80% of events resolved.
Oedema: The most frequently reported event was peripheral oedema (72.5% of patients), followed by oedema (8.3%) and generalised oedema (6.7%). Median time to onset of any-grade oedema was 9.1 weeks. The median time to resolution was 71 weeks, 39.2% of events resolved. 8% of patients had oedema events leading to permanent treatment discontinuation, of whom 5.4% had peripheral oedema. 28.4% of patients temporarily discontinued treatment and 21.7% of patients had dose reductions due to oedema. Most frequently peripheral oedema led to temporary treatment discontinuation and dose reductions (19.8% and 15.7%, respectively). Generalised oedema events led to a dose reduction in 3.2% of patients, to temporary treatment discontinuation in 4.8% and to permanent discontinuation in 0.6%.
Increase in creatinine: Increase in creatinine led to permanent treatment discontinuation in 2 patients (0.6%), temporary treatment discontinuation in 5.8% of patients and dose reduction in 2.9% of patients. Median time to onset of increase in creatinine reported as an adverse event by investigators was 3.4 weeks. The median time to resolution was 9.1 weeks, 78% of events resolved. The observed increases in creatinine are thought to occur mainly due to inhibition of renal tubular secretion (see Precautions).
Hypoalbuminaemia: Hypoalbuminaemia appeared to be long-lasting but did not lead to permanent treatment discontinuation. Dose reduction (1.6%) and temporary discontinuation (1.9%) were infrequent. Median time to onset of any-grade hypoalbuminaemia reported as an adverse event by investigators was 9.4 weeks. The median time to resolution was 28.9 weeks, 48% of events resolved.
Increase in amylase or lipase: Increases in amylase or lipase reported as an adverse event by investigators were asymptomatic and not associated with pancreatitis. 3.2% of patients temporarily discontinued treatment and there were no permanent treatment discontinuation or dose reduction. Median time to onset of any grade in lipase/amylase increase was 15 weeks. The median time to resolution was 6.1 weeks, 83% of events resolved.
QTc prolongation: QTcF prolongation to >500 ms was observed in 8 patients (2.6%) and a QTcF prolongation by at least 60 ms from baseline in 19 patients (6.1%) (see Precautions). The findings were isolated and asymptomatic; the clinical significance is unknown.
Additional information on special populations: Elderly: Of 313 patients with METex14 skipping alterations in the VISION study who received 450 mg tepotinib once daily, 79% were 65 years or older, and 8% were 85 years or older. The occurrence of grade ≥3 events increased with age. Treatment-related serious events were more frequent in patients aged ≥75 years and <85 years (21%) or those aged ≥85 years (20.8%) when compared to those younger than 65 years (10.4%), although this comparison is limited by the small sample size in patients aged ≥85 years.

Pharmacokinetic interactions: CYP inducers and P-gp inducers: Tepotinib is a substrate for P-glycoprotein (P-gp) (see Pharmacology: Pharmacokinetics under Actions). Strong P-gp inducers may have the potential to decrease tepotinib exposure. Strong CYP inducers may also decrease tepotinib exposure. Concomitant use of strong P-gp inducers (e.g. carbamazepine, phenytoin, rifampicin, St. John's wort) should be avoided.
Dual strong CYP3A inhibitors and P-gp inhibitors: The effect of strong CYP3A inhibitors or P-gp inhibitors on tepotinib has not been studied clinically. However, metabolism and in vitro data suggest concomitant use of medicinal products that are strong CYP3A inhibitors and P-gp inhibitors may increase tepotinib exposure (see Pharmacology: Pharmacokinetics under Actions), which may increase the incidence and severity of adverse reactions of tepotinib. Concomitant use of tepotinib with dual strong CYP3A and P-gp inhibitors (e.g. itraconazole) should be avoided.
P-gp substrates: Tepotinib can inhibit the transport of sensitive substrates of P-gp (see Pharmacology: Pharmacokinetics under Actions). Monitoring of the clinical effects of P-gp-dependent substances with a narrow therapeutic index (e.g. digoxin) is recommended during co-administration with TEPMETKO.
BCRP substrates: Tepotinib can inhibit the transport of sensitive substrates of the breast cancer resistance protein (BCRP) (see Pharmacology: Pharmacokinetics under Actions). Monitoring of the clinical effects of sensitive BCRP substrates is recommended during co-administration with TEPMETKO.
Metformin: Based on in vitro data, tepotinib or its metabolite may have the potential to alter the exposure to co-administered metformin in humans through inhibition of metformin's renal excretion or hepatic uptake mediated via OCT1 and 2 and MATE1 and 2 (see Pharmacology: Pharmacokinetics under Actions). Monitoring of the clinical effects of metformin is recommended during co-administration with TEPMETKO.

Incompatibilities: Not applicable.
Special precautions for disposal: No special requirements.

This medicinal product does not require special temperature storage conditions. Store in the original package in order to protect from moisture.
Shelf life: 3 years.

Targeted Cancer Therapy

L01EX21 - tepotinib ; Belongs to the class of other protein kinase inhibitors. Used in the treatment of cancer.

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