TEPMETKO SIDE EFFECTS
- Generic Name: tepotinib tablets
- Brand Name: Tepmetko
- Drug Class: MET Tyrosine Kinase Inhibitors
SIDE EFFECTS
The following adverse reactions are described in greater detail elsewhere in the labeling:
- Interstitial Lung Disease/Pneumonitis
- Hepatotoxicity
Clinical Trials Experience
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
The pooled safety population described in the WARNINGS AND PRECAUTIONS reflect exposure to TEPMETKO in 448 patients with solid tumors enrolled in five open-label, single-arm studies receiving TEPMETKO as single agent at a dose of 450 mg once daily. This included 255 patients with NSCLC positive for METex14 skipping alterations, who received TEPMETKO in VISION. Among 448 patients who received TEPMETKO, 32% were exposed for 6 months or longer, and 12% were exposed for greater than one year.
The data described below reflect exposure to TEPMETKO 450 mg once daily in 255 patients with metastatic non-small cell lung cancer (NSCLC) with METex14 skipping alterations in VISION.
Serious adverse reactions occurred in 45% of patients who received TEPMETKO. Serious adverse reactions in > 2% of patients included pleural effusion (7%), pneumonia (5%), edema (3.9%), dyspnea (3.9%), general health deterioration (3.5%), pulmonary embolism (2%), and musculoskeletal pain (2%). Fatal adverse reactions occurred in one patient (0.4%) due to pneumonitis, one patient (0.4%) due to hepatic failure, and one patient (0.4%) due to dyspnea from fluid overload.
Permanent discontinuation due to an adverse reaction occurred in 20% of patients who received TEPMETKO. The most frequent adverse reactions (> 1%) leading to permanent discontinuations of TEPMETKO were edema (5%), pleural effusion (2%), dyspnea (1.6%), general health deterioration (1.6%), and pneumonitis (1.2%).
Dosage interruptions due to an adverse reaction occurred in 44% of patients who received TEPMETKO. Adverse reactions which required dosage interruption in > 2% of patients who received TEPMETKO included edema (23%), increased blood creatinine (6%), pleural effusion (4.3%), increased ALT (3.1%), and pneumonia (2.4%).
Dose reductions due to an adverse reaction occurred in 30% of patients who received TEPMETKO. Adverse reactions which required dose reductions in > 2% of patients who received TEPMETKO included edema (19%), pleural effusion (2.7%), and increased blood creatinine (2.7%).
The most common adverse reactions (≥ 20%) in patients who received TEPMETKO were edema, fatigue, nausea, diarrhea, musculoskeletal pain, and dyspnea. The most common Grade 3 to 4 laboratory abnormalities (≥ 2%) were decreased lymphocytes, decreased albumin, decreased sodium, increased gamma-glutamyltransferase, increased amylase, increased ALT, increased AST, and decreased hemoglobin.
Table 1 summarizes the adverse reactions in VISION.
Table 1: Adverse Reactions in ≥ 10% of Patients with NSCLC with METex14 Skipping Alterations Who Received TEPMETKO in VISION
| Adverse Reactions | TEPMETKO (N = 255) |
|
| All Grades (%) | Grades 3 to 4 (%) | |
| General disorders and administration-site conditions | ||
| Edema a | 70 | 9 |
| Fatigue b | 27 | 1.6 |
| Gastrointestinal disorders | ||
| Nausea | 27 | 0.8 |
| Diarrhea | 26 | 0.4 |
| Abdominal Pain c | 16 | 0.8 |
| Constipation | 16 | 0 |
| Vomiting d | 13 | 1.2 |
| Musculoskeletal and Connective Tissue Disorders | ||
| Musculoskeletal Pain e | 24 | 2.4 |
| Respiratory, thoracic, and mediastinal disorders | ||
| Dyspnea f | 20 | 2 |
| Cough g | 15 | 0.4 |
| Pleural effusion | 13 | 5 |
| Metabolism and nutrition disorders | ||
| Decreased appetite | 16 | 1.2 |
| Infections and Infestations | ||
| Pneumonia h | 11 | 3.9 |
| a Edema includes eye edema, face edema, generalized edema, localized edema, edema, genital edema, peripheral edema, peripheral swelling, periorbital edema, and scrotal edema. b Fatigue includes asthenia and fatigue. c Abdominal Pain includes abdominal discomfort, abdominal pain, abdominal pain lower, abdominal pain upper, gastrointestinal pain, and hepatic pain. d Vomiting includes retching and vomiting. e Musculoskeletal Pain includes arthralgia, arthritis, back pain, bone pain, musculoskeletal chest pain, musculoskeletal pain, myalgia, non-cardiac chest pain, pain in extremity, and spinal pain. f Dyspnea includes dyspnea, dyspnea at rest, and dyspnea exertional. g Cough includes cough, and productive cough. h Pneumonia includes pneumonia, pneumonia aspiration, and pneumonia bacterial. |
||
Clinically relevant adverse reactions in < 10% of patients who received TEPMETKO included ILD/pneumonitis, rash, fever, dizziness, pruritus, and headache.
Table 2 summarizes the laboratory abnormalities observed in VISION.
Table 2: Select Laboratory Abnormalities (≥ 20%) That Worsened from Baseline in Patients Who Received TEPMETKO in VISION
| Laboratory Abnormalities | TEPMETKO1 | |
| Grades 1 to 4 (%) | Grades 3 to 4 (%) | |
| Chemistry | ||
| Decreased albumin | 76 | 9 |
| Increased creatinine | 55 | 0.4 |
| Increased alkaline phosphatase | 50 | 1.6 |
| Increased alanine aminotransferase | 44 | 4.1 |
| Increased aspartate aminotransferase | 35 | 2.5 |
| Decreased sodium | 31 | 8 |
| Increased potassium | 25 | 1.6 |
| Increased gamma-glutamyltransferase | 24 | 5 |
| Increased amylase | 23 | 4.6 |
| Hematology | ||
| Decreased lymphocytes | 48 | 11 |
| Decreased hemoglobin | 27 | 2 |
| Decreased leukocytes | 23 | 0.8 |
| 1 The denominator used to calculate the rate varied from 207 to 246 based on the number of patients with a baseline value and at least one post-treatment value. | ||
A clinically relevant laboratory abnormality in < 20% of patients who received TEPMETKO was increased lipase in 18% of patients, including 3.7% Grades 3 to 4.
Increased Creatinine
A median increase in serum creatinine of 31% was observed 21 days after initiation of treatment with TEPMETKO. The serum creatinine increases persisted throughout treatment and were reversible upon treatment completion.
SRC: NLM .