Applies to tepotinib: oral tablet.

Serious side effects of Tepotinib

Along with its needed effects, tepotinib may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur while taking tepotinib:

More common

• Anxiety
• chest pain or tightness
• cough
• dark urine
• difficult or labored breathing
• dizziness or lightheadedness
• fainting
• fast heartbeat
• fever or chills
• general feeling of discomfort or illness
• loss of appetite
• muscle or bone pain
• nausea or vomiting
• sneezing
• sore throat
• stomach pain
• thickening of bronchial secretions
• trouble breathing
• unusual tiredness or weakness
• yellow eyes or skin

Other side effects of Tepotinib

Some side effects of tepotinib may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects.

Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

More common

• Constipation
• diarrhea

For Healthcare Professionals

Applies to tepotinib: oral tablet.

General

The most frequently reported side effects included edema, fatigue, nausea, diarrhea, musculoskeletal pain, and dyspnea. The most common serious side effects included pleural effusion, pneumonia, dyspnea, general health deterioration, peripheral edema, generalized edema, musculoskeletal pain, and pulmonary embolism.^[Ref]

Dermatologic

Frequency not reported: Rash, pruritus^[Ref]

Gastrointestinal

Very common (10% or more): Nausea (up to 27%), diarrhea (up to 26.3%), increased amylase (includes increased amylase, hyperamylasemia; up to 23%), increased serum lipase (up to 18%), abdominal pain (includes abdominal discomfort, abdominal pain, lower abdominal pain, upper abdominal pain, gastrointestinal pain, hepatic pain; up to 16.5%), constipation (up to 16%), vomiting (includes retching, vomiting; up to 13%)^[Ref]

Based on laboratory assessment, increases in amylase and lipase from baseline were reported in 21.6% and 17.3% of patients, respectively; grade 3 or 4 increases in amylase and lipase were reported in 4.3% and 3.9% of patients, respectively. No pancreatitis was observed in a clinical study. The median time to onset of any grade in lipase/amylase increase was 11.9 weeks (range: 0.1 to 96.3 weeks) and the median time to resolution was 6 weeks (range: 0.6 to over 186.4 weeks).^[Ref]

Hematologic

Very common (10% or more): Decreased lymphocytes (up to 48%), decreased hemoglobin (up to 27%), decreased leukocytes (up to 23%)^[Ref]

Hepatic

Based on laboratory assessment, ALT and AST increases from baseline were reported in 42% and 32.9% of patients, respectively; grade 3 or higher ALT and AST were reported in 3.9% and 2.4% of patients, respectively. A fatal adverse reaction of hepatic failure occurred in 1 patient. The median time to first onset was 6.1 weeks (range: 0.1 to 34 weeks) for any grade of ALT and/or AST increase and the median time to resolution was 5 weeks (range: 0.1 to 31.1 weeks).^[Ref]

Very common (10% or more): Increased ALT (up to 44%), increased AST (up to 35%), increased GGT (up to 24%)

Frequency not reported: Hepatic failure, hepatotoxicity^[Ref]

Metabolic

Very common (10% or more): Decreased albumin (up to 76%), hypoalbuminemia (includes hypoalbuminemia, decreased blood albumin; up to 23.9%), decreased appetite (up to 16%)^[Ref]

Based on laboratory assessment, decrease in albumin from baseline by 1 grade was reported in 38.4% of patients; decreases of 2 and 3 grades were observed in 29.8% and 2.7%, respectively. The median time to onset of any-grade hypoalbuminemia was 9.4 weeks (range: 0.1 to 150.3 weeks) and the median time to resolution ranged between 0.3 and over 124.9 weeks. Hypoalbuminemia appeared to be long-lasting but did not lead to permanent treatment discontinuation.^[Ref]

Musculoskeletal

Very common (10% or more): Musculoskeletal pain (includes arthralgia, arthritis, back pain, bone pain, musculoskeletal chest pain, musculoskeletal pain, myalgia, noncardiac chest pain, pain in extremity, spinal pain; up to 24%)^[Ref]

Nervous system

Frequency not reported: Dizziness, headache^[Ref]

Other

Edema was reported in 69.8% of patients; it included peripheral edema (which was the most frequent at 60%), generalized edema, and localized edema (e.g., edema of the face, periorbital edema, genital edema). The median time to onset of any-grade edema was 7.9 weeks (range: 0.1 to 58.3 weeks) and the median time to resolution was about 67 weeks (range: 0.1 to over 162 weeks).

Based on laboratory assessment, increased alkaline phosphatase from baseline was reported in 47.5% of patients; grade 3 or 4 increases occurred in 1.6% of patients. The median time to first onset for increased alkaline phosphatase of any grade was 5.7 weeks (range: 0.7 to 28 weeks) and the median time to resolution was 9.8 weeks (range: 0.9 to over 45.3 weeks). The observed alkaline phosphatase increase was not associated with cholestasis.^[Ref]

Very common (10% or more): Edema (includes eye edema, face edema, generalized edema, localized edema, edema, genital edema, peripheral edema, peripheral swelling, periorbital edema, scrotal edema; up to 70%), peripheral edema (up to 60%), increased alkaline phosphatase (up to 50%), decreased sodium (up to 31%), fatigue/asthenia (up to 27.5%), increased potassium (up to 25%)

Common (1% to 10%): General health deterioration, generalized edema

Frequency not reported: Fever^[Ref]

Renal

Based on laboratory assessment, increases in creatinine from baseline were reported in 52.9% of patients; grade 3 occurred in 1 patient. The observed increases in creatinine were thought to occur due to competition of renal tubular secretion. The median time to onset of increased creatinine was 3.1 weeks (range: 0.1 to 78.4 weeks) and the median time to resolution was 12.1 weeks (range: 0.4 to 104.3 weeks).^[Ref]

Very common (10% or more): Increased creatinine (includes increased blood creatinine, hypercreatinaemia; up to 55%)^[Ref]

Respiratory

In a clinical study, 2.4% of patients developed ILD or ILD-like reactions; 1 fatal case of acute respiratory failure secondary to ILD was reported. The median time to onset was 9.1 weeks (range: 3 to 42.1 weeks).^[Ref]

Very common (10% or more): Dyspnea (includes dyspnea, dyspnea at rest, exertional dyspnea; up to 20%), cough (includes cough, productive cough; up to 15%), pleural effusion (up to 13%), pneumonia (includes pneumonia, aspiration pneumonia, bacterial pneumonia; up to 11%)

Common (1% to 10%): Pulmonary embolism, interstitial lung disease (ILD)/ILD-like reactions (includes ILD, pneumonitis, acute respiratory failure), pneumonitis^[Ref]