Scemblix
- Generic Name: asciminib tablets
- Brand Name: Scemblix
Scemblix (Asciminib Tablets) side effects drug center
Scemblix Side Effects Center
What Is Scemblix?
Scemblix (asciminib) is a kinase inhibitor indicated for the treatment of adult patients with Philadelphia chromosome-positive chronic myeloid leukemia (Ph+ CML) in chronic phase (CP), previously treated with two or more tyrosine kinase inhibitors (TKIs) and Ph+ CML in CP with the T315I mutation.
What Are Side Effects of Scemblix?
Side effects of Scemblix include:
- upper respiratory tract infections,
- musculoskeletal pain,
- fatigue,
- nausea,
- rash,
- diarrhea,
- platelet count decreased,
- triglycerides increased,
- neutrophil count decreased,
- hemoglobin decreased,
- creatine kinase increased,
- alanine aminotransferase increased,
- lipase increased, and
- amylase increased.
Dosage for Scemblix
The recommended dosage of Scemblix in Philadelphia chromosome-positive chronic myeloid leukemia (Ph+ CML) in chronic phase (CP) is 80 mg orally once daily or 40 mg twice daily.
The recommended dosage of Scemblix in Ph+ CML in CP with the T315I mutation is 200 mg orally twice daily.
Scemblix In Children
The safety and efficacy of Scemblix in pediatric patients have not been established.
What Drugs, Substances, or Supplements Interact with Scemblix?
Scemblix may interact with other medicines such as:- strong CYP3A4 inhibitors,
- itraconazole oral solution containing hydroxypropyl-β-cyclodextrin,
- CYP3A4 substrates,
- CYP2C9 substrates, and
- P-gp substrates.
Scemblix During Pregnancy and Breastfeeding
Tell your doctor if you are pregnant or plan to become pregnant before using Scemblix; it may harm a fetus. The pregnancy status of females of reproductive potential should be verified prior to starting treatment with Scemblix. Females of reproductive potential should use effective contraception during treatment with Scemblix and for 1 week after the last dose. It is unknown if Scemblix passes into breast milk or how it could affect a nursing child. Because of the potential for serious adverse reactions in the breastfed child, breastfeeding is not recommended during treatment with Scemblix and for 1 week after the last dose. Consult your doctor before breastfeeding.Additional Information
Our Scemblix (asciminib) Tablets, for Oral Use Side Effects Drug Center provides a comprehensive view of available drug information on the potential side effects when taking this medication.
This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.
Scemblix Professional Information
SIDE EFFECTS
The following clinically significant adverse reactions can occur with SCEMBLIX and are discussed in greater detail in other sections of the labeling:
- Myelosuppression [see WARNINGS AND PRECAUTIONS]
- Pancreatic Toxicity [see WARNINGS AND PRECAUTIONS]
- Hypertension [see WARNINGS AND PRECAUTIONS]
- Hypersensitivity [see WARNINGS AND PRECAUTIONS]
- Cardiovascular Toxicity [see WARNINGS AND PRECAUTIONS]
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 WARNING AND PRECAUTIONS reflect exposure to SCEMBLIX at 10 mg to 200 mg orally twice daily (between 0.25 to 5 times the recommended dosage for the 80 mg daily dosage and between 0.05 times and up to the recommended dosage for the 200 mg twice daily dosage) in 356 patients enrolled in one of two clinical trials , including patients with Ph+ CML in chronic (CP) receiving SCEMBLIX as monotherapy: study CABL001A2301 (ASCEMBL) and study CABL001X2101 [see Clinical Studies]. Among the 356 patients receiving SCEMBLIX, the median duration of exposure to SCEMBLIX was 89 weeks (range, 0.1 to 342 weeks).
Adverse Reactions In Patients With Ph+ CML-CP, Previously Treated With Two Or More TKIs
The clinical trial randomized and treated 232 patients with Ph+ CML-CP, previously treated with two or more TKIs to receive SCEMBLIX 40 mg twice daily or bosutinib 500 mg once daily (ASCEMBL) [see Clinical Studies]. The safety population (received at least 1 dose of SCEMBLIX) included 156 patients with Ph+ CML-CP, previously treated with two or more TKIs. Among patients who received SCEMBLIX, 83% were exposed for 24 weeks or longer and 67% were exposed for 48 weeks or longer.
Serious adverse reactions occurred in 15% of patients who received SCEMBLIX. Serious adverse reactions in ≥ 1% included pyrexia (1.9%), cardiac failure congestive (1.3%), thrombocytopenia (1.3%), and urinary tract infection (1.3%). Two patients (1.3%) had a fatal adverse reaction, one each for mesenteric artery thrombosis and ischemic stroke.
Permanent discontinuation of SCEMBLIX due to an adverse reaction occurred in 7% of patients. Adverse reactions which resulted in permanent discontinuation of SCEMBLIX in > 2% of patients included thrombocytopenia (3.2%) and neutropenia (2.6%).
Dosage interruptions of SCEMBLIX due to an adverse reaction occurred in 38% of patients. Adverse reactions which required dosage interruption in > 5% of patients included thrombocytopenia (19%) and neutropenia (18%).
Dose reductions of SCEMBLIX due to an adverse reaction occurred in 7% of patients. Adverse reactions which required dose reductions in > 1% of patients included thrombocytopenia (4.5%) and neutropenia (1.3%).
The most common (≥ 20%) adverse reactions in patients who received SCEMBLIX were upper respiratory tract infections and musculoskeletal pain.
The most common select laboratory abnormalities that worsened from baseline in ≥ 20% of patients who received SCEMBLIX were platelet count decreased, triglycerides increased, neutrophil count decreased, hemoglobin decreased, creatine kinase increased, and alanine aminotransferase (ALT) increased.
Table 3 summarizes the adverse reactions in ASCEMBL.
Table 3: Adverse Reactions (≥ 10%) in Patients with Ph+ CML in CP, Previously Treated with Two or More TKIs Who Received SCEMBLIX in ASCEMBL
| Adverse Reaction | SCEMBLIX N = 156 |
Bosutinib N = 76 |
||
| All Grades % | Grade 3 or 4 % | All Grades % | Grade 3 or 4 % | |
| Infections and infestations | ||||
| Upper respiratory tract infectiona | 26 | 0.6 | 12 | 1.3 |
| Musculoskeletal and connective tissue disorders | ||||
| Musculoskeletal painb | 22 | 2.6 | 16 | 1.3 |
| Arthralgia | 12 | 0 | 3.9 | 0 |
| Nervous system disorders | ||||
| Headache | 19 | 1.9 | 15 | 0 |
| General disorders and administration-site conditions | ||||
| Fatiguec | 17 | 0.6 | 11 | 1.3 |
| Skin and subcutaneous tissue disorders | ||||
| Rashd | 17 | 0.6 | 30 | 8 |
| Vascular disorders | ||||
| Hypertensione | 13 | 6 | 5 | 3.9 |
| Gastrointestinal disorders | ||||
| Diarrheaf | 12 | 0 | 71 | 11 |
| Nausea | 12 | 0.6 | 46 | 0 |
| Abdominal paing | 10 | 0 | 24 | 2.6 |
| Abbreviations: Ph+ CML in CP, Philadelphia chromosome-positive chronic myeloid leukemia (Ph+ CML) in chronic phase (CP); TKIs, tyrosine kinase inhibitors. aUpper respiratory tract infection includes: nasopharyngitis, upper respiratory tract infection, rhinitis, pharyngitis, respiratory tract infection, and pharyngotonsillitis. bMusculoskeletal pain includes: pain in extremity, back pain, myalgia, non-cardiac chest pain, neck pain, bone pain, spinal pain, arthritis, and musculoskeletal pain. cFatigue includes: fatigue and asthenia. dRash includes: rash, rash maculopapular, dermatitis acneiform, rash pustular, eczema, dermatitis, skin exfoliation, dermatitis exfoliative generalised, rash morbilliform, drug eruption, erythema multiforme, and rash erythematous. eHypertension includes: hypertension and hypertensive crisis. fDiarrhea includes: diarrhea and colitis. gAbdominal pain includes: abdominal pain, abdominal pain upper, abdominal discomfort, abdominal pain lower, abdominal tenderness, and epigastric discomfort. |
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Clinically relevant adverse reactions in < 10% of patients treated with SCEMBLIX in ASCEMBL included: cough, dyspnea, pleural effusion, dizziness, neuropathy peripheral, edema, pyrexia, vomiting, constipation, dyslipidemia, decreased appetite, pruritus, urticaria, lower respiratory tract infection, influenza, urinary tract infection, pneumonia, hemorrhage, arrhythmia (including electrocardiogram QT prolonged), palpitations, cardiac failure congestive, vision blurred, dry eye, hypothyroidism, and febrile neutropenia.
Table 4 summarizes the laboratory abnormalities in ASCEMBL.
Table 4: Select Laboratory Abnormalities (≥ 10%) That Worsened from Baseline in Patients with Ph+ CML in CP, Previously Treated with Two or More Tyrosine Kinase Inhibitors Who Received SCEMBLIX in ASCEMBL
| Laboratory Abnormality | SCEMBLIX1 | Bosutinib1 | ||
| All Grades % | Grade 3 or 4 % | All Grades % | Grade 3 or 4 % | |
| Hematologic parameters | ||||
| Platelet count decreased | 46 | 24 | 36 | 12 |
| Neutrophil count decreased | 39 | 17 | 33 | 13 |
| Hemoglobin decreased | 35 | 2 | 54 | 5 |
| Lymphocyte count decreased | 18 | 2 | 34 | 2.6 |
| Biochemical parameters | ||||
| Triglycerides increased | 44 | 5 | 29 | 2.6 |
| Creatine kinase increased | 27 | 2.6 | 22 | 5 |
| Alanine aminotransferase (ALT) increased | 23 | 0.6 | 50 | 16 |
| Aspartate aminotransferase (AST) increased | 19 | 1.9 | 46 | 7 |
| Uric acid increased | 19 | 6 | 17 | 2.6 |
| Phosphate decreased | 17 | 6 | 18 | 7 |
| Lipase increased | 14 | 3.9 | 18 | 7 |
| Calcium corrected decreased | 14 | 0.6 | 20 | 0 |
| Creatinine increased | 14 | 0 | 26 | 0 |
| Amylase increased | 12 | 1.3 | 13 | 0 |
| Bilirubin increased | 12 | 0 | 4.2 | 0 |
| Cholesterol increased | 11 | 0 | 8 | 0 |
| Potassium decreased | 10 | 0 | 9 | 0 |
| 1 The denominator used to calculate the rate for SCEMBLIX and bosutinib varied from 145 to 156 and 71 to 76, respectively, based on the number of patients with a baseline value and at least one post-treatment value. | ||||
CTCAE version 4.03.
Adverse Reactions In Patients With Ph+ CML-CP With The T315I Mutation
The single-arm clinical trial enrolled patients with Ph+ CML-CP with the T315I mutation [see Clinical Studies]. The safety population (received at least 1 dose of SCEMBLIX) included 48 patients with Ph+ CML-CP with the T315I mutation who received 200 mg of SCEMBLIX twice daily. Among these patients, 83% were exposed for 24 weeks or longer and 75% were exposed for 48 weeks or longer.
Serious adverse reactions occurred in 23% of patients who received SCEMBLIX. Serious adverse reactions in > 1% included abdominal pain (4.2%), vomiting (4.2%), pneumonia (4.2%), musculoskeletal pain (2.1%), headache (2.1%), hemorrhage (2.1%), constipation (2.1%), arrhythmia (2.1%), and pleural effusion (2.1%).
Permanent discontinuation of SCEMBLIX due to an adverse reaction occurred in 10% of patients. Adverse reactions which resulted in permanent discontinuation of SCEMBLIX in > 2% of patients included pancreatic enzymes increased (2.1%).
Dosage interruptions of SCEMBLIX due to an adverse reaction occurred in 31% of patients. Adverse reactions which required dosage interruption in > 5% of patients included pancreatic enzymes increased (17%) and thrombocytopenia (8%).
Dose reductions of SCEMBLIX due to an adverse reaction occurred in 23% of patients. Adverse reactions which required dose reductions in > 1% of patients included pancreatic enzymes increased (10%), abdominal pain (4.2%), anemia (2.1%), blood bilirubin increased (2.1%), dizziness (2.1%), fatigue (2.1%), hepatic enzymes increased (2.1%), musculoskeletal pain (2.1%), nausea (2.1%), neutropenia (2.1%), pruritus (2.1%), and thrombocytopenia (2.1%).
The most common (≥ 20%) adverse reactions in patients who received SCEMBLIX were musculoskeletal pain, fatigue, nausea, rash, and diarrhea.
The most common select laboratory abnormalities that worsened from baseline in ≥ 20% of patients who received SCEMBLIX were alanine aminotransferase (ALT) increased, lipase increased, triglycerides increased, hemoglobin decreased, neutrophil count decreased, lymphocyte count decreased, phosphate decreased, aspartate aminotransferase (AST) increased, amylase increased, platelet count decreased, and bilirubin increased.
Table 5 summarizes adverse reactions in study X2101.
Table 5: Adverse Reactions (≥ 10%) in Patients with Ph+ CML in CP with the T315I Mutation Who Received SCEMBLIX in X2101
| Adverse Reaction | SCEMBLIX 200 mg twice daily N = 48 |
|
| All Grades % | Grade 3 or 4 % | |
| Musculoskeletal and connective tissue disorders | ||
| Musculoskeletal paina | 42 | 4.2 |
| Arthralgia | 17 | 0 |
| General disorders and administration-site conditions | ||
| Fatigueb | 31 | 2.1 |
| Edema | 10 | 4.2 |
| Gastrointestinal disorders | ||
| Nausea | 27 | 0 |
| Diarrhea | 21 | 2.1 |
| Vomiting | 19 | 6 |
| Abdominal painc | 17 | 8 |
| Skin and subcutaneous tissue disorders | ||
| Rashd | 27 | 0 |
| Pruritus | 13 | 0 |
| Nervous system disorders | ||
| Headachee | 19 | 2.1 |
| Respiratory, thoracic, and mediastinal disorders | ||
| Coughf | 15 | 0 |
| Vascular disorders | ||
| Hemorrhageg | 15 | 2.1 |
| Hypertensionh | 13 | 8 |
| Infections and infestations | ||
| Upper respiratory tract infectioni | 13 | 0 |
| aMusculoskeletal pain includes: pain in extremity, back pain, myalgia, musculoskeletal pain, non-cardiac chest pain, bone pain, arthritis, and musculoskeletal chest pain. bFatigue includes: fatigue and asthenia. cAbdominal pain includes: abdominal pain and hepatic pain. dRash includes: rash, rash maculopapular, dermatitis acneiform, eczema, rash papular, skin exfoliation, and dyshidrotic eczema. eHeadache includes: headache and migraine. fCough includes: cough and productive cough. gHemorrhage includes: epistaxis, ear hemorrhage, mouth hemorrhage, post procedural hemorrhage, skin hemorrhage, and vaginal hemorrhage. hHypertension includes: hypertension and hypertensive crisis. iUpper respiratory tract infection includes: upper respiratory tract infection, nasopharyngitis, rhinitis, and pharyngitis. |
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Clinically relevant adverse reactions in < 10% of patients treated with SCEMBLIX in X2101 included: constipation, pancreatitis, pyrexia, dizziness, neuropathy peripheral, pneumonia, lower respiratory tract infection, dyspnea, pleural effusion, dry eye, vision blurred, arrhythmia, palpitations, cardiac failure congestive, decreased appetite, dyslipidemia, and urticaria.
Table 6 summarizes laboratory abnormalities in X2101.
Table 6: Select Laboratory Abnormalities (≥ 10%) That Worsened from Baseline in Patients with Ph+ CML in CP with the T315I Mutation in X2101
| Laboratory Abnormality | SCEMBLIX1 200 mg twice daily | |
| All Grades % | Grade 3-4 % | |
| Hematologic parameters | ||
| Hemoglobin decreased | 44 | 4.2 |
| Neutrophil count decreased | 44 | 15 |
| Lymphocyte count decreased | 42 | 4.2 |
| Platelet count decreased | 25 | 15 |
| Biochemical parameters | ||
| Alanine aminotransferase (ALT) increased | 48 | 6 |
| Potassium increased | 48 | 2.1 |
| Triglycerides increased | 46 | 2.1 |
| Lipase increased | 46 | 21 |
| Phosphate decreased | 40 | 6 |
| Uric acid increased | 40 | 4.2 |
| Aspartate aminotransferase (AST) increased | 35 | 2.1 |
| Calcium corrected decreased | 33 | 0 |
| Creatinine increased | 31 | 0 |
| Amylase increased | 29 | 10 |
| Bilirubin increased | 23 | 0 |
| Cholesterol increased | 15 | 0 |
| Alkaline phosphatase (ALP) increased | 13 | 0 |
| 1The denominator used to calculate the rate was 48 based on the number of patients with a baseline value and a least one post-treatment value. CTCAE version 4.03. |
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DRUG INTERACTIONS
Effect Of Other Drugs On SCEMBLIX
Strong CYP3A4 Inhibitors
Asciminib is a CYP3A4 substrate. Concomitant use of SCEMBLIX with a strong CYP3A4 inhibitor increases both the asciminib Cmax and AUC, which may increase the risk of adverse reactions [see CLINICAL PHARMACOLOGY]. Closely monitor for adverse reactions in patients treated with SCEMBLIX at 200 mg twice daily with concomitant use of strong CYP3A4 inhibitors.
Itraconazole Oral Solution Containing Hydroxypropyl-β-cyclodextrin
Concomitant use of SCEMBLIX with itraconazole oral solution containing hydroxypropyl-β-cyclodextrin decreases asciminib Cmax and AUC, which may reduce SCEMBLIX efficacy [see CLINICAL PHARMACOLOGY]. Avoid coadministration of SCEMBLIX at all recommended doses with itraconazole oral solution containing hydroxypropyl-βcyclodextrin.
Effect Of SCEMBLIX On Other Drugs
Certain CYP3A4 Substrates
Asciminib is a CYP3A4 inhibitor. Concomitant use of SCEMBLIX increases the Cmax and AUC of CYP3A4 substrates, which may increase the risk of adverse reactions of these substrates [see CLINICAL PHARMACOLOGY].
Closely monitor for adverse reactions in patients treated with SCEMBLIX at 80 mg total daily dose with concomitant use of certain CYP3A4 substrates, where minimal concentration changes may lead to serious adverse reactions. Avoid coadministration of SCEMBLIX at 200 mg twice daily with certain CYP3A4 substrates, where minimal concentration changes may lead to serious adverse reactions.
CYP2C9 Substrates
Asciminib is a CYP2C9 inhibitor. Concomitant use of SCEMBLIX increases the Cmax and AUC of CYP2C9 substrates, which may increase the risk of adverse reactions of these substrates [see CLINICAL PHARMACOLOGY].
Avoid coadministration of SCEMBLIX at 80 mg total daily dose with certain CYP2C9 substrates, where minimal concentration changes may lead to serious adverse reactions. If coadministration is unavoidable, reduce the CYP2C9 substrate dosage as recommended in its prescribing information.
Avoid coadministration of SCEMBLIX at 200 mg twice daily with sensitive CYP2C9 substrates and certain CYP2C9 substrates, where minimal concentration changes may lead to serious adverse reactions. If coadministration is unavoidable, consider alternative therapy with non-CYP2C9 substrate.
Certain P-gp Substrates
Asciminib is a P-gp inhibitor. Concomitant use of SCEMBLIX increases the plasma concentrations of P-gp substrates, which may increase the risk of adverse reactions of these substrates [see CLINICAL PHARMACOLOGY].
Closely monitor for adverse reactions in patients treated with SCEMBLIX at all recommended doses with concomitant use of P-gp substrates, where minimal concentration changes may lead to serious toxicities.
Read the entire FDA prescribing information for Scemblix (Asciminib Tablets)
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