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IBTROZI offers simple, once-daily dosing1
Recommended dosing
IBTROZI 600 mg should be taken orally daily and continued until disease progression or unacceptable toxicity
Take three 200 mg IBTROZI capsules at approximately the same time each day. Swallow IBTROZI capsules whole. Do not open, chew, crush, or dissolve the capsule prior to swallowing
Take IBTROZI on an empty stomach (no food intake at least 2 hours before and 2 hours after taking IBTROZI)
Avoid food or drink containing grapefruit during treatment with IBTROZI.
Minimize sun exposure and use sun protection, including broad-spectrum sunscreen, during treatment with IBTROZI and for at least 5 days after discontinuation.
If a dose is missed, take the next dose at its scheduled time on the following day. If vomiting occurs at any time after taking a dose, take the next dose at its scheduled time on the following day.
Before initiating IBTROZI, evaluate liver function tests (including ALT, AST, and bilirubin), electrolytes, ECG, and uric acid.
Recommended dose reductions for adverse reactions
RECOMMENDED DOSE REDUCTIONS1
| DOSAGE | RECOMMENDED DOSE |
|---|---|
| First dose reduction | 400 mg once daily |
| Second dose reduction | 200 mg once daily |
- Permanently discontinue IBTROZI capsules in patients unable to tolerate 200 mg once daily
Drug interactions
DRUG INTERACTIONS1
| Strong and moderate CYP3A inhibitors | Avoid concomitant use with strong or moderate CYP3A inhibitors. Taletrectinib is a CYP3A substrate. Concomitant use of IBTROZI with a strong or moderate CYP3A inhibitor increases taletrectinib exposure, which may increase the risk of IBTROZI ARs |
| Strong and moderate CYP3A inducers | Avoid concomitant use with strong or moderate CYP3A inducers. Concomitant use of IBTROZI with a strong or moderate CYP3A inducer decreases taletrectinib exposure, which may reduce the effectiveness of IBTROZI |
| Gastric acid-reducing agents | Avoid concomitant use with PPIs and H2 receptor antagonists. Administer locally acting antacids at least 2 hours before or 2 hours after taking IBTROZI. Concomitant use of a PPI decreases taletrectinib exposure, which may reduce the effectiveness of IBTROZI |
| Drugs that prolong the QTc interval | Avoid concomitant use of IBTROZI with other drug(s) with a known potential to prolong the QTc interval, such as antiarrhythmic drugs. If concomitant use cannot be avoided, adjust the frequency of monitoring as recommended. Withhold IBTROZI if the QTc interval is >500 msec or the change from baseline is >60 msec. IBTROZI causes QTc interval prolongation. Concomitant use of IBTROZI with other drugs known to prolong the QTc interval may increase the risk of QTc interval prolongation |
PPI=proton pump inhibitor; QTc=corrected QT interval.
Dose modifications for adverse reactions
DOSE MODIFICATIONS FOR ADVERSE REACTIONS1
| ADVERSE EVENT | SEVERITY | DOSAGE MODIFICATIONS |
|---|---|---|
| Hepatotoxicity (elevation of ALT or AST) | Grade 3 (>5-20 × ULN) | Withhold IBTROZI until recovery to grade ≤1 or baseline
Recurrence:
|
| Grade 4 (>20 × ULN) | Withhold IBTROZI until recovery to grade ≤1 or baseline
Recurrence:
| |
| ALT or AST ≥3 × ULN with concurrent total bilirubin ≥2 × ULN (in the absence of cholestasis or hemolysis) |
| |
| ILD/pneumonitis | Grade 1 | Withhold IBTROZI if ILD/pneumonitis occurs or is suspected until recovery to grade 0 or baseline
Recurrence:
|
| Grade 2 | Withhold IBTROZI if ILD/pneumonitis occurs or is suspected until recovery to grade 0 or baseline
Recurrence:
| |
| Grade 3 or 4 |
| |
| QTc interval prolongation | Grade 2 (QTc interval 481-500 msec) | Withhold IBTROZI until recovery to grade ≤1 or baseline
|
| Grade 3 (QTc interval ≥501 msec or QTc interval increase of >60 msec from baseline) | Withhold IBTROZI until recovery to grade ≤1 or baseline
| |
| Grade 4 (Torsade de pointes; polymorphic ventricular tachycardia; signs/symptoms of serious arrhythmia) |
| |
| Hyperuricemia | Grade 3 or 4 | Withhold IBTROZI until improvement of signs or symptoms
|
| Creatine phosphokinase elevation | CPK elevation >5 times ULN | Withhold until recovery to baseline or to ≤2.5 times ULN, then resume at same dose |
| CPK elevation >10 times ULN or second occurrence of CPK elevation of >5 times ULN | Withhold until recovery to baseline or to ≤2.5 times ULN, then resume at reduced dose | |
| Other ARs | Grade 3 | Withhold IBTROZI until recovery to grade ≤1 or baseline
Recurrence:
|
| Grade 4 | Withhold IBTROZI until recovery to grade ≤1 or baseline. Resume IBTROZI at reduced dose or permanently discontinue as clinically indicated Recurrence:
|
ALT=alanine aminotransferase; AST=aspartate aminotransferase; CPK=creatine phosphokinase; ILD=interstitial lung disease; ULN=upper limit of normal.
Recommended monitoring
MONITORING FOR ADVERSE REACTIONS1
| TEST | PRIOR TO INITIATION/AT BASELINE | MONITORING |
|---|---|---|
| Liver function tests | Monitor AST, ALT, and bilirubin prior administration of IBTROZI | Evaluate every 2 weeks during the first 2 months of treatment, and then monthly as clinically indicated, with more frequent testing in patients who develop transaminase elevations |
| Pulmonary function tests | No initial evaluation needed | Monitor patients for new or worsening pulmonary symptoms indicative of ILD/pneumonitis |
| Electrocardiogram | Monitor ECGs and electrolytes prior to administration of IBTROZI | Monitor periodically thereafter as clinically indicated during treatment. Adjust the frequency of monitoring based on risk factors such as known long QT syndromes, clinically significant bradyarrhythmias, severe or uncontrolled heart failure, and concomitant medications associated with QTc interval prolongation |
| Uric acid | Monitor serum uric acid levels prior to administration of IBTROZI | Monitor periodically during treatment |
| Creatine phosphokinase | No initial evaluation needed | Advise patients to report any unexplained muscle pain, tenderness, or weakness. Monitor serum CPK levels during IBTROZI treatment every 2 weeks during the first month of treatment and then as clinically indicated |
ECG=electrocardiogram.
IBTROZI has specific dose modifications for hepatotoxicity, ILD/pneumonitis, QTc interval prolongation, hyperuricemia, creatine phosphokinase elevation, and other ARs. See dose modifications for more information.
INDICATION
IBTROZI™ (taletrectinib) is indicated for the treatment of adult patients with locally advanced or metastatic ROS1-positive non-small cell lung cancer (NSCLC).
IMPORTANT SAFETY INFORMATION
WARNINGS AND PRECAUTIONS
Hepatotoxicity: Hepatotoxicity, including drug-induced liver injury and fatal adverse reactions, can occur. 88% of patients experienced increased AST, including 10% Grade 3/4. 85% of patients experienced increased ALT, including 13% Grade 3/4. Fatal liver events occurred in 0.6% of patients. Median time to first onset of AST or ALT elevation was 15 days (range: 3 days to 20.8 months).
Increased AST or ALT each led to dose interruption in 7% of patients and dose reduction in 5% and 9% of patients, respectively. Permanent discontinuation was caused by increased AST, ALT, or bilirubin each in 0.3% and by hepatotoxicity in 0.6% of patients.
Concurrent elevations in AST or ALT ≥3 times the ULN and total bilirubin ≥2 times the ULN, with normal alkaline phosphatase, occurred in 0.6% of patients.
Monitor liver function tests (AST, ALT, and bilirubin) prior to treatment, every 2 weeks during the first 2 months, and then monthly thereafter as clinically indicated. Test more frequently if transaminase elevations occur. Advise patients to immediately report symptoms of hepatotoxicity. Based on severity and resolution, withhold, then resume at a reduced dose or permanently discontinue.
Interstitial Lung Disease (ILD)/Pneumonitis: Severe, life-threatening, or fatal ILD or pneumonitis can occur. ILD/pneumonitis occurred in 2.3% of patients, including 1.1% Grade 3/4. One fatal ILD case occurred at the 400 mg daily dose. Median time to first onset of ILD/pneumonitis was 3.8 months (range: 12 days to 11.8 months).
ILD/pneumonitis led to dose interruption in 1.1% of patients, dose reduction in 0.6% of patients, and permanent discontinuation in 0.6% of patients.
Monitor patients for new or worsening pulmonary symptoms. Advise patients to report symptoms. If ILD/pneumonitis is suspected, immediately withhold; based on severity and resolution, resume at same or reduced dose, or permanently discontinue.
QTc Interval Prolongation: QTc interval prolongation can occur, which can increase the risk for ventricular tachyarrhythmias (e.g., torsades de pointes) or sudden death. IBTROZI prolongs the QTc interval in a concentration-dependent manner.
In patients who received IBTROZI and underwent at least one post baseline ECG, QTcF increase of >60 msec compared to baseline and QTcF >500 msec occurred in 13% and 2.6% of patients, respectively. 3.4% of patients experienced Grade ≥3. Median time from first dose of IBTROZI to onset of ECG QT prolongation was 22 days (range: 1 day to 38.7 months). Dose interruption and dose reduction each occurred in 2.8% of patients.
Monitor ECGs and electrolytes prior to start of therapy, and then periodically thereafter as clinically indicated. Adjust frequency based on risk factors such as known long QT syndromes, clinically significant bradyarrhythmias, severe or uncontrolled heart failure, and concomitant medications.
Significant QTc interval prolongation may occur when IBTROZI is taken with food, strong and moderate CYP3A inhibitors, and/or drugs with a known potential to prolong QTc. Administer IBTROZI on an empty stomach. Avoid concomitant use with strong and moderate CYP3A inhibitors and/or drugs with a known potential to prolong QTc.
Advise patients to immediately report any symptoms of QT interval prolongation. Based on severity and resolution, withhold, then resume at same or reduced dose, or permanently discontinue.
Hyperuricemia: Hyperuricemia can occur and was reported in 14% of patients, with 16% of these requiring urate-lowering medication without pre-existing gout or hyperuricemia. 0.3% of patients experienced Grade ≥3. Median time to first onset was 2.1 months (range: 7 days to 35.8 months). Dose interruption occurred in 0.3% of patients.
Monitor serum uric acid levels prior to initiating and periodically during treatment. Initiate urate-lowering medications as clinically indicated. Advise patients to report symptoms. Based upon severity and resolution, withhold, then resume at same or reduced dose, or permanently discontinue.
Myalgia with Creatine Phosphokinase (CPK) Elevation: Myalgia with or without CPK elevation can occur. Myalgia occurred in 10% of patients. Median time to first onset was 11 days (range: 2 days to 10 months).
Concurrent myalgia with increased CPK within a 7-day time period occurred in 0.9% of patients. Dose interruption occurred in 0.3% of patients with myalgia and concurrent CPK elevation.
Advise patients to report any unexplained muscle pain, tenderness, or weakness. Monitor serum CPK levels during treatment every 2 weeks during the first month, and then as clinically indicated. Based on severity, withhold, then resume at same or reduced dose upon improvement.
Skeletal Fractures: IBTROZI can increase the risk of fractures. ROS1 inhibitors as a class have been associated with skeletal fractures. 3.4% of patients experienced fractures, including 1.4% Grade 3. Some fractures occurred in the setting of a fall or other predisposing factors such as osteoporosis, bone metastasis, and age-related degenerative conditions. Median time to first onset of fracture was 10.7 months (range: 26 days to 29.1 months). Dose interruption occurred in 0.3% of patients.
Advise patients to immediately report symptoms. Promptly evaluate patients with signs or symptoms (e.g., pain, changes in mobility, deformity) of fractures.
There are no data on the effects of IBTROZI on healing of known fractures and risk of future fractures.
Embryo-Fetal Toxicity: Based on literature, animal studies, and its mechanism of action, IBTROZI can cause fetal harm when administered to a pregnant woman. Verify the pregnancy status of females of reproductive potential prior to initiating IBTROZI. Advise females to inform their healthcare provider of a known or suspected pregnancy.
Advise pregnant women and females of reproductive potential of the potential risk to a fetus. Advise females of reproductive potential and male patients with female partners of reproductive potential to use effective contraception during treatment and for 3 weeks following the last dose.
ADVERSE REACTIONS
Among patients who received IBTROZI, the most frequently reported adverse reactions (≥20%) were diarrhea (64%), nausea (47%), vomiting (43%), dizziness (22%), rash (22%), constipation (21%), and fatigue (20%).
The most frequently reported Grade 3/4 laboratory abnormalities (≥5%) were increased ALT (13%), increased AST (10%), decreased neutrophils (5%), and increased creatine phosphokinase (5%).
DRUG INTERACTIONS
- Strong and Moderate CYP3A Inhibitors: Avoid concomitant use.
- Strong and Moderate CYP3A Inducers: Avoid concomitant use.
- Gastric Acid Reducing Agents: Avoid concomitant use with PPIs and H2 receptor antagonists. If an acid-reducing agent cannot be avoided, administer locally acting antacids at least 2 hours before or 2 hours after taking IBTROZI.
- Drugs that Prolong the QTc Interval: Avoid concomitant use. If concomitant use cannot be avoided, adjust the frequency of monitoring as recommended. Withhold IBTROZI if the QTc interval is >500 msec or the change from baseline is >60 msec.
OTHER CONSIDERATIONS
- Pregnancy: Please see important information in Warnings and Precautions under Embryo-Fetal Toxicity.
- Lactation: Advise women not to breastfeed during treatment and for 3 weeks after the last dose.
- Effect on Fertility: Based on findings in animals, IBTROZI may impair fertility in males and females. The effects on animal fertility were reversible.
- Pediatric Use: The safety and effectiveness of IBTROZI in pediatric patients has not been established.
- Photosensitivity: IBTROZI can cause photosensitivity. Advise patients to minimize sun exposure and to use sun protection, including broad-spectrum sunscreen, during treatment and for at least 5 days after discontinuation.