e unable to tolerate the 60 mg once daily dose.
Recommendations for dose modifications of ALUNBRIG for the management of adverse reactions are provided in Table 2.
Table 2: Recommended ALUNBRIG Dose Modifications for Adverse Reactions
Adverse Reaction Severity* Dose Modification
bpm = beats per minute; DBP = diastolic blood pressure; HR = heart rate; SBP = systolic blood pressure; ULN = upper limit of normal
* Graded per National Cancer Institute Common Terminology Criteria for Adverse Events. Version 4.0 (NCI CTCAE v4).
Interstitial Lung Disease (ILD) /Pneumonitis [see WARNINGS AND PRECAUTIONS (5.1)] Grade 1
If new pulmonary symptoms occur during the first 7 days of treatment, withhold ALUNBRIG until recovery to baseline, then resume at same dose and do not escalate to 180 mg if ILD/pneumonitis is suspected.
If new pulmonary symptoms occur after the first 7 days of treatment, withhold ALUNBRIG until recovery to baseline, then resume at same dose.
If ILD/pneumonitis recurs, permanently discontinue ALUNBRIG.
Grade 2
If new pulmonary symptoms occur during the first 7 days of treatment, withhold ALUNBRIG until recovery to baseline. Resume at next lower dose (Table 1) and do not dose escalate if ILD/pneumonitis is suspected.
If new pulmonary symptoms occur after the first 7 days of treatment, withhold ALUNBRIG until recovery to baseline. If ILD/pneumonitis is suspected, resume at next lower dose (Table 1); otherwise, resume at same dose.
If ILD/pneumonitis recurs, permanently discontinue ALUNBRIG.
Grade 3 or 4 Permanently discontinue ALUNBRIG for ILD/pneumonitis.
Hypertension [see WARNINGS AND PRECAUTIONS (5.2)] Grade 3 hypertension (SBP greater than or equal to 160 mmHg or DBP greater than or equal to 100 mmHg, medical intervention indicated, more than one anti-hypertensive drug, or more intensive therapy than previously used indicated)
Withhold ALUNBRIG until hypertension has recovered to Grade 1 or less (SBP less than 140 mmHg and DBP less than 90 mmHg), then resume ALUNBRIG at next lower dose (Table 1).
Recurrence: withhold ALUNBRIG until recovery to Grade 1 or less, and resume at next lower dose (Table 1) or permanently discontinue treatment.
Grade 4 hypertension (life- threatening consequences, urgent intervention indicated)
Withhold ALUNBRIG until recovery to Grade 1 or less, and resume at next lower dose (Table 1) or permanently discontinue treatment.
Recurrence: permanently discontinue ALUNBRIG for recurrence of Grade 4 hypertension.
Bradycardia (HR less than 60 bpm) [see WARNINGS AND PRECAUTIONS (5.3)] Symptomatic bradycardia
Withhold ALUNBRIG until recovery to asymptomatic bradycardia or to a resting heart rate of 60 bpm or above.
If a concomitant medication known to cause bradycardia is identified and discontinued or dose-adjusted, resume ALUNBRIG at same dose upon recovery to asymptomatic bradycardia or to resting heart rate of 60 bpm or above.
If no concomitant medication known to cause bradycardia is identified, or if contributing concomitant medications are not discontinued or dose-adjusted, resume ALUNBRIG at next lower dose (Table 1) upon recovery to asymptomatic bradycardia or to resting heart rate of 60 bpm or above.
Bradycardia with life-threatening consequences, urgent intervention indicated
Permanently discontinue ALUNBRIG if no contributing concomitant medication is identified.
If contributing conc |
