Brigatinib Dosage

Medically reviewed by Drugs.com. Last updated on Jun 13, 2023.

Usual Adult Dose for Non-Small Cell Lung Cancer

Initial dose: 90 mg orally once a day for the first 7 days
Maintenance dose: 180 mg orally once a day

Comments:

• Patients should be selected for the treatment of metastatic NSCLC based on the presence of ALK positivity in tumor specimens.
• FDA-approved test for the detection of ALK rearrangements in NSCLC is available at http://www.fda.gov/CompanionDiagnostic
• Treatment should be continued until disease progression or unacceptable toxicity.

Use: For treatment of patients with anaplastic lymphoma kinase (ALK)-positive metastatic non-small cell lung cancer (NSCLC) as detected by an FDA-approved test

Renal Dose Adjustments

Mild to moderate renal dysfunction (CrCl 30 to 89 mL/min): No adjustment recommended.
Severe renal dysfunction (CrCl 15 to 29 mL/min): Reduce once daily dose by approximately 50% (i.e., from 180 mg to 90 mg OR 90 mg to 60 mg).

Liver Dose Adjustments

Mild to moderate liver dysfunction (Child-Pugh A to B) : No adjustment recommended.
Severe liver dysfunction (Child-Pugh C): Reduce once daily dose by approximately 40% (i.e., from 180 mg to 120 mg, OR 120 mg to 90 mg, OR 90 mg to 60 mg).

Dose Adjustments

DOSE REDUCTION FOR ADVERSE REACTIONS:
STARTING DOSE 90 MG ONCE A DAY:

• First reduction: 60 mg once a day
• Second reduction: Permanently discontinue therapy.
• Third reduction: N/A

STARTING DOSE 180 MG ONCE A DAY:

• First reduction: 120 mg once a day
• Second reduction: 90 mg once a day
• Third reduction: 60 mg once a day

Comments:

• Once the dose is reduced, do not subsequently increase the dose.
• Permanently discontinue this drug if patients are unable to tolerate 60 mg once a day.
• Dosing interruption of 14 days or longer (for reasons other than adverse reactions): Resume at 90 mg once a day for 7 days before increasing to the previously tolerated dose.

STRONG OR MODERATE CYP450 3A INHIBITORS:

• Avoid concomitant use.
• If concomitant use of a strong CYP450 3A inhibitor cannot be avoided, reduce the once a day dose of this drug by approximately 50% (i.e., from 180 mg to 90 mg OR from 90 mg to 60 mg).
• If coadministration of a moderate CYP450 3A inhibitor cannot be avoided, reduce the once daily dose of this drug by approximately 40% (i.e., from 180 mg to 120 mg, OR 120 mg to 90 mg, OR from 90 mg to 60 mg).
• After discontinuation of a strong or moderate CYP450 3A inhibitor, resume the dose of this drug that was tolerated prior to initiating the CYP450 3A inhibitor.

MODERATE CYP450 3A INDUCERS:

• Avoid concomitant use.
• If coadministration of a moderate CYP450 3A inducer cannot be avoided, increase the once daily dose of this drug in 30 mg increments after 7 days of therapy with the current dose as tolerated, up to a maximum of twice the dose that was tolerated prior to initiating the moderate CYP450 3A inducer.
• After discontinuation of a moderate CYP450 3A inducer, resume the dose of this drug that was tolerated prior to initiating the moderate CYP450 3A inducer.

DOSE MODIFICATIONS FOR ADVERSE REACTIONS:
INTERSTITIAL LUNG DISEASE (ILD)/PNEUMONITIS:
*GRADE 1:

• If new pulmonary symptoms occur during the first 7 days of therapy, withhold this drug until recovery to baseline, then resume at the 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 therapy, withhold this drug until recovery to baseline, then resume at same dose.
• If ILD/pneumonitis recurs, permanently discontinue this drug.

*GRADE 2:

• If new pulmonary symptoms occur during the first 7 days of therapy, withhold this drug until recovery to baseline; resume at next lower dose and do not dose escalate if ILD/pneumonitis is suspected.
• If new pulmonary symptoms occur after the first 7 days of therapy, withhold this drug until recovery to baseline.
• If ILD/pneumonitis is suspected, resume at next lower dose; otherwise, resume at same dose.
• If ILD/pneumonitis recurs, permanently discontinue this drug.

*Grade 3 or 4: Permanently discontinue this drug.
HYPERTENSION:
*GRADE 3 (SBP 160 mmHg or greater or DBP 100 mmHg or greater, medical intervention indicated, more than 1 antihypertensive drug, or more intensive therapy than previously used indicated):

• Withhold dosing until recovery to Grade 1 or less (SBP less than 140 mmHg and DBP less than 90 mmHg) then resume at the next lower dose.
• Recurrence: Withhold the drug until recovery to Grade 1 or less and resume at next lower dose or permanently discontinue this drug.

GRADE 4 (life-threatening consequences, urgent intervention indicated):

• Withhold this drug until recovery to Grade 1 or less and resume at the next lower dose OR permanently discontinue this drug.

*GRADE 4 RECURRENCE: Permanently discontinue this drug.
BRADYCARDIA (HR less than 60 bpm):
*SYMPTOMATIC BRADYCARDIA:

• Withhold this drug 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 this drug 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 this drug at next lower dose upon recovery to asymptomatic bradycardia or to resting heart rate of 60 bpm or above.

*LIFE-THREATENING BRADYCARDIA (urgent intervention indicated):

• Permanently discontinue this drug if no contributing concomitant medication is identified.
• If contributing concomitant medication is identified and discontinued or dose-adjusted, resume this drug at next lower dose upon recovery to asymptomatic bradycardia or to a resting heart rate of 60 bpm or above, with frequent monitoring as clinically indicated.
• Recurrence: Permanently discontinue this drug.

VISUAL DISTURBANCE:
*GRADE 2 OR 3: Withhold this drug until recovery to Grade 1 or baseline, then resume at the next lower dose.
*GRADE 4: Permanently discontinue this drug.
CREATINE PHOSPHOKINASE (CPK) ELEVATION:
*GRADE 3 OR 4 CPK ELEVATION (greater than 5 times upper level of normal [ULN] with Grade 2 or higher muscle pain or weakness):

• Withhold this drug until recovery to Grade 1 or less ((less than or equal to 2.5 x ULN) or to baseline, then resume at the same dose.
• Recurrence: Withhold until recovery to Grade 1 or less (less than or equal to 2.5 x ULN) or to baseline, then resume at next lower dose

LIPASE/AMYLASE ELEVATION:
*GRADE 3 (greater than 2 x ULN): Withhold this drug until recovery to Grade 1 or less (1.5 x ULN or less) or to baseline, then resume at the same dose.
*RECURRENCE: Withhold until recovery to Grade 1 or less (less than or equal to 1.5 x ULN) or to baseline, then resume at next lower dose.
*GRADE 4 (greater than 5 x ULN): Withhold dosing until recovery to Grade 1 or less (1.5 x ULN or less) or to baseline, then resume at the next lower dose.
HYPERGLYCEMIA:
*GRADE 3 (greater than 250 mg/dL OR 13.9 mmol/L) OR GRADE 4:

• Withhold this drug until adequate hyperglycemic control is achieved and resume at next lower dose OR permanently discontinue therapy.

OTHER ADVERSE REACTIONS:
*GRADE 3:

• Withhold this drug until recovery to baseline, then resume at the same dose.
• Recurrence: Withhold this drug until recovery to baseline, then resume at the next lower dose OR discontinue therapy.

*GRADE 4:

• Withhold dosing until recovery to baseline, then resume at the next lower dose.
• Recurrence: Permanently discontinue therapy.

Precautions

CONTRAINDICATIONS:

• None

Safety and efficacy have not been established in patients younger than 18 years.

Consult WARNINGS section for additional precautions.

Dialysis

Data not available

Other Comments

Administration advice:

• Swallow tablets whole; do not crush or chew.
• Administer with or without food.
• In the event of a missed or vomited dose, skip that dose and administer the next dose at the regularly scheduled time.

Storage requirements:

• Store at 20C to 25C (68F to 77F); excursions are permitted between 15C to 30C (59F to 86F).

Monitoring:

• Cardiovascular: Blood pressure (at 2 weeks, then at least monthly), heart rate (during treatment)
• Endocrine: Fasting serum glucose (prior to treatment initiation, then periodically thereafter)
• Gastrointestinal: Amylase and lipase (during treatment)
• Musculoskeletal: Creatine phosphokinase levels (during treatment)
• Respiratory: New or worsening respiratory symptoms (during treatment, particularly during the first week)

Patient advice:

• This drug may cause side effects such as double vision; avoid potentially dangerous activities such as driving and operating machinery until you know how this drug affects you.
• Advise diabetic patients that hyperglycemic medications may need to be adjusted during treatment.
• Advise patients to inform their healthcare provider of any new or worsening vision symptoms.
• Advise patients to report any new or worsening respiratory symptoms immediately.
• Advise patients to inform their healthcare provider of any new or worsening symptoms of unexplained muscle pain, tenderness, or weakness.
• Advise patients to report any bradycardia symptoms and inform their healthcare provider about the use of heart and blood pressure medications.
• Advise patients of risks of hypertension and to promptly report signs or symptoms of hypertension.
• Advise patients to limit sun exposure during treatment and for at least 5 days after the last dose.
• To help protect against sunburn, advise patients to wear protective clothing and use a broad-spectrum sunscreen and lip balm (SPF 30 or greater).
• Inform patients of the signs and symptoms of pancreatitis and the need to monitor for amylase and lipase elevations during treatment.
• Avoid grapefruit and grapefruit juice while taking this drug.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

Medical Disclaimer