Alunbrig

Name: Alunbrig

In case of emergency/overdose

In case of overdose, call your local poison control center at 1-800-222-1222. If the victim has collapsed or is not breathing, call local emergency services at 911.

What other information should I know?

Keep all appointments with your doctor and the laboratory. Your doctor will order certain lab tests before and during your treatment to check your body's response to brigatinib.

Do not let anyone else take your medication. Ask your pharmacist any questions you have about refilling your prescription.

It is important for you to keep a written list of all of the prescription and nonprescription (over-the-counter) medicines you are taking, as well as any products such as vitamins, minerals, or other dietary supplements. You should bring this list with you each time you visit a doctor or if you are admitted to a hospital. It is also important information to carry with you in case of emergencies.

Brand names

  • Alunbrig®

Cautions for Alunbrig

Contraindications

None.1

Warnings/Precautions

Interstitial Lung Disease (ILD)/Pneumonitis

Severe, life-threatening, and fatal pulmonary adverse reactions consistent with interstitial lung disease (ILD)/pneumonitis have occurred with brigatinib.1

In Trial ALTA (ALTA), ILD/pneumonitis occurred in 3.7% of patients in the 90 mg group (90 mg once daily) and 9.1% of patients in the 90→180 mg group (180 mg once daily with 7-day lead-in at 90 mg once daily).1

Adverse reactions consistent with possible ILD/pneumonitis occurred early (within 9 days of initiation of brigatinib; median onset was 2 days) in 6.4% of patients, with Grade 3 to 4 reactions occurring in 2.7%.1

Monitor for new or worsening respiratory symptoms (e.g., dyspnea, cough, etc.), particularly during the first week of initiating brigatinib. Withhold brigatinib in any patient with new or worsening respiratory symptoms, and promptly evaluate for ILD/pneumonitis or other causes of respiratory symptoms (e.g., pulmonary embolism, tumor progression, and infectious pneumonia). For Grade 1 or 2 ILD/pneumonitis, either resume brigatinib with dose reduction after recovery to baseline or permanently discontinue brigatinib. Permanently discontinue brigatinib for Grade 3 or 4 ILD/pneumonitis or recurrence of Grade 1 or 2 ILD/pneumonitis.1

Hypertension

In ALTA, hypertension was reported in 11% of patients in the 90 mg group who received brigatinib and 21% of patients in the 90→180 mg group. Grade 3 hypertension occurred in 5.9% of patients overall.1

Control blood pressure prior to treatment with brigatinib. Monitor blood pressure after 2 weeks and at least monthly thereafter during treatment with brigatinib. Withhold brigatinib for Grade 3 hypertension despite optimal antihypertensive therapy. Upon resolution or improvement to Grade 1 severity, resume brigatinib at a reduced dose. Consider permanent discontinuation of treatment with brigatinib for Grade 4 hypertension or recurrence of Grade 3 hypertension.1

Use caution when administering brigatinib in combination with antihypertensive agents that cause bradycardia.1

Bradycardia

Bradycardia can occur with brigatinib. In ALTA, heart rates less than 50 beats per minute (bpm) occurred in 5.7% of patients in the 90 mg group and 7.6% of patients in the 90→180 mg group. Grade 2 bradycardia occurred in 1 (0.9%) patient in the 90 mg group.1

Monitor heart rate and blood pressure during treatment with brigatinib. Monitor patients more frequently if concomitant use of drug known to cause bradycardia cannot be avoided.1

For symptomatic bradycardia, withhold brigatinib and review concomitant medications for those known to cause bradycardia. If a concomitant medication known to cause bradycardia is identified and discontinued or dose adjusted, resume brigatinib at the same dose following resolution of symptomatic bradycardia; otherwise, reduce the dose of brigatinib following resolution of symptomatic bradycardia. Discontinue brigatinib for life-threatening bradycardia if no contributing concomitant medication is identified.1

Visual Disturbance

In ALTA, adverse reactions leading to visual disturbance including blurred vision, diplopia, and reduced visual acuity, were reported in 7.3% of patients receiving brigatinib in the 90 mg group and 10% of patients in the 90→180 mg group. Grade 3 macular edema and cataract occurred in one patient each in the 90→180 mg group.1

Advise patients to report any visual symptoms. Withhold brigatinib and obtain an ophthalmologic evaluation in patients with new or worsening visual symptoms of Grade 2 or greater severity. Upon recovery of Grade 2 or Grade 3 visual disturbances to Grade 1 severity or baseline, resume brigatinib at a reduced dose. Permanently discontinue treatment with brigatinib for Grade 4 visual disturbances.1

Creatine Phosphokinase (CPK) Elevation

In ALTA, creatine phosphokinase (CPK) elevation occurred in 27% of patients receiving brigatinib in the 90 mg group and 48% of patients in the 90 mg→180 mg group. The incidence of Grade 3-4 CPK elevation was 2.8% in the 90 mg group and 12% in the 90→180 mg group.1

Dose reduction for CPK elevation occurred in 1.8% of patients in the 90 mg group and 4.5% in the 90→180 mg group.1

Advise patients to report any unexplained muscle pain, tenderness, or weakness. Monitor CPK levels during brigatinib treatment. Withhold brigatinib for Grade 3 or 4 CPK elevation. Upon resolution or recovery to Grade 1 or baseline, resume brigatinib at the same dose or at a reduced dose.1

Pancreatic Enzyme Elevation

In ALTA, amylase elevation occurred in 27% of patients in the 90 mg group and 39% of patients in the 90→180 mg group. Lipase elevations occurred in 21% of patients in the 90 mg group and 45% of patients in the 90→180 mg group. Grade 3 or 4 amylase elevation occurred in 3.7% of patients in the 90 mg group and 2.7% of patients in the 90→180 mg group. Grade 3 or 4 lipase elevation occurred in 4.6% of patients in the 90 mg group and 5.5% of patients in the 90→180 mg group.1

Monitor lipase and amylase during treatment with brigatinib. Withhold brigatinib for Grade 3 or 4 pancreatic enzyme elevation. Upon resolution or recovery to Grade 1 or baseline, resume brigatinib at the same dose or at a reduced dose. 1

Hyperglycemia

In ALTA, 43% of patients who received brigatinib experienced new or worsening hyperglycemia. Grade 3 hyperglycemia, based on laboratory assessment of serum fasting glucose levels, occurred in 3.7% of patients. Two of 20 (10%) patients with diabetes or glucose intolerance at baseline required initiation of insulin while receiving brigatinib.1

Assess fasting serum glucose prior to initiation of brigatinib and monitor periodically thereafter. Initiate or optimize anti-hyperglycemic medications as needed. If adequate hyperglycemic control cannot be achieved with optimal medical management, withhold brigatinib until adequate hyperglycemic control is achieved and consider reducing the dose of brigatinib or permanently discontinuing brigatinib.1

Embryo-fetal Toxicity

Based on its mechanism of action and findings in animals, brigatinib can cause fetal harm when administered to pregnant women. There are no clinical data on the use of brigatinib in pregnant women. Administration of brigatinib to pregnant rats during the period of organogenesis resulted in dose-related skeletal anomalies at doses as low as 12.5 mg/kg/day (approximately 0.7 times the human exposure by AUC at 180 mg once daily) as well as increased post implantation loss, malformations, and decreased fetal body weight at doses of 25 mg/kg/day (approximately 1.26 times the human exposure at 180 mg once daily) or higher.1

Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to use effective non-hormonal contraception during treatment with brigatinib and for at least 4 months following the final dose. Advise males with female partners of reproductive potential to use effective contraception during treatment and for at least 3 months after the last dose of brigatinib.1

Specific Populations

Pregnancy

Based on its mechanism of action and findings in animals, brigatinib can cause fetal harm when administered to a pregnant woman. There are no clinical data on the use of brigatinib in pregnant women. Administration of brigatinib to pregnant rats during the period of organogenesis resulted in dose-related skeletal anomalies at doses as low as 12.5 mg/kg/day (approximately 0.7 times the human exposure by AUC at 180 mg once daily) as well as increased post-implantation loss, malformations, and decreased fetal body weight at doses of 25 mg/kg/day (approximately 1.26 times the human exposure at 180 mg once daily) or greater. If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, advise the patient of the potential risk to a fetus. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.1

In an embryo-fetal development study in which pregnant rats were administered daily doses of brigatinib during organogenesis, dose-related skeletal (incomplete ossification, small incisors) and visceral anomalies were observed at doses as low as 12.5 mg/kg/day (approximately 0.7 times the human exposure by AUC at 180 mg once daily). Malformations observed at 25 mg/kg/day (approximately 1.26 times the human AUC at 180 mg once daily) included anasarca (generalized subcutaneous edema), anophthalmia (absent eyes), forelimb hyperflexion, small, short and/or bent limbs, multiple fused ribs, bent scapulae, omphalocele (intestine protruding into umbilicus), and gastroschisis (intestines protruding through a defect in the abdominal wall) along with visceral findings of moderate bilateral dilatation of the lateral ventricles.1

Lactation

There are no data regarding the secretion of brigatinib in human milk or its effects on the breastfed infant or milk production. Because of the potential for adverse reactions in breastfed infants, advise lactating women not to breastfeed during treatment with brigatinib and for 1 week following the final dose.1

Females and Males of Reproductive Potential

Brigatinib can cause fetal harm.1

Advise females of reproductive potential to use effective non-hormonal contraception during treatment with brigatinib and for at least 4 months after the final dose. Counsel patients to use a non-hormonal method of contraception since brigatinib can render some hormonal contraceptives ineffective.1

Because of the potential for genotoxicity, advise males with female partners of reproductive potential to use effective contraception during treatment with brigatinib and for at least 3 months after the final dose.1

Based on findings in male reproductive organs in animals, brigatinib may cause reduced fertility in males.1

Pediatric Use

The safety and efficacy of brigatinib in pediatric patients have not been established.1

Geriatric Use

Clinical studies of brigatinib did not include sufficient numbers of patients aged 65 years and older to determine whether they respond differently from younger patients. Of the 222 patients in ALTA, 19.4% were 65-74 years and 4.1% were 75 years or older. No clinically relevant differences in safety or efficacy were observed between patients ≥65 years and younger patients.1

Hepatic Impairment

No dose adjustment is recommended for patients with mild hepatic impairment (total bilirubin within upper limit of normal [ULN] and AST greater than ULN or total bilirubin greater than 1 and up to 1.5 times ULN and any AST). The pharmacokinetics and safety of brigatinib in patients with moderate or severe hepatic impairment have not been studied.1

Renal Impairment

No dose adjustment is recommended for patients with mild and moderate renal impairment [creatinine clearance (CLcr 30 to 89 mL/min estimated by Cockcroft-Gault)]. The pharmacokinetics and safety of brigatinib in patients with severe renal impairment (CLcr 15 to 29 mL/min estimated by Cockcroft-Gault) have not been studied.1

Common Adverse Effects

The most common adverse reactions (≥25%) with brigatinib were nausea, diarrhea, fatigue, cough, and headache.1

Uses For Alunbrig

Brigatinib is used to treat metastatic (cancer that has already spread) non-small cell lung cancer in patients who have certain types of abnormal anaplastic lymphoma kinase (ALK) gene. It is used in patients who have already received crizotinib, but their condition got worse or the medicine has stopped working. Brigatinib is an antineoplastic (cancer) agent. It interferes with the growth of cancer cells, which are eventually destroyed by the body.

This medicine is available only with your doctor's prescription.

What do I need to tell my doctor BEFORE I take Alunbrig?

  • If you have an allergy to Alunbrig (brigatinib) or any part of this medicine.
  • If you are allergic to any drugs like this one, any other drugs, foods, or other substances. Tell your doctor about the allergy and what signs you had, like rash; hives; itching; shortness of breath; wheezing; cough; swelling of face, lips, tongue, or throat; or any other signs.
  • If you have high blood pressure.
  • If you are taking any of these drugs: Carbamazepine, phenytoin, rifampin, or St. John's wort.
  • If you are breast-feeding. Do not breast-feed while you take Alunbrig and for 1 week after your last dose.

This is not a list of all drugs or health problems that interact with this medicine.

Tell your doctor and pharmacist about all of your drugs (prescription or OTC, natural products, vitamins) and health problems. You must check to make sure that it is safe for you to take Alunbrig with all of your drugs and health problems. Do not start, stop, or change the dose of any drug without checking with your doctor.

What are some side effects that I need to call my doctor about right away?

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

  • Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.
  • Signs of high blood pressure like very bad headache or dizziness, passing out, or change in eyesight.
  • Signs of high blood sugar like confusion, feeling sleepy, more thirst, more hungry, passing urine more often, flushing, fast breathing, or breath that smells like fruit.
  • Signs of a pancreas problem (pancreatitis) like very bad stomach pain, very bad back pain, or very bad upset stomach or throwing up.
  • Slow heartbeat.
  • Chest pain.
  • Change in eyesight.
  • Seeing double.
  • If bright lights bother your eyes.
  • Muscle pain or weakness.
  • Muscle spasm.
  • Fever.
  • A burning, numbness, or tingling feeling that is not normal.
  • Feeling very tired or weak.
  • Very bad and sometimes deadly lung problems have happened with this medicine. Call your doctor right away if you have lung or breathing problems like trouble breathing, shortness of breath, or a cough that is new or worse.

What are some other side effects of Alunbrig?

All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:

  • Upset stomach or throwing up.
  • Loose stools (diarrhea).
  • Hard stools (constipation).
  • Belly pain.
  • Not hungry.
  • Feeling tired or weak.
  • Headache.
  • Back pain.
  • Joint pain.
  • Not able to sleep.

These are not all of the side effects that may occur. If you have questions about side effects, call your doctor. Call your doctor for medical advice about side effects.

You may report side effects to the FDA at 1-800-FDA-1088. You may also report side effects at http://www.fda.gov/medwatch.

Dosage Forms and Strengths

  • 30 mg, round, white to off-white film-coated tablet with "U3" debossed on one side and plain on the other side
  • 90 mg, oval, white to off-white film-coated tablet with "U7" debossed on one side and plain on the other side

Use in specific populations

Pregnancy

Risk Summary

Based on its mechanism of action and findings in animals, Alunbrig can cause fetal harm when administered to a pregnant woman [see Data and Clinical Pharmacology (12.1)]. There are no clinical data on the use of Alunbrig in pregnant women. Administration of brigatinib to pregnant rats during the period of organogenesis resulted in dose-related skeletal anomalies at doses as low as 12.5 mg/kg/day (approximately 0.7 times the human exposure by AUC at 180 mg once daily) as well as increased post-implantation loss, malformations, and decreased fetal body weight at doses of 25 mg/kg/day (approximately 1.26 times the human exposure at 180 mg once daily) or greater. If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, advise the patient of the potential risk to a fetus.

In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.

Data

Animal Data

In an embryo-fetal development study in which pregnant rats were administered daily doses of brigatinib during organogenesis, dose-related skeletal (incomplete ossification, small incisors) and visceral anomalies were observed at doses as low as 12.5 mg/kg/day (approximately 0.7 times the human exposure by AUC at 180 mg once daily). Malformations observed at 25 mg/kg/day (approximately 1.26 times the human AUC at 180 mg once daily) included anasarca (generalized subcutaneous edema), anophthalmia (absent eyes), forelimb hyperflexion, small, short and/or bent limbs, multiple fused ribs, bent scapulae, omphalocele (intestine protruding into umbilicus), and gastroschisis (intestines protruding through a defect in the abdominal wall) along with visceral findings of moderate bilateral dilatation of the lateral ventricles.

Lactation

Risk Summary

There are no data regarding the secretion of brigatinib in human milk or its effects on the breastfed infant or milk production. Because of the potential for adverse reactions in breastfed infants, advise lactating women not to breastfeed during treatment with Alunbrig and for 1 week following the final dose.

Females and Males of Reproductive Potential

Contraception

Alunbrig can cause fetal harm [see Use in Specific Populations (8.1)].

Females

Advise females of reproductive potential to use effective non-hormonal contraception during treatment with Alunbrig and for at least 4 months after the final dose. Counsel patients to use a non-hormonal method of contraception since Alunbrig can render some hormonal contraceptives ineffective [see Drug Interaction (7.3]).

Males

Because of the potential for genotoxicity, advise males with female partners of reproductive potential to use effective contraception during treatment with Alunbrig and for at least 3 months after the final dose [see Nonclinical Toxicology (13.1)].

Infertility

Based on findings in male reproductive organs in animals, Alunbrig may cause reduced fertility in males [see Nonclinical Toxicology (13.1)].

Pediatric Use

The safety and efficacy of Alunbrig in pediatric patients have not been established.

Geriatric Use

Clinical studies of Alunbrig did not include sufficient numbers of patients aged 65 years and older to determine whether they respond differently from younger patients. Of the 222 patients in ALTA, 19.4% were 65-74 years and 4.1% were 75 years or older. No clinically relevant differences in safety or efficacy were observed between patients ≥65 years and younger patients.

Hepatic Impairment

No dose adjustment is recommended for patients with mild hepatic impairment (total bilirubin within upper limit of normal [ULN] and AST greater than ULN or total bilirubin greater than 1 and up to 1.5 times ULN and any AST). The pharmacokinetics and safety of Alunbrig in patients with moderate or severe hepatic impairment have not been studied [see Clinical Pharmacology (12.3)].

Renal Impairment

No dose adjustment is recommended for patients with mild and moderate renal impairment [creatinine clearance (CLcr) 30 to 89 mL/min estimated by Cockcroft-Gault)]. The pharmacokinetics and safety of Alunbrig in patients with severe renal impairment (CLcr 15 to 29 mL/min estimated by Cockcroft-Gault) have not been studied [see Clinical Pharmacology (12.3)].

How Supplied/Storage and Handling

30 mg tablets: round, white to off-white film-coated tablet with "U3" debossed on one side and plain on the other side; available in:

Bottles of 21 tablets NDC 76189-113-21
Bottles of 180 tablets NDC 76189-113-18

90 mg tablets: oval, white to off-white film-coated tablet with "U7" debossed on one side and plain on the other side; available in:

Bottles of 7 tablets NDC 76189-119-07
Bottles of 30 tablets NDC 76189-119-30

Store at controlled room temperature 20°C to 25°C (68°F to 77°F); excursion permitted between 15°C to 30°C (59°F to 86°F) (see USP).

Before taking this medicine

You should not use Alunbrig if you are allergic to brigatinib.

To make sure Alunbrig is safe for you, tell your doctor if you have ever had:

  • lung disease or breathing problems;

  • slow heartbeats;

  • high blood pressure;

  • diabetes or glucose intolerance;

  • pancreas problems; or

  • vision problems.

Alunbrig can harm an unborn baby. Use effective birth control to prevent pregnancy while you are using this medicine, whether you are a man or a woman. Men should use condoms. Alunbrig use by either parent may cause birth defects.

Use a barrier form of birth control (condom or diaphragm with spermicide). Hormonal contraception (birth control pills, injections, implants, skin patches, and vaginal rings) may not be effective enough to prevent pregnancy during your treatment.

If you are a woman, keep using birth control for at least 4 months after your last dose of Alunbrig. If you are a man, keep using condoms for at least 3 months after your last dose. Tell your doctor right away if a pregnancy occurs while either the mother or the father is using brigatinib.

It is not known whether brigatinib passes into breast milk or if it could harm a nursing baby. You should not breast-feed while using this medicine.

What are some other side effects of this drug?

All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:

  • Upset stomach or throwing up.
  • Loose stools (diarrhea).
  • Hard stools (constipation).
  • Belly pain.
  • Not hungry.
  • Feeling tired or weak.
  • Headache.
  • Back pain.
  • Joint pain.
  • Not able to sleep.

These are not all of the side effects that may occur. If you have questions about side effects, call your doctor. Call your doctor for medical advice about side effects.

You may report side effects to the FDA at 1-800-FDA-1088. You may also report side effects at http://www.fda.gov/medwatch.

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