Brigatinib oral
- Drugs List
- Therapeutic Indications
- Dosage
- Contraindications
- Precautions and Warnings
- Pregnancy and Lactation
- Side Effects
- Monograph
Presentation
Oral formulations of brigatinib.
Drugs List
Therapeutic Indications
Uses
Anaplastic lymphoma kinase (ALK)+ve advanced non-small cell lung cancer
Anaplastic lymphoma kinase (ALK) positive advanced non-small cell lung cancer (NSCLC), not previously treated with an ALK inhibitor.
Anaplastic lymphoma kinase (ALK) positive advanced non-small cell lung cancer (NSCLC), when previously treated with crizotinib.
Dosage
Whilst the doses stated below are those recommended by the manufacturer, local cancer network protocols for the relevant indication should be consulted.
Adults
Starting dose
90mg once daily for 7 days.
Maintenance dose
180mg once daily.
Patients with Renal Impairment
Starting dose
60mg once daily for 7 days.
Maintenance dose
90mg once daily.
Patients with Hepatic Impairment
Starting dose
60mg once daily for 7 days.
Maintenance dose
120mg once daily.
Additional Dosage Information
Dose reduction levels
First 7 days of treatment (starting dose)
First reduction: Reduce to 60mg once daily.
Second reduction: Permanently discontinue brigatinib.
8 or more days of treatment (maintenance dose)
First reduction: Reduce to 120mg once daily.
Second reduction: Reduce to 90mg once daily.
Third reduction: Reduce to 60mg once daily.
Fourth reduction: Permanently discontinue brigatinib.
Interstitial lung disease (ILD)/pneumonitis
Grade 1
First 7 days of treatment: Withhold brigatinib. Upon recovery to baseline, resume brigatinib at the same dose level. Do not escalate to 180mg. If ILD/pneumonitis recurs, discontinue brigatinib.
8 or more days of treatment: Withhold brigatinib. Upon recovery to baseline, resume brigatinib at the same dose level. If ILD/pneumonitis recurs, discontinue brigatinib.
Grade 2
First 7 days of treatment: Withhold brigatinib. Upon recovery to baseline, resume brigatinib at one lower dose level. Do not escalate to 180mg. If ILD/pneumonitis recurs, discontinue brigatinib.
8 or more days of treatment: Withhold brigatinib. Upon recovery to baseline, resume brigatinib at one lower dose level. If ILD/pneumonitis recurs, discontinue brigatinib.
Grade 3
Permanently discontinue brigatinib.
Hypertension
Grade 3
First occurrence: Withhold brigatinib. Upon recovery to grade 1 or lower, resume brigatinib at the same dose level.
Recurrence: Withhold brigatinib. Upon recovery to grade 1 or lower, resume brigatinib at one lower dose level, or discontinue brigatinib.
Grade 4
First occurrence: Withhold brigatinib. Upon recovery to grade 1 or lower, resume brigatinib at one lower dose level, or discontinue brigatinib.
Recurrence: Discontinue brigatinib.
Bradycardia
Symptomatic bradycardia
Caused by concomitant medication: Withhold brigatinib. Discontinue or modify the dosage of medication known to cause bradycardia. Upon recovery to asymptomatic bradycardia or heart rate above 60bpm, resume brigatinib at the same dose level.
Not caused by concomitant medication/concomitant medication cannot be modified: Withhold brigatinib. Upon recovery to asymptomatic bradycardia or heart rate above 60bpm, resume brigatinib at one lower dose level.
Life threatening bradycardia
Caused by concomitant medication: Withhold brigatinib. Discontinue or modify the dosage of medication known to cause bradycardia. Upon recovery to asymptomatic bradycardia or heart rate above 60bpm, resume brigatinib at one lower dose level, and monitor patient frequently. If life threatening bradycardia recurs, discontinue brigatinib.
Not caused by concomitant medication/concomitant medication cannot be modified: Discontinue brigatinib.
Creatine phosphokinase elevations
Grade 3 or 4 - greater than 5 times the upper limit of normal (ULN) with greater than or equal to grade 2 muscle pain or weakness
First occurrence: Withhold brigatinib. Upon recovery to grade 1 (less than or equal to 2.5 times the upper limit of normal) or less, resume brigatinib at the same dose level.
Recurrence: Withhold brigatinib. Upon recovery to grade 1 or lower, resume brigatinib at one lower dose level.
Lipase and amylase elevations
Grade 3- greater than 2 times the upper limit of normal (ULN)
First occurrence: Withhold brigatinib. Upon recovery to grade 1 (less than or equal to 1.5 times the upper limit of normal) or less, resume brigatinib at the same dose level.
Recurrence: Withhold brigatinib. Upon recovery to grade 1 or lower, resume brigatinib at one lower dose level.
Grade 4- greater than 5 times ULN
Withhold brigatinib. Upon recovery to grade 1 or lower, resume brigatinib at one lower dose level.
Hepatotoxicity
Grade 3 or more ALT/AST elevations (greater than 5 times ULN) with concurrent bilirubin elevations 2 or more times ULN
Withhold brigatinib. Upon recovery to baseline or less than or equal to AST/ALT 3 times ULN, resume brigatinib at one lower dose level.
Grade 2 or more ALT/AST elevations (greater than 3 times ULN) with concurrent bilirubin elevations 2 or more times ULN, without cholestasis or haemolysis
Withhold brigatinib. Discontinue brigatinib.
Hyperglycaemia
Grade 3 or more (greater than 250mg/dL, or 13.9mmol/L)
If adequate hyperglycaemic control cannot be achieved with optimal medical management, withhold brigatinib. Upon recovery of adequate hyperglycaemic control, resume brigatinib at one lower dose level, or discontinue.
Visual disturbances
Grade 2 or 3
Withhold brigatinib. Upon recovery to grade 1 or lower, resume brigatinib at one lower dose level.
Grade 4
Discontinue brigatinib.
Other adverse reactions
Grade 3
First occurrence: Withhold brigatinib. Upon recovery to baseline, resume brigatinib at the same dose level.
Recurrence: Withhold brigatinib. Upon recovery to baseline, resume brigatinib at one lower dose level, or discontinue brigatinib.
Grade 4
First occurrence: Withhold brigatinib. Upon recovery to baseline, resume brigatinib at one lower dose level.
Recurrence: Withhold brigatinib. Upon recovery to baseline, resume brigatinib at one lower dose level, or discontinue brigatinib.
Missed dose
If a dose is missed or vomiting occurs after taking a dose, the patient should wait until the next schedueld dose time, and should not take an additional dose.
Contraindications
Children under 18 years
Breastfeeding
Galactosaemia
Pregnancy
Precautions and Warnings
Glucose-galactose malabsorption syndrome
Lactose intolerance
Renal impairment - eGFR below 30ml/minute/1.73m sq
Severe hepatic impairment - Child-Pugh score greater than or equal to 10
Reduce dose in patients with severe hepatic impairment
Reduce dose in patients with severe renal impairment
Advise ability to drive/operate machinery may be affected by side effects
Confirm ALK-positive status prior to treatment
Treatment to be initiated and supervised by a specialist
Contains lactose
Consult local policy on the safe use of oral anti-cancer drugs
Staff: Not to be handled by pregnant staff
Monitor fasting serum glucose prior to and periodically during treatment
Monitor hepatic function prior to treatment
If visual disturbances occur, perform ophthalmic evaluation
Monitor creatine kinase levels in all patients
Monitor heart rate and blood pressure regularly
Monitor hepatic function every 2 weeks for first 3 months then periodically
Monitor respiratory function
Monitor serum amylase and lipase regularly
Advise patient to report new visual problems and symptoms
Advise patients to report muscle pain/tenderness/weakness
Consider dose modification in non-haematological toxicity
Advise patient not to take St John's wort concurrently
Advise patient to avoid grapefruit products
Male: May cause infertility
Female:Barrier contraception required during & for 4 months after treatment
Male: Contraception required during and for 3 months after treatment
Pregnancy and Lactation
Pregnancy
Brigatinib is contraindicated in pregnancy.
The manufacturer recommends brigatinib is not used pregnancy unless the clinical condition of the mother requires treatment.
At the time of writing there is limited data on the use of brigatinib in pregnant women. Animal studies have shown reproductive toxicity.
Lactation
Brigatinib is contraindicated in breastfeeding.
The manufacturer recommends that breastfeeding is discontinued during treatment with brigatinib.
It is not known if brigatinib or its metabolites are excreted in breast milk. LactMed suggests avoiding breastfeeding for 1 week after the final dose of brigatinib.
Side Effects
Abdominal pain
Anaemia
Arthralgia
Bradycardia
Chest discomfort
Constipation
Cough
Creatine phosphokinase increased
Decreased appetite
Diarrhoea
Dizziness
Dry mouth
Dry skin
Dysgeusia
Dyspepsia
Dyspnoea
Electrolyte disturbances
Elevated amylase levels
Elevated serum lipase
Fatigue
Flatulence
Headache
Hyperbilirubinaemia
Hyperglycaemia
Hyperinsulinemia
Hypertension
Hypophosphataemia
Impaired memory
Increase in alkaline phosphatase
Increase in ALT level
Increase in AST level
Increase in lactate dehydrogenase
Increased partial thromboplastin time
Insomnia
Myalgia
Nausea
Non-cardiac chest pain
Oedema
Pain - generalised
Painful extremities
Palpitations
Pancreatitis
Peripheral neuropathy
Pneumonia
Pneumonitis
Prolongation of QT interval
Pruritus
Pyrexia
Rash
Reduced lymphocyte count
Reduced neutrophil count
Reduced platelet count
Serum creatinine increased
Stiffness
Stomatitis
Tachycardia
Upper respiratory tract infection
Visual disturbances
Vomiting
Weight loss
White blood cell count decreased
Overdosage
It is strongly recommended that the UK National Poisons Information Service be consulted on cases of suspected or actual overdose where there is doubt over the degree of risk or about appropriate management.
The following number will direct the caller to the relevant local centre (0844) 892 0111
Information may be obtained if you have access to ToxBase the primary clinical toxicology database of the National Poisons Information Service. This is available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).
Further Information
Last Full Review Date: October 2020
Reference Sources
Summary of Product Characteristics: Alunbrig 30mg film coated tablets. Takeda UK Ltd. Revised April 2020.
Summary of Product Characteristics: Alunbrig 90mg film coated tablets. Takeda UK Ltd. Revised April 2020.
Summary of Product Characteristics: Alunbrig 180mg film coated tablets. Takeda UK Ltd. Revised April 2020.
US National Library of Medicine. Toxicology Data Network. Drugs and Lactation Database (LactMed).
Available at: https://www.ncbi.nlm.nih.gov/books/NBK501922/
Brigatinib. Last revised: 03 December 2018
Last accessed: October 2020
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