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Alunbrig is a brand name for Brigatinib. The medicine, its uses, side effects and dosage are the same regardless of brand.
Used for: Alunbrig is indicated as monotherapy for the treatment of adult patients with anaplastic lymphoma kinase (ALK)-positive advanced non-small cell lung cancer (NSCLC) previously not treated with an ALK inhibitor. Alunbrig is indicated as monotherapy for the treatment of adult patients with ALK-positive advanced NSCLC…
Verbatim from this product's EMA label. Tap a section to expand.
Treatment with Alunbrig should be initiated and supervised by a physician experienced in the use of anticancer medicinal products. ALK-positive NSCLC status should be known prior to initiation of Alunbrig therapy. 1). Assessment for ALK-positive NSCLC should be performed by laboratories with demonstrated proficiency in the specific technology being utilised.
Posology The recommended starting dose of Alunbrig is 90 mg once daily for the first 7 days, then 180 mg once daily. If Alunbrig is interrupted for 14 days or longer for reasons other than adverse reactions, treatment should be resumed at 90 mg once daily for 7 days before increasing to the previously tolerated dose.
If a dose is missed or vomiting occurs after taking a dose, an additional dose should not be administered and the next dose should be taken at the scheduled time. Treatment should continue as long as clinical benefit is observed. Dose adjustments Dosing interruption and/or dose reduction may be required based on individual safety and tolerability.
Alunbrig dose reduction levels are summarised in Table 1.
Table 1:
Recommended Alunbrig dose reduction levels Dose Dose reduction levels First Second Third 90 mg once daily (first 7 days) reduce to 60 mg once daily permanently discontinue not applicable 180 mg once daily reduce to 120 mg once daily reduce to 90 mg once daily reduce to 60 mg once daily Alunbrig should be permanently discontinued if patient is unable to tolerate the 60 mg once daily dose.
Recommendations for dose modifications of Alunbrig for the management of adverse reactions are summarised in Table 2. 4 Table 2: Recommended Alunbrig dose modifications for adverse reactions Adverse reaction Severity* Dose modification Interstitial lung disease (ILD)/pneumonitis Grade 1 • If event occurs during the first 7 days of treatment, Alunbrig should be withheld until recovery to baseline, then resumed at same dose level and not escalated to 180 mg once daily.
• If ILD/pneumonitis occurs after the first 7 days of treatment, Alunbrig should be withheld until recovery to baseline, then resumed at same dose level. • If ILD/pneumonitis recurs, Alunbrig should be permanently discontinued. Grade 2 • If ILD/pneumonitis occurs during the first 7 days of treatment, Alunbrig should be withheld until recovery to baseline, then resumed at next lower dose level as described in Table 1 and not escalated to 180 mg once daily.
Summary of the safety profile The most common adverse reactions (≥ 25%) reported in patients treated with Alunbrig at the recommended dosing regimen were increased AST, increased CPK, hyperglycaemia, increased lipase, hyperinsulinaemia, diarrhoea, increased ALT, increased amylase, anaemia, nausea, fatigue, hypophosphataemia, decreased lymphocyte count, cough, increased alkaline phosphatase, rash, increased APTT, myalgia, headache, hypertension, decreased white blood cell count, dyspnoea, and vomiting.
The most common serious adverse reactions (≥ 2%) reported in patients treated with Alunbrig at the recommended dosing regimen other than events related to neoplasm progression were pneumonia, pneumonitis, dyspnoea and pyrexia. Tabulated list of adverse reactions The data described below reflect exposure to Alunbrig at the recommended dosing regimen in three clinical trials: a Phase 3 trial (ALTA 1L) in patients with advanced ALK-positive NSCLC previously not treated with an ALK-inhibitor (N = 136), a Phase 2 trial (ALTA) in patients treated with Alunbrig with ALK-positive NSCLC who previously progressed on crizotinib (N = 110), and a phase 1/2 dose escalation/expansion trial in patients with advanced malignancies (N = 28).
8 months. Adverse reactions reported are presented in Table 3 and are listed by system organ class, preferred term and frequency. Frequency categories are very common (≥ 1/10), common (≥ 1/100 to < 1/10) and uncommon (≥ 1/1 000 to < 1/100).
Within each frequency grouping, undesirable effects are presented in order of frequency. 03) at the 180 mg regimen (N = 274) System organ class Frequency category Adverse reactions† all grades Adverse reactions Grade 3-4 Infections and infestations Very common Pneumoniaa,b Upper respiratory tract infection Common Pneumoniaa Blood and lymphatic system disorders Very common Anaemia Lymphocyte count decreased APTT increased White blood cell count decreased Neutrophil count decreased Lymphocyte count decreased Common Decreased platelet count APTT increased Anaemia Uncommon Neutrophil count decreased Metabolism and nutrition disorders Very common Hyperglycaemia Hyperinsulinaemiac Hypophosphataemia Hypomagnesaemia Hypercalcaemia Hyponatraemia Hypokalaemia Decreased appetite Common Hypophosphataemia Hyperglycaemia Hyponatraemia Hypokalaemia Decreased appetite Psychiatric disorders Common Insomnia Nervous system disorders Very common Headached Peripheral neuropathye Dizziness Common Memory impairment Dysgeusia Headached Peripheral neuropathye Uncommon Dizziness Eye disorders Very common Visual disturbancef Common Visual disturbancef Cardiac disorders Common Bradycardiag Electrocardiogram QT prolonged Tachycardiah Palpitations Electrocardiogram QT prolonged Uncommon Bradycardiag Vascular disorders Very common Hypertensioni Hypertensioni Respiratory, thoracic and mediastinal disorders Very common Cough Dyspnoeaj Common Pneumonitisk Pneumonitisk Dyspnoeaj 14 System organ class Frequency category Adverse reactions† all grades Adverse reactions Grade 3-4 Gastrointestinal disorders Very common Lipase increased Diarrhoea Amylase increased Nausea Vomiting Abdominal painl Constipation Stomatitism Lipase increased Common Dry mouth Dyspepsia Flatulence Amylase increased Nausea Abdominal painl Diarrhoea Uncommon Pancreatitis Vomiting Stomatitism Dyspepsia Pancreatitis Hepatobiliary disorders Very common AST increased ALT increased Alkaline phosphatase increased Common Blood lactate dehydrogenase increased Hyperbilirubinaemia ALT increased AST increased Alkaline phosphatase increased Uncommon Hyperbilirubinaemia Skin and subcutaneous tissue disorders Very common Rashn Prurituso Common Dry skin Photosensitivity reactionp Rashn Photosensitivity reactionp Uncommon Dry skin Prurituso Musculoskeleta l and connective tissue disorders Very common Blood CPK increased Myalgiaq Arthralgia Blood CPK increased Common Musculoskeletal chest pain Pain in extremity Musculoskeletal stiffness Uncommon Pain in extremity Musculoskeletal chest pain Myalgiaq Renal and urinary disorders Very common Blood creatinine increased General disorders and administration site conditions Very common Fatiguer Oedemas Pyrexia Common Non-cardiac chest pain Chest discomfort Pain Fatiguer Uncommon Pyrexia Oedemas Non-cardiac chest pain 15 System organ class Frequency category Adverse reactions† all grades Adverse reactions Grade 3-4 Investigations Common Blood cholesterol increasedt Weight decreased Uncommon Weight decreased † The frequencies for ADR terms associated with chemistry and haematology laboratory changes were determined based on the frequency of abnormal laboratory shifts from baseline.
8). Most pulmonary adverse reactions were observed within the first 7 days of treatment. Grade 1-2 pulmonary adverse reactions resolved with interruption of treatment or dose modification. Increased age and shorter interval (less than 7 days) between the last dose of crizotinib and the first dose of Alunbrig were independently associated with an increased rate of these pulmonary adverse reactions.
These factors should be considered when initiating treatment with Alunbrig. Patients with a history of ILD or drug-induced pneumonitis were excluded from the pivotal trials. Some patients experienced pneumonitis later in treatment with Alunbrig.
), particularly in the first week of treatment. Evidence of pneumonitis in any patient with worsening respiratory symptoms should be promptly investigated. , pulmonary embolism, tumour progression, and infectious pneumonia). 2). 8). Blood pressure should be monitored regularly during treatment with Alunbrig.
Hypertension should be treated according to standard guidelines to control blood pressure. Heart rate should be monitored more frequently in patients if concomitant use of a medicinal product known to cause bradycardia 8 cannot be avoided.
For severe hypertension (≥ Grade 3), Alunbrig should be withheld until hypertension has recovered to Grade 1 or to baseline. 2). 8). Caution should be exercised when administering Alunbrig in combination with other agents known to cause bradycardia.
Heart rate and blood pressure should be monitored regularly. If symptomatic bradycardia occurs, treatment with Alunbrig should be withheld and concomitant medicinal products known to cause bradycardia should be evaluated. 2). 2). 8). Patients should be advised to report any visual symptoms.
2). 8). Patients should be advised to report any unexplained muscle pain, tenderness, or weakness. CPK levels should be monitored regularly during Alunbrig treatment. 2). 8). Lipase and amylase should be monitored regularly during treatment with Alunbrig.
1.
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• If ILD/pneumonitis occurs after the first 7 days of treatment, Alunbrig should be withheld until recovery to baseline. Alunbrig should be resumed at next lower dose level as described in Table 1. • If ILD/pneumonitis recurs, Alunbrig should be permanently discontinued.
Grade 3 or 4 • Alunbrig should be permanently discontinued. Hypertension Grade 3 hypertension (SBP ≥ 160 mmHg or DBP ≥ 100 mmHg, medical intervention indicated, more than one anti-hypertensive medicinal product, or more intensive therapy than previously used indicated) • Alunbrig should be withheld until hypertension has recovered to Grade ≤ 1 (SBP < 140 mmHg and DBP < 90 mmHg), then resumed at same dose.
• If Grade 3 hypertension recurs, Alunbrig should be withheld until hypertension has recovered to Grade ≤ 1 then resumed at the next lower dose level per Table 1 or permanently discontinued. Grade 4 hypertension (life threatening consequences, urgent intervention indicated) • Alunbrig should be withheld until hypertension has recovered to Grade ≤ 1 (SBP < 140 mmHg and DBP < 90 mmHg), then resumed at the next lower dose level per Table 1 or permanently discontinued.
• If Grade 4 hypertension recurs, Alunbrig should be permanently discontinued. 5 Adverse reaction Severity* Dose modification Bradycardia (heart rate less than 60 bpm) Symptomatic bradycardia • Alunbrig should be withheld until recovery to asymptomatic bradycardia or to a resting heart rate of 60 bpm or above.
• If a concomitant medicinal product known to cause bradycardia is identified and discontinued, or its dose is adjusted, Alunbrig should be resumed at same dose upon recovery to asymptomatic bradycardia or to a resting heart rate of 60 bpm or above.
• If no concomitant medicinal product known to cause bradycardia is identified, or if contributing concomitant medicinal products are not discontinued or dose modified, Alunbrig should be resumed at the next lower dose level per Table 1 upon recovery to asymptomatic bradycardia or to a resting heart rate of 60 bpm or above.
Bradycardia with life-threatening consequences, urgent intervention indicated • If contributing concomitant medicinal product is identified and discontinued, or its dose is adjusted, Alunbrig should be resumed at the next lower dose level per Table 1 upon recovery to asymptomatic bradycardia or to a resting heart rate of 60 bpm or above, with frequent monitoring as clinically indicated.
• Alunbrig should be permanently discontinued if no contributing concomitant medicinal product is identified. • Alunbrig should be permanently discontinued in case of recurrence. 5 × ULN) elevation of CPK or to baseline, then resumed at the same dose.
5 × ULN) elevation of CPK or to baseline, then resumed at the next lower dose level per Table 1. 5 × ULN) or to baseline, then resumed at same dose. 5 × ULN) or to baseline, then resumed at the next lower dose level per Table 1. […]
a Includes atypical pneumonia, pneumonia, pneumonia aspiration, pneumonia cryptococcal, lower respiratory tract infection, lower respiratory tract infection viral, lung infection b Includes Grade 5 events c Grade not applicable d Includes headache, sinus headache, head discomfort, migraine, tension headache e Includes paraesthesia, peripheral sensory neuropathy, dysaesthesia, hyperaesthesia, hypoaesthesia, neuralgia, neuropathy peripheral, neurotoxicity, peripheral motor neuropathy, polyneuropathy, burning sensation, post herpetic neuralgia f Includes altered visual depth perception, cataract, colour blindness acquired, diplopia, glaucoma, intraocular pressure increased, macular oedema, photophobia, photopsia, retinal oedema, vision blurred, visual acuity reduced, visual field defect, visual impairment, vitreous detachment, vitreous floaters, amaurosis fugax g Includes bradycardia, sinus bradycardia h Includes sinus tachycardia, tachycardia, atrial tachycardia, heart rate increased i Includes blood pressure increased, diastolic […]
2). 8). Liver function, including AST, ALT and total bilirubin should be assessed prior to the initiation of Alunbrig and then every 2 weeks during the first 3 months of treatment. Thereafter, monitoring should be performed periodically.
2). Hyperglycaemia Elevations of serum glucose have occurred in patients treated with Alunbrig. Fasting serum glucose should be assessed prior to initiation of Alunbrig and monitored periodically thereafter. Antihyperglycaemic treatment should be initiated or optimised as needed.
If adequate hyperglycaemic control cannot be achieved with optimal medical management, Alunbrig should be withheld until adequate hyperglycaemic control is achieved; upon recovery reducing the dose as described in Table 1 may be considered or Alunbrig may be permanently discontinued.
9 Drug-drug interactions The concomitant use of Alunbrig with strong CYP3A inhibitors should be avoided. If concomitant use of strong CYP3A inhibitors cannot be avoided, the dose of Alunbrig should be reduced from 180 mg to 90 mg, or from 90 mg to 60 mg.
After discontinuation of a strong CYP3A inhibitor, Alunbrig should be resumed at the dose that was tolerated prior to the initiation of the strong CYP3A inhibitor. 5). If concomitant use of moderate CYP3A inducers cannot be avoided, the dose of Alunbrig may be increased in 30 mg increments after 7 days of treatment with the current Alunbrig dose as tolerated, up to a maximum of twice the Alunbrig dose that was tolerated prior to the initiation of the moderate CYP3A inducer.
After discontinuation of a moderate CYP3A inducer, Alunbrig should be resumed at the dose that was tolerated prior to the initiation of the moderate CYP3A inducer. Photosensitivity and photodermatosis Photosensitivity to sunlight has […]