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Prescribing ALUNBRIG  (brigatinib)

ALUNBRIG ordering process for UK Healthcare Professionals

ALUNBRIG is available in 3 strengths (4 pack sizes)

Name Strength Pack Size EAN Code PIP Code
ALUNBRIG (brigatinib) 30 mg 56 tablets 5060065110439 USP0993
ALUNBRIG (brigatinib) 90 mg 7 tablets 5060065110392 USP0944
ALUNBRIG (brigatinib) 90 mg 28 tablets 5060065110408 USP0951
ALUNBRIG (brigatinib) 180 mg 28 tablets 5060065110415 USP0956

Takeda is partnering with Alloga to distribute ALUNBRIG in the UK.

Alloga contact details and lead times:
Alloga UK Ltd
Telephone: +44 (0)1773 441 702
Fax: +44 (0)1773 810 644
E-mail: allogauk.orders@alloga.co.uk

Orders placed with Alloga before 3pm will be delivered the next day for hospitals. Other wholesales are Day 1 for Day 3.

Before prescribing ALUNBRIG

Therapeutic indication1

ALUNBRIG is indicated as monotherapy for the treatment of adult patients with anaplastic lymphoma kinase positive (ALK+) advanced non-small cell lung cancer (aNSCLC) previously treated with crizotinib.

Contraindications1

Hypersensitivity to the active substance or to any of the excipients listed below:


ALUNBRIG pill

Tablet core

  • Lactose monohydrate
  • Microcrystalline cellulose
  • Sodium starch glycolate (type A)
  • Silica colloidal hydrophobic
  • Magnesium stearate

Tablet coating

  • Talc
  • Macrogol
  • Polyvinyl alcohol
  • Titanium dioxide

Special warnings and precautions for use1

Pulmonary adverse reactions

Severe, life threatening, and fatal pulmonary adverse reactions, including those with features consistent with ILD/pneumonitis, can occur in patients treated with ALUNBRIG.

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 trial.

Some patients experienced pneumonitis later in treatment with ALUNBRIG.

Patients should be monitored for new or worsening respiratory symptoms (e.g., dyspnoea, cough, etc.), particularly in the first week of treatment. Evidence of pneumonitis in any patient with worsening respiratory symptoms should be promptly investigated. If pneumonitis is suspected, the dose of ALUNBRIG should be withheld, and the patient evaluated for other causes of symptoms (e.g., pulmonary embolism, tumour progression, and infectious pneumonia). The dose should be modified accordingly.

Hypertension

Hypertension has occurred in patients treated with ALUNBRIG .

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 cannot be avoided. For severe hypertension (≥ Grade 3), ALUNBRIG should be withheld until hypertension has recovered to Grade 1 or to baseline. The dose should be modified accordingly.

Bradycardia

Bradycardia has occurred in patients treated with ALUNBRIG . 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. Upon recovery, the dose should be modified accordingly. In case of life-threatening bradycardia, if no contributing concomitant medication is identified or in case of recurrence, treatment with Alunbrig should be discontinued.

Visual disturbance

Visual disturbance adverse reactions have occurred in patients treated with ALUNBRIG . Patients should be advised to report any visual symptoms. For new or worsening severe visual symptoms, an ophthalmologic evaluation and dose reduction should be considered.

Creatine phosphokinase (CPK) elevation

Elevations of CPK have occurred in patients treated with ALUNBRIG. Patients should be advised to report any unexplained muscle pain, tenderness, or weakness. CPK levels should be monitored regularly during ALUNBRIG treatment. Based on the severity of the CPK elevation, treatment with ALUNBRIG should be withheld, and the dose modified accordingly.

Elevations of pancreatic enzymes

Elevations of amylase and lipase have occurred in patients treated with ALUNBRIG. Lipase and amylase should be monitored regularly during treatment with ALUNBRIG. Based on the severity of the laboratory abnormalities, treatment with ALUNBRIG should be withheld, and the dose modified accordingly.

Hepatotoxicity

Elevations of hepatic enzymes (aspartate aminotransferase, alanine aminotransferase) and bilirubin have occurred in patients treated with ALUNBRIG. 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. Based on the severity of the laboratory abnormalities, treatment should be withheld, and the dose modified accordingly.

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 described below under the heading 'dose modifications for adverse reactions', may be considered or ALUNBRIG may be permanently discontinued.

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.

The concomitant use of Alunbrig with strong and moderate CYP3A inducers should be avoided.

Fertility

Women of childbearing potential should be advised to use effective non-hormonal contraception during treatment with ALUNBRIG and for at least 4 months following the final dose. Men with female partners of childbearing potential should be advised to use effective contraception during treatment and for at least 3 months after the last dose of ALUNBRIG.

Lactose

ALUNBRIG contains lactose monohydrate. Patients with rare hereditary problems of galactoseintolerance, total lactase deficiency, or glucose-galactose malabsorption should not take this medicinal product.

Starting patients on ALUNBRIG


  • When starting patients on ALUNBRIG, ensure they are supplied with the Patient Alert Card
  • ALUNBRIG is available in 180 mg, 90 mg, and 30 mg tablets
Patient Alert Card

Dose modifications for adverse reactions


Interstitial lung disease(ILD)/pneumonitis

Severity:

Grade 1

Dose modification:

  • If event occurs during the first 7 days of treatment, ALUNBRIG should be withheld until recovery to baseline, then resumed at the 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 the same dose level.
  • If ILD/pneumonitis recurs, ALUNBRIG should be permanently discontinued.

Severity:

Grade 2

Dose modification:

  • If ILD/pneumonitis occurs during the first 7 days of treatment, ALUNBRIG should be withheld until recovery to baseline, then resumed at the next lower 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. ALUNBRIG should be resumed at next lower dose level*.
  • If ILD/pneumonitis recurs, ALUNBRIG should be permanently discontinued.

Severity:

Grade 3 or 4

Dose modification:

  • ALUNBRIG should be permanently discontinued.

*Starting dose, 90 mg once daily (first 7 days): first reduce to 60 mg once daily; second permanently discontinue1

Starting dose, 180 mg once daily: first reduce to 120 mg once daily; second reduce to 90 mg once daily; third reduce to 60 mg once daily1

ALUNBRIG should be permanently discontinued if patient is unable to tolerate 60 mg once daily dose1

Hypertension

Severity:

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)

Dose modification:

  • 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* or permanently discontinued.

Severity:

Grade 4 hypertension (life threatening consequences, urgent intervention indicated)

Dose modification:

  • ALUNBRIG should be withheld until hypertension has recovered to ≤1 (SBP <140 mmHg and DBP <90 mmHg), then resumed at the next lower dose level* or permanently discontinued.
  • If Grade 4 hypertension recurs, ALUNBRIG should be permanently discontinued.

*Starting dose, 90 mg once daily (first 7 days): first reduce to 60 mg once daily; second permanently discontinue1

Starting dose, 180 mg once daily: first reduce to 120 mg once daily; second reduce to 90 mg once daily; third reduce to 60 mg once daily1

ALUNBRIG should be permanently discontinued if patient is unable to tolerate 60 mg once daily dose1

Bradycardia (HR < 60 bpm)

Severity:

Symptomatic bradycardia

Dose modification:

  • ALUNBRIG should be withheld until recovery to asymptomatic bradycardia or to a resting heart rate of 60 bpm or above.
  • If 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 medications are not discontinued to dose modified, ALUNBRIG should be resumed at the next lower dose level* upon recovery to asymptomatic bradycardia or to a resting heart rate of 60 bpm or above.

Severity:

Bradycardia with life-threatening consequences, urgent intervention indicated

Dose modification:

  • If contributing concomitant medicinal product is identified and discontinued, or its dose is adjusted, ALUNBRIG should be resumed at the next lower dose level* 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.

*Starting dose, 90 mg once daily (first 7 days): first reduce to 60 mg once daily; second permanently discontinue1

Starting dose, 180 mg once daily: first reduce to 120 mg once daily; second reduce to 90 mg once daily; third reduce to 60 mg once daily1

ALUNBRIG should be permanently discontinued if patient is unable to tolerate 60 mg once daily dose1

Elevation of CPK

Severity:

Grade 3 elevation of CPK (>5.0 x ULN)

Dose modification:

  • ALUNBRIG should be withheld until recovery to Grade ≤1 (≤2.5 x ULN) or to baseline, then resumed at the same dose.
  • If Grade 3 elevation of CPK recurs, ALUNBRIG should be withheld until recovery to Grade ≤1 (≤2.5 x ULN) or to baseline, then resumed at the next lower dose level*.

Severity:

Grade 4 elevation of CPK (>10.0 x ULN)

Dose modification:

  • ALUNBRIG should be withheld until recover to Grade ≤1 (≤2.5 x ULN) or to baseline, then resumed at the next lower does level*.

*Starting dose, 90 mg once daily (first 7 days): first reduce to 60 mg once daily; second permanently discontinue1

Starting dose, 180 mg once daily: first reduce to 120 mg once daily; second reduce to 90 mg once daily; third reduce to 60 mg once daily1

ALUNBRIG should be permanently discontinued if patient is unable to tolerate 60 mg once daily dose1

Elevation of lipase or amylase

Severity:

Grade 3 elevation or lipase or amylase (>2.0 x ULN)

Dose modification:

  • ALUNBRIG should be withheld until recovery to Grade ≤1 (≤1.5 x ULN) or to baseline, then resumed at the same dose.
  • If Grade 3 elevation of lipase and amylase recurs, ALUNBRIG should be withheld until recover to Grade ≤1 (≤1.5 x ULN) or to baseline, then resumed at the next lower dose level*.

Severity:

Grade 4 elevation or lipase or amylase (>5.0 x ULN)

Dose modification:

  • ALUNBRIG should be withheld until recovery to Grade ≤1 (≤1.5 x ULN), then resumed at the next lower dose level*.

*Starting dose, 90 mg once daily (first 7 days): first reduce to 60 mg once daily; second permanently discontinue1

Starting dose, 180 mg once daily: first reduce to 120 mg once daily; second reduce to 90 mg once daily; third reduce to 60 mg once daily1

ALUNBRIG should be permanently discontinued if patient is unable to tolerate 60 mg once daily dose1

Hepatotoxicity

Severity:

Grade ≥3 elevation (>5.0 x ULN) or either alanine aminotransferase (ALT) or aspartate aminotransferase (AST) with bilirubin ≤2 x ULN

Dose modification:

  • ALUNBRIG should be withheld until recovery to baseline or less than or equal to 3 x ULN, then resumed at next lower dose level*.

Severity:

Grade ≥2 elevation (>3 x ULN) of ALT or AST with concurrent total bilirubin elevation >2 x ULN in the absence of cholestasis or haemolysis

Dose modification:

  • ALUNBRIG should be permanently discontinued.

*Starting dose, 90 mg once daily (first 7 days): first reduce to 60 mg once daily; second permanently discontinue1

Starting dose, 180 mg once daily: first reduce to 120 mg once daily; second reduce to 90 mg once daily; third reduce to 60 mg once daily1

ALUNBRIG should be permanently discontinued if patient is unable to tolerate 60 mg once daily dose1

Hyperglycaemia

Severity:

For Grade 3 (>250 mg/dL or 13.9 mmol/L) or greater

Dose modification:

  • If adequate hyperglycaemic control cannot be achieved with optimal medical management, ALUNBRIG should be withheld until adequate hyperglycaemic control is achieved. Upon recovery, ALUNBRIG may either be resumed at the next lower dose level* or permanently discontinued.

*Starting dose, 90 mg once daily (first 7 days): first reduce to 60 mg once daily; second permanently discontinue1

Starting dose, 180 mg once daily: first reduce to 120 mg once daily; second reduce to 90 mg once daily; third reduce to 60 mg once daily1

ALUNBRIG should be permanently discontinued if patient is unable to tolerate 60 mg once daily dose1

Visual disturbance

Severity:

Grade 2 or 3

Dose modification:

  • ALUNBRIG should be withheld until recovery to Grade 1 or baseline, then resumed at the next lower dose level*.

Severity:

Grade 4

Dose modification:

  • ALUNBRIG should permanently discontinued.

*Starting dose, 90 mg once daily (first 7 days): first reduce to 60 mg once daily; second permanently discontinue1

Starting dose, 180 mg once daily: first reduce to 120 mg once daily; second reduce to 90 mg once daily; third reduce to 60 mg once daily1

Other adverse reactions

Severity:

Grade 3

Dose modification:

  • ALUNBRIG should be withheld until recovery to baseline, then resumed at the same dose level.
  • If the Grade 3 event recurs, ALUNBRG should be withheld until recovery to baseline, then resumed at the next lower dose level* or permanently discontinued.

Severity:

Grade 4

Dose modification:

  • ALUNBRIG should be withheld until recovery to baseline, then resumed at the next lower dose level*.
  • If the Grade 4 event recurs, ALUNBRG should be withheld until recovery to baseline, then resumed at the next lower dose level* or permanently discontinued.

*Starting dose, 90 mg once daily (first 7 days): first reduce to 60 mg once daily; second permanently discontinue1

Starting dose, 180 mg once daily: first reduce to 120 mg once daily; second reduce to 90 mg once daily; third reduce to 60 mg once daily1

ALUNBRIG should be permanently discontinued if patient is unable to tolerate 60 mg once daily dose1

Concomitant Medicinal Products1*

  • Avoid concomitant use of strong CYP3A inhibitors, or reduce ALUNBRIG dose if unavoidable
  • Avoid concomitant use of strong and moderate CYP3A inducers
  • Avoid grapefruit or grapefruit juice
  • Avoid coadministration with CYP3A substrates with a narrow therapeutic index (e.g. alfentanil, fentanyl, quinidine, cyclosporine, sirolimus, tacrolimus)
  • Monitor closely if coadministered with moderate CYP3A inhibitors or substrates of P-gp, BCRP, OCT1, MATE1, or MATE2K transporters (e.g. digoxin, dabigatran, methotrexate)

*Please refer to the Summary of Product Characteristics for full details.1

Special populations


Elderly patients

The limited data on the safety and efficacy of ALUNBRIG in patients aged 65 years and older suggest that a dose adjustment is not required in elderly patients. There are no available data on patients over 85 years of age.

Hepatic impairment

No dose adjustment of ALUNBRIG is required for patients with mild hepatic impairment (Child-Pugh class A) or moderate hepatic impairment (Child-Pugh class B). A reduced starting dose of 60 mg once daily for the first 7 days, then 120 mg once daily is recommended for patients with severe hepatic impairment (Child-Pugh class C).

Renal impairment

No dose adjustment of ALUNBRIG is required for patients with mild or moderate renal impairment (estimated glomerular filtration rate (eGFR) ≥ 30 mL/min). A reduced starting dose of 60 mg once daily for the first 7 days, then 90 mg once daily is recommended for patients with severe renal impairment (eGFR < 30 mL/min). Patients with severe renal impairment should be closely monitored for new or worsening respiratory symptoms that may indicate ILD/pneumonitis (e.g., dyspnoea, cough, etc.) particularly in the first week.

Paediatric population

The safety and efficacy of ALUNBRIG in patients less than 18 years of age have not been established. No data are available.