Respiratory and thoracic cancers:

Indications for ALUNBRIG:

Treatment of adults with anaplastic lymphoma kinase (ALK)-positive, metastatic non-small cell lung cancer (NSCLC), as determined by an FDA-approved test.

Adult:

Swallow whole. 90mg once daily for first 7 days; then increase to 180mg once daily. Continue until disease progression or unacceptable toxicity. If dose interrupted for ≥14 days (not due to adverse reactions), resume at 90mg daily for 7 days then re-titrate. Concomitant strong or moderate CYP3A inhibitors: avoid; if strong inhibitor required, reduce Alunbrig dose by ~50%; if moderate inhibitor required, reduce Alunbrig dose by ~40%. Concomitant moderate CYP3A inducers: avoid; if required, increase Alunbrig dose in 30mg increments after 7 days of current Alunbrig dose as tolerated; up to max twice the Alunbrig dose prior to initiating the moderate inducer. Severe hepatic impairment (Child-Pugh C): reduce Alunbrig dose by ~40%. Severe renal impairment: (CrCl 15–29mL/min): reduce Alunbrig dose by ~50%. Dose modifications for adverse reactions: see full labeling.

Children:

Not established.

Warnings/Precautions:

Monitor for new or worsening respiratory symptoms esp. during 1st week of initiation; if occurs, withhold and evaluate for ILD/pneumonitis; reduce dose or permanently discontinue based on severity. Control BP prior to initiation; monitor after 2 weeks and at least monthly thereafter; withhold, reduce dose, or permanently discontinue based on severity. Monitor HR and BP regularly; if symptomatic bradycardia occurs, withhold and evaluate any concomitant drugs known to cause bradycardia; resume at same or reduced dose after resolution; discontinue for life-threatening bradycardia if no contributing concomitant medication identified. Withhold and evaluate for new or worsening visual symptoms of Grade ≥2; reduce dose or permanently discontinue based on severity. Monitor CPK, lipase, and amylase levels during treatment; withhold for Grade 3/4 elevation; resume at same or reduced dose upon recovery to Grade 1 or baseline. Assess fasting serum glucose prior to initiation and periodically thereafter; if not adequately controlled with optimal antihyperglycemics, withhold then consider dose reduction, or permanently discontinue based on severity. Severe hepatic or severe renal impairment. Embryo-fetal toxicity. Pregnancy: exclude status prior to initiation. Advise to use effective non-hormonal contraception during and for at least 4 months (females of reproductive potential) or 3 months (males w. female partners) after final dose. Nursing mothers: not recommended (during and for 1 week after final dose).

Pharmacologic Class:

Kinase inhibitor.

Interactions:

Avoid concomitant strong or moderate CYP3A inhibitors (eg, itraconazole); see Adults. Avoid grapefruit or grapefruit juice. Avoid concomitant strong or moderate CYP3A inducers (eg, rifampin); see Adults. May reduce efficacy of sensitive CYP3A substrates (eg, hormonal contraceptives). Caution with antihypertensives that cause bradycardia.

Adverse Reactions:

Diarrhea, fatigue, nausea, rash, cough, myalgia, headache, hypertension, vomiting, dyspnea; pneumonia, ILD/pneumonitis, pyrexia, pulmonary embolism, asthenia; possible infertility in males.

Metabolism:

CYP2C8, CYP3A4.

Elimination:

Fecal (major), renal. Half-life: 25 hours.

Generic Availability:

NO

How Supplied:

Tabs 30mg—30; 90mg—7, 30; 180mg—23, 30; Initiation pack—7 (90mg) + 23 (180mg)