Alunbrig for metastatic ALK-positive non-small cell lung cancer

Alunbrig is an oral kinase inhibitor approved for treating adult patients with anaplastic lymphoma kinase (ALK)-positive metastatic non-small cell lung cancer (NSCLC). It is designed to target and block ALK activity in cancer cells, helping to control disease progression.

Indication: Alunbrig is used to treat adults with metastatic NSCLC confirmed to be ALK-positive by an FDA-approved test. It is administered orally until disease progression or unacceptable toxicity occurs.

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Alunbrig works by inhibiting the activity of the anaplastic lymphoma kinase (ALK), a protein that promotes cancer cell growth in ALK-positive NSCLC. By blocking ALK signaling pathways, Alunbrig helps to slow or stop tumor growth.

The recommended starting dose of Alunbrig is 90 mg orally once daily for the first 7 days. After 7 days, the dose is increased to 180 mg orally once daily. The medication may be taken with or without food, and tablets should be swallowed whole without crushing or chewing.

If treatment is interrupted for 14 days or more (except due to adverse reactions), resume at 90 mg once daily for 7 days before increasing to the previously tolerated dose. If a dose is missed or vomiting occurs after dosing, do not take an extra dose; take the next dose at the scheduled time.

Dosage reductions for adverse reactions:

• From 180 mg: reduce to 120 mg, then to 90 mg, then 60 mg daily before discontinuation.
• From 90 mg: reduce to 60 mg daily before discontinuation.

Once the dose is reduced, do not increase again. Permanently discontinue if the patient cannot tolerate 60 mg once daily.

Dose modifications for specific adverse reactions: Adjustments depend on severity and type, including for interstitial lung disease/pneumonitis, hypertension, bradycardia, visual disturbances, elevated creatine phosphokinase, lipase/amylase, hepatotoxicity, and hyperglycemia. In general, withhold until recovery then resume at the same or lower dose; permanently discontinue for severe or recurrent events.

Modifications with drug interactions:

• Avoid strong or moderate CYP3A inhibitors; if unavoidable, reduce dose by approximately 50% for strong inhibitors and 40% for moderate inhibitors.
• Avoid moderate CYP3A inducers; if unavoidable, increase dose in 30 mg increments up to twice the tolerated dose.

Adjustments for impairment:

• Severe hepatic impairment (Child-Pugh C): reduce dose by approximately 40%.
• Severe renal impairment (creatinine clearance 15-29 mL/min): reduce dose by approximately 50%.

Serious risks and precautions include:

• Interstitial Lung Disease (ILD)/Pneumonitis: May cause new or worsening lung symptoms. Monitor closely, withhold and adjust dose as recommended, and permanently discontinue for recurrent or severe cases.
• Hypertension: Monitor blood pressure; withhold and adjust dose for Grade 3 or 4 hypertension. Consider permanent discontinuation if severe hypertension recurs.
• Bradycardia: Monitor heart rate; withhold and adjust dose for symptomatic bradycardia. Permanently discontinue if life-threatening bradycardia recurs without a contributing medication cause.
• Visual disturbances: Withhold and reduce dose for moderate visual symptoms; discontinue for severe disturbance.
• Liver toxicity: Monitor liver enzymes; withhold and reduce dose for elevated ALT/AST. Permanently discontinue if bilirubin is also elevated significantly.
• Elevations in muscle enzymes (CPK) and pancreatic enzymes (lipase/amylase): Monitor and adjust dose for significant elevations with symptoms.
• Hyperglycemia: Monitor blood glucose; withhold and adjust dose if control is inadequate despite management.

Common side effects are not detailed in the provided label excerpt. Serious adverse reactions requiring dose modification or treatment interruption include ILD/pneumonitis, hypertension, bradycardia, visual disturbances, elevated liver and muscle enzymes, and hyperglycemia.

Avoid coadministration of strong or moderate CYP3A inhibitors; if unavoidable, reduce Alunbrig dose by approximately 50% for strong inhibitors and 40% for moderate inhibitors. Avoid moderate CYP3A inducers; if unavoidable, increase dose in 30 mg increments after 7 days, up to twice the tolerated dose. After stopping inhibitors or inducers, resume the prior tolerated dose.