Respiratory and thoracic cancers:
Indications for LORBRENA:
Metastatic non-small cell lung cancer (NSCLC) in patients whose tumors are ALK (+) as detected by an FDA-approved test.
Confirm presence of ALK (+) in tumor specimens. Swallow whole. 100mg once daily until disease progression or unacceptable toxicity. Avoid concomitant moderate CYP3A inducers; if unavoidable, increase Lorbrena dose to 125mg once daily. Avoid concomitant strong CYP3A inhibitors; if unavoidable, reduce Lorbrena dose to 75mg once daily; or to 50mg once daily (see full labeling); increase dose after inhibitor is discontinued. Avoid concomitant fluconazole; if unavoidable, reduce Lorbrena dose to 75mg once daily. Severe renal impairment (CrCl 15–<30mL/min): reduce Lorbrena dose to 75mg once daily. Dose modifications for adverse reactions: see full labeling.
Concomitant strong CYP3A inducers.
Risk of severe hepatotoxicity with concomitant strong CYP3A inducers. Withhold and resume (at same or reduced dose) or permanently discontinue based on severity if CNS effects occur. Monitor serum cholesterol and TGs prior to treatment, at Months 1 and 2, and periodically thereafter; withhold and resume (at same or reduced dose) based on severity, if hypercholesterolemia or hypertriglyceridemia occurs. Monitor ECG prior to treatment and periodically thereafter; withhold and resume (at same or reduced dose) if undergoing pacemaker placement; permanently discontinue if AV block recurs in patients without a pacemaker. Withhold if interstitial lung disease (ILD)/pneumonitis is suspected; permanently discontinue for treatment-related ILD/pneumonitis of any severity. Control BP prior to initiation, then monitor after 2 weeks and at least monthly thereafter; withhold and resume at reduced dose or permanently discontinue based on severity. Monitor fasting serum glucose prior to initiation and periodically thereafter; withhold and resume at reduced dose or permanently discontinue based on severity. Moderate (total bilirubin ≥1.5–3×ULN with any AST) or severe (total bilirubin >3×ULN with any AST) hepatic impairment. Severe renal impairment (CrCl 15–<30mL/min): reduce Lorbrena dose (See Adult). Embryo-fetal toxicity. Advise to use effective non-hormonal contraception during and for ≥6 months (females of reproductive potential) or ≥3 months (males w. female partners) after the last dose. Pregnancy: exclude status prior to initiation. Nursing mothers: not recommended (during and for ≥7 days after the last dose).
See Contraindications. Antagonized by strong CYP3A inducers (eg, rifampin). Discontinue strong CYP3A inducers for 3 plasma half-lives prior to treatment. Antagonized by moderate CYP3A inducers (eg, modafinil); see Adult dose. Potentiated by strong CYP3A inhibitors (eg, itraconazole); see Adult dose. May be potentiated by fluconazole; see Adult dose. Antagonizes CYP3A or P-gp substrates (eg, midazolam, fexofenadine); if unavoidable, increase substrate dose accordingly.
Edema, peripheral neuropathy, weight gain, cognitive effects, fatigue, dyspnea, arthralgia, diarrhea, mood effects, cough, hypercholesterolemia, hypertriglyceridemia; serious hepatotoxicity, hyperlipidemia, AV block, ILD/pneumonitis, hypertension, hyperglycemia.
Generic Drug Availability: