Usual Adult Dose for Non-Small Cell Lung Cancer

100 mg orally once a day

Comments:

• Select patients for the treatment of metastatic non-small cell lung cancer (NSCLC) based on the presence of ALK positivity in tumor specimens.
• Therapy should be continued until disease progression or unacceptable toxicity.

Use: For the treatment of adult patients with metastatic NSCLC whose tumors are anaplastic lymphoma kinase (ALK)-positive as detected by an FDA-approved test

Renal Dose Adjustments

• Mild or moderate renal dysfunction (CrCl 30 to 89 mL/min): No adjustment recommended.
• Severe renal dysfunction (CrCl 15 to less than 30 mL/min): 75 mg orally once a day

Liver Dose Adjustments

• Mild liver dysfunction (total bilirubin less than or equal to upper limit of normal (ULN) with AST greater than ULN or total bilirubin greater than 1 to 1.5 x ULN with any AST): No adjustment recommended.
• Moderate or severe live dysfunction: Data not available

Dose Adjustments

Dose Modifications for Adverse Reactions:

• First dose reduction: 75 orally once a day
• Second dose reduction: 50 mg orally once a day
• Permanently discontinue therapy in patients who are unable to tolerate 50 mg orally once daily.

Central Nervous System Adverse Effects:

• Grade 1: Continue at same dose or withhold the dose until recovery to baseline; resume at the same dose or at reduced dose.
• Grade 2 or 3: Withhold dose until recovery to Grade 0 or 1; resume at reduced dose.
• Grade 4: Permanently discontinue therapy.

Hyperlipidemia:
Grade 4 hypercholesterolemia OR Grade 4 hypertriglyceridemia: Withhold until recovery to Grade 2 or less; resume at same dose. If severe hypercholesterolemia and/or hypertriglyceridemia recurs, resume at reduced dose.

Atrioventricular (AV) Block:

• Second-degree AV block: Withhold until PR interval is less than 200 ms; resume at reduced dose.
• First occurrence of complete AV block: Withhold until pacemaker placed OR PR interval is less than 200 ms; if a pacemaker is placed, resume at same dose; if no pacemaker is placed, resume at reduced dose.
• Recurrent complete AV block: Place pacemaker or permanently discontinue this drug.

Interstitial Lung Disease (ILD)/Pneumonitis:

• Any Grade treatment-related ILD/pneumonitis: Permanently discontinue this drug.

Hypertension:

• Grade 3 (SBP greater than or equal to 160 mmHg or DBP greater than or equal to 100 mmHg; medical intervention indicated; more than one antihypertensive drug, or more intensive therapy than previously used indicated): Withhold until hypertension has recovered to Grade 1 or less (SBP less than 140 mmHg and DBP less than 90 mmHg), then resume at the same dose.
• If Grade 3 hypertension recurs, withhold until recovery to Grade 1 or less, and resume at a reduced dose. Permanently discontinue, if adequate hypertension control cannot be achieved with optimal medical management.

Grade 4 (life-threatening consequences, urgent intervention indicated): Withhold until recovery to Grade 1 or less, and resume at a reduced dose or permanently discontinue. Permanently discontinue, if Grade 4 hypertension recurs.

Hyperglycemia:
Grade 3 (greater than 250 mg/dL) despite optimal anti-hyperglycemic therapy OR Grade 4: Withhold until hyperglycemia is adequately controlled, then resume at the next lower dosage. If adequate hyperglycemic control cannot be achieved with optimal medical management, permanently discontinue

Other Adverse Reactions:

• Grade 1 or 2: Continue at same or reduced dose.
• Grade 3 or 4: Withhold until symptoms resolve to Grade 2 or less or baseline; resume at reduced dose.

Concomitant Use of Strong CYP450 3A Inducers:

• This drug is contraindicated in patients taking strong CYP450 3A inducers. Discontinue strong CYP450 3A inducers for 3 plasma half-lives prior to initiating this drug.

Concomitant Use of Moderate CYP450 3A Inducers:

• Avoid concomitant use of this drug with moderate CYP450 3A inducers.
• If concomitant use with moderate CYP450 3A inducers is unavoidable, increase the dose of this drug to 125 mg once a day.

Dose Modification for Strong CYP450 3A Inhibitors:

• Avoid concomitant use of this drug with strong CYP450 3A inhibitors. If concomitant use with a strong CYP450 3A inhibitor cannot be avoided, reduce the starting dose of this drug from 100 mg once a day to 75 mg orally once a day.
• In patients who have had a reduction to 75 mg orally once a day due to adverse reactions and who initiate a strong CYP450 3A inhibitor, reduce the dose of this drug to 50 mg orally once a day.
• If concomitant use of a strong CYP450 3A inhibitor is discontinued, increase the dose of this drug (after 3 plasma half-lives of the strong CYP450 3A inhibitor) to the dose that was used before starting the strong inhibitor.

Precautions

CONTRAINDICATIONS:

• Concomitant administration with strong CYP450 3A inducers because of the potential for serious hepatotoxicity

Safety and efficacy have not been established in patients younger than 18 years.

Consult WARNINGS section for additional precautions.

Dialysis

Data not available

Other Comments

Administration advice:

• This drug may be taken with or without food.
• Swallow tablets whole, do not chew, crush or split.
• Do not ingest if tablets are broken, cracked, or otherwise not intact.
• If a dose is missed, take the missed dose unless the next dose is due within 4 hours; do not take 2 doses at the same time to make up for a missed dose.
• Do not take an additional dose if vomiting occurs but continue with the next scheduled dose.

Storage requirements:

• Store at 20C to 25C (68F to 77F); excursions permitted between 15C to 30C (59F to 86F).

Monitoring:

• Monitor blood pressure after 2 weeks and then at least monthly during treatment.
• Monitor serum cholesterol and triglycerides before initiating treatment, after 1 and 2 months during treatment, and periodically thereafter.
• Monitor ECG prior to initiating treatment and periodically thereafter.
• Obtain fasting serum glucose prior to initiating treatment and monitor periodically thereafter.

Patient advice:

• Advise the patient to read the FDA-approved patient labeling (Patient Information).
• Inform patients of the potential risk of hepatotoxicity with the concomitant use of strong CYP450 3A inducers.
• Advise patients to inform their healthcare providers of all medications they are taking, including prescription medicines, over-the-counter drugs, vitamins, and herbal products (e.g., St. John's wort).
• Advise patients to notify their healthcare provider if they experience new or worsening CNS symptoms.
• Advise patients that initiation or an increase in the dose of lipid-lowering agents may be required, depending on measured readings.
• Advise patients to contact their healthcare provider immediately to report new or worsening cardiac symptoms.
• Advise patients to contact their healthcare provider immediately to report new or worsening respiratory symptoms.
• Advise patients of the risks of hypertension and to promptly report signs or symptoms of hypertension to their healthcare provider and that antihypertension medications may need to be initiated or adjusted during treatment.
• Advise patients with newly occurring hyperglycemia during treatment that antihyperglycemic medications may need to be initiated.
• Inform patients with diabetes mellitus or glucose intolerance to monitor glucose levels periodically and that antihyperglycemic medications may need to be adjusted during treatment , depending on reading.
• Advise females of reproductive potential of the potential risk to a fetus and to inform their healthcare provider of a known or suspected pregnancy.
• Advise females of reproductive potential to use effective non-hormonal contraception during treatment and for at least 6 months after the final dose.
• Advise male patients with female partners of reproductive potential to use effective contraception during treatment and for at least 3 months after the final dose
• Advise women not to breastfeed during treatment and for 7 days after the final dose.
• Advise males of reproductive potential that this drug may transiently impair fertility.

Frequently asked questions

• What type of drug is Lorbrena?