GENERIC NAME: Lorlatinib 25 mg, 100 mg Tablets.
 

PRESENTATION: 30 tablets with a with concentration of 25 mg and 100 mg.

INDICATION(s): LORBRENA™ is indicated for the treatment of adult patients with metastatic non-small cell lung cancer (NSCLC) whose tumors are anaplastic lymphoma kinase (ALK)-positive as detected by an FDA-approved test.
 

DOSAGE AND ADMINISTRATION: The recommended dosage of LORBRENA is 100 mg orally once daily, with or without food, until disease progression or unacceptable toxicity. Swallow tablets whole. Do not chew, crush or split tablets. Do not ingest if tablets are broken, cracked, or otherwise not intact. Take LORBRENA at the same time each day. If a dose is missed, then 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 after LORBRENA but continue with the next scheduled dose.
 

DOSE MODIFICATION FOR ADVERSE REACTIONS: The recommended dose reductions are:

First dose reduction: LORBRENA 75 mg orally once daily.
Second dose reduction: LORBRENA 50 mg orally once daily Permanently discontinue LORBRENA in patients who are unable to tolerate 50 mg orally once daily.
Concomitant Use of Strong CYP3A Inducers: LORBRENA is contraindicated in patients taking strong CYP3A inducers. Discontinue strong CYP3A inducers for 3 plasma half-lives of the strong CYP3A inducer prior to initiating LORBRENA.
Concomitant Use of Moderate CYP3A Inducers: Avoid concomitant use of moderate CYP3A inducers with LORBRENA.If concomitant use with moderate CYP3A inducers is unavoidable, increase the LORBRENA dose to 125 mg once daily. 
Dosage Modification for Strong CYP3A Inhibitors: Avoid concomitant use of LORBRENA with strong CYP3A inhibitors. If concomitant use with a strong CYP3A inhibitor is unavoidable, reduce

the starting dose of LORBRENA from 100 mg orally once daily to 75 mg orally once daily. In patients who have had a dose reduction to 75 mg orally once daily due to adverse reactions and who initiate a strong CYP3A inhibitor, reduce the LORBRENA dose to 50 mg orally once daily.If concomitant use of a strong CYP3A inhibitor is discontinued, increase the LORBRENA dose (after 3 plasma half-lives of the strong CYP3A inhibitor) to the dose that was used before starting the strong inhibitor.
Dosage Modification for Fluconazole: Avoid concomitant use of LORBRENA with fluconazole. If concomitant use is unavoidable, reduce the starting dose of LORBRENA from 100 mg orally once daily to 75 mg orally once daily.
Dosage Modification for Severe Renal Impairment: Reduce the recommended dosage of LORBRENA for patients with severe renal impairment (creatinine clearance [CLcr] 15 to < 30 mL/min, estimated by Cockcroft-Gault) from 100 mg to 75 mg orally once daily.
 

CONTRAINDICATIONS: LORBRENA is contraindicated in patients taking strong CYP3A inducers, due to the potential for serious hepatotoxicity.
 

WARNING AND PRECAUTIONS: Risk of Serious Hepatotoxicity with
Concomitant Use of Strong CYP3A Inducers: Severe hepatotoxicity occurred in 10 of 12 healthy subjects receiving a single dose of LORBRENA with multiple daily doses of rifampin, a strong CYP3A inducer. Central Nervous System
Effects: A broad spectrum of central nervous system (CNS) effects can occur in patients receiving LORBRENA. These include seizures, psychotic effects and changes in cognitive function, mood (including suicidal ideation), speech, mental status, and sleep.
 

Hyperlipidemia: Increases in serum cholesterol and triglycerides can occur in patients receiving LORBRENA. 
Atrioventricular Block: PR interval prolongation and atrioventricular (AV) block can occur in patients receiving LORBRENA. 
Interstitial Lung Disease/Pneumonitis: Severe or life-threatening pulmonary adverse reactions consistent with interstitial lung disease (ILD)/pneumonitis can occur with LORBRENA. Hypertension: Hypertension can occur in patients receiving LORBRENA. Hyperglycemia: Hyperglycemia can occur in patients receiving LORBRENA.
Embryo-Fetal Toxicity: Based on findings from animal studies and its mechanism of action, LORBRENA can cause fetal harm when administered to a pregnant woman. 
Lactose intolerance: This medicinal product contains lactose as an excipient. Patients with rare hereditary problems of galactose intolerance, total lactase deficiency, or glucose-galactose malabsorption should not take this medicinal product. 
ADVERSE REACTIONS: Most common (incidence ≥20%) adverse reactions and Grade 3-4 laboratory abnormalities are edema, peripheral neuropathy, weight gain, cognitive effects, fatigue, dyspnea, arthralgia, diarrhea, mood effects, hypercholesterolemia, hypertriglyceridemia, and cough.
 

DRUG INTERACTIONS: Strong CYP3A Inducers: Contraindicated. Moderate CYP3A Inducers: Avoid concomitant use. If coadministration cannot be avoided, increase the LORBRENA dose. Strong CYP3A Inhibitors: Avoid concomitant use; reduce LORBRENA dose if concomitant use cannot be avoided. Fluconazole: Avoid concomitant use; reduce LORBRENA dose if concomitant use cannot be avoided. Certain CYP3A Substrates: Avoid concomitant use with CYP3A substrates for which minimal concentration changes may lead to serious therapeutic failures. Certain P-gp Substrates: Avoid concomitant use with P-gp substrates for which minimal concentration changes may lead to serious therapeutic failures. 
USE IN SPECIFIC POPULATIONS: Pregnancy: Based on findings from animal studies and its mechanism of action. LORBRENA can cause embryo-fetal harm when administered to a pregnant woman. There are no available data on LORBRENA use in pregnant women. 
Lactation: There are no data on the presence of lorlatinib or its metabolites in either human or animal milk or its effects on the breastfed infant or on milk production. Because of the potential for serious adverse reactions in breastfed infants, instruct women not to breastfeed during treatment with LORBRENA and for 7 days after the final dose. 
Females and Males of Reproductive Potential: Advise female patients of reproductive potential to use effective non-hormonal contraception during treatment with LORBRENA and for at least 6 months after the final dose. Based on genotoxicity findings, advise males with female partners of reproductive potential to use effective contraception during treatment with LORBRENA and for at least 3 months after the final dose. 
Pediatric Use: The safety and effectiveness of LORBRENA in pediatric patients have not been established. Geriatric Use: No clinically important differences in safety or efficacy were observed between patients aged 65 years or older and younger patients. Hepatic Impairment: No dose adjustment is recommended for patients with mild hepatic impairment. The recommended dose of LORBRENA has not been established for patients with moderate or severe hepatic impairment. 
Renal Impairment: Reduce the dose when administering LORBRENA to patients with severe renal impairment. No dose adjustment is recommended for patients with mild or moderate renal impairment. 

STORAGE AND HANDLING: Store at 20oC to 25oC (68oF to 77oF); excursions permitted between 15oC to 30oC (59oF to 86oF).

REFERENCE: LORBRENA™ EGYPT LPD Revision date March 2021
Please consult the full prescribing information