LORBRENA Film-coated tablet (2021)

Βιβλιογραφική αναφορά

Συγγραφείς

Pfizer Laboratories Div Pfizer Inc

Λέξεις κλειδιά

0069-0227 0069-0231

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1. Indications and Usage

LORBRENA is indicated for the treatment of patients with anaplastic lymphoma kinase (ALK)-positive metastatic non-small cell lung cancer (NSCLC) whose disease has progressed on crizotinib and at least ...

2. Dosage and Administration

2.1 Recommended Dosage The recommended dosage of LORBRENA is 100 mg orally once daily, with or without food, until disease progression or unacceptable toxicity [see Clinical Pharmacology (12.3)] ...

3. Dosage Forms and Strengths

Tablets: 25 mg: 8 mm round, tan, immediate release, film-coated, debossed with Pfizer on one side and 25 and LLN on the other side. 100 mg: 8.5 mm × 17 mm oval, lavender, immediate release, ...

4. Contraindications

LORBRENA is contraindicated in patients taking strong CYP3A inducers, due to the potential for serious hepatotoxicity [see Warnings and Precautions (5.1)].

5. Warnings and Precautions

5.1 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 ...

6. Adverse Reactions

The following adverse reactions are described elsewhere in the labeling: Risk of Serious Hepatotoxicity with Concomitant Use of Strong CYP3A Inducers [see Warnings and Precautions (5.1)] Central ...

6.1. Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another ...

7. Drug Interactions

7.1 Effect of Other Drugs on LORBRENA Strong CYP3A Inducers Concomitant use of LORBRENA with a strong CYP3A inducer decreased lorlatinib plasma concentrations [see Clinical Pharmacology (12.3)] ...

8.1. Pregnancy

Risk Summary Based on findings from animal studies and its mechanism of action [see Clinical Pharmacology (12.1)], LORBRENA can cause embryo-fetal harm when administered to a pregnant woman. There ...

8.2. Lactation

Risk Summary 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 ...

8.3. Nursing Mothers

Pregnancy Testing Verify pregnancy status in females of reproductive potential prior to initiating LORBRENA [see Use in Specific Populations (8.1)]. Contraception LORBRENA can cause embryo-fetal ...

8.4. Pediatric Use

The safety and effectiveness of LORBRENA in pediatric patients have not been established.

8.5. Geriatric Use

Of the 295 patients in Study B7461001 who received 100 mg LORBRENA orally once daily, 18% of patients were aged 65 years or older. Although data are limited, no clinically important differences in safety ...

8.6. Hepatic Impairment

No dose adjustment is recommended for patients with mild hepatic impairment (total bilirubin ≤ upper limit of normal [ULN] with AST > ULN or total bilirubin >1 to 1.5 × ULN with any AST). The recommended ...

8.7. Renal Impairment

No dose adjustment is recommended for patients with mild or moderate renal impairment (creatinine clearance [CLcr] 30 to 89 mL/min estimated by Cockcroft-Gault). The recommended dose of LORBRENA has not ...

11. Description

LORBRENA (lorlatinib) is a kinase inhibitor for oral administration. The molecular formula is C21H19FN6O2 (anhydrous form) and the molecular weight is 406.41 ...

12.1. Mechanism of Action

Lorlatinib is a kinase inhibitor with in vitro activity against ALK and ROS1 as well as TYK1, FER, FPS, TRKA, TRKB, TRKC, FAK, FAK2, and ACK. Lorlatinib demonstrated in vitro activity against multiple ...

12.2. Pharmacodynamics

Exposure-response relationships for Grade 3 or 4 hypercholesterolemia and for any Grade 3 or 4 adverse reaction were observed at steady-state exposures achieved at the recommended dosage, with higher probability ...

12.3. Pharmacokinetics

Steady-state lorlatinib maximum plasma concentration (Cmax) increases proportionally and AUC increased slightly less than proportionally over the dose range of 10 mg to 200 mg orally once daily ...

13.1. Carcinogenesis, Mutagenesis, Impairment of Fertility

Carcinogenicity studies have not been conducted with lorlatinib. Lorlatinib was aneugenic in an in vitro assay in human lymphoblastoid TK6 cells and positive for micronuclei formation in vivo in the bone ...

13.2. Animal Toxicology and/or Pharmacology

Distended abdomen, skin rash, and increased cholesterol and triglycerides occurred in animals. These findings were accompanied by hyperplasia and dilation of the bile ducts in the liver and acinar atrophy ...

14. Clinical Studies

14.1 ALK-Positive Metastatic NSCLC Previously Treated with an ALK Kinase Inhibitor The efficacy of LORBRENA was demonstrated in a subgroup of patients with ALK-positive metastatic non-small cell lung cancer ...

16.1. How Supplied

Table 7 describes the available strengths and package configurations for LORBRENA: Table 7. LORBRENA Tablets: Package Configuration Strength (mg) NDC Description 30 count bottle with ...

16.2. Storage and Handling

Store at 20°C to 25°C (68°F to 77°F); excursions permitted between 15°C to 30°C (59°F to 86°F) [see USP Controlled Room Temperature].

17. Patient Counseling Information

Advise the patient to read the FDA-approved patient labeling (Patient Information). Risk of Serious Hepatotoxicity with Concomitant Use of Strong C Inducers Inform patients of the potential risk of hepatoxicity ...