Although there is no formal data available on the use of lorlatinib in pregnant women, based on findings from animal studies and its mechanism of action, it is believed that lorlatinib can cause embryo-fetal harm when administered to a pregnant woman FDA Label.

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 FDA Label. Because of the potential for serious adverse reactions in breastfed infants, instruct women not to breastfeed during treatment with lorlatinib and for 7 days after the final dose FDA Label.

Advise female patients of reproductive potential to use effective non-hormonal contraception during treatment with lorlatinib and for at least 6 months after the final dose FDA Label. Advise females of reproductive potential to use a non-hormonal method of contraception, because lorlatinib can render hormonal contraceptives ineffective FDA Label.

Based on genotoxicity findings, advise males with female partners of reproductive potential to use effective contraception during treatment with lorlatinib and for at least 3 months after the final dose FDA Label.

Based on findings from animal studies, use of lorlatinib may transiently impair male fertility FDA Label.

The safety and effectiveness of lorlatinib in pediatric patients have not been established FDA Label.

Of the 295 patients in Study B7461001 who received 100 mg lorlatinib orally once daily, 18% of patients were aged 65 years or older FDA Label. Although data are limited, no clinically important differences in safety or efficacy were observed between patients aged 65 years or older and younger patients FDA Label.

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) FDA Label. The recommended dose of lorlatinib has not been established for patients with moderate or severe hepatic impairment FDA Label.

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) FDA Label. The recommended dose of lorlatinib has not been established for patients with severe renal impairment FDA Label.

Carcinogenicity studies have not been conducted with lorlatinib FDA Label. Lorlatinib was aneugenic in an in vitro assay in human lymphoblastoid TK6 cells and positive for micronuclei formation in vivo in the bone marrow of rats. Lorlatinib was not mutagenic in an in vitro bacterial reverse mutation (Ames) assay FDA Label.

Dedicated fertility studies were not conducted with lorlatinib FDA Label. Findings in male reproductive organs occurred in repeat-dose toxicity studies and included lower testicular, epididymal, and prostate weights; testicular tubular degeneration/atrophy; prostatic atrophy; and/or epididymal inflammation at 15 mg/kg/day and 7 mg/kg/day in rats and dogs, respectively (approximately 8 and 2 times, respectively, the human exposure at the recommended dose of 100 mg based on AUC) FDA Label. The effects on male reproductive organs were reversible FDA Label.

Distended abdomen, skin rash, and increased cholesterol and triglycerides occurred in animals FDA Label. These findings were accompanied by hyperplasia and dilation of the bile ducts in the liver and acinar atrophy of the pancreas in rats at 15 mg/kg/day and in dogs at 2 mg/kg/day (approximately 8 and 0.5 times, respectively, the human exposure at the recommended dose of 100 mg based on AUC) FDA Label. All effects were reversible within the recovery period FDA Label.