y 0.6 times the human exposure at the recommended dose of 100 mg) toxicities included increased post-implantation loss and malformations including rotated limbs, malformed kidneys, domed head, high arched palate, and dilation of the cerebral ventricles. In rats, administration of lorlatinib resulted in total loss of pregnancy at doses of 4 mg/kg (approximately 5 times the human exposure at the recommended dose of 100 mg) or greater. At a dose of 1 mg/kg (approximately equal to the human exposure at the recommended dose of 100 mg) there was increased post-implantation loss, decreased fetal body weight, and malformations including gastroschisis, rotated limbs, supernumerary digits, and vessel abnormalities.
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 serious adverse reactions in breastfed infants, instruct women not to breastfeed during treatment with LORBRENA and for 7 days after the final dose.
8.3 Females and Males of Reproductive Potential
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 harm when administered to a pregnant woman [see USE IN SPECIFIC POPULATIONS (8.1)].
Females
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. Advise females of reproductive potential to use a non-hormonal method of contraception, because LORBRENA can render hormonal contraceptives ineffective [see DRUG INTERACTIONS (7.2)].
Males
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 [see NONCLINICAL TOXICOLOGY (13.1)].
Infertility
Males
Based on findings from animal studies, LORBRENA may transiently impair male fertility [see NONCLINICAL TOXICOLOGY (13.1)].
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 or efficacy were observed between patients aged 65 years or older and younger patients.
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 dose of LORBRENA has not been established for patients with moderate or severe hepatic impairment [see CLINICAL PHARMACOLOGY (12.3)].
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 been established for patients with severe renal impairment [see CLINICAL PHARMACOLOGY (12.3)].
11 DESCRIPTION
LORBRENA (lorlatinib) is a kinase inhibitor for oral administration. The molecular formula is C21H19FN6O2 (anhydrous form) and the molecular weight |
