Indications
⚠️ Always consult a registered physician before taking any medicine.
Pharmacology
Lorlatinib is a kinase inhibitor. In laboratory (in vitro) tests it was active against ALK and ROS1, and also against TYK1, FER, FPS, TRKA, TRKB, TRKC, FAK, FAK2 and ACK. It also showed in vitro activity against many mutant forms of the ALK enzyme, including some mutations found in tumors when the disease progressed on crizotinib and other ALK inhibitors.
In mice with tumors implanted under the skin, carrying EML4 fusions with either ALK variant 1 or ALK mutations, lorlatinib produced antitumor activity. These mutations included G1202R and 11171T, both found in tumors when the disease progressed on ALK inhibitors. Mice with EML4-ALK-driven tumor cell lines implanted intracranially also showed antitumor activity and longer survival. Across the in vivo models, the antitumor effect depended on the dose and went along with inhibition of ALK phosphorylation.
Pregnancy & Breastfeeding
Women who could become pregnant should be advised to avoid pregnancy while taking Lorlatinib. Female patients need a highly effective non-hormonal method of contraception during treatment, because Lorlatinib can make hormonal contraceptives ineffective. If a hormonal method can't be avoided, a condom must be used together with it. Effective contraception must continue for at least 35 days after therapy is completed. Male patients with female partners who could become pregnant must use effective contraception, including a condom, during treatment and for at least 14 weeks after the final dose. Male patients with pregnant partners must use condoms. Studies in animals have shown embryo-fetal toxicity, and there are no data on the use of Lorlatinib in pregnant women. It may cause fetal harm when given to a pregnant woman, so it is not recommended during pregnancy, or for women of childbearing potential who are not using contraception. It is not known whether Lorlatinib and its metabolites pass into human milk, and a risk to newborns and infants can't be excluded. The medicine should not be used during breastfeeding. Breastfeeding should be stopped during treatment and for 7 days after the final dose. Based on non-clinical safety findings, male fertility may be compromised during treatment. It is not known whether Lorlatinib affects female fertility. Men should seek advice on effective fertility preservation before treatment.
⚠️ Talk to your doctor before taking any medicine during pregnancy or while breastfeeding.
Side Effects & Interactions
Side Effects
No side-effect data recorded yet.