Lorlak

Lorlatinib

Adult patients w/ anaplastic lymphoma kinase (ALK) +ve advanced NSCLC whose disease has progressed after previously treated w/ ≥1 ALK tyrosine kinase inhibitors (TKIs).

Recommended dose: 100 mg once daily continuously as long as clinical benefit is derived, at approx the same time each day. 1st dose reduction: 75 mg once daily; 2nd dose reduction: 50 mg once daily.

May be taken with or without food: Take at approx the same time each day. Swallow whole, do not chew/crush/split.

Hypersensitivity. Concomitant use of strong CYP3A inducers.

W/hold &/or permanently discontinue therapy based on severity. Monitor serum cholesterol & triglycerides before initiation, at 2, 4 & 8 wk after initiation, & periodically thereafter; lipase & amylase elevations prior to therapy & regularly thereafter; BP after 2 wk & at least mthly thereafter during therapy. Dose modification or discontinuation may be required for patients who develop CNS effects. Dose modification may be required for patients who develop AV block. Promptly evaluate patient who presents w/ worsening of resp symptoms indicative of pneumonitis. Assess fasting serum glucose prior to initiation of therapy & monitor periodically thereafter. Male fertility may be compromised during treatment. Not recommended during pregnancy or for women of childbearing potential not using contraception. Not to be used during breastfeeding.

Anaemia; hypercholesterolaemia; hypertriglyceridaemia; mood, cognitive effects; peripheral neuropathy; headache; vision disorder; HTN; diarrhoea; nausea; constipation; rash; arthralgia; myalgia; oedema; fatigue; wt, lipase, amylase increased. Hyperglycaemia; psychotic effects; mental status changes; speech effects; pneumonitis.

CYP3A inhibitors: Boceprevir, cobicistat, conivaptan, itraconazole, ketoconazole, posaconazole, telaprevir, troleandomycin, voriconazole, ritonavir, paritaprevir in combination w/ ritonavir & ombitasvir &/or dasabuvir, & ritonavir in combination w/ either danoprevir, elvitegravir, indinavir, lopinavir, saquinavir, or tipranavir; grapefruit products. CYP3A inducers: Rifampin, carbamazepine, enzalutamide, mitotane, phenytoin & St. John's wort. PPIs, H₂-receptor antagonists, or locally-acting antacids. May alter plasma conc of CYP3A substrates: Hormonal contraceptives, alfentanil, cyclosporine, dihydroergotamine, ergotamine, fentanyl, pimozide, quinidine, sirolimus, & tacrolimus. CYP2B6 substrates: Bupropion. CYP2C9 substrates: Tolbutamide, coumarin anticoagulants. UGT substrates: Acetaminophen. P-gp substrates: Fexofenadine, digoxin, dabigatran etexilate.

Targeted Cancer Therapy

L01ED05 - lorlatinib ; Belongs to the class of anaplastic lymphoma kinase (ALK) inhibitors. Used in the treatment of cancer.

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