Lorviqua

Lorlatinib

Monotherapy for adult patients w/ anaplastic lymphoma kinase (ALK)-+ve advanced NSCLC whose disease has progressed after alectinib or ceritinib as the 1st ALK tyrosine kinase inhibitor (TKI) therapy; or crizotinib & at least 1 other ALK TKI.

100 mg once daily as long as patient is deriving clinical benefit w/o unacceptable toxicity. Dose interruption/reduction: 1st dose reduction: 75 mg once daily; 2nd dose reduction: 50 mg once daily. Patient concomitantly taking strong CYP3A4/5 inhibitors Reduce the 100 mg dose to 75 mg once daily. If discontinued, resume at the dose used prior to the initiation of strong CYP3A4/5 inhibitor & after a washout period of 3-5 t_½ of the strong CYP3A4/5 inhibitor.

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

Hypersensitivity. Concomitant use of strong CYP3A4/5 inducers.

Monitor serum cholesterol & triglycerides before initiation of treatment; 2, 4, & 8 wk after initiating treatment; & regularly thereafter. May modify dose or discontinue therapy in patients who develop CNS effects. Monitor ECG prior to initiating treatment & mthly thereafter, particularly in patients w/ predisposing conditions to the occurrence of cardiac events; may modify dose for patients who develop AV block. Consider cardiac monitoring, including left ventricular ejection fraction (LVEF) assessment at baseline & during treatment in patients w/ cardiac risk factors, w/ conditions affecting LVEF & who develop cardiac signs/symptoms. Risk of pancreatitis; monitor lipase & amylase elevations prior to the start of treatment & regularly thereafter. Evaluate patients w/ worsening of resp symptoms indicative of ILD/pneumonitis; withhold treatment &/or permanently discontinue treatment based on severity. Concomitant use w/ strong CYP3A4/5 inducer is contraindicated; avoid use w/ moderate CYP3A4/5 inducers; avoid concomitant use w/ CYP3A4/5 substrates w/ narrow therapeutic indices including alfentanil, ciclosporin, dihydroergotamine, ergotamine, fentanyl, hormonal contraceptives, pimozide, quinidine, sirolimus & tacrolimus. Galactose intolerance, total lactase deficiency, or glucose-galactose malabsorption. Patients on low Na diet. Moderate influence on the ability to drive & use machines. Not recommended in moderate to severe hepatic & severe renal impairment. Male patients w/ female partners of childbearing potential & pregnant partners must use effective contraception eg, condoms, during treatment & for at least 14 days after the final dose. Avoid becoming pregnant during treatment. Continue effective contraception for at least 35 days after completing therapy. Pregnancy. Discontinue breastfeeding during treatment & for 7 days after the final dose. Severe renal & moderate to severe hepatic impairment. Paed patients <18 yr. Elderly ≥65 yr.

Anaemia; hypercholesterolaemia, hypertriglyceridaemia; mood effects; cognitive effects, peripheral neuropathy, headache; vision disorder; diarrhoea, nausea, constipation; rash; arthralgia, myalgia; oedema, fatigue; increased wt, lipase & amylase. Hallucinations; speech effects; pneumonitis.

Reduced AUC_inf & C_max, decreased plasma conc & increased AST & ALT w/ strong CYP3A4/5 inducers (eg, rifampicin, carbamazepine, enzalutamide, mitotane, phenytoin & St. John's wort). Increased mean AUC_inf, C_max, & plasma conc w/ strong CYP3A4/5 inhibitors (eg, boceprevir, cobicistat, itraconazole, ketoconazole, posaconazole, troleandomycin, voriconazole, ritonavir, paritaprevir in combination w/ ritonavir & ombitasvir &/or dasabuvir, & ritonavir in combination w/ either elvitegravir, indinavir, lopinavir or tipranavir; increased plasma conc w/ grapefruit products. May reduce conc of CYP3A4/5 substrates w/ narrow therapeutic indices (alfentanil, ciclosporin, dihydroergotamine, ergotamine, fentanyl, hormonal contraceptives, pimozide, quinidine, sirolimus, & tacrolimus. May decrease AUC_inf & C_max of bupropion, tolbutamide, acetaminophen & fexofenadine. May change plasma exposure of substrates of BCRP, OATP1B1, OATP1B3, OCT1, MATE1 & OAT3.

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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