Lorviqua

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

100 mg once daily, continued until disease progression or unacceptable toxicity. Dose interruption/reduction: 1st dose reduction: 75 mg once daily; 2nd dose reduction: 50 mg once daily. Concomitant use w/ strong CYP3A4/5 inhibitors Reduce 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. Severe renal impairment (absolute eGFR <30 mL/min) 75 mg once daily.

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.

Withhold &/or permanently discontinue treatment based on severity of ILD/pneumonitis; HTN; hyperglycaemia. May modify dose or discontinue therapy in patients who develop CNS effects; for patients who develop AV block. Risk of pancreatitis. 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. Monitor ECG prior to initiating treatment & mthly thereafter, particularly in patients w/ predisposing conditions to the occurrence of cardiac events; lipase & amylase elevations prior to the start of treatment & regularly thereafter; serum cholesterol & triglycerides before initiation of treatment; 2, 4, & 8 wk after initiating treatment; & regularly thereafter. Control BP prior to initiation of treatment & monitor after 2 wk & at least mthly thereafter during treatment. Assess fasting serum glucose prior to treatment & monitor periodically thereafter. Evaluate patients w/ worsening of resp symptoms indicative of ILD/pneumonitis (eg, dyspnoea, cough, & fever). Concomitant use w/ strong CYP3A4/5 inducer is contraindicated. Avoid 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. Not recommended during pregnancy or for women of childbearing potential not using contraception. Discontinue breastfeeding during treatment & for 7 days after the final dose. Paed patients <18 yr. Elderly ≥65 yr.

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

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. Reduced plasma conc of CYP3A4/5 substrates w/ narrow therapeutic indices (alfentanil, ciclosporin, dihydroergotamine, ergotamine, fentanyl, hormonal contraceptives, pimozide, quinidine, sirolimus, & tacrolimus; P-gp substrates w/ narrow therapeutic index (eg, digoxin, dabigatran etexilate). Decreased AUC_inf & C_max of bupropion, tolbutamide, acetaminophen & fexofenadine. Changes in 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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