Lorlak

Lorlatinib

Lorlak is indicated for the treatment of adult patients with anaplastic lymphoma kinase (ALK)-positive advanced non-small cell lung cancer (NSCLC) whose disease has progressed after previously treated with one or more ALK tyrosine kinase inhibitors (TKIs).

The recommended dose schedule of Lorlak is 100 mg taken orally once daily continuously. Continue treatment as long as the patient is deriving clinical benefit from therapy. Lorlak may be taken with or without food. Patients should be encouraged to take their dose of lorlatinib at approximately the same time each day. Tablets should be swallowed whole (tablets should not be chewed, crushed or split prior to swallowing). No tablet should be ingested if it is broken, cracked, or otherwise not intact. If a dose of lorlatinib is missed, then it should be taken as soon as the patient remembers unless it is less than 4 hours before the next dose, in which case the patient should not take the missed dose. Patients should not take 2 doses at the same time to make up for a missed dose. Dose Modification: First dose reduction: Lorlak 75 mg taken orally once daily. Second dose reduction: Lorlak 50 mg taken orally once daily. Lorlak should be permanently discontinued if the patient is unable to tolerate Lorlak 50 mg taken orally once daily.

Hypersensitivity to lorlatinib or to any of the excipients listed (Microcrystalline cellulose; Dibasic calcium phosphate anhydrous/Calcium hydrogen phosphate; Sodium starch glycolate; Magnesium stearate, Hydroxypropyl methylcellulose (HPMC)/Hypromellose; Lactose monohydrate; Macrogol/Polyethylene glycol (PEG) 3350; Triacetin; Titanium dioxide; Ferrosoferric oxide/Iron oxide black; Iron oxide red). Concomitant use of strong CYP3A inducers with lorlatinib is contraindicated due to the potential for serious hepatotoxicity (aspartate aminotransferase [AST] and alanine aminotransferase [ALT] elevations).

Hyperlipidemia: Serum cholesterol and triglycerides should be monitored before initiation of lorlatinib; 2, 4, and 8 weeks after initiating lorlatinib; and periodically thereafter.
Central nervous system effects: Dose modification or discontinuation may be required for those patients who develop CNS effects.
Atrioventricular block: Dose modification may be required for those patients who develop AV block.
Lipase and amylase increase: Patients should be monitored for lipase and amylase elevations prior to the start of lorlatinib treatment and regularly thereafter as clinically indicated.
Pneumonitis: Any patient who presents with worsening of respiratory symptoms indicative of pneumonitis (e.g., dyspnea, cough, and fever) should be promptly evaluated for pneumonitis. Lorlatinib should be withheld and/or permanently discontinued based on severity.
Hypertension: Blood pressure should be monitored after 2 weeks and at least monthly thereafter during treatment with lorlatinib. Lorlatinib should be withheld and resumed at a reduced dose or permanently discontinued based on severity.
Hyperglycemia: Fasting serum glucose should be assessed prior to initiation of lorlatinib and monitored periodically thereafter. Lorlatinib should be withheld and resumed at a reduced dose or permanently discontinued based on severity.
Risk of serious hepatotoxicity with concomitant use of strong CYP3A inducers: Concomitant use of any strong CYP3A inducer is contraindicated. No clinically meaningful changes in liver function tests were seen in healthy subjects after receiving a combination of lorlatinib with the moderate CYP3A inducer modafinil.

There are no data in pregnant women using lorlatinib. Lorlak may cause fetal harm when administered to a pregnant woman. Lorlak is not recommended during pregnancy or for women of childbearing potential not using contraception. Lorlak should not be used during breastfeeding. Male fertility may be compromised during treatment with Lorlak. It is not known whether Lorlak affects female fertility.

Very common: Anaemia; Hypercholesterolaemia; Hypertriglyceridaemia; Mood effects; Cognitive effects; Peripheral neuropathy; Headache; Vision disorder; Hypertension; Diarrhoea; Nausea; Constipation; Rash; Arthralgia; Myalgia; Oedema; Fatigue; Weight increased; Lipase increased; Amylase increased.
Common: Hyperglycaemia; Psychotic effects; Mental status changes; Speech effects; Pneumonitis.

Lorlatinib is primarily metabolized by CYP3A4 and uridine diphosphate-glucuronosyltransferase (UGT) 1A4, with minor contributions from CYP2C8, CYP2C19, CYP3A5, and UGT1A3. CYP3A inhibitors: boceprevir, cobicistat, conivaptan, itraconazole, ketoconazole, posaconazole, telaprevir, troleandomycin, voriconazole, ritonavir, paritaprevir in combination with ritonavir and ombitasvir and/or dasabuvir, and ritonavir in combination with either danoprevir, elvitegravir, indinavir, lopinavir, saquinavir, or tipranavir; grapefruit products. CYP3A inducers: rifampin, carbamazepine, enzalutamide, mitotane, phenytoin, and St. John’s wort. Proton-Pump inhibitors, H2-receptor antagonists, or locally-acting antacids. Drugs whose plasma concentrations may be altered by lorlatinib. CYP3A substrates: hormonal contraceptives, alfentanil, cyclosporine, dihydroergotamine, ergotamine, fentanyl, pimozide, quinidine, sirolimus, and tacrolimus. CYP2B6 substrates: bupropion. CYP2C9 substrates: tolbutamide, coumarin anticoagulants. UGT substrates: acetaminophen. P-glycoprotein substrates: fexofenadine, digoxin, dabigatran etexilate.

Store below 30°C.

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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