▼This medicinal product is subject to additional monitoring. This will allow quick identification of new safety information. Healthcare professionals are asked to report any suspected adverse reactions. Refer to section 4.8 of the SPC for how to report adverse reactions.

Lorviqua®▼ 25 mg and 100 mg film-coated tablets IE Prescribing Information: Before prescribing Lorviqua (lorlatinib) please refer to the full Summary of Product Characteristics (SmPC). Presentation: Each 25 mg film-coated tablet contains 25 mg lorlatinib; Each 100 mg film-coated tablet contains 100 mg lorlatinib. Indications: Lorviqua as monotherapy is indicated for the treatment of adult patients with anaplastic lymphoma kinase (ALK) positive advanced non-small cell lung cancer (NSCLC) previously not treated with an ALK inhibitor. Lorviqua as monotherapy is indicated for the treatment of adult patients with ALK-positive advanced NSCLC whose disease has progressed after alectinib or ceritinib as the first ALK tyrosine kinase inhibitor (TKI) therapy, or crizotinib and at least one other ALK TKI. Dosage and Administration: Treatment should be initiated and supervised by a physician experienced in the use of anticancer medicinal products. Detection of ALK positive NSCLC is necessary for selection of patients for treatment with lorlatinib because these are the only patients for whom benefit has been shown. Assessment for ALK positive NSCLC should be performed by laboratories with demonstrated proficiency in the specific technology being utilised. Improper assay performance can lead to unreliable test results. The recommended dose is 100 mg lorlatinib taken orally once daily. Treatment should be continued until disease progression or unacceptable toxicity. If a dose is missed, then it should be taken as soon as the patient remembers unless it is less than 4 hours before the next dose. Patients should not take 2 doses at the same time to make up for a missed dose. To manage adverse reaction, dose interruption or dose reduction see SmPC section 4.2. Concurrent use of lorlatinib with medicinal products that are strong CYP3A4/5 inhibitors and grapefruit juice products may increase lorlatinib plasma concentrations, see SmPC section 4.2 for further information. Special populations: Elderly (≥ 65 years): There are limited data on this population, no dose recommendation can be made for patients aged 65 years and older (see section 5.2). Renal impairment: See SmPC section 4.2. No dose adjustment is required for patients with mild or moderate renal impairment. A reduced dose of lorlatinib is recommended in patients with severe renal impairment (absolute eGFR < 30 mL/min), e.g. a once daily starting dose of 75 mg taken orally (see SmPC section 5.2). No information is available for patients on renal dialysis. Hepatic impairment: See SmPC section 4.2. No dose adjustment is required for patients with mild hepatic impairment. No information is available for lorlatinib in patients with moderate or severe hepatic impairment. Therefore, lorlatinib is not recommended in patients with moderate to severe hepatic impairment (see section 5.2). Paediatric population: The safety and efficacy of lorlatinib in children and adolescents < 18 years of age have not been established. Method of administration: Lorlatinib is for oral use. Patients should be encouraged to take their dose of lorlatinib at approximately the same time each day with or without food (see SmPC section 5.2). The 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. Contra-indications: Hypersensitivity to the active substance or to any of the excipients (see SmPC section 6.1). Concomitant use of strong CYP3A4/5 inducers (see SmPC sections 4.4 and 4.5). Special Warnings and Precautions: Hyperlipidaemia: The use of lorlatinib has been associated with increases in serum cholesterol and triglycerides (see SmPC section 4.8). Serum cholesterol and triglycerides should be monitored before initiation of lorlatinib; 2, 4 and 8 weeks after initiating lorlatinib and regularly thereafter. Initiate or increase the dose of lipid-lowering medicinal products, if indicated (see SmPC section 4.2). Central nervous system (CNS) effects: CNS effects have been observed in patients receiving lorlatinib, including psychotic effects and changes in cognitive function, mood, mental status or speech (see SmPC section 4.8). Dose modification or discontinuation may be required for those patients who develop CNS effects (see SmPC section 4.2). Atrioventricular block: Lorlatinib was studied in a population of patients that excluded those with second-degree or third-degree AV block (unless paced) or any AV block with PR interval > 220 msec. PR interval prolongation and AV block have been reported in patients receiving lorlatinib (see SmpC section 5.2). Monitor electrocardiogram (ECG) prior to initiating lorlatinib and monthly thereafter, particularly in patients with predisposing conditions to the occurrence of clinically significant cardiac events. Dose modification may be required for those patients who develop AV block (see SmPC section 4.2). Left ventricular ejection fraction decrease: Left ventricular ejection fraction (LVEF) decrease has been reported in patients receiving lorlatinib who had baseline and at least one follow-up LVEF assessment. In patients with cardiac risk factors and those with conditions that can affect LVEF, cardiac monitoring, including LVEF assessment at baseline and during treatment, should be considered. In patients who develop relevant cardiac signs/symptoms during treatment, cardiac monitoring, including LVEF assessment, should be considered. Lipase and amylase increase: Elevations of lipase and/or amylase have occurred in patients receiving lorlatinib (see SmPC section 4.8). Risk of pancreatitis should be considered in patients receiving lorlatinib due to concomitant hypertriglyceridemia and/or a potential intrinsic mechanism. Patients should be monitored for lipase and amylase elevations prior to the start of lorlatinib treatment and regularly thereafter as clinically indicated (see SmPC section 4.2). Interstitial lung disease/Pneumonitis: Severe or life-threatening pulmonary adverse reactions consistent with ILD/pneumonitis have occurred with lorlatinib (see SmPC section 4.8). Any patient who presents with worsening of respiratory symptoms indicative of ILD/pneumonitis (e.g. dyspnoea, cough and fever) should be promptly evaluated for ILD/pneumonitis. Lorlatinib should be withheld and/or permanently discontinued based on severity (see SmPC section 4.2). Hypertension: Hypertension has been reported in patients receiving lorlatinib (see SmPC section 4.8). Blood pressure should be controlled prior to initiation of lorlatinib. 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 (see SmPC section 4.2). Hyperglycaemia: Hyperglycaemia has occurred in patients receiving lorlatinib (see SmPC section 4.8). Fasting serum glucose should be assessed prior to initiation of lorlatinib and monitored periodically thereafter according to national guidelines. Lorlatinib should be withheld and resumed at a reduced dose or permanently discontinued based on severity (see SmPC section 4.2). Interactions: Concomitant use of a strong CYP3A4/5 inducer is contraindicated (see SmPC sections 4.3 and 4.5). No clinically meaningful changes in liver function tests were seen in healthy subjects after receiving a combination of lorlatinib with the moderate CYP3A4/5 inducer modafinil (see section 4.5). Concurrent administration of lorlatinib with CYP3A4/5 substrates with narrow therapeutic indices, including but not limited to alfentanil, ciclosporin, dihydroergotamine, ergotamine, fentanyl, hormonal contraceptives, pimozide, quinidine, sirolimus and tacrolimus, should be avoided since the concentration of these medicinal products may be reduced by lorlatinib (see SmPC section 4.5). If a strong CYP3A4/5 inhibitor must be concomitantly administered, a dose reduction of lorlatinib is recommended (see SmPC section 4.2). Lorlatinib is a weak inducer of CYP2B6, no dose adjustment is necessary when lorlatinib is used in combination with medicinal products that are mainly metabolised by CYP2B6 (see SmPC section 4.5). Lorlatinib is a weak inducer of CYP2C9, no dose adjustment is required for medicinal products that are mainly metabolised by CYP2C9. Patients should be monitored in case of concomitant treatment with medicinal products with narrow therapeutic indices metabolised by CYP2C9 (e.g. coumarin anticoagulants) (see SmPC section 4.5). Lorlatinib is a weak inducer of UGT, no dose adjustment is required for medicinal products that are mainly metabolised by UGT. Patients should be monitored in case of concomitant treatment with medicinal products with narrow therapeutic indices metabolised by UGT (see SmPC Section 4.5). Lorlatinib is a moderate inducer of P-gp. Medicinal products that are P-gp substrates with narrow therapeutic indices (e.g. digoxin, dabigatran etexilate) should be used with caution in combination with lorlatinib due to the likelihood of reduced plasma concentrations of these substrates. Lorlatinib should be used with caution in combination with substrates of BCRP, OATP1B1, OATP1B3, OCT1, MATE1 and OAT3 as clinically relevant changes in the plasma exposure of these substrates cannot be ruled out (see SmPC section 4.5). Fertility, pregnancy and Breast-feeding: Fertility: Male fertility may be compromised during treatment with lorlatinib (see SmPC section 5.3). Men should seek advice on effective fertility preservation before treatment. It is not known whether lorlatinib affects female fertility. Pregnancy: Lorlatinib is not recommended during pregnancy or for women of childbearing potential not using contraception. Women of childbearing potential should be advised to avoid becoming pregnant while receiving lorlatinib. A highly effective non-hormonal method of contraception is required for female patients during treatment because lorlatinib can render hormonal contraceptives ineffective (see SmPC sections 4.4 and 4.5). If a hormonal method of contraception is unavoidable, then a condom must be used in combination with the hormonal method. Effective contraception must be continued for at least 35 days after completing therapy (see SmPC section 4.6). During treatment and for at least 14 weeks after the final dose, male patients with female partners of childbearing potential must use effective contraception, including a condom, and male patients with pregnant partners must use condoms (see SmPC section 4.6). Breast-feeding: Lorlatinib should not be used during breast-feeding. Breast-feeding should be discontinued during treatment and for 7 days after the final dose. Lactose intolerance: This medicinal product contains lactose as an excipient. Patients with rare hereditary problems of galactose intolerance, total lactase deficiency, or glucose-galactose malabsorption should not take this medicinal product. Dietary sodium: Patients on low sodium diets should be informed that this product is essentially “sodium‑free”. Effects on ability to drive and use machines: Lorlatinib has moderate influence on the ability to drive and use machines. Caution should be exercised when driving or operating machines as patients may experience CNS effects (see SmPC section 4.8). Undesirable Effects: See SmPC section 4.8. The overall safety profile of lorlatinib is presented from data from 476 adults treated with lorlatinib 100 mg once daily with advanced NSCLC from Study A (N=327) and CROWN study (N=149). The most common (≥2%) Grade ≥3 adverse reactions of lorlatinib were Anaemia, Hypercholesterolaemia, Hypertriglyceridaemia, Hyperglycaemia, Cognitive effects, Peripheral neuropathy, Hypertension, Oedema, Weight increased, Lipase increased, Amylase increased. Commonly reported adverse events (≥ 1/100 to < 1/10) were Hyperglycaemia, Psychotic effects, Mental status changes, Speech effects, Pneumonitis, Proteinuria. Dose reductions due to adverse reactions occurred in 20.0% of patients receiving lorlatinib. Very common (≥ 1/10) adverse reactions in patients receiving lorlatinib in this study were Anaemia, Hypertension, Hypercholesterolaemia, Hypertriglyceridaemia, Mood effects, Cognitive effects, Peripheral neuropathy, Headache, Vision disorder, Diarrhoea, Nausea, Constipation, Rash, Arthralgia, Myalgia, Oedema, Fatigue, Weight increased, Lipase increased, Amylase increased. Common (≥ 1/100 to < 1/10) adverse effects were Speech effects, Pneumonitis. Overdose: Treatment of overdose with the medicinal product consists of general supportive measures. Given the dose‑dependent effect on PR interval, ECG monitoring is recommended. There is no antidote for lorlatinib. Legal Category: S1A. Package quantities and Marketing Authorisation Numbers: Lorviqua 25 mg film-coated tablets EU/1/19/1355/003, 90 tablets. Lorviqua 100 mg film-coated tablets EU/1/19/1355/002, 30 tablets. For further information on this medicine please contact: Pfizer Medical Information on 1800 633 363 or at [email protected] For queries regarding product availability please contact: Pfizer Healthcare Ireland, Pfizer Building 9, Riverwalk, National Digital Park, Citywest Business Campus, Dublin 24 + 353 1 4676500. Marketing Authorisation Holder: Pfizer Europe MA EEIG, Boulevard de la Plaine 17, 1050 Bruxelles, Belgium.

Date of Preparation: 01/2024
 
Ref: LQ 7_2