Lorviqua Special Precautions

Hyperlipidaemia: The use of lorlatinib has been associated with increases in serum cholesterol and triglycerides (see Adverse Reactions). Median time of occurrence of severe increase in serum cholesterol and triglycerides is 104 days (range: 29 to 518 days) and 120 days (range: 15 to 780 days), respectively. 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 Dosage & Administration).
Central nervous system effects: Central nervous system (CNS) effects have been observed in patients receiving lorlatinib, including psychotic effects and changes in cognitive function, mood, mental status or speech (see Adverse Reactions). Dose modification or discontinuation may be required for those patients who develop CNS effects (see Dosage & Administration).
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 Pharmacology: Pharmacokinetics under Actions). 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 Dosage & Administration).
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. Based on the available clinical study data, it is not possible to determine a causal relationship between effects on changes in cardiac contractility and lorlatinib. 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 Adverse Reactions). Median time of occurrence of increase in serum lipase and amylase is 141 days (range: 1 to 1091 days) and 138 days (range: 1 to 1,112 days), respectively. 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 Dosage & Administration).
Interstitial lung disease/Pneumonitis: Severe or life-threatening pulmonary adverse reactions consistent with ILD/pneumonitis have occurred with lorlatinib (see Adverse Reactions). 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 Dosage & Administration).
Hypertension: Hypertension has been reported in patients receiving lorlatinib (see Adverse Reactions). 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 Dosage & Administration).
Hyperglycaemia: Hyperglycaemia has occurred in patients receiving lorlatinib (see Adverse Reactions). 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 Dosage & Administration).
Drug-drug interactions: In a study conducted in healthy volunteers, the concomitant use of lorlatinib and rifampin, a strong CYP3A4/5 inducer, was associated with increases of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) with no increase of total bilirubin and alkaline phosphatase (see Interactions). Concomitant use of a strong CYP3A4/5 inducer is contraindicated (see Contraindications and Interactions). 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 Interactions).
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 Interactions).
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: This medicinal product contains less than 1 mmol sodium (23 mg) per 25 mg or 100 mg tablet. 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 Adverse Reactions).
Use in Pregnancy: Fertility and pregnancy: During treatment with lorlatinib 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 Use in Pregnancy & Lactation). Male fertility may be compromised during treatment with lorlatinib (see Pharmacology: Toxicology: Preclinical safety data under Actions). Men should seek advice on effective fertility preservation before treatment. 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 with lorlatinib, because lorlatinib can render hormonal contraceptives ineffective (see Interactions and Use in Pregnancy & Lactation). 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 Use in Pregnancy & Lactation). It is not known whether lorlatinib affects female fertility.