LORVIQUA® (lorlatinib) as monotherapy is indicated for the first-line treatment of adult patients with anaplastic lymphoma kinase (ALK)-positive advanced non-small cell lung cancer (NSCLC) or for patients with ALK-positive metastatic 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 TKI1
Hyperlipidemia CNS effects Interstitial lung disease/pneumonitis Lipase/amylase increase
PR interval prolongation/AV block Hypertension Hyperglycaemia Other adverse drug reactions

Therapy Management Strategies for Specific Adverse Reactions

Hyperlipidemia

Therapy management guidance for hyperlipidemia​​​​​​​
  • The median time to onset was 15 days for both hypercholesterolemia and hypertriglyceridemia
  • Monitor serum cholesterol and triglycerides before initiation of LORVIQUA®; 2, 4 and 8 weeks after initiating LORVIQUA®; and periodically thereafter
  • Initiation, or increase in the dose, of lipid-lowering agents is required
​​​​​​​

Adverse drug reaction1

Dosage modifications1

Mild OR moderate

Cholesterol between ULN and 400 mg/dL, or between ULN and 10.34 mmol/L

OR

Triglycerides between 150–500 mg/dL, or 1.71–5.7 mmol/L

  • ​​​​​​​Introduce or modify lipid-lowering therapy (LLT)* in accordance with respective prescribing information
  • Continue LORVIQUA® at same dose

Severe

Cholesterol between 401–500 mg/dL, or between 10.35–12.92 mmol/L

OR

Triglycerides between 501–1000 mg/dL or 5.71–11.4 mmol/L

  • Introduce the use of LLT*
  • If currently on LLT, increase the dose of this therapy* in accordance with respective prescribing information, or change to a new LLT
  • Continue LORVIQUA® at the same dose without interruption​​​​​​​

Life-threatening

Cholesterol >500 mg/dL or >12.92 mmol/L​​​​​​​

OR

Triglycerides >1000 mg/dL or >11.4 mmol/L

  • Introduce the use of LLT* or increase the dose of this therapy* in accordance with respective prescribing information or change to a new LLT
  • Withhold LORVIQUA® until recovery of hypercholesterolaemia and/or hypertriglyceridaemia to moderate or mild severity grade
  • Re-challenge at same LORVIQUA® dose while maximising LLT in accordance with respective prescribing information
  • If severe hypercholesterolaemia and/or hypertriglyceridaemia recur(s) despite maximal LLT* in accordance with respective prescribing information, reduce LORVIQUA® by 1 dose level
*LLT may include: HMG GoA reductase inhibitor, nicotinic acid, fibric acid, or ethyl esters of omega-3 fatty acids
HMG CoA, 3-hydroxy-2-methyl-glutaryl coenzyme A; LLT, lipid-lowering therapy; ULN, upper limit of normal.
Please refer to the LORVIQUA®(lorlatinib) Prescribing Information or medical information for dose recommendations for different grades of adverse reactions.
Reference
1.Pfizer. LORVIQUA® (lorlatinib) Prescribing Information, Available from:  http://labeling.pfizer.com/ShowLabeling.aspx?id=12540 Accessed 6 January, 2022..

The use of lorlatinib has been associated with increases in serum cholesterol and triglycerides. Serum cholesterol and triglycerides should be monitored before the initiation of lorlatinib; 2, 4, and 8 weeks after initiating lorlatinib, and periodically thereafter. Initiation, or increase in the dose, of lipid-lowering agents is required.
Central nervous system (CNS) effects have been observed in patients receiving lorlatinib including seizures, psychotic effects, changes in cognitive function, mood (including suicidal ideation), mental status, sleep, and speech. Dose modification or discontinuation may be required for those patients who develop CNS effects.
PR interval prolongation and atrioventricular (AV) block events have been reported in patients receiving lorlatinib. 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.
Elevations of lipase and/or amylase have occurred in patients receiving lorlatinib. Median time of occurrence of increase in serum lipase and amylase is 70 days (range: 7 days to 696 days) and 41 days (range: 7 days to 489 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.
Severe or life threatening pulmonary adverse drug reactions consistent with ILD/pneumonitis have occurred with lorlatinib. Any patient who presents with worsening of respiratory symptoms indicative of ILD/pneumonitis (e.g., dyspnea, cough and fever) should be promptly evaluated for ILD/pneumonitis. Lorlatinib should be withheld and/or permanently discontinued based on severity.
Hypertension has been reported in patients receiving lorlatinib. Blood pressure should be controlled prior to the 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.
Hyperglycemia has occurred in patients receiving lorlatinib. Fasting serum glucose should be assessed prior to the initiation of lorlatinib and monitored periodically thereafter. Lorlatinib should be withheld and resumed at a reduced dose or permanently discontinued based on severity.
Concomitant use of any strong CYP3A inducer is contraindicated. Any strong CYP3A inducers have to be discontinued for at least 3 plasma half-lives of the strong CYP3A inducer before lorlatinib treatment is started. 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.
Women of childbearing potential should be advised to avoid getting pregnant while receiving lorlatinib. Male fertility may be compromised during treatment with lorlatinib. Men should seek advice on effective fertility preservation before treatment.

​​​​​​​LORVIQUA® Efficacy

​​​​​​​LORVIQUA
® Safety Profile
LORVIQUA® Dosing and Therapy
​​​​​​​Management
Click here for LORVIQUA® Prescribing Information

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