LORVIQUA® (Lorlatinib)| Therapy Management| PfizerPro Ireland

Therapy management for specific adverse reactions

There are specific recommendations for dose modifications related to particular adverse reactions. Click on an adverse reaction below to see the recommendations.

Hyperlipidaemia¹

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Severity¹	Guidance¹
MILD Cholesterol ULN-300 mg/dL OR Triglycerides 150-300 mg/dL OR MODERATE Cholesterol 301-400 mg/dL OR Triglycerides 301-500 mg/dL	Introduce or modify lipid-lowering therapy^a Continue LORVIQUA at the same dose
SEVERE Cholesterol 401-500 mg/dL OR Triglycerides 501-1000 mg/dL	Introduce lipid-lowering therapy^a If currently on lipid-lowering therapy, increase the dose of lipid-lowering therapy or change to a new lipid-lowering therapy^a Continue LORVIQUA at the same dose without interruption
LIFE-THREATENING Cholesterol >500 mg/dL OR Triglycerides >1000 mg/dL	Introduce lipid-lowering therapy, increase the dose of lipid-lowering therapy, or change to a new lipid-lowering therapy^a Withhold LORVIQUA until recovery of hypercholesterolaemia and/or hypertriglyceridaemia to moderate or mild severity grade Rechallenge at same LORVIQUA dose while maximising lipid-lowering therapy^a If severe hypercholesterolaemia and/or hypertriglyceridaemia recur despite maximal lipid-lowering therapy,^a reduce LORVIQUA by 1 dose level^b

^a Lipid-lowering therapy may include HMG-CoA reductase inhibitor, nicotinic acid, fibric acid derivatives, or ethyl esters of omega-3 fatty acids.

^b The recommended dose of LORVIQUA is 100 mg taken orally, once daily. The first dose reduction level is 75 mg once daily.¹

CNS effects¹

CNS effects were primarily cognitive effects, mood effects, speech effects, and psychotic effects, and were generally mild, transient, and typically reversible upon dose delay and/or dose reduction¹

Patients and their caregivers should be advised to notify their healthcare team if they experience or observe new or worsening CNS effects²

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Severity¹	Guidance¹
Grade 2: Moderate OR Grade 3: Severe	Withhold dose until toxicity is ≤Grade 1 Then resume LORVIQUA at 1 reduced dose level^a
Grade 4: Life-threatening/urgent intervention indicated	Permanently discontinue LORVIQUA

^a The recommended dose of LORVIQUA is 100 mg taken orally, once daily. The first dose reduction level is 75 mg once daily.¹

Lipase/amylase increase¹

Patients should be monitored for lipase and amylase elevations¹:

Prior to the start of treatment

Regularly thereafter as clinically indicated

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Severity¹	Guidance¹
Grade 3: Severe OR Grade 4: Life-threatening/urgent intervention indicated	Withhold LORVIQUA until lipase or amylase returns to baseline Then resume LORVIQUA at 1 reduced dose level^a

^aThe recommended dose of LORVIQUA is 100 mg taken orally, once daily. The first dose reduction level is 75 mg once daily.¹

ILD/pneumonitis¹

Any patient who presents with worsening of respiratory symptoms indicative of ILD/pneumonitis (eg, dyspnoea, cough, and fever) should be promptly evaluated.¹

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Severity¹	Guidance¹
Grade 1: Mild OR Grade 2: Moderate	Withhold LORVIQUA until symptoms have returned to baseline, and consider initiating corticosteroids Then resume LORVIQUA at 1 reduced dose level^a Permanently discontinue LORVIQUA if ILD/pneumonitis recurs or fails to recover after 6 weeks of withholding LORVIQUA and treating with steroids
Grade 3: Severe OR Grade 4: Life-threatening/urgent intervention indicated	Permanently discontinue LORVIQUA

^aThe recommended dose of LORVIQUA is 100 mg taken orally, once daily. The first dose reduction level is 75 mg once daily.¹

First-degree AV block¹

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Severity¹	Guidance¹
First-degree AV block: Asymptomatic	Continue LORVIQUA at the same dose without interruption Consider effects of concomitant medicinal products Assess and correct electrolyte imbalance that may prolong PR interval Monitor ECG/symptoms potentially related to AV block closely
First-degree AV block: Symptomatic	Withhold LORVIQUA Consider effects of concomitant medicinal products Assess and correct electrolyte imbalance that may prolong PR interval Monitor ECG/symptoms potentially related to AV block closely If symptoms resolve, resume LORVIQUA at 1 reduced dose level^a

^aThe recommended dose of LORVIQUA is 100 mg taken orally, once daily. The first dose reduction level is 75 mg once daily.¹

Second-degree AV block¹

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Severity¹	Guidance¹
Second-degree AV block: Asymptomatic	Withhold LORVIQUA Consider effects of concomitant medicinal products Assess and correct electrolyte imbalance that may prolong PR interval Monitor ECG/symptoms potentially related to AV block closely If subsequent ECG does not show second-degree AV block, resume LORVIQUA at 1 reduced dose level^a
Second-degree AV block: Symptomatic	Withhold LORVIQUA Consider effects of concomitant medicinal products Assess and correct electrolyte imbalance that may prolong PR interval Refer for cardiac observation and monitoring Consider pacemaker placement if symptomatic AV block persists If symptoms and the second-degree AV block resolve, or if patient reverts to asymptomatic first-degree AV block, resume LORVIQUA at 1 reduced dose level^a

Severity¹

Guidance¹

Second-degree AV block: Asymptomatic

Withhold LORVIQUA
Consider effects of concomitant medicinal products
Assess and correct electrolyte imbalance that may prolong PR interval
Monitor ECG/symptoms potentially related to AV block closely
If subsequent ECG does not show second-degree AV block, resume LORVIQUA at 1 reduced dose level^a

Second-degree AV block: Symptomatic

Withhold LORVIQUA
Consider effects of concomitant medicinal products
Assess and correct electrolyte imbalance that may prolong PR interval
Refer for cardiac observation and monitoring
Consider pacemaker placement if symptomatic AV block persists
If symptoms and the second-degree AV block resolve, or if patient reverts to asymptomatic first-degree AV block, resume LORVIQUA at 1 reduced dose level^a

^aThe recommended dose of LORVIQUA is 100 mg taken orally, once daily. The first dose reduction level is 75 mg once daily.¹

Complete AV block¹

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Severity¹	Guidance¹
Complete AV block	Withhold LORVIQUA Consider effects of concomitant medicinal products Assess and correct electrolyte imbalance that may prolong PR interval Refer for cardiac observation and monitoring Pacemaker placement may be indicated for severe symptoms associated with AV block If AV block does not resolve, placement of a permanent pacemaker may be considered If pacemaker is placed, resume LORVIQUA at full dose If no pacemaker is placed, resume LORVIQUA at 1 reduced dose level^a only when symptoms resolve and PR interval is less than 200 msec

Severity¹

Guidance¹

Complete AV block

Withhold LORVIQUA
Consider effects of concomitant medicinal products
Assess and correct electrolyte imbalance that may prolong PR interval
Refer for cardiac observation and monitoring
Pacemaker placement may be indicated for severe symptoms associated with AV block
If AV block does not resolve, placement of a permanent pacemaker may be considered
If pacemaker is placed, resume LORVIQUA at full dose
If no pacemaker is placed, resume LORVIQUA at 1 reduced dose level^a only when symptoms resolve and PR interval is less than 200 msec

^aThe recommended dose of LORVIQUA is 100 mg taken orally, once daily. The first dose reduction level is 75 mg once daily.¹

Hypertension¹

Blood pressure should be controlled prior to initiation of LORVIQUA and monitored after 2 weeks and at least monthly thereafter during treatment with LORVIQUA.¹

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Severity¹	Guidance¹
Grade 3: SBP ≥160 mmHg OR DBP ≥100 mmHg Medical intervention indicated >1 antihypertensive drug, or more intensive therapy than previously used, indicated	Withhold LORVIQUA until hypertension has recovered to ≤Grade 1 (SBP <140 mmHg and DBP <90 mmHg), then resume LORVIQUA at the same dose If Grade 3 hypertension recurs, withhold LORVIQUA until recovery to ≤Grade 1 and resume at a reduced dose^a If adequate hypertension control cannot be achieved with optimal medical management, permanently discontinue LORVIQUA
Grade 4: Life-threatening consequences, urgent intervention indicated	Withhold LORVIQUA until recovery to ≤Grade 1, and resume at a reduced dose^a or permanently discontinue LORVIQUA If Grade 4 hypertension recurs, permanently discontinue LORVIQUA

^aThe recommended dose of LORVIQUA is 100 mg taken orally, once daily. The first dose reduction level is 75 mg once daily.¹

Hyperglycaemia¹

Fasting serum glucose should be assessed prior to initiation of LORVIQUA and monitored periodically thereafter.¹

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Severity¹	Guidance¹
Grade 3 OR Grade 4: Persistent hyperglycaemia >250 mg/dL despite optimal antihyperglycaemic therapy	Withhold LORVIQUA until hyperglycaemia is adequately controlled, then resume LORVIQUA at the next lower dosage^a If adequate hyperglycaemic control cannot be achieved with optimal medical management, permanently discontinue LORVIQUA

^aThe recommended dose of LORVIQUA is 100 mg taken orally, once daily. The first dose reduction level is 75 mg once daily.¹

Other adverse reactions^1,a

Fasting serum glucose should be assessed prior to initiation of LORVIQUA and monitored periodically thereafter.¹

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Severity¹	Guidance¹
Grade 1: Mild OR Grade 2: Moderate	Consider no dose modification, or reduce by 1 dose level,^b as clinically indicated
≥Grade 3: Severe	Withhold LORVIQUA until symptoms resolve to ≤Grade 2 or baseline Then resume LORVIQUA at 1 reduced dose level^b

^aOther adverse reactions may include oedema, peripheral neuropathy, gastrointestinal effects, or weight increase.²

^bThe recommended dose of LORVIQUA is 100 mg taken orally, once daily. The first dose reduction level is 75 mg once daily.¹

AV=atrioventricular; CNS=central nervous system; DBP=diastolic blood pressure; ECG=electrocardiogram; ILD=interstitial lung disease; SBP=systolic blood pressure; ULN=upper limit of normal.

References:

Pfizer. LORVIQUA (lorlatinib) Summary of Product Characteristics.

Bauer TM, Felip E, Solomon BJ, et al. Clinical management of adverse events associated with lorlatinib. Oncologist. 2019;24(8):1103-1110.

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