Dosing and Therapy Management

LORBRENA™ has a once-daily dosing schedule¹

Dosing recommendations¹

	The recommended dose for LORBRENA™ is 100 mg taken orally once daily, with or without food.

	If a dose reduction is needed, LORBRENA™ is also available as a 25 mg tablet.

Not actual size of tablets

Dosing guidance¹

	LORBRENA™ tablets should be swallowed whole.

	The tablets should not be chewed, crushed or split prior to swallowing.

	LORBRENA™ is contraindicated in patients taking strong CYP3A inducers.*

	While taking LORBRENA™, consider alternative medicinal products to strong CYP3A inhibitors with less potential to inhibit CYP3A.*

*Please refer to the full LORBRENA LPD for recommendations regarding the use of CYP3A4/5 inducers and CYP3A4/5 inhibitors.¹

LORBRENA™ is contraindicated in patients taking strong CYP3A inducers, due to the potential for serious hepatotoxicity.¹

Abbreviations: CYP, Cytochrome; LPD, Local Product Document.

References:

Lorbrena™ EDA leaflet approval date 26/4/2021.

Dose modifications may enable patients to remain on treatment¹

Dose modifications* can be used to manage adverse reactions associated with LORBRENA™^1†

LORBRENA™ dose modifications: Hyperlipidemia¹

Hyperlipidemia was generally managed with lipid-lowering agents and dose interruptions, with or without dose modifications.²

Patients should have their serum cholesterol and triglycerides monitored:¹

Before initiation of LORBRENA™
1 and 2 months after initiating LORBRENA™
Periodically thereafter

LORBRENA™ dose modifications: CNS adverse reactions¹

Advise patients to notify their healthcare provider if they experience new or worsening CNS symptoms.¹

In some cases, LORBRENA™ needs to be withheld and then the dose reduced. For Grade 4 adverse reactions, permanently discontinue LORBRENA™.¹

CNS adverse reactions experienced with LORBRENA™ include seizures, psychotic effects and changes in cognitive function, mood (including suicidal ideation), speech, mental status, and sleep.¹

LORBRENA™ dose modifications: ILD/pneumonitis¹

Severe or life-threatening pulmonary adverse reactions consistent with ILD/pneumonitis have occurred with LORBRENA™.¹

Any Grade treatment–related ILD/Pneumonitis, permanently discontinue LORBRENATM¹

Any patient who presents with worsening of respiratory symptoms indicative of ILD/pneumonitis should be promptly evaluated. Symptoms include:¹

Dyspnea
Cough
Fever

Immediately withhold LORBRENA^TM in patients with suspected ILD/pneumonitis. Permanently discontinue LORBRENATM for treatment-related ILD/pneumonitis of any severity.

LORBRENA™ dose modifications: AV block¹

PR interval prolongation^‡ and AV block have been reported in patients receiving LORBRENA™.¹

AV block occurred in 1.9% experienced AV block and 0.2% experienced Grade 3 AV block and underwent pacemaker placement^{1 §}

The recommendations for dose modifications vary according to the degree of AV block.¹

Recommendations for monitoring patients:¹

Monitor ECG prior to initiating LORBRENA™ and monthly thereafter, particularly in patients with predisposing conditions to clinically significant cardiac events

LORBRENA™ dose modifications: Other adverse reactions¹

Grades 1 and 2 adverse reactions:¹

Consider no dose modification or reduce by one dose level, as clinically indicated

Grade ≥3 adverse reactions:¹

Withhold LORBRENA™ until symptoms resolve to ≤ Grade 2 or baseline,and then resume LORBRENA™ at one reduced dose level

Please refer to the LORBRENA™ Local Product Document, Therapy Management package (available from your representative) or medical information for dose recommendations for different grades of adverse reactions.

*Dose interruptions associated with TRAEs were reported in 83 patients (30%). Dose reductions due to TRAEs were reported in 61 patients (22%).³
ing adverse events: hyperlipidemia, CNS effects, increased lipase/amylase, ILD/pneumonitis, AV block. Please refer to the LORBRENA™ Local Product Document, Therapy Management package (available from your representative), or medical information for dose recommendations for these adverse reactions.
^‡LORBENA™ to be withhold until PR interval is less than 200 ms.

^§ 0.2% experienced Grade 3 AV block and underwent pacemaker placement.

Abbreviations: AV, Atrioventricular; CNS, Central nervous system; ILD, Interstitial lung disease; TRAEs, Treatment-related adverse events.

References:

Lorbrena™ EDA leaflet approval date 26/4/2021.

Bauer TM, Felip E, Solomon BJ, et al. Clinical Management of Adverse Events Associated with Lorlatinib. Oncologist. 2019;24(8):1103-1110

Solomon BJ, Besse B, Bauer TM, et al. Lorlatinib in patients with ALK-positive non-small-cell lung cancer: results from a global phase 2 study. Lancet Oncol. 2018;19(12):1654–1667.