nable to tolerate 50 mg orally once daily.
Dosage modifications for adverse reactions of LORBRENA are provided in Table 1.
Table 1 Recommended LORBRENA Dosage Modifications for Adverse Reactions
Adverse Reaction* Dosage Modifications
Abbreviation: AV=atrioventricular.
*
Grade based on National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.
Central Nervous System Effects [see Warnings and Precautions (5.2)]
Grade 1 Continue at the same dose or withhold the dose until recovery to baseline. Resume LORBRENA at the same dose or at a reduced dose.
Grade 2 OR Grade 3 Withhold dose until Grade 0 or 1. Resume LORBRENA at a reduced dose.
Grade 4 Permanently discontinue LORBRENA.
Hyperlipidemia [see Warnings and Precautions (5.3)]
Grade 4 hypercholesterolemia OR
Grade 4 hypertriglyceridemia Withhold LORBRENA until recovery of hypercholesterolemia and/or hypertriglyceridemia to less than or equal to Grade 2. Resume LORBRENA at the same dose.
If severe hypercholesterolemia and/or hypertriglyceridemia recurs, resume LORBRENA at a reduced dose.
Atrioventricular (AV) Block [see Warnings and Precautions (5.4)]
Second-degree AV block Withhold LORBRENA until PR interval is less than 200 ms. Resume LORBRENA at a reduced dose.
First occurrence of complete AV block Withhold LORBRENA until
pacemaker placed OR
PR interval less than 200 ms.
If a pacemaker is placed, resume LORBRENA at the same dose.
If no pacemaker is placed, resume LORBRENA at a reduced dose.
Recurrent complete AV block Place pacemaker or permanently discontinue LORBRENA.
Interstitial Lung Disease (ILD)/Pneumonitis [see Warnings and Precautions (5.5)]
Any Grade treatment–related ILD/Pneumonitis Permanently discontinue LORBRENA.
Other Adverse Reactions
Grade 1 OR Grade 2 Continue LORBRENA at same dose or reduced dose.
Grade 3 OR Grade 4 Withhold LORBRENA until symptoms resolve to less than or equal to Grade 2 or baseline. Resume LORBRENA at reduced dose.
2.3Concomitant Use of Strong or Moderate CYP3A Inducers
LORBRENA is contraindicated in patients taking strong CYP3A inducers. Discontinue strong CYP3A inducers for 3 plasma half-lives of the strong CYP3A inducer prior to initiating LORBRENA. Avoid concomitant use of LORBRENA with moderate CYP3A inducers [see Warnings and Precautions (5.1), Clinical Pharmacology (12.3)].
2.4Dosage Modification for Strong CYP3A Inhibitors
Avoid concomitant use of LORBRENA with strong CYP3A inhibitors. If concomitant use with a strong CYP3A inhibitor cannot be avoided, reduce the starting dose of LORBRENA from 100 mg orally once daily to 75 mg orally once daily.
In patients who have had a dose reduction to 75 mg orally once daily due to adverse reactions and who initiate a strong CYP3A inhibitor, reduce the LORBRENA dose to 50 mg orally once daily.
If concomitant use of a strong CYP3A inhibitor is discontinued, increase the LORBRENA dose (after 3 plasma half-lives of the strong CYP3A inhibitor) to the dose that was used before starting the strong inhibitor [see Clinical Pharmacology (12.3)].
3DOSAGE FORMS AND STRENGTHS
Tablets:
25 mg: 8 mm round, tan, immediate release, film-coated, debossed with "Pfizer" on one side and "25" and "LLN" on the other side
100 mg: 8.5 mm × 17 mm oval, lavender, immediate release, film-coated, debossed with " |
