Olaparib

Anemia, neutropenia, thrombocytopenia, and lymphopenia have been reported. Monitor complete blood counts at baseline and monthly thereafter; do not initiate olaparib until any hematologic toxicity caused by previous chemotherapy has resolved to ≤ grade 1. If prolonged hematologic toxicity occurs during therapy, interrupt treatment and monitor blood counts weekly until recovered; if counts do not recover to ≤ grade 1 after 4 weeks, further evaluation (including bone marrow and cytogenetic analyses) is necessary.

Nausea and vomiting (usually mild to moderate) may commonly occur.

Hypersensitivity reactions, including rash and dermatitis, have been reported.

Pneumonitis (including some fatalities) has occurred rarely. Interrupt treatment for new or worsening respiratory symptoms such as cough, dyspnea, fever, wheezing, or radiologic abnormalities; evaluate promptly. Discontinue treatment if pneumonitis is confirmed.

Myelodysplastic syndrome/acute myeloid leukemia (MDS/AML) have been reported (rarely) in clinical trials and long-term follow up, mostly in patients with documented BRCA mutation. Most MDS/AML cases were fatal. Additional cases of MDS/AML have been reported in patients treated with olaparib in combination studies. The duration of olaparib therapy prior to development of the secondary cancers ranged from 2 years; all patients had received prior chemotherapy with platinum agents and/or other DNA-damaging medications, including radiation; some of these patients had a prior history of more than one primary malignancy or bone marrow dysplasia. If prolonged hematologic toxicity occurs and blood counts do not recover to ≤ grade 1 after 4 weeks, further evaluation (including bone marrow and cytogenetic analyses) is necessary. If MDS/AML is confirmed, discontinue therapy. Disease-related concerns:

Monitor closely for toxicity in patients with mild or moderate renal impairment. Dosage adjustment is recommended for moderate impairment. Concurrent drug therapy issues:

Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information. Dosage form specific issues:

Olaparib is available as 100 mg and 150 mg tablets and as 50 mg capsules. Do not substitute the 50 mg capsules for the 100 mg or 150 mg tablets on a mg-per-mg basis due to differences in dosing and bioavailability. Other warnings/precautions:

Select patients for the treatment of advanced ovarian cancer or HER2-negative metastatic breast cancer based on the presence of deleterious or suspected deleterious BRCA-mutations. Information on approved tests for the detection of BRCA-mutations may be found at http://www.fda.gov/companiondiagnostics.