Safety and Tolerability

Adverse reactions have been reported in patients taking LYNPARZA.1 Please see Important Safety Information with serious warnings and precautions below.

SOLO-2

Study 19

Most common adverse reactions for LYNPARZA in SOLO-21

ADVERSE REACTIONS* IN SOLO-2 (patients with platinum-sensitive gBRCAm)1

(≥20% of patients who received LYNPARZA)

LYNPARZA tablets(n=195) Placebo(n=99)
Adverse Reactions Grades 1-4 (%) Grades 3-4 (%) Grades 1-4 (%) Grades 3-4 (%)
Blood and lymphatic disorders
Anemia 44 20 9 2
Gastrointestinal disorders
Nausea 76 3 33 0
Vomiting 37 3 19 1
Diarrhea 33 2 22 0
Stomatitis 20 1 16 0
Infections and infestations
Nasopharyngitis/ URI/sinusitis/ rhinitis/influenza 36 0 29 2
General disorders and administration site conditions
Fatigue (including asthenia) 66 4 39 2
Metabolism and nutrition disorders
Decreased appetite 22 0 11 0
Musculoskeletal and connective tissue disorders
Arthralgia/myalgia 30 0 28 0
Nervous system disorders
Dysgeusia 27 0 7 0
Headache 26 1 14 0

gBRCAm=germline BRCA mutation; URI=upper respiratory infection.

*Graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), version 4.0.1

Represents grouped term consisting of anemia, hematocrit decreased, hemoglobin decreased, iron deficiency, mean cell volume increased, and red blood cell count decreased.1

Represents grouped term consisting of abscess oral, aphthous ulcer, gingival abscess, gingival disorder, gingival pain, gingivitis, mouth ulceration, mucosal infection, mucosal inflammation, oral candidiasis, oral discomfort, oral herpes, oral infection, oral mucosal erythema, oral pain, oropharyngeal discomfort, and oropharyngeal pain.1

  • In addition, the adverse reactions observed in SOLO-2 that occurred in <20% of patients receiving LYNPARZA were neutropenia, rash, cough, dyspepsia, leukopenia, hypomagnesemia, dizziness, thrombocytopenia, increase in creatinine, lymphopenia, and edema1
  • Monitor patients for hematological toxicity at baseline and monthly thereafter1
SOLO-2: Tablets vs Placebo1
Dose reduction due to adverse reactions 27% 3%
Discontinuation due to adverse reactions 11% 2%
Dose interruptions due to adverse reactions of any grade 45% 18%

SOLO-2 LABORATORY ABNORMALITIES REPORTED IN ≥25% OF PATIENTS1

LYNPARZA tablets(n=195) Placebo(n=99)
Laboratory Parameter* Grades1-4 (%) Grades3-4 (%) Grades1-4 (%) Grades3-4 (%)
Increase in mean corpuscular volume 89 - 52 -
Decrease in hemoglobin 83 17 69 0
Decrease in leukocytes 69 5 48 1
Decrease in lymphocytes 67 11 37 1
Decrease in absolute neutrophil count 51 7 34 3
Increase in serum creatinine 44 0 29 0
Decrease in platelets 42 2 22 1

*Patients were allowed to enter clinical studies with laboratory values of CTCAE Grade 1.

Represents the proportion of subjects whose mean corpuscular volume was > upper limit of normal.

Most common adverse reactions for LYNPARZA in Study 191

ADVERSE REACTIONS* IN STUDY 19 (patients with platinum-sensitive disease—regardless of BRCA status)1,2

(≥20% of patients who received LYNPARZA)

  LYNPARZA tablets (n=136) Placebo (n=128)
Adverse Reactions Grades 1-4 (%) Grades 3-4 (%) Grades 1-4 (%) Grades 3-4 (%)
Blood and lymphatic disorders
Anemia 23 7 7 1
Gastrointestinal disorders
Nausea 71 2 36 0
Vomiting 35 2 14 1
Diarrhea 28 2 25 2
Constipation 22 1 12 0
General disorders and administration site conditions
Fatigue (including asthenia) 63 9 46 3
Infections and infestations
Respiratory tract infection 22 2 11 0
Metabolism and nutrition disorders
Decreased appetite 21 0 13 0
Nervous system disorders
Headache 21 0 13 1

*Graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), version 4.0.

Represents grouped terms of related terms that reflect the medical concept of the adverse reaction.

  • In addition, the adverse reactions in Study 19 that occurred in <20% of patients receiving LYNPARZA were dyspepsia, stomatitis, dysgeusia, dizziness, increase in creatinine, neutropenia, thrombocytopenia, leukopenia, lymphopenia, dyspnea, pyrexia, and edema1
STUDY 19 capsules vs Placebo1
Dose reduction due to adverse reactions 26% 4%
Discontinuation due to adverse reactions 6% 2%
Dose interruptions due to adverse reactions 35% 10%

STUDY 19 LABORATORY ABNORMALITIES* REPORTED IN ≥25% OF PATIENTS1

  LYNPARZA capsules(n=136) Placebo(n=129)
Laboratory Parameter* Grades1-4 (%) Grades3-4 (%) Grades1-4 (%) Grades3-4 (%)
Decrease in hemoglobin 82 8 58 1
Increase in mean corpuscular volume 82 - 51 -
Decrease in leukocytes 58 4 37 2
Decrease in lymphocytes 52 10 32 3
Decrease in absolute neutrophil count 47 7 40 2
Increase in serum creatinine 45 0 14 0
Decrease in platelets 36 4 18 0

*Patients were allowed to enter clinical studies with laboratory values of CTCAE Grade 1.

Represents the proportion of subjects whose mean corpuscular volume was > upper limit of normal.

These safety data support the long-term use of LYNPARZA in the use of a maintenance setting.1

 

INDICATIONS

LYNPARZA is a poly (ADP-ribose) polymerase (PARP) inhibitor indicated:

  • For the maintenance treatment of adult patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer, who are in complete or partial response to platinum-based chemotherapy

  • For the treatment of adult patients with deleterious or suspected deleterious germline BRCA-mutated advanced ovarian cancer who have been treated with 3 or more prior lines of chemotherapy. Select patients for therapy based on an FDA-approved companion diagnostic for LYNPARZA

IMPORTANT SAFETY INFORMATION

DOSING AND ADMINISTRATION

To avoid substitution errors and overdose, do not substitute LYNPARZA tablets with LYNPARZA capsules on a milligram-to-milligram basis due to differences in the dosing and bioavailability of each formulation. Recommended tablet dose is 300 mg, taken orally twice daily, with or without food. Continue treatment until disease progression or unacceptable toxicity. For adverse reactions, consider dose interruption or dose reduction.

WARNINGS AND PRECAUTIONS

There are no contraindications for LYNPARZA.

Myelodysplastic Syndrome/Acute Myeloid Leukemia (MDS/AML): Occurred in <1.5% of patients exposed to LYNPARZA monotherapy, and the majority of events had a fatal outcome. The duration of therapy in patients who developed secondary MDS/AML varied from <6 months to >2 years. All of these patients had previous chemotherapy with platinum agents and/or other DNA-damaging agents, including radiotherapy, and some of these patients also had a history of previous cancer or bone marrow dysplasia.

Do not start LYNPARZA until patients have recovered from hematological toxicity caused by previous chemotherapy (≤Grade 1). Monitor complete blood counts for cytopenia at baseline and monthly thereafter for clinically significant changes during treatment. For prolonged hematological toxicities, interrupt LYNPARZA and monitor blood counts weekly until recovery. If the levels have not recovered to Grade 1 or less after 4 weeks, refer the patient to a hematologist for further investigations, including bone marrow analysis and blood sample for cytogenetics. Discontinue LYNPARZA if MDS/AML is confirmed.

Pneumonitis: Occurred in <1% of patients exposed to LYNPARZA, and some cases were fatal. If patients present with new or worsening respiratory symptoms such as dyspnea, cough, and fever, or a radiological abnormality occurs, interrupt treatment with LYNPARZA and initiate prompt investigation. Discontinue LYNPARZA if pneumonitis is confirmed and treat patient appropriately.

Embryo-Fetal Toxicity: Based on its mechanism of action and findings in animals, LYNPARZA can cause fetal harm. A pregnancy test is recommended for females of reproductive potential prior to initiating treatment. Advise females of reproductive potential of the potential risk to a fetus and to use effective contraception during treatment and for 6 months after receiving the final dose.

ADVERSE REACTIONS—Maintenance Setting

Most common adverse reactions (Grades 1-4) in ≥20% of patients in clinical trials of LYNPARZA in the maintenance setting for SOLO-2: nausea, fatigue (including asthenia), anemia, vomiting, nasopharyngitis/upper respiratory tract infection (URI)/influenza, diarrhea, arthralgia/myalgia, dysgeusia, headache, decreased appetite, and stomatitis.

Study 19: nausea, fatigue (including asthenia), vomiting, diarrhea, anemia, respiratory tract infection, constipation, headache, and decreased appetite.

Most common laboratory abnormalities (Grades 1-4) in ≥25% of patients in clinical trials of LYNPARZA in the maintenance setting (SOLO-2/Study 19) were: increase in mean corpuscular volume, decrease in hemoglobin, decrease in leukocytes, decrease in lymphocytes, decrease in absolute neutrophil count, increase in serum creatinine, and decrease in platelets.

ADVERSE REACTIONS—Advanced gBRCAm ovarian cancer

Most common adverse reactions (Grades 1-4) in ≥20% of patients in clinical trials of LYNPARZA for advanced gBRCAm ovarian cancer after 3 or more lines of chemotherapy (pooled from 6 studies) were: fatigue (including asthenia), nausea, vomiting, anemia, diarrhea, nasopharyngitis/upper respiratory tract infection (URI), dyspepsia, myalgia, decreased appetite, and arthralgia/musculoskeletal pain.

Most common laboratory abnormalities (Grades 1-4) in ≥25% of patients in clinical trials of LYNPARZA for advanced gBRCAm ovarian cancer after 3 or more lines of chemotherapy (pooled from 6 studies) were: decrease in hemoglobin, increase in mean corpuscular volume, decrease in lymphocytes, increase in serum creatinine, decrease in platelets, and decrease in absolute neutrophil count.

DRUG INTERACTIONS

Anticancer Agents: Clinical studies of LYNPARZA in combination with other myelosuppressive anticancer agents, including DNA-damaging agents, indicate a potentiation and prolongation of myelosuppressive toxicity.

CYP3A Inhibitors: Avoid concomitant use of strong or moderate CYP3A inhibitors. If a strong or moderate CYP3A inhibitor must be co-administered, reduce the dose of LYNPARZA. Advise patients to avoid grapefruit, grapefruit juice, Seville oranges, and Seville orange juice during LYNPARZA treatment.

CYP3A Inducers: Avoid concomitant use of strong or moderate CYP3A inducers when using LYNPARZA. If a moderate inducer cannot be avoided, be aware of a potential for decreased efficacy of LYNPARZA.

USE IN SPECIFIC POPULATIONS

Pediatric Use: The safety and efficacy of LYNPARZA have not been established in pediatric patients.

Lactation: No data are available regarding the presence of olaparib in human milk, the effects on the breastfed infant, or the effects on milk production. Because of the potential for serious adverse reactions in the breastfed infant, advise a lactating woman not to breastfeed during treatment with LYNPARZA and for 1 month after receiving the final dose.

Hepatic Impairment: No adjustment to the starting dose is required in patients with mild hepatic impairment (Child-Pugh classification A). There are no data in patients with moderate or severe hepatic impairment.

Renal Impairment: No adjustment to the starting dose is necessary in patients with mild renal impairment (CLcr 51-80 mL/min). In patients with moderate renal impairment (CLcr 31-50 mL/min), reduce the dose to 200 mg twice daily. There are no data in patients with severe renal impairment or end-stage renal disease (CLcr ≤30 mL/min).

Please see complete Prescribing Information, including Patient Information (Medication Guide).

You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.FDA.gov/medwatch or call 1-800-FDA-10881-800-FDA-1088.