Safety and Tolerability

Consider the safety and tolerability of LYNPARZA1

Adverse reactions have been reported in patients taking LYNPARZA.1

Please see Important Safety Information with serious warnings and precautions below.

SOLO-1

SOLO-2

Study 19

The safety profile of LYNPARZA was observed in SOLO-11

SOLO-1: Grades 1-4 adverse reactions* in ≥10% of patients on LYNPARZA1

Safety profile of LYNPARZA® (olaparib) as observed in SOLO-1

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

Includes asthenia, fatigue, lethargy, and malaise.

Includes abdominal pain, abdominal pain lower, abdominal pain upper, abdominal distension, abdominal discomfort, and abdominal tenderness.

§Includes colitis, diarrhea, and gastroenteritis.

||Includes neutropenia and febrile neutropenia.

Includes dyspnea and dyspnea exertional.

#Includes leukopenia and white blood cell count decreased.

**Includes urosepsis, urinary tract infection, urinary tract pain, and pyuria.

††Includes platelet count decreased and thrombocytopenia.

‡‡Includes stomatitis, aphthous ulcer, and mouth ulceration.

SOLO-1 Laboratory Abnormalities1

LYNPARZA Tablets(n=260) Placebo(n=130)
Laboratory Parameter* Grades1-4 (%) Grades3-4 (%) Grades1-4 (%) Grades3-4 (%)
Decrease in hemoglobin 87 19 63 2
Increase in mean corpuscular volume 87 0 43 0
Decrease in leukocytes 70 7 52 1
Decrease in lymphocytes 67 14 29 5
Decrease in absolute neutrophil count 51 9 38 6
Increase in serum creatinine 34 0 18 0
Decrease in platelets 35 1 20 2

*Patients were allowed to enter clinical studies with laboratory values of NCI CTCAE Grade 1.1

This number represents the safety population. The derived values in the table are based on the total number of evaluable patients for each laboratory parameter.1

  • Monitor patients for hematological toxicity at baseline and monthly thereafter

The safety profile of LYNPARZA was observed in SOLO-21

SOLO-2: Grades 1-4 adverse reactions* in ≥20% of patients on LYNPARZA1

Adverse reactions of LYNPARZA® (olaparib) as observed in SOLO-2

URI=upper respiratory infection.

*Graded according to 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 (19%), cough (18%), leukopenia (16%), hypomagnesemia (14%), thrombocytopenia (14%), dizziness (13%), dyspepsia (11%), increase in creatinine (11%), edema (8%), rash (6%), and lymphopenia (1%).

ADVERSE REACTIONS (ARs) OF SPECIAL INTEREST FROM SOLO-21,2

  • Grades 1-4 psychiatric ARs observed in women who received LYNPARZA included anxiety (6.2%), insomnia (5.6%), and depression (4.6%)2,§
  • Grades 1-4 cardiovascular ARs observed in women who received LYNPARZA included hypertension (2.6%), tachycardia (0.5%), pericarditis (0.5%), deep vein thrombosis (1.0%), and chest pain (0.5%)4,§
    • No cardiac monitoring is required with LYNPARZA1
  • Patients studied did not experience Grades 3-4 nasopharyngitis, URI, sinusitis, rhinitis, influenza, decreased appetite, arthralgia, myalgia, or dysgeusia while taking LYNPARZA or placebo1
  • In SOLO-2, some women taking LYNPARZA experienced Grades 3-4 hematologic ARs. These included anemia (shown above), neutropenia (5.1%), thrombocytopenia (1.0%), lymphopenia (0.5%), and leukopenia (1.5%)2,§

These are not all of the adverse reactions reported in SOLO-2 that were deemed related to the study drug.

PARPi=poly (ADP-ribose) polymerase inhibitor; URI=upper respiratory infection.

§Causality due to study drug not assessed.

SOLO-2 Laboratory Abnormalities1

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 NCI CTCAE Grade 1.1

Represents the proportion of subjects whose mean corpuscular volume was > upper limit of normal.1

  • Monitor patients for hematological toxicity at baseline and monthly thereafter1
  • In SOLO-2, hepatic abnormalities, including elevated ALT/AST, gamma-glutamyltransferase increase, hypertransaminasemia, and hepatic neoplasm, were observed in <6% of women taking LYNPARZA2,‡
    • Elevated ALT (all grades): 5.1% with LYNPARZA and 4.0% with placebo§
    • Elevated AST (all grades): 2.1% with LYNPARZA and 4.0% with placebo§
  • In SOLO-2, no women taking LYNPARZA experienced Grades 3-4 elevated ALT/AST2

ALT=alanine aminotransferase; AST=aspartate aminotransferase.

Other Grades 1-4 lab abnormalities reported in women treated with LYNPARZA in SOLO-2 included hypomagnesemia, hypokalemia, hyperglycemia, hypertransaminasemia, blood creatine phosphokinase increase, and erythroblast count increase.2

§Causality due to study drug not assessed.

The safety profile of LYNPARZA was observed in Study 191

Study 19: Grades 1-4 adverse reactions* in ≥20% of patients on LYNPARZA1

Adverse reactions of LYNPARZA® (olaparib) as observed in Study 19

*Graded according to the NCI CTCAE, version 4.0.1

Represents grouped terms of related terms that reflect the medical concept of the adverse reaction.1

  • In addition, the adverse reactions in Study 19 that occurred in <20% of patients receiving LYNPARZA were dysgeusia (16%), dizziness (15%), dyspnea (13%), pyrexia (10%), stomatitis (9%), edema (9%), increase in creatinine (7%), neutropenia (5%), thrombocytopenia (4%), leukopenia (2%), and lymphopenia (1%).

ADVERSE REACTIONS OF SPECIAL INTEREST FROM STUDY 191,3

  • Grades 1-4 psychiatric disorders observed in women who received LYNPARZA included insomnia (1.5%), anxiety (0.7%), confusional state (0.7%), depression (0.7%), altered mood (0.7%), mood swings (0.7%), nightmares (0.7%), and sleep disorder (0.7%)3,‡
  • Grades 1-4 cardiovascular adverse reactions observed in women who received LYNPARZA included palpitations (1.5%), tachycardia (0.7%), flushing (0.7%), hot flush (2.2%), hypertension (0.7%), pallor (0.7%), and peripheral coldness (0.7%)3,‡
    • No cardiac monitoring is required with LYNPARZA1
  • Patients studied did not experience Grades 3-4 decreased appetite or headache while taking LYNPARZA or placebo1
  • In Study 19, some women taking LYNPARZA experienced Grades 3-5 hematologic ARs. These included anemia (shown above), neutropenia (3.7%), pancytopenia (1.5%), and thrombocytopenia (0.7%)3,§

These are not all of the adverse reactions reported in Study 19 that were deemed related to the study drug.

Investigator-assessed causality.

§Causality due to study drug not assessed.

Study 19 Laboratory Abnormalities1,*

  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 NCI CTCAE Grade 1.1

Represents the proportion of subjects whose mean corpuscular volume was > upper limit of normal.1

  • In Study 19, hepatic abnormalities, including elevated ALT/AST, were observed in <1% of women taking LYNPARZA3,‡
    • Elevated ALT (all grades): 0.7% with LYNPARZA and 1.6% with placebo
    • Elevated AST (all grades): 0% with LYNPARZA and 1.6% with placebo
  • In Study 19, no women taking LYNPARZA experienced Grades 3-4 elevated ALT/AST3

Investigator-assessed causality.1

AstraZeneca offers resources that may help with managing your patients’ adverse events.

In 3 pivotal trials, most women taking LYNPARZA were able to continue treatment at the full recommended dose1

In three pivotal trials, most women taking LYNPARZA® (olaparib) were able to continue treatment at the optimal dose

~9 out of 10 women remained on LYNPARZA without AR-related discontinuation1

~3 out of 4 women remained on the full recommended dose1

 

INDICATIONS

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

First-Line Maintenance BRCAm Advanced Ovarian Cancer

For the maintenance treatment of adult patients with deleterious or suspected deleterious germline or somatic BRCA-mutated (gBRCAm or sBRCAm) advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in complete or partial response to first-line platinum-based chemotherapy. Select patients for therapy based on an FDA-approved companion diagnostic for LYNPARZA.

Maintenance Recurrent Ovarian Cancer

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.

Advanced gBRCAm Ovarian Cancer

For the treatment of adult patients with deleterious or suspected deleterious germline BRCA-mutated (gBRCAm) 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

CONTRAINDICATIONS

There are no contraindications for LYNPARZA.

WARNINGS AND PRECAUTIONS

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 also had a history of more than one primary malignancy or of bone marrow dysplasia.

Do not start LYNPARZA until patients have recovered from hematological toxicity caused by previous chemotherapy (≤Grade 1). Monitor complete blood count for cytopenia at baseline and monthly thereafter for clinically significant changes during treatment. For prolonged hematological toxicities, interrupt LYNPARZA and monitor blood count 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 LYNPARZA treatment 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.

Females

Advise females of reproductive potential of the potential risk to a fetus and to use effective contraception during treatment and for 6 months following the last dose.

ADVERSE REACTIONS—First-Line Maintenance BRCAm Advanced Ovarian Cancer

Most common adverse reactions (Grades 1-4) in ≥10% of patients in clinical trials of LYNPARZA in the first-line maintenance setting for SOLO-1 were: nausea (77%), fatigue (67%), abdominal pain (45%), vomiting (40%), anemia (38%), diarrhea (37%), constipation (28%), upper respiratory tract infection/influenza/nasopharyngitis/bronchitis (28%), dysgeusia (26%), decreased appetite (20%), dizziness (20%), neutropenia (17%), dyspepsia (17%), dyspnea (15%), leukopenia (13%), UTI (13%), thrombocytopenia (11%), and stomatitis (11%).

Most common laboratory abnormalities (Grades 1-4) in ≥25% of patients in clinical trials of LYNPARZA in the first-line maintenance setting for SOLO-1 were: decrease in hemoglobin (87%), increase in mean corpuscular volume (87%), decrease in leukocytes (70%), decrease in lymphocytes (67%), decrease in absolute neutrophil count (51%), decrease in platelets (35%), and increase in serum creatinine (34%).

ADVERSE REACTIONS—Maintenance Recurrent Ovarian Cancer

Most common adverse reactions (Grades 1-4) in ≥20% of patients in clinical trials of LYNPARZA in the maintenance setting for SOLO-2 were: nausea (76%), fatigue (including asthenia) (66%), anemia (44%), vomiting (37%), nasopharyngitis/upper respiratory tract infection (URI)/influenza (36%), diarrhea (33%), arthralgia/myalgia (30%), dysgeusia (27%), headache (26%), decreased appetite (22%), and stomatitis (20%).

Study 19: nausea (71%), fatigue (including asthenia) (63%), vomiting (35%), diarrhea (28%), anemia (23%), respiratory tract infection (22%), constipation (22%), headache (21%), decreased appetite (21%) and dyspepsia (20%).

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 (89%/82%), decrease in hemoglobin (83%/82%), decrease in leukocytes (69%/58%), decrease in lymphocytes (67%/52%), decrease in absolute neutrophil count (51%/47%), increase in serum creatinine (44%/45%), and decrease in platelets (42%/36%).

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/asthenia (66%), nausea (64%), vomiting (43%), anemia (34%), diarrhea (31%), nasopharyngitis/upper respiratory tract infection (URI) (26%), dyspepsia (25%), myalgia (22%), decreased appetite (22%), and arthralgia/musculoskeletal pain (21%).

Most common laboratory abnormalities (Grades 1-4) in ≥25% of patients in clinical trials of LYNPARZA for advanced gBRCAm ovarian cancer (pooled from 6 studies) were: decrease in hemoglobin (90%), mean corpuscular volume elevation (57%), decrease in lymphocytes (56%), increase in serum creatinine (30%), decrease in platelets (30%), and decrease in absolute neutrophil count (25%).

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, there is a potential for decreased efficacy of LYNPARZA.

USE IN SPECIFIC POPULATIONS

Lactation: No data are available regarding the presence of olaparib in human milk, its effects on the breastfed infant or 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.

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

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

Renal Impairment: No adjustment to the starting dose is necessary in patients with mild renal impairment (CLcr=51-80 mL/min), but patients should be monitored closely for toxicity. 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).

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