CONTRAINDICATIONS
There are no contraindications for LYNPARZA.
WARNINGS AND PRECAUTIONS
- Myelodysplastic Syndrome/Acute Myeloid Leukemia (MDS/AML):
Occurred in approximately 1.2% of patients (26/2219) with
various
BRCAm, gBRCAm, HRR gene-mutated or HRD-positive cancers who received LYNPARZA in
clinical studies as a single agent or as part of a combination regimen, consistent with the
approved indications, and
the majority of events had a fatal outcome. The median duration of therapy in patients who
developed MDS/AML was approximately 2 years (range: <6 months to >4
years). All of these patients had previous chemotherapy with platinum agents and/or
other DNA-damaging agents, including radiotherapy.
- In SOLO-1, patients with newly diagnosed advanced BRCAm ovarian cancer, the incidence of
MDS/AML was 1.9% (5/260) in patients who received LYNPARZA and 0.8% (1/130) in patients who
received placebo based on an updated analysis. In PAOLA-1, of patients with newly diagnosed
advanced ovarian cancer with HRD-positive status, the incidence of MDS/AML was 1.6% (4/255) in
patients who received LYNPARZA and 2.3% (3/131) in the control arm.
- In SOLO-2, patients with BRCAm platinum-sensitive relapsed ovarian cancer, the incidence
of MDS/AML was 8% (15/195) in patients who received LYNPARZA and 4% (4/99) in patients who
received placebo. The duration of LYNPARZA treatment prior to the diagnosis of MDS/AML ranged
from 0.6 years to 4.5 years.
- 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 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: Including severe and fatal cases, has occurred in
patients treated with LYNPARZA. In clinical studies, among patients who received LYNPARZA as a
single agent or as part of a combination regimen, the incidence of pneumonitis, including fatal
cases, was 1.0% (29/2851). If
patients present with new or worsening respiratory symptoms such as
dyspnea, cough, and fever, or a radiological abnormality occurs, interrupt LYNPARZA treatment
and promptly assess the source of the symptoms. If pneumonitis is confirmed, discontinue
LYNPARZA treatment and treat the patient appropriately.
- Venous Thromboembolism (VTE): Including severe or fatal
pulmonary embolism (PE), occurred in patients treated with LYNPARZA. In the combined data of two
randomized, placebo-controlled clinical studies (PROfound and
PROpel)
in patients with metastatic castration-resistant prostate cancer (N=1180), VTE occurred in 8% of
patients who received LYNPARZA, including pulmonary embolism in 6%. In the control arms, VTE
occurred in 2.5%, including pulmonary embolism in 1.5%. Monitor patients for signs and symptoms
of venous thrombosis and pulmonary embolism, and treat as medically appropriate, which may
include long-term anticoagulation as clinically indicated.
- Hepatotoxicity, including Drug-Induced Liver Injury (DILI):
Hepatotoxicity, including severe and potentially fatal cases of DILI has occurred in patients
treated with LYNPARZA. Evaluate bilirubin and transaminases at baseline and throughout treatment
with LYNPARZA. For patients who develop abnormal liver tests after LYNPARZA, monitor more
frequently for liver test abnormalities and clinical signs and symptoms of hepatic toxicity. If
DILI is suspected, withhold LYNPARZA. Upon confirmation of DILI, discontinue LYNPARZA.
- Embryo-Fetal Toxicity: Based on its mechanism of action and
findings in animals, LYNPARZA can cause fetal harm. Verify pregnancy status in 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.
- Males Advise male patients with female partners of
reproductive potential or who are pregnant to use effective contraception during treatment and
for 3 months following the last dose of LYNPARZA
and to not donate sperm during this time.
ADVERSE REACTIONS—First-Line Maintenance BRCAm Advanced Ovarian Cancer
Most common adverse reactions (all Grades) in ≥10% of patients who received 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%), urinary tract
infection (13%), thrombocytopenia
(11%), and stomatitis (11%).
Most common laboratory abnormalities (Grades 1-4) in ≥25% of patients who
received 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—First-Line Maintenance Advanced Ovarian Cancer in Combination with Bevacizumab
Most common adverse reactions (Grades 1-4) in ≥10% of patients treated with LYNPARZA/bevacizumab and
at a ≥5% frequency compared to placebo/bevacizumab in the first-line maintenance setting for PAOLA-1 were: nausea (53%), fatigue (including asthenia) (53%), anemia
(41%), lymphopenia (24%), vomiting (22%), and leukopenia (18%). In addition,
the most common adverse reactions (≥10%) for patients receiving LYNPARZA/bevacizumab irrespective of
the frequency compared with the placebo/bevacizumab arm were: diarrhea (18%), neutropenia (18%),
urinary tract infection (15%), and
headache (14%).
In addition, venous thromboembolism occurred more commonly in patients receiving LYNPARZA/bevacizumab
(5%) than in those receiving placebo/bevacizumab (1.9%).
Most common laboratory abnormalities (Grades 1-4) in ≥25% of patients for
LYNPARZA in combination with bevacizumab in the first-line maintenance setting for PAOLA-1 were: decrease in hemoglobin (79%), decrease in lymphocytes
(63%), increase in serum creatinine (61%), decrease in leukocytes (59%), decrease
in absolute neutrophil count (35%), and decrease in platelets (35%).
ADVERSE REACTIONS—Maintenance gBRCAm Recurrent Ovarian Cancer
Most common adverse reactions (Grades 1-4) in ≥20% of patients who received 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)/sinusitis/rhinitis/influenza (36%), diarrhea (33%), arthralgia/myalgia (30%), dysgeusia (27%), headache (26%),
decreased appetite (22%), and stomatitis (20%).
Most common laboratory abnormalities (Grades 1-4) in ≥25% of patients who
received LYNPARZA in the maintenance setting for SOLO-2 were: increase in mean corpuscular volume (89%),
decrease in hemoglobin (83%), decrease in leukocytes (69%), decrease in lymphocytes (67%), decrease
in absolute neutrophil count (51%), increase in serum creatinine (44%), and
decrease in platelets (42%).
ADVERSE REACTIONS—Adjuvant Treatment of gBRCAm, HER2-Negative,
High-Risk Early Breast Cancer
Most common adverse reactions (Grades 1-4) in ≥10% of patients who received LYNPARZA in the adjuvant setting for OlympiA were:
nausea (57%), fatigue (including asthenia) (42%),
anemia (24%), vomiting (23%), headache (20%), diarrhea (18%), leukopenia (17%), neutropenia (16%),
decreased appetite (13%), dysgeusia (12%), dizziness (11%),
and stomatitis (10%).
Most common laboratory abnormalities (Grades 1-4) in ≥25% of patients who received LYNPARZA in the
adjuvant setting for OlympiA were:
decrease in lymphocytes (77%), increase in mean corpuscular volume (67%), decrease in hemoglobin
(65%), decrease in leukocytes (64%),
and decrease in absolute neutrophil count (39%).
ADVERSE REACTIONS—gBRCAm, HER2-Negative Metastatic Breast
Cancer
Most common adverse reactions (Grades 1-4) in ≥20% of patients who received LYNPARZA in the
metastatic setting for OlympiAD
were: nausea (58%), anemia (40%), fatigue (including asthenia) (37%), vomiting (30%), neutropenia
(27%), respiratory tract infection (27%), leukopenia (25%), diarrhea
(21%), and headache (20%).
Most common laboratory abnormalities (Grades 1-4) in ≥25% of patients who received LYNPARZA in the
metastatic setting for OlympiAD
were: decrease in hemoglobin (82%), decrease in lymphocytes (73%), decrease in leukocytes (71%),
increase in mean corpuscular volume (71%), decrease in absolute neutrophil
count (46%), and decrease in platelets (33%).
ADVERSE REACTIONS—First-Line Maintenance gBRCAm Metastatic Pancreatic
Adenocarcinoma
Most common adverse reactions (all Grades) in ≥10% of patients who received LYNPARZA in the
first-line maintenance setting for
POLO were: fatigue (60%), nausea (45%), abdominal pain (34%),
diarrhea (29%), anemia (27%), decreased appetite (25%), constipation (23%), vomiting (20%), back
pain (19%), arthralgia (15%), rash (15%), thrombocytopenia
(14%), dyspnea (13%), neutropenia (12%), nasopharyngitis (12%), dysgeusia (11%),
and stomatitis (10%).
Most common laboratory abnormalities (Grades 1-4) in ≥25% of patients who received LYNPARZA in the
first-line
maintenance setting for
POLO were: increase in serum creatinine (99%), decrease in
hemoglobin (86%), increase in mean corpuscular volume (71%), decrease in lymphocytes (61%), decrease
in platelets (56%), decrease in leukocytes (50%), and
decrease in absolute neutrophil count (25%).
ADVERSE REACTIONS—HRR Gene-mutated Metastatic Castration-Resistant Prostate Cancer
Most common adverse reactions (Grades 1-4) in ≥10% of patients who received LYNPARZA for PROfound were: anemia (46%), fatigue (including
asthenia) (41%), nausea (41%), decreased appetite (30%), diarrhea (21%), vomiting (18%),
thrombocytopenia (12%), cough (11%), and dyspnea (10%).
Most common laboratory abnormalities (Grades 1-4) in ≥25% of patients who received LYNPARZA for PROfound were: decrease in hemoglobin (98%), decrease
in lymphocytes (62%), decrease in leukocytes (53%), and decrease in absolute neutrophil count (34%).
ADVERSE REACTIONS—Metastatic Castration-Resistant Prostate Cancer in Combination with Abiraterone
and Prednisone or Prednisolone
Most common adverse reactions (Grades 1-4) in ≥10% of patients who received LYNPARZA/abiraterone with
a difference of ≥5% compared to placebo/abiraterone for PROpel were: anemia
(48%), fatigue (including asthenia) (38%), nausea (30%), diarrhea (19%), decreased appetite (16%),
lymphopenia (14%), dizziness (14%), and abdominal pain (13%).
Most common laboratory abnormalities (Grades 1-4) in ≥20% of patients who received
LYNPARZA/abiraterone for PROpel were: decrease in hemoglobin (97%),
decrease in lymphocytes (70%), decrease in platelets (23%), and decrease in absolute neutrophil
count (23%).
DRUG INTERACTIONS
- Anticancer Agents: Clinical studies of LYNPARZA with other
myelosuppressive anticancer agents, including DNA-damaging agents,
indicate a potentiation and prolongation of
myelosuppressive toxicity.
- CYP3A Inhibitors: Avoid coadministration of strong or moderate
CYP3A inhibitors when using LYNPARZA. If a strong or moderate CYP3A inhibitor must be
coadministered, reduce the dose of LYNPARZA. Advise patients to avoid grapefruit, grapefruit
juice, Seville oranges, and Seville orange juice during
LYNPARZA treatment.
- CYP3A Inducers: Avoid coadministration of strong or moderate
CYP3A inducers when using 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 dosage modification is recommended in
patients with mild renal impairment (CLcr 51-80 mL/min estimated by
Cockcroft-Gault). In
patients with moderate renal impairment (CLcr 31-50 mL/min), reduce
the dose of LYNPARZA to 200
mg twice daily. There are no data in patients with severe renal impairment or end-stage renal disease (CLcr ≤30 mL/min).
