HIGHLIGHTS OF PRESCRIBING INFORMATION
WARNINGS AND PRECAUTIONS -
These
highlights do not include all the information needed to use LYNPARZA safely and
effectively. See full prescribing information for LYNPARZA. LYNPARZA®
(olaparib) tablets, for oral use Initial U.S. Approval: 2014
INDICATIONS AND USAGE --------------------------
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 a
complete or partial response to platinum-based chemotherapy. (1.1) • for the treatment of adult patients with deleterious or suspected
deleterious germline BRCA-mutated advanced ovarian cancer who have been treated
with three or more prior lines of chemotherapy. Select patients for therapy
based on an FDA-approved companion diagnostic
DOSAGE 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.
(2.1) • Recommended tablet dose is 300 mg taken orally
twice daily with or without food. (2.2) • Continue
treatment until disease progression or unacceptable toxicity. (2.2) • For adverse reactions, consider dose interruption or dose
reduction. (2.4) • For moderate renal impairment (CLcr
31-50 mL/min), reduce dose to 200 mg twice daily
DOSAGE FORMS AND STRENGTHS -------------------
Tablets: 150 mg,
CONTRAINDICATIONS ----------------------------
None (4) •
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. Monitor
patients for hematological toxicity at baseline and monthly thereafter.
Discontinue if MDS/AML is confirmed. (5.1) • Pneumonitis: Occurred in <1% of patients exposed to Lynparza,
and some cases were fatal. Interrupt treatment if pneumonitis is suspected.
Discontinue if pneumonitis is confirmed. (5.2) • Embryo-Fetal Toxicity: Lynparza can cause fetal harm. Advise females of
reproductive potential of the potential risk to a fetus and to use effective
contraception
ADVERSE REACTIONS ---------------------------- • Most common adverse reactions (≥20%) in clinical trials were anemia, nausea, fatigue (including
asthenia), vomiting, nasopharyngitis/upper respiratory tract infection/influenza,
diarrhea, arthralgia/myalgia, dysgeusia, headache, dyspepsia, decreased
appetite, constipation. and stomatitis. (6.1) • Most
common laboratory abnormalities (≥25%) were decrease in
hemoglobin, increase in mean corpuscular volume, decrease in lymphocytes,
decrease in leukocytes, decrease in absolute neutrophil count, increase in
serum creatinine and decrease in platelets. (6.1) To report SUSPECTED ADVERSE
REACTIONS, contact AstraZeneca at 1-800-236-9933 or FDA at 1-800-FDA-1088 or
www.fda.gov/medwatch.
DRUG INTERACTIONS ----------------------------
• CYP3A Inhibitors: Avoid concomitant use of strong or moderate CYP3A
inhibitors. If the inhibitor cannot be avoided, reduce the olaparib dose. (2.5,
7.2) • CYP3A Inducers: Avoid concomitant use of strong
or moderate
CYP3A
inducers as decreased efficacy can occur. (7.3, 12.3) ----------------------
- USE IN SPECIFIC POPULATIONS ---------------------
Lactation:
Advise women not to breastfeed. (8.2) See 17 for PATIENT COUNSELING INFORMATION
and MEDICATION GUIDE Revised: 8/2017
FULL PRESCRIBING INFORMATION:
CONTENTS*
1 INDICATIONS AND USAGE
1.1
Maintenance Treatment of Recurrent Ovarian Cancer
1.2
Advanced gBRCA-mutated Ovarian Cancer After 3 or More Lines of Chemotherapy
2 DOSAGE AND ADMINISTRATION
2.1
Important Administration Instructions 2.2 Recommended Dosing 2.3 Patient
Selection for gBRCA-mutated Advanced Ovarian Cancer 2.4 Dose Adjustments for
Adverse Reactions 2.5 Dose Modifications for Use with CYP3A Inhibitors 2.6 Dose
Modifications for Patients with Renal Impairment
3 DOSAGE
FORMS AND STRENGTHS
4
CONTRAINDICATIONS
5 WARNINGS
AND PRECAUTIONS
5.1
Myelodysplastic Syndrome/Acute Myeloid Leukemia 5.2 Pneumonitis 5.3
Embryo-Fetal Toxicity
6
ADVERSE REACTIONS 6.1 Clinical Trial Experience 6.2 Postmarketing
Experience
7 DRUG
INTERACTIONS 7.1 Anticancer Agents 7.2 Drugs That May Increase Olaparib Plasma
Concentrations 7.3 Drugs That May Decrease Olaparib Plasma Concentrations
8 USE IN
SPECIFIC POPULATIONS
8.1
Pregnancy 8.2 Lactation 8.3 Females and Males of Reproductive Potential 8.4
Pediatric Use 8.5 Geriatric Use 8.6 Hepatic Impairment 8.7 Renal
Impairment
10
OVERDOSAGE
11
DESCRIPTION
12
CLINICAL PHARMACOLOGY
12.1
Mechanism of Action 12.2 Pharmacodynamics 12.3 Pharmacokinetics
13
NONCLINICAL TOXICOLOGY
13.1
Carcinogenesis, Mutagenesis, Impairment of Fertility
14
CLINICAL STUDIES
14.1
Maintenance Treatment of Recurrent Ovarian Cancer
14.2
Advanced gBRCA-mutated Ovarian Cancer Treated with 3 or More Prior Lines of
Chemotherapy
16 HOW
SUPPLIED/STORAGE AND HANDLING
16.1
How Supplied 16.2 Storage
17 PATIENT
COUNSELING INFORMATION *Sections or subsections omitted from the full
prescribing information are not listed. 1 Reference ID: 4140621
FULL
PRESCRIBING INFORMATION
1
INDICATIONS AND USAGE
1.1
Maintenance Treatment of Recurrent Ovarian Cancer Lynparza is indicated for the
maintenance treatment of adult patients with recurrent epithelial ovarian,
fallopian tube or primary peritoneal cancer, who are in a complete or partial
response to platinum-based chemotherapy.
1.2
Advanced gBRCA-mutated Ovarian Cancer After 3 or More Lines of Chemotherapy
Lynparza is indicated for the treatment of adult patients with deleterious or
suspected deleterious germline BRCA-mutated (gBRCAm) advanced ovarian cancer
who have been treated with three or more prior lines of chemotherapy. Select
patients for therapy based on an FDA-approved companion diagnostic for
Lynparza.
2 DOSAGE
AND ADMINISTRATION
2.1
Important Administration Instructions Lynparza is also available as a 50 mg
capsule. DO NOT substitute Lynparza tablets (100 mg and 150 mg) with Lynparza
capsules (50 mg) on a milligram-to-milligram basis due to differences in the
dosing and bioavailability of each formulation [see Clinical Pharmacology
(12.3)]. Refer to the full prescribing information for Lynparza capsules for
specific capsule dosing.
2.2
Recommended Dosing The recommended dose of Lynparza is 300 mg (two 150 mg
tablets) taken orally twice daily, with or without food, for a total daily dose
of 600 mg. The 100 mg tablet is available for dose reduction. Continue
treatment until disease progression or unacceptable toxicity. If a patient
misses a dose of Lynparza, instruct patient to take their next dose at its scheduled
time. Swallow tablets whole. Do not chew, crush, dissolve, or divide tablet
[see How Supplied/Storage and Handling (16.2)].
2.3
Patient Selection for gBRCA-mutated Advanced Ovarian Cancer Select patients for
the treatment of advanced ovarian cancer with Lynparza based on the presence of
deleterious or suspected deleterious BRCA-mutations [see Indications and Usage
(1.2) and Clinical Studies (14.2)]. Information on FDA-approved tests for the
detection of BRCA-mutations is available at http://www.fda.gov/companiondiagnostics.
2.4 Dose
Adjustments for Adverse Reactions
To manage
adverse reactions, consider interruption of treatment or dose reduction. 2
Reference ID: 4140621 The recommended dose reduction is to 250 mg (one 150 mg
tablet and one 100 mg tablet) taken twice daily, for a total daily dose of 500
mg. If a further dose reduction is required, then reduce to 200 mg (two 100 mg
tablets) taken twice daily, for a total daily dose of 400 mg.
2.5 Dose
Modifications for Use with CYP3A Inhibitors Avoid concomitant use of strong or
moderate CYP3A inhibitors and consider alternative agents with less CYP3A
inhibition. If a strong CYP3A inhibitor must be co-administered, reduce the
Lynparza dose to 100 mg (one 100 mg tablet) taken twice daily (equivalent to a
total daily dose of 200 mg). If a moderate CYP3A inhibitor must be
co-administered, reduce the Lynparza dose to 150 mg (one 150 mg tablet) taken
twice daily (equivalent to a total daily dose of 300 mg) [see Drug Interactions
(7.2) and Clinical Pharmacology (12.3)].
2.6 Dose
Modifications for Patients with Renal Impairment Patients with mild renal
impairment (CLcr 51-80 mL/min as estimated by Cockcroft-Gault equation) do not
require an adjustment in Lynparza dosing. In patients with moderate renal
impairment (CLcr 31-50 ml/min) the recommended dose reduction is to 200 mg (two
100 mg tablets) twice daily, for a total daily dose of 400 mg. The
pharmacokinetics of Lynparza have not been evaluated in patients with severe
renal impairment or end-stage renal disease (CLcr ≤30 mL/min) [see Use in Specific Populations (8.7) and Clinical
Pharmacology (12.3)].
3 DOSAGE FORMS AND STRENGTHS
Tablets: • 150 mg: green to green/grey, oval, bi-convex, film-coated, with
debossment ‘OP150’ on one side
and plain on the reverse side. •
100 mg:
yellow to dark yellow, oval, bi-convex, film-coated, with debossment ‘OP100’ on one side and plain on the reverse
side.
4 CONTRAINDICATIONS
None.
5 WARNINGS AND PRECAUTIONS
5.1
Myelodysplastic Syndrome/Acute Myeloid Leukemia Overall, the incidence of
Myelodysplastic Syndrome/Acute Myeloid Leukemia (MDS/AML) in patients treated
with Lynparza monotherapy in clinical trials, including long-term follow up,
was <1.5% (21/ 1680) and the majority of events had a fatal outcome. Of
these, 19/21 patients had a documented BRCA mutation, 1 patient had gBRCA
wildtype and in 1 patient the BRCA mutation status was unknown. Additional
cases of MDS/AML have been documented in patients treated with Lynparza in
combination studies. The duration of therapy with Lynparza in patients who
developed secondary MDS/cancer-therapy related AML varied from < 6 months to
> 2 years. All of these patients had received previous 3 Reference ID:
4140621 chemotherapy with platinum agents and/or other DNA damaging agents
including radiotherapy. 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 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. If MDS/AML is
confirmed, discontinue Lynparza.
5.2
Pneumonitis Pneumonitis, including fatal cases, occurred in < 1% of patients
treated with Lynparza. 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.
5.3
Embryo-Fetal Toxicity
Lynparza
can cause fetal harm when administered to a pregnant woman based on its
mechanism of action and findings in animals. In an animal reproduction study,
administration of olaparib to pregnant rats during the period of organogenesis
caused teratogenicity and embryo-fetal toxicity at exposures below those in patients
receiving the recommended human dose of 300 mg twice daily. Apprise pregnant
women of the potential hazard to a fetus. Advise females of reproductive
potential to use effective contraception during treatment and for 6 months
following the last dose of Lynparza [see Use in Specific Populations (8.1, 8.3)
and Clinical Pharmacology (12.1)].
6 ADVERSE REACTIONS
The
following adverse reactions are discussed elsewhere in the labeling: •
Myelodysplastic
Syndrome/Acute Myeloid Leukemia [see Warnings and Precautions (5.1)] • Pneumonitis [see Warnings and Precautions (5.2)]
6.1 Clinical Trial Experience
Because
clinical trials are conducted under widely varying conditions, adverse reaction
rates observed in the clinical trials of a drug cannot be directly compared to
rates in the clinical trials of another drug and may not reflect the rates
observed in practice. Adverse reactions presented below were reported from
clinical trials in 782 patients with ovarian cancer (555 received Lynparza, 227
received placebo). 4 Reference ID: 4140621
Maintenance
Treatment of Recurrent Ovarian Cancer SOLO-2
The safety
of Lynparza for the maintenance treatment of patients with platinum sensitive
gBRCAm ovarian cancer was investigated in SOLO-2. This study was a placebo-controlled,
double-blind study in which 294 patients received either Lynparza 300 mg (2 x
150 mg tablets) twice daily (n=195) or placebo tablets twice daily (n=99) until
disease progression or unacceptable toxicity.
The median
duration of study treatment was 19.4 months for patients who received Lynparza
and 5.6 months for patients who received placebo. Dose interruptions due to an
adverse reaction of any grade occurred in 45% of patients receiving Lynparza
and 18% of those receiving placebo; dose reductions due to an adverse reaction
occurred in 27% of Lynparza patients and 3% of placebo patients.
The most
frequent adverse reactions leading to dose interruption or reduction of
Lynparza were anemia (22%), neutropenia (9%), and fatigue/asthenia (8%). Discontinuation
occurred in 11% of Lynparza patients and 2% in placebo patients. Table 1
summarizes the adverse reactions that occurred in at least 20% of patients who
received Lynparza in SOLO-2.
Table 2
presents the laboratory abnormalities that occurred in at least 25 % of
patients who received Lynparza in SOLO-2. 5 Reference ID: 4140621 Table 1
Adverse Reactionsa in SOLO-2 (≥20% of
Patients who Received Lynparza) Adverse Reactions Lynparza tablets n=195
Placebo n=99 Grades 1-4 % Grades 3-4 % Grades 1-4 % Grades 3-4 % Blood and
lymphatic disorders Anemiab 44 20 9 2 Gastrointestinal disorders Nausea 76 3 33
0 Vomiting 37 3 19 1 Diarrhea 33 2 22 0 Stomatitisc 20 1 16 0 Infections and
Infestations Nasopharyngitis/ URI/ sinusitis/ rhinitis/ influenza 36 0 29 0
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 disorder Arthralgia/myalgia 30 0 28 0
Nervous system disorders Dysgeusia 27 0 7 0 Headache 26 1 14 0 a Graded
according to the National Cancer Institute Common Terminology Criteria for
Adverse Events (NCI CTCAE ), version 4.0. b Represents grouped term consisting
of anemia, hematocrit decreased, hemoglobin decreased, iron deficiency, mean
cell volume increased and red blood cell count decreased. c 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.
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 edema. 6 Reference ID: 4140621
Table
2 Laboratory Abnormalities Reported in ≥25% of
Patients in SOLO-2 Laboratory Parametera Lynparza tablets n=195 Placebo n=99
Grades 1-4 % Grades 3-4 % Grades 1-4 % Grades 3-4 % Increase in mean
corpuscular volumeb 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 a Patients were allowed to enter clinical studies with
laboratory values of CTCAE Grade 1. b Represents the proportion of subjects
whose mean corpuscular volume was > upper limit of normal (ULN).
Study
19
The safety
of Lynparza capsules as maintenance monotherapy was also evaluated in patients
with platinum sensitive ovarian cancer who had received 2 or more previous
platinum containing regimens in Study 19, a randomized, placebo-controlled,
double-blind, multi-center study in which 264 patients received Lynparza 400 mg
twice daily (n=136) or placebo (n=128). At the time of final analysis, the
median duration of exposure was 8.7 months in patients who received Lynparza
and 4.6 months in patients who received placebo. Adverse reactions led to dose
interruptions in 35% of those receiving Lynparza and 10% of those receiving placebo;
dose reductions in 26% of Lynparza and 4% of placebo; and discontinuation in 6%
of Lynparza and 2% in placebo. Table 3 summarizes the adverse reactions that
occurred in at least 20% of patients who received Lynparza in Study 19. Table 4
presents the laboratory abnormalities that occurred in at least 25% of patients
from Study 19. 7 Reference ID: 4140621
Table
3 Adverse Reactionsa in Study 19 (≥20% of
Patients who Received Lynparza)
Adverse
Reactions Lynparza capsules n=136 Placebo n=128 Grades 1-4 % Grades 3-4 %
Grades 1-4 % Grades 3-4 % Blood and lymphatic disorders Anemiab 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 a Graded according to NCI
CTCAE 4.0. b 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 edema. Table 4
Laboratory Abnormalities Reported in ≥25% of
Patients in Study 19 Laboratory Parametera Lynparza capsules n=136 Placebo
n=129 Grades 1-4 % Grades 3-4 % Grades 1-4 % Grades 3-4 % Decrease in
hemoglobin 82 8 58 1 Increase in mean corpuscular volumeb 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 a Patients were allowed to enter clinical studies with
laboratory values of CTCAE Grade 1. b Represents the proportion of subjects
whose mean corpuscular volume was > ULN. Treatment of Advanced gBRCAm
Ovarian Cancer After 3 or More Lines of Chemotherapy Pooled data Treatment with
Lynparza (capsule formulation) as monotherapy was studied in 223 patients
(pooled from 6 studies) with gBRCAm advanced ovarian cancer who had received 3
or more prior lines of 8 Reference ID: 4140621 chemotherapy.
Adverse
reactions led to dose interruption in 40% of patients, dose reduction in 4% of
patients, and discontinuation in 7% of patients. There were 8 (4%) patients
with adverse reactions leading to death, two were attributed to acute leukemia,
and one each was attributed to COPD, cerebrovascular accident, intestinal
perforation, pulmonary embolism, sepsis, and suture rupture. The median
exposure to Lynparza capsules in these patients was 5.2 months. Table 5
presents adverse reactions reported in ≥20% of
patients and Table 6 presents laboratory abnormalities that occurred in at
least 25% of patients from the pooled studies.
Table 5
Adverse Reactions Reported in Pooled Data (≥20% of Patients who Received Lynparza)
Adverse
Reactions 3 or more lines of prior Chemotherapy Grades 1-4 n=223 % Grades 3-4
n=223 % Blood and Lymphatic disorders Anemia 34 18 Gastrointestinal disorders
Decreased appetite 22 1 Nausea 64 3 Vomiting 43 4 Diarrhea 31 1 Dyspepsia 25 0
General disorders Fatigue/asthenia 66 8 Infections and infestations
Nasopharyngitis/URI 26 0 Musculoskeletal and Connective Tissue disorders
Arthralgia/musculoskeletal pain 21 0 Myalgia 22 0 9 Reference ID: 4140621
Table 6
Laboratory Abnormalities Reported ≥25% of
Patients in Pooled Data Laboratory Parametera 3 or more lines of prior
Chemotherapy Grades 1-4 n=223 (%) Grades 3-4 n=223 (%) Decrease in hemoglobin
90 15 Decrease in absolute neutrophil count 25 7 Decrease in platelets 30 3
Decrease in lymphocytes 56 17 Mean corpuscular volume elevation 57 - Increase
in creatinine 30 2 a Patients were allowed to enter clinical studies with
laboratory values of CTCAE Grade 1. The following adverse reactions and
laboratory abnormalities have been identified in ≥10 to
<20% of the 223 patients receiving Lynparza and not included in the table:
cough, constipation, dysgeusia, peripheral edema, back pain, dizziness,
headache, urinary tract infection, dyspnea, and rash. The following adverse
reactions and laboratory abnormalities have been identified in ≥1 to <10% of the 223 patients receiving Lynparza and not included
in the table: leukopenia, stomatitis, peripheral neuropathy, pyrexia,
hypomagnesemia, and venous thrombosis (including pulmonary embolism). 6.2
Postmarketing Experience The following adverse reactions have been identified
during post-approval use of Lynparza capsules. Because these reactions are
reported voluntarily from a population of uncertain size, it is not always
possible to reliably estimate their frequency or establish a causal
relationship to drug exposure. Immune System Disorders: Hypersensitivity
(rash/dermatitis).
7 DRUG INTERACTIONS
7.1
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.
7.2 Drugs
That May Increase Olaparib Plasma Concentrations
Olaparib
is primarily metabolized by CYP3A. In patients (N=57), co-administration of
itraconazole, a strong CYP3A inhibitor, increased AUC of olaparib by 170%. A
moderate CYP3A inhibitor, fluconazole, is predicted to increase the AUC of
olaparib by 121%. Avoid concomitant use of strong CYP3A inhibitors such as
itraconazole, telithromycin, clarithromycin, ketoconazole, voriconazole, nefazodone,
posaconazole, ritonavir, lopinavir/ritonavir, indinavir, saquinavir,
nelfinavir, boceprevir, and telaprevir. Avoid use of moderate CYPA inhibitors
such as amprenavir, aprepitant, atazanavir, ciprofloxacin, crizotinib,
darunavir/ritonavir, diltiazem, erythromycin, fluconazole, fosamprenavir,
imatinib, and verapamil. If the strong or moderate CYP3A inhibitors must be
co-administered, reduce the dose of Lynparza [see Dosage and Administration
(2.5)]. 10 Reference ID: 4140621 Avoid grapefruit, grapefruit juice, Seville
oranges, and Seville orange juice during Lynparza treatment since they are
CYP3A inhibitors [see Dosage and Administration (2.5) and Clinical Pharmacology
(12.3)].
7.3 Drugs
That May Decrease Olaparib Plasma Concentrations
In
patients (N=22), co-administration of rifampicin, a strong CYP3A inducer,
decreased AUC of olaparib by 87%. A moderate CYP3A inducer, efavirenz, is
predicted to decrease the AUC of olaparib by approximately 60%. Avoid
concomitant use of strong CYP3A inducers such as phenytoin, rifampicin,
carbamazepine, and St. John’s Wort.
Avoid concomitant use of moderate CYP3A4 inducers such as bosentan, efavirenz,
etravirine, modafinil, and nafcillin. If a moderate CYP3A inducer cannot be
avoided, there is a potential for decreased efficacy of Lynparza [see Clinical
Pharmacology (12.3)].
8 USE IN
SPECIFIC POPULATIONS
8.1
Pregnancy Risk Summary Based on findings in animals and its mechanism of action
[see Clinical Pharmacology (12.1)], Lynparza can cause fetal harm when
administered to a pregnant woman. There are no available data on Lynparza use
in pregnant women to inform the drug associated risk. In an animal reproduction
study, the administration of olaparib to pregnant rats during the period of
organogenesis caused teratogenicity and embryo-fetal toxicity at exposures
below those in patients receiving the recommended human dose of 300 mg twice
daily [see Data]. Apprise pregnant women of the potential hazard to the fetus
and the potential risk for loss of the pregnancy. The estimated background risk
of major birth defects and miscarriage for the indicated population is unknown.
The estimated background risk in the U.S. general population of major birth
defects is 2-4%; and the risk for spontaneous abortion is approximately 15-20%
in clinically-recognized pregnancies. Data Animal Data In a fertility and early
embryonic development study in female rats, olaparib was administered orally
for 14 days before mating through to day 6 of pregnancy, which resulted in
increased post-implantation loss at a dose level of 15 mg/kg/day (with maternal
systemic exposures approximately 7% of the human exposure (AUC0-24h) at the
recommended dose). In an embryo-fetal development study, pregnant rats received
oral doses of 0.05 and 0.5 mg/kg/day olaparib during the period of
organogenesis. A dose of 0.5 mg/kg/day (with maternal systemic exposures
approximately 0.18% of human exposure (AUC0-24h) at the recommended dose)
caused embryo-fetal toxicities including increased post-implantation loss and
major malformations of the eyes (anophthalmia, microphthalmia), vertebrae/ribs
(extra rib or ossification center; fused or absent neural arches, ribs, and
sternebrae), skull (fused exoccipital) and diaphragm (hernia). Additional
abnormalities or variants 11 Reference ID: 4140621 included incomplete or
absent ossification (vertebrae/sternebrae, ribs, limbs) and other findings in
the vertebrae/sternebrae, pelvic girdle, lung, thymus, liver, ureter and
umbilical artery. Some findings noted above in the eyes, ribs and ureter were
observed at a dose of 0.05 mg/kg/day olaparib at lower incidence.
8.2
Lactation Risk Summary
No data
are available regarding the presence of olaparib in human milk, or on its
effects on the breastfed infant or on milk production. Because of the potential
for serious adverse reactions in the breastfed infants from Lynparza, advise a
lactating woman not to breastfeed during treatment with Lynparza and for one
month after receiving the last dose.
8.3
Females and Males of Reproductive Potential
Pregnancy
Testing Pregnancy testing is recommended for females of reproductive potential
prior to initiating treatment with Lynparza. Contraception Females Lynparza can
cause fetal harm when administered to a pregnant woman [see Use in Specific Populations
(8.1)]. Advise females of reproductive potential to use effective contraception
during treatment with Lynparza and for at least 6 months following the last
dose.
8.4
Pediatric Use
The
safety and efficacy of Lynparza have not been established in pediatric
patients.
8.5
Geriatric Use
In
clinical studies of Lynparza enrolling 482 patients with advanced solid tumors
who received Lynparza tablets 300 mg twice daily as monotherapy, 135 (28%)
patients were aged ≥65 years. There appeared to be no major difference in
the safety profile of patients treated with olaparib aged <65 years versus ≥65 years, nor within the age categories of 65 to 74 years, 75 to 84
years. No patients were aged ≥85 years.
8.6
Hepatic Impairment
No
adjustment to the starting dose is required in patients with mild hepatic
impairment. A 15% increase in mean exposure (AUC) was observed in patients with
mild hepatic impairment (based on Child-Pugh classification A) compared to
patients with normal hepatic function. There are no data in patients with
moderate or severe hepatic impairment [see Clinical Pharmacology (12.3)].
8.7 Renal
Impairment
No
adjustment to the starting dose is required in patients with mild renal
impairment, but patients should be monitored closely for toxicity. A 24%
increase in mean exposure (AUC) was observed in patients with mild renal
impairment (CLcr = 51-80 mL/min) compared to patients with normal renal
function (CLcr 12 Reference ID: 4140621 >80 mL/min). A 44% increase in AUC
was observed in patients with moderate renal impairment (CLcr 31-50 mL/min)
compared to patients with normal renal function (CLcr >80 mL/min). For
patients with moderate renal impairment, reduce the dose of Lynparza to 200 mg
twice daily [see Dosage and Administration (2.6)]. There are no data in
patients with severe renal impairment or end-stage disease (CLcr ≤30 mL/min) [see Clinical Pharmacology (12.3)].
10 OVERDOSAGE
There is
no specific treatment in the event of Lynparza overdose, and symptoms of
overdose are not established. In the event of an overdose, physicians should
follow general supportive measures and should treat the patient
symptomatically.
11 DESCRIPTION
Olaparib
is an inhibitor of the mammalian polyadenosine 5’-diphosphoribose polymerase (PARP) enzyme. The chemical name is
4-[(3-{[4-(cyclopropylcarbonyl)piperazin-1-yl]carbonyl}-4
fluorophenyl)methyl]phthalazin-1(2H)-one and it has the following chemical
structure: The empirical molecular formula for Lynparza is C24H23FN4O3 and the
relative molecular mass is 434.46. Olaparib is a crystalline solid, is
non-chiral and shows pH-independent low solubility across the physiological pH
range.
Lynparza
tablets for oral administration contain 100 mg or 150 mg of olaparib.
Inactive
ingredients in the tablet core are copovidone, mannitol, colloidal silicon
dioxide and sodium stearyl fumarate. The tablet coating consists of
hypromellose, polyethylene glycol 400, titanium dioxide, ferric oxide yellow
and ferrosoferric oxide (150 mg tablet only). 13 Reference ID: 4140621
12 CLINICAL PHARMACOLOGY
12.1 Mechanism of Action
Lynparza
is an inhibitor of poly (ADP-ribose) polymerase (PARP) enzymes, including
PARP1, PARP2, and PARP3. PARP enzymes are involved in normal cellular
functions, such as DNA transcription and DNA repair.
Olaparib
has been shown to inhibit growth of select tumor cell lines in vitro and
decrease tumor growth in mouse xenograft models of human cancer, both as
monotherapy or following platinumbased chemotherapy. Increased cytotoxicity and
anti-tumor activity following treatment with olaparib were noted in cell lines
and mouse tumor models with deficiencies in BRCA and non-BRCA proteins involved
in the homologous recombination repair (HRR) of DNA damage and correlated with
platinum response.
In
vitro studies have shown that olaparib-induced cytotoxicity may involve
inhibition of PARP enzymatic activity and increased formation of PARP-DNA
complexes, resulting in DNA damage and cancer cell death.
12.2 Pharmacodynamics
Cardiac
Electrophysiology
The effect
of olaparib on cardiac repolarization was assessed in 119 patients following a
single dose of 300 mg and in 109 patients following multiple dosing of 300 mg
twice daily. No clinically relevant effect of olaparib on QT interval was
observed.
12.3 Pharmacokinetics
Lynparza
is available as a tablet and capsule formulation.
The oral
bioavailability of the tablet formulation is higher than the capsule
formulation. Population pharmacokinetic analyses have shown that the steady
state exposure (AUC) following 300 mg tablet twice daily was 77% higher
compared to that following 400 mg capsule twice daily. The olaparib geometric
mean AUC and Cmax following a single 300 mg tablet dose were 42.0 μg*h/mL (n=204) and 5.8 μg/mL (n=204),
respectively, and the steady state geometric mean AUC and Cmax following 300 mg
tablet twice daily were 49.0 μg*h/mL (n=227) and 7.7 μg/mL (n=227), respectively. Olaparib showed time-dependent PK that
the steady state clearance decreased by 15% after multiple dosing. Absorption
Following oral administration of olaparib, absorption is rapid with median peak
plasma concentrations typically achieved 1.5 hours after dosing. An AUC mean
accumulation ratio of 1.8 is observed at steady state following multiple dosing
of 300 mg tablets twice daily. Systemic exposure (single dose AUC) to olaparib
increases approximately proportionally with doses over the dose range of 25 mg
to 450 mg, Cmax increased slightly less than proportionally for the same dose
range. Co-administration of a high fat meal with olaparib slowed the rate (tmax
delayed by 2.5 hours) of absorption, but did not significantly alter the extent
of olaparib absorption (mean AUC increased by approximately 8%).
14
Reference ID: 4140621
Distribution
Olaparib had a mean (± standard deviation) apparent
volume of distribution of 158 ± 136 L after a single
300 mg dose of olaparib. The in vitro protein binding of olaparib is
approximately 82%. Metabolism In vitro, CYP3A4/5 were shown to be the enzymes
primarily responsible for the metabolism of olaparib. Following oral dosing of
14C-olaparib to female patients, unchanged olaparib accounted for the majority
of the circulating radioactivity in plasma (70%). It was extensively
metabolized with unchanged drug accounting for 15% and 6% of radioactivity in
urine and feces, respectively. The majority of the metabolism is attributable
to oxidation reactions with a number of the components produced undergoing
subsequent glucuronide or sulfate conjugation. Excretion A mean (± standard deviation) terminal plasma half-life of 14.9 ± 8.2 hours and apparent plasma clearance of 7.4 ± 3.9 L/h were observed after a single 300 mg dose of olaparib.
Following a single dose of 14C-olaparib, 86% of the dosed radioactivity was
recovered within a 7-day collection period, 44% via the urine and 42% via the
feces. The majority of the material was excreted as metabolites. Drug
Interactions Based on the data from a drug-interaction trial (N=57), the AUC
and Cmax of olaparib increased by 170% and 42%, respectively, when olaparib was
administered in combination with itraconazole, a strong CYP3A inhibitor.
Simulations
suggested that a moderate CYP3A inhibitor (fluconazole) may increase the AUC
and Cmax of olaparib by 121% and 14%, respectively. Based on the data from a
drug-interaction trial (N=22), the AUC and Cmax of olaparib decreased by 87%
and 71%, respectively, when olaparib was administered in combination with
rifampicin, a strong CYP3A inducer. Simulations suggested that a moderate CYP3A
inducer (efavirenz) may decrease the AUC and Cmax of olaparib by approximately
60% and 31%, respectively. In vitro studies have shown that olaparib is both an
inhibitor and inducer of CYP3A and an inducer of CYP2B6. Olaprib is predicted
to be a weak CYP3A inhibitor in humans. In vitro studies also indicated that
olaparib is an inhibitor of UGT1A1, BCRP, OATP1B1, OCT1, OCT2, OAT3, MATE1 and
MATE2K.
The
clinical relevance of these findings is unknown. In vitro, olaparib is a
substrate of, and inhibits, the efflux transporter P-gp. The potential for
olaparib to induce P-gp has not been evaluated. Pharmacokinetics in Specific
Populations Hepatic Impairment In a hepatic impairment trial, the mean AUC
increased by 15% and the mean Cmax by 13% when olaparib was dosed in patients
with mild hepatic impairment (Child-Pugh classification A; N=9) compared with
15 Reference ID: 4140621 patients with normal hepatic function (N=13).
Mild
hepatic impairment had no effect on the protein binding of olaparib and
therefore total plasma exposure was representative of free drug. There are no
data in patients with moderate or severe hepatic impairment. Renal Impairment
In a renal impairment trial, the mean AUC increased by 24% and Cmax by 15%,
when olaparib was dosed in patients with mild renal impairment (CLcr = 51-80
mL/min defined by the Cockcroft-Gault equation; N=13) and by 44% and 26%,
respectively, when olaparib was dosed in patients with moderate renal
impairment (CLcr = 31-50 mL/min; N=13), compared to those with normal renal
function (CLcr ≥81 mL/min; N=12). There was no evidence of a
relationship between the extent of plasma protein binding of olaparib and
creatinine clearance.
There are
no data in patients with severe renal impairment or end-stage renal disease
(CLcr ≤ 30 mL/min).
13 NONCLINICAL TOXICOLOGY
13.1
Carcinogenesis, Mutagenesis, Impairment of Fertility
Carcinogenicity
studies have not been conducted with olaparib. Olaparib was clastogenic in an
in vitro chromosomal aberration assay in mammalian Chinese hamster ovary (CHO)
cells and in an in vivo rat bone marrow micronucleus assay. This clastogenicity
is consistent with genomic instability resulting from the primary pharmacology
of olaparib and indicates potential for genotoxicity in humans.
Olaparib
was not mutagenic in a bacterial reverse mutation (Ames) test.
In a
fertility study, female rats received oral olaparib at doses of 0.05, 0.5, and
15 mg/kg/day for at least 14 days before mating through the first week of
pregnancy. There were no adverse effects on mating and fertility rates at doses
up to 15 mg/kg/day (maternal systemic exposures approximately 7% of the human
exposure (AUC0-24h) at the recommended dose).
In a
male fertility study, olaparib had no effect on mating and fertility in rats at
oral doses up to 40 mg/kg/day following at least 70 days of olaparib treatment
(with systemic exposures of approximately 5% of the human exposure (AUC0-24h)
at the recommended dose).
14 CLINICAL STUDIES
14.1
Maintenance Treatment of Recurrent Ovarian Cancer The efficacy of Lynparza was
investigated in two randomized, placebo-controlled, double-blind, multicenter
studies in patients with recurrent ovarian cancers who were in response to
platinum-based therapy.
SOLO-2
SOLO-2 (NCT01874353) was a double-blind, placebo-controlled trial in which
patients (N=295) with germline BRCA-mutated (gBRCAm) ovarian, fallopian tube,
or primary peritoneal cancer were randomized (2:1) to receive Lynparza tablets
300 mg orally twice daily or placebo until unacceptable toxicity or progressive
disease. Randomization was stratified by response to last platinum chemotherapy
(complete versus partial) and time to disease progression in the penultimate
platinum-based chemotherapy 16 Reference ID: 4140621 prior to enrollment (6-12
months versus > 12 months).
All patients
had received at least two prior platinum-containing regimens and were in
response (complete or partial) to their most recent platinumbased regimen. All
patients had a deleterious or suspected deleterious germline BRCA-mutation as
detected either by a local test (n= 236) or central Myriad CLIA test (n=59),
subsequently confirmed by BRAC Analysis CDx (n= 286).
The major
efficacy outcome was investigator-assessed progression-free survival (PFS)
evaluated according to Response Evaluation Criteria in Solid Tumors (RECIST),
version 1.1. Additional endpoints included overall survival (OS). The median
age of patients treated with Lynparza was 56 years (range: 28 to 83) and 56
years (range: 39 to 78) among patients treated with placebo. ECOG performance
score was 0 in 83% of patients receiving Lynparza and 78% of patients receiving
placebo. Of all patients, 89% were White, 17% were enrolled in the U.S. or
Canada, 47% were in complete response to their most recent platinum-based
regimen, and 40% had a progression-free interval of 6-12 months since their
penultimate platinum regimen. Prior bevacizumab therapy was reported for 17% of
those treated with Lynparza and 20% of those receiving placebo.
Approximately
44% of patients on the Lynparza arm and 37% on placebo had received three or
more lines of platinum-based treatment. SOLO-2 demonstrated a statistically
significant improvement in investigator-assessed PFS in patients randomized to
Lynparza as compared with placebo (Table 7 and Figure 1). Results from a blinded
independent review were consistent.
At the
time of the analysis of PFS, overall survival (OS) data were not mature with
24% of events.
Table 7
Efficacy Results – SOLO-2 (Investigator Assessment) Lynparza tablets
(n=196) Placebo (n=99) Progression-Free Survival Number of events (%) 107
(54.6%) 80 (80.8%) Median, months 19.1 5.5 Hazard ratioa (95% CI) 0.30 (0.22,
0.41) p-valueb <0.0001 a Hazard ratio from the stratified proportional
hazards model, stratified by response to last platinum chemotherapy (complete
versus partial) and time to disease progression in the penultimate
platinum-based chemotherapy prior to enrollment. b The p-value is derived from
a stratified log-rank test. 17 Reference ID: 4140621 Figure 1: Kaplan-Meier
Curves of Investigator-Assessed Progression-Free Survival – SOLO-2 Study 19 Study 19 (NCT00753545) was a double-blind,
placebo-controlled trial in which patients (N=265) with platinum-sensitive
ovarian cancer who had received 2 or more previous platinum-containing regimens
were randomized (1:1) to receive Lynparza capsules 400 mg orally twice daily or
placebo until unacceptable toxicity or progressive disease. Randomization was
stratified by response to last platinum chemotherapy (CR versus PR), time to
disease progression in the penultimate platinum-based chemotherapy (6-12 months
versus > 12 months), and descent (Jewish versus non-Jewish). The major
efficacy outcome measure of the study was investigator-assessed PFS evaluated
according to RECIST, version 1.0. The median age of patients treated with
Lynparza (n=136) was 58 years (range: 21 to 89) and 59 years (range 33 to 84)
among patients treated with placebo (n=129).
ECOG
performance status was 0 in 81% of patients receiving Lynparza and 74% of
patients receiving placebo. Of all patients, 97% were White, 19% were enrolled
in the US or Canada, 45% were in complete response following their most recent
platinum chemotherapy regimen, and 40% had a progression-free interval of 6-12
months since their penultimate platinum.
Prior bevacizumab
therapy was reported for 13% of patients receiving Lynparza and 16% of patients
receiving placebo. A retrospective analysis for germline BRCA mutation status,
some performed 18 Reference ID: 4140621 using the Myriad test, indicated that
36% (n=96) of patients from the ITT population had deleterious gBRCA mutation,
including 39% (n=53) of patients on Lynparza and 33% (n=43) of patients on
placebo. Study 19 demonstrated a statistically significant improvement in
investigator-assessed PFS in patients treated with Lynparza versus placebo
(Table 8 and Figure 2).
Table 8
Efficacy Results - Study 19 (Investigator Assessment) Lynparza capsules (n=136)
Placebo (n=129) Progression-Free Survival Number of events (%) 60 (44%) 94
(73%) Median, months 8.4 4.8 Hazard ratioa (95% CI) 0.35 (0.25, 0.49) p-valueb
<0.0001 Overall Survivalc Number of events (%) 98 (72%) 112 (87%) Median,
months 29.8 27.8 Hazard ratio (95% CI) 0.73 (0.55, 0.95) a Hazard ratio is
derived from a stratified proportional hazards model, stratified by response to
last platinum chemotherapy, time to disease progression in the penultimate
platinum-based chemotherapy and Jewish and nonJewish descent. b The p-value is
derived from a stratified log-rank test. c Without adjusting for multiple analyses.
19 Reference ID: 4140621
Figure 2:
Kaplan-Meier Curves of Investigator-Assessed Progression-Free Survival –
Study 19
14.2 Advanced gBRCA-mutated Ovarian Cancer Treated with 3 or More Prior Lines
of Chemotherapy The efficacy of Lynparza was also investigated in a single-arm
study of patients with deleterious or suspected deleterious gBRCAm advanced
cancers. A total of 137 patients with measurable, advanced gBRCAm ovarian
cancer treated with three or more prior lines of chemotherapy were enrolled.
All patients received Lynparza capsules at a dose of 400 mg twice daily as
monotherapy until disease progression or intolerable toxicity. Objective
response rate (ORR) and duration of response (DOR) were assessed by the
investigator according to RECIST, version 1.0. The median age of the patients
was 58 years, the majority were White (94%) and 93% had an ECOG PS of 0 or 1.
Deleterious or suspected deleterious gBRCAm status was verified retrospectively
in 97% (59/61) of the patients for whom blood samples were available by the
BRAC Analysis CDxTM. Efficacy results are summarized in Table 9. 20 Reference
ID: 4140621
Table 9
Overall Response and Duration of Response in Patients with gBRCA-mutated
Advanced Ovarian Cancer Who Received 3 or More Lines of Chemotherapy n=137
Objective Response Rate (95% CI) 34% (26, 42) Complete Response 2% Partial
Response 32% Median DOR in months (95% CI) 7.9 (5.6, 9.6) 16 HOW
SUPPLIED/STORAGE AND HANDLING 16.1 How Supplied Lynparza is available as 150 mg
and 100 mg tablets. • 150 mg tablets: green to
green/grey, oval, bi-convex film-coated tablet, with debossment ‘OP150’ on one side and plain on the reverse,
are available in: o Bottles of 60 tablets (NDC 0310-0679-60) and o Bottles of
120 tablets (NDC 0310-0679-12). • 100 mg tablets:
yellow to dark yellow, oval, bi-convex, film-coated tablet, with debossment ‘OP100’on one side and plain on the reverse,
are available in: o Bottles of 60 tablets (NDC 0310-0668-60) and o Bottles of
120 tablets (NDC 0310-0668-12). 16.2 Storage Store at 20ºC to 25ºC (68°F to
77°F), excursions permitted to 15ºC to 30ºC (59ºF to
86ºF) [see USP Controlled Room Temperature]. Store in
original bottle to protect from moisture.
17 PATIENT COUNSELING INFORMATION
Advise the
patient to read the FDA-approved patient labeling (Medication Guide).
• Administration Instructions:
Inform
patients that Lynparza should be taken twice daily with or without food.
Instruct
patients that if they miss a dose of Lynparza, they should take their next
normal dose at the usual time. Swallow each tablet whole. Do not chew, crush,
dissolve, or divide tablet. Do not take more than 4 tablets daily [see Dosage
and Administration (2.2)].
Inform
patients to avoid grapefruit, grapefruit juice, Seville oranges, and Seville
orange juice while taking Lynparza [see Drug Interactions (7.3)].
Inform
patients not to substitute Lynparza tablets (100 mg and 150 mg) with Lynparza
capsules (50 mg) on a milligram-to-milligram basis due to differences in the
dosing and bioavailability of each formulation [see Dosage and Administration
(2.1)].
• MDS/AML: Advise patients to contact their healthcare provider if
they experience weakness, feeling tired, fever, weight loss, frequent
infections, bruising, bleeding easily, breathlessness, blood in urine 21
Reference ID: 4140621 or stool, and/or laboratory findings of low blood cell
counts, or a need for blood transfusions. This may be a sign of hematological
toxicity or a more serious uncommon bone marrow problem called ‘myelodysplastic syndrome’ (MDS) or ‘acute myeloid leukemia’ (AML) which have
been reported in patients treated with Lynparza [see Warnings and Precautions
(5.1)].
• Pneumonitis: Advise patients to contact their healthcare provider
if they experience any new or worsening respiratory symptoms including
shortness of breath, fever, cough, or wheezing [see Warnings and Precautions
(5.2)].
• Embryo-Fetal Toxicity: Advise females to inform their healthcare
provider if they are pregnant or become pregnant. Inform female patients of the
risk to a fetus and potential loss of the pregnancy [see Use in Specific
Populations (8.1)]. Advise females of reproductive potential to use effective
contraception during treatment with Lynparza and for 6 months after receiving
the last dose [see Warnings and Precautions (5.3) and Use in Specific
Populations (8.1, 8.3)].
• Lactation: Advise patients not to breastfeed while taking Lynparza
and for one month after receiving the last dose [see Use in Specific
Populations (8.2)].
• Nausea/Vomiting: Advise patients that mild or moderate nausea
and/or vomiting is very common in patients receiving Lynparza and that they
should contact their healthcare provider who will advise on available
antiemetic treatment options. 22 Reference ID: 4140621 Medication Guide
Lynparza (Lin-par-zah) (olaparib) tablets What is the most important
information I should know about Lynparza? Lynparza may cause serious side
effects, including: Bone marrow problems called Myelodysplastic Syndrome (MDS)
or Acute Myeloid Leukemia (AML). Some people who have ovarian cancer and who
have received previous treatment with chemotherapy, radiotherapy or certain
other medicines for their cancer have developed MDS or AML during treatment
with Lynparza. MDS or AML may lead to death. If you develop MDS or AML, your
healthcare provider will stop treatment with Lynparza. Symptoms of low blood
cell counts are common during treatment with Lynparza, but can be a sign of
serious bone marrow problems, including MDS or AML.
Symptoms
may include: • weakness • weight loss • fever • frequent infections • blood in urine or stool • shortness of
breath • feeling very tired • bruising or bleeding more easily Your healthcare provider will do blood tests
to check your blood cell counts: • before treatment
with Lynparza • every month during treatment with
Lynparza • weekly if you have low blood cell counts
that last a long time. Your healthcare provider may stop treatment with
Lynparza until your blood cell counts improve. Lung problems (pneumonitis).
Tell
your healthcare provider if you have any new or worsening symptoms of lung
problems, including shortness of breath, fever, cough, or wheezing. Your
healthcare provider may do a chest x-ray if you have any of these symptoms.
Your healthcare provider may temporarily stop treatment or completely stop
treatment if you develop pneumonitis. Pneumonitis may lead to death.
What is
Lynparza? Lynparza is a prescription medicine used for:
• the maintenance treatment of adults with ovarian cancer, fallopian
tube cancer, or primary peritoneal cancer, when the cancer has come back.
Lynparza is used after the cancer has responded to treatment with
platinum-based chemotherapy.
• the treatment of adults who have a certain type of abnormal
inherited BRCA gene advanced ovarian cancer, and have received treatment with 3
or more prior types of chemotherapy medicines. Your healthcare provider will
perform a test to make sure that Lynparza is right for you. It is not known if
Lynparza is safe and effective in children. What should I tell my healthcare
provider before taking Lynparza? Before you take Lynparza, tell your healthcare
provider about all of your medical conditions, including if you:
• have lung or breathing problems • have
liver problems • have kidney problems • are pregnant or plan to become pregnant. Lynparza can harm your
unborn baby and may cause loss of pregnancy (miscarriage). o If you are able to
become pregnant, your healthcare provider may do a pregnancy test before you
start treatment with Lynparza. o Females who are able to become pregnant should
use effective birth control (contraception) 23 Reference ID: 4140621 during
treatment with Lynparza and for 6 months after receiving the last dose of
Lynparza.
Talk
to your healthcare provider about birth control methods that may be right for
you.
Tell
your healthcare provider right away if you become pregnant. • are breastfeeding or plan to breastfeed. It is not known if
Lynparza passes into your breast milk. Do not breastfeed during treatment with
Lynparza and for 1 month after receiving the last dose of Lynparza.
Talk to
your healthcare provider about the best way to feed your baby during this
time.
Tell your
healthcare provider about all the medicines you take, including prescription
and over-thecounter medicines, vitamins, and herbal supplements.
Taking
Lynparza and certain other medicines may affect how Lynparza works and may
cause side effects. How should I take Lynparza? •
Take
Lynparza tablets exactly as your healthcare provider tells you.
• Your healthcare provider may temporarily stop treatment with
Lynparza or change your dose of Lynparza if you experience side effects.
• Lynparza comes as tablets and capsules. Lynparza tablets and
capsules are not the same. If your healthcare provider prescribes Lynparza
tablets for you, do not take Lynparza capsules. Do not take more than 4
Lynparza tablets in 1 day. If you have any questions about Lynparza, talk to
your healthcare provider or pharmacist. • Take Lynparza
by mouth 2 times a day.
• Each dose should be taken about 12 hours apart.
• Swallow Lynparza tablets whole. Do not chew, crush, dissolve, or
divide the tablets.
• Take Lynparza with or without food.
• If you miss a dose of Lynparza, take your next dose at your usual
scheduled time. Do not take an extra dose to make up for a missed dose.
• If you take too much Lynparza, call your healthcare provider or go
to the nearest hospital emergency room right away. What should I avoid while
taking Lynparza?
• Avoid grapefruit, grapefruit juice, Seville oranges and Seville
orange juice during treatment with Lynparza since they may increase the level
of Lynparza in your blood. What are the possible side effects of Lynparza?
Lynparza may cause serious side effects. See “What is
the most important information I should know about Lynparza?” The most common side effects of Lynparza are:
• nausea or vomiting. Tell your healthcare provider if you get nausea
or vomiting. Your healthcare provider may prescribe medicines to treat these
symptoms. • tiredness or weakness • diarrhea • headache • changes in kidney function blood test • low
number of platelets • changes in the way food tastes • loss of appetite • low number of red or
white blood cells • mouth sores • respiratory infections These are not all the possible side effects
of Lynparza. Call your healthcare provider for medical advice about side
effects. You may report side effects to FDA at 1-800-FDA-1088.
How should
I store Lynparza? • Store Lynparza at room temperature, between 68°F to 77°F (20°C to
25°C). • Store Lynparza in the
original bottle to protect it from moisture. Keep Lynparza and all medicines
out of the reach of children. 24 Reference ID: 4140621 General information
about the safe and effective use of Lynparza Medicines are sometimes prescribed
for purposes other than those listed in a Medication Guide. Do not use Lynparza
for a condition for which it was not prescribed. Do not give Lynparza to other
people, even if they have the same symptoms you have. It may harm them.
You can
ask your healthcare provider or pharmacist for information about Lynparza that
is written for health professionals.
What are
the ingredients in Lynparza?
Active
ingredient: olaparib
Inactive
ingredients: Tablet contains: copovidone, mannitol, colloidal silicon dioxide
and sodium stearyl fumarate Tablet coating contains: hypromellose, polyethylene
glycol 400, titanium dioxide, ferric oxide yellow and ferrosoferric oxide (150
mg tablet only) Lynparza is a registered trademark of the AstraZeneca group of
companies.
