DOSING & MANAGEMENT

Dosing and adverse reaction management strategies for LYNPARZA

LYNPARZA® (olaparib) dose interruption LYNPARZA® (olaparib) dose interruption

Consider dose interruption if a patient experiences an AR

See the complete Prescribing Information for detailed dose interruption instructions for select ARs

DOSE INTERRUPTION1

DOSE REDUCTION1

If an AR continues after restarting LYNPARZA following dose interruption, consider dose reduction

Initial reduction to 250 mg Initial reduction to 250 mg

INITIAL REDUCTION

Initial reduction to 250 mg (one 150 mg tablet and one 100 mg tablet) taken twice daily (total 500 mg daily)

Final reduction to 200 mg Final reduction to 200 mg

FINAL REDUCTION

Final reduction to 200 mg (two 100 mg tablets) taken twice daily (total 400 mg daily)

Dose modifications due to an AR from 4 pivotal trials1-6

~9 in 10 patients remained on LYNPARZA without AR-related discontinuation1
Dose modifications due to an adverse reaction from 4 pivotal trials – ovarian cancer
Dose modifications due to an adverse reaction from 4 pivotal trials – ovarian cancer

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~3 in 4 patients remained on the full recommended dose (total of 600 mg daily)1

ARs were usually managed by dose interruption or dose reduction, rather than by discontinuation.2

*In SOLO-1, SOLO-2, and Study 19, patients received LYNPARZA or placebo. In OlympiAD, patients received LYNPARZA or HCP's chemotherapy of choice (capecitabine, eribulin, or vinorelbine).1

In Study 19, patients received LYNPARZA 400-mg capsules twice daily (total of 800 mg daily) or placebo.1 As of September 2018, capsules are no longer commercially available in the United States.

In clinical studies of LYNPARZA, certain common ARs resolved over time5,7-9

Consider the median duration of common ARs seen with LYNPARZA when deciding on your management approach

MEDIAN DURATION OF ARs:
SOLO-1, SOLO-2, Study 19, OlympiAD

Median duration of adverse reactions in ovarian cancer
Median duration of adverse reactions in ovarian cancer

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  • Median time to first adverse reaction in Study 19: nausea, 3 days; vomiting, 49 days; fatigue/asthenia, 24 days; anemia, 28 days5
  • In SOLO-1, median time to first event of vomiting, nausea, anemia, and fatigue/asthenia was <3 months8
  • In SOLO-2, median duration of common adverse reactions (all grades) averaged 2.6 months.5 In Study 19, the average was 2.0 months9
  • Adverse reactions were graded in SOLO-1 and SOLO-2 using the NCI CTCAE, version 4.0. Adverse reaction data were collected for the duration of the study treatment and during the 30-day post-treatment follow-up period8,9

Median time to onset of common ARs5,7-9

SOLO-1

  • Median time to first onset of the most commonly reported nonhematologic ARs (nausea, fatigue/asthenia, vomiting) and hematologic ARs (anemia, neutropenia, thrombocytopenia) was <3 months in the olaparib arm

SOLO-2

  • Most common ARs occurred within the first month of treatment

Study 19

  • Most common ARs occurred within the first 2 months of treatment

OlympiAD

  • Median time to first onset of nausea, vomiting, and anemia was 5, 19, and 44 days, respectively

Data not reported for fatigue.

AR=adverse reaction; HER2-negative=human epidermal growth factor receptor 2–negative.

This website contains management strategies for some of the most common adverse reactions associated with LYNPARZA. Your patients may experience other side effects than the ones listed here.

The strategies offered here are not meant to replace your clinical judgment.

Please refer to the full Prescribing Information for additional safety information about LYNPARZA.

Assessing the severity of anemia

The National Cancer Institute (NCI) defines the grades for anemia10

NCI CTCAE GRADE DESCRIPTION
1 Hemoglobin (Hgb) <LLN - 10.0 g/dL; <LLN - 6.2 mmoI/L; <LLN - 100 g/L
2 Hgb <10.0 - 8.0 g/dL; <6.2 - 4.9 mmoI/L; <100 - 80 g/L
3 Hgb <8.0 g/dL; <4.9 mmoI/L; <80 g/L; transfusion indicated
4 Life-threatening consequences; urgent intervention indicated
5 Death
PRESENTATION
A disorder characterized by a reduction in the amount of hemoglobin in 100 mL of blood. Signs and symptoms of anemia may include pallor of the skin and mucous membranes, shortness of breath, palpitations of the heart, soft systolic murmurs, lethargy, and fatigability.

Management strategies for anemia

The following management strategies were derived from clinical studies that tested LYNPARZA or established medical protocol.
The information on this website is not meant to replace the clinical judgment of the attending physician.

Clinical evaluation icon

Clinical evaluation11


  • Ensure that patient has recovered from hematological toxicity caused by previous anticancer therapy
  • Hemoglobin, platelet, and neutrophil levels should be within normal range or CTCAE Grade 1
  • Test for a baseline in order to monitor for any clinically significant changes during treatment
Patient counseling icon

Patient counseling1,11


  • Advise patients that hematological side effects are common when receiving LYNPARZA
  • Help them understand that management strategies exist to aid in alleviation of AR symptoms
  • Explain to patients that regular blood tests are necessary to monitor for ARs
  • Prepare them for the possibility that a blood transfusion may be required
  • Let them know that communication with their care team is essential to adherence and potential resulting outcomes
Prescribing icon

Consider prescribing11


  • Iron bivalent compounds
  • Vitamin B12

If symptoms do not resolve or worsen in severity:

Consider managing with transfusions11

If transfusions do not resolve the AR: Consider dose interruption —Restart treatment at lower dose when anemia is Grade ≤1 within a maximum of 28 days1,11

Depending on the duration and severity of the AR, dose modification or discontinuation may be necessary1,11:
If event grade is ≤1 within a maximum of 28 days, consider dose modification:

Dose modification instructions

If event grade is >2 after 28 days and the patient has already undergone 2 dose reductions (to a minimum of 100 mg twice daily)11:

  • Discontinue therapy
  • Recommend hematologist consult
  • Perform a clinical evaluation
    • Bone marrow analysis, blood sample for cytogenetics, rule out myelodysplastic syndrome

CTCAE=Common Terminology Criteria for Adverse Events; LLN=lower limit of normal.

Assessing the severity of constipation

The NCI defines the grades for constipation10

NCI CTCAE GRADE DESCRIPTION
1 Occasional or intermittent symptoms; occasional use of stool softeners, laxatives, dietary modification, or enema
2 Persistent symptoms with regular use of laxatives or enemas; limiting instrumental ADL
3 Obstipation with manual evacuation indicated; limiting self-care ADL
4 Life-threatening consequences; urgent intervention indicated
5 Death

Management strategies for constipation

The following management strategies were derived from clinical studies that tested LYNPARZA or established medical protocol.
The information on this website is not meant to replace the clinical judgment of the attending physician.

Patient counseling icon

Patient counseling


  • Advise patients that constipation is a potential side effect when receiving LYNPARZA1
  • Help them understand that management strategies exist to aid in alleviation of AR symptoms12
  • Let them know that communication with their care team is essential to adherence and potential resulting outcomes13,14
Advise patients icon

Advise patients to12,15


  • Consume non-caffeinated fluids
  • Increase their fiber intake
  • Consider taking an over-the-counter laxative, stool softener, or enema
Prescribing icon

Consider prescribing15


  • Prokinetic agents
  • Peripherally acting mu-opioid receptor antagonists
  • Secretagogues

REMEMBER TO EVALUATE CONCOMITANT MEDICATIONS THAT MAY CONTRIBUTE TO CONSTIPATION.1,12

ADL=activities of daily living.

Assessing the severity of diarrhea

The NCI defines the grades for diarrhea10

NCI CTCAE GRADE DESCRIPTION
1 Increase of 1–3 stools per day over baseline; mild increase in ostomy output compared with baseline
2 Increase of 4–6 stools per day over baseline; moderate increase in ostomy output compared with baseline; limiting instrumental ADL
3 Increase of ≥7 stools per day over baseline; hospitalization indicated; severe increase in ostomy output compared with baseline; limiting self-care ADL
4 Life-threatening consequences; urgent intervention indicated
5 Death

Management strategies for diarrhea

The following management strategies were derived from clinical studies that tested LYNPARZA or established medical protocol.
The information on this website is not meant to replace the clinical judgment of the attending physician.

Patient counseling icon

Patient counseling


  • Advise patients that diarrhea is a potential side effect when receiving LYNPARZA1
  • Help them understand that management strategies exist to aid in alleviation of AR symptoms16
  • Let them know that communication with their care team is essential to adherence and potential resulting outcomes13,14
Advise patients icon

Advise patients to16,17


  • Eat smaller, more frequent meals
  • Adhere to the BRAT diet: bananas, rice, applesauce, and toast
  • Avoid foods with sorbitol
  • Increase fluid intake
  • Ensure that fiber intake is predominantly soluble
Prescribing icon

Consider prescribing16


  • Antidiarrheal agents
  • Peristalsis inhibitors

If symptoms do not resolve or worsen in severity:

Consider dose interruption

Restart treatment at same or lower dose when symptoms are Grade ≤1 or at a maximum of 4 weeks1,16-20

Consider dose modification1,16:

Dose modification instructions

Assessing the severity of dysgeusia

The NCI defines the grades for dysgeusia10,21

NCI CTCAE GRADE DESCRIPTION
1 Altered taste but no change in diet
2 Altered taste with change in diet (eg, oral supplements); noxious or unpleasant taste; loss of taste
PRESENTATION
Impaired or distorted ability to taste. Severity depends on extent of impairment and resultant changes in dietary habits.

Management strategies for dysgeusia

The following management strategies were derived from clinical studies that tested LYNPARZA or established medical protocol.
The information on this website is not meant to replace the clinical judgment of the attending physician.

Patient counseling icon

Patient counseling


  • Advise patients that dysgeusia is a potential side effect when receiving LYNPARZA1
  • Help them understand that management strategies exist to aid in alleviation of AR symptoms16
  • Let them know that communication with their care team is essential to adherence and potential resulting outcomes13,14
  • Advise patients to make small changes at home, such as16:
    • Adjusting food temperature to cool or room temperature
    • Adding sweet flavors to bitter-tasting foods
    • Using saliva substitutes
    • Rinsing mouth with baking soda solution
    • Practicing good dental hygiene
Prescribing icon

Consider prescribing


  • Cholinergic agents to promote production of saliva16,22

If symptoms do not resolve or worsen in severity:

Consider dose interruption

Restart treatment at lower dose when dysgeusia is Grade ≤1 within a maximum of 4 weeks1,11,17-20

Consider dose modification1,11:

If event grade is ≤1 within a maximum of 28 days, consider dose modification:

Dose modification instructions

Assessing the severity of dyspepsia and abdominal pain

The NCI defines the grades for dyspepsia and abdominal pain10,23

DYSPEPSIA
NCI CTCAE GRADE DESCRIPTION
1 Mild symptoms; intervention not indicated
2 Moderate symptoms; medical intervention indicated
3 Severe symptoms; operative intervention indicated
PRESENTATION
Sensation of pain or discomfort in the upper abdomen or lower chest following eating. May be accompanied by heartburn, flatulence, or nausea. Severity of symptoms directly correlated with NCI CTCAE grade.
ABDOMINAL PAIN
NCI CTCAE GRADE DESCRIPTION
1 Mild pain
2 Moderate pain; limiting instrumental ADL
3 Severe pain; limiting self-care ADL
PRESENTATION
A disorder characterized by a sensation of marked discomfort in the abdominal region.

Management strategies for dyspepsia and abdominal pain

The following management strategies were derived from clinical studies that tested LYNPARZA or established medical protocol.
The information on this website is not meant to replace the clinical judgment of the attending physician.

Patient counseling icon

Patient counseling


  • Advise patients that dyspepsia and abdominal pain are potential side effects when receiving LYNPARZA1
  • Help them understand that management strategies exist to aid in alleviation of AR symptoms16
  • Let them know that communication with their care team is essential to adherence and potential resulting outcomes13,14
Assess adverse reaction icon

Assess the cause of the abdominal pain24


  • First, evaluate the location of the pain
  • Onset, duration, severity, and quality of pain may also inform cause
  • Once these factors are identified, use your clinical judgment to manage the symptom
Prescribing icon

For dyspepsia, consider prescribing


  • Proton pump inhibitors16

If symptoms do not resolve or worsen in severity:

Consider referring patients to a gastroenterologist16

Consider dose interruption

Restart treatment at same or lower dose when symptoms are back to baseline or at a maximum of 4 weeks1,16-20

Consider dose modification1,16:

Dose modification instructions

Assessing the severity of fatigue

The NCI defines the grades for fatigue10,23

NCI CTCAE GRADE DESCRIPTION
1 Fatigue relieved by rest
2 Fatigue not relieved by rest; limiting instrumental ADL
3 Fatigue not relieved by rest; limiting self-care ADL
PRESENTATION
Lack of strength brought on by mental or physical activity and associated with a range of symptoms, including muscle pain, headaches, poor sleep, disturbed moods, and impaired concentration.

Management strategies for fatigue

The following management strategies were derived from clinical studies that tested LYNPARZA or established medical protocol.
The information on this website is not meant to replace the clinical judgment of the attending physician.

Patient counseling icon

Patient counseling


  • Advise patients that fatigue is a potential side effect when receiving LYNPARZA1
  • Help them understand that management strategies exist to aid in alleviation of AR symptoms11
  • Let them know that communication with their care team is essential to adherence and potential resulting outcomes13,14
  • Advise patients to make small changes at home, such as11,16:
    • Exercising to help alleviate fatigue
    • Prioritizing tasks to conserve energy
    • Avoiding multitasking
    • Taking brief naps in the afternoon for the first 4–6 weeks of treatment to combat fatigue and help improve symptoms
Prescribing icon

Consider prescribing16


  • Psychostimulants
  • Treatments or therapies that address potential contributing factors, such as pain, depression, or sleep disturbances

If symptoms do not resolve or worsen in severity:

Consider dose interruption

Allow fatigue to return to baseline1,16

Resume therapy

At ≤4 weeks, resume previous dose16-20

If symptoms are severe, consider dose modification1,16:

Dose modification instructions

Assessing the severity of headache

The NCI defines the grades for headache10,25

NCI CTCAE GRADE DESCRIPTION
1 Mild pain
2 Moderate pain; limiting instrumental ADL
3 Severe pain; limiting self-care ADL
PRESENTATION
Bilateral pressure of varying severity—may exhibit increased sensitivity to pressure and electrical/thermal stimuli.
Determination of severity is dependent on degree of pain and resultant disruptions in patients' daily activities.

Management strategies for headache

The following management strategies were derived from clinical studies that tested LYNPARZA or established medical protocol.
The information on this website is not meant to replace the clinical judgment of the attending physician.

Patient counseling icon

Patient counseling


  • Advise patients that headache is a potential side effect when receiving LYNPARZA1
  • Help them understand that management strategies exist to aid in alleviation of AR symptoms26
  • Let them know that communication with their care team is essential to adherence and potential resulting outcomes13,14
Assess adverse reaction icon

Rule out other causes of headache26,27


  • Infection
  • Anemia
  • Hypercalcemia
  • Thrombocytopenia
  • Dehydration
  • Brain metastases
Advise patients icon

Advise patients on26


  • Sleep hygiene
  • Stress reduction
  • Massage
  • Visual imagery
  • Acupuncture
  • Relaxation therapy
  • Over-the-counter pain relief
Prescribing icon

Consider prescribing26,28


  • Prophylactic tricyclic antidepressants for chronic, tension-type headaches
  • Serotonin receptor agonists (triptans) for mild migraines

AVOID PRESCRIBING OPIATES/BARBITURATES FOR PATIENTS WHO ARE EXPERIENCING MIGRAINE HEADACHES AS THESE MEDICATIONS ARE NOT PREFERRED AGENTS FOR THE TREATMENT OF HEADACHE.28

Assessing the severity of nausea and vomiting

The NCI defines the grades for nausea and vomiting10

NAUSEA
NCI CTCAE GRADE DESCRIPTION
1 Loss of appetite without alteration in eating habits
2 Oral intake decreased without significant weight loss, dehydration, or malnutrition
3 Inadequate oral caloric or fluid intake; tube feeding, total parenteral nutrition (TPN), or hospitalization indicated
VOMITING
NCI CTCAE GRADE DESCRIPTION
1 Intervention not indicated
2 Outpatient IV hydration; medical intervention indicated
3 Tube feeding, TPN, or hospitalization indicated
4 Life-threatening consequences
5 Death

Management strategies for nausea and vomiting

The following management strategies were derived from clinical studies that tested LYNPARZA or established medical protocol.
The information on this website is not meant to replace the clinical judgment of the attending physician.

Patient counseling icon

Patient counseling


  • Olaparib (LYNPARZA) is categorized by NCCN Clinical Practice Guidelines In Oncology (NCCN Guidelines®) as moderate to high emetic risk (≥30% of patients experience symptoms)29
  • Help them understand that management strategies exist to aid in alleviation of AR symptoms11
  • Let them know that communication with their care team is essential to adherence and potential resulting outcomes13,14
  • Offer them advice for managing the symptoms at home
  • National Comprehensive Cancer Network® (NCCN®) suggests lifestyle measures such as29,30:
    • Eating small frequent meals
    • Choosing healthful or bland foods (eg, white toast, clear broth, plain yogurt)
    • Controlling the amount of food consumed
    • Sipping clear liquids slowly
    • Not skipping meals
    • Eating food at room temperature
  • A dietary consult may also be useful
Prescribing icon

NCCN Recommended Options29


Antiemetic prophylaxis for oral chemotherapy with high-to-moderate emetic risk*:
  • Serotonin (5-HT3) receptor antagonist
Breakthrough treatment for chemotherapy-induced nausea/vomiting*:
  • Oral antipsychotics
  • Benzodiazepines
  • Phenothiazines
  • Corticosteroids

*Refer to the NCCN Guidelines® for specific treatment recommendations; not all agents in a drug class are recommended.

The general principle of breakthrough treatment is to add one agent from a different drug class to the current antiemetic regimen. For uncontrolled nausea and vomiting, clinicians can reevaluate and consider dose adjustments and/or sequentially add one agent from a different drug class.29

If symptoms do not resolve or worsen in severity:

Consider dose interruption

Hold dose until symptoms have returned to baseline for a day or two (no longer than 4 weeks)1,16-20

Resume therapy

May permit successful reintroduction of LYNPARZA at the same dose16

Perform a clinical evaluation

Confirm there are no secondary aggravating factors and ensure that nausea/vomiting therapy is optimized16

Consider dose modification1:

Dose modification instructions

See NCCN Guidelines for Antiemesis for recommendations about uncontrolled nausea and vomiting.29

NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way.

Assessing the severity of neutropenia

The NCI defines the grades for neutropenia10,31

NEUTROPENIA*
NCI CTCAE GRADE DESCRIPTION
1 <LLN - 1500/mm3; <LLN - 1.5 x 109/L
2 <1500 - 1000/mm3; <1.5 - 1.0 x 109/L
3 <1000 - 500/mm3; <1.0 - 0.5 x 109/L
4 <500/mm3; <0.5 x 109/L
5 -------------------------------------------------
FEBRILE NEUTROPENIA
NCI CTCAE GRADE DESCRIPTION
1 -------------------------------------------------
2 -------------------------------------------------
3 ANC <1000/mm3 and a single temperature of >38.3°C (101°F) or a sustained temperature of ≥38°C (100.4°F) for >1 hour
4 Life-threatening consequences; urgent intervention indicated
5 Death

Other hematologic ARs were observed at Grade ≥3 in women taking LYNPARZA18,32-34

In SOLO-1, these included thrombocytopenia (0.4%), leukopenia (1.5%), and lymphopenia (0.8%).

In SOLO-2, these included thrombocytopenia (1.0%), lymphopenia (0.5%), and leukopenia (1.5%).

In Study 19, these included pancytopenia (1.5%) and thrombocytopenia (0.7%).

In OlympiAD, these included leukopenia (2.5%), lymphopenia (1.0%), and thrombocytopenia (1.5%).

*A disorder characterized by a reduction in the absolute neutrophil count (ANC); associated with a progressively greater risk of infection, and with fever often being the only symptom of infection.31

Causality due to study drug not assessed.1

Investigator-assessed causality.1

Management strategies for neutropenia

The following management strategies were derived from clinical studies that tested LYNPARZA or established medical protocol.
The information on this website is not meant to replace the clinical judgment of the attending physician.

Clinical evaluation icon

Clinical evaluation for neutropenia31


Triage patients with fever seeking emergency medical care ≤6 weeks of receiving chemotherapy; assume that fever with neutropenia is due to an infection if alternative explanation does not exist.

Clinical evaluation icon

Clinical evaluation for febrile neutropenia31


  • Complete history and physical examination; complete blood count with leukocyte differential count, hemoglobin, and platelet count
  • ≥2 blood cultures from different sites and cultures from other sites (eg, urine or wounds)
  • Chest imaging for patients with symptoms of lower respiratory tract infection; nasopharyngeal swab for patients with an influenza-like illness
Patient counseling icon

Patient counseling1,11


  • Advise patients that hematologic side effects are common when receiving LYNPARZA
  • Help them understand that management strategies exist to aid in alleviation of AR symptoms
  • Explain to patients that regular blood tests are necessary to monitor for ARs
  • Let them know that communication with their care team is essential to adherence and potential resulting outcomes

If symptoms do not resolve or worsen in severity:

Consider dose interruption

Restart treatment at lower dose when neutropenia is Grade ≤1 or at a maximum of 4 weeks1,11,17-20

Consider dose modification1:

Dose modification instructions

FOR PATIENTS WITH FEBRILE NEUTROPENIA31

Empirical therapy administered ≤1 hour after triage; patients with febrile neutropenia should receive an intravenous dose of therapy while undergoing evaluation

  • An antipseudomonal β-lactam agent is recommended, but other antibacterials may be added for management of complications or if resistance is suspected
  • If patients are appropriate for outpatient management, observe for ≥4 hours before discharge

IMPORTANT SAFETY INFORMATION

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.

First-Line Maintenance HRD-Positive Advanced Ovarian Cancer in Combination with Bevacizumab

In combination with bevacizumab for the maintenance treatment of adult patients with advanced epithelial ovarian, fallopian tube or primary peritoneal cancer who are in complete or partial response to first-line platinum-based chemotherapy and whose cancer is associated with homologous recombination deficiency (HRD) positive status defined by either:

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.

gBRCAm, HER2-Negative Metastatic Breast Cancer

For the treatment of adult patients with deleterious or suspected deleterious gBRCAm, human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer who have been treated with chemotherapy in the neoadjuvant, adjuvant, or metastatic setting. Patients with hormone receptor (HR)-positive breast cancer should have been treated with a prior endocrine therapy or be considered inappropriate for endocrine therapy. Select patients for therapy based on an FDA-approved companion diagnostic for LYNPARZA.

First-Line Maintenance gBRCAm Metastatic Pancreatic Cancer

For the maintenance treatment of adult patients with deleterious or suspected deleterious gBRCAm metastatic pancreatic adenocarcinoma whose disease has not progressed on at least 16 weeks of a first-line platinum-based chemotherapy regimen. Select patients for therapy based on an FDA-approved companion diagnostic for LYNPARZA.

HRR Gene-mutated Metastatic Castration-Resistant Prostate Cancer

For the treatment of adult patients with deleterious or suspected deleterious germline or somatic homologous recombination repair (HRR) gene-mutated metastatic castration-resistant prostate cancer (mCRPC) who have progressed following prior treatment with enzalutamide or abiraterone. 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.

FemalesAdvise 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.

Venous Thromboembolic Events: Including pulmonary embolism, occurred in 7% of patients with metastatic castration-resistant prostate cancer who received LYNPARZA plus androgen deprivation therapy (ADT) compared to 3.1% of patients receiving enzalutamide or abiraterone plus ADT in the PROfound study. Patients receiving LYNPARZA and ADT had a 6% incidence of pulmonary embolism compared to 0.8% of patients treated with ADT plus either enzalutamide or abiraterone. 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.

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—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 compared to a ≥5% frequency for 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 thromboembolic events 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 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%).

ADVERSE REACTIONS—gBRCAm, HER2-Negative Metastatic Breast Cancer

Most common adverse reactions (Grades 1-4) in ≥20% of patients in 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 in 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 (Grades 1-4) in ≥10% of patients in clinical trials of 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 in clinical trials of 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 in clinical trials of 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 in clinical trials of LYNPARZA for PROfound were: decrease in hemoglobin (98%), decrease in lymphocytes (62%), decrease in leukocytes (53%), and decrease in absolute neutrophil count (34%).

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).

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