MANAGEMENT SUPPORT FOR YOUR PATIENTS TAKING LYNPARZA:

Dosing and Adverse Events

You can help encourage adherence and provide a more positive treatment experience by proactively managing common adverse events (AEs) that patients may encounter while taking LYNPARZA® (olaparib).1-3 The following management strategies were derived from clinical studies that tested LYNPARZA (SOLO-1, Study 19, SOLO-2, and OlympiAD) or established medical protocol. This information is not meant to replace the clinical judgment of the attending physician.

Select a common AE below for management strategies

LYNPARZA is a twice-daily oral treatment with 2 available tablet strengths4

LYNPARZA recommended dose – Two 150 mg tablets in the morning and at night – 600 mg total

RECOMMENDED DOSE

Two 150 mg tablets in the morning and at night

600 mg total

LYNPARZA initial reduction - One 150 mg tablet and one 100 mg tablet in the morning and at night – 500 mg total

INITIAL REDUCTION DUE TO AN AE

One 150 mg tablet and one 100 mg tablet in the morning and at night

500 mg total

LYNPARZA final reduction – Two 100 mg tablets in the morning and at night – 400 mg total

FINAL REDUCTION DUE TO AN AE

Two 100 mg tablets in the morning and at night

400 mg total

Does not represent actual tablet size.

Trials limited the maximum duration of interruption to 4 weeks before suggesting a dose adjustment. Studies that placed limits on recurring interruptions restricted subsequent interruptions to 14 days.5-8

Resources for your patients

My LYNPARZA Support Program

You can refer your patients to the My LYNPARZA support program for additional support while taking LYNPARZA. Patients who enrolled in the My LYNPARZA program were dispensed a median of 29 more days of LYNPARZA compared with patients who did not enroll.9,* By clicking the link below, patients can select their cancer type and sign up for My LYNPARZA in the resources section.

Sign up for My LYNPARZA

A TOOL TO HELP IDENTIFY SIDE EFFECTS

Help your patients better understand common side effects by downloading this brochure. It covers questions that patients can ask you, as well as tips they can use to best communicate symptoms with their health care team.

Download the guide

gBRCAm=germline BRCA-mutated; HER2=human epidermal growth factor receptor 2; mBC=metastatic breast cancer.

*These results apply only to patients taking LYNPARZA for advanced ovarian cancer.

Anemia

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 (SOLO-1, Study 19, SOLO-2, and OlympiAD) or established medical protocol. The information on this Web site is not meant to replace the clinical judgment of the attending physician.

Clinical evaluation3

  • Ensure that patient has recovered from hematologic 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 counseling3,4

  • Advise patients that hematologic side effects are common when receiving LYNPARZA
  • Help them understand that management strategies exist to aid in alleviation of AE symptoms
  • Explain to patients that regular blood tests are necessary to monitor for AEs
  • 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

Consider prescribing3

  • Iron bivalent compounds
  • Vitamin B12

If symptoms do not resolve or worsen in severity:

Consider managing with transfusions3

If transfusions do not resolve the AE: Consider dose interruption—Restart treatment at lower dose when anemia is Grade ≤1 within a maximum of 28 days3,4

Depending on the duration and severity of the AE, dose modification or discontinuation may be necessary3,4:

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

LYNPARZA dose modification

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)3:

  • Discontinue therapy3
  • Recommend hematologist consult3
  • Perform a clinical evaluation3
    • Bone marrow analysis, blood sample for cytogenetics, rule out myelodysplastic syndrome

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

SELECT SAFETY INFORMATION

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.

Please see Important Safety Information

Constipation

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 (SOLO-1, Study 19, SOLO-2, and OlympiAD) or established medical protocol. The information on this Web site is not meant to replace the clinical judgment of the attending physician.

Patient counseling

  • Advise patients that constipation is a potential side effect when receiving LYNPARZA4
  • Help them understand that management strategies exist to aid in alleviation of AE symptoms11
  • Let them know that communication with their care team is essential to adherence and potential resulting outcomes2,12

Advise patients to11,13

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

Consider prescribing13

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

Remember to evaluate concomitant medications that may contribute to constipation.4,11

ADL=activities of daily living.

SELECT SAFETY INFORMATION

WARNINGS AND PRECAUTIONS (CONT’D)

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.

Please see Important Safety Information

Diarrhea

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 (SOLO-1, Study 19, SOLO-2, and OlympiAD) or established medical protocol. The information on this Web site is not meant to replace the clinical judgment of the attending physician.

Patient counseling

  • Advise patients that diarrhea is a potential side effect when receiving LYNPARZA4
  • Help them understand that management strategies exist to aid in alleviation of AE symptoms14
  • Let them know that communication with their care team is essential to adherence and potential resulting outcomes2,12

Advise patients to14,15

  • 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

Consider prescribing14

  • 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 weeks4-8,14

Consider dose modification4,14

LYNPARZA dose modification

SELECT SAFETY INFORMATION

WARNINGS AND PRECAUTIONS (CONT’D)

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

Embryo-Fetal Toxicity: Based on its mechanism of action and findings in animals, LYNPARZA can cause fetal harm. A pregnancy test is recommended for females of reproductive potential prior to initiating treatment.

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

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.

Please see Important Safety Information

Dysgeusia

Assessing the severity of dysgeusia

The NCI defines the grades for dysgeusia10,16

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 (SOLO-1, Study 19, SOLO-2, and OlympiAD) or established medical protocol. The information on this Web site is not meant to replace the clinical judgment of the attending physician.

Patient counseling

  • Advise patients that dysgeusia is a potential side effect when receiving LYNPARZA4
  • Help them understand that management strategies exist to aid in alleviation of AE symptoms14
  • Let them know that communication with their care team is essential to adherence and potential resulting outcomes2,12
  • Advise patients to make small changes at home, such as14:
    • 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

Consider prescribing

  • Cholinergic agents to promote production of saliva14,17

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 weeks3-8

Consider dose modification3,4

LYNPARZA dose modification

SELECT SAFETY INFORMATION

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%).

Please see Important Safety Information

Dyspepsia and abdominal pain

Assessing the severity of dyspepsia and abdominal pain

The NCI defines the grades for dyspepsia and abdominal pain10,18

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 (SOLO-1, Study 19, SOLO-2, and OlympiAD) or established medical protocol. The information on this Web site is not meant to replace the clinical judgment of the attending physician.

Patient counseling

  • Advise patients that dyspepsia and abdominal pain are potential side effects when receiving LYNPARZA4
  • Help them understand that management strategies exist to aid in alleviation of AE symptoms14
  • Let them know that communication with their care team is essential to adherence and potential resulting outcomes2,12

Assess the cause of abdominal pain19

  • 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

For dyspepsia, consider prescribing

  • Proton pump inhibitors14

If symptoms do not resolve or worsen in severity:

Consider referring patients to a gastroenterologist14

Consider dose interruption

Restart treatment at same or lower dose when symptoms are back to baseline or at a maximum of 4 weeks4-8,14

Consider dose modification4,14

LYNPARZA dose modification

SELECT SAFETY INFORMATION

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%).

Please see Important Safety Information

Fatigue

Assessing the severity of fatigue

The NCI defines the grades for fatigue10,18

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 (SOLO-1, Study 19, SOLO-2, and OlympiAD) or established medical protocol. The information on this Web site is not meant to replace the clinical judgment of the attending physician.

Patient counseling

  • Advise patients that fatigue is a potential side effect when receiving LYNPARZA4
  • Help them understand that management strategies exist to aid in alleviation of AE symptoms3
  • Let them know that communication with their care team is essential to adherence and potential resulting outcomes2,12
  • Advise patients to make small changes at home, such as3,14:
    • 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

Consider prescribing14

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

If symptoms do not resolve but are still mild to moderate:

Consider dose interruption

Allow fatigue to return to baseline4,14

Resume therapy

At ≤4 weeks, resume previous dose5-8,14

If symptoms are severe, consider dose modification4,14

LYNPARZA dose modification

SELECT SAFETY INFORMATION

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%).

Please see Important Safety Information

Headache

Assessing the severity of headache

The NCI defines the grades for headache10,20

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 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 (SOLO-1, Study 19, SOLO-2, and OlympiAD) or established medical protocol. The information on this Web site is not meant to replace the clinical judgment of the attending physician.

Patient counseling

  • Advise patients that headache is a potential side effect when receiving LYNPARZA4
  • Help them understand that management strategies exist to aid in alleviation of AE symptoms21
  • Let them know that communication with their care team is essential to adherence and potential resulting outcomes2,12

Rule out other causes of headache21,22

  • Infection
  • Anemia
  • Hypercalcemia
  • Thrombocytopenia
  • Dehydration
  • Brain metastases

Advise patients on21

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

Consider prescribing23

  • 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.23

SELECT SAFETY INFORMATION

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%).

Please see Important Safety Information

Nausea and Vomiting

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 (SOLO-1, Study 19, SOLO-2, and OlympiAD) or established medical protocol. The information on this Web site is not meant to replace the clinical judgment of the attending physician.

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)24
  • Help them understand that management strategies exist to aid in alleviation of AE symptoms3
  • Let them know that communication with their care team is essential to adherence and potential resulting outcomes2,12
  • Offer them advice for managing the symptoms at home
  • NCCN suggests lifestyle measures such as24,25:
    • 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

Consider prescribing24

Prophylaxis:

  • Serotonin (5-HT3) receptor antagonist

Breakthrough:

  • Oral antipsychotics
  • Benzodiazepines
  • Phenothiazines
  • Corticosteroids

See NCCN Guidelines® for Antiemesis for further information.

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)4-8,14

Resume therapy

May permit successful reintroduction of LYNPARZA at the same dose14

Perform a clinical evaluation

Confirm there is no secondary aggravating factors and ensure that nausea/vomiting therapy is optimized14

Consider dose modification4

LYNPARZA dose modification

NCCN=National Comprehensive Cancer Network®.

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.

SELECT SAFETY INFORMATION

DRUG INTERACTIONS

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

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

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

Please see Important Safety Information

Neutropenia

Assessing the severity of neutropenia

The NCI defines the grades for neutropenia10,26

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

Management strategies for neutropenia

The following management strategies were derived from clinical studies that tested LYNPARZA (SOLO-1, Study 19, SOLO-2, and OlympiAD) or established medical protocol. The information on this Web site is not meant to replace the clinical judgment of the attending physician.

Clinical evaluation for neutropenia26

  • 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 for febrile neutropenia26

  • 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 counseling3,4

  • Advise patients that hematologic side effects are common when receiving LYNPARZA
  • Help them understand that management strategies exist to aid in alleviation of AE symptoms
  • Explain to patients that regular blood tests are necessary to monitor for AEs
  • 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 weeks3-8

Consider dose modification3,4

LYNPARZA dose modification

FOR PATIENTS WITH FEBRILE NEUTROPENIA26

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

SELECT SAFETY INFORMATION

USE IN SPECIFIC POPULATIONS

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

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

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

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

Please see Important Safety Information

IMPORTANT SAFETY INFORMATION

CONTRAINDICATIONS

There are no contraindications for LYNPARZA.

WARNINGS AND PRECAUTIONS

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

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

If the levels have not recovered to Grade 1 or less after 4 weeks, refer the patient to a hematologist for further investigations, including bone marrow analysis and blood sample for cytogenetics. Discontinue LYNPARZA if MDS/AML is confirmed.

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

Embryo⁠-⁠Fetal Toxicity: Based on its mechanism of action and findings in animals, LYNPARZA can cause fetal harm. A pregnancy test is recommended for females of reproductive potential prior to initiating treatment.

Females

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

Males

Advise male patients with female partners of reproductive potential or who are pregnant to use effective contraception during treatment and for 3 months following the last dose of LYNPARZA and to not donate sperm during this time.

ADVERSE REACTIONS—First-Line Maintenance BRCAm Advanced Ovarian Cancer

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

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

ADVERSE REACTIONS—Maintenance Recurrent Ovarian Cancer

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

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

Most common laboratory abnormalities (Grades 1⁠-⁠4) in ≥25% of patients in clinical trials of LYNPARZA in the maintenance setting (SOLO⁠-⁠2/Study 19) were: increase in mean corpuscular volume (89%/82%), decrease in hemoglobin (83%/82%), decrease in leukocytes (69%/58%), decrease in lymphocytes (67%/52%), decrease in absolute neutrophil count (51%/47%), increase in serum creatinine (44%/45%), and decrease in platelets (42%/36%).

ADVERSE REACTIONS—Advanced gBRCAm Ovarian Cancer

Most common adverse reactions (Grades 1⁠-⁠4) in ≥20% of patients in clinical trials of LYNPARZA for advanced gBRCAm ovarian cancer after 3 or more lines of chemotherapy (pooled from 6 studies) were: fatigue/asthenia (66%), nausea (64%), vomiting (43%), anemia (34%), diarrhea (31%), nasopharyngitis/upper respiratory tract infection (URI) (26%), dyspepsia (25%), myalgia (22%), decreased appetite (22%), and arthralgia/musculoskeletal pain (21%).

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

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%).

DRUG INTERACTIONS

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

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

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

USE IN SPECIFIC POPULATIONS

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

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

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

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

INDICATIONS

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

First-Line Maintenance BRCAm Advanced Ovarian Cancer

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

Maintenance Recurrent Ovarian Cancer

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

Advanced gBRCAm Ovarian Cancer

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

gBRCAm, HER2-Negative Metastatic Breast Cancer

In 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.

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