Dosing & Uses
Dosage Forms & Strengths
tablet
- 100mg
- 150mg
Ovarian Cancer
Recurrent ovarian cancer
- Indicated as maintenance treatment for recurrent ovarian cancer (including epithelial ovarian, fallopian tube or primary peritoneal cancer) in adults who are in complete or partial response to platinum-based chemotherapy
- 300 mg PO BID
- Continue until disease progression, unacceptable toxicity
Advanced ovarian cancer (monotherapy)
- Indicated as first-line maintenance treatment for deleterious or suspected deleterious somatic or germline BRCA-mutated (gBRCAm) advanced ovarian cancer in patients who are in complete or partial response to first-line platinum-based chemotherapy
- 300 mg PO BID
- Continue until disease progression, unacceptable toxicity, or completion of 2 years of treatment
-
Completion of 2 years of treatment
- Patients with complete response (no radiologic evidence): Stop treatment
- Patients with evidence of disease and may benefit from continuous treatment: Treat beyond 2 years
Advanced ovarian cancer (combination therapy)
- Indicated as first-line maintenance treatment for advanced ovarian cancer in combination with bevacizumab for adults 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 a deleterious or suspected deleterious BRCA mutation, and/or genomic instability
- Olaparib 300 mg PO BID, plus
- Bevacizumab 15 mg/kg IV q3Weeks for a total of 15 months (including with chemotherapy and as maintenance)
- Continue until disease progression, unacceptable toxicity, or completion of 2 years of treatment
- Refer to prescribing information for bevacizumab when used in combination with olaparib for more information
-
Completion of 2 years of treatment
- Patients with complete response (no radiologic evidence): Stop treatment
- Patients with evidence of disease and may benefit from continuous treatment: Treat beyond 2 years
Advanced ovarian cancer (after ≥3 lines of chemotherapy)
- Indicated for treatment of adults with deleterious or suspected deleterious gBRCAm advanced ovarian cancer who have been treated with ≥3 prior lines of chemotherapy
- 300 mg PO BID
- Continue treatment until disease progression or unacceptable toxicity
Breast Cancer
Indicated for deleterious or suspected deleterious gBRCAm, human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer
Patients 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 prior endocrine therapy or be considered inappropriate for endocrine therapy
300 mg PO BID
Continue treatment until disease progression or unacceptable toxicity
Pancreatic Cancer
Indicated for first-line maintenance treatment of adults 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
300 mg PO BID
Continue treatment until disease progression or unacceptable toxicity
Metastatic Castration-Resistant Prostate Cancer
Indicated for deleterious or suspected deleterious germline or somatic homologous recombination repair (HRR) gene-mutated metastatic castration-resistant prostate cancer (mCRPC) in adults who have progressed following prior treatment with enzalutamide or abiraterone
300 mg PO BID
Continue until disease progression or unacceptable toxicity
Should also receive a gonadotropin-releasing hormone (GnRH) analog concurrently or should have had bilateral orchiectomy
Dosage Modifications
Management of adverse reactions
- Consider dose interruption or dose reduction to manage adverse reactions
-
Tablets
- Recommended dose reduction: 250 mg (one 150-mg tablet and one 100-mg tablet) PO BID
- If a further final dose reduction is required, then reduce to 200 mg (two 100-mg tablets) PO BID
Coadministration with CYP3A inhibitors
- Strong or moderate CYP3A inhibitors: Avoid use, consider alternatives
- If strong CYP3A inhibitors cannot be avoided: Reduce olaparib dose to 100 mg (one 100-mg tablet) PO BID
- If moderate CYP3A inhibitors cannot be avoided: Reduce olaparib dose to 150 mg (one 150-mg tablet) PO BID
Hepatic impairment
- Mild to moderate hepatic impairment (Child-Pugh Class A and B): No dosage adjustment necessary
- Severe hepatic impairment (Child-Pugh Class C): Not studied
Renal impairment
- Mild (CrCl 50-80 mL/min): No dosage adjustment necessary
- Moderate (CrCl 31-50 mL/min): Reduce dose to 200 mg (two 100-mg tablets) BID
- Severe (CrCl <30 mL/min or dialysis): Not evaluated
Dosing Considerations
Withdrawal of capsules
- In 2017, FDA reported olaparib capsules were being phased out of the US market
- Capsules were withdrawn from the market to avoid confusion and potential dosing errors with the tablets, and to reduce the pill burden
Patient selection
- Select patients based on suspected or deleterious HRR gene mutations (eg, BRCA mutations, genomic instability based on indication, biomarker, sample type)
- Information on FDA-approved tests is available at http://www.fda.gov/companiondiagnostics
-
Indications supported by diagnostic tests
- Germline or somatic BRCA-mutated advanced ovarian cancer
- HRD-positive advanced ovarian cancer in combination with bevacizumab
- Recurrent ovarian cancer
- Germline BRCA-mutated HER2-negative metastatic breast cancer
- Germline BRCA-mutated metastatic pancreatic adenocarcinoma
- Germline or somatic HRR gene-mutated mCRPC
Safety and efficacy not established
Interactions
Interaction Checker
No Results
Contraindicated
Serious - Use Alternative
Significant - Monitor Closely
Minor
Adverse Effects
All grades of severity are listed unless otherwise indicated
>10% (Maintenance Treatment for BRCA-mutated Advanced Ovarian)
Decreased hemoglobin (87%)
Increased mean corpuscular volume (87%)
Nausea (77%)
Decrease leukocytes (70%)
Fatigue (67%)
Decreased lymphocytes (67%)
Decreased ANC (51%)
Abdominal pain (45%)
Vomiting (40%)
Anemia (38%)
Diarrhea (37%)
Decreased platelets (35%)
Increased serum creatinine (34%)
Constipation (28%)
Upper respiratory tract infection (eg, influenza, nasopharyngitis, bronchitis) (28%)
Dysgeusia (26%)
Anemia, Grade 3 or 4 (21%)
Dizziness (20%)
Decreased appetite (20%)
Decreased hemoglobin, Grade 3 or 4 (19%)
Neutropenia (17%)
Dyspepsia (17%)
Dyspnea (15%)
Decreased lymphocytes, Grade 3 or 4 (14%)
Urinary tract infection (13%)
Thrombocytopenia (11%)
Stomatitis (11%)
>10% (Maintenance Treatment for Recurrent Advanced Ovarian)
Increased mean corpuscular volume (89%)
Decreased hemoglobin (83%)
Nausea (76%)
Decreased leukocytes (69%)
Decreased lymphocytes (67%)
Fatigue (66%)
Decreased ANC (51%)
Anemia (44%)
Increased serum creatinine (44%)
Decreased platelets (42%)
Vomiting (37%)
Upper respiratory tract infection (36%)
Diarrhea (33%)
Arthralgia/myalgia (30%)
Dysgeusia (27%)
Headache (26%)
Decreased appetite (22%)
Stomatitis (20%)
Neutropenia (19%)
Cough (18%)
Leukopenia (16%)
Hypomagnesemia (14%)
Thrombocytopenia (14%)
Dizziness (13%)
Dyspepsia (11%)
Increased creatinine (11%)
1-10% (BRCA-mutated Advanced Ovarian)
Maintenance treatment
- Neutropenia, Grade 3 or 4 (6%)
- Fatigue, Grade 3 or 4 (4%)
- Leukopenia, Grade 3 or 4 (3%)
- Diarrhea, Grade 3 or 4 (3%)
- Abdominal pain, Grade 3 or 4 (2%)
- Thrombocytopenia, Grade 3 or 4 (1%)
- Nausea, Grade 3 or 4 (1%)
1-10% (Maintenance Treatment for Recurrent Advanced Ovarian)
Edema (8%)
Rash (6%)
Fatigue, Grade 3 or 4 (4%)
Nausea, Grade 3 or 4 (3%)
Vomiting, Grade 3 or 4 (3%)
Diarrhea, Grade 3 or 4 (2%)
Lymphopenia (1%)
Headache, Grade 3 or 4 (1%)
Stomatitis, Grade 3 or 4 (1%)
Postmarketing Reports
Hypersensitivity (rash, dermatitis, angioedema)
Cough
Thrombocytopenia
Dysgeusia
Lymphopenia
Dizziness
Stomatitis
Upper abdominal pain
Warnings
Contraindications
None
Cautions
Pneumonitis, including fatal cases, occurred in <1%; interrupt treatment if pneumonitis is suspected; discontinue if pneumonitis is confirmed
Can cause fetal harm when administered to a pregnant woman based on its mechanism of action and findings in animals; (see Pregnancy)
Venous thromboembolic events, including pulmonary embolism, occurred in mCRPC patients who were treated with olaparib and androgen deprivation therapy; monitor for signs and symptoms of venous thrombosis and pulmonary embolism and treat as medically appropriate, which may include long-term anticoagulation as clinically indicated
Myelodysplastic syndrome/ acute myeloid leukemia
- Myelodysplastic syndrome/acute myeloid leukemia (MDS/AML) occurred in clinical trials
- Monitor complete blood cell count for cytopenia at baseline and monthly thereafter for clinically significant changes during treatment
- Do not initiate treatment until hematological toxicity caused by previous chemotherapy (Grade ≤1) resolves
- For prolonged hematological toxicities, interrupt treatment and promptly assess source of symptoms; monitor blood counts weekly until recovery
- If levels have not recovered to Grade ≤1 after 4 weeks, refer to a hematologist for further investigations, including bone marrow analysis and blood sample for cytogenetics
- All patients with myelodysplastic syndrome reported to have received previous chemotherapy with platinum agents and/or other DNA damaging agents including radiotherapy; some of these patients also had a history of more than one primary malignancy or of bone marrow dysplasia
- If MDS/AML is confirmed, discontinue olaparib
Drug interactions overview
- Clinical studies of olaparib in combination with other myelosuppressive anticancer agents (eg, DNA damaging agents) indicate a potentiation and prolongation of myelosuppressive toxicity
-
CYP3A4 inhibitors
- Olaparib is a CYP3A4 substrate; coadministration of strong or moderate CYP3A4 inhibitors may increase olaparib plasma concentrations
- Avoid concomitant use of strong or moderate CYP3A inhibitors (see Dosage Modifications)
- If strong or moderate CYP3A inhibitors must be coadministered, reduce dose of olaparib (see Dosage Modifications)
- Avoid grapefruit, grapefruit juice, Seville oranges and Seville orange juice during olarparib treatment since they are CYP3A inhibitors
-
CYP3A4 inducers
- Coadministration of strong or moderate CYP3A4 inducers may decrease olaparib plasma concentrations
- Avoid concomitant use of strong or moderate CYP3A inducers
- If a strong or moderate CYP3A inducer cannot be avoided, be aware of a potential for decreased efficacy of olaparib (see Dosage Modifications)
Pregnancy & Lactation
Pregnancy
Based on findings in animals and mechanism of action, fetal harm may occur when administered to a pregnant woman; there are no available data on use in pregnant women to inform of drug associated risk
Olaparib was teratogenic and caused embryo-fetal toxicity in rats at exposures below those in patients receiving the recommended human dose of 400 mg BID
Contraception
- In women of childbearing potential, avoid pregnancy by using effective contraception during treatment and for at least 6 month after receiving the last dose; pregnancy testing is recommended for females of reproductive potential prior to initiating treatment
- Based on findings in genetic toxicity and animal reproduction studies, 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 olaparib
- Advise male patients not to donate sperm during therapy and for 3 months following the last dose of olaparib
Lactation
No data are available regarding presence of olaparib in human milk, or on effects on breastfed infant or on milk production; because of potential for serious adverse reactions in breastfed infants from therapy, advise lactating women not to breastfeed during treatment and for 1 month after receiving last dose
Pregnancy Categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk. C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done. D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk. X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist. NA: Information not available.Pharmacology
Mechanism of Action
Inhibitor of poly (ADP-ribose) polymerase (PARP) enzymes, including PARP1, PARP2, and PARP3
PARP enzymes are involved in normal cellular homeostasis, such as DNA transcription, cell cycle regulation, and DNA repair
Absorption
Bioavailability of tablet formulation is higher than the capsule formulation (AUC at steady-state 77% higher with tablet)
Peak plasma time: 1.5 hr (tablet); 1-3 hr (capsule)
Peak plasma concentration: 7.7 mcg/mL (tablet at steady-state)
AUC: 49 mcg·hr/mL (tablet at steady-state)
Steady-state achieved: 3-4 days
Coadministration with a high-fat meal slowed the rate (Peak plasma time delayed by 2.5 hr [tablet] or 2 hr [capsule]) of absorption, but did not significantly alter the extent of absorption (mean AUC increased by ~8% [tablet] or ~20% [capsule])
Distribution
Protein bound: 82%
Vd: 158 L (tablet); 167 L (capsule)
Metabolism
Metabolized primarily by CYP3A4/5
Elimination
Half-life: 14.9 hr (tablet); 11.9 hr (capsule)
Plasma clearance: 7.4 L/hr (tablet); 8.6 L/hr (capsule)
Excretion: 44% urine; 42% feces
Excreted mostly as metabolites
Pharmacogenomics
Indicated as monotherapy in patients with deleterious or suspected deleterious germline BRCA-mutated (as detected by an FDA-approved test) advanced ovarian cancer or breast cancer
Information on FDA-approved test for the detection of BRCA mutations is available at http://www.fda.gov/companiondiagnostics
Administration
Oral Administration
To avoid substitution errors and overdose, do not substitute olaparib tablets with olaparib capsules on a mg-to-mg basis due to differences in the dosing and bioavailability of each formulation
May take with or without food
Swallow tablets whole; do not chew, crush, dissolve or divide
Missed dose: Instruct patient to take their next dose at its scheduled time
Storage
Tablets: Store at 20-25ºC (68-77°F), excursions permitted to 15-30ºC (59-86°F)
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Patient Handout
Formulary
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