Les renseignements du Formulaire de médicaments s’adressent aux professionnels de la santé. Il ne s’agit pas d’un avis médical. Certains des renseignements, y compris ceux sur le financement des médicaments anticancéreux, ne s’appliquent pas à tous les patients. Les plans de traitement du cancer sont propres à chaque patient. Si vous êtes un patient, veuillez parler avec votre équipe soignante pour comprendre comment ces renseignements s’appliquent à vous.
Olaparib is a selective inhibitor of human poly (ADP-ribose) polymerase enzymes (PARP-1, PARP-2 and PARP-3) involved in DNA repair. Olaparib has been shown to inhibit the growth of solid tumours, especially those deficient in BRCA function (e.g., BRCA mutation-positive ovarian tumours).
Olaparib is absorbed rapidly with peak concentration achieved 1.5 hours after a single dose.
| Effects with food |
Co-administration with food slowed the rate of absorption but did not significantly affect the extent of absorption |
| PPB |
82% |
Olaparib is extensively metabolized in the liver by CYP3A isoenzymes. It is currently unknown whether metabolites are active.
| Half-life |
terminal elimination: approx. 15 hours |
| Feces |
42% in 7 days |
| Urine |
44% in 7 days |
- Ovarian cancer
- Breast cancer
- Prostate cancer
- Pancreatic cancer
Refer to the product monograph for a full list of approved indications and details.
Emetogenic Potential:
Extravasation Potential: Not applicable
The following adverse effects were reported in patients in the phase III trial comparing olaparib monotherapy to placebo in patients with ovarian, fallopian tube or primary peritoneal cancer who responded to first-line platinum-based chemotherapy. Severe adverse effects from other studies or post-marketing are also included.
| ORGAN SITE | SIDE EFFECT* (%) | ONSET** | |||
|---|---|---|---|---|---|
| Cardiovascular | Venous thromboembolism (2%) (8% in mCRPC) | E | |||
| Dermatological | Rash (10%) | E | |||
| Gastrointestinal | Abdominal pain (18%) | E | |||
| Anorexia (20%) | E | ||||
| Constipation (28%) | E | ||||
| Diarrhea (34%) (3% severe) | E | ||||
| Dyspepsia (17%) | E | ||||
| Mucositis (11%) | E | ||||
| Nausea, vomiting (77%) (1% severe) | I E | ||||
| General | Fatigue (64%) (4% severe) | E | |||
| Hematological | Myelosuppression ± infection, bleeding (39%) (22% severe; including anemia) | E | |||
| Hepatobiliary | Hepatotoxicity (rare) | E | |||
| Hypersensitivity | Hypersensitivity (2%) | I | |||
| Neoplastic | Secondary malignancy (1%) (MDS, AML) | D L | |||
| Nervous System | Dizziness (20%) | E | |||
| Dysgeusia (26%) | E | ||||
| Headache (23%) | E | ||||
| Renal | Creatinine increased (8%) | E | |||
| Respiratory | Cough, dyspnea (18%) | E | |||
| Pneumonitis (rare) | E D | ||||
* "Incidence" may refer to an absolute value or the higher value from a reported range.
"Rare"
may refer to events with < 1% incidence, reported in post-marketing, phase 1 studies,
isolated data or anecdotal
reports.
** I = immediate (onset in hours to days)
E = early (days to weeks)
D = delayed (weeks to months)
L = late (months to years)
The most common side effects for olaparib include nausea, vomiting, fatigue, myelosuppression ± infection, bleeding, diarrhea, constipation, dysgeusia, headache, anorexia, dizziness and abdominal pain.
Nausea and vomiting were generally reported with early onsets, but most of these events improved over time without intervention.
Myelodysplastic syndrome (MDS) and/or Acute myeloid leukemia (AML) have been reported rarely and were fatal in most cases. Affected patients received olaparib for less than 6 months to over 4 years and had other contributing factors, including previous treatment with DNA damaging agents (radiation, platins, etc.). Most were in germline BRCA mutation carriers and some had a history of previous cancer or bone marrow dysplasia. In the SOLO2 study, patients with BRCAm platinum-sensitive relapsed ovarian cancer who had received at least 2 prior lines of platinum chemotherapy had a higher incidence (8%) of MDS/AML.
Severe myelosuppression has been reported, including hemorrhagic stroke associated with thrombocytopenia. Anemia is the most common severe adverse effect reported in clinical trials. Levels appeared to return to normal after treatment discontinuation and did not appear to have any clinical consequences.
Pneumonitis, including fatal cases, have been reported rarely.
Cases of drug-induced liver injury (DILI) have been observed during post-marketing.
Venous thromboembolic events, including pulmonary embolism have been observed and had no consistent clinical pattern. A higher incidence was reported in patients with metastatic castration resistant prostate cancer who received olaparib with androgen deprivation therapy (ADT), compared with other indications. Monitoring is recommended and treatment may be necessary.
Refer to protocol by which the patient is being treated.
Screen for hepatitis B virus in all cancer patients starting systemic treatment. Refer to the hepatitis B virus screening and management guideline.
Various treatment indications require a validated test to determine BRCA or ATM mutation status. Refer to the product monograph for details.
In ovarian cancer, treatment should start no later than 8 weeks after completion of platinum-containing chemotherapy. (Refer to EAP for detailed funding criteria).
In metastatic castration-resistant prostate cancer (mCRPC), patients should also receive a gonadotropin-releasing hormone (GnRH) analog concurrently, or should have had bilateral orchiectomy.
For adjuvant treatment of HER2-negative high risk early breast cancer, continue concurrent endocrine therapy in patients with hormone receptor positive breast cancer as per clinical guidelines. Start olaparib at least 2 weeks (no more than 12 weeks) after completion of the last treatment, including surgery, chemotherapy, or radiation therapy (Refer to CADTH recommendations).
Patients should have recovered from prior hematologic toxicities before starting olaparib (Hgb, ANC and platelets ≤ grade 1).
| Dose Level | Olaparib Dose |
| 0 | 300 mg BID |
| -1 | 250 mg BID |
| -2 | 200 mg BID |
| -3 | Discontinue |
| Toxicity | Severity | Action |
| Platelets or ANC | ≥ Grade 3 or blood transfusion dependence |
Hold up to 4 weeks* and monitor CBC. Then, may consider dose reduction. |
| Hemoglobin |
Hold up to 4 weeks* and monitor CBC. Then, consider a dose reduction after severe anemia, to avoid multiple transfusions. |
|
| Signs and symptoms of pneumonitis | Any |
Hold and investigate. If confirmed, discontinue and treat appropriately. |
| Hepatotoxicity | Any |
Hold and investigate. Consider discontinuing if severe drug-induced liver injury and manage appropriately. |
| MDS, AML or other clonal disorders |
Hold and investigate. If confirmed, discontinue and treat appropriately. |
|
| Other non-hematologic | Grade 3 or 4 |
Hold up to 4 weeks** Upon recovery, consider dose reduction. |
*Hold until ≤ grade 1. If blood parameters remain abnormal after 4 weeks, bone marrow analysis and/or blood cytogenetic analysis are recommended.
**Hold until ≤ grade 1. If toxicity recurs, reduce an additional dose level. Discontinue if more than 2 dose reductions are required.
| Hepatic Impairment | Olaparib Dose |
| Child-Pugh A or B | No dose adjustment required |
| Child-Pugh C | Not recommended (not studied) |
| Creatinine Clearance (mL/min) | Olaparib Dose |
| > 50 | No dose adjustment required |
| 31-50 | 200 mg BID |
| ≤ 30 or end stage renal disease | Not recommended (limited data) |
Dose adjustment is not required. There is limited data in patients aged 75 and older.
Safety and efficacy have not been established in pediatric patients.
-
Olaparib can be taken with or without food.
-
Tablets should be swallowed whole and not chewed, crushed, dissolved or divided.
-
Avoid grapefruit, starfruit, pomegranate, Seville oranges, their juices or products during treatment.
-
If a dose is missed, the next dose should be taken at the regular scheduled time. A double dose should not be taken to make up for forgotten tablets.
-
Store between 2 to 30oC in original packaging to protect from moisture.
- Patients who have a hypersensitivity to this drug or any of its components
- Do not co-administer with other myelosuppressive agents.
- Use with caution in patients who have received prior DNA damaging agents. MDS and AML have been reported.
- Use with caution in patients with lung cancer or metastases to the lungs, underlying pulmonary disease, smoking history and/or previous chemotherapy and radiotherapy as these patients are at increased risk of pneumonitis
- Patients experiencing fatigue and dizziness should use caution when driving or operating machines.
Other Drug Properties:
-
Carcinogenicity:
Probable
Carcinogenicity studies have not been performed; however, secondary hematologic malignancies have been reported.
-
Clastogenicity:
Yes
-
Fetotoxicity:
Documented in animals
-
Teratogenicity:
Documented in animals
-
Embryotoxicity:
Documented in animals
-
Pregnancy:
- Olaparib is not recommended for use in pregnancy.
- Adequate contraception should be used by patients who can become pregnant and their partners during treatment, and for 6 months after the last dose. Consider an additional non-hormonal (e.g., barrier) method of contraception as it is uncertain whether olaparib reduces the effectiveness of hormonal contraceptives. For patients with hormone dependent cancer, consider two non-hormonal contraceptive methods.
- Adequate contraception should be used by patients who produce sperm and their partners during treatment, and for 3 months after the last dose.
- Patients should not donate sperm during therapy and for 3 months after the last dose; it is unknown whether olaparib is found in seminal fluid.
-
Breastfeeding:
Breastfeeding is not recommended during treatment and for 1 month after the last dose.
-
Fertility effects:
Probable
Documented in animal studies with female animals
Olaparib is primarily metabolized by CYP3A and is susceptible to inhibitors and inducers of this isoenzyme. Olaparib is a substrate and inhibitor of MDR1 and a weak inhibitor of BCRP.
The possibility of CYP2C9 induction by olaparib and reduced substrate exposure (including hormonal contraceptives) cannot be excluded. Consider an additional non-hormonal (e.g., barrier) method of contraception. For women with hormone dependent cancer, consider two non-hormonal contraceptive methods.
| AGENT | EFFECT | MECHANISM | MANAGEMENT |
|---|---|---|---|
| CYP3A inducers (i.e. phenytoin, rifampin, dexamethasone, carbamazepine, phenobarbital, St. John’s Wort, etc) | ↓ olaparib concentration and/or efficacy | ↑ metabolism of olaparib | Co-administration with strong and moderate CYP3A inducers is not recommended. There is potential for substantially decreased olaparib efficacy with strong inducers. |
| CYP3A inhibitors (i.e. ketoconazole, clarithromycin, ritonavir, fruit or juice from grapefruit, Seville oranges, pomegranate or starfruit) | ↑ olaparib concentration and/or toxicity | ↓ metabolism of olaparib | Co-administration with strong and moderate CYP3A inhibitors is not recommended. If the combination cannot be avoided, the dose of olaparib should be reduced to 100 mg bid (strong) or 150 mg bid (moderate). |
| CYP3A4 substrates (e.g. cyclosporine, pimozide, tacrolimus, triazolo-benzodiazepines, dihydropyridine calcium-channel blockers, certain HMG-CoA reductase inhibitors) | ↑ substrate exposure | Olaparib is predicted to be a weak inhibitor of CYP3A4 in vitro | Caution and monitor closely, especially with narrow therapeutic window substrates. |
| CYP 2B6 substrates (i.e. bupropion, cyclophosphamide, selegiline) | ↓ substrate exposure | Olaparib induces CYP2B6 in vitro | Caution and monitor closely |
| Substrates of hepatic uptake transporters OATP1B1, OCT1 (e.g. bosentan, repaglinide, statins, metformin) | ↑ substrate exposure | Olaparib inhibits OATP1B1, OCT1 in vitro | Caution and monitor closely, especially in combination with statins. |
| Substrates of renal uptake transporters OCT2, OAT3, MATE1, MATE2K (e.g. furosemide, methotrexate, metformin, cisplatin) | ↑ substrate exposure | Olaparib inhibits renal uptake transporters in vitro | Caution and monitor closely |
| Myelosuppressive anticancer agents | potentiation and prolongation of myelosuppression | Additive | Avoid combining with other myelosuppressive agents |
Treating physicians may decide to monitor more or less frequently for individual patients but should always consider recommendations from the product monograph.
Refer to the hepatitis B virus screening and management guideline for monitoring during and after treatment.
| Monitor Type | Monitor Frequency |
|---|---|
CBC |
Baseline and monthly for the first 12 months, then periodically thereafter, and as clinically indicated |
Liver function tests |
Baseline and as clinically indicated |
Renal function tests |
Baseline and as clinically indicated |
Clinical toxicity assessment for nausea and other GI and respiratory effects, fatigue, anemia, MDS, infection, bleeding and venous thromboembolism |
At each visit |
Grade toxicity using the current NCI-CTCAE (Common Terminology Criteria for Adverse Events) version
Exceptional Access Program (EAP Website)
- olaparib - For the maintenance treatment of BRCA-mutated, high grade epithelial ovarian, fallopian tube, or primary peritoneal cancer in adult patients, based on criteria
- olaparib - For the treatment of metastatic castration resistant prostate cancer (mCRPC), based on criteria
- olaparib - For the treatment of adult patients with deleterious or suspected deleterious germline BRCA-mutated, human epidermal growth factor receptor 2-negative high risk early breast cancer, based on criteria
- olaparib - In combination with abiraterone, and prednisone or prednisolone for the treatment of metastatic castration resistant prostate cancer (mCRPC), based on criteria
CADTH reimbursement recommendation: Olaparib (adjuvant treatment of adult patients with deleterious or suspected deleterious germline BRCA-mutated, human epidermal growth factor receptor 2-negative high risk early breast cancer). March 2023.
De Bono J, Mateo J, Fizazi K, et al. Olaparib for metastatic castration-resistant prostate cancer. N Engl J Med 2020 May 28;382(22):2091-2102.Golan T, Hammel P, Reni M, et al. Maintenance Olaparib for Germline BRCA-Mutated Metastatic Pancreatic Cancer. N Engl J Med 2019 Jul 25;381(4):317-27.
Golan T, Hammel P, Reni M, et al. Maintenance olaparib for germline BRCA-mutated metastatic pancreatic cancer. N Engl J Med 2019 Jul 25;381(4):317-27.
Ledermann J, Harter P, Gourley C, et al. Olaparib maintenance therapy in patients with platinum-sensitive relapsed serous ovarian cancer: a preplanned retrospective analysis of outcomes by BRCA status in a randomised phase 2 trial. Lancet Oncol. 2014 Jul;15(8):852-61.
Moore K, Colombo N, Scambia G et al. Maintenance olaparib in patients with newly diagnosed advanced ovarian cancer. N Engl J Med 2018;379:2495-505.
Product information: Lynparza (Olaparib). AstraZeneca AB. August 20, 2024.
Product monograph: Lynparza (olaparib tablets). AstraZeneca Canada Inc., September 27, 2024.
Pujade-Lauraine E, Ledermann JA, Selle F, et al. Olaparib tablets as maintenance therapy in patients with platinum-sensitive, relapsed ovarian cancer and a BRCA1/2 mutation (SOLO2/ENGOT-Ov21): a double-blind, randomised, placebo-controlled, phase 3 trial. Lancet Oncol. 2017 Jul 25 (published online).
Robson M, Im SA, Senkus E, et al. Olaparib for Metastatic Breast Cancer in Patients with a Germline BRCA Mutation. N Engl J Med 2017;377(6):523-33.
Tew WP, Lacchetti C, Ellis A, et al. PARP Inhibitors in the Management of Ovarian Cancer: ASCO Guideline. J Clin Oncol 2020 Oct 20;38(30):3468-93.
Winship AL, Griffiths M, Requesens CL, et al. The PARP inhibitor, olaparib, depletes the ovarian reserve in mice: implications for fertility preservation. Hum Reprod 2020 Aug 1;35(8):1864-1874.
December 2024 Updated Adverse effects, Dosing, and Pregnancy/lactation sections
Refer to the New Drug Funding Program or Ontario Public Drug Programs websites for the most up-to-date public funding information.
The information set out in the drug monographs, regimen monographs, appendices and symptom management information (for health professionals) contained in the Drug Formulary (the "Formulary") is intended for healthcare providers and is to be used for informational purposes only. The information is not intended to cover all possible uses, directions, precautions, drug interactions or adverse effects of a particular drug, nor should it be construed to indicate that use of a particular drug is safe, appropriate or effective for a given condition. The information in the Formulary is not intended to constitute or be a substitute for medical advice and should not be relied upon in any such regard. All uses of the Formulary are subject to clinical judgment and actual prescribing patterns may not follow the information provided in the Formulary.
The format and content of the drug monographs, regimen monographs, appendices and symptom management information contained in the Formulary will change as they are reviewed and revised on a periodic basis. The date of last revision will be visible on each page of the monograph and regimen. Since standards of usage are constantly evolving, it is advised that the Formulary not be used as the sole source of information. It is strongly recommended that original references or product monograph be consulted prior to using a chemotherapy regimen for the first time.
Some Formulary documents, such as the medication information sheets, regimen information sheets and symptom management information (for patients), are intended for patients. Patients should always consult with their healthcare provider if they have questions regarding any information set out in the Formulary documents.
While care has been taken in the preparation of the information contained in the Formulary, such information is provided on an “as-is” basis, without any representation, warranty, or condition, whether express, or implied, statutory or otherwise, as to the information’s quality, accuracy, currency, completeness, or reliability.
CCO and the Formulary’s content providers shall have no liability, whether direct, indirect, consequential, contingent, special, or incidental, related to or arising from the information in the Formulary or its use thereof, whether based on breach of contract or tort (including negligence), and even if advised of the possibility thereof. Anyone using the information in the Formulary does so at his or her own risk, and by using such information, agrees to indemnify CCO and its content providers from any and all liability, loss, damages, costs and expenses (including legal fees and expenses) arising from such person’s use of the information in the Formulary.