This site is intended for UK healthcare professionals
Medscape UK Univadis Logo
Medscape UK Univadis Logo

Olaparib oral

Updated 2 Feb 2023 | Olaparib

Presentation

Oral formulations of olaparib.

Drugs List

  • LYNPARZA 100mg tablets
  • LYNPARZA 150mg tablets
  • olaparib 100mg tablets
  • olaparib 150mg tablets
  • Therapeutic Indications

    Uses

    Breast cancer
    Fallopian tube cancer
    Locally advanced or metastatic adenocarcinoma of pancreas
    Metastatic castration-resistant prostate cancer
    Platinum sensitive high grade epithelial ovarian cancer
    Primary peritoneal cancer

    Tablets
    Ovarian cancer
    Maintenance monotherapy for advanced (FIGO stages III and IV) BRCA1/2-mutated (germline and/or somatic) high-grade epithelial ovarian, fallopian tube or primary peritoneal cancer who are in response (complete or partial) following completion of first-line platinum-based chemotherapy.

    Maintenance monotherapy for platinum sensitive relapsed high grade serous epithelial ovarian, fallopian tube or primary peritoneal cancer who are in response (complete response or partial response) to platinum-based chemotherapy.

    In combination with bevacizumab for the maintenance treatment of advanced (FIGO stages III and IV) high-grade epithelial ovarian, fallopian tube or primary peritoneal cancer who are in response (complete or partial) following completion of first-line platinum-based chemotherapy in combination with bevacizumab and whose cancer has had homologous recombination deficiency (HRD) positive status defined by either a BRCA1/2 mutation or genomic instability.

    Breast cancer
    Monotherapy or in combination with endocrine therapy for HER2 negative high risk early breast cancer with germline BRCA1/2 mutations, who have previously be treated with neoadjuvant or adjuvant chemotherapy.

    Monotherapy for HER2 negative locally advanced or metastatic breast cancer in patients with germline BRCA1/2-mutations. Patients should have previously been treated with an anthracycline and a taxane in the (neo)adjuvant or metastatic setting unless unsuitable for this treatment.

    Adenocarcinoma of the pancreas
    Maintenance monotherapy for metastatic adenocarcinoma of the pancreas in patients with germline BRCA1/2 mutations who have not progressed after a minimum of 16 weeks of platinum treatment within a first-line chemotherapy regimen.

    Prostate cancer
    Monotherapy for metastatic castration-resistant prostate cancer with germline or somatic BRCA1/2 mutations who have progressed following prior therapy with a new hormonal agent.

    Dosage

    Whilst the doses stated below are those recommended by the manufacturer, local cancer network protocols for the relevant indication should be consulted.

    Capsule formulations should not be substituted for tablet formulations on a milligram-to-milligram basis due to differences in the dosing and bioavailability for each formulation. Therefore the specific dose recommendations for each formulation should be followed.

    Adults

    Tablets
    300mg twice daily.

    Patients with platinum-sensitive relapsed (PSR) high-grade epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in complete or partial response to platinum-based chemotherapy should start treatment with olaparib no later than 8 weeks after completing their final dose of platinum containing regimen.

    Duration of treatment
    First-line maintenance treatment of BRCA-mutated advanced ovarian cancer
    Treatment can be continued until radiological disease progression, unacceptable toxicity or for up to 2 years if there is no radiological evidence of disease after 2 years of treatment. Patients with evidence of disease after 2 years can continue to be treated with olaparib beyond 2 years if the treating physician believes that patient can derive further benefit form continuing treatment.

    Maintenance treatment with platinum-sensitive relapsed ovarian cancer
    Treatment can be continued until progression of the underlying disease or unacceptable toxicity.

    First-line maintenance treatment of HRD positive advanced ovarian cancer in combination with bevacizumab
    Treatment can be continued until radiological disease progression, unacceptable toxicity or for up to 2 years if there is no radiological evidence of disease after 2 years of treatment. Patients with evidence of disease after 2 years can continue to be treated with olaparib beyond 2 years if the treating physician believes that patient can derive further benefit form continuing treatment.

    Adjuvant treatment of germline BRCA-mutated high risk early breast cancer
    Treatment can be continued for up to 1 year, or until disease recurrence, or unacceptable toxicity.

    gBRCA1/2-mutated HER2-negative metastatic breast cancer
    Treatment can be continued until progression of the underlying disease or unacceptable toxicity.

    First-line maintenance treatment of gBRCA-mutated metastatic adenocarcinoma of the pancreas
    Treatment can be continued until progression of the underlying disease or unacceptable toxicity.

    BRCA1/2-mutated metastatic castration-resistant prostate cancer
    Treatment can be continued until progression of the underlying disease or unacceptable toxicity.

    Patients with Renal Impairment

    Tablets
    Creatinine clearance 31 to 50 ml/minute: Reduce dose to 200mg twice a day.

    Creatinine clearance less than 31 ml/minute: Not recommended.

    Additional Dosage Information

    If a patient misses a dose, they should take their next dose at the normal scheduled time.

    Consider interrupting treatment and/or dose reductions to manage adverse reactions such as nausea, vomiting, diarrhoea and anaemia.

    Recommended dose reductions for tablets:
    Reduce to 250mg twice daily. If further dose reduction is required, reduce to 200mg twice daily.

    Contraindications

    Children under 18 years
    Breastfeeding
    Pregnancy
    Renal impairment - creatinine clearance below or equal to 30ml/minute
    Severe hepatic impairment - Child-Pugh score greater than or equal to 10

    Precautions and Warnings

    Females of childbearing potential
    History of radiotherapy
    Patients over 75 years
    Tobacco smoking
    Lung cancer
    Myelosuppression
    Pulmonary disease
    Renal impairment - creatinine clearance 30-50ml/minute

    Advise ability to drive/operate machinery may be affected by side effects
    Not all formulations are licensed for all uses
    Treatment to be initiated and supervised by a specialist
    Consult local policy on the safe use of oral anti-cancer drugs
    Staff: Not to be handled by pregnant staff
    Monitor blood counts before, monthly for 1 year and then periodically
    Exclude pregnancy before issuing each prescription
    Monitor for signs and symptoms of pneumonitis
    Reduce dose in patients with creatinine clearance below 51ml/min
    Advise patient to report any new or worsening respiratory symptoms
    Increased risk of myelodysplastic syndrome & non-lymphocytic leukaemia
    Consider dose interruption & reduction in non-haematological toxicity
    Consider treatment interruption & dose reduction in haematological toxicity
    Discontinue if MDS or AML occurs requiring additional anticancer therapy
    Discontinue if treatment related pneumonitis is diagnosed
    Bioavailability differs with preparations;caution on changing formulations
    Advise patient not to take St John's wort concurrently
    Advise patient grapefruit products may increase plasma level
    Female: Barrier or non-hormonal contraception advised during treatment
    Female: Contraception required during and for 6 months after treatment
    Female: Two reliable methods of contraception must be used simultaneously
    Male: Contraception required during and for 3 months after treatment
    Breastfeeding: Do not breastfeed during & for 1 month after treatment
    Male: Contraception required for partners for 3 months after treatment
    Patients should not donate semen during or for 3 months after treatment

    Treatment should only be initiated once haematological toxicity caused by previous anticancer therapy has returned to grade 1 or baseline.

    Patients who develop severe haematological toxicity or blood transfusion dependence should interrupt treatment and appropriate haematological testing should be carried out. If blood parameters remain abnormal after 4 weeks of dose interruption bone marrow analysis and/or blood cytogenetic analysis are recommended.

    Patient selection
    First line maintenance treatment of BRCA-mutated advanced ovarian cancer
    Patients must have confirmation of BRCA1/2 deleterious or suspected deleterious germline and/or somatic mutation status prior to first-line maintenance treatment of high-grade epithelial ovarian cancer (EOC), fallopian tube cancer (FTC) or primary peritoneal cancer (PPC).

    Maintenance treatment of platinum-sensitive relapsed ovarian cancer
    There is no requirement for BRCA1/2 testing prior to using olaparib for the monotherapy maintenance treatment of relapsed EOC, FTC or PPC who are in a complete or partial response to platinum-based therapy.

    First-line maintenance treatment of HRD positive advanced ovarian cancer
    Patients must have confirmation of BRCA1/2 deleterious or suspected deleterious mutation and/or genomic instability status prior to first-line maintenance treatment of high-grade epithelial ovarian cancer (EOC), fallopian tube cancer (FTC) or primary peritoneal cancer (PPC).

    Adjuvant treatment of germline BRCA-mutated high risk early breast cancer
    Patients must have confirmation of germline BRCA1/2 deleterious or suspected deleterious mutation status prior to treatment of adjuvant treatment of HER2 negative high risk early breast cancer.

    gBRCA1/2-mutated HER2-negative metastatic breast cancer
    Patients must have confirmation of germline BRCA1/2 deleterious or suspected deleterious mutation status prior to treatment of adjuvant treatment of HER2 negative locally advanced or metastatic breast cancer.

    First-line maintenance treatment of gBRCA-mutated metastatic adenocarcinoma of the pancreas
    Patients must have confirmation of germline BRCA1/2 deleterious or suspected deleterious mutation status prior to first-line maintenance treatment of gBRCA1/2-mutated metastatic adenocarcinoma of the pancreas.

    BRCA1/2-mutated metastatic castration-resistant prostate cancer
    Patients must have confirmation of BRCA1/2 deleterious or suspected deleterious mutation status prior to treatment of BRCA1/2-mutated metastatic castration-resistant prostate cancer.

    Pregnancy and Lactation

    Pregnancy

    Olaparib is contraindicated during pregnancy.

    The manufacturer recommends that olaparib should not be used during pregnancy or in women of child bearing potential not using reliable contraception during therapy and for 6 months after last dose. At the time of writing there is limited data on the use of olaparib in human pregnancy. Animals studies have shown reproductive toxicity including serious teratogenic effects and effects on embryofoetal survival.

    Lactation

    Olaparib is contraindicated during breastfeeding.

    The manufacturer advises that breastfeeding should be avoided during treatment, and for one month after receiving the last dose of olaparib. At the time of writing it is unknown whether olaparib is excreted in human breast milk, a risk to neonates cannot be excluded.

    Side Effects

    Abdominal pain
    Acute myeloid leukaemia
    Anaemia
    Angioedema
    Asthenia
    Cough
    Decreased appetite
    Dermatitis
    Diarrhoea
    Dizziness
    Dysgeusia
    Dyspepsia
    Dyspnoea
    Erythema nodosum
    Fatigue
    Headache
    Hypersensitivity reactions
    Increase in mean corpuscular volume (MCV)
    Leucopenia
    Lymphopenia
    Myelodysplastic syndrome
    Nausea
    Neutropenia
    Pneumonitis
    Rash
    Serum creatinine increased
    Stomatitis
    Thrombocytopenia
    Upper abdominal pain
    Vomiting

    Overdosage

    It is strongly recommended that the UK National Poisons Information Service be consulted on cases of suspected or actual overdose where there is doubt over the degree of risk or about appropriate management.

    The following number will direct the caller to the relevant local centre (0844) 892 0111

    Information may be obtained if you have access to ToxBase the primary clinical toxicology database of the National Poisons Information Service. This is available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

    Further Information

    Last Full Review Date: September 2019

    Reference Sources

    Summary of Product Characteristics: Lynparza 100mg + 150mg tablets. AstraZeneca UK Ltd. Revised September 2022.

    Access the full UK drug database with a FREE Medscape UK Account
    It takes just a few minutes, and you’ll get unlimited access to information on over 11,000 UK drugs.
    Register for Free

    Already a member? Log in

    Medscape UK | Univadis prescription drug monographs & interactions are based on FDB Multilex Content

    FDB Logo

    FDB Disclaimer : FDB Multilex is intended for the use of healthcare professionals and is provided on the basis that the healthcare professionals will retain FULL and SOLE responsibility for deciding what treatment to prescribe or dispense for any particular patient or circumstance.