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Olaparib

  • PARP inhibitorsPARP inhibitors
  • High alertAn error with this medicine can cause serious harm: double checks and protocols are used.
  • Pregnancy: avoidAvoid in pregnancy. Can harm the fetus: a pregnancy test is done before starting, effective contraception is used during treatment and for a time afterwards (by women and by men…

The first PARP inhibitor: an oral drug for BRCA-mutated ovarian, breast, pancreatic and prostate cancers. Watch blood counts and the lungs.

Updated

Quick facts

Group
PARP inhibitors
Target
Poly(ADP-ribose) polymerases PARP1 and PARP2
Used for
Maintenance in advanced · HER2-negative breast cancer
Key effects
Nausea · Fatigue and anaemia · Muscle
Monitor
Complete blood count at baseline · New cough
ATC
L01XK01

No doses: the clinician sets them by the current guideline.

Mechanism of action

The figure shows olaparib in the NAD+ site of the human PARP1 catalytic domain.

Target in 3D: Poly(ADP-ribose) polymerases PARP1 and PARP2. PDB structure 7KK4 (RCSB PDB, public domain). View the structure at RCSB PDB

Olaparib inhibits PARP1, PARP2 and PARP3 by occupying the NAD+ site, and traps PARP on damaged DNA. Single-strand breaks persist and become double-strand breaks when the cell replicates. Tumours with BRCA1/2 mutations or other homologous recombination defects cannot repair them and die, while normal cells survive.

  1. Olaparib fills the NAD+ site and traps PARP on DNA
  2. Single-strand breaks become double-strand breaks
  3. BRCA-deficient cells cannot repair them and die

Indications

  • Maintenance in advanced or recurrent ovarian, fallopian tube or primary peritoneal cancer after a response to platinum chemotherapy (BRCA-mutated, or with bevacizumab in homologous recombination-deficient disease). Ovarian cancer →
  • HER2-negative breast cancer with germline BRCA mutation: high-risk early disease after chemotherapy, and metastatic disease. Breast cancer →
  • Maintenance in metastatic pancreatic cancer with germline BRCA mutation that has not progressed on first-line platinum. Pancreatic cancer →
  • Metastatic castration-resistant prostate cancer: alone with homologous recombination repair gene mutations, or with abiraterone with BRCA mutations. Prostate cancer →

Adverse effects

Common

  • Nausea, vomiting, decreased appetite, taste changes
  • Fatigue and anaemia
  • Muscle, joint and back pain
  • Diarrhoea or constipation, heartburn
  • Headache, dizziness, mouth sores, rash

Contraindications

  • No absolute contraindications in the label apart from hypersensitivity; see the warnings

Key interactions

Strong CYP3A4 inhibitors (clarithromycin, itraconazole, ketoconazole, ritonavir) and grapefruit
Raise olaparib exposure.
Strong CYP3A4 inducers (rifampicin, carbamazepine, phenytoin, St John's wort)
Lower its levels and can make it fail.
Grapefruit, Seville oranges and their juices
Can raise olaparib levels; they are avoided.

What is monitored

  • BRCA or homologous recombination test before starting
  • Complete blood count at baseline and during treatment
  • New cough, wheeze or breathlessness
  • Signs of deep vein thrombosis or pulmonary embolism

Administration and safety

  • Oral; swallowed whole, never split, crushed, chewed or opened.
  • Grapefruit, Seville oranges, their juices and St John's wort are avoided.

Pregnancy and breastfeeding

Avoid in pregnancy. Can harm the fetus: a pregnancy test is done before starting, effective contraception is used during treatment and for a time afterwards (by women and by men with partners who could conceive), and breastfeeding is avoided.

Nursing care

  • Review blood counts before and during treatment; teach to report pallor, fatigue, bruising, bleeding or fever.
  • Teach to report new cough, wheeze, breathlessness or fever.
  • Teach the signs of a leg clot (pain, swelling) and of pulmonary embolism (chest pain, sudden breathlessness).
  • Contraception for women and for men with partners who could conceive; men do not donate sperm during treatment and for months after.

Pharmacokinetics

Absorption
Oral tablets, rapidly absorbed, with or without food.
Metabolism
Liver, mainly CYP3A4.
Half-life
About 15 hours.

Test yourself

Think of the answer, then tap the question to see it.

Why does olaparib kill BRCA-mutated cancer cells but spare normal cells?

Normal cells repair the resulting double-strand breaks by homologous recombination; BRCA-deficient cells cannot (synthetic lethality).

In which four cancers is olaparib used?

Ovarian (with fallopian tube and peritoneal), breast, pancreatic and prostate cancer.

Which rare but often fatal complication requires blood count monitoring on olaparib?

Myelodysplastic syndrome or acute myeloid leukaemia.

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More Pharmacology questions →

Connections

← Back to the class: PARP inhibitors

Educational content on how drugs work; not a prescribing guide and no substitute for a health professional's advice. No doses are given.

Sources: Olaparib: MedlinePlus Drug Information (MedlinePlus (U.S. National Library of Medicine), 2023); Olaparib - NCI (National Cancer Institute, 2025); ATCDDD - ATC/DDD Index (WHO Collaborating Centre for Drug Statistics Methodology, 2026).

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Representative model, for educational purposes only.