Lynparza (Olaparib)

What Is Lynparza and What Is It Used For?

Lynparza contains the active substance olaparib, which belongs to a class of anticancer medicines known as PARP inhibitors (poly[adenosine diphosphate-ribose] polymerase inhibitors). PARP enzymes play a critical role in repairing single-strand DNA breaks in cells. When PARP is blocked by olaparib, cancer cells that already have defective DNA repair mechanisms – such as those with BRCA1 or BRCA2 gene mutations – are unable to repair their DNA effectively, leading to an accumulation of DNA damage and ultimately cell death. This concept is known as synthetic lethality.

Normal, healthy cells retain alternative DNA repair pathways and are therefore less affected by PARP inhibition. This selectivity gives Lynparza a favourable therapeutic window: it preferentially kills cancer cells while largely sparing normal tissue. The cancer cells that are susceptible to Lynparza can be identified through genetic testing for BRCA mutations or through assessment of genomic instability, which indicates broader homologous recombination deficiency (HRD).

When Lynparza is used in combination with abiraterone (an androgen receptor signalling inhibitor), the combination can help improve effectiveness against prostate cancer cells regardless of whether they carry faulty DNA repair genes (such as BRCA mutations). This broader applicability is an important clinical advancement for patients with metastatic castration-resistant prostate cancer.

Approved Indications

Lynparza has received regulatory approval from the European Medicines Agency (EMA), the U.S. Food and Drug Administration (FDA), and other international regulatory bodies for the following indications:

• BRCA-mutated ovarian cancer: As maintenance therapy after first-line or subsequent platinum-based chemotherapy in patients with BRCA-mutated high-grade serous ovarian cancer that has responded to treatment
• Recurrent ovarian cancer: As maintenance therapy in patients with recurrent ovarian cancer that has responded to platinum-based chemotherapy, regardless of BRCA status
• HRD-positive ovarian cancer with bevacizumab: As maintenance therapy in combination with bevacizumab in patients with HRD-positive (defined by a BRCA mutation or genomic instability) advanced ovarian cancer that has responded to first-line platinum-based chemotherapy plus bevacizumab
• BRCA-mutated, HER2-negative early breast cancer: As adjuvant (post-surgery) treatment in patients at high risk of recurrence who have received prior chemotherapy. Patients with hormone receptor-positive cancer may also receive concurrent hormonal therapy
• BRCA-mutated, HER2-negative metastatic breast cancer: In patients who have received prior chemotherapy
• BRCA-mutated pancreatic cancer: As maintenance therapy in patients with germline BRCA-mutated metastatic pancreatic adenocarcinoma that has not progressed on first-line platinum-based chemotherapy
• BRCA-mutated metastatic prostate cancer: As monotherapy in patients with metastatic castration-resistant prostate cancer (mCRPC) who have progressed after prior hormonal therapy (such as enzalutamide or abiraterone)
• Metastatic prostate cancer (combination therapy): In combination with abiraterone and prednisone or prednisolone for mCRPC, regardless of BRCA status
• Mismatch repair proficient endometrial cancer: In combination with durvalumab for advanced or recurrent endometrial cancer with mismatch repair proficiency (pMMR) that has not progressed after initial platinum-based chemotherapy in combination with durvalumab

What Should You Know Before Taking Lynparza?

Contraindications

You must not take Lynparza if you have a known allergy (hypersensitivity) to olaparib or to any of the inactive ingredients in the tablets. Allergic reactions can range from mild skin rash to severe symptoms including difficulty breathing, swelling of the face (angioedema), and anaphylaxis. You must also not take Lynparza while breastfeeding, as it is unknown whether olaparib passes into breast milk and could potentially harm a nursing infant.

If you are uncertain whether any of these contraindications apply to you, speak with your oncologist, pharmacist, or nurse before starting treatment with Lynparza.

Warnings and Precautions

Talk to your doctor, pharmacist, or nurse before or during treatment with Lynparza if any of the following apply to you:

• Low blood cell counts: Lynparza commonly causes anaemia (low red blood cells), neutropenia (low white blood cells), and thrombocytopenia (low platelets). If your blood counts are already low before starting treatment, your doctor will monitor you especially carefully. In a small number of patients, persistently low blood counts may be a sign of more serious bone marrow disorders such as myelodysplastic syndrome (MDS) or acute myeloid leukaemia (AML).
• Lung inflammation (pneumonitis): A small number of patients treated with Lynparza have developed inflammation in the lungs. Symptoms include new or worsening shortness of breath, cough, or wheezing. Pneumonitis is a serious condition that often requires hospital treatment.
• Blood clots: Some patients taking Lynparza have developed deep vein thrombosis (DVT, usually in the leg) or pulmonary embolism (blood clot in the lungs). Seek immediate medical attention if you experience pain or swelling in your arms or legs, shortness of breath, chest pain, or an unusually rapid heartbeat or breathing rate.
• Liver problems: Contact your doctor immediately if you notice yellowing of the skin or eyes (jaundice), unusually dark urine, pain in the right side of the abdomen, tiredness, reduced appetite, or unexplained nausea and vomiting, as these may be signs of liver dysfunction.

Blood Tests and Monitoring

Before and during treatment with Lynparza, your doctor will perform regular blood tests to monitor your blood cell counts and organ function. Blood tests are typically performed:

• Before starting treatment (baseline)
• Every month during the first year of treatment
• At regular intervals determined by your doctor after the first year

If your blood counts become too low, your doctor may pause or reduce your dose of Lynparza, or you may require a blood transfusion. Persistent abnormalities may require further investigation, including bone marrow biopsy, to rule out MDS or AML.

Pregnancy and Breastfeeding

For female patients: You must not take Lynparza if you are pregnant or could become pregnant, as the medicine may harm an unborn baby. A pregnancy test must be performed before starting treatment, at regular intervals during treatment, and 6 months after the last dose. You must use two effective methods of contraception during treatment and for 6 months after your last dose. It is not known whether Lynparza affects hormonal contraceptives; your doctor may recommend adding a non-hormonal method. You must not breastfeed during treatment or for 1 month after your last dose.

For male patients: You must use a condom during sexual intercourse with a female partner (even if she is pregnant) during treatment and for 3 months after your last dose, as it is not known whether olaparib passes into semen. Your female partner should also use reliable contraception. You must not donate sperm during treatment or for 3 months after your last dose.

Driving and Using Machines

Lynparza may affect your ability to drive and use machines. If you feel dizzy, weak, or tired while taking Lynparza, do not drive or operate machinery until the symptoms have resolved. Fatigue and dizziness are common side effects and may impair your concentration and reaction time.

How Does Lynparza Interact with Other Drugs?

Olaparib is primarily metabolised by the cytochrome P450 enzyme CYP3A4/5. This means that any drug which inhibits or induces this enzyme system can significantly alter olaparib blood levels, potentially leading to increased toxicity or reduced therapeutic effect. Additionally, olaparib itself is an inhibitor of certain drug transporters (P-glycoprotein, OATP1B1, OCT1, OCT2, OAT3, MATE1, MATE2K, and BCRP), which means it can increase the blood levels of other drugs that are substrates of these transporters.

Always inform your doctor, pharmacist, or nurse about all medications you are taking, including prescription medicines, over-the-counter products, and herbal remedies. The following table summarises the most clinically significant drug interactions with Lynparza:

This is not an exhaustive list. Always tell your doctor about all medicines, supplements, and herbal products you are taking. Your oncologist and pharmacist can assess potential interactions and adjust your treatment plan accordingly.

What Is the Correct Dosage of Lynparza?

Always take Lynparza exactly as your doctor, pharmacist, or nurse has told you. It is important to take the full recommended dose each day and to continue taking it as directed. Lynparza tablets should be swallowed whole – do not chew, crush, dissolve, or split the tablets, as this may affect how quickly the medicine enters your body.

Standard Adult Dose

Dose Adjustments

Your doctor may prescribe a different dose in the following circumstances:

Treatment Duration

The duration of Lynparza treatment varies by indication. For maintenance therapy in ovarian cancer, treatment typically continues for up to 2 years or until disease progression, whichever comes first. For adjuvant breast cancer treatment, the recommended duration is also up to 2 years. For prostate and pancreatic cancer, treatment generally continues until disease progression or unacceptable toxicity. Your oncologist will determine the appropriate treatment duration for your specific situation.

Missed Dose

If you forget to take a dose of Lynparza, take your next dose at the usual scheduled time. Do not take a double dose (two doses at the same time) to make up for a missed dose. If you are unsure what to do, contact your pharmacist or nurse for advice.

Overdose

If you take more Lynparza than your usual dose, contact your doctor or go to the nearest hospital emergency department immediately. Bring the medicine packaging with you so that medical staff can identify what you have taken.

What Are the Side Effects of Lynparza?

Like all medicines, Lynparza can cause side effects, although not everyone gets them. The side effects listed below have been reported in clinical trials of patients receiving Lynparza as monotherapy. Some side effects may occur at different frequencies when Lynparza is used in combination with other medicines (such as durvalumab). Tell your doctor immediately if you experience any symptoms of serious side effects.

Side Effect Frequency Overview (Lynparza Monotherapy)

Additional Side Effects with Durvalumab Combination

When Lynparza is used in combination with durvalumab for endometrial cancer, the following additional side effects have been reported at higher frequencies than with Lynparza alone:

• Very common: Low platelet count (thrombocytopenia), rash
• Common: Allergic reactions (hypersensitivity), pure red cell aplasia (PRCA – cessation of red blood cell production)

Your doctor will perform blood tests monthly during the first year and periodically thereafter to detect any changes in your blood counts or organ function that may require treatment adjustments.

How Should You Store Lynparza?

Keep Lynparza out of the sight and reach of children. Do not use this medicine after the expiry date stated on the carton and blister pack after “EXP”. The expiry date refers to the last day of that month.

There are no special temperature storage requirements for Lynparza tablets. However, keep the tablets in their original blister packaging to protect them from moisture. Do not remove tablets from the blister until you are ready to take them.

Do not dispose of Lynparza tablets via household waste or wastewater. Return any unused or expired tablets to your pharmacist for safe disposal. These measures help to protect the environment, as olaparib is a potent anticancer agent.

What Does Lynparza Contain?

Active Ingredient

Each Lynparza 100 mg film-coated tablet contains 100 mg of olaparib. Each Lynparza 150 mg film-coated tablet contains 150 mg of olaparib.

Inactive Ingredients (Excipients)

Tablet core: Copovidone, colloidal anhydrous silica, mannitol, sodium stearyl fumarate.

Film coating: Hypromellose, macrogol 400, titanium dioxide (E171), yellow iron oxide (E172), black iron oxide (E172) (150 mg tablets only).

This medicine contains less than 1 mmol sodium (23 mg) per 100 mg or 150 mg tablet, meaning it is essentially sodium-free.

Tablet Appearance

Lynparza 100 mg tablets are yellow to dark yellow, oval, biconvex, film-coated tablets debossed with “OP100” on one side and plain on the other.

Lynparza 150 mg tablets are green to grey-green, oval, biconvex, film-coated tablets debossed with “OP150” on one side and plain on the other.

Lynparza is available in packs of 56 film-coated tablets (7 blisters of 8 tablets each) or multipacks of 112 tablets (2 packs of 56). Not all pack sizes may be marketed in all countries.

How Does Lynparza Work? (Mechanism of Action)

DNA is constantly being damaged by normal cellular processes and environmental factors. Cells have evolved multiple pathways to repair this damage and maintain genomic integrity. Two of the most important repair pathways are base excision repair (BER), which handles single-strand DNA breaks, and homologous recombination repair (HRR), which repairs double-strand DNA breaks.

PARP enzymes, particularly PARP-1 and PARP-2, play a central role in BER. When a single-strand break occurs, PARP binds to the break site, recruits repair proteins, and facilitates repair. Olaparib both inhibits PARP enzymatic activity and “traps” PARP on the DNA at the break site, preventing the break from being repaired and converting it into a more lethal double-strand break during DNA replication.

In normal cells, these double-strand breaks can be repaired by the HRR pathway, which relies on functioning BRCA1 and BRCA2 proteins (among others). However, in cancer cells that carry BRCA1 or BRCA2 mutations – or other defects in the HRR pathway – this backup repair mechanism is non-functional. Without either BER (blocked by olaparib) or HRR (disabled by the mutation), the cancer cell cannot repair its DNA and dies. This elegant concept of targeting two complementary weaknesses is called synthetic lethality.

This mechanism explains why genetic testing is so important before starting Lynparza: the drug is most effective in cancers that already have impaired DNA repair. Beyond BRCA mutations, other genes involved in HRR (such as ATM, PALB2, RAD51, CHEK2, and others) may also predict response to PARP inhibition, and ongoing research continues to expand the understanding of which patients benefit most.

After oral administration, olaparib is rapidly absorbed, reaching peak plasma concentrations within approximately 1.5 hours. It has a mean elimination half-life of about 12 hours, supporting twice-daily dosing. Olaparib is metabolised primarily by the CYP3A4/5 enzyme system and is eliminated roughly equally through urine (44%) and faeces (42%).

Frequently Asked Questions