Lynparza

RED FLAG (IMPORTANT) INFORMATION — LYNPARZA (OLAPARIB)

• Myelosuppression is common → monitor FBC monthly (or more often initially). Risk of anaemia, neutropenia, thrombocytopenia.

• Risk of MDS/AML (rare but serious) — consider if persistent cytopenias, fatigue, frequent transfusions.

• Pulmonary toxicity → new cough, dyspnoea, fever → evaluate for pneumonitis; stop if confirmed.

• Significant drug interactions via CYP3A → avoid strong CYP3A inhibitors (e.g., ketoconazole, clarithromycin) and inducers (rifampicin, carbamazepine, phenytoin, St John's Wort).

• Not to be used with other DNA-damaging agents or high-dose radiation (increased toxicity).

• Renal impairment requires dose adjustment (CrCl <50 mL/min).

• Embryo-foetal toxicity → avoid in pregnancy; use effective contraception.

• Risk of GI toxicity (nausea, vomiting, appetite loss) — commonly requires supportive care.

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1. BASIC INFORMATION

Generic name: Olaparib
Brand name: Lynparza
Drug class: PARP inhibitor (Poly ADP-ribose polymerase inhibitor)
Formulation: Film-coated tablets
Strengths: 100 mg, 150 mg
Mechanism of action:
Inhibits PARP-1, PARP-2 and PARP-3 → prevents single-strand DNA repair → tumour cell death, especially in BRCA-mutated and homologous recombination deficient (HRD+) cancers.

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2. INDICATIONS

Ovarian Cancer

• Maintenance treatment for platinum-sensitive relapsed ovarian cancer (BRCA-mutated).

• First-line maintenance therapy in BRCA-mutated advanced ovarian cancer.

Breast Cancer

• HER2-negative metastatic breast cancer with germline BRCA mutation.

Pancreatic Cancer

• Maintenance treatment for germline BRCA-mutated metastatic pancreatic cancer (post-platinum).

Prostate Cancer

• Metastatic castration-resistant prostate cancer (mCRPC) with HRR gene mutations (e.g., BRCA1/2).

• Use in combination with androgen deprivation therapy (ADT).

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3. DOSING & ADMINISTRATION

Standard dose:

• 300 mg twice daily (two 150 mg tablets twice daily)

• Total daily dose = 600 mg

Administration:

• Oral, swallow tablets whole.

• Can be taken with or without food.

• Avoid grapefruit / Seville oranges (CYP3A interaction).

Missed dose:

• Skip if >2 hours; do NOT double dose.

Treatment duration:

• Continue until disease progression or unacceptable toxicity.

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4. DOSE MODIFICATIONS

Renal impairment:

• CrCl 31–50 mL/min: Reduce dose to 200 mg twice daily

• CrCl ≤30 mL/min: Not recommended (insufficient data)

Hematological toxicity:

• Hold for haemoglobin <8 g/dL, neutrophils <1.0 ×10⁹/L, or platelets <50 ×10⁹/L.

• Resume when recovered; consider dose reduction.

Non-haematological toxicity:

• Hold for grade ≥3 toxicity; restart at reduced dose once resolved.

Dose reduction steps:

1. 250 mg BID

2. 200 mg BID
   (Do not reduce below 200 mg BID.)

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5. CO-MEDICATIONS

Avoid:

• Strong CYP3A inhibitors: ketoconazole, itraconazole, clarithromycin, ritonavir.

• Moderate CYP3A inhibitors: diltiazem, erythromycin, fluconazole → may require dose reduction.

• Strong CYP3A inducers: rifampicin, phenytoin, carbamazepine, St John’s Wort → drastically reduce olaparib levels.

Caution with:

• Drugs causing myelosuppression (e.g., cytotoxics, linezolid).

• Anticoagulants if thrombocytopenia occurs.

Safe:

• Standard anti-emetics, analgesics, PPIs, ADT (in prostate cancer).

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6. CONTRAINDICATIONS

• Hypersensitivity to olaparib or excipients.

• Pregnancy and breastfeeding.

• Severe renal impairment (CrCl <30 mL/min) — avoid.

• Not indicated in children.

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7. MONITORING REQUIREMENTS

Before starting:

• FBC

• Renal function

• Pregnancy test (if applicable)

• Baseline respiratory symptoms

During treatment:

• FBC monthly (most critical)

• Renal function periodically

• Monitor for respiratory symptoms

• Assess for prolonged cytopenias → rule out MDS/AML

• Monitor for GI tolerance and weight loss

Long-term:

• Persistent anaemia, neutropenia or thrombocytopenia → investigate for MDS/AML with bone marrow biopsy if needed.

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8. SIDE EFFECTS & MANAGEMENT

Very Common (>10%)

• Anaemia (may require transfusions)

• Nausea, vomiting

• Fatigue

• Diarrhoea/constipation

• Decreased appetite

• Dyspepsia

• Headache

• Cough/dyspnoea (monitor for pneumonitis)

Common (1–10%)

• Neutropenia

• Thrombocytopenia

• Weight loss

• Abdominal pain

• Dizziness

• Taste changes

• Increased creatinine

Serious (<1–2%)

• Myelodysplastic syndrome (MDS)

• Acute myeloid leukaemia (AML)

• Pneumonitis

• Severe cytopenias

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9. USE IN SPECIAL POPULATIONS

Elderly: No routine dose adjustment; monitor closely.
Renal impairment: Dose reduction below CrCl <50.
Hepatic impairment: No change for mild–moderate; avoid severe.
Pregnancy: Teratogenic; avoid.
Breastfeeding: Contraindicated.
Men (fertility): May cause infertility; consider sperm storage before starting.

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10. DURATION OF USE / WHEN TO STOP

Stop immediately if:

• Confirmed MDS/AML

• Severe persistent cytopenias

• Confirmed pneumonitis

• Severe hypersensitivity or intolerable toxicity

Otherwise continue until disease progression or intolerance.

 

 

https://pi-pil-repository.sahpra.org.za/wp-content/uploads/2024/07/pi-lynparza_20240701.pdf