What is the recommended starting dose of olaparib (Lynparza) for adult patients, and how should the dose be adjusted in moderate renal impairment (creatinine clearance 30–50 mL/min) or moderate hepatic impairment (bilirubin >1.5× upper limit of normal or AST/ALT >2.5× upper limit of normal)?

Olaparib Dosing Recommendations

The recommended starting dose of olaparib tablets is 300 mg twice daily (two 150 mg tablets), and this dose should be reduced to 200 mg twice daily in patients with moderate renal impairment (creatinine clearance 30–50 mL/min). 1

Standard Dosing for Adult Patients

• The approved tablet formulation of olaparib is dosed at 300 mg twice daily (two 150 mg tablets) for most adult patients 2, 3
• This tablet dose replaced the older capsule formulation (400 mg twice daily as eight 50 mg capsules) due to improved bioavailability and reduced pill burden 2
• The capsule and tablet formulations are not interchangeable due to different bioavailability profiles, so prescribers must strictly adhere to the dosing instructions specific to each formulation 2

Dose Adjustment in Moderate Renal Impairment (CrCl 30–50 mL/min)

• Reduce the dose to 200 mg twice daily in patients with moderate renal impairment (estimated creatinine clearance 31–50 mL/min) 1
• This recommendation is based on pharmacokinetic data showing a 44% increase in olaparib exposure (area under the curve) in patients with moderate renal impairment compared to those with normal renal function 1
• The maximum plasma concentration increased by 26% in moderate renal impairment 1
• Close monitoring is essential in this population, even with dose reduction, due to the increased drug exposure 1

Dose Adjustment in Mild Renal Impairment (CrCl 51–80 mL/min)

• No dose adjustment is required for patients with mild renal impairment 1
• Although olaparib exposure increases by approximately 24% in mild renal impairment, this increase is not considered clinically significant 1
• The standard dose of 300 mg twice daily can be maintained 1

Hepatic Impairment Considerations

• No specific dose adjustment recommendations exist for moderate hepatic impairment (bilirubin >1.5× upper limit of normal or AST/ALT >2.5× upper limit of normal) in the available evidence
• The provided studies focused exclusively on renal impairment and did not evaluate hepatic dysfunction 1
• Olaparib is partially renally cleared, but hepatic metabolism also contributes to its elimination 1

Safety Profile and Monitoring

• The most common adverse events with olaparib include anemia (17% grade ≥3), fatigue, nausea, and vomiting 4, 5
• Grade ≥3 adverse events occur in approximately 54% of patients, with anemia being the most frequent serious toxicity 4
• In patients with renal impairment receiving dose-adjusted olaparib, no new safety signals were detected beyond the known toxicity profile 1
• Myelodysplastic syndrome and acute myeloid leukemia occurred in 2% of patients in registration trials, representing a serious but rare complication 5

Critical Dosing Pitfalls to Avoid

• Do not use the capsule dosing (400 mg twice daily) when prescribing tablets, as the formulations have different bioavailability and are not equivalent 2
• Do not fail to adjust the dose in moderate renal impairment, as the 44% increase in exposure significantly raises the risk of toxicity 1
• Do not assume hepatic impairment requires the same approach as renal impairment, as specific data are lacking and clinical judgment with close monitoring is required
• In the real-world study, all patients started at 300 mg twice daily, and 16% required dose adjustments due to adverse events, but none discontinued treatment 3