Should olaparib tablets be taken with food or on an empty stomach, and does the formulation or renal/hepatic impairment alter this recommendation?

Olaparib Tablet Administration with Food

Olaparib tablets can be taken with or without food, as food has minimal clinical impact on drug exposure. 1

Food Effect on Olaparib Pharmacokinetics

The definitive Phase I study evaluating food effects on olaparib 300 mg tablets demonstrated that:

• A high-fat meal decreases the rate of absorption and peak concentration (Cmax) by approximately 21%, but increases total drug exposure (AUC) by only 8% 1
• The time to peak concentration (Tmax) is delayed by 2.5 hours when taken with food 1
• The AUC treatment ratio (fed vs. fasted) falls within bioequivalence limits of 0.80-1.25, confirming no clinically significant difference 1

This minimal 8% increase in AUC when taken with food is not clinically meaningful and does not require dosing adjustments or specific timing instructions relative to meals. 1

Standard Dosing Recommendations

Tablet Formulation (Current Standard)

• The recommended dose is 300 mg (two 150 mg tablets) twice daily, taken with or without food 2, 3, 1
• This tablet formulation replaced the original capsule formulation due to improved bioavailability and reduced pill burden 3, 4

Critical Formulation Distinction

The capsule and tablet formulations are NOT bioequivalent and doses are NOT interchangeable: 5, 3

• The 300 mg tablet dose provides 13% higher AUC exposure than the previous 400 mg capsule dose 4
• Patients transitioning from 400 mg capsules twice daily should switch to 300 mg tablets twice daily 5, 3

Dose Modifications for Renal Impairment

Renal function significantly impacts olaparib dosing, unlike food intake:

• Mild renal impairment (CrCl 51-80 mL/min): No dose adjustment needed; the 24% increase in AUC is not clinically significant 6
• Moderate renal impairment (CrCl 31-50 mL/min): Reduce tablet dose to 200 mg twice daily due to 44% increase in drug exposure 6
• Severe renal impairment (CrCl <30 mL/min): Avoid use; insufficient safety data 6

These renal adjustments apply regardless of whether olaparib is taken with or without food. 6, 1

Hepatic Impairment Considerations

The provided evidence does not contain specific olaparib dosing recommendations for hepatic impairment. However, based on general principles:

• No hepatic dose adjustments are explicitly mentioned in the available guidelines for olaparib 2
• Patients with hepatic impairment should be monitored closely, but the food administration recommendation (with or without food) remains unchanged 1

Practical Clinical Algorithm

For all patients prescribed olaparib tablets:

1. Standard dose: 300 mg twice daily, taken with or without food 1
2. Check renal function (CrCl):
   • CrCl ≥51 mL/min → 300 mg twice daily 6
   • CrCl 31-50 mL/min → 200 mg twice daily 6
   • CrCl <30 mL/min → Avoid use 6
3. Patient counseling: Emphasize that tablets can be taken at any time relative to meals for convenience 1
4. Transitioning from capsules: Use conversion table (400 mg capsules = 300 mg tablets; 200 mg capsules = 250 mg tablets) 5

Common Pitfalls to Avoid

• Do not instruct patients to take olaparib on an empty stomach—this is unnecessary and reduces adherence without clinical benefit 1
• Do not interchange capsule and tablet doses—they have different bioavailability profiles 5, 3, 4
• Do not overlook renal function—moderate renal impairment requires dose reduction regardless of food timing 6
• Do not assume the 8% AUC increase with food requires dose adjustment—this falls within acceptable bioequivalence limits 1