Table 1

Summary of pharmacokinetic and dose schedules

PARPiDoseTerminal half-lifeTarget and affinityMetabolismBaseline renal adjustmentHepatic adjustmentFoodInteractionStorage
Olaparib
tablet
300 mg twice daily
  • DL -1: 250 mg twice daily

  • DL -2: 200 mg twice daily


Capsule
formulation
400 mg twice daily
  • DL -1: 200 mg twice daily

  • DL -2: 100 mg twice daily*


Capsule and tablet doses are not bioequivalent.
15 hoursPARP1++
PARP2++++
CYP3A4/5Mild (CrCl 51–80 mL/min): no adjustment
Moderate (CrCl 31–50 mL/min): 200 mg twice daily
Severe (≤30 mL/min): no data
Mild: no adjustment
Moderate-severe: no data
Can be taken with/without food.
Avoid grapefruit, pomegranate, star fruit, and Seville oranges.
CYP3A inhibitor (eg, itraconazole, fluconazole.
CYP3A inducer (eg, rifampizine, efivarenz)
If administered with strong CYP3A inhibitor: reduce olaparib to 100 mg twice daily. Moderate inhibitor: olaparib 150 mg twice daily.
Store between 2°C and 30°C in original package
Niraparib
capsule
300 mg once daily *
  • DL -1: 200 mg once daily

  • DL -2: 100 mg once daily

36−48 hoursPARP1+++
PARP2+++
Metabolized by carboxylesterases, to form an inactive metabolite, which undergoes glucorinidationMild to moderate (CrCl 30–89 mL/min): no adjustment
Severe (≤30 mL/min): no data
Mild: no adjustment
Moderate-severe: no data
Can be taken with/without foodNiraparib is a weak inducer of CYP1A2. Caution is recommended for drugs that are sensitive substrates of CYP1A2.
Niraparib is also a substrate and weak inhibitor of P-gp, and weak inhibitor of BCRP. Caution with drugs that use these transporters.
Store up to 25°C in original package
Rucaparib
tablet
600 mg twice daily
  • DL -1: 500 mg twice daily

  • DL -2: 400 mg twice daily

  • DL -3: 300 mg twice daily

17–19 hoursPARP++++Mainly CYP2D6
CYP1A2 and CYP3A4 to a lesser extent
Mild to moderate (CrCl 30–89 mL/min): no adjustment
Severe (≤30 mL/min): no data
Mild: no adjustment
Moderate-severe: no data
Can be taken with/without food.
Rucaparib may increase the blood levels and effects of caffeine.
CYP1A2, CYP3A4, CYP2C9, CYP2C19, P-gp and BCRP inhibitor. Caution with sensitive substrates.Store between 20°C to 25°C in original package
Veliparib
capsule
With chemotherapy†:
150 mg twice daily
  • DL -1: 100 mg twice daily

  • DL-2: 50 mg twice daily


Maintenance:
400 mg twice daily
  • DL-1: 300 mg twice daily

  • DL -2: 250 mg twice daily

6 hoursPARP1++
PARP2+++
Mainly CYP2D6Mild (CrCl 60–89 mL/min): no adjustment
Recommend dose adjust according to CrCl
Mild: no adjustment
Moderate-severe: no data
Can be taken with/without foodDrug interactions are unlikelyStore between 15°C and 25°C in original package
Talazoparib
capsule
1 mg once daily
  • DL -1: 0.75 mg once daily

  • DL -2: 0.5 mg once daily

  • DL -3: 0.25 mg once daily

90 hoursPARP1++++Minimal hepatic metabolism.Mild (CrCl 60–89 mL/min): no adjustment
Moderate (CrCl 31–59 mL/min): 0.75 mg
Severe (≤30 mL/min): no data
Mild: no adjustment
Moderate-severe: no data
Can be taken with/without food.P-gp inhibitors (eg, amiodarone, carvedilol, clarithromycin, itraconazole, verapamil). Reduce talazoparib dose.Store between 15°C and 30°C in original package
  • *Niraparib starting dose to be calculated based on baseline platelets and weight. If weight <77 kg or platelet count <150×109 cells/L, a starting dose of 200 mg daily is recommended.

  • †Veliparib in combination with carboplatin and paclitaxel as part of VELIA clinical trial.

  • BCRP, breast cancer resistance protein; CrCl, creatinine clearance; CYP, cytochrome P450; DL, Dose level; PARPi, poly (ADP-ribose) polymerase (PARP) inhibitor; P-gp, P-glycoprotein.