Practical considerations for clinicians for transitioning patients on maintenance therapy with olaparib capsules to the tablet formulation of olaparib

Abstract

Purpose Olaparib was originally formulated as 50 mg capsules with a recommended dose of 400 mg twice daily which requires patients to take 16 capsules a day. More recently, a tablet formulation with equivalent efficacy has become available and reduces the pill burden for patients to two tablets twice daily which is more convenient for patients. However, it is important to understand the key differences between the olaparib capsule and tablet formulations as they are not bioequivalent, and the doses are not interchangeable. Educating patients when transitioning from capsules to tablets is critical to avoid dosing errors and maintain both safety and efficacy of olaparib maintenance therapy. Main recommendations There are no established guidelines on transitioning patients from capsules to tablets. Patients taking 400 mg of the capsules twice daily should be switched to 300 mg of the tablets twice daily. In patients on a reduced dose of 200 mg capsules twice daily, consider switching to 250 mg twice daily of the tablet formulation. In patients on 100 mg capsules twice daily, consider 200 mg tablets twice daily. Particular care should be taken in transitioning patients who are on a reduced dose due to anemia and who have a low hemoglobin (9 g/dL) where a lower dose of the tablets should be considered initially. Close monitoring of patients for the first 3 months with further dose reductions based on tolerability is recommended. The tablet dose can be escalated or de‐escalated depending on tolerance.

Real-World Experience of Olaparib Maintenance in High-Grade Serous Recurrent Ovarian Cancer Patients with BRCA1/2 Mutation: A Korean Multicenter Study

“…In Study 19, which administered olaparib in capsule form, 68.4% of patients experienced nausea and 16.9% experienced anemia [3] compared to 76% with nausea and 43% with anemia in the SOLO2 study that administered olaparib in tablet form. Currently, there are no established guidelines for transitioning patients from capsules to tablets for olaparib [11]. However, there should be further studies of capsules and tablets to determine their relative efficacy and safety.…”

Olaparib dose re‐escalation in ovarian cancer patients who experienced severe and/or uncommon adverse events: A case series

“…In real‐world studies, dose adjustments occurred in about 20% of patients 19 . Friedlander et al 20 . recommended that dose re‐escalation may be reasonable for AEs that are self‐limiting (e.g., nausea, which tends to improve over time), but may demand more caution in anemic patients requiring transfusions.…”

Adverse events in women switching from olaparib capsules to tablets: retrospective observational study of US claims data

“…Switching patients from olaparib capsules to tablets may help to improve compliance by reducing pill burden and offering a more convenient dosage regimen [3]. Switching from olaparib capsules to tablets may appear challenging for clinicians and patients, because capsule and tablet doses are not interchangeable, patients require close monitoring for AEs during the first 3 months, and dose adjustment may be required [14]. Real-world data evaluating tolerability and dosing outcomes among patients who switch from olaparib capsules to tablets are therefore desirable.…”

“…Despite dosing and bioavailability differences between olaparib capsules and tablets, consistency of clinical outcomes between the 400 mg bid capsule dose and the 300 mg bid tablet dose suggest similar benefit-risk profiles [13,14]. Adverse events (AEs) appear comparable; for example, nausea and vomiting are generally low grade and manageable for both formulations [9,[12][13][14][15].…”

“…The capsule and tablet doses are not interchangeable, due to differences in bioavailability [11], and physicians are advised to adhere strictly to the dosing instructions provided in the prescribing information when transitioning patients from capsules to tablets [5,7,14]. Practical guidelines recommend that patients switching from olaparib capsules to tablets should be monitored closely for the first 3 months and their dose adjusted according to tolerability; particular care should be taken when transitioning patients who are prescribed capsules below the licensed starting dose [14].…”