From the Guidelines
Sunitinib is typically taken orally as a capsule once daily with or without food, with a recommended dose of either 37.5 mg daily without interruption or 50 mg daily on a schedule of 4 weeks on treatment followed by 2 weeks off. The dosing regimen may vary depending on the specific condition being treated and potential interactions with other medications 1. It is essential to take sunitinib at approximately the same time each day to maintain consistent blood levels. If a dose is missed, patients should not double the next dose but instead continue with the regular schedule the following day. Some key points to consider when taking sunitinib include:
- Swallowing the capsules whole with water and not crushing or opening them
- Monitoring for common side effects such as fatigue, diarrhea, nausea, skin discoloration, and high blood pressure throughout treatment
- Potential interactions with other medications, particularly CYP3A4 inhibitors or inducers, which may require dose modification 1
- The importance of selecting an alternate concomitant medication with no or minimal enzyme induction potential to minimize potential interactions. Given the potential for significant interactions and side effects, it is crucial to closely monitor patients taking sunitinib and adjust the dosing regimen as needed to minimize adverse effects while maximizing therapeutic benefits 1.
From the FDA Drug Label
The pharmacokinetics of sunitinib and sunitinib malate have been evaluated in healthy subjects and in patients with solid tumors. Following oral administration of sunitinib, the time to maximum plasma concentration (T max) ranged from 6 to 12 hours The administration of a single dose of sunitinib 50 mg with a high-fat, high-calorie meal (consisting of approximately 150 protein calories and 500 to 600 fat calories) in healthy subjects had no clinically significant effect on sunitinib or active metabolites exposure.
Sunitinib Administration: Sunitinib is taken orally. The administration of sunitinib with a high-fat, high-calorie meal has no clinically significant effect on sunitinib exposure 2.
From the Research
Administration of Sunitinib
- Sunitinib is taken orally, with a typical dosing schedule of 50 mg daily for 4 weeks, followed by a 2-week rest period 3, 4, 5.
- The dosing schedule can be modified to a continuous daily administration at a lower dose, with the goal of maintaining the highest tolerable dose in individual patients 3.
- Food does not appear to affect the bioavailability of sunitinib 5.
Dosing Considerations
- The approved dose of sunitinib is 50 mg/d PO for 4 weeks, followed by a 2-week rest; this pattern is repeated until tumor progression or the occurrence of intolerable adverse effects 5.
- Therapeutic drug monitoring (TDM) may be useful in optimizing sunitinib exposure, with a target therapeutic range of 50-100 ng/mL for total (sunitinib + N-desethylsunitinib) trough levels 6, 7.
- Dose reduction may be necessary in patients who experience toxicity, with the goal of reducing sunitinib exposure to a safe and effective level 6, 7.
Pharmacokinetics
- Sunitinib is metabolized by cytochrome P450 (CYP) 3A4 to an active metabolite, SU12662, which is further metabolized by CYP3A4 to an inactive moiety 5.
- The parent compound and active metabolite have similar biochemical activity and potency, and reach similar plasma concentrations 5.
- Steady-state concentrations of both active entities are reached after 10 to 14 days of therapy 5.