Q1. Do you need to take TAF with food? How does food affect the bioavailability of the drug?

Do you need to take TAF with food? How does food affect the bioavailability of the drug?

依據 VEMLIDY^® 仿單， TAF 的建議劑量為每日一次口服 25 mg（一錠）。 TAF 單劑與高脂食物（約 800 大卡，50% 脂肪）併服，會增加 65% 的藥物暴露量 ¹。 Per the VEMLIDY US PI, the recommended dose of TAF is one tablet taken orally once daily with food.² Relative to fasting conditions, the administration of a single dose of TAF with a high fat meal resulted in a 65% increase in TAF exposure.³
一項單中心、隨機分配、開放標籤、交叉設計的第一期臨床試驗，探討食物對 TAF 的影響。40 位健康受試者分為禁食組與飲食組（800 kcal / ~50% 脂肪），兩組受試者皆在藥物洗除期（washout period）投予一錠 TAF（25 mg）。所有受試者的 TAF 暴露量皆在療效與安全性的臨床試驗範圍內（AUC: 17.3 – 2690 h•ng/mL; TAF: 8 – 120 mg）（Figure 1）³。
The effect of TAF and food and was studied in 40 healthy subjects in a phase 1, single-center, randomized, open label, two treatment, two period, crossover study. Patients from both the fasted and fed (high calorie/high fat; 800 kcal/~50% fat) groups were given a single dose of 25 mg of TAF followed by a washout period.³
- The overall TAF exposures in the present study under both fasted and fed conditions were in the range of exposures associated with efficacy and safety in the TAF CHB Phase 1B study (n=41; AUC range 17.3-1630 h•ng/mL; TAF evaluated at 8, 25, 40, and 120 mg) and Phase 3 study (n=698) AUC range was 56.6-2690 h•ng/mL for patients taking TAF 25 mg.
近期一項治療 96 週的次分析，探討食物攝取對 TAF 療效與安全性的影響，資料取自試驗 4018。分析結果顯示 ⁴：
A recent 96 weeks sub-analysis from study 4018 looked at the effect of food intake on the safety and efficacy with TAF.⁴
- TAF 的抗病毒療效可持續 96 週，服藥時搭配食物與否並不會影響療效（Figure 2）。
  At Week 96, antiviral efficacy was maintained, and treatment responses were similar in those taking study drug without vs with food.
- TAF 無論是否與食物併服，病人的腎功能和髖骨／脊椎骨密度皆有所改善（Figure 3, 4）。
  Improvements in eGFR and in hip/spine BMD were observed without regard to food.
- TAF 無論是否與食物併服，第 3 – 4 級不良事件和嚴重不良反應皆相近。
  Grade 3 or 4 adverse events and serious adverse events were generally comparable for those taking drug without vs with food, and in patients who took TAF without food for 96 weeks (TAF-TAF) or for 48 weeks (TDF-TAF).

AUC, area under the curve; BMD, bone mineral density; CHB, chronic hepatitis B; CI, confidence interval; CrCl, creatinine clearance; CV, coefficient of variation; eGFR, estimated glomerular filtration rate; GMR, geometric means ratio; PI, prescribing information; PK, pharmacokinetics; Q, quartile; SD, standard deviation; TAF, tenofovir alafenamide; TDF, tenofovir disoproxil fumarate; US, United States.

References: 1. 韋立得膜衣錠。中文仿單［TWN-NOV20-US-FEB20-（EU-NOV17）］; 2. VEMLIDY^® [prescribing information]. Foster City, CA: Gilead Sciences, Inc.; August 2020; 3. Custodio JM, et al. IWCPHT, 2016, #P_46; 4. Kao J-H, et al. AASLD 2020. 795.

TW-VEM-0044