Q2. PK and DDI: What are the DDIs with TAF?

PK and DDI:
What are the DDIs with TAF?

TAF 是 P 醣蛋白（P-gp）和乳癌抗性蛋白（BCRP）的作用受質。具誘導 P-gp 活性的藥物預期會降低 TAF 的吸收，從而導致 TAF 血中濃度下降，導致 TAF 療效減少 ¹。
TAF is transported by P-gp and BCRP. Drugs that strongly affect P-gp activity may lead to changes in TAF absorption. Drugs that induce P-gp activity are expected to decrease the absorption of TAF, resulting in decreased plasma concentrations of TAF, which may lead to loss of therapeutic effect of TAF.⁴
TAF 與下列藥物併用，並未發現任何具臨床意義的藥物交互作用（DDI）：ethinyl estradiol、midazolam、norgestimate、sertraline ¹。
TAF does not have clinically significant DDI with ethinyl estradiol, midazolam, norgestimate, and sertraline.⁴
有別於 TDF，TAF 與 C 型肝炎抗病毒藥物（例如 LDV/SOF、SOF/VEL、SOF/VEL/VOX）之間無明顯的 DDI ^1,2。
Unlike TDF, TAF does not have significant DDI with HCV antivirals such as LDV/SOF, SOF/VEL, SOF/VEL/VOX.⁴
抑制 P-gp 和 / 或 BCRP 的藥物，例如 cobicistat，可能會增加 TAF 的吸收。然而 TAF 及其活性代謝物 TFV 的暴露量，依然在療效與安全性的範圍內 ³。
When both TAF and TDF are administered with P-gp inhibitors, an increase in absorption may be observed.^4,5
- Patients receiving VIREAD concomitantly with lopinavir/ritonavir, ritonavir-boosted atazanavir, or ritonavir-boosted darunavir should be monitored for VIREAD-associated adverse reactions. VIREAD should be discontinued in patients who develop VIREAD-associated adverse reactions.⁵
Drugs that inhibit P-gp and/or BCRP, such as cobicistat, may increase the absorption of TAF. However, the overall TAF and TFV exposure observed are encompassed within the wide ranges of exposure shown to be safe and efficacious.⁶
- DESCOVY (F/TAF, TAF 25mg): no clinically significant drug interactions have been either observed or are expected when DESCOVY is combined with the following antiretroviral agents: atazanavir with ritonavir or cobicistat, darunavir with ritonavir or cobicistat, dolutegravir, efavirenz, ledipasvir, lopinavir/ritonavir, maraviroc, nevirapine, raltegravir, rilpivirine, and sofosbuvir.⁷
- GENVOYA (E/C/F/TAF, TAF 10mg): its availability is increased by cobicistat and a further increase of TAF concentration is not expected upon coadministration of an additional P-gp and or BCRP inhibitor.⁸

其他可能導致 TAF 濃度下降的藥物 ^1,4（Table 1）：
- 抗癲癇藥物：carbamazepine^*、oxcarbazepine^#、phenobarbital^#、phenytoin^#。
- 抗分枝桿菌藥物：rifabutin# 、rifampin# 、rifapentine^#。
- 草藥製劑：聖約翰草（貫葉連翹）［St John’s wort (Hypericum perforatum)］。
^*與 carbamazepine 併用時，應將 TAF 的劑量提高至 2 錠每日一次。
^#不建議與 TAF 併用。

References: 1. 韋立得膜衣錠。中文仿單［TWN-NOV20-US-FEB20-（EU-NOV17）］; 2. 惠立妥錠劑。中文仿單^® （TWN-APR19-US-JUL2018）; 3. Custodio JM, et al. IWCPHT, 2016, #P_59; 4. VEMLIDY^® [prescribing information]. Foster City, CA: Gilead Sciences, Inc.; August 2020; 5. VIREAD^® [prescribing information]. Foster City, CA: Gilead Sciences, Inc.; July 2018; 6. Custodio, 17th International Workshop on Clinical Pharmacology of HIV and Hepatitis Therapy, 2016; 7. DESCOVY^® [prescribing information] Foster City, CA. Gilead Sciences, Inc.: September 2017; 8. GENVOYA^® [prescribing information]. Foster City, CA: Gilead Sciences, Inc.; November 2017.

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