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ID Week October 11-15, 2023; Boston USA

Global DDI Solutions

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During ID Week in Boston we launched the Fungal infections DDI Manager! In addition, we attended several presentations during this congress. In this meeting report, a couple of interesting presentations are summarized.

Pharmacokinetic Analysis of Co-Administering Doravirine, Tenofovir Disoproxil Fumarate, Estradiol, and Spironolactone

Lam et al.

This study is a two-way drug interaction trial between combination of doravirine, lamivudine and tenoforvir disoproxil fumarate (DOR/3TC/TDF) and estradiol and spironolactone in transgender women (man-to-woman). The aim was to research the effect of DOR/3TC/TDF on the pharmacokinetics of estradiol and spironolactone and vice versa. In addition, the safety and tolerability of the drug combination was defined with adverse effects. The effect of coadministration of DOR/3TC/TDF and estradiol and spironolactone on the testosterone concentrations was also determined.

The results shows no clinically significant interactions between DOR/3TC/TDF and estradiol and spironolactone in transgender women. The log paired difference (90% CI) of the AUC of DOR, TDF and estradiol were -0.03%, 0.15% and -0.03%, respectively.

Also, the combination of DOR/3TC/TDF and estradiol and spironolactone is safe and tolerable to use. Mild adverse events in intensity were observed, which were not related to the study interventions, and these were resolved before the end of the trial without additional action.
The concentration of testosterone was not changed by adding estradiol and spironolactone to the treatment with DOR/3TC/TDF.

In conclusion, the combination of DOR/3TC/TDF with estradiol and spironolactone in transgender women can used safely.

The Impact of Rifampicin on Blood Pressure in Patients Receiving Nifedipine: A Retrospective Study

Eljaady et al.

In this retrospective study, the effect of rifampicin on the systolic blood pressure (SBP) in patients who use nifedipine was researched in King Abdulaziz University Hospital. Rifampicin and nifedipine is a known DDI, due to induction of CYP3A4 by rifampicin and nifedipine is metabolized by CYP3A4. The effect of rifampicin on SBP is unknown.

Patients >18 years old with treatment of nifedipine were included. Patients with uncontrolled hypertension (>140 mmHg baseline SBP) and betablockers in use were excluded from the study. The treatment of rifampicin was initiated on day 1. The study outcomes were the change of SBP on day 1 to 8 compared to baseline.

16 patients were included in this study. The median maximum increase in SBP after starting rifampicin was 24 mmHg. The median SBP from day 2 to 8 are shown in the table. From day 3 with rifampicin the change in SBP was significant and clinically relevant.

DAY SYSTOLIC BLOOD PRESSURE (MMHG)

2 135 [128.5-141.5] (P=0.147)

3 146.5 [140.5-154.25] (P=0.002)

4 142.5 [132.75-160.5] (P=0.009)

5 149.5 [136-159.75] (P=0.005)

6 146.5 [134.25-159.5] (P=0.012)

7 149 [143.25-154.5] (p=0.007)

8 151.5 [143.75-163] (P=0.007)

In conclusion, rifampicin is associated with a significant and clinically relevant increase in SBP. To prevent increases in SBP, it is important for patients using nifedipine to substitute temporarily to another class of antihypertensive medications when rifampicin is initiated.