1.
The Effect of Switching from Tenofovir Disoproxil Fumarate (TDF) to Tenofovir Alafenamide (TAF) on Liver Enzymes, Glucose, and Lipid Profile.
Squillace, N, Ricci, E, Menzaghi, B, De Socio, GV, Passerini, S, Martinelli, C, Mameli, MS, Maggi, P, Falasca, K, Cordier, L, et al
Drug design, development and therapy. 2020;:5515-5520
Abstract
OBJECTIVE We aimed to investigate the effect of switching from tenofovir disoproxil fumarate (TDF) to tenofovir alafenamide (TAF) on the hepatic safety and metabolic profile. METHODS Consecutive HIV patients, enrolled in the Surveillance Cohort Long-term Toxicity Antiretrovirals/Antivirals (SCOLTA) project, switching from TDF to TAF were included. Changes from baseline (T0) to 6-month follow-up (T1) were evaluated using paired t-test and signed rank test. RESULTS A total of 190 patients switched from TDF to TAF and had one 6-month follow-up visit. They were 80% male, 74.2% at CDC stage A-B, 93.7% with undetectable HIV-viral load. Mean age was 46.7±10.7 years, body mass index was 25.0±3.9 kg/m2, median CD4 cell count was 634 cell/µL (interquartile range [IQR]=439-900), aspartate aminotransferase (AST) was 23 (IQR=19-30) IU/L, and alanine aminotransferase (ALT) was 24 (IQR=17-34) IU/L. At T1, both AST (median=-1, IQR=-5-2 IU/L, P=0.004) and ALT (median=-2, IQR=-7-3 IU/L, P=0.0004) showed a significant decrease. Among 28 patients with ALT >40 at baseline, reduction was significant both clinically (-17, IQR=-32--1) and statistically (P=0.0003). Total cholesterol levels (TC) increased (+13.4±3.8 mg/dL, P=0.0006), as well as HDL-cholesterol (HDL-C) (+3.8±1.2 mg/dL, P=0.02), LDL Cholesterol (LDL-C) (+7.6±3.4, P=0.03) and glucose (+4.0±1.8 mg/dL, P=0.02). D:A:D: and Framingham risk score did not change at 6 months after switch. CONCLUSION A significant reduction of liver enzymes was observed after switching from TDF to TAF, especially in subjects with initial level of ALT >40 IU/L. Glucose, TC, HDL-C, and LDL-C increased, with no effect on cardiovascular risk scores.
2.
Ergotism and factitious hypotension associated with interaction of ergotamine with CYP3A4 inhibitors.
Srisuma, S, Lavonas, EJ, Wananukul, W
Clinical toxicology (Philadelphia, Pa.). 2014;(7):674-7
Abstract
BACKGROUND Although uncommon, severe ergotism continues to occur. The purpose of this study is to describe causes and clinical effects of ergotism in recent years. METHODS This is an observational case series with data obtained retrospectively from all patients with ergotism referred to Ramathibodi Poison Center in Bangkok, Thailand from January 2006 to August 2013. RESULT Twelve cases of ergotism were identified. All cases involved ergotamine 1 mg/caffeine 100 mg combination tablets. Nine cases (75%) were precipitated by drug-drug interactions with CYP3A4 inhibitors. The other cases involved suicidal attempt (2 cases) and pediatric unsupervised ingestion (1 case). Ten patients (83%) had signs of peripheral vascular insufficiency. Five of these patients initially had factitiously low or unmeasurable blood pressure using non-invasive technique and had paradoxical increase following intravenous vasodilator administration. Two patients required partial foot amputations due to gangrene. Two patients, including a 15-month-old boy with an unsupervised ingestion, died. DISCUSSION In this series, most cases of severe ergotism were associated with interaction with CYP3A4 inhibitors, which increase ergotamine bioavailability. Factitious low blood pressure in these cases was likely caused by severe vasospasm. CONCLUSION Critical ergotism continues to occur in Thailand, most commonly associated with the drug-drug interactions.