Purpose Ethanol as an excipient is used to enhance the solubility of gemcitabine, but, sometimes, the dose of ethanol a patient may be given is much higher than the dose considered to be toxic. We aimed to assess ethanol-related symptoms and signs in patients receiving two formulations of gemcitabine, with and without ethanol. Methods A randomized double blind cross-over study was conducted. All patients being treated with gemcitabine received two consecutive doses of the drug, one diluted from a concentrate for solution for infusion (CSI) containing ethanol and the other from a lyophilized powder, without ethanol, which was used as control group. After each administration, patients were surveyed in order to assess the appearance of any alcohol consumption symptoms (dizziness, difficulty speaking, unsteady walking, impaired balance, mood swings and slower reactions). Widmark formula and the amount of alcohol measured on the breath (breathalyzer) were used to estimate blood alcohol concentration. Results Twenty-four patients received both formulations and were included in the analysis. Mean administered ethanol dose when prepared from CSI was 15.81 ± 2.25 g (mean ± SD). When using CSI gemcitabine, estimated blood ethanol concentration was 0.033 g/dl according to Widmark formula and 0.02 g/dl according to breathalyzer results. Although overall incidence of symptoms was higher in the study group, the difference was not statistically significant (33% vs. 25%; p = 0.53). Conclusions These findings prove there is no difference in the onset of ethanol related symptoms when using CSI instead of lyophilized powder on the reconstitution of gemcitabine.

Background Tenofovir (TNF) is one of the most used antiretroviral drugs for treatment of HIV infection worldwide. Although well tolerated, effects of TNF on renal function are still of concern. Purpose To assess the incidence of tenofovir-associated renal toxicity in HIV-infected patients and which factors may contribute to this adverse effect. Materials and methods Retrospective observational study in HIV-infected adult patients treated with TNF (January 2010–December 2012). Inclusion criteria: baseline normal creatinine clearance (CrCl), more than six months on TNF treatment and three CrCl determinations. Incidence of moderate (CrCl <60 ml/min) and severe (CrCl <30 ml/min) renal toxicity was calculated. Potential risk factors analysed were: age, gender, baseline CD4 and HIV-RNA, hepatitis, hypertension, diabetes, cardiovascular disease (CVD), AIDS, previous treatments and concomitant antiretroviral drugs. Continuous variables were compared by univariate analysis: T-Student or Mann-Whitney test and with Chi-square test for categorical variables. Multivariate analysis was performed on parameters with p < 0.10 in univariate models. p-values <0.05 were regarded as significant. Results 232 patients were included (72% male, mean age 42.5 ± 8.7 years). At baseline, comorbidity rates were: 8% diabetes, 17% dyslipidaemia, 9% CVD, 14% hypertension, 7% hepatitis B and 61% hepatitis C co-infection. 30% of patients had AIDS. Mean number of treatment lines prior to TNF was 2.4 ± 2.1 and 22% of patients were treatment-naïve. The incidence of moderate renal insufficiency was 23.9 per 1000 patient-years (IC95%:33.3–14.5) and 1.9 per 1000 patient-years (IC95%:0.0–4.5) for severe renal insufficiency. In the univariate analysis, variables related to toxicity were age, baseline creatinine, hypertension, and boosted protease inhibitor (PI) treatment. Treatment with non-analogues and treatment-naïve status were protective factors. In multivariate analysis, independent risk factors were age (OR = 1.1; IC95%1.5–7.7; p < 0.01), hypertension (OR = 2.8; IC95%1.2–6.8; p = 0.03), PI (OR = 3.2; IC95%1.3–6.9; p < 0.01) and baseline creatinine (OR = 37.9; IC95%3.5–410; p < 0.01). Conclusions Renal toxicity among tenofovir-treated patients is common although severe cases are scarce. Caution should be observed in older patients and those with hypertension, PI and higher baseline creatinine even within the normal range. No conflict of interest.