Current information on drug interactions between sunitinib and other drugs is scarce and most of the times it is difficult to apply to clinical practice. Even so, this difficulty in managing drug interactions should not be a reason to ignore them as they can help to explain intolerances and treatment failures.
Background As vaginal flucytosine is not commercially available, it is necessary to prepare this formulation in the Pharmacy Department. Purpose To describe the preparation of flucytosine 15.5% (FLUCY15.5), and flucytosine 17% + amphotericin 3% (FLUAM) creams for vaginal use and their efficacy in the treatment of Candida glabrata and Candida tropicalis. Materials and methods FLUCY15.5 was prepared as follows: Twenty-eight 500 mg capsules of flucytosine (Ancotil) were opened into a mortar and the contents crushed. The powder was mixed with glycerine to form a paste. Cold Cream was added up to 90 g. It was blended until smooth. The procedure for preparing FLUAM was: Thirty-one 500 mg capsules of flucytosine were opened into a mortar and the contents crushed. Then 2.7 g of amphotericin B powder were added and mixed with glycerine to create a paste. Acuagel was added to a total weight of 90 g. It was blended until smooth. An expiry date of 14 days was given, although according to the Spanish Pharmacopoeia the stability of these formulations is 3 months. Vaginal applicators were used to apply the cream intravaginally. Results A 36-year-old woman with vulvovaginitis (positive culture for C. glabrata resistant to itraconazole and sensitive to amphotericin B, flucytosine, fluconazole and voriconazole in January 2009), was treated with oral and intravenous fluconazole, vaginal ketoconazole, intravenous voriconazole and vaginal boric acid. However, in February 2009 the culture was still positive. The physician prescribed 5 g/day vaginal FLUCY 15.5 for 14 days. For preparation details see materials and methods. After this treatment, the culture became negative (April 2009). Unfortunately, in March 2010, the patient again developed pain and vaginal itching. Culture of vaginal discharge was positive for C. tropicalis. The physician prescribed 5 g/day vaginal FLUAM and oral fluconazole 50 mg/day for 14 days. It was prepared as indicated above. After this treatment, the culture was negative (April 2010). Conclusions Local treatment with flucytosine and amphotericin B was effective against vaginal infections caused by non-albicans Candida species.
Background Valproic acid (VPA) is 90–95% protein bound to albumin; this binding can be saturated so other parameters that can modify the free fraction of VPA should be taken into account. Purpose To identify areas for improvement in VPA use and monitoring in a tertiary hospital where the pharmacy service does not routinely send pharmacokinetic dose adjustment recommendations. Materials and MethodsA retrospective study was conducted from February to April 2012. All patients treated with VPA were included and grouped depending on whether VPA was part of their home treatment or not. Variables collected were: dose, indication, total VPA serum concentration (C), drug interactions classified as ≥C by Lexi-Comp, glomerular filtration rate (GFR), Child-Pugh score, albumin and bilirubin. Results 30 patients were treated with VPA, 24 of whom were on VPA before admission (15 epilepsy, 9 psychiatric disorders and 1 unknown reason). Reasons for admission were: 5 convulsions, 12 psychiatric disorders and 13 causes unrelated to VPA. At discharge 27 patients continued on VPA with a mean dose similar to the dose at admission. C was determined in 14 patients: 5 were within the reference range (50–100 mg/L); 2 above, achieving therapeutic levels before discharge and 7 below. In these latter cases, 3 had an albumin <4.2 g/dL, but none reached C > 50 mg/L after correcting it with the J. Hermida formula which is a theoretical method for normalising C in hypoalbumenic patients. GFR, Child-Pugh score and bilirubin were normal. Mean time between changes in dose and C determinations was 1.5 days (0–5 days). 21 drug interactions were detected in 15 patients, involving a total of 10 drugs. Only 2 interactions were reported: VPA meropenem and VPA lamotrigine. Conclusions Changes in free fraction of VPA, due to hypoalbuminaemia, liver or kidney disease and hyperbilirubinaemia, must be detected. C should be measured once a steady state has been achieved (3–5 days). Drug interactions affecting VPA should be added to the pharmacy service’s interaction notification programme. No conflict of interest.
Background During recent years, an increase in the incidence of Invasive Fungal Infections (IFI) has been observed, in parallel to a progressive shift of invasive species from Candida albicans to fungi resistant to previously-effective treatments. The use of echinocandins in this context is spreading as an alternative to azoles. Purpose To determine the distribution of invasive fungal species in the population of patients treated with echinocandins in our hospital and the outcomes in this context over a year. Materials and methods All patients treated with echinocandins during 2010 were evaluated. Data such as sex, age and length of hospital stay were taken from the electronic chart. Information regarding treatment with caspofungin and anidulafungin was taken from electronic prescription programs. Results The authors identified 136 patients: 97 were men, the median of age was 65 years (17 months to 84 years) and median duration of hospital stay 37 days (2-137 days). There were 160 prescriptions: 127 for caspofungin, 33 for anidulafungin. The median duration of treatment was 7 days (1-37 days). In 52 prescriptions a positive isolate for fungi was detected. Of them, 26.9% (14) cultures were positive for C. albicans, 14 positive for species less susceptible to echinocandins (C. parapsilosis and A. fumigatus) and 29 positive for non-albicans susceptible species. In 5 cultures, two different species were found. 28.6% of patients exposed to species less susceptible to echinocandins died during the treatment (4 patients). Among the population whose positive cultures were sensitive to echinocandins, there were 6 deaths (15.8%). Conclusions The population studied confirms the tendency pointed out on the literature, a shift towards species different from C. albicans in IFI. Though the use of echinocandins seems to be effective and safe, attention should be paid to local sensitivities since less susceptible species such as C. parapsilosis and A. fumigatus are spreading
Background Linezolid is an antimicrobial approved for the treatment of hospital or community-acquired pneumonia and complicated skin and soft tissue infections due to Gram positive bacteria. Its use, though effective, is not free from possible harm. PurposeTo describe the incidence and nature of the adverse reactions related to linezolid, taking place before and after the 28-day limit given in the label information. Materials and MethodsAll the linezolid treatments over one year (September 2011–September 2012) were recorded. Data sources were the electronic chart as well as the electronic prescription programme. Results280 cases were recorded, the median treatment duration being 8 days (1 to 73 days). 4 treatments were interrupted early due to potential interactions with antidepressants. A total of 27 patients developed adverse reactions. Among the 255 patients treated for less than 28 days, 19 developed adverse reactions. 14 presented suppression of at least one myeloid cell line, 7 of them requiring transfusions (one with adverse skin reaction as well). Among the others, two had diarrhoea, one a skin reaction, one vomiting and the remaining patient, asthenia. Median treatment duration in patients with adverse reactions treated for less than 28 days was 12 days (3 to 27 days) 25 patients exceeded 28 days of treatment, 8 of whom had adverse reactions. Seven presented suppression of at least one myeloid cell line, 5 of whom required transfusion. The other patient suffered from asthenia. Median treatment duration in these patients was 37 days (32 to 56 days). Conclusions Attention should be paid to blood cell counts from the beginning of the treatment, since, as seen, hematologic adverse reactions are not limited to treatments lasting more than 28 days. The same is applicable to other less frequent reactions such as skin reactions, vomiting and asthenia. No conflict of interest.
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