Influence of the number of daily pills and doses on adherence to antiretroviral treatment: a 7-year study.

WHAT IS KNOWN AND OBJECTIVE: Antiretroviral treatment (ART) is hampered by complicated regimens, high pill burden, drug-drug interactions, and frequent short- and long-term adverse effects, leading to decreased adherence. Over recent years, considerable effort has been directed at developing regimens that are less burdening. We undertook a 7-year retrospective study of the records of 264 HIV-infected subjects enrolled in a pharmaceutical care programme to document the progress made and to study the influence of the number of ART pills and doses on the level of treatment adherence. METHODS: Antiretroviral dispensing records were analysed for the number of pills and doses administered and the ART adherence rate estimated. RESULTS AND DISCUSSION: In 2005, the patients took a mean of 6·2 pills daily (CI 95%: 5·9-6·6), and 92·9% of them were on a twice-a-day (BID) dosage regimen. By 2012, the mean number of pills was reduced to 4·1 (CI 95%: 3·8-4·4), and only 50·9% were on a BID regimen. No statistically significant relation was observed between number of daily pills and doses and ART adherence reached by the patients in any of the analyses performed. WHAT IS NEW AND CONCLUSIONS: There has been a continuous reduction in the number of pills and doses of antiretrovirals taken by individual patients over the last 7 years due largely to the introduction of improved treatments and regimens. More daily pills or doses was not associated with worse ART adherence in our pharmaceutical care programme.

[Prevalence and factors associated with preventable adverse drug events leading to hospital admission]. / Prevalencia y factores asociados a los acontecimientos adversos prevenibles por medicamentos que causan el ingreso hospitalario.

OBJECTIVE: To determine the prevalence of adverse drug events (ADEs) leading to hospital admission, and to assess those that were potentially preventable, identifying the drug classes involved, types of medication errors and the factors associated with the preventable ADEs. METHOD: An observational study, over a six-month period on ADEs that lead or contributed to hospital admissions, carried out in 6 medical units of a university hospital. RESULTS: A total of 259 ADEs were detected of which 159 (61.4%) were assessed to be potentially preventable. The overall prevalence of admissions directly due to ADEs was of 6.7% (177) and to preventable ADEs of 4.7% (125). In addition, 82 ADEs that contributed to hospital admission were detected. Risk factors for preventable ADEs were patient age of 65-74 (OR = 1.40) or = 75 years (OR = 2.70), self-medication (OR = 15.55), prescription in primary care (OR = 2,88) and the use of narrow therapeutic index drugs (OR = 2.40). The drug classes most frequently involved in preventable ADEs were NSAID and aspirin (32.5%), diuretics (15.3%), antihypertensives (9.1%) and digoxin (7.7%). Inadequate therapy monitoring (20.7%), prescription of an inappropriate drug (15.7%) or of an excessive dosage (12.0%), lack of preventive treatment (15.7%), non-adherence (10.6%) and inappropriate self-medication (10.1%) were the most commonly identified types of error. CONCLUSIONS: A high proportion (4.7%) of hospital admissions are caused by potentially preventable ADEs. Results obtained justified the need to adopt measures directed at improving surveillance and prescription quality, and educating patients in safe drug use, focusing especially on older patients and narrow therapeutic index drugs.

[Cost-utility analysis of relapsing-remitting multiple sclerosis treatment with azathioprine or interferon beta in Spain]. / Análisis coste-utilidad del tratamiento de la esclerosis múltiple remitente-recidivante con azatioprina o interferón beta en España.

AIM: To carry out a cost-utility analysis of the treatment of relapsing-remitting multiple sclerosis (RRMS) with azathioprine (Imurel) or beta interferon (all, Avonex, Rebif and Betaferon). MATERIAL AND METHODS: Pharmacoeconomic Markov model comparing treatment options by simulating the life of a hypothetical cohort of women aged 30, from the societal perspective. The transition probabilities, utilities, resource utilisation and costs (direct and indirect) were obtained from Spanish sources and from bibliography. Univariant sensitivity analyses of the base case were performed. RESULTS: In the base case analysis, the average cost per patient (euros in 2003) of a life treatment, considering a life expectancy of 53 years, would be 620,205, 1,047,836, 1,006,014, 1,161,638 and 968,157 euros with Imurel, all interferons, Avonex, Rebif and Betaferon, respectively. Therefore, the saving with Imurel would range between 327,000 and 520,000 euros approximately. The quality-adjusted life years (QALY) obtained with Imurel or interferons would be 10.08 and 9.30, respectively, with an average gain of 0.78 QALY per patient treated with Imurel. The sensitivity analyses confirmed the robustness of the base case. The cost of one additional QALY with interferons would range between 413,000 and 1,308,000 euros approximately in the hypothetical worst scenario for Imurel. CONCLUSIONS: For a typical patient with RRMS, treatment with Imurel would be more efficient than interferons and would dominate (would be more efficacious with lower costs) beta interferon.

[Antisense therapy in oncology: present situation]. / Terapia antisentido en oncología: situación actual.

The purpose of antisense therapy is to control the regulation of genes contributing to cancer progression while sparing normal cell growth, which represents a novel alternative with fewer side effects when compared to conventional chemotherapy. Antisense oligonucleotides control cell proliferation by specifically blocking the expression of selected genes, and hence they are being developed as molecular drugs with potential activity for cancer treatment. Extensive clinical information and a number of clinical trials show encouraging results. This review discusses the most significant aspects of this new therapeutic alternative in oncology. Clinical trials performed thus far have demonstrated their short- to mid-term efficacy and safety; however, long-term studies are needed to definitely define their clinical effectiveness and true toxic profile.

Peri-incisional and preoperative administration of cefmetazole for the prophylaxis of wound infection after appendicectomy.

The tissue and blood levels of Cefmetazole are compared after preoperative administration of a single dose of 30 mg/K body weight of the antibiotic administered intravenously (15 patients) and peri-incisionally (30 patients) to patients scheduled for emergency appendicectomy. Local and general tolerance to the antibiotic was good by both routes. No local or general complications arose in any of the patients. As expected, the tissue concentrations achieved with peri-incisional infiltration were significantly higher than those obtained by the intravenous route. With the blood levels, exactly the opposite happens at the start of the operation whereas at the end, there were no significant differences between the two routes employed. The prophylactic administration by peri-incisional infiltration is an easy and safe method which provides high tissue concentrations simultaneously with adequate blood levels and should be considered as useful in the preoperative administration of antibiotics for prophylaxis.

Pharmacogenetic analysis of SNPs in genes involved in the pharmacokinetics and response to lopinavir/ritonavir therapy.

Despite the known benefits and the experienced use of lopinavir/ritonavir (LPV/r) in the management of HIV infection, important interindividual variability in the pharmacokinetics (PKs) and the response to treatment with standard doses of this drug has been observed. Host genetic factors have been recently suggested as being responsible for part of this variability as they may affect the expression and functional activity of many proteins involved in the kinetic behavior, the immune recovery or the adverse effects related to LPV/r. Here, we present a genetic association study in 106 HIV-infected individuals collected over a period of 5 years with the aim of identifying and confirming single nucleotide polymorphisms (SNPs) with a significant influence on the PK parameters of LPV/r, the immunovirological response or toxicity derived from treatment with the studied drug. Genotyping was performed by MALDI-TOF and KASPar; LPV/r plasma concentrations were quantified using high-performance liquid chromatography with an ultraviolet detection system and the PK parameters were estimated using Bayesian algorithms. Genetic association analysis was performed with SPSS. The most significant associations were found between SNPs in the dopamine receptor D3 gene and the PK of LPV/r. Additionally, other suggestive relationships were established between genetic factors and the response during treatment with this drug. Thereby, identifying HIV-infected individuals who are at increased risk of achieve non-optimal LPV/r plasma concentrations with the emergence of toxicity, drug resistance or absence of clinical response could be helpful as a tool to optimize the LPV/r-based antiretroviral therapy.

[Biosimilars: assessment of efficacy, safety and cost]. / Biosimilares: balance de eficacia, seguridad y coste.

A biosimilar medicinal product is a successor to a biological medicinal product for which patent protection no longer applies. Manufactured by recombinant DNA technology (insertion of gene into the host cell to produce the protein). Comparable with the selected comparator, reference product, in terms of quality, safety and efficacy. The biosimilar product is usually approved for the same indications as the comparator reference product given that they share the same mode of actions.

[Meropenem: pharmacologic advantages of clinical interest]. / Meropenem: ventajas farmacológicas de interés clínico.

The pharmacokinetic profile of meropenem is similar to that of imipenem/cilastatin. It differs in resistance to hydrolysis by the methaloenzyme, dehydropeptidase I, and therefore does not require the combination of cilastatin, being administered alone. Similar to other beta-lactamic drugs, it is mainly distributed in the extravascular space (apparent Vd, 21 I) with an half life of elimination of approximately one hour. A low proportion binds to plasma proteins (< 20%). The tissue concentrations are maintained for prolonged periods at values greater than the MIC of most pathogens. In LCR and aqueous humor it has limited penetration. Nonetheless, the levels achieved in patients with meningitis (40 mg/kg/8 h) range between 0.9 and 6.5 micrograms/ml, greater than the MIC of most pathogens associated with this disease. The renal clearance of meropenem surpasses that of creatinine, thereby indicating excretion by glomerular filtration and tubular secretion. The doses in patients with renal insufficiency should be reduced according to creatinine clearance. Modification of the dosage is not necessary in patients with hepatic failure. Administered at a doses of 1 g/8 hours meropenem presented a value of (AUICo infinity) 60-90 micrograms/h/ml. The (AUIC)24 = 125 ensures that the serum concentrations are maintained above 3 micrograms/ml during a period greater than 80% of the dosage interval.

Oral absorption of ofloxacin administered together with aluminum.

A clinical study was carried out to establish the influence of aluminum on the oral absorption of ofloxacin. Ten healthy volunteers were included in a crossover study based on a Latin square design. The treatments that all volunteers received were A, consisting of 400 mg of ofloxacin, and B, consisting of 400 mg of ofloxacin plus 11 g of colloidal aluminum phosphate. The absorption constant and other ofloxacin parameters were calculated from data on levels in plasma by using model-independent calculation methods. There were no statistically significant differences between the mean values of the areas under the curve corresponding to the administration of ofloxacin alone and those of ofloxacin with aluminum. Regarding the other pharmacokinetic parameters, a significant difference between the absorption constants was found. The presence of aluminum reduces the absorption rate of this quinolone but does not modify the percentage of the absorbed dose.

Contribution of serum level monitoring in the individualization of carbamazepine dosage regimens.

The aim of the present work was to assess the forecasting efficiency of methods of dosage individualization for carbamazepine according to mean population pharmacokinetic parameters (method 1) and from information relating to one (method 2) or more (method 3) measured steady-state serum drug levels in 344 epileptic patients. All the individuals studied were outpatients on a multiple dosage regimen with carbamazepine. Carbamazepine serum levels were analyzed by an enzyme multiplied immunoassay technique (EMIT). The accuracy and precision of methods 1, 2 and 3 were judged by the mean prediction error (m.e.) and the root mean squared error (m.s.e.) that had values of -1.1 +/- 3.5 and 2.8 +/- 2.3; 0.3 +/- 2.0 and 1.4 +/- 1.5 and -0.15 +/- 1.9 and 1.4 +/- 1.2 for methods 1, 2 and 3, respectively. From the statistical analysis of the experimental data and those predicted by the three methods studied, it may be inferred that the availability of data referring to the drug serum levels contributes decisively to the establishment of a correct dosage regimen.