Factors associated with acute-phase response of bisphosphonate-naïve or pretreated women with osteoporosis receiving an intravenous first dose of zoledronate or ibandronate.

A first intravenous dose of bisphosphonates may be associated with an acute-phase response (APR). In bisphosphonate-naïve women with postmenopausal osteoporosis, the characteristics and frequency of APR may differ by compound. Prior bisphosphonate exposure was predictive of APR risk and severity. INTRODUCTION: Intravenous (IV) administration of bisphosphonates (BP), such as zoledronate (ZOL) and ibandronate (IBN), may be associated with an APR. The characteristics of APR may differ by compound. The aim of the present study was to evaluate the characteristics of APR (rates, signs and symptoms, severity), in the absence of any preventive measure, after a first IV application of ZOL or IBN in patients naïve or previously exposed to BP in a real-world clinical setting. METHODS: This is an open-label prospective exploratory study with two cohorts of consecutive postmenopausal women with osteoporosis treated with either IV ZOL or IBN at the Department of Osteoporosis of the University Hospital of Berne, Switzerland. RESULTS: Intravenous BP was administered to 725 women (411 ZOL and 314 IBN). Prior oral or IV BP use was less frequent in the ZOL group (61.8 vs. 71.7%, p = 0.005). In total, 301 women (41.5%) reported the presence of one or more signs or symptoms of APR with rates for ZOL and IBN of 47.7 and 33.4%, respectively (p < 0.001). Corresponding APR rates in the subgroup of BP-naïve patients were 55.6 and 32.4%, respectively (p < 0.001). The leading APR clinical sign was the presence of post-dose myalgia or arthralgia (68.1%). Prior BP exposure was predictive of both APR risk and severity, and lower serum 25-hydroxy vitamin D (25(OH)D) levels were possibly predictive of severity. CONCLUSIONS: In a real-world setting, APR rates with ZOL and IBN may be higher than reported in randomised controlled trials and may differ by compound, prior BP exposure, and serum 25(OH)D levels.

[Interactions with antiretroviral drugs]. / Arzneimittelinteraktionen mit antiretroviralen Medikamenten.

Drug-drug interactions are frequently encountered in the therapy of HIV-infected patients, since the highly active antiretroviral therapy always contains several drugs. Drugs against opportunistic infections and concomitant diseases are added frequently. All protease inhibitors are inhibitors of CYP3A, which is important in the metabolism of approximately 50% of all drugs, e.g. simvastatin, atorvastatin, sildenafil, and clarithromycin. Among the protease inhibitors, ritonavir is the strongest inhibitor of CYP3A activity. This inhibition is also used to enhance ("boost") the bioavailability of other protease inhibitors. The nonnucleoside reverse transcriptase inhibitors (NNRTI) efavirenz and nevirapine lead to an increase in CYP3A activity during long-term treatment. To prevent interactions, doses of CYP3A substrates have to be adapted in the beginning and at the end of CYP3A activity-modifying treatments. Interactions can also be a result of modifications in the activities of glucuronosyltransferases and of transport proteins. Ritonavir is an inhibitor of P-glycoprotein, which leads to increased expositions towards many antineoplastic drugs.