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Background: Nintedanib is a substrate for p-glycoprotein which can impact bioavailability. We investigated the effects of ketoconazole, a p-glycoprotein inhibitor, and rifampicin, a p-glycoprotein inducer, on the pharmacokinetics of nintedanib., Methods: In the ketoconazole study, 34 healthy subjects received nintedanib 50 mg orally alone and 1 h after the last dose of ketoconazole given orally at a dose of 400 mg once daily for 3 days in 1 of 2 randomized sequences. In the rifampicin study, 26 subjects received nintedanib 150 mg orally alone and the morning after the last dose of rifampicin given orally at a dose of 600 mg once daily for 7 days. The primary objective was to determine the relative bioavailability of nintedanib administered following multiple doses of ketoconazole or rifampicin versus alone, based on AUC from time 0 extrapolated to infinity (AUC 0-∞ ) and maximum concentration (C max ) calculated using an analysis of variance. Geometric mean ratios and 2-sided 90% CIs were calculated., Results: Exposure to nintedanib increased when it was administered following ketoconazole versus alone (AUC 0-∞ : geometric mean ratio, 160.5% [90% CI, 148.2-173.7]; C max : geometric mean ratio, 179.6% [90% CI, 157.6-204.8]) and decreased when it was administered following rifampicin versus alone (AUC 0-∞ : geometric mean ratio, 50.1% [90% CI, 47.2-53.3]; C max : geometric mean ratio, 59.8% [90% CI, 53.8-66.4]). The time to reach C max (t max ) and half-life (t ½ ) of nintedanib were unaffected by co-administration of ketoconazole or rifampicin., Conclusions: Exposure to nintedanib is increased by co-administration of ketoconazole and decreased by co-administration of rifampicin, likely due to effects on bioavailability of the absorbed fraction. ClinicalTrials.govidentifiers:NCT01679613, NCT01770392.

Coronary heart disease (CHD) remains the leading cause of death in Germany despite statin use to reduce low-density lipoprotein cholesterol (LDL-C) levels; improving lipids beyond LDL-C may further reduce cardiovascular risk. A fixed-dose combination of extended-release niacin (ERN) with laropiprant (LRPT) provides comprehensive lipid management. We adapted a decision-analytic model to evaluate the economic value (incremental cost-effectiveness ratio [ICER] in terms of costs per life-years gained [LYG]) of ERN/LRPT 2 g over a lifetime in secondary prevention patients in a German setting. Two scenarios were modelled: (1) ERN/LRPT 2 g added to simvastatin 40 mg in patients not at LDL-C goal with simvastatin 40 mg; (2) adding ERN/LRPT 2 g compared with titration to simvastatin 40 mg in patients not at LDL-C goal with simvastatin 20 mg. In both scenarios, adding ERN/LRPT was cost-effective relative to simvastatin monotherapy at a commonly accepted threshold of €30,000 per LYG; ICERs for ERN/LRPT were €13,331 per LYG in scenario 1 and €17,684 per LYG in scenario 2. Subgroup analyses showed that ERN/LRPT was cost-effective in patients with or without diabetes, patients aged ≤ 65 or >65 years and patients with low baseline high-density lipoprotein cholesterol levels; ICERs ranged from €10,342 to €15,579 in scenario 1, and from €14,081 to €20,462 in scenario 2. In conclusion, comprehensive lipid management with ERN/LRPT 2 g is cost-effective in secondary prevention patients in Germany who have not achieved LDL-C goal with simvastatin monotherapy.

Background: Since 2006 in Germany six different target drugs for therapy in metastatic renal cell cancer (mRCC) have been used. Comparative studies for the application with the same indication are absent, and the order of potential sequential therapy is up to now unclear. The aim of the study was to collect data on therapy decisions in Germany regarding mRCC in the age of "targeted therapy". At the same time the study addressed the central question of sequencing of the different therapy options. In addition, the data of this study were to be compared to a study already published in 2008., Patients and Methods: In 2010, four groups of doctors specialized in the therapy of patients with mRCC were asked for their behaviour in the first-, second- and third-line or sequential therapy. Those questioned included urologists in private practice (n=40), oncologists in private practice (n=40), hospital urologists (n=35) and hospital oncologists (n=35). Further the reasons for a therapy decision should be stated or weighted., Results: Altogether 92% of all patients with mRCC were treated. Urologists in private practice treat only 30% of their patients themselves. The earlier used immune therapies (IFN, IL-2) no longer play a role. Sunitinib is used most often in first-line therapy by urologists in private practice (50.4%) and oncologists in private practice (47.1%). In second- and third-line therapy everolimus is used by urologists in private practice (27.1%, 26.3%) and sorafenib (28.6%) or everolimus (26.4%) by oncologists in private practice. Hospital oncologists use primarily sunitinib (56.1%), in second-line sorafenib (45.5%) and in third-line above all everolimus (19.4%). Hospital urologists use sunitinib most often for first-line therapy (57.6%) and sorafenib for second-line treatment (37.3%), while in third-line therapy temsirolimus (49.6%) and also everolimus (30.4%) were used., Conclusions: The therapy of mRCC is determined very strongly by the substances sunitinib and sorafenib. The mTOR inhibitors have recently been increasingly included in the second- and third-line therapy. With the introduction of the new targeted therapies, the treatment of these special patients is performed less by urologists and increasingly more by oncologists. This trend is strengthened in comparison to the DGFIT study from 2008.

Purpose: To describe the current use and administration of multitargeted tyrosine kinase inhibitors (sunitinib and sorafenib) in the management of metastatic renal cell carcinoma (RCC) and to characterise frequent adverse events., Materials and Methods: A questionnaire was sent to 104 urologists and medical oncologists having their own practice. The common use of medical treatment with sunitinib and sorafenib in patients with metastatic RCC was recorded. Data on the most frequent drug-associated adverse events were registered and described in a preliminary patient cohort., Results: Medical oncologists in private practice treat over twice as many patients with metastatic RCC (8/year) as established urologists. Most medical oncologists but not urologists already use multitargeted tyrosine kinase inhibitors. For the initiation of treatment, most urologists admit patients to a hospital, whereas medical oncologists start and carry out medical treatment themselves. In all patients adverse events occurred due to medical treatment, leading to therapy stop or pause in 53% of patients. The most frequent adverse events were abnormal fatigue, arterial hypertension, diarrhoea and the hand-foot skin syndrome., Conclusions: Multitargeted tyrosine kinase inhibitor therapy in Germany is currently done predominantly by medical oncologists rather than urologists. Adverse events caused by sunitinib and sorafenib frequently required medical care, and in our initial series of patients prompted physicians to pause treatment.

Ropinirole is a non-ergot-selective D2 dopamine agonist. Its efficacy, tolerability, and safety have been extensively proven in controlled, double-blind trials. The present prospective, multicentre, postmarketing surveillance study tested whether the results of controlled clinical trials are also valid in routine clinical practice. For evaluation, international rating scales for tremor and activities of daily living were applied in a slightly modified manner. In 172 German centres, 453 parkinsonian patients (272 men, 174 women, average age 67 years) in advanced stages of the disease were treated with ropinirole alone or in combination with L-dopa. Activities of daily living and tremor significantly improved. This is the first prospective study which demonstrates beneficial effects of ropinirole on PD tremor. The dosage of L-dopa could be reduced in 31% of the patients. Side effects were reported in only 7.6%. The results of this postmarketing study corroborate the good clinical efficacy of ropinirole together with high safety under routine clinical conditions.