Combined use of an ACE-inhibitor and spironolactone in patients with heart insufficiency. / Risikoreiche Kombination oder leitliniengerechte Verordnung? ACE-Hemmer und Spironolacton: Bei Herzinsuffizienz indiziert.

A patient with cardiac insufficiency takes the ACE-Inhibitor Enalapril as well as Spironolactone regularly. In the interaction monographs of the German ABDA-database there is a note that combined use of these substances should be avoided due to an increased risk of hyperkalemia ­ is there a medication related problem? There is evidence from clinical studies, that combined use of ACE-inhibitors and potassium-sparing agents indeed increases the risk of severe hyperkalemia. The risk seems to be related to the dose of the potassium-sparing agent. However, in patients with cardiac insufficiency NYHA-class II-IV and an ejection fraction of ≤ 35%, the addition of spironolactone to an ACE-inhibitor and betablocking agent reduces mortality and hospitalization for cardiovascular problems. Therefore the combination is indicated in these patients. To minimize the risk for severe adverse events close monitoring of serum potassium and renal function is mandatory. Moreover, additional risk factors for hyperkalemia such as intake of potassium supplements or NSAID should be avoided.

Evaluation of a program of integrated care to reduce recurrent osteoporotic fractures.

PURPOSE: To evaluate the outcomes of patients participating in a program of integrated care for osteoporosis in terms of medication supply, fracture incidence and expenses. METHODS: Outcomes were assessed from secondary data provided by the AOK PLUS health insurance for 2455 participants of the program and the same number of matched controls who were also diagnosed with osteoporosis but did not participate in the program. Supply with Calcium and Vitamin D, antiresorptive agents and analgesics was assessed by defined daily doses. Osteoporotic fractures were identified by hospitalization data. Costs for fracture treatment, medication supply and additional expenses of the program were also included in the dataset. RESULTS: Patients enrolled in the program of integrated care received significantly more medication to treat osteoporosis than controls. There was no significant reduction in fracture incidence among participants of integrated care, but a reduced need of analgesics was noted. Additional costs for patients enrolled in the program were caused by a higher number of drug prescriptions, higher costs for stationary treatment and additional expenses for program related care and diagnostics. CONCLUSIONS: The program of integrated care was not found to be effective in reducing recurrent fractures. Cost effectiveness defined as a reduced rate of fractures in integrated care patients could not be shown by the assessed outcome measures. This missing reduction in fracture incidence may be explained by a non-sufficient improvement - compared to a placebo-controlled clinical trial - in medication supply and non-comparability of our real-world patient population with highly controlled clinical trial participants.

[Medication reviews in community pharmacies: An approach to external quality assessment]. / Medikationsanalysen in öffentlichen Apotheken: Konzept zur externen Qualitätsüberprüfung.

BACKGROUND: A medication review aims at the optimization of medication use, the detection of drug-related problems (DRPs) and the recommendation of interventions. As part of the pilot project "Arzneimittelinitiative Sachsen-Thüringen" (ARMIN) and caused by the introduction of several training programs, numerous public pharmacies in Germany currently offer medication reviews for patients. However, a standardized method for external quality control has so far not been established. METHODS: A round robin test for medication reviews was designed in written form by five pharmacists with expertise in different areas (Drug information service ARMIN, Saxonian Chamber of pharmacists, public pharmacy, hospital pharmacy), based on the recommendations of the guideline for medication reviews of the German Federal Chamber of Pharmacists (Bundesapothekerkammer). On the basis of a fictitious case study the participants were asked to check a patient's medication data for the presence of DRPs, propose possible solutions and generate a medication plan. The solutions were assessed by two pharmacists of the drug information service ARMIN on the basis of a best practice solution that had been consented in the study group beforehand. RESULTS: 102 pharmacists and 13 pharmacy students in internship took part in the round robin test. On average, participants achieved a score of 7,62 out of 9 for recognizing DRPs and recommending solutions and a score of 0,79 out of 1 for generating a correct medication plan. 106 participants (92%) met the requirements for successful participation (recognizing the three most relevant DRPs and at least one further DRP as well as generating an adequate medication plan). The implementation of the approach described here proved to be practicable The State Directorate of Saxony accepted the round robin test as a measure for external quality assessment in accordance with legal requirements. CONCLUSIONS: Due to the nationwide introduction of medication reviews as a pharmaceutical service in June 2022, medication reviews performed by German community pharmacies will gain in importance in the coming years. This is why quality assurance is necessary. Since the participants' performance in medication analysis becomes comparable by completing the round robin test, this instrument appears to be potentially suitable for the external quality assessment of medications reviews nationwide.

Potentially inappropriate prescribing for elderly outpatients in Germany: a retrospective claims data analysis.

OBJECTIVE: To quantify the frequency of potentially inappropriate medication (PIM) prescribing for outpatients aged 65 years and older using claims data of a German statutory health insurance. METHODS: Based on the 2002 Beers criteria for PIM use, a retrospective evaluation of drug prescription data in outpatient care was conducted for the years 2003 and 2004 using data from a German statutory health insurance (AOK) in the area of Saxony. The study was limited to those drugs classified as being potentially inappropriate according to the criteria independent of existing medical conditions and without any restrictions concerning dosage or duration of use, because this information was not available from the data. RESULTS: In 2003, 3.3% (408,375) of all 12,513,584 drug prescriptions for patients 65 years and older which were analyzed included a PIM from the Beers list. In 2004, it was 2.9% (297,524) of 10,126,809 (p < 0.001). The most frequently prescribed PIMs were short-acting nifedipine (13.4%), indomethacin (12.3%) and diazepam (11.8%) in 2003, and diazepam (14.6%) followed by indomethacin (13.7%) and doxazosin (10.9%) in 2004. 21.7% (119,482) and 18.2% (98,465) of patients 65 years or older received at least one prescription of a PIM in 2003 and 2004, respectively (p < 0.001). In a multivariate logistic regression model female gender and a higher number of prescribed drugs were significantly associated with an increased frequency of receiving a PIM in both years. CONCLUSIONS: In our study, approximately every 5th older patient was prescribed at least one PIM. For the future an ongoing update of the Beers criteria to further include newer agents and an adaptation to the different situation in European countries is desirable.

[Medication management: Simvastatin and Amlodipin - a clinically relevant drug-interaction?] / Medikationsmanagement: Simvastatin und Amlodipin: Eine klinisch relevante Wechselwirkung?

The clinical relevance of the drug-drug interaction simvastatin and amlodipine is appraised controversially by german simvastatin Summary of Product Characteristics (SPCs) and different drug interaction databases. Results of clinical trials have shown that simultaneous administration of simvastatin and amlodipine can increase simvastatin bioavailability. However, it is unclear whether this increase is associated with a higher risk for adverse drug events. So far there is no evidence that the combination might increase cases of myopathy or rhabdomyolysis. Therefore combined treatment with amlodipine and up to 40 mg simvastatin daily seems clinically justifiable if the patient does not report adverse events. If myopathy or muscle weakness occur, simvastatin dose should be reduced to 20 mg daily or the patient should be switched to pravastatin, fluvastatin or rosuvastatin. The highest approved dose of simvastatin (80 mg) is generally not recommended in new patients because of increased risk of muscle damage.

Determination of the novel melatonin agonist Neu-P11 in plasma samples by liquid chromatography-tandem mass spectrometry.

Melatonin is a major chronobiological regulator involved in circadian phasing, sleep, and numerous other functions. The novel melatonin agonist Neu-P11 is used in treatment of physiological insomnia. In animal studies Neu-P11 showed sleep-promoting effect. In a phase 1 study Neu-P11 was administered to cohorts of healthy young male volunteers in an ascending single dose study. Up to now no method for measurement of the new drug in human plasma was described and validated. The aim of this study was to develop a suitable analytical procedure. With solid phase extraction (SPE) for sample preparation and liquid chromatography tandem mass spectrometry (LC/MS/MS) a sensitive method with a lower limit of quantification of 0.39 ng/ml was found. For SPE samples were put into Strada C18 cartridges and automatically extracted by a Gilson Automatic Sample Processor ASPEC XL. The HPLC was carried out with a Purospher C18 column and mobile phase gradient with acetonitrile, and ammonium acetate. The precision ranged from 0.4% to 9.5%. The deviation of the measured from the true value, of the standard samples and QCSs was lower than 10%. The method was specific, precise and accurate and the analyte was stable under the conditions of measurement. Results show that the method is suitable for the quantification of NeuP11 in human plasma after a single dose of 5, 20, 50 or 200mg.