Using a computerised drug-interaction program, a high proportion of patients was detected with at least one potential DDI in the medication prescribed at discharge. However, the proportion of DDIs associated with potentially relevant clinical consequences appeared to be relatively low.

Pharmacotherapy is complex in cirrhotic patients. Hepatologists should know the principles of dose adjustment in cirrhosis and renal failure, but also the most important pDDIs of the drugs used to treat liver disease and comorbidities in this population.

Inappropriate drug use as defined by the Beers criteria was common in both medical and geriatric inpatients. Compared with internists, geriatricians appear to be more aware of PIMs that should generally be avoided, but less aware of PIMs related to a specific diagnosis, and of the need to avoid anticholinergic drug use. However, the results of this study should be interpreted with caution because some of the drugs identified as potentially inappropriate may in fact be beneficial when the patient's clinical condition is taken into consideration.

Aim and background To assess drug-related problems in patients with liver cirrhosis by investigating the prevalence of inadequately dosed drugs and their association with adverse drug reactions (ADRs) and hospitalizations. Methods This was a cross-sectional retrospective study assessing the dose adequacy of drug treatment of 400 cirrhotic patients at hospital admission based on the authors' own previous studies and standard literature. The prevalence of total and preventable ADRs and of hospitalizations due to preventable ADRs was determined. Results Of all 1653 drugs prescribed (median 4 per patient), 336 (20 %) drugs were inadequately dosed in 184 patients. Overall, 210 ADRs (78 % preventable) occurred in 120 patients. Sixty-nine ADRs (33 % of all ADRs) were associated with inadequate drug dosing in 46 patients, of which 68 % were preventable. Nonsteroidal anti-inflammatory drugs and psycholeptics in particular frequently caused preventable ADRs associated with inadequate drug dosing. Inadequate drug dosing was more frequently associated with ADRs than adequate drug dosing, and patients receiving inadequately dosed drugs were more frequently admitted to the hospital due to ADRs. Hospitalization of patients receiving inadequately dosed drugs that caused preventable ADRs resulted in 94 additional hospital days. ConclusionIn this retrospective study, inadequate drug dosing was associated with an increased frequency of ADRs, hospital admissions and hospital days in cirrhotic patients. We therefore conclude that the careful dosing of critical drugs is important in patients with liver cirrhosis.

The aim of this study was to assess the frequency of potential drug-drug interactions (pDDIs) and adverse drug events (ADEs) associated with antimycotics in hospitalized patients with hematopoietic SCT (HSCT). Of the 120 HSCT recipients evaluated, 36 received antimycotics. A total of 124 ADEs were recorded in 32 of the 36 patients treated, with 54 ADEs being possibly and 9 probably related to antimycotics. Of the treatments with amphotericin B, 93% were associated with one or more possible and 36% with probable ADEs. The corresponding figures for lipid-based amphotericin B were 100% and 7%, for voriconazole 68% and 11% and for caspofungin 70% and 0%. A total of 57 potentially severe DDIs associated with antimycotics were detected in 31 of the 36 patients. Of these, 14 DDIs were a possible cause of an ADE and 5 (4 times a combination of voriconazole with CYA and once a combination of CYA with conventional amphotericin B) were probably related. Although the prevalence of pDDIs and ADEs is high in HSCT patients, ADEs related with a high probability to treatment with antimycotics are rare. Regarding the high prevalence of pDDIs, our findings underscore the importance of close monitoring of laboratory and clinical parameters, as well as dose adjustment for critical drugs, in patients with HSCT.

Compared with younger patients, elderly dyslipidaemic patients are at a higher risk for clinically relevant pDDIs, mainly because of a higher number of drugs prescribed. In addition, patients aged > or = 75 years were prescribed more drugs with a high potential for DDIs, especially drugs used for the treatment of arrhythmias and heart failure. The risk for adverse reactions associated with pDDIs may often be reduced by dose adjustment, close monitoring or selection of an alternative drug.

Dose adjustment of psychotropic drugs in patients with liver cirrhosis may be important as most of these drugs are predominantly eliminated by the liver and many of them are associated with dose-dependent adverse reactions. As no surrogate parameter is available to predict hepatic metabolism of drugs, dose adjustment according to pharmacokinetic properties of the drugs is proposed. Psychotropic drugs (antiepileptics, antiparkinsonian drugs, psycholeptics such as antipsychotics, anxiolytics, sedatives and hypnosedatives, and psychoanaleptics such as antidepressants, psychostimulants and antidementia drugs) marketed in Switzerland in 2006 were therefore classified according to their hepatic extraction and/or bioavailability to predict their kinetic behaviour in patients with cirrhosis. The expected changes in hepatic metabolism predicted by pharmacokinetic properties were compared with the results from kinetic studies carried out in patients with liver disease. These studies were identified using MEDLINE searches. Of the 116 psychotropic drugs available on the Swiss market by the year 2006, only 12 were predominantly eliminated through the kidney. For five substances, no Q(0) value (the dose fraction metabolized or excreted extra-renally) could be determined because of lack of pharmacokinetic data. Of 99 drugs with predominant hepatic metabolism, 29.3% were categorized as high, 25.2% as intermediate and 38.4% as low extraction drugs, while seven substances could not be classified. Pharmacokinetic studies in patients with liver disease were available for 55 of these 99 drugs eliminated predominantly by the liver (Q(0)-value > or = 0.5). Only a few kinetic studies in patients with liver disease were found for antipsychotics, antiparkinsonian drugs and antidepressants, except for selective serotonin reuptake inhibitors and some newer antidepressants. The expected changes in pharmacokinetics were generally in good agreement with the changes reported in pharmacokinetic studies. For 12 drugs, the observed changes in pharmacokinetics from clinical studies were different from the changes expected based on their classification. However, for low extraction drugs metabolized by cytochrome P450 isozymes, clearance may be reduced by up to 50%. In conclusion, the classification of drugs according to their hepatic extraction and/or bioavailability is a useful tool for dose adjustment, if information from clinical studies is lacking. There is a gap in information about pharmacokinetic changes in patients with liver cirrhosis for a large number of centrally acting drugs. Kinetic studies for centrally acting drugs with predominant hepatic metabolism should be carried out in patients with liver disease to allow precise dose recommendations for enhanced patient safety.

Coadministration of rofecoxib and lithium may result in life-threatening lithium intoxication, especially in patients with a preexisting decrease in renal function and/or decreased intravascular volume.