Utilization review of concomitant use of potentially interacting drugs in Thai patients using warfarin therapy

PURPOSE: In Thailand, there has been no study determining the concomitant use of medications, known to potentially interact with warfarin, in patients receiving warfarin therapy. This paper examined the frequency of which specific interacting drugs were concomitantly used in warfarin users. METHODS: We retrospectively examined the database of warfarin outpatient medical records from a regional 756-bed hospital located in the north of Thailand. All patients receiving warfarin from 10 June 1999 to 4 August 2004 were reviewed to identify all drugs possessing interaction potential with warfarin. The potential of significant interactions were divided into high, moderate and low, according to the extent of evidence documented in textbooks and literature. RESULTS: Among 1093 patients receiving warfarin therapy, 914 (84%) patients received at least one potentially interacting drug and half of them (457 patients) received at least one drug with high potential for interaction. The most frequently concomitant drug that increased INR was acetaminophen (63%, 316/457). Propylthiouracil was the most frequently concomitant drug that decreased INR response (4%, 19/457), while diclofenac was the most frequently concomitant drug that increased bleeding risk (16%, 73/457). CONCLUSIONS: About a half of patients receiving warfarin therapy was prescribed concomitant drug(s) that has a high potential of interactions with warfarin. These patients should be closely monitored and counselled to watch for signs and symptoms of bleeding and thrombosis to avoid adverse events associated with drug interactions.     

Quantity and quality of potential drug interactions with coumarin anticoagulants in the Netherlands

Objective Coumarin anticoagulants are prone to potentially life-threatening drug-drug interactions due to a combination of unfavorable properties. However, real life data on the actual occurrence are scarce. The aim of this study was to quantify and qualify potential drug interactions with coumarin anticoagulants in daily practice. Methods A cohort study including all users of phenprocoumon or acenocoumarol during the period 1991–2003 in the PHARMO Record Linkage System. All 24 individual drugs and 11 drug groups interacting with coumarins according to central database used in the Dutch pharmacies were considered. Main outcome measure Frequency and type of potential drug interactions during anticoagulant therapy with coumarins. Results 48,627 out of 76,455 mainly acenocoumarol-users (64%) were dispensed at least one potentially interacting drug (PID) during anticoagulant therapy. About 35% of these cases were dispensed a (very) strongly interacting drug, whereas 3% were dispensed a contraindicated drug. Antibacterial drugs and NSAIDs (39% and 37% of all users, respectively) were the most frequently dispensed PIDs. Conclusion Potential drug interactions with coumarins frequently occur in daily practice, confronting two-thirds of patients with an increased risk of bleeding. To a large part, this is attributable to commonly prescribed medication like antibacterial drugs and NSAIDs. This situation substantiates the need for proper monitoring or new anticoagulants with less drug–drug interactions.     

Drug information centre queries and responses about drug interactions over 10 years—A descriptive analysis

Many people are treated with ≥1 drug, implying that risks of drug interactions need to be considered. The aim of this study was to describe drug interaction queries from healthcare professionals to a drug information centre in Sweden over 10 years focusing on drugs frequently asked about and the advice provided. Advice was recorded in mutually exclusive groups: Avoid, Adjust dose, Separate intake, Vigilance or No problem. For queries with Avoid, Adjust dose or Separate intake advice, alerts were extracted from an interaction database (Janusmed). Of 4335 queries to the centre in 2008‐2017, 589 (14%) concerned interactions. Most were posed by physicians (91%) and concerned a specific patient (83%) before treatment initiation (76%). Sertraline, warfarin and methotrexate were the most frequently asked about, whereas queries about cyclophosphamide and rifampicine occurred most often in relation to the number of exposed patients. Advice provided in 557 (95%) replies comprised Avoid: n = 85 (15%), Adjust dose: n = 57 (10%), Separate intake: n = 17 (3%), Vigilance: n = 235 (42%) or No problem: n = 163 (29%). In all, 113 (71%) of 159 queries with Avoid/Adjust dose/Separate intake advice elicited an action alert on Janusmed, whereas 31 (20%) did not result in any alert at all. Summarized, seven in ten replies from the drug information centre recommended an explicit drug treatment action, regarding either specific prescribing aspects, for instance dose adjustments, or active follow‐up including monitoring potential adverse reactions and/or laboratory results. Readily accessible decision support regarding drug interactions often provides relevant action alerts, but cannot be solely relied on.     

Pharmacokinetic interactions between clozapine and sertraline in smokers and non‐smokers

Clozapine is an effective antipsychotic drug for treatment‐resistant schizophrenia. Sertraline is a widely prescribed antidepressant and often concomitantly applied to address negative symptoms or depression. However, data on interactions between clozapine and sertraline are inconsistent. The aim of our study was to evaluate pharmacokinetic interactions between clozapine and sertraline analysing a therapeutic drug monitoring database of 1644 clozapine‐medicated patients. We compared four groups: non‐smokers (n = 250) and smokers (n = 326) with co‐medication without known effects on cytochrome P450 and without sertraline, and non‐smokers (n = 18) and smokers (n = 17) with sertraline co‐medication. Measured and dose‐corrected concentrations (C/D) of clozapine were compared between the groups using non‐parametrical tests with a significance level of 0.05. Post hoc analyses included pairwise comparisons to account for smoking status. Although we detected significant differences for clozapine levels and C/D values between study groups (P < .001 for Kruskal‐Wallis test in both cases), post hoc analyses revealed no differences for concentrations and C/D values of clozapine (P > .05 for Mann‐Whitney U test in both cases). A negative correlation between the sertraline dose and the clozapine concentration was found in non‐smokers (Spearman's rank correlation, rs = ?0.535, P = .048). A potential pharmacokinetic interaction between clozapine and a standard therapeutic sertraline dose seems to be of minor clinical importance.     

Potentially inappropriate drug prescribing among first-visit elderly outpatients in Taiwan

STUDY OBJECTIVE: To determine the prevalence and risk factors of potentially inappropriate drug prescribing among first-visit elderly outpatients. DESIGN: Cross-sectional survey. SETTING: An urban tertiary care and academic medical center in southern Taiwan. PATIENTS: Eight hundred eighty-two patients aged 65 years or older who were prescribed drugs at their first visit to either the medical center's outpatient internal medicine clinic or family medicine clinic between March 1, 2001, and July 31, 2001. MEASUREMENTS AND MAIN RESULTS: Potentially inappropriate drug prescribing was assessed according to updated Beers criteria. Ninety-seven potentially inappropriate drugs were identified in 93 (10.5%) patients. The most common classes were sedative-hypnotics (18.6%) and muscle relaxants (17.5%). Twenty (20.6%) of these inappropriate drugs had a high severity potential according to the Beers criteria. Patients prescribed potentially inappropriate drugs were more likely to be prescribed several drugs versus those who were not prescribed potentially inappropriate drugs (4.0+/-1.9 vs 2.8+/-1.4, p<0.001). Multiple logistic regression analysis revealed an interaction between age and the number of prescribed drugs on the risk of having potentially inappropriate drugs prescribed. In patients who were prescribed four agents or less, the risk was not associated with increasing age; in those who were prescribed five drugs or more, the risk was positively associated with increasing age. CONCLUSION: Potentially inappropriate drug prescribing among first-visit elderly outpatients was relatively low. Increasing patient age combined with increased number of drugs prescribed was associated with increased risk of having potentially inappropriate drugs prescribed.