Clinical Relevant Interactions Research Articles

DeepARV: ensemble deep learning to predict drug-drug interaction of clinical relevance with antiretroviral therapy

Drug-drug interaction (DDI) may result in clinical toxicity or treatment failure of antiretroviral therapy (ARV) or comedications. Despite the high number of possible drug combinations, only a limited number of clinical DDI studies are conducted. Computational prediction of DDIs could provide key evidence for the rational management of complex therapies. Our study aimed to assess the potential of deep learning approaches to predict DDIs of clinical relevance between ARVs and comedications. DDI severity grading between 30,142 drug pairs was extracted from the Liverpool HIV Drug Interaction database. Two feature construction techniques were employed: 1) drug similarity profiles by comparing Morgan fingerprints, and 2) embeddings from SMILES of each drug via ChemBERTa, a transformer-based model. We developed DeepARV-Sim and DeepARV-ChemBERTa to predict four categories of DDI: i) Red: drugs should not be co-administered, ii) Amber: interaction of potential clinical relevance manageable by monitoring/dose adjustment, iii) Yellow: interaction of weak relevance and iv) Green: no expected interaction. The imbalance in the distribution of DDI severity grades was addressed by undersampling and applying ensemble learning. DeepARV-Sim and DeepARV-ChemBERTa predicted clinically relevant DDI between ARVs and comedications with a weighted mean balanced accuracy of 0.729 ± 0.012 and 0.776 ± 0.011, respectively. DeepARV-Sim and DeepARV-ChemBERTa have the potential to leverage molecular structures associated with DDI risks and reduce DDI class imbalance, effectively increasing the predictive ability on clinically relevant DDIs. This approach could be developed for identifying high-risk pairing of drugs, enhancing the screening process, and targeting DDIs to study in clinical drug development.

Structural insights into multiplexed pharmacological actions of tirzepatide and peptide 20 at the GIP, GLP-1 or glucagon receptors

Glucose homeostasis, regulated by glucose-dependent insulinotropic polypeptide (GIP), glucagon-like peptide-1 (GLP-1) and glucagon (GCG) is critical to human health. Several multi-targeting agonists at GIPR, GLP-1R or GCGR, developed to maximize metabolic benefits with reduced side-effects, are in clinical trials to treat type 2 diabetes and obesity. To elucidate the molecular mechanisms by which tirzepatide, a GIPR/GLP-1R dual agonist, and peptide 20, a GIPR/GLP-1R/GCGR triagonist, manifest their multiplexed pharmacological actions over monoagonists such as semaglutide, we determine cryo-electron microscopy structures of tirzepatide-bound GIPR and GLP-1R as well as peptide 20-bound GIPR, GLP-1R and GCGR. The structures reveal both common and unique features for the dual and triple agonism by illustrating key interactions of clinical relevance at the near-atomic level. Retention of glucagon function is required to achieve such an advantage over GLP-1 monotherapy. Our findings provide valuable insights into the structural basis of functional versatility of tirzepatide and peptide 20.

Management of clinical relevant drug-drug interactions with antipsychotics in nursing homes

Introduction Antipsychotics (APs) have been linked to several clinically relevant drug-drug interactions (leading, e.g. to QT-prolongation, torsades de pointes) but little is known about their management in nursing homes residents. Our aim was to characterise clinically relevant drug-drug interactions involving APs and to assess their prevalence in nursing homes residents. Materials and methods We conducted a cross-sectional study in two nursing homes in Portugal. Patients were included if they were older ≥65 and prescribed at least one AP (registered in medical charts). Interactions were identified using Drug Interaction Chequer (Medscape [1]) and supplemented with the summary of product characteristics (SmPC) when deemed necessary. Clinical relevant interactions were defined as serious or contraindicated interactions according to Medscape tool. Data were analysed using univariate statistics (Microsoft Excel 2016). Results A total of 59 patients (83.7 ± 7.1 years) were analysed, 79.7% (n = 47) females. A mean of 1.6 ± 0.7 antipsychotics were prescribed/patient, mostly on a regular basis (61.0%; n = 36). The majority were exclusively prescribed atypical APs (59.3%; n = 35), 28.8% (n = 17) simultaneously atypical and typical APs and 11.9% (n = 7) prescribed only typical APs. Nearly 90% (n = 52; 88.1%) of patients reported interactions with APs, (mean = 2.9 ± 2.3/patient). A total of 169 interactions with APs were found, mainly with antidepressants (27.2%; n = 46), benzodiazepines (22.4%; n = 38), and other antipsychotics (10.6%; n = 18). The majority of AP-drug interactions (83.4%; n = 141) were classified as “to be closely monitored”, mostly due to the sedation effect (56.7%; n = 80). Quetiapine was the AP most often involved in interactions (45.6%; n = 77), where 9.1% (n = 7) were considered “serious”. Haloperidol also registered 37 interactions (21.9%), four of which resulted in increased QTc interval (10.8%). Discussion and conclusions Data showed that one third of patients had clinically relevant AP-drug interactions. Future work will include the development of a user-friendly booklet on clinical relevant drug-drug interactions in elderly patients using APs, expected to contribute to enhanced patient safety and a more rational use of medicines.

Interactions of clinical relevance associated with concurrent administration of prescription drug and food or medicinal plants: a systematic review protocol

BackgroundAn inadequate combination of prescription drugs with food or medicinal plants could cause adverse effects in patients or produce negative therapeutic results. Therefore, this generic systematic review protocol aims to identify and synthesize the literature on clinical characteristics and safety issues of these types of pharmacological interactions occurring in children, adolescents, adults, pregnant/lactating women, and older adults.Methods/designThis generic protocol follows the stated guidelines from the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols (PRISMA-P) statement. A literature search will be performed in PubMed, Scopus, and Virtual Health Library (VHL) electronic databases from 1960 till present for studies reporting clinical characteristics and safety issues associated with pharmacological interactions occurring between prescription drugs and food or medicinal plants in participants from birth-age to ≥ 65-year-old, including pregnant/lactating women. Lateral searching will be carried out in PubMed via related citation. Two reviewers will carry out an independent evaluation of eligible studies as well as the corresponding data extraction of the selected ones. Subsequently, the methodological quality evaluation of the selected articles will be completed using the corresponding Joanna Briggs Institute Checklists. Moreover, the quality of evidence will be graded according to the criteria of the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) Working Group. Quantitative research in humans comprising clinical trials and clinical, comparative and, observational studies will be included. The main outcomes of this protocol involve reported potential food-drug and herb-drug interactions, associated safety issues, and adverse reactions along with the generic name of the prescribed drug and the scientific name of the food and medicinal plants involved in these types of pharmacological interactions. Finally, findings extracted from the selected studies will be summarized in a narrative synthesis.DiscussionThis generic systematic review protocol seeks to synthesize and critically evaluate current knowledge besides to identify any comprehension gaps in the concurrent administration of prescription drugs with food and herbs. By achieving a better understanding of this topic, this information will allow healthcare professionals to develop useful strategies to recognize, manage, and prevent these types of pharmacological interactions at different age stages, including pregnant/lactating women.Systematic review registrationPROSPERO CRD42018117308

Clinically relevant drug interactions between statins and antidepressants.

Statins, also known as 3-hydroxy-3-methylglutaryl-CoA reductase inhibitors, and antidepressant drugs are frequently used in combination due to the high and growing incidence of cardiovascular diseases and psychiatric disorders worldwide. Several aspects on management, the risk of adverse events (AEs) occurrence and the potential clinically relevant pharmacokinetic (PK) and pharmacodynamic (PD) drug-drug interactions (DDIs) between these two classes have not been well investigated. The aim of the present review was to describe the PK and PD interactions, of clinical relevance, between statins and antidepressant drugs and provide a comprehensive overview of their pharmacological features for appropriate multiple drug regimens. Relevant studies were identified through a literature search of PubMed and the Cochrane databases focusing on clinically relevant DDIs between statins and antidepressants. Only papers in English were included in the search. Pharmacodynamic (PD) drug-drug interactions (DDIs) are unlikely to occur as statins are highly selective inhibitors of HMG-CoA reductase with no relevant effect on other enzymes or receptor systems. Despite the numerous PK studies on individual drugs belonging to statins and antidepressant agents, only a few case reports regarding specific DDIs are present in the literature and no clinical studies have been performed. PK data allow to speculate on potential DDIs, comparing the metabolic pathways, intestinal and liver transporters and elimination routes. Overall, second-generation antidepressants, in particular citalopram, escitalopram, mirtazapine, reboxetine and venlafaxine, have weak inhibitory effects on various cytochrome (CYP) isozymes and seem to have a more advantageous DDIs profile in vivo. Conversely, nefazodone, fluoxetine, paroxetine and fluvoxamine influence considerably CYPs activity with potential effects on statins plasma levels, although pravastatin, pitavastatin and rosuvastatin are not susceptible to inhibition by any CYP. Albeit no studies have been performed on P-glycoprotein (P-gp), interactions of clinical relevance are unlikely. Although DDIs with antidepressants are potentially, but rarely clinically significant, the use of antidepressants with a more favourable drug interaction profile is advisable. An evaluation on DDIs between these drugs can be useful for future PK/PD studies on drug-drug interaction to provide clinicians with more data for appropriate multiple drug regimens.

Complementary medicine use during cancer treatment and potential herb-drug interactions from a cross-sectional study in an academic centre

Complementary medicine (CM) is used by one third to one half of cancer patients throughout the world. The objective of this study was to describe the prevalence of CM use and the potential for interactions with cancer treatments in an academic oncology centre. A cross-sectional study was conducted among patients undergoing current cancer treatment. Among 132 included patients, 56% had used CM since their cancer diagnosis and 45% were using CM during cancer treatment at the time of the survey. The main CM used were green tea (35%), herbal tea (35%), homeopathy (27%), dietary supplements (27%), and herbal medicines (27%). A small majority of patients (58%) spontaneously mentioned the use of CM to their oncologist. Of 42 identified combinations of concomitant use of biologically based CM and anticancer agents among the study patients, the potential for pharmacokinetic interactions of clinical relevance was not expected in 17 combinations (40%), hypothetical and deemed unlikely in 23 (55%), and of probable low clinical relevance in 2 (5%). Considering the high prevalence of CM use, active enquiries should be made by healthcare professionals to detect symptoms that may relate to CM tolerance and effects or that suggest interactions between CM and cancer treatments.

Interactions from complementary and alternative medicine in patients with melanoma.

Biological-based (BbCAM) methods from complementary and alternative medicine (CAM) may interact with cancer treatments, reduce efficacy, or enhance adverse effects. Although CAM usage has been evaluated well in other cancer entities, data on melanoma patients are still missing. The aim of this study was to determine CAM usage of melanoma patients using a standardized questionnaire to identify potential interactions with established and new systemic melanoma therapies. This multicenter study was carried out in seven German skin cancer centers. During routine care contact, CAM usage of former and current melanoma treatment was assessed in melanoma patients. The probability of interaction was classified into four categories ranging from 'interaction unlikely' (I), 'possible' (II), 'likely' (III), or 'no data' (IV). The questionnaire was filled out by 1157 patients, of whom 1089 were eligible for evaluation. CAM usage was reported by 41% of melanoma patients, of whom 63.1% took BbCAM such as vitamins, trace elements, supplements, or phytotherapeuticals. Of 335 patients with former or current therapy, 28.1% used BbCAM. The melanoma treatment included interferon, radiotherapy, chemotherapy, BRAF-inhibitor, or other tyrosine kinase inhibitors and ipilimumab. On the basis of our model of likelihood of interaction, we found that 23.9% of those on cancer therapy and 85.1% of those also using BbCAM were at some risk of interactions. The main limitation of our study is that no reliable and comprehensive database on clinical relevant interactions with CAM in oncology exists. Most patients receiving a melanoma-specific treatment and using BbCAM methods are at risk for interactions, which raises concerns on the safety and treatment efficacy of these patients. To protect melanoma patients from potential harm by the combination of their cancer treatment and CAM usage, patients should systematically be encouraged to report their CAM use, while oncologists should be trained on evidence of CAM, and patient guidance for saver CAM use.

The clinical relevance of drug interactions in patients with human immunodeficiency virus infection: update 2009-2014

To update information about drug interactions in patients with HIV/AIDS. Comprehensive literature review in MEDLINE/PubMed database from May of 2009 to December of 2014, using the Mesh terms: Anti-retroviral agents and drug interactions or herb-drug interactions or food-drug interactions. Publications with drug interactions in humans, in English or Spanish, and with full text were retrieved. Additionally, citation lists from identified articles were reviewed. The study inclusion was assessed by three independent researchers and by consensus among them when was necessary. Clinical relevance of drug interaction was grouped into four levels according to seriously and probability of occurrence. Global, 546 different references were retrieved and 243 were selected. In addition 11 further manuscripts were identified in the references of the included articles. Overall, 935 pairs of drug interactions were identified, 95.7% pharmacokinetic (823 by enzyme induction or inhibition and 67 by changes in bioavailability). Of the 935 pairs of drug interactions, 402(43%) were classified as levels 1 or 2. The most clinically relevant antiretroviral drug interactions are due to pharmacokinetic mechanism, mainly induction or enzyme inhibition, according to previous reviews, the protease inhibitors remain as the antiretrovirals with the highest number of clinical relevant interactions.

Assessment of interaction potential of AZD2066 using in vitro metabolism tools, physiologically based pharmacokinetic modelling and in vivo cocktail data

Static and dynamic (PBPK) prediction models were applied to estimate the drug-drug interaction (DDI) risk of AZD2066. The predictions were compared to the results of an in vivo cocktail study. Various in vivo measures for tolbutamide as a probe agent for cytochrome P450 2C9 (CYP2C9) were also compared. In vitro inhibition data for AZD2066 were obtained using human liver microsomes and CYP-specific probe substrates. DDI prediction was performed using PBPK modelling with the SimCYP simulator™ or static model. The cocktail study was an open label, baseline, controlled interaction study with 15 healthy volunteers receiving multiple doses of AD2066 for 12days. A cocktail of single doses of 100mg caffeine (CYP1A2 probe), 500mg tolbutamide (CYP2C9 probe), 20mg omeprazole (CYP2C19 probe) and 7.5mg midazolam (CYP3A probe) was simultaneously applied at baseline and during the administration of AZD2066. Bupropion as a CYP2B6 probe (150mg) and 100mg metoprolol (CYP2D6 probe) were administered on separate days. The pharmacokinetic parameters for the probe drugs and their metabolites in plasma and urinary recovery were determined. In vitro AZD2066 inhibited CYP1A2, CYP2B6, CYP2C9, CYP2C19 and CYP2D6. The static model predicted in vivo interaction with predicted AUC ratio values of >1.1 for all CYP (except CYP3A4). The PBPK simulations predicted no risk for clinical relevant interactions. The cocktail study showed no interaction for the CYP2B6 and CYP2C19 enzymes, a possible weak inhibition of CYP1A2, CYP2C9 and CYP3A4 activities and a slight inhibition (29%) of CYP2D6 activity. The tolbutamide phenotyping metrics indicated that there were significant correlations between CLform and AUCTOL, CL, Aemet and LnTOL24h. The MRAe in urine showed no correlation to CLform. DDI prediction using the static approach based on total concentration indicated that AZD20066 has a potential risk for inhibition. However, no DDI risk could be predicted when a more in vivo-like dynamic prediction method with the PBPK with SimCYP™ software based on early human PK data was used and more parameters (i.e. free fraction in plasma, no DDI risk) were taken into account. The clinical cocktail study showed no or low risks for clinical relevant DDI interactions. Our findings are in line with the hypothesis that the dynamic prediction method predicts DDI in vivo in humans better than the static model based on total plasma concentrations.

The co-use of conventional drugs and herbs among patients in Norwegian general practice: a cross-sectional study.

BackgroundDifferent patient groups are known to use herbal remedies and conventional drugs concomitantly (co-use). This poses a potential risk of herb-drug interaction through altering the drug’s pharmacokinetics or pharmacodynamics. Little is known about co-use among patients in general practice. The primary aim of this study was to compare patients in general practice that co-use herbal remedies and conventional drugs with those who do not. The secondary aim was to register the herb-drug combinations with potential clinical relevant interactions among the co-users.MethodA questionnaire based cross-sectional study conducted in the autumn 2011 in a general practice office with four general practitioners (GPs) and one intern in Western Norway. Adults >18 years who came for an office visit were invited. The questionnaire asked about demographics, herbal use, conventional drug use and communication about herbal use. Multivariable logistic regression was used to compare co-users to the other patients.ResultsOf the 381 patients who completed the questionnaire, the prevalence of herbal use was 44%, with bilberry (41%), green tea (31%), garlic (27%), Aloe vera (26%) and echinacea (18%) as the most frequently used. Among those using conventional drugs regularly, 108 (45%) co-used herbs. Close to 40% of patients on anticoagulants co-used herbs, with garlic and bilberry as the most frequent herbs. Compared to all other patients, co-users had significantly (p < 0.05) increased odds to be female (adjOR 2.0), age above 70 years (adjOR 3.3), use herbs to treat an illness (adjOR 4.2), use two or more herbs (polyherbacy, adjOR 12.1) and having experienced adverse effects of herbal use (adjOR 37.5). Co-use was also associated with use of analgesics or dermatological drugs (adjOR 5.1 and 7.9 respectively). Three out of four patients did not discuss herbal use with any health care professional.ConclusionA sizable proportion of the GP patients co-used herbs with conventional drugs, also combinations with reported interaction potential or additive effects like anticoagulants and garlic. The low disclosure of herbal use to their GP, polyherbacy and the risk of interactions in vulnerable groups like elderly and chronically ill patients, warrant increased awareness among GPs.

AB0057 Influence of PVA coated nanoparticles on survival and functionality of human immune cells

BackgroundNanotechnology has developed into a key technology of the 21st century. Over the recent years, the number of nanotechnical products has received an enormous boost. More and more efforts are...

GRP-169 Screening For Clinically Relevant Interactions in Liver Transplant Patients

BackgroundDrug-drug interactions are a frequent problem in liver transplant (LT) patients, further hindering pharmacotherapeutic management, which is a very important risk to the patient’s life.PurposeTo detect drug-drug interaction of clinical...

Metformin: an old but still the best treatment for type 2 diabetes

The management of T2DM requires aggressive treatment to achieve glycemic and cardiovascular risk factor goals. In this setting, metformin, an old and widely accepted first line agent, stands out not only for its antihyperglycemic properties but also for its effects beyond glycemic control such as improvements in endothelial dysfunction, hemostasis and oxidative stress, insulin resistance, lipid profiles, and fat redistribution. These properties may have contributed to the decrease of adverse cardiovascular outcomes otherwise not attributable to metformin’s mere antihyperglycemic effects. Several other classes of oral antidiabetic agents have been recently launched, introducing the need to evaluate the role of metformin as initial therapy and in combination with these newer drugs. There is increasing evidence from in vivo and in vitro studies supporting its anti-proliferative role in cancer and possibly a neuroprotective effect. Metformin’s negligible risk of hypoglycemia in monotherapy and few drug interactions of clinical relevance give this drug a high safety profile. The tolerability of metformin may be improved by using an appropiate dose titration, starting with low doses, so that side-effects can be minimized or by switching to an extended release form. We reviewed the role of metformin in the treatment of patients with type 2 diabetes and describe the additional benefits beyond its glycemic effect. We also discuss its potential role for a variety of insulin resistant and pre-diabetic states, obesity, metabolic abnormalities associated with HIV disease, gestational diabetes, cancer, and neuroprotection.

Evidence-based intravenous pain treatment with analgesic infusion regimens

To survey all bedside-prepared analgesic infusions (two or more drugs within one vehicle) at a 1000-bed general hospital. To evaluate appropriate vehicles and acceptable drug combinations in analgesic infusions with regard to evidence-based therapy. Literature review; computer simulation of pharmacokinetics with MATLAB 6.5; evaluation of pharmacokinetic or pharmacodynamic interactions and dose regimens. Categorisation of 19 infusion combinations used for the management of pain into acceptable and questionable combinations of components in terms of quality assurance evaluation. Diclofenac sodium (CAS 15307-79-6), metamizole sodium (CAS 68-89-3) and tramadol hydrochloride (CAS 36282-47-0) were combined with diazepam (CAS 439-14-5), B-vitamins (CAS 67-03-8, 130-40-5, 58-56-0, 68-19-9, 98-92-0, 137-08-6), lidocaine hydrochloride (CAS 73-78-9), metoclopramide dihydrochloride (CAS 54143-57-6) and pantoprazole sodium (CAS 138786 7-1). The vehicles were Ringer, Ringer lactate, normal saline or an infusion product containing diclofenac sodium and orphenadrine citrate (CAS 4682-36-4). In 37% the vehicle used was not one recommended by the manufacturer or an incompatibility was mentioned in the product information. The combinations of diclofenac sodium or tramadol with diazepam induce a long-lasting sedative effect by diazepam and its metabolite, but only a moderate duration of analgesia. The combination of diclofenac sodium and metamizole sodium is acceptable, although, at a lower dosage of metamizole, the duration of analgesia is shortened. No or insufficient data on therapeutic plasma levels and safe dosages has been reported for lidocaine and B-vitamins. For all of the drug combinations in use, no interactions of clinical relevance are to be expected. In 37% of the nineteen bedside-prepared infusions, the vehicle was not suitable or incompatibilities were cited in the product information. The combinations of metamizole sodium and diclofenac sodium or tramadol in normal saline solution were in accordance with evidence-based medicine. However, changing some infusion regimens might achieve optimisation of pain treatment with respect to duration of analgesia, and the applied number of drugs could be reduced by omitting additives with little clinical effectiveness.

Medikamenteninteraktionen in der Geriatrie

Drug interactions are often seen in elder patients due to polymedication. They can lead to unwanted side effects attended with unspecific symptoms such as vertigo, lateropulsion, fatigue or confusion. This can result in a prescribing cascade. Interactions can take place on all pharmacodynamic and pharmacokinetic levels, whereas the CYP enzyme-dependent metabolism seems to play a key role. The incidence of drug interactions is quite high and clinical relevant interactions are also not uncommon. Especially drugs with a low therapeutic index are more likely to be the target of clinical relevant interactions. However, most of the drug interactions can be managed by dose-reduction or by replacing one of the possibly interacting drugs. An important point is to remember the possibility of drug interactions.

Interacciones medicamentosas. Nuevos aspectos

A drug interaction is the quantitative or qualitative modification of the effect of a drug by the simultaneous or successive administration of a different one. The simultaneous administration of several medicines to the same patient can facilitates their appearance. It is difficult to determine their incidence, but it is related to the number of drugs administered simultaneously. Although it is impossible to remember all the clinical relevant interactions, to bare in mind their existence and the possible mechanisms of production can help to identify them and to contribute to their prevention. The most frequent interactions related with clinical problems are the pharmacokinetic ones, mainly those related to the metabolism through the cytochrome P450 system or the presystemic clearance by means of the P-glycoprotein and other drug transporters. Interactions between drugs and grapefruit juice or St John's wort are frequent and it is important to bear in mind in clinical practice.

In vitro metabolism of zolmitriptan in rat cytochromes induced with β-naphthoflavone and the interaction between six drugs and zolmitriptan

Zolmitriptan is a novel and highly selective 5-HT 1B/1D receptor agonist used as an acute oral treatment for migraine. There are few reports regarding the in vitro metabolism of zolmitriptan. Previous studies indicated zolmitriptan was metabolized via CYP1A2 in human hepatic microsomes. In order to study the enzyme kinetics and drug interaction, the metabolism of zolmitriptan and possible drug–drug interactions were investigated in rat hepatic microsomes induced with different inducers. An active metabolite, N-demethylzolmitriptan, was detected and another minor, inactive metabolite that was reported in human hepatic microsomes was not detected in this study. The enzyme kinetics for the formation of N-demethylzolmitriptan from zolmitriptan in rat liver microsomes pretreated with BNF were 96±22 μM ( K m), 11±3 pmol min −1 mg protein −1 ( V max), and 0.12±0.02 μl min −1 mg protein −1 ( CL int). Fluvoxamine and diphenytriazol inhibited zolmitriptan N-demethylase activity catalyzed by CYP1A2 ( K i=3.8±0.3 and 3.2±0.1 μM, respectively). Diazepam and propranolol elicited a slight inhibitory effect on the metabolism of zolmitriptan ( K i=70±11 and 90±18 μM, respectively). Cimetidine and moclobemide produced no significant effect on the metabolism of zolmitriptan. Fluvoxamine yielded a k inactivation value of 0.16 min −1, and K i of 57 μM. The results suggest that rat hepatic microsomes are a reasonable model to study the metabolism of zolmitriptan, although there is a difference in the amount of minor, inactive metabolites between human hepatic microsomes and rat liver microsomes. The results of the inhibition experiments provided information for the interactions between zolmitriptan and drugs co-administrated in clinic, and it is helpful to explain the drug–drug interactions of clinical relevance on enzyme level. This study aso demonstrated that fluvoxamine may be a mechanism-based inactivator of CYP1A2.

Interacciones farmacológicas en tratamientos crónicos: medidas correctoras para su prevención en un área básica de salud rural

To identify the pharmacological interactions of clinical relevance (PICR) in the medication authorization cards (MAC) of the chronically ill and to establish strategies to minimise their appearance. Cross-sectional descriptive study. Rural primary care centre. Random sample of 626 MAC out of a total of 1306. In December 1998, the following was gathered for every MAC with more than one drug treatment: age, sex, number of drugs, intrinsic value, drugs prescribed, daily dose and pharmacological interactions (PI), classified (using the scale of Hansten 1996) into light and clinically relevant. Mantel-Haenszel (alpha = 0.05). Patients' mean age was 69.1 (95% CI, +/- 1.2). Mean number of drugs per MAC was 4 (95% CI, +/- 0.2). 341 PI affecting 197 patients (31.5%, 95% CI, +/- 3.6) were identified. 24.9% (95% CI, +/- 4.5) were PICR, detected in 11.7% (95% CI, +/- 2.5) of the MAC. The existence of PI was related to the number of drugs prescribed to each patient (p < 0.01). There were 26 PI with drugs of low intrinsic value (7.6%; 95% CI, +/- 2.8). 74.1% (95% CI, +/- 9.3) of the total PICR could be avoided by simple recommendations; and the remaining 25.9% (95% CI, +/- 9.3) by monitoring and follow-up of patients. It is important to identify the medications most commonly involved in the PICR so as to establish corrective measures to minimise the risks arising from multiple medication. Four educational messages advise on over 60% of the PICR detected.