Probable Drug Interaction Research Articles

A Review on medicinal plants in dentistry

The dental afflictions are indubitably the most important global infectious diseases affecting both children and adults. The most significant dental illness is dental caries and periodontal pathologies. The major reason of oral health troubles is more inhabitants with pathogenic bacteria and for this reason, conservative treatment can often be in efficient because of bacterial resistance or may have unpleasant side effects.For that reason, studies in the field have focused on finding new therapeutic alternatives.The use of natural medicines for dental care is an ancient cross-cultural practice that persists in the majority of cultures today.Over the past decade, interest in drugs derived from medicinal plants has markedly increased. This study was designed at a literature review focusing on studies investigating herbal drugs and their therapeutic application, mechanism of action, side effects, toxicities and probable drug interactions. A small number of studies were established to hold their rational employ in dentistry. Because there is a rising employ of phytotherapeutic agents in dentistry, additional studies are required to evaluate their safety and efficacy for clinical use.
 Keywords: Herbal medicine, Oral health, Dentistry, Caries, Infections

Drug-drug interactions between COVID-19 treatments and antipsychotics drugs: integrated evidence from 4 databases and a systematic review.

RationaleManagement of anxiety, delirium, and agitation cannot be neglected in coronavirus disease (COVID-19). Antipsychotics are usually used for the pharmacological management of delirium, and confusion and behavioral disturbances. The concurrent use of treatments for COVID-19 and antipsychotics should consider eventual drug-drug interactionsObjectiveTo systematically review evidence-based available on drug-drug interactions between COVID-19 treatments and antipsychotics.Evidence reviewThree databases were consulted: Lexicomp® Drug Interactions, Micromedex® Solutions Drugs Interactions, and Liverpool© Drug Interaction Group for COVID-19 therapies. To acquire more information on QT prolongation and Torsade de Pointes (TdP), the CredibleMeds® QTDrugs List was searched. The authors made a recommendation agreed to by consensus. Additionally, a systematic review of drug-drug interactions between antipsychotics and COVID-19 treatment was conducted.ResultsThe main interactions between COVID-19 drugs and antipsychotics are the risk of QT-prolongation and TdP, and cytochromes P450 interactions. Remdesivir, baricinitib, and anakinra can be used concomitantly with antipsychotics without risk of drug-drug interaction (except for hematological risk with clozapine and baricinitib). Favipiravir only needs caution with chlorpromazine and quetiapine. Tocilizumab is rather safe to use in combination with antipsychotics. The most demanding COVID-19 treatments for coadministration with antipsychotics are chloroquine, hydroxychloroquine, azithromycin, and lopinavir/ritonavir because of the risk of QT prolongation and TdP and cytochromes interactions. The systematic review provides highly probable drug interaction between lopinavir/ritonavir plus quetiapine and ritonavir/indinavir plus risperidone.ConclusionsClinicians prescribing antipsychotics should be aware of the likely risk of drug-drug interaction with COVID-19 medication and may benefit from taking into account present recommendations of use to preserve patient safetySupplementary InformationThe online version contains supplementary material available at 10.1007/s00213-020-05716-4.

Case series of immunosuppressant drug interactions with flucloxacillin in heart transplant recipients

AbstractBackgroundAfter heart transplantation, the International Society for Heart and Lung Transplantation (ISHLT) recommends calcineurin inhibitor (CNI)‐based immunosuppressant therapy with mycophenolate or a mammalian target of rapamycin (mTOR) inhibitor. Both CNIs and mTOR inhibitors are extensively metabolised by the cytochrome P450 enzyme pathway and are substrates of P‐glycoprotein (PGP), making drug interactions with these therapies an important consideration. Herein we report four cases of probable drug interactions between tacrolimus and everolimus with flucloxacillin in orthotopic heart transplant recipients. The effects were subtherapeutic immunosuppressant concentrations and cellular rejection.Clinical detailsAll four heart transplant recipients received intravenous (IV) flucloxacillin for methicillin‐sensitive Staphylococcus aureus infections in conjunction with immunosuppression regimens containing everolimus and/or tacrolimus. Despite tacrolimus and everolimus dose adjustments, Grade 2R rejection was diagnosed in all four patients in association with subtherapeutic immunosuppressant concentrations.OutcomesA considerable increase in tacrolimus and everolimus trough concentrations was observed following cessation of IV flucloxacillin. The rise in concentrations occurred despite no change in or dose reductions of immunosuppressants. A possible mechanism for the interaction is via pregnane X receptor activation.ConclusionThese cases provide support that flucloxacillin significantly reduces tacrolimus and everolimus trough concentrations in heart transplant recipients. Dosage adjustments and close monitoring of drug concentrations or consideration of alternative antimicrobial therapy is required to avoid episodes of rejection or adverse events upon commencing and ceasing flucloxacillin therapy.

The Role of Cytochrome P450 3A5 Enzyme on the Metabolism of Tacrolimus in Rats

Purpose: The present study was designed to determine the effect ratio of CYP3A5 on the metabolism of tacrolimus that is used as an immunosuppressant for tissue transplantation.Methods: To determine the role of CYP3A4 and CYP3A5 on tacrolimus metabolism, rats were divided into five groups as: group 1 control group, tacrolimus only 1 mg/kg i.v. , group 2 pretreated with ritonavir 5 mg/kg, i.v. 1 h before administration of tacrolimus , group 3 pretreated with indinavir 10 mg/kg, i.v. 1 hour before administration of tacrolimus , groups 4 and 5, in addition to the protocol of groups 2 and groups 3. Dexamethasone 100 mg/kg, p.o. was administered for 2 days before the experimental study to each group. To estimate the area under curve AUC of tacrolimus, the blood samples were collected after 15, 30, 60, 75, and 90 min and after 2, 3, 4, 8, and 24 h, and MEIA method was used to determine whole blood levels of tacrolimus.Results: Although the AUCs of tacrolimus in group 2 533.5±139.85 ng.h/mL and group 3 3428±683 ng.h/mL were higher than the control group 394±127 ng.h/mL , the only significant difference was found in ritonavir pretreated group group 3 . In dexamethasone pretreated groups, the AUC values were similar to control group.Conclusion: These results suggest that the role of CYP3A5 enzyme has to be taken into account for probable drug interactions and sufficient immunosuppression in patients who are treated with tacrolimus

Objective Structured Clinical Examination in Undergraduate Pharmacy Students: Time to Switching to an Alternative Exam for Clerkship Courses

Abstract: Background: Significant changes in the clinical context of health professional education and impressive body of research on the measurement of clinical competence support the use of the Objective Structured Clinical Exam (OSCE) as the preferred means of performance-based assessment to current teaching and evaluation method. The objective of this paper is to describe how the OSCE method was developed and applied to an undergraduate community pharmacy clerkship course, as a pilot for assessing clinical competence and skills of these students. Methods: A seven-station OSCE was designed and implemented to assess the learning objectives of community pharmacy clerkship course(s) in the Pharmacy Doctorate program of pharmacy curriculum of the Isfahan University of Medical Sciences. The key process in designing and implementing the OSCE includes: development and face-validation of seven stations in accordance with our learning objectives of the course; designing of dichotomous performance checklists or suitable assessment instruments for individual stations; and conducting of the final examination. The broad competencies tested in the OSCE included: drug labeling, patient education and counseling, drug usage instruction, reading and evaluating prescriptions and use of drug information resources (electronic or hard copy texts) for determining probable drug interactions. Results: The students scored the highest marks in use of drug information resources for determining probable drug interactions (mean ± SD: 5.6 ± 0.68) and the lowest marks in drug usage instruction (mean ± SD: 4.8 ± 0.56). Most of the students (84%) found OSCE as an appealing and useful method of assessment. Conclusion: The assessment methods and educational objectives should be aligned with each other. Although OSCE is not commonly used in Iranian pharmacy schools, however, due to the practical nature of clerkship courses of the pharmacy doctorate program, OSCE seems to be a more suitable and relevant method to evaluate the community pharmacy clerkship course compared to conventional written exams. Key words: Educational Assessment, Pharmacy Students, Pharmacy Education, Clinical Clerkships, Educational Measurements.

Interaction between Meropenem and Valproate:Not to overlook

Background Valproic acid is commonly used to treat various types of seizures and follows non-linear pharmacokinetics with a therapeutic range of 50 – 150 ug/ml. Several retrospective studies have reported that concomitant administration of VPA and carbapenem lead to decrease in VPA levels significantly and results in failure of seizure control. Different studies suggest the mechanism of interaction as (i) carbapenem may inhibit the gastrointestinal absorption of VPA (ii) meropenem accelerated the glucuronidation of VPA to VPA glucuronide (VPA-G) and inhibited the hydrolysis of VPA-G back to the VPA thus increasing the clearance of VPA and VPA-G and (iii) due to fast erythrocyte distribution of VPA by carbapenem, VPA levels has been reduced. Purpose To report four cases who were maintained on therapeutic levels of VPA and had sub-therapeutic levels afterward due to the administration of meropenem. Method through CPOE system of AKUH the cases in 2014 were identified who were on valproate-meropenem combination with the available pre and post meropenem valproate levels. Result Patients of different age group showed significant reduction in VPA levels within 48 hour of administration of meropenem. Conclusion This case series describing the clinical importance of this probable drug interaction and promote its awareness among physicians in Pakistan. If a patient was therapeutic on the same dose of valproate and need broad spectrum coverage, a dose adjustment of valproate should not be done and physicians should consider either alternative broad spectrum antibiotic or renaly cleared antiepileptic to avoid this frequently used dangerous drug combination.

Increased Bleeding Tendency from Interaction between Rivaroxaban and Topical Miconazole: Case Report

Novel oral anticoagulants (OAC) are being increasingly used. We describe a case of increased bleeding tendency resulting from probable drug interaction between rivaroxaban and topical miconazole. Recognition of this possible interaction is important during concomitant use to prevent adverse outcome arising from over-anticoagulation.

Probable fatal drug interaction between intravenous fenretinide, ceftriaxone, and acetaminophen: a case report from a New Approaches to Neuroblastoma (NANT) Phase I study

BackgroundPatients with relapsed/refractory stage 4 high-risk neuroblastoma were enrolled on a phase I study (NANT2004-03) of intravenous fenretinide emulsion. Pharmacokinetic samples were collected during and after the infusion, and the levels were measured using an HPLC system. A likely case of a fatal drug interaction between fenretinide, ceftriaxone, and acetaminophen is described, including the pharmacokinetics of fenretinide, laboratory data, and post-mortem autopsy in a pediatric neuroblastoma patient treated on this study.Case presentationOn Day 4 of a scheduled 5-day-infusion of intravenous fenretinide, the patient developed a fever, acetaminophen was started, ceftriaxone initiated for possible bacteremia, and fenretinide level doubled from 56 to 110 μM. Over the next three days, although blood cultures remained negative, the patient’s condition deteriorated rapidly. Acute liver failure was diagnosed on Day 7, and the patient expired on Day 20 of fulminant hepatic failure with associated renal, cardiac, and hemorrhagic/coagulation toxicities. Autopsy showed extensive hemorrhagic necrosis of the liver, marked bile duct proliferation, and abundant hemosiderin, consistent with cholestasis and drug toxicity.ConclusionsAfter extensive review of patient data, the clinical course, and the literature, we conclude that observed hepatic toxicity was likely due to a drug interaction between fenretinide and concomitant ceftriaxone and acetaminophen. None of the other 16 patients treated on this study experienced significant hepatic toxicity. Although the prevalence of cholestasis with ceftriaxone usage is relatively high, the potential drug interaction with these concomitant medications has not been previously reported. Concomitant use of fenretinide, ceftriaxone, and acetaminophen should be avoided.

Drug Interaction Between Oral Cyclosporine Modified and Iron.

To describe a recent case of suspected interaction between oral cyclosporine modified and iron. A 33-year-old man underwent urgent cardiac transplantation for refractory cardiogenic shock caused by acute myocarditis. The patient had persistently low levels of cyclosporine despite a dose increase of the drug after the change of administration route from intravenous to oral. Spacing the administration of cyclosporine modified from oral iron resolved the problem. This drug interaction was reported as "probable" as determined by a Drug Interaction Probability Scale score of 7. Using this scoring system, the patient experienced a probable drug interaction between cyclosporine and iron both administered orally, and we surmise that the mechanism is that iron physicochemically destabilizes the cyclosporine microemulsion when both are administered concurrently. This may be because of the interaction between cyclosporine microemulsion and iron because this cation can destabilize the immunosuppressant dosage form. Taking into account that joint administration of oral iron and cyclosporine modified can generate a physicochemical interaction that involves a decrease in the absorption of cyclosporine modified, we believe that it is necessary to recommend spacing administrations of both drugs as well as monitoring levels of cyclosporine in order to ensure optimal levels of immunosuppression.

Drug Interaction between Sirolimus and Ranolazine in a Kidney Transplant Patient

Purpose. The case of a kidney transplant recipient who experienced a probable drug interaction between sirolimus and ranolazine is reported. Summary. The narrow therapeutic window of immunosuppressive therapy in transplant recipients requires close monitoring for potential drug-drug interactions. The patient, a 57-year-old Caucasian male kidney transplant recipient, was stable for years on sirolimus as his primary immunosuppressive agent and had a history of chronic angina, for which he was prescribed ranolazine. Upon addition and dose escalation of ranolazine, whole blood sirolimus levels more than tripled, rising to immeasurably high concentrations. After holding sirolimus on multiple occasions and reducing dosage more than 50%, blood levels returned to therapeutic range, while continuing ranolazine. Conclusion. Since ranolazine is a documented P-GP and CYP3A inhibitor, and sirolimus a known substrate for both pathways, it is proposed that ranolazine inhibition of P-GP and CYP3A4 contributed to the significant elevation in sirolimus exposure. No alternative causes for the rise in sirolimus exposure were found, and assessment with the Drug Interaction Probability Scale finds this interaction to be probable. Clinicians should be aware of the potential for this interaction to cause elevated sirolimus exposure and subsequent increase in clinical effect or toxicity, in this case overimmunosuppression.

Inadvertent Exaggerated Anticoagulation Following Use of Bismuth Subsalicylate in an Enterally Fed Patient Receiving Warfarin Therapy

We report a case of an inadvertent increase in the international normalized ratio (INR) after the addition of bismuth subsalicylate for the treatment of diarrhea in an enterally fed patient receiving warfarin therapy. A 56-year-old Caucasian female presented to the trauma intensive care unit (ICU) with multiple lower extremity fractures. Warfarin was initiated for deep vein thrombosis prophylaxis due to the patient's inability to ambulate. The target INR was 2-3. Continuous intragastric enteral feeding was withheld 1 hour before and 1 hour after intragastric administration of warfarin. Bismuth subsalicylate 30 mL every 4 hours was prescribed for diarrhea. Within 3 days after starting bismuth subsalicylate therapy, the patient's INR increased from 2.56 to 3.54 and minor bleeding was noted from the patient's tracheostomy site. No significant change in warfarin dosage, variability in vitamin K intake, or medications that potentially alter warfarin metabolism were present during the unexpected rise in INR. When the bismuth subsalicylate was discontinued, the patient's INR stabilized into the target range on the same warfarin dose given at the time of the supratherapeutic INR. Salicylate displaces warfarin from plasma protein binding sites and may result in a significant increase in INR secondary to redistribution of warfarin to the free active form. Evaluation of this case report using the Drug Interaction Probability Scale and Naranjo Adverse Drug Reaction Probability Scale yielded scores consistent with a probable adverse drug interaction. Bismuth subsalicylate exaggerates warfarin's anticoagulant response and its concurrent use during warfarin therapy should be avoided.

Significant Interaction between Activated Charcoal and Antiretroviral Therapy Leading to Subtherapeutic Drug Concentrations, Virological Breakthrough and Development of Resistance

A 42-year-old, treatment-experienced woman, virologically suppressed on tenofovir/emtricitabine and boosted atazanavir, experienced virological breakthrough, drop in CD4(+) T-cell count and undetectable drug concentrations. Adherence to treatment was confirmed, but repeat testing yielded similar results. After 2 months, the patient stated that she had been taking activated charcoal to manage gastrointestinal symptoms associated with her combination antiretroviral therapy, but she had recently discontinued the charcoal. Atazanavir concentrations were therapeutic but the patient's viral load rebounded and genotype testing revealed new reverse transcriptase mutations. The patient was changed to zidovudine, lamivudine, and boosted darunavir and achieved viral suppression. At 1 year follow-up, her viral load remained <40 copies/ml. According to the drug interaction probability scale, our patient experienced a probable drug interaction between activated charcoal and atazanavir/ritonavir leading to virological breakthrough and development of resistance.

A Probable Interaction between Warfarin and the Antiretroviral TRIO Study Regimen

To report a probable drug interaction between the antiretroviral TRIO regimen (ritonavir-boosted darunavir, etravirine, and raltegravir) and warfarin in an HIV-infected patient. In January 2010, a 50-year-old transgender female with HIV infection and recurrent deep vein thrombosis began treatment with the TRIO study regimen. Treatment had been maintained with warfarin for the past 5 years and emtricitabine monotherapy for the preceding 22 months. Emtricitabine was discontinued when the TRIO regimen was started. The mean weekly warfarin dose while the patient was receiving emtricitabine monotherapy was 13.3 mg (95% CI 12.7 to 13.8), with a mean international normalized ratio (INR) of 2.8 (95% CI 2.5 to 3.1). Following the initiation of the TRIO regimen, the mean weekly warfarin dose was increased to 19.3 mg (95% CI 18.5 to 20.1) and was maintained over the ensuing 71 weeks with a mean INR of 2.6 (95% CI 2.2 to 3.0). Information on the effect of newer antiretrovirals on warfarin metabolism, as well as the collective contribution of combination antiretroviral therapy including multiple agents that may alter warfarin metabolism, is limited. We predicted that warfarin dose requirements would change upon initiation of the TRIO regimen. Given the variability in INR that can occur with chronic warfarin treatment, weekly warfarin doses were averaged during emtricitabine monotherapy (90 weeks) and TRIO regimen (71 weeks) periods. Mean weekly warfarin doses increased by 45% (p < 0.001) following initiation of the TRIO regimen. Mean INR results for the 2 time periods were not significantly different, demonstrating that stable anticoagulation was maintained. The Horn drug interaction probability scale score to assess causation indicated a probable interaction. An increased weekly warfarin dose requirement is predicted when warfarin is used concurrently with the antiretroviral TRIO regimen. Increased INR monitoring is prudent when the combination is administered.

Probable Drug Interaction Between Intravenous Ciprofloxacin and Mycophenolate Mofetil in a Bone Marrow Transplant Recipient

Several studies have reported that oral antibacterials, including ciprofloxacin, administered during mycophenolate mofetil therapy may reduce mycophenolic acid (the active drug moiety) exposure. To our knowledge, however, this effect has never been described with antibiotics administered by the parenteral route. We describe a 17‐year‐old female who received intravenous mycophenolate mofetil after bone marrow transplantation, with therapeutic drug monitoring performed during therapy. On day 2 of mycophenolate mofetil therapy, the mycophenolic acid area under the plasma concentration‐time curve was 30.3 mg•hour/L. On day 8, although her mycophenolate mofetil dosage had remained unchanged, the mycophenolic acid area under the plasma concentration‐time curve was unexpectedly lower at 10.7 mg•hour/L. A drug interaction was suspected. Three intravenous antiinfective drugs had been introduced after initial therapeutic drug monitoring had been performed—ciprofloxacin, trimethoprim‐sulfamethoxazole, and caspofungin. The patient subsequently developed severe graft‐versus‐host disease during mycophenolate mofetil therapy and died. Use of the Horn drug interaction probability scale indicated a probable interaction between intravenous mycophenolate mofetil and intravenous ciprofloxacin in this patient. The available literature does not support the role of either trimethoprim‐sulfamethoxazole or caspofungin in a drug interaction with mycophenolate mofetil. Published studies have shown that ciprofloxacin is partially excreted by transintestinal elimination after intravenous administration and that it may greatly reduce the levels of enterobacteria of gastrointestinal flora, which are responsible for mycophenolic acid enterohepatic recirculation. Clinicians should be aware that ciprofloxacin, even administered intravenously, may modify the pharmacokinetics of mycophenolate mofetil. Ciprofloxacin should be used with caution in patients receiving mycophenolate mofetil; if this antiinfective must be used, therapeutic drug monitoring should be performed to guide dosage adjustments.

Probable tacrolimus toxicity from tibolone co-administration in a woman: a case report

IntroductionTibolone is a synthetic steroid, used with increasing frequency to treat symptoms of menopause, including patients with solid-organ transplants who are taking concurrent immune suppression. To the best of our knowledge, there are no reported drug interactions between tibolone and tacrolimus, one of the principal immune suppressants used in kidney transplantation.Case presentationWe report the case of a 49-year-old Caucasian woman who had received a kidney transplant and who developed acute kidney injury secondary to tacrolimus toxicity 10 days after starting tibolone therapy. No alternative causes were found. Tibolone is known to be a weak competitive inhibitor of CYP3A4, which is involved in tacrolimus metabolism.ConclusionsDespite a careful evaluation, no alternative reason was found for the acute kidney injury, and her kidney function returned to the previous baseline within several days of cessation of the medication, and with no other specific treatment. Using the Drug Interaction Probability Scale we conclude that she experienced a probable drug interaction. We believe that transplant clinicians should utilise frequent therapeutic drug monitoring of tacrolimus in patients starting or stopping tibolone therapy.

Warfarin and bosentan interaction in a patient with pulmonary hypertension secondary to bilateral pulmonary emboli

Background: Bosentan is an endothelin-receptor antagonist that reportedly induces both cytochrome P450 (CYP) 3A4 and CYP2C9 enzymes, which are also involved in warfarin metabolism. We present a case report describing a probable drug interaction between warfarin and bosentan in a patient with pulmonary hypertension. Case summary: A 52-year-old black female (weight, 77 kg) diagnosed with pulmonary hypertension secondary to bilateral pulmonary emboli had a stable international normalized ratio (INR; target range, 2-3) with a weekly warfarin dose of 52.5 mg for 2 months before the initiation of bosentan therapy. Other concurrent medications included telmisartan/ hydrochlorothiazide 40/12.5 mg once daily and a daily multivitamin (which contained no vitamin K). Three weeks after starting bosentan 62.5 mg BID, a therapeutic INR concentration was reached with a weekly warfarin dose 14% higher (an increase of 7.5 mg/wk) than her weekly warfarin dose before initiation of bosentan. After a brief discontinuation (7 days) and retitration of bosentan and warfarin, the final weekly warfarin dose (75 mg/wk) was 43% greater (an increase of 22.5 mg/wk) than the previously stable dose, which enabled the patient to reach her therapeutic INR goal range of 2 to 3. Conclusions: Bosentan has CYP3A4- and CYP2C9-inducing properties and is therefore likely to cause decreased concentrations of warfarin. We describe here a probable drug interaction between bosentan and warfarin that resulted in a 43% increase in warfarin dose to maintain the patient's therapeutic INR.

Probable Drug Interaction Between Warfarin and Hormonal Contraceptives

To report a single patient case that presented with a probable drug interaction between warfarin and 3 methods of hormonal contraceptives, as assessed by the Horn Interaction Probability Scale. A 33-year-old female patient required long-term anticoagulation following an aortic valve replacement. While taking warfarin (38.5 mg weekly), she transitioned from a monophasic combined oral contraceptive (ethinyl estradiol plus norethindrone) to an implantable progestin-only contraceptive (etonogestrel) on the advice of her cardiologist. Nineteen days following etonogestrel implant insertion, her international normalized ratio (INR) decreased to 1.8 and required a 55.8% warfarin dose increase (resulting dose of 60 mg weekly). Within 10 months, the patient elected to have the implant removed due to vaginal bleeding. Nine days following removal of etonogestrel, she experienced a transient INR increase to 6.5. Her INR returned to within goal range after her warfarin dose was decreased to 55.5 mg weekly. After using barrier methods of contraception for 48 days, she initiated an oral progestin-only contraceptive (norethindrone). Further warfarin dose adjustments were made, resulting in a weekly warfarin dose of 53.5 mg. Thirty-nine days after initiation of oral norethindrone, she elected to discontinue use due to vaginal bleeding and no longer uses hormonal contraceptive methods. No further adjustments to her warfarin dose were warranted. The increased warfarin requirement observed in this patient may have been a result of multiple factors. Based on a literature review, we hypothesize that the predominant mechanism of interaction was ethinyl estradiol inhibition of CYP1A2 and 2C19. We recommend that further in vivo studies be completed to definitively identify the mechanism of the interaction. It is necessary to intensify warfarin monitoring upon initiation or alteration of hormonal contraceptives.

Severe synergistic toxicity from docetaxel in a patient treated concurrently with protease inhibitors as part of HIV post-exposure prophylaxis: a case report

IntroductionDocetaxel is a semisynthetic taxane commonly used in solid tumour oncology. Its pharmacokinetics has been widely studied, and it is well established that it is metabolized to pharmacologically inactive products by the cytochrome P450 3A iso-enzymes. However, there have been few reports of the consequences of drug interactions between taxanes and other drugs metabolized by the cytochrome P450 pathway. To the best of our knowledge, this is the first case report of the potentially life-threatening interaction that can occur between docetaxel and the protease inhibitors lopinavir and ritonavir.Case presentationA 30-year-old Caucasian woman presented with symptoms suggestive of severe docetaxel toxicity, that is, prolonged myelosuppression, grade 4 mucositis and desquamating rash, following the commencement of post-exposure prophylaxis for a needlestick injury. She had previously received docetaxel chemotherapy with minimal side effects.ConclusionThis case report highlights a probable and novel drug interaction between docetaxel and lopinavir and/or ritonavir, which is largely unreported in the medical literature. Even though these interactions may be more relevant in the field of HIV medicine, knowledge of these interactions is also beneficial to oncologists and dermatologists, as well as those providing acute medical care.

Probable Interaction Between Tolterodine and Warfarin

53-year-old woman with a history of deep vein thrombosis and pulmonary embolism was receiving warfarin to prevent thromboembolic complications; her international normalized ratio (INR) had been stable for 1 month. Extended-release tolterodine 4 mg/day was then prescribed to manage overactive bladder. On her next anticoagulation clinic visit, the patient's INR had increased, although the dosage of warfarin had been reduced when the tolterodine had been prescribed. Due to the absence of other contributing factors and the temporal relationship between tolterodine and prolonged INR, the event was determined to be a probable drug interaction. When patients are prescribed tolterodine and warfarin concurrently, clinicians should monitor INR carefully, and a reduction in warfarin dosage may be required.

Revisión de las interferencias entre los medicamentos más prescritos en el servicio de atención primaria de L’Hospitalet de Llobregat (ICS) y los análisis clínicos

To analyse the concordance of published information on probable drug interactions and the results of clinical analyses. Bibliographical review of the 50 most commonly prescribed drug products at the Primary Health Centre of L'Hospitalet de Llobregat, Barcelona, Spain, in 2002 and 2003. Six bibliographical sources consisting of drug product catalogues and reference books. Interference with the 56 drug products studied. Most theoretical interference belonged to the therapeutic group of anti-inflammatory drugs. The drug products with most interference were hydrochlorothiazide (diuretic) and gliclazide (lipid lowering). The most frequent interference was in the increase of transaminases, thrombocytopaenia, leukopaenia, hyperglycaemia, and hyperuricaemia. Only in 12% of the points of interference analysed was the rate of concordance among the various bibliographical sources reviewed higher than 50%. The highest rate of concordance was found in the diuretics. Consultation of a single bibliographical source does not necessarily ensure the obtaining of reliable data on possible drug interference. This study demonstrates the need to standardize information on drug interference and to include the medication that the patient follows on the analysis application form.