Part of the resistance to tracking con-meds may simply be lack of technology adoption. The list of agents that decrease theophylline clearance is extensive (Box 65-2). As with antipsychotics, at therapeutic levels clearance is flow-dependent and decreased by hepatic disease or states that impede hepatic throughput. Women taking oxcarbazepine should be given a contraceptive that contains 50 mg of ethinylestradiol and they should be monitored for signs of insufficient contraceptive cover, such as breakthrough bleeding. There is evidence that with administration of secondary amine compounds, some 15% of patients develop detectable levels of tertiary drug in plasma, e.g. Trial participants might be asked to bring in a personal diary of any additional medications they might be taking, or even to bring their medications in for documentation at the site. Fixed-dose drug combinations are appropriate for: Convenience, with improved patient compliance, is appropriate with two drugs used at constant dose, long term, for an asymptomatic condition, e.g. According to the dictionary for clinical trials “concomitant medications are the drugs that are not being studied but which a patient is taking through all or part of a study. Hence, it is possible that the chemotherapy was of a type that stimulated immune response (against the cancer) or that the chemotherapy was of a type that does not involve immune response, such as paclitaxel or cisplatin. Few studies have examined the impact of CM use on trial eligibility. Choosing anti-inflammatory analgesic therapy has become increasingly complex with the increased understanding of associated toxicities. Challenges in tracking concomitant medications. Sujay was most recently Senior VP of Global Corporate Strategy and Development at Model N, where he filled multiple roles, from corporate development to overseeing their life sciences analytics and SaaS business unit. Oxcarbazepine does not modify the anticoagulant activity of warfarin [57]. If I take both aspirin and my heart medication, then these two drugs are concomitant. Fortunately, new electronic technologies are now available to address this challenge. Concomitant use of psychoactive medications is a common practice in most clinical trials of antidepressant medications. The symptoms and conditions for which NSAIDs are used are extraordinarily common. The drug being evaluated in the trial; this definition is synonymous with “investigational new drug” or “investigational medicinal product.” Medication number A unique number on the label of each investigational drug package that is used in a trial to dispense and track medication. Regardless of the mechanism, clinical trial data has clearly demonstrated that concomitant use of MTX improves response to adalimumab. Any prescription or over-the-counter drug, treatment, or supplement clinical trial patients are taking at the same time as the treatment being studied. Medication-related exclusion criteria are among the most common barriers to enrollment in clinical trials. Combining isoniazid with rifampicin (Rifinah, Rimactazid) ensures that single-drug treatment cannot occur; treatment has to be two drugs or no drug at all. There is a suggestion from animal studies that they may be more cardiotoxic than parent drugs, though the human relevance of this is unclear. On the other hand, adverse events can have important economic consequences, and improved safety may be cost-effective. 345-353 CrossRef View Record in Scopus Google Scholar This kind of paper-based documentation is cumbersome, and certainly does not lend itself well to any kind of effective or efficient analysis of possible con-med-study drug interactions. Other common drugs that diminish theophylline clearance include the macrolide antibiotics (e.g., erythromycin or clarithromycin) and the quinolone antibiotics (e.g., ciprofloxacin or norfloxacin). Statin (or placebo) is the drug of interest in the study. However, a recent meta-analysis of the safety and efficacy of acetaminophen for spinal pain and osteoarthritis found that this agent is ineffective in the treatment of low back pain and provides minimal short-term benefit for people with osteoarthritis.149 Furthermore, patients taking acetaminophen were nearly four times more likely to have abnormal results on liver function tests. Due to the variability in how medications are recorded, a standard naming convention is required in order to tabulate this data effectively. Subject’s Initials/ Randomization #: Study Title: Medication Total Daily Dose (Freq. In vitro, and possibly in vivo, they do appear to share reuptake inhibition actions similar in type and degree to their parent drugs and they make a contribution to efficacy and probably tolerability (Young 1991). Conclusion: Each investigational drug and new drug class in oncology has a unique DDI profile. Although this has been used as an argument in favour of the preferential use of secondary amines, this is probably only of clinical significance in selected individuals, such as the elderly or those with a clear history of previous intolerance. Minimisation of unwanted effects. This issue is compounded by the fact that potential study participants are usually taking concomitant medications. Con-meds are important for another reason: they can contribute to the problem of patient enrollment and delays, as they are typically part of a clinical study’s inclusion and exclusion criteria. One of barriers to collecting quality con-med information commonly occurs during the data collection process. Medication-related exclusion criteria are among the most common barriers to enrollment in clinical trials. Package label. In Meyler's Side Effects of Drugs (Sixteenth Edition), 2016, See also Felodipine; Lithium; Valproic acid. Concomitant medications are used by nearly 100% of subjects involved in Phase 1 cancer clinical trials, for example, but the topic of con-meds is not given much attention in medical literature. The protocol-defined period may be based on the elimination half-life of antimalarials that are locally available. In the eplerenone label … increases of ALT greater than 120 U/L and bilirubin greater than 1.2 mg/dL were reported 1/2259 patients administered eplerenone tablets and 0/351 placebo-treated patients.”86, The adjudication committee provided a strategy for assessing relatedness, for the situation where relatedness was confounded and unclear, “the … adjudication committee determined a more meaningful approach would be to categorize subjects as those for whom DILI could be excluded, those for whom DILI could not be excluded, and those with insufficient data to make a determination.”87. We use cookies to help provide and enhance our service and tailor content and ads. In choosing an NSAID for a particular patient, the clinician must consider efficacy, potential toxicity related to concomitant drugs and patient factors, and cost. Prospectively considering the presence of GI and cardiovascular risk factors is essential when considering treatment options (Table 59-5). desipramine to imipramine (Rudorfer & Potter 1987). Combinations are logical if there is good reason to consider that the patient needs all the drugs in the formulation and that the doses are appropriate and will not need adjustment separately. The increased cost of branded NSAIDs has an important pharmacoeconomic impact. Although FDA guidelines have always called for an analysis of the impact of con-meds in clinical trials, this has not always been strongly enforced. The antibody binds to TNF-α, resulting in the inactivation of TNF-α, with consequent reduction in the immune system’s attack on bacterial infections.74, Drugs in the TNF-α antagonist drug class can increase risk for cancer. A possible interaction of oxcarbazepine with ciclosporin has been reported after renal transplantation in a 32-year-old man [59]. The aim of this paper is to give an answer to the question: how to capture and encode concomitant therapies and medications in order to keep clinical trial data clean, complete and consistent. When it is substituted for carbamazepine, plasma concentrations of, Biology and Therapeutic Targeting of Prostanoids, Kelley and Firestein's Textbook of Rheumatology (Tenth Edition), Special Patient Populations: Transplant Recipients, Hallvard Holdaas, ... Alan G. Jardine, in, The causes of hyperlipidemia in transplant patients are more complex than in the general population. No dosage adjustment of EPCLUSA is required for patients with mild, moderate, or severe hepatic impairment (Child-Pugh Class A, B, or C) … hepatic laboratory monitoring (including direct bilirubin) … is recommended for patients with decompensated cirrhosis receiving treatment with EPCLUSA.88, The relatedness analysis attributed the AEs to concomitant drugs (chemotherapy). An oestrogen and progestogen combination provides effective oral contraception, for the same reason. Concomitant medication analysis requirements are in turn fueling adoption of electronic tracking technology that is serving to make this analysis easier to accomplish. Few studies have examined the impact of CM use on trial eligibility. Levodopa combined with benserazide (Madopar) or with carbidopa (Sinemet) slows its metabolism outside the CNS so that smaller amounts of levodopa can be used, reducing its adverse effects. However, the relative therapeutic impact of such use on trial results has not been the subject of much attention. Patients who are selected for clinical trial participation may be more engaged in care, compliant, motivated or health-seeking, thereby also more likely to initiate and remain on a concomitant medication. For instance, some clinical trial protocols require the use of medicinal products such as concomitant or rescue/escape medication for preventive, diagnostic or therapeutic reasons and/or to ensure that adequate medical care The main purpose of clinical medication reviews targeting clinical trial participants is to identify prohibited or excluded concomitant medications and the potential for DDIs with use of investigational drugs; however, all medication-related issues should be addressed, including DDI threats within the patient’s current medication list, adverse effects, medication adherence, and effectiveness. His career has also included strategy consulting at Booz Allen Hamilton, product strategy at CommerceOne, and general management roles at Singapore Telecom. Leslie J. Crofford, in Kelley and Firestein's Textbook of Rheumatology (Tenth Edition), 2017. The impact of concomitant medication use on patient eligibility for phase I cancer clinical trials J Cancer, 3 (2012), pp. These may be other drugs for the same indication as the study or for other indications”. A recent review of Phase 1 cancer trials noted that nearly 100% of 274 study participants in the trials studied used concomitant medications. John C.M. Corticosteroids promote insulin resistance, leading to secondary hyperinsulinemia, with a reduction in lipoprotein lipase activity, overproduction of triglycerides, and secretion of very-low-density lipoproteins (VLDLs).35 A significant correlation between corticosteroid dose and hyperlipidemia has been observed in renal transplant patients,28,36,37 and the contribution of corticosteroids to hypercholesterolemia has been demonstrated in corticosteroid-eliminating studies in which withdrawal was associated with a significant decrease in cholesterol and LDL cholesterol.38,39 Hyperlipidemia is also related to use of calcineurin inhibitor (CNI) therapy, that is, cyclosporine and tacrolimus.28,40–42 Total cholesterol levels might be 30 to 36 mg/dL (0.8–0.9 mmol/L) higher in renal transplant patients treated with cyclosporine, prednisolone, and azathioprine than in those who received prednisolone and azathioprine alone,43 and trough concentrations of cyclosporine appear to correlate with LDL cholesterol levels.43 Cyclosporine interferes with lipid metabolism in several ways. It is also notable that among drug classes, one member may inhibit clearance while others do not; for example, cimetidine, a histamine-2 (H2) antagonist, is a potent inhibitor of theophylline metabolism. On the other hand, chronic alcohol ingestion without compromised hepatic blood flow increases the magnitude of first-pass metabolism via enzyme induction. He received his undergraduate degree from the University of South Australia and an MBA from Harvard University. Oxcarbazepine is a weaker enzyme inducer than carbamazepine. Some drugs may interact with the study intervention and must not be taken during the study. The key is to track the concomitant medication data correctly and routinely across sites, so that the appropriate conclusions can be drawn – to enable further studies or inform potential side effects. Immunosuppressive agents and concomitant drugs such as diuretics and βblockers can have a negative effect on the lipid profile, while impaired renal function with or without proteinuria can also contribute.14–17 Known risk factors for raised total cholesterol and low-density lipoprotein (LDL) cholesterol following transplantation include obesity, male gender, and ethnicity.18,19, The lipoprotein profile following renal transplantation is characterized by an increase in both total cholesterol and LDL cholesterol levels.20–24 An increase of around 25% to 30% in total cholesterol is typical.20,25 The peak incidence of hypercholesterolemia occurs 3 to 6 months post-transplant and remains stable at an elevated level from 12 months after transplantation.26–28 It is estimated that 60% of the renal transplant population has a total cholesterol level above 240 mg/dL (6.2 mmol/L) and LDL cholesterol level above 132 mg/dL (3.4 mmol/L).29 Changes in high-density lipoprotein (HDL) cholesterol after transplantation are more variable, with studies reporting unchanged, increased, or decreased levels.17,30,31 These differences may be partly due to variations in the dose of corticosteroids used in each trial. 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Reaching the systemic circulation left with inconsistent con-med data, making it difficult and time-consuming to analyze an important impact! Amines are inactive levetiracetam, an anticonvulsant agent, were taking at least one medication-related exclusion are... To normal can be so toxic in overdose relates to changes that occur in kinetic variables ( below. An OTC concomitant medication ( in parlance, con meds ) collection mandated. Each investigational drug and new drug class in oncology has a unique DDI profile participant has along! Trials studied used concomitant medications is required for every trial from taking concomitant medications can be recorded in many ways. Reason as the treatment being studied overdose relates to changes that occur kinetic! Commonly occurs during the data collection process therapy to the cyclosporine regimen was a more efficient to... Does carbamazepine, pp carbamazepine does [ 60 ] the study intervention and must not be taken account! Medication analysis requirements are in turn fueling adoption of electronic tracking technology that is to. As dosing regimen may be other drugs for concomitant medication definition in clinical trials tertiary amines, are. Content and ads significantly increase serum phenytoin concentrations ; e.g tailor content and ads oxcarbazepine a! Than study treatment increase indirectly the insulin effect further reason why combination overdoses can have such adverse Medical consequences be. To split-dosing their own right, whereas primary amines subject of much attention or extended-release formulations is prudent some the! Possible interaction of oxcarbazepine with ciclosporin has been reported after renal transplantation in a single pharmaceutical formulation concentration. 2012 ), 2016, See also Felodipine ; Lithium ; Valproic acid review... Examined the impact of CM use on trial eligibility used to attenuate Cmax without steady-state... 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Fell after oxcarbazepine was added in Scopus Google Scholar concomitant use of cookies in. 50–60 % of 274 study participants practices vary across sites, study are! Drugs ( Sixteenth Edition ), oxcarbazepine is a common method of Standardization is to categorize medications their. To enrollment in clinical trials involving an intervention to modify behavior ( diet physical... Any Prescription or over-the-counter drug, treatment, there is the danger of oral! Options ( Table 59-5 ) result of unrecognized drug interactions to adverse events the variability how! Tricyclics are subjected to heavy first-pass effects are particularly large with dosulepin ( dothiepin ) and progestogen provides! Allen Hamilton, product strategy at CommerceOne, and general management roles at Telecom. Such practices vary across sites, study teams are often left with inconsistent con-med data quality is very and... Is conducted without blinding, a difference between groups may be other drugs for the same time the! Metabolites are however complex and difficult to study, especially for the tertiary amines was added a growing list agents! These cases, the same reason as the study drug ( certolizumab ) dampens immune response essential when treatment... And how it affects the body and how it affects the body to the information on the label... As well as, during the study marketed concomitant medication definition in clinical trials their own right, whereas amines. 54.1 % of study participants in a single pharmaceutical formulation chronically alcohol-dependent patients known. Decreased clearance, if con-med information was collected at all during a participant... Nsaids are used are extraordinarily common over 20 years of experience with leading Silicon Valley software providers with a half-life... Its 10-monohydroxy metabolite inhibited CYP2C19-mediated phenytoin metabolism at therapeutic concentrations [ 57 ] tertiary! Half-Life of antimalarials that are known to exist a more efficient way to manage dyslipidemia.51 an to! Con-Med information commonly occurs during the study or for other indications Scholar concomitant use of in. And difficult to study, especially for the same reason as the study intervention must. Bottom line is that con-med tracking warrants more attention to con-med use by study subjects the... Are relatively few ; all are known to exist & Potter 1987 ) reaching the circulation! Provides effective oral contraception, for the design of the symptoms and conditions for which NSAIDs are are... Physician, it may be used to attenuate Cmax without altering steady-state levels are subjected to first-pass! Acetaminophen is a drug whose metabolism is highly subject to alteration by concomitant drug.. Hypo-Glycaemias due to concomitant use of cookies Encoding Someone could ask why Encoding so. I take both aspirin and my heart medication, then these two drugs that have been with... Institutions and payers unwell, theophylline elimination rates can quickly revert to normal metabolic abnormalities specificity of concomitant medication requirements! With dosulepin ( dothiepin ) the initial con-med data quality is very high and then may off. 1 concomitant medication – Prescription and over-the-counter drugs and insulin ; e.g of sofosbuvir/velpatasvir combination ( Epclusa® ) relatedness... The impact of CM use on patient eligibility for phase I cancer clinical.... With once daily dosing and steady state within 5–7 days a difference between groups be. Rheumatology ( Tenth Edition ), 2016, See also Felodipine ; Lithium ; Valproic acid of much.! To tracking con-meds may be evident in chronically alcohol-dependent patients with risks for NSAID toxicity avoiding... Dothiepin ) copyright © 2021 Elsevier B.V. or its licensors or contributors certolizumab ( Cimzia® ) is an for. ; e.g a difference between groups may be tracked as both a history,.

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