Evaluation of the systemic and therapeutic repercussions caused by drug interactions in oncology patients.

Rev Assoc Med Bras (1992). 2019 Jun 03;65(5):611-617

Authors: Monteiro CRA, Schoueri JHM, Cardial DT, Linhares LC, Turke KC, Steuer LV, Menezes LWA, Argani IL, Sette C, Cubero DIG, Giglio AD

Abstract
INTRODUCTION: Drug interaction is an important cause of global morbidity. It is of particular importance in cancer patients since they are often in use of polypharmacy, related to interactions between the drugs and the chemotherapeutics used.
OBJECTIVE: To evaluate the drug interaction between chemotherapy and other drugs in cancer patients.
METHODS: a cross-sectional study carried out in the outpatient oncology department of a public tertiary hospital. Two hundred thirty-five patients were included, and the drugs they were using were identified. Using the MedScape and Epocrates database, we evaluated the interactions between medications and chemotherapy by defining their frequency and dividing their severity from interaction into mild, close monitoring necessity and severe.
RESULTS: 161 patients had some drug interaction. We identified 9 types of mild interactions, 23 types of interactions with close monitoring necessity, and 2 types of serious interactions. The most frequent interactions were between fluorouracil and leucovorin (32 cases) and cyclophosphamide and doxorubicin (19 cases). Serious interactions were between aspirin and pemetrexed; and leucovorin and Bactrim.
CONCLUSION: In the present study, drug interactions were frequent, including serious interactions with a potential increase in morbidity and mortality. Thus, it is necessary for oncologists to draw up a therapeutic plan considering potential interactions between prescribed chemotherapy and current medications in use by patients.

PMID: 31166436 [PubMed - indexed for MEDLINE]

Historical Perspective of Nephrotoxicity.

Toxicol Sci. 2018 08 01;164(2):377-378

Authors: Rankin GO, Valentovic MA

PMID: 30053230 [PubMed - indexed for MEDLINE]

[Drug related harm in Chilean hospitals: prevalence analysis 2010-2017].

Rev Med Chil. 2019 Apr;147(4):416-425

Authors: Collao JF, Favereau R, Miranda R, Aceitón C

Abstract
BACKGROUND: Medication related adverse events are an important cause of hospital admission or prolonged stay.
AIM: To assess medication related adverse events in a hospital discharge database.
MATERIAL AND METHODS: Revision of the Chilean hospital discharge database from 2010 to 2017 searching for ICD- 10 diagnostic codes corresponding to medication related adverse events.
RESULTS: The number of medication related adverse events was stable across the studied time lapse, but admission length increased. Between 34 and 111 people died every year due to medication related adverse events. Lactating babies, toddlers, adolescents and people over 80 years of age are at greater risk of experiencing these events.
CONCLUSIONS: Medication related adverse events are more common than expected.

PMID: 31344202 [PubMed - in process]

Adverse drug reactions on sexual functioning: a systematic overview.

Drug Discov Today. 2019 03;24(3):890-897

Authors: Gordijn R, Teichert M, Nicolai MPJ, Elzevier HW, Guchelaar HJ

Abstract
Adverse drug reactions (ADRs) that diminish sexual functioning can seriously affect a person's quality of life and can also affect drug adherence. However, no comprehensive overview on the subject is available and a lack of knowledge among healthcare professionals might be present. This systematic review of Summary of Products Characteristics identified 346 drugs registered with at least one sexual ADR. The drug class 'nervous system' (N) was represented most frequently with 105 drugs, followed by 'cardiovascular system' (C) with 89 drugs. For 16 drugs an incidence rate for sexual ADR of >10% was reported and for 98 drugs there was an incidence rate >1%. Because sexual ADRs occur in frequently used drugs, they should be considered in clinical practice to optimize drug treatment.

PMID: 30690197 [PubMed - indexed for MEDLINE]

[Research initiative of new thought on "main effect" of TCM formulae--new thinking on mechanism of compound action and compatibility mechanism of Chinese herbal compound formulae].

Zhongguo Zhong Yao Za Zhi. 2018 Sep;43(18):3782-3786

Authors: Weng XG, Li YJ, Chen Y, Yang Q, Wang YJ, Li Q, Cai WY, Zhu XX

Abstract
This article proposes a new thought on the study of "main effect" of traditional Chinese medicine (TCM) formulae. The blood concentrations of the pharmacodynamic substances of Chinese material medica（CMM）are usually very low, with lower toxic and side effects than western medicine. Therefore, according to a recent hypothesis of additive effect of multiple components for a single target, local targets in multi-component multi-target synergistic effect network of TCM may have the additive effect of similar components. Studies on the disposition of CMM showed that a constituent could bebio-transformed to many metabolites; these compounds with a similar structure are likely to have the same pharmacological effects on the same target, which could provide experimental evidences for the hypothesis of "additive effect". The authors of this article further believe that additive effect of TCM multi-components only comes up under a limited conditions/concentration. Because of the complexity of TCM-organism system, the complex effect of multicomponent addition and competition/antagonism is more likely to appear in single targets of drug effect. This complex effect may be the key to impact the synergistic effect of TCM multi-targets. In theory, choose and create a single target additive effect could realize the scientific compatibility of TCM and improve the curative effect and attenuate toxicity. According to the clinical demand and under the guidance of the above thought, we proposed the "main effect" of TCM formulae. Because traditional Chinese medicine (compounds) have diverse and complex effects, how to better study TCM formulae compatibility mechanism and improve the curative effect? Efforts shall be made to select one or several effects relating to clinical specific syndromes from the complex and diverse effects of TCM as the "main effect". The "main effect" of TCM formulae is the macroscopic manifestation of the synergistic effect of multi-component/multi-target. The study of the Formulae "main effect" can contain at least two aspects: one is the study of pharmacokinetic application of TCM formulae, and another is the study for pharmacodynamics effect. In the study of main effect, there are two main elements. First, which drug targets are directly related to the main effect? This requires identifying the target network. Second, which drug components positively or negatively control the single target of the target network? And what change in single target effect as well as the multi-target synergistic effect will be caused by the regulatory component concentration or the change in number? These two elements is the key to elucidate the mechanism of compound action and compatibility mechanism of Chinese herbal compound formulae. Through the study of the main effect, the clinical curative effect and the mechanism of the TCM formulae shall be improved.

PMID: 30384546 [PubMed - indexed for MEDLINE]

[Drug Therapy Safety: Digital and interprofessional for and with patients].

Bundesgesundheitsblatt Gesundheitsforschung Gesundheitsschutz. 2018 Sep;61(9):1059-1061

Authors: Schubert I, Thürmann PA

PMID: 30109364 [PubMed - indexed for MEDLINE]

[Action plan of the Federal Ministry of Health for improvement of medication safety in Germany : An inventory].

Bundesgesundheitsblatt Gesundheitsforschung Gesundheitsschutz. 2018 Sep;61(9):1062-1065

Authors: Sommer H, Dwenger A

Abstract
In 2008, the Federal Ministry of Health launched an action plan for the improvement of medication safety. The action plan includes measures to prevent medication errors. Implementation of the action plan is supported by national associations of all professional groups involved in the medication process as well as patient associations. The major importance of medication safety has been recognised not only by scientists and researchers but also by political decision-makers. More efforts are clearly needed to translate the findings gleaned from the action plans into binding regulations to secure their nationwide implementation and, in the process, the further material improvement of medication safety. Irrespective of any such regulations-which is for the legislator or regulator to take-the fact remains that the greatest contributions towards this goal must come not only from the medical and nursing professionals in their daily clinical practice but also, and even to a far greater extent than has been the case so far, from the patients themselves.

PMID: 30003285 [PubMed - indexed for MEDLINE]

Hepatotoxicity in an Adolescent with Black Iced Tea Overconsumption.

Pediatr Gastroenterol Hepatol Nutr. 2019 Jul;22(4):387-391

Authors: Hadjipanayis A, Efstathiou E, Papaevangelou V

Abstract
Tea is the most widely consumed beverage after water in the world. The consumption of iced tea has increased in Western countries and spiked among teenagers for enjoyment, freshening up and alertness. A teenager presented with symptoms of hepatitis. Liver ultrasound revealed sludge in the gallbladder. Laboratory investigations excluded all known causes of hepatotoxicity. Detail nutritional history revealed that the patient had been drinking 1.5-2 liters of black iced tea per day for the last three months. He was immediately advised to stop drinking any tea. Gradually all symptoms disappeared and two months after discontinuation of the tea, all liver enzymes returned to normal and the sludge in the gallbladder disappeared. This case report underlines the importance of a meticulous assessment of a child's dietary behavior when investigating a case of hepatotoxicity and raises awareness about the potential side effects of tea overconsumption.

PMID: 31338314 [PubMed]

Association of lenvatinib trough plasma concentrations with lenvatinib-induced toxicities in Japanese patients with thyroid cancer.

Med Oncol. 2019 Mar 27;36(5):39

Authors: Nagahama M, Ozeki T, Suzuki A, Sugino K, Niioka T, Ito K, Miura M

Abstract
The aim of this study was to examine the association of lenvatinib-induced adverse events with the trough plasma concentration (C0) in Japanese patients with thyroid cancer. Patients received lenvatinib 24 mg as an initial dose, and sequential dose reductions were conducted based on the grade of each side effect. Assessment of adverse events, assay of lenvatinib C0, and analysis of clinical laboratory tests were performed at the same time of day and were retrospectively analyzed. There were no significant differences in lenvatinib C0 among grades of hypertension, proteinuria, hand-foot syndrome, and diarrhea. However, levels of aspartate transaminase, alanine transaminase, and total bilirubin were significantly higher in lenvatinib C0 quartile (Q) 4 (≥ 88 ng/mL) than in Q1 (< 42 ng/mL) and Q2-3 (42-88 ng/mL). Additionally, platelet counts were highest in the lowest Q1 group. The median dose of lenvatinib in patients with UGT1A1*6/*6 or *6/*28 (poor metabolizers [PMs]) was significantly lower than that in patients with UGT1A1*1/*1 (10 and 14 mg, respectively), whereas the median bilirubin levels were significant higher in UGT1A1 PMs (0.9 and 0.5 mg/dL, respectively). There were no significant differences in median lenvatinib C0 values between patients with UGT1A1*1/*1 and PMs (58.0 and 50.0 ng/mL, respectively). The threshold between the C0 and toxicity of lenvatinib may be more than 88 ng/mL. Therefore, the dose of lenvatinib could be controlled to maintain a lower C0 of less than 88 ng/mL. The target C0 for lenvatinib as the threshold between the C0 and optimal response may be in the range from 42 to 88 ng/mL; however, further studies are necessary.

PMID: 30919115 [PubMed - indexed for MEDLINE]

Impact of diabetes comorbidity on the efficacy and safety of FOLFOX first-line chemotherapy among patients with metastatic colorectal cancer: a pooled analysis of two phase-III studies.

Clin Transl Oncol. 2019 Apr;21(4):512-518

Authors: Abdel-Rahman O

Abstract
BACKGROUND: The current analysis aims to provide an evaluation of the impact of diabetes mellitus (DM) on the efficacy and safety of first-line FOLFOX chemotherapy for patients with metastatic colorectal cancer (mCRC).
METHODS: This is a pooled analysis of the comparator arms of two clinical trials (NCT00272051; NCT00305188) which evaluated first-line FOLFOX chemotherapy for patients with mCRC. The overall survival and progression-free survival according to patient subsets (non-diabetic and diabetic patients) were assessed through Kaplan-Meier analysis and log-rank testing. Propensity score matching was additionally conducted to account for heterogeneity in baseline characteristics of different subsets of patients.
RESULTS: A total of 756 patients were enrolled in the current analysis; of which 64 patients have pre-existing DM while 692 patients were non-diabetic. Through Kaplan-Meier analysis, no evidence for overall or progression-free survival difference was found among the two patient subsets (P = 0.501; P = 0.960, respectively). Moreover, metformin treatment does not affect overall or progression-free survival among diabetic patients (P = 0.598; P = 0.748, respectively). Repetition of overall and progression-free survival assessment following propensity score matching does not reveal any differences. Comparing diabetic to non-diabetic patients, there were no differences between the two groups in terms of acute oxaliplatin-induced neurological symptoms including cold-induced dysthesia (P = 0.600), laryngeal dysthesia (P = 0.707), jaw pain (P = 0.743) or muscle pain (P = 0.506). Moreover, no difference was seen between the two groups in terms of the incidence of long-term oxaliplatin-induced paresthesia (P = 0.107), highest grade of paresthesia (P = 0.498) or rates of recovery from paresthesia (P = 0.268). Diabetic patients have, however, a shorter time to develop oxaliplatin-induced paresthesia (P = 0.024).
CONCLUSION: DM does not seem to affect overall or progression-free survival of mCRC patients treated with first-line FOLFOX chemotherapy. Moreover, DM does not influence the incidence or severity of oxaliplatin-induced paresthesia in those patients while it might lead to a shorter time to develop oxaliplatin-induced paresthesia compared to non-diabetic patients.

PMID: 30182209 [PubMed - indexed for MEDLINE]

[Acute life-threatening drug reactions of the skin].

Hautarzt. 2018 May;69(5):364-375

Authors: Mockenhaupt M

Abstract
Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are acutely occurring, unpredictable, often life-threatening reactions that are a huge challenge in clinical practice. They are characterized by extensive blistering of skin and mucosa and are considered as one disease entity of different severity. Thus, they are summarized as SJS/TEN or EN (for epidermal or epithelial necrolysis). The diagnosis can be confirmed through synopsis of clinical pattern and histopathological findings. To identify the inducing factors, it is crucial to obtain a detailed and thorough medication and infection history. Based on the results of large epidemiological studies, potentially inducing drugs can be narrowed down even in cases of multimedication and underlying diseases. Agents with a high risk for SJS/TEN are allopurinol, antibacterial sulfonamides, non-steroidal anti-inflammatory drugs of the oxicam-type, various antiepileptics and nevirapine. They alone explain more than half of the cases of SJS/TEN. Typically, the reaction occurs during the first continuous use of the medication, while the beginning of use most often is one to four weeks prior to reaction onset. However, a drug is not always the cause of the reaction, but in approximately 70-75% of the cases very likely. In other cases infections may be potential causes. If certain medications are thought to be the inducing factors, they should be withdrawn without delay. In addition, symptomatic treatment should be initiated. In case of progression, an additional immunomodulating therapy should be considered. In this respect, systematic reviews have shown best results for cyclosporine A and systemic steroids.

PMID: 29721625 [PubMed - indexed for MEDLINE]

Chinese Herbal Medicine Combined With EGFR-TKI in EGFR Mutation-Positive Advanced Pulmonary Adenocarcinoma (CATLA): A Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial.

Front Pharmacol. 2019;10:732

Authors: Jiao L, Xu J, Sun J, Chen Z, Gong Y, Bi L, Lu Y, Yao J, Zhu W, Hou A, Feng G, Jia Y, Shen W, Li Y, Zhang Z, Chen P, Xu L

Abstract
Background: To determine the clinical activity and safety of Chinese herbal medicine (CHM) combined with epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKI) in patients with advanced pulmonary adenocarcinoma (ADC) and the ability of CHM combined with EGFR-TKI to activate EGFR mutations. Methods: Three hundred and fifty-four patients were randomly assigned to EGFR-TKI (erlotinib 150 mg/d, gefitinib 250 mg/d, or icotinib 125 mg tid/d) plus CHM (TKI+CHM, N = 185) or EGFR-TKI plus placebo (TKI+placebo, N = 169). Progression-free survival (PFS) was the primary end point; the secondary end points were overall survival (OS), objective response rate (ORR), disease control rate (DCR), quality of life [Functional Assessment of Cancer Therapy-Lung (FACT-L) and Lung Cancer Symptom Scale (LCSS)], and safety. Results: The median PFS was significantly longer for the TKI+CHM group (13.50 months; 95% CI, 11.20-16.46 months) than with the EGFR-TKI group (10.94 months; 95% CI, 8.97-12.45 months; hazard ratio, 0.68; 95% CI, 0.51-0.90; P = 0.0064). The subgroup analyses favored TKI+CHM as a first-line treatment (15.97 vs. 10.97 months, P = 0.0447) rather than as a second-line treatment (11.43 vs. 9.23 months, P = 0.0530). Patients with exon 19 deletion had a significantly longer PFS than with 21 L858R. The addition of CHM to TKI significantly improved the ORR (64.32% vs. 52.66%, P = 0.026) and QoL. Drug-related grade 1-2 adverse events were less common with TKI+CHM. Conclusions: TKI+CHM improved PFS when compared with TKI alone in patients with EGFR mutation-positive advanced non-small-cell lung cancer (NSCLC). Clinical Trial Registration: www.ClinicalTrials.gov, identifier NCT01745302.

PMID: 31333456 [PubMed]

Adverse Effects Associated with Long-Term Administration of Azole Antifungal Agents.

Drugs. 2019 Jun;79(8):833-853

Authors: Benitez LL, Carver PL

Abstract
Azole antifungals are first-line options in the prophylaxis and treatment of invasive fungal infections. They are often used for prolonged (weeks to months) periods of time, particularly in patients with hematologic malignancies, or in those who have received a solid organ or hematopoietic stem cell transplant. Long-term use of azoles is associated with hepatotoxicity and hormone-related effects, including gynecomastia, alopecia, decreased libido, oligospermia, azoospermia, impotence, hypokalemia, hyponatremia, and (rarely) adrenal insufficiency. Voriconazole and posaconazole have been associated with peripheral neuropathies, and itraconazole and voriconazole with pancreatitis. In addition, voriconazole has been associated with periostitis, phototoxic reactions, and squamous cell carcinoma. Since many at-risk patients are commonly receiving multiple medications, it can be difficult for care providers to identify antifungal agent causality or contribution to patient symptoms. Knowledge and recognition of adverse events caused by azoles, leading to dose reduction or discontinuation, can generally reverse these adverse events.

PMID: 31093949 [PubMed - indexed for MEDLINE]

Drug-Induced Retinal Toxicity.

Adv Exp Med Biol. 2018;1085:227-232

Authors: Tsang SH, Sharma T

Abstract
Drug-induced retinal toxicity can occur from the use of systemic, intravitreal, or topical medications. Despite the presence of the blood-ocular barrier, the retina is vulnerable to toxic effects of systemic medications leading to dysfunction and retinal degeneration. These toxicities can be categorized as damage to the retinal pigment epithelium (RPE) and photoreceptor complex, vascular damage, ganglion cell or optic nerve damage, cystoid macular edema, crystalline retinopathy, uveitis, changes in color vision and electroretinography (ERG), and other miscellaneous effects.

PMID: 30578521 [PubMed - indexed for MEDLINE]

Tramadol-induced parkinsonism: a case report of a 75-year-old woman.

J Basic Clin Physiol Pharmacol. 2018 Nov 17;30(2):275-278

Authors: Singh R

Abstract
Adverse drug reaction (ADR) is a form of unwanted reaction and is the crucial reason for illness and death. Tramadol-induced parkinsonism is a kind of ADR that occurs after the repeated intake of tramadol. Long-term exposure to tramadol has been known to induce tremor and alter the functioning of dopamine. This case report introduces a 75-year-old woman diagnosed with tramadol-induced parkinsonism due to the administration of tramadol for the treatment of post-operated (breast cancer) acute onset of severe pain on the left side of the chest. The assessment of the offending drug was carried out via Naranjo probability scale. A score of 6 was reported for this patient, defining tramadol as a probable cause of this reaction. For the management of the drug-induced parkinsonism, levodopa/carbidopa was prescribed and the symptoms related to parkinsonism resolved within a week. The age of the patient and the female gender is considered to be the main risk factor for the occurrence of such reaction. This case report is an attempt to spread awareness about the negative consequences of long-term use of tramadol in old patients. Thus, the medical practitioners must be very careful while administering tramadol to the old aged population.

PMID: 30447142 [PubMed - indexed for MEDLINE]

Adverse Drug Reactions (ADR) and Emergencies.

Dtsch Arztebl Int. 2018 04 13;115(15):251-258

Authors: Schurig AM, Böhme M, Just KS, Scholl C, Dormann H, Plank-Kiegele B, Seufferlein T, Gräff I, Schwab M, Stingl JC

Abstract
BACKGROUND: Adverse drug reactions (ADR) are a common reason for emergency room visits and for hospitalization. An ADR is said to have occurred when the patient's symptoms and signs are considered to be possibly, probably, or definitely related to the intake of a drug.
METHODS: In four large hospital emergency departments, one in each of four German cities ( Ulm, Fürth, Bonn, and Stuttgart), the percentage of suspected ADR cases among all patients presenting to the emergency room was determined during a 30-day period of observation. ADRs were ascertained by screening the digital records of all patients seen in the emergency room; causality was assessed as specified by the WHO-UMC (Uppsala Monitoring Center).
RESULTS: ADR were sought in a total of 10 174 emergency department visits. 665 cases of suspected ADR were found, yielding a prevalence of 6.5%. The prevalence of ADR among patients with documented drug intake was 11.6%. Among the patients with documented suspected ADRs, 89% were hospitalized (in contrast to the 43.7% hospitalization rate in the entire group of 10 174 emergency department visits). A possible causal relationship between the patient's symptoms and signs and the intake of a drug was found in 74-84% of cases. Patients with ADR were found to be taking a median of 7 different drugs simultaneously.
CONCLUSION: Adverse drug reactions are a relevant cause of emergency department visits, accounting for 6.5% of the total visits in this study, and often lead to hospital admission. The ADRED (Adverse Drug Reactions in Emergency Departments) study, which is now being conducted, is intended to shed further light on their causes, patient risk factors, and potential avoidability.

PMID: 29735005 [PubMed - indexed for MEDLINE]

[Side effects of drug therapy in urology].

Urologe A. 2017 Apr;56(4):449-450

Authors: Grimm MO, Lümmen G

PMID: 28246757 [PubMed - indexed for MEDLINE]

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Faecal microbiota transplantation for diarrhoea-predominant irritable bowel syndrome: a double-blind, randomised, placebo-controlled trial.

Lancet Gastroenterol Hepatol. 2019 Jul 17;:

Authors: Aroniadis OC, Brandt LJ, Oneto C, Feuerstadt P, Sherman A, Wolkoff AW, Kassam Z, Sadovsky RG, Elliott RJ, Budree S, Kim M, Keller MJ

Abstract
BACKGROUND: Faecal microbiota transplantation (FMT) has shown promise in alleviating the symptoms of irritable bowel syndrome (IBS); however, controlled data on this technique are scarce. The aim of this clinical trial was to assess the efficacy of FMT in alleviating diarrhoea-predominant IBS (IBS-D).
METHODS: We did a double-blind, randomised, placebo-controlled crossover trial in patients aged 18-65 years with moderate-to-severe IBS-D defined by an IBS-Symptom Severity Score (IBS-SSS) of more than 175, recruited from three US centres. Patients were randomly assigned (1:1) in blocks of four with a computer-generated randomisation sequence to receive FMT capsules followed by identical-appearing placebo capsules, or placebo capsules followed by FMT capsules. All participants and study team members were masked to randomisation. An independent staff member assigned the treatments according to consecutive numbers. Patients received either 75 FMT capsules (each capsule contained approximately 0·38 g of minimally processed donor stool) or 75 placebo capsules over 3 days (25 capsules per day). All patients crossed over to the alternate treatment at 12 weeks. The primary outcome was difference in IBS-SSS between the groups at 12 weeks. Intention-to-treat analyses were done and all patients who received study drug were included in an adverse events analysis. The trial was terminated during recruitment because results from an interim analysis revealed futility. The study is registered with ClinicalTrials.gov, number NCT02328547.
FINDINGS: From May 28, 2015, to April 21, 2017, 48 patients were randomly assigned to receive FMT first (n=25) or placebo first (n=23). Three participants were lost to follow-up in the FMT group. IBS-SSS did not differ between FMT recipients (mean 221 [SD 105]) and placebo recipients (236 [95]) at 12 weeks (p=0·65), after adjustment for baseline scores. The most common drug-related adverse events included abdominal pain (five [10%] of the 48 participants while receiving FMT capsules vs four [8%] while receiving placebo), nausea (four [8%] vs two [4%]), and exacerbation of diarrhoea (three [6%] vs eight [17%]). One serious adverse event that was unrelated to study drug (acute cholecystitis) was reported in a patient while receiving placebo capsules.
INTERPRETATION: FMT was safe, but did not induce symptom relief at 12 weeks compared with placebo. Additional studies are needed to determine the efficacy of FMT for IBS-D.
FUNDING: National Institutes of Health.

PMID: 31326345 [PubMed - as supplied by publisher]

Efficacy and safety of prolonged-release tacrolimus in stable pediatric allograft recipients converted from immediate-release tacrolimus.

Transpl Int. 2019 Jul 20;:

Authors: Rubik J, Debray D, Kelly D, Iserin F, Webb NJA, Czubkowski P, Vondrak K, Sellier-Leclerc AL, Rivet C, Riva S, Tönshoff B, D'Antiga L, Marks SD, Raymond R, Kazeem G, Undre N

Abstract
There are limited clinical data regarding prolonged-release tacrolimus (PR-T) use in pediatric transplant recipients. This Phase 2 study assessed the efficacy and safety of PR-T in stable pediatric kidney, liver, and heart transplant recipients (aged ≥5-≤16 years) over 1 year following conversion from immediate-release tacrolimus (IR-T), on a 1:1 mg total-daily-dose basis. Endpoints included the incidence of acute rejection (AR), a composite endpoint of efficacy failure (death, graft loss, biopsy-confirmed AR, and unknown outcome), and safety. Tacrolimus dose and whole-blood trough levels (target 3.5-15 ng/mL) were also evaluated. Overall, 79 patients (kidney, n=48; liver, n=29; heart, n=2) were assessed. Following conversion, tacrolimus dose and trough levels remained stable; however, 7.6-17.7% of patients across follow-up visits had trough levels below the target range. Two (2.5%) patients had AR, and 3 (3.8%) had efficacy failure. No graft loss or deaths were reported. No new safety signals were identified. Drug-related treatment-emergent adverse events occurred in 28 patients (35.4%); most were mild, and all resolved. This study suggests that IR-T to PR-T conversion is effective and well tolerated over 1 year in pediatric transplant recipients, and highlights the importance of therapeutic drug monitoring to maintain target tacrolimus trough levels. This article is protected by copyright. All rights reserved.

PMID: 31325368 [PubMed - as supplied by publisher]