Long-term Outcomes of Thalidomide Therapy for Adults With Refractory Crohn's Disease.

Clin Gastroenterol Hepatol. 2016 Jul;14(7):966-972.e2

Authors: Simon M, Pariente B, Lambert J, Cosnes J, Bouhnik Y, Marteau P, Allez M, Colombel JF, Gornet JM

Abstract
BACKGROUND & AIMS: Little is known about the efficacy and safety of thalidomide therapy for patients with refractory Crohn's disease (CD), particularly in respect to long-term outcomes of patients.
METHODS: We conducted a retrospective multicenter observational study to evaluate thalidomide efficacy and the probability of its withdrawal because of either toxicity or lack/loss of efficacy. We analyzed data from 77 patients with active intestinal and/or perineal CD, refractory to conventional immunosuppressive therapies, treated with thalidomide at 5 tertiary referral inflammatory bowel disease centers in France. We also analyzed the long-term efficacy of thalidomide.
RESULTS: Fifty-four percent of the patients were in clinical remission after thalidomide treatment within the first year. The proportions of patients from whom thalidomide was withdrawn because of lack/loss of efficacy and/or toxicity were 35% at 3 months of treatment, 69% at 12 months, and 88% at 24 months. The proportions of patients from whom thalidomide was withdrawn because of toxicity alone were 22% at 3 months, 34% at 12 months, and 46% at 24 months. Overall, neuropathy occurred in 30 patients and was the main reason for thalidomide withdrawal.
CONCLUSIONS: On the basis of a retrospective multicenter observational study, thalidomide therapy is effective in most patients with refractory active intestinal and/or perineal CD. However, its toxicity limits its use as a maintenance therapy.

PMID: 26598226 [PubMed - indexed for MEDLINE]

12 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

("drug-induced" OR "drug-related") AND ("adverse events" OR "side effects" OR "side-effects")

These pubmed results were generated on 2017/08/19

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13 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

("drug-induced" OR "drug-related") AND ("adverse events" OR "side effects" OR "side-effects")

These pubmed results were generated on 2017/08/19

PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

12 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

("drug-induced" OR "drug-related") AND ("adverse events" OR "side effects" OR "side-effects")

These pubmed results were generated on 2017/08/18

PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

A Case of IVIG-Induced Aseptic Chemical Meningitis.

S D Med. 2017 Mar;70(3):119-121

Authors: Patel A, Potu KC, Sturm T

Abstract
Intravenous immunoglobulin (IVIG) is a commonly used and generally well-tolerated medication. Common side effects include flu-like symptoms such as fevers, headaches, myalgia, fatigue, and nausea. One of the more rare side effects is aseptic meningitis, with a reported incidence rate of around 0.067 percent of all IVIG infusions. In this paper, we describe a 47-year-old female patient with a history of myasthenia gravis who presented with a headache, neck pain, and neck stiffness while undergoing IVIG infusions for a myasthenia crisis. On admission day, the patient was afebrile with stable vital signs. A physical examination revealed nuchal rigidity and tenderness with no focal neurological deficits. Cerebrospinal fluid (CSF) cytology noted an elevated white blood cell (WBC) count of 1,138 cells/μL with a neutrophil predominance (96 percent). CSF red blood cell count was unremarkable at 1 cell/μL. The patient's IVIG infusions were stopped, suspecting chemical meningitis. Given the markedly elevated CSF WBC count with neutrophil predominance, she was started on vancomycin and ceftriaxone to also cover for bacterial meningitis. The patient's meningeal signs and symptoms significantly improved 24 hours after admission. Given the clear temporal relationship to IVIG administration and the rapid improvement of symptoms, IVIG-induced aseptic meningitis is strongly suspected. The patient's antibiotics were discontinued. Forty-eight hours after stopping IVIG and 24 hours after discontinuing antibiotics, her meningitis symptoms completely resolved with the use of analgesics alone. The patient was then discharged uneventfully. CSF viral and bacterial studies, including a gram stain and cultures, did not result in anything noteworthy. Our case presents an interesting diagnostic dilemma where drug-induced (IVIG) aseptic meningitis mimics bacterial meningitis clinically and on CSF analysis. The clear temporal relationship to IVIG administration and the rapid resolution of symptoms upon stopping the drug can aid in the diagnosis of this rare event and help doctors avoid the use of unnecessary antibiotic therapy.

PMID: 28813773 [PubMed - in process]

Deprescribing: A simple method for reducing polypharmacy.

J Fam Pract. 2017 Jul;66(7):436-445

Authors: McGrath K, Hajjar ER, Kumar C, Hwang C, Salzman B

Abstract
Polypharmacy brings with it increased risks for adverse drug events and reduced functional capacity. This 4-step plan will help you safely deprescribe in older adults.

PMID: 28700758 [PubMed - indexed for MEDLINE]

Pretreatment serum uracil concentration as a predictor of severe and fatal fluoropyrimidine-associated toxicity.

Br J Cancer. 2017 May 23;116(11):1415-1424

Authors: Meulendijks D, Henricks LM, Jacobs BAW, Aliev A, Deenen MJ, de Vries N, Rosing H, van Werkhoven E, de Boer A, Beijnen JH, Mandigers CMPW, Soesan M, Cats A, Schellens JHM

Abstract
BACKGROUND: We investigated the predictive value of dihydropyrimidine dehydrogenase (DPD) phenotype, measured as pretreatment serum uracil and dihydrouracil concentrations, for severe as well as fatal fluoropyrimidine-associated toxicity in 550 patients treated previously with fluoropyrimidines during a prospective multicenter study.
METHODS: Pretreatment serum concentrations of uracil and dihydrouracil were measured using a validated LC-MS/MS method. The primary endpoint of this analysis was global (any) severe fluoropyrimidine-associated toxicity, that is, grade ⩾3 toxicity according to the NCI CTC-AE v3.0, occurring during the first cycle of treatment. The predictive value of uracil and the uracil/dihydrouracil ratio for early severe fluoropyrimidine-associated toxicity were compared. Pharmacogenetic variants in DPYD (c.2846A>T, c.1679T>G, c.1129-5923C>G, and c.1601G>A) and TYMS (TYMS 5'-UTR VNTR and TYMS 3'-UTR 6-bp ins/del) were measured and tested for associations with severe fluoropyrimidine-associated toxicity to compare predictive value with DPD phenotype. The Benjamini-Hochberg false discovery rate method was used to control for type I errors at level q<0.050 (corresponding to P<0.010).
RESULTS: Uracil was superior to the dihydrouracil/uracil ratio as a predictor of severe toxicity. High pretreatment uracil concentrations (>16 ng ml(-1)) were strongly associated with global severe toxicity (OR 5.3, P=0.009), severe gastrointestinal toxicity (OR 33.7, P<0.0001), toxicity-related hospitalisation (OR 16.9, P<0.0001), as well as fatal treatment-related toxicity (OR 44.8, P=0.001). None of the DPYD variants alone, or TYMS variants alone, were associated with severe toxicity.
CONCLUSIONS: High pretreatment uracil concentration was strongly predictive of severe, including fatal, fluoropyrimidine-associated toxicity, and is a highly promising phenotypic marker to identify patients at risk of severe fluoropyrimidine-associated toxicity.

PMID: 28427087 [PubMed - indexed for MEDLINE]

Clinical impact of pharmacogenetic profiling with a clinical decision support tool in polypharmacy home health patients: A prospective pilot randomized controlled trial.

PLoS One. 2017;12(2):e0170905

Authors: Elliott LS, Henderson JC, Neradilek MB, Moyer NA, Ashcraft KC, Thirumaran RK

Abstract
BACKGROUND: In polypharmacy patients under home health management, pharmacogenetic testing coupled with guidance from a clinical decision support tool (CDST) on reducing drug, gene, and cumulative interaction risk may provide valuable insights in prescription drug treatment, reducing re-hospitalization and emergency department (ED) visits. We assessed the clinical impact of pharmacogenetic profiling integrating binary and cumulative drug and gene interaction warnings on home health polypharmacy patients.
METHODS AND FINDINGS: This prospective, open-label, randomized controlled trial was conducted at one hospital-based home health agency between February 2015 and February 2016. Recruitment came from patient referrals to home health at hospital discharge. Eligible patients were aged 50 years and older and taking or initiating treatment with medications with potential or significant drug-gene-based interactions. Subjects (n = 110) were randomized to pharmacogenetic profiling (n = 57). The study pharmacist reviewed drug-drug, drug-gene, and cumulative drug and/or gene interactions using the YouScript® CDST to provide drug therapy recommendations to clinicians. The control group (n = 53) received treatment as usual including pharmacist guided medication management using a standard drug information resource. The primary outcome measure was the number of re-hospitalizations and ED visits at 30 and 60 days after discharge from the hospital. The mean number of re-hospitalizations per patient in the tested vs. untested group was 0.25 vs. 0.38 at 30 days (relative risk (RR), 0.65; 95% confidence interval (CI), 0.32-1.28; P = 0.21) and 0.33 vs. 0.70 at 60 days following enrollment (RR, 0.48; 95% CI, 0.27-0.82; P = 0.007). The mean number of ED visits per patient in the tested vs. untested group was 0.25 vs. 0.40 at 30 days (RR, 0.62; 95% CI, 0.31-1.21; P = 0.16) and 0.39 vs. 0.66 at 60 days (RR, 0.58; 95% CI, 0.34-0.99; P = 0.045). Differences in composite outcomes at 60 days (exploratory endpoints) were also found. Of the total 124 drug therapy recommendations passed on to clinicians, 96 (77%) were followed. These findings should be verified with additional prospective confirmatory studies involving real-world applications in larger populations to broaden acceptance in routine clinical practice.
CONCLUSIONS: Pharmacogenetic testing of polypharmacy patients aged 50 and older, supported by an appropriate CDST, considerably reduced re-hospitalizations and ED visits at 60 days following enrollment resulting in potential health resource utilization savings and improved healthcare.
TRIAL REGISTRATION: ClinicalTrials.gov NCT02378220.

PMID: 28151991 [PubMed - indexed for MEDLINE]

Postmarketing Safety Events Relating to New Drugs Approved in Brazil Between 2003 and 2013: A Retrospective Cohort Study.

J Clin Pharmacol. 2017 Apr;57(4):493-499

Authors: Botelho SF, Martins MA, Vieira LB, Reis AM

Abstract
This study investigated postmarketing safety events (PMSEs) for new drugs approved in Brazil and evaluated whether a range of drug characteristics influenced the time between approval and the first PMSE. This retrospective study included new drugs registered between 2003 and 2013 by the National Health Surveillance Agency (ANVISA), which is responsible for medicines approval in Brazil. PMSEs were defined as any drug safety alert or drug withdrawal from the market. The existence of risk evaluation and mitigation strategies (REMS) by the US Food and Drug Administration (FDA) and Brazil were recorded. A Kaplan-Meier survival curve of the period between the date of ANVISA registration and the PMSE was calculated. We found a statistically significant difference between the time to PMSE for drugs with an FDA REMS compared with those without a REMS, with a log rank value (Mantel Cox) of 0.002. There was no association between the time to PMSE and the other drug characteristics investigated. This study demonstrated that the frequency of PMSEs for new drugs approved by ANVISA was statistically associated with the existence of an FDA REMS. The time between approval and first PMSE was shorter for drugs with an FDA REMS, and this finding may contribute to improved awareness of the risk/benefit balance required to ensure continued safe and effective use of new drugs.

PMID: 27568487 [PubMed - indexed for MEDLINE]

The principle of safety evaluation in medicinal drug - how can toxicology contribute to drug discovery and development as a multidisciplinary science?

J Toxicol Sci. 2016;41(Special):SP49-SP67

Authors: Horii I

Abstract
Pharmaceutical (drug) safety assessment covers a diverse science-field in the drug discovery and development including the post-approval and post-marketing phases in order to evaluate safety and risk management. The principle in toxicological science is to be placed on both of pure and applied sciences that are derived from past/present scientific knowledge and coming new science and technology. In general, adverse drug reactions are presented as "biological responses to foreign substances." This is the basic concept of thinking about the manifestation of adverse drug reactions. Whether or not toxic expressions are extensions of the pharmacological effect, adverse drug reactions as seen from molecular targets are captured in the category of "on-target" or "off-target", and are normally expressed as a biological defense reaction. Accordingly, reactions induced by pharmaceuticals can be broadly said to be defensive reactions. Recent molecular biological conception is in line with the new, remarkable scientific and technological developments in the medical and pharmaceutical areas, and the viewpoints in the field of toxicology have shown that they are approaching toward the same direction as well. This paper refers to the basic concept of pharmaceutical toxicology, the differences for safety assessment in each stage of drug discovery and development, regulatory submission, and the concept of scientific considerations for risk assessment and management from the viewpoint of "how can multidisciplinary toxicology contribute to innovative drug discovery and development?" And also realistic translational research from preclinical to clinical application is required to have a significant risk management in post market by utilizing whole scientific data derived from basic and applied scientific research works. In addition, the significance for employing the systems toxicology based on AOP (Adverse Outcome Pathway) analysis is introduced, and coming challenges on precision medicine are to be addressed for the new aspect of efficacy and safety evaluation.

PMID: 28250284 [PubMed - indexed for MEDLINE]

14 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

("drug-induced" OR "drug-related") AND ("adverse events" OR "side effects" OR "side-effects")

These pubmed results were generated on 2017/08/15

PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

Pharmacovigilance Skills, Knowledge and Attitudes in our Future Doctors - A Nationwide Study in the Netherlands.

Basic Clin Pharmacol Toxicol. 2017 May;120(5):475-481

Authors: Schutte T, Tichelaar J, Reumerman MO, van Eekeren R, Rissmann R, Kramers C, Richir MC, van Puijenbroek EP, van Agtmael MA, Education Committee/Working Group Research in Education of the Dutch Society of Clinical Pharmacology and Biopharmacy (NVKF&B), Utrecht, The Netherlands

Abstract
Pharmacovigilance centres monitor the safety of drugs, based on adverse drug reactions (ADRs) reported by doctors, pharmacists and pharmaceutical companies. However, the under-reporting of ADRs remains a major problem. Our aim was to investigate preparedness of future doctors for their role in pharmacovigilance, by assessing their pharmacovigilance awareness, skills and knowledge. The study was a nationwide e-survey among medical students (third to sixth year) of all eight medical schools in the Netherlands. The survey consisted of questions regarding pharmacovigilance awareness, skills and knowledge. Overall, 874 students provided informed consent and participated (response 12%). Almost all students (96%) intended to report serious ADRs in their future practice. Almost half (44%) of the students did not know where to report an ADR, and 78% did not know which items were necessary for a good-quality ADR report. While more than 78% of the students agreed that pharmacovigilance is an important topic in their medical education, only 26% found that their current curriculum covered pharmacovigilance adequately. Although ADR reporting is considered relevant and important among future doctors, many do not know where and what to report. This is highly undesirable and should have consequences for pharmacotherapy teaching.

PMID: 27883270 [PubMed - indexed for MEDLINE]

The Effect of Pharmacist-led Psychiatric Pharmacotherapy Conferences on the Appropriate Use of Antipsychotics.

Yakugaku Zasshi. 2017;137(5):603-610

Authors: Sano T, Inoue M, Takizawa M, Shimamori Y, Kurosawa N

Abstract
　The Hakodate Watanabe Hospital has held pharmacist-led multidisciplinary psychiatric pharmacotherapy conferences since September 2013 in order to optimize pharmacotherapy. The effects of holding regular conferences on the correction of high-dose antipsychotic polypharmacy, prevention and reduction of adverse reactions to antipsychotics, and reduction of the drug costs were investigated in psychiatric inpatients prescribed 4 or more antipsychotics. The results revealed that the number of antipsychotics and number of all drugs were significantly reduced by 1, the chlorpromazine (CP)-equivalent dose was significantly reduced by approximately 350 mg, and the drug costs were significantly reduced by 176.5 yen/d. In regard to the effects on the laboratory test data, the blood glucose and hemoglobin A1c (HbA1c) levels were significantly reduced. In addition, 84.8% of the patients were assessed as "unchanged" using the Clinical Global Impression of Change (CGI-C), indicating the absence of any significant changes in the severity of the clinical psychiatric symptoms. The results confirm that psychiatric pharmacotherapy conferences are effective for promoting appropriate use of antipsychotics, reducing the incidence of metabolic adverse reactions, such as elevation of the blood glucose, and also reducing the drug costs. The above results suggest that psychiatric pharmacotherapy conferences encourage psychiatric medical teams to adjust prescriptions while sharing information, and are effective for optimizing pharmacotherapy.

PMID: 28458292 [PubMed - indexed for MEDLINE]

[Levodopa-carbidopa intestinal gel in the treatment of patients with Parkinson disease: results of a 12-month open study].

Zh Nevrol Psikhiatr Im S S Korsakova. 2017;117(2):22-31

Authors: Skoromets AA, Odinak MM, Yakupov EZ, Litvinenko IV, Zalyalova ZA, Timofeeva AA, Kirtaev SY, Bogdanov RR, Agafina AS, Chatamra K, Robieson W, Benesh J, Latypova GR, Ershova MV, Illarioshkin SN

Abstract
AIM: To evaluate the long-term safety and efficacy of intrajejunal levodopa-carbidopa intestinal gel (LCIG) infusion in the treatment of patients with severe stages of Parkinson disease (PD) who did not respond adequately to treatment with oral drugs.
MATERIAL AND METHODS: A large-scale international prospective open-label 54-week study of LCIG in patients with PD with severe motor fluctuations was carried out. A total of 48 patients were enrolled in Russia, 46 patients (95.8%) had PEG-J inserted, and 43 of them completed the study. The safety, including adverse events (AEs), infusion system and pump failures analysis, number of patients completely terminated the study, and efficacy (duration of "off" periods, "on" periods with or without troublesome dyskinesias, UPDRS scores, Clinical Global Impression, Quality of Life (PDQ-39, EQ-5D и EQ-VAS) dynamics, an analysis of patient's diaries) were assessed throughout the whole study.
RESULTS: The majority of AEs were mild or moderate with most AEs connected with infusion system application (28.3% patients) including procedure pain. Serious AEs were registered in 8 patients (16.7%). 3 patients (6.3%) discontinued their participation in the study due to AEs. Mean duration of "off" periods by the end of the study decreased by 5.35±2.59 hours (p<0.001), duration of "on" periods without troublesome dyskinesia increased by 5.74±3.91 hours (p<0.001), reduction of "on" periods duration with troublesome dyskinesia became statistically significant by week 36 (p=0.020). The statistically significant improvement of UPDRS (generally and in respect to sub-scales), Clinical Global Impression, and Quality of Life scores was observed throughout the study. Levodopa dose remained stable throughout the 54 treatment weeks. Forty-three patients (93.5%) received LCIG monotherapy throughout the whole study.
CONCLUSION: LCIG intrajejunal infusion during 54 weeks showed the favorable safety profile, high tolerability, and efficacy in PD motor symptoms correction.

PMID: 28374689 [PubMed - indexed for MEDLINE]

Naringin Ameliorates HIV-1 Nucleoside Reverse Transcriptase Inhibitors- Induced Mitochondrial Toxicity.

Curr HIV Res. 2016;14(6):506-516

Authors: Oluwafeyisetan A, Olubunmi A, Peter O

Abstract
BACKGROUND: Mitochondrial reactive oxygen species (ROS) generation and defective oxidative phosphorylation (OXPHOS) have been proposed as possible mechanisms underlying the development of nucleoside reverse transcriptase inhibitors (NRTIs)-induced mitochondrial toxicities. Available options in managing these complications have, so far, produced controversial results, thus necessitating further research into newer agents with promise. Antioxidant and free-radical scavenging effects of naringin, a plant-derived flavonoid, have previously been demonstrated.
OBJECTIVE: This study was designed to investigate the effects of naringin on NRTIs-induced mitochondrial toxicity.
METHODS: Wistar rats were randomly divided into Zidovudine (AZT)-only (100 mg/kg body weight BW); AZT+Naringin (100+50 mg/kg BW); AZT+Vitamin E (100+100 mg/kg BW); Stavudine (d4T)- only (50 mg/kg BW); d4T+Naringin (50+50 mg/kg BW); d4T+Vitamin E (50+100 mg/kg BW) and Vehicle (3.0 mL/kg BW)-treated groups, respectively. After 56 days of oral daily dosing, rats were euthanized by halothane overdose, blood collected by cardiac puncture and livers promptly excised for further biochemical and ultrastructural analyses. &lt;/p&gt; Results: AZT- or d4T-only caused significant mitochondrial dysfunction and mitochondrial ultrastructural damage compared to controls, while either naringin or vitamin E reversed indices of mitochondrial dysfunction evidenced by significantly reduced mitochondrial malondialdehyde (MDA) and blood lactate concentrations, increased liver manganese superoxide dismutase (MnSOD) activity and upregulate expression of mitochondrial-encoded subunit of electron transport chain (ETC) complex IV protein compared to AZT- or d4T-only treated rats. Furthermore, naringin or vitamin E, respectively, ameliorated mitochondrial damage observed in AZT- or d4T-only treated rats.
CONCLUSION: Naringin ameliorated oxidative stress and NRTI-induced mitochondrial damage and might, therefore, be beneficial in managing toxicities and complications arising from NRTI use.

PMID: 27197616 [PubMed - indexed for MEDLINE]

Medication Complexity, Medication Number, and Their Relationships to Medication Discrepancies.

Ann Pharmacother. 2016 Jul;50(7):534-40

Authors: Patel CH, Zimmerman KM, Fonda JR, Linsky A

Abstract
BACKGROUND: Medication reconciliation to identify discrepancies is a National Patient Safety Goal. Increasing medication number and complex medication regimens are associated with discrepancies, nonadherence, and adverse events. The Medication Regimen Complexity Index (MRCI) integrates information about dosage form, dosing frequency, and additional directions.
OBJECTIVE: This study evaluates the association of MRCI scores and medication number with medication discrepancies and commissions, a discrepancy subtype.
METHODS: This was a retrospective cohort study of a convenience sample of 104 ambulatory care patients seen from April 2010 to July 2011 within the Department of Veterans Affairs. Primary outcomes included any medication discrepancy and commissions. Primary exposures included MRCI scores and medication number. Multivariable logistic regression models associated MRCI scores and medication number with discrepancies. Receiver operating characteristic (ROC) curves provided discrepancy thresholds.
RESULTS: For the 104 patients analyzed, the median MRCI score was 25 (interquartile range [IQR] = 14-43), and the median medication number was 8 (IQR = 5-13); 60% of patients had any discrepancy, whereas 36% had a commission. In adjusted analyses, patients with MRCI scores ≥25 or medication number ≥8 were more likely to have commissions (odds ratio [OR] = 3.64, 95% CI = 1.41-9.41; OR = 4.51, 95% CI = 1.73-11.73, respectively). The unadjusted ROC threshold for commissions was 36 for MRCI (sensitivity, 59%; specificity, 82%) and 9 for medication number (sensitivity 68%; specificity 67%).
CONCLUSION: Patients with either MRCI scores ≥25 or ≥8 medications were more likely to have commissions. Given equal performance in predicting discrepancies, the efficiency and simplicity of medication number supports its use in identifying patients for intensive medication review beyond medication reconciliation.

PMID: 27147704 [PubMed - indexed for MEDLINE]

Potentially Inappropriate Medications in Older Adults: Why the Revised Criteria Matter.

Ann Pharmacother. 2016 Jul;50(7):599-603

Authors: Barenholtz Levy H, Marcus EL

Abstract
The 2 most widely used explicit criteria regarding inappropriate medication use in older adults are the American Geriatrics Society's Beers Criteria and the Screening Tool of Older People's Prescriptions/Screening Tool to Alert to Right Treatment (STOPP/START). Both documents were updated recently. They are important educational tools that highlight medications for which risks of use may often exceed benefits in older adults and situations in which potentially appropriate medications should be considered for use. The application of these tools has the potential to significantly affect patient care. Thus, it is important for clinicians to be familiar with both documents.

PMID: 27083921 [PubMed - indexed for MEDLINE]

13 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

("drug-induced" OR "drug-related") AND ("adverse events" OR "side effects" OR "side-effects")

These pubmed results were generated on 2017/08/10

PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

How Common Are Pulmonary and Hepatic Adverse Effects in Older Adults Prescribed Nitrofurantoin?

J Am Geriatr Soc. 2017 Jun;65(6):1316-1320

Authors: Claussen K, Stocks E, Bhat D, Fish J, Rubin CD

Abstract
OBJECTIVES: To determine the frequency of serious pulmonary and hepatic adverse events (AEs) in persons aged 65 and older prescribed nitrofurantoin.
DESIGN: Retrospective electronic health record (EHR) audit of nitrofurantoin prescriptions and associated AEs.
SETTING: Urban academic medical center.
PARTICIPANTS: All inpatients and outpatients aged 65 and older prescribed nitrofurantoin from January 1, 2010, to December 31, 2014.
MEASUREMENTS: The number of nitrofurantoin prescriptions and pulmonary and hepatic AEs associated with nitrofurantoin use was acquired by data extraction from EHRs.
RESULTS: Of 3,400 individuals aged 65 and older prescribed nitrofurantoin during the study period, 641 were identified as possibly having one of five targeted symptoms or disease complications (pulmonary and hepatic) associated with nitrofurantoin. After a detailed chart audit, 89% were deemed to have no adverse reaction, 7% had a minor side effect or allergy, and 3.9% met criteria for suspicion of a nitrofurantoin-induced AE, five of whom were rated as being highly suspicious for nitrofurantoin toxicity; four of the five were identified with pulmonary toxicity and one with hepatotoxicity. Four of five of these individuals used nitrofurantoin chronically.
CONCLUSION: Nitrofurantoin was prescribed for 3,400 individuals aged 65 and older during the 5-year study period. Serious side effects appeared to be uncommon, but chronic use appeared to be at greater risk.

PMID: 28306135 [PubMed - indexed for MEDLINE]

Amikacin use and therapeutic drug monitoring in adults: do dose regimens and drug exposures affect either outcome or adverse events? A systematic review.

J Antimicrob Chemother. 2016 Oct;71(10):2754-9

Authors: Jenkins A, Thomson AH, Brown NM, Semple Y, Sluman C, MacGowan A, Lovering AM, Wiffen PJ, (BSAC Working Party on Therapeutic Drug Monitoring)

Abstract
OBJECTIVES: The objectives of this study were to identify the amikacin dosage regimens and drug concentrations consistent with good outcomes and to determine the drug exposures related to nephrotoxicity and ototoxicity.
METHODS: A literature review was conducted in Medline, EMBASE and the Cochrane Central Register of Controlled Trials. Full journal articles reporting randomized controlled trials, controlled clinical trials, interrupted time series trials, and controlled before and after studies involving amikacin therapeutic drug monitoring (TDM) and dose adjustment were considered for inclusion.
RESULTS: Seventeen studies for inclusion were identified, comprising 1677 participants. Amikacin doses ranged from 11 to 15 mg/kg/day with 13 studies using 15 mg/kg/day. Studies were generally designed to compare different aminoglycosides rather than to assess concentration-effect relationships. Only 11 papers presented data on target concentrations, rate of clinical cure and toxicity. Target peak concentrations ranged from 15 to 40 mg/L and target troughs were typically <10 or <5 mg/L. It was not clear whether these targets were achieved. Measured peaks averaged 28 mg/L for twice-daily dosing and 40-45 mg/L for once-daily dosing; troughs averaged 5 and 1-2 mg/L, respectively. Fifteen of the included studies reported rates of nephrotoxicity; auditory and vestibular toxicities were reported in 12 and 8 studies.
CONCLUSIONS: This systematic review found little published evidence to support an optimal dosage regimen or TDM targets for amikacin therapy. The use of alternative approaches, such as consensus opinion and a review of current practice, will be required to develop guidelines to maximize therapeutic outcomes and minimize toxicity with amikacin.

PMID: 27494904 [PubMed - indexed for MEDLINE]