Generalized Intense Pruritus During Canagliflozin Treatment: Is it an Adverse Drug Reaction?

Curr Drug Saf. 2018;13(1):38-40

Authors: Vasapollo P, Cione E, Luciani F, Gallelli L

Abstract
BACKGROUND: Selective agents able to locate and identify unique targets represent a crucial aspect of modern pharmacology. The exclusive location of Sodium-Glucose co-Transporter-2 (SGLUT2) on kidneys prompt companies to develop SGLT2 inhibitors that today are the latest class of drugs for diabetes treatment. In particular, canagliflozin blocks the re-absorption of glucose in the kidney lowering blood glucose levels by increasing glucose excretion.
CASE DESCRIPTION: We report a 61-year old woman who developed an intense and severe pruritus during the treatment with canagliflozin. Clinical and laboratory findings excluded the presence of systemic or skin diseases able to induce pruritus. The discontinuation of canagliflozin and the treatment with pioglitazone/metformin fixed combination induced a remission of pruritus.
CONCLUSION: This case emphasizes the need to consider pruritus as a differential diagnosis during the treatment with canagliflozin.

PMID: 27048192 [PubMed - indexed for MEDLINE]

Effect of a High-Fat Meal on the Pharmacokinetics of the HIV Integrase Inhibitor Cabotegravir.

Clin Pharmacol Drug Dev. 2018 Sep 19;:

Authors: Patel P, Ford SL, Lou Y, Bakshi K, Tenorio AR, Zhang Z, Pan R, Spreen W

Abstract
Cabotegravir is an integrase inhibitor in clinical development for the treatment and prevention of HIV infection using oral tablets for short-term, lead-in use before subsequent administration of a long-acting injectable formulation. This phase 1, single-center, randomized, 2 × 2 crossover study evaluated the effect of a high-fat meal on the pharmacokinetics (PK) of oral cabotegravir. Healthy adults received oral cabotegravir 30 mg as a single dose on 2 separate occasions, either after fasting or following a high-fat meal (∼53% fat, ∼870 kcal). Safety evaluations and serial PK samples were collected, and a mixed-effects model was used to determine within-participant treatment comparison of noncompartmental PK parameters. Twenty-four patients were enrolled and had a mean body mass index of 25.6 kg/m2 ; 67% were male. Compared with the fasting state, coadministration of cabotegravir with a high-fat meal increased plasma cabotegravir area under the concentration-time curve and maximal drug concentration, each by 14%. The slight 14% to 17% increase in exposure associated with a high-fat, high-calorie meal was not considered clinically significant. No grade 3/4 adverse events (AEs), drug-related AEs, or AEs leading to discontinuation were reported.

PMID: 30230694 [PubMed - as supplied by publisher]

Biomarkers of drug-induced acute kidney injury: a regulatory perspective.

Expert Opin Drug Metab Toxicol. 2018 Sep;14(9):929-936

Authors: Blank M, Thompson A, Hausner E, Rouse R

Abstract
INTRODUCTION: Biomarkers are one of the drug development tools that are being developed through collaborative efforts among multiple stakeholder communities to enhance the drug development process. Biomarkers of acute drug-induced renal injury as used in drug development are more commonly referred to as renal safety biomarkers, the focus of this manuscript. Areas covered: This manuscript provides an overview of the history and evolution of the United States Food and Drug Administration's Center for Drug Evaluation and Research's Biomarker Qualification Program. In addition, a regulatory perspective on the potential for renal safety biomarkers to accelerate medical and pharmaceutical research is presented. The first qualification submissions (acute kidney injury biomarkers) are discussed, including how the FDA review process affected the evolution of the biomarker qualification process and the future of biomarker discovery, development, and use. This manuscript also discusses a new repository for data on novel translational safety biomarkers from drug development programs. Expert opinion: In addition to the qualification of novel biomarkers, a key achievement of the first submission for qualification was the bringing together of multiple stakeholder communities to optimize the process. Early qualification reviews provided valuable lessons that informed an overarching approach of how to develop a biomarker for regulatory use.

PMID: 30099912 [PubMed - indexed for MEDLINE]

Characterization of drug-drug interactions in patients whose substance intake was objectively identified by detection in urine.

Expert Opin Drug Metab Toxicol. 2018 Sep;14(9):973-978

Authors: Schrecker J, Puet B, Hild C, Schwope DM

Abstract
BACKGROUND: Identification of drug-drug interactions (DDIs) typically relies on patient medication lists which are prone to inaccuracies. This study describes use of a mass spectrometry test to detect recently ingested substances in urine with subsequent identification of DDIs.
RESEARCH DESIGN AND METHODS: This was a retrospective analysis of the prevalence of DDIs identified in patients with chronic pain, addiction and/or behavioral health conditions in the U.S. Relationships between patient demographics, polypharmacy and the occurrence of DDIs were also described.
RESULTS: Of 15,004 patients, 2964 (20%) had a DDI identified. There was a positive association between the number of substances detected in urine and the number of interactions identified (r = 0.5033, p-value = 0.0001). Of patients with polypharmacy, 15.6% had contraindicated or severe interactions identified compared to only 3.2% of those without polypharmacy. For polypharmacy patients, the youngest population studied had a much higher likelihood of having one or more DDIs identified compared to the other age groups (p-value = 0.0002).
CONCLUSIONS: By utilizing a mass spectrometry test to objectively detect recently ingested substances followed by identification of DDIs, healthcare providers may be able to better characterize the true incidence of DDIs. Study findings may not be generalizable to healthcare populations outside of pain management, addiction treatment, and behavioral health.

PMID: 30092669 [PubMed - indexed for MEDLINE]

Incidence and Preventability of Medication Errors and ADEs in Ambulatory Care Older Patients.

Consult Pharm. 2018 Aug 01;33(8):454-466

Authors: Díaz Hernández SH, Cruz-Gonzalez I

Abstract
OBJECTIVE: To assess the incidence of medication errors, adverse drug events (ADEs), and potential ADEs (poADEs) in patients 65 years of age and older.
DESIGN: This is a retrospective cohort study (2011 to 2014).
SETTING: The study was performed at a section 330 federally funded ambulatory health care center.
PATIENTS: The study was a convenience sample selected in a nonrandomized way from event reports filed in those years.
INTERVENTION: Data were collected through event reports and medical record review. Descriptive statistics and chi-square were employed to analyze data.
RESULTS: During the study period, at least one medication error, poADE, or ADE report was documented in 170 out of 2,218 older patients (incidence: 12.5, 9.4, and 5.0 per 100 patient-years, respectively); 42.9% of ADEs were preventable. The chronic conditions most frequently related to ADEs were diabetes (18%), hypertension (18%), and hyperlipidemia (12%). The use of hypoglycemic agents was commonly associated with ADEs (14%; P = 0.001). An increased number of prescribed medications were significantly associated with all the adverse events.
CONCLUSIONS: Medication errors, poADEs, and ADEs are common in patients 65 years of age or older taking more than three medications. Almost half of the detected ADEs were preventable.

PMID: 30068439 [PubMed - indexed for MEDLINE]

Communicating for Drug Safety.

Consult Pharm. 2018 Aug 01;33(8):406-408

Authors: Davidson HE

PMID: 30068434 [PubMed - indexed for MEDLINE]

11 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")

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19 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 2018/09/18

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.

[Suprapubic Nicolau syndrome following subcutaneous injection of glatiramer acetate].

Ann Dermatol Venereol. 2018 Sep 11;:

Authors: Blind A, Lenormand C, Schissler C, Cribier B, Lipsker D

Abstract
BACKGROUND: Subcutaneous glatiramer acetate, commercialized under the name of Copaxone®, is licensed for the treatment of relapsing multiple sclerosis. Its major adverse effects are skin reactions at the injection site. Nicolau syndrome is a rare but serious iatrogenic accident. Herein we report a case seen in a setting of change of dosage and administration rate of Copaxone®.
PATIENTS AND METHODS: A 64-year-old woman, treated since 2010 with daily sub-cutaneous injections of Copaxone® 20mg/L, reported the appearance of a painful, indurated and erythematous plaque in the suprapubic area following changeover to 40mg/mL injections three times weekly. The suprapubic injections were continued and ugly greyish spots with stellate purpuric borders appeared. Fournier gangrene was ruled out by means of a soft tissue scan.
DISCUSSION: We report this latest case of Nicolau syndrome to alert readers to the non-exceptional nature of this complication associated with use of glatiramer acetate, particularly at a dosage of 40mg/L injections three times weekly. In our case, onset of Nicolau syndrome appears to have been favored by continued injection in areas already showing inflammation. Re-injection of the drug in these areas should thus be proscribed.

PMID: 30217685 [PubMed - as supplied by publisher]

[Adverse effects of long-term proton-pump inhibitor therapy on adults].

Orv Hetil. 2018 May;159(19):735-740

Authors: Igaz I, Simonyi G, Balogh S, Szathmári M

Abstract
In the last few decades, proton-pump inhibitors have become the mainstay of the treatment of acid-related disorders. Despite their efficacy, these drugs are not without risks. Recently several articles have been published on their long-term adverse effects. Among these adverse effects, the higher risk of bone fractures, the vitamin B12 and magnesium deficiencies and the higher risk of Clostridium difficile infection may be relevant. As these drugs are prescribed more and more frequently all over the world, the knowledge of the long-term adverse effects is very important not only for the specialists but for the general practitioners as well. In this review, the authors discuss the recent findings in this field, emphasising that the long-term use of these drugs must be based on an adequate and strong indication. Orv Hetil. 2018; 159(19): 735-740.

PMID: 29730946 [PubMed - indexed for MEDLINE]

Drug-Associated Risk Tool: development and validation of a self-assessment questionnaire to screen for hospitalised patients at risk for drug-related problems.

BMJ Open. 2018 03 09;8(3):e016610

Authors: Kaufmann CP, Stämpfli D, Mory N, Hersberger KE, Lampert ML

Abstract
INTRODUCTION: Identifying patients with a high risk for drug-related problems (DRPs) might optimise the allocation of targeted pharmaceutical care during the hospital stay and on discharge.
OBJECTIVE: To develop a self-assessment screening tool to identify patients at risk for DRPs and validate the tool regarding feasibility, acceptability and the reliability of the patients' answers.
DESIGN: Prospective validation study.
SETTING: Two mid-sized hospitals (300-400 beds).
PARTICIPANTS: 195 patients, exclusion criteria: under 18 years old, patients with a health status not allowing a meaningful communication (eg, delirium, acute psychosis, advanced dementia, aphasia, clouded consciousness state), palliative or terminally ill patients.
METHODS: Twenty-seven risk factors for the development of DRPs, identified in a previous study, provided the basis of the self-assessment questionnaire, the Drug-Associated Risk Tool (DART). Consenting patients filled in DART, and we compared their answers with objective patient data from medical records and laboratory data.
RESULTS: One hundred and sixty-four patients filled in DART V.1.0 in an average time of 7 min. After a first validation, we identified statements with a low sensitivity and revised the wording of the questions related to heart insufficiency, renal impairment or liver impairment. The revised DART (V.2.0) was validated in 31 patients presenting heart insufficiency, renal impairment or liver impairment as comorbidity and reached an average specificity of 88% (range 27-100) and an average sensitivity of 67% (range 21-100).
CONCLUSIONS: DART showed a satisfying feasibility and reliability. The specificity of the statements was mostly high. The sensitivity varied and was higher in statements concerning diseases that require regular disease control and attention to self-care and drug management. Asking patients about their conditions, medications and related problems can facilitate getting a first, broad picture of the risk for DRPs and possible pharmaceutical needs.

PMID: 29523558 [PubMed - indexed for MEDLINE]

Usefulness of basophil activation test for the diagnosis of IgE mediated hypersensitivity to tetanus toxoid vaccine.

J Immunol Methods. 2018 03;454:86-88

Authors: Herreros B, Méndez Y, Feo-Brito F, Urra JM

Abstract
A great number of vaccinated patients develop specific anti-tetanus toxoid IgE, but usually do not undergo any adverse effect. Most of the allergic reactions to tetanus toxoid vaccine usually present with unspecific symptoms of local inflammation. In the presence of severe reactions, and in a special way if the vaccine is provided together with other drugs, it is difficult to establish which is the harmful drug responsible for IgE-mediated adverse reaction. A patient with an anaphylactic reaction after the administration of Toxoid Tetanic (TT) along with several drugs is described. All skin test were negative. The basophils activation test (BAT) in a clear way, identified TT as the allergen that triggered anaphylaxis. The results achieved demonstrates the usefulness of BAT to clarify patients with hypersensibility to tetanus toxoide when the clinic is severe and the vaccine has been administered together with other drugs.

PMID: 29162425 [PubMed - indexed for MEDLINE]

The Change of Reference to Post-Marketing Surveillance Based on the Sequence of Revising the Pharmaceutical Affairs Law.

Yakushigaku Zasshi. 2016;51(1):29-39

Authors: Takahashi H

Abstract
The present Pharmaceutical Affairs Law (PAL) was promulgated in October 1960 and enforced in February 1961．Thereafter, PAL has been frequently revised, was renamed the Pharmaceuticals and Medical Devices Act (PMD Act) in November 2013, and the PMD Act was enforced in November 2014. It describes the change of reference to Post-Marketing Surveillance (PMS) based on the sequence of revisions of PAL for approximately 50 years. Although the purpose of PAL in 1960 was “to control and regulate drugs, quasi-drugs, cosmetics and medical devices (drugs, etc.), and to contrive proper use,” it did not include rules regarding PMS. Thereafter, “to assure the quality, efficacy and safety of drugs, etc.,” “to promote research and development of orphan drugs, etc.” and “to regulate designated substances” were added to the purpose of PAL over a period of time. At the time of establishing the PMD Act, “to assure the quality, efficacy and safety of regenerative products, to promote their research and development, and to prevent the onset and spread of hazards to public health and hygiene through the use of drugs, etc. ”was added to the purpose. Simultaneously, the matters of control and regulation using PAL were increased whenever PAL was revised. Additionally, the PMS systems, such as adverse drug reactions reporting, drug reevaluation and drug reexamination, and the Good Post-Marketing Surveillance Practice (GPMSP) regarding the enforcement standards of PMS, etc. were initiated by regulatory directions and legislated after their establishment. Moreover, an infection reporting system and early-phase pharmcovigilance, etc. were added to the PMS systems. Furthermore, GPMSP was divided into the Good Vigilance Practice (GVP) for marketing license conditions and the Good Post-Marketing Study Practice (GPSP) for enforcement standards regarding post-marketing investigations and clinical trials, and both are regulated.

PMID: 30183145 [PubMed - indexed for MEDLINE]

Rituximab Treatment in Myasthaenia Gravis: Report of two paediatric cases.

Sultan Qaboos Univ Med J. 2018 May;18(2):e223-e227

Authors: Koul R, Al-Futaisi A, Abdelrahim R, Mani R, Abdwani R, Al-Asmi A

Abstract
Myasthaenia gravis (MG) is an auto-immune disease involving the postsynaptic receptors in the neuromuscular junction. The condition is characterised by fatigable weakness of the skeletal muscles and is uncommon in children. Acetylcholinesterase inhibitors and immune-modifying medications are usually considered the mainstay of treatment. However, these medications have to be given on a lifelong basis so that patients remain in remission; furthermore, drug-related side-effects can have a major impact on quality of life. We report two paediatric cases who were treated for MG at the Sultan Qaboos University Hospital, Muscat, Oman, in 2007 and 2008, respectively. Rituximab was eventually administered to each patient after their condition failed to improve despite several years of standard treatment with acetylcholinesterase inhibitors and immune-modifying medications. Overall, rituximab resulted in complete remission in one case and significant clinical improvement in the other case.

PMID: 30210856 [PubMed - in process]

Adverse effects of modified release oxycodone/naloxone in patients with moderate to severe liver impairment.

Med J Aust. 2018 Sep 17;209(6):279-280

Authors: Pattullo V, Pattullo GG, Strasser SI

PMID: 30208822 [PubMed - in process]

Comparing the Effects of Atorvastatin With Sodium Valproate (Divalproex) on Frequency and Intensity of Frequent Migraine Headaches: A Double-blind Randomized Controlled Study.

Clin Neuropharmacol. 2018 May/Jun;41(3):94-97

Authors: Hesami O, Sistanizad M, Asadollahzade E, Johari MS, Beladi-Moghadam N, Mazhabdar-Ghashghai H

Abstract
OBJECTIVES: To evaluate the prophylactic effects of atorvastatin on frequency, intensity, and duration of migraine attacks compared with sodium valproate.
METHODS: In this randomized, double-blind, single-center controlled trial, patients with 6 to 15 migraine attacks per month, which were candidates of preventive treatment, were recruited. The patients were randomly allocated into 2 groups. The first group (A) received atorvastatin 40 mg daily, and the second group (B) received sodium valproate 500 mg daily. All patients were visited each month and followed up for 3 months. The characteristics of migraine headaches including frequency, intensity, and duration of attacks were recorded, as well as the number of analgesics taken per each attack and probable adverse effects.
RESULTS: From 100 patients enrolled in the study, 18 cases were excluded owing to adverse effects (2 cases) or lost to follow-up (16 cases). From 82 patients who completed the trial, 46 and 36 were in group A (atorvastatin) and group B (sodium valproate), respectively. Mean age of the patients was not significantly different in the 2 arms of the study (33.56 ± 8.51 in group A and 33.25 ± 9.91 years in group B, P = 0.877). Number, duration, and intensity of attacks and number of analgesics taken during attacks decreased significantly in both groups in monthly follow-ups. However, there was no statistically significant difference between 2 arms of the study in terms of attenuation in the characteristics of migraine attacks. On the other hand, patients in group A suffered fewer adverse effects compared with group B.
CONCLUSIONS: This study indicates that atorvastatin could be an alternative for sodium valproate in migraine prophylaxis with comparable efficacy and fewer adverse effects. Multicenter studies with larger sample size are recommended.

PMID: 29746282 [PubMed - indexed for MEDLINE]

Adverse events following vaccination of older people may be under-reported.

Med J Aust. 2017 09 02;207(7):301-302

Authors: Clothier HJ, Crawford NW, Russell M, Buttery JP

PMID: 28954616 [PubMed - indexed for MEDLINE]

[Precision medicine-oriented safety assessment strategy for traditional Chinese medicines: disease-syndrome-based toxicology].

Yao Xue Xue Bao. 2016 11;51(11):1681-8

Authors: Wang JB, Cui HR, Bai ZF, Xiao XH

Abstract
Drug toxicity is commonly divided into intrinsic and idiosyncratic types. The former can be generally uncovered in the preclinical safety evaluation stage by conventional toxicological experiments, while the latter is usually found only in the clinical evaluation stage, which is the main cause of severe adverse reactions and withdrawal of post-marketing drugs. Assessment and prediction of idiosyncratic toxicity is a challenging problem worldwide, and is an essential in the development of translational toxicology and precision medicine. Since traditional Chinese medicines (TCMs) have been applied for thousands of years with long experience in clinical efficacy and safety, idiosyncratic toxicity is regarded as an important factor for traditional "non-toxic" medicines and is associated with multiple individual states including different diseases, syndromes, habitus, etc. However, these individual conditions related to disease are often difficult to be resolved in conventional toxicological experiments, leading to insufficient translation of the experimental results into clinical application. We took an approach of systematic analysis of the differences and similarities in toxic property, medication rule and evaluating requirement between TCMs and chemical synthetic medicines. We present a novel and clinic-associated safety assessment strategy, namely as "disease-syndrome-based toxicology", for TCMs. The strategy is able to access the relativity, susceptibility and controllability of the toxicity of TCMs. The new strategy provides a theoretical and methodological guidance to practice and development of the TCM in favor of precision medicine.

PMID: 29908110 [PubMed - indexed for MEDLINE]

Pain-prescription differences - an analysis of 500,000 discharge summaries.

Curr Drug Abuse Rev. 2018 Sep 10;:

Authors: Preissner S, Siramshetty VB, Dunkel M, Steinborn P, Luft FC, Preissner R

Abstract
BACKGROUND: Pain-relief prescriptions have led to an alarming increase in drug-related abuse. In this study we estimate the pain reliever prescription rates at a major German academic hospital center and compare with the nationwide trends from Germany and prescription reports from the USA.
METHODS: We analysed >500,000 discharge summaries from Charite, encompassing the years 2006 to 2015, and extracted the medications and diagnoses from each discharge summary. Prescription reports from the USA and Germany were collected and compared with the trends at Charite to identify the frequently prescribed pain relievers and their world-wide utilization trends. The average costs of pain therapy were also calculated and compared between the three regions.
RESULTS: Metamizole (dipyrone), a non-opioid analgesic, was the most commonly prescribed pain reliever at Charité (59%) and in Germany (23%) while oxycodone (29%), a semi-synthetic opioid, was most commonly ordered in the USA. Surprisingly, metamizole was prescribed to nearly 20% of all patients at Charite, a drug that has been banned for safety reasons (agranulocytosis) in most developed countries including Canada, United Kingdom, and USA. Large number of prospective cases with high risk for agranulocytosis and other side effects were found. Average cost of pain therapy greatly varied between the USA (125.3 EUR) and Charite (17.2 EUR).
CONCLUSIONS: The choice of pain relievers is varies regionally and is often in disagreement with approved indications and regulatory guidelines. A pronounced East-West gradient was observed with metamizole use and the opposite with prescription opioids.

PMID: 30207223 [PubMed - as supplied by publisher]

Assessing and Treating Chronic Pain in Patients with End-Stage Renal Disease.

Drugs. 2018 Sep 11;:

Authors: Coluzzi F

Abstract
Pain is one of the most common symptoms among patients with end-stage renal disease (ESRD), and is often under recognized and not adequately managed in hemodialysis (HD) patients. Barriers to adequate pain management include poor awareness of the problem, insufficient medical education, fears of possible drug-related side effects, and common misconceptions about the inevitability of pain in elderly and HD patients. Caregivers working in HD should be aware of the possible consequences of inadequate pain assessment and management. Common pain syndromes in HD patients include musculoskeletal diseases and metabolic neuropathies, associated with typical intradialytic pain. Evaluating the etiology, nature, and intensity of pain is crucial for choosing the correct analgesic. A mechanism-based approach to pain management may result in a better outcome. Pharmacokinetic considerations on clearance alterations and possible toxicity in patients with ESRD should drive the right analgesic prescription. Comorbidities and polymedications may increase the risk of drug-drug interactions, therefore drug metabolism should be taken into account when selecting analgesic drugs. Automedication is common among HD patients but should be avoided to reduce the risk of hazardous drug administration. Further research is warranted to define the efficacy and safety of analgesic drugs and techniques in the context of patients with ESRD as generalizing information from studies conducted in the general population could be inappropriate and potentially dangerous. A multidisciplinary approach is recommended for the management of complex pain syndromes in frail patients, such as those suffering from ESRD.

PMID: 30206801 [PubMed - as supplied by publisher]