Examining patterns of multimorbidity, polypharmacy and risk of adverse drug reactions in chronic obstructive pulmonary disease: a cross-sectional UK Biobank study.

BMJ Open. 2018 01 14;8(1):e018404

Authors: Hanlon P, Nicholl BI, Jani BD, McQueenie R, Lee D, Gallacher KI, Mair FS

Abstract
OBJECTIVE: This study aims: (1) to describe the pattern and extent of multimorbidity and polypharmacy in UK Biobank participants with chronic obstructive pulmonary disease (COPD) and (2) to identify which comorbidities are associated with increased risk of adverse drug reactions (ADRs) resulting from polypharmacy.
DESIGN: Cross-sectional.
SETTING: Community cohort.
PARTICIPANTS: UK Biobank participants comparing self-reported COPD (n=8317) with no COPD (n=494 323).
OUTCOMES: Multimorbidity (≥4 conditions) and polypharmacy (≥5 medications) in participants with COPD versus those without. Risk of ADRs (taking ≥3 medications associated with falls, constipation, urinary retention, central nervous system (CNS) depression, bleeding or renal injury) in relation to the presence of COPD and individual comorbidities.
RESULTS: Multimorbidity was more common in participants with COPD than those without (17% vs 4%). Polypharmacy was highly prevalent (52% with COPD taking ≥5 medications vs 18% in those without COPD). Adjusting for age, sex and socioeconomic status, those with COPD were significantly more likely than those without to be prescribed ≥3 medications contributing to falls (OR 2.27, 95% CI 2.13 to 2.42), constipation (OR 3.42, 95% CI 3.10 to 3.77), urinary retention (OR 3.38, 95% CI 2.94 to 3.87), CNS depression (OR 3.75, 95% CI 3.31 to 4.25), bleeding (OR 4.61, 95% CI 3.35 to 6.19) and renal injury (OR 2.22, 95% CI 1.86 to 2.62). Concomitant cardiovascular disease was associated with the greatest risk of taking ≥3 medications associated with falls/renal injury. Concomitant mental health conditions were most strongly associated with medications linked with CNS depression/urinary retention/bleeding.
CONCLUSIONS: Multimorbidity is common in COPD and associated with high levels of polypharmacy. Co-prescription of drugs with various ADRs is common. Future research should examine the effects on healthcare outcomes of co-prescribing multiple drugs with similar potential ADRs. Clinical guidelines should emphasise assessment of multimorbidity and ADR risk.

PMID: 29332840 [PubMed - indexed for MEDLINE]

Improved drug safety through intensive pharmacovigilance in hospitalized pediatric patients.

BMC Pharmacol Toxicol. 2017 Dec 08;18(1):79

Authors: Vázquez-Alvarez AO, Brennan-Bourdon LM, Rincón-Sánchez AR, Islas-Carbajal MC, Huerta-Olvera SG

Abstract
BACKGROUND: The aim of this study was to detect and analyze Adverse Drug Reactions (ADRs) through Intensive Pharmacovigilance (IPV) in hospitalized pediatric patients to improve drug safety.
METHODS: A prospective 6-month cross-sectional study was performed in the pediatric service of a regional hospital in Mexico in order to assess hospitalized children from 1 day to 18 years old. The inclusion criteria were: both genders, all hospitalization causes, and at least one prescribed medication (indistinct drug group). Notifications were performed through medical visits, phone calls, or spontaneous reports. ADR suspicions were assessed with severity scales: Naranjo algorithm, Schumock & Thornton and Hartwig and Siegel.
RESULTS: From a total of 1083 hospital admissions, 19 ADRs were recorded. The average age of patients in years was 7.2 (±5.9). The causality assessment in this study showed that most of the ADRs were probable (68.4%) and 4 certain (8.2%); causality was mainly attributed to antibiotics (AB) and an antiepileptic drug. We found a relationship of AB with ADRs (p < 0.05) with an increased risk at the third day of prescription (p < 0.05). The average severity was level 2 and 21% were classified as "preventable". Lastly, an increase in hospital stay associated with ADRs (p < 0.05) and with concomitant medications (p < 0.05), was also found. The most severe ADRs were hemolysis and toxic epidermal necrolysis.
CONCLUSIONS: IPV was an effective tool for ADR prevention, detection, and treatment in hospitalized patients. The intensive monitoring approach in pharmacovigilance amplifies ADR detection and this translates into the improvement of drug safety in children.

PMID: 29216902 [PubMed - indexed for MEDLINE]

Short-term adverse effects of testosterone used for priming in prepubertal boys before growth hormone stimulation test.

J Pediatr Endocrinol Metab. 2018 Jan 26;31(1):21-24

Authors: Albrecht A, Penger T, Marx M, Hirsch K, Dörr HG

Abstract
BACKGROUND: Despite the fact that priming with sex steroids in prepubertal children before growth hormone (GH) provocative tests is recommended, there is an ongoing controversial discussion about the appropriate age of the children, the drug used for priming, the dose and the period between priming and the GH test. Interestingly, there is no discussion on the safety of this procedure. To date, only little data have been available on the possible side effects of priming with testosterone.
METHODS: We analyzed the outcome in 188 short-statured prepubertal boys who had been primed with testosterone enanthate (n=136: 50 mg; n=51: 125 mg, and accidentally one boy with 250 mg) 7 days prior to the GH test. Serum testosterone levels were measured on the day of the GH test in 99 boys.
RESULTS: Overall, only five boys developed adverse side effects. Two boys (dose 125 mg) showed severe low-flow priapism and had to undergo decompression of the corpora cavernosa. One boy suffered from self-limiting priapism and testicular pain (dose 50 mg). Two patients reported testicular pain (each dose 50 mg). The single patient with 250 mg testosterone did not show any adverse effects. The total side effect rate was 2.7%. The serum testosterone levels of the boys with side effects were not different from the testosterone levels of the boys without any side effects.
CONCLUSIONS: Parents and patients should be informed about the possible side effects of priming with testosterone such as priapism and testicular pain. However, the overall side effect rate is low. We found no correlation between the outcome and the testosterone dose used and/or the level of serum testosterone.

PMID: 29197861 [PubMed - indexed for MEDLINE]

Frequency, characteristics and risk factors of QT interval prolonging drugs and drug-drug interactions in cancer patients: a multicenter study.

BMC Pharmacol Toxicol. 2017 Dec 01;18(1):75

Authors: Khan Q, Ismail M, Khan S

Abstract
BACKGROUND: Cancer patients may receive a high number of medications with the potential to prolong QT interval and subsequent TdP (torsades de pointes). This study aimed to identify the prevalence of QT prolonging drugs, their TdP risk, QT prolonging drug-drug interactions (QT-DDIs), levels, predictors, and TdP risk of drugs involved in QT-DDIs.
METHODS: This multicenter study included cancer patients from three major tertiary care hospitals of Khyber-Pakhtunkhwa, Pakistan. Micromedex DrugReax® was used for identification of QT-DDIs. TdP risks were identified by AZCERT (Arizona Center for Education and Research on Therapeutics) classification. Logistic regression analysis was performed to identify predictors of QT-DDIs.
RESULTS: Of 555 patients, 51% were females. Mean age was 46.9 ± 15.7 years. Total 28 distinct QT prolonging drugs were identified in 92.6% of the patients. Overall 21.8% patients were presented with QT-DDIs. Of total 288 identified QT-DDIs, all were of major-severity and fair-documentation. According to AZCERT classification, 59.9% of the interacting drugs were included in list-1 (known risk of TdP), 4.7% in list-2 (possible risk of TdP) and 6.8% in list-3 (conditional risk of TdP). Univariate logistic regression analysis showed significant results for various predictors such as, 8-9 prescribed medications (p < 0.001) and ≥10 medications (p < 0.001), 2 QT drugs (p < 0.001) and ≥3 QT drugs (p < 0.001), breast cancer (p = 0.03), gastrointestinal cancer (p = 0.03), 4-5 supportive care drugs (p < 0.001), 6-8 supportive care drugs (p < 0.001) and >8 supportive care drugs (p < 0.001).
CONCLUSIONS: A high prevalence of QT prolonging drugs and QT-DDIs was reported in oncology. Appropriate precautions are needed to prevent harmful consequences of these interactions.

PMID: 29191244 [PubMed - indexed for MEDLINE]

Successful treatment of bilateral endogenous Fusarium solani endophthalmitis in a patient with acute lymphocytic leukaemia.

Mycoses. 2018 Jan;61(1):53-60

Authors: Rizzello I, Castagnetti F, Toschi PG, Bertaccini P, Primavera L, Paolucci M, Faccioli L, Spinardi L, Lewis RE, Cavo M, Stanzani M

Abstract
Fusarium spp. are an uncommon cause of fungaemia in immunocompromised and neutropenic patients that may hematogenously disseminate to the eyes. Herein, we describe a patient with acute lymphoblastic leukaemia and a prior history of extensive corticosteroid exposure who developed disseminated Fusarium solani infection following chemotherapy despite posaconazole prophylaxis. She was successfully treated with combination liposomal amphotericin B and voriconazole, intraocular injections of voriconazole, topical amphotericin B and bilateral vitrectomy. We also review published literature describing the management of endogenous Fusarium endophthalmitis in immunocompromised hosts.

PMID: 28872724 [PubMed - indexed for MEDLINE]

Characteristics of adverse drug reactions in a vemurafenib early post-marketing phase vigilance study in Japan.

Clin Transl Oncol. 2018 Feb;20(2):169-175

Authors: Uhara H, Kiyohara Y, Tsuda A, Takata M, Yamazaki N

Abstract
BACKGROUND: Post-approval research or monitoring is important to determine real-world safety of new products; however, evidence is scant for vemurafenib in Japanese patients. In Japan, a unique system is officially obligated to investigate post-approval safety. Here we report the first adverse drug reaction (ADR) data from vemurafenib-treated Japanese patients with metastatic melanoma. Data were collected in an early post-marketing phase vigilance (EPPV) study.
METHODS: ADRs were events for which a causal relationship with vemurafenib could not be ruled out or was unknown. ADR data were collected for patients treated with vemurafenib (960 mg bid) between 26 February and 25 August 2015.
RESULTS: Among 95 patients, 46 patients had 118 ADRs (24 serious ADRs in 13 patients). The most common serious ADRs were hypersensitivity (n = 1; 3 events), arthralgia (n = 2; 2 events), pyrexia (n = 2; 2 events) and drug eruption (n = 2; 2 events). Seven patients had serious skin disorders or hypersensitivity, six of whom had prior anti-programmed cell death-1 (PD-1) antibodies 5-35 days before starting vemurafenib. ADR reports of serious skin disorders appeared to be collected more rapidly than previously reported. Cutaneous squamous cell carcinoma developed in only one patient.
CONCLUSIONS: EPPV in Japanese vemurafenib-treated patients identified no new safety signals. The most serious skin and hypersensitivity ADRs occurred in patients with prior anti-PD-1 exposure. Cutaneous squamous cell carcinoma appeared to be rare in Japanese patients. Further research is needed to clarify whether prior treatment with anti-PD-1 agents or racial differences affect the characteristic profile of cutaneous ADRs in Japanese patients.

PMID: 28674996 [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 2018/08/17

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.

Antibiotic-Related Adverse Drug Reactions at a Tertiary Care Hospital in South Korea.

Biomed Res Int. 2017;2017:4304973

Authors: Jung IY, Kim JJ, Lee SJ, Kim J, Seong H, Jeong W, Choi H, Jeong SJ, Ku NS, Han SH, Choi JY, Song YG, Park JW, Kim JM

Abstract
Background: Adverse drug reactions (ADRs) are any unwanted/uncomfortable effects from medication resulting in physical, mental, and functional injuries. Antibiotics account for up to 40.9% of ADRs and are associated with several serious outcomes. However, few reports on ADRs have evaluated only antimicrobial agents. In this study, we investigated antibiotic-related ADRs at a tertiary care hospital in South Korea.
Methods: This is a retrospective cohort study that evaluated ADRs to antibiotics that were reported at a 2400-bed tertiary care hospital in 2015. ADRs reported by physicians, pharmacists, and nurses were reviewed. Clinical information reported ADRs, type of antibiotic, causality assessment, and complications were evaluated.
Results: 1,277 (62.8%) patients were considered antibiotic-related ADRs based on the World Health Organization-Uppsala Monitoring Center criteria (certain, 2.2%; probable, 35.7%; and possible, 62.1%). Totally, 44 (3.4%) patients experienced serious ADRs. Penicillin and quinolones were the most common drugs reported to induce ADRs (both 16.0%), followed by third-generation cephalosporins (14.9%). The most frequently experienced side effects were skin manifestations (45.1%) followed by gastrointestinal disorders (32.6%).
Conclusion: Penicillin and quinolones are the most common causative antibiotics for ADRs and skin manifestations were the most frequently experienced symptom.

PMID: 29457026 [PubMed - indexed for MEDLINE]

Medication administration and interruptions in nursing homes: A qualitative observational study.

J Clin Nurs. 2018 Mar;27(5-6):1113-1124

Authors: Odberg KR, Hansen BS, Aase K, Wangensteen S

Abstract
AIMS AND OBJECTIVES: To contribute in-depth knowledge of the characteristics of medication administration and interruptions in nursing homes. The following research questions guided the study: How can the medication administration process in nursing homes be described? How can interruptions during the medication administration process in nursing homes be characterized?
BACKGROUND: Medication administration is a vital process across healthcare settings, and earlier research in nursing homes is sparse. The medication administration process is prone to interruptions that may lead to adverse drug events. On the other hand, interruptions may also have positive effects on patient safety.
DESIGN: A qualitative observational study design was applied.
METHODS: Data were collected using partial participant observations. An inductive content analysis was performed.
RESULTS: Factors that contributed to the observed complexity of medication administration in nursing homes were the high number of single tasks, varying degree of linearity, the variability of technological solutions, demands regarding documentation and staff's apparent freedom as to how and where to perform medication-related activities. Interruptions during medication administration are prevalent and can be characterised as passive (e.g., alarm and background noises), active (e.g., discussions) or technological interruptions (e.g., use of mobile applications). Most interruptions have negative outcomes, while some have positive outcomes.
CONCLUSIONS: A process of normalisation has taken place whereby staff put up with second-rate technological solutions, noise and interruptions when they are performing medication-related tasks. Before seeking to minimise interruptions during the medication administration process, it is important to understand the interconnectivity of the elements using a systems approach.
RELEVANCE TO CLINICAL PRACTICE: Staff and management need to be aware of the normalisation of interruptions. Knowledge of the complexity of medication administration may raise awareness and highlight the importance of maintaining and enhancing staff competence.

PMID: 29076582 [PubMed - indexed for MEDLINE]

Azathioprine combination therapy for steroid-refractory hepatic immune system-related adverse events.

Eur J Dermatol. 2017 06 01;27(3):301-303

Authors: Iwamoto K, Ishitsuka Y, Tanaka R, Sekine I, Fujimoto M

PMID: 28468733 [PubMed - indexed for MEDLINE]

Treatment complexities among patients with tuberculosis in a high HIV prevalence cohort in the United States.

AIDS Res Hum Retroviruses. 2018 Aug 14;:

Authors: Bizune D, Kempker R, Kagei M, Yamin A, Mohamed O, Holland DP, Oladele A, Wang YF, Rebolledo PA, Blumberg H, Ray SM, Schechter MC

Abstract
The association between human immunodeficiency virus (HIV) infection and tuberculosis (TB) mortality has been studied extensively, but the impact of HIV on other clinically relevant aspects of TB care such as TB drug-related adverse events (AE), hospital readmissions, and TB treatment duration is less well characterized. We describe the association of HIV infection with TB clinical complexities and outcomes in a high HIV prevalence cohort in the United States. This is a retrospective cohort study among patients treated for culture-confirmed TB between 2008-2015 at an inner-city hospital in Atlanta, GA. Univariate analysis was used to estimate association of HIV with TB treatment interruption due to AE, hospital readmissions, and treatment duration. Final unfavorable TB treatment outcome was defined as death, loss to follow-up, or recurrent TB. Logistic regression modeling was used to estimate association of HIV with final unfavorable outcomes. Among 274 patients with TB, 96 (35%) had HIV co-infection. HIV-positive patients had more TB treatment interruptions due to AE (34% vs 15%), were more likely to have a hospital readmission (50% vs 21%), and received longer TB treatment (9.9 vs 8.8 months) compared to HIV-negative patients (p<.01 for all). HIV-infection was not associated with final unfavorable outcomes in univariate [odds ratio (OR)=1.86; 95%CI 0.99-3.49] or multivariate analysis (aOR=1.13; 95%CI 0.52-2.39) (p≥.05 for both). While HIV infection was not associated with final unfavorable TB outcomes, TB/HIV co-infected patients had more complex treatment course underscoring the importance of maintaining resources and expertise to treat co-infected patients in our and similar settings.

PMID: 30105915 [PubMed - as supplied by publisher]

A new non-dilution rapid desensitization protocol successfully applied to all-grade platinum hypersensitivity.

Cancer Chemother Pharmacol. 2018 Aug 13;:

Authors: Chung SJ, Kang SY, Kang RY, Kim YC, Lee KH, Kim TY, Han SW, Kang HR

Abstract
PURPOSE: Desensitization is a safe alternative for patients with hypersensitivity reactions (HSRs) to platinum-based chemotherapeutic agents and widely used in real practice by employing stepwise administration of multiple serial dilutions of the culprit drugs. However, its labor-intensive nature has required a simpler protocol that is easier to prepare and perform.
METHODS: We performed an observational study of patients with platinum HSR who underwent a new non-dilution one-bag desensitization protocol. Premedication consisted of Montelukast as well as H1 and H2 blockers. The outcomes and safety profiles of a new protocol were assessed.
RESULTS: A total of 36 patients were recruited (oxaliplatin 23, carboplatin 9, and cisplatin 4) and the most common grade of HSR presented was grade 2 (61.1%), followed by grade 3 (25%), and grade 1 (13.9%). Of 175 desensitization procedures, all cases were successfully completed in re-administration of culprit chemotherapeutic platinum agents; 146 (83.4%) had no breakthrough reactions (BTRs) while 29 (16.6%) did. Most BTRs were mild reactions (grade 1, 51.7%) or moderate reactions (grade 2, 44.8%) of Brown's Scale. Although there was one case of asymptomatic mild hypotension (grade 3, 3.5%), categorized as severe reaction, dyspnea, desaturation, and anaphylaxis did not occur. The proportion of severe HSRs was significantly lower than that of initial HSRs (3.5% vs. 25%, P = 0.0167).
CONCLUSIONS: The new non-dilution desensitization protocol was safe and effective for re-administration of culprit platinum agents in patients with a history of HSRs. Therefore, this new protocol can be used as an alternative to existing protocols using multiple serial dilutions.

PMID: 30105458 [PubMed - as supplied by publisher]

Genetic polymorphisms associated with adverse reactions of molecular-targeted therapies in renal cell carcinoma.

Med Oncol. 2018 Jan 04;35(2):16

Authors: Yamamoto K, Yano I

Abstract
The prognosis of patients with metastatic renal cell carcinoma has drastically improved due to the development of molecular-targeted drugs and their use in clinical practice. However, these drugs cause some diverse adverse reactions in patients and sometimes affect clinical outcomes of cancer therapy. Therefore, predictive markers are necessary to avoid severe adverse reactions, to establish novel and effective prevention methods, and to improve treatment outcomes. Some genetic factors involved in these adverse reactions have been reported; however, perspectives on each adverse response have not been integrated yet. In this review, genetic polymorphisms relating to molecular-targeted therapy-induced adverse reactions in patients with renal cell carcinoma are summarized in the points of pharmacokinetic and pharmacodynamic mechanisms. We also discuss about the relationship between systemic drug exposure and adverse drug reactions.

PMID: 29302760 [PubMed - indexed for MEDLINE]

Hematological adverse effects in breast cancer patients treated with cyclin-dependent kinase 4 and 6 inhibitors: a systematic review and meta-analysis.

Breast Cancer. 2018 Jan;25(1):17-27

Authors: Kassem L, Shohdy KS, Lasheen S, Abdel-Rahman O, Bachelot T

Abstract
BACKGROUND: The introduction of specific cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors significantly improved progression-free survival in hormone receptor-positive metastatic breast cancer. CDK 4/6 inhibitors induce cell cycle arrest via liberating the tumor suppressor retinoblastoma protein from CDK4/6 inhibitory effect. Preliminary studies suggested an increase in the hematological toxicities which might affect the quality of life in such palliative setting.
METHODS: We searched PubMed, ASCO, ESMO and San Antonio meeting databases for randomized phase II/III trials in metastatic breast cancer receiving CDK4/6 inhibitors with safety data provided on the incidence of hematological adverse effects.
RESULTS: Our search identified 1012 citations that were screened for relevance. Thirty-six studies were found to be potentially eligible. After excluding the ineligible studies, six studies were deemed to be eligible for meta-analysis. The risk ratio (RR) was 11.31 [95% confidence interval (CI) 8.06-15.87; p < 0.0001] for all-grade leucopenia, 14.86 (95% CI 11.37-19.41; p < 0.0001) for all-grade neutropenia, 9.04 (95% CI 3.78-21.63; p < 0.0001) for all-grade thrombocytopenia and 3.57 (95% CI 2.65-4.81; p < 0.0001) for all-grade anemia. The RR for grade 3/4 leucopenia was 33.86 (95% CI 14.59-78.57; p < 0.0001), for grade 3/4 neutropenia was 44.00 (95% CI 24.72-78.33; p < 0.0001), for grade 3/4 thrombocytopenia was 5.70 (95% CI 2.03-16.01; p = 0.001) and for grade 3/4 anemia was 2.80 (95% CI 1.45-5.41; p = 0.002). There was no significant increase in the RR of febrile neutropenia with RR of 3.29 (95% CI 0.93-11.57; p = 0.06).
CONCLUSION: Our analysis provides evidence that the use of CDK 4/6 inhibitors is associated with an increased risk of all-grade and high-grade hematological adverse events, which seems to be a class-effect, but not of febrile neutropenia compared with hormonal therapy alone.

PMID: 29147869 [PubMed - indexed for MEDLINE]

So Many Antihyperglycemics: How to Choose? A Practical Approach.

Can J Diabetes. 2017 Oct;41(5):469-473

Authors: Cheng AYY

Abstract
Guidelines from around the world have stressed the importance of glycemic control in the management of patients with type 2 diabetes (T2DM) to reduce the risk of developing complications. To achieve this goal, both lifestyle and pharmacologic therapies are available. There are 9 classes of antihyperglycemic therapies available in Canada and each class provides a different mechanism of action to address the pathophysiology of T2DM. Metformin remains the first choice for pharmacologic therapy. Thereafter, individualization is essential. If there is significant hyperglycemia at diagnosis, initial combination therapy should be considered. The choice of therapy after metformin depends on a number of factors with the first consideration being the presence or absence of cardiovascular disease. If present, an agent with proven cardiovascular benefit should be added. Otherwise, individualization should be based on desired glycemic lowering, risk of hypoglycemia, effect on weight, cardiovascular effects, other side effects and accessibility.

PMID: 28600118 [PubMed - indexed for MEDLINE]

17 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 2018/08/14

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.

17 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 2018/08/14

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.

Phase I, open-label study of pasireotide in patients with BRAF-wild type and NRAS-wild type, unresectable and/or metastatic melanoma.

ESMO Open. 2018;3(5):e000388

Authors: Dummer R, Michielin O, Nägeli MC, M Goldinger S, Campigotto F, Kriemler-Krahn U, Schmid H, Pedroncelli A, Micaletto S, Schadendorf D

Abstract
Introduction: Somatostatin analogues exert antitumour activity via direct and indirect mechanisms. The present study was designed to assess the safety and efficacy of pasireotide in patients with BRAF-wild type (WT) and NRAS-WT metastatic melanoma.
Patients and methods: Patients with unresectable and/or metastatic melanoma or Merkel cell carcinoma were eligible. Pasireotide was administered at different doses for ≤8 weeks in dose-escalation phase, followed by long-acting pasireotide 80 mg or lower dose in case of toxicity in follow-up phase up to six additional months. Primary endpoint was safety in the first 8 weeks of dose-escalation phase.
Results: The study was terminated early due to slow recruitment. Of the 10 patients with metastatic melanoma enrolled, only four reached the high dose level: two patients reached 3600 µg in dose-escalation and follow-up phases and two patients reached 3600 µg in dose-escalation and long-acting pasireotide 80 mg in follow-up phases and were stable for >5 months. Most common adverse events (AEs) during dose-escalation phase in ≥2 patients (20%) were: diarrhoea (50%), nausea (50%), fatigue (20%), hyperglycaemia (20%), hypophosphatemia (20%), chills (20%) and tumour pain (20%). Grade 3 or 4 study drug-related AEs were diarrhoea and nausea, reported in one patient. Partial response was documented in one patient and stable disease in another.
Conclusions: Pasireotide was well tolerated, and safety results were similar to those previously reported in other indications. Further studies are needed to evaluate its antitumour activity alone and in combination with other drugs in melanoma.

PMID: 30094073 [PubMed]

Identifying Adverse Events Using International Classification of Diseases, Tenth Revision Y Codes in Korea: A Cross-sectional Study.

J Prev Med Public Health. 2018 Jan;51(1):15-22

Authors: Ock M, Kim HJ, Jeon B, Kim YJ, Ryu HM, Lee MS

Abstract
Objectives: The use of administrative data is an affordable alternative to conducting a difficult large-scale medical-record review to estimate the scale of adverse events. We identified adverse events from 2002 to 2013 on the national level in Korea, using International Classification of Diseases, tenth revision (ICD-10) Y codes.
Methods: We used data from the National Health Insurance Service-National Sample Cohort (NHIS-NSC). We relied on medical treatment databases to extract information on ICD-10 Y codes from each participant in the NHIS-NSC. We classified adverse events in the ICD-10 Y codes into 6 types: those related to drugs, transfusions, and fluids; those related to vaccines and immunoglobulin; those related to surgery and procedures; those related to infections; those related to devices; and others.
Results: Over 12 years, a total of 20 817 adverse events were identified using ICD-10 Y codes, and the estimated total adverse event rate was 0.20%. Between 2002 and 2013, the total number of such events increased by 131.3%, from 1366 in 2002 to 3159 in 2013. The total rate increased by 103.9%, from 0.17% in 2002 to 0.35% in 2013. Events related to drugs, transfusions, and fluids were the most common (19 446, 93.4%), followed by those related to surgery and procedures (1209, 5.8%) and those related to vaccines and immunoglobulin (72, 0.3%).
Conclusions: Based on a comparison with the results of other studies, the total adverse event rate in this study was significantly underestimated. Improving coding practices for ICD-10 Y codes is necessary to precisely monitor the scale of adverse events in Korea.

PMID: 29397642 [PubMed - indexed for MEDLINE]

Potential drug-drug interactions of OMBITASVIR, PARITAPREVIR/ritonavir ± DASABUVIR ± ribavirin in clinical practice.

J Gastroenterol Hepatol. 2018 May;33(5):1100-1107

Authors: González-Colominas E, Londoño MC, Morillas RM, Torras X, Mojal S, Lens S, López D, Gallego A, Mariño Z, Ardèvol M, Pagès N, Solà R, Carrión JA

Abstract
BACKGROUND & AIMS: Drug-drug interactions (DDIs) with ombitasvir/paritaprevir/ritonavir with or without dasabuvir and with or without ribavirin (OBV/PTV/r ± DSV ± RBV) are common in clinical trials. Our aim was to analyze the prevalence and management of potential DDIs and adverse events (AEs) related to DDIs in patients with chronic hepatitis C (CHC) receiving OBV/PTV/r ± DSV ± RBV in clinical practice.
METHODS: 177 CHC patients started OBV/PTV/r ± DSV ± RBV in 4 Spanish hospitals and were screened for potential DDIs using the University of Liverpool database. Patients were classified according to the most serious potential DDIs at baseline and AEs during therapy.
RESULTS: At least one potential DDI was found in 110 (62.1%) patients: 100 (56.5%) had at least one manageable potential DDI and 10 (5.6%) at least one contraindicated. Patients with potential DDIs were receiving a higher number of concomitant drugs (4 vs. 2, P < 0.001). Routine medication was modified at baseline due to potential DDIs in 49 (27.7%) patients. During antiviral treatment, 67 (37.9%) patients presented at least one AE. In 9 (4.5%) patients, a DDI was suspected between OBV/PTV/r ± DSV ± RBV and the concomitant drug, requiring antiviral discontinuation in 4 patients.
CONCLUSIONS: Potential DDIs are frequent with OBV/PTV/r ± DSV ± RBV, although a change in baseline medication is made in only one-quarter of patients. More than half of potential DDIs were only followed, and only 5% of patients developed AEs in which the implication of DDIs could not be excluded.

PMID: 28994141 [PubMed - indexed for MEDLINE]