BACKGROUND: Potential drug-drug interactions (pDDIs) with immunosuppressive drugs are frequently observed in renal transplant recipients. Drug interaction programs are acknowledged as a fundamental tool to alert physicians to pDDIs, but there is a high concern about variation among different programs in terms of quality and reliability of information.OBJECTIVES: To (a) characterize the difference in severity levels of pDDIs with tacrolimus and cyclosporine provided by 3 drug interaction programs and (b) identify clinically relevant DDIs with these immunosuppressive drugs in renal transplant recipients.METHODS: This study was conducted in a nephrology outpatient clinic at the University Research & Training Hospital between November 2017 and February 2018. A clinical pharmacist attended clinic visits with physicians and evaluated drug interactions. Micromedex, Medscape, and Lexicomp drug interaction programs were used to identify pDDIs and their severities. Furthermore, Drug Interaction Probability Scale (DIPS) criteria were applied to identify clinically relevant drug interactions seen in clinic patients. Finally, a clinical pharmacist intervened to manage clinically relevant drug interactions identified by DIPS. RESULTS: 80 patients (54 under tacrolimus; 26 under cyclosporine treatment) were included in this study. The 3 drug interaction programs generated 648 pDDIs, 63 of which were different drug interaction pairs. Ninety-eight pDDIs were common to all 3 drug interaction programs. Sixtythree different drug interaction pairs were evaluated according to severity level, and 3 drug interaction pairs were at the same level (moderate) among the programs. The Fleiss' kappa overall interrater agreement was poor. The kappa revealed a moderate agreement for interaction pairs with a "severe" rating and a slight agreement for interaction pairs with a "major" rating. According to the DIPS evaluation, 11 pDDIs were classified as "possible," and the percentage of clinically relevant drug-drug interactions was 4.0% (10/248), 4.2% (11/265), and 8.2% (11/135) for Medscape, Lexicomp, and Micromedex, respectively. Although daily doses of immunosuppressive drugs were not changed, the blood concentrations of these drugs increased after administration of an interacting drug. As a result, in order to maintain normal therapeutic range of concentrations, dose reduction or drug change was applied where appropriate. CONCLUSIONS: Interaction checker programs are commonly used by health institutions, since they provide quick and summarized information on mechanism and management of drug interactions, when no clinical pharmacist is present to interpret. However, the likelihood of detecting clinically relevant DDIs by interaction checker programs is relatively low, and there are inconsistencies among different programs. Individualized patient monitoring should be maintained by a multidisciplinary health care team that includes a clinical pharmacist, and decision making should be based on professional assessment of the renal transplant patient.

Does therapeutic drug monitoring of hydroxychloroquine improve treatment outcome in intensive care unit patients with COVID-19?To The Editor, COVID-19 is a newly emerging human infectious disease of SARS-CoV-2 origin that has spread from China. The global COVID-19 situation was described as a pandemic by the WHO on 11 March 2020. Several treatment strategies are being considered and evaluated in numerous clinical trials. Among several treatment strategies, hydroxychloroquine (HCQ) has been suggested as potential treatment option for COVID-19. However, it has very long half-life(5-40 days) and large volume of distribution into blood and tissues which causes variability in treatment response. It is known that, the steady-state concentration is reached within weeks and differs according to individual factors (eg, obesity, sepsis, burn, ascites, pregnancy, critical illness) even at the same dose regime especially in the treatment of rheumatic diseases. 1 In contrast, the usage of HCQ is limited to 5 days and the mean time to reach the minimum therapeutic drug concentration (1 mg/L) is 3-4 days in patients with Patients in intensive care unit (ICU) present certain characteris-LETTER

To the Editor, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the virus strain that typically causes acute respiratory distress in patients, and its associated disease was named CoV Disease-19 (COVID-19). Presence of comorbid diseases and suppressed immune systems, especially in advanced age (>60 years), have been shown to be risk factors for COVID-19. 1 Both cancer and its treatment can weaken the immune system of patients which leads cancer patients become more vulnerable to infections. Cytopenias such as neutropenia, anemia, and thrombocytopenia, which are seen as a result of myelosuppression, are particularly important problems that can affect the treatment process. Depending on the chemotherapy regimen used, patients may present different myelosuppressive side effects. The National Comprehensive Cancer Network (NCCN) guideline classified chemotherapy regimens according to the risk of neutropenia as: high (>20%), intermediate (10-20%), and low (<10%). 2 In the view of this guideline, topotecan used in the treatment of small cell lung cancer is at high risk, cisplatin-paclitaxel, cisplatinvinorelbine, cisplatin-docetaxel, cisplatin-etoposide, carboplatin-paclitaxel, and docetaxel regimens used in the treatment of non-small cell lung cancer are considered to be at intermediate risk. 2 Prophylactic use of granulocyte colony stimulating factor is recommended to prevent complications of neutropenia in patients using high-risk treatment regimens, and patients using medium-risk treatment regimens if more than one risk factor exists. 2 Immunotherapeutic agents (such as anti-PD-1/PD-L1 drugs) may have myelosuppressive side effects similar to cytotoxic agents, but data are limited. 3 The myelosuppressive effect of cytotoxic agents is cumulative and the risk is further increased in the later stages of treatment. 3 The most important fatal adverse effects of anti-PD-1/PD-L1 drugs are known as pneumonitis (35%). 3 Therefore, determining the risk status of cancer patients and re-evaluation of treatment during COVID-19 is important. Assessment of cancer as a risk factor for COVID-19 has not yet been fully defined. However, the study of Liang et al. described the COVID-19 and cancer relationship with limited data. 4 According to the study, the prognosis of COVID-19 was shown to be worse in cancer patients compared to the others and the most common type is lung cancer seen in patients with COVID-19, which also has the high mortality rate. 5 There is currently no approved treatment for COVID-19, but hydroxychloroquine, azithromycin, lopinavir-ribonavir, remdesivir, tocilizumab, favipiravir, and plasma antibody therapy are considered potential treatment option worldwide. Cancer often requires a long-term treatment in cycles, and drug treatment may have cumulative and/ or immediate effects. Cumulative effects of drug treatment can cause a risk for potential drug interactions with drugs used in COVID-19 treatment. The drugs used in the treatment of COVID-19, such as hydroxychloroquine and tocilizumab, have a long...

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COVID-19 is a newly emerging human infectious disease of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) origin described as a pandemic by the World Health Organisation (WHO) on March 11, 2020. There is currently no definitive cure for COVID-19; however, among the many treatment strategies, hydroxychloroquine has been suggested as a potential treatment. The purpose of this article was to review the pharmacological properties and mechanism of COVID-19 treatment with hydroxychloroquine and its potential use on the current COVID-19 pandemic.