- Therapeutic Dose Monitoring of Busulfan is Associated with a Reduction in Risk of Relapse in Non-Hodgkin Lymphoma Patients Undergoing Autologous Stem Cell Transplantation. [Journal Article]Biol Blood Marrow Transplant 2019BB
- CONCLUSIONS: Compared to WBD, PK-directed TDM of Bu reduces relapse incidence when used in combination with Cy and E for NHL patients undergoing ASCT, particularly for patients in less than CR. These data support continued use of personalized PK-guided dosing for all NHL patients undergoing ASCT with Bu-containing preparative regimens.
- Switching to Fixed-Dose Bictegravir, Emtricitabine, and Tenofovir Alafenamide (B/F/TAF) in Virologically Suppressed HIV-1 Infected Women: A Randomized, Open-Label, Multicenter, Active-Controlled, Phase 3, Noninferiority Trial. [Journal Article]J Acquir Immune Defic Syndr 2019; 82(3):321-328JA
- CONCLUSIONS: Fixed-dose combination B/F/TAF provides a safe and efficacious option for ongoing treatment of HIV in women. This study contributes important data on safety, tolerability, and outcomes of antiretroviral therapy among women living with HIV.
- Erratum to: SD1000: High Sustained Viral Response Rate in 1361 Patients With Hepatitis C Genotypes 1, 2, 3, and 4 Using a Low-cost, Fixed-dose Combination Tablet of Generic Sofosbuvir and Daclatasvir: A Multicenter, Phase III Clinical Trial. [Journal Article]Clin Infect Dis 2019CI
- Fixed and Low-Dose Combinations of Blood Pressure-Lowering Agents: For the Many or the Few? [Journal Article]Drugs 2019D
- Despite the widespread availability of several effective classes of drugs, systemic arterial hypertension remains poorly controlled in the majority of patients worldwide. In this article, we discuss the different modalities and effects of combination therapy and possible future research questions. Treatment with a single antihypertensive agent can effectively reduce blood pressure in only a limit…
Despite the widespread availability of several effective classes of drugs, systemic arterial hypertension remains poorly controlled in the majority of patients worldwide. In this article, we discuss the different modalities and effects of combination therapy and possible future research questions. Treatment with a single antihypertensive agent can effectively reduce blood pressure in only a limited number of patients, while most require therapy with two or more agents to achieve target levels. As initial therapy, American and European guidelines suggest a combination of two antihypertensive drugs and the use of a third antihypertensive drug when hypertension is still uncontrolled. Initial combination therapy is recommended in high-risk patients for an immediate blood pressure response, improved tolerability and possibly increased patient adherence. In addition to the potential benefits of combining different drug classes with synergistic pharmacological and physiological actions, this approach is useful for increasing the patient compliance with treatment, in particular if provided at fixed doses in a single pill. The minimisation of side effects is critical for the long-term treatment of a largely asymptomatic condition such as systemic hypertension. Low-dose combinations of different drugs from classes with complementary actions may provide the best ratio of lower side effects and improved tolerability with a significant blood pressure reduction, particularly in high-risk patients. This approach could be aided by a multidisciplinary lifestyle intervention on risk factors.
- The efficacy and safety of elbasvir/grazoprevir treatment in HCV genotype 1 patients in Taiwan. [Journal Article]J Med Virol 2019JM
- CONCLUSIONS: This study confirmed that EBR/GZR is safe and effective for treating patients with HCV GT1 and exhibited excellent overall clinical efficacy in Taiwan. The therapeutic effects are unrelated to factors such as sex, HCV RNA level before treatment, and history of liver cirrhosis. This article is protected by copyright. All rights reserved.
- Effects of Fimasartan/Amlodipine Fixed-Dose Combination on Left Ventricular Systolic Function and Infarct Size in Rat Myocardial Infarction Model. [Journal Article]Chonnam Med J 2019; 55(3):144-149CM
- The aim of this study was to evaluate the effects of fimasartan/amlodipine fixed-dosed combination (F/A) on left ventricle (LV) systolic function and infarct size in the rat myocardial infarction (MI) model. We induced MI in 20 rats by ligation of the left anterior descending coronary artery and they were divided into two groups [MI group (n=10) vs. MI+F/A 10 mg/kg group (n=10)]. F/A was administ…
The aim of this study was to evaluate the effects of fimasartan/amlodipine fixed-dosed combination (F/A) on left ventricle (LV) systolic function and infarct size in the rat myocardial infarction (MI) model. We induced MI in 20 rats by ligation of the left anterior descending coronary artery and they were divided into two groups [MI group (n=10) vs. MI+F/A 10 mg/kg group (n=10)]. F/A was administered for 28 days between day-7 and day-35 in the MI+F/A group and echocardiography was performed at day-7 and at day-35 after the induction of MI. Picrosirius red staining was performed to confirm the fibrotic tissue and infarct size was measured using image analysis program for Image J. At the 35-day follow-up, the LV ejection fraction (EF) was significantly higher (38.10±3.92% vs. 29.86±4.56%, p<0.001) and delta (day-35 minus day-7) EF was significantly higher (0.14±2.66% vs. -8.53±2.66%. p<0.001) in the MI+F/A group than the MI group. Systolic blood pressure was significantly lower in the MI+F/A group than the MI group (103.23±13.35 mmHg vs. 123.43±14.82 mmHg, p<0.01). The MI+F/A group had a smaller infarct size (26.84±5.31% vs. 36.79±3.10%, p<0.01) than the MI group at the 35-day follow-up. Oral administration of F/A 10 mg/kg could improve LV systolic function and reduce infarct size in a rat MI model.
- Brinzolamide/brimonidine fixed-dose combination bid as an adjunct to a prostaglandin analog for open-angle glaucoma/ocular hypertension. [Journal Article]Eur J Ophthalmol 2019; :1120672119878044EJ
- CONCLUSIONS: BBFC + PGA significantly reduced mean diurnal intraocular pressure than PGA alone in patients with open-angle glaucoma or ocular hypertension. The safety findings with BBFC + PGA were consistent with the known safety profile of the individual medications.
- Netarsudil/latanoprost fixed-dose combination for the treatment of open-angle glaucoma or ocular hypertension. [Journal Article]Drugs Today (Barc) 2019; 55(9):563-574DT
- The fixed-dose combination (FDC) of netarsudil 0.02%/ latanoprost 0.005% was approved by the United States Food and Drug Administration (FDA) on March 12, 2019, for the reduction of intraocular pressure (IOP) in patients with open-angle glaucoma (OAG) and ocular hypertension (OHT). Netarsudil is a Rho kinase (ROCK) inhibitor and latanoprost is a prostaglandin analogue (PGA). Once-daily administra…
The fixed-dose combination (FDC) of netarsudil 0.02%/ latanoprost 0.005% was approved by the United States Food and Drug Administration (FDA) on March 12, 2019, for the reduction of intraocular pressure (IOP) in patients with open-angle glaucoma (OAG) and ocular hypertension (OHT). Netarsudil is a Rho kinase (ROCK) inhibitor and latanoprost is a prostaglandin analogue (PGA). Once-daily administration of this FDC reduces IOP by enhancing aqueous outflow through both the trabecular pathways (ROCK inhibition) and uveoscleral pathways (PGA). Two phase III clinical trials, MERCURY-1 and MERCURY-2, confirmed significantly greater efficacy of the FDC than the individual components, with IOP reductions of 30% or greater observed in 59-65% of subjects treated with FDC compared with 29-37% of subjects treated with latanoprost alone and 21-29% of subjects treated with netarsudil alone. The FDC was well tolerated with mostly mild ocular side effects and limited systemic side effects. This paper will review the work leading to FDA approval and the clinical indications for the use of this combination.
- As-needed ICS-LABA in Mild Asthma: What Does the Evidence Say? [Journal Article]Drugs 2019D
- For the last three decades, the guidelines for asthma management have supported a stepwise therapeutic approach, based on the administration of controller medications (especially inhaled corticosteroids) complemented by on-demand use of rescue medication. Classically, the rescue medication recommended comprised short-acting β agonists (SABA). Some years ago, the use of Symbicort Maintenance and R…
For the last three decades, the guidelines for asthma management have supported a stepwise therapeutic approach, based on the administration of controller medications (especially inhaled corticosteroids) complemented by on-demand use of rescue medication. Classically, the rescue medication recommended comprised short-acting β agonists (SABA). Some years ago, the use of Symbicort Maintenance and Reliever Therapy (SMART) demonstrated the benefits of a combination of budesonide-formoterol, an inhaled corticosteroid, and a long-acting β agonist (ICS-LABA) as rescue medication in moderate and severe asthma. The results were enthusiastically received, and this therapeutic option was adopted in the guidelines for moderate to severe asthma patients. Recently, four trials (two randomised placebo control trials under the auspices of the SYGMA project and two real-life studies, Novel START, and the PRACTICAL trial) have explored the potential benefits of substituting SABA with budesonide-formoterol as rescue medication in mild asthma patients. The SYGMA 1 and 2 studies showed that the combination with formoterol-budesonide as rescue medication provides better asthma control than short-acting β-agonists alone in GINA step 2 patients, although the superiority was slight. Compared to budesonide maintenance therapy, the fixed combination of ICS-LABA on demand provides poorer asthma control. Regarding exacerbations, the fixed dose ICS-LABA combination on demand showed the same benefits for the prevention of exacerbations as chronic ICS treatment in mild asthma patients. The Novel START study, which assessed a population with milder symptoms, concluded that the fixed dose ICS-LABA combination used as needed was superior to SABA (albuterol) as needed for the prevention of asthma exacerbations. These results in fact show that, in undertreated GINA step 2 with only SABA as needed, ICS-LABA is more effective than SABA. The authors of PRACTICAL concluded that the study provided modest evidence that the ICS-LABA combination used as-needed for symptom relief reduces the rate of severe exacerbations compared with maintenance low-dose budesonide plus terbutaline as needed, although the study was not limited to mild asthma since according to the treatment consumed, it was evident that they had recruited some moderate asthma patients. Despite this poor evidence, and ignoring the clinical histological benefits of chronic inhaled corticosteroids (especially when administered promptly), GINA 2019 recently recommended daily low dose ICS or ICS-ICS as needed as a first option for step 2 patients. For step 1, symptom-driven or as-needed treatment with ICS-LABA is recommended rather than SABA alone (the preferred option until the last GINA update). Finally, the SIENA study showed that 73% of patients with mild asthma do not have an eosinophilic phenotype and that these patients have a similar clinical response to ICS (mometasone) and antimuscarinic drugs (tiotropium), results that challenge the indication of a drug combination that incorporates ICS as a first option. Overall, we believe there is insufficient evidence for the systematic recommendation of as-needed ICS-LABA instead of SABA on request for GINA step 1 or as a replacement for chronic ICS in GINA step 2.
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- Supersaturating drug delivery system of fixed drug combination: sulfamethoxazole and trimethoprim. [Journal Article]Expert Rev Anti Infect Ther 2019; :1-10ER
- CONCLUSIONS: For the first time, a supersaturating drug delivery system was developed to the complementary antibacterial drugs. This ternary formulation is a powerful alternative to improve oral absorption of recognized safety drugs, reducing the dose and consequently the antibiotic resistance emergence.