Review on the Clinical Pharmacology of Hydroxychloroquine Sulfate for the Treatment of COVID-19

2020 ◽  
Vol 21 (6) ◽  
pp. 427-435 ◽  
Author(s):  
Cheng Cui ◽  
Siqi Tu ◽  
Valerie Sia Jie En ◽  
Xiaobei Li ◽  
Xueting Yao ◽  
...  
Keyword(s):  
Drug Interactions ◽  
Clinical Efficacy ◽  
Relevant Literature ◽  
The United States ◽  
Efficacy And Safety ◽  
Open Label ◽  
Infected People ◽  
Treatment Regimens ◽  
Therapeutic Drugs

Background: As the number of severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) infected people is greatly increasing worldwide, the international medical situation becomes very serious. Potential therapeutic drugs, vaccine and stem cell replacement methods are emerging, so it is urgent to find specific therapeutic drugs and the best treatment regimens. After the publications on hydroxychloroquine (HCQ) with anti- SARS-COV-2 activity in vitro, a small, non-randomized, open-label clinical trial showed that HCQ treatment was significantly associated with reduced viral load in patients with coronavirus disease-19 (COVID-19). Meanwhile, a large prophylaxis study of HCQ sulfate for COVID-19 has been initiated in the United States. HCQ offered a promising efficacy in the treatment of COVID-19, but the optimal administration is still being explored. Methods: We used the keyword "hydroxychloroquine" to conduct a literature search in PubMed to collect relevant literature on the mechanism of action of HCQ, its clinical efficacy and safety, pharmacokinetic characteristics, precautions for clinical use and drug interactions to extract and organize information. Results: This paper reviews the mechanism, clinical efficacy and safety, pharmacokinetic characteristics, exposureresponse relationship and precautions and drug interactions of HCQ, and summarizes dosage recommendations for HCQ sulfate. Conclusion: It has been proved that HCQ, which has an established safety profile, is effective against SARS-CoV-2 with sufficient pre-clinical rationale and evidence. Data from high-quality clinical trials are urgently needed worldwide.

scholarly journals Efficacy, Safety, and Tolerability of Gepotidacin (GSK2140944) in the Treatment of Patients with Suspected or Confirmed Gram-Positive Acute Bacterial Skin and Skin Structure Infections

2017 ◽  
Vol 61 (6) ◽  
Author(s):  
William O'Riordan ◽  
Courtney Tiffany ◽  
Nicole Scangarella-Oman ◽  
Caroline Perry ◽  
Mohammad Hossain ◽  
...  
Keyword(s):  
Adverse Events ◽  
Clinical Utility ◽  
The United States ◽  
Phase 2 ◽  
Efficacy And Safety ◽  
Open Label ◽  
Gram Positive ◽  
Double Blind ◽  
Skin Structure

ABSTRACT Gepotidacin is a novel, first-in-class, triazaacenaphthylene antibacterial agent which has in vitro activity against causative pathogens of acute bacterial skin and skin structure infections (ABSSSIs). This phase 2, randomized, 2-part, multicenter, dose-ranging, response-adaptive study with optional intravenous-oral switch evaluated the efficacy and safety of gepotidacin for the treatment of Gram-positive ABSSSIs in 122 adult patients in the United States. The study had a double-blind phase (part 1; intravenous [750 mg or 1,000 mg every 12 h {q12h}]) and an open-label phase (part 2; intravenous [750 mg q12h, 1,000 mg q12h, or 1,000 q8h]). The primary endpoint was a composite of efficacy and safety which consisted of the early cure rate and the withdrawal rate due to drug-related adverse events and utilized a clinical utility index for dose selection. At the early efficacy visit (48 to 72 h after the first dose), the 750-mg q12h and 1,000-mg q8h groups met prespecified success criteria for clinical utility in terms of efficacy and safety; however, the 1,000-mg q12h group did not meet these criteria due to observed lower efficacy rates. The most frequently reported adverse events were nausea (20%) and diarrhea (13%). These encouraging phase 2 results demonstrate the potential for gepotidacin to meet the medical need for novel antibacterial agents to treat ABSSSIs due to drug-resistant pathogens through a unique mechanism of action. (This study has been registered at ClinicalTrials.gov under registration no. NCT02045797.)

Oral Terbinafine: A New Antifungal Agent

1997 ◽  
Vol 31 (4) ◽  
pp. 445-456 ◽  
Author(s):  
Susan M Abdel-Rahman ◽  
Milap C Nahata
Keyword(s):  
Adverse Effects ◽  
Drug Interactions ◽  
Fungal Infections ◽  
Case Reports ◽  
Current Standard ◽  
Open Label ◽  
Double Blind ◽  
Pathogenic Yeast

Objective To review the pharmacology, pharmacokinetics, efficacy, adverse effects, drug interactions, and dosage guidelines of terbinafine. Available comparative data of terbinafine and other antimycotic agents are described for understanding the potential role of terbinafine in patient care. Data Sources A MEDLINE search restricted to English language during 1966–1996 and extensive review of journals was conducted to prepare this article. MeSH headings included allylamines, terbinafine, SF 86–327, dermatophytosis, dermatomycosis. Data Extraction The data on pharmacokinetics, adverse effects, and drug interactions were obtained from open-label and controlled studies and case reports. Controlled single- or double-blind studies were evaluated to describe the efficacy of terbinafine in the treatment of various fungal infections. Data Synthesis Terbinafine is the first oral antimycotic in the allylamines class: a fungicidal agent that inhibits ergosterol synthesis at the stage of squalene epoxidation. Terbinafine demonstrates excellent in vitro activity against the majority of dermatophyte species including Trichophyton rubrum, Trichophyton mentagrophytes, and Epidermophyton floccosum; less activity is seen against Dematiaceae and the filamentous fungi. It is least active against the pathogenic yeast and this correlates with the relatively poor efficacy against these organisms in vivo. High concentrations of terbinafine are achieved in keratinous tissues, the site of superficial infections, and these concentrations are maintained for up to 3 months. The clinical efficacy of terbinafine against a number of dermatophyte infections exceeds that of the current standard of therapy, griseofulvin. The efficacy of terbinafine may be as good or better than that of the azole antifungals. Additional studies are required to confirm these observations. Terbinafine demonstrates a good safety profile, and relatively few drug interactions have been identified. Conclusions Terbinafine is more effective than the gold standard, griseofulvin, in the treatment of tinea pedis and tinea unguinum, with considerably shorter treatment duration in the latter. It has been proven as effective as griseofulvin in the treatment of tinea capitis, tinea corporis, and tinea cruris. Terbinafine does not appear to offer any advantage in the treatment of nondermatophyte infections; its utility in the treatment of systemic infections has yet to be established. Depending on individual institutional costs, terbinafine may be a front-line drug for some superficial infections responding poorly to the current standard of therapy.

scholarly journals A randomized, multicentre, open-label phase II proof-of-concept trial investigating the clinical efficacy and safety of the addition of convalescent plasma to the standard of care in patients hospitalized with COVID-19: the Donated Antibodies Working against nCoV (DAWn-Plasma) trial

Trials ◽  
2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Timothy Devos ◽  
Tatjana Geukens ◽  
Alexander Schauwvlieghe ◽  
Kevin K. Ariën ◽  
Cyril Barbezange ◽  
...  
Keyword(s):  
Treatment Group ◽  
Phase Ii ◽  
Clinical Efficacy ◽  
Active Treatment ◽  
Standard Of Care ◽  
Active Treatment Group ◽  
Proof Of Concept ◽  
Efficacy And Safety ◽  
Open Label ◽  
Open Label Phase

Abstract Background The COVID-19 pandemic has imposed an enormous burden on health care systems around the world. In the past, the administration of convalescent plasma of patients having recovered from SARS and severe influenza to patients actively having the disease showed promising effects on mortality and appeared safe. Whether or not this also holds true for the novel SARS-CoV-2 virus is currently unknown. Methods DAWn-Plasma is a multicentre nation-wide, randomized, open-label, phase II proof-of-concept clinical trial, evaluating the clinical efficacy and safety of the addition of convalescent plasma to the standard of care in patients hospitalized with COVID-19 in Belgium. Patients hospitalized with a confirmed diagnosis of COVID-19 are eligible when they are symptomatic (i.e. clinical or radiological signs) and have been diagnosed with COVID-19 in the 72 h before study inclusion through a PCR (nasal/nasopharyngeal swab or bronchoalveolar lavage) or a chest-CT scan showing features compatible with COVID-19 in the absence of an alternative diagnosis. Patients are randomized in a 2:1 ratio to either standard of care and convalescent plasma (active treatment group) or standard of care only. The active treatment group receives 2 units of 200 to 250 mL of convalescent plasma within 12 h after randomization, with a second administration of 2 units 24 to 36 h after ending the first administration. The trial aims to include 483 patients and will recruit from 25 centres across Belgium. The primary endpoint is the proportion of patients that require mechanical ventilation or have died at day 15. The main secondary endpoints are clinical status on day 15 and day 30 after randomization, as defined by the WHO Progression 10-point ordinal scale, and safety of the administration of convalescent plasma. Discussion This trial will either provide support or discourage the use of convalescent plasma as an early intervention for the treatment of hospitalized patients with COVID-19 infection. Trial registration ClinicalTrials.govNCT04429854. Registered on 12 June 2020 - Retrospectively registered.

scholarly journals Clinical Efficacy and Safety of Injection of Stromal Vascular Fraction Derived from Autologous Adipose Tissues in Systemic Sclerosis Patients with Hand Disability: A Proof-Of-Concept Trial

2020 ◽  
Vol 9 (9) ◽  
pp. 3023
Author(s):  
Youngjae Park ◽  
Yoon Jae Lee ◽  
Jung Hee Koh ◽  
Jennifer Lee ◽  
Hong-Ki Min ◽  
...  
Keyword(s):  
Systemic Sclerosis ◽  
Clinical Efficacy ◽  
Stromal Vascular Fraction ◽  
Skin Fibrosis ◽  
Therapeutic Modality ◽  
Efficacy And Safety ◽  
Open Label ◽  
Adipose Tissues ◽  
Hand Disability

Background: Stromal vascular fraction (SVF) has recently emerged as a potential therapeutic modality, due to its multipotent cellular components in tissue regeneration. Systemic sclerosis (SSc) is a progressive autoimmune disease that results in hand disability by skin fibrosis and microangiopathies. We performed an open-label study to investigate the efficacy and safety of SVF injection in SSc patients (Clinical Trial number: NCT03060551). Methods: We gathered 20 SSc patients with hand disability, planning for a 24-week follow-up period. SVF was extracted from autologous adipose tissues, processed by the closed system kit, and injected into each finger of SSc patients. We observed various efficacy and safety profiles at each follow-up visit. Results: Among the 20 initially enrolled patients, eighteen received SVF injection, and were completely followed-up for the whole study period. Patients received 3.61 × 106 mesenchymal stem cells into each finger on average. Skin fibrosis, hand edema, and quality of life were significantly improved, and 31.6% of active ulcers were healed at 24 weeks after injections. Semiquantitative results of nailfold capillary microscopy were ameliorated. There was no single serious adverse event related to the procedure. Conclusions: Injection of SVF derived from autologous adipose tissues is tolerable, and shows clinical efficacy in SSc patients.

scholarly journals The efficacy and safety of enzalutamide with trastuzumab in patients with HER2+ and androgen receptor-positive metastatic or locally advanced breast cancer

2021 ◽  
Author(s):  
Andrew Wardley ◽  
Javier Cortes ◽  
Louise Provencher ◽  
Kathy Miller ◽  
A. Jo Chien ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Androgen Receptor ◽  
Locally Advanced Breast Cancer ◽  
Locally Advanced ◽  
Eastern Cooperative Oncology Group ◽  
Malignant Neoplasm ◽  
Efficacy And Safety ◽  
Open Label ◽  
Group Status

Abstract Purpose Androgen receptor (AR) expression occurs in up to 86% of human epidermal growth factor receptor 2-positive (HER2+) breast cancers. In vitro, AR inhibitors enhance antitumor activity of trastuzumab, an anti-HER2 antibody, in trastuzumab-resistant HER2+ cell lines. This open-label, single-arm, phase II study evaluated the efficacy and safety of enzalutamide, an AR-signaling inhibitor, in patients with advanced HER2+ AR+ breast cancer previously treated with trastuzumab. Methods Eligible patients had measurable or non-measurable evaluable disease per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1, Eastern Cooperative Oncology Group status ≤ 1, no history of brain metastases, and previously received ≥ 1 anti-HER2 regimen for advanced disease. Patients received 160 mg oral enzalutamide daily and 6 mg/kg intravenous trastuzumab every 21 days until disease progression or unacceptable toxicity. Primary end point was clinical benefit rate at 24 weeks (CBR24); secondary end points included progression-free survival (PFS) and safety. Results Overall, 103 women were enrolled [median age 60 years (range 34–83)]; 62% had received ≥ 3 lines of prior anti-HER2 therapy. CBR24, comprising patients with confirmed partial responses (5%) and durable stable disease at 24 weeks (19%), was 24% in the efficacy evaluable set (n = 89). CBR24 did not seem related to AR-expression levels or hormone receptor status. Median PFS was 3.4 months (95% confidence interval 2.0–3.8). Overall, 97 (94%) patients experienced treatment-emergent adverse events (TEAEs), with fatigue most common (34%). Dyspnea (4%) and malignant neoplasm progression (3%) were the only TEAEs grade ≥ 3 reported in ≥ 3 patients. 22 patients (21%) reported serious TEAEs. Four patients (4%) experienced fatal, non-drug-related TEAEs. Conclusions Enzalutamide plus trastuzumab was well tolerated, and a subset of patients in this heavily pretreated population had durable disease control. Determination of biomarkers is needed to identify patients most likely to benefit from this combination. ClinicalTrials.gov number NCT02091960

Clinical Efficacy and Safety of “Vasavaleha” in the Management of Stable Chronic Bronchitis: A Prospective Open Label Multicenter Study

2017 ◽  
Vol 1 (4) ◽  
pp. 231-237
Author(s):  
Varanasi Subhose ◽  
Shweta Chaudhary ◽  
G Babu ◽  
Milind Suryavanshi ◽  
Hari ML Meena ◽  
...  
Keyword(s):  
Chronic Bronchitis ◽  
Clinical Efficacy ◽  
Multicenter Study ◽  
Efficacy And Safety ◽  
Open Label

Clinical Efficacy and Safety of Brahma Rasayana in Apparently Healthy Elderly Persons: A Prospective Multicenter Open-label Study

2018 ◽  
Vol 2 (4) ◽  
pp. 217-224
Author(s):  
Pradeep Dua ◽  
Rakesh Rana ◽  
Richa Singhal ◽  
Bhagwan Sahai Sharma ◽  
G Venkateswarlu ◽  
...  
Keyword(s):  
Clinical Efficacy ◽  
Elderly Persons ◽  
Efficacy And Safety ◽  
Open Label ◽  
Open Label Study ◽  
Label Study ◽  
Healthy Elderly ◽  
Apparently Healthy

Oxymorphone and oxymorphone extended release: A pharmacotherapeutic review

2018 ◽  
Vol 4 (3) ◽  
pp. 131 ◽  
Author(s):  
Paul Alexander Sloan, MD ◽  
Robert L. Barkin, PharmD, MBA
Keyword(s):  
Chronic Pain ◽  
Extended Release ◽  
Analgesic Efficacy ◽  
Opioid Analgesics ◽  
Immediate Release ◽  
The United States ◽  
Efficacy And Safety ◽  
Open Label ◽  
Opioid Agonist ◽  
Noncancer Pain

The treatment of chronic pain remains an enormous challenge in the United States. Opioid analgesics are an important component of pharmacotherapy for chronic pain and have proven efficacy in the management of cancer and noncancer chronic pain. The newest addition to oral opioid pharmacotherapy is oral oxymorphone, a semisynthetic opioid agonist that is now available in oral immediate-release (IR) and extended-release (ER) formulations. This review discusses the pharmacology, pharmacokinetics, pharmacodynamics, pharmacotherapeutics, and clinical use of oral oxymorphone IR and ER formulations for the management of moderate to severe pain for different types of patients in a variety of settings. Two published studies evaluated the efficacy and safety of oxymorphone IR in patients with moderate to severe postoperative pain and demonstrated that it provides rapid and effective analgesia and is generally well tolerated. Six published randomized controlled trials and three published open-label studies evaluated the efficacy and safety of oxymorphone ER for chronic cancer or noncancer pain. These trials found analgesic efficacy and tolerability comparable to that provided by morphine controlled release (CR) or oxycodone CR; treatment effects with oxymorphone ER were durable for treatment periods of 12 weeks at the same dose or up to 1 year with little dose escalation. Titrated doses of oxymorphone ER were effective and generally well tolerated in both opioid-experienced and opioid-naïve patients. Aspects of oxymorphone metabolism and limited protein binding may simplify treatment in certain populations.

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