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.

Update on Drug Interactions with Azole Antifungal Agents

1998 ◽  
Vol 32 (9) ◽  
pp. 915-928 ◽  
Author(s):  
Ben M Lomaestro ◽  
Michelle Ann Piatek
Keyword(s):  
Drug Interactions ◽  
Clinical Relevance ◽  
Antimicrobial Agents ◽  
Antifungal Agents ◽  
Fungal Infections ◽  
Case Reports ◽  
Improve Patient Care ◽  
Double Blind ◽  
Medline Search

OBJECTIVE: T o review and update the incidence, mechanism, and clinical relevance of drug interactions with itraconazole, ketoconazole, and fluconazole. DATA SOURCES: Literature was identified by MEDLINE search (from January 1990 to May 1997) using the name of each antifungal and the term “interaction” as MeSH headings. Abstracts were identified by literature citation and by review of Interscience Conference on Antimicrobial Agents and Chemotherapy from 1995 to 1996. STUDY SELECTION: Randomized, controlled, double-blind studies were emphasized; however, uncontrolled studies and case reports were also included. In vitro data were selected from literature review and citations. DATA EXTRACTION: Data were evaluated with respect to study design, clinical relevance, magnitude of interaction, and recommendations provided. DATA SYNTHESIS: The incidence of fungal infections and consequent azole antifungal usage continues to increase. By virtue of their antifungal mechanism (i.e., inhibition of cytochrome P450 fungal enzyme systems), azoles have been investigated and implicated in several drug interactions. The magnitude of interactions can vary from trivial to potentially fatal, and also vary with specific azole and interactant. CONCLUSIONS: The azole antifungal agents represent a commonly used class of agents with a broad range of potential interactions. Recent data have increased our understanding of drug-drug interactions with azoles. Pharmacists are in a unique position to identify these interactions and to intervene to decrease their morbidity and improve patient care.

Rifabutin: A Review with Emphasis on its Role in the Prevention of Disseminated Mycobacterium Avium Complex Infection

1994 ◽  
Vol 28 (11) ◽  
pp. 1250-1254 ◽  
Author(s):  
Daniel S. Maddix ◽  
Kimberly B. Tallian ◽  
Paul S. Mead
Keyword(s):  
Clinical Trials ◽  
Adverse Effects ◽  
Mycobacterium Avium ◽  
Mycobacterium Avium Complex ◽  
Aids Patients ◽  
Double Blind ◽  
Medline Search ◽  
Cd4 Lymphocyte

OBJECTIVE: To discuss the mechanism of action, in vitro and in vivo activity, pharmacokinetics, clinical trials, adverse effects, drug interactions, and dosage guidelines of rifabutin. DATA SOURCES: Pertinent literature published between 1982 and 1993 was identified via a MEDLINE search. Published proceedings of selected conferences were also reviewed. STUDY SELECTION: Selected basic science, microbiologic, and pharmacokinetic articles were evaluated. Because only limited data regarding rifabutin were available in the literature, all clinical trials involving the use of rifabutin in the prevention of Mycobacterium avium complex (MAC) infection in AIDS patients were reviewed. DATA SYNTHESIS: Rifabutin is a rifamycin derivative that was approved recently for the prevention of disseminated MAC disease in patients with advanced HIV infection. The drug has in vitro and in vivo activity against gram-positive bacteria, gram-negative bacteria, and mycobacteria. Two prospective, randomized, double-blind, placebo-controlled, multicenter trials demonstrated that rifabutin decreased the progression to MAC bacteremia in AIDS patients by about 50 percent. Adverse effects that resulted in the discontinuation of rifabutin prophylaxis occurred in 16 percent of patients. Rifabutin induces hepatic enzymes to a lesser extent than does rifampin, but dosage adjustment of drugs that are known to interact with rifampin may be required. CONCLUSIONS: Rifabutin is the only drug shown to be effective in the prevention of MAC bacteremia in AIDS patients; therefore, it should be made available as a formulary agent. It may be reasonable to delay initiation of rifabutin prophylaxis until CD4 lymphocyte counts are less than 75–50/mm3.

scholarly journals COVID-19 Tedavisinde Favipiravir Kullanımı

2021 ◽  
Vol 26 (1) ◽  
pp. 1-11
Author(s):  
Emre Kara ◽  
Ahmet Çağkan İnkaya ◽  
Kutay Demirkan ◽  
Serhat Ünal
Keyword(s):  
Adverse Effects ◽  
Drug Interactions ◽  
Literature Search ◽  
Case Reports ◽  
Treatment Options ◽  
Controlled Trials ◽  
Randomized Controlled ◽  
The World

There are treatment options with partially shown efficacy against SARS-CoV-2. A drug with proven effect on survival has not yet been developed for the new coronavirus disease (COVID-19) defined in December 2019. Many chemicals that are being used or developed for different indications have been used for COVID-19 treatment, based on their effects observed in in vitro studies. Favipiravir, one of these drugs, was first used in Wuhan, the starting center of the pandemic. Since the spread of the infection to the world, it has been used in our country as well as countries such as Italy, Japan, Russia, Ukraine, Uzbekistan, Moldova and Kazakhstan, Bangladesh, Egypt, India. There are few studies conducted and published to evaluate the effectiveness of favipiravir, but many studies are ongoing. In this review, it was aimed to review and evaluate the studies and case reports reporting the efficacy of favipiravir in the treatment of COVID-19. With the literature search, 223 results were reached, 210 articles were fully accessed, and a total of 34 articles were included in the analysis. In the scope of the review, under the title of pharmacology of favipiravir, adverse effects and drug interactions in addition to pharmacokinetic and pharmacodynamic properties are mentioned. Favipiravir is one of the options for the treatment of COVID-19 patients, but randomized, controlled trials involving much more patients and longer follow-up periods need to be planned and the results of ongoing trials evaluated.

Abstract 229: Correlation of in vitro Studies and Human Drug Interaction Studies with Gemcabene

2016 ◽  
Vol 36 (suppl_1) ◽  
Author(s):  
Margaret McShane ◽  
Louis Radulovic ◽  
Charles L Bisgaier
Keyword(s):  
Drug Interaction ◽  
Drug Interactions ◽  
Adverse Drug Reactions ◽  
Multiple Dose ◽  
Drug Reactions ◽  
Open Label ◽  
Transport Pathways ◽  
Dose Study

Background: Gemcabene is a novel lipid-regulating compound being developed as an adjunct to diet and statin therapy for dyslipidemia treatment. Patients with dyslipidemia typically take many medications often including statins and it is essential to understand potential risk of drug-drug interactions (DDI) to minimize the risk of adverse drug reactions. In the best circumstances, drugs entering the market will provide metabolic or transport pathways that do not interfere with commonly co-administered drugs. The current studies provide the analysis of potential drug interactions with gemcabene both in vitro and in vivo . Methods: Caco-2 cells were used to assess the potential P-gp substrate and inhibitor interaction and the major drug-metabolizing CYP450 isozymes and FMO-3 were used to assess the potential CYP450 and FM0-3 metabolism interaction. The results from the in vitro P-gp and CYP450 studies was correlated with the results of three DDI clinical studies with digoxin, atorvastatin and simvastatin. Results: In an open-label, multiple-dose study in 12 healthy subjects, gemcabene (900 mg) did not significantly affect the exposure (Cmax and AUC 0-24 ) of digoxin (0.25 mg). Specifically, the 90% confidence interval for digoxin AUC (0-24) ratios were within the 80% to 125% range, thus confirming the in vitro results of no DDI with a P-gp substrate. In two open-label, multiple-dose studies in healthy volunteers, gemcabene (900 mg) did not significantly affect the exposure (Cmax and AUC 0-24 ) of atorvastatin (80 mg) or simvastatin (80 mg) thus confirming the in vitro results of no DDI with CYP450 (see Figure below). Conclusion: These results suggest gemcabene is unlikely to elicit a metabolic (i.e., CYP450 or FMO3) or P-gp-mediated drug interaction. Gemcabene (900 mg) was well-tolerated in combination with highest dose of atorvastatin and simvastatin. Clinical Implications: Understanding potential for drug interactions minimizes the risk of adverse drug reactions.

Atovaquone: A Review with Emphasis on its Role in the Treatment of Pneumocystis Carinii Pneumonia

1994 ◽  
Vol 10 (4) ◽  
pp. 151-155
Author(s):  
Daniel S. Maddix
Keyword(s):  
Clinical Trials ◽  
Adverse Effects ◽  
Mechanism Of Action ◽  
Pneumocystis Carinii Pneumonia ◽  
Pneumocystis Carinii ◽  
Plasmodium Species ◽  
Double Blind ◽  
Medline Search

Objective: To discuss the mechanism of action, in vitro and in vivo activity, pharmacokinetics, clinical trials, adverse effects, drug interactions, and dosage guidelines of atovaquone. Data Sources: Pertinent literature published since 1988 was identified via a MEDLINE search. Published proceedings of selected conferences were also used. Study Selection: All basic science, microbiologic, and pharmacokinetic articles were evaluated. Since only limited data regarding atovaquone are available in the literature, all clinical trials involving the use of atovaquone in the treatment of Pneumocystis carinii pneumonia were reviewed. Data Synthesis: Atovaquone is an antiprotozoal agent that was recently approved for the treatment of mild to moderate P. carinii pneumonia (PCP) in patients who are intolerant of trimethoprim/sulfamethoxazole (TMP/SMX). The exact mechanism of action of atovaquone against P. carinii has not been determined. The drug has in vitro and in vivo activity against P. carinii, Toxoplasma gondii, and Plasmodium species. The bioavailability of oral atovaquone is highly variable. The drug must be administered with food to enhance absorption. In a double-blind comparative trial in AIDS patients with mild to moderate PCP, those who were treated with atovaquone had a significantly higher mortality rate than those treated with TMP/SMX. More patients who received TMP/SMX experienced adverse effects that resulted in discontinuation of therapy. Conclusions: Because of concerns of increased mortality in atovaquone recipients, the drug should be reserved for the treatment of mild to moderate PCP in patients who are unable to tolerate TMP/SMX and trimethoprim-dapsone.

scholarly journals Amphotericin B, the Wonder of Today’s Pharmacology Science: Persisting Usage for More Than Seven Decades

2020 ◽  
Author(s):  
Falah Hasan Obayes AL-Khikani
Keyword(s):  
Adverse Effects ◽  
Fungal Infection ◽  
Amphotericin B ◽  
Antimicrobial Agents ◽  
Fungal Infections ◽  
Wide Spectrum ◽  
Antifungal Drugs ◽  
Systemic Fungal Infection

Background: Despite several available topical and systemic antifungal drugs for the treatment of fungal infections, Amphotericin B (AmB) is still one of the most common first-line choices in treating systemic fungal infection for more than seven decades after its discovery.  Objectives: Amphotericin B which belongs to the polyene group has a wide spectrum of in vitro and in vivo antifungal activity. Its mechanism of antifungal action is characterized by creating a pore in the fungal plasma membrane leading to cell death. Methods: In addition to the old formula of deoxycholate-Amphotericin B (D-AmB), three lipid formulas have been developed to reduce the adverse effects of conventional AmB (D-AmB) in the human body and increase its therapeutic efficacy. All of the known available formulas of AmB are administrated via intravenous injection to treat severe systemic fungal infections, while the development of the topical formula of AmB is still under preliminary research. Numerous pharmaceutical formulas of systemic and topical applications with clinical uses of AmB in just humans, not in vitro or animals model, against various fungal infections are discussed in this review. Topical AmB formulas are a promising way to develop effective management and to reduce the adverse effects of intravenous formulas of AmB without laboratory monitoring. Results: The wonderful pharmacological properties of AmB with its prolonged use for about seven decades may help researchers to apply its unique features on other various antimicrobial agents by more understanding about the AmB mechanisms of actions. Conclusion: Amphotericin B is widely used intravenously for the treatment of systemic fungal infection, while the topical formula of AmB is still under experimental study. 

Olanzapine: A New Antipsychotic Agent with Efficacy in the Management of Schizophrenia

1997 ◽  
Vol 31 (11) ◽  
pp. 1325-1334 ◽  
Author(s):  
Judith C Kando ◽  
John C Shepski ◽  
Winston Satterlee ◽  
Jayendra K Patel ◽  
Stephen G Reams ◽  
...  
Keyword(s):  
Adverse Effects ◽  
Negative Symptoms ◽  
Antipsychotic Agent ◽  
Current Data ◽  
Phase Iii ◽  
Typical Antipsychotic ◽  
Open Label ◽  
Double Blind ◽  
Advantages And Disadvantages

OBJECTIVE: To review the pharmacology, pharmacokinetics, efficacy data, and adverse effects of olanzapine as a treatment for schizophrenia and to determine the advantages and disadvantages of this atypical antipsychotic agent compared with currently marketed agents. DATA SOURCES: A MEDLINE computer literature search was conducted to retrieve all English-language studies and review articles involving olanzapine published as of October 1, 1996. The manufacturer of the drug, Eli Lilly and Company, provided the clinical investigator's brochure and abstracts of unpublished Phase III clinical trials. STUDY SELECTION: Animal studies evaluating the pharmacology of olanzapine were evaluated, as were all open-label and double-blind studies involving the evaluation of olanzapine for the treatment of patients with schizophrenia. DATA EXTRACTION: All available clinical studies were reviewed and the interpretation of data for each study was influenced by the size of the study sample, the nature of the inclusion and exclusion criteria, and the data analysis techniques used. DATA SYNTHESIS: Olanzapine is a thienobenzodiazepine analog with an in vitro receptor affinity profile similar to that of clozapine. Olanzapine exhibits linear kinetics over the dosage range studied and is extensively metabolized in humans. Clinical evaluations to date have shown olanzapine to be at least as efficacious as typical antipsychotic agents in the treatment of the acute phase of schizophrenia. The drug was well tolerated, with significantly fewer extrapyramidal adverse effects than haloperidol. Current data suggest that olanzapine may be more effective than haloperidol for the treatment of negative symptoms; moreover, preliminary data suggest that fewer relapses occur over the course of treatment in patients treated with olanzapine compared with those taking haloperidol. CONCLUSIONS: The exact place of olanzapine in the therapy of psychotic patients remains unclear, as more data are needed to evaluate the long-term efficacy of this agent, its impact on negative symptoms, and its potential use in patients resistant to the standard agents. Despite limitations in the current database, olanzapine is a promising treatment option for patients with schizophrenia.

scholarly journals Retinoids in Fungal Infections: From Bench to Bedside

2021 ◽  
Vol 14 (10) ◽  
pp. 962
Author(s):  
Terenzio Cosio ◽  
Roberta Gaziano ◽  
Guendalina Zuccari ◽  
Gaetana Costanza ◽  
Sandro Grelli ◽  
...  
Keyword(s):  
Fungal Pathogens ◽  
English Language ◽  
Fungal Infections ◽  
In Vivo Studies ◽  
Current Evidence ◽  
Candida Spp ◽  
Double Blind ◽  
Wide Range

Retinoids—a class of chemical compounds derived from vitamin A or chemically related to it—are used especially in dermatology, oncohematology and infectious diseases. It has been shown that retinoids—from their first generation—exert a potent antimicrobial activity against a wide range of pathogens, including bacteria, fungi and viruses. In this review, we summarize current evidence on retinoids’ efficacy as antifungal agents. Studies were identified by searching electronic databases (MEDLINE, EMBASE, PubMed, Cochrane, Trials.gov) and reference lists of respective articles from 1946 to today. Only articles published in the English language were included. A total of thirty-nine articles were found according to the criteria. In this regard, to date, In vitro and In vivo studies have demonstrated the efficacy of retinoids against a broad-spectrum of human opportunistic fungal pathogens, including yeast fungi that normally colonize the skin and mucosal surfaces of humans such as Candida spp., Rhodotorula mucilaginosa and Malassezia furfur, as well as environmental moulds such as Aspergillus spp., Fonsecae monofora and many species of dermatophytes associated with fungal infections both in humans and animals. Notwithstanding a lack of double-blind clinical trials, the efficacy, tolerability and safety profile of retinoids have been demonstrated against localized and systemic fungal infections.

scholarly journals Posaconazole as Salvage Therapy for Zygomycosis

2006 ◽  
Vol 50 (1) ◽  
pp. 126-133 ◽  
Author(s):  
R. N. Greenberg ◽  
K. Mullane ◽  
J.-A. H. van Burik ◽  
I. Raad ◽  
M. J. Abzug ◽  
...  
Keyword(s):  
Salvage Therapy ◽  
Standard Therapy ◽  
Fungal Infections ◽  
Oral Solution ◽  
Open Label ◽  
Underlying Illness ◽  
Affected Tissue ◽  
And Control

ABSTRACT Zygomycosis, an infection that is associated with significant morbidity and mortality, is becoming common in immunocompromised patients. Posaconazole is a new extended-spectrum azole antifungal that has demonstrated in vitro and in vivo activity against zygomycetes. This report provides the results from the first 24 patients with active zygomycosis who were enrolled in two open-label, nonrandomized, multicentered compassionate trials that evaluated oral posaconazole as salvage therapy for invasive fungal infections. Posaconazole was usually given as an oral suspension of 200 mg four times a day or 400 mg twice a day. Eleven (46%) of the infections were rhinocerebral. Duration of posaconazole therapy ranged from 8 to 1,004 days (mean, 292 days; median, 182 days). Rates of successful treatment (complete cure and partial response) were 79% in 19 subjects with zygomycosis refractory to standard therapy and 80% in 5 subjects with intolerance to standard therapy. Overall, 19 of 24 subjects (79%) survived infection. Survival was also associated with surgical resection of affected tissue and stabilization or improvement of the subjects' underlying illnesses. Failures either had worsening of underlying illnesses or requested all therapy withdrawn; none of the failures received more than 31 days of posaconazole. Posaconazole oral solution was well tolerated and was discontinued in only one subject due to a drug rash. Posaconazole appears promising as an oral therapy for zygomycosis in patients who receive required surgery and control their underlying illness.

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.

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