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.

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.

Voriconazole: A New Triazole Antifungal Agent

2003 ◽  
Vol 37 (3) ◽  
pp. 420-432 ◽  
Author(s):  
Margaret M Pearson ◽  
P David Rogers ◽  
John D Cleary ◽  
Stanley W Chapman
Keyword(s):  
Amphotericin B ◽  
Antifungal Agent ◽  
Fungal Pathogens ◽  
Antimicrobial Agents ◽  
Case Reports ◽  
Empirical Therapy ◽  
Immunocompromised Patients ◽  
In Vitro Susceptibility ◽  
Medline Search

OBJECTIVE: To review the pharmacology, in vitro susceptibility, pharmacokinetics, clinical efficacy, and adverse effects of voriconazole, a triazole antifungal agent. DATA SOURCES: A MEDLINE search, restricted to English language, was conducted from 1990 to June 2002. Supplementary sources included program abstracts from the Interscience Conference on Antimicrobial Agents and Chemotherapy and the Infectious Diseases Society of America from 1996 to 2001 and manufacturer information available through the Food and Drug Administration's Web site. DATA EXTRACTION: All published and unpublished trials and abstracts citing voriconazole were selected. DATA SYNTHESIS: Voriconazole has shown in vitro activity against many yeasts and a variety of mold and dermatophyte isolates. Voriconazole can be administered either orally or parenterally. It exhibits good oral bioavailability, wide tissue distribution including distribution into the central nervous system, and hepatic metabolism. Drug interactions occur through inhibition of the CYP2C9, CYP2C19, and CYP3A4 isoenzymes, resulting in alterations in kinetic parameters of either voriconazole or the interacting agent. Efficacy has been illustrated in open, noncomparative studies of aspergillosis in immunocompromised patients. Human case reports describe successful treatment of rare fungal pathogens. The most commonly reported adverse events include visual disturbances and elevations in liver function tests. CONCLUSIONS: Voriconazole is at least as effective as amphotericin B in the treatment of acute invasive aspergillosis in immunocompromised patients. It has similar efficacy as fluconazole in treatment of esophageal candidiasis. Voriconazole did not achieve statistical non-inferiority to liposomal amphotericin B for empirical therapy in patients with neutropenia and persistent fever, diminishing enthusiasm for use in this indication until additional trials are completed. Based on case reports and in vitro efficacy, voriconazole may prove to be a clinically useful agent in the treatment of other fungal disease.

scholarly journals Antifungal Combinations in Dermatophytes

2021 ◽  
Author(s):  
Lucia Brescini ◽  
Simona Fioriti ◽  
Gianluca Morroni ◽  
Francesco Barchiesi
Keyword(s):  
Antifungal Agent ◽  
Antifungal Agents ◽  
Fungal Infections ◽  
Case Reports ◽  
Antifungal Susceptibility ◽  
Calcineurin Inhibitors ◽  
Clinical Results ◽  
In Vitro Studies ◽  
Superficial Infection

Dermatophytes are the most common cause of fungal infections worldwide, affecting millions of people annually. The emergence of resistance among dermatophytes along with the availability of antifungal susceptibility procedures suitable for testing antifungal agents against this group of fungi make the combinatorial approach particularly interesting to be investigated. Therefore, we reviewed the scientific literature concerning the antifungal combinations in dermatophytes. A literature search on the subject performed in PubMed yielded 68 publications: 37 articles referring to in vitro studies, and 31 articles referring to case reports/clinical studies. In vitro studies involved over 400 clinical isolates of dermatophytes (69% Trichophyton spp., 29% Microsporum spp., and 2% Epidermophyton floccosum). Combinations included two antifungal agents or an antifungal agent plus another chemical compound including plant extracts/essential oils, calcineurin inhibitors, peptides, disinfectant agents and others. In general, drug combinations yielded variable results spanning from synergism to indifference. Antagonism was rarely seen. In over 700 patients with documented dermatophyte infections an antifungal combination approach could be evaluated. The most frequent combination included a systemic antifungal agent administered orally (i.e.: azole [mainly itraconazole], terbinafine or griseofulvin) plus a topical medication (i.e.: azole, terbinafine, ciclopirox, amorolfine) for several weeks. Clinical results indicate that association of antifungal agents is effective, and it might be useful in accelerate the clinical and microbiological healing of a superficial infection. Antifungal combinations in dermatophytes have gained considerable scientific interest over the years and, in consideration of the interesting results available as far, it is desirable to continue the research in this field.

scholarly journals Antifungal Combinations in Dermatophytes

2021 ◽  
Vol 7 (9) ◽  
pp. 727
Author(s):  
Lucia Brescini ◽  
Simona Fioriti ◽  
Gianluca Morroni ◽  
Francesco Barchiesi
Keyword(s):  
Antifungal Agent ◽  
Antifungal Agents ◽  
Fungal Infections ◽  
Case Reports ◽  
Antifungal Susceptibility ◽  
Calcineurin Inhibitors ◽  
Clinical Results ◽  
In Vitro Studies ◽  
Superficial Infection

Dermatophytes are the most common cause of fungal infections worldwide, affecting millions of people annually. The emergence of resistance among dermatophytes along with the availability of antifungal susceptibility procedures suitable for testing antifungal agents against this group of fungi make the combinatorial approach particularly interesting to be investigated. Therefore, we reviewed the scientific literature concerning the antifungal combinations against dermatophytes. A literature search on the subject performed in PubMed yielded 68 publications: 37 articles referring to in vitro studies and 31 articles referring to case reports or clinical studies. In vitro studies involved over 400 clinical isolates of dermatophytes (69% Trichophyton spp., 29% Microsporum spp., and 2% Epidermophyton floccosum). Combinations included two antifungal agents or an antifungal agent plus another chemical compound including plant extracts or essential oils, calcineurin inhibitors, peptides, disinfectant agents, and others. In general, drug combinations yielded variable results spanning from synergism to indifference. Antagonism was rarely seen. In over 700 patients with documented dermatophyte infections, an antifungal combination approach could be evaluated. The most frequent combination included a systemic antifungal agent administered orally (i.e., terbinafine, griseofulvin, or azole—mainly itraconazole) plus a topical medication (i.e., azole, terbinafine, ciclopirox, amorolfine) for several weeks. Clinical results indicate that association of antifungal agents is effective, and it might be useful to accelerate the clinical and microbiological healing of a superficial infection. Antifungal combinations in dermatophytes have gained considerable scientific interest over the years and, in consideration of the interesting results available so far, it is desirable to continue the research in this field.

Potential of Nanoparticles in Combating Candida Infections

2019 ◽  
Vol 16 (5) ◽  
pp. 478-491 ◽  
Author(s):  
Faizan Abul Qais ◽  
Mohd Sajjad Ahmad Khan ◽  
Iqbal Ahmad ◽  
Abdullah Safar Althubiani
Keyword(s):  
Targeted Delivery ◽  
Recent Progress ◽  
Antifungal Agents ◽  
Fungal Infections ◽  
Fold Increase ◽  
Antifungal Drugs ◽  
Low Toxicity ◽  
Candida Infections ◽  
Made In

Aims: The aim of this review is to survey the recent progress made in developing the nanoparticles as antifungal agents especially the nano-based formulations being exploited for the management of Candida infections. Discussion: In the last few decades, there has been many-fold increase in fungal infections including candidiasis due to the increased number of immunocompromised patients worldwide. The efficacy of available antifungal drugs is limited due to its associated toxicity and drug resistance in clinical strains. The recent advancements in nanobiotechnology have opened a new hope for the development of novel formulations with enhanced therapeutic efficacy, improved drug delivery and low toxicity. Conclusion: Metal nanoparticles have shown to possess promising in vitro antifungal activities and could be effectively used for enhanced and targeted delivery of conventionally used drugs. The synergistic interaction between nanoparticles and various antifungal agents have also been reported with enhanced antifungal activity.

Interactions between SSRI's and statins: Clinical relevance versus statistical significance

2017 ◽  
Vol 41 (S1) ◽  
pp. S757-S758 ◽  
Author(s):  
S. Petrykiv ◽  
L. De Jonge ◽  
M. Arts
Keyword(s):  
Drug Interactions ◽  
Clinical Relevance ◽  
Selective Serotonin Reuptake Inhibitors ◽  
Absolute Risk ◽  
Statistical Significance ◽  
Developed Countries ◽  
Lipid Lowering ◽  
Supporting Evidence ◽  
Cytochrome P450 Enzyme

IntroductionDepression and hypercholesterolemia are two of the most commonly treated conditions in the developed countries, while the lipid–lowering agents and antidepressants are among the most widely prescribed drugs in the world. There is a common concern that selective serotonin reuptake inhibitors (SSRIs) can trigger statin adverse effects, especially myopathy. However, the supporting evidence originates from studies in-vitro and big epidemiological studies. Recent pharmacokinetic insights indicate that the magnitude of pharmacokinetic interaction between SSRIs and statins is likely to be below the threshold for clinical significance.Objectives and aimsExplorative study on pharmacokinetic effects of SSRIs on statin drugs.MethodsWe performed a detailed literature review through PubMed, EMBASE and Cochran's Library to assess the clinical relevance of combined SSRIs and statin use. To address pharmacokinetic interactions between two drug groups, we focused on:– cytochrome P450 enzyme metabolism of statins;– CYP enzyme inhibition by SSRIs;– SSRIs–statin drug interactions;– non-CYP pharmacokinetic pathways.ResultsWith regard to pharmacokinetic drug interactions and the risk of statin related myopathy, escitalopram, citalopram, and paroxetine are to be safe in co-therapy with all statins. Rosuvastatin and pravastatin are almost certain to be safe in co-therapy with all SSRIs. Fluoxetine and sertraline are also likely to be safe, even when combined with atorvastatin, simvastatin, and lovastatin.ConclusionThough the absolute risk of concomitant use of SSRIs with statins seems to be negligible, even this risk can be minimized by using lower statin doses and monitoring the patient.Disclosure of interestThe authors have not supplied their declaration of competing interest.

scholarly journals Acylhydrazones as Antifungal Agents Targeting the Synthesis of Fungal Sphingolipids

2018 ◽  
Vol 62 (5) ◽  
Author(s):  
Cristina Lazzarini ◽  
Krupanandan Haranahalli ◽  
Robert Rieger ◽  
Hari Krishna Ananthula ◽  
Pankaj B. Desai ◽  
...  
Keyword(s):  
Mammalian Cells ◽  
Antifungal Agents ◽  
Fungal Infections ◽  
Antifungal Drugs ◽  
Fungal Resistance ◽  
Content Type ◽  
Highly Active ◽  
Pharmacokinetic Properties ◽  
Pass Through

ABSTRACTThe incidence of invasive fungal infections has risen dramatically in recent decades. Current antifungal drugs are either toxic, likely to interact with other drugs, have a narrow spectrum of activity, or induce fungal resistance. Hence, there is a great need for new antifungals, possibly with novel mechanisms of action. Previously our group reported an acylhydrazone called BHBM that targeted the sphingolipid pathway and showed strong antifungal activity against several fungi. In this study, we screened 19 derivatives of BHBM. Three out of 19 derivatives were highly active againstCryptococcus neoformansin vitroand had low toxicity in mammalian cells. In particular, one of them, called D13, had a high selectivity index and showed better activity in an animal model of cryptococcosis, candidiasis, and pulmonary aspergillosis. D13 also displayed suitable pharmacokinetic properties and was able to pass through the blood-brain barrier. These results suggest that acylhydrazones are promising molecules for the research and development of new antifungal agents.

The Contact System

2002 ◽  
Vol 126 (11) ◽  
pp. 1382-1386 ◽  
Author(s):  
Craig S. Kitchens
Keyword(s):  
Antiphospholipid Syndrome ◽  
English Language ◽  
Case Reports ◽  
Data Extraction ◽  
Meta Analysis ◽  
Factor Xii ◽  
Activity Levels ◽  
Medline Search ◽  
Apparent Association

Abstract Objectives.—To review the literature for conditions, diseases, and disorders that affect activity of the contact factors, and further to review the literature for evidence that less than normal activity of any of the contact factors may be associated with thrombophilia. Data Sources.—MEDLINE search for English-language articles published from 1988 to 2001 and pertinent references contained therein, as well as search of references in recent relevant articles and reviews. Study Selection.—Relevant clinical and laboratory information was extracted from selected articles. Meta-analysis was not feasible because of heterogeneity of reports. Data Extraction and Synthesis.—Evidence for association of altered levels of the contact factors and thrombophilia was sought. A wide variety of disorders is associated with decreased activity of the contact factors; chief among these disorders are liver disease, hepatic immaturity of newborns, the antiphospholipid syndrome, and, for factor XII, being of Asian descent. These disorders are more common than homozygous deficiency. The few series and case reports of thrombophilic events in patients homozygous for deficiency of contact factors are not persuasive enough to support causality. The apparent association between levels consistent with heterozygosity (40%–60% of normal) of any of the contact factors (but especially factor XII) in persons with antiphospholipid antibodies appears to be due to falsely decreased in vitro activity levels of these factors, which are normal on antigenic testing. The apparent association with thrombosis is better explained by the antiphospholipid syndrome than by the modest reduction of the levels of contact factors. Conclusions.—Presently, it is not recommended to measure activity of contact factors during routine evaluation of patients who have suffered venous or arterial thromboembolism or acute coronary syndromes.

scholarly journals In Vitro Antimicrobial Activity of the Decontaminant HybenX® Compared to Chlorhexidine and Sodium Hypochlorite against Common Bacterial and Yeast Pathogens

Antibiotics ◽  
2019 ◽  
Vol 8 (4) ◽  
pp. 188 ◽  
Author(s):  
Alberto Antonelli ◽  
Luca Giovannini ◽  
Ilaria Baccani ◽  
Valentina Giuliani ◽  
Riccardo Pace ◽  
...  
Keyword(s):  
Antimicrobial Activity ◽  
Sodium Hypochlorite ◽  
Fungal Pathogens ◽  
Antimicrobial Agents ◽  
Fungal Infections ◽  
Yeast Strains ◽  
Low Concentrations ◽  
Endodontic Infections ◽  
Reference Strains

The recent increase in infections mediated by drug-resistant bacterial and fungal pathogens underlines the urgent need for novel antimicrobial compounds. In this study, the antimicrobial activity (inhibitory and cidal) of HybenX®, a novel dessicating agent, in comparison with commonly used sodium hypochlorite and chlorhexidine, against a collection of bacterial and yeast strains representative of the most common human pathogenic species was evaluated. The minimal inhibitory, bactericidal, and fungicidal concentrations (MIC, MBC, and MFC, respectively) of the three different antimicrobial agents were evaluated by broth microdilution assays, followed by subculturing of suitable dilutions. HybenX® was active against 26 reference strains representative of staphylococci, enterococci, Enterobacterales, Gram-negative nonfermenters, and yeasts, although at higher concentrations than sodium hypochlorite and chlorhexidine. HybenX® MICs were 0.39% for bacteria (with MBCs ranging between 0.39% and 0.78%), and 0.1–0.78% for yeasts (with MFCs ranging between 0.78% and 1.6%). HybenX® exhibited potent inhibitory and cidal activity at low concentrations against several bacterial and yeast pathogens. These findings suggest that HybenX® could be of interest for the treatment of parodontal and endodontic infections and also for bacterial and fungal infections of other mucous membranes and skin as an alternative to sodium hypochlorite and chlorhexidine.

scholarly journals Current and Emerging Azole Antifungal Agents

1999 ◽  
Vol 12 (1) ◽  
pp. 40-79 ◽  
Author(s):  
Daniel J. Sheehan ◽  
Christopher A. Hitchcock ◽  
Carol M. Sibley
Keyword(s):  
Fungal Pathogens ◽  
Antifungal Agents ◽  
Susceptibility Testing ◽  
Fungal Infections ◽  
Mechanisms Of Action ◽  
Current Status ◽  
In Vitro Susceptibility ◽  
Clinical Resistance ◽  
In Vitro Susceptibility Testing

SUMMARY Major developments in research into the azole class of antifungal agents during the 1990s have provided expanded options for the treatment of many opportunistic and endemic fungal infections. Fluconazole and itraconazole have proved to be safer than both amphotericin B and ketoconazole. Despite these advances, serious fungal infections remain difficult to treat, and resistance to the available drugs is emerging. This review describes present and future uses of the currently available azole antifungal agents in the treatment of systemic and superficial fungal infections and provides a brief overview of the current status of in vitro susceptibility testing and the growing problem of clinical resistance to the azoles. Use of the currently available azoles in combination with other antifungal agents with different mechanisms of action is likely to provide enhanced efficacy. Detailed information on some of the second-generation triazoles being developed to provide extended coverage of opportunistic, endemic, and emerging fungal pathogens, as well as those in which resistance to older agents is becoming problematic, is provided.

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