Safety review of the oral antifungal agents used to treat superficial mycoses.
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Administration, Oral↗
Biomedical subjects
N H Shear
Publications and source records attributed to N H Shear.
Age- and gender-related use of low-dose drug therapy: the need to manufacture low-dose therapy and evaluate the minimum effective dose.
OBJECTIVES: Low-dose drug therapy is promoted as a way to maximize benefit and minimize adverse drug effects when prescribing for older adults. This population-based study evaluates the age and sex-related use of two common therapies: thiazide diuretics, where evidence supports the use of low-dose therapy, and beta-blockers, where trials have not evaluated the minimum effective dose. DESIGN: Using linked administrative databases we identified all of the 120,613 persons dispensed a thiazide diuretic therapy and 12,908 myocardial infarction survivors dispensed beta-blocker therapy in Canada's largest province. We used logistic regression models to study the association of age and sex with dispensing of low-dose thiazide diuretic and beta-blocker therapy at doses lower than evaluated in trials. RESULTS: Of 120,613 older people dispensed a thiazide diuretic, 32,372 (26.8%) were dispensed a low dose. Patients 85 years of age or older, relative to the youngest group, were 30% more likely to be dispensed low-dose therapy (OR=1.31; 95% CI, 1.27 to 1.36; P < .001). Women were 8% more likely than men to be dispensed a low-dose thiazide diuretic (OR=1.08; 95% CI, 1.05 to 1.11; P < .001). Of 10,991 myocardial infarction survivors dispensed atenolol, metoprolol, propranolol, or timolol, 9458 (86.1%) were dispensed a lower-than-evaluated dose. Patients 85 years of age or older, relative to those in the youngest group, were more than twice as likely to be dispensed a lower-than-evaluated beta-blocker therapy dose (OR=2.28; 95% CI, 1.74 to 3.04; P < .001). No difference was noted in the use of beta-blocker therapy dose by sex (OR=1.0; 95% CI, .89 to 1.15; P = .95). CONCLUSIONS: Low-dose thiazide diuretic therapy prescribed widely to older people, particularly those of advanced age and women. The vast majority of myocardial infarction survivors were dispensed beta-blocker therapy at lower-than-evaluated doses. These findings highlight the need to manufacture low-dose thiazide diuretic therapy and to evaluate the minimum effective dose of beta-blocker therapy.
Adrenergic beta-Antagonists↗
Needs survey of Canadian rosacea patients.
BACKGROUND: In 1995, a Rosacea Awareness Program (RAP) was initiated in Canada to make available educational resources for physicians and rosacea patients. Material is in French or English, and is accessible though physician offices and by toll-free telephone. Information was communicated to the public via noncommercial, editorial media. The RAP created a database of rosacea patients in Canada. OBJECTIVE: We investigated if individuals in the database had a confirmed diagnosis of rosacea, how they perceived their treatment by the medical system, and identified their needs. METHODS: A two-page questionnaire was mailed to 7874 individuals registered with the RAP. Thirty percent of these individuals responded. Where comparisons were made a chi-squared statistic was used. RESULTS: Over 70% learned of the RAP via public media. It took patients an average of 5 years to have a diagnosis made after the first symptoms appeared. In the majority of patients (53%) the diagnosis was ultimately made by a specialist. Fifty-eight individuals said they had not discussed their condition with their doctor. Patients were likely to continue on medication that was prescribed (60%) and topical metronidazole was the most common medication used, mostly the gel formulation. Most patients used these twice daily. Patients were very satisfied with treatments and almost 90% had reduced symptoms. Despite receiving explanations and written material, patients expressed a strong interest in more information being available on skin care, make-up, and psychological aspects of rosacea. CONCLUSIONS: The RAP provides a needed educational service and is a useful database. Patients are very knowledgeable about their disease, but despite this and excellent therapeutic responses, the patients demand more information.
Administration, Cutaneous↗
Anticonvulsant hypersensitivity syndrome: incidence, prevention and management.
Although the anticonvulsant hypersensitivity syndrome was first described in 1950, confusion still abounds regarding the syndrome. The triad of fever, rash and internal organ involvement occurring 1 to 8 weeks after exposure to an anticonvulsant heralds this rare (1 in 1,000 to 10,000 exposures) but serious reaction. Aromatic anticonvulsants [phenytoin, phenobarbital (phenobarbitone) and carbamazepine] are the most frequently involved drugs; however, there have also been several cases of anticonvulsant hypersensitivity syndrome associated with lamotrigine. Fever, in conjunction with malaise and pharyngitis, is often the first sign. This is followed by a rash which can range from a simple exanthem to toxic epidermal necrolysis. Internal organ involvement usually involves the liver, although other organs such as the kidney, CNS or lungs may be involved. Hypothyroidism may be a complication in these patients approximately 2 months after occurrence of symptoms. The aromatic anticonvulsants are metabolised to hydroxylated aromatic compounds, such as arene oxides. If detoxification of this toxic metabolite is insufficient, the toxic metabolite may bind to cellular macromolecules causing cell necrosis or a secondary immunological response. Cross-reactivity among the aromatic anticonvulsants may be as high as 75%. In addition, there is a familial tendency to hypersensitivity to anticonvulsants. Discontinuation of the anticonvulsant is essential in patients who develop symptoms compatible with anticonvulsant hypersensitivity syndrome. A minimum battery of laboratory tests, such as liver transaminases, complete blood count and urinalysis and serum creatinine, should be performed. Corticosteroids are usually administered if symptoms are severe. Patients with anticonvulsant hypersensitivity syndrome should avoid all aromatic anticonvulsants; benzodiazepines, valproic acid (sodium valproate) or one of the newer anticonvulsants can be used for seizure control. However, valproic acid should be used very cautiously in the presence of hepatitis. There is no evidence that lamotrigine cross-reacts with aromatic anticonvulsants. In addition, family counselling is a vital component of patient management.
Anticonvulsants↗
The effectiveness of antidepressants in elderly depressed outpatients: a prospective case series study.
BACKGROUND: This study examined the effectiveness of antidepressants in a group of elderly depressed outpatients by assessing depression prevalence and recording adverse events over time. METHOD: A prospective practice-based observational study (1991-1994) included consecutive outpatients at least 65 years of age with a DSM-III-R diagnosis of major affective disorder and who were prescribed antidepressant medications. Depressive symptoms were examined over time (stage 1 = 0 to 2 months; stage 2 = 2 to 6 months; stage 3 = 6 months to 2 years) with the Montgomery-Asberg Depression Rating Scale (MADRS). The cutoff scores of MADRS <18 and MADRS > or =18 were used in survival statistics. Adverse events were recorded systematically. RESULTS: A total of 213 patients were seen over 2677 visits (mean +/- SD age = 75.5+/-6.1 years). MADRS scores for 85.8% of patients declined to below 18 within the first 2 months of antidepressant treatment. MADRS scores were above 18 for 37.3% of patients after 6 months and for 37.1% after 2 years. The mean time to decline in MADRS scores to below 18 in stage 1 was 36.1 days, and there was a significant difference between the antidepressant classes (log rank = 8.3, df = 3, p = .04), with tricyclic antidepressants (TCAs) and monoamine oxidase inhibitors (MAOIs)/reversible inhibitors of monoamine oxidase A (RIMAs) having shorter times to response. The mean time to reach scores above cutoff during stage 2 was 144.3 days (log rank = 5.7, df = 3, p = .13) and during stage 3, 538.6 days (log rank = 9.8, df = 3, p = .02). Patients receiving TCAs and MAOIs/RIMAs had longer durations of MADRS scores below cutoff during stage 3 than those taking atypical antidepressants and selective serotonin reuptake inhibitors. All antidepressant classes reported similar adverse event profiles. CONCLUSION: This study systematically examined antidepressant effectiveness in a prospective design. TCAs and MAOIs/RIMAs were shown to be superior in effectiveness during 2 of the 3 treatment stages.
Age Factors↗
The new oral antifungal agents for onychomycosis of the toenails.
OBJECTIVE: To review the use of the new oral antifungal agents, itraconazole, terbinafine and fluconazole for the treatment of onychomycosis of the toenails. BACKGROUND: Until about 10 years ago the two oral agents available to treat onychomycosis were griseofulvin and ketoconazole. Since then the new oral antifungal agents have superseded the traditional oral agents for the management of toenail onychomycosis. METHODS: Literature review. RESULTS AND CONCLUSION: Itraconazole, terbinafine and fluconazole have been used approximately 100 million times to treat superficial mycoses. These agents are more effective than the traditional antimycotics for the treatment of pedal onychomycosis; furthermore, the new agents have a broader spectrum of action than griseofulvin. In general, itraconazole, terbinafine and fluconazole have a favorable adverse-effects profile with drug interactions that are usually predictable and manageable. The new oral antifungal agents have a high benefit-to-risk ratio when used to treat toenail onychomycosis.
Administration, Oral↗
Drug eruptions in children.
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Acne Vulgaris↗
Role of cytokines in ethanol-induced cytotoxicity in vitro in Hep G2 cells.
BACKGROUND & AIMS: As shown previously by us, ethanol (EtOH) causes time- and concentration-dependent reduction in cytoviability. Tauroursodeoxycholic acid (TUDCA) and ursodeoxycholic acid (UDCA) were shown to reduce cytotoxicity. Long-term EtOH exposure leads to immunoregulatory and detoxification impairment. This study aimed to determine the relationship between cytokine (interleukin [IL]-1 alpha and IL-6 and tumor necrosis factor [TNF]-alpha) production and expression, glutathione (GSH) status, and EtOH-induced cytotoxicity on Hep G2 cells. METHODS: Cells were incubated with 80 mmol/L EtOH or alpha-minimal essential medium (control) in the presence or absence of 50 mumol/L TUDCA or UDCA. Cytokine release was quantitated by enzyme-linked immunosorbent assay. Cytokine expression was measured by reverse-transcription polymerase chain reaction. GSH content was determined in both the cytosolic and mitochondrial fractions. RESULTS: After 24 hours of EtOH exposure, the release of IL-1 alpha doubled, that of IL-6 increased 10 times, and that of TNF-alpha increased 3.5 times. Cytokine expression was up-regulated compared with control for IL-1 alpha (42%), IL-6 (26%), and TNF-alpha (52%). Addition of 50 mumol/L TUDCA or UDCA reduced cytokine release and expression. TNF-alpha increased cytotoxicity by 18%. Anti-TNF-alpha antibody almost abolished it. EtOH depleted mGSH levels by 55% (P < 0.001). TUDCA replenished them by 88%. CONCLUSIONS: EtOH up-regulated expression of cytokines in Hep G2 cells is down-regulated by bile acids. Increased amounts of TNF-alpha and depletion in both cytosolic and mitochondrial GSH contribute to EtOH cytotoxicity. Bile acids prevent toxicity.
Apoptosis↗
Skin reactions associated with bisphosphonates: a report of 3 cases and an approach to management.
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Adult↗
Severe neutropenia associated with oral terbinafine therapy.
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Administration, Oral↗
The spectrum of cutaneous reactions associated with diltiazem: three cases and a review of the literature.
BACKGROUND: Cutaneous reactions ranging from exanthems to severe adverse events have been reported in association with calcium channel blockers. OBJECTIVE: Our purpose was to document cutaneous eruptions resulting from use of diltiazem. METHODS: We describe three patients who experienced a cutaneous reaction (i.e., hypersensitivity syndrome reaction, pruritic exanthematous eruption, and acute generalized exanthematous pustulosis) possibly induced by diltiazem, summarize adverse reaction reports obtained from the Health Protection Branch, and review the literature on calcium channel blockers inducing cutaneous reactions. RESULTS: Of the 315 cases of possible diltiazem-induced adverse reactions that were reported to the Health Protection Branch, 151 (48%) were cutaneous. The number of diltiazem-induced cutaneous events was significantly greater than those induced by either nifedipine or verapamil. However, no difference was found in the proportion of serious cutaneous adverse events to either of the three drugs. CONCLUSION: Diltiazem has been associated with a variety of cutaneous reactions that appear to occur more frequently than with other calcium channel blockers.
Calcium Channel Blockers↗
Fever, lymphadenopathy, eosinophilia, lymphocytosis, hepatitis, and dermatitis.
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Adverse Drug Reaction Reporting Systems↗
The risks of systemic corticosteroid use.
Because of their potent antiinflammatory and immunosuppressive properties, systemic corticosteroids are used to modify a vast array of diseases. This class of drugs, however, has the potential to produce multiple adverse effects presenting the dermatologist with difficult decisions in the management of patients with potentially steroid responsive disorders. This article reviews the side effects of systemic corticosteroids, comments on strategies to minimize these side effects, as well as, outlining suggested mechanisms by which physicians may minimize the risks of medical legal consequences owing to adverse reactions to these drugs.
Administration, Oral↗
Cutaneous adverse effects associated with terbinafine therapy: 10 case reports and a review of the literature.
Terbinafine is an allylamine antifungal agent widely used to treat dermatophyte onychomycosis and dermatomycoses. We report 10 severe cutaneous adverse reactions associated with terbinafine therapy which required discontinuation of the antifungal agent: erythema multiforme (five patients), erythroderma (one), severe urticaria (one), pityriasis rosea (one) and worsening of pre-existing psoriasis (two patients). The spectrum of cutaneous adverse effects associated with terbinafine therapy is reviewed. Patients should be counselled about discontinuing terbinafine at the onset of a cutaneous eruption and about seeking medical advice about further management.
Adult↗
Hepatitis associated with terbinafine therapy: three case reports and a review of the literature.
Terbinafine is an allylamine antifungal agent first launched in the USA in May 1996 with an estimated 7.5 million individuals worldwide having used the drug. Given orally it is effective for the treatment of dermatophyte infections and is prescribed predominantly for the superficial mycoses. Adverse effects have been reported in 46.7% of patients receiving the oral drug (compared with 29.2% receiving placebo, the attributable risk to terbinafine being 17.5%). Thus, oral terbinafine is associated with the rare development of symptomatic idiosyncratic hepatobiliary dysfunction (1:45,000-1:54,000) and we now describe three patients who developed this disorder whilst taking the medication. The hepatitis produced has the features of both hepatocellular necrosis (with elevations of hepatic enzyme concentrations) and cholestatic injury (with elevations of alkaline phosphatase and cholesterol levels), the latency period between the start of medication and the development of liver injury being approximately 4-6 weeks. The US terbinafine product monograph recommends that serum hepatic enzymes should be assessed in individuals receiving terbinafine for more than 6 weeks, as a result of which some physicians monitor these values at baseline and at 4-6 weeks.
Adult↗
Pharmacoeconomic analysis of topical treatments for tinea infections.
BACKGROUND: A payor-perspective economic analysis of the topical creams ciclopirox, clotrimazole, ketoconazole, miconazole, and terbinafine (TER) used to treat dermatophytosis has been made. This pharmacoeconomic evaluation was conducted in Austria, Germany, and Switzerland. METHODS: A four-phase approach was used. Phase 1: experts were assembled to identify the standard approach for management of fungal infections and a decision tree was constructed to model the process. Phase 2: meta-analysis was used to determine success, failure, and relapse rates. Phase 3: economic analyses performed included cost of regimen, total expected cost, and cost-effectiveness. Phase 4: sensitivity analyses (robustness analysis) were also executed to determine the validity of the assumptions. RESULTS: In the total expected cost analysis, TER demonstrated the lowest overall cost of treating patients. Terbinafine also provided the highest number of disease-free days during the analytic time horizon and, consequently, the lowest cost per disease-free day. Sensitivity analyses suggest that TER is the most cost-effective topical product for treating dermatophytosis in Austria, Germany, and Switzerland. CONCLUSIONS: All analytic scenarios suggest that TER therapy demonstrates lower expected costs and generates more DFDs when compared with the fungistatic topical therapies included in this pharmacoeconomic analysis. Terbinafine is expected to be the most cost-effective choice in Austria, Germany, and Switzerland for treatment of dermatophytosis minor.
Administration, Topical↗
A questionnaire study on the management of onychomycosis: a Canadian perspective.
BACKGROUND: Onychomycosis of the toenails is a condition that responds poorly to griseofulvin. The introduction of terbinafine in Canada in May 1993 resulted in a marked shift in the choice of treatment for pedal onychomycosis. METHODS: A questionnaire survey was carried out in 1996 among Canadian dermatologists regarding the management of onychomycosis. RESULTS: There were 160 respondents from the roughly 350 practicing dermatologists. The dermatologists saw 8 +/- 0.6 patients per week (average +/- standard error (SE) with suspected or diagnosed onychomycosis, with 5 +/- 0.5 patients per week consulting the dermatologists for the first time. Most dermatologists performed mycological testing prior to starting treatment for onychomycosis. The management options for onychomycosis (mean +/- SE) were oral systemic antifungal therapy 51 +/- 3%, no therapy 31 +/- 3%, and nondrug therapy 9 +/- 2%. The majority of dermatologists (83%) used terbinafine as first-line therapy if, indeed, they used oral antifungal agents. In contrast, griseofulvin and ketoconazole were used as first-line therapy in 5% and 1% of cases, respectively. In Canada, there are no monitoring requirements when using oral terbinafine for onychomycosis. Therefore, it is not surprising that only 30% of dermatologists performed monitoring with terbinafine. In contrast, the frequency of monitoring with griseofulvin and ketoconazole was 40% and 80%, respectively. The subset of dermatologists who reported monitoring carried it out in only a fraction of their patients: 47%, 53% and 83% for terbinafine, griseofulvin, and ketoconazole, respectively. Therefore, the overall number of patients in whom regular monitoring was performed was 14.1% 21.2%, and 71.4% for terbinafine, griseofulvin, and ketoconazole, respectively. The perceived cure rates with terbinafine and griseofulvin (mean +/- SE) were 83.7 +/- 1% and 41 +/- 3.1%, respectively. CONCLUSIONS: In May 1996, within three years of the introduction of terbinafine to Canada, this agent has become the drug of choice for the treatment of pedal onychomycosis (at the time of the survey neither itraconazole or fluconazole were approved for onychomycosis). Terbinafine has been found to be very effective and safe, and only a minority of dermatologists perform regular monitoring with this drug.
Administration, Oral↗
Antiepileptic drug hypersensitivity syndrome.
The antiepileptic drug hypersensitivity syndrome (AHS) is an adverse drug reaction associated with the aromatic antiepileptic drugs (AEDs) phenytoin (PHT), carbamazepine (CBZ), phenobarbital (PB), and primidone. The syndrome is defined by the triad of fever, skin rash, and internal organ involvement. It can also be caused by other drugs, such as sulfonamides, dapsone, minocycline, terbinafine, azathioprine, and allopurinol. Diagnosis of AHS may be difficult because of the variety of clinical and laboratory abnormalities and manifestations and because the syndrome may mimic infectious, neoplastic, or collagen vascular disorders. The incidence is approximately 1 in 3,000 exposures. AHS starts with fever, rash, and lymphadenopathy, within the first 2-8 weeks after initiation of therapy. Internal manifestations include, among others, agranulocytosis, hepatitis, nephritis, and myostitis. AHS is associated with a relative excess of reactive oxidative metabolites of the AED. Insufficient detoxification may lead to cell death or contribute to the formation of antigen that triggers an immune reaction. Crossreactivity among PHT, CBZ, and PB is as high as 70-80%.
Anticonvulsants↗