itraconazole
Regulatory sources consulted
Approved indications
- Superficial and systemic fungal infections susceptible to itraconazole, with a regimen specific to site and pathogen.
Contraindications
Absolute
- Hypersensitivity to itraconazole.
- Ventricular dysfunction or history of heart failure, except for life-threatening infection.
- Pregnancy except for life-threatening mycosis; concomitant use of expressly contraindicated CYP3A4 substrates because of QT or severe toxicity risk.
Clinical warnings
- It may cause heart failure through a negative inotropic effect; discontinue if dyspnea, edema, or rapid weight gain develops. — CIMA/AEMPS, ficha técnica 65773
- It may cause severe or fulminant hepatotoxicity; monitor liver function and discontinue with injury signs. — CIMA/AEMPS, ficha técnica 65773
Drug interactions
- HighCritical CYP3A4 substrates, including antiarrhythmic/QT drugs, ergots, simvastatin/lovastatin, and oral midazolam or triazolam
Mechanism: Potent CYP3A4/P-gp/BCRP inhibition may cause extreme exposure and toxicity.
Recommendation: Do not combine during itraconazole and observe a window of up to 2 weeks afterward when required by the substrate label.
CIMA/AEMPS, ficha técnica 65773
- HighAntacids, proton-pump inhibitors, or H2 antagonists
Mechanism: Increased gastric pH reduces capsule absorption.
Recommendation: Separate antacids by at least 2 hours and review the acid-suppression strategy.
CIMA/AEMPS, ficha técnica 65773
Adverse events
Common (≥1%)
Headache, abdominal pain, and nausea
Rare but serious
Heart failure, fulminant hepatotoxicity, neuropathy, and severe skin reactions
Pregnancy and lactation
Avoid during pregnancy except for life-threatening infection. Use contraception during treatment and until the next menstrual period. Weigh breastfeeding against treatment need.
Recent literature (PubMed)
The International Society for Human and Animal Mycology (ISHAM) working group proposed recommendations for managing allergic bronchopulmonary aspergillosis (ABPA) a decade ago. There is a need to update these recommendations due to advances in diagnostics and therapeutics. An international expert group was convened to develop guidelines for managing ABPA (caused by Aspergillus spp.) and allergic bronchopulmonary mycosis (ABPM; caused by fungi other than Aspergillus spp.) in adults and children using a modified Delphi method (two online rounds and one in-person meeting). We defined consensus as ≥70% agreement or disagreement. The terms "recommend" and "suggest" are used when the consensus was ≥70% and <70%, respectively. We recommend screening for A. fumigatus sensitisation using fungus-specific IgE in all newly diagnosed asthmatic adults at tertiary care but only difficult-to-treat asthmatic children. We recommend diagnosing ABPA in those with predisposing conditions or compatible clinico-radiological presentation, with a mandatory demonstration of fungal sensitisation and serum total IgE ≥500 IU·mL-1 and two of the following: fungal-specific IgG, peripheral blood eosinophilia or suggestive imaging. ABPM is considered in those with an ABPA-like presentation but normal A. fumigatus-IgE. Additionally, diagnosing ABPM requires repeated growth of the causative fungus from sputum. We do not routinely recommend treating asymptomatic ABPA patients. We recommend oral prednisolone or itraconazole monotherapy for treating acute ABPA (newly diagnosed or exacerbation), with prednisolone and itraconazole combination only for treating recurrent ABPA exacerbations. We have devised an objective multidimensional criterion to assess treatment response. We have framed consensus guidelines for diagnosing, classifying and treating ABPA/M for patient care and research.
Dermatophytes represent the largest and most common group of fungal infections, impacting 25% of the global population. Among them, Trichophyton rubrum has emerged as the predominant species, responsible for a range of conditions such as tinea corporis, tinea pedis, onychomycosis, tinea cruris, and tinea manuum. Although dermatophyte incidence varies geographically, there is a noticeable rise in cases caused by T. indotineae, a strain that exhibits resistance to terbinafine. In the past decade zoophilic dermatophyte T. mentagophytes genotype VII (now known as T. interdigitale) gains a growing importance, due to its increasing frequency, the severity of the clinical manifestation and mode of transmission. Tinea infections present with various clinical symptoms and can affect individuals of all ages, from tinea pedis in adults to tinea capitis in children. Among adults globally, tinea unguium (onychomycosis) is the most common form of dermatophytosis, affecting 5.5% of the general population. Tinea unguium is more frequently seen in developed countries, while tinea capitis is more common in developing nations. The COVID-19 pandemic has led to an increase in cases of tinea faciei, likely due to prolonged mask-wearing. Terbinafine remains the preferred treatment for dermatophyte infections worldwide due to its potent fungicidal properties, minimal risk of drug interactions, and fewer side effects compared to other oral antifungals. Itraconazole and terbinafine appear to be equally effective and safe for treating tinea cruris and tinea corporis. However, the rising resistance of dermatophytes to these antifungal drugs, along with frequent recurrences of dermatophytosis in certain regions, is becoming a significant public health concern.
Tinea pedis is one of the most common superficial fungal infections of the skin, with various clinical manifestations. This review aims to familiarize physicians with the clinical features, diagnosis and management of tinea pedis. A search was conducted in April 2023 in PubMed Clinical Queries using the key terms 'tinea pedis' OR 'athlete's foot'. The search strategy included all clinical trials, observational studies and reviews published in English within the past 10 years. Tinea pedis is most often caused by Trichophyton rubrum and Trichophyton interdigitale. It is estimated that approximately 3% of the world population have tinea pedis. The prevalence is higher in adolescents and adults than in children. The peak age incidence is between 16 and 45 years of age. Tinea pedis is more common amongst males than females. Transmission amongst family members is the most common route, and transmission can also occur through indirect contact with contaminated belongings of the affected patient. Three main clinical forms of tinea pedis are recognized: interdigital, hyperkeratotic (moccasin-type) and vesiculobullous (inflammatory). The accuracy of clinical diagnosis of tinea pedis is low. A KOH wet-mount examination of skin scrapings of the active border of the lesion is recommended as a point-of-care testing. The diagnosis can be confirmed, if necessary, by fungal culture or culture-independent molecular tools of skin scrapings. Superficial or localized tinea pedis usually responds to topical antifungal therapy. Oral antifungal therapy should be reserved for severe disease, failed topical antifungal therapy, concomitant presence of onychomycosis or in immunocompromised patients. Topical antifungal therapy (once to twice daily for 1-6 weeks) is the mainstay of treatment for superficial or localized tinea pedis. Examples of topical antifungal agents include allylamines (e.g. terbinafine), azoles (e.g. ketoconazole), benzylamine, ciclopirox, tolnaftate and amorolfine. Oral an
Vulvodynia affects 7% of American women, yet clinicians often lack awareness of its presentation. It is underdiagnosed and often misdiagnosed as vaginitis. The etiology of vulvodynia remains unknown, making it difficult to identify or develop effective treatment methods. The purpose of this article is to (1) review the presentation and evaluation of vulvodynia, (2) review the research on vulvodynia treatments, and (3) aid the clinician in the selection of vulvodynia treatment methods. The level of evidence to support vulvodynia treatment varies from case series to randomized controlled trials (RCTs). Oral desipramine with 5% lidocaine cream, intravaginal diazepam tablets with intravaginal transcutaneous electric nerve stimulation (TENS), botulinum toxin type A 50 units, enoxaparin sodium subcutaneous injections, intravaginal TENS (as a single therapy), multimodal physical therapy, overnight 5% lidocaine ointment, and acupuncture had the highest level of evidence with at least one RCT or comparative effectiveness trial. Pre to posttest reduction in vulvar pain and/or dyspareunia in non-RCT studies included studies of gabapentin cream, amitriptyline cream, amitriptyline with baclofen cream, up to 6 weeks' oral itraconazole therapy, multimodal physical therapy, vaginal dilators, electromyography biofeedback, hypnotherapy, cognitive behavioral therapy, cold knife vestibulectomy, and laser therapy. There is a lack of rigorous RCTs with large sample sizes for the treatment of vulvodynia, rendering it difficult to determine efficacy of most treatment methods. Clinicians will be guided in the selection of best treatments for vulvodynia that have the highest level of evidence and are least invasive.
Onychomycosis is a fungal infection of the nail, and the most common nail infection worldwide, causing discoloration and thickening of the nail plate. It is predominantly caused by dermatophytes. Clinical presentation is polymorphous. Diagnosis must be confirmed by mycological examination before initiating any therapy. Management is an ongoing challenge, often requiring several months' treatment, with a high risk of recurrence. Treatment must be adapted to clinical presentation and severity and to the patient's history and wishes. Debridement of all infected keratin is the first step, reducing fungal load. Systemic treatments are more effective than topical treatments, and combining the two increases the cure rate. Terbinafine is the drug of choice for dermatophyte onychomycosis, due to low drug interaction and good cost-effectiveness. Itraconazole and fluconazole are broad-spectrum antifungals that are effective against dermatophytes, yeasts, and some non-dermatophytic molds. Recurrence rates for onychomycosis are high. Prophylactic application of topicals and avoiding walking barefoot in public places may help prevent recurence.