JUBLIA (Efinaconazole 10% Solution) in the Treatment of Pediatric Onychomycosis.

Onychomycosis is a chronic fungal infection of the nails and is commonly observed in adults, especially the elderly, those who are diabetic, have poor peripheral circulation, and are immunocompromised; however, onychomycosis in children is being reported more frequently, especially in older children. There could also be a genetic predisposition to developing onychomycosis. Given that onychomycosis is uncommon in children, it is important to confirm the diagnosis mycologically. Treatment of onychomycosis includes oral or topical antifungal agents. In North America, the available oral antifungal agents are terbinafine, itraconazole, and fluconazole; however, none of these agents are approved by Food and Drug Administration (FDA) for children with onychomycosis. Terbinafine is, however, approved for tinea capitis in children aged 4 years and older. In general, these oral agents have been found to be safe and effective for pediatric onychomycosis. The available topical agents are efinaconazole solution 10%, tavaborole solution 5%, and ciclopirox nail lacquer topical solution 8%. The former two are approved by the FDA for the treatment of pediatric onychomycosis in children aged 6 years and older, while the third one is approved in children over the age of 12 years who have onychomycosis. In a phase-IV, multicenter, open label study, efinaconazole solution 10% was administered to children aged 6-16 years with culture positive, mild-to-severe distal and lateral subungual onychomycosis affecting ≥20% of at least one great toenail. Treatment was for 48 weeks, with follow-up at week 52. Efinaconazole solution 10% was found to be safe and well tolerated in this pediatric population. By week 52, the mycological cure was 65%, and the complete cure was 40%. The topical agents could be an important addition to the armamentarium of therapies available to treat pediatric onychomycosis safely and effectively.

One size does not fit all: the need for individualized treatment based on factors that may affect the therapeutic outcome of efinaconazole 10% solution for the treatment of toenail onychomycosis.

Successful management of onychomycosis is a challenge because cure rates with most antifungals are relatively low and recurrence rates are high. A drug-based approach by treating the nail alone may not suffice. There are several host-related factors (age, sex, body mass index [BMI], and patient's quality of life), disease-related factors (disease severity, duration, and the number of toenails affected), and comorbidities (tinea pedis and diabetes) that may affect treatment efficacy. Here, we review the post hoc analyses of the phase III trials of efinaconazole 10% solution that have investigated the impact of these factors on topical therapy for toenail onychomycosis. The significant clinical variables that may affect the efficacy of efinaconazole include sex, BMI, disease severity, disease duration, and tinea pedis. As older patients may have slower toenail growth and more severe, longstanding disease compared with younger patients, they may require longer treatment duration, beyond the 48-week standard regimen. Treatment compliance may need to be discussed for an improved health outcome. Therefore, these prognostic factors need to be carefully evaluated, which may aid in formulating individualized therapy to maximize treatment success.

Role of guaifenesin in the management of chronic bronchitis and upper respiratory tract infections.

Guaifenesin, a mucoactive drug, acts by loosening mucus in the airways and making coughs more productive. It is used for relief of wet cough and chest congestion due to the common cold, and remains the only legally marketed expectorant in the US (per OTC Monograph). An ingredient in numerous over-the-counter (OTC) cough/cold medications, guaifenesin has a secondary indication for use in stable chronic bronchitis (professional indication). Clinical pharmacology and patient studies support the clinical utility of guaifenesin in respiratory conditions where mucus hypersecretion is prevalent: acute upper respiratory tract infections (URTIs), stable chronic bronchitis, and possibly rhinosinusitis. Guaifenesin has a well-established and favorable safety and tolerability profile in adult and pediatric populations. Its dosing range (200-400 mg 4-hourly, up to 6× daily) allows flexible dose titration to allow an increase of plasma concentrations. Multiple daily doses are needed to maintain 24-h therapeutic effect with immediate-release formulations. Extended-release guaifenesin tablet formulations are available, providing convenience with 12-hourly dosing and portability compared to liquids. Guaifenesin is considered as a safe and effective expectorant for the treatment of mucus-related symptoms in acute URTIs and stable chronic bronchitis. Its clinical efficacy has been demonstrated most widely in chronic respiratory conditions, where excess mucus production and cough are more stable symptoms. Progress is being made to establish clinical models and measures that are more appropriate for studying symptomatic relief with guaifenesin in acute respiratory infections. This will help generate the up-to-date and high-quality data needed to optimize guaifenesin's effectiveness in established uses, and in new respiratory indications associated with mucus hypersecretion.

Extended-Release Guaifenesin/Pseudoephedrine Hydrochloride for Symptom Relief in Support of a Wait-and-See Approach for the Treatment of Acute Upper Respiratory Tract Infections: A Randomized, Double-Blind, Placebo-Controlled Study.

BACKGROUND: Despite the well-known fact that antibiotics (AB) are not effective against viruses, many patients ask for - and all too often doctors provide - AB for treating URTIs. Over-prescribing of AB is one of the key causes for the development of bacterial resistance, which the U.S. Centers for Disease Control and Prevention (CDC) calls "one of the world's most pressing public health problems". In addition to the CDC initiated "Get Smart About Antibiotics" campaign, focused on educating doctors the public about the importance of appropriate AB use, other programs tackling this problem include the development of new treatment paradigms. Data published at the Oregon Health & Science University demonstrated that a 'wait-and-see' approach, without an AB prescription for the treatment of acute childhood ear infections, was as quick, safe, and effective in resolving the infections as an AB prescription (Spiro DM, Tay KY, Arnold DH, Dziura JD, Baker MD, Shapiro ED. Wait-and-See Prescription for the Treatment of Acute Otitis Media. JAMA 2006; 296:1235-1241). OBJECTIVE: To try and reduce inappropriate prescribing practices, a wait and see or delayed approach requires patients to return for a prescription if their symptoms persist or worsen. The aim of this study was to determine whether treatment with Mucinex D (Reckitt Benckiser LLC, Parsippany, New Jersey) lowers the use of antibiotics in the treatment of URTIs when compared with placebo. METHODS: Patients aged 18 to 75 years with symptoms of acute URTIs were randomized to 1200 mg guaifenesin/120 mg pseudoephedrine hydrochloride extended-release, bilayer tablets or matching placebo for 7 consecutive days. Eligible patients met physician's criteria for antibiotic therapy but were considered suitable for a wait and see approach (withholding antibiotics for ≥48 hours). Patients recorded symptom ratings via an interactive voice response system. RESULTS: One thousand one hundred eighty-nine patients enrolled; data are presented for the modified intent-to-treat population (n = 1179). At Day 8, significantly fewer patients receiving guaifenesin/pseudoephedrine versus placebo desired antibiotics (4.2% vs 8.0%). No adverse effects were reported due to patients not taking antibiotics. Significant reductions in URTI symptoms were observed for extended-release guaifenesin/pseudoephedrine versus placebo, from Day 1 throughout the study; however, the proportion of patients experiencing overall relief at the Day 4 evening assessment (primary end point) did not reach statistical significance. Treatment-related adverse events were reported in 9.8% and 4.7% of patients receiving guaifenesin/pseudoephedrine and placebo, respectively. CONCLUSIONS: The study found that a wait and see approach was associated with decreased antibiotic use. In addition, the use of a guaifenesin pseudoephedrine combination product provided an effective symptom control compared to a placebo and a well-tolerated first-line strategy for the management of URTIs. This study was not designed to assess the effects of guaifenesin or pseudoephedrine individually. Other limitations include the need for better clinical methods to assess the effectiveness of treatments for acute symptoms of patients with URTIs. ClinicalTrials.gov identifier: NCT01202279.