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Abstract Background Patients with type 2 diabetes mellitus (T2DM) are characterized by an elevated glycemic index and are at a higher risk for complications such as cardiovascular disease, nephropathy, retinopathy and peripheral neuropathy. Normalization of glycemic index can be achieved by dosing combinations of metformin with other anti-diabetic drugs. The present study (Clintrials number NCT00519480) was conducted to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of remogliflozinetabonate, an SGLT2 inhibitor, withdoses (500 mg and 750 mg BID) greater than the commercial dose (100 mg BID)in combination with metformin with minimum daily dose of 2000 mg given in two divided doses. Methods This was a randomized, double-blinded, repeat dose study in 50 subjects with T2DM. The study was conducted in three phases; run-in, randomization, and treatment. All subjects were on a stable metformin dosing regimen. Cohort 1 subjects were randomly allocated to receive either remogliflozin etabonate 500 mg BID or placebo BID (2:1) in addition to metformin. Cohort 2 subjects were administered with either remogliflozin etabonate 750 mg BID or placebo BID (2:1) in addition to metformin for 13 days. All the subjects were assessed for safety (adverse events, lactic acid levels, vital signs, electrocardiogram [ECG]), pharmacokinetic evaluation, and pharmacodynamics (Oral Glucose Tolerance Testing) parameters. Results Co-administration of remogliflozin etabonate and metformin was well tolerated in all subjects during the observation period. There were no severe or serious adverse events (SAEs) and no increase in lactic acid concentration was reported during the study. The statistical results showed that concomitant administration of remogliflozin etabonate, either 500 mg or 750 mg BID, with metformin had no effect on the pharmacokinetics of metformin. The accumulation ratios, Day 13 vs. Day 1, for AUC values of remogliflozin etabonate and its metabolites were all very close to 1, indicating no accumulation in plasma concentrations of remogliflozin etabonate and its metabolites. Mean glucose values from baseline and glucose and insulin values following oral glucose tolerance test (OGTT) were decreased in all treatment groups. Conclusion Co-administration of doses of remogliflozin etabonate (500 mg BID or 750 mg BID) greater than the commercial dose (100 mg BID) with metformin (2000 mg BID) was shown to be safe and effective during the observation period. Trial registration ClinicalTrials.gov , NCT00519480 . Registered:22 August 2007.

Super-bioavailable itraconazole (SB ITZ) overcomes the limitations of conventional itraconazole (CITZ) such as interindividual variability and reduced bioavailability. It has been approved for systemic mycoses in Australia and Europe as 50 mg and the USA as 65 mg and in India as 50 mg, 65 mg, 100 mg, and 130 mg. However, data on the ideal dose and duration of SB ITZ treatment in managing dermatophytosis are insufficient. This consensus discusses the suitability, dosage, duration of treatment, and relevance of using SB ITZ in managing dermatophytosis in different clinical scenarios. Sixteen dermatologists (>15 years of experience in the field and ≥2 years clinical experience with SB ITZ), formed the expert panel. A modified Delphi technique was employed, and a consensus was reached if the concordance in response was >75%. A total of 26 consensus statements were developed. The preferred dose of SB ITZ is 130 mg once daily and if not tolerated, 65 mg twice daily. The preferred duration for treating naïve dermatophytosis is 4–6 weeks and that for recalcitrant dermatophytosis is 6–8 weeks. Moreover, cure rates for dermatophytosis are a little better with SB ITZ than with CITZ with a similar safety profile as of CITZ. Better patient compliance and efficacy are associated with SB ITZ than with CITZ, even in patients with comorbidities and special needs such as patients with diabetes, extensive lesions, corticosteroid abuse, adolescents, and those on multiple drugs. Expert clinicians reported that the overall clinical experience with SB ITZ was better than that with CITZ. [ABSTRACT FROM AUTHOR]

The rising challenge of carbapenem-resistant Enterobacterales (CRE) infections in Indian healthcare settings calls for clear clinical guidance on the management of these infections. The Indian consensus on the management of CRE infection in critically ill patients (ICONIC-II) is a follow-up of the ICONIC-I study, which was undertaken in 2019. A modified Delphi method was used to build expert consensus on CRE management in India, involving online surveys, face-to – face expert meetings, and a literature review. A panel of 12 experts was formed to develop potential clinical consensus statements (CCSs), which were rated through two survey rounds. The CCSs were finalized in a final face-to – face discussion. The finalized CCSs were categorized as consensus, near consensus, and no consensus. The outcomes included 46 CCSs (consensus: 40; near consensus: 3; and no consensus: 3). The expert panel discussed and achieved consensus on various strategies for managing CRE infections, emphasizing the significance of existing and emerging resistance mechanisms, prompt and tailored empiric therapy, and use of combination therapies. The consensus statements based on the collective expertise of the panel can potentially assist clinicians in the management of CRE infections that lack high-level evidence. [ABSTRACT FROM AUTHOR]

Background: Although second-generation antihistamines (SGAHs) are recommended as first-line drugs in chronic spontaneous urticaria (CSU), symptom relief has been reported in <50% of patients at licensed doses and up to fourfold dosing is recommended for these patients. Bilastine (SGAH), at licensed doses and higher doses, is efficacious in CSU. However, large-scale real-world data is scarce. Objectives: To report the real-world evidence of the safety and effectiveness of bilastine at a double dose (40-mg per day) in CSU management. Materials and Methods: In this retrospective questionnaire-based study carried out from February 2022 to July 2022, a pre-validated questionnaire was used to gather data on patients with CSU in dermatology practice from 62 centres across India. Adult patients of either gender diagnosed with CSU and switched over to bilastine 40 mg/day due to a non-satisfactory response (UCT score <12) to other antihistamines at double dose were considered for analysis. Based on UCT scores, patients were classified as responders (UCT ≥12) and non-responders at follow-up assessment at 2 weeks as compared to baseline. Results: 177 patients with a mean disease duration of 2.11 ± 1.48 years were included in the final analysis, with 53% females and 47% males. At the end of two weeks, 74/177 (42%) patients were classified as responders, and 103/177 (58%) were non-responders to Bilastine 40 mg/day. The mean change of UCT score from 5.0 ± 2.2 at baseline to 8.08 ± 5.41 (62% improvement) was significant (P < 0.001). Sedation was reported by ten patients without any discontinuation of treatment. Conclusion: Bilastine 40 mg/day was effective and well-tolerated in controlling CSU symptoms refractory to antihistamines at double doses. [ABSTRACT FROM AUTHOR]

Background: In spite of the availability of multiple consensus statements on dermatophytosis management, different treatment approaches have been experienced in India and require more scrutiny to further update guidelines and improve patient care. Aim: To determine the different approaches in dermatophytosis diagnosis and management among dermatologists in India. Materials and Methods: A web-based questionnaire was created and validated by five panelists with experience of >15 years in dermatophytosis and then circulated to about 2,000 dermatologists in India in September 2021 for a real-world management scenario. Results: Out of 2,000 dermatologists, 459 responded. About half of the dermatologists (51%) routinely conduct potassium hydroxide mount (KOH) at the initiation of therapy. Similarly, about 53% of dermatologists initiate the management of dermatophytosis with combination therapy in all types of dermatophytosis for 4-6 weeks depending upon severity. Different types of combinations are being practiced, such as either two systemic and one topical, two topicals and one systemic, but the combination of one systemic and one topical (69%) is the most commonly practiced. Itraconazole (100 mg twice a day) and luliconazole are the most commonly prescribed antifungal medications. In case of non-response to routine dose of systemic anti-fungals, about 72% of dermatologists up dose them. Most of them continue these drugs for additional 1-2 weeks after clearance of the disease. Additionally, keratolytics and moisturizers are commonly prescribed. Additionally, 62% advise liver function tests (LFTs) at the initiation of therapy, whereas 72% advise monitoring adverse effects due to systemic antifungal drugs during treatment. Conclusion: Combination therapy stood out as the need of the hour in the current menace of dermatophytosis with timely monitoring of laboratory tests for adverse events due to the use of systemic antifungals for a longer duration. [ABSTRACT FROM AUTHOR]