Tafenoquine for Plasmodium vivax malaria: Concerns regarding efficacy & safety.

Plasmodium vivax (P. vivax) malaria is a major problem in various countries such as America, Southeast Asia, Africa and the Eastern Mediterranean. The major barrier in controlling P. vivax malaria is its ability to remain in the liver as a hypnozoite form which is responsible for relapse of P. vivax malaria; hence it is necessary to target both the blood (schizont) as well as the liver (hypnozoite) stages of P. vivax to prevent its relapse. A number of factors limit the use of primaquine (PQ), the currently available therapy for P. vivax (hypnozoite stage), such as haemolysis in glucose-6-phosphate dehydrogenase-deficient patients and being contraindicated in pregnant women. Another problem associated with PQ is the poor adherence rate to the 14-day treatment regimen. Single-dose tafenoquine (TQ), an 8-aminoquinoline, has recently been approved by the U.S. FDA for the treatment of P. vivax malaria along with a blood schizonticidal. TQ is active against all stages of P. vivax lifecycle. In published studies, TQ is considered a better alternative to PQ in terms of adherence, but there are some concerns regarding its safety, efficacy and study designs of trials conducted on TQ. In this context, this review, discusses the potential safety concerns, efficacy data, summary and an appraisal of findings of the important published trials of TQ.

Decoding the Roadmap for Capacity Building of Pharmacology Academicians in Catering to Drug Information Center Services in a Developing Country.

Background: Very few medical institutions are currently providing drug information center (DIC) services in low-resource countries. Objective: To assess whether academician pharmacologists of India are prepared to deliver countrywide services with regard to DICs. Methods: A cross-sectional knowledge attitude and practice study was planned in the form of an online survey. A hyperlink to the questionnaire was sent to academician pharmacologists via email, Facebook, and WhatsApp. Determinants associated with pharmacologists' capacity and willingness in uplifting the DIC services were determined using logistic regression. Results: One hundred and thirteen academician pharmacologists responded. Participants who were working in limited functional DIC had 0.30 (95% confidence interval [CI] = 0.09-0.98) times association with answering that referring to promotional drug literature is an inappropriate practice for DIC services to that of nonfunctional DIC participants. However, the same had 5.28 (95% CI = 1.74-16.00) times association with referring to literature for establishing and running the services more as compared with participants with nonfunctional DIC. Participants from fully functional DICs in their departments had 6.31 (95% CI = 1.92-20.70) times association with identifying that adverse event reporting is not the function of DIC as compared with participants from a non-functional DIC. Participants with more academic experience had 6.7 (95% CI = 1.36 to 32.93) times association with an identification of challenges as compared with that of less experience participants. Conclusion: Academician pharmacologists need to be trained in critical appraisal of published literature and guided on how to establish and maintain the services for hospital clinicians. Senior pharmacology academicians' advice will be crucial in strengthening the roadmap for capacity building.

Impact of regulatory spin of pioglitazone on prescription of antidiabetic drugs among physicians in India: A multicentre questionnaire-based observational study.

Background & objectives: Pioglitazone was suspended for manufacture and sale by the Indian drug regulator in June 2013 due to its association with urinary bladder carcinoma, which was revoked within a short period (July 2013). The present questionnaire-based nationwide study was conducted to assess its impact on prescribing behaviour of physicians in India. Methods: Between December 2013 and March 2014, a validated questionnaire was administered to physicians practicing diabetes across 25 centres in India. Seven hundred and forty questionnaires fulfilling the minimum quality criteria were included in the final analysis. Results: Four hundred and sixteen (56.2%) physicians prescribed pioglitazone. Of these, 281 used it in less than the recommended dose of 15 mg/day. Most physicians (94.3%) were aware of recent regulatory events. However, only 333 (44.8%) changed their prescribing pattern. Seventeen of the 416 (4.1%) physicians who prescribed pioglitazone admitted having come across at least one type 2 diabetes mellitus patient (T2DM) who had urinary bladder carcinoma, and of these 13 said that it was in patients who took pioglitazone for a duration of more than two years. Only 7.8 per cent of physicians (n=58) categorically advocated banning pioglitazone, and the rest opined for its continuation or generating more evidence before decision could be taken regarding its use in T2DM. Interpretation & conclusions: Majority of the physicians though were aware of the regulatory changes with regard to pioglitazone, but their prescribing patterns were not changed for this drug. However, it was being used at lower than the recommended dose. There is a need for generating more evidence through improved pharmacovigilance activities and large-scale population-based prospective studies regarding the safety issues of pioglitazone, so as to make effectual risk-benefit analysis for its continual use in T2DM.

Difference in occurrence of muscle-related adverse effects of statins among male and female geriatric patients: A cross-sectional observational study.

BACKGROUND: Statins are the most widely used agents for the treatment of dyslipidaemias in geriatric patients. Muscle-related adverse effects (MRAE) are one of the most common toxicities of statins. Female gender has been mentioned as the risk factor for the development of MRAE of statins; however, there are inconclusive data regarding the difference in the occurrence of MRAE among male and female geriatric users. OBJECTIVES: The main objective was to find the difference in the occurrence of MRAE of statins among male and female geriatric statin users. METHODS: In this cross-sectional, observational, comparative study, relevant patient information and MRAE associated with statin use were noted. Creatine phosphokinase (CPK) levels were obtained for all patients as this is considered as the marker for statin-induced muscle damage. The parameters were compared among male and female geriatric statin users. RESULTS: 172 geriatric patients (86 male and 86 female statin users) were enrolled in the study. 38 (22%) geriatric statin users were found to have MRAE and significantly more number of female patients had MRAE as compared to male patients (25 vs. 13 P = 0.02). Significantly more number of female patients had elevated CPK as compared to male patients (20 vs. 8, P = 0.01). No significant difference was observed in CPK levels among male and female statin users. CONCLUSIONS: Statin-induced MRAE tend to occur with more frequency in geriatric female patients as compared to male geriatric patients; however, further research in the form of prospective studies is warranted.

Inter-eye differences in patients with pseudoexfoliation syndrome presenting with intraocular lens dislocation.

PURPOSE: To analyze differences in glaucoma diagnosis and glaucoma severity between fellow eyes in patients with pseudoexfoliation syndrome (PXF) who present with intraocular lens (IOL) dislocation. DESIGN: Retrospective matched case-control study. Eyes presenting with IOL dislocation (case group) were compared with fellow eyes (control group). PARTICIPANTS: Patients from a tertiary referral practice in Mississauga, Ontario, Canada. METHODS: Consecutive patients with PXF and prior bilateral uneventful cataract surgeries with in-the-bag IOLs who presented with IOL dislocation between 2008 and 2013 were identified (n=71). Indicators of glaucoma severity were compared between fellow eyes using McNemar's test and Wilcoxon signed-rank tests. Indicators of glaucoma severity were also compared pre- and post-IOL exchange/repositioning in the eye with IOL dislocation. MAIN OUTCOME MEASURES: Glaucoma diagnosis, corrected distance visual acuity (CDVA), intraocular pressure (IOP), optic nerve cup-to-disc (C/D) ratio, mean deviation (MD) on visual field, retinal nerve fiber layer (RNFL) thickness, and glaucoma medication requirements (GMRs). RESULTS: Seventy-one participants were included. The affected eye was more likely to have glaucoma (P<0.0001) and have more severe glaucoma (P=0.0001). In addition, the affected eye had worse mean CDVA (1.14±0.79 logarithm of the minimum angle of resolution [logMAR] vs. 0.35±0.46 logMAR, P<0.0005), higher mean IOP (19.2±7.2 vs. 14.7±3.6, P<0.0005), higher C/D ratio (0.54±0.22 vs. 0.51±0.20, P=0.006), greater mean number of glaucoma medication classes (1.4±1.4 vs. 0.5±1.1, P<0.0005), worse MD (-13.83±6.89 decibels [dB] vs. -6.59±6.63 dB, P<0.0005), and worse mean RNFL thickness (69.2±26.3 vs. 82.4±13.7, P=0.001). In the affected eye, there were early postoperative improvements in mean CDVA, IOP, and GMRs. CONCLUSIONS: In patients with PXF, the eye presenting with IOL dislocation was more likely than its fellow eye to have a diagnosis of glaucoma and to have glaucoma of greater severity.

Comparison of teneligliptin and other gliptin-based regimens in addressing insulin resistance and glycemic control in type 2 diabetic patients: a cross-sectional study.

INTRODUCTION: The objective of this study was to compare the effects of teneligliptin-based regimens and other gliptin-based regimens with respect to insulin resistance and glycemic control in patients with type 2 diabetes mellitus (T2DM). METHODS: We enrolled T2DM subjects, inadequately controlled with metformin and glimepiride and taking one of the gliptins, and divided them into two groups, i.e. group 1 (teneligliptin-based regimens) and group 2 (other gliptin-based regimens). Fasting plasma insulin, adiponectin levels, homeostatic model assessment for insulin resistance (HOMA-IR), glycated hemoglobin (HbA1c), and fasting blood glucose (FBG) were measured and compared. Costs of different gliptins were noted, and mean cost of per day therapy was compared. RESULTS: Eighty-six subjects participated in this study (43 each in group 1 and group 2). No significant differences were observed in FBG, HbA1c, insulin levels, and HOMA-IR, but the trend was in favor of teneligliptin-based regimens. A significantly higher number of subjects achieved HbA1c target in group 1 (P < 0.001). Teneligliptin had significantly lower cost of per day therapy as compared to other dipeptidyl peptidase-4 inhibitors. CONCLUSION: Teneligliptin seems to be cost-effective and safer option in T2DM subjects who were not adequately controlled with metformin and sulfonylureas. However, further prospective studies are needed.

Integrating clinical pharmacology and artificial intelligence: potential benefits, challenges, and role of clinical pharmacologists.

INTRODUCTION: The integration of artificial intelligence (AI) into clinical pharmacology could be a potential approach for accelerating drug discovery and development, improving patient care, and streamlining medical research processes. AREAS COVERED: We reviewed the current state of AI applications in clinical pharmacology, focusing on drug discovery and development, precision medicine, pharmacovigilance, and other ventures. Key AI applications in clinical pharmacology are examined, including machine learning, natural language processing, deep learning, and reinforcement learning etc. Additionally, the evolving role of clinical pharmacologists, ethical considerations, and challenges in implementing AI in clinical pharmacology are discussed. EXPERT OPINION: The AI could be instrumental in accelerating drug discovery, predicting drug safety and efficacy, and optimizing clinical trial designs. It can play a vital role in precision medicine by helping in personalized drug dosing, treatment selection, and predicting drug response based on genetic, clinical, and environmental factors. The role of AI in pharmacovigilance, such as signal detection and adverse event prediction, is also promising. The collaboration between clinical pharmacologists and AI experts also poses certain ethical and practical challenges. Clinical pharmacologists can be instrumental in shaping the future of AI-driven clinical pharmacology and contribute to the improvement of healthcare systems.

Dipeptidyl peptidase 4 (DPP-4) inhibitors and the risk of lung cancer: current evidence and future directions.

INTRODUCTION: Recent evidence has linked long-term use of angiotensin converting enzyme (ACE) inhibitors with the risk of developing lung cancer by increasing levels of substance P (SP) and bradykinin in lung tissue. DPP-4 inhibitors, by virtue of their mechanism of action, may increase the level of SP and pose a similar risk of incident lung cancer. Concomitant use of DPP-4 inhibitors and ACE inhibitors may further exaggerate this plausible risk. AREA COVERED: Here we discuss both direct and indirect evidence involving mechanisms by which DPP-4 inhibitors may increase the risk of lung cancer in treated patients. We highlight that increased levels of SP with DPP-4 inhibitor monotherapy and raised levels of both SP and bradykinin with add-on ACE inhibitor therapy may further enhance this risk. EXPERT OPINION: DPP-4 inhibitors are prescribed in type-2 diabetes mellitus patients with or without cardiovascular disease. When used together, ACE inhibitors and DPP-4 inhibitors may act synergistically and further amplify the lung cancer risk. Consequently, physicians should consider this plausible association while prescribing them concomitantly especially in high-risk individuals. Well-planned research studies are required to assess the association of DPP-4 inhibitors with lung cancer and other adverse effects linked to increased levels of SP and bradykinin.

Finding the most cost-effective option from commonly used Dipeptidyl peptidase-4 inhibitors in India: a systematic study.

OBJECTIVE: To identify a preferred and cost-effective drug among Dipeptidyl peptidase-4 inhibitors (DPP4Is) for Indian patients with T2DM. METHODS: We performed a systematic literature search using standard databases for relevant literature. Original studies comparing the efficacy and/or safety of different DPP4Is were included. Two authors independently performed the literature search, screening, and collected relevant data from the selected studies. The costs of all brands of individual DPP4Is were noted and compared for lowest, highest, and average cost. Finally, we summarized the information with respect to Efficacy, safety, suitability, and cost to find the most cost-effective DPP4I. RESULTS: We found 13 eligible studies containing data on 15,720 subjects. These studies showed similar efficacy (or better) and safety with teneligliptin as compared to other DPP4Is. Teneligliptin also showed additional benefits other than the glycemic control. The average cost per tablet of teneligliptin 20 mg was markedly lower as compared to sitagliptin, vildagliptin, and other commonly used DPP4Is. Teneligliptin also outscored other commonly used DPP4Is in India in suitability and seems to have better patient compliance. CONCLUSIONS: Teneligliptin 20 mg could be considered as the preferred and most cost-effective agent among commonly used DPP4Is for the effective management of patients with T2DM in India.

Efficacy of ab-interno gelatin microstent implantation in primary and refractory glaucoma.

OBJECTIVE: To evaluate the outcomes of ab interno gelatin microstent implantation alone and in combination with phacoemulsification for the reduction of intraocular pressure (IOP). DESIGN: Retrospective cohort study. PARTICIPANTS: 141 eyes of 141 patients with any glaucoma subtype, including refractory glaucoma, operated in the Centre Hospitalier de l'Université de Montréal (CHUM) from 2015-2018. Patients were included if they were over 40 years of age and had a preoperative IOP of >18 mm Hg on maximum tolerated medical therapy. METHODS: All patients received ab-interno microstent implantation (XEN-45, Allergan, Madison, NJ) with mitomycin C +/- combined phacoemulsification. The primary outcome was complete surgical success (IOP 6-18 mm Hg and <20% reduction from baseline without IOP medications or reoperations or cyclophotocoagulation); secondary outcomes included qualified success allowing for medications, percentage reduction in mean IOP and medications, and reduction in number of complications, interventions, and reoperations. RESULTS: Mean follow-up was 30.5 ± 10.2 months (±SD). Mean IOP was 23.3 ± 7.0 mm Hg on 3.4 ± 0.8 medications at baseline and 13.3 ± 4.7 mm Hg on 1.9 ± 1.5 medications at 24 months of follow-up (p < 0.001). From 24-month survival analysis estimates, complete success was achieved in 34.1% of microstent eyes versus 20.7% with combined phacoemulsification (p = 0.02); 79.1% versus 75.1% achieved qualified success, respectively (p = 0.86). Cases with combined phacoemulsification had a higher rate of failure (hazard ratio [HR] = 1.6, 95% CI 1.1-2.3, p = 0.02). Needling with mitomycin-C or 5-fluorouracil postoperatively occurred in 54 eyes (38.3%). Complications included transient hypotony (10.6%), transient hyphema (6.4%), macular edema (4.3%), and microstent exposure (2.8%). There were 33 eyes (23.4%) with reoperations and 14 (9.9%) requiring subsequent cyclophotocoagulation lasers. CONCLUSIONS: Microstent implantation required topical therapy in most cases 24 months following surgery in primary and refractory glaucoma and, when combined with phacoemulsification, had a higher risk of failure.

Potential approaches using teneligliptin for the treatment of type 2 diabetes mellitus: current status and future prospects.

INTRODUCTION: Based on pharmacological properties and results from clinical studies, teneligliptin has a great potential to be used as an alternate-day therapy and also the daily dose can be reduced to 10 mg. Clinical data also suggest its excellent efficacy and safety among older subjects. AREAS COVERED: We have reviewed and discussed potential approaches using teneligliptin for the treatment of type 2 diabetes mellitus (T2DM) including alternate-day therapy and reduction of dose from 20 mg to 10 mg per day. We have also discussed the potential of teneligliptin to address the needs of older patients with T2DM. EXPERT OPINION: It is an excellent option for use in older patients as studies in the geriatric population have shown encouraging results. Teneligliptin has a desirable pharmacokinetic profile that makes it a potential drug for use on an alternate-day basis. Teneligliptin has shown anti-diabetic efficacy even at a dose of 10 mg. These approaches may improve treatment satisfaction and patient compliance and can lower the cost; however, it is crucial to identify the subset of T2DM patients who can obtain maximum benefits. To verify these effects, large clinical investigations need to be planned and robust clinical evidence should be generated.

Assessing the Incidence of New-onset Diabetes Mellitus with Statin Use: A Systematic Review of the Systematic Reviews and Meta-analyses.

Statin use has been linked with new-onset diabetes mellitus (NODM). In the present systematic review, we aimed to determine the incidence of NODM with statin use by assessing and summarizing the data generated by different systematic reviews and metaanalyses published on this topic. We conducted a systematic review of systematic reviews and meta-analyses using a pre-defined study protocol. Two authors independently performed a literature search using PubMed, Embase and the Cochrane Central Register of Controlled Trials (CENTRAL) for studies reporting data on statin use and NODM incidence and screened and extracted data for the outcomes of interest. The Assessing the Methodological Auality of Systematic Reviews 2 (AMSTAR 2) checklist was used to evaluate the quality of the included systematic reviews and meta-analyses. The initial search yielded 621 potential records, and 16 relevant systematic reviews and meta-analyses were included in the present systematic review. The included studies showed an increase in the risk of NODM with statin use. In particular, rosuvastatin and atorvastatin were associated with NODM in many systematic reviews or meta-analyses; however, pravastatin and pitavastatin were found to be associated with lower or no risk. We observed a positive trend of development of NODM with statin use became more evident with advancing years as more number of studies were added. Intensive doses of statins and use in older subjects were found to be important risk factors for NODM. Finally, the quality assessment revealed that the included systematic reviews and metaanalyses were of critically low or low quality. We concluded that statin use carries a risk of causing NODM. Statins should not be discouraged in anticipation of NODM. However, glycaemic monitoring should be encouraged with the on-going statin therapy. Furthermore, clinical studies addressing the use of statins and the incidence of NODM as their primary objective should be planned.

Alternate-day add-on therapy with dapagliflozin in patients with type 2 diabetes mellitus: potential benefits and concerns.

INTRODUCTION: Factors such as compliance, cost and safety play a major role in achieving the long-term goal in the management of type 2 diabetes mellitus (T2DM). Dapagliflozin carries a great potential of becoming an alternate-day therapy because of its favorable pharmacological properties. AREAS COVERED: In this review, we have discussed and hypothesized the potential of dapagliflozin as an alternate-day add-on drug in T2DM patients. We have discussed the properties by virtue of which it carries a potential to become an alternate-day therapy. We have also explained the potential benefits and concerns of using this approach. EXPERT OPINION: Alternate-day add-on therapy with dapagliflozin could be a promising approach in reducing the cost, improving the treatment satisfaction and reducing the adverse effects. However, this propsed indication demands an in-depth investigation among T2DM subjects who are not able to achieve glycemic control with standard monotherapy or combination therapy. Pilot studies or some small-scale investigator-initiated trials or academic clinical trials may be carried out to explore this concept. At the same time, large industry sponsored multicenter clinical trials including pharmacoeconomic analyses may be planned to have a more detailed investigation.

Metformin: Activation of 5' AMP-activated protein kinase and its emerging potential beyond anti-hyperglycemic action.

Metformin is a plant-based drug belonging to the class of biguanides and is known to treat type-2 diabetes mellitus (T2DM). The drug, combined with controlling blood glucose levels, improves the body's response to insulin. In addition, trials have identified the cardioprotective potential of metformin in the diabetic population receiving the drug. Activation of 5' AMP-activated protein kinase (AMPK) is the major pathway for these potential beneficial effects of metformin. Historically, much emphasis has been placed on the potential indications of metformin beyond its anti-diabetic use. This review aims to appraise other potential uses of metformin primarily mediated by the activation of AMPK. We also discuss various mechanisms, other than AMPK activation, by which metformin could produce beneficial effects for different conditions. Databases including PubMed/MEDLINE and Embase were searched for literature relevant to the review's objective. Reports from both research and review articles were considered. We found that metformin has diverse effects on the human body systems. It has been shown to exert anti-inflammatory, antioxidant, cardioprotective, metabolic, neuroprotective, anti-cancer, and antimicrobial effects and has now even been identified as effective against SARS-CoV-2. Above all, the AMPK pathway has been recognized as responsible for metformin's efficiency and effectiveness. Owing to its extensive potential, it has the capability to become a part of treatment regimens for diseases apart from T2DM.

Pharmacotherapy of schizophrenia: immunological aspects and potential role of immunotherapy.

INTRODUCTION: Schizophrenia is a complex disorder owing to diversity in clinical phenotypes, overlapping symptoms, and heterogeneous clinical presentation. Even after decades of research, the exact causative mechanisms of schizophrenia are not completely known. Recent evidence indicates the role of immune dysfunction in schizophrenia pathogenesis as observed from alteration in immune cells, increased activity of complement cascade, and development of autoantibodies against neurotransmitter receptors. Immunotherapy involving immunosuppressants and cytokine-targeting drugs, have shown promising results in several clinical studies and it demands further research in this area. AREAS COVERED: Here, the authors review the immunopathogenesis of schizophrenia, limitations of conventional, and atypical antipsychotic drugs and the potential role and limitations of immunotherapeutic drugs in schizophrenia management. EXPERT OPINION: Schizophrenia is a complex disorder and poses a challenge to the currently available treatment approaches. Nearly 30% schizophrenia patients exhibit minimal response toward conventional and atypical antipsychotic drugs. Immune system dysfunction plays an important part of schizophrenia pathophysiology and existing monoclonal antibody (mAb) drugs targeting specific components of the immune system are being repositioned in schizophrenia. The authors call upon public and private funders to facilitate urgent and rigorous research efforts in exploring potential role of immunotherapy in schizophrenia.

Micropulse trans-scleral laser therapy outcomes for uncontrolled glaucoma: a prospective 18-month study.

OBJECTIVE: To evaluate the efficacy and safety of micropulse trans-scleral laser therapy (mTLT) in glaucomatous patients. DESIGN: Prospective, interventional study in a university hospital setting. PARTICIPANTS: Fifty-two eyes of 52 adult patients with uncontrolled glaucoma despite maximal tolerated medical treatment, and/or poor candidates for filtering surgery. METHODS: Participants received a 360-degree mTLT diode laser treatment (2000mW, 31.33% duty cycle), with duration adjusted to iris pigmentation and glaucoma severity (160-320 seconds). They were followed for 18 months to assess intraocular pressure (IOP), number of medications, corrected distance visual acuity (CDVA), glaucoma progression based on Humphrey Sita 24-2 perimetry and Cirrus high-definition optical coherence tomography, and complications. The primary outcome measure was the absolute success at 18 months. Absolute success was defined as an IOP 6-21 mm Hg and at least 25% IOP reduction, with equal or less number of IOP medications. Qualified success allowed for an increased number of IOP medications. Failure was defined as an inability to meet the criteria for success or the need for incisional glaucoma surgery. RESULTS: Treatment absolute success was 61.5% at 12 months and 59.6% at 18 months. Mean IOP was reduced by 35.6% at 18 months (23.6 ± 6.5 mm Hg at baseline; 15.2 ± 4.1 mm Hg at 18 months, p < 0.001). mTLT did not significantly reduce the number of topical glaucoma medications (p = 0.075); however, 15 eyes (29%) had systemic oral glaucoma treatment at baseline and 10 eyes (20%) at 18 months. Eight patients (15%) experienced vision loss of ≥2 lines after the procedure. Three patients (6%) regained their preoperative CDVA by 1 month, and 3 patients (6%) by 3 months, while 2 patients (4%) sustained persistent visual loss. No ocular complications were noted in 84.6%. Incisional surgery was required in 25% of eyes owing to inadequately controlled glaucoma despite mTLT. CONCLUSIONS: mTLT is a good therapeutic option for moderate IOP reduction, while being safe and predictable. This improved safety profile makes mTLT a treatment to be considered earlier in the management of glaucoma.

Hydroxychloroquine for the treatment and prophylaxis of COVID-19: The journey so far and the road ahead.

As mortality and morbidity from novel coronavirus disease (COVID-19) continue to mount worldwide, the scientific community as well as public health systems are under immense pressure to contain the pandemic as well as to develop effective medical countermeasures. Meanwhile, desperation has driven prescribers, researchers as well as administrators to recommend and try therapies supported by little or no reliable evidence. Recently, hydroxychloroquine-sulfate (HCQS) has got significant media and political attention for the treatment as well as prophylaxis of COVID-19 despite the lack of convincing and unequivocal data supporting its efficacy and safety in these patients. This has unfortunately, yet foreseeably led to several controversies and confusion among the medical fraternity, the patient community as well as the general public. Based on the available studies, many with high risk of bias, relatively small sample sizes, and abbreviated follow-ups, HCQS is unlikely to be of dramatic benefit in COVID-19 patients and yet has the potential to cause harm, particularly when used in combination with azithromycin or other medications in high risk individuals with comorbidities. Although definitive data from larger well-controlled randomized trials will be forthcoming in the future, and we may be able to identify specific patient subpopulations likely to benefit from hydroxychloroquine, till that time it will be prudent to prescribe it within investigational trial settings with close safety monitoring. Here we review the current evidence and developments related to the use of HCQS in COVID-19 patients and highlight the importance of risk-benefit assessment and rational use of HCQS during this devastating pandemic.

Safety of pharmacological options for the management of COVID-19 in pregnant women: An Indian perspective.

Coronavirus disease 2019 (COVID-19) is a viral illness caused by severe acute respiratory syndrome coronavirus 2 (SARS- CoV-2) presenting with pulmonary and extra-pulmonary manifestations. The first case was reported in Wuhan, China in December 2019 and it has rapidly progressed to the form of a pandemic. The presentation is mild in about 80 percent of the cases but the disease can also progress to a severe form of respiratory illness leading to acute respiratory distress syndrome (ARDS) and sometimes multi-organ failure, especially in people with other co-morbidities. Pregnant women also appear to be at a greater risk of acquiring a severe infection due to physiological changes during pregnancy. Many drugs with in vitro activity against the virus or an immunomodulatory effect have been considered for repurposing or have been tried as off-label drugs. The safety data regarding the use of newly approved or off-label or investigational drugs in pregnant women is limited and this poses a great challenge for clinicians. Therefore, it is important to know the utility and safety of the medications to avoid untoward adverse effects on pregnant women and fetuses. In this review, we aim to provide an overview of the approved, off-label, unlicensed, new and some promising pharmacological options for their use in the treatment of COVID-19 and the safety profile in pregnancy in an Indian scenario.

Minocycline for the management of multiple sclerosis: repositioning potential, opportunities, and challenges.

INTRODUCTION: Multiple sclerosis (MS) is a chronic demyelinating inflammatory disorder with variable clinical and pathologic characteristics reflecting multiple underlying pathophysiologic mechanisms. Repositioning of existing drugs for the new indications offers several advantages including significant reduction in the cost and time of drug development and exemption from early phase clinical trials. Minocycline has been reported to exhibit immunomodulation in several pre-clinical and clinical studies through suppression of migratory inflammatory cells, modulation of peripheral immune response, and inhibition of microglial activation within the CNS. AREAS COVERED: Here, the authors review the repositioning potential of minocycline for the treatment of MS along with appraisal of the evidence obtained from preclinical and clinical research. The authors also discuss the advantages and potential safety concerns related to the use of minocycline for the management of MS. EXPERT OPINION: Minocycline offers several distinct advantages in terms of well-known safety profile, lower cost of therapy, widespread availability, and being available as an oral formulation. The authors call upon the public and private funders to facilitate well designed and adequately powered randomized clinical trials that can provide conclusive evidence regarding the safety and efficacy of minocycline in patients with MS.