Current drug safety最新文献

Introduction/objective: Childhood underweight and low body mass index are major public health concerns. There is no definitive evidence on the dosage adjustment of Cyproheptadine as an appetite stimulant. This study aimed to evaluate the effect of Cyproheptadine on Body Mass Index (BMI) in underweight children and assess its associated adverse effects.

Methods: This randomized double-blinded clinical trial study was conducted on thin children aged 2 to 10 years. The study was conducted on three groups of 92 children receiving low-dose Cyproheptadine, standard-dose Cyproheptadine, or placebo. Children were assessed monthly for 4 months for changes in anthropometric indices and treatment-related side effects. Data were analyzed using SPSS version 23 Results: Mean BMI showed significant between-group differences at three and four months (p = 0.001 and p < 0.001, respectively). Drowsiness occurred significantly more often in the standard- dose group than in the low-dose group at all visits (p < 0.001). No significant differences between groups in terms of irritability (p > 0.05). Mood swings were consistently more frequent in both Cyproheptadine groups than in the placebo group (p = 0.03).

Discussion: These results are consistent with prior evidence supporting Cyproheptadine's role in promoting weight gain and add important insight into dose-related safety. However, the short follow-up period limits conclusions about long-term outcomes.

Conclusions: Low-dose cyproheptadine is an effective and safer therapeutic option for increasing BMI in children, offering efficacy comparable to the standard dose with fewer adverse effects. These results also highlight the necessity of long-term monitoring to ensure sustained efficacy and safety.

Direct oral anticoagulants (DOACs) are widely prescribed in patients at risk of thromboembolism. Although they are generally safer than warfarin, DOACs still carry a risk of bleeding and drug-drug interactions (DDIs). Nociceptive pain is common and may frequently occur in patients receiving DOAC therapy. In these cases, the European Society of Cardiology recommends avoiding non-steroidal anti-inflammatory drugs (NSAIDs) and preferring acetaminophen. However, acetaminophen is not effective when an inflammatory component is present. Consequently, non-pharmacological approaches or topical NSAIDs are suggested, while, in selected cases, lower-risk NSAIDs such as ibuprofen may be considered. Available evidence clearly indicates that concomitant treatment with NSAIDs and DOACs is associated with an increased risk of bleeding, although the magnitude of risk appears to differ across compounds. In this narrative review, we summarize the current evidence on bleeding risk associated with NSAID-DOAC coadministration, discuss potential DDIs from a pharmacokinetic perspective, and outline directions for future research.

Introduction: The Siddha formulation Gandhaga Rasayanam (GRM) is a classical polyherbo-mineral medicine containing purified sulphur and other herbal ingredients, including Schedule E(1) drugs. It is traditionally used to manage chronic ailments and dermatological conditions. Limited safety data have been documented for Siddha medicines; this report highlights a suspected adverse cutaneous reaction probably associated with GRM.

Case summary: A 36-year-old female treated for residual Padarthamarai (Tinea cruris) developed elevated plaque with ill-defined, diffuse borders over the neck and upper back on Day 3 of therapy with GRM in combination with other Siddha medicines. This lesion was inflamed, warm to the touch, and associated with pruritus, itching, and burning. The lesions subsided markedly upon GRM withdrawal and resolved completely after a short course of levocetirizine. The patient was advised to resume other internal medicines, excluding GRM, the most suspected drug, and no recurrence was observed. This implicates GRM as the probable cause of the adverse reaction.

Conclusion: This case highlights the potential for adverse reactions even with traditionally regarded safe Ayush formulations and emphasizes the need for vigilant pharmacovigilance and systematic documentation of adverse events to ensure patient safety.

Introduction: Itraconazole, a widely prescribed triazole antifungal agent, is generally well tolerated but can rarely cause neurotoxicity. Motor-sensory polyneuropathy secondary to itraconazole use is an exceptionally uncommon and underrecognized adverse effect. Although reversibility has been reported in several cases, delayed diagnosis or continued exposure may result in persistent neurological impairment. This case report aims to highlight a rare but clinically significant adverse effect-motor-sensory polyneuropathy-associated with prolonged itraconazole use in an otherwise healthy young adult.

Case presentation: We report the case of a 21-year-old previously healthy Indian male student who developed progressive weakness and sensory disturbances in both lower limbs, more pronounced on the left side, after two months of oral itraconazole therapy for onychomycosis. He presented with intermittent headaches for 20 days and worsening lower limb weakness over five days. Neurological examination revealed decreased power in the lower limbs (3/5 in the right lower limb and 2/5 in the left lower limb) and impaired sensation in all upper and lower limbs. Cerebrospinal fluid analysis and brain MRI were normal. Laboratory investigations excluded metabolic, infectious, and autoimmune causes. Nerve conduction studies confirmed motor-sensory polyneuropathy. Based on the clinical course, temporal association, and exclusion of other causes, itraconazole-induced neuropathy was diagnosed. The drug was discontinued, and supportive physiotherapy was initiated. The patient showed significant improvement during hospitalization and at one-month follow-up (5/5 in the right lower limb and 4+/5 in the left lower limb).

Conclusion: This case emphasizes the importance of considering itraconazole-induced neuropathy in patients presenting with new-onset neurological symptoms, particularly when there is a clear history of recent itraconazole use. Early recognition and prompt withdrawal of the drug are crucial to prevent permanent neurological deficits and achieve functional recovery.

Introduction: Simvastatin is a lipid-lowering drug with pleiotropic effects. Several studies have shown that it may have a protective effect on reducing morbidity and mortality from infections. One of the most devastating complications of orthopedic surgery is ImplantAssociated Infections (IAIs). Recently, newer strategies have been tried to reduce implant-related infections. Nanoparticles with antibacterial properties and coating on the healing implant abutment can improve implant performance. This study aimed to investigate the biocompatibility and antimicrobial effects of healing abutments coated with simvastatin nanoparticles (SIM-NPs).

Methods: The MTT assay was used to investigate the biocompatibility, and the time-kill assay was used to assess the antibacterial effect of abutments coated with SIM-NPs.

Results: The results showed that SIM-NPs coated on implant healing abutments had no cytotoxic effect. The time-kill assay showed that SIM-NP coating conferred antibacterial activity on implant healing abutments (p<0.05).

Discussion: The results emphasize the dual advantage of SIM-NP coatings that combine biocompatibility with antibacterial function. Their non-toxic profile protects surrounding tissues, while their antimicrobial function helps prevent initial bacterial attachment and peri-implant infections.

Conclusion: The observaitons of this study suggest that SIM-NP coatings may be a valuable alternative to systemic antibiotic therapy, thereby reducing the possibility of antibiotic resistance and minimizing systemic side effects. However, additional studies in animal and clinical studies should be conducted before consideration for clinical application.

Introduction: Type 2 Diabetes Mellitus (T2DM) very often leads to adverse changes in body composition, including increased fat mass and sarcopenic obesity. Sodium-Glucose Co- Transporter 2 inhibitors are effective hypoglycaemic medications that also promote weight loss, but their specific impact on body composition remains unclear, particularly in Indian populations. Hence, this study intended to determine the extent of alterations in body composition parameters in T2DM patients on SGLT 2 inhibitor therapy using Bioelectrical Impedance Analysis (BIA).

Methods: This prospective observational study enrolled 60 adults with T2DM initiated on SGLT2 inhibitors along with standard therapy. BIA measurements were taken at baseline, 30 days, and 90 days. Parameters included Body Weight (BW), Body Mass Index (BMI), Skeletal Muscle Mass (SMM), Body Fat Mass (BFM), visceral fat percent, and ECW/TBW. Data from 55 patients were analysed. Descriptive statistics were calculated at baseline, 30 days, and 90 days and expressed as mean ± SD. The data were compared by means of repeated measures ANOVA.

Results: No significant changes in body composition were observed at 30 days. After 90 days, a statistically significant (p < 0.05) decrease in BW (73.4 ± 10.1 vs 70.4 ± 7.5), BMI (28.5 ± 3.0 vs 27.4 ± 2.6), BFM (30.7 ± 7.3 vs 28.6 ± 5.7), and visceral fat% (13.8 ± 4.4 vs 12.4 ± 3.0) was observed. SMM and ECW/TBW ratio remained unchanged.

Discussion: The results demonstrated no significant change in body composition parameters within the first 30 days of SGLT2 inhibitor therapy. However, by 90 days, there was a significant fall in body composition in terms of body weight, BMI, body fat mass, and visceral fat. No changes were observed in skeletal muscle mass and fluid composition during follow-up. The discrepancy in body composition could be due to variation in the patients' baseline measures and lifestyle habits, including diet and physical activity. Our study was limited by its short duration and use of BIA, which is an easy, non-invasive, and more practical modality, but lacks the precision of imaging modalities like DXA or MRI. Furthermore, muscle function was not assessed, which would provide more clinical relevance in interpreting muscle mass changes.

Conclusion: Short-term (90-day) SGLT2 inhibitor therapy, primarily Dapagliflozin in T2DM patients, resulted in statistically substantial reductions in BW, BMI, BFM, and visceral fat percentage, with preservation of SMM and fluid balance. Future studies should target a larger sample size, longer follow-up durations, and include assessment of muscle strength. Additionally, the effect of lifestyle modification along with drugs on body composition can also be investigated.

Introduction: Metronidazole-induced encephalopathy (MIE) is a rare but potentially reversible adverse effect associated with prolonged metronidazole use.

Case presentation: We report a case of a 65-year-old male who developed progressive dizziness, ataxia, and confusion after 43 days of metronidazole therapy initiated for a ruptured liver abscess. MRI of the brain revealed bilateral symmetrical T2/FLAIR hyperintensities involving the dentate nuclei and dorsal brainstem, consistent with MIE. Cerebrospinal fluid analysis was inconclusive for infection. Prompt discontinuation of metronidazole led to rapid clinical improvement, with complete resolution of symptoms within 3 to 4 days. No corticosteroids were used.

Conclusion: This case emphasizes the importance of considering MIE in patients on long-term metronidazole who present with neurological symptoms and highlights the role of MRI in diagnosis. Early recognition and withdrawal of the offending drug are critical to prevent permanent neurological damage.

Introduction: Sertraline is a first-line pharmacological treatment for Major Depressive Disorder (MDD) but can cause adverse effects, including acute hepatitis. This study aims to investigate, using an experimental male rat model, the effects of different therapeutic doses of sertraline on liver damage.

Material and methods: Forty adult male Wistar rats were randomly divided into 5 groups (n=8): a control group and four groups receiving daily oral sertraline at doses of 20, 50, 100, and 200 mg/kg for two months. After the treatment period, serum levels of liver enzymes (AST, ALT, ALP), bilirubin, lipid profile (cholesterol, LDL, HDL), and inflammatory cytokines (TNF-α, IL- 6) were measured. Data were analyzed using SPSS 20 software with one-way ANOVA and ttest.

Results: The control group showed the lowest mean levels of all measured parameters. A clear dose-dependent increase was observed for cholesterol, LDL, bilirubin, AST, ALT, ALP, TNF-α, and IL-6, with the 200 mg/kg group consistently exhibiting the highest values. All variables in the 200 mg/kg group were significantly elevated compared to the control group (p<0.05). Among liver enzymes, ALP demonstrated the most pronounced dose-response, whereas bilirubin showed the weakest association with sertraline dosage.

Discussion: The findings demonstrate clear dose-dependent hepatotoxicity for sertraline, involving hepatic enzyme leakage, dyslipidemia, and pro-inflammatory cytokine activation. This provides experimental validation for clinical case reports of sertraline-induced liver injury.

Conclusion: Sertraline causes dose-dependent liver damage in male rats, characterized by elevated liver enzymes, increased inflammatory markers, and adverse lipid changes. These results highlight the need for vigilant liver function monitoring in patients on higher therapeutic doses.

Background: Linezolid is an oxazolidinone antibiotic widely prescribed for actinomycetoma. Haematological adverse reactions, such as thrombocytopenia, have been widely reported due to linezolid. We report an unusual case of pancytopenia and hyponatremia secondary to injectable linezolid treatment for actinomycetoma. This case is peculiar as previous long-term exposure to oral linezolid one year back was uneventful.

Case report: A 31-year-old male patient, a known case of actinomycetoma, presented to the dermatology outpatient department (OPD) with progressively worsening lesions for which injectable linezolid, meropenem, and sulfamethoxazole-trimethoprim combination were given. Patient developed pancytopenia with hyponatremia within 10 days of therapy initiation. Linezolid was stopped and replaced with doxycycline, whereas other drugs were continued. The test results were normalized within a week. Previous long-term exposure to similar oral therapy one year back did not cause any haematological or electrolyte abnormalities.

Conclusion: Based on the World Health Organization-Uppsala Monitoring Centre (WHOUMC) causality assessment scale, the association between linezolid and pancytopenia with hyponatremia is considered probable in this case. This case report emphasizes that clinicians should be cautious, as these serious adverse effects can occur on re-exposure to linezolid, even if absent during previous use.

Diabetes mellitus is a common long-term illness that requires steady medical treatment. Standard oral medicines for diabetes often have problems like low absorption, being broken down by the liver before they work, and patients forgetting to take their doses. Buccal drug delivery, which means giving medicine through the inside lining of the mouth, is a promising alternative. It helps control how fast the drug is released and avoids breakdown by the liver. This review examines the structure and function of the buccal mucosa, its drug-absorption capacity, and its utility for drug delivery. Different systems, such as tablets, patches, films, gels, and sticky polymers, are discussed, along with methods to help drugs pass through the mouth lining more easily. The article also explains how buccal drug delivery affects the behavior of medicines in the body, especially for diabetes drugs like Metformin and Glibenclamide. Clinical benefits, recent research, and future opportunities with new technologies are highlighted. Buccal drug delivery is convenient and can improve absorption, but it has limitations, such as poor absorption, mouth irritation, a small absorption area, salivary washout, low permeability, and commercial unavailability for some drugs. Similarly, many oral diabetes medicines, like metformin and alpha-glucosidase inhibitors, can irritate the stomach and intestines, making it harder for patients to continue treatment. These irritations can occur due to changes in pH, changes in gut motility and bile salts, fermentation of food, causing extra fluid in the intestines, or infections such as fungal overgrowth with SGLT2 inhibitors. This review aims to give a clear overview of buccal drug delivery for diabetes and its potential to improve treatment.