Current drug safety最新文献

Introduction: This case study presents a rare and fatal instance of Toxic Epidermal Necrolysis (TEN) and Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) syndrome in a 51-year-old male patient diagnosed with Rheumatoid Arthritis (RA).

Case presentation: The patient was initially treated with sulfasalazine, leflunomide, and hydroxychloroquine, following which he developed a rash, fever, and loose stools. Drug allergy was suspected, and the antirheumatic medications were withdrawn, following which, the patient improved. A subsequent attempt was made to treat the RA with methotrexate, prednisolone, and hydroxychloroquine, following which the rash returned along with an increase in severity, including detachment of the epidermis and mucosa, and systemic involvement, both hepatic and renal. The patient ultimately succumbed to multiple organ dysfunction syndrome and neutropenic sepsis.

Conclusion: This case highlights the possibility of DRESS syndrome and Stevens-Johnson Syndrome (SJS)/TEN following treatment with anti-rheumatic medications. Evidence of this is rare, with the exception of sulfasalazine. This case also considers that the signs of a moderately severe adverse drug reaction could be the early warning signs of DRESS syndrome, which can be difficult to manage and may turn to be fatal. Additionally, this case highlights the need for maintenance of quality health records in low- and middle-income countries due to the failure to identify hydroxychloroquine as a suspected drug inducing the initial adverse reaction that resulted in it being prescribed again, leading to a fatal outcome.

Background: For surgical procedures of the upper limbs, ultrasound-guided supraclavicular brachial plexus block (SCBPB) represents a safe substitute for general anesthesia. The present study evaluated the effectiveness and safety of incorporating 1μg/kg dexmedetomidine (DEX) into 20 ml bupivacaine, as opposed to using 20 ml and 30 ml bupivacaine without additives, in SCBPB.

Methods: This randomized, controlled, double-blind study included 75 patients assigned to elective upper-limb surgery under the mid-humerus level. Patients were randomized into three equal groups to receive US-guided SCBPB with 20 ml bupivacaine 0.5% + 1 μg/kg DEX in group BD, 20 ml bupivacaine 0.5% without additives in group B20, and 30 ml bupivacaine 0.5% in group B30 (control).

Results: Compared to group B20, groups BD and B30 had significantly quicker onset times for sensory and motor blocks. Groups BD and B30 had a more significant block duration than group B20. Group BD experienced considerably lower intraoperative hemodynamics than groups B20 and B30. Groups BD and B30 had a significantly delayed time to first rescue analgesia and consumed less pethidine than group B20. Compared to group B20, the pain score was significantly reduced in groups BD and B30. Comparable levels of pain score, rescue analgesia time, total pethidine consumption, and motor and sensory block onset and duration were seen in the BD and B30 groups.

Conclusion: DEX with a lower volume(20 ml) of bupivacaine reaches the same result as a higher volume of bupivacaine(30ml) in managing perioperative pain and hemodynamic stability without the risk of the high volume of bupivacaine. Further, adding DEX to small dose of bupivacaine (20ml) is more effective than small dose of bupivacaine(20ml) alone without additives in prolonging the duration of sensory and motor block, reducing pain intensity, and delaying the need for rescue analgesia.

Background: The Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) is a serious adverse reaction that occurs weeks after the onset of drug exposure. DRESS syndrome is commonly associated with antiseizure drugs, sulfa drugs, and antibiotics.

Case presentation: This was a case report of a 20-year-old female who suffered from DRESS due to vancomycin with symptoms similar to the Redman syndrome. The patient had a case of infectious endocarditis due to methicillin-resistant Staphylococcus aureus (MRSA), and vancomycin was intravenously administered. On the 18^th day, during the administration of vancomycin, the patient developed sudden severe flushing over the face and trunk. The offending drug was suspended and treated with antihistamines in view of Redman syndrome. Later, the patient developed uncontrolled fever, desquamating rash all over the body, severe pruritis, and eosinophilia. On applying the RegiScar score, a probable case of DRESS was diagnosed. The patient was managed symptomatically and discharged.

Discussion: The clinical presentation of DRESS includes skin rash, fever, eosinophilia, and organ involvement. But, in this case, there was a varied initial presentation of DRESS with severe flushing, which mimics the Redman syndrome due to vancomycin. Difficulty in establishing organ involvement remained a challenge in diagnosing DRESS.

Conclusion: DRESS can have a varied clinical presentation. Careful monitoring of all vital parameters is important in preventing the misdiagnosis of DRESS syndrome.

Background: The COVID-19 pandemic has called for the rapid development and use of antiviral drugs to effectively control the disease. Nirmatrelvir/Ritonavir (Paxlovid), Molnupiravir, and Remdesivir have been pivotal in therapeutic approaches, although they raise concerns regarding adverse drug reactions (ADRs).

Objective: This study aimed to thoroughly assess the ADRs associated with these drugs by utilizing the Adverse Event Reporting System (FAERS) database of the Food and Drug Administration (FDA).

Methods: ADR reports for Paxlovid, Molnupiravir, and Remdesivir throughout the period of January 2022 to May 2023 were extracted and classified according to the severity, type of reaction, and demographic variables. Reporting Odds Ratios (RORs) with 95% confidence intervals were calculated to evaluate the relationship between antiviral medications and various ADRs.

Results: The study established notable correlations between Paxlovid and the recurrence of the disease (40.08%) and dysgeusia (16.29%). Molnupiravir was linked to gastrointestinal (16.73%) and skin reactions (9.47%), while Remdesivir had impairments in the liver (25.21%) and kidneys (13.34%). ADRs were more commonly observed in female patients treated with Paxlovid (57.95%) and Molnupiravir (49.40%), whereas Remdesivir ADRs were mostly reported in males (58.56%). Paxlovid and Remdesivir ADRs were frequently reported in adults between the ages of 18 and 64 (46.01% and 45.01%), while Molnupiravir ADRs were more common in older individuals aged 65 to 85 (40.38%).

Conclusion: This thorough assessment emphasizes the importance of careful surveillance and control of ADRs linked to COVID-19 antiviral therapies. It is essential to customize treatments by considering specific patient histories, particularly for pre-existing diseases.

Background: Mycophenolate mofetil (MMF) is an immunosuppressant commonly used for treating autoimmune diseases.

Case presentation: We report a diagnostically challenging case of MMF-induced colitis in a patient after 3 years of initiation of MMF therapy. A 76-year-old Caucasian female with a history of Chronic inflammatory demyelinating polyneuropathy receiving MMF presented to the hospital with a 7-weeks history of watery diarrhoea and crampy abdominal pains. Routine blood investigations, CMV-PCR, stool culture, viral PCR, Colonoscopy, and CT scan of the abdomen were broadly within normal limits. Histopathological changes were not significantly diagnostic apart from ischaemic-type changes. Finally, the reduction of the MMF dose caused the cessation of diarrhoea. Diagnosing MMF-induced colitis can be challenging, especially in patients on immunosuppressive medications. Further, long latency periods and non-specific colonoscopic and histopathologic changes add to the diagnostic dilemma.

Conclusion: MMF-induced diarrhoea should be part of the clinician's differentials, and the decision to reduce the dose of MMF needs to be considered once infection and other causes have been ruled out.

The presence of N-nitrosamine impurities in pharmaceutical products is well known. In 2019, it resulted in drug recall by the Food and Drug Administration (FDA). Soon, several groups identified the presence of many N-nitrosamines (NAs) in various Active Pharmaceutical Ingredients (APIs) and drug formulations worldwide. Moreover, in the last two years, another type of NAs was identified and detected in several pharmaceutical products. These are easily formed from the parent drug molecule and are known as Nitrosamine drug-related substances (NDSRIs). The amine group plays a major and unique role in the synthesis of many drug molecules, and hence, it is practically impossible to eliminate the presence of NAs and NDSRIs from drug products. The risk assessment of the health hazard to the patient was done, and the FDA has set the maximum daily acceptable intake (AI) at 18 ng/day for NAs. This limit poses a significant challenge in isolating, identifying and quantifying NAs and NDSRIs in APIs and formulations. For small, simple NAs, a lot of toxicological information and carcinogenetic data is available; however, for NDSRIs, such data is practically absent. This review article attempts to gather the toxicological data for a few NAs and NDSRIs and tries to assess the genotoxicity potential of some NDSRIs. The possible sources of NAs and NDSRIs, including synthetic methodology and processes, impurities associated with intermediates or raw materials, stability of the API, packaging materials, imprinting inks, and excipients, are also discussed. A summary of different analytical techniques used for the detection of these NAs and NDSRIs in different pharmaceutical products has also been included. Finally, various strategies employed for the minimization of these impurities along with additional control strategies to mitigate NAs and NDSRIs below acceptable limits, have also been discussed.

Background: Stevens-Johnson Syndrome (SJS) is an infrequent yet severe mucocutaneous reaction that involves less than 10% of the Body Surface Area (BSA). It is predominantly induced by certain medications, including anticonvulsants (e.g., Lamotrigine, Carbamazepine, Phenytoin, Phenobarbitone), Allopurinol at doses above 100 mg per day, and sulphonamides (e.g., Cotrimoxazole, Sulfasalazine). Genetic predispositions, particularly the presence of the HLA-B*1502 allele, significantly increase the risk of developing SJS. This case report discusses a unique presentation of SJS in a young female patient, emphasizing the critical need for genetic screening and careful monitoring when prescribing Carbamazepine, especially in populations at higher genetic risk.

Case presentation: A 19-year-old female patient, who had been on Phenytoin and Sodium Valproate for epilepsy management over the past year, was newly prescribed Carbamazepine. Within a week of initiating Carbamazepine, the patient experienced a seizure, followed by the sudden onset of fever, painful sores, and blisters covering the upper body, along with mucous discharge from both eyes. These symptoms rapidly worsened. Based on clinical presentations and the extent of epidermal detachment, the patient was diagnosed with SJS. The severity and mortality risks were assessed using the SCORTEN score. Therapeutic interventions included intravenous Ranitidine, Ondansetron, Paracetamol, Midazolam, Levetiracetam, and Dexamethasone, along with oral Fluconazole, Chlorpheniramine tablets, and Ciprofloxacin eye drops. The patient showed significant improvement and was discharged after fourteen days with followup advice.

Conclusion: This case underscores the critical importance of performing genetic testing for the HLA-B*1502 allele and conducting baseline blood tests before initiating Carbamazepine therapy. Such precautionary measures can significantly mitigate the risk of severe adverse reactions like SJS. This report adds to the scientific literature by highlighting the potential dangers associated with anticonvulsant therapies and the necessity for personalized medicine approaches in preventing life-threatening conditions. The main takeaway is the pivotal role of genetic screening and vigilant monitoring in the management of patients requiring anticonvulsant medications to prevent serious adverse reactions.

Aim: The eventuality of tirzepatide, a binary GIP and GLP- 1 receptor agonist, as a treatment for rotundity and metabolic diseases is addressed in this comprehensive review.

Background: A definition of tirzepatide is that it is an implicit intervention for rotundity, given its effectualness per the cure-dependent effect. Beyond the beneficial effects on body weight loss, tirzepatide also brings about an improvement in lipid biographies and insulin perceptivity, in harmony with binary receptor activation.

Methodology: Assaying data from seven phases 3 trials, it's constantly shown that tirizepatide reduces body weight in a significant and clinically meaningful way for a variety of party biographies and lengths of time.

Results: The drug's effect was supported by its favorable safety profile, which shows low prevalence rates of common adverse goods. Its efficacy in the management of type 2 diabetes is supported by relative evaluations, underscoring the inevitability of its breakthrough as a therapeutic volition. Treatment individualization is key, as evidenced by the tailor-made response proposed by group analysis based on birth BMI. The efficacy, safety, and demand for personalized treatment plans of tirzepatide are each supported in recommendations for clinical practice.

Conclusion: Tirzepatide's eventuality as a long-term strategy for habitual rotundity is corroborated by long-term follow-up studies that show sustained weight loss. Indeed with these encouraging results, further study and clinical experience are demanded to completely comprehend the safety, optimal integration, and long-term effectiveness of tirzepatide in a multiplicity of patient populations.