Current Drug Safety - Volume 20, Issue 3, 2025

Paxlovid (nirmatrelvir/ritonavir) is the first oral therapy approved by the US FDA to treat patients with mild-to-moderate COVID-19.

Our current review focuses on clinical data related to tacrolimus toxicity induced by Paxlovid currently available.

A number of online databases, including LitCovid, Scopus, Web of Science, Embase, EBSCO host, Google Scholar, Science Direct, and the reference lists were searched to identify articles related to Paxlovid-induced tacrolimus toxicity, using keywords, like drug interactions, Paxlovid, ritonavir, nirmatrelvir, tacrolimus, pharmacokinetic interactions, and CYP3A.

Tacrolimus is a substrate of CYP3A enzymes and ritonavir of Paxlovid has been identified as a potent inhibitor of CYP3A enzymes. Hence, Paxlovid can inhibit the CYP3A-mediated metabolism of tacrolimus, resulting in elevated plasma concentrations of tacrolimus and toxicity.

A number of case reports and case series have been published to highlight the association of Paxlovid and tacrolimus toxicity in transplant recipients with COVID-19 infection. Various recommendations have been proposed to prevent and mitigate the adverse events related to the DDI of Paxlovid and tacrolimus. Transplant physicians should be aware of this DDI and collaborate with clinical pharmacists on this issue.

Emerging studies have reported the potential anticancer activity of FDA-approved benzimidazole-based anthelmintics against lung cancer. Therefore, the current systematic review aimed to explore the anticancer activity of benzimidazole-based anthelmintics in lung cancer animal models.

The databases including Pubmed, ScienceDirect, and Google Scholar were searched till April 2024 for the animal studies evaluating the anticancer activity of benzimidazole-based anthelmintics against lung cancer. The relevant data was extracted in the prepared format in Microsoft Excel. Systematic Review Center for Laboratory Animal Experimentation (SYRCLE) risk of bias (RoB) was used to assess the quality of included studies. The protocol for this study has been registered in PROSPERO (Registration number: CRD42022352141).

Initially, we obtained 4150 articles, and finally eight articles were included in the current study. The information in the included studies was a bit diversified including different benzimidazole-based anthelmintics, dosage, route of administration, and duration of experiments. However, all studies reported that exposure to benzimidazole-based anthelmintics decreased tumor size and tumor volume in animal models of lung cancer.

In conclusion, benzimidazole-based anthelmintics have the potential to treat lung cancer. However, more controlled and thorough preclinical studies are required to evaluate its efficacy, safety, and mechanism of anticancer activities.

In recent years, it has been reported that long-term use of Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) may have protective effects against neurodegenerative diseases by inhibiting the activity of cholinesterase enzymes. The exact biological mechanism of these protective effects is not yet known. This study aims to assess the in vivo and in vitro effects of aspirin and ibuprofen injection on the activity of acetylcholinesterase and butyrylcholinesterase.

In this experimental study, 70 adult male mice (20-25 g) were divided randomly into 7 groups (n= 10) including a control group that received normal saline and other groups that received different dosages of aspirin and ibuprofen (100, 200, and 300 mg/kg) in the form of intraperitoneal injection. Mice were anesthetized by ether, and blood samples were taken from the heart. Ellman´s methods were used to measure cholinesterase, erythrocytes, and serum, respectively.

The activity of cholinesterase enzymes in serum and erythrocytes decreased significantly (P<0.0001) in treated groups with aspirin and ibuprofen compared to the control samples after 3 and 24 hours. However, these inhibitory effects were variable depending on the dose of the injected drugs, and they were statistically significant at higher injection doses in vitro and in vivo analysis.

The result of this study showed that non-steroidal anti-inflammatory drugs can inhibit the activity of the cholinesterase enzymes in both in vivo and in vitro conditions compared to the control group.

All stakeholders must address the global health concern of an increasing frequency of adverse drug reactions (ADRs), regardless of the practice settings. Adverse drug reactions have been found to be a significant cause of morbidity and death across all age groups, hospital admissions, and a significant financial burden on society and healthcare systems. The main objective of this study was to measure patients' awareness and knowledge of reporting adverse drug reactions using a questionnaire and then to help patients become more aware of and sensitive to reporting ADRs.

The current investigation was carried out in the OPD Block of the All India Institute of Medical Sciences in Deoghar using a pre-experimental study with one group pre-test post-test design. One hundred and ninety-nine patients who were visiting different OPDs and IPDs participated in this study.

The average age of the 199 study participants was 34.6 years. The majority of participants were male, illiterate and belonged to rural areas. We found a statistically significant difference [-11.90(0.000*)] in the pre-test and post-test knowledge questionnaire scores of the participants, indicating the efficacy of awareness and sensitization for patients on ADR reporting.

This survey aims to inform patients about the pharmacovigilance Program in India. The questions are structured in a way that allows patients to reflect and become more self-aware while reading them. They also function as a set introduction to ADR (Adverse Drug Reaction) monitoring centers and increase patient awareness of reporting ADRs.

Infections with Soil-transmitted Helminths (STHs) impact about 24% of the global population. A disproportionate number of individuals, particularly those from low socioeconomic backgrounds, live in emerging nations. In India, between the ages of one and fourteen, almost 220 million children are susceptible to intestinal worm infestations caused by parasites. The National Deworming Day (NDD) initiative was started by the Indian government in February 2015 as a part of the National Health Mission to address this problem. Though the adverse effects of albendazole in routine therapy are known, the mass administration of the medicine in children as part of a public health program has not been adequately studied.

This study aimed to determine the occurrence, type, and severity of adverse drug reactions resulting from mass administration of albendazole in school children aged 6-19 years in a district of northern India.

Twenty specified clusters were randomly chosen from a total of 96 clusters in the district to participate in this prospective, descriptive, observational study that was carried out in Karnal, Haryana. Both a passive approach and an active adverse drug reaction reporting system were used in the study. The six-step process known as Deb’s Active Surveillance & Assisted Reporting System was employed in our study. Adverse drug reactions were recorded using the suspected Adverse Drug Reaction (ADR) reporting form of the Pharmacovigilance Programme of India (PvPI).

Twenty clusters with a combined total of 94 schools and 12,751 students were observed during the study. In this study, there were more female participants (N = 8,060; 63.21%) than male participants (N = 4,691; 36.78%). A total of 29 ADRs were reported. All reported ADRs were mild in nature. It was discovered that there were 1.37 incidences for every 1000 individuals. As illustrated in Fig. (1), the most frequently reported Adverse Drug Reactions (ADRs) were vomiting (N = 10), nausea (N = 4), abdominal pain (N = 2), and headache (N = 1). The majority of ADRs were categorized as probable (N=18; 62.06%), followed by possible (N=11; 37.93%).

An active surveillance system alongside voluntary passive reporting during the mass administration of medicines can help evaluate the safety profile of the medicinal products. The occurrence of ADRs following mass administration of albendazole in school children was found to be only 1.37 incidences for every 1000 recipients, being mild in nature, with vomiting being the most common.

The study examines how chronic resveratrol administration affects behavioral and neurochemical changes caused by Lorazepam (LZP), a classical anti-anxiety medicine associated with neurodegenerative and neurological problems.

Forty male rats were placed into four groups: a control group receiving 1% Tween 80, the LZP group receiving 2 mg/kg/day, the Resveratrol group receiving 50 mg/kg/day, and the LZP plus resveratrol group receiving the same doses of LZP and Resveratrol. Oral therapy was given daily for 6 weeks. The animals were euthanized after open field and Y maze behavioral tests. In specific brain regions, neurochemical analyses were performed on GABA, glutamic acid, monoamines (norepinephrine, dopamine, and serotonin) and their metabolites, DNA fragmentation (8-hydroxy-2–deoxyguanosine or 8-HdG), brain-derived neurotrophic factor (BDNF), and Ca-ATPase.

Resveratrol therapy improved GABA, glutamic acid, monoamines, and their metabolites in the cerebral cortex, hippocampus, and striatum. Additionally, it reduced DNA fragmentation (8-HdG) and counteracted LZP-induced Ca-ATPase downregulation at a significant level (p < 0.05). Resveratrol also reversed LZP-induced behavioral changes in the Y maze and open field tests.

Resveratrol has anxiolytic-like actions like benzodiazepines and neuroprotective capabilities against LZP-induced adverse effects.

Adverse Drug Reactions (ADR) are one of the common causes of hospital admissions and pose a significant clinical and economic burden on the healthcare system. The Adverse Drug Reaction Monitoring Centre (AMC) in JIPMER functioning under the Pharmacovigilance Programme of India (PvPI) plays a vital role in ensuring medication safety by routinely detecting and monitoring ADRs. Hence, this study aimed to assess the characteristics of ADR reported from 2010 to 2020 in AMC JIPMER and to detect signals, if any.

To study the characteristics of Adverse Drug Reactions (ADR) reported to a regional ADR monitoring center from 2010 to 2020 and to detect signals of disproportionate reporting (SDRs) if any from the reported ADRs.

A total of 6007 ADR reports with a single suspect drug were included for analysis from 2010 to 2020. The characteristics of these reports, including patient’s age and gender, Number and percentage of ADRs, the causality of ADR using WHO UMC (World Health Organization-Uppsala Monitoring Centre) scale, the seriousness of the ADR, and outcome were collected from the ADR reports. MedDRA (Medical Dictionary for Regulatory Activities) Preferred Terms (PT) were used to classify adverse drug reactions. Causality analysis using the Naranjo Algorithm and Preventability using Modified Schumock and Thornton criteria were performed for the ADRs. The number and percentage of severe ADRs were analyzed. The System Organ class of all the ADRs was enumerated. ADRs not mentioned in the US FDA (United States Food and Drug Administration) product label (unlabelled reactions) were documented. Unlabeled reactions with ≥3 ADR reports were included for signal detection by disproportionality analysis.

Antineoplastic drugs, followed by antimicrobials, anticonvulsants, Anti snake venom, and NSAID were the most common drugs implicated in ADRs. Skin and subcutaneous tissue disorders were the most common System Organ Class (SOC) involved in the ADRs. Among the 6007 reports, 19.2% were serious ADRs. Most of the ADR reports were of possible causality followed by probable and certain as per WHO UMC and Naranjo causality scales. Only ten ADRs were preventable and one reaction (Tamoxifen-induced neuropathy) was eligible for signal detection. Disproportionality analysis using a 2x2 contingency table showed insignificant signal detection using the Reporting Odds Ratio (ROR) and Proportional Reporting Ratio (PRR).

Analysis of ADRs from an ADR Monitoring center functioning in a tertiary care hospital shows antineoplastic drugs to be the most common drugs associated with adverse drug reactions, with rash being the most common adverse effect. The majority of the ADRs were not preventable. No Signals of Disproportionate Reporting (SDR) were detected in our study.

Non-small Cell Lung Cancer (NSCLC) makes up about 85% of lung cancer cases, mainly adenocarcinoma and squamous cell carcinoma. Recently, PD-1 inhibitors have become crucial in NSCLC treatment, significantly enhancing survival for some. However, side effects, like skin reactions and hematotoxicity, limit their use, with drug-induced TEN and immunotherapy-induced agranulocytosis as severe adverse effects.

Herein, we have reported the case of a 75-year-old male diagnosed with metastatic Lung Squamous cell Carcinoma (LUSC) in the left lung. He received first-line treatment with one cycle of tislelizumab in combination with nab-paclitaxel and carboplatin, after which he developed Toxic Epidermal Necrolysis (TEN) and granulocytopenia. To address these two serious immune-related Adverse Events (irAEs), the patient was administered methylprednisolone in combination with gamma globulin for TEN and dexamethasone in combination with G-CSF for agranulocytosis. Antibiotics were also administered according to the patient’s medication regimen. After treatment, the patient recovered and was discharged from the hospital. It was also noted that the lung tumor condition improved.

Effective management of severe immune-related side effects from tislelizumab, including TEN and agranulocytosis, can be partly achieved through steroids, gamma globulin, G-CSF, and antibiotics. This strategy not only alleviates these adverse effects, but also potentially improves tumor conditions, highlighting the crucial role of vigilant monitoring and management in immunotherapy.

Acute Pancreatitis (AP) is an uncommon complication that rarely occurs during Rheumatoid Arthritis (RA). Among the varied etiologies of AP, Drug-induced Pancreatitis (DIP) remains a rare entity and a rather challenging condition. A large panel of drugs have been reported to cause pancreatitis; however, there are no cases of tofacitinib-induced pancreatitis reported in the literature.

We have, herein, reported the case of a Tunisian 58-year-old woman with a four-year history of RA who experienced two episodes of AP; the first one occurred on the second day of a 3-day series of methylprednisolone intravenous injections, and the second episode occurred on the sixth-day of tofacitinib administration. Each time, she presented acute abdominal pain with characteristic radiation to the back. Symptoms resolved spontaneously once the suspected drug was discontinued. In the event of a negative investigation, including abdominal ultrasonography and magnetic resonance imaging, and assessment of albumin, calcemia, triglyceridemia, serum ferritin, and IgG4 levels, DIP was the most likely diagnosis.

Although DIP is still a rare condition, it remains serious with an increased risk of mortality. We intended to alert clinicians that in addition to the known side effects of tofacitinib, pancreatitis may be induced by this drug, especially in predisposed patients.

Methimazole is an antithyroid drug known to cause hematological toxicity, including agranulocytosis and, very rarely, pancytopenia. We herein present a case of a patient with Graves' Disease (GD) who developed methimazole-induced pancytopenia.

A 53-year-old Peruvian woman with GD, initially treated with methimazole 20 mg BID, experienced odynophagia, fever, and malaise after 37 days of treatment. The initial diagnosis was agranulocytosis, leading to the discontinuation of methimazole and initiation of antibiotics. Due to persistent neutropenia, a Granulocyte Colony-stimulating Factor (G-CSF) was administered. Eight days later, she developed pancytopenia and was managed with hematopoietic agents and platelet transfusions. The patient recovered with normalization of the blood count, eliminating the need for Bone Marrow (BM) examination. Radioiodine therapy was chosen as the definitive treatment, resulting in hypothyroidism. Currently, the patient is thyroidal and hematologically stable.

Methimazole-induced pancytopenia is a rare and serious complication; however, with appropriate treatment, complete recovery can be achieved.

It is essential to exclude other causes, such as autoimmune diseases and bacterial infections, before attributing cutaneous/systemic vasculitis to drug use.

This report discusses the case of a young man who developed multi-organ failure and cutaneous vasculitis following the use of antifungal medications (terbinafine and itraconazole) for dermatophyte infections. Tests for autoimmune diseases and infections were negative. Given his drug history and a skin biopsy indicating leukocytoclastic vasculitis, it was inferred that the vasculitis was likely drug-induced. Despite treatment with steroids, intravenous immunoglobulins, and plasmapheresis, the patient did not survive, possibly due to delayed diagnosis and treatment.

In community practice, Drug-induced Vasculitis (DIV) is frequently overlooked. When patients present with skin rash, fever, and multi-organ dysfunction, DIV should be considered, particularly in the context of recent drug use. Over-the-counter antifungals, like terbinafine or itraconazole, can cause DIV and may be fatal if not promptly diagnosed and treated.

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.

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 follow-up advice.

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.

Adverse Drug Reactions (ADRs) are unexpected reactions to a medicine administered in the correct manner and at the proper dosage. Drug Rash with Eosinophilia and Systemic Symptoms syndrome (DRESS syndrome) is a Severe Cutaneous Adverse Reaction (SCAR) type of ADR with complicated clinical features involving several organ systems of the body; frequently involved organs are the liver, kidney, lungs, and other organs. Prompt recognition and correct diagnosis, followed by withdrawal of the causative agent, can promote appropriate treatment, accelerate recovery, and reduce the related morbidity and mortality.

We have, herein, presented a case of a 42-year-old female with a history of leflunomide intake for plantar fasciitis. The patient subsequently developed fever, gastrointestinal tract disturbance, facial edema, liver injury, skin rash, hematologic abnormalities (eosinophilia), hepatosplenomegaly, and lymph node enlargement. The probability of leflunomide-induced DRESS syndrome was rated as “definite”, with with a score of eight graded by RegiSCAR. The suspected causative agent was withdrawn, and the patient was managed symptomatically. Following her management and discharge, she again encountered similar complaints after administration of the cefuroxime tablet. The causality assessment of the reactions was done using the WHO-UMC scale and Naranjo’s assessment scale, and a “probable” reaction was found for both drugs.

The presented case contributes to the existing global literature regarding exceptional clinical presentations. Leflunomide and cefuroxime drugs have the potential to cause DRESS syndrome. Thus, they should be handled cautiously, and if such a reaction occurs, it should be reported to the responsible authorities.

Imipenem-cilastatin, a carbapenem antibiotic, is commonly used for severe bacterial infections. While generally well-tolerated, it can rarely cause central nervous system toxicity, including seizures. We have, herein, reported a case of imipenem-cilastatin-induced seizure in a 20-year-old patient.

A 20-year-old male was admitted to the intensive care unit for febrile status epilepticus and acute respiratory distress syndrome. Initial evaluations ruled out underlying causes and anti-epileptic treatment has been initiated. Despite having an effective anti-epileptic treatment for three months of hospitalization, seizure recurrence occurred, leading to antibiotic regimen adjustment as the imputability of imipenem-cilastatin was suspected. After discontinuation of the involved drug, the patient remained neurologically stable. Previous literature has reported cases of imipenem-cilastatin-induced seizures, particularly in elderly patients or at higher dosages. The causality assessment was conducted using the updated French method, which rated the chronological criterion as C2 and the semiological criterion as S2. The intrinsic imputability score was I3, indicating plausible causality, and the extrinsic bibliographic score was B3.

Our case has highlighted the importance of promptly recognizing imipenem-cilastatin-induced epileptic seizures in order to treat them more effectively and thus optimize the patient’s care. Therefore, we emphasize that clinicians be vigilant about the side effects of its use, particularly in patients with neurological susceptibilities. We also advocate a personalized choice of antibiotics, taking into account both antimicrobial efficacy and potential adverse effects, for better outcomes with fewer risks.