Current Drug Safety - Volume 19, Issue 1, 2024

A number of journal articles written by researchers claiming Tinospora cordifolia (Giloy) is to blame for liver damage have sparked a wide range of debates between Ayush and the allopathic medical community, particularly in India. Some even argue that promoting Giloy-based formulations to the general public is a bad idea. In this backdrop, the purpose of this essay is to provide a counter-narrative based on some of the major gaps in the research that implicated Giloy in Drug-induced Liver Injury (DILI). Time-tested herb, Giloy, which has been used for pharmacological benefits since antiquity, as well as clinical and toxicological evidence suggest that Giloy is safe, and the observed negative effects can be attributed to Tinospora crispa, a herb that resembles Tinospora cordifolia in appearance. Holding Giloy species to be detrimental is unjustifiable unless other variables such as authentication, standardization, Good Agricultural and Collection Practices (GACP), Good Manufacturing Practices (GMP), regularization of the market are considered. This article emphasizes the importance of strategic collaboration between plants and contemporary medicine in order to eliminate concerns about the use of Giloy by the general public.

Background: There exists a paucity of data on pharmacoepidemiologic and drug utilization patterns of non-steroidal anti-inflammatory drugs (NSAIDs) in the Middle East region. Objective: The objective of this study was to provide a critical appraisal of the prescription patterns of NSAIDs in the Middle East region. Methods: A literature search was conducted on the electronic databases such as MEDLINE, Google Scholar, and ScienceDirect for studies conducted on prescription pattern of NSAIDs using the keywords “Non-steroidal Anti-inflammatory Drugs”, “NSAIDs”, “Non-opioid Analgesics”, “Antipyretics”, “Prescription Pattern”, “Drug Use indicators”, “Drug Utilization Pattern”, “Pharmacoepidemiology”. The search was conducted within 5 months, from January to May 2021. Results: Studies from twelve Middle Eastern countries were analyzed and critically discussed. The findings indicated widespread and clinically significant inappropriate prescribing in all Middle East countries and territories. Furthermore, NSAIDs prescription pattern in the region extensively varies with healthcare settings, patient’s age, patient’s medical presentation, history of comorbid conditions, insurance type, and prescribers’ specialization and years of experience, among several other factors. Conclusion: Low-quality prescribing based on indicators of the World Health Organization/ International Network of Rational Use of Drugs suggests the need to further improve the current drug utilization trend in the region.

Pharmacovigilance is important for generating accurate safety of herbal medications information. The present methods were designed for synthetic medications and will need to be modified to account for the unique characteristics of medicinal plants. The objective of pharmacovigilance is to identify, measure, and explain adverse effects or other potential drug-related issues associated with herbal, traditional, and complementary therapies, as well as to avoid them. Required data for pharmcovigilance of herbal drugs and formulation were obtained from electronic sources (google scholar, PubMed, Scopus, Web of Science), several textbooks. The keywords used to search for various journal publishers such as Willey Online Library, Springer, Wolters Kluwer and Elsevier were closely monitored. This review article covers all the relevant information on issues and challenges in pharmacovigilance of formulation covering Herbal drugs.

Background: Tuberculosis is still one of the top causes of infection-related death globally. Drug-resistant tuberculosis has a high mortality rate and is still a serious public health concern around the world. The appearance of multidrug-resistant and extensively drug-resistant strains of tuberculosis has increased the need for new therapeutic options against these strains. Most of the drugs used to treat them have been poorly tested and have serious negative effects. Patients with drug-resistant tuberculosis have been fighting for access to experimental medications, particularly bedaquiline. Objective: The study aimed to summarise the existing evidence of bedaquiline's safety on drugresistant tuberculosis treatment outcome and look for bedaquiline-related adverse drug reactions in the Pharmacovigilance Programme of India and World Health Organisation - Uppsala Monitoring Centre database. Methods: We searched the PubMed database for relevant studies on the safety profile of bedaquiline used in the treatment of drug-resistant tuberculosis and bedaquiline-related adverse drug reactions in the Pharmacovigilance Programme of India and World Health Organisation - Uppsala Monitoring Centre database published up to April 25, 2022. Results: A total of 190 abstracts were identified through the Pubmed database. In a list of 157 fulltext eligible articles assessed, 149 were excluded as they did not meet the inclusion criteria. The complete articles of the remaining 8 studies were further evaluated. There were 4 prospective cohorts, 2 retrospective cohorts, and 2 case series. Conclusion: Pharmacovigilance and medication safety monitoring of newer treatments, like bedaquiline, are critical for enhancing treatment support and adherence, especially among drugresistant tuberculosis patients.

Background: Cholinesterase inhibitors, such as neostigmine and edrophonium, commonly used to reverse the residual effects of nondepolarizing neuromuscular blocking drugs at the end of surgery are associated with a high rate of residual neuromuscular blockade (NMB). Due to its direct mechanism of action, sugammadex is associated with rapid and predictable reversal of deep NMB. The current analysis compares the clinical efficacy and risk of postoperative nausea and vomiting (PONV) on using sugammadex or neostigmine for routine NMB reversal in adult and pediatric populations. Methods: PubMed and ScienceDirect were searched as the primary databases. Randomized controlled trials comparing sugammadex with neostigmine for routine NMB reversal in adult and pediatric patients have been included. The primary efficacy endpoint was the time from initiation of sugammadex or neostigmine to the recovery of a time-of-four ratio (TOF) ≥ 0.9. PONV events have been reported as secondary outcomes. Results: A total of 26 studies have been included in this meta-analysis, 19 for adults with 1574 patients and 7 for children with 410 patients. Sugammadex, when compared to neostigmine, has been reported to take a shorter time to reverse NMB in adults (mean difference = -14.16 min; 95% CI [-16.88, -11.43], P < 0.01), as well as in children (mean difference = -26.36 min; 95% CI [- 40.16, -12.57], P < 0.01). Events of PONV have been found to be similar in both the groups in adults, but significantly lower in children treated with sugammadex,i.e., 7 out of 145 with sugammadex versus 35 out of 145 with neostigmine (odds ratio = 0.17; 95% CI [0.07, 0.40]). Conclusion: Sugammadex is associated with a significantly shorter period of reversal from NMB in comparison to neostigmine in adult and pediatric patients. Regarding PONV, the use of sugammadex for NMB antagonism may offer a better option for pediatric patients.

Background: Paraquat is a highly toxic quaternary ammonium herbicide widely used in agriculture. It is an agent that induces pulmonary toxicity via the redox cyclic reaction. Objective: The present study investigated the protective effect of quercetin against paraquatinduced brain mitochondria disruption in mice. Methods: Paraquat (1.25 mg/kg, intraperitoneally) was administered to the mice, and then quercetin (50, 100, 200 mg/kg) was injected i.p. Oxidative damage biomarkers such as reactive oxygen species, protein carbonyl, lipid peroxidation, glutathione content, and mitochondrial function were assessed in the brain mitochondria. Results: The results showed that paraquat significantly (P < 0.001) increased the reactive oxygen species, protein carbonyl, and lipid peroxidation and significantly (P < 0.0001) decreased the glutathione content and mitochondrial function in the brain cells. Administration of the quercetin at doses of 50, 100, and 200 mg/kg significantly reduced reactive oxygen species, lipid peroxidation, and protein carbonyl and improved mitochondrial function and glutathione content in the mice brain mitochondrial compared to the paraquat group. Quercetin at 200 mg/kg dose had better effectiveness than 50 and 100 mg/kg doses. Conclusion: Our results suggest that quercetin in a dose-dependent manner has neuroprotective effects, probably by free radicals scavenging or enhancing the antioxidant mechanisms in the brain mitochondria. It seems that quercetin could modulate protein and lipid oxidation and improve oxidative damage induced by paraquat in the early stages.

Objectives: Berberine is a plant derived alkaloid present in many plants that may has ameliorating potential influences against inflammatory and oxidative conditions. The current study aimed to evaluate the possible protective activity of berberine and investigate its probable mechanisms against sodium nitrite toxicity in the liver. Methods: Forty male rats were divided into five groups. Group one, as the control group, received normal saline, group two received berberine (100 mg.kg^-1), and group three received sodium nitrite (80 mg.kg^-1). Groups four and five received berberine in doses of 50 and 100 mg.kg^-1, respectively, and sodium nitrite (80 mg.kg^-1) was given orally. All the doses were orally administrated for two months. Then, at the end of the 60^th day, the animals were sacrificed, and the liver homogenate was prepared. For evaluating the oxidative injury the levels of albumin (ALB) and aspartate transaminase (AST) in the serum and oxidative stress parameters in the liver were analyzed. Results: Treatment of rats with sodium nitrite considerably increased the levels of serum AST and liver superoxide anion and significantly reduced the levels of serum ALB, hepatic superoxide dismutase (SOD), total antioxidant capacity (TAC), and catalase (CAT) activity in the liver tissue. Berberine treatment could ameliorate all these parameters dose dependently. Berberine at a dose of 100 mg.kg^-1 had the best impact and reached the values of oxidative stress parameters to the normal level. Conclusion: Our results demonstrated that berberine in a dose-dependent manner offered protection against sodium nitrite-induced oxidative injury in liver, which possibly reflects the antioxidant abilities of this alkaloid.

Background: Aspergillosis is a severe and fatal complication that causes infection in transplant recipients and patients with immunodeficiency syndrome, neutropenia, chronic granulomatosis, and hematologic malignancies. Invasive Aspergillosis has been reported as one of the fungal infections with high mortality in transplant recipients. This study aimed to describe the manifestations, prevalence, management and outcome of invasive Aspergillosis fungal infections in liver transplant patients. Methods: This descriptive cross-sectional study was conducted on patients with liver transplantation who were infected with invasive Aspergillosis fungal infections. The data were extracted from the medical records of the archive of Montasryieh Hospital, Mashhad, Iran, between August 2019 and August 2020. Results: In general, 86 patients who had liver transplantation were hospitalized at Montasryieh Hospital from August 2019 to August 2020. Among them, 10 patients were infected with invasive Aspergillosis. Only 6.7% of the patients were categorized under late-onset (> 90 days after liver transplantation), and 93.3% of them were early-onset (< 90 days after liver transplantation). Invasive Aspergillosis fungal infections were suspected based on clinical or radiological signs (possible in 30% of cases; n = 3). The probable diagnosis was reported in 60% (n = 6), and the proven diagnosis was observed only in one patient. In addition, 80% of the patients were diagnosed with Pulmonary Aspergillosis, and two patients had pulmonary Aspergillosis in combination with the central nervous system and cutaneous Aspergillosis. A correlation was found between a comorbid disease and the type of Aspergillosis (r = 0.69; P = 0.02). Voriconazole was effective to treat invasive Aspergillosis in all patients. Conclusion: The prevalence rate of Aspergillosis is relatively high among liver transplant recipient populations (11%). All recipients infected with Aspergillosis had at least one risk factor, including an underlying disease. It seems that Voriconazole therapy is effective among transplant patients with pulmonary Aspergillosis.

Introduction: Health science students are prone to self-medication due to easy accessibility to medicines, background medical knowledge, and their ability to diagnose illnesses. The ongoing COVID-19 pandemic has further encouraged this practice due to the fear of contracting the virus by visiting healthcare establishments. Objectives: This study was conducted to assess the perception and practices of self-medication among health science students during the background of the COVID-19 pandemic. Methods: This cross-sectional study was conducted in July 2021 during the second wave of COVID-19. Data were collected using a Microsoft form circulated among students using WhatsApp or email. Results: The mean age of the 350 participants was 20.8 ± 1.5 years. About 165(47.1%) participants had self-medicated over the past one year. The most common mode of self-medication was using previous consultation notes [121(73.3%)]. The most common reason for self-medication stated was the mild nature of the illness [131(79.4%)]. Fifteen (9.1%) participants reported changes in medication from one to another during self-medication. Sixteen (9.7%) participants increased drug dosage during self-medication. Sixteen (26.2%) out of 61 participants who self-medicated with antibiotics did not complete the course. Forty-six (27.9%) out of the 165 participants were not aware of the adverse effects of the drugs being self-medicated on most occasions. One hundred and sixty seven (47.7%) of the total participants did not feel that self-medication practices are harmful. Ninety-five (27.1%) felt that self-medication practices are acceptable during the COVID-19 pandemic. Eighty-six (90.5%) of them thought so to avoid getting COVID-19 infection by visiting healthcare establishments. In multivariable analysis, participants in the final year and those with chronic morbidities were associated with self-medication practices. Conclusion: Self-medication practices were present among 47.1% of participants. More than onefourth of them were not aware of the side effects of self-medicated drugs on most occasions. About 47.7% participants felt that self-medication practices are not harmful and more than one-fourth of them felt that it was acceptable during the COVID-19 pandemic. Therefore, the students need to be made aware of the harmful consequences of self-medication.

Background: Cystic fibrosis is an autosomal recessive disease that causes respiratory tract infection. These patients use nebulized antibiotics such as tobramycin and gentamicin plus amikacin. Due to the high price of tobramycin and the inaccessibility of this drug in Iran at different periods, we aimed to compare the efficacy and safety of nebulized plus amikacin and tobramycin in patients with cystic fibrosis. Methods: In this analytic cross-sectional study, data were collected from the records of all patients with cystic fibrosis. They were divided into two groups by their type of nebulized antibiotic. Group 1 included 41 patients who received 80 mg gentamicin and 500 mg amikacin as a nebulized antibiotic every other month, whereas, group 2 consisted of 9 patients who received 300 mg nebulized tobramycin. Collected data were pulmonary function parameters, body mass index, the frequency of hospitalization, infection progress, Shwachman-Kulczycki score, and renal complications. The data were compared in terms of efficacy and renal adverse effects by independent t-test and repeated measure ANOVA. Results: A total of 50 cystic fibrosis patients were evaluated and there was no significant difference between group 1 and group 2 in terms of pulmonary function, frequency of hospitalizations, body mass index, Shwachman-Kulczycki score, infection progress, and renal complications. Notably, pulmonary function factors were reduced in both groups over time during their treatment. Conclusion: Nebulized tobramycin and gentamicin plus amikacin had similar efficacy against Pseudomonas aeruginosa in cystic fibrosis and had no serious renal complications.

Background: The labelling of dispensed medicines (LDM) ensures that optimum therapeutic treatment levels are achieved, and medication errors are prevented. In Malaysia, LDM is enforced under the Poisons Act 1952. Objective: To explore the knowledge, perception, and practices of community pharmacists (CP) and general practitioners (GP) on LDM. Methods: A cross-sectional study was conducted from April 2019 until March 2020 among CP and GP practising in Sarawak, Malaysia. Sample sizes were 90 and 150 for CP and GP, respectively. Proportionate stratified random sampling was employed. A self-administered structured questionnaire pre-tested and pilot-tested was used to explore knowledge and perception. Practices were assessed by having participants prepare dispensed medicine labels (DML) using simulated prescriptions. Results: 250 participants; 96 CP and 154 GP participated. While most of them perceived that they knew the requirements of LDM (n = 244; 97.6%), their median knowledge score was poor (57.1%). The mean knowledge score of CP (62.0%) was significantly higher (P = 0.002) than GP (51.0%). The majority of participants perceived that LDM is important (n = 237; 94.8%) and necessary (n = 239; 95.6%) and perceived that poor compliance with the requirements would lead to medication errors (n = 243; 97.2%). Although their knowledge was poor, their median practice score (100.0%) was excellent. There was no correlation between knowledge and perception with the practice of LDM. Conclusion: The majority of CP and GP perceived that LDM is important. Interestingly, although their knowledge of the requirements of LDM was poor, their practices were sound.

Background: The evolution of COVID-19 vaccinations, which are mostly seen as crucial to curb the epidemic, is a result of remarkable and ground-breaking researches by scientists around the world. Objective: The main goal of this study was to identify the significant adverse reactions of these vaccines, specifically in Homo sapiens. Methods: In this research, a trial version of Qualtrics CoreXM software was used, and 18 questionnaires were prototyped as part of an online survey that was done in the northern part of India. Results: The dataset included survey responses from 286 vaccinated (Corbevax) respondents' samples detailing their demographics, daily activities, type of gastronomic preferences, and any prior illnesses. The data were collected between March 24, 2022, and April 26, 2022. After analysis, 70.98% of respondents who took the first dose of the medication experienced side effects, while 50.62% of respondents who took the second dose of the medication stated the same. The major side effects reported were injection site pain, fever, tiredness, body ache, headache, etc. Conclusion: After conducting a poll on children (aged 12-18) who had received the COVID-19 vaccination, we concluded that immunizations rarely cause moderate side effects that are manageable.

Background: Periodontal disease’s initiation and propagation is through a dysbiosis of the commensal oral microbiota. But recently, through the extraordinary progress, the interrelationship that exists between periodontal disease and systemic health has been unveiled. Through various studies, it has been revealed that vitamin D deficiency may be associated with a greater risk of developing chronic periodontitis and vitamin D supplementation may help to preserve periodontal health. Aim: To find a co-relation between 25-hydroxy vitamin D status and the severity of periodontal diseases. To evaluate and compare the effect of non-surgical periodontal therapy alone and in combination with vitamin D supplementation in reducing the severity of periodontal diseases. Methods: The present study was conducted on 90 non-menopausal female subjects who divided into 3 groups. Group I comprised of healthy controls. Group II comprised of patients with moderate chronic periodontitis who were assigned to receive only Scaling and root planing (SRP). While group III included patients with moderate chronic periodontitis who were assigned to receive SRP along with Vitamin D supplementation. The periodontal parameters and serum levels of 25- hydroxy vitamin D were recorded for all the participants at baseline. Group II and group III participants were reassessed at an interval of 3 months post-treatment. Results: The results indicated that vitamin D deficiency affected periodontal health negatively. Statistically highly significant improvement was observed in Group III as compared to group II, signifying the efficacy of vitamin D supplementation adjunctive to SRP. Conclusion: Regular evaluation of Vitamin D levels and supplementation to treat the deficiency may have potential periodontal health benefits.

Background: Statins are widely used in the treatment of hyperlipidemia and in the prevention of cardiovascular diseases. However, they may induce muscular adverse effects that range from asymptomatic elevation of creatine kinase to life threatening rhabdomyolysis. Objective: The aim of the study was to describe epidemiological and clinical characteristics of patients with muscular adverse effects. Methods: We conducted a retrospective and descriptive study over a ten-year period from January 2010 to December 2019. We included all cases of statin associated muscular adverse effects notified to the Tunisian National Centre of Pharmacovigilance during this period. Results: The study involved 22 muscular adverse effects related to statins (28% of all adverse events reported with statins during this period). Patient’s mean age was 58.7 years and the sex ratio was 1.6. There were 12 cases of isolated creatine kinase elevation, 5 cases of myalgia, 3 cases of myopathy, one case of myositis and one case of rhabdomyolysis. Muscular adverse effects occurred 7 days to 15 years after starting this drug. In all cases, the statin was withdrawn after muscular adverse effects and resolution of symptoms was observed within 10 days to 18 months. In seven cases, creatine kinase persisted elevated for 18 months. Involved statins were atorvastatin, simvastatin, rosuvastatin and fluvastatin. Conclusion: Early recognition of muscle symptoms is required to prevent rhabdomyolysis. Further researchare needed to completely elucidate the pathophysiology of statin-induced muscular adverse effects.

Background: Adverse drug reactions (ADR) are considered any harmful and unintended side effects associated with the use of a drug at the usual therapeutic dose, in which skin is involved in most cases. Therefore, the availability of epidemiological information on reactions, reaction patterns, and their causative drugs can be helpful in timely diagnosis and necessary measures, such as caution in prescribing causative drugs to prevent these types of reactions. Methods: In this retrospective descriptive study, the archived files of patients with dermatoses due to ADR referred to Taleghani University Hospital, Urmia, Iran, during 2015-2020 were studied. Patterns and frequency of skin reactions, demographic data, and the frequency of chronic comorbidities were identified. Results: A total of 50 patients with drug-induced skin rash were found, of which 14 were male (28%) and 36 were female (72%). Skin rashes were most frequently found in patients aged 31-40 years. In 76% of patients, there was at least one chronic underlying disease. The most common reaction pattern was maculopapular rash (44%), and the most common causative drugs were antiepileptic drugs (34%) and antibiotics (22%). Mortality was found in 4 cases, which was due to antibiotics and antiepileptic drugs that caused toxic SJS/TEN and erythroderma. The hospital stays were highest in SJS and lowest in a maculopapular rash. Conclusion: Knowledge about the epidemiology and the frequency of adverse drug reactions may be helpful in increasing the awareness of physicians for correct and rational drug prescriptions, which can reduce unnecessary hospital referrals and treatment costs.

Background: Early signal detection from post-marketing studies play a vital role in the safety of patients. Recent case reports have indicated the association of clindamycin with renal failure acute. However, renal failure acute is not known to be associated with clindamycin. The aim of the study was the identification of the potential signal of clindamycin-associated renal failure acute. Methods: The OpenVigil 2.1-MedDRA-v24 was used to query the FAERS database. The Reporting Odds Ratio (ROR) with a 95% confidence interval, was used to assess the association between clindamycin and renal failure acute. Results: A total of 22326 cases associated with renal failure acute were found in OpenVigil 2.1- MedDRA-v24. Among these 125 were associated with clindamycin. The ROR was found to be 3.2 (2.7, 3.8) which indicates a statistically significant association between clindamycin and renal failure acute reporting. The signal strength was decreased after removing the cases of concomitantly administered drugs, however, the association of clindamycin with renal failure acute reporting remains statistically significant. The subgroup analysis results have also shown a positive signal of clindamycin with renal failure acute. Conclusion: The current study identified a positive signal of clindamycin as renal failure acute. However, further validation and causality assessment are required.

Background: Nutritional factors in developing some malignancies have been investigated recently. Objective: In this study, we evaluated the role of vitamin D in advanced laryngeal cancer and its association with the development of pharyngocutaneous fistula (PCF) following total laryngectomy. Study Design: A cross-sectional, case-control study was conducted. Methods: Fifty-five patients with advanced laryngeal cancer referred for total laryngectomy were included. We also considered 55 healthy individuals after matching age and sex as a control group. Serum levels of 25(OH)D3 were measured using a commercially available enzyme-linked immunosorbent assay (ELISA) kit. The association of serum 25(OH)D3 with PCF following total laryngectomy was also determined. Results: Vitamin D was significantly lower in patients with advanced laryngeal cancer than in the control group (p < 0.001). Moreover, our results showed that a mean serum concentration of 25(OH)D3 in patients with PCF was significantly lower than in patients without PCF (p < 0.001). Conclusion: Vitamin D deficiency is highly prevalent in advanced laryngeal cancer, most pronounced in those who develop a PFC following total laryngectomy.

Background: Methemoglobinemia is a life-threatening disorder, with levels above 1 percent considered abnormal and typically resulting from drug or toxic substance exposure. Case Presentation: In this study, we describe a case of a 43-year-old woman with a long-standing complaint of fatigue. Iron deficiency anemia was diagnosed based on the blood test findings of hemoglobin of 101 g/L, mean red blood cell volume of 75 fL, ferritin of 2.81 ug/L, transferrin saturation of 4.3 percent, and C-reactive protein of 0.6 mg/L. As a preferred treatment option, 1000 mg ferric carboxymaltose on two distinct days was preferred. After administering the first dose of the medication, we noticed incidentally that methemoglobin levels increased to 2.3%. When venous blood gas was repeated before and after administration of the second dose of the drug, methemoglobin levels were found to be 0.8% and 1.8%, respectively. There was no change in vital signs in both two dosages, and she only suffered a temporary sore throat. Her anemia improved with intravenous iron therapy, and she is currently being followed in our clinic. Conclusion: No case or research reporting an increase in methemoglobin levels following oral and/or intravenous treatment to patients with iron deficiency anemia has been found in the literature. Therefore, this is the first contribution to the existing literature.

Introduction: We reported a patient with rheumatoid arthritis who received chronic methotrexate (MTX) therapy and experienced several adverse reactions like hemocytopenia and renal impairment. Under the monitoring of the therapeutic drug concentration, calcium folate and other measures were used to accelerate methotrexate excretion and eliminate adverse reactions. Case Presentation: A 66-year-old man with rheumatoid arthritis received MTX and developed adverse effects of bone marrow suppression, like pancytopenia. He had a black stool, and he tested positive for occult blood, which was considered gastrointestinal bleeding. The blood MTX concentration reached 4.07 μmol/L, and leucovorin was administered to rescue the patient's life. Besides, hydration and alkaline urine were applied to quickly clear methotrexate inside the body. Conclusion: Low-dose MTX has fewer adverse reactions but may cause bone marrow suppression- related side effects. Blood concentration monitoring can be used to guide the rescue of MTX poisoning.

Background: Phenprocoumon is a vitamin K antagonist that is widely prescribed in Europe and Latin America for the prophylaxis and treatment of thromboembolic events. Case Presentation: A 90-year-old female was admitted to our hospital with tonic-clonic seizures, possibly due to dementia syndrome. Valproic acid (VPA) was prescribed for the treatment of seizures. VPA is an inhibitor of cytochrome P450 (CYP) 2C9 enzymes. A pharmacokinetic interaction with phenprocoumon occurred, which is a substrate for CYP2C9 enzymes. The interaction resulted in a strong INR increase and subsequent clinically relevant bleeding in our patient. Valproic acid is not specifically mentioned in the phenprocoumon drug label as a CYP2C9 inhibitor, and in the Dutch medication surveillance database, no medication alert is shown when prescribing this combination, and no interaction with phenprocoumon has been reported so far. Conclusion: When prescribing this combination, the prescriber should be warned and advised to intensify INR monitoring if the combination is to be continued.

Background: The development of direct-acting antivirals directed against the Hepatitis C Virus has dramatically modified the therapeutic approach to chronic hepatic viral disease. Larger use of such drugs has also led to increasing reports about their adverse effects. This report aimed to describe a case of leucocytoclasic vasculitis following treatment based on the sofosbuvir/ledipasvir regimen with complete disappearance shortly after withdrawal in a 61-year-old patient treated for genotype 1 hepatitis C. Case Presentation: A 61-year-old Tunisian woman with a history of hepatitis C virus genotype 1 infection developed palpable purpura in front of low extremity articulation, five weeks after the onset of sofosbuvir/Ledipasvir. The histological examination concluded with leucocytoclasic vasculitis, with total disappearance three days after withdrawal. The pre-therapeutic assessment showed no positivity of Cryoglobulinemia. Anti-neutrophil cytoplasmic antibodies (ANCA) were negative. A sustained viral response was obtained only 5 weeks after treatment without an increase of viral load during follow-up. Conclusion: There was a temporal relationship between antiviral treatment and non-ANCA skin vasculitis. The pharmacological department concluded the imputability of antiviral treatment (score I2B2).

Introduction: Pantoprazole is a proton pump inhibitor mainly used to treat conditions causing excess stomach acid. Stevens-Johnson syndrome (SJS) is a rare bullous disease. The main etiologic factors are drugs, especially antibiotics, anticonvulsants, oxicam and allopurinol. Proton pump inhibitors have been rarely reported as a causative agent in SJS, and only sporadic cases secondary to pantoprazole have just been mentioned in the literature. Case Report: A 49-year-old woman was referred to the dermatology department for a pruritic generalized eruption, associated with erosive cheilitis. The patient reported self-medication by pantoprazole for two weeks. Physical examination revealed target-like lesions with bullous center in some areas. A skin detachment on the left breast and the neck affecting 10% of the total body surface area was observed. Mucosal examination revealed erosive, painful cheilitis covered by large hemorrhagic crusts and erosions of the nasal cavity. The lesions cleared completely few days after pantoprazole withdrawal and local corticosteroids. Further investigations ruled out infectious etiologies. Conclusion: This case highlights the possible occurrence of hypersensitivity reactions due to the use of a PPI, which is a widely used medication and a generally well-tolerated drug.

>Introduction: Linezolid is increasingly utilized to treat gram-positive bacteria that are resistant to other antibiotics like vancomycin-resistant Staphylococcus aureus, methicillinresistant Staphylococcus aureus as well as drug-resistant tuberculosis. It acts by inhibiting protein synthesis in bacteria. Although it is a relatively safe medicine, many reports of hepatotoxicity and neurotoxicity linked to long-term usage have been received but patients with pre-existing risk factors, such as diabetes and alcoholism, may have toxicity even after short-term use of linezolid. Case Presentation: Here we are presenting a case of a 65-year-old female with diabetes who developed hepatic encephalopathy after one week of treatment with linezolid prescribed for nonhealing diabetic ulcer after a culture sensitivity test. After the use of linezolid 600 mg BD for 8 days patient developed altered sensorium and breathlessness and had high bilirubin, SGOT, and SGPT. She was diagnosed with hepatic encephalopathy. Linezolid was withdrawn and after 10 days all laboratory parameters for liver function test were improved. Conclusion: Care should be taken when prescribing linezolid in such patients with pre-existing risk factors as they are prone to develop hepatotoxic and neurotoxic adverse effects even after short-term use of linezolid.

Introduction: Reported cases after the post-commercialization phase of mRNA vaccines against COVID-19 have revealed that myocarditis and pericarditis may occur predominantly in male adolescents after the second dose of the vaccine. Case Presentation: We report two cases of cardiac disorders associated with mRNA COVID-19 vaccination, both of them in 15 year-old males. One of the patients presented acute pericarditis and the second one presented acute myocarditis with left ventricular dysfunction at hospital discharge. Discussion and Conclusion: Physicians should be aware with the typical manifestations of these cardiovascular events after the vaccination and report suspicious cases to pharmacovigilance agencies as soon as possible. The population should rely on the pharmacovigilance system that continues to recommend vaccination as the most effective strategy to reduce the negative consequences of the pandemic.