Guillain-Barré syndrome after COVID-19 vaccines: A Tunisian case series.

As the COVID-19 vaccination campaign progresses worldwide, Guillain-Barré syndrome (GBS) vaccine-related cases have been reported. We carried out a retrospective, descriptive study of GBS patients following COVID-19 vaccine, submitted to the National Pharmacovigilance Center of Tunis during the period between March 2021 and May 2022. Our study aimed to identify epidemiological and clinical features of COVID-19 vaccine-associated GBS. We found 9 cases of GBS post COVID-19 vaccination; 5 of them were excluded due to the lack of information, whereas 4 cases were included in this study. Men represented 75% (3/4) of the cases. The most frequently reported vaccine type was ChAdOx1 nCoV-19 vaccine (n = 2 reports [50%]), Ad26.COV2.S vaccine and BNT162b2 vaccine in 1. The mean time interval from vaccination to symptom onset was 15.3 days. Clinical manifestations were different: classical GBS in two cases and GBS with unilateral facial palsy in the other 2 cases. All patients were treated with a course of intravenous immunoglobulin for 5 days. Three patients reported clinical improvement while one case (25%) showed treatment-related fluctuations. Our observations suggest that COVID-19 vaccines may be associated with GBS. Continuous surveillance and further studies are warranted to assess the significance of the association.

[Antiepileptic drugs administration by nasogastric tube in comatose patients]. / Modalités d'administration des antiépileptiques par sonde nasogastrique chez des patients comateux : étude des connaissances, attitudes et pratiques.

AIM: To evaluate the modalities of administration of antiepileptic drugs (AED) with nasogastric tube (NGT) by nurses and to draw up recommendations. METHODS: Our study consisted on investigating the modalities of administration of AED's with NGT by nurses during four months. We prepared 10 questions including demographic information. Participation was voluntary and anonymous. The questionnaire was distributed in seven intensive care departments after authorization of each head of the department. Thus, 45 nurses were included. RESULTS: Nurses sex ratio was 1.5 and mean age was 31 years (25 to 37 years). Among the nurses, 60% mentioned that the NGT were silicone made and 4% that they were PVC made. The mean duration before replacing the NGT was thought to be 5±3 days. Among the nurses, 91% affirmed to clear the NGT after each use. All the nurses had agreed that the solid form is the most commonly used pharmaceutical form in the NGT. AED were associated with the enteral feeding solution in 56%. The AED should be crushed before administration for 98% of the nurses even in case of polymedication. Among them, 62% recommended to crush all of the associated drugs together. Before introducing the AED into the NGT, 93% of the nurses reported mixing with tap water. We have noticed that 62% of nurses felt the need to improve their knowledge AED administration with NGT. CONCLUSION: To optimize AED therapy, modalities of administration by NGT in epileptic comatose patients should be enhanced.

Therapeutic monitoring of antiepileptic drugs in comatose patients.

OBJECTIVE: In this study, we aimed to analyze the trough plasmatic levels (C0) of the antiepileptic drugs (AED) administered by nasogastric tubes (NGT) in comatose patients and to draw up recommendations for therapeutic drug monitoring (TDM) and for the modalities of AED administration by NGT. METHODS: We conducted a retrospective study on comatose patients addressed over six years and 10 months in Clinical Pharmacology for C0 measurement of AED administered by NGT. RESULTS: In this study, the sex-ratio was 2.38 (44 patients). The patients' median age was 24 years. There was 14.5% of children (≤16 years). Among the 103 samples, C0 measurement concerned valproic acid in 57%, phenobarbital in 28 % and carbamazepine in 15%. Two AED or more were associated in 42% of patients. AED were associated to other drugs in 85% of cases. The AED C0 were subtherapeutic in 71% of cases. C0/Dp lower than recommanded in 65 %. In these samples, 55% presented at least one drug association with the concerned AED. In 45% of the cases, there was no drug association but a non-respect of modalities of AED administration by NGT in patients. CONCLUSION:   The drug monitoring is a useful tool to assess drug-drug interactions and to control modalities of AED administration in comatose patients.

Fatal Kounis syndrome with stent thrombosis secondary to amoxicillin/clavulanic acid use: A case report and literature review.

Anaphylactic reactions are often induced by drugs, and the most frequent ones are penicillin derivates. The concurrence of acute coronary syndrome with hypersensitivity and anaphylactic or anaphylactoid reactions constitutes the Kounis syndrome. We report a case of a coronary stent thrombosis with a fatal outcome complicating an anaphylactic shock induced by amoxicillin-clavulanic acid association. A 58-year-old woman with a history of triple coronary stenting was treated by amoxicillin/clavulanic acid association for pharyngitis. One hour after the first drug intake, she developed an anaphylactic shock with acute constricting chest pain. She received intravenous hydrocortisone and was transferred to emergency department. The patient received epinephrine intravenously with fluid perfusion and oxygen. Electrocardiogram showed Pardee waves in the anterior precordial leads. Cardiac enzyme levels (troponin I) were disturbed. The patient was transferred to the coronary care unit with a diagnosis of acute myocardial infarction. The coronary angiography revealed anterior interventricular stent thrombosis. The patient experienced a cardiogenic shock with an important hemodynamic repercussion, and she died few hours later despite emergency care. The responsibility of amoxicillin-clavulanic acid association was retained in the genesis of this anaphylactic shock in front of a suggestive delay, a compatible evolution and a high semiotic score. Amoxicillin/clavulanic acid use may cause Kounis syndrome. The use of epinephrine is a challenging decision. We suggest that Kounis syndrome should be considered in the differential diagnosis of acute coronary syndrome.

DRESS Syndrome Following Levofloxacin Exposure With Positive Patch-test.

Drug rash with eosinophilia and systemic symptoms (DRESS syndrome) in a severe cutaneous drug reaction, which can be life threatening. Levofloxacin has not been reported in literature as a causative drug. We are presenting an exceptional case of levofloxacin-induced DRESS without eosinophilia and with positive patch-tests to levofloxacin.

Bullous Eruption Associated With Dihydropyridines With Cross Reactivity.

The spectrum of cutaneous eruptions associated with dihydropyridines is extensive, varying from exanthemas to severe adverse events. We report a case of bullous eruption, one month after starting nicardipine and lercanidipine. The same symptoms recurred few days after taking nitrendipine.

Facial hyperpigmentation during imatinib therapy for gastrointestinal stromal tumor.

We report a rare case of facial hyperpigmentation during imatinib therapy for a gastrointestinal stromal tumor.

[Fixed pigmented erythema antihistamine H1: about 2 cases and review of the literature]. / Érythème pigmenté fixe aux antihistaminiques H1 : à propos de 2 cas et revue de la littérature.

We describe two cases of fixed drug eruptions induced by pheniramine (1(st) case) and loratadine (2(nd) case).

[Not Available]. / Érythème pigmenté fixe aux antihistaminiques H1 : à propos de 2 cas et revue de la littérature.

We describe two cases of fixed drug eruptions induced by pheniramine (1(st) case) and loratadine (2(nd) case).

Lichen associated with metformin.

We report an exceptional case of bullous lichen induced by metformin in a patient with diabetes mellitus.

Drug-Drug Interaction between Tacrolimus and Fluconazole in a Kidney Transplant Recipient.

We report a case of tacrolimus and fluconazole drug-drug interaction in a 20-year-old female kidney transplant recipient with stable kidney function. The patient's tacrolimus blood concentrations were in the therapeutic range until fluconazole was administrated for Candida albicans infection, on day 58 posttransplant. Tacrolimus blood concentration increased by 125% (18.4 ng/mL) on day 79 and by 212% (25.4 ng/mL) on day 84 posttransplant. On day 92, tacrolimus trough blood concentration returned to the therapeutic range (5.6 ng/mL), with decrease of tacrolimus daily dose by 50% (to 4 mg). After fluconazole withdrawal, the patient was returned to the initial tacrolimus daily dose (8 mg) to maintain a tacrolimus trough blood concentration in the therapeutic range. Fluconazole coadministration with tacrolimus shows a significant clinical effect on tacrolimus trough blood concentration in kidney transplant patients. Maintaining a tacrolimus trough blood concentration in the therapeutic range is crucial for these patients; therefore, physicians should be aware of fluconazole prescriptions.

Interaction Between Tacrolimus and Proton Pump Inhibitor in a Kidney Transplant Recipient.

We aimed to present a drug monitoring profile of tacrolimus and proton pump inhibitor coadministration in a 23-year-old male patient with a history of high blood pressure who underwent kidney transplant. The patient's serum trough levels of tacrolimus were in the therapeutic range until omeprazole 20 mg daily was prescribed. Tacrolimus trough serum level increased to 29.5 ng/mL under the same daily dose and to 13.9 ng/mL after tacrolimus daily dose was decreased to 6 mg/day. This increase in tacrolimus serum level was behind a renal function alteration. After withdrawal of omeprazole, tacrolimus trough serum level returned to the therapeutic range. Because interactions between tacrolimus and omeprazole could result in toxicities, careful monitoring of tacrolimus serum levels should be considered to adjust the dosage.

Therapeutic Drug Monitoring of Tacrolimus in Tunisian Renal Transplant Patients during the Tuberculosis Infection: A Retrospective, Observational, Single-centre Analysis.

Tuberculosis is a challenge in organ transplantation due to the interaction between Anti- Tuberculosis Treatment (ATT) and immunosuppressive drugs, such as Tacrolimus (TAC). This study aimed to assess this interaction and discuss the guidelines used in this specific case. METHODS: A retrospective, observational, single-center analysis was performed at the Department of Clinical Pharmacology (National Centre of Pharmacovigilance, Tunisia). We analyzed the database of patients who received TAC from 2009 until 2018. We included samples provided from renal transplant patients infected by Mycobacterium tuberculosis after transplantation. Trough blood levels (C0) were determined using an immunoassay analyzer. The Therapeutic Range (TR) of TAC was considered between 5 and 10 ng/mL. Pharmacokinetic parameters were compared between the period of co-administration of TAC/ATT (period A) and the period during which patients received only TAC (period B). RESULTS: Seven renal transplant patients treated by TAC were included. 41 samples were analyzed (16; period A, 25; period B). Only 6 % of C0 values were found within TR during period A, while this rate was 44% during period B. During period A, 88% of TAC C0 was under the lower limit of TR, indicating a high risk of transplant rejection. The mean C0 and C0/D were significantly lower during period A (3.11±1.53 ng/mL vs 7.11 ± 3.37 ng/mL; p = 0.001 and 33.06 ± 24.89 vs 83.14 ± 44.46; p = 0.0006, respectively), without difference in doses between periods. CONCLUSION: Considering the results of this study, clinicians are suggested to monitor TAC closely in this particular circumstance.

DRESS Syndrome Associated with Liposomal Amphotericin-B in a Kidney Transplant Patient: A Case Report.

INTRODUCTION: Liposomal amphotericin B is a widely used broad-spectrum antifungal drug. It was developed to reduce nephrotoxicity and maximize the therapeutic utility of amphotericin B in the treatment of invasive fungal infections. Drug Rash with Eosinophilia and Systemic Symptoms (DRESS) syndrome is a severe drug-induced hypersensitivity syndrome commonly associated with aromatic antiepileptic drugs. Liposomal amphotericin-B was associated with DRESS syndrome in only one case. CASE REPORT: We report an exceptional case of possible DRESS syndrome associated with liposomal amphotericin B in a 31-year-old male renal transplant recipient. Seventeen days after starting liposomal amphotericin B for visceral leishmaniosis, he developed a skin rash with elevated liver tests. Liposomal amphotericin B was then discontinued. A favourable outcome was slowly observed in one month. RESULTS AND CONCLUSION: This case scored two (possible case) based on the criteria adopted by the European group RegiSCAR. The Naranjo score for liposomal amphotericin B was four (possible).

Erythema multiforme reactions following Pfizer/BioNTech (tozinameran) vaccination: two case-reports with positive rechallenge and review of the literature.

AIM: Pfizer/BioNTech (BNT162b2) is a COVID-19 vaccine with a reassuring safety profile. The main adverse reactions are mild local reactions. Cutaneous reactions are generally minor. The most common cutaneous reaction reported was a local injection-site reaction. CASE STUDY: Here we present 2 cases of erythema multiform (EM) following BNT162b2 vaccination with positive rechallenge. The 1st case was about a 51-year-old woman who developed 5 days after the 1st dose of the mRNA Pfizer/BioNTech (BNT162b2) a macular, erythematous, round-shaped lesions on the hands, knees and soles. She experienced a positive rechallenge one month later. In the 2nd case, a 55-year-old man presented 6 days following the 2nd shot of the mRNA Pfizer/BioNTech (BNT162b2), targetoid eruption on the upper and lower members. The patient reported that he had the same skin lesions in ankles and soles few days following the 1st shot of the same vaccine. CONCLUSION: Few cases of EM following COVID-19 vaccination were reported in the literature and positive rechallenge in only one case. Rechallenge was not performed in most cases. Our two cases are particular because of the positive rechallenge in both patients. This is the gold standard to confirm that the vaccine was the culprit agent in inducing EM.

Cutaneous adverse effects of antiepileptic drugs.

Antiepileptic drugs (AED) are widely used in therapy. They are mainly indicated in the treatment of epilepsy and some psychiatric pathologies as well as for their analgesic action. Their cutaneous adverse effects (CAE) are common, often mild but sometimes serious. The aim of this work was to study the epidemiological and clinical features of CAE occurring in adults and elderly patients (aged over 20 years-old) and to identify the most implicated AED. We conducted a descriptive retrospective study over a period of five years from January 2017 to December 2022 about CAE of AED in adults and elderly patients notified to The National Center Chalbi Belkahia of Pharmacovigilance (Tunis,Tunisia). All cases were analyzed according to the updates French methods of imputability. We collected 71 cases of patients aged over 20 years old who presented CAE to AED. The age ranged from 20 to 79 years (mean age=44.8 years). The sex ratio F/M was 0.7. AED were indicated for neurological pathology in 70.5% of cases, for psychiatric pathology in 15.9% of cases and for their analgesic action in 12.9% of cases. Epilepsy was the first indication (51.1% of cases). The most notified CAE in our study were drug reaction with eosinophilia and systemic symptoms (DRESS syndrome; 34% of cases), maculopapular exanthema (MPE; 26% of cases), erythematous rash (8% of cases) and photosensitivity in 5% of cases. Severe cutaneous adverse reactions were accounted for 37% of all CAE. The most implicated AED were carbamazepine (52%), phenobarbital (24%) and lamotrigine (18%). However, further study with a larger number of patients and in collaboration with prescribing physicians are needed to better clarify features of CAE associated with AED intake and specify the risk factors, specific to our Tunisian population.

Serious adverse drug reactions in older adults notified to pharmacovigilance.

PURPOSE: To report the serious adverse drug reactions (ADRs) in older adults notified to pharmacovigilance, to identify the incriminated drugs and to search for risk factors of occurrence. METHODS: A retrospective study including 106 serious adverse drug reactions notified to pharmacovigilance in patients aged of 65 years and more, over a period of 16 years. Imputation was established according to the French method and seriousness according to the World Health Organisation (WHO) criteria. RESULTS: Adverse drug reactions were essentially systemic. Incriminated drugs were mainly antibiotics, allopurinol and cardio-vascular drugs. Gender, age and number of administered drugs did not seem to be risk factors of serious ADRs occurrence. Among older adults, 4% died further to a serious ADRs. CONCLUSION: Systemic notification to pharmacovigilance will allow a better analysis of risk factors of serious ADRs occurrence and to insure safety and health to the older adults.

Adverse drug reactions in older adults: a retrospective study from pharmacovigilance.

PURPOSE: To assess the adverse drug reactions notified in older adults to pharmacovigilance and to identify the incriminated drugs in their genesis. METHODS: A retrospective study including 688 notifications of adverse drug reactions to pharmacovigilance in patients aged of 65 years and more, over a period of 16 years and where the responsibility of one drug or more was incriminated in the genesis of the adverse reaction. Imputation was established according to the French method and seriousness according to the World Health Organization (WHO) criteria. RESULTS: Sex-ratio W/M was 1.2. Average age was 71.3 years. The average number of administered drugs was 3.64 and polymedication was noted in 30% of cases. Adverse drug reactions were essentially cutaneous and systemic. Incriminated drugs were mainly antibiotics and cardio-vascular drugs. Serious adverse drug reactions were noted in 26%. CONCLUSION: In older adults, adverse drug reactions' notification to pharmacovigilance is necessary and allows assessing large scale epidemiologic studies to identify iatrogenic risk factors.

Seizures after vaccines.

Immunization plays an important role in achieving global health goals. Thus, vaccination is one of the essential means of preventing infectious and viral diseases. The onset of adverse events following immunization (AEFI) is common and most of the time it is a mild effect. However, stimulating the immune system during critical periods of brain development can lead to neurological effects. Among the neurological effects, we were interested in this work by seizures appearing following vaccination.

Comparing real-life carbamazepine exposure between innovator and generic formulation.

BACKGROUND: Carbamazepine is an anticonvulsant largely used in the treatment of epilepsy. The use of generic antiepileptic drugs (AEDs) is controversial because of the eventual possibility to loss seizures control. The aim of our study was to compare the concentration over dose ratio of two products containing carbamazepine, the innovator (Tégrétol®-NOVARTIS) and the generic (Taver®-MEDOCHEMIE). METHODS: It is a retrospective study (2009-2016) including 32 patients treated with carbamazepine. Patients were treated initially by innovator then switched to generic or vice versa. All patients have at least one level of carbamazepine plasma concentration (C0) with the innovator or the generic formulation. Monitoring of carabamazepine was made using immunoassay method (ARCHITECT-ABOTT®). RESULTS: The mean age of our patients was 28.4 years and ranged from 2 to 55 years. The sex ratio M/F was 1.46. The mean ratio C0/dose for the innovator group was 0.723 (min/max: 0.017/1.73), and the mean ratio C0/dose for the generic group was also 0.607 (min/max: 0.064/1.68). There was no statistically significant difference between both groups (P=0.16). CONCLUSION: Our results confirm the difference between the innovator and the generic formulation of carbamazepine. So, switching from innovator to generic seems to be safe and exposure to carbamazepine remains the same.