Birth defects observed with maternal carbimazole treatment: Six cases reported to Nice's Pharmacovigilance Center.

GOALS: To report cases of embryopathy occurring following first trimester exposure to anti-thyroid drugs. METHODS: Retrospective screening of the database of our Pharmacovigilance Center from 1987 to date. RESULTS: We report six cases of embryopathy, all following carbimazole exposure during the first trimester: two cases of abdominal wall defect, including one associated with facial dysmorphia; one case of digestive malformation (patent omphalomesenteric duct); two cases of aplasia cutis including one with facial dysmorphism; one case of bilateral choanal atresia with aorta coarctation associated with poorly controlled insulin dependent diabetes. Four out of five patients were euthyroid with treatment during the first trimester. We found a context suggesting genetic predisposition to congenital malformation in three cases: two cases of parental cleft lip/palate, one case of consanguinity. Outcome was favorable in all cases. CONCLUSIONS: We want to raise awareness about the potential teratogenicity of carbimazole, probably on a predisposed genetic background. We suggest better reporting of congenital anomalies in children of women with Graves'disease, with or without in utero exposure to anti-thyroid drugs. In light of current literature, propylthiouracil should be the first line treatment for hyperthyroid women wishing a pregnancy.

Adverse effects of parenteral antimicrobial therapy for chronic bone infections.

Responsible pathogens of chronic bone infections (CBI) are frequently resistant, requiring parenteral antimicrobial therapy. Therefore, adverse effects may be observed. We have determined the rate of adverse effects of antimicrobial therapy for CBI in a retrospective study of all patients receiving parenteral drugs via an implantable port. Patients from one medical ward (n = 89) and from one surgical ward (n = 40) between January 1995 and December 2005 were included in this study. The CBI included were 85 osteomyelitis (66%) and 44 prosthetic joint infections (34%). The main group of pathogens was gram positive cocci (n = 144; 65%). The total duration of antibiotic treatment was 205 +/- 200 days, including 133 +/- 100 days for parenteral therapy. Thirty-three catheter-related complications were observed in 27 patients (21%). All complications led to hospitalization but none led to death. Twenty-one antibiotic-related complications occurred in 18 patients (16%), and one allergic reaction led to death. The mean duration of follow-up was 290 days. Remission was observed in 84 patients (65%). In multivariate analysis, adverse effects were mostly observed in the medical department. Adverse effects affect at least one third of the patients treated for CBI with parenteral antimicrobial therapy and are related to both the implantable port and the antibiotic compounds.

[Topiramate and acute myopia with angle-closure glaucoma: case report and literature review]. / Topiramate et myopie avec crise aiguë de fermeture de l'angle irido-cornéen: cas clinique et revue de la littérature.

Topiramate, an antiepileptic medication, has been widely used since its recent indication for migraine prophylaxis. We report a case of bilateral angle-closure glaucoma and acute myopia in a 44-year-old woman on oral topiramate therapy initiation for migraine prophylaxis. Intraocular pressure was 31 mmHg right and 32 mmHg left, myopia was 4 diopters. Topiramate was interrupted and general and local hypotensive treatment begun and rapidly stopped after improvement. Iridotomy was also performed. Fifteen days later, complete resolution was observed on ophthalmologic examination: anterior chambers were deep, myopia fully regressed, intraocular pressure returned to normal, and the visual field was complete. This new case prompts discussion on current reports in the literature and French drug monitoring database cases in this context.

[Alveolar hypoxemic interstitial pneumonia related to rituximab therapy]. / Une pneumopathie alvéolo-interstitielle hypoxémiante associée à la prise de rituximab.

INTRODUCTION: Rituximab is indicated for the treatment of low-grade lymphoma. Pulmonary toxicity related to rituximab is exceptional. CASE REPORT: Here we report a patient with non-Hodgkin lymphoma treated with "CHOP" chemotherapy (cyclophosphosphamide, adriamycin, vincristine and prednisolone) and rituximab who developed an interstitial pneumonia with acute respiratory failure. The differential diagnosis of this clinical and radiological diagnosis is discussed. CONCLUSION: Although cases of interstitial pneumonia associated with rituximab are rare, they may be severe and thus any patient experiencing respiratory symptoms on this therapy should be monitored closely.

Iatrogenic Cushing's syndrome in an HIV-infected patient treated with inhaled corticosteroids (fluticasone propionate) and low dose ritonavir enhanced PI containing regimen.

In HIV-infected patients, ritonavir, a potent cytochrome P450 inhibitor, is increasingly used to improve the pharmacokinetic profile of the associated protease inhibitor. HIV physicians are often faced with potential drug-drug interaction while treating associated diseases. We report the case of an HIV-infected patient with clinical features of Cushing's syndrome due to the interaction of low dose ritonavir with inhaled fluticasone propionate (FP). Safety of life-long CYP450 inhibition has still to be demonstrated.

[Anti-TNF alpha monoclonal antibodies (infliximab) and tuberculosis: apropos of 3 cases]. / Anticorps anti-TNF alpha (infliximab) et tuberculose: à propos de trois cas.

INTRODUCTION: Monoclonal TNF alpha antibodies are a new treatment of severe rheumatoid arthritis. One of the possible side effects is the appearance of opportunistic infections. We report here on three cases of disseminated tuberculosis observed in patients undergoing treatment with infliximab. EXEGESIS: A 45-year-old woman, treated with infliximab, was hospitalised after five infusions for fever and dyspnoea. The exams showed pulmonary and peritoneal tuberculosis. The second case is a 75-year-old woman whose symptoms were fever, cough and cervical adenopathy after three infliximab infusions. Diagnosis was disseminated tuberculosis. The third case is a 59-year-old man who was hospitalised for an infectious syndrome with dyspnoea, after two infliximab infusions. We discovered pulmonary tuberculosis. CONCLUSION: These three cases added to the 68 cases of tuberculosis registered with the treatment of infliximab. This confirms the risk of severe opportunist infectious side effects. TNF alpha is a cytokine which has anti-infectious properties. These tuberculoses are severe and generalized. It is recommended to search for an active or latent tuberculosis before beginning treatment with infliximab, and to check these patients frequently.

Nitroso-urea-cisplatin-based chemotherapy associated with valproate: increase of haematologic toxicity.

BACKGROUND: The incidence of haematologic toxicity of valproate (VPA) ranges from 1% to 32% and consists mainly of asymptomatic, dose-dependent thrombopenia. We describe a potentiation of haematologic side-effects of nitroso-urea (NU) when prescribed in association with VPA. PATIENTS AND METHODS: We followed a cohort of 70 patients (58 men, 22 women, mean age: 56 years, range 20-75 years). Patients with high-grade gliomas were treated with up-front chemotherapy regimen consisting of fotemustine (d3: 100 mg/m2), cisplatin (d1-3: 33 mg/m2) and etoposide (d1-3: 75 mg/m2) followed by whole brain radiotherapy at progression. Sixty patients required anti-epileptic drugs (AED) for either a single, well-documented epileptic seizure, or immediatly initiated after neurosurgical procedures. AED included VPA (35 of 60), phenobarbital (PB) (17 of 60), carbamazepine (CBZ) (2 of 60) and phenytoin (PHT) (3 of 60). Two patients had both PB and CBZ and one PB and PHT. RESULTS: Haematologic toxicity (grade 3-4 thrombopenia, neutropenia or both) was observed in 37 of 70 (52.85%) patients. Among them 24 (65%) had VPA. Group C were patients treated with fotemustine alone with or without VPA (23 patients). CONCLUSION: When prescribed in association with a fotemustine-cisplatin regimen, VPA treatment results in a three-fold higher incidence of reversible thrombopenia, neutropenia or both. Haematologic side-effects decrease after AED modification during the continued chemotherapy. This adverse event should be managed with caution.

[Drug-induced oral ulcerations]. / Les ulcérations orales d'origine médicamenteuse.

Different side effects of drugs have been described in the oral cavity, including oral ulcerations. Direct contact between drugs and oral mucosa may induce chemical burn or local hypersensitivity. Less frequently, these drug-induced oral ulcerations are part of a complex reaction with cutaneous or systemic manifestations. Sometimes, one or more oral ulcerations appear as the main side-effect of a drug, or exceptionally as solitary lesions. Solitary oral ulcerations usually appear after few weeks of treatment. In most of cases, these lesions resist to conventional treatments, with a rapid healing following the suppression of the responsible drug. This diagnosis is usually difficult, particularly with patients receiving multiple drug therapy. Besides, special attention must be paid to new drugs. Oral ulcerations following symptoms of burning mouth, metallic taste, dysgueusia or agueusia are strongly suggestive of a pharmacological origin. Most of the molecules able to induce solitary oral ulcerations are commonly prescribed in a) rheumatology: NSAI (diclofenac, flurbiprofen, indomethacin, naproxen), long-term rheumatoid arthritis therapy (azathioprine, methotrexate, penicillamine, gold compounds, tiopronin); b) cardiology: angiotensin-converting-enzyme inhibitors (captopril, enalapril), angiotensin 2-receptor antagonist (losartan), anti-angorous (nicorandil), c) psychiatry: antidepressants (fluoxetine, lithium), d) AIDS therapy (foscarnet, zalcitabine).

[Pharmacovigilance in practice]. / La pharmacovigilance en pratique.

Directed by the French Agency for the Safety of Health Products (AFSSAPS), the French pharmacovigilance system is in charge of the surveillance of drugs after they have been provided by AFSSAPS with official marketing authorizations that are in France either 'new drug approval certificates' (AMM) or 'temporary utilization authorizations' (ATU). About 3,700 pharmaceutical products are concerned which are used either for treatment (all drugs and remedies, inclusive plasma-derived blood products), prevention (vaccines, oral contraception), diagnosis (contrast products, ...), or to modify a physiologic function (general or local anesthetics). At the national level, the main actors of the system are AFSSAPS and its National Commission, the 31 Regional Centers of Pharmacovigilance, all the health professionnals, and the pharmaceutical laboratories. Health professionnals are held to notify any suspected serious or unexpected adverse effects as quickly as possible. The analysis of data collected by the national report bank permits alerts and inquiries about drug safety. Furthermore regional centers of pharmacovigilance are responsible for drug information. The French pharmacovigilance system works in cooperation with the European Agency for the Evaluation of Medicinal Products.

[Visceral leishmaniasis associated with Wegener disease. Use of lipid complex amphotericin B and liposomal amphotericin B]. / Leishmaniose viscérale associée à une maladie de Wegener. Utilisation de l'amphotéricine B en complexes lipidiques et de l'amphotéricine B liposomale.

BACKGROUND: Leishmaniasis in a patient with Wegenerís disease raises the problem of amphotericin toxicity further compromising the pre-existing renal disorder. CASE REPORT: An anemic patient treated for Wegenerís disease developed visceral leishmaniasis. This renal failure patient was treated with lipid complex amphotericin B and liposomal amphotericin B. We report outcome at 10 months follow-up. DISCUSSION: The new formulations of amphotericin B allow effective treatment of visceral leishmaniasis in renal failure patients. Long-lasting results are probably favored by the interruption of immuno-suppressive therapy.

Acute hepatitis, autoimmune hemolytic anemia, and erythroblastocytopenia induced by ceftriaxone.

An 80-yr-old man developed acute hepatitis shortly after ingesting oral ceftriaxone. Although the transaminases gradually returned to baseline after withholding the beta lactam antibiotic, there was a gradual increase in serum bilirubin and a decrease in hemoglobin concentration caused by an autoimmune hemolytic anemia and erythroblastocytopenia. These responded to systemic steroids and immunoglobulins. Despite the widespread use of these agents this triad of side effects has not previously been reported in connection with beta lactam antibiotics.

Efficacy and safety of vancomycin constant-rate infusion in the treatment of chronic Gram-positive bone and joint infections.

OBJECTIVE: To evaluate the efficacy and safety of vancomycin constant-rate infusion over 24 h in the treatment of Gram-positive bone infections, METHODS: Vancomycin (40 mg/kg/day) was administered without a loading dose to 15 patients (12 male, three female) aged 23--90 years, weighing 46--85 kg, with postoperative chronic bone and joint infections. The 24-h dose was adjusted to maintain plasma levels between 25 and 35 mg/L. Mean duration of therapy was 6.2 months (4--8.5) via a portable infusion pump. Sites of infection included hip and femur (10), tibia (three), patella (one) and vertebrae (one). Sequestrectomy (two), removal of material (7/8 prosthetic hips, 1/5 metal implants) and debridement (two) were performed at the beginning of the treatment. Involved bacteria included Staphylococcus aureus (eight, six methicillin resistant), S. epidermidis (four methicillin-resistant), Enterococcus faecalis (one), Enterococcus avium (one) and Streptococcus bovis (one). RESULTS: MIC of vancomycin ranged from 1 to 4 mg/L. The mean vancomycin bone concentration when available was 67.7plus minus38.9 microg/L. Based on a mean post-treatment follow-up of 14plus minus4 months (6--20.6), cure was achieved in 10 patients (66.6%). Failures were related to the inability to remove the infected prosthesis (one) or implants (three) and to the persistence of a deep wound abcess (one). Adverse events included pruritus (four cases), tinnitus (two), mild transient elevation of creatinine level (three) and transient neutropenia (two). Vancomycin was maintained in all the patients. CONCLUSIONS: Prolonged treatment with vancomycin constant-rate infusion is effective and safe for treatment of Gram-positive chronic bone and joint infections, providing that complete surgical débridement and prosthetic material removal are performed.

[Public health education integrated in hospital. An internship proposal, "Medical information and pharmacology"]. / Enseignement de santé publique intégré aux stages hospitaliers. Une proposition de stage "Information médicale et pharmacologie".

According to a recent circular reforming french medical studies, we propose a teaching of medical information and pharmacology in situ within hospital instructions. Students could acquire an investigation methodology on the medicine economy. It will cover in four sessions the succeeding stages of medical information processing and be subject to an assessment: case studies and appreciation on student's, instruction record. By combining public health teaching with clinical practice, our project promotes its development in contact with other learnings and activities such as clinical research.