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E Autret-Leca

Publications and source records attributed to E Autret-Leca.

52 records · Page 3Linked to original sources
PubMed1999

[Adverse effects of the vaccines Tétracoq, IPAD/DTCP and DTCP. A French study of regional drug monitoring centers].

UNLABELLED: On request of the French Drug Agency, the Regional Pharmacovigilance Center (RPVC) of Tours has been in charge of the analysis of adverse events (AEs) associated with tetravalent vaccines IPAD/DTCP, DTCP and Tétracoq, and reported to the RPVC or to the pharmaceutical companies that produce them. METHODS: All AEs spontaneously reported during use of one of these vaccines to one of the French Pharmacovigilance Centers or to the responsible firms between January 1, 1986 and December 31, 1990 were take into account. An AE was noted as "serious" in accordance with the European criteria. The incidence of adverse effects was estimated by evaluating the ratio of adverse effects and the number of sales of the vaccine for the same period. RESULTS: From 1986 to 1990, 631 AEs (with 19 duplicate cases) associated with tetravalent vaccines in 606 children (75% < 1 year) were reported. The most frequent AEs were: local AEs at the site of injection (43%), neurologic disorders (12%), hyperthermia (10%) and allergic reactions (10%). Serious AEs represented 25% of all AEs and were similar to those usually described with these vaccines, particularly persistent crying (23), febrile seizures (12), apyretic seizures (14), uneasiness (28) and, rarely, shock (3). CONCLUSION: Incidences of AEs reported with pentavalent vaccines are very low, probably underestimated because of the under-notification by prescribers of AEs of vaccines licensed some time ago. It will be interesting to compare these data with AEs of penta- and hexavalent vaccines since they have replaced tetravalent vaccines.

Adult↗
PubMed1999

Prediction of methotrexate elimination after high dose infusion in children with acute lymphoblastic leukaemia using a population pharmacokinetic approach.

High-dose methotrexate (HD-MTX) with leucovorin rescue is a component of therapy in children with acute lymphoblastic leukaemia. Since MTX toxicity is related to drug exposure, a monitoring of serum MTX concentrations at H24, H48, H72 and until the concentration is less than 0.2 micromol/L is commonly performed. However, a number of patients may reach concentrations of less than 0.2 micromol/L long before the next sampling is scheduled. The aim of our study was to develop a Bayesian method predicting the time at which MTX concentration reaches 0.2 micromol/L in order to decrease the number of samples drawn and to allow for a more rapid patient discharge. Methotrexate population parameters were estimated from a retrospective analysis of 60 infusions in 23 children and MTX concentrations were predicted from an independent set of 20 courses in 14 children with a Bayesian approach using either one (H48) or two (H24 and H48) samples. The following population parameters were obtained using a two-compartment model: CL = 3.51 L/h (inter-individual variability: 66%), Vd = 8.67 L (58%), k12 = 0.0044 h(-1)(105%), k21 = 0.039 h(-1)(25%). Clearance and Vd were found to increase with weight and age respectively. Both sampling schedules tested for the Bayesian estimation enabled accurate prediction of concentrations and provided satisfactory precision despite a small bias. When considering the ability to predict the time at which the threshold was reached, the one-sample (H48) schedule gave the best results. We conclude that a sampling schedule involving only one sample and Bayesian parameter estimation may be able to predict the delay necessary to reach 0.2 micromol/L in each individual.

Adolescent↗
PubMed1999

[Should folic acid be given to women treated with valproic acid and/or carbamazepine? Folic acid and pregnancy in epilepsy].

Fetal exposure to valproic acid or carbamazepine increases the risk of neural tube defect (NTD). The risk of a mother having a baby with spina bifida has been estimated at 1-2 p. 100, close to the rate of risk of recurrent cases. No study has evaluated the effect of folic acid in neonates of women treated with valproic acid or carbamazepine although the protective effect against NTD has been proven in other populations. Periconceptional folic acid supplementation, 0.4 to 1 mg/day, for at least one month prior to conception and until the date of the second missed menstrual period or later decreases the incidence of a first occurrence of neural tube defect. Periconceptional folic acid supplementation, 4 mg/day, decreases the recurrence of NTD in women who had previously had a child with NTD. It seems pertinent to recommend periconceptional folic acid supplementation in women treated with carbamazepine or valporic acid. There are very few data in women on which to base a decision to advise taking 4 mg/day (as used in recurrence prevention) or low doses of 0.4 mg/day (used in primary prevention).

Anticonvulsants↗
PubMedDate not supplied

[Adverse effects of glycolic irrigation solutions].

The aim of this study was to evaluate the frequency and the gravity of Trans Urethral Resection of the Prostate Syndrome or 'TURP Syndrome,' which occurs when irrigating fluids containing 1.5 per cent glycocolle are used. All the adverse effects that occurred with 5 products containing 1.5 per cent glycocolle which were notified to the pharmacovigilance structures in France were reviewed. The adverse effects notified comprised 24 cases of TURP Syndrome and 5 of renal failure. TURP Syndrome consisted of neurological signs (92 per cent); cardiovascular signs (54 per cent); visual disturbance (42 per cent) and digestive signs (25 per cent). Hyponatraemia occurred in all patients (mean 113 +/- 6 mmol.l-1) and 25 per cent of patients died. In 27 per cent of cases TURP Syndrome occurred when glycocolle was in contravention of AMM guidelines. The Drugs Agency has requested that modification be included in the Vidal pharmacopoeia (warnings and adverse reactions) and on glycocolle bags and that surgeons and anaesthetists be informed.

Adult↗
PubMedDate not supplied

[Issues in therapeutic drug monitoring evaluation].

A reassessment of the interest of therapeutic drug monitoring (TDM) is needed for a better definition of its applications. It rests on the hypothesis of the existence of an interindividual variability of the dose-effect relationship, this variability being influenced by pharmacokinetic variability. Different types of endpoints were used in validation studies (pharmacokinetic, indirect, economic) and few studies have used clinical endpoints. The question should be: does TDM allow for a better dose adjustment than one based only on criteria other than drug concentration? Retrospective studies have a 'diagnostic test' approach and only prospective clinical trials will provide a real validation. Factors which limit the setting up of such studies are: the number of subjects to include, the often imprecise measurement of drug exposure and poor knowledge of the pharmacokinetic-pharmacodynamic relationship and its variability.

Dose-Response Relationship, Drug↗
PubMedDate not supplied

Ciprofloxacin pharmacokinetics in young cystic fibrosis patients after repeated oral doses.

Until recently, only compassionate use of ciprofloxacin in children with cystic fibrosis was possible despite limited pharmacokinetic data. We studied five subjects with cystic fibrosis and exacerbation of pulmonary infection. A 15 mg/kg b.i.d. regimen of oral ciprofloxacin was administered. On the 15th day, eight blood samples were collected and plasma concentrations were measured by HPLC. The actual dose administered ranged from 10 to 14 mg/kg b.i.d., due to the fixed-dosage formulation. Corresponding AUC0-12 ranged from 8.2 to 11.9 mg.h/L. Plasma concentrations were maintained above individual MICs for a median time of 12.7 h over 24 h. The median area under the inhibitory curve was 52.8, which is about half the proposed target value for ciprofloxacin in pulmonary infections with Gram-negative bacteria such as Pseudomonas aeruginosa. A higher dose, administered from a specific formulation to ensure precise dosing, must be given in order to obtain adequate concentrations in cystic fibrosis children.

Administration, Oral↗
PubMedDate not supplied

[Pharmacokinetic studies in neonatology: regulatory and methodologic problems].

Pharmacokinetic studies in neonates are essential because of maturational changes in physiological functions during this period. International harmonization conferences have established guidelines for such studies, including recommendations on age ranges to be studied and description of methods and study design. Multiple blood sampling to obtain a full pharmacokinetic profile cannot be proposed in neonates. Population pharmacokinetic analysis, with minimal sampling schemes, is more appropriate but involves more subjects than the traditional approach. Population pharmacokinetic analysis also focuses on the influence of individual factors on pharmacokinetic parameters. Most studies performed with neonates have involved drugs with a narrow safety margin and cleared by renal or metabolic routes to study the impact of immaturity on drug concentrations and on clinical effects.

Humans↗
PubMedDate not supplied

[New antiepileptic drugs in pregnancy: outcome of 12 exposed pregnancies].

There is currently little evidence available concerning the risks of foetal exposure to new anti-epileptic drugs such as lamotrigine, vigabatrin, gabapentine, topiramate. A small number of malformations without organ specificity have been described and are not easy to interpret because of the existence of concomitant treatments. We have reported a series of 12 pregnancies with exposure to recent anti-epilepticdrugs and that were reported to the Post-marketing Surveillance office in Tours, France. Five concerned Lamictal of which 2 related to monotherapy, one concerned Epitomax used in monotherapy and there were 6 cases of polytherapy including Sabril. Associated drug therapies were Depakine, Tegretol, Rivotril and Urbanyl. Six of the patients were on folic acid supplements. The average age of the women was 26.5 years. In each case, treatment had been initiated before conception and was continued for at least 3 months. Of the 12 babies born, only one presented with a malformation (aplasia of the muscle of the left lower lip and asymmetrical abduction of the hips) following exposure to Lamictal and Depakine. Four infants, two of whom were premature, showed signs of neonatal stress: transient respiratory distress and difficulty in taking feeding-bottles following exposure throughout the pregnancy to Epitomax; suction disorders, hypotonia and vomiting were observed after exposure to Sabril, Tegretol and Rivotril throughout the pregnancy; respiratory distress and apnoea--bradycardia were observed after exposure throughout the pregnancy to Lamictal and Urbanyl; respiratory distress and thrombocytopaenia were observed after exposure throughout the pregnancy to Lamictal". This small series confirms that the current data concerning the teratogenicity of new anti-epileptic drugs are as yet insufficient to exclude any teratogenic risk. Consequently, strict adherence to current recommendations relating to drug use during pregnancy is essential. The treatment of all patients wishing to become pregnant should be discussed.

Adult↗
PubMedDate not supplied

[Clinical relevance of N-acetyltransferase type 2 (NAT2) genetic polymorphism].

Polymorphic N-acetyltransferase (NAT2) is involved in the metabolism of several compounds relevant in pharmacology or toxicology, with diverse clinical consequences. Inter-ethnic variations in distribution of the acetylation phenotype are significant. The caffeine test is most often used to assess the acetylation phenotype and to identify rapid and slow acetylators. The NAT2 phenotype could account for the increased risk of certain side effects in slow acetylators treated with isoniazid (particularly peripheral neuropathies and lupus erythematosus), although therapeutic efficacy seems to be independent of the acetylation status. Hypersensibility reactions with sulfonamides (including Lyell and Stevens-Johnson syndromes) are more frequent in slow acetylators, who also show poor tolerance to sulfasalazine and dapsone. In contrast, myelotoxicity induced by amonafide is more frequent in rapid acetylators, probably because of increased production of a toxic metabolite of the drug. In carcinogenesis, NAT2 may play a protective role against bladder cancer, although studies have shown contradictory results. Slow acetylators may have a risk of developing primitive liver cancer. For lung cancer, data are not conclusive, but slow acetylation status may predispose to mesothelioma in subjects exposed to asbestos. No relation has been found between acetylation phenotype and breast cancer. Contradictory results were reported on its role in colorectal cancer. Non-smoking type 1 diabetics may be at increased risk of nephropathy if they are rapid acetylators. Parkinson's disease may be more frequent among slow acetylators, but again, data have shown contradictory results. Finally, a poor acetylator phenotype may predispose to atopic diseases.

Acetylation↗
PubMedDate not supplied

[Drugs associated with acute generalized exanthematic pustulosis].

INTRODUCTION: Acute generalized exanthematous pustulosis is a severe eruption which is usually drug related. If the causative drug is discontinued, acute generalized exanthematous pustulosis resolves spontaneously in ten days. The aim of this study was to compare drugs suspected of causing acute generalized exanthematous pustulosis reported to French Pharmacovigilance centres and those reported in the literature. MATERIALS AND METHODS: All cases of "pustular eruption" qualified as "serious" reported to the French Pharmacovigilance Centers between January 1985 and December 2001 were analyzed. Cases for which the diagnosis of acute generalized exanthematous pustulosis was not clearly identified were reviewed by a dermatologist. The relationship between acute generalized exanthematous pustulosis and drug exposure was re-examined by one of us. An exhaustive review of the literature was also performed. RESULTS: Review of the data base revealed 207 cases of serious acute generalized exanthematous pustulosis leading to death in 4 cases (2%). Of these cases of acute generalized exanthematous pustulosis, only one drug was suspected in 107 cases (51.6%). The main drugs involved were: pristinamycin (18 cases), amoxicillin (+/- clavulanic acid) (16 cases), hydroxychloroquine (8 cases) and a combination of spiramycin + metronidazole (5 cases). DISCUSSION: The most frequent causal drugs in our study and in the literature are: amoxicillin +/- clavulanic acid, pristinamycin, hydroxychloroquine, ampicillin, diltiazem, co-trimoxazole, terbinafine, carbamazepine and spiramycin +/- metronidazole. Only pristinamycin and diltiazem have information in their summary of product characteristics regarding the risk of acute generalized exanthematous pustulosis. Because it is essential to discontinue the causative drug as soon as possible if a pustular eruption occurs, physicians must be informed of the risk, which should be added to the "adverse events", and "warnings" sections of the summary of product characteristics of the drugs concerned. CONCLUSION: Our results show the relevance of notification of side effects by physicians to pharmacovigilance centres, leading to the identification of a signal and public health dissemination of warnings.

Acute Disease↗