Safety of intravitreal injection of ranibizumab in early pregnancy: a series of three cases.

PurposeRanibizumab is used in the treatment of choroidal neovascularization (CNV). Although systemic exposure to ranibizumab is low after ocular administration, its mechanism of action must be regarded as potentially teratogenic and embryo-fetotoxic. Women are advised to wait 3 months after the last dose of treatment with ranibizumab before conceiving. Little is known about the fetal side-effects of this drug.MethodsThree pregnant women were treated with ranibizumab. One patient had idiopathic CNV.ResultsAfter receiving injections at 10 and 21 weeks after her last menstrual period (LMP), she gave birth to a healthy child. The second patient had myopic choroidal neovascularization (mCNV) and was treated by a single injection at 17 weeks post LMP. She gave birth to a healthy child after an uneventful pregnancy. The third patient had CNV secondary to a punctuate inner choroiditis. The injection was performed at 8 weeks post LMP. This patient presented a cholestasis of pregnancy at 36 weeks post LMP and gave birth at 38 weeks post LMP to a child that did not present any malformations.ConclusionsThis case series describes three women who underwent intravitreal ranibizumab treatment during pregnancy without showing any obstetric, embryofetal or neonatal complications.

[Methotrexate pharmacology]. / Pharmacologie du méthotrexate.

Methotrexate is a folic acid analog, which is a thymidylate synthetase and dihydrofolate reductase inhibitor. It is used in oncology, dermatology and rheumatology and off labelling in the treatment of ectopic pregnancies. This paper is a review of methotrexate pharmacology with focus on data concerning ectopic pregnancies.

[Evidence-based evaluation and expertise of methotrexate off label use in gynaecology and obstetrics: work of the CNGOF]. / États des lieux et expertise de l'usage hors AMM du méthotrexate en gynécologie-obstétrique: travail du CNGOF.

In the absence of contraindication, methotrexate by intramuscular unique injection of 1mg/kg or 50mg/m(2) is the medical treatment recommended for tubal ectopic pregnancy (EP; LE1). It can be renewed once, at the same dose, according to hCG rates decrease. The pretherapeutic biological assessment contains blood cells numeration, renal and hepatic function. Methotrexate therapy constitutes an alternative conservative treatment to laparoscopic salpingotomy for non-complicated tubal EP (LE1) with hCG level <5000 UI/L (LE2). When the rates of hCG are <1000 UI and or presented a spontaneous decreasing kinetics, the simple prospect (LE2) is preferred. It is recommended to use intramuscular methotrexate in case of surgical conservative treatment failure or more prematurely if the follow-up is not possible (LE3). Except in particular cases there is no indication to use methotrexate in local injection under sonographic control in usual tubal EP (LE2). The use of in situ injection methotrexate is an option to handle the cervical, interstitial or on caesareans scar pregnancies (LE2). In front of a persistent undetermined location pregnancy, after more than 10 days of survey, in an asymptomatic woman and/or at rate of hCG >2000 UI/L, the systematic treatment by methotrexate is an option. The methotrexate is not indicated for first trimester termination of pregnancy or miscarriage neither in placentas accreta nor in association with other treatments such myfegine or potassium.

The PREGVAXGRIP study: a cohort study to assess foetal and neonatal consequences of in utero exposure to vaccination against A(H1N1)v2009 influenza.

BACKGROUND: In October 2009, in the context of an A(H1N1)v2009 influenza pandemic, a vaccination campaign was launched in France, in which one of the priority groups was pregnant women, on account of the high risk of developing complications following infection by this virus. OBJECTIVE: The aim of this multicentric, prospective, observational study was to assess safety and pregnancy outcomes in a cohort of pregnant women when receiving the A(H1N1)v2009 influenza pandemic vaccine. METHODS: This was a prospective study that followed up pregnant women recruited mainly in vaccination centres and maternity departments. Following the expected delivery date, follow-up data were collected concerning the delivery, the infant, and, if appropriate, the reasons why the pregnancy did not reach its term. RESULTS: Between 1 November 2009 and 31 March 2010, 2,415 pregnant women were included at the time of vaccination; 97.6 % of women received a vaccine without adjuvant and 2.4 % received an adjuvanted vaccine. Ninety-two (3.9 %) women were vaccinated during the first trimester of pregnancy, 1,090 (46.5 %) during the second trimester, and 1,162 (49.6 %) during the third trimester. One hundred and thirty-three adverse events (5.5 % of women) were reported, of which 12 were unexpected or serious. There were 2,246 (93.0 %) known pregnancy outcomes with 12 spontaneous abortions (0.5 %), 6 stillbirths (0.3 %), and 4 therapeutic abortions (0.2 %). There were 65 neonates with congenital anomalies, among which 31 were major. But only one congenital malformation (1.4 %) was reported for the 92 women vaccinated in their first trimester. Of the women, 93.3 % were delivered full term and 6.7 % preterm. For 96 (4.2 %) neonates, a disorder was reported in the neonatal period and 130 (5.6 %) were transferred to the neonatology department. CONCLUSIONS: This study suggests that exposure to the A(H1N1)v2009 pandemic influenza vaccine during pregnancy does not increase the risk of adverse pregnancy outcomes. However, because of the relatively small number of women exposed during the first trimester, other studies are needed to exclude an increased risk of malformation.

Hepatotoxicity associated with the use of a fixed combination of chloroquine and proguanil.

Here we report on a case of hepatotoxicity associated with the use of a fixed combination of chloroquine and proguanil. Alternative causes of liver injury were excluded. The pathophysiological mechanism remains unclear, with a possibility of allergic reaction. In view of the widespread use of both drugs, clinicians should be aware of this drug-induced liver injury.

[Retrospective study of adverse drug reactions in the elderly: experience of regional center for pharmacovigilance]. / Etude rétrospective de la iatrogénie médicamenteuse chez le sujet âgé: expérience d'un centre régional de pharmacovigilance.

Cases of adverse drug reactions which occurred in the elderly, and were notified to the Regional Centre of Pharmacovigilance of Angers between 1995 and 1998, were analysed in two subgroups: from 75- to 84-years-old and older than 84 years. Among the 263 cases recorded in the elderly, there was no significant difference between the 75- to 84-year-old patients (180 cases) and the patients older than 84 years (83 cases) concerning past medical history, severity of effects or medication. Side-effects in patients over 74 were mainly cutaneous, haematological and neuropsychiatric, involving in decreasing order of frequency cardiovascular, neuropsychiatric, antibiotic, analgesic and anti-inflammatory drugs. In comparison with patients under 75, adverse drug reactions are more frequent and more serious, notably overdose and drug interactions, in elderly people. The occurrence of some avoidable side-effects justifies the strengthening of information about therapeutic safety in the elderly.