Microsoft word - embarazo.doc
1) Pharmacokinetics of topical application of gynaecological formulations: In a study conducted in 12 healthy women the tolerance and kinetic behaviour after single and repeated dose of sertaconazole 2% vaginal cream and single 500 mg vaginal tablet was studied. In this study, sertaconazole plasma levels were not detected in any of the plasma samples collected, either during the single and repeated vaginal cream administration or after the tablet formulation. For the detection, HPLC method with ultraviolet detector was used. The concentrations of sertaconazole found in urine with both preparations were very small and erratic, showing a large intra- and intervariability, which probably reflects contaminations from the vaginal tract. Sertaconazole levels in high concentrations persisted in vaginal fluid for over 72h(1).
Systemic absorption of 14C radiolabelled 300 mg sertaconazole ovule in 4 healthy postmenopausal women was assessed. No radioactivity was found in plasma or blood samples. Very small quantities of radioactivity were measured in faeces (0.16 ± 0.18 of the administered dose). The percentage or radioactivity found in urine was 4.44 ± 3.18% of the administered dose. Radioactivity in urine and faeces was probably due to closeness of collection and administration areas, since it was essentially detected in the first urine sample collected (0-12 hours after adminstration)(2). The systemic absorption after applying sertaconazole topically as ovule in 4 different trials has been reviewed by De Lunardo et al (3). In this 4 studies, the primary or secondary objective was to assess the product kinetics using sertaconazole, administered as a vaginal suppository, after single or repeated administration, on healthy vaginal mucosa or Candida infected mucosa, with a 14C labelled or non labelled product, in volunteer postmenopausal or in child-bearing age women. The results of all these studies showed no evidence of presence of sertaconazole in plasma in all the treated women, measured by HPLC and being the limit of quantification very low (2.5-2.6 ng/ml). Very low quantities of sertaconazole were detected in in the urine of all women (mean percentage of urinary excretion ranged from 0.59± 0.21% to 1.05±0.64% for administered dose of unlabelled sertaconazole; percentage of urinary radioactivity was a 4 .44± 3.18% of the administered dose, for the labelled product). The presence of sertaconazole in urine is due to neigbourhood contamination. Vaginal radioactivity was noted for at least 96 hours in all women
2) Safety of imidazolic antifungal agents applied by vaginal route: Reviewing the literature to assess the safety of the azole antifungal drugs in pregnant and non pregnant women, the following data have been achieved. In a study, named OMEGA, realized by the Pharmacovigilance Center in Nice in which 612 women were interviewed about the intake of drugs during pregnancy, the results showed that 168 women (27.5%) had applied a at least one treatment by vaginal route. In 130 cases, topic imidazolic drugs had been used. According to the results of this study, no evidence of increase in miscarriage or foetal malformations due to the studied gynaecologic treatments has been found(4). In the other hand, reviewing the tolerability of the topical applied imidazolic antifungal drugs, Dr. Chichmanian of the Phamacovigilance Centre of the Pasteur Hospital in Nice(5), has found that the adverse events of this kind of drugs are essentially local, its intensity is generally mild, and in most of the cases, no stop of the treatment is needed. The systemic adverse events due to topically applied imidazolic antifungal agents are very rare and due to the systemic absortion of some of them. The vaginal resorption rate of terconazole ranges from 5 to 16%; the one of butoconazole is of 5.5%; clotrimazole ranges from 3 to 10%; econazole from 3 to 7% and miconazole only 1%. From the results of the studies we have previously seen, the absorption rate of sertaconazole is neglectible(1,2,3). Actually, most of the authors state that topical antifungal drugs can be use in pregnant women, even in the first three months (6,7,8). 3) Conclusions: About the use of sertaconzole during pregnancy, no specific clinical trials have been conducted in this population, but analysing the results of all the pharmacokinetic studies which show that there is no systemic absorption of sertaconazole after vaginal application, and the safety data about imidazolic antifungal drugs, we can conclude that the possibility of systemic adverse events, miscarriage or foetal malformations in pregnant women is neglectible.
1) Azcona et al. Curr Ther Res 1991; 49(6):1046-1060. 2) Guérin et al. Systemic absorption of 14C-radiolabelled sertaconazole administrered
in 300 MG prolonged-liberation vaginal suppository form to four healthy post-menopausal women. J Mycol Med. 1996; 6: 63-67.
3) De Lunardo et al. Caractéristiques pharmacocinétiques d´un nouvel antifongique
imidazolé: le nitrate de sertaconazole. J Mycol Med 1999; 9: 137-142.
4) Spreux et al. Survelleillance foetale après administration d´ovules et des comprimés
gynécologiques pendant la grossesse. Therapie 1993; 48:483-501.
5) Chichmanian, RM. Tolérance des agents antifongiques azolés, topiques et oraux,
utilisés dans le traitement de la candidose vulvovaginal: revue de la littérature. Centre de Pharmacovigilance de Nice. Fév. 1999
6) Reef, S. E.; Levine, W. C.; McNeil, M. M.; Fisher-Hoch, S.; Holmberg, S. D.;
Duerr, A.; Smith, D.; Sobel, J. D.; Pinner, R. W. Treatment options for vulvovaginal candidiasis. Clin Infect Dis 1995; 20 Suppl 1(S80-S90).
7) Sobel, J. D.; Faro, S.; Force, R. W.; Foxman, B.; Ledger, W. J.; Nyirjesy, P. R.;
Reed, B. D.; Summers, P. R. Vulvovaginal candidiasis: epidemiologic, diagnostic, and therapeutic considerations. Am J Obstet Gynecol1998;178 (2):203-11.
8) Ernest, J. M. Topical antifungal agents. Obstet Gynecol Clin North Am 1992;19(3):
TITULO PRIMERO Objetivos de la Carta de Inversiones Artículo primero Son fijados, en conformidad-con el segundo apartado del articulo 45 de la Constitución. los objetivos fundamentales de la acción del Estado durante los próximos diez años para el desarrollo y la promoción de las inversiones por medio de la mejora del clima y de las condiciones de inversión, la revisión de
Dexamethasone USP Micronized NOMENCLATURE Pregna-1,4-diene-3,20-dione, 9-fluoro-11,17,21-trihydroxy-16-methyl, (11β,16α)- 9-Fluoro-11β,17,21-trihydroxy-16α-methylpregna-1,4-diene-3,20-dione DESCRIPTION Dexamethasone from Pfizer is a white to practically white, odorless crystalline powder. It is stable in air and melts at about 250°C, with some decomposition. It is practically