Prenatal and developmental toxicity study of meclizine and caffeine combination in female albino wistar rats.

Meclizine and caffeine combination is used for the treatment of morning sickness. Both compounds are teratogenic and caffeine is known to possess anti-fertility activity also. The present study was undertaken to evaluate the reproductive toxic effect of meclizine and caffeine combination. Three doses were taken for the study; low dose (LD; meclizine 3.7 mg/kg and caffeine 3 mg/kg) was selected from commercially available formulation, middle dose (MD; meclizine 37 mg/kg and caffeine 30 mg/kg) and high dose (HD; meclizine 370 mg/kg and caffeine 300 mg/kg). The mixture was administered 1-7 days and 8-14 days for fertility and embryotoxic studies respectively. Laparotomy was done on 10th day of gestation period. Number of implants and corpora lutea were counted, pre and post-implantation losses were determined. In embryo toxicity study fetuses were evaluated for external, skeletal and visceral examination. High dose was removed from both fertility and embryotoxicity studies due to its severe toxicity to the dam. Significant anti-fertility activity was observed at middle dose. Embryotoxicity study showed significant reduction in fetal body weight, body length and body mass index, dam body weight gain on gestation day 14. Absolute kidney weight in MD and absolute and relative spleen weight in both LD and MD were significantly reduced. There was no increase in external or internal congenital anomalies at both LD and MD. The, results suggest that prescription of meclizine and caffeine for morning sickness in early pregnancy should be reviewed carefully.

Medicamentos antieméticos no tratamento da náusea e vômitos associados à gestação / Antiemetic medications in the treatment of nausea and vomiting associated with pregnancy

Náusea e vômitos (NV) são os sintomas mais comuns durante a gravidez, geralmente iniciando-se entre a 6ª e a 8ª semana, atingindo a intensidade máxima em torno da 9ª semana e resolvendo-se até a 12ª semana. Embora sua etiologia seja, provavelmente, multifatorial, seu curso clínico se correlaciona com as concentrações plasmáticas da gonadotrofina coriônica humana. Por comprometerem a qualidade de vida, NV devem ser abordados com modificações dietéticas que incluem dieta fracionada e redução do consumo de alimentos gordurosos, entre outras. O uso de piridoxina pode melhorar a náusea de intensidade leve, embora não diminua significantemente os episódios de vômitos. Os anti-histamínicos são os medicamentos mais utilizados como terapia medicamentosa de primeira linha e têm sua segurança comprovada; dentre eles, o dimenidrinato determina início de ação mais rápido e menor sedação que a meclizina. Entre os antagonistas dopaminérgicos, a prometazina e a metoclopramida podem ser utilizadas, mas apresentam como desvantagem o potencial de eventos adversos maternos. O antagonista dos receptores 5-HT3, ondansetrona, pode ser considerado quando outros medicamentos não foram efetivos no tratamento de NV de intensidade grave. Do mesmo modo, os corticosteroides devem ter seu uso reservado para casos não responsivos a outros medicamentos e preferencialmente após a 10ª semana de gestação...

Enhancement of dissolution rate of rapidly dissolving oral film of meclizine hydrochloride by complexation of Meclizine hydrochloride with ß-cyclodextrine.

Motion sickness is a very common disturbance of the inner ear that is caused by repeated motion such as from the swell of the sea, the movement of a car, the motion of a plane in turbulent air, etc. Most medications for motion sickness need to be taken at least 30 minutes prior exposure to the activity that can cause the problem. This project is based on the hypothesis that Mouth Dissolving Films (MDF) are rapidly dissolving dosage forms which when placed in the mouth release the drug immediately. These dosage forms would be preferred by pediatric and geriatric patients since these are not associated with fear of choking. The fast dissolving films prepared by solvent casting method with suitable appearance, mechanical strength, peelability and disintegration time were obtained using Methocel E-5 as a primary film former. Meclizine HCl, a poorly water soluble and bitter drug could be successfully incorporated in the fast dissolving films with the help of solubilizers such as β-Cyclodextrine and PEG-400.