Revisiting doxycycline in pregnancy and early childhood – time to rebuild its reputation?

Abstract

Introduction: Doxycycline is highly effective, inexpensive with a broad therapeutic spectrum and exceptional bioavailability. However these benefits have been overshadowed by its classification alongside the tetracyclines – class D drugs, contraindicated in pregnancy and in children under 8 years of age. Doxycycline-treatable diseases are emerging as leading causes of undifferentiated febrile illness in Southeast Asia. For example scrub typhus and murine typhus have an unusually severe impact on pregnancy outcomes, and current mortality rates for scrub typhus reach 12-13% in India and Thailand. The emerging evidence for these important doxycycline-treatable diseases prompted us to revisit doxycycline usage in pregnancy and childhood. Areas Covered: A systematic review of the available literature on doxycycline use in pregnant women and children revealed a safety profile of doxycycline that differed significantly from that of tetracycline; no correlation between the use of doxycycline and teratogenic effects during pregnancy or dental staining in children was found. Expert Opinion: The change of the US FDA pregnancy classification scheme to an evidence-based approach will enable adequate evaluation of doxycycline in common tropical illnesses and in vulnerable populations in clinical treatment trials, dosage-optimization pharmacokinetic studies and for the empirical treatment of undifferentiated febrile illnesses, especially in pregnant women and children.

Diagnosis and Management of Tickborne Rickettsial Diseases: Rocky Mountain Spotted Fever and Other Spotted Fever Group Rickettsioses, Ehrlichioses, and Anaplasmosis — United States

“…The risk for cosmetic staining of the primary teeth by doxycycline could not be determined because of limited data (214). A recent systematic review reported no evidence of teratogenicity associated with doxycycline use during pregnancy; however, limited data and a lack of controlled studies were limitations (216). No reports of maternal hepatic toxicity associated with doxycycline use have been published (215)(216)(217).…”

“…A recent systematic review reported no evidence of teratogenicity associated with doxycycline use during pregnancy; however, limited data and a lack of controlled studies were limitations (216). No reports of maternal hepatic toxicity associated with doxycycline use have been published (215)(216)(217). Rarely, fatty liver of pregnancy has occurred in patients who received high-dose intravenous tetracycline (215,218); however, the dosages administered in these cases exceeded what is recommended for the treatment of tickborne rickettsial disease.…”

Microglia Activation and Schizophrenia: Lessons From the Effects of Minocycline on Postnatal Neurogenesis, Neuronal Survival and Synaptic Pruning

“…Doxycycline, which belongs to the same group as minocycline, do not to display any visible neurodevelopmental disturbances following its use in pregnancy and early childhood. 37 Hereby it is important to mention that possible differences between animal model experiments and human studies may be influenced by several factors, like possible differences in dosing, routes of administration, and the generation of species-specific metabolites. Therefore, we think that at the present time-point it is premature to make definitive statements regarding the safety of the use of these drugs in children or the monitoring of their use.…”

Algunas consideraciones diagnósticas y terapéuticas del paciente con síndrome febril en Colombia

“…Proponen, en cambio, la terapia con macrólidos como antibióticos de segunda línea (en enfermedad no complicada), siempre teniendo en cuenta que la primera línea de elección es la doxiciclina 8,9 . Respecto a este último antibiótico, reciente-mente se publicó una revisión sistemática de la literatura, donde se reevaluó la «mala reputación» de dicha tetraciclina y se demostró que es un antibiótico seguro, altamente efectivo, y se desmintieron sus efectos adversos con relación a ninos˜ menores de 8 anos˜ y a mujeres embarazadas 9,10 . En conclusión, resaltamos la inclusión de la enfermedad de Chagas aguda, bien sea con relación a transmisión vectorial o transmisión oral, como diagnóstico diferencial dentro del síndrome febril agudo en Colombia, teniendo en cuenta su abordaje diagnóstico relativamente simple a través del frotis de sangre periférica y los beneficios del tratamiento antiparasitario en dicha fase de la enfermedad (tasas de curación de 80-100%) que, a su vez, contribuyen a la disminución de posibles casos de enfermedad crónica futura.…”