Contraceptives for lactating women: A comparative trial of a progesterone-releasing vaginal ring and the Copper T 380A IUD

Sivin, Irving; Dı́az, Soledad; Croxatto, Horacio B.; Miranda, Patricia Y.; Shaaban, Mamdouh M.; Sayed, Ezzat H.; Xiao, Biao; Wu, Shang Chun; Du, Minquan; Alvarez, Francisco; Brache, Vivian; Basnayake, Sriani; McCarthy, Terry; Lacarra, Maria; Mishell, Daniel R.; Koetsawang, Suporn; Stern, Janet; Jackanicz, Theodore M.

doi:10.1016/s0010-7824(97)00008-5

Cited by 72 publications

(59 citation statements)

References 17 publications

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“…Biological matter has been observed on the surface of IVRs in other in vivo IVR studies and has not noticeably increased vaginal inflammation (13,27,40). The impact of biological matter adhesion on drug release has not been reported in literature but could potentially affect drug elution and the corresponding pharmacokinetics.…”

Section: Discussionmentioning

confidence: 98%

Safe and Sustained Vaginal Delivery of Pyrimidinedione HIV-1 Inhibitors from Polyurethane Intravaginal Rings

Johnson

Srinivasan²,

Albright

et al. 2012

Antimicrob Agents Chemother

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The potent antiretroviral pyrimidinediones IQP-0528 (PYD1) and IQP-0532 (PYD2) were formulated in polyurethane intravaginal rings (IVRs) as prophylactic drug delivery systems to prevent the sexual transmission of HIV-1. To aid in the selection of a pyrimidinedione candidate and the optimal loading of the drug in the IVR delivery system, four pyrimidinedione IVR formulations (PYD1 at 0.5 wt% [PYD1 0.5wt% ], PYD1 1wt% , PYD2 4wt% , and PYD2 14wt% ) were evaluated in pigtail macaques over 28 days for safety and pyrimidinedione vaginal biodistribution. Kinetic analysis of vaginal proinflammatory cytokines, native microflora, and drug levels suggested that all formulations were safe, but only the high-loaded PYD2 14wt% IVR demonstrated consistently high pyrimidinedione vaginal fluid and tissue levels over the 28-day study. This formulation delivered drug in excess of 10 g/ml to vaginal fluid and 1 g/g to vaginal tissue, a level over 1,000 times the in vitro 50% effective concentration. The in vitro release of PYD1 and PYD2 under nonsink conditions correlated well with in vivo release, both in amount and in kinetic profile, and therefore may serve as a more biologically relevant means of evaluating release in vitro than typically employed sink conditions. Lastly, the pyrimidinediones in the IVR formulation were chemically stable after 90 days of storage at elevated temperature, and the potent nanomolar-level antiviral activity of both molecules was retained after in vitro release. Altogether, these results point to the successful IVR formulation and vaginal biodistribution of the pyrimidinediones and demonstrate the usefulness of the pigtail macaque model in evaluating and screening antiretroviral IVR formulations prior to preclinical and clinical evaluation.

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Section: Discussionmentioning

confidence: 98%

Safe and Sustained Vaginal Delivery of Pyrimidinedione HIV-1 Inhibitors from Polyurethane Intravaginal Rings

Johnson

Srinivasan²,

Albright

et al. 2012

Antimicrob Agents Chemother

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“…Bounds et al studied an early version of the hormone replacement therapy ring Femring that had remarkable mechanical stiffness, and it was concluded that the ring contributed to the creation of ulcerative lesions in the vagina (5). Subsequently, several large clinical safety studies have evaluated an array of medicated and nonmedicated IVRs composed of silicone and ethylene vinyl acetate polymers comprising various dimensions and varied ring stiffness (14,27,41,43,47,59). None of these studies found a significant ring contribution in creating epithelial lesions and/or altering vaginal microflora when tested for up to 1 year.…”

Section: Fig 7 Proximal and Distal Tfv Vaginal Tissue Concentrations mentioning

confidence: 99%

A 90-Day Tenofovir Reservoir Intravaginal Ring for Mucosal HIV Prophylaxis

Johnson

Clark

Albright

et al. 2012

Antimicrob Agents Chemother

117

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A vaginal gel containing the antiretroviral tenofovir (TFV) recently demonstrated 39% protection against HIV infection in women. We designed and evaluated a novel reservoir TFV intravaginal ring (IVR) to potentially improve product effectiveness by providing a more controlled and sustained vaginal dose to maintain cervicovaginal concentrations. Polyurethane tubing of various hydrophilicities was filled with a high-density TFV/glycerol/water semisolid paste and then end-sealed to create IVRs. In vitro, TFV release increased with polyurethane hydrophilicity, with 35 weight percent water-swelling polyurethane IVRs achieving an approximately 10-mg/day release for 90 days with mechanical stiffness similar to that of the commercially available NuvaRing. This design was evaluated in two 90-day in vivo sheep studies for TFV pharmacokinetics and safety. Overall, TFV vaginal tissue, vaginal fluid, and plasma levels were relatively time independent over the 90-day duration at approximately 10 4 ng/g, 10 6 ng/g, and 10 1 ng/ml, respectively, near or exceeding the highest observed concentrations in a TFV 1% gel control group. TFV vaginal fluid concentrations were approximately 1,000-fold greater than levels shown to provide significant protection in women using the TFV 1% gel. There were no toxicological findings following placebo and TFV IVR treatment for 28 or 90 days, although slight to moderate increases in inflammatory infiltrates in the vaginal epithelia were observed in these animals compared to naïve animals. In summary, the controlled release of TFV from this reservoir IVR provided elevated sheep vaginal concentrations for 90 days to merit its further evaluation as an HIV prophylactic. R ecent progress in antiretroviral HIV prevention research has advanced the field from concept toward medical practice (46). The CAPRISA 004 study demonstrated that a vaginal gel containing the reverse transcriptase inhibitor tenofovir (TFV) was partially effective in preventing HIV transmission in women (1), with significant protection observed in women who maintained preventative TFV concentrations of at least 1,000 ng/ml in vaginal fluid (23). However, the overall effectiveness (39%) was likely reduced by poor user adherence to the inconvenient before-andafter-sex dosing regimen. The correlation of adherence and TFV vaginal fluid concentrations to protection was a key finding (23,24), indicating the need for vaginal drug delivery systems that attain and maintain elevated user adherence and vaginal drug concentrations. More recently, the VOICE trial tested the same TFV 1% gel formulation as CAPRISA 004 but with a once-daily dosage regimen and failed to show any effectiveness in women. Here, as well, low adherence may have contributed to the gel's inability to prevent HIV transmission (54). As a result, we (6, 21) and others (4,35,36,44,49) aim to develop TFV drug delivery systems to provide sustained protective vaginal tissue concentrations and potentially increase user adherence.The micromolar anti-HIV activity of TFV motivated sel...

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“…Su uso es continuo, y debe ser reemplazado cada 90 días, hasta máximo un año desde el posparto. (6)(7) Los efectos colaterales descritos son mínimos, siendo estos irritación, dolor y aumento de la secreción vaginal. (3) Esto último puede ser considerado como un beneficio, debido a la sequedad vaginal descrita en el periodo de lactancia.…”

Section: Anillo Vaginal De Progesterona (Avp)unclassified

Criterios Médicos de elegibilidad para el uso de anticonceptivos de la OMS

2017

Rev. chil. obstet. ginecol.

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RESUMENIntroducción: Los "Criterios Médicos de Elegibilidad para el Uso de Anticonceptivos" de la Organización Mundial de la Salud (OMS) son una guía para la correcta elección y uso de los métodos anticonceptivos en variadas condiciones de salud. En este documento revisaremos las principales modificaciones en su quinta y última edición publicada en inglés el año 2015.Desarrollo: Las modificaciones de la quinta edición son fundamentalmente la adición de nuevos métodos y la modificación de la categoría de recomendación para algunas condiciones de salud. Se agregan el acetato de medroxiprogesterona de depósito vía subcutánea, el anillo vaginal de progesterona, el implante anticonceptivo subcutáneo sinoimplant(II)® y el método anticonceptivo de emergencia acetato de ulipristal. Se modifican las recomendaciones para las mujeres en lactancia, permitiendo el uso de algunos métodos de progestágeno solo desde el posparto inmediato, salvo el acetato de medroxiprogesterona de depósito por entregar una dosis elevada del esteroide y el dispositivo intrauterino (DIU) con levonorgestrel, el cual sigue las normas de los DIU con cobre. También hay modificación en las recomendaciones en cuanto al uso de anticonceptivos combinados en el puerperio, con más restricciones para mujeres sin lactancia. Por último, sobre el uso de terapia antiretroviral, cambian algunas categorías y se amplía el listado de fármacos detallados. Conclusión: Es necesario que los profesionales de salud conozcan estas modificaciones para poder entregar una atención de calidad a las usuarias de anticoncepción.Palabras clave: anticoncepción, lactancia materna, medroxiprogesterona, levonorgestrel, ulipristal SUMMARY Introduction: The "Medical Eligibility Criteria for Contraceptive Use" published by the World Health Organization (WHO) is a guide for the correct choice and use of the contraceptive methods in many different health conditions. In this document we will review the main changes made in the fifth and last edition of this guide published in English in 2015. Development: The modifications of this last edition are the addition of new contraceptive methods and the modification of the category of the recommendation for some health conditions. It adds the medroxiprogesterone acetate subcutaneous injection, the progesterone vaginal ring, the subcutaneous contraceptive implant sinoimplant(II)® and ulipristal acetate as emergency contraception. There are modifications of the recommendations for breastfeeding women, allowing the use of some progestin only

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Contraceptives for lactating women: A comparative trial of a progesterone-releasing vaginal ring and the Copper T 380A IUD

Cited by 72 publications

References 17 publications

Safe and Sustained Vaginal Delivery of Pyrimidinedione HIV-1 Inhibitors from Polyurethane Intravaginal Rings

Safe and Sustained Vaginal Delivery of Pyrimidinedione HIV-1 Inhibitors from Polyurethane Intravaginal Rings

A 90-Day Tenofovir Reservoir Intravaginal Ring for Mucosal HIV Prophylaxis

Criterios Médicos de elegibilidad para el uso de anticonceptivos de la OMS

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