Pill Packs Research Articles

Abstract NS6: Connecting the Dots; a Pharmacist-Led Care Transition Model for Stroke Patients Post-Discharge

Background/Purpose: Stroke is a leading cause of adult disability worldwide, and one in four is due to recurrence, with the highest risk within the first 30 days post-discharge. Post-discharge follow-up is key to preventing hospital readmission and recurrent stroke. At our hospital, adult ischemic stroke (IS) patients are auto-enrolled in a pharmacist-led transitions of care program. Initially, our pharmacy team completes a medication history and reconciliation. Prior authorization and financial assistance services are offered. Patients who choose to remain enrolled are discharged with a 28-day supply of their medications, followed by all subsequent medications sent in adherence pill packs. Patients then receive a call 5-to-7 days post-discharge from a pharmacist to provide counseling on secondary stroke prevention and the importance of medication adherence. The pharmacist also ensures that the patient has scheduled follow-up appointments with both their primary care provider and the stroke clinic. Methods: In this retrospective cohort study, we included adult IS patients discharged from our center between October 2021 and July 2022. We compared those who chose to continue with our services beyond discharge with patients who opted out of our program. The primary outcome is medication adherence. The secondary outcome is the readmission rate. Results: Participation in our program resulted in an adherence rate of 98.5% compared with an adherence rate of 70.2% in those who declined to participate. Readmission was lower for participation, although not significantly so. Conclusions: Our program resulted in an improvement in medication adherence and a trend towards lower readmission rates amongst participating IS patients post-discharge. Further studies should be completed to examine the additional impacts of a pharmacist-led post-discharge program on secondary stroke prevention related to surrogate markers (Blood pressure, lipids, A1C, etc.) over time.

Multifactor Quality and Safety Analysis of Antimicrobial Drugs Sold by Online Pharmacies That Do Not Require a Prescription: Multiphase Observational, Content Analysis, and Product Evaluation Study.

Antimicrobial resistance is a significant global public health threat. However, the impact of sourcing potentially substandard and falsified antibiotics via the internet remains understudied, particularly in the context of access to and quality of common antibiotics. In response, this study conducted a multifactor quality and safety analysis of antibiotics sold and purchased via online pharmacies that did not require a prescription. The aim of this paper is to identify and characterize "no prescription" online pharmacies selling 5 common antibiotics and to assess the quality characteristics of samples through controlled test buys. We first used structured search queries associated with the international nonproprietary names of amoxicillin, azithromycin, amoxicillin and clavulanic acid, cephalexin, and ciprofloxacin to detect and characterize online pharmacies offering the sale of antibiotics without a prescription. Next, we conducted controlled test buys of antibiotics and conducted a visual inspection of packaging and contents for risk evaluation. Antibiotics were then analyzed using untargeted mass spectrometry (MS). MS data were used to determine if the claimed active pharmaceutical ingredient was present, and molecular networking was used to analyze MS data to detect drug analogs as well as possible adulterants and contaminants. A total of 109 unique websites were identified that actively advertised direct-to-consumer sale of antibiotics without a prescription. From these websites, we successfully placed 27 orders, received 11 packages, and collected 1373 antibiotic product samples. Visual inspection resulted in all product packaging consisting of pill packs or blister packs and some concerning indicators of potential poor quality, falsification, and improper dispensing. Though all samples had the presence of stated active pharmaceutical ingredient, molecular networking revealed a number of drug analogs of unknown identity, as well as known impurities and contaminants. Our study used a multifactor approach, including web surveillance, test purchasing, and analytical chemistry, to assess risk factors associated with purchasing antibiotics online. Results provide evidence of possible safety risks, including substandard packaging and shipment, falsification of product information and markings, detection of undeclared chemicals, high variability of quality across samples, and payment for orders being defrauded. Beyond immediate patient safety risks, these falsified and substandard products could exacerbate the ongoing public health threat of antimicrobial resistance by circulating substandard product to patients.

S3462 Oh, My Blister Pack! A Case of Ingestion and Perforation

Introduction: Perforation of the small bowel resulting in resection due to foreign body ingestion occurs in less than 1% of all foreign body ingestions (FBI). Commonly FBI occurs in children and the elderly, due to shared risk factors including age and poor cognitive function. The main purpose of blister pill packs is to prevent tampering and most importantly seal individual tablets for protection and safety against ultraviolet light. Here we describe accidental ingestion of a blister pill pack presenting as abdominal pain, resulting in a small bowel resection. Case Description/Methods: An 86-year-old female presented with a chief complaint of abdominal pain. She rated the pain at an 8 out of 10. She noted that movement made the pain worse, and no activity made it better. She denied any hematochezia, melena, diarrhea, or constipation. Initial diagnostic workup for abdominal pain included computed tomography (CT) of the Abdomen and Pelvis. CT scan revealed a partial small bowel obstruction with dilated, fecalized small bowel proximal to the blister pack and non-distended small bowel distally (Figure A). Subsequently, the patient was taken to the operating room, where the blister pack was turned 180 degrees and found to be adherent to the right lower quadrant of the small bowel (Figure B). Small bowel resection was completed successfully with anastomosis of the bowel. Patient had resumed diet with resumption of bowel movements within 10 days post-operation. Discussion: Foreign body ingestion is a common occurrence in children and elderly people. Most locations of impaction include the stomach and esophagus. Rare effects of blister pack ingestion may include small bowel obstruction leading to perforation as seen in our case. Clinicians should be aware of a broad differential when considering ingestion of an unknown substance, including small bowel obstruction, perforation, or aspiration.Figure 1.: 1a: Left Image 1b: Right.

Feasibility and Acceptability of a Mobile Application to Monitor Opioid Use and Promote Behavior Modification Following Cesarean Section

Opioid misuse and associated negative sequelae, including opioid use disorder and overdose, continue to comprise a public health crisis of epidemic proportions. One opportunity for upstream primary prevention of opioid misuse is the management of opioid use during the postoperative period, including following cesarean section. Research shows that most patients who have a cesarean delivery receive a prescription for opioids on discharge, though limited data exist on postoperative opioid use and misuse. Continuous Precision Medicine (CPM) has developed a mobile application that allows patients to track their pain and usage of both opiates and non-steroidal anti-inflammatory (NSAID) medications and includes elements intended to promote behavior modification through psychoeducation and gamification. The aims of this study were to determine logistical and technological feasibility and acceptability of the mobile application by patients and clinicians and to assess preliminary postoperative opioid use and misuse patterns to inform future directions. Participants (N = 9) were women between the ages of 23 and 41 years old who underwent a repeat cesarean section at an inner-city academic hospital and were without a history of self-reported opioid use. Participants received a tablet loaded with the mobile application and electronic pill packs with the standard postoperative prescription of 14 Roxicodone tablets. On review, 53% of opioids were unused. Four patients took four or fewer Roxicodone pills, with three patients taking none. Additionally, three were noted to have aberrant behavior that was inconsistent with prescribed instructions provided to the patient by the provider. Results of this feasibility study suggest that the CPM mobile application is feasible and acceptable for both patients and practitioners and provides traceability for clinicians to make better-informed decisions regarding patient care. Preliminary data suggest an excess of prescribed narcotics as well as a potential concern for utilization of medication not as prescribed.

Impact on patients' compliance with medication using prepacked blisters for multidrug medical therapy: I-COMPLY Study.

Studies have supported the use of packaging interventions such as pillboxes or blister packs to improve medication adherence but have not evaluated the efficacy of these interventions in a population of low socioeconomic status. The aim of this study was to assess the effect of home-delivered pill packs on medication adherence in a low-income Black American population with Medicaid insurance. This study was an open-label, randomized, controlled trial. The patient population studied included 80 patients followed by primary care physicians at the Cleveland Clinic. Patients were randomized to a study group who received delivery of their multidrug medical therapy, defined as a minimum of 4 medications daily, in prepackaged blisters or a control group who obtained their prescriptions from their routine pharmacy. The primary analysis compared the mean percentage of missed pills between the 2 groups using t-test analysis. The percentage of missed pills in the study group was significantly lower than in the control group (mean [SD]: 3.7% [6.0%] vs 17.4% [16.6%] missed daily pills; P < 0.001). The number of daily missed doses was also significantly lower in the study group (0.3 [0.5] vs 0.7 [0.6]; P = 0.002). Patients were on a mean of 8.1 (SD, 2.3) and 8.1 (SD, 2.6) medications in the study and control groups, respectively (P = 0.96). Delivery of prepackaged medications in a low-income Black American community was demonstrated to improve medication adherence. The use of prepackaged blisters for medication home delivery is a model that can be utilized on a larger scale for patients on multidrug medical therapy.

Potential public sector cost-savings from over-the-counter access to oral contraceptives

ObjectiveThis study estimates how making oral contraceptive pills (OCPs) available without a prescription may affect contraceptive use, unintended pregnancies and associated contraceptive and pregnancy costs among low-income women. Study DesignBased on published figures, we estimate two scenarios [low over-the-counter (OTC) use and high OTC use] of the proportion of low-income women likely to switch to an OTC pill and predict adoption of OCPs according to the out-of-pocket costs per pill pack. We then estimate cost-savings of each scenario by comparing the total public sector cost of providing OCPs OTC and medical care for unintended pregnancy. ResultsTwenty-one percent of low-income women at risk for unintended pregnancy are very likely to use OCPs if they were available without a prescription. Women's use of OTC OCPs varies widely by the out-of-pocket pill pack cost. In a scenario assuming no out-of-pocket costs for the over-the counter pill, an additional 11–21% of low-income women will use the pill, resulting in a 20–36% decrease in the number of women using no method or a method less effective than the pill, and a 7–25% decrease in the number of unintended pregnancies, depending on the level of use and any effect on contraceptive failure rates. ConclusionsIf out-of-pocket costs for such pills are low, OTC access could have a significant effect on use of effective contraceptives and unintended pregnancy. Public health plans may reduce expenditures on pregnancy and contraceptive healthcare services by covering oral contraceptives as an OTC product. ImplicationsInterest in OTC access to oral contraceptives is high. Removing the prescription barrier, particularly if pill packs are available at low or zero out-of-pocket cost, could increase the use of effective methods of contraception and reduce unintended pregnancy and healthcare costs for contraceptive and pregnancy care.

Perforation of the gastrointestinal tract caused by inadvertent ingestion of blister pill packs: report of two cases diagnosed by MDCT with emphasis on maximal intensity and volume rendering reformations

We report two cases of elderly patients presenting with life-threatening complications due to inadvertent accidental ingestion of blister pill packs (BPPs). The first patient presented with obstruction followed by anemia and finally perforation of the small bowel. The second presented with rapidly lethal mediastinitis due to a large perforation of the lower esophagus. The responsible BPPs were identified by multidetector computed tomography and the best result in their characterization was obtained through maximal intensity projections and volume rendering reformations.

Does the Use of Electronic Interactive Social Networking Increase the Compliance Rate in Adolescent First Time Oral Contraceptive Users?

Background: Oral contraceptive pills (OCPs) are prescribed to adolescent girls for a variety of reasons and can provide relief for many gynecologic conditions and prevent unintended pregnancy. Research studies have highlighted high discontinuation rates in OCP users during the first few months. The objective of this study is to evaluate the effectiveness of an interactive social networking intervention on the compliance rate of firsttime adolescent oral contraceptive pill users. Methods: This prospective interventional study was approved by our Institutional Review Board. Patients between the ages of 13-21 presenting to our ambulatory center for gynecologic care and receiving a prescription of OCPs for the first time were offered enrollment. All participants possessed a cell phone with text messaging and photo capabilities. Nonpossession of a cell phone with texting and media capturing capabilities, previous OCP users and patients whom were actively pregnant were excluded. All eligible individuals agreed to participate. Participants received traditional verbal contraceptive counseling and chose a 21-day active pill or a three month extended cycle pill regimen. Participants chose to take their pill in the morning or in the evening. Pre and post intervention questionnaires were obtained documenting the participants perceived compliance rate. Participants were instructed to set a daily alarm on their phone to serve as a reminder and were registered for an online patient portal. A method for a three month follow up either in person, via telephone, or via the online portal was chosen. Daily text message reminders were sent Monday through Friday at either 0700 or 1645. The participants were prompted in the daily text messages to send a reply photo of their OCP pack. Although the number of participants enrolled in our study does not allow statistically significant comparison to historical controls regarding OCP compliance, several of our observational findings are reported. Results: To date, out of twenty participants, ten have completed the three month texting intervention. 51% of text messaging requests for photos of pill packs were returned. Frequency of text messaging was highest in weeks 1 and 8 (Fig, 1). Eight of the ten participants complied with a three month follow up. The rate of photo response was high in all participants who followed up after three months and low in the two patients that did not follow up. In the follow up group, patients recalled missing pills 3% of the time and all planned to continue use of an OCP. Based on photo responses, only two instances of missed pills were detected. Patients overwhelmingly preferred to follow up with text messaging in lieu of other methods. All incidences (3) of participant misuse errors were discovered via photo. All patients utilized interactive text messaging liberally for other concerns.

Patient-centred care

Thank you for your recent editorial1 with its entertaining and informative example of patient-centred care (PCC). (Since I already serve ethically sourced coffee and have lovely plants, the only thing lacking in my practice seems to be a leather sofa. . . .) I do position myself as a PCC provider, so I started to think of my own patient interactions that could exemplify “a professional obligation to take responsibility for, and provide care targeted to, the individual patient’s needs.”1 Like most community pharmacies, I provide weekly pill pack medications that aim to increase ease of adherence to the chosen drug therapy. But what if the patient is consistently not able to access their pill packs, resulting in (undisclosed) undertreatment? CH, a 47-year-old woman with fibromyalgia, hypertension, hypercholesterolemia, depression and restless leg syndrome, came into the pharmacy with her 12-year-old daughter to pick up her 4-week pill packs. Previously, we had provided CH with a separate bedtime pill pack, since her bedroom was on the second storey of their home and her pill pack was usually left in the kitchen (to facilitate better adherence of other medications). CH reported the separate bedtime pill pack to be extremely useful. Upon reviewing the contents of her current pill pack, CH’s daughter disclosed that her mother’s supper pills were often “left over.” CH explained that it was difficult to remember to take the supper pills and that they were often skipped. The medications that were intended for supper dosing were as follows: Ramipril 10 mg (1 of 2 daily doses) Nifedipine XL 20 mg (entire daily dose) Rabeprazole 20 mg (1 of 2 daily doses) Pregabalin 50 mg (1 of 3 daily doses) Undertreatment of her hypertension was my first concern. Although CH did not have time for me to take her blood pressure, I did request that we check it at her next visit. She did admit to not feeling the “greatest” and sleeping poorly. I also inquired about her previous stomach complaints. CH reported that the rabeprazole was to treat belching following eating meat, which had neither gotten worse or better since the physician initiated the treatment and even increased the dose from every day to twice a day, although many of the second doses were admittedly missed. I reviewed the supper dosing with CH and asked if she would be agreeable to switching the medications over to bedtime if it was reasonable to do so. CH agreed, and I called the physician to discuss CH’s medication management. According to the physician, CH’s blood pressure (as per clinic visits) had not been well controlled, so the physician agreed to institute my changes before increasing doses or adding any new medications. CH’s objective and subjective symptoms would be reviewed at the next clinic visit, as well as at the next pharmacy visit. The following were the changes made for CH: Ramipril 10 mg AM and supper changed to AM and before bedtime Nifedipine XL 20 mg at supper changed to before bedtime Rabeprazole 20 mg AM and supper changed to once a day, since it had not been any more effective for her “burping” after meat consumption with the twice-a-day dosing Pregabalin 50 mg AM, supper and before bedtime changed to 50 mg AM and 100 mg before bedtime Follow-up with CH on adherence and disease management is still pending. I feel that this scenario is a good example of listening to the patient’s needs and creating medication management techniques that are better suited to the individual while still optimizing pharmacological effectiveness. There are more glamorous examples of patient-centred care, but this is a simple example of potentially preventing unnecessary increases in medication therapy. PS: I also really appreciated the literature review on the top 5 cardiology studies from 2011 to 2012. I do hope you provide us with more! ■

A randomized controlled study of two educational interventions on adherence with oral contraceptives and condoms

BackgroundThe study was conducted to examine the effectiveness of two different interventions on oral contraception (OC) adherence and condom use. Study DesignA total of 1,155 women 16–24 years of age requesting OC were randomized to receive either face-to-face behavioral counseling and education at their baseline clinic visit (C group; n=383) or this same intervention followed by monthly phone calls for 6 months (C+P group; n=384) or standard care (S group; n=388). Phone interviews at 3, 6 and 12 months after the initial visit as well as a medical record review assessed OC continuation, condom use and several other secondary and clinically meaningful outcomes such as pregnancy and sexually transmitted infection (STI) rates and correct use of pills. ResultsThe interventions did not have a significant effect on OC continuation after 3 (C+P: 58%; C: 50%; S: 55%), 6 (39%; 32%; 37%) or 12 months (20%; 18%; 20%) (p>.05). Condom use at last sexual intercourse did not differ by intervention methods (p>.05). Moreover, no effect was observed on pregnancy [S=48 (12.4%), C =63 (16.5%), C+P=52 (13.5%); p=.22] and STI [S=18 (4.6%), C=12 (3.1%), C+P=13 (3.4%); p=.50] rates, and mean number of correctly used pill packs (p=.06). However, those randomized to C+P were more likely than C and S patients to identify a cue and report that the cue worked as a reminder to take their OC on time based on 3 and 6 months follow-up information (p<.01 for all relationships). ConclusionsNeither intervention in this study improved OC adherence among young women.

Metabolic profile of a continuous versus a cyclic low-dose combined oral contraceptive after one year of use

Objectives To compare the effects of a combined oral contraceptive (COC) taken continuously with those of one of similar composition taken cyclically on 30 variables related to haemostasis, lipids, carbohydrates, bone metabolism, and sex hormone-binding globulin (SHBG).Methods Randomised, open-label, multicentre, comparative substudy of a larger phase 3 trial involving 147 healthy women (age 18−49 years). Participants received the COC either continuously (levonorgestrel [LNG] 90 μg/ethinylestradiol [EE] 20 μg) or cyclically (21/7 days pattern; LNG 100 μg/EE 20 μg).Results After 13 pill packs, changes in total cholesterol (+0.23 vs. −0.06 mmol/l), low-density lipoprotein cholesterol (+0.25 vs. −0.12 mmol/l), and high-density lipoprotein cholesterol3 (−0.06 vs. −0.15 mmol/l) differed significantly (p<0.05) between the continuous and cyclic regimens, respectively. Increases were significantly greater (p <0.05) for protein C antigen (+11.8% vs. +6.1%) and SHBG (+791 vs. +565 nmol/l), and significantly smaller (p <0.05, ranks) for D-dimer (+19 vs. +37 μg FE/l).Conclusions Overall, the continuous and cyclic regimens affected metabolic variables similarly. The larger increase in SHBG with the continuous COC is consistent with a higher net oestrogenic effect due to a lower daily dose of LNG. Prospective studies are required to determine the long-term effects of this continuous COC regimen.

Continuation of Prescribed Compared With Over-the-Counter Oral Contraceptives

To estimate differences in continuation of oral contraceptive pills (OCPs) between U.S. resident women obtaining pills in U.S. family planning clinics compared with over-the-counter in Mexican pharmacies. In El Paso, Texas, we recruited 514 OCP users who obtained pills over the counter from a Mexican pharmacy and 532 who obtained OCPs by prescription from a family planning clinic in El Paso. A baseline interview was followed by three consecutive surveys over 9 months. We asked about date of last supply, number of pill packs obtained, how long they planned to continue use, and experience of side effects. Retention was 90%, with only 105 women lost to follow-up. In a multivariable Cox proportional hazards model, discontinuation was higher for women who obtained pills in El Paso clinics compared with those who obtained their pills without a prescription in Mexico (hazard ratio 1.6, 95% confidence interval [CI] 1.1-2.3). Considering the number of pill packs dispensed to clinic users, discontinuation rates were higher (hazard ratio 1.8, 95% CI 1.2-2.7) for clinic users who received one to five pill packs. However, there was no difference in discontinuation between clinic users receiving six or more pill packs and users obtaining pills without a prescription. Results suggest providing OCP users with more pill packs and removing the prescription requirement would lead to increased continuation.

Does convenience matter? Oral contraceptive continuation along the US–Mexico border

It has been argued that making contraception more convenient could increase use and continuation. Suggestions for making oral contraceptives (OCs) more convenient include (1) removing the prescription requirement and (2) providing users with more pill packs. We test the association of both of these measures with OC continuation in a setting where low-income women can obtain OCs without a prescription by crossing the border into Mexico.

Continuous, daily levonorgestrel/ethinyl estradiol vs. 21-day, cyclic levonorgestrel/ethinyl estradiol: efficacy, safety and bleeding in a randomized, open-label trial

Background This Phase 3, randomized, open-label, multicenter study conducted at 44 sites in Europe evaluated the safety and efficacy of a continuous, daily regimen of levonorgestrel (LNG) 90 mcg/ethinyl estradiol (EE) 20 mcg compared with a 21-day, cyclic LNG 100 mcg/EE 20 mcg regimen. Study Design Three hundred twenty-three healthy women were randomized to continuous LNG 90 mcg/EE 20 mcg and 318 subjects to cyclic LNG 100 mcg/EE 20 mcg for 1 year (13 pill packs). Pearl index, adverse event (AE) incidence and bleeding profiles were assessed. Results No pregnancies occurred with the continuous oral contraceptive (OC) (Pearl index=0.00). As the study progressed, the percentage of women who achieved amenorrhea during each 28-day pill pack increased: 40% at pill pack 7, 53% at pill pack 13. The percentage of women with no bleeding [with or without spotting (defined as not requiring sanitary protection)] was 50%, 69% and 79% at pill packs 3, 7 and 13, respectively. The incidence of AEs was similar to that of the cyclic OC (except for metrorrhagia and vaginal bleeding in the first 6 months). Conclusions Continuous LNG 90 mcg/EE 20 mcg was shown to be a safe and effective OC in this direct comparison to a cyclic OC. Suppression of menses and the potential for no bleeding requiring sanitary protection may be provided by this continuous, low-dose OC.

Altered Regimen Might Help Prevent Oral Contraceptive Failures When Pill Packs Are Started Late

Dosing errors are common in women who use oral contraceptives (OCs). Patients often fail to take the first few pills of a new pack, especially if their

Analysis of characteristics of women with early amenorrhea or persistent unscheduled bleeding with cycle-free LNG/EE, a continuous-use oral contraceptive (OC)

Most women (62%) taking cycle-free LNG/EE (levonorgestrel 90 μg/ethinyl estradiol 20 μg) as a continuous-use OC experienced amenorrhea (no bleeding or spotting) during the 28 days following 12 pill packs of use in a phase III trial. The bleeding profile was highly variable between women, and analyses of the total population for possible predictors of amenorrhea or bleeding were inconclusive. We therefore looked for clinically useful differences between subpopulations of women at the extremes of the amenorrhea/bleeding response: women with early amenorrhea or persistent unscheduled bleeding with cycle-free LNG/EE.

Ensuring the Future of Family Planning

Despite the popularity of hormonal contraceptives in the United States consistent use is infrequent and continuation rates are disappointing. In this issue of Obstetrics & Gynecology two articles examine aspects of adherence to oral contraceptive regimens. In the first article Westhoff et al describe the results of a randomized controlled trial comparing oral contraceptive continuation rates in women using a traditional Sunday start compared with Quick Start (ingestion of the first pill during the contraceptive clinic visit). This well-designed study found that Quick Start was a safe method of contraceptive initiation that was rated as acceptable or preferable to a traditional start by 81% of women. Quick Start increased the users likelihood of taking the second pill pack (odds ratio 1.5 95% confidence interval 1.0 -2.1) but unfortunately not the third or sixth and is therefore unlikely to have long-term benefits in preventing unintended pregnancy. Although the Westhoff study was not designed to examine unintended pregnancy the authors found that the number of pill packs dispensed may be a critical determinant of continuation and bears further study due to the common limitations placed on pill provision by payers in the United States. (excerpt)

Foreign body ingestion of blister pill pack causing small bowel obstruction

We report a case of foreign body ingestion of a blister pill pack, causing small bowel obstruction. A 76-year-old woman on multiple medications presented with 3 days of progressive abdominal distention, nausea, and vomiting. A computed tomography (CT) scan demonstrated small bowel obstruction with a distinctive metallic foreign body in the distal ileum with associated wall thickening and mesenteric inflammatory changes. At exploratory laparotomy, an impacted, intact blister pill pack was removed from the distal ileum. The ingestion of blister pill packs has been associated with a range of clinical and imaging findings. To our knowledge, this is the only reported case of CT diagnosis of small bowel obstruction caused by blister pack ingestion. Early recognition of the imaging findings of an ingested blister pill pack is important to expedite appropriate management.

Endometrial histology following 1 year of a continuous daily regimen of levonorgestrel 90 μg/ethinyl estradiol 20 μg

Objective The objective of this study was to evaluate the effect of a continuous daily regimen of levonorgestrel (LNG) 90 μg/ethinyl estradiol (EE) 20 μg on endometrial histology. Methods This was a substudy of a large phase 3 trial conducted in six sites in North America. Healthy and sexually active women aged between 18 and 49 years took LNG 90 μg/EE 20 μg daily for 1 year. Results from endometrial biopsies performed at pretreatment baseline and those after at least 6 months of treatment were compared. Results Of the 146 participants, 93 had a baseline biopsy and completed at least six pill packs. Before treatment, 56 subjects (60%) had an endometrial biopsy with findings classified as “weakly proliferative or proliferative.” During the last on-therapy visit, 48 subjects (52%) had an endometrium categorized as “other,” which included primarily an inactive or benign endometrium ( n=42). No hyperplasia or malignancy was observed during the study. Conclusion The results of a 1-year continuous regimen of LNG 90 μg/EE 20 μg were shown to have a good endometrial safety profile.

A Continuous-Use Regimen of Levonorgestrel/Ethinyl Estradiol Significantly Alleviates Cycle-Related Symptoms: Results of a Phase 3 Study

To evaluate the effect of a novel continuous-use regimen of levonorgestrel 90μg/ethinyl estradiol 20μg (LNG/EE Continuous) on cycle-related symptoms (CRS) and work productivity. CRS were assessed in a baseline cycle and during 3 pill packs of study drug use in a phase 3 open-label 1-year trial of contraception. Healthy women aged 18 to 49 years took 1 pill of LNG 90 μg/EE 20 μg daily starting on the first day of the first menstrual cycle and continuing through the study with no pill-free intervals. Besides inclusion criteria for the phase 3 study, CRS subjects had to have a history of CRS or dysmenorrhea. They were categorized per predefined criteria as having premenstrual syndrome (PMS) or milder cyclic symptoms, and/or dysmenorrhea based on symptoms/severity experienced in the screening cycle. Antidepressant or anxiolytic use was prohibited during the CRS portion (first 84 days). Subjects maintained the Penn Daily Symptom Rating (DSR) diary, a validated tool for assessing CRS, for 1 baseline cycle and 3 pill packs; scores ranged from 0 (not present) to 4 (severe). The 17-item Penn DSR had 4 subscales: mood, behavior, pain, and physical. CRS scores were reported as mean total and mean item scores for the last 6 days (premenstrual) and days 6 to 11 (postmenstrual) of each cycle/pill pack. Dysmenorrhea scores were reported for the first 5 days of each cycle/pill pack. Work productivity was also evaluated, using the Endicott Work Productivity Scale (EWPS) that was completed weekly at baseline and in the 3 pill packs for subjects who worked or volunteered. In the PMS group (n = 78), premenstrual total scores, all 17 item scores, as well as the difference between pre- and postmenstrual total scores decreased from baseline at all 3 pill packs (p < 0.001). Postmenstrual total scores were consistent across pill packs but higher than baseline (p < 0.002). Analysis of DSR subscales showed that all premenstrual subscale scores decreased from baseline (p < 0.001) at each pill pack, as did the difference between pre-and postmenstrual subscale scores (p < 0.001); postmenstrual subscale scores increased (p < 0.001). Results were similar in the cyclic symptoms group (n = 36): premenstrual total, all subscale scores, and the difference between pre-and postmenstrual total and subscale scores decreased at all 3 pill packs (p < 0.001). Postmenstrual total scores increased (p < 0.05), as did postmenstrual mood, behavioral, and pain subscale scores (p < 0.001). In women who reported dysmenorrhea (n = 259), LNG/EE Continuous was very effective in reducing cramps; scores decreased from baseline by 71% and 85% in pill packs 2 and 3, respectively (p < 0.001). Work productivity analyses results were consistent with those of CRS analyses, and showed rapid improvement through pill pack 3. EWPS total score decreased from baseline at pill pack 1 (p < 0.001) in PMS and dysmenorrhea groups, and was 37% and 53%, respectively, of baseline score by pill pack 3. LNG/EE Continuous is the first low-dose continuous-use oral contraceptive that significantly alleviates cycle-related symptoms. Relief of these symptoms is more marked and comprehensive than that reported with selective serotonin reuptake inhibitors in the treatment of PMS. In addition, work productivity was improved. LNG/EE Continuous is an option for women seeking relief from cycle-related symptoms and their effects, and who also desire contraception.