BackgroundHyperphosphatemia is associated with increased morbidity and mortality in patients with end-stage kidney disease (ESKD). Whereas clinical and observational studies have demonstrated the effectiveness of sucroferric oxyhydroxide (SO) in controlling serum phosphorus (sP) in ESKD, data on the real-world impact of switching to SO in patients on peritoneal dialysis (PD) are limited. In this retrospective database analysis, we examine the impact of SO on sP management over a 1-year period among PD patients prescribed SO as part of routine clinical care.MethodsWe analyzed de-identified data from adults on PD in Fresenius Kidney Care clinics who were prescribed SO monotherapy between May 2018 and December 2019 as part of routine clinical management. Changes from baseline in sP levels, phosphate binder (PB) pill burden, and laboratory parameters were evaluated during the four consecutive 91-day intervals of SO treatment.ResultsThe mean age of the 402 patients who completed 1 year of SO was 55.2 years at baseline, and they had been on PD for an average of 19.9 months. SO was initiated with no baseline PB recorded in 36.1% of patients, whereas the remaining 257 patients were switched to SO from sevelamer (39.7%), calcium acetate (30.4%), lanthanum (1.2%), ferric citrate (14.0%), or more than one PB (14.8%). Mean sP at baseline was 6.26 mg/dL. After being prescribed SO, the percentage of patients achieving sP ≤ 5.5 mg/dL increased from 32.1% (baseline) to 46.5–54.0% during the 1-year follow-up, whereas the mean number of PB pills taken per day decreased from 7.7 at baseline (among patients on a baseline PB) to 4.6 to 5.4. Serum phosphorus and PB pill burden decreased regardless of changes in residual kidney function over the 12-month period. Similar results were observed for the full cohort (976 patients who either completed or discontinued SO during the 1-year follow-up).ConclusionsPatients on PD who were prescribed SO as part of routine care for phosphorus management experienced significant reductions in SP and PB pills per day and improvements in sP target achievement, suggesting the effectiveness of SO on SP management with a concurrent reduction in pill burden.

IntroductionChronic kidney disease-related mineral and bone disorder (CKD-MBD), characterized by abnormalities in calcium, phosphate, and parathyroid hormone metabolism, with impaired bone turnover and extravascular calcification is a known complication of advanced chronic kidney disease (CKD). Secondary hyperparathyroidism (SHPT) develops early in the disease and its prevalence gradually increases with the disease progression, becoming almost universal in patients with end-stage renal disease (ESRD). The treatment for SHPT includes synthetic vitamin D analogs, calcitriol or calcimimetics. Recently, intravenous etelcalcetide was introduced as a second-generation calcimimetic. This article provides the real-world experience of using etelcalcetide in multiethnic Asian patients receiving hemodialysis at community-based hemodialysis centers in Singapore.MethodsThis study was real-world evidence, generated by a retrospective clinical audit of routine clinical care of hemodialysis patients in community-based centers in Singapore who received etelcalcetide for treating SHPT. The information on the starting and maximum dose of etelcalcetide, duration of treatment on hemodialysis, parathyroid hormone (PTH) levels, dialysate calcium, concomitant medications, and reasons for discontinuation were collected from the medical records. PTH levels were collected at four-, eight-, and twelve-month intervals.ResultsA total of 148 patients received etelcalcetide during the study period. Ten patients died and twenty discontinued their treatment, with 118 patients remaining on treatment. Demographically, the patients included Chinese, Malay, Indians, and those belonging to other racial groups. The starting dose of etelcalcetide ranged from 2.5 mg once per week to 7.5 mg three times a week. There was a 16.8% reduction (p=<0.001) in intact-PTH after four months of therapy. Target intact-PTH level of less than 60 pmol/L, was reported as 1.4% at baseline, with 22.3% at four months (p<0.001) and 25.9% at eight months (p=0.028). Calcium and phosphate levels were also tracked as part of the safety and efficacy measures of using etelcalcetide. No symptomatic hypocalcemia was noted and phosphate levels were noted to decline significantly. Overall, the calcium-phosphate product reduced at four months (13.2%, p=<0.001) and eight months (12.7%, p<0.05). An analysis of concomitant medication usage, dialysate calcium utilized, and the side effects of etelcalcetide were also recorded. Finally, a brief descriptive analysis of the patient's subjective feedback regarding etelcalcetide was also reported, especially regarding the reduction in pill burden and overall compliance to medications.ConclusionEtelcalcetide is safe and effective for treating SHPT in multi-ethnic Asian hemodialysis patients and can be considered an alternative to oral cinacalcet. Our study showed no side effects, which was one of the key reasons for non-compliance to traditional calcimimetics. A favorable compliance profile with reduced pill burden was noted by using this intravenous calcimimetic.

IntroductionComplex polypharmacy regimens to manage persistent motor fluctuations result in significant pill burden for patients with advanced Parkinson’s disease (APD). This study evaluated the effectiveness of carbidopa/levodopa enteral suspension (CLES) and deep brain stimulation (DBS) on reducing pill burden in APD patients.MethodsWe utilized 100% Medicare fee-for-service claims from 2014 to 2018 linked to CLES Patient Support Program (PSP) data. CLES initiators (CLES-I) were propensity matched 1:1 with patients enrolled in PSP who did not initiate treatment (CLES-NI) (N = 188) or undergo DBS, and 1:3 with patients who received DBS (N = 204, N = 612). Average daily pill burden and levodopa equivalent daily dosage (LEDD) were measured at baseline, 0–6 months and 7–12 months follow-up.ResultsCLES-I and CLES-NI had higher pill burden than DBS patients at baseline. However, at 6 months post-treatment, CLES-I had significantly fewer pills/day than CLES-NI (4.7 versus 11.4, p < 0.05) and DBS (4.8 versus 7.4, p < 0.05). A significant reduction in pill burden was observed at 0–6 months (46.3%) and 7–12 months (68.3%) follow-up for CLES-I (p < 0.001) versus increased burden for CLES-NI (+10.5%, p < 0.05 and +8.2%, p > 0.05) and insignificant reductions for DBS (−3.9% and −6.1%, p > 0.05). Mean adjusted pill burden showed 57.3% fewer pills at 0–6 months and 74.1% at 7–12 months among CLES-I compared with CLES-NI, and 49.6% and 70.1% reduction compared with DBS. CLES-I showed a decrease in LEDD at 7–12 months compared with baseline (935 to 237 mg) and to CLES-NI (237 mg versus 1112 mg) and DBS patients (236 mg versus 594 mg).ConclusionCLES led to a significant reduction in pill burden and oral LEDD compared with CLES-NI and DBS patients. Pill burden reduction could be considered a treatment goal for patients with APD challenged by complex polypharmacy regimens that interfere with activities of daily living and quality of life.Graphical

Chronic spontaneous urticaria (CSU) in children is mostly spontaneous in onset (57%). Treatment comprises long-term antihistaminic therapy without need for elaborate investigations. A subset of such patients don't respond to conventional treatment and novel therapies to help reduce pill burden is the need of the hour. To determine the efficacy and safety of autologous serum therapy (AST) in pediatric patients with chronic spontaneous urticaria. All pediatric patients, aged between 6-16 years, attended to our OPD from March 2019 to March 2020 were recruited. Clinico-demographic data and baseline investigations of all patients were performed. Two-weekly AST therapy was given for 8 visits with levocetrizine tablet 5mg on an on-demand basis. Urticaria activity score (UAS) sheet was provided to record and return every 2 weeks. Statistical analysis was done using the IBM SPSS 26 software package. Autologous serum skin test (ASST) was positive in 63% patients. Both the ASST positive and ASST negative group showed significant reduction in UAS7 score at week 14 compared to baseline. The reduction in mean UAS7 score was associated with a decreased pill burden and positive response in the patient and physician global assessment scale. No statistically significant difference between the two groups in terms of mean UAS7 reduction was found. This study has explored the efficacy and safety of autologous serum therapy in the pediatric CSU patients. Both ASST positive and ASST negative group respond to AST therapy.

Abstract Background Hospital at Home is a rapidly growing initiative whereby patients are offered hospital equivalent interventions at their home. Given that patient numbers under the care of this team are often smaller than those on inpatient hospital wards, there is often more time to develop a personalised approach to medicine optimisation. Methods All 42 patients under the care of the local 'Hospital at Home' team had their medication reviewed by the team's Consultant Pharmacist for Older People. Using the STOP START tool with information from patients and carers each patient's medication was optimised. Results This data was analysed by a research pharmacist and anticholinergic burden, Eadon score, pill burden, adverse drug events and average direct drug cost savings were identified. All residents had their medication optimised. 5.25 clinical interventions per resident 81% were Eadon Grade 4. Medication appropriateness improved with downwards trend, pre and post intervention. The mean anticholinergic burden reduced to less than 3. (pre 3.63 vs post 2.63). An overall reduction in pill burden; for every 1 drug started 3 drugs were stopped (mean number of drugs 16 vs 13, pre and post intervention respectively). 50% of residents had an adverse drug event (causing harm) identified. Average direct drug costs savings of £385.28 per patient per annum. Conclusion This research shows the importance of the role of the 'Consultant Pharmacist for OIder People' in medicine optimisation in the 'Hospital at Home' team. It also highlights the benefit of the 'Hospital at Home' service to facilitate the often time-consuming task of effective medicine optimisation.

Combined antiretroviral therapy (cART) is treatment with a combination of several antiretroviral drugs that block multiple stages in the virus replication cycle. An estimated 60% of the 38 million HIV-1 patients globally receive some form of cART. The benefits of cART for controlling HIV-1 replication, transmission, and infection rates have led to its universal recommendation. Implementation has caused a substantial reduction in morbidity and mortality of persons living with HIV-1/AIDS (PLWHA). More specifically, standard cART has provided controlled, undetectable levels of viremia, high treatment efficacy, reduction in pill burden, and an improved lifestyle in HIV-1 patients overall. However, HIV-1 patients living with AIDS (HPLA) generally show high viral loads upon cART interruption. Latently infected resting CD4+ T cells remain a major barrier to curing infected patients on long-term cART. There is a critical need for more effective compounds and therapies that not only potently reactivate latently infected cells, but also lead to the death of these reactivated cells. Efforts are ongoing to better control ongoing viral propagation, including the identification of appropriate animal models that best mimic HIV-1 pathogenesis, before proceeding with clinical trials. Limited toxicity profiles, improved drug penetration to certain tissues, and extended-release formulations are needed to cover gaps in existing HIV-1 treatment options. This review will cover past, current, and new cART strategies recently approved or in ongoing development.

Aim and Objective: To find the association between polypharmacy and health consequences in type 2 diabetes mellitus (T2DM). Materials and Methods: 50 patients with multiple drugs (two or more) and morbidity, glycemic control, macrovascular complications, hospitalization, gastrointestinal disorders, cost of medicine were studied. History, physical examination, relevant investigation, and consequences of drugs were also studied. Results: Male to female: 32:18; average age: 44 years. Findings were: hyperglycemia is seen in 34 patients, hypoglycemia in 2, retinopathy in 10, coronary artery disease (CAD) by electrocardiogram (ECG) and 2D echo in 12, old myocardial infarction in 3, renal function test abnormality in 6, stroke in 2, hypertension in 15, dyslipidemia in 13, hypothyroidism in 3, and hospitalization due to any of the above in 5. Conclusion: Diabetes, a metabolic disorder, due to chronicity leads to macrovascular and microvascular complications which in turn are compelled to increase the number of medications due to uncontrolled hyperglycemia. More than two-third of patients in our study showed uncontrolled hyperglycemia. Diabetes has multiple sites and mechanisms of altered physiological and pathological processes. It is practical to have the requirement of more than two drugs when blood sugar in diabetes is not controlled. Also, it is obvious that the simultaneous use of more than one drug-having different mechanism of action appears to have an impact on treatments to control hyperglycemia. Sometimes, multiple drugs/therapy may give rise to undesirable side effects and it may be due to drug-drug or disease drug interaction. Furthermore, the activity of multiple targets by multiple drugs requires additional study. Multiple drugs in diabetes were seen more in males with geriatric age groups. Main reasons being comorbidities, which may be the main cause of morbidity and mortality, especially CAD, heart failure and diabetic cardiomyopathy. There is an indirect relationship between the glycemic control and the development and progression of clinical manifestations of comorbidities. Various comorbid diseases in diabetes require concomitant medications, that increases pill burden. Tailoring medical therapies to the patient’s biological characteristics may help to optimize disease treatment, thereby improving overall prognosis and decreasing comorbidities’ risk. Appropriate exercise and diet may reduce hyperglycemia with reduction in pill burden.

Antiretroviral (ARV) therapy in people living with HIV (PLWH) and end-stage renal disease (ESRD) on hemodialysis (HD) is complicated, requiring renally adjusted nucleoside reverse transcriptase inhibitors (NRTIs) and daily administration of non-renally eliminated agents. Recent data in PLWH with ESRD on HD demonstrate maintenance of viral suppression (82% with viral loads (VLs) <50 copies/mL) and favorable safety/tolerability profiles after ARV simplification with a fixed dose combination single tablet [elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (E/C/F/TAF)]. Extrapolation of these data to all F/TAF formulations would allow ARV simplification to most PLWH with ESRD receiving HD. The objective of this retrospective study was to identify if ARV-experienced PLWH with ESRD on HD receiving renally adjusted NRTIs may be simplified to once daily ARV formulations without adverse effects while maintaining viral suppression. This single-center retrospective analysis assessed virologic control (3-12months) and ARV tolerability post-regimen simplification (primarily NRTI once-daily dose adjustment) in PLWH with ESRD on thrice weekly HD receiving human immunodeficiency virus (HIV) care in an ambulatory clinic. Seventeen PLWH with ESRD on HD were included after documented ARV simplification. At 12months, 12 patients (71%) remained undetectable (HIV VL <50 copies/mL) with two additional maintaining viral suppression (<200 copies/mL). One patient remained undetectable at month eight but became non-adherent with viral rebound. Two patients did not complete the 6- and 12-month evaluation after documented nonadherence (N = 1) and an adverse effect (pruritus) (N = 1). At 12months, virologic suppression and tolerability resulted after a simplified ARV regimen including once daily F/TAF was initiated in PLWH with ESRD on thrice weekly HD with a reduction in pill burden.

Association of Deprescribing With Reduction in Mortality and Hospitalization: A Pragmatic Stepped-Wedge Cluster-Randomized Controlled Trial

BackgroundPhosphate binders are widely used to achieve serum phosphorus control in patients with end-stage renal disease. However, the large pill burden associated with these medications may decrease adherence to therapy. In clinical trials, sucroferric oxyhydroxide (SO) demonstrated equivalent control of serum phosphorus to sevelamer, with a lower daily pill burden. We examined changes in phosphate binder pill burden, medication possession ratio (MPR), and phosphorus control among in-center hemodialysis (ICHD) patients converting to SO from another phosphate binder as part of routine care.Materials and methodsPatients included in this retrospective analysis (N=490) were ≥18 years old, received ICHD at a large dialysis organization (LDO), and were enrolled in the LDO’s pharmacy service. Patients converting to SO were those who had supply of another phosphate binder, received a first prescription fill for SO, and subsequently did not refill the non-SO phosphate binder. Patients were followed over the 6 months before and 6 months following the first SO fill and were censored from the analysis upon modality change, loss to follow-up, discontinuation of SO, or fill of a prescription for another phosphate binder after SO initiation (number censored=361). Outcome measures assessed were total phosphate binder pill burden and MPR, serum phosphorus, and percentage of patients with serum phosphorus ≤5.5 mg/dL.ResultsAmong patients converting to SO, mean phosphate binder pill burden was 10.8 pills/day during baseline; this decreased to 5.5 pills/day during follow-up (P<0.001). The percentage of patients with serum phosphorus ≤5.5 mg/dL increased from 22.0% to 30.0% (P<0.001). Among patients not using the LDO pharmacy’s automated refill management service (N=30), mean phosphate binder MPR increased from 0.68 during baseline to 0.80 during follow-up (P=0.01).ConclusionIn a cohort of ICHD patients, conversion to SO was associated with a reduction in pill burden, better adherence, and improvements in phosphorus control.

Background:It is widely accepted that for HIV-positive persons on highly active antiretroviral treatment, high levels of adherence to treatment regimens are essential for promoting viral suppression and preventing drug resistance.Objectives:This qualitative study examines factors affecting the adherence to HIV/AIDS treatment among patients with HIV/AIDS at a local hospital in Malaysia.Methods:The data from purposefully selected patients were collected by in-depth interviews using a pretested interview guide. Saturation was reached at the 13th interview. All interviews were audio-taped and transcribed verbatim for analysis using thematic content analysis.Results:Fear and stigma of perceived negative image of HIV diagnosis, lack of disease understating, poor support from the community, and perceived severity or the treatment side effects were among the reasons of nonadherence. Appropriate education and motivation from the doctors and reduction in pill burden were suggested to improve adherence.Conclusion:Educational interventions, self-management, and peer and community supports were among the factors suggested to improve adherence. This necessitates uncovering efficient ways to boost doctor–patient communication and recognizing the role of support group for the social and psychological well-being of the patients.

Epilepsy is one of the most common chronic neurologic disorders that affects individuals of all ages. It is primarily managed with antiepileptic drugs (AEDs), with the goal of maintaining complete seizure control combined with minimal or no adverse effects. Oral administration is the mainstay of AED delivery for patients with chronic epilepsy and consists essentially of immediate-release (IR) and modified-release (delayed-release and extended-release [ER]) dosage formulations. Extended-release formulations (hydrophilic or hydrophobic matrix systems, reservoir systems, and osmotic-release systems) release a drug in a controlled manner during an extended period of time following administration. Extended-release formulations have many advantages compared with IR formulations, including simplification of dosing regimens, reduction in pill burden, and reduction in the peak-to-trough fluctuations in serum drug concentration that may be associated with a decreased risk of adverse effects and of seizures. These advantages have the potential to increase adherence to antiepileptic therapy, improve the quality of life of patients, and reduce health care costs. This article, which is intended as a practical guide for clinicians, reviews the properties of the different ER AED formulations currently available and discusses the advantages of ER over IR formulations. Subsequently, an explanation of the technologic basis of the different oral ER formulations, the critical attributes that differentiate ER products, and their individual strengths and weaknesses is provided. Specific recommendations to practitioners on treating patients with ER formulations are included.

Reducing polypharmacy directly improves quality use of medicines, a key arm of the Australian National Medicines Policy. Numerous studies have illustrated that a reduction in pill burden improves patient compliance, reduces drug economics and minimizes therapy-related adverse effects. Phosphate binders are the single largest contributor to the daily pill burden in chronic kidney disease patients undergoing renal replacement therapy. The aim of this study was to examine the relationship between pill burden and cost of phosphate binders with biochemical parameters in patients undergoing centre-based haemodialysis within the Kidney Health Service of the Metro North Hospital and Health Service. Centre-based haemodialysis patients from three geographically different kidney units in Queensland, Australia, underwent a single, cross-sectional assessment of total daily pill burden from phosphate binders between May 2015 and August 2015. The total number of phosphate binder pills per week comprised of calcium carbonate, aluminium hydroxide, sevelamer hydrochloride, lanthanum and cinacalcet. The urea reduction ratio, serum albumin, serum calcium, serum phosphate and serum parathyroid hormone (PTH) were averaged across this period. Of the 138 patients in this study, 62 (44.9%) patients were from the Royal Brisbane and Women’s Hospital (RBWH), 40 (29.0%) patients were from Redcliffe Satellite Unit and 36 (26.1%) patients were from the Northlakes Satellite Unit. Eighty-two (59.4%) were male and the mean age was 66 (standard deviation 15) years. Between hospital comparisons of baseline co-morbidities revealed significant difference in hypertension (P = 0.014) only. Sevelamer hydrochloride was most commonly used at RBWH at 41%, followed by calcium carbonate (32%) and aluminium hydroxide (22%). In contrast, both Northlakes and Redcliffe had similar phosphate binder use with calcium carbonate being most popular (36% and 58% respectively), followed by sevelamer hydrochloride (33% and 15% respectively) and aluminium hydroxide (8% and 14% respectively). Forty-two percent of RBWH patients, 45% of Redcliffe patients and 58% of Northlakes patients were taking two or more classes of phosphate binders. There were no statistically significant differences across the three kidney health services in relation to total pill burden (P = 0.17), weekly phosphate binder cost (P = 0.13), or serum calcium (P = 0.35), serum phosphate (P = 0.61) and serum PTH (P = 1.00). Comparison of weekly phosphate binder cost between the three sites revealed no significant difference (P = 0.12) with RBWH $41.58 (1.89–84.58), Redcliffe $5.32 (1.89–46.52) and Northlakes $44.87 (5.20–87.52). No appreciable differences in the pill burden and phosphate binder cost per week were associated with biochemical outcomes between the RBWH, Northlakes and Redcliffe kidney health service. Several studies have recently emerged regarding the lack of efficacy and survival benefit of phosphate binders in patients undergoing centre-based haemodialysis. This study reinforces ongoing concerns regarding the minimal biochemical and economic improvement associated with phosphate binder use in this group of dialysis patients. Future studies should compare the cost and pill burden of phosphate binders in other Australian centres and ascertain whether any biochemical and economic changes occur in patients undergoing haemodialysis in the home environment.

Proton pump inhibitors (PPIs) are a class of medications that reduce acid secretion and are used for treating many conditions such as gastroesophageal reflux disease (GERD), dyspepsia, reflux esophagitis, peptic ulcer disease, and hypersecretory conditions (e.g. Zollinger-Ellison syndrome), and as part of the eradication therapy for Helicobacter pylori bacteria. However, approximately 25% to 70% of people are prescribed a PPI inappropriately. Chronic PPI use without reassessment contributes to polypharmacy and puts people at risk of experiencing drug interactions and adverse events (e.g. Clostridium difficile infection, pneumonia, hypomagnesaemia, and fractures). To determine the effects (benefits and harms) associated with deprescribing long-term PPI therapy in adults, compared to chronic daily use (28 days or greater). We searched the following databases: Cochrane Central Register of Controlled Trials (CENTRAL; 2016, Issue 10), MEDLINE, Embase, clinicaltrials.gov, and the World Health Organization International Clinical Trials Registry Platform (WHO ICTRP). The last date of search was November 2016. We handsearched the reference lists of relevant studies. We screened 2357 articles (2317 identified through search strategy, 40 through other resources). Of these articles, we assessed 89 for eligibility. We included randomized controlled trials (RCTs) and quasi-randomized trials comparing at least one deprescribing modality (e.g. stopping PPI or reducing PPI) with a control consisting of no change in continuous daily PPI use in adult chronic users. Outcomes of interest were: change in gastrointestinal (GI) symptoms, drug burden/PPI use, cost/resource use, negative and positive drug withdrawal events, and participant satisfaction. Two review authors independently reviewed and extracted data and completed the risk of bias assessment. A third review author independently confirmed risk of bias assessment. We used Review Manager 5 software for data analysis. We contacted study authors if there was missing information. The review included six trials (n = 1758). Trial participants were aged 48 to 57 years, except for one trial that had a mean age of 73 years. All participants were from the outpatient setting and had either nonerosive reflux disease or milder grades of esophagitis (LA grade A or B). Five trials investigated on-demand deprescribing and one trial examined abrupt discontinuation. There was low quality evidence that on-demand use of PPI may increase risk of 'lack of symptom control' compared with continuous PPI use (risk ratio (RR) 1.71, 95% confidence interval (CI) 1.31 to 2.21), thereby favoring continuous PPI use (five trials, n = 1653). There was a clinically significant reduction in 'drug burden', measured as PPI pill use per week with on-demand therapy (mean difference (MD) -3.79, 95% CI -4.73 to -2.84), favoring deprescribing based on moderate quality evidence (four trials, n = 1152). There was also low quality evidence that on-demand PPI use may be associated with reduced participant satisfaction compared with continuous PPI use. None of the included studies reported cost/resource use or positive drug withdrawal effects. In people with mild GERD, on-demand deprescribing may lead to an increase in GI symptoms (e.g. dyspepsia, regurgitation) and probably a reduction in pill burden. There was a decline in participant satisfaction, although heterogeneity was high. There were insufficient data to make a conclusion regarding long-term benefits and harms of PPI discontinuation, although two trials (one on-demand trial and one abrupt discontinuation trial) reported endoscopic findings in their intervention groups at study end.

Combining antihyperglycemic agents with complementary mechanisms of action is a cornerstone of type 2 diabetes mellitus (T2DM) management. Although several fixed-dose combinations (FDCs) are available, representing standard types of combination therapy in T2DM, use of these products has been limited. To address the likely concerns of prescribers and patients regarding the use of FDCs in the treatment of T2DM, literature searches were performed to ascertain the bioavailability, efficacy, tolerability, and cost-effectiveness of the currently approved FDCs compared with their individual component drugs given as separate pills in combination. Additionally, data were collected on rates of adherence, clinical outcomes, and overall treatment costs with FDCs versus dual therapy with the same constituent drugs. Bioavailability is equivalent for FDCs and dual therapy used in T2DM. Efficacy and tolerability also appear to be at least as good with FDCs as with dual therapy. Retrospective analyses have suggested that FDCs can enhance adherence to therapy, presumably as a result of the reduction in pill burden, and improved adherence may result in improved glycemic control and reduced disease management costs. In addition, because currently available FDCs come in two or more dose-strength formulations, they also afford some measure of dosing flexibility. The available evidence supports the wider use of FDCs in the treatment of patients with T2DM.

Introduction: Ritonavir, a protease inhibitor (PI), is commonly used in the treatment of HIV-1 infection. It is a potent inhibitor of the hepatic cytochrome P450 superfamily. Therefore, its usage with other PI medications leads to significant increases in the levels of the latter PI, which allows a reduction in pill burden. Intranasal and inhaled corticosteroids are widely used for the treatment of allergic rhinitis and asthma. Inhaled steroids do not usually lead to systemic adverse events, since their plasma concentrations are quite low due to extensive first-pass metabolism and clearance by CYP3A4. However, the coadministration of Ritonavir with inhaled (or intranasal) corticosteroids may result in an increase in the plasma corticosteroid levels due to the potent CYP3A4 inhibition by Ritonavir. This may cause Cushing’s syndrome (laboratory and clinical) with adrenal suppression. Methods: Plasma cortisol and urinary-free cortisol levels were determined using immunoassays. In the Synacthen test, plasma cortisol levels were measured at time 0 as well as at times 60, 120, and 150 minutes following an intramuscular injection of 0.25 mg Synacthen. Results: We present here three HIV-1 female patients aged 12, 55 and 65 years who developed iatrogenic Cushing’s syndrome with adrenal suppression following the coadministration of Ritonavir and inhaled Fluticasone, both at the standard recommended doses. Conclusions: The coadministration of Ritonavir and Fluticasone at the recommended doses caused, in our three patients, iatrogenic Cushing’s syndrome with adrenal suppression. We suggest that this adverse event is underdiagnosed and high clinical suspicion is needed for early diagnosis and prenention of Addisonian crises. Thus, Fluticasone treatment should be avoided in patients who are treated with Ritonavir. Alternative therapeutic options for asthma control such as oral Montelukast or bronchodilators alone should be considered.