Association Between Baseline Diastolic Blood Pressure and the Efficacy of Intensive vs Standard Blood Pressure-Lowering Therapy.

Importance: Low diastolic blood pressure (DBP) has been found to be associated with increased adverse cardiovascular events; however, it is unknown whether intensifying blood pressure therapy in patients with an already low DBP to achieve a lower systolic blood pressure (SBP) target is safe or effective. Objective: To evaluate whether there is an association of baseline DBP and intensification of blood pressure-lowering therapy with the outcomes of all-cause death and cardiovascular events. Design, Setting, and Participants: This cohort study analyzed patients who were randomized to intensive or standard BP control in the Action to Control Cardiovascular Risk in Diabetes-Blood Pressure (ACCORD-BP) trial and Systolic Blood Pressure Intervention Trial (SPRINT). Data were collected from September 1999 to June 2009 (ACCORD-BP) and from October 2010 to August 2015 (SPRINT). Data were analyzed from December 2020 to June 2021. Exposures: Baseline DBP as a continuous variable. Main Outcomes and Measures: All-cause death and a composite cardiovascular end point (CVE) that included cardiovascular death, nonfatal myocardial infarction, and nonfatal stroke. Results: A total of 14 094 patients (mean [SD] age, 66.2 [8.9] years; 8504 [60.4%] men) were included in this analysis. There were significant nonlinear associations between baseline DBP and all-cause death (eg, baseline DBP 50 vs 80 mm Hg: hazard ratio [HR], 1.48; 95% CI, 1.06-2.08; P = .02) and the composite CVE (eg, baseline DBP 50 vs 80 mm Hg: HR, 1.45; 95% CI, 1.27-3.04; P = .003) observed among all participants. Findings for the interaction between baseline DBP and treatment group assignment for all cause death did not reach statistical significance. For intensive vs standard therapy, the HR of death for a baseline DBP of 50 mm Hg was 1.80 (95% CI, 0.95-3.39; P = .07) and that for a baseline DBP of 80 mm Hg was 0.77 (95% CI, 0.59-1.01; P = .05). Overall, there was no interaction found between baseline DBP and treatment group assignment for the composite CVE. Over the range of baseline DBP values, significant reductions in the composite CVE for patients assigned to intensive vs standard therapy were found for baseline DBP values of 80 mm Hg (HR, 0.78; 95% CI, 0.62-0.98; P = .03) and 90 mm Hg (HR, 0.74; 95% CI, 0.55-0.98; P = .04). Conclusions and Relevance: This pooled cohort study found no evidence of a significant interaction between baseline DBP and treatment intensity for all-cause death or for a composite CVE. These results are hypothesis generating and merit further study.

This is not the time to modify a HTN regimen.

Intensifying hypertension regimens at discharge increases risk in older patients.

Pharmaceutical company payments to authors of the Japanese guidelines for the management of hypertension.

ABSTRACT: Antihypertensive drugs have been of significant interest to the pharmaceutical industry due to increasing sales opportunities in a global market. The financial relationships between pharmaceutical companies and the Japanese Society of Hypertension (JSH) have a possible influence on clinical practices in Japan. This study examined the distribution of pharmaceutical payments made to the authors of the revised Guidelines for the Management of Hypertension (JSH2019) and the transparency of the Conflict of Interest disclosure that each author made.We retrospectively obtained publicly available data regarding payments made by Japanese pharmaceutical companies to all authors of the JSH2019 in 2016. We also collected data on individual financial disclosure of JSH2019 authors to investigate whether their self-reported financial relationship with companies were compliant to the financial disclosure policy of JSH2019.The total and mean payment values reported by pharmaceutical companies were $4,246,436 and $21,447, respectively. Of the 198 authors, 171 (86.4%) authors received at least 1 payment. Of 74 authors required to disclose their conflict of interest (COI) the authors, one-third failed to follow the COI policy covering the clinical guidelines.Major pharmaceutical companies selling antihypertensive drug products in the Japanese market had a significant financial connection with the JSH2019 authors. Financial relationships between pharmaceutical companies and authors or Japanese medical societies are raising significant concerns about the credibility of clinical guidelines and the potentially biases and undue influences that they may cause, especially with respect to adverse prescription patterns.

Improving transitions of care for critically ill adult patients on pulmonary arterial hypertension medications.

PURPOSE: The purpose of this report is to describe the activities of critical care and ambulatory care pharmacists in a multidisciplinary transitions-of-care (TOC) service for critically ill patients with pulmonary arterial hypertension (PAH) receiving PAH medications. SUMMARY: Initiation of medications for treatment of PAH involves complex medication access steps. In the ambulatory care setting, multidisciplinary teams often have a process for completing these steps to ensure access to PAH medications. Patients with PAH are frequently admitted to an intensive care unit (ICU), and their home PAH medications are continued and/or new medications are initiated in the ICU setting. Inpatient multidisciplinary teams are often unfamiliar with the medication access steps unique to PAH medications. The coordination and completion of medication access steps in the inpatient setting is critical to ensure access to medications at discharge and prevent delays in care. A PAH-specific TOC bundle for patients prescribed a PAH medication who are admitted to the ICU was developed by a multidisciplinary team at an academic teaching hospital. The service involves a critical care pharmacist completing a PAH medication history, assessing for PAH medication access barriers, and referring patients to an ambulatory care pharmacist for postdischarge telephone follow-up. In collaboration with the PAH multidisciplinary team, a standardized workflow to be initiated by the critical care pharmacist was developed to streamline completion of PAH medication access steps. Within 3 days of hospital discharge, the ambulatory care pharmacist calls referred patients to ensure access to PAH medications, provide disease state and medication education, and request that the patient schedule a follow-up office visit to take place within 14 days of discharge. CONCLUSION: Collaboration by a PAH multidisciplinary team, critical care pharmacist, and ambulatory care pharmacist can improve TOC related to PAH medication access for patients with PAH. The PAH TOC bundle serves as a model that may be transferable to other health centers.

Substandard and Falsified Antibiotics and Medicines against Noncommunicable Diseases in Western Cameroon and Northeastern Democratic Republic of Congo.

Falsified and substandard medicines may undermine the progress toward the Sustainable Development Goals. The present study investigated the quality of 13 essential medicines in Cameroon and the Democratic Republic of Congo (DR Congo). Five hundred six medicine samples were collected from the government and faith-based health facilities, private pharmacies, and informal vendors (total 60 facilities). Collected samples were analyzed according to the U.S. Pharmacopeia (USP) for identity, content, and dissolution of their active pharmaceutical ingredients (APIs) and for uniformity of dosage units. Three samples (0.6%) were identified as falsified. Overall, 8.5% of the samples failed USP specifications for the content of the API and 11.7% failed dissolution testing. Medicines from informal vendors showed a higher out-of-specification rate (28.2%) than other types of drug outlets (12.3%; P < 0.0001). All three falsified medicines had been sold by informal vendors. The failure rate of medicines stated to be produced in Europe (5.1%) was lower than that for medicines from Asia (17.7%; P = 0.0049) and Africa (22.2%; P = 0.0042). Medicines against noncommunicable diseases showed a higher failure rate than antibiotics (25.3% versus 12.1%; P = 0.0004). Four hundred fifty-one of the samples were analyzed in Cameroon and the DR Congo with the Global Pharma Health Fund Minilab (thin-layer chromatography and disintegration testing). The three falsified medicines were readily detected in Minilab analysis. However, substandard samples were detected with low sensitivity. A well-enforced ban of medicine sales by informal vendors and increased attention to supplier qualification in the procurement process may reduce the prevalence of substandard and falsified medicines.

Effectiveness of a multifactorial intervention, consisting of self-management of antihypertensive medication, self-measurement of blood pressure, hypocaloric and low sodium diet, and physical exercise, in patients with uncontrolled hypertension taking 2 or more antihypertensive drugs: The MEDICHY study.

INTRODUCTION: High blood pressure is the leading modifiable risk factor for cardiovascular disease, and is associated with high morbidity and mortality and with significant health care costs for individuals and society. However, fewer than half of the patients with hypertension receiving pharmacological treatment have adequate blood pressure control. The main reasons for this are therapeutic inertia, lack of adherence to treatment, and unhealthy lifestyle (i.e., excess dietary fat and salt, sedentary lifestyle, and overweight). Cardiovascular risk and mortality are greater in hypertensive patients who are receiving treatment but have suboptimal control of blood pressure. METHODS/DESIGN: This is a multicentre, parallel, 2-arm, single-blind (outcome assessor), controled, cluster-randomized clinical trial. General practitioners and nurses will be randomly allocated to the intervention group (self-management of antihypertensive medication, self-measurement of blood pressure, hypocaloric and low sodium diet, and physical exercise) or the control group (regular clinical practice). A total of 424 patients in primary care centers who use 2 or more antihypertensive drugs and blood pressure of at least 130/80 during 24-hambulatory blood pressure monitoring will be recruited. The primary outcome is systolic blood pressure at 12 months. The secondary outcomes are blood pressure control (<140/90 mm Hg); quality of life (EuroQol 5D); direct health care costs; adherence to use of antihypertensive medication; and cardiovascular risk (REGICOR and SCORE scales). DISCUSSION: This trial will be conducted in the primary care setting and will evaluate the impact of a multifactorial intervention consisting of self-management of blood pressure, antihypertensive medications, and lifestyle modifications (hypocaloric and low sodium diet and physical exercise).

Efficacy of catheter-based renal denervation in the absence of antihypertensive medications (SPYRAL HTN-OFF MED Pivotal): a multicentre, randomised, sham-controlled trial.

BACKGROUND: Catheter-based renal denervation has significantly reduced blood pressure in previous studies. Following a positive pilot trial, the SPYRAL HTN-OFF MED (SPYRAL Pivotal) trial was designed to assess the efficacy of renal denervation in the absence of antihypertensive medications. METHODS: In this international, prospective, single-blinded, sham-controlled trial, done at 44 study sites in Australia, Austria, Canada, Germany, Greece, Ireland, Japan, the UK, and the USA, hypertensive patients with office systolic blood pressure of 150 mm Hg to less than 180 mm Hg were randomly assigned 1:1 to either a renal denervation or sham procedure. The primary efficacy endpoint was baseline-adjusted change in 24-h systolic blood pressure and the secondary efficacy endpoint was baseline-adjusted change in office systolic blood pressure from baseline to 3 months after the procedure. We used a Bayesian design with an informative prior, so the primary analysis combines evidence from the pilot and Pivotal trials. The primary efficacy and safety analyses were done in the intention-to-treat population. This trial is registered at ClinicalTrials.gov, NCT02439749. FINDINGS: From June 25, 2015, to Oct 15, 2019, 331 patients were randomly assigned to either renal denervation (n=166) or a sham procedure (n=165). The primary and secondary efficacy endpoints were met, with posterior probability of superiority more than 0·999 for both. The treatment difference between the two groups for 24-h systolic blood pressure was -3·9 mm Hg (Bayesian 95% credible interval -6·2 to -1·6) and for office systolic blood pressure the difference was -6·5 mm Hg (-9·6 to -3·5). No major device-related or procedural-related safety events occurred up to 3 months. INTERPRETATION: SPYRAL Pivotal showed the superiority of catheter-based renal denervation compared with a sham procedure to safely lower blood pressure in the absence of antihypertensive medications. FUNDING: Medtronic.

Effectiveness of two-drug therapy versus monotherapy as initial regimen in hypertension: A propensity score-matched cohort study in the UK Clinical Practice Research Datalink.

PURPOSE: To compare the effectiveness on blood pressure (BP) of initial two-drug therapy versus monotherapy in hypertensive patients. METHODS: Using the Clinical Practice Research Datalink, linked with Hospital Episode Statistics and Office for National Statistics, we identified a cohort of adults with uncontrolled hypertension, initiating one or two antihypertensive drug classes between 2006 and 2014. New users of two drugs and monotherapy were matched 1:2 by propensity score. Main exposure was "as-treated," ie, until first regimen change. Primary and secondary endpoints were systolic and diastolic BP control and major adverse cardiovascular event (MACE), respectively. Hazard ratios (HR) and 95% confidence intervals (CI) were estimated using Cox proportional hazard models. RESULTS: Of 54 523 eligible patients, 3256 (6.0%) were initiated to a two-drug combination. Of these, 2807 were matched to 5614 monotherapy users. Mean exposure duration was 12.7 months, with 76.5% patients changing their initial regimen. Two-drug therapy was associated with a clinically significant BP control increase in all hypertensive patients (HR = 1.17 [95%CI: 1.09-1.26]), more so in patients with grade 2-3 hypertension (HR = 1.28 [1.17-1.41]). An increase of 27% in BP control (HR = 1.27 [1.08-1.49]) was observed in patients initiating an ACEi+CCB combination compared with initiators of either single class. No significant association was found between two-drug therapy and MACE. Several sensitivity analyses confirmed the main findings. CONCLUSIONS: Few patients initiated therapy with two drugs, reflecting UK guidelines' recommendation to start with monotherapy. This study supports the greater effectiveness of two-drug therapy as the initial regimen for BP control.

Equivalence in Active Pharmaceutical Ingredient of Generic Antihypertensive Medicines Available in Nigeria (EQUIMEDS): A Case for Further Surveillance.

BACKGROUND: Widespread access to good quality antihypertensive medicines is a critical component for reducing premature cardiovascular disease (CVD) mortality. Poor-quality medicines pose serious health concerns; however, there remains a knowledge gap about the quality of cardiovascular medicines available in low- and middle-income countries. OBJECTIVES: The aim of this study was to determine the quality of generic antihypertensive medicines available in the retail market of a developing country. METHODS: Samples of the 2 most commonly prescribed classes of antihypertensive medicines were collected from 3 states in 3 different geopolitical zones in Nigeria following a semirandom sampling framework. Medicine samples were purchased by mystery shoppers from 22 pharmacy outlets from 6 local government areas across the 3 states. Medicine quality was determined by measuring the amount of stated active pharmaceutical ingredient using high-performance liquid chromatography with photodiode array detection and classified according to their compliance to the specified pharmacopeia tolerance limits for each antihypertensive drug. RESULTS: Amlodipine and lisinopril were identified as the most commonly prescribed antihypertensive drugs in Nigeria. In total, 361 samples from 22 pharmacies were collected and tested. In total, 24.6% of amlodipine and 31.9% of lisinopril samples were of substandard quality and significantly more samples purchased in rural (59 of 161, 36.7%) compared with urban (32 of 200, 16%) outlets were found to be of substandard quality (p < 0.001). No falsified samples of either amlodipine or lisinopril were detected. There was large variation in price paid for the antihypertensive medicines (range ₦150 to ₦9,750). Of the 24 pharmacy outlets surveyed, 46% stated that patients did not always require a prescription and 21% had previously reported a medicine as falsified or substandard. CONCLUSIONS: More than one-quarter of some commonly prescribed antihypertensive medicines available in Nigeria may be of substandard quality. Enhanced quality assurance processes in low- and middle-income countries, such as Nigeria, are needed to support optimum management.

Considerable international variation exists in blood pressure control and antihypertensive prescription patterns in chronic kidney disease.

Although blood pressure control is a major goal in chronic kidney disease, no worldwide overview of either its achievement or antihypertensive prescriptions is currently available. To evaluate this we compared crude prevalence of uncontrolled blood pressure among 17 cohort studies, including 34 602 individuals with estimated glomerular filtration rate under 60 ml/min/1.73 m2 and treated hypertension across four continents, and estimated observed to expected prevalence ratios, adjusted for potential confounders. Crude prevalence of blood pressure of 140/90 mm Hg or more varied from 28% to 61% and of blood pressure of 130/80 or more from 54% to 84%. Adjusted prevalence ratios indicated poorer hypertension control than expected in cohorts from European countries, India, and Uruguay, and better control in patients from North American and high-income Asian countries. Four antihypertensive drug classes or more were prescribed to more than 30% of participants in North American and some European cohorts, but this practice was less common elsewhere. Renin angiotensin-aldosterone system inhibitors were the most common antihypertensive drugs, prescribed for 54% to 91% of cohort participants. Differences for other drug classes were much stronger, ranging from 11% to 79% for diuretics, 22% to 70% for beta-blockers, and 27% to 75% for calcium-channel blockers. The confounders studied explain only a part of the international variation in blood pressure control among individuals with chronic kidney disease. Thus, considerable heterogeneity in prescription patterns worldwide calls for further investigation into the impact of different approaches on patient outcomes.

Evaluating the quality of antihypertensive drugs in Lagos State, Nigeria.

BACKGROUND: As the burden of noncommunicable diseases grows, access to safe medical therapy is increasing in importance. The aim of this study was to develop a method for evaluating the quality of antihypertensive drugs and to examine whether this prevalence varies by socioeconomic variables. METHODS: We conducted a cross-sectional survey of registered pharmacies in 6 local government areas (LGAs) in Lagos State, Nigeria. In each LGA, we sampled 17 pharmacies from a list of all registered pharmacies derived from the Pharmacists Council of Nigeria. We assessed drug quality based on (1) the level of active pharmaceutical ingredients (APIs), which identified falsely labeled drug samples; and (2) the amount of impurities, which revealed substandard drug samples in accordance with the international pharmacopoeia guidelines. Good-quality drugs met specifications for both API and impurity. RESULTS: Of the 102 drug samples collected, 30 (29.3%) were falsely labeled, 76 (74.5%) were substandard,78 (76.5%) were of poor quality and 24 (23.5%) were of good quality.Among the falsely labeled drugs, 2 samples met standards set for purity while 28 did not. Among the 76 substandard drug samples, 28 were also falsely labeled. Of the falsely labeled drugs, 17 (56.7%) came from LGAs with low socioeconomic status, and 40 (52.6%) of the substandard drug samples came from LGAs with high socioeconomic status. Most of the good-quality drug samples, 14 (58.3%), were from LGAs with low socioeconomic status. Eighteen (60%) of the falsely labeled samples, 37 (48.7%) of the substandard samples, and 15 (62.5%) of the good-quality drug samples were from manufacturers based in Asia. The average price was 375.67 Nigerian naira (NGN) for falsely labeled drugs, 383.33 NGN for substandard drugs, and 375.67 NGN for good-quality drugs. The prevalence of falsely labeled and substandard drug samples did not differ by LGA-level socioeconomic status (P = .39) or region of manufacturer (P = .24); however, there was a trend for a difference by price (P = .06). CONCLUSION: The prevalence of falsely labeled and substandard drug samples was high in Lagos. Treatment of noncommunicable diseases in this setting will require efforts to monitor and assure drug quality.

Sufficient and Persistent Blood Pressure Reduction in the Final Long-Term Results From SYMPLICITY HTN-Japan　- Safety and Efficacy of Renal Denervation at 3 Years.

BACKGROUND: SYMPLICITY HTN-Japan is a prospective, randomized, controlled trial comparing renal denervation (RDN) with standard pharmacologic therapy for treatment of uncontrolled hypertension (HTN). Methods and Results: Patients enrolled had uncontrolled HTN, defined as office systolic blood pressure (SBP) ≥160 mmHg and 24-h ambulatory SBP ≥135 mmHg, on ≥3 antihypertensive drugs of maximally tolerated dose for at least 6 weeks prior to enrollment. Randomization was 1:1 to RDN or maintenance of current medical therapy (control). Patients were followed every 6 months post-randomization for up to 36 months. There were 22 patients randomized to RDN and 19 to control, and 11 patients were crossed over and received RDN at 6 months post-randomization. For the RDN group (n=22), office SBP reduction was -32.8±20.1 mmHg and office DBP reduction was -15.8±12.6 mmHg at 36 months post-procedure, both P<0.001. For the combined RDN and crossover group (n=33), office SBP reduction was -26.7±18.9 mmHg and office DBP reduction was -12.7±11.8 mmHg at 30 months post-procedure, both P<0.001. There were no procedural-, device- or treatment-related safety events through 36 months. CONCLUSIONS: SYMPLICITY HTN-Japan is the first randomized controlled trial to evaluate RDN in an Asian population. Despite the small number of enrollments, results show patients who received RDN therapy maintained SBP reduction out to 36 months.

Analysis of an Impurity, N-Nitrosodimethylamine, in Valsartan Drug Substances and Associated Products Using GC-MS.

Valsartan products, commonly used to treat high blood pressure and heart failure, have been recalled in many countries due to the presence of an impurity, N-nitrosodimethylamine (NDMA), in the recalled products. We present and evaluate a GC-MS-based analytical method for the determination of NDMA levels and attempt an investigation of NDMA concentrations in valsartan drug substances and associated products. The limit of detection and limit of quantification for the method were estimated to be 0.1 and 0.5 µg/g, respectively, when testing a 0.5-g sample. A good trueness (99%) with a small relative standard deviation (1.9%) was obtained for a valsartan product spiked with NDMA at a concentration of 1.0 µg/g. Additionally, a valsartan drug substance and the associated product, which were previously determined to have NDMA contamination, were analyzed by the method. The NDMA content by our method was very close to previously determined values. Finally, six samples, including valsartan drug substances and associated, commercially available products in Japan, all of which were derived from the company implicated in the NDMA contamination, were analyzed by our method, revealing that none of these samples contained detectable concentrations of NDMA. Overall, the data indicate that the present method is reliable and useful for determination of NDMA in valsartan drug substances and associated products.

Isolation, identification, characterization, synthesis and quality control strategy of new process-related impurities in ambrisentan.

Ambrisentan is a highly selective endothelin-A receptor antagonist for the treatment of pulmonary arterial hypertension (PAH). The analysis of the process-related impurities will help not only to optimize the process parameters but also to develop reasonable analytical methods and set the quality standard for a quality control strategy in pharmaceutical manufacturing. During the manufacture of ambrisentan, five unknown impurities were detected in pilot batches ranging from 0.05% to 0.15% by HPLC. All of these impurities were isolated and synthesized successfully and were identified and characterized by LC-MS, HRMS, ESI-MS/MS(Q-Tof), 1D-NMR (1H, 13C, DEPT) and 2D-NMR (COSY, HSQC, HMBC) techniques. The formation mechanisms that yield these impurities are discussed for the first time. Quality control strategies to deal with these impurities are developed to obtain bulk drug of ICH-grade quality.

[Limits to the treatment of hypertension]. / Grenzen aan de behandeling van hypertensie.

According to the 2011 Dutch guideline on Cardiovascular risk management 1 in 5 hypertensive patients are eligible for blood pressure lowering treatment. The Dutch guideline recommends striving for a systolic blood pressure (SBP) of < 140 mmHg in adult patients who have no cardiovascular disease or diabetes mellitus, while the recent American guideline now recommends an SBP target value of < 130 mmHg for all adult patients. An important reason for using a stricter SBP target value are the results of randomised studies and meta-analyses that looked at the effect of intensive antihypertensive therapy on the risk of mortality and cardiovascular disease. Based on the literature, there appears to be sufficient evidence that intensive antihypertensive therapy (SBP target value of < 130 mmHg) is useful in patients with cardiovascular disease and in patients with high cardiovascular risk. Currently, there is insufficient evidence that intensive antihypertensive therapy is useful in patients who have diabetes mellitus or who are over 80 years old.

Survey to Identify Substandard and Falsified Tablets in Several Asian Countries with Pharmacopeial Quality Control Tests and Principal Component Analysis of Handheld Raman Spectroscopy.

The World Health Organization has warned that substandard and falsified medical products (SFs) can harm patients and fail to treat the diseases for which they were intended, and they affect every region of the world, leading to loss of confidence in medicines, health-care providers, and health systems. Therefore, development of analytical procedures to detect SFs is extremely important. In this study, we investigated the quality of pharmaceutical tablets containing the antihypertensive candesartan cilexetil, collected in China, Indonesia, Japan, and Myanmar, using the Japanese pharmacopeial analytical procedures for quality control, together with principal component analysis (PCA) of Raman spectrum obtained with handheld Raman spectrometer. Some samples showed delayed dissolution and failed to meet the pharmacopeial specification, whereas others failed the assay test. These products appeared to be substandard. Principal component analysis showed that all Raman spectra could be explained in terms of two components: the amount of the active pharmaceutical ingredient and the kinds of excipients. Principal component analysis score plot indicated one substandard, and the falsified tablets have similar principal components in Raman spectra, in contrast to authentic products. The locations of samples within the PCA score plot varied according to the source country, suggesting that manufacturers in different countries use different excipients. Our results indicate that the handheld Raman device will be useful for detection of SFs in the field. Principal component analysis of that Raman data clarify the difference in chemical properties between good quality products and SFs that circulate in the Asian market.

Stability of an extemporaneously compounded minoxidil oral suspension.

PURPOSE: Results of a study to determine the stability of an extemporaneously compounded minoxidil oral suspension under various temperature and stress conditions are reported. METHODS: Commercially available minoxidil tablets (10 mg) were crushed to a fine powder, and predetermined amounts of 2 suspending vehicles were added to produce a 1-mg/mL suspension, which was stored in glass bottles at room temperature (25 ± 2 °C) or in a refrigerator (4 ± 2 °C). To simulate daily patient use, 5 days weekly 1 bottle of the suspension was removed from refrigerated storage and shaken and 0.5 mL of the contents discarded. At each specified time point, samples were analyzed in duplicate (n = 6 for each test condition) using a validated high-performance liquid chromatography method. Samples were visually observed and their pH measured at each time point. Microbiological studies were performed on day 0 and at week 24. RESULTS: The mean percentage of initial minoxidil concentration remaining in all refrigerated samples exceeded 90% throughout the 24-week study, with no change in appearance, pH, microbial activity, odor, or redispersibility. During storage at room temperature, the suspension exhibited a color change at week 4, with slight sedimentation after 6 weeks, although minoxidil recovery exceeded 90% for 10 weeks. CONCLUSION: An extemporaneously compounded minoxidil oral suspension was stable for 24 weeks when stored in a refrigerator. This suspension can be used for up to 3 weeks when stored at room temperature.

Substandard drugs among five common antihypertensive generic medications: an analysis from 10 African countries.

OBJECTIVE: Hypertension results in more deaths than any other risk factor and has been on the rise in sub-Saharan Africa over the past few decades. Generic drugs have helped improve accessibility and affordability of antihypertensive therapy in developing countries. However, assessment of quality standards of these products is important. We performed a quality assessment of five commonly used antihypertensive generic drugs in 10 sub-Saharan African countries and studied the impact of price on quality. METHODS: Drug samples were prospectively collected using standardized methods between 2012 and 2014. We developed a validated reversed-phase liquid chromatography with tandem mass spectrometry method to accurately quantify the active ingredient in a certified public laboratory. Quality was defined based on the percentage ratio of measured to expected dosage of active ingredient. RESULTS: A total of 1185 samples were assessed, of which 70.0% were generic (n = 830). Among the generic drugs, the percentage of poor-quality drugs was 24.3% (n = 202/830). The percentage ratio of measured to expected dosage of active ingredient ranged from 49.2 to 111.3%; the majority (81.7%) of the poor-quality samples had insufficient quantity of the active ingredient. Moreover, poor quality was not associated with purchase price of the drug. CONCLUSION: In this study from 10 sub-Saharan African countries, nearly one-quarter of the available generic antihypertensive drugs were found to be of poor quality. Concerted measures to improve the quality of antihypertensive drugs could lead to major improvements in hypertension control with attendant reduction of its deleterious consequences in low-income and middle-income countries.