Fixed-dose Combination Research Articles

Simultaneous Estimation of Orlistat and Clomiphene by Hplc: Stability-Indicating Method Development and Validation.

Aim: To quantify Clomiphene and Orlistat in pharmaceutical formulations simultaneously, this study is set out to create a sensitive, fast, and accurate stability-indicating RP-HPLC method. Materials and Methods: The isocratic method was used to achieve the chromatographic separation of the Clomiphene and Orlistat mixture. A mobile phase was prepared using a 60:40% v/v ratio of acetonitrile to 0.01N Potassium dihydrogen orthophosphate (PH 4.8). The Agilent C18 column, with dimensions of 150 x 4.6mm, a 5µm particle size, and a flow rate of 1.0 mL/min was used. With an injection volume of 10.0 mL, the detection system was observed at a maximum wavelength of 240 nm. Results: The retention time for Orlistat was 2.12 minutes while that for Clomiphene was 2.88 minutes. Various factors, including heat, acidity, oxidation, photolysis, and alkalinity, were used to test the combined medication formulation of Clomiphene and Orlistat. To ensure that this method is accurate, precise, linear, and sensitive, it was validated according to the standards set out by the ICH. Conclusion: The run time was reduced to 6.0 minutes, enhancing the method’s precision and cost-effectiveness. Stability studies confirmed the technique’s suitability for assessing the degradation of Clomiphene and Orlistat. The proposed method is well-suited for routine analysis in pharmaceutical quality control.

Preparation of Mouth Dissolving Sublingual Film of Fixed Dose Combination of Hydrochlorothiazide and Losartan Potassium and Statistical Optimization of Film.

Fast-dissolving films (FDFs) are innovative dosage forms offering advantages such as improved patient compliance, rapid onset of action, precise dosing, and favorable taste. Particularly beneficial for patients unable to swallow or require immediate drug absorption, FDFs dissolve rapidly in the mouth, releasing medication directly into the oral cavity. The sublingual application enhances drug delivery due to the high permeability of the sublingual mucosa, bypassing hepatic first-pass metabolism. This route is advantageous for drugs like losartan potassium (LP) and hydrochlorothiazide (HCZ), which benefit from enhanced bioavailability and faster onset of action. Preformulation studies included UV spectroscopy for λmax determination (LP: 282 nm, HCZ: 250 nm), DSC for thermal analysis (LP: 289.11°C, HCZ: 104.76°C), and solubility studies confirming LP’s solubility in acidic pH and HCZ’s increased solubility in pH 6.7 buffer. Compatibility studies using FTIR and DSC validated stability with excipients. Formulation optimization with HPMC E15 resulted in films with characteristics like film weight (145.66–167.0 mg), thickness (0.246–0.326 mm), folding endurance (898.0–1274.0), pH (6.0–6.70), disintegration time (77.66–174.6 s), tensile strength (77.04–141.90 g/cm²), and drug release profiles (LP: 68.78–96.22%, HCZ: 59.49–95.43% at 21 minutes). In summary, this study successfully developed LP and HCZ FDFs with optimized characteristics, demonstrating their potential in hypertension management and improving therapeutic outcomes.

In-Depth Analysis of Molecular Network Based on Liquid Chromatography Coupled with Tandem Mass Spectrometry in Natural Products: Importance of Redundant Nodes Discovery.

The identification of molecules within complex mixtures is a major bottleneck in natural products (NPs) research. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) has emerged as the main tool for the high-throughput characterization of NPs. The large amount of data sets by LC-MS/MS presents a challenge for data processing and interpretation, and the LC-MS/MS molecular network (MN) is one of the most prominent tools for analyzing large MS/MS data sets, widely used for rapid classification, identification, and structural speculation of unknown compounds. However, the existence of a large number of redundant nodes leads to false-positive results. To solve this problem, we proposed the in-depth analysis of MN. In this study, in-depth analysis of MN of five NPs representing the common structures of saponin, steroid, flavonoid, alkaloid, and phenolic acid revealed the presence of redundant nodes (including other adducts, isotope, and in-source fragmentation) in addition to the normal nodes, which can lead to false-positive identification results. Additionally, the reasons for different redundant nodes are discussed and experimentally verified, and it was found that the impact of redundant nodes can be mitigated by optimizing the experimental conditions and employing Feature-Based Molecular Networking. Furthermore, Ion Identity Molecular Networking can rapidly discover and screen redundant nodes, simplifying the in-depth analysis of MN and improving the network connectivity of structurally related molecules. Finally, a combination formulation of 7 NPs is used as an example to provide a guide for in-depth analysis of MN for comprehensive characterization of complex systems. This study highlights the importance of an in-depth analysis of MN for better understanding and utilization of MS/MS data in complex systems to reduce the false-positive rate of identification by screening and filtering redundant nodes.

Evaluation of Efficacy of Present Fixed Dose Combinations for Daily Antitubercular Treatment Under RNTCP

Evaluation of Efficacy of Present Fixed Dose Combinations for Daily Antitubercular Treatment Under RNTCP

Efficacy and Safety of Pioglitazone/Metformin Fixed-Dose Combination Versus Uptitrated Metformin in Patients with Type 2 Diabetes without Adequate Glycemic Control: A Randomized Clinical Trial.

We aim to evaluate the efficacy and safety of pioglitazone/metformin fixed-dose combination (FDC) versus uptitrated metformin in patients with type 2 diabetes mellitus (T2DM) without adequate glycemic control. A total of 304 patients were recruited from 15 hospitals in China and randomly assigned (1:1) to the test group (pioglitazone/metformin FDC, 15/500mg) or the control group (uptitrated metformin, 2000-2500mg/day). The primary endpoint was the proportion of patients with glycated hemoglobin A1c (HbA1c) ≤ 6.5% and ≤ 7.0% at week 16. The secondary outcomes included the change from baseline in glucose, serum lipids, and liver function. Full analysis set (FAS) and per-protocol set (PPS) were used for analyses. In the test group, 103 (69.59%) patients reached HbA1c ≤ 7.0% (FAS, P = 0.009), with 68 (45.95%) patients achieved HbA1c ≤ 6.5 (FAS, P = 0.043). More reduction in HbA1c, homeostatic model assessment for insulin resistance, and diastolic pressure was found. Bodyweight, body mass index, and high-density lipoprotein cholesterol increased markedly. The changes of triglycerides, alanine transaminase, aspartate aminotransferase, and high-sensitivity C-reactive protein decreased noticeably. There were no significant differences in rates of adverse events between the two groups. Pioglitazone/metformin FDC was superior to uptitrated metformin among patients with T2DM without adequate glycemic control. This trial is registered with the Chinese Clinical Trial Registry (ChiCTR1900028606).

Polypills in the Management of Cardiovascular Risk-A Perspective.

Cardiovascular disease and cardiovascular risk factors are global healthcare problems, given their high prevalence and the recognized low rates of adequate control despite the abundant body of evidence on different therapeutic options. The World Heart Federation has scrutinized the reasons for poor control of cardiovascular risk factors. Among these reasons, patients' poor adherence to treatment regimens as well as limited rates of evidence-based therapy prescription from healthcare providers play a substantial role in the challenge of cardiovascular risk management. Polypills are fixed-dose combinations including two or more active drugs, from different pharmacological classes, combined in a single dosage form. Polypills were designed to simplify the clinical management of pharmacotherapy and increase adherence to treatment. From this perspective, we discuss the current literature on the use of polypills in the primary and secondary prevention of cardiovascular disease as well as future challenges and the potentials of this treatment strategy.

Triple Fixed-dose combination of Dapagliflozin, Sitagliptin, and Metformin for People with Type 2 Diabetes in Indian Settings

Objective: This study assessed the bioequivalence of a fixed-dose combination (FDC) therapy containing extended-release Metformin (Metformin XR), Dapagliflozin, and Sitagliptin for treating type 2 diabetes (T2D). The objective was to compare the absorption rate and extent of the FDC with two reference products: Sitagliptin 100mg tablets (R1) and a combination of Dapagliflozin 10mg plus Metformin 1000mg extended-release tablets (R2) in healthy adult males under fed conditions. Methods: An open-label, randomized, cross-over study was conducted with 24 healthy male participants. Each participant received a single dose of the test FDC and the reference products, with blood samples collected over 72 hours to evaluate pharmacokinetic parameters (Cmax, AUC0-t, AUC0-inf, Tmax, Kel, AUC_% Extrap_obs, and t1/2). Bioequivalence was determined based on the 90% confidence intervals (CIs) of the geometric mean ratios for AUC0-t and Cmax, within a predefined range of 80.00%-125.00%. Safety and tolerability were also assessed. Results: Pharmacokinetic analysis was performed on 22 subjects. The geometric mean ratios for the FDC compared to the reference products were within the predefined bioequivalence range, indicating that the absorption profiles of the FDC and the reference products were similar. The mean plasma concentration-time curves for Dapagliflozin, Sitagliptin, and Metformin XR were almost identical between the FDC and reference products, demonstrating consistent drug release and absorption. No significant differences were observed in Tmax, t1/2, or other pharmacokinetic parameters, further supporting bioequivalence. Additionally, the FDC was well-tolerated, with no serious adverse events reported, and all subjects completed the study without complications. Conclusion: The study confirmed that the FDC of Dapagliflozin, Sitagliptin, and Metformin XR is bioequivalent to the reference products in healthy adult males under fed conditions. This bioequivalence supports the use of the FDC as an effective treatment option to improve glycemic control in adults with T2D, particularly in the Indian context, promoting the benefits of combined therapy in managing diabetes. Keywords: Bioequivalence, Fixed-dose combination (FDC), Type 2 diabetes (T2D), Pharmacokinetics, Dapagliflozin, Metformin XR, Sitagliptin

Citral-thymol based synergistic shellac coatings enhanced shelf life of Kinnow fruit stored under low temperature conditions

Microbial spoilage incurs the main cause of reduced shelf life of Kinnow during storage and transportation. This study aimed to evaluate the postharvest application of plant-derived citral and thymol-based shellac wax coatings on ‘Kinnow’ mandarin under controlled conditions (5–7 °C, 90–95 % relative humidity (RH)) over a 75-day storage period. The fruit were coated with shellac wax (SH) supplemented with citral (1.0 %, CSH), thymol (1.0 %, TSH) and citral-thymol combined formulation (1.0 %, CTSH (1:1)). Rheology studies revealed that the Herschel–Bulkley model was the best fit for all coating solutions, ensuring desirable spreadability and adhesion. The CTSH-coating outperformed all other treatments by reducing mean spoilage to 0.46% as compared to commercial shellac (6.71%) over a period of 75 days under cold store conditions. The treated fruit could control the physiological weight loss to 5.73 % as compared to commercial SH coatings (7.62 %) for 60 days. The study concluded that CTSH-coated Kinnow fruit can be stored up to 60 days under cold store conditions at 5–7 °C and 90–95 % RH with acceptable fruit quality (sensory score 7.83). The activities of cell wall degrading enzymes such as Pectin methylesterase (PME) and cellulase were also found to be retarded, contributing to prolonged shelf life. Therefore, these coatings may offer a green substitute to the synthetic analogues, with no health side effects for extending the postharvest shelf life of Kinnow up to 60 days under cold store conditions.

New topical combinations in acne therapy

Introduction. Therapeutic treatment modalities for acne involve both topical and oral medications. Fixed-dose combinations that affect all components of the pathogenesis of acne vulgaris are given preference among topical medications.Aim. To evaluate the efficacy and tolerability of Metrogyl® a topical drug, containing adapalene and metronidazole, which is used as topical therapy in patients with mild to moderate acne.Materials and methods. A prospective, open-label, randomized, single-centre comparative study was conducted in 2022. A total of 60 patients were subjected to the Mir-O-Med clinic-based observation (Krasnodar): 19 men and 41 women aged 18 to 45 years with mild to moderate acne. Group 1 received a fixed-dose combination of adapalene 1.0 mg and metronidazole10.0 mg (Metrogyl® A); Group 2 – a fixed-dose combination of adapalene 0.1% and clindomycin phosphate 1%; Group 3 – a fixed-dose combination of adapalene 0.1% and benzoyl peroxide 2.5% gel; Group 4 – adapalene 0.1%. Group 5, a separately created group, included patients from Group 1, who continued therapy for another 3 months.Results. After therapy, 6 (40%) patients from Group 1 archived clinical remission, and 9 (60%) patients found significant improvement. No deterioration in patients’ condition or absence of clinical effects was observed during therapy. The combination of adapalene and metronidazole (Metrogyl® A) to treat mild to moderate acne is comparable in terms of efficacy to the combination of adapalene and benzoyl peroxide, 10% more efficient than topical adapalene therapy and 30% more efficient than topical antibiotics combination.Conclusion. The obtained results showed high therapeutic efficacy, good tolerability and safety of Metrogyl® A, which allows to use it as monotherapy and as part of combination with other agents in patients with mild to moderate acne.

Optimization of a Twin screw melt granulation process for fixed dose combination immediate release Tablets: Differential amorphization of one drug and crystalline continuance in the other

Interest in Twin Screw Melt Granulation (TSMG) processes is rapidly increasing, along with the search for suitable excipients. This study aims to optimize the TSMG process for immediate-release tablets containing two different drugs. The hypothesis is that one poorly water-soluble drug requires amorphous conversion for improved dissolution, while the other water-soluble drug, with a higher melting point (Tm), remains more stable in its crystalline form. Ibuprofen (IBU) and Acetaminophen (APAP) were chosen as the model drug combination to test this hypothesis. Various diluents, binders, and disintegrating agents were assessed for their impact on processability, crystallinity, disintegration, and dissolution during development. The temperatures used during processing were below the Tm of all components, except for IBU. Melted IBU acted as a granulating aid in addition to the binders in the formulation, facilitating granule formation. Physicochemical analyses by Differential Scanning Calorimetry (DSC) and X-ray Diffraction (XRD) confirmed the complete conversion of IBU into an amorphous state and the preserved crystalline nature of APAP. Saturation solubility studies showed an improvement in IBU’s solubility by ∼ 32-fold in 0.1 N HCl. Poor tablet disintegration performance led to the addition of disintegrating agents, where osmotic agents (sorbitol and NaCl) were found to significantly enhance disintegration compared to super disintegrants. The optimized formulation showed an enhanced IBU release (∼20 %) compared to the physical mixture (∼12.5) in 0.1 N HCl dissolution studies.

Formulation and evaluation of novel orodispersible tablet by drug-drug solid dispersion of metoprolol tartrate and hydrochlorothiazide

This study investigates the effect of a novel drug-drug solid dispersion approach on the dissolution of hydrochlorothiazide in a fixed-dose combination with metoprolol tartrate. Solid dispersions of hydrochlorothiazide and metoprolol tartrate (12.5 mg: 25 mg) were prepared using the solvent evaporation technique. These dispersions were characterized by differential scanning calorimetry (DSC), Fourier-transform infrared spectroscopy (FTIR). The prepared solid dispersions, along with selected excipients, were compressed into orodispersible tablets and evaluated for precompression and post compression parameters. The solubility of hydrochlorothiazide was observed to increase with the concentration of metoprolol tartrate, as demonstrated by phase solubility studies and comparative solubility studies. Stability studies on the tablets indicated no significant changes in disintegration time, dissolution profile, or overall stability. The findings of this study suggest that the novel drug-drug solid dispersion approach is promising for enhancing the dissolution of poorly soluble drugs, when combined with soluble drugs in fixed-dose combinations.

Multimodal Analgesia Approach in Acute Low Back Pain Management: A Phase III Study of a Novel Analgesic Combination of Etoricoxib/Tramadol.

Pain and disability management are crucial for a speedy recovery. Combining analgesics with different mechanisms of action provides greater pain relief with lower doses, promoting efficient multimodal analgesia. This study evaluated the efficacy and safety between two fixed-dose combinations (FDC): etoricoxib/tramadol compared to paracetamol/tramadol for the management of acute low back pain (LBP) in a 7-day treatment. We conducted a phase IIIb, prospective, randomized, and multicenter study in patients with acute LBP treated with etoricoxib 90mg/tramadol 50mg (one packet of granules diluted in 100ml of water, once a day [QD], for 7 days) or paracetamol 975mg/tramadol 112.5mg (one tablet of 325mg/37.5mg, three times a day [TID], for 7 days) to assess the efficacy (in terms of pain and disability improvement) and safety. One hundred and twenty-four patients were randomized to receive either etoricoxib/tramadol QD (n = 61) or paracetamol/tramadol TID (n = 63). From the magnitude of change in pain evaluations, differences were observed between the treatment groups at 3 [p = 0.054, CI 95% -0.648 (-0.010 to 1.306)] and 5days (p = 0.041). The proportion of patients with a 30% reduction in Visual Analogue Scale (VAS) score was statistically significant when comparing the treatment groups on the third day of follow-up [p = 0.008, CI 95% 0.241 (0.061-0.421)]. An improvement in LBP's disability to perform activities of daily routine (Oswestry and Roland-Morris questionnaires) was observed in both treatment groups. A total of 79 adverse events (AEs) (38 [48.1%] with etoricoxib/tramadol and 41 [51.9%] with paracetamol/tramadol) were reported. The most frequent AEs were nausea (17.7%) and dizziness (16.4%). The results show the clinical benefits of etoricoxib/tramadol FDC, such as the sparing effect of tramadol dose per day, early therapeutic response rate compared with paracetamol/tramadol; which translates into faster pain relief, better adherence, less tramadol drug dependency, and a reduction of related AEs incidence. ClinicalTrials.gov identifier, NCT04968158.

Multicentric Post-Marketing Surveillance (PMS) Observational Study of Ascorbic Acid and Zinc Effervescent Tablets in Indian Patients with Vitamin C and Zinc Deficiency.

The objective of this Multicentric Post-Marketing Surveillance (PMS) study was to evaluate the safety and tolerance of vitamin C and zinc tablets in the Indian population experiencing deficiencies of these nutrients. Furthermore, the study aimed to provide insights into physicians' prescription practices and characterise the patient population receiving the study medication. This prospective observational study involved 358 participants from 8 study sites across India (including 2 government hospital sites), spanning a duration of approximately 12 weeks (3 months). The primary aim was to evaluate the safety and tolerability of zinc and ascorbic acid effervescent tablets for those who were deficient in zinc and vitamin C. Throughout the study period, adverse events were monitored and categorised by MedDRA Primary System Organ Class and Preferred Term. The analysis included evaluating the incidence, percentage, and correlation of adverse events with the treatment (safety population). Additionally, the frequencies of adverse drug reactions were examined across all enrolled patients. Vital signs and symptom-focused physical examinations were conducted during each visit in the safety population. Out of 358 (100%) patients, only 12 (3.35%) experienced minor symptoms in the study period. The majority of patients reported gastrointestinal disorders, i.e., two (0.6%) patients reported constipation and gastritis, respectively. Diarrhoea was reported by four (1.1%) patients. One (0.3%) patient reported gastrointestinal pain. Three (0.8%) patients reported vomiting. Diarrhoea was the most common symptom reported. All patients possess a mild intensity of adverse drug reactions in safety populations. The P-value is less than 0.05 (p-value < 0.05), and therefore there is a statistically significant relationship between the predictor variables and the response variable (i.e., the expected count of adverse drug reactions). The fixed-dose combination of vitamin C and zinc effervescent tablets appears to be safe and tolerable for the treatment of vitamin C and zinc deficiencies in Indian patients. The favorable outcome underscores the mild nature of the adverse reactions and the right medical interventions and support.<p>.

Errors associated with co-names of medicines: The nomenclature of combination medicinal products.

In comparison to the efforts required to bring a new drug or formulation to the clinic, bestowing a name on a medicine is relatively simple. However, if the name we choose causes confusion-by making its contents ambiguous or if it is too alike another drug-it can precipitate clinical errors. This prompted the World Health Organization to set up the International Nonproprietary Naming Committee in the 1970s to select unambiguous names for drugs. Unfortunately, multidrug products-which are becoming increasingly popular-do not fall under the remit of conventional International Non-proprietary Nomenclature. We have identified 26 combination formulations that have been historically named with the co-drug format in the United Kingdom. Most of them have also been prescribed in the United Kingdom in the past year, and although several of them are not prescribed very often, 11 were prescribed more than 2000 times. In this paper, we have explored the literature to identify prescribing errors with co-drug products and found several idiosyncrasies that have caused drug errors in the past. We advocate for a standard nomenclature (state the international nonproprietary name [INN] of each component followed by dose information in the x + y format) for these products on the box and in prescribing resources. We hope that this will enhance clarity and safety during prescribing and administration, particularly for high-volume drugs like paracetamol + codeine (co-codamol), amoxicillin + clavulanic acid (co-amoxiclav) and trimethoprim + sulfamethoxazole (co-trimoxazole).

Stability-indicating green HPLC method for fixed-dose tablets containing remogliflozin etabonate and teneligliptin: an AQbD approach

Background In June 2021, the Central Drug Standards Control Organization approved a fixed-dose combination tablet containing remogliflozin etabonate (100 mg) and teneligliptin (10 mg) to manage type II diabetes. Objective This study aims to develop a stability-indicating RP-HPLC method for quantifying remogliflozin etabonate and teneligliptin in tablet formulations via analytical quality by design (AQbD) principles. Methods Risk assessment, Plackett–Burman design, and central composite design were employed to understand the impact of independent variables on critical analytical attributes. The stationary phase was a HyperClone BDS C18 column, and the mobile phase consisted of acetonitrile and phosphate buffer (20 mM, pH 5) at a 45:55% (v/v) ratio. Results The method, validated per ICH Q2 (R1), resulted in retention times of 3.395 and 12.308 min for teneligliptin and remogliflozin etabonate, respectively. Forced degradation studies confirmed robustness, with clear peak separation and no interference from degradation products. The AGREE score of 0.65 supports its green applicability for tablet analysis in quality control. Conclusion The AQbD-assisted RP-HPLC method developed in this study offers environmental friendliness, efficient separation with well-defined peaks, and simple mobile phase combination.

M2e nanovaccines supplemented with recombinant hemagglutinin protect chickens against heterologous HPAI H5N1 challenge

Current poultry vaccines against influenza A viruses target the globular head region of the hemagglutinin (HA1), providing limited protection against antigenically divergent strains. Experimental subunit vaccines based on the conserved ectodomain of the matrix protein 2 (M2e) induce cross-reactive antibody responses, but fail to fully prevent virus shedding after low pathogenic avian influenza (LPAI) virus challenge, and are ineffective against highly pathogenic avian influenza (HPAI) viruses. This study assessed the benefits of combining nanoparticles bearing three tandem M2e repeats (NR-3M2e nanorings or NF-3M2e nanofilaments) with an HA1 subunit vaccine in protecting chickens against a heterologous HPAI H5N1 virus challenge. Chickens vaccinated with the combined formulations developed M2e and HA1-specific antibodies, were fully protected from clinical disease and mortality, and showed no histopathological lesions or virus shedding, unlike those given only HA1, NR-3M2e, or NF-3M2e. Thus, the combined vaccine formulations provided complete cross-protection against HPAI H5N1 virus, and prevented environmental virus shedding, crucial for controlling avian influenza outbreaks.

Patient-Reported Outcomes After Switching to a 2-Drug Regimen of Fixed-Dose Combination Dolutegravir/Lamivudine: 48-Week Results from the SALSA Study.

Patient-reported outcomes (PROs) facilitate communication between patients and providers, enhancing patient-centered care. We report PROs for virologically suppressed people living with HIV-1 who switched to dolutegravir/lamivudine (DTG/3TC) or continued their 3- or 4-drug current antiretroviral regimen (CAR) in the phase 3 SALSA study. Secondary endpoints included change from baseline in HIV Treatment Satisfaction Questionnaire (status version; HIVTSQs) and HIV Symptom Distress Module (HIV-SDM) at Weeks 4, 24, and 48. A post hoc analysis assessed change in HIVTSQs and HIV-SDM by age (≥ 50 and < 50 years). Higher HIVTSQs scores represent greater treatment satisfaction (range, 0-60); lower HIV-SDM scores indicate less symptom bother (range, 0-80). Participants in the DTG/3TC (n = 246) and CAR (n = 247) groups reported comparable baseline HIVTSQs total scores (mean [SD], 55.2 [6.5] and 55.8 [5.5], respectively). Beginning at Week 4, mean HIVTSQs scores in the DTG/3TC group further increased vs. CAR and were sustained through Week 48. Baseline mean (SD) HIV-SDM symptom bother scores were comparable between the DTG/3TC (9.0 [9.9]) and CAR (7.9 [9.3]) groups. Small improvements in HIV-SDM scores favoring DTG/3TC were observed at Weeks 4 and 24 and sustained through Week 48 (though not significant between groups). Participants aged ≥ 50 and < 50 years who switched to DTG/3TC reported higher satisfaction and less symptom distress vs. CAR; these results were generally comparable between age groups. Participants who switched to DTG/3TC reported rapid and sustained improvements in treatment satisfaction compared with those who continued CAR, reinforcing the benefits of DTG/3TC beyond virologic suppression (NCT04021290; registration date, 7/11/2019).

P026 A PRESCRIPTION TREND ANALYSIS OF ANTIHYPERTENSIVE PHARMACOTHERAPY ACROSS DIFFERENT SPECIALTIES IN INDIA

Objective: To evaluate the temporal trends in the prescription patterns of antihypertensive medications among healthcare practitioners in India. Methods: The IQVIA (formerly Quintiles and IMS Health) prescription audit data came from prescriptions of a panel of 6000 private sector primary care clinicians for the different classes of antihypertensive drugs; beta-blockers(BB), calcium channel blockers(CCB), angiotensin receptor blockers(ARB), angiotensin-converting enzyme(ACE) inhibitors, and diuretics were examined. The analysis encompassed the period from 2014 to 2022. Additionally, combinations of these drug classes involving two or three medications were also subject to analysis. Results: Cardiologists’ prescription rates for antihypertensive medications stood at 21% in 2017 and decreased to 19% by 2023. In 2023, the highest rate of prescribing antihypertensive drugs was observed among consultant physicians, with a rate of 30%, followed by general practitioners at 27%. In addition, during COVID-19, the prescription share of general practitioners was highest (31%). Among antihypertensive medications, the prescription rates for BBs were highest (32%), followed by ARBs &amp; CCBs (25% &amp; 24% respectively). Single-drug formulation of anti-hypertensive medications was the most preferred (60%) among Indian clinicians. Prescription shares of fixed-dose combinations (FDC) of two antihypertensive drugs showed a slight decline (36% in 2017 to 34% in 2023) &amp; FDCs of triple-drug exhibited an upward trend (3% in 2017 to 5% in 2023). Among the two drug FDCs, ARB &amp; diuretics were most preferred (25% prescription share) &amp; triple drug FDCs, CCB, ARB &amp; diuretics were most preferred. Conclusions: Cardiovascular medications are prominent in the Indian pharmaceutical market, with antihypertensives standing out as one of the most frequently prescribed treatments. Consultant physicians and general practitioners manage the majority of hypertension cases. Notably, there has been an observed rise in preference for triple-drug combinations of antihypertensive medications, indicating a trend toward a more aggressive approach to hypertension management among Indian clinicians. The insights gleaned from this investigation can further assist healthcare professionals in crafting tailored treatment strategies for individuals grappling with hypertension. Such personalized approaches hold promise in enhancing treatment adherence and ultimately improving the QoL.

Abstract P304: A Prescription Trend Analysis of Antihypertensive Pharmacotherapy across Different Specialties in India

Objective: To evaluate the temporal trends in the prescription patterns of antihypertensive medications among healthcare practitioners in India. Methods: The prescription audit data utilized in this study, sourced from IQVIA, originated from a panel comprising 6000 clinicians practicing within the private sector. These prescriptions encompassed various classes of antihypertensive drugs, namely beta-blockers (BB), calcium channel blockers (CCB), angiotensin receptor blockers (ARB), angiotensin-converting enzyme (ACE) inhibitors, and diuretics. The analysis spanned the period from 2014 to 2022. The study also included an examination of combinations involving two or three medications from these drug classes. Results: Cardiologists' prescription rates for antihypertensive medications stood at 21% in 2017 and decreased to 19% by 2023. In 2023, the highest rate of prescribing antihypertensive drugs was observed among consultant physicians, with a rate of 30%, followed by general practitioners at 27%. Among anti-hypertensive medications, the prescription rates for BBs were highest (32%), followed by ARBs &amp; CCBs (25% &amp; 24% respectively); which remained almost constant throughout the study period. Single-drug formulation of antihypertensive medications was the most preferred (60%) among Indian clinicians. Prescription shares of fixed-dose combinations (FDC) of two antihypertensive drugs showed a slight decline (36% in 2017 to 34% in 2023) &amp; FDCs of triple-drug exhibited an upward trend (3% in 2017 to 5% in 2023). Among the two drug FDCs, ARB &amp; diuretics were most preferred (25% prescription share) &amp; triple drug FDCs, CCB, ARB &amp; diuretics were most preferred (76% prescription share). Conclusions: Antihypertensive drugs are the most commonly prescribed medication in the cardiology segment. Consultant physicians and general practitioners manage the majority of hypertension cases. Notably, there has been an observed rise in the preference for triple-drug combinations of antihypertensive medications, indicating a trend toward a more aggressive approach to hypertension management among Indian clinicians. The insights gleaned from this investigation can further assist healthcare professionals in crafting tailored treatment strategies for individuals grappling with hypertension. Such personalized approaches hold promise in enhancing treatment adherence and ultimately improving the quality of life for patients.

Abstract P438: Is aprocitentan also sympatholytic in patients with resistant hypertension?

Background: Aprocitentan is an endothelin ET A /ET B receptor antagonist (ERA) approved for the treatment of hypertension not adequately controlled on other drugs. Resistant hypertension is associated with sympathetic activation. The insufficient blood pressure (BP) lowering of many patients at night (non-dipping) and an often-increased heart rate are signs of sympathetic activation. Because ET A and ET B receptors participate in adrenaline and noradrenaline release and dual ERAs have been shown to decrease catecholamines, we hypothesized that aprocitentan might, among the various effects of dual blockade, behave as a sympathetic inhibitor. To assess this hypothesis, we investigated the effect of aprocitentan on nighttime BP and heart rate, both influenced by the sympathetic system. Methods: In the PRECISION study, where enrolled subjects were still hypertensive despite being on a standard fixed-dose background combination therapy composed of amlodipine, valsartan and hydrochlorothiazide, 730 patients were randomized to receive aprocitentan 12.5 mg, 25 mg or placebo for the first 4 weeks (double-blind placebo-controlled phase). 24-hour ambulatory BP monitoring (ABPM) was recorded in all randomized patients at baseline and Week 4. Results: At baseline, 60% of patients were non-dippers at night . Among those, 25%, 39% and 37% were reverted to dippers in the placebo, aprocitentan 12.5 and 25 mg groups, respectively, at Week 4. Accordingly, aprocitentan 12.5 mg and 25 mg decreased nighttime BP by -8.1 and -11 mmHg, respectively, vs -2.6 mmHg on placebo at Week 4. This reduction in nighttime BP by aprocitentan was larger than the reduction in daytime BP (-6.2 and -7.8 mmHg decrease at 12.5 and 25 mg, respectively, vs -2.3 mmHg on placebo). At baseline, mean heart rate, measured by office BP measurement at trough, was 74 beats/min. At Week 4, aprocitentan 12.5 mg and 25 mg, despite the respective 15.3 and 15.5 mmHg reduction of office BP from baseline, did not increase heart rate (-3.3 and -2.6 beats/min at 12.5 and 25 mg, respectively, versus -2.7 beats/min on placebo). Conclusion: We conclude that, by blocking ET A and ET B receptors, aprocitentan may have downstream sympatholytic effects, which may help its efficacy on nighttime BP – a prognostic factor for CV events in hypertension – and allow marked BP lowering without any reactive tachycardia.