Fixed Drug Combinations Research Articles

Treatment of acute hepatitis C genotypes 1 and 4 with 8 weeks of grazoprevir plus elbasvir (DAHHS2): an open-label, multicentre, single-arm, phase 3b trial

Direct-acting antivirals effectively treat chronic hepatitis C virus (HCV) infection but there is a paucity of data on their efficacy for acute HCV, when immediate treatment could prevent onward transmission. We assessed the efficacy of grazoprevir plus elbasvir treatment in acute HCV infection and investigated whether treatment can be shortened during the acute phase of HCV infection. The Dutch Acute HCV in HIV study number 2 (DAHHS2) study was a single-arm, open-label, multicentre, phase 3b trial. Adult patients (≥18 years) with acute HCV genotype 1 or 4 infection (duration of infection 26 weeks or less, according to presumed day of infection) were recruited at 15 HIV outpatient clinics in the Netherlands and Belgium. All patients were treated with 8 weeks of grazoprevir 100 mg plus elbasvir 50 mg administered as one oral fixed drug combination tablet once daily. The primary efficacy endpoint was sustained virological response at 12 weeks after the end of treatment (SVR12; HCV RNA <15 IU/mL) in all patients who started treatment. Reinfection with a different HCV virus was not considered treatment failure in the primary analysis. This trial is registered with ClinicalTrials.gov, number NCT02600325. Between Feb 15, 2016, and March 2, 2018, we assessed 146 patients with a recently acquired HCV infection for eligibility, of whom 86 were enrolled and 80 initiated therapy, all within 6 months after infection. All patients who initiated treatment completed treatment and no patients were lost to follow-up. 79 (99%, 95% CI 93-100) of 80 patients achieved SVR12. All 14 patients who were infected with a virus carrying a clinically significant polymorphism in NS5A were cured. If reinfections were considered treatment failures, 75 (94%, 86-98) of 80 patients achieved SVR12. Two serious adverse events not considered related to the treatment were reported (traumatic rectal bleeding and low back surgery). The most common adverse event was a new sexually transmitted infection (19 [24%] of 80 patients). The most common reported possibly drug-related adverse events were fatigue (11 [14%] patients), headache (seven [9%] patients), insomnia (seven [9%] patients), mood changes (five [6%] patients), dyspepsia (five [6%] patients), concentration impairment (four [5%] patients), and dizziness (4 [5%] patients), all of which were regarded as mild by the treating physician. No adverse events led to study drug discontinuation. 8 weeks of grazoprevir plus elbasvir was highly effective for the treatment of acute HCV genotype 1 or 4 infection. The ability to treat acute HCV immediately after diagnosis might help physicians to reach the WHO goal of HCV elimination by 2030. Merck Sharp and Dohme and Health-Holland.

Novel RP-HPLC method development and validation for simultaneous estimation of metformin, voglibose and pioglitazone in bulk and triple fixed drug combinations pharmaceutical dosage form

Reducing treatment complexity can be achieved through the use of single-tablet triple fixed-dose combinations of oral hypoglycemic agents. A simple, precise and accurate reverse-phase high-performance liquid chromatographic (RP-HPLC) method was developed and validated for the simultaneous determination of Metformin (MET), Voglibose (VOG) and Pioglitazone (PIO) in pharmaceutical dosage forms. Chromatographic separation was achieved on an Younglin (SK) gradient System with UV 730 D detector and Cosmosil C18 (250 x 4.6 mm, 5μm) column, maintained at 45°C using 0.1% v/v acetonitrile: triethylamine (30:70, v/v), pH 2.5 with flow rate 0.8 ml/min with injection volume at 20 μl and wavelength ultraviolet detection at 232 nm. MET, PIO and VOG obey Beer–Lambert’s law over the concentration range of 200-600 µg/ml, 30-90 µg/ml and 0.08-0.24 µg/ml, respectively, with regression equations y=2.021x -186.7 (MET) (R2 = 0.998), y=9.876x-202.31 (PIO) (R2 = 0.999), and y= 502.3x-17.23 (VOG) (R2 = 0.999). % RSD and recoveries were 100.57-101.60 for MET, 99.79-102.61 for PIO and 100.02-101.05 for VOG indicate good accuracy of method. The marketed formulation analyzed using developed method and mean % amount were found 101.62, 100.38 and 98.75 for MET, PIO and VOG respectively with % RSD values NMT 2.0%. The developed spectrophotometric method can be employed for routine analysis of MET, VOG and PIO in bulk and tablet formulation. The developed RP-HPLC method was sensitive and selective for estimation of metformin, voglibose and pioglitazone in combined dosage form. The method was validated as per ICH guidelines.&#x0D; Keywords: RP-HPLC, ICH guidelines, Metformin, Voglibose, Pioglitazone, Validation

Drug utilization and prescription pattern study in medicine intensive care unit at tertiary care teaching hospital

Background: Drug utilization evaluation performs a key role in the managing health-care system to evaluate, understand, interpret, and improve the prescribing, administration, and use of medications. Aims and Objectives: The aim of the study is to evaluate and compare the drug prescribing trends in the intensive care unit (ICU) and correlate them with the disease patterns and patients outcome. Materials and Methods: The case records of 150 patients admitted to the ICU at Shri. Chhatrapati Shivaji Maharaj Sarvopchar Rugnalaya, a teaching hospital in Solapur, during 1-year period from June 1, 2017, to May 31, 2018, were analyzed. The variables collected were demographic and clinical characteristics. We also considered the duration of hospitalization, indications, and utilization of different drugs. The total number of drugs, dose, route, sensitivity pattern, and cost was collected from patients’ case paper. Results: Among 150 evaluated patients, the average age was 45 ± 17 years. The average length of stay at ICU was 4 to 10 days. The average number of drugs per prescription was 5 to 10. The parenteral route (61%) followed by the enteral route (27%) was common route used. Antimicrobial drugs and gastrointestinal drugs were the most commonly prescribed class of drugs, i.e., (30%) and (21%), respectively. The 1235 generic and 174 branded drugs were prescribed. The fixed drug combinations were 427 while single drug utilization was 715 in number. Conclusion: Antimicrobials are the most commonly used drugs. There is a need of antimicrobial agents’ usage guidelines and restriction policies for the rational prescribing of antimicrobials.

Drug utilization study of antipsychotic drugs in the psychiatry outpatient department of a tertiary care hospital

Background: Prescribing pattern of antipsychotics has changed over the decade with availability of newer antipsychotics. Aims and Objectives: This study aims to analyze the utilization pattern of antipsychotics at our hospital. Materials and Methods: A retrospective study of case files of patients receiving antipsychotics was carried out in the psychiatry outpatient department of new civil hospital, Surat, for a period of 6 months. Pattern of antipsychotic prescription, the World Health Organization (WHO) prescribing indicators, defined daily dose (DDD)/1000 inhabitants/day (DID), prescribed daily dose (PDD), and the PDD-to-DDD ratio were assessed. Results: A total of 2115 drugs were prescribed in 631 prescriptions, of which 804 (38.01%) were antipsychotics. Schizophrenia (55.31%) was the most common diagnosis. Sedative-hypnotics (30.23%) were the most common coprescribed drug group. Atypical antipsychotics were more commonly prescribed – olanzapine: 47.39%, risperidone: 27.49%, clozapine: 13.06%, and others: 12.06%. The average number of antipsychotics/prescription: 1.29 ± 0.53; prescribing of antipsychotics by generic name: 95.02%; prescribing from the WHO essential medicines list: 43.66%; prescribing from National List of Essential Medicines: 47.89%; prescribing for injections of antipsychotics: 0.62%; prescriptions of fixed-drug combinations: 0.50%, and DID of antipsychotics: 0.014 mg. PDD-to-DDD ratios for trifluoperazine, ziprasidone, amisulpride, and clozapine were 1. Conclusion: The second‑generation antipsychotic olanzapine was the most commonly prescribed antipsychotic. The prescriptions were complete and followed principles of rational prescribing in majority of cases. Prescribing the drugs available from hospital supply will decrease cost of therapy in chronic psychiatric disorders.

Pharmacokinetics of isoniazid in Indian children with tuberculosis on daily treatment.

To assess the pharmacokinetics of isoniazid (INH) at 10 mg/kg/day among Indian children. INH levels were estimated using liquid chromatography-tandem mass spectroscopy in 35 children aged 1-15 years on daily anti-tuberculosis treatment. Blood samples were collected 0, 1, 2, 3, 6 and 24 h after INH administration. The maximum concentration (Cmax) and area under the curve (AUC0-24) were determined. The normal therapeutic range for Cmax is 3-5 μg/ml. An AUC of <10.52 μg•h/ml for INH is low. The mean Cmax was 8.3 ± 4.28 μg/ml and was attained in 1.22 ± 0.5 h, with a median time to Cmax (Tmax) of 1 h. The mean AUC for INH was 46.23 ± 34.82 μg•h/ml. Children aged 1-4.9 years, 5-10 years and >10 years had a mean Cmax of respectively 9.87 ± 5.75 μg/ml, 7.62 ± 3.37 μg/ml and 7.21 ± 2.50 μg/ml (P = 0.08) and a mean AUC of respectively 60.97 ± 49.90 μg•h/ml, 38.95 ± 22.28 μg•h/ml and 36.09 ± 13.56 μg•h/ml (P = 0.29). The mean Cmax in children taking fixed-drug combinations and individual drugs was respectively 9.07 ± 4.67 μg/ml and 7.43 ± 3.71 μg/ml (P = 0.26); the mean AUC was respectively 50.48 ± 38.38 μg•h/ml and 41.20 ± 30.52 μg•h/ml (P = 0.44). Two children had hepatitis. Most Indian children had higher than normal INH AUC and Cmax values. It is necessary to determine the ideal dose of INH in Indian children using the genotypic acetylator status of the patients and pharmacokinetic toxicity analysis.

Thiotepa-Fludarabine-Treosulfan (TFT) Conditioning for 2nd Allogeneic Peripheral Blood Hematopoietic Cell Transplantation (HCT) from a Second Unrelated Donor in Patients with Acute Myeloid Leukemia (AML) Relapsed after Prior Allogeneic HCT: A Prospective Multicenter Phase II Trial

Introduction: Relapse of AML after allogeneic HCT has a dismal prognosis. Long-term survival after 2nd allogeneic HCT has been described in selected patients. Here we tested a specific protocol with a fixed drug combination for myeloablative conditioning and GvHD prophylaxis for 2nd allogeneic HCT from a different unrelated donor. (EudraCT no.: 2012-005414-18, German Clinical Trials Registry no.: DRKS00005126)Methods:Aim of the trial was to show efficacy and safety of a 2nd alloHCT from an unrelated donor after a uniform conditioning with Treosulfan 3x12gm/m2, Fludarabin 3x30mg/m2, and Thiotepa 3x 5mg/kg (TFT), and GvHD prophylaxis with cyclosporine A (CyA) /Mycophenolate and ATG-F (Neovii) 3x10mg/kg. Eligible were adult patients with AML, ECOG ≤ 2, with sensitive or refractory hematologic relapse (≥ 20% blasts) > 6 months after a prior allogeneic HCT , including secondary (s) and/ or tAML. CR prior 2nd HCT was no prerequisite.The primary endpoint of the study was disease-free survival (DFS) defined as being alive and free of disease at 1 year post 2nd HCT. Secondary endpoints were relapse, relapse mortality (RM), NRM, overall survival (OS), acute GvHD, chronic GvHD, engraftment, and adverse events. According to the Fleming one-stage design, 50 evaluable patients had to be included. If 16 or more patients were alive and free of disease at 1 year post 2nd SCT, the regimen could be considered as successful for evaluation in further trials. With this decision rule, it can be shown at one-sided α=0.1 that the probability of DFS at 1 year post 2nd HCT is higher than 23% with a power of 90%, when it is at least 40%. This is a first analysis of the study covering the first year after 2nd HCT of each patient. The analysis is based on the full analysis set, which includes all patients, for whom the conditioning regimen TFT and the GvHD prophylaxis regimen CyA, MPA/MMF, ATG-F has started, and for whom allogeneic HCT from an unrelated donor has been performed.Results: Fifty-two patients were registered for the study from 25th March 2014 up to 10th March 2017 from 9 German centres. The full analysis set includes 50 patients (median age 53.5 years). ECOG was median 1. Donors for 1st allo HCT had been related (n=11 (22.0%)) or unrelated (n=39 (78.0%)) (n=48 PBSCT, n=2 bone marrow). Conditioning for 1st HCT was myeloablative in 23 (46.0%) patients. After 1st HCT, the rate of acute GvHD I-IV was 34.0%, and of chronic GvHD was 40.0%. Median time from 1st HCT to relapse was 17.2 months and from relapse after 1st HCT to 2nd HCT 2.5 months. Thirty-six (72%) patients had received induction chemotherapy for relapse prior to 2nd HCT, 11 (22.0%) patients had received azacytidine or decitabine, and 11 (22.0%) had received donor lymphocyte infusions (DLI). Remission status prior to 2nd HCT was complete remission in 16 (32.0%) patients, chemo-refractory relapse in 33 (66.0%), one patient was in partial remission.With regard to the primary endpoint, 23 (46%, 95%-CI (31.8-60.7%) of the patients were alive and free of relapse at 1 year after 2nd SCT. With regard to the secondary endpoints at 1 year, the cumulative incidence of relapse (95%-CI) was 26 (17-42)%, 9/50 patients (18 (10-33)%) died after relapse of AML, NRM was 14/50 patients (28 (18-44)%, cause: infection n=6, infection after aGvHD n=6, PTLD n=2), OS was 54 (39-66)%. Four patients are alive after relapse. aGvHD rate was 54 (42-70)%, aGvHD III-IV 26 (16-42)%, cGvHD 26 (16-42)%, extensive cGvHD 20 (12-35)%, engraftment rate with ANC > 1.0 x 103/µl was 92 (85-100)%, with platelets > 20 x 103/µl was 80 (70-92)%, and with platelets > 100 x 103/µl was 66 (54-81)%. After 1 year, 4 patients had received DLI for prophylaxis, and 5 patients for mixed chimerism as per protocol.Conclusion:Second alloHCT with an ablative double alkylator containing conditioning regimen with Thiotepa, Fludarabine, and Treosulfan is feasible and can result in sustained disease control in patients with AML relapse after a first alloHCT, and therefore seems to be a valid option in this otherwise detrimental setting. DisclosuresFinke:Novartis: Consultancy, Honoraria, Other: travel grants, Research Funding; Riemser: Consultancy, Honoraria, Research Funding; Neovii: Consultancy, Honoraria, Other: travel grants, Research Funding; Medac: Consultancy, Honoraria, Other: travel grants, Research Funding. Stelljes:Pfizer: Consultancy, Honoraria, Research Funding; MSD: Consultancy; Novartis: Honoraria; Amgen: Honoraria; JAZZ: Honoraria. Burchert:Novartis: Research Funding; Bayer: Research Funding; AOP Orphan: Honoraria, Research Funding; Bristol Myers Squibb: Honoraria, Research Funding; Pfizer: Honoraria. Schub:Affimed: Research Funding. Kobbe:Celgene: Honoraria, Other: Travel Support, Research Funding; Roche: Honoraria, Research Funding; Amgen: Honoraria, Research Funding.

Amphiphilic Drug Conjugates as Nanomedicines for Combined Cancer Therapy.

Chemotherapy suffers from some limitations such as poor bioavailability, rapid clearance from blood, poor cellular uptake, low tumor accumulation, severe side effects on healthy tissues and most importantly multidrug resistance (MDR) in cancer cells. Nowadays, a series of smart drug delivery system (DDS) based on amphiphilic drug conjugates (ADCs) has been developed to solve these issues, including polymer-drug conjugate (PDC), phospholipid-mimicking prodrugs, peptide-drug conjugates (PepDCs), pure nanodrug (PND), amphiphilic drug-drug conjugate (ADDC), and Janus drug-drug conjugate (JDDC). These ADCs can self-assemble into nanoparticles (NPs) or microbubbles (MBs) for targeted drug delivery by minimizing the net amount of excipients, realizing great goals, such as stealth behavior and physical integrity, high drug loading content, no premature leakage, long blood circulation time, fixed drug combination, and controlled drug-release kinetics. Besides, these self-assembled systems can be further used to load additional therapeutic agents and imaging contrast agents for combined therapy, personalized monitoring of in vivo tumor targeting, and the pharmacokinetics of drugs for predicting the therapeutic outcome. In this review, we will summarize the latest progress in the development of ADCs based combination chemotherapy and discuss the important roles for overcoming the tumor MDR.

An analysis of adherence to the World Health Organisation guidelines pertaining to drug promotional literature by pharmaceutical firms

Background: Pharmaceutical companies used Drug Promotion Literatures (DPLs) as a major tool to advertise their new products. World Health Organization (WHO) has set some guidelines for promotion of drug literature. Thus, this study aimed to evaluate various DPLs for their accuracy and credibility as per WHO ethical criteria.Methods: This was an observational and cross-sectional study. Total 100 drugs advertisements published in various medical journals were collected from the library of the college. Advertisements were selected based on inclusion and exclusion criteria. The selected advertisements were evaluated based on the WHO ethical criteria for drug promotion.Results: From 100 advertisements, 73 were single drug whereas 27 were fixed drug combinations. Antimicrobials (16%) were the most promoted advertisements. Only 28% of the advertisements carried references to support their claim. Out of which majority (91.78%) were from journal articles. The generic name, brand name, names of active ingredients, manufacturer, distributor and dosage regimen were mentioned in majority of advertisements. Drug interactions (12%), contraindications (22%), precautions (24%) and side effects (22%) were least mentioned in the advertisements.Conclusions: It was observed that none of the advertisement followed all the guidelines laid down by WHO. Pharmaceutical companies should follow ethical regulatory measures to promote their product in various journals. The regulatory authority must ensure the pharmaceutical companies to follow ethical guidelines for publishing various drug promotional literatures.

Prescription Pattern of fixed dose drug combinations in obstetrics and gynecology department of a tertiary care hospital in Puducherry, India: an observational study

Background: Fixed drug combinations (FDCs)have various advantages and disadvantages. In countries like India there are numerous irrational prescriptions as highlighted by the recent banning of FDCs in October 2018. Studying the prescription pattern helps in developing national database which can be used to promote rational use of drugs.Methods: All the Outdoor Patient Department (OPD) prescriptions from department of Obstetrics and Gynecology (OBG) during the study period were used for the study. The drugs were classified according to Anatomical Therapeutic Chemical (ATC) classification. Other data studied were the number of FDCs and the number of currently banned combinations which were used during the study period.Results: The 41% of the drugs prescribed as FDCs. Most FDCs belonged to alimentary system followed by anti-infectives and blood and blood forming organs group. Vitamin D3 and Calcium combination was the most commonly prescribed FDC. Approximately 20% of these prescribed drugs are currently banned.Conclusions: A significant number of drugs are being prescribed as FDCs which also includes various irrational combinations.

PRIMARY MASTITIS TUBERCULOSIS CLINICALLY MIMICKING FIBROADENOMA MAMMAE

Introduction: Breast tuberculosis (mastitis TB) is a rare extrapulmonary presentation of tuberculosis that marked pathologily with involvement extensively mamma lobules, which because of infection of Mycobacterium tuberculosis. Many epidemiology studies stated that the incidence of mastitis TB is more common in developing countries than developed countries. Mastitis TB occurs mainly in reproductive woman.&#x0D; &#x0D; Case: A 32-year-old woman came to Surgery Department with chief complaint right upper quadrant palpable breast lump for 4 months. Mammae dextra physical examination confirmed single nodule, size ± 3cm x 3cm x 2.5cm in superior quadrant, mobile, tender, well defined shape, feel like marble, reddish skin, warm, no skin retraction and no nipple discharge. VAS score 2. Mammosonogram was performed and indicated mastitis in the superior quadrant of mammae dextra. Fine needle aspiration revealed negative malignant cells and granulomatous with suppurative inflammation. The histopathological evaluation from mammae excision confirmed datia langhans cells and indicated granulomatous mastitis. Then patient referred to the Pulmonary Department. On TB pulmonary examination confirmed normal chest x-ray and negative acid fast basil (AFB). Patient was diagnosed with primary mastitis TB. Patient was treated with anti-tuberculosis drug (OAT) and gave good response and no side effects.&#x0D; &#x0D; Discussion: Based on the International Standards for Tuberculosis Care (ISTC) diagnosis of mastitis TB can be confirm by anamnesis, physical examination, and also some additional diagnostic test such as sonomammographic imaging, fine needle aspiration or surgical specimens for pathology examination and culture or AFB with Ziehl-Neelsen staining. In Indonesian National Guidelines for TB Control, mastitis TB was treated with fixed drug combination (FDC), intensive phase in 2 months using 4 FDC and advanced phase in 4 months using 2 FDC. In case followed up in 2 months, patient recovered very well and advised to continue the treatment.&#x0D; &#x0D; Conclusions: TB mastitis is rare even in countries with TB endemic. Diagnosis of primary mastitis TB based on clinical, radiological, pathological and microbiological. Treatment of mastitis TB with FDC for 6 months consists of an intensive phase and an advanced phase in this patient gave good outcome.&#x0D; &#x0D; Keywords: Mastitis tuberculosis, diagnosis, treatment.

Pharmaco epidemiology of drugs used in post-cataract surgery patients in tertiary care hospital

Background: In India cataract is the principal cause of blindness responsible for 62.6% as per national programme for control of blindness survey and as per our knowledge, very few systematically analysed data are available on the drug utilization study pattern of medical intervention for post cataract surgery in India. Hence, the present study was under taken to generate baseline drug use data and analyse various aspects of drug prescribing practices.Methods: This study was conducted in department of ophthalmology BIMS Belagavi. A total of 449 patients’ prescription was analysed prospectively. The data was analysed statistically, and results were expressed as numbers and percentage.Results: A total of 2306 drugs were prescribed for 449 patients who underwent cataract surgery. All patients received topical eye drops includes bromfenac 0.1% eye drop and other one is a fixed drug combination of dexamathasone 0.1% plus ofloxacin 0.3% eye drop. Use of antibiotic in association with sex found to be significant (p- value &lt;0.004). Average number of drugs per prescription was 5.1 and drugs which prescribed in generic name were 60.99% and overall percentage of drugs prescribed by brand name was 38.94% which includes 100% eye drops were prescribed by brand names. Fixed drug combination includes 19.50% and drugs from essential drug list used were 80.49%.Conclusions: Health care providers have to take initiative for rational prescribing keeping in mind that it is not only a matter of national policy but also to wellbeing of individual patient.

A viewpoint on rational and irrational fixed-drug combinations

ABSTRACTIntroduction: Considering that there are around 30% of patients with epilepsy resistant to monotherapy, the use of synergistic combinations of antiepileptic drugs is of particular importance. This review shows most beneficial as well as irrational combined treatments both from an experimental and clinical point of view.Areas covered: Preferably, experimental data derived from studies evaluating synergy, additivity, or antagonism by relevant methods, in terms of anticonvulsant or neurotoxic effects and pharmacokinetic data have been considered. Although there have been no randomized clinical trials on this issue, the clinical data have been analyzed from studies on considerable numbers of patients. Case-report studies have been not considered.Expert commentary: The experimental data provide a strong support that co-administration of lamotrigine with carbamazepine is negative, considering the anticonvulsant and neurotoxic effects. Clinical reports do not entirely support this conclusion. Other experimentally documented negative combinations comprise lamotrigine+ oxcarbazepine and oxcarbazepine+ phenytoin. From the experimental and clinical point of view, a combination of lamotrigine+ valproate may deserve recommendation. Other most positive experimental and clinical combinations include carbamazepine+valproate, phenytoin+phenobarbital, carbamazepine+gabapentin, carbamazepine+topiramate, levetiracetam+valproate, levetiracetam+carbamazepine. Certainly, experimental data have some limitations (non-epileptic animals, acute administration of antiepileptic drugs) so all experimental recommendations need a careful clinical evaluation.

The Effect of Exforge-HCT on Blood Pressure Control in Omani Hypertensive Patients Attending Sultan Qaboos University Hospital

Background: Hypertension is worldwide health burden. The major concern about hypertension is that it is usually asymptomatic until it causes end organ damages. The management of hypertension usually starts with monotherapy which fails in achieving targeted BP control in many patients. Therefore, they are switched to combination therapy. Fixed combination therapy is proven to be more effective in controlling hypertension than free combination therapy. Exforge-HCT is a fixed combination drug consisting of Amlodipine, Valsartan and Hydrochlorothiazide. Its effectiveness is not known in Omani hypertensive patients. Aim: To evaluate the role of exforge-HCT in control of blood pressure in Omani hypertensive patients attending SQUH and its effectiveness based on gender. Method: This is a retrospective study. Data was gathered using HIS from January 2013 to June 2016. Patients taking Exforge-HCT were screened for eligibility for the study. Blood pressure measurements before and after using Exforge-HCT were recorded. Patients were grouped according to gender, number of co-morbidities and number of medications used before EXFORGE-HCT into two groups; group one: those who were on triple free drug combination therapy and group two: those who were on dual free drugs. P value of less than 0.05 was considered significant. Results: Total number of patients was 115 with female being 57% and male being 42%. The Level of control of hypertension increased from 22% to 33%. Over all Significant reduction in blood pressure was observed, but there was no gender difference in response to Exforge-HCT. There was significant difference in the response to Exforge-HCT between the medication groups but the response according to gender in each group remains the same. Response to Exforge-HCT was the same regardless the number of co-morbidities in both gender. Conclusion: Exforge-HCT showed significant reduction in BP but no gender difference in response. There was significant difference in the response between the two medication groups. However, the response between genders remains the same in each co-morbidity and medication group. Further prospective study is needed to confirm these findings.

Quality assurance of rifampicin-containing fixed-drug combinations in South Africa: dosing implications.

SETTING:Rifampicin (RMP) drives treatment response in drug-susceptible tuberculosis. Low RMP concentrations increase the risk of poor outcomes, and drug quality needs to be excluded as a contributor to low RMP exposure.OBJECTIVES AND DESIGN:We performed an open-label, three-way cross-over study of three licensed RMP-containing formulations widely used in South Africa to evaluate the bioavailability of RMP in a two-drug fixed-dose combination tablet (2FDC) and a four-drug FDC (4FDC) against a single-drug reference. RMP dosed at 600 mg was administered 2 weeks apart in random sequence. Plasma RMP concentrations were measured pre-dose and 1, 2, 3, 4, 6, 8 and 12 h post-dose. The area under the concentration-time curve (AUC0–12) of the FDCs was compared to the single drug reference. Simulations were used to predict the impact of our findings.RESULTS:Twenty healthy volunteers (median age 22.8 years, body mass index 24.2 kg/m2) completed the study. The AUC0–12 of the 4FDC/reference (geometric mean ratio [GMR] 78%, 90%CI 69–89) indicated an average 20% reduction in RMP bioavailability in the 4FDC. The 2FDC/reference (GMR 104%, 90%CI 97–111) was bioequivalent. Simulations suggested dose adjustments to compensate for the poor bioavailability of RMP with the 4FDC, and revised weight-band doses to prevent systematic underdosing of low-weight patients.CONCLUSION:Post-marketing surveillance of in vivo bioavailability of RMP and improved weight band-based dosing are recommended.

A study on the usage of antimicrobial agents and adverse drug reaction of antimicrobial used in a tertiary care hospital in North East India

Background: Irrational use of antimicrobial agents (AMAs) has led to large scale development of drug resistance and adverse drug reactions (ADRs) which has become a growing world -wide concern. The study was conducted to analyze the prescribing pattern of AMAs and to evaluate the reported ADR of the AMAs prescribed.Methods: A prospective study was conducted by analyzing 900 case sheets receiving AMAs in a tertiary care hospital. The study plan included analysis of average number of AMA prescribed, morbidity profile of patients, types of AMAs used, drug prescribed by generic/brand name, injectable AMA preparations and appropriateness of indication of AMA used. Thirty reported cases of ADR were evaluated for their casualty by Narnajo’s scale and severity by Hartwigs scale.Results: Average number of drugs per prescription was 1.54. Most common morbidity was fever due to various causes. 86.2% of AMA used was antibiotics. About 72.0% of AMAs were prescribed by generic name. Percentage of injectable preparation was 85.0%. 65.0% of drugs were prescribed from Essential drug list (EDL). Most offending drug for ADR was fixed drug combination (FDC) 30.0%. Common organ system involved was skin (63.3%). Most of the ADR were possible (80.0%) and mild (76.6%) in nature.Conclusions: Average number of AMAs per prescription was1.54. Percentage of drug prescribed by generic name is encouraging. However use of injectable preparation was very high. Majority of AMAs prescribed were antibiotics which is also very high. Periodic prescription audit will provide feedback to the prescribers and help in reducing the prescribing error and ADR cases.

Drug usage pattern of anti-hypertensive drugs in elderly diabetic, hypertensive in-patients with or without impaired renal function in a tertiary care hospital

Background: Hypertension (HTN) and Diabetes mellitus (DM) are the leading contributors to the cardiovascular mortality and morbidity. Drug utilisation studies (DUS) are potential tools in the evaluation in health care systems. Objectives was to analyse the drug usage pattern of anti-hypertensives in elderly hypertensive diabetic in-patients in a tertiary hospital. To analyse drug usage pattern of anti-hypertensives in elderly hypertensive, diabetic in-patients with renal impairment in a tertiary hospital.Methods: The study population consisted of 165 hypertensive diabetic in-patients at Shri Dharmasthala Manjunatheshwara (SDM) Hospital. Questionnaire based study was conducted and prescriptions of patient with HTN and DM at and above the age of 60 years irrespective of gender were included.Results: Our study revealed that angiotensin receptor blockers (ARBs) were the most commonly prescribed (42.4%) class of anti-hypertensive drugs. In patients with impaired renal function also ARBs were the most common class prescribed (22.0%). Out of 35 anti-hypertensive fixed drug combinations (FDCs) prescribed the most frequent combination was combination with an ARBs (85.7%). There was a significant increase in the number of anti-hypertensive drugs prescribed in patients with impaired renal function when compared to patients without impaired renal function (p &lt;0.05). The cost index was high, and the percentage cost variation was more than 100% in most of the anti-hypertensive drugs prescribed.Conclusions: This study shows that the most commonly prescribed anti-hypertensive drug class was ARBs in patients with and in patients without impaired renal function.

Recent Prescribing Trends of Anti- Microbial Agents and their Sensitivity Pattern in an Intensive Care Unit of a Tertiary Care Teaching Hospital

Background: Due to the injudicious and indiscriminate use of Anti-Microbial Agents (AMAs) among hospitalized patients especially in ICUs, it is extremely imperative to monitor and refine the prescribing pattern of antibiotics regularly. Hence an effective surveillance team consisting of a physician, a pharmacologist and a microbiologist should develop and implement an antimicrobial stewardship program based on the local antibiogam to increase the therapeutic benefits and curb the menace of Anti-Microbial Resistance (AMR). Aims:-To study the prescribing pattern of Anti-Microbial Agents and to evaluate the antimicrobial sensitivity pattern of common bacterial isolates in Medical ICU (MICU) of a tertiary care hospital. Methods: After taking approval from the Institutional ethical committee, this prospective observational study was conducted in the department of Pharmacology and Microbiology over a period of six months. Patient records were reviewed and analyzed to assess the prescribing pattern of antibiotics and Culture-sensitivity reports of various specimen from MICU were collected to determine the antibiotic sensitivity pattern. Results: Ceftriaxone (26%) was the most commonly prescribed drug followed by Metronidazole (16%). Fixed drug combinations such as Piperacillin+Tazobactam (14%), Amoxicillin + clavulanic acid (10%) and Cefoperazone + Sulbactam (8%) were also frequently used. The most predominant organism isolated was Klebseilla species (25%) followed by Acenitobacter species (19.4%). Colistin /Imipenem and Vancomycin/Linezolid depicted100% sensitivity for Gram-Negative (GNIs) and Gram-Positive Isolates (GPIs) respectively. Conclusions: The need of the hour is to preserve the power of the almost exhausted antimicrobial armamentarium against the rampantly emerging multidrug resistant organisms.

Bioequivalence of Dapagliflozin/Metformin Extended-release Fixed-combination Drug Product and Single-component Dapagliflozin and Metformin Extended-release Tablets in Healthy Russian Subjects

PurposeFixed-combination drug products (FCDPs) combining dapagliflozin and metformin extended release (XR) may provide patients with type 2 diabetes mellitus with an alternative antihyperglycemic treatment, which could improve adherence by reducing tablet burden. This study evaluated the bioequivalence of dapagliflozin/metformin XR FCDP versus the co-administration of the individual monotherapy tablets currently available for use in the Russian Federation. MethodsHealthy subjects aged 18 to 45 years were enrolled in this randomized, open-label, 2-period crossover study, conducted in a single Russian center. Pharmacokinetic parameters (AUC0–t, Cmax, and Cmax/AUC0–t) were used to assess bioequivalence of dapagliflozin/metformin XR (10/1000 mg) FCDP to the individual component tablets (dapagliflozin [10 mg] plus metformin XR [2 × 500 mg]) under standard fed conditions. Safety and tolerability were also assessed. FindingsForty healthy subjects were included (47.5% male; mean age, 30 years; and mean body mass index, 24.2 kg/m2). Dapagliflozin and metformin XR in the FCDP were bioequivalent to the individual component tablets marketed in the Russian Federation, with the 90% CIs of the geometric least-squares mean ratios for all key pharmacokinetic parameters being contained within the 80% to 125% bioequivalence limits. Both FCDP and the individual component formulations were well tolerated, with no serious adverse events. ImplicationsBioequivalence of dapagliflozin/metformin XR FCDP and the individual components was established without any new safety concerns, presenting a safe alternative for patients currently receiving regimens including each component individually. ClinicalTrials.gov identifier: NCT02722239.

Update on trends in childhood tuberculosis.

Although tuberculosis (TB) causes much morbidity and mortality in children, diagnosis and treatment remain challenging. Recently, children have gained increasing attention in research and clinical trials driving improved contact management, case identification and treatment of both drug-susceptible and drug-resistant TB. This review highlights some recent advances. The tuberculin skin test is the most widely used test to distinguish Mycobacterium tuberculosis (M. tuberculosis) infection from active TB, however, using M. tuberculosis-specific, antigenic stimulation of CD4 and CD8 cells appear more effective. The use of Xpert MTB/RIF to identify M. tuberculosis in clinical samples, together with novel sampling methods have in part, overcome the difficulty of sampling and increased case identification capacity. Advances in treating both drug-susceptible and drug-resistant childhood TB show promise in being more paediatric friendly and improving adherence. Dosing strategies for drug-sensitive TB have improved with dispersible fixed drug combinations now available. In the treatment and prevention of drug-resistant TB, however, research involving the use of newer and more effective drugs currently recommended for adults, are still ongoing in children. The World Health Organization aims to end the TB epidemic by 2035 whereas the United Nations' Sustainable Developmental Goals sets this ambitious target for 2030. Therefore, adequate funding and implementing effective national TB programs must be prioritized, particularly in high-burden, low-income settings.

A Study of Anti-hypertensive Drug Prescription Patterns in Hypertensive Post-menopausal women

&lt;p&gt;&lt;strong&gt;Background:&lt;/strong&gt; Drug prescription in menopause is complex as estrogen deficiency, hypertension (HT) and other risk factors, rapidly increase the risk of cardiovascular diseases (CVD) in post-menopausal women (PMW).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Objectives:&lt;/strong&gt; To evaluate the prescription trends of anti-hypertensive drugs in PMW.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods:&lt;/strong&gt; This was an observational, cross sectional study conducted over a period of 1 year, on hypertensive PMW. The prescriptions were evaluated for antihypertensive drug use patterns and also as per WHO core drug indicators.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results:&lt;/strong&gt; 21.82% of prescriptions had monotherapy, amongst which angiotensin receptor blockers (ARB) (10%) and individually, telmisartan (5.45%) were most commonly prescribed. Majority of prescriptions had two drug therapy (44.09%), among which ARB + beta-blockers (BB) (20.91%) and individually, Telmisartan + Metoprolol (13.64%) were most frequently prescribed. ARB + Diuretic (DI) (9.55%) was the most common fixed drug combination (FDC) prescribed. ARB + BB + DI (10.45%), ARB + 2DI + BB (4.09%) and ARB + 2DI + BB + Calcium channel blocker (1.82%) were most commonly prescribed three, four and ≥five drug combinations, respectively. Hypolipidemic drugs (60.45%) were maximally co-prescribed. Percentage of drugs prescribed by generic name was 4.63% and from essential drug list was 32.62%.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions:&lt;/strong&gt; A high trend of polypharmacy was observed in hypertensive PMW. HT, being a multifactorial disease, deserves a multidisciplinary and a comprehensive approach in the care of this population subgroup. Knowledge of prescription pattern and thus the rational utilisation of drugs will help achieve better control rates of HT and hence curb down the burden of CVDs in PMW.&lt;/p&gt;