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Background: Brand-name dasatinib was approved for newly diagnosed chronic myeloid leukemia-chronic phase (CML-CP) patients due to its deeper and faster molecular response than imatinib. Generics, as the alternative, low-cost forms, are much in demand. This study aimed to evaluate the efficacy and safety of generic dasatinib (Yinishu) as a first-line treatment in CML-CP., Materials and Methods: This was a prospective, multicenter, single-arm study from May 2016 to October 2018 with a 2-year follow-up analysis. All patients were given 100 mg/d (initial dose) of the generic dasatinib once a day. The primary endpoint was the major molecular response (MMR) calculated based on the BCR-ABL1 gene mutation rate of ≤ .1% at 12 months., Results: Among 55 patients in CP observed for at least 3 months, 80.4% achieved MMR at 12 months. The cumulative MR4.5 was 58.2% by 24 months. Responses occurred rapidly, with 69.1% of patients achieving complete cytogenetic response (CCyR) by 3 months and 70.9% achieving CCyR by 6 months. The estimated 2-year PFS and OS were both 96%, with a median follow-up time of 24 months. Grade 3 neutropenia occurred in 8.5% of patients, and thrombocytopenia occurred in 11.9% of patients. Nonhematologic toxicity was usually mild and manageable. Pleural effusion occurred in 20.3% of patients, and only 1 patient (1.7%) had a grade 3 pleural effusion. No grade 4 adverse events were observed., Conclusion: Generic dasatinib is an effective option for newly diagnosed CML-CP patients, producing an MMR early in a greater number of patients during their therapy., (Copyright © 2022. Published by Elsevier Inc.)

Although the 3Rs are broadly applied in nonclinical testing, a better appreciation of the 3Rs is needed in the field of differentiated or value-added pharmaceutical generics because the minor changes in formulation, dosage form, indication, and application route often do not require additional safety testing. The US FDA and the EU EMA have comprehensive regulations for such drugs based on quality, therapeutic equivalence, and safety guidelines. However, no scientific publications on how the concept of replacement and reduction from 3Rs principles can be applied in the safety assessment of differentiated generics were found in the public domain. In this review, we discuss the application of 3Rs in nonclinical testing requirements for differentiated generics. Practical examples are provided in the form of case studies from regulated markets. We highlight the need for utilization of existing data to establish equivalence (differentiated generic vs innovator) in efficacy and safety. The case studies indicate that data requirements from animal experiments have been reduced to a large extent in some major markets without compromising quality and safety. In this context, we also highlight the problem that on a global scale, a true reduction of animal experiments will only be achieved when all countries adopt similar practices., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Introduction: To compare the efficacy and safety of generic and branded imatinib in adults with newly diagnosed chronic myeloid leukemia in the chronic phase (CML-CP), we retrospectively reviewed data from patients CML-CP who received generic or branded imatinib., Patients and Methods: A propensity score matching (PSM) study was performed. A Cox regression model was used to identify factors associated with responses and outcomes., Results: Four hundred forty-two adults receiving generic imatinib (n = 236) or Glivec (Novartis, Basel, Switzerland; n = 206) were included. There were more patients with rural household registration (P < .001), lower education level (P < .001), divorced or widowed status (P = .009), higher white blood cell counts (P = .019), splenomegaly (P < .001), and longer intervals from diagnosis to imatinib initiation (P = .033) in the generic cohort. During the follow-up, there was no significant difference between the 2 cohorts in the 4-year probabilities of achieving a complete cytogenetic response (97.0% vs. 97.3%; P = .736), major molecular response (87.8% vs. 90.1%; P = .113), and molecular response 4.5 (32.5% vs. 38.8%; P = .186), as well as failure-free survival (77.3% vs. 81.4%; P = .313), progression-free survival (94.4% vs. 95.8%; P = .489), and overall survival (96.8% vs. 98.3%; P = .088). Multivariate analyses showed that the drug type was not associated with responses and outcomes. After the PSM procedure, 177 pairs of patients with comparable baseline characteristics were reanalyzed. Multivariate analyses confirmed that generic or branded imatinib used as first-line therapy was not associated with either responses or outcomes., Conclusion: Sociodemographic characteristics might influence the tyrosine kinase inhibitor that patients chose. Generic and branded imatinib as first-line therapy had comparable efficacy and safety in CML-CP patients., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Teicoplanin formulations are marketed as antibiotic mixtures with several compounds that share the same core structure. Recent studies conducted in vitro have reported differences in the composition ratio of different teicoplanin products. In this retrospective study, we examined the trough blood concentration of the originator brand and a generic teicoplanin product. Target patients were retrospectively assigned to the originator (Targocid) or generic group. The groups were matched 1:1 using propensity scores. The initial trough blood concentration analysis identified 44 matches. In both groups, the median dosing day for the first measurements was 4, respectively. The initial trough blood concentration of the originator group was significantly higher (mean ± SD, 16.3 ± 4.5 mg/L) than that of the generic group (12.8 ± 4.7 mg/L; 95% CI, -5.4 to -1.6). A significant difference was observed in the frequency of serum creatinine elevation in the study of the frequency of adverse events using Common Terminology Criteria for Adverse Events (originator group, 41.9% vs generic group, 20.9%). In cases where discontinuation was necessary due to side effects, there were three patients in the originator group and one patient in the generic group. This study found that trough blood concentration differed between formulations. Therefore, correction might be necessary while monitoring drug concentration in the blood. Trough blood concentrations are used as surrogate markers for efficacy and safety, so further studies on differences in efficacy and safety between formulations are required., (Copyright © 2019 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

There is a need of a relatively simple and inexpensive method for the determination of relative potency of various generic brands of antibiotics in comparison to original products. The current study describes an agar diffusion method which can be performed in any microbiology laboratory, is cheap (costs $2 per test) and its results can be available after overnight incubation. The results show that neither all generics are reliable nor are all generic antibiotics of poor quality., Competing Interests: None

Purpose: Levetiracetam is one of the most widely used antiepileptic drugs, but the evidence related to the safety of substitution from brand name to generic levetiracetam is scarce. The present study evaluated the risk of increased frequency of seizures after replacement of a brand-name levetiracetam with a generic product., Methods: We enrolled patients with epilepsy who were treated with branded levetiracetam for at least 6 months of sustained use. Patients were advised to switch to the generic levetiracetam. We analyzed data from 6 months before, to 6 months after, generic substitution. Increased seizure frequency was defined as a≥ 50% increase in seizure frequency after conversion date compared with seizure frequency before the conversion date. We analyzed changes in seizure frequency and performed subgroup analysis according to changes in seizure frequency., Results: We analyzed 148 epilepsy patients. Among the 148 patients, 109 (73.6%) were seizure-free before substitution and 105 patients remained seizure-free after switching. After generic substitution, an increased seizure frequency was noted in seven patients (4.7%), and a decreased seizure frequency was noted in 10 (6.8%). Patients with decreased seizure frequency were significantly younger (p = 0.035) than those with an unchanged seizure frequency., Conclusion: This study suggests that the risk of increased seizure frequency after generic substitution was minimal. The generic substitution of levetiracetam was generally safe, although larger prospective studies are warranted to corroborate our findings., (Copyright © 2018 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.)

Introduction: Generic imatinib therapy is being globally considered owing to cost considerations. However, evidence of its efficacy and safety in Middle Eastern clinical settings is scarce., Patients and Methods: The efficacy and safety of generic imatinib (Cemivil) were assessed among Jordanian patients diagnosed with chronic myeloid leukemia using an observational, multicenter, prospective study design. Responses were defined using European LeukemiaNet 2009 guidelines and assessed by complete blood counts, fluorescence in situ hybridization, and real-time quantitative polymerase chain reaction., Results: All patients (N = 91) were adults with chronic myeloid leukemia treated with generic imatinib 400 mg/day. Thirty-three patients received generic imatinib as first-line therapy, and 58 switched from patented imatinib to generic imatinib after a median of 4.5 years (range, 0.5-13.6 years) of imatinib therapy. The majority (85%; n = 28) of the first-line patients achieved complete hematologic response within 3 months of starting generic imatinib therapy (100% after 6 months [n = 33]). The 12-month major molecular response rate in the intention-to-treat population was 45%. The 12-month major molecular response rate was 88% for patients who switched therapy. The 12-month progression-free and overall survival rates were 92% and 100%, respectively. Most (85%; n = 144) adverse events were mild. Frequencies of drug-related adverse events were similar to patented imatinib., Conclusion: This study suggests that the efficacy and safety of generic imatinib in this Middle Eastern population in routine clinical practice are comparable to patented imatinib, and to that of the global population., (Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose: The therapeutic equivalence of generic and brand antiepileptic drugs, based on studies performed on healthy volunteers, has been questioned. We compare, in a routine clinical setting, brand versus generic levetiracetam (LEV) bioequivalence in patients with epilepsy and also the clinical efficacy and tolerability of the substitution., Methods: A prospective, open-label, non-randomized, steady-state, multiple-dose, bioequivalence study was conducted in 12 patients with epilepsy (5 females), with a mean age of 38.4±16.2 years. Patients treated with the brand LEV (Keppra; UCB Pharma) were closely followed for a four-week period and subsequently switched to a generic LEV (Pharmaten) and followed for another four-week period. Blood samples were collected at the end of each 4-week period, during a dose interval for each formulation, for LEV concentration measurements by liquid chromatography mass spectrometry. Steady-state area under the curve (AUC) and peak plasma concentration (Cmax) data were subjected to conventional average bioequivalence analysis. Secondary clinical outcomes, including seizure frequency and adverse events, were recorded., Results: Patients had epilepsy for a mean period of 14.1±10.6years and the mean daily LEV dose was 2583.3±763.7mg. The mean AUC±SD and Cmax±SD was 288.4±86.3(mg/L)h and 37.8±10.4mg/L respectively for brand LEV and 319.2±104.7(mg/L)h and 41.6±12.3mg/L respectively for the generic LEV. Statistic analysis showed no statistical significant difference in bioequivalence. Also, no change in seizures frequency and/or adverse events was recorded., Conclusions: In our clinical setting, generic LEV was determined to be bioequivalent to brand LEV. Furthermore, seizures frequency or/and adverse events were not affected upon switching from brand to generic LEV., (Copyright © 2017 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.)

Background: In 2006 Nolvadex was discontinued and replaced by a variety of alternative generic tamoxifen brands for the adjuvant treatment of breast cancer. Anecdotally, patients are switching brands and taking alternative medications to reduce treatment related symptoms. Nevertheless, more severe side effects may equate to better relapse prevention. This study evaluates generic tamoxifen adherence and its correlation with side effects and brand switch., Methods: Consecutive disease free ER positive patients (stage I-III) were invited to respond to a questionnaire. 165 of 327 questionnaires were returned (50% response). Pearson's Chi Square test was used for data analysis., Results: 63 patients (38%) reported a switch between generic tamoxifen. 59% of all patients experienced side effects associated with tamoxifen treatment of which 53% were severe. Patients experiencing differential symptoms dependent on tamoxifen brand reported more severe side effects (p = 0.02). Non-prescribed supplements were taken by 42% of all patients with no significant improvement in climacteric symptoms (p = 0.05). The concomitant use of SSRIs appeared to have no effect on symptoms. A significant number of patients considered discontinuing tamoxifen because of the side effects (p = 0.001), yet this did not translate into discontinuation or non-adherence (p = 0.8 and 0.08 respectively)., Conclusion: Severe tamoxifen side effects are commonly experienced by breast cancer patients and can be significantly altered by change in tamoxifen brand. Most patients will continue to take tamoxifen, despite side effects to avoid cancer relapse. Supplementation and antidepressants did not improve tamoxifen related side effects in our cohort., (Crown Copyright © 2016. Published by Elsevier Ltd. All rights reserved.)

Objectives: The aim of this study was to investigate whether the 2 tirofiban formulations tested in the early and late phases of the PRISM (Platelet Receptor Inhibitor in Ischemic Syndrome Management) trial might differ with respect to risk for thrombocytopenia and clinical outcomes compared with unfractionated heparin (UFH)., Background: Citrate-buffered tirofiban is currently marketed as brand-name drug. However, tirofiban has recently been promoted in some countries as a generic drug with different formulations, such as phosphate-buffered product., Methods: In the PRISM trial 3,232 patients were randomly assigned to receive tirofiban or UFH. In the early phase, 879 patients were allocated to phosphate-buffered tirofiban and 874 patients to UFH group. After a protocol amendment due to a study drug instability report, citrate-buffered tirofiban replaced the phosphate-buffered formulation. Therefore, in the late phase, 737 and 742 patients were treated with citrate-buffered tirofiban and UFH, respectively., Results: The relative risk for thrombocytopenia (nadir <90,000/mm(3) or <100,000/mm(3)) was increased in patients treated with phosphate-buffered tirofiban in the early phase (odds ratio [OR]: 3.51; 95% confidence interval [CI]: 1.15 to 10.73; p = 0.027; and OR: 2.83; 95% CI: 1.11 to 7.22; p = 0.029, respectively) but not in patients treated with citrate-buffered tirofiban in the late phase (OR: 1.01; 95% CI: 0.20 to 5.05; p = 0.987; and OR: 0.99; 95% CI: 0.26 to 3.45; p = 0.991, respectively). Using a combined definition of thrombocytopenia (nadir <150,000/mm(3) or a decrease ≥50%), the randomization period significantly modified the effect of the treatment (tirofiban vs. UFH) on platelet decrease (p for interaction = 0.024). Thrombocytopenia was associated with a 5- to 10-fold increased risk for TIMI (Thrombolysis In Myocardial Infarction) bleeding and a 2-fold increased risk for net adverse cardiovascular events., Conclusions: Phosphate-buffered tirofiban, currently marketed as a generic drug, is associated with a higher rate of thrombocytopenia with a potentially increased risk for adverse clinical outcomes compared with citrate-buffered tirofiban., (Copyright © 2016 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Liposomes are known to activate the complement (C) system, which can lead in vivo to a hypersensitivity syndrome called C activation-related pseudoallergy (CARPA). CARPA has been getting increasing attention as a safety risk of i.v. therapy with liposomes, whose testing is now recommended in bioequivalence evaluations of generic liposomal drug candidates. This review highlights the adverse consequences of C activation, the unique symptoms of CARPA triggered by essentially all i.v. administered liposomal drugs, and the various features of vesicles influencing this adverse immune effect. For the case of Doxil, we also address the mechanism of C activation and the opsonization vs. long circulation (stealth) paradox. In reviewing the methods of assessing C activation and CARPA, we delineate the most sensitive porcine model and an algorithm for stepwise evaluation of the CARPA risk of i.v. liposomes, which are proposed for standardization for preclinical toxicology evaluation of liposomal and other nanoparticulate drug candidates., (Copyright © 2015 Elsevier Inc. All rights reserved.)

We report for the first time the lack of therapeutic effects after the switch from a brand formulation of allopurinol to a generic one. A 56-year-old man, with a 5 years history of well-treated gout arthropathy with allopurinol (Zyloric(®) 300 mg/die), developed acute gout arthropathy after the switch from the brand formulation of allopurinol to a generic one. Clinical evaluation and laboratory findings confirmed the diagnosis of acute gout arthropathy. Generic formulation of the drug was dismissed and Zyloric(®) was administered with an improvement of both clinical symptoms and laboratory findings. In conclusion, even if generic formulations are considered to have the same effects in comparison to the brand one, more data are necessaries in order to well define their effectiveness and rationale use., (Copyright © 2013 Elsevier Ltd and Faculty of Forensic and Legal Medicine. All rights reserved.)

Background: Because generic medications are less expensive than brand-name medications, government and private insurers have encouraged and/or mandated the use of generics., Objective: This study aimed at evaluating perceptions about generic medications among English-speaking women of childbearing age currently enrolled in U.S. TennCare (Medicaid)., Methods: We recruited a convenience sample of patients from the waiting room of a primary care/gynecology health clinic, with 80% recruitment rate among those approached. We orally administered a 25-item questionnaire to gather sociodemographic information and to assess beliefs regarding the efficacy, safety, cost, and preferences for personal use of generic medications., Results: The average age of the women (n=172) was 28.8 ± 6.4 years, and most were white (82.0%) and currently married (58.1%). Nearly one-fifth (19.2%) had not completed high school. Most women believed that generic medications were less expensive (97.6%) and better value (60.5%) than brand-name medications, but only 45.3% preferred to take generics themselves. About a quarter (23.3%) believed that brand-name medications were more effective than generics, whereas 13.4% believed that generics caused more side effects. Few women reported that their doctor (29.7%) and/or pharmacist (35.5%) had ever talked to them about taking generics., Conclusion: Awareness of the benefits of generics did not equal preferences for personal use of generics among this sample of women enrolled in U.S. TennCare. Furthermore, women reported that providers-both physicians and pharmacists-infrequently discussed generic substitution with them., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Background: This prospective noninterventional study assessed the contraceptive efficacy, safety and the effects on signs of androgenization of the generic oral contraceptive containing 2 mg chlormadinone acetate/0.03 mg ethinylestradiol (CMA/EE) in a real-world setting., Study Design: A total of 1440 women were investigated during a six-cycle period by 229 gynecological practices throughout Germany., Results: The adjusted Pearl index was 0.136 (unadjusted: 0.271). Of 463 patients with cycle irregularities at baseline, 83.4% had regular cycles after six cycles. Likewise, 74.1% of 162 patients with spotting or breakthrough bleeding at baseline were free from these symptoms at the end of study. The percentage of patients with dysmenorrhea decreased significantly from baseline (36.5%) to visit 3 after six cycles (12.3%; p=.0001), with a significant reduction in the use of pain medication (p<.0001). Additionally, the number of patients with skin and hair problems was significantly reduced (skin: 56.3% at baseline, 19.6% after six cycles; hair: 45.7% at baseline, 13.4% after six cycles; p=.001). CMA/EE was well tolerated by the patients, and 89.44% of the gynecologists were satisfied with the treatment., Conclusion: Generic CMA/EE exhibits very good contraceptive efficacy, cycle control and dysmenorrhea reduction. Furthermore, treatment with generic CMA/EE led to a favorable reduction of skin and hair problems in our study., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Background: Generic medicines are commonly used in New Zealand; however, Pharmaceutical Management Agency of New Zealand (PHARMAC) has indicated a need for better information to the public. Studies on consumers' perceptions suggest that pharmacists play an important role in consumers' choice; hence, "quality use of generic medicines" can be promoted with a better understanding of pharmacists' views, knowledge, and perception., Objectives: (1)To evaluate pharmacists' perceptions, views, and knowledge of and willingness to recommend generic medicines. (2) To explore pharmacists perceptions of the safety, quality, and efficacy of generic medicines. (3) To assess pharmacists' views on current policy with respect to substitution of generic medicines., Methods: A cross-sectional survey using a postal questionnaire was conducted, and questionnaires were sent to 625 randomly selected pharmacists from a list of 1594 pharmacists who had agreed to release their details for research purposes., Results: Three-hundred and sixty pharmacists responded to the questionnaire (a response rate of 58%). Seventy percent of pharmacists stated there is no difference in safety between original brand and generic medicines. However, 65% stated that original brand medicines were of higher quality than their generic counterparts, and half stated that generic medicines and original brand medicines are equally effective. A large number of pharmacists reported concerns regarding brand substitution and offered suggestions, such as the need for advertising campaigns, patient pamphlets, updating prescribers' software, and distinct packaging for generic medicines. It was found that pharmacists' perceptions of generic medicines are primarily driven by PHARMACs policies and their experiences with consumers., Conclusions: About one-third of pharmacists correctly defined the term "generic medicines," suggesting discrepancies in pharmacists' knowledge and perceptions of generic medicines. Concerns were raised regarding: quality, safety, and effectiveness; however, most of the pharmacists acknowledged the economic benefits to the health care system., (Copyright © 2011 Elsevier Inc. All rights reserved.)

When the patent of a small molecule drug expires generics may be introduced. They are considered therapeutically equivalent once pharmaceutical equivalence (i.e. identical active substances) and bioequivalence (i.e. comparable pharmacokinetics) have been established in a cross-over volunteer study. However this generic paradigm cannot be applied to complex drugs as biologics and a number of other therapeutic modalities. For copies of biologics the European Medicine Agency and other regulatory agencies have introduced a new regulatory biosimilar pathway which mandates clinical trials to show therapeutic equivalence. However for other complex drugs such as the iron-carbohydrate drugs, low molecular weight heparins (LMWHs), liposomal drugs and the glatiramoids regulatory guidance is still mostly lacking. In this paper we will discuss (therapeutic) experience obtained so far with these different classes of 'complex drugs' and their specifics to provide scientific arguments and criteria for consideration for a regulatory framework for the market authorization for these type of drugs., (Copyright © 2010 Elsevier Inc. All rights reserved.)

Introduction: Small joint arthralgia has been anecdotally reported for many years by women taking generic Tamoxifen (gT). However, it is a symptom that is absent from the side effect profile of the original Tamoxifen preparation Nolvadex. Our aim was to determine the prevalence of arthralgia in Tamoxifen users and to investigate whether it was associated with the excipient profile of the newer, generic formulations of Tamoxifen., Methods: Women diagnosed with oestrogen receptor positive breast cancer between 2001 and 2005 were eligible. Those with new-onset arthralgia following commencement of gT were entered into a one year double crossover study. Patients were swapped from gT to Nolvadex for 6 months, the response noted, and then swapped back to gT for 6 months., Results: Of 1020 new breast cancer patients, 918 (90%) were oestrogen receptor (OR) positive and were started on gT as part of their treatment. Of those, a total of 121 (13.2%) suffered with arthralgia. All 121 patients agreed to enter the study and swap treatment to Nolvadex for 6 months 114 patients (94.2%) had resolution of their arthralgia whilst on Nolvadex (p < 0.05)., Conclusion: Our findings suggest that there is an arthralgia syndrome which is prevalent in women taking generic Tamoxifen preparations. Symptoms are abolished when Nolvadex is used instead of gT. This suggests that the excipient profiles are an important factor. We hypothesise that either the excipient profile of gT induces arthralgia, or an unknown excipient of Nolvadex has a protective effect., (Copyright (c) 2010 Elsevier Ltd. All rights reserved.)

Objective: The role of oxidative stress in disease progression has been shown to be more complicated in HIV-infected individuals receiving highly active antiretroviral therapy (HAART) compared to those who remain treatment-naïve. This study examined the changes in the antioxidant profile of HIV-infected subjects who remained HAART-naïve due to a high CD4 cell count and HIV-negative controls, over a 12-month follow-up period at YRG CARE, a tertiary HIV referral centre in southern India., Methods: We prospectively studied 35 HIV-infected participants (18 on d4T+3TC+EFV (stavudine+lamivudine+efavirenz), eight on AZT+3TC+EFV (zidovudine+lamivudine+efavirenz), and nine who were antiretroviral therapy-naïve) and 20 HIV-negative controls. Antioxidant profile (total antioxidant status, glutathione reductase, glutathione peroxidase, uric acid, ceruloplasmin, zinc, and albumin), CD4 cell count, plasma viral load, dietary intake, and history of smoking and alcohol use were determined at baseline and at twelve months., Results: At 12 months, participants on HAART showed a significant increase in glutathione peroxidase (baseline: 1765 vs. 12 months: 2850U/l; p<0.001) and albumin (3.6 vs. 4.4g/dl; p<0.001), and a significant decrease in glutathione reductase (52.6 vs. 50.5U/l; p=0.054) and uric acid (5.4 vs. 4.8mg/dl; p=0.027) compared to baseline. Also HAART-naïve participants had a significant increase in albumin (baseline: 3.7 vs.12 months: 4.3g/dl; p=0.023) and a significant decrease in zinc levels (baseline: 79.0 vs.12 months: 74.5microg/dl; p=0.052) from baseline to 12 months. HIV-negative subjects had a significant increase in glutathione reductase at 12 months from baseline (baseline: 37 vs.12 months: 39U/l; p=0.002). No significant difference in total antioxidant status, ceruloplasmin, and zinc levels were observed in HAART-experienced subjects and negative controls over the 12-month follow-up period., Conclusion: This study documents changes in antioxidants over a period of time in HAART-experienced subjects in a southern India setting.

Background: Generic fixed-dose combinations have been prequalified by WHO to treat HIV-infected patients in resource-limited countries. Despite their widespread use they are, however, not yet recommended by some of the major donor agencies owing to scarcity of clinical data on effectiveness, safety, and quality. We aimed to assess these issues for one of the most frequently prescribed treatments in Africa, a generic fixed-dose combination of nevirapine, stavudine, and lamivudine., Methods: 60 patients were followed in an open-label, 24-week multicentre trial in Cameroon. All patients received one tablet of the fixed-dose combination drug twice daily. The primary outcome measure was the proportion of patients with viral load less than 400 copies per mL at the end of the study period, in an intention-to-treat analysis., Findings: At baseline, 92% of patients (n=55) had AIDS; median CD4 count was 118 cells per microL (IQR 78-167) and median plasma HIV-1 RNA was 104?736 copies per mL (40804-243787). The proportion of patients with undetectable viral load (<400 copies per mL) after 24 weeks of treatment was 80% (95% CI 68-89). Median (IQR) change in viral load was -3.1 log10 copies per mL (-2.5 to -3.6) and in CD4 count 83 cells per microL (40-178). The probability of remaining alive or free of new AIDS-defining events was 0.85 (95% CI 0.73-0.92). Frequency of disease progression was 32.0 (95% CI 16.6-61.5), severe adverse effects 17.8 (7.4-42.7), and genotypic resistance mutations 7.1 (1.8-28.4) per 100 person-years. Mean reported adherence rate was 99%. Median drug concentrations in tablets were 96% of expected values for nevirapine, 89% for stavudine, and 99% for lamivudine., Interpretation: Our findings lend support to use and funding of a generic fixed-dose combination of nevirapine, stavudine, and lamivudine as first-line antiretroviral treatment in developing countries.

Presently, the lowest effective estrogen dose available as a combination oral contraceptive (OC) in the United States is 20 microg of ethinyl estradiol (EE) with different progestins. Twenty micrograms of EE coupled with levonorgestrel results in fewer side effects and cycle control comparable with higher-dose pills. Differences between therapeutically equivalent and brand-name, low-dose oral contraceptives, with respect to the bioavailability of hormones, may interfere with contraceptive efficacy and increase breakthrough bleeding. One of the most common reasons why women discontinue OCs is increased breakthrough bleeding. Because after OC discontinuation most women switch to a less-effective method, or no method, of contraception, an increase in breakthrough bleeding could ultimately result in an increase in unintended pregnancy. Thus, substituting a therapeutically equivalent for a brand-name low-dose oral contraceptive may have significant clinical and economic effects on individual and public health.