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Since July 2017, different generic imatinib formulations have been introduced in Italy for the treatment of patients with chronic myeloid leukemia (CML). We analyzed 168 chronic phase CML patients treated with branded imatinib for a median of 12 years (range 1-16) at a single institution who switched to a single generic formulation in order to assess the safety and impact on molecular response. The Sokal risk was low/intermediate/high in 63%, 33%, and 4% of patients, respectively. The median duration of generic imatinib treatment was 19 months (range 4-22). Twenty-seven percent of patients were in MMR and 73% were in deep molecular responses (MR4-4.5) at the time of the switch. After 12 months of treatment with generic imatinib, 140 patients were evaluable for response: 23.6% and 76.4% were respectively in MMR and in deep molecular response. When the degree of response was compared with the best molecular response observed with branded imatinib, it was found that 84% of patients maintained the response previously achieved, 6% improved it, and 10% of patients had a molecular fluctuation from the previous deep molecular response to MMR. Only 1 patient lost the MMR and no patient switched to another TKI for inefficacy. In terms of safety, 20% of patients reported new or worsening side effects, but only 2 patients returned to branded imatinib for toxicity. Our data show that the switch to generic imatinib in patients who have been previously treated with branded imatinib appears to maintain efficacy, although a proportion of patients experience new or worsening side effects.

Background: For a patient, drug switches are not desirable (either between a brand-name drug and a generic drug, or between two generic drugs of the same active substance). Research into the causes of drug switches, and related adverse drug reactions, is hampered by the absence of quantitative data on drug switches., Methods: We describe the frequency of drug switches in the Netherlands for a selection of active substances. A retrospective cohort study was conducted using the Drug Information System of the National Health Care Institute in the Netherlands. We studied the Dutch patient population from mid-2009 to 2016. The selection of active substances (n = 20) was made based on a report by Lareb, the Netherlands Pharmacovigilance Centre, on adverse drug reactions related to drug switching, and we used qualitative and quantitative descriptive analyses. A drug switch is defined as the replacement of a patient's prescribed drug with a similar drug from a different manufacturer., Results: We identified 23.8 million drug switches on a total of 206 million (11.6%) similar drug dispenses. The frequency of drug switches demonstrated a yearly peak in the period from January to March. In some months, for atorvastatin, losartan, pantoprazole, and irbesartan, more than 60% of similar drug dispenses were drug switches. Most drug switches (80.3%) were between two generic drugs, and 0.12% of these involved a drug from a European parallel import. The proportion of drug switches between two brand-name drugs decreased from 14.5 to 5.53% during our study period, and of these, 86.5% involved a drug from a European parallel import., Conclusions: Drug switching is common in the Netherlands, and most of the drug switches we studied are between generic drugs. The observed annual peak of drug switches is most likely explained by a specific Dutch reimbursement policy. Not only are the data valuable as is, but they also serve as a first step towards elucidating the reasons for the occurrence of these drug switches. In addition, these data can be used to put into perspective the adverse drug reactions associated with drug switching.

Introduction: Nearly 90% of drugs dispensed in the US are generic products., Objective: The aim of this study was to develop and implement a tool for analyzing manufacturer-level drug utilization and switching patterns within the US Food and Drug Administration's Sentinel system., Methods: A descriptive tool was designed to analyze data in the Sentinel common data model and was tested with two case studies-metoprolol extended release (ER) and lamotrigine ER-using claims data from four Sentinel data partners. We plotted initiators of each brand and generic product over time. For metoprolol ER, we evaluated rates of switching from generics around the time of manufacturing issues. For lamotrigine ER, we examined rates of switching back to the brand among those who switched from brand to generic., Results: We identified 1,651,285 initiators of metoprolol ER products between July 2008 and September 2015. We observed a large decrease in monthly metoprolol ER initiators (from 25,465 in December 2008 to 13,128 in February 2009), corresponding to recalls by generic manufacturers. We observed simultaneous increases in utilization of the authorized generic and brand products. We identified 4266 initiators of lamotrigine ER with an epilepsy diagnosis between January 2012 and September 2015. Among those who switched from brand to generic, the cumulative incidence of switching back was close to 20% at 2 years. Switchback rates were higher for the first available generic products., Conclusions: This developed tool was able to elucidate novel utilization and switching patterns in two case studies. Such information can be used to support surveillance of generic drugs and biosimilars.

Substitution by generic drugs is allowed when bioequivalence to the originator drug has been established. However, it is known that similarity in exposure may not be achieved at every occasion for all individual patients when switching between formulations. The ultimate aim of our research is to investigate if pharmacokinetic subpopulations exist when subjects are exposed to bioequivalent formulations. For that purpose, we developed a pharmacokinetic model for gabapentin, based on data from a previously conducted bioavailability study comparing gabapentin exposure following administration of the gabapentin originator and three generic gabapentin formulations in healthy subjects. Both internal and external validation confirmed that the optimal model for description of the gabapentin pharmacokinetics in this comparative bioavailability study was a two-compartment model with absorption constant, an absorption lag time, and clearance adjusted for renal function, in which each model parameter was separately estimated per administered formulation., (© 2018 The Authors. Clinical Pharmacology & Therapeutics published by Wiley Periodicals, Inc. on behalf of American Society for Clinical Pharmacology and Therapeutics.)

Small changes in bioavailability of narrow therapeutic index (NTI) drugs can alter clinical outcomes, raising concern over generic NTI substitution. We surveyed pharmacists to identify their perceptions of generic NTI drugs, their frequency of performing generic NTI substitution, and predictors of this behavior. Of 710 respondents (33% response rate), 87% perceived generic NTI drugs as effective as their brand-name versions and 94% as safe. Whereas 82% almost always performed generic NTI substitution for initial prescriptions, only 60% did for refills. Pharmacists in non-chain settings (odds ratio (OR) = 2.37; 95% confidence interval (CI) = 1.40-4.02), in practice longer (per year OR = 1.04; 95% CI = 1.02-1.06), in states with affirmative patient consent laws (OR = 1.88; 95% CI = 1.06-3.32), and in states with NTI-specific substitution requirements (OR = 1.95; 95% CI = 1.16-3.26) were more likely not to substitute initial prescriptions. Education of non-chain and veteran pharmacists and elimination of affirmative patient consent and NTI-specific substitution requirements could increase generic NTI substitution., (© 2017 American Society for Clinical Pharmacology and Therapeutics.)

Background: Although cancer drug shortages are a persistent problem in oncology, little is known about the awareness and perspectives of the US population with respect to shortages., Methods: In 2016, we administered a 13-item cross-sectional survey to 420 respondents who were randomly selected from an online, probability-based sample demographically representative of the adult US population with respect to sex, age, race/ethnicity, education, geography, and income. Analyses applied poststratification sampling weights to draw national inferences., Results: Overall, 16% of respondents reported being aware of drug shortages. Those with a personal history of cancer were more likely to be aware (31% vs 14% [P = .03]). In the overall cohort, most reported wanting to be informed about a substitution due to shortage: 87% and 82% for major or minor differences in efficacy, and 87% and 83% for major or minor differences in side effects. Most also reported they would transfer care to avoid a substitution: 72% for major differences in efficacy, and 61% for major differences in side effects. Black respondents, the uninsured, the unemployed, those with lower income, and the less well-educated were all less likely to report that they would transfer care to avoid major differences in efficacy (all P < .05)., Conclusion: These data suggest that the US population is largely unaware of cancer drug shortages. Moreover, if being treated for cancer, most people would want to know about drug substitutions, even if it were to result in only minor differences in efficacy or side effects. With more significant differences, many would transfer care. Cancer 2018;124:2205-11. © 2018 American Cancer Society., (© 2018 American Cancer Society.)

Since the enforcement of Generics Act (1999), three types of pharmaceutically equivalent products are marketed in Brazil: innovative reference (REF), "similar" (S) and generic (G) drugs. The S (brand name) and G (generic name) borrow from REF (brand name) clinical data on safety and efficacy and dosage regimen. G (but not S) is bioequivalent to and interchangeable with REF. Starting in 2003, Brazilian Sanitary Surveillance Agency (Anvisa) has required data on relative bioavailability tests (with REF) to approve (or renew registration of) S drugs. In 2014, Anvisa extended interchangeability notion to similar drugs with a "comparable" bioavailability, i.e., an "equivalent" similar drug (EQ). Drugs for chronic diseases and "critical dose medicines" are listed among the EQ drugs approved. Interchangeability of nonbioequivalent medicines raises deep concerns regarding therapeutic failures and adverse events. Concerns are even more worrisome if patients switch from one drug to another during an ongoing treatment for illnesses such as epilepsy, congestive heart failure, hypertension, diabetes and/or substitutable drugs have a narrow therapeutic index.

Study Objective: Generic drugs contain identical active ingredients as their corresponding brand drugs and are pharmaceutically equivalent and bioequivalent, whereas authorized generic drugs (AGs) contain both identical active and inactive ingredients as their corresponding brand drugs but are marketed as generics. This study compares generic-to-brand switchback rates between generic and AGs., Design: Retrospective cohort study., Data Source: Claims and electronic health record data from a regional U.S. health care system., Patients: The full cohort consisted of 5542 unique patients who received select branded drugs during the 6 months prior to their generic drug market availability (between 1999 and 2014) and then were switched to an AG or generic drug within 30 months of generic drug entry. For these patients, 5929 unique patient-drug combinations (867 with AGs and 5062 with generic drugs) were evaluated., Measurements and Main Results: Ten drugs with AGs and generics marketed between 1999 and 2014 were evaluated. The date of the first generic prescription was considered the index date for each drug, and it marked the beginning of follow-up to evaluate the occurrence of generic-to-brand switchback patterns over the subsequent 30 months. Switchback rates were compared between patients receiving AGs versus those receiving generics using multivariable Cox proportional hazards models, controlling for individual drug effects, age, sex, Charlson Comorbidity Score, pre-index drug use characteristics, and pre-index health care utilization. Among the 5542 unique patients who switched from brand to generic or brand to AG, 264 (4.8%) switched back to the brand drug. Overall switchback rates were similar for AGs compared with generics (hazard ratio [HR] 0.86, 95% confidence interval [CI] 0.65-1.15). The likelihood of switchback was higher for alendronate (HR 1.64, 95% CI 1.20-2.23) and simvastatin (HR 1.81, 95% CI 1.30-2.54) and lower for amlodipine (HR 0.27, 95% CI 0.17-0.42) compared with the other drugs evaluated., Conclusion: Overall switchback rates were similar between AG and generic drug users, indirectly supporting similar efficacy and tolerability profiles for brand and generic drugs. Reasons for differences in switchback rates among specific products need to be explored further., (© 2017 Pharmacotherapy Publications, Inc.)

As lower-cost versions of original biologic drugs made by different manufacturers, follow-on biologics offer the promise of meaningful savings for the US health care system and improved patient health outcomes through greater medication adherence. Fulfillment of this promise, however, is predicated on the prescribing of such products. Under state drug product selection laws, pharmacists may substitute prescriptions for brand name, small-molecule drugs with their generic equivalents, but will be indefinitely prohibited from substituting prescriptions for original biologics with their follow-on biologic counterparts given a lack of product-specific guidance on demonstrating interchangeability. Even when interchangeable follow-on biologics become available, they will face heightened barriers to substitution following the enactment of so-called carve-outs in several states. Data collected to date suggest that a substantial proportion of US physicians remain skeptical of follow-on biologics despite their long record of safe and effective use in Europe. Active surveillance of follow-on biologics within the US market using insurance claims databases can help address this skepticism and help answer key questions concerning the safety of switching between original and follow-on products or between different follow-on products, and of extrapolating to broader indications. Funding is needed to support such surveillance activities and to disseminate the findings to key stakeholders.

Purpose: US Food and Drug Administration approval for generic drugs relies on demonstrating pharmaceutical equivalence and bioequivalence; however, some drug products have unique attributes that necessitate product-specific approval pathways. We evaluated rates of patients' switching back to brand-name versions from generic versions of four drugs approved via such approaches., Methods: We used data from Optum LifeSciences Research Database to identify patients using a brand-name version of a study drug (acarbose tablets, salmon calcitonin nasal spray, enoxaparin sodium injection, and venlafaxine extended release tablets) or a control drug. We followed patients to identify switching to generic versions and then followed those who switched to identify whether they switched back to brand-name versions. We calculated switch and switch-back rates and used Kaplan-Meier and log-rank tests to compare rates between study and control drugs., Results: Our cohort included 201 959 eligible patients. Brand-to-generic switch rates ranged from 66 to 106 switches per 100 person-years for study drugs and 80 to 110 for control drugs. Rates of switch-back to brand-name versions ranged from 5 to 37 among study drugs and 3 to 53 among control drugs. Switch-back rates were higher for venlafaxine vs. sertraline (p < 0.01) and calcitonin vs. alendronate (p = 0.01). Switch-back rates were lower for venlafaxine vs. paroxetine (p < 0.01) and acarbose vs. nateglinide (p < 0.01). Rates were similar for acarbose vs. glimepiride (p = 0.97) and for enoxaparin vs. fondiparinux (p = 0.11)., Conclusion: As compared to control drugs, patients were not more likely to systematically switch back from generic to brand-name versions of the four study drugs. Copyright © 2016 John Wiley & Sons, Ltd., (Copyright © 2016 John Wiley & Sons, Ltd.)

Generic substitution of antiepileptic drugs (AEDs) is still a matter of controversy and concern among clinicians and patients. We aimed to assess intrasubject variation in plasma concentrations of lamotrigine (LTG), levetiracetam (LEV) and topiramate (TPM) after generic substitution compared with a stable brand-name drug regimen in a population of patients with epilepsy. A retrospective analysis was performed on prospectively collected and stored data from our therapeutic drug monitoring (TDM) database for the years 2009-2014. The main outcome variable was the proportion of patients who, after switching from branded to generic formulations, showed a greater than ±20% change in AED plasma concentrations compared to the proportion of control patients showing a change in AED plasma concentrations of the same extent while receiving stable branded formulations over repeated TDM tests. Fifty patients on LTG, 27 on LEV and 16 on TPM showing at least one TDM test while receiving generic products fulfilled the inclusion/exclusion criteria for the analysis and were compared with 200 control patients for LTG, 120 for LEV and 80 for TPM. The proportion of patients showing an intrasubject change greater than ±20% in AED plasma concentrations was similar in the brand name vs generic group compared with the control one for LTG (22% vs 33%) and LEV (44% vs 38%), while it was higher in the control group for TPM (41% vs 6%, p<0.01). These are the first data in the literature about the within-patient variation in steady-state plasma concentrations of a series of stable treatments with brand-name AEDs in a real clinical setting. In conclusion, a significant interday variability in intrapatient LTG, LEV and TPM plasma concentrations can be observed even in patients stabilized with the same brand name product over time. This suggests that any change in plasma AED concentration and possible related clinical effects after generic substitution may be not necessarily related to the switch. Our results should be confirmed by large, prospective, blinded, randomized controlled studies in people with epilepsy., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Background: Patients and clinicians share concerns that generic drug substitution might lead to loss of efficacy or emergence of adverse events. In this trial, we assessed US Food and Drug Administration (FDA) bioequivalence standards by studying the effects of switching between two disparate generic immediate-release lamotrigine products in patients with epilepsy., Methods: The Equivalence among Generic Antiepileptic Drugs (EQUIGEN) chronic-dose study was a randomised, double-blind, crossover study that enrolled adults (aged ≥18 years) with epilepsy from six epilepsy centres at academic institutions across the USA who were receiving immediate-release lamotrigine dosed at 100 mg, 200 mg, 300 mg, or 400 mg twice daily. Eligible patients were randomly allocated (1:1) to one of two treatment sequences (sequence 1 or sequence 2), comprising four study periods of 14 days each. During each 14-day treatment period, patients received balanced doses of an oral generic lamotrigine product every 12 h (200-800 mg total, identical to lamotrigine dose prior to study enrolment); after each 14-day period, patients were crossed over to receive the other generic product. Computer-based randomisation was done using random permuted blocks of size two or four for each site to prevent sequence predictability. Both patients and study personnel were masked to the generic products selected, their predicted exposure (ie, "high" vs "low"), and their group allocation. The primary outcome of this trial was bioequivalence between the generic products, which was assessed at the end of the study through a comparison of maximum plasma concentration (Cmax) and area under the concentration-time curve (AUC) for each product in the analysis population (all patients who completed all four treatment periods). Bioequivalence was established if the 90% CIs of the ratios of these two parameters for the two products were within equivalence limits (80-125%) in the analysis population. This study is registered with ClinicalTrials.gov\, number NCT01713777., Findings: Between April 25, 2013, and Aug 12, 2014, 35 eligible patients were enrolled and randomly assigned to treatment sequence 1 (n=15) or treatment sequence 2 (n=20). 33 patients completed all four treatment periods and were included in the primary outcome analysis. The 90% CIs of the ratios of both Cmax and AUC were within equivalence limits (AUC 90% CI 98-103, Cmax 90% CI 99-105), showing that lamotrigine exposures were equivalent between the generic products. No significant changes in seizure frequency or adverse events were recorded. No deaths, study-related serious adverse events, or changes in clinical laboratory values or vital signs occurred during this study., Interpretation: Disparate generic lamotrigine products in patients with epilepsy showed bioequivalence with no detectable difference in clinical effects, confirming that US Food and Drug Administration bioequivalence standards are appropriate., Funding: American Epilepsy Society, Epilepsy Foundation, and US Food and Drug Administration., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Drugs are the third largest source of expenditure under Switzerland's compulsory basic health insurance. Generics, the price of which should be at least 30 per cent less than the cost of the original drugs, can potentially allow substantial savings. Their approval requires bioequivalence studies and their use is safe, although some factors may influence patients' and physicians' acceptance. The increased substitution of biosimilar drugs for more expensive biotech drugs should allow further cost savings. In an attempt to extend the monopoly granted by the original drug patent, some pharmaceutical companies implement "evergreening" strategies including small modifications of the original substance for which the clinical benefit is not always demonstrated.

Objective: To study the health impact on adult New Zealand patients who switch from originator brand to generic venlafaxine., Methods: The national pharmacy database was used to select patients using venlafaxine for at least 6 months. Switchers and nonswitchers were identified, and switch behavior was compared for a 12-month follow-up period. Change in health service use following switching was also compared between switchers and nonswitchers including use of the emergency department, hospital, and specialist outpatient services over the same period., Results: Approximately 12% of all originator brand users switched to generic venlafaxine, at least half of whom continued to use the generic throughout the follow-up period to August 1, 2012. Almost 60% of new users of the generic venlafaxine, however, switched to using the originator brand. Aside from a slight reduction in the use of outpatient services among switchers, there were no significant differences in health services use between switchers and nonswitchers for either existing or new venlafaxine users., Conclusions: Although both products remain fully subsidized and available, there is little incentive for prescribers, pharmacists, or patients to switch to the less expensive generic brand. If savings to the national New Zealand budget are to be realized, additional policy measures should be implemented to minimize incentives for multiple and reverse switching, and prescribers, as key opinion leaders, could take the lead in promoting generics to their patients., (Copyright © 2015. Published by Elsevier Inc.)

Biosimilars are biological products that are highly similar to their biological reference products, notwithstanding minor differences in clinically inactive components. However, unlike generics of small-molecule drugs, biosimilars are not identical to their reference products, since each manufacturer uses unique cell lines and processes, and these lead to slight structural differences between products. Because these structural variations can lead to differences in clinical response, clinical studies demonstrating biosimilarity are required before and robust pharmacovigilance after approval. Although the FDA has not yet issued formal guidance on interchangeable biosimilars, higher standards of similarity will be required in order to achieve an interchangeable designation. In this commentary, we review the differences between generics and biosimilars, describe their respective regulatory approval pathways, discuss interchangeability and substitution, and review substitution of interchangeable biosimilars, focusing on key professional considerations for pharmacists.

Objectives: To identify patient demographics and characteristics associated with compliance to statin therapy after switching from branded to generic agents, Design: Retrospective cohort study using electronic health records and pharmacy claims data from Sutter Health's ambulatory-care medical network, Patients: Managed-care beneficiaries, ≥ 18 years of age, who were switched from branded to generic statins between 1 January 2003 and 31 December 2012 MAIN MEASURES: Compliance was calculated as days of therapy dispensed divided by days from first to last generic prescription fill over 6 months, and was defined as a medication possession ratio ≥ 0.80. We used multivariable logistic regression to assess factors associated with compliance. Adjusted ORs and 95% CI were generated., Key Results: We identified 5,156 patients who were switched from branded to generic statins; 73% of patients were compliant in the 6 months after switching. After statistical adjustment, higher compliance was associated with each 10-year increase in age (OR: 1.13; 95% CI: 1.07, 1.19; p < 0.001), receipt of a generic statin equivalent in potency to the prior branded statin (OR: 1.41; 95% CI: 1.16, 1.70; p < 0.001), and compliance with prior branded statin (OR: 4.68; 95% CI: 4.07, 5.39; p < 0.001). Lower compliance was seen among Hispanic patients compared to non-Hispanic white patients (OR: 0.68; 95% CI: 0.52, 0.91; p = 0.009). Also, a switch to a higher potency generic statin, regardless of prior dose/potency, was negatively associated with compliance after switching (OR: 0.87; 95% CI: 0.80, 0.94; p = 0.001)., Conclusions: The majority of patients switched from branded to generic agents were compliant with therapy in the first 6 months after switching. The potential for non-compliance to generic statin therapy, particularly among younger or Hispanic patients or when dose/potency changes are made, should be considered prior to switching. For these patients, counseling or close monitoring may be required to optimize generic interchange.

Introduction: Generic products of antiepileptic drugs (AEDs) are currently a controversial topic as neurologists and patients are reluctant to switch from brand products to generics and to switch between generics., Objective: The aim of this study was to provide enlightenment on issues of bioequivalence (BE) and interchangeability of AED products., Methods: Monte Carlo simulations of the classic 2 × 2 BE studies were performed to study the effect of sample size, within-subject variability, and the true difference in pharmacokinetic values of the products under comparison on BE acceptance of generic AED products. Simulations were extended to study the comparative performance of two generic AED products against the same innovative product. The simulated results are compared with literature data on AEDs., Results: The question with regard to bioavailability (BA) is whether two formulations are different, while for BE the question is whether two formulations are sufficiently similar in terms of extent and rate of absorption. Therefore, the criteria for BA and BE and the statistical analysis involved in their analysis are different. Two generic formulations that meet regulatory approval requirements for generics by being bioequivalent to the same innovative AED may not be bioequivalent to one another and therefore should not be regarded as equal or as therapeutically equivalent products. A switch from a standard or an immediate-release formulation to a modified-release product, which comprises extended-release or delayed-release formulations, should not be regarded as a switch between generics, but rather as a switch between different formulation types., Discussion: Switches between bioequivalent generic AED products could potentially lead to larger changes in plasma levels and exposure than the brand-to-generic switch. The simulation work verified the clinical findings that not all generic AED products bioequivalent to the same innovative product are bioequivalent to one another., Conclusions: Two generic formulations that meet regulatory approval requirements for generics, by being bioequivalent to the innovative AED, may not be bioequivalent to one another. Additional BE criteria are needed for a formulation switch, particularly in epilepsy, where a breakthrough seizure may change a patient's status from seizure-free to refractory.

Background: Generic substitution has been implemented in many countries, but knowledge about patients' attitudes, beliefs and experiences is still sparse., Aim: To assess associations between generic switching and patients' attitudes, beliefs and experiences with previous generic switching., Design and Setting: A cross-sectional study comprising questionnaire responses from 2,476 randomly selected patients aged 20 years or older and living in the Region of Southern Denmark, who had redeemed substitutable drugs., Methods: The questionnaire included items on beliefs about medicine, views on generic medicine and confidence in the healthcare system. Only prescriptions issued by the general practitioners were included. For each patient, we focused on one purchase of a generically substitutable drug (index drug). Patients were identified by means of a dispensing database., Results: Earlier generic switches within the index ATC code were statistically significantly associated with experience of a generic switch (adjusted OR 5.93; 95 % CI 4.70-7.49). Having had more than five earlier switches within other ATC codes and having negative views on generic medicines reduced the odds of experiencing a generic switch. No associations were found between generic substitution and gender, drug group, number of different drugs used by the patient, confidence in the health care system and beliefs about medicine in general., Conclusion: Patients who had once experienced a generic switch were more likely to accept a future generic switch within the same ATC code. Negative views on generic medicines were negatively associated with switching, while beliefs about medicine and confidence in the healthcare system had no influence.

Teicoplanin is an antibiotic made by fermentation in which a glycopeptide core is substituted by different fatty acids. The chemical structure and proportion of the various components are strictly dependent on the production process (Actinoplanes sp. strain, cell culture conditions and downstream process). Thus, a relevant variability can be introduced from different manufacturers. Interchangeability or substitution among the originator and the generic products of teicoplanin for injection is under debate with respect to pharmaceutical similarity. In fact, depending on the manufacturer, the six major components of teicoplanin show different quantitative distributions compared to that of the originator. The European Pharmacopoeia fixed an undifferentiated upper limit for the component content. A statistical approach is required for comparing complex products. In this paper the use of principal component analysis (PCA) as a tool for identifying the pharmaceutical equivalence among teicoplanin products from different sources was explored. The results obtained show that PCA can distinguish the differing origin of this biological drug., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Background: Numerous patients are subject to drug-related problems (DRPs) every day, resulting in sub-optimal therapy, suffering and decreased quality of life, as well as in high societal health care costs. Classifying DRPs is important for the development of counselling skills and for pharmaceutical care practice and research, including assessments of the value of pharmacists' clinical interventions. Pharmacy practitioners have also reported to become more attentive to patients' drug-related needs, when requested to document their clinical interventions. Several studies have been conducted on DRPs, but there is still a need for a more thorough knowledge about their nature and the reasons for their occurrence. To examine DRP characteristics and causes by retrospectively analysing data and patient case histories, as documented by pharmacy practitioners in the Swedish national DRP database., Setting: Community pharmacy based patient documentation, entered into the Swedish national DRP database., Method: Documented DRPs, clinical interventions and patient data were retrospectively examined and analysed. Particular attention was paid to case history reports in free text fields. Only reports containing adequate information for analysis and actual, correctly categorised DRPs were included., Main Outcome Measure: Subdivided DRP characteristics and causes., Results: Both similarities and differences between DRP subclasses of prescription patients (n = 5,571) and OTC drug consumers (n = 2,894) were observed. Most DRP categories could be subdivided into at least three subclasses, according to their characteristics. Causes of DRPs could be extracted from free text field reports in four prescription DRP categories and three OTC DRP categories. Uncertainty about the aim of the drug was commonly characterised by a lack of knowledge about the indication in prescription patients and in an inappropriate drug selection in OTC drug consumers. A switch from a brand-name drug to a generic drug or from one generic to another was the cause in half of the therapy failures, which in turn was a frequent reason for overuse of drug., Conclusion: The study demonstrates the multi-facetted drug-related problems in patients and confirms the importance of attention by pharmacy practitioners for the detection of and intervention for DRPs.

Background: Upon admission to a hospital patients' medications are frequently switched to alternative drugs compiled in so called hospital drug formularies. This substitution process is a laborious and error-prone task which should be supported by sophisticated electronic tools. We developed a computerised decision support system and evaluated benefit and potential harm associated with its use., Methods: Based on a multi-step algorithm we identified drug classes suitable for exchange, defined conversion factors for therapeutic interchange, built a web-based decision support system, and implemented it into the computerised physician order entry of a large university hospital. For evaluation we compared medications manually switched by clinical pharmacists with the results of automated switching by the newly developed computer system and optimised the system in an iterative process. Thereafter the final system was tested in an independent set of prescriptions., Results: After iterative optimisation of the logical framework the tool was able to switch drugs to pharmaceutical equivalents and alternatives; in addition, it contained 21 different drug classes for therapeutic substitution. In this final version it switched 91.6% of 202 documented medication consultations (containing 1,333 drugs) automatically, leaving 8.4% for manual processing by clinical professionals. No incorrect drug switches were found., Conclusion: A large majority (>90%) of drug switches performed at the interface between primary and tertiary care can be handled automatically using electronic decision support systems, indicating that medication errors and workload of healthcare professionals can be considerably reduced.

Long-term success in solid organ transplantation strongly depends on the optimal use of maintenance immunosuppressive treatment. Cyclosporin and tacrolimus are the most frequently administered immunosuppressants and they are designed to narrow therapeutic index drugs. The substitution of the branded formulation by their generic counterparts may lead to economic benefit only if equivalent clinical outcomes can be achieved. There is no published evidence to date on the guarantee of their long-term therapeutic equivalence and cases of therapeutic failures have been reported due to inadvertent drug conversion. The disadvantageous clinical consequences of a non medical, mechanistic forced switch from the original to generic formulation of tacrolimus and the estimated loss of the payer's presumed savings are presented in a kidney transplant recipient population. Special problems related to pediatric patients, drug interactions with concurrent medications and the burden of additional therapeutic drug monitoring and follow up visits are also discussed. The authors are convinced that the implementation of the European Society of Organ Transplantation guidelines on generic substitution may provide a safe way for patients and healthcare payers.

Unlabelled: Automatic generic substitution of alendronate products, used to reduce drug costs, and medication persistence was studied retrospectively between 2006 and 2009. During this period the number of, and the rate of substitution between, alendronate products increased while persistence decreased. Patient preferences should be considered when designing and evaluating generic policies., Introduction: Automatic generic substitution (AGS) was implemented in Sweden in 2002. The objective of this study was to investigate the association between AGS and persistence with alendronate treatment of primary osteoporosis in Sweden., Methods: An open historical cohort of women and men (n = 36,433) was identified in the Swedish Prescribed Drug Register through filled prescriptions for alendronate or risedronate between 2005 and 2009. Co-morbidity data was extracted from the National Patient Register. The association between AGS and medication persistence was investigated using non-parametric and parametric survival analysis., Results: Between 2006 and 2009, the number of alendronate products increased from 15 to 25, the proportion of prescriptions constituting a substitution increased from 10.8% to 45.2%, and the proportion of patients persisting with alendronate treatment for 12 months fell from 66.9% to 51.7%. Patients starting alendronate treatment in 2006 had lower risk of stopping treatment compared with those starting in 2007 (HR 1.34, 95% CI 1.29-1.39), 2008 (HR 1.49, 95% CI 1.43-1.55), and 2009 (HR 1.50, 95% CI 1.40-1.60). No difference was observed in persistence with proprietary risedronate during the same period. Individuals who had their alendronate product substituted at the first prescription refill had significantly higher probability of discontinuation (HR 1.25, 95% CI 1.20-1.30)., Conclusion: AGS causes increased product substitution which appears to be associated with reduced treatment persistence. Poor health outcomes and associated costs due to forgone drug exposure should be taken into account in the design and evaluation of policies implemented to encourage utilisation of generic medicines.

Aggravation of asthmatic response (asthmatic attack, 2 cases) and adverse events (tremor, 1 case) due to a switch from a brand-name tulobuterol tape to a generic tape were recently reported. These changes disappeared after reformulation from generic to the brand-name tape. To investigate this issue, we conducted a questionnaire survey on changes of asthmatic response, adverse events and product usability due to a switch between tulobuterol tapes. We identified 44 cases (18 from doctors, 26 from pharmacists) in which changes of asthmatic response or adverse events had occurred due to a switch between tulobuterol tapes. Aggravation of asthmatic response had occurred in 30 cases and adverse events in 21 cases due to switch from brand-name tulobuterol tape to generic tape. As regards change of product usability, we obtained 96 relevant responses (18 from doctors, 78 cases pharmacists), and the major response was that generic tulobuterol tape peeled off the skin more easily than did the brand-name tape (60 cases). These results suggest that changes of asthmatic response, adverse events and product usability should be carefully monitored when switching tulobuterol tapes.

Purpose: This study aims to explore how long-term drug users with a Pakistani background living in Oslo (Norway) perceive generic substitution and how generic substitution influences drug adherence in this population., Methods: Personal interviews using a semi-structured questionnaire were carried out with 83 Pakistani immigrants (aged 40-80 years) who were using antihypertensives, antidiabetics, and/or cholesterol-lowering drugs., Results: In all, 73% of the participants were using generic drugs at the time of the interview. Of these, 10% were erroneously using two equivalent generics at the same time. One quarter of the participants were of the opinion that cheaper generic drugs were counterfeit drugs. Two thirds had accepted generic substitution in the pharmacy whereas the remaining participants had either opposed or were unaware of the substitution. Of those who had accepted substitution, 27% claimed that the effect of the new drug was poorer and 20% reported more side-effects. Generic substitution had resulted in concerns about the therapy in 41% of the patients, and 26% thought it had become more demanding to keep track of their medication. Poor adherence tended to be most common among patients who were not fluent in Norwegian, patients who had concerns about medicine use, and patients who had accepted generic substitution in the pharmacy., Conclusion: This study shows that generic substitution may have a negative effect on drug adherence in Pakistani immigrants in Oslo (Norway) because of concerns and misconceptions, including confusion with regard to counterfeit drugs. Problems result primarily from inadequate information caused by language barriers but also from culturally conditioned views on encounters with the health care system.