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Generic drugs: Th e benefi ts and risks of making the switch When is it safe to substitute a generic drug for a brand-name medication, and when should a switch be avoided? Here's a look at the evidence. E ach year, Americans save an estimated $8 billion to $10 billion at retail pharmacies by purchasing generic drugs rather than brand-name medications, the US Food and Drug Administration (FDA) reports. 1 Th e lower cost, of course, is the key advantage of generics. But the very reason for the cost savings—the fact that generic drugs do not have to undergo the large, expensive clinical trials that are required for approval of brand-name medications—gives rise to questions about the quality and safety of generics. Are these concerns justifi ed? Under what circumstances is it safe to prescribe generics, or to substitute a generic for a brand-name drug? Are brand-name drugs always better? To answer these questions, we conducted a thorough evidence review, which included numerous randomized controlled trials (RCTs) and case reports, as well as a single meta-analysis that assessed the benefi ts and risks of generics. Generics: On the positive side Safety and effi cacy. Our literature search yielded little evidence that generic drugs are less safe or less eff ective than their brand-name equivalents. Th e meta-analysis, for example , 2 included 47 studies (38 of 47 were RCTs) covering 9 subclasses of cardiovascular medications. In trials involving beta-blockers, diuretics, calcium channel blockers, antiplate-let agents, statins, angiotensin-converting enzyme inhibitors, and alpha-blockers, no evidence of superiority of brand-name drugs vs generics was found. 2 ❚ Cost. Generic drugs typically cost 30% to 60% less than their brand-name counterparts, 3 and widespread use of ge-nerics has the potential to reduce the price of other brand-name drugs by creating more competition.
VOL 59, NO 11
Generic drugs:
e bene ts and risks
of making the switch
When is it safe to substitute a generic drug for a brand-
name medication, and when should a switch be avoided?
Here’s a look at the evidence.
Each year, Americans save an estimated $8 billion to
$10 billion at retail pharmacies by purchasing generic
drugs rather than brand-name medications, the US
Food and Drug Administration (FDA) reports.1 e lower
cost, of course, is the key advantage of generics. But the very
reason for the cost savings—the fact that generic drugs do not
have to undergo the large, expensive clinical trials that are re-
quired for approval of brand-name medications—gives rise
to questions about the quality and safety of generics.
Are these concerns justi ed? Under what circumstances
is it safe to prescribe generics, or to substitute a generic for a
brand-name drug? Are brand-name drugs always better? To
answer these questions, we conducted a thorough evidence
review, which included numerous randomized controlled tri-
als (RCTs) and case reports, as well as a single meta-analysis
that assessed the bene ts and risks of generics.
Generics: On the positive side
Safety and ef cacy. Our literature search yielded little evi-
dence that generic drugs are less safe or less e ective than
their brand-name equivalents.  e meta-analysis, for ex-
ample,2 included 47 studies (38 of 47 were RCTs) covering
9 subclasses of cardiovascular medications. In trials involving
beta-blockers, diuretics, calcium channel blockers, antiplate-
let agents, statins, angiotensin-converting enzyme inhibitors,
and alpha-blockers, no evidence of superiority of brand-
name drugs vs generics was found.2
Cost. Generic drugs typically cost 30% to 60% less than
their brand-name counterparts,3 and widespread use of ge-
nerics has the potential to reduce the price of other brand-
name drugs by creating more competition.
Another plus: Patients taking generic drugs appear to be
Pawel Lewek, MD;
Przemyslaw Kardas,
The First Department of
Family Medicine, Medical
University of Lodz, Poland
Dr. Kardas reported that he
receives research support from
Polpharma SA and serves as
a consultant to Boehringer
Ingelheim, Egis
Pharmaceuticals, and
Polpharma SA. Dr. Lewek
reported no potential con ict of
interest relevant to this article.
Do not authorize the phar-
macy to switch patients from
a brand-name antiepileptic
drug to a generic without
your approval. C
Use caution when switch-
ing a patient to a generic
modi ed-release formulation,
which may not have the same
pharmacokinetic pro le as its
brand-name counterpart. C
Consult the FDAs
Orange Book: Approved Drug
Products with  erapeutic
Equivalence Evaluations,
available at http://www.
cder/ob/default.cfm for details
on generic substitution. C
Strength of recommendation (SOR)
G ood-quality patient-oriented
Inconsistent or limited-quality
patient-oriented evidence
Consensus, usual practice,
opinion, disease-oriented
evidence, case series
more willing to continue therapy than those
taking brand-name medications.4 Lower co-
pays are a key factor. In 1 recent study of pa-
tients with hypercholesterolemia or diabetes,
those taking generics had greater adherence
compared with patients receiving brand-
name drugs.5
Quality. It is important to note that
many generic medications are produced
under the license of the manufacturer of
the original brand-name product, with the
lower-cost equivalent often introduced after
the drug’s patent has expired. Even when dif-
ferent manufacturers produce the branded
product and the generic, strict standards ex-
ist to guarantee the quality of generic drugs.
The journey to market—
the similarities, the differences
Both brand-name and generic medications
undergo similar new drug application (NDA)
procedures.  e manufacturers of both are
required to submit detailed evidence of the
chemistry, manufacturing, controls, labeling,
and testing processes. From there, brand-
name and generic products take divergent
paths to market.
New nongeneric drugs must undergo
rigorous animal and human studies, includ-
ing large RCTs comparing the e cacy of the
new product with that of a placebo and care-
fully tracking side e ects. Bioavailability test-
ing is required, as well. For generic drugs, the
process is known as an abbreviated new drug
application (ANDA), and bioequivalence
studies are su cient.1,6
e bioequivalence studies required for
a new generic are based on pharmacokinetic
parameters, most notably, the area under
the plasma concentration curve (AUC)—a
measure of overall drug exposure—and the
maximal plasma concentration (Cmax). If AUC
and Cmax are within an acceptance range
(0.80–1.25 of the brand-name product pa-
rameters), the therapeutic equivalence of a
generic drug is substantiated.7,8
Concerns about testing,
Opponents of widespread use of generics
point out that they are tested on only a few
young, healthy individuals, compared with
the large numbers of patients who participate
in clinical trials of the original drug.
According to guidelines from the World
Health Organization (WHO), 18 to 24 healthy
Generic substitution of antiepileptic agents:
Where the American Academy of Neurology stands18
The AAN opposes:
generic substitution of anticonvulsant drugs for the treatment of epilepsy without the attending
physician’s approval.
generic substitution of anticonvulsants for patients with epilepsy at the point of sale without prior
consent of both the physician and the patient.
state and federal legislation that would impede the ability of physicians to determine which
anticonvulsant drugs to prescribe for the treatment of patients with epilepsy.
The AAN believes:
formulary policies should recognize and support physician autonomy in prescribing, and patients in
accessing, the full range of anticonvulsants for epilepsy.
The AAN supports:
legislation that would require informed consent of physicians and patients before generic
substitutions of anticonvulsants are made at the point of sale.
The AAN recognizes:
that different strategies may be appropriate in using anticonvulsants for the treatment of
conditions other than epilepsy. According to the
World Health
18 to 24 healthy
adult volunteers
are generally
suf cient for a
In a study
Tegretol with
3 generic
formulations of
1 of the generics
was not
adult volunteers are considered su cient for
a bioequivalence study.9 e number of par-
ticipants may be greater, however, if absorp-
tion or clearance of the drug is highly variable.
What’s more, the people who volunteer for
generic drug studies cannot smoke or take
concurrent medication. To exclude the pos-
sibility that food coadministration a ects the
generic medication being studied, the FDA
further recommends bioequivalence test-
ing of oral formulations on volunteers eating
standardized meals.8 ese criteria help min-
imize the magnitude of intersubject variabil-
ity and reduce the possibility of bias—which
could be caused by the disease process, con-
current conditions, or medication interac-
tion, rather than by formulation di erences.8
To further minimize the effects of
nondrug-related variation, bioequivalence
studies typically use a crossover design: Half
the subjects receive the test drug  rst, fol-
lowed by the brand-name product, with a
washout period in between.  e other half re-
ceive the drugs in reverse order.10 ( e study
format is altered, as needed, for extended-
release products, topical agents, and drugs
that are not absorbed systemically. A gener-
ic version of cholestyramine, for example,
which acts by sequestering bile salts within
the intestine, would be approved on the basis
of in vitro studies that quantify the binding of
the bile salts.10)
But does this testing mimic the real
world? While possible confounding factors
are controlled for in bioequivalence studies
of generics, critics point out that this is not
the case in the real world.  us, they worry
that when generics are taken by patients
with actual illnesses, concurrent use of other
medications, medical conditions, and the
like may result in di erences in treatment
that did not occur in the highly controlled
environment in which the equivalency stud-
ies were conducted.11
Differences in formulation
Another concern centers on formulation dif-
ferences, which have the potential to a ect
patients taking generic drugs. A generic copy
of a brand-name drug must contain the same
active ingredient, in the identical quantity, as
the branded product—in the same dose for-
mulation and route of administration. It must
also meet standards for strength, purity, qual-
ity, and identity.11
However, the inert ingredients in the ge-
neric version do not have to be the same as
those in the brand-name drug (although the
ratio of inert to active compound must be
similar).12 Because drugs tested in bioequiva-
lence studies are administered in single dos-
es, many experts wonder whether the inert
compounds used in the generics may a ect
the distribution, metabolism, or absorption
of a drug when it is administered in multiple
doses, or whether the serum concentration of
the generic drug may be elevated when it is
taken for long periods.
Proceed with caution
in these situations
For most patients taking most medications,
generic drugs pose no problems, and provide
an opportunity to obtain the same therapeu-
tic bene t at a considerably lower cost. How-
ever, making the switch with certain classes
of drugs, and with drugs that have a narrow
therapeutic range, poses potential problems
and must be done with caution—if at all.
Antiepileptic drugs. e FDA indicates
that many people who are on antiseizure
medications re-experience seizures despite
continued treatment,1 and that switching to a
generic does not increase the risk of treatment
failure.1,13 Nonetheless, there are numerous
reports of di erences between generic and
brand-name antiseizure medications (and
small studies indicating improper seizure
control after switching patients from a brand-
name to a generic antiepileptic drug).14
For example:
Researchers compared the pharmacoki-
netic parameters of Tegretol with 3 generic
formulations of carbamazepine, and found
that 1 of the 3 was not bioequivalent.15
In a crossover study of 18 healthy volun-
teers, 3 generic formulations of carbam-
azepine were all within the acceptable
bioequivalence range, but were absorbed
more rapidly than the brand-name drug.16
Di erences in the bioavailability of brand-
name and generic products have also
been reported with phenytoin, primi-
of amitriptyline/
and venlafaxine
may not be
according to
the FDA.
done, and valproic acid, but the di er-
ences were not statistically signi cant.17
e American Academy of Neurology
has issued a set of recommendations con-
cerning the use of generic antiepileptic drugs
Narrow therapeutic ratio. e poten-
tial for complications increases in drugs with
a narrow therapeutic ratio, de ned by the
FDA as <2-fold di erence between the medi-
an lethal dose and the median e ective dose,
or between the minimum toxic concentra-
tion and minimum e ective concentration in
the blood.19 e safe and e ective use of such
drugs—carbamazepine, divalproex, lithium,
phenytoin, and warfarin, to name a few—
requires careful dosage titration and patient
Water solubility and nonlinear phar-
macokinetics may present problems in
drugs with a narrow therapeutic ratio,
especially phenytoin.2 e drugs serum
concentration is allowed to range from 8 to
20 mg/L. A concentration above this range
increases the risk for acute cerebellar syn-
drome, delirium, and coma; a concentration
below the range may cause seizures.12
Warfarin is also of particular concern, as
there is always the possibility that a switch
from Coumadin to a generic equivalent could
result in under- or overcoagulation. However,
studies have shown that the use of generic
warfarin in patients previously receiving
Coumadin did not a ect the international
normalized ratio more than continued use of
the brand-name anticoagulant.20,21
Psychotropic agents. ere has been
a number of case reports of problems occur-
ring following a switch from a brand-name
antidepressant to a generic—or from 1 ge-
neric antidepressant to another. (See “Did
a switch to a generic antidepressant cause
relapse?” J Fam Pract. 2008;58:109-114.) In
fact, the FDA cites some psychotropic drugs
for which generic formulations may not be
interchangeable—including amitriptyline/
perphenazine and venlafaxine—and others
for which generic formulations may not be
bioequivalent at all doses.22
Thyroid medication. ere are also
concerns about levothyroxine (LT4) admin-
istration, and major medical societies debate
the use of generic substitution. According to a
recent survey from the American Association
of Clinical Endocrinologists, the American
yroid Association, and  e Endocrine Soci-
ety, clinical use of generic LT4 continues to be
associated with adverse outcomes.23 Most of
the adverse events (89%) reported by survey
respondents were associated with a change,
either from a brand-name drug to a generic
or from 1 particular generic LT4 to another.
Modi ed-release formulations
may also pose a problem
Problems may also occur with generics in
modi ed-release formulations, which may
not have the same pharmacokinetic pro les
as their brand-named counterparts.  e
British National Formulary has advised that
prescriptions for modi ed-release diltiazem
hydrochloride, nifedipine, and theophylline
be  lled with the brand-name drug only.24,25
Morever, a recent study concluded that
2 modi ed-release products of methylpheni-
date and nifedipine had concentration pro-
les that strongly diverged during the period
of absorption, although the formulations met
the regulatory criteria for bioequivalence. 26
The type of salt used to form a com-
pound is also important. Salt-joining makes
a hydrophobic molecule hydrophilic; the
result, especially in psychoactive drugs, is
improved kinetics, absorption, or physico-
chemical properties (eg, stability, hygro-
scopicity,  uidity).27 is may be the reason
for di erences identi ed between generic
and brand-name amitriptyline, nortripty-
line, desipramine, and trimipramine.28 To
avoid problems, physicians should prescribe
generics containing the same salt as their
brand-name counterparts.
When in doubt …
Brand-name drugs are, and always will be,
the best proven therapy, because of the
number and extent of clinical trials they go
through. In most cases, however, there is
no evidence-based reason to avoid generic
substitution for patients who cannot a ord
the brand-name drug. When in doubt, con-
sult the FDAs Orange Book: Approved Drug
Products with  erapeutic Equivalence Eval-
Clinical use of
generic LT4
continues to be
associated with
uations, available at http://www.accessdata., before
making a switch.
Pawel Lewek, MD, The First Department of Family
Medicine, Medical University of Lodz,60 Narutowicza
Street, 90-136 Lodz, Poland;
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bioequivalence. London, England: EMEA; 2000;CPMP/EWP/
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studies for orally administered drug products—general con-
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guidance/4964dft.pdf. Accessed January 11, 2009.
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neric drug substitution. Clin  er. 2003;25:2875-2890.
12. Nakai K, Fujita M, Ogata H. International harmonization
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Yak uga ka Z as shi . 2000;120:1193-1200.
13. Randomized study of antiepileptic drug withdrawal in patients
in remission. Medical Research Council Antiepileptic Drug
Withdrawal Study Group. Lancet. 1991;337:1175-1180.
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problems with generic substitution of antiepileptic drugs? A
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15. Silpakit O, Amornpichetkoon M, Kaojarern S. Compara-
tive study of bioavailability and clinical e cacy of carbam-
azepine in epileptic patients. Ann Pharmacother. 1997;31:
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of two carbamazepine-containing sustained release formu-
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... Although many generic drugs have been shown to be as safe and effective as brand-name medications, randomized controlled trials are required for each drug to confirm that this is the case [6]. AEDs are a type of generic medications that may require more attention on using generic medications due to increasing risk of treatment failure [6]. ...
... Although many generic drugs have been shown to be as safe and effective as brand-name medications, randomized controlled trials are required for each drug to confirm that this is the case [6]. AEDs are a type of generic medications that may require more attention on using generic medications due to increasing risk of treatment failure [6]. Generic carbamazepine may not be equal bioequivalent with the brandname one [6]. ...
... AEDs are a type of generic medications that may require more attention on using generic medications due to increasing risk of treatment failure [6]. Generic carbamazepine may not be equal bioequivalent with the brandname one [6]. Although there has been a generic version of IV LEV (Focale Ò ) available for several years, there have been few clinical studies comparing it with brand-name IV LEV (Keppra Ò ). ...
Full-text available
Introduction Intravenous levetiracetam (IV LEV) is approved for treatment status epilepticus (SE). However, the drug’s high cost must be considered when deciding on a treatment strategy. This study aimed to compare the efficacy of brand-name and generic IV LEV for acute repetitive convulsive seizure (ARCS) or SE. Methods Forty patients aged 18 years or older who had been diagnosed with SE or ARCS were included in this double-blind study. Patients were randomly assigned at a 1:1 ratio (via computer-generated code) to receive either brand-name or generic IV LEV. The primary outcomes were seizure control and the number of seizure exacerbations during the 24 h after drug administration, while the secondary outcomes were electroencephalographic (EEG) findings, serious adverse events, and clinical outcome at hospital discharge. Results Forty patients were randomly assigned administration with either brand-name IV LEV (10 SE and 10 ARCS patients) or generic IV LEV; 7 SE and 13 ARCS patients). There was no significant difference in patients’ baseline characteristics. The seizure control rate was 75% in the brand-name IV LEV group and 65% in the generic IV LEV group (p value: 0.490). Five (25%) patients in the brand-name IV LEV group, and six (30%) patients in the generic IV LEV group developed seizure exacerbations within 24 h after drug administration (p value 0.723). There were no reports of drug-related adverse events. Two of the patients taking brand-name IV LEV and one taking the generic IV LEV died (p value > 0.999). Conclusion Treatment with the generic IV LEV had comparable outcomes with brand-name IV LEV. The generic IV LEV may be an alternative medication for the treatment of SE and ARCS to reduce treatment costs. Trial Registration TCTR20190513001. Funding Great Eastern Drug Company.
... Before registration, as with all medicines, including original medicines, a generic medicine must pass a rigorous registration process and stringent requirements to ensure its quality, safety and efficacy, and it must meet all the required standards (Wonga et al., 2014). According to Kardas and Lewek (2010), generic medications are produced under the license of the original medicine manufacturers. This implies that there should be similarity with original medicines so that the quality, safety and efficacy of the generic medicine are not compromised. ...
... Despite the bioequivalence of generic medicines, they are estimated to be between 10 and 90% cheaper than the original medicines in many countries (Fraeyman et al., 2015;Dylst et al., 2013;Zeng, 2013;Bera and Mukherjee, 2012;Kardas and Lewek, 2010). They are cheaper because their preproduction does not involve research and development costs, as is the case with original medicine (Ahire et al., 2013). ...
Full-text available
Purpose – Cheaper generic anti-retroviral medicines are encouraged and often prescribed in South Africa for HIV/AIDS treatment. However, the medicines’ acceptance rate is relatively low. This has been attributed to inadequate brand knowledge of the bioequivalence of generic medicines. Studies have examined how brand knowledge structure lead to purchase. The contributions of brand relationship builders (i.e., trust and satisfaction), which are indicators of sustainable purchase are rarely considered. This study adapted Esch, Langner, Schmitt and Geus’ (2006) brand knowledge structure and relationship model to examine the impact of South African young adults’ brand knowledge structure (brand awareness, brand image and brand beliefs) and trust on brand satisfaction and purchase. Design/methodology/approach – Cross-sectional data was quantitatively collected from 207 young adults through self-administered, paper-based questionnaires. Data was analysed with structural equation modelling. Findings – Brand awareness, image, trust and belief in efficacy positively influenced purchase. All these factors, except brand awareness, positively led to satisfaction. The tested adapted model explained 53.0% and 58.5% variances of purchase and brand satisfaction respectively. Practical implications – Considering how much brand knowledge structure and trust explained purchase and satisfaction from the tested model, South African government, pharmaceutical marketers and consumer interest groups should educate young adults about the bioequivalence, safety and efficacy of generic medicines. With greater knowledge of these qualities, satisfaction is gained from purchase decision. Originality/value – Instead of the usual examination of demographic differences in generic medicine beliefs and perception, this study contributes by revealing brand-related drivers of purchase and satisfaction. Keywords – Generic medicine; brand knowledge structure; brand trust; brand satisfaction; purchase decision; South African young adults
... But the fact that generic drugs need not have to go through the large and costly clinical trials that are required for approval of innovator medicines, ultimately leading to lower price of generics, may raise doubt about their efficacy, safety, and quality. 19 But in this study, majority of physicians were found to be comfortable with the efficacy and safety of generic medications in spite of knowing that generic drug manufacturer need not repeat the preclinical and clinical studies required for originator medicines. As a matter of fact there are no ample proofs that generic drugs are less safe or less effective than their brand-name counterparts. ...
... The regulatory body appraises the manufacturer's compliance to the GMP guidelines before the drug is marketed, and the manufacturer need to give detailed information about the facilities it uses for production, packaging, labelling, among others, of the generic drug. 19,20 In this study, majority of doctors did not agree that generic drugs are made in substandard manufacturing facility. Majority of the doctors were found to have a greater trust in generic drugs and they prescribed them to a greater degree. ...
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Background: The assessment of doctors’ perceptions and understanding about generic medicines may help in recognizing the key areas which may act as hurdle to mass scale use of generics. The primary objective of this study was to explore the knowledge, attitude, and practice (KAP) of doctors toward generic medicines.Methods: A cross-sectional study was carried out using a pretested questionnaire in a tertiary care teaching hospital of Jammu (J and K). The questionnaire was designed to assess the KAP about generic medicines. The doctors working in this institute during the study period were included. Data was compiled and analysed using online website, P-values of < 0.05 were considered to indicate statistical significance.Results: A 62.9% doctors agreed to the fact that generic medicines were intended to be interchangeable with a branded drug (p=0.0139). Among the doctors, 77.5% were aware that generic drug manufacturers need to conduct studies to show bioequivalence between the generic medicine and their branded counterparts (p =0.0001). 88.8% of the doctors agreed that importance of generic medicines should be taught in early part of internship. 80.9% doctors did not think that switching a patient from a brand-name to generic drug may change the outcome of the therapy (p <0.0001).Conclusion: The present study showed that a good percentage of doctors were well aware of generic medicines’ usage. However due to concerns expressed by a certain fraction of participants, further work is needed on how interventions for medical professionals and for the public can lead to increase in the awareness and acceptability of generic medicines.
... In such a case, at least a partial solution of this problem could be provided by a wider use of generic drugs. Current evidence supports this point, proving that more expensive drugs might be safely replaced by their more affordable generic equivalents [5]. ...
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High medication costs are one of the major barriers to patient adherence. Medication affordability might be improved by generic substitution. The aim of this study was to assess the effectiveness of the implementation of generic substitution mechanisms in Poland. This was a retrospective analysis of nationwide real-world big data corresponding to dispensation of metformin preparations in 2019 in Poland. Relevant prescription and dispensation data were compared to assess the prevalence of generic substitution and its economic consequences. Among the 1,135,863 e-prescriptions analysed, a generic substitution was found in only 4.81% of the packs dispensed, based on e-prescriptions issued for metformin under its originator version and 2.73% under generic drugs. It is estimated that if these values were applied to the total Polish drug market, patients could lose the opportunity to lower their co-payment by 15.91% and the national payer to reduce its reimbursement expenditures by 8.31%. Our results point at the suboptimal implementation of generic substitution in Poland. Therefore, relevant actions need to be taken in order to maximise the benefits provided by this mechanism. It could not only lead to the win-win scenario in which both patients and the national payer are secured substantial savings, but it could also have a positive impact on patient adherence.
Generic medications are drugs that are manufactured to be as alternatives for already marketed brand medications. Their use has been emphasized by governments focused on the economic advantages and several policies have been established among countries to increase their use. Simultaneously, there is increasing debate and discussion regarding the equivalence, quality and safety of generic medicines. The aim of this review is to provide some evidence on the quality of generic medications and to report healthcare and patient perspectives on these medications. Overall, the reviewed studies showed either comparable effectiveness or adverse effects associated with generic medicines. Studies that reported perceptions about generic medications from either healthcare professionals’ or patients’ perspectives showed different views and perceptions about the quality and safety of generic medications, where they mainly favor brand medications over generic medications due to the negative perceptions on generic medications quality and safety. A key aspect in enhancing knowledge and confidence towards generic medications is the implementation of educational programmes and awareness campaigns for both healthcare professionals and patients.
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Objectives: The study aim was to explore the knowledge, perceptions, and attitudes of Iraqi physicians regarding generic and locally manufactured medicines. Methods: A total of 124 physicians were involved in this cross -sectional study. The convenience sample was collected from five public hospitals in Baghdad. A self-administered questionnaire was distributed and collected in-person. Fisher's Exact Test was used to measure the association between physician years of experience, gender and categorical (perception and knowledge) variables. Results: Most respondent answers regarding the knowledge of generic medicines were incorrect. Only up to one-third of the participants knew that generic medicines are therapeutically equivalent to brand name medicines (26.6%), as safe as brand name medicines (34.7%) and required to meet similar safety standards as brand name medicines (12.1%). With respect to perception, many physicians had negative perceptions about generic medicines such as viewing generic medicines as lower quality (57.3%) and cause more side effects (41.1%) compared to brand name medicines. Regarding physician attitudes toward generic medicines, about two-thirds (64.5%) of the physicians were willing to prescribe low cost medicines; however, only about half (51.6%) of the physicians reported they offer generic medicines to their patients. Finally, 64.5% of the participants were not comfortable with pharmacist replacing prescribed brand with generic medicines. Conclusions: In general, Iraqi physicians have negative perceptions and attitudes about generic and locally manufactured medicines. Significant gaps were identified in the knowledge and perceptions among physicians regarding generic medicines especially in relation to efficacy and safety of generic medicines. Article Type: Original Research
Technical Report
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Non-partisan analysis of the medical effectiveness, cost and utilization, and public health impacts of insurance coverage for Drug Utilization Management Exceptions
Technical Report
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Non-partisan analysis of the medical effectiveness, cost and utilization, and public health impacts of insurance coverage for HIV Specialists
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Background: The wrong prescription pattern on NSAIDs also often results in side effects and drug interactions that cause serious and detrimental drug reactions. Drug use research is needed to describe the pattern of drug use, early signs of rational drug use, interventions to improve drug use, cycles of quality control, and continuous quality improvement. Aim: This study aimed to determine the prescribing pattern of NSAIDs at outpatient Pediatric Poly at Universitas Sumatera Utara Hospital, Medan, Indonesia in 2017. Methods: This descriptive retrospective study was conducted from October to November 2016 with data from July and August 2017. Result: The study showed, outpatient of pediatric poly at Universitas Sumatera Utara Hospital in Medan there were 45,000 prescriptions, and 62 (0.15%) prescriptions contained NSAIDs. The most frequently prescribed NSAIDs 53 (85.48%) of prescriptions for outpatient pediatric poly was paracetamol. The most use of NSAIDs was consumed by a female in the age group of 3 years-12 years was 35 (58.06%). The highest frequency of NSAIDs utilisation was 7 days with 25 prescriptions (40.32%). There were 17 (27.42%) prescriptions with inappropriate dose, and the most widely prescribed dosage form was syrup for 34 (54.83%) prescriptions. The most duration of treatment with NSAIDs drugs which is paracetamol reached up to seven-days 25 (40.32%). The most frequently prescribed drugs 57 (91.93%) were generic drugs. Conclusion: It can be concluded that there are still inappropriate doses and frequency of NSAIDs utilisation.
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To demonstrate that current regulatory requirements for bioequivalence (BE) do not always reflect therapeutic equivalence. To investigate the potential usefulness of an additional metric, the partial AUC. Pharmacokinetic information was reviewed and evaluated on the pharmacokinetics of modified-release methylphenidate and nifedipine products. In studies of modified-release products of methylphenidate as well as of nifedipine, traditional regulatory criteria found two formulations to be bioequivalent even though their concentration profiles strongly diverged during the period of absorption. An additional metric, partial AUC, discriminated strongly between the concentrations of the drug products. The current regulatory criteria for the acceptance of BE do not always reflect the therapeutic equivalence of modified-release drug products. With some modified-release products, the application of an additional metric, the partial AUC, yields an improved discriminatory representation.
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To assess whether lower copayments charged for generic drugs explain the improved drug adherence associated with use of generics. We analyzed 2001-2004 healthcare claims data from 45 large employers. Study subjects were age > or = 18 years, had 1 or more of 5 study conditions (hypercholesterolemia, hypertension, hypothyroidism, seizure disorders, type 2 diabetes), and new use of generic-only or brand-only drug therapy for that condition. We measured adherence as the medication possession ratio (MPR), and adequate adherence as MPR > or = 80%. Logistic regressions were conducted to assess adequate adherence, adjusting for copayments. We identified 327,629 new users of drug therapy. The proportion starting generic therapies ranged from 9% (hypothyroidism) to 45% (hypertension). After 1 year, 66.2% of individuals with hypothyroidism achieved an MPR > or = 80% compared with 53.4% with hypertension, 53.2% with hypercholesterolemia, 52.0% with diabetes, and 42.2% with seizure disorders. Generics were associated with greater adherence than brands in patients with hypercholesterolemia or diabetes (P <.05). Lower adherence was seen in patients with hypertension or hypothyroidism (P <.05). There was no difference in seizure disorders. The likelihood of achieving an MPR =80% with $0 copayments compared with $1 to $9 ranged from an adjusted odds ratio (AOR) of 1.32 for seizure disorders (95% confidence interval [CI] = 1.41, 1.43) to an AOR of 1.45 for hypothyroidism (95% CI = 1.43, 1.48). Generic prescribing was associated with modestly improved adherence in 2 of 5 study conditions. Copayments of $0 were associated with improved adherence across all conditions.
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Use of generic drugs, which are bioequivalent to brand-name drugs, can help contain prescription drug spending. However, there is concern among patients and physicians that brand-name drugs may be clinically superior to generic drugs. To summarize clinical evidence comparing generic and brand-name drugs used in cardiovascular disease and to assess the perspectives of editorialists on this issue. Systematic searches of peer-reviewed publications in MEDLINE, EMBASE, and International Pharmaceutical Abstracts from January 1984 to August 2008. Studies compared generic and brand-name cardiovascular drugs using clinical efficacy and safety end points. We separately identified editorials addressing generic substitution. We extracted variables related to the study design, setting, participants, clinical end points, and funding. Methodological quality of the trials was assessed by Jadad and Newcastle-Ottawa scores, and a meta-analysis was performed to determine an aggregate effect size. For editorials, we categorized authors' positions on generic substitution as negative, positive, or neutral. We identified 47 articles covering 9 subclasses of cardiovascular medications, of which 38 (81%) were randomized controlled trials (RCTs). Clinical equivalence was noted in 7 of 7 RCTs (100%) of beta-blockers, 10 of 11 RCTs (91%) of diuretics, 5 of 7 RCTs (71%) of calcium channel blockers, 3 of 3 RCTs (100%) of antiplatelet agents, 2 of 2 RCTs (100%) of statins, 1 of 1 RCT (100%) of angiotensin-converting enzyme inhibitors, and 1 of 1 RCT (100%) of alpha-blockers. Among narrow therapeutic index drugs, clinical equivalence was reported in 1 of 1 RCT (100%) of class 1 antiarrhythmic agents and 5 of 5 RCTs (100%) of warfarin. Aggregate effect size (n = 837) was -0.03 (95% confidence interval, -0.15 to 0.08), indicating no evidence of superiority of brand-name to generic drugs. Among 43 editorials, 23 (53%) expressed a negative view of generic drug substitution. Whereas evidence does not support the notion that brand-name drugs used in cardiovascular disease are superior to generic drugs, a substantial number of editorials counsel against the interchangeability of generic drugs.
A prospective multicentre randomised study of continued antiepileptic treatment vs slow withdrawal was conducted in 1013 patients who had been free of seizures for at least 2 years. Comparison of randomised and eligible, but nonrandomised, patients suggests the results should be applicable to a wider patient population. By 2 years after randomisation, 78% of patients in whom treatment was continued and 59% of those in whom it was withdrawn remained seizure free, but thereafter the differences between the two groups diminished. Non-compliance with continued treatment accounted for only a small proportion of the risk to the group continuing with treatment. The most important factors determining outcome were longer seizure-free periods (reducing the risk) and more than one antiepileptic drug and a history of tonic-clonic seizures (increasing the risk). Other factors (eg, history of neonatal seizures, specific electroencephalographic features) seemed to have smaller effects, but even in such a large study the confidence intervals for these observations were wide.
For economic reasons, the use of generic substitution is increasingly being supported by health authorities. Potentially, this may be problematic for drugs with a narrow therapeutic window if quality control and/or bioequivalence is not optimal. Many developing countries do not have the resources or expertise to carry out appropriate quality control resulting in widespread distribution of substandard or even counterfeit drugs. Even in countries where procedures are well regulated, substandard drugs reach the market from time to time. Interchangeability of drugs is determined by bioequivalence studies comparing the serum concentration versus time curves for the products following single dose administration to fasting volunteers in a randomised crossover design. A number of reports, largely anecdotal, of treatment failure or increased adverse events after switching brands has cast some doubts upon whether bioequivalence testing is sufficient in all cases. These reports have covered cardiovascular, respiratory, hormonal, psychotropic, anticonvulsant, anti-infective and anti-inflammatory drugs. Equivalence is particularly difficult to obtain with many sustained-release formulations. The WHO has initiated programs to prevent the distribution of substandard preparations and has drafted guidelines for testing bioequivalence based on internationally accepted reference products. Until such time as means can be provided — first, to enforce internationally accepted production standards, and second, to permit uniform testing of therapeutic agents — the safest clinical choice, particularly in countries where registration requirements and quality control are minimal, must remain the branded product.
Changing the salt form of a drug affects its clinical efficacy and safety. This article discusses the potential issues related to the use of different salts of drugs.
To survey physicians to determine whether potency and consistency issues with levothyroxine sodium (LT4) have been resolved and to assess current experience regarding safety of substituting LT4 products. Members of the American Association of Clinical Endocrinologists, American Thyroid Association, and The Endocrine Society collaborated to create a survey instrument that would effectively sample the clinical experience of their society members and frequent prescribers of LT4. More than 18,000 e-mailed requests for information were generated, and the Web sites of each society provided links to the data collection form. The survey provided an opportunity to collect clinical observations of adverse events or product availability problems from physicians caring for patients with thyroid disease who required use of contemporary LT4 preparations. After adjustment for known reasons for unstable results from thyroid function tests, 199 reports of adverse events associated with changes in thyrotropin values were further analyzed. One hundred seventy-seven reports (88.9%) were associated with a change in the source of LT4; no change was noted in 21 (10.6%). Details regarding the circumstances of the change were provided in 167 of the 177 reports (94.4%), The reporting physicians themselves or their office staff had changed the LT4 preparation in only 1 of the 167 cases (0.6%). The remainder of changes had been made by the patient's pharmacy, either with the physician's knowledge (in 13 of 167 cases [7.8%]) or without his/her knowledge (in 153 of 167 cases [91.6%]). Fifty-four of 199 cases (27.1%) described serious adverse events; 52 of these (96.3%) were associated with a substitution of one LT4 preparation for another. The clinical use of contemporary LT4 products continues to be associated with some adverse outcomes. A small number of reports were associated with continued use of the same LT4 products. The most frequently reported adverse outcomes were associated with the approved generic substitution of LT4 products, frequently without the prescribing physician's knowledge.
This article discusses the history and evolution of the process for generic drug evaluation and approval in the United States, with emphasis on locally acting dermatologic products. The requirements for in vivo bioequivalence (BE) testing and the statistical criteria for BE are discussed, and an example of a topical antifungal dermatologic product is used to demonstrate the BE determination for locally acting drugs. Other factors in the dispensing of prescription medications that are not within the Food and Drug Administration regulatory authority are also mentioned.