Review

Controversies in off-label prescriptions in dermatology: the

perspective of the patient, the physician, and the
pharmaceutical companies
ß a, MD, PhD
Katlein Franc , and Sergio Litewka, MD

Department of Dermatology & Cutaneous Abstract

Surgery, Institute for Bioethics & Health The term “off-label drug use” involves the prescription of medications for unapproved
Policy, University of Miami Miller School of
indications or in unapproved dosage, dosage form, or route of administration. Off-label
Medicine, Miami, FL, USA
medications are common in the management of dermatologic diseases. In the recent
Correspondence years, new indications for botulinum toxin, biologics, spironolactone, topical calcineurin,
Katlein Francßa, MD, PhD and topical vitamin D analogues emerged, and these drugs are being used off-label to treat
Department of Dermatology & Cutaneous a variety of conditions. The high cost and long time required for the approval discourage
Surgery
pharmaceutical companies from developing studies and pursuing the approval by
Institute for Bioethics & Health Policy
regulatory agencies. Patients and physicians may have a different perspective regarding
University of Miami Miller School of
Medicine the off-label use of medications. The ethical discussion is based on the different opinions
1400 NW 10th Avenue concerning the need for informed consent by the patient and how this could be applicable
Suite 912 in the clinical practice.
Miami, FL 33136
USA
E-mail: k.franca@med.miami.edu

Funding: None.
Conflicts of interest: None.

doi: 10.1111/ijd.14222

strategies for managing risks.4 The process of drug develop-

Introduction
The term “off-label drug use” involves the prescription of medi-
cations for unapproved indications or in unapproved dosage,
dosage form, or route of administration. Government drug regu-
latory agencies are responsible for confirming the efficacy and
safety of medications after performing rigorous evaluations of
preclinical and clinical studies.1 The US Food and Drug Admin-
istration (FDA) is the regulatory agency for all food and drugs
sold in the United States. This agency is also responsible for
the oversight of many other products such as cosmetics, dietary
supplements, vaccines, and biologics, among others.2 The Cen-
ter for Drug Evaluation and Research (CDER) is the main FDA
division responsible for the approval of drugs. The CDER is
responsible for evaluating over-the-counter and prescription
drugs, including biological therapeutics and generic drugs
before they can be marketed in the United States and ensures
their safety and efficacy and that the health benefits outweigh
the known risks.3 The drug approval process takes place within
a structured framework that includes three main steps: analysis
of the target condition or illnesses and available treatments,
assessment of benefits and risks from clinical data, and
ment, from initial development through final market approval,
requires 10 years on average.2 Since the FDA does not regu-
late the practice of medicine, an off-label prescription is gener-
ally legal unless it violates ethical guidelines. Off-label
prescriptions in dermatology empower and give options to
physicians allowing them to innovate within the scope of their
clinical practice and may be particularly useful for patients not
responding to standard treatments.5 On the other hand, the
inappropriate use of off-label drugs raises significant concerns
about safety. To limit liability, physicians are advised to pre-
scribe medications that have a well-accepted therapeutic value
in the medical community, proven efficacy from results of clini-
cal trials, and only for indications that they believe are in the
best interest of the patient.6,7
Off-label prescriptions: clinical research vs.
medical treatment
When a new drug is approved and becomes available on the
market, all the information about it is based on pre-marketing
studies. Preclinical studies start with the development of the
1

ª 2018 The International Society of Dermatology International Journal of Dermatology 2018

2 Review Controversies in off-label prescriptions in dermatology
molecule, followed by experimental studies in animals to identify
its effects and toxicity. If no unacceptable toxic effects are
observed, the first clinical trials in humans are conducted.
These are named phase I, II, and III studies. They investigate
aspects of the pharmacokinetics, toxicity, safety, and efficacy in
humans.8 All clinical trials should follow ethical guidelines,
requiring the approval of the institutional ethics committee and
written informed consent from the participants of the study.9
Drawing a clear line of demarcation between drugs used in
research vs. medical treatment can be challenging. The general
idea is that when a product is used to treat a patient, it is con-
sidered therapy and when it is used to conduct a clinical trial, it
is medical research. However, it is not always clear when an
off-label medication is being used for experimental research or
not.5 A common mistake belief among patients is that when a
physician prescribes an off-label medication, he is conducting
experimental research on the patient. Riley et al. suggest that
the most basic test for whether an off-label use qualifies as
experimental research is to focus on the physician’s motivations
and goals in prescribing that medication for off-label use. The
National Commission for the Protection of Human Subjects of
Biomedical and Behavioral Research explains: “The distinction
between research and practice is blurred partly because both
often occur together (as in research designed to evaluate a
therapy) and partly because notable departures from standard
practice are often called ‘experimental’ when the terms ‘experi-
mental’ and ‘research’ are not carefully defined.”6,10
International perspective: regulations and
frequency of off-label prescriptions in
different countries
Off-label prescriptions occur in all medical specialties, but they
may be more common in areas of medicine in which the patient
population is less likely to participate in clinical trials, for exam-
ple psychiatric, pediatric, geriatric, oncology, and pregnant
patients, or in rapidly evolving medical specialties like dermatol-
ogy, considering the need to repurpose existing therapies for
cutaneous conditions, given the broad variety of pathophysio-
logic processes affecting the skin and long time to approve new
drugs.5,7 It is estimated that 21% of the prescriptions in the Uni-
ted States are off-label. Radley et al. analyzed nationally repre-
sentative data from the 2001 IMS Health National Disease and
Therapeutic Index (NDTI) to define prescribing patterns by diag-
nosis for 160 commonly prescribed drugs and found that off-
label use was most common among cardiac medications (46%,
excluding antihyperlipidemic and antihypertensive agents) and
anticonvulsants (46%), whereas gabapentin (83%) and
amitriptyline hydrochloride (81%) had the greatest proportion of
off-label use among specific medications. The authors found
that 73% of off-label mentions had little or no scientific sup-
port.11 In France, in 2012, a scandal involving the prescription
of Mediator (benfluorex) – a fenfluramine derivative approved
International Journal of Dermatology 2018
Francß a and Litewka
for the treatment of diabetes but prescribed for weight loss,
caused fatal valvular heart disease in some patients and led to
a controversial discussion and changes in the regulatory sys-
tem. A law that aimed at strengthening of the safety of medici-
nes and healthcare products and a related decree regarding
“Temporary Recommendations for Use” filled part of the gap,
providing France with a regulatory process for temporarily
supervising the off-label prescribing drugs. Emmerich et al.
explained, “The intention of the French law and the TRU decree
is to open a relatively long observation window to assess the
benefits and risks of a marketed drug for an unlicensed indica-
tion and to collect scientific information to ensure its safe use. A
TRU is granted for a maximum of 3 years, a window that should
permit the manufacturer to expand its marketing authorization
through the usual procedures.”12 Pediatric patients in France
are one of the groups most exposed to off-label medications. A
study involving 2,313 pediatric patients showed that 1960 were
exposed to ≥1 prescribed drug. Among children with prescrip-
tions, 37.6% were exposed to ≥1 off-label prescription and 6.7%
to ≥1 unlicensed drug. Off-label prescribing involved an unap-
proved indication in 56.4% of cases, a lower dosage (26.5%) or
higher dosage (19.5%) than specified, age not labeled (7.2%),
incorrect route of administration (3.5%), and contraindication
(0.3%). This study highlighted the high prevalence of off-label
prescriptions among pediatric patients in that country despite
the innumerous initiatives toward the promotion of rational use
of medications in children.13 Picard et al. performed a study to
access off-label prescribing in dermatology in France. The
authors found that 86% of the prescriptions were labeled and
14% were off-label. The most frequent indications for off-label
prescriptions were inflammatory and hypersensitivity dermato-
sis. Topical corticosteroids and methotrexate were the most pre-
scribed off-label medications. The authors also found that 70%
of these off-label prescriptions were not based on strong data
from evidence-based medicine.14 In Portugal, in 2014, an
administrative guideline from the Portuguese Health’s Direction
(DGS) recommended a written informed consent for all off-label
prescriptions. Portuguese health authorities consider it neces-
sary to inform the patient on the particular therapy, its potential
risks and benefits, and the reasons that led the physician to
prescribe an off-label medication and not an approved one. All
information should be comprehensibly noted in the patient’s
records to ensure protection for the patient and the physician.
The challenge remains on adjusting this demand with the elec-
tronic medical records and with mechanisms like the Por-
tuguese Health Data Platform, which is a Personal Electronic
Health record, a National Electronic Mechanism to share data
from federated systems, and a basis for innovation in eHealth in
Portugal.15,16 Just like in other countries, the use of off-label
medications among the pediatric population is a common prac-
tice. Silva et al. analyzed 1,011 prescriptions in neonatology of
84 active substances, made in 218 hospital admissions. The
authors found that in 42.9% of the cases, medicines were used
ª 2018 The International Society of Dermatology
Francß a and Litewka
according to the Summary of Product Characteristics informa-
tion; 27.9% of drugs were approved for neonatal period but
used in an off-label manner; off-label drugs for neonates were
used in 10.1%, whereas those with undetermined approval state
and contraindicated were used 6.0 and 8.7% of the cases,
respectively, and unlicensed prescriptions accounted for 4.4%
of total.17 Another study including patients aged from 4 days to
18 years assisted in a Portuguese pediatric emergency unit
found that of the 724 medicines prescribed, 32.2% were off-
label. At least one drug was used off-label in 28.1% of the stud-
ied population, corresponding to 46.1% of the 427 children that
received prescriptions. “Alteration in dosage” was the common-
est reason for off-label prescribing (28.2%).18 Among the many
dermatology diseases, the off-label prescriptions in pediatric
psoriasis have been widely discussed by dermatologists in Por-
tugal. Psoriasis is a chronic inflammatory systemic disease that
causes important physical and physiological burden. One-third
of the cases have their onset during the pediatric age, although
some of them may not be diagnosed until the patient reaches
adulthood. The correct diagnosis and treatment during child-
hood can delay and prevent comorbidities. Most of the treat-
ments prescribed to these patients are off-label and based on
therapies only approved for adults. Reivas et al. highlighted,
“Because children are not just ‘small adults’, specific guidelines
for the diagnosis, management, and treatment of psoriasis are
of extreme importance.”19
In Germany, off-label prescriptions can cause financial
responsibilities for the physician. Insurance companies tend to
accept off-label prescriptions only in cases of severe, potentially
life-threatening diseases. Seidenschnur et al. explain that to
avoid reimbursement claims following the prescription of off-
label medications, physicians in Germany should – on a case-
by-case basis – file an application for cost coverage with the
competent health insurance before treatment initiation. These
authors performed a chart review for cost coverage requests
submitted by two outpatient clinics at a university-affiliated der-
matology department between 2010 and 2012 and found that in
the majority of cases (56.8% of applications were approved dur-
ing the first round), health insurers in Germany have agreed to
reimburse the costs of proposed off-label therapies.20
In Brazil, the regulatory agency responsible for the approval
of medications is ANVISA (Age ^ncia Nacional de Vigila ^ncia
ria). In general terms, ANVISA follows the same proce-
Sanita
dures of FDA to approve a drug.21 However, the approval of a
medication in Brazil can take longer since some medications
are first approved in the USA and only later the registration for
approval is requested in Brazil. It is also possible that a medica-
tion could receive the approval by another regulatory agency
based only on preliminary studies or incomplete studies, and
this is not acceptable by ANVISA.22 Brazilian healthcare institu-
tions have created pharmacology committees to evaluate the
~o Paulo, the Health
off-label use of drugs. In the State of Sa
Surveillance Center acts as a pharmacovigilance institution and
ª 2018 The International Society of Dermatology
Controversies in off-label prescriptions in dermatology Review 3
publishes “Therapeutic Alerts” on pharmacovigilance in the
official journal. The goal is to alert following adverse reactions
from the off-label use of drugs. These public measures to
restrict off-label prescriptions are more common in the control
of the incentives and the dissemination of information to the
medical community.8,22 Just like in the US, the regulatory agen-
cies cannot restrict off-label prescriptions beyond educational
campaigns and have no jurisdiction on the practice of medicine.
Brazilian legislation on this subject still lacks greater investiga-
tion and subsequent measures. In Brazil, off-label prescription
in pediatrics is also a frequent practice. A study involving pedi-
atric patients from southern Brazil showed that the frequency of
off-label medications prescribed was 31.7%. The highest preva-
lence was antihistamines and antiasthmatics (32.3% and
31.5%, respectively), and the main type of off-label prescription
was dose (38.8%), followed by age range (31.5%), and the fre-
quency of administration (29.3%). Regarding the dosage, over-
dose was more frequent (93.3%) than underdose (6.7%).23
Off-label prescriptions in dermatology
Off-label medications are common in the management of der-
matologic diseases. New therapeutic approaches for common
or rare dermatosis are continually being released, as well as
new indications for old drugs. Dermatologists are the medical
professionals qualified to diagnose and treat more than 3,000
different diseases. These multitudes of diagnosis, the need for
therapeutic options, and the long time required by the regulatory
agencies to approve new medications make off-label prescrip-
tions for dermatologic diseases so common. These experiences
of off-label use, if analyzed within the context of a carefully
designed methodology, may provide scientific data that can
influence or even improve further concepts of therapy. However,
the blurred boundaries between what constitutes medical treat-
ment, that is, focused on the patient, or research (aimed to gen-
erate knowledge) represent a fertile ground for ethical and legal
controversies. A study that analyzed data from the 1990–1997
National Ambulatory Medical Care Survey, performed by the
National Center for Health Statistics, assessed medications pre-
scribed at office visits for dermatologic conditions. The authors
found that the range of off-label prescribing varied from 17 to
73%. The conditions most frequently treated with off-label pre-
scriptions were acne rosacea (73%) and actinic keratosis
(52%), whereas those with the fewest off-label prescriptions
were atopic dermatitis (17%) and psoriasis (16%). The use of
off-label prescriptions by dermatologists in the diseases studied
ranged from 7 to 73% whereas the range for non-dermatolo-
gists was 18 to 96%.24
Botulinum toxin
Botulinum toxin is a neurotoxin produced by the bacteria
Clostridium Botulinum. This substance has been widely used in
the dermatological practice. It acts by blocking the nerve signals
International Journal of Dermatology 2018
4 Review Controversies in off-label prescriptions in dermatology
that contract muscles resulting in temporary paralysis of the
muscles.25 It is approved by the FDA for facial esthetic treat-
ments (temporary reduction of crow’s feet, glabellar lines, and
moderate to severe forehead lines) and primary axillary hyper-
hidrosis.26 Botulinum toxin has been used off-label for the treat-
ment of many other dermatological conditions with variable
results.27 A review study published in the Journal of the Euro-
pean Academy of Dermatology showed growing evidence sup-
porting the use of botulinum toxin in non-cosmetic
dermatological disorders such as pruritic dermatosis (pom-
pholyx, idiopathic pruritus, lichen planus), acantholytic disorders
(Hailey-Hailey disease, Darier0 s disease), inflammatory der-
matosis (hidradenitis suppurativa, flexural psoriasis), scarring,
fissures and ulceration (anal fissures, Raynaud0 s disease and
ulcers), and painful disorders such as vulvodynia and cutaneous
leiomyomas.28 The treatment of keloids and hypertrophic scars,
alopecia, facial erythema and flushing, oily skin, Raynaud phe-
nomenon, chromhidrosis and bromhidrosis, and postherpetic
neuralgia with botulinum toxin are also under investigation.29 In
psychodermatology, botulinum toxin has been used for the com-
plementary treatment of depression with positive results.30 This
potent drug is being used for several off-label indications of
interest for dermatologists. However, further clinical trials are
still needed to better understand the efficacy and safety of
these new indications and to standardize dose protocols.29
Biologics
Biologics or biologic drugs are a protein-based drug derived
from living cells cultured in a laboratory. Biologics have been
used in medicine for more than 100 years, but in the 21st
century, new agents had a remarkable impact on the fields
of dermatology, rheumatology, and gastroenterology. These
drugs target specific parts of the immune system and are
different from traditional treatments that affect the entire
immune system.31 Biologic drugs have revolutionized the
treatment of patients with psoriasis. The biologic agents
approved by the Food and Drug Administration for psoriasis
and psoriatic arthritis include adalimumab, etanercept, inflix-
imab, ustekinumab, and secukinumab. There are several
reports of off-label uses of these drugs for vasculitis such as
polyarteritis nodosa, giant cell arteritis, granulomatosis with
polyangiitis, and Behcet disease, for eczema such as atopic
dermatitis and dyshidrotic eczema, and for inflammatory
conditions such as hidradenitis suppurativa, pityriasis rubra
pilaris, lichen planus, graft-versus-host disease, erythema
annulare centrifugum, toxic epidermal necrolysis, acne
vulgaris, SAPHO (synovitis, acne, pustulosis, hyperostosis,
and osteitis) syndrome, alopecia areata, aphthous stomatitis,
primary amyloidosis, pruritus, keloid, wound healing, and
pityriasis lichenoides chronica.32 Biologics may be regarded
as a tool for the treatment of several dermatologic condi-
tions, although new clinical trials are needed to better
assess their efficacy and safety.
International Journal of Dermatology 2018
Francß a and Litewka
Spironolactone
Spironolactone is a potassium-sparing diuretic that has been
used since 1954 for the treatment of hyperaldosteronism.33
Other indications include heart failure, primary hyperaldostero-
nism, cirrhosis of the liver accompanied by edema and ascites,
and nephrotic syndrome. The anti-androgenic activity of
spironolactone discovered in 1969 led to the future uses in der-
matology. Nowadays spironolactone is used in dermatology, off-
label, to manage androgen-dependent conditions like adult
female acne, female pattern hair loss, hidradenitis suppurativa,
and hirsutism.7,34 This medication is considered a useful tool in
the dermatologic treatment armamentarium; however, further
studies are necessary to establish the safety, efficacy, and new
indications for the treatment of dermatologic diseases.34
Topical calcineurin inhibitors
Topical calcineurin inhibitors act by inhibiting synthesis of proin-
flammatory cytokines. The only FDA approved indication is for
the treatment of atopic dermatitis in patients 2 years old or
older. It can be used as an alternative therapy to corticosteroids
without the side effects commonly associated with the use of
steroids. Topical calcineurin inhibitors have been investigated
for the off-label treatment of allergic contact dermatitis, psoria-
sis, lichen planus, vitiligo, rosacea, and seborrheic dermatitis.
Although it only received regulatory approval for one indication,
this medication has shown promise in the off-label treatment of
other skin conditions.35
Topical vitamin D analogues
Topical vitamin D analogues are approved by the FDA for the
treatment of psoriasis but are also used off-label in the treat-
ment of a variety of cutaneous disorders despite a lack of scien-
tific evidence of efficacy. A systematic review involving 165
articles showed a moderate to strong recommendation for the
use of topical vitamin D analogues in combination with corticos-
teroids and phototherapy in vitiligo and as monotherapy for
ichthyoses, morphea, pityriasis alba, prurigo nodularis, and
polymorphous light eruption. It may be ineffective in the treat-
ment of actinic keratosis, seborrheic keratosis, lichen planus,
seborrheic dermatitis, alopecia areata, chemotherapy-induced
alopecia, and hypertrophic scars.36
Ethical discussion: patient, physician, and
industry perspectives
The patient perspective
Patients who are receiving off-label medications are not always
informed that they are a part of an experimental treatment.
Some off-label uses can be beneficial, mainly when therapeutic
options are restricted and when the patient is facing an orphan
disease where sometimes it can be the only available treat-
ment.1,37 However, in order to be morally acceptable, off-label
indications should be supported by well-formulated hypotheses
ª 2018 The International Society of Dermatology
Francß a and Litewka
and not merely by curiosity or baseless experimentation. Even
considering the uncertainty of innovative therapeutic options,
the lack of an adequate study design might expose the patients
to disproportionate risks.
Another topic to be considered is the patient’s right to be
informed about his participation that is, eventually, an experi-
mental one. The prescription of off-label medications without full
disclosure by the physician raises many complex ethical and
legal concerns.38
Wilkes and Johns propose that the doctrine of informed con-
sent should be rigorously applied to require doctors to disclose
to the patients when they are prescribing a drug off-label. These
authors argue, “The same process of the informed consent
required before enrolling a patient in a research study should
be applied when a drug is being prescribed off-label as each
such prescription is just like a mini research study.” This would
be a way of respecting the patient’s autonomy and encouraging
them to share in decision making in situations of medical uncer-
tainty.39 Shared decision making is one the most important
aspects of the contemporaneous medical practice and requires
that both the physician and patient share information and work
together to decide on the best treatment plan. Clearly, withhold-
ing the intent to prescribe an off-label drug fails to honor this
approach to the patient-physician relationship.40
In the context of off-label prescriptions, from a moral stand-
point, it must be considered that “a valid, yet ignorant consent
is enough permission for therapy but not for experimentation.”41
Two other issues generate ethical tensions: therapeutic mis-
conceptions and the possibility of undisclosed conflicts of
interests.
Therapeutic misconception occurs when individuals mistak-
enly believe that the aim of the treatment is to directly benefit
them, while, in fact, they are subjects in an experimental
protocol.42
The use of off-label prescription is particularly challenging
since is not totally experimental (although the treatment out-
comes may be published as if it were research and, eventually,
these studies may be submitted to the regulatory agency for
approval) but may be presented to the patient as some sort of
“innovative therapy.”
The physician perspective
Off-label prescriptions are considered legal, and physicians
have the freedom to prescribe any approved drug for any other
indication, regardless of the fact that the indication is not
approved by regulatory agencies.43 Physicians tend to prescribe
off-label drugs when the standard treatments are non-existent
or fail. Some drugs take time to be approved by regulatory
agencies. While the drug is going through the approval process,
a new indication can be discovered by an independent scientist.
Even before the approval, high impact factor journals already
publish scientific evidence about a new use of a particular drug.
Physicians have the option and freedom to use these new
ª 2018 The International Society of Dermatology
Controversies in off-label prescriptions in dermatology Review 5
therapeutic options based on the latest scientific evidence,
although there is lack of evaluation of efficacy and safety of
these drugs.1 The ethical controversy lies on whether the physi-
cian should disclose to the patient that he is prescribing an off-
label drug or not. Wittich et al. explained that there are two
arguments used by those who are against the disclosure. The
first one that “disclosure may unduly frighten patients” and sec-
ond that “the extensive burden placed on physicians to con-
stantly review and communicate medication risk and benefit
information may divert attention away from other more important
patient care issues.”5 Meadows and Hollowell argued that “the
doctor’s decision to inform the patient of the ‘off-label’ status of
the prescription is not relevant to the physician’s standard of
care for an informed consent case, and the doctor’s duty is to
practice medicine and treat his patient, not inform the patient of
the FDA’s non-medically related labeling. Therefore, doctors
should not be branded with the additional duty of disclosing
non-pertinent information, such as the FDA’s medically irrele-
vant distinction, to their patients.”44 The majority of dermatolo-
gists prescribe off-label medications without informing their
patients that the drug was not approved for that indication. This
can be considered an unethical practice that violates patients’
right to information. Considering that physicians are legally
bound to inform patients of risks and the fact that there is a lack
of research for off-label medications, this practice should be
considered a risk to the patient, and it could be argued that the
physician who withholds this information is violating the ethical
duty to secure the patient’s informed consent and autonomy.40
The presence of possible undisclosed conflicts of interest by
the physician adds another layer of complexity that must be
taken in consideration. Conflict of interest, by definition is a “set
of circumstances that creates a risk that the professional judg-
ment or actions regarding a primary interest will be unduly influ-
enced by a secondary interest.”45
For the physician, the “primary interest” is the patient, and for
the researcher, it might be the generation of knowledge. These
competing interests are intangible, therefore difficult to assess.
However, financial conflicts of interest are a more concrete
possibility. Is the physician experimenting with different doses
or indications based on previous clinical experiences? Or is he
acting as an agent of the industry, carrying out a protocol that
is being tested in different sites by different medical providers?
If the latter is the case, then it should be disclosed to the
patient and informed consent must be sought.
The pharmaceutical company perspective
Upon the discovery and development of a drug, it may be found
that this drug could be useful for the treatment of different dis-
eases. However, pharmaceutical companies usually select few
or the most important indications to develop further research.1
The cost of the process of getting a drug approved by a regula-
tory agency is high, and there is an increase in the number of
patients and time required to complete the clinical trials.37
International Journal of Dermatology 2018
6 Review Controversies in off-label prescriptions in dermatology
These are decisive factors on the number of indications that the
industry will select for further evaluation. The same challenging
process is faced when the pharmaceutical company wants to
get approval for new uses of old medications. Gupta et al.
explain “From a business point of view, to seek supplemental
approval for new uses late in a drug’s patent life is not very
enticing for pharmaceutical companies. The developmental cost
of new uses of an old drug might exceed the benefit of regula-
tory approval.”1 These are discouraging factors to pharmaceuti-
cal companies to conduct well-controlled clinical studies.46 Still,
off-label medications sell worth many billion dollars resulting in
huge revenue.1
Conclusion
In recent years, new indications for botulinum toxin, biologics,
spironolactone, topical calcineurin, and topical vitamin D ana-
logues emerged, and these drugs are being used off-label to
treat a variety of conditions. Off-label prescriptions can be bene-
ficial to patients, allowing them to receive new therapeutic
options. However, the safety and efficacy of these drugs are
not confirmed by the regulatory agencies, and patients may be
exposed to unrestricted experimentation and to an ineffective or
risky medication. The high cost and long time required for
approval discourage pharmaceutical companies from developing
studies and pursuing the approval by regulatory agencies.
Patients and physicians may have a different perspective
regarding the off-label use of medications. The ethical discus-
sion is based on the different opinions concerning the need for
informed consent by the patient and how this could be applica-
ble in the clinical practice. While there is no consensus on this
subject, physicians are advised to prescribe medications that
have a well-accepted therapeutic value in the medical commu-
nity and only for indications that they believe are in the best
interest of the patient.
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