Off-label drug use involves prescribing approved medications for indications, dosages, or patient populations that are different than what is specified in the drug's approved labeling. It occurs commonly where patients have been excluded from clinical trials. While it can provide early access to potentially valuable treatments, it also increases risks like adverse drug reactions. Regulatory guidelines on off-label use vary globally, and in India, off-label prescribing was previously illegal but amendments may have changed that. Drug repositioning, where existing drugs are tested for new uses, can be an efficient alternative to traditional drug development by building on existing safety data. Physicians are encouraged to base off-label prescribing decisions on credible evidence alone.

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OFF LABEL USE :
An Overview
Dr.RENJU.RAVI MD
MUHS - MSc Pharmaceutical Medicine class

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Definitions and overlapping terms
Types of ‘off-label‘ use and examples
Consequences following ‘off-label’ use
Regulatory and legal aspects
Drug repositioning
Summary
OUTLINE
MUHS - MSc Pharmaceutical Medicine class

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Definitio
• the use of an authorised medicine by a
healthcare professional to treat a patient in a
way not covered by Marketing Authorisation
(MA) and detailed in the Summary of Product
Characteristics (SmPC) of the medicine
• prescribing currently available and marketed
medications but for an indication that has never
received regulatory approval
MUHS - MSc Pharmaceutical Medicine class

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• does not have a Marketing Authorisation (MA)
• It can only be used in clinical studies or for
compassionate use/expanded access setting
• involves a medicine that is licensed (has an MA)
• is a medicine used in a different way than authorised
• when using a different dosing regime; for a different
indication/disease;
• when it is used for a different population, for example, using it for
paediatric (children) use, when the medicine is only intended for
use in adults
Unlicensed
medicines
Off-label
use
Eg.
Unlicensed medicines versus Off-label use
MUHS - MSc Pharmaceutical Medicine class

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Medication
error-
treatment
process
related, not
intentional
Misuse, abuse -
may be intentio
nal or non-
intentional, ‘off–
label ‘use or
medication error
Compassionate
use(?)-
unauthorized
drug, intentional
Orphan
disease t
treatment-
intentional
Overlapping terms
MUHS - MSc Pharmaceutical Medicine class

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Propranolol for Performance Anxiety
Clomiphene for Male Infertility
Quetiapine for Insomnia
Memantine for OCD
Clonidine for ADHD
Sildenafil for Female Sexual Arousal Disorder
Prazosin for Nightmares
List of off-label uses for prescription
drugs
MUHS - MSc Pharmaceutical Medicine class

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Clinical indications associated with on-label
and off-label uses for top 14 drugs
https://med.stanford.edu/news/all-news/2008/11/14-drugs-identified-as-most-urgently-needing-study-
for-off-label-use-stanford-professor-says.html

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A medication may not have been studied and approved for a specific
population
A life-threatening condition may motivate a HPC to give any treatment
that is logical and available, whether approved or not
If the pathophysiology of 2 conditions are similar, a physician may use
a medication approved for 1 of these conditions for both
If one medication from a class of drugs has approval, physicians
commonly use other medications in the same class without specific
regulatory approval for that use for the same indication
Factors motivating Off-label drug use
MUHS - MSc Pharmaceutical Medicine class

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prescription and use may be of benefit for a specific patient
Outcome of ‘off- label’ use (outside of formal clinical trials)
are of interest including for pharmacovigilance
Permits innovation in clinical practice
Offers early access to potentially valuable medication
Treatment in “orphan” conditions
‘Off- label‘ use or prescription: a bad thing?
MUHS - MSc Pharmaceutical Medicine class

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Therapeutic advances
are more rapid
compared to clinical
trial and regulatory
approval process
Once patents have
expired, no financial
motivation for
pharmaceuticals to
conduct trials for new
indications
Potential new
indication might not
be commercially viable
for the industry
Why do drugs remain off label???
MUHS - MSc Pharmaceutical Medicine class

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• Drugs given at doses other than those stated in
approved product information
Based on dose
• Drugs prescribed outside approved age rangeBased on age
• Drugs administered by unapproved route of
administration
Based on route
• Drugs used for indications other those stated in
approved product information
Based on indications
• Preparations of suspensions from capsules or
tablet; Using an oral preparation as a topical
agent
Modification of registered
medication
Types
MUHS - MSc Pharmaceutical Medicine class

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Obtaining written consent may be appropriate in some cases
Documentation of the consent process is recommended and,
As the medicine is being used off-label, additional information about
any uncertainties should be given
A healthcare professional’s decision whether to prescribe a medicine
off-label or not should be guided by evidence based medicine and
the best interest and medical needs of patients
3/20/2018MUHS - MSc Pharmaceutical Medicine class
Patient consent

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MUHS - MSc Pharmaceutical Medicine class
Professional conduct – controlled by Professional Conduct, Etiquette and
Ethics Regulations, 2017, ICMRPrescription of drugs
- Should not violate Drugs and Cosmetics Act (steroids, psychotropic
and narcotic drugs)
- Should not violate human rights
- Should not violate ICMR guidelines for research
no mention regarding “off-label” use
Regulatory guideline in India regarding off-label use

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MUHS - MSc Pharmaceutical Medicine class
Govt. of India, 2004 →
committee under Indian
Medical Association to make
specific guidelines
governing off-label drug use
Strongly favored off-label use of
drugs (if evidence based)
Indian law does not currently allow drugs to
be prescribed for indications for which they
have not been approved
Amendments to the
Indian Medical Council
Act 2 years ago made
off-label prescribing
illegal
Marketing such drugs by
pharmaceutical company is
considered as contravention of the
law and action is taken under the
Drugs and Magic Remedies
(Objectionable Advertisements) Act,
1954
BUT
Regulatory guideline in India
regarding off-label use

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MUHS - MSc Pharmaceutical Medicine class
Bavdekar SB, Sadawarte PA, Gogtay
NJ, Jain SS, Jadhav S. Offlabel drug use
in a Pediatric Intensive Care Unit.
Indian J Pediatr. 2009
Nov;76(11):1113-8
• Out of 2237 prescriptions in children , 1579 (70.58%)
were off-label in nature
Kharadi D, Patel K, Rana D, Patel V.
Off-label drug use in Psychiatry
Outpatient Department: A Prospective
Study at a Tertiary Care Teaching
Hospital. Journal of Basic and Clinical
Pharmacy 6.2 (2015): 45–9
• Of 250 patients in psychiatry OPD, 198 (79.2%)
received at least one off-label drug
What Is the current status in India???

16. Pros Cons
Early access to potentially valuable
medicine / may become standard of care
Increases likelihood of ADR
Tailor and improve individual patient care Easiest way for industry to bypass
approval process and expand market
Only choice in palliative settings / orphan
status
Medicolegal concerns
Pediatrics, geriatrics and obstetrics Increases healthcare costs
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Pros and cons of off-label use of drugs
MUHS - MSc Pharmaceutical Medicine class

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MUHS - MSc Pharmaceutical Medicine class
Drug repositioning
• Drug repurposing, Drug reprofiling, Therapeutic
switching and Drug retasking
• It is the application of known drugs and compounds
to new indications (new diseases)
• Using drug repositioning, pharmaceutical companies
have achieved of number successes
• Example –Sildenafil in erectile dysfunction and
thalidomide in severe erythema nodosum leprosum

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MUHS - MSc Pharmaceutical Medicine class
Repositioned drug has already passed a
significant number of toxicity and other tests
Its safety is known
The risk of failure for reasons of adverse
toxicology are reduced
Advantage of drug repositioning over traditional
drug development

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MUHS - MSc Pharmaceutical Medicine class
Off-label drug
use involves
prescribing
medications for
an indication, or
using a dosage or
dosage form, that
has not been
approved by the
regulatory
approval
• Since the FDA
/DCGI does not
regulate the
practice of
medicine,
OLDU has
become
common
It occurs more
common in areas
in which the
patient population
is less likely to be
included in clinical
trials
Physicians should
prescribe
medications only
for indications - on
the basis of the
most credible
available evidence
Summary

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THANK YOU