off label use of drugs

1. OFF LABEL USE OF DRUGS
PRESENTED BY
DR. SAJEENA JOSE. C
DEPT OF PHARMACOLOGY
AMALA INSTITUTE OF MEDICAL SCIENCES,THRISSUR

2. DEFINITION
• 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

3. Unlicensed medicines versus Off-label use
Unlicensed
medicines
• does not have a Marketing Authorisation (MA) •
• It can only be used in clinical studies or for
compassionate use/expanded access setting
Off-label use • 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
Eg. indication/disease;
• when it is used for a different population, for
example, using it for paediatric (children) use,

4. List of off-label uses for prescription drugs
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

5. Clinical indications associated with on-label and off-label uses for top 14 drugs
Rank Drug (brand name) Most common on-label use Most common off-label use
1 Quetiapine (Seroquel) Schizophrenia Bipolar, maintenance
2 Warfarin (Coumadin) Atrial fibrillation Hypertensive heart disease
3 Escitalopram (Lexapro) Depression Bipolar
4 Risperidone (Risperdal) Schizophrenia Bipolar, maintenance
5 Montelukast (Singulair) Asthma COPD
6 Bupropion (Wellbutrin) Depression Bipolar
7 Sertraline (Zoloft) Depression Bipolar
8 Venlafaxine (Effexor) Depression Bipolar
9 Celecoxib (Celebrex) Joint sprain/strain Fibromatosis
10 Lisinopril (Prinivil, Zestril) Hypertension Coronary artery disease
11 Duloxetine (Cymbalta) Depression Anxiety
12 Trazodone (Desyrel) Depression Sleep disturbance
13 Olanzapine (Zyprexa) Schizophrenia Depression
14 Epoetin alfa (Procrit, Epogen) Chronic renal failure Anemia of chronic disease

6. Factors motivating Off-label drug use
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

7. ‘Off- label‘ use or prescription: a bad thing?
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

8. Why do drugs remain off label???
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

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

10. Patient consent
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
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

11. Regulatory guideline in India regarding off-label use
Professional conduct – controlled by Professional Conduct,
Etiquette and Ethics Regulations, 2017, ICMR
Prescription 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

12. Regulatory guideline in India regarding off-label use
 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)
 But , 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,

13. What Is the current status in India???
Out of 2237 prescriptions in children , 1579 (70.58%) were off-label in
nature (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)
Of 250 patients in psychiatry OPD, 198 (79.2%) received at least one
off-label drug
(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)

14. Pros and cons of off-label use of drugs
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

15. 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

16. Advantage of drug repositioning over traditional
drug development
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

17. Summary
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

18. THANK YOU