A complete description of the off label use of drugs.

1. OFF-LABEL USE OF DRUGS
PRESENTED BY-
Dr. Aakanksha Priya,
JR-1,
Dept. of Pharmacology,
AIIMS, Patna.

2. OVERVIEW
Introduction
Reasons
Types
Examples
Pros and Cons
Regulation
Conclusion.

3. WHAT DOES OFF LABEL DRUG USE MEAN?
When a drug is used in a way that is different from
what is described in the FDA- approved drug
label/other regulatory bodies, then it is said to be an
“Off Label Use”

4.  WHY DO A DRUG REMAIN AN OFF-LABEL?
Therapeutic advances are often achieved at a rapid rate while
progress through licensing authority may be slow.
 once patents have expired, no financial motivation for
pharmaceutical industry to conduct trials for new indication.
Potential new indication may be benefit to a small number of
patients, may be costly for the industry.

5.  FREQUENCY OF OFF-LABEL DRUG USE
 Up to 1/5th of over all drug prescribed are off-label.
Anti-Psychiatric drug- 31%
Anti-Cancer drug-33%

6.  MOTIVATION BEHIND ITS USE
A Medication may not have been studied and approved for specific
population (E.g Pediatric, Geriatric, or Pregnant patients)
Life-threatening or terminal medical illness may motivate healthcare
professional to give any treatment that is logical.
Other medication from same class which is FDA approved for
specific indication
Disease with similar Pathophysiology (E.g Diabetes and Metabolic
syndrome)

7.  TYPES OF OFF-LABEL DRUG USE
TYPES OF OFF-LABEL
DRUGS
Use of
registered
medications
Use of
unregistered
medications

8. OFF-LABEL USE OF REGISTERED DRUGS
BASED ON DOSE EXAMPLES
Drugs given at doses other than
those stated in the approved
products.
Calcitriol used at a dose higher
than those recommended for
osteoporosis, (hypocalcemia
secondary to renal failure)
BASED ON AGE EXAMPLES
Drugs prescribed outside approved
age limit.
Valacyclovir used in children less
than 12 years.

9. CONT…
BASED ON INDICATIONS EXAMPLES
Drugs given for indications other
than those stated in the approved
products.
1. Risperidone for Autism
2. Azithromycin for anti
inflammatory effects in Cystic
fibrosis.
BASED ON ROUTE EXAMPLES
Drugs administered by
unapproved route of
administration.
Tobramycin injection used as
inhalational form in cystic fibrosis.

10. OFF-LABEL USE OF UNREGISTERED DRUGS
MODIFICATION OF REGISTERED
MEDICATIONS
EXAMPLES
Preparation of suspension from
capsule or tablets
Sotalol and indomethacin
mixtures(for Pediatric pts.)
Changing PK Reforming of Methylphenidate to a
long acting preparation (ADHD)
DRUGS UNDER CLINICAL TRIALS EXAMPLES
Drugs available only through the
clinical trial process
Newer Anti-cancer drugs

11. CONT…
MEDICINES REQUIRING SPECIAL
ACCESS
EXAMPLES
Medicines awaiting
registration/medicines registered
in other countries.
1.Thalidomide tablets
2. Liothyronine tablets

12. EXAMPLES OF OFF-LABEL DRUGS
Medication Off-label use
Allergy
Diphenhydramine Chemotherapy related emesis,
insomnia
Cardiology
Aspirin Antithrombosis in AF, Kawasaki
disease.

13. CONT….
Medication Off-label use
Dermatology
Azathioprine Atopic Dermatitis, Psoriasis
Biologic agents Alopecia Areata, Atopic Dermatitis.
Infectious disease
Linezolid Infective Endocarditis
Obstetrics
Magnesium Sulfate Premature Labour.

14. Medication Off-Label Use
Pediatrics
Amoxicillin Otitis Media in children.
Atenolol Hypertension in children.
Intranasal desmopressin Nocturnal Enuresis

15. PROS AND CONS OF OFF LABEL DRUG USE
PROS
It provides earlier access to
potentially valuable medicines
and thus improving patient care.
It may be the only available
option when all approved
therapies have failed.
It has potential for establishing
new uses old drugs(e.g
Thalidomide for multiple
myeloma)
In rare disease conditions, such
use may provide only available
therapy.
CONS
Increase in healthcare cost.
It may increase likelihood of
adverse drug effects.
It may discourage evidence
based practice in physicians.
Off-label use may affect
innovation adversely.

16. REGULATION OF OFF-LABEL USE IN
VARIOUS COUNTRIES
 UNITED STATES
 Physician are allowed to prescribe a drug for its off-label use
(provided there has to be extensive medical literature to support the
use)
Pharmaceutical industry are not allowed to promote a drug for any
other purpose without FDA approval.

17.  PENALTIES PAID BY PHARMACEUTICAL
COMPANIES IN RECENT PAST
Pharmaceutical
company(year)
Off- label drugs
promoted
Settlement cost paid
Pfizer(2005) Valdecoxib(Bextra) 2.3 Billion US$
Eli Lily(2009) Olanzapine for
dementia
1.4 Billion US$
Novartis (2010) Oxcarbazepine 422.5 million US$
Allergan (2010) Onabotulinum A 600 million US$
Merck (2012) Rofecoxib 950 million US$

18. UNITED KINGDOM
Physician are allowed to prescribe a drug for its off-label use
British General Medical Council- off-label prescription must better
serve patients needs than alternatives and must be supported by
evidence to demonstrate efficacy and safety.

19. INDIA
Drug controller General of India(DCGI) is regulatory body for approval
of new medicines for use.(But it doesn’t regulate off label use of
drugs).
In 2004, a committee of IMA was set up by the govt. of India to make
specific guidelines governing the off label drug use.
The committee strongly favored the off label drug use, when they
were based on evidence.

20. INDIA
Professional conduct is controlled by-
 Professional Conduct, Etiquette and Ethics Regulations, 2002 of Indian
Medical Council.
Prescription drugs
 Should not violate Drug and Cosmetic Act
 Should not violate ICMR guidelines for research
 Should not violate human rights.

21. PERSPECTIVES OF STAKEHOLDERS ON OFF
LABEL USE
Patients
Physicians
Industry
Regulatory authorities
Insurance agencies.

22.  PATIENT’S PERSPECTIVES
Increasing expectation of patients from healthcare providers.
Patient wants safe, cost-effective and evidence based medicine.

23.  PHYSICIAN’S PERSPECTIVES
Physician needs freedom to exercise best of clinical judgement for
managing individual patients.
Autonomy to innovate
Doing things in the best of patients interest- “Do no harm”
Off-label drug use- “Not Illegal”.

24. INDUSTRY’S PERSPECTIVES
Would seek to promote off label use to expand their product market.
More profit by evading costly and time consuming trials
Promoting off-label use- IILEGAL

25. REGULATORY BODY’S PROSPECTIVES
Only authorised marketing of drugs and products labelling and
claims.
Do not regulate off label prescribing by physicians

26. INSURANCE COMPANY’S PRESPECTIVES
Why pay for unproven and costlier off-label drugs?

27. NEED OF THE HOUR
Rational Prescribing- it should be used only when it is appropriate i.e
when approved therapies fails and only alternative is available, the
possible benefits outweigh the risks and the patient has been
informed and consent obtained.
Evaluation of supporting scientific evidence- the prescribing
physician should critically appraise the medical material available on
the particular drug.
Safety monitoring- some methods like ADR reporting, observational
epidemiological studies may be implemented to identify, analyse,
and monitor ADRs due to use of off-label drugs.

28. CONCLUSION
• The magnitude of general off-label use of drugs is reportedly
increasing and is likely to increase further, exposing patients to
increased risks of ADEs.
• The patients generally expect that the prescribed drugs will be safe.
They want to administer evidence based approved medicines. Some
of them have even started expressing that these evidences must also
be disclosed to them.
• Hence, there seems to exist a clear conflict of interest in this
matter between the patients, drug manufacturers and perhaps the
doctors, as well.