edit offlabeluse When a drug is used in a way that is different from what is described in the FDA

edit off label use
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”

1. OFF-LABEL USE OF DRUGS Presenter: Dr Sujitha Moderator: Dr Eesha Rao 1

2. Contents Introduction Emergence of off-label use Regulating Agencies Examples Advantages and Disadvantages Conclusion References 2

3. Introduction "Off-label"  When a drug is used in a way that is different from what is described in the FDA- approved drug label/other regulatory bodies It means when drugs are used for an - unapproved indication - unapproved age group - unapproved dosage - unapproved form of administration I ncludes both prescription drugs and over-the-counter drugs (OTCs) 3

4. Introduction This type of use is legal unless some specific ethical guidelines or safety regulations has been violated I t does carry health risks and differences in legal liability Recently, off-label use of drugs have become common use Up to 1/5 th of over all drug prescribed are off-label Anti-Psychiatric drug- 31% Anti-Cancer drug-33% 4

5. History of emergence of off-label use of drugs 1938: establishment of U.S. Food and Drug Administration (FDA), which required drugs to be proven safe for specific uses 1962 : Kefauver-Harris Amendment stated that drugs were prescribed without rigorous proof of effectiveness for particular conditions & concept of "off-label" didn’t exist as it does today 1970s & 1980s : off-label prescribing became more widespread as medical knowledge expanded Mid-to-late 20th century: off-label use likely became more prominent 5

6. Key factors in emergence of off-label use of drugs Limitations of approved therapies : In some cases, no drugs have been specifically approved to treat particular condition. Off-label use allows to explore existing drugs when patients have exhausted other treatment options Drug repurposing : Some medications initially developed for one condition may show efficacy in treating other conditions Paediatric and rare diseases: Since clinical trials often exclude children and people with rare diseases, off-label prescriptions are frequently used to address these diseases 6

7. Key factors in emergence of off-label use of drugs Slow drug approval process: Getting new indication for drug can be time-consuming & expensive. Off-label prescribing allows use of promising therapies without waiting for formal approval for each condition Regulatory flexibility: Regulatory agencies permit off-label use as long as it's based on clinical judgment Innovation and Case Studies: Case reports & small studies sometimes show potential benefits of drug for unapproved conditions 7

8. Examples of Off-label Drugs Drugs (for Unapproved Indication) Approved use Off-label use Gabapentin Postherpetic Neuralgia (900–1800 mg/Day) Anxiety (300–900 mg/Day) Bipolar Disorder Dexamethasone Asthma, Anaphylaxis (6–10 mg once Daily) Premature Labour( 12 mg IM every 24 Hours ) Buprenorphine Opioid Withdrawal Management(2-4 mg Sublingually) Refractory Depression (0.2-2 mg/Day Sublingually) 8

9. Examples of Off-label Drugs Drugs (for Unapproved Form of Administration) Approved route Off-label use Thiamine Oral (25 mg - 100 mg) Injection- Wernicke’s Encephalopathy (200-500mg) Tobramycin IV (3-6 mg/kg/day) Inhalation- Cystic Fibrosis (300 mg) 9

10. Examples of Off-label Drugs Drugs (for Unapproved Age Group) Approved use Off-label use Amphetamine ADHD in children (5-10 mg) ADHD in adults (5-40 mg) Valaciclovir Herpes infection (1000 mg) Under 12 years (250-500 mg) Quetiapine Schizophrenia, bipolar disorders (300 mg) Under 10 years (50 mg) 10

11. Examples of Off-label Drugs Drugs (for Unapproved Dosage) Approved use Off-label use Melatonin Insomnia (2 mg tablet) Insomnia (3 mg capsules) Calcitriol Osteoporosis (0.25 mcg) Used at dose higher than those recommended in Hypocalcaemia secondary to renal impairment (0.5 mcg to 1 mcg) 11

12. Advantages Provides best intervention for heath problems when there is no relief from standard drug In rare diseases it only provides available therapy Patients suffering from cancer are benefitted It provides earlier access to valuable medicines & improves patient care It may be the only available option when all approved therapies have failed In pediatric malignancies 70% cure rate achieved 12

13. Disadvantages Off-label use may affect innovation adversely Increases healthcare cost It may increase likelihood of adverse drug effects It may discourage evidence based practice in physicians 13

14. Role of regulatory agencies In Japan: It is a very liberal process where a new drug application permits approval of off-label usages In France: Marketing drug agencies prohibit dissemination of information on off-label use EMA are supporting clinical trial of off-label drugs in children FDA is providing sponsors, marketing and encouraging studies in paediatric population 14

15. Role of regulatory agencies In United States: 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 15

16. Role of regulatory agencies In India: Drug controller General of India(DCGI) is regulatory authority Not started any clear guidelines on off-label use of drugs DCGI doesn’t regulate off label use of drugs. In 2004- committee of IMA was set up by govt. to make specific guidelines governing off label drug use The committee strongly favored off label drug use, when they were based on evidence Off-label marketing by pharmaceutical companies – offence under drug and magic remedies act 1954 16

17. Conclusion Off-label use of drugs is not an uncommon medical Off-label use of medicine involves physicians, pharmaceutical companies and regulatory agencies Therapeutic advantage might get restricted without off-label prescribing in some patient population Off-label use of drugs have several advantages and therefore Government of India, DCGI in association with IMA should find out ways to streamline this practice 17

18. References U.S. Food and Drug Administration. Understanding unapproved use of approved drugs “off label”. February 5, 2018. Accessed November 30, 2022. Moulis F, Durrieu G, Lapeyre -Mestre M. Off-label and unlicensed drug use in children population. 2018;73(2):135–149. Reichert S, Simon T, Halm EA. Physicians’ attitudes about prescribing and knowledge of the costs of common medications. Arch Intern Med. 2000;160:2799–2803. Syed SA, Dixson BA, Constantino E, Regan J. The law and practice of off-label prescribing and physician promotion. J Amer Acad Psych Law. 2021;49:53–59. Sougata Sarkar- postgraduate pharmacology- 1 st edition 18