Year : 2017 | Volume
: 5 | Issue : 1 | Page : 1--2
Off-label use of medication: A strong case for advocacy with government
Barun K Nayak
P.D. Hinduja National Hospital and MRC, Veer Savarkar Marg, Mumbai, Maharashtra, India
Barun K Nayak
P.D. Hinduja National Hospital and MRC, Veer Savarkar Marg, Mumbai, Maharashtra
|How to cite this article:|
Nayak BK. Off-label use of medication: A strong case for advocacy with government.J Clin Ophthalmol Res 2017;5:1-2
|How to cite this URL:|
Nayak BK. Off-label use of medication: A strong case for advocacy with government. J Clin Ophthalmol Res [serial online] 2017 [cited 2022 Aug 10 ];5:1-2
Available from: https://www.jcor.in/text.asp?2017/5/1/1/195292
Subsequent to certain incidences related to use of intravitreal injections of Avastin and Ringer's lactate solution as an intraocular irrigating solution, the ophthalmologists of the country are in a fix regarding their use. The media also sensationalized these incidences by reporting only limited facts in a breaking news style. The doctors and institutions were in the center of a storm as these uses are termed as off-label. The purpose of this editorial is to emphasize the need for a strong advocacy with the government to protect doctors as the medical science cannot function optimally and progress without off-label medication.
Off-label use of drugs is the use of drugs outside the mentioned information in the drug insert leaflet in terms of indications, contraindications, patient age, dose, and route of administration.  Furthermore, it is important to understand that license for the use of any drug can only be obtained by the manufacturer. The researchers or medical professionals cannot apply for any license to the licensing authorities, although they might have conducted extensive research on the subject, the outcome of which may satisfy the criteria.
The use of "off-label" drug cannot be avoided because it is not possible to study all age-groups of patients and for all possible indications in the beginning itself. In reality, ethics committee will always be reluctant in giving permission to conduct research in certain groups of the patient such as pediatric patients, pregnant women, lactating mothers for obvious reasons of possible harm to the vulnerable baby or mothers. When a product is launched in the market, the doctors try out other possible indications, routes of administration, and different dose forms. Without this, the medical science will not progress. If the use of off-label drug is prohibited, these groups of patients will go without treatment. There will be utter chaos in treatment of neonates, infants, pregnant women, lactating mothers, onco-medicine, if off-label use of drug is not allowed.
When off-label use of a drug is reported in literature in form of case report, case series or randomized clinical trials, others also start using them in that condition and start reporting. This creates a huge data bank which may be much more than a research done on a limited sample done for licensing purpose. However, still, the use of this drug remains off-label. It is also important to understand that a research trial cannot be conducted on a rare disease, the so-called "orphan disease."
The off-label use is prevalent globally and is not regulated uniformly. The off-label use is allowed quite liberally in Japan without even having any preliminary evidence.  The dissemination of information regarding the use of off-label drug is prohibited in France. However, the European medicine agency sometimes promotes trials to be conducted on off-label indications. The off-label usage can be as high as 90% in pediatric population and 40% in adults. 
The off-label use of drug is quite prevalent in Ophthalmology, as well. The need arises mainly in two broad situations. First, the injections of antibiotics given by different route such as intravitreally in cases of infective endophthalmitis. It is well established in literature that in this condition the intravitreal produces the best outcome, but it remains off-label usage. Second, the licensed drug may be costly, and an alternate drug does exist with a similar efficacy at much lower price but is considered off-label if not approved by the proper authority. The use of Avastin intravitreally has been found to be equally effective in cases of age-related macular degeneration as compared to lucentis. In fact, many fold more intravitreal injection of Avastin than Lucentis has been given world over, but the irony is that the use of former is off-label and that of latter is label use. The price of Avastin is much lower as compared to Lucentis. Similarly, Ringer's lactate used as intraocular irrigating solution becomes off-label and balanced salt solution plus (BSS Plus) is labeled use. It has been found to be equally safe and effective to use Ringer's Lactate as compared to BSS Plus in cataract surgery. ,,, About more than 80% ophthalmologists use Ringer's lactate during intraocular surgery by a rough estimate, still its usage is off-label.
The position of off-label use of drug in India is not clear.  In cases of mishaps, even if not related to the use of off-label drug, the doctors are left alone to defend themselves in a court of law. The Indian Medical Association has sought legislation changes for doctors in India to be able to prescribe off-label medication. 
All India Ophthalmological Society has taken a lead in this regard and submitted a dossier to the Health Secretary and Health Minister to provide provision under law that the off-label use be legitimized if it is supported by sufficient evidence in literature and the patients have been informed and explained about it.
Off-label use is the need of the hour and has many advantages. We only hope that the Government of India and Drug Controller General of India should together look into this important matter and protect the medical professionals in justified use of off-label medication. This will help in the better care of the patients at large in addition to bringing down the cost of treatment which will result in huge national savings if we consider the entire country.
|1||Conroy S. Unlicensed and off-label drug use: Issues and recommendations. Paediatr Drugs 2002;4:353-9.|
|2||Morita T, Hori A, Narimatsu H, Tanimoto T, Kami M. Current status of development of anticancer agents in Japan. Int J Hematol 2008;87:484-9.|
|3||Gazarian M, Kelly M, McPhee JR, Graudins LV, Ward RL, Campbell TJ. Off-label use of medicines: Consensus recommendations for evaluating appropriateness. Med J Aust 2006;185:544-8.|
|4||Nayak BK, Shukla RO. Effect on corneal endothelial cell loss during phacoemulsification: Fortified balanced salt solution versus Ringer lactate. J Cataract Refract Surg 2012;38:1552-8.|
|5||Puckett TR, Peele KA, Howard RS, Kramer KK. Intraocular irrigating solutions. A randomized clinical trial of balanced salt solution plus and dextrose bicarbonate lactated Ringer's solution. Ophthalmology 1995;102:291-6.|
|6||Vasavada V, Vasavada V, Dixit NV, Raj SM, Vasavada AR. Comparison between Ringer's lactate and balanced salt solution on postoperative outcomes after phacoemulsfication: A randomized clinical trial. Indian J Ophthalmol 2009;57:191-5.|
|7||Lucena DR, Ribeiro MS, Messias A, Bicas HE, Scott IU, Jorge R. Comparison of corneal changes after phacoemulsification using BSS Plus versus Lactated Ringer's irrigating solution: A prospective randomised trial. Br J Ophthalmol 2011;95:485-9.|
|8||Oberoi SS. Regulating off-label drug use in India: The arena for concern. Perspect Clin Res 2015;6:129-33.|
|9||Mudur G. Indian Medical Association wants off-label prescribing. BMJ 2004;328:974.|