|Year : 2017 | Volume
| Issue : 7 | Page : 549-550
A tale of two drugs: Off and on-label
Raja Narayanan1, Santosh G Honavar2
1 Head of Clinical Research, L. V. Prasad Eye Institute, Hyderabad, Telangana, India
2 Center for Sight, Hyderabad, Telangana, India
|Date of Web Publication||20-Jul-2017|
Head of Clinical Research, L. V. Prasad Eye Institute, Hyderabad, Telangana
Source of Support: None, Conflict of Interest: None
|How to cite this article:|
Narayanan R, Honavar SG. A tale of two drugs: Off and on-label. Indian J Ophthalmol 2017;65:549-50
Every prescription drug marketed in India carries an individual, Drug Controller General of India (DCGI) approved label. This label is a written report that provides detailed instructions regarding the approved uses and doses, which are based on evidence from clinical studies that the drug maker submitted to the regulatory authorities. The word off label means relating to the prescription of a drug for a condition other than that for which it has been officially approved. This could be use in another disease, age group, dose, or route of administration of the drug.
Off-label use is generally accepted unless it violates ethical guidelines or safety considerations. The ability to prescribe drugs for uses beyond the officially approved indications is commonly used to good effect by health-care providers, usually based on evidence, and the judgment of health-care providers. For example, aspirin is commonly used off-label by cardiologists to prevent heart attacks although the original label was for headache, toothache, muscle pain, and fever. This was a prime example of off-label use.
Children and pregnant women are most likely to be prescribed off-label drugs since most trials are never performed in this subset of population for ethical reasons. Off-label use of drugs, such as antibiotics, is life-saving in children and pregnant women. Many diseases do not have approved “labeled” drugs, partly because the diseases are rare or conducting clinical trials and marketing the drug for such diseases may not be profitable.
However, off-label needs an acceptable evidence of safety and efficacy in the professional community. Regulatory authorities provide label to a pharmaceutical company for marketing. For off-label use, medical professionals rely on evidence based on actual use or from trials performed either by professional medical bodies or, in rare instance, health ministries. Examples of health ministries performing trials for off-label use are rare. A unique example is that of The National Institutes of Health, an agency of the US Department of Health and Human Services, which conducted a large trial to generate evidence on the safety and efficacy of bevacizumab compared to ranibizumab in age-related macular degeneration.
Drug manufacturers, for valid reasons, are not legally permitted to encourage the use of regulated drugs for any indications that have not been formally approved by the country's government, even if significant scientific evidence exists for that unapproved indication, or even if another country's drug agency has approved that indication. However, health-care providers may not limit prescriptions or recommendations to the indications approved by their country's drug regulatory agency, taking into account evidence-based judgment on efficacy and risks of a drug.
To give an example, in the United States, there is no law that prohibits a physician from prescribing an approved medication for off-label use. The American Academy of Pediatrics published a statement in 2014 regarding the off-label use of pharmaceuticals in children. They recommended that off-label use is neither incorrect nor investigational if based on sound scientific evidence, expert medical judgment, or published literature. Evidence, and not label, should be the gold standard for practitioners to base their judgment when making therapeutic decisions for their patients.
There are numerous examples of off-label use in medicine. Tricyclic antidepressants are used to treat neuropathic pain, such as after herpes zoster infection. Although this class of antidepressants is not often used for clinical depression due to side effects, they are often used for treating neuropathic pain. Propranolol, another medicine to control blood pressure, is used in children with cyanotic congenital heart disease as off label. Antibiotics for intravitreal injections in cases of endophthalmitis are not available as “labeled” drugs, and doctors frequently use intravenous antibiotics for injection in the eye for sight-threatening eye infections. According to the American Cancer Society, cancer treatment often involves using certain chemotherapy drugs off label because a chemotherapy drug approved for one type of cancer may actually target many different types of tumors. A generalized prohibition of off-label use of drugs can cause disastrous consequences to the health of the population.
Ophthalmology is not a stranger to the debate on off-label use of drugs. On January 21, 2016, the DCGI took the bold step of prohibiting the use of intraocular bevacizumab as off-label treatment for various retinal diseases. Unfortunately, DCGI's decision put a large portion of the population at risk of denial of access to treatment for common blinding retinal diseases. After 2 months, the DCGI agreed to withdraw the alert notice, enabling retinal surgeons to use bevacizumab. This decision may be a landmark judgment for India and other countries around the world to look at evidence-based off-label use of drugs.
The global use of bevacizumab, though evidence-based, has strained the relationship between physicians, authorities, pharmaceutical industry, insurers, and payers because of its off-label use, and has deprived the pharmaceutical companies of significant revenue. However, the issue is much larger than cost of drugs. This calls for all stakeholders, including physicians, industry, policymakers, and health economists to work together for strengthening the access to treatment for all segments of the population, off- or on-label.
We are grateful to the contribution of Dr. Y. V. Reddy, IAS (Retd.), Former Governor of the Reserve Bank of India for his inputs.