A new study
finds that 'off-label' drug use puts patients at risk for serious side effects
in the United States, especially when scientific evidence is lacking.
refers to the use of medications for an unproven indication or in an unproven
age group, dosage, or route of administration.
‘We don’t want to say that off-label is bad. But when it's off-label, and there's no reliable scientific evidence, there's a high risk for adverse drug events, said Dr. Tewodros Eguale, who led a research team at McGill University in Montreal.’
prescribe 'off-label' when they suggest medications for uses that have not been
recommended by the U.S. Food and Drug Administration. The practice is legal and
widely prevalent in the country.
practice is very difficult to track, because U.S. clinicians aren't required to
document an explanation for prescribing treatment.
The study led by
a Canadian-U.S. research team found that patients prescribed off-label drugs
without strong scientific evidence were 54% more likely to suffer from an adverse event
, such as an allergic response or drug interaction. They also note that those events force them to stop taking the drugs.
"We are not
saying that off-label is bad. But when it's off-label, and there's no strong
scientific evidence, we showed that there's a high risk of adverse drug
events," said Dr. Tewodros Eguale, who led a research team at McGill
University in Montreal.
commonly prescribed off-label, the antidepressant
(Oleptro), often ordered to treat insomnia
linked to hallucinations. The schizophrenia drug Zyprexa
, which is frequently suggested for depression, was
associated with weight gain.
said that the off-label drug suggestion should be part of the discussion
between physicians and their patients.
many reasons to go with an off-label prescription. The choices of drugs to deal
with a disease may be limited, drugs with good evidence may not have been
approved by the regulator or patients may have exhausted other treatment
use is higher than it should be, in part because the FDA does less than
physicians and the public thinks it does," said Dr. Randall Stafford, director
of the Program on Prevention Outcomes and Practices at Stanford University,
He said the U.S.
FDA confirms a medication's safety and efficacy for a single clinical
clinicians think of the regulator's mandate as a blanket endorsement, and this
leads to using of drugs for diseases that have not been examined.
licensed to treat depression, is frequently prescribed off-label to prevent a migraine
. But according to experts, almost half of amitriptyline's off-label uses are backed by authentic scientific evidence.
is often suggested for leg cramps and restless leg syndrome
despite warnings it can cause serious bleeding.
Experts note that all kinds of off-label uses of the three drugs - quetiapine (Seroquel)
, risperidone (Risperdal)
and Zyprexa - lack authentic scientific evidence.
For the study,
researchers analyzed electronic health record data on around 46,000 patients.
The participants received more than 151,000 prescriptions from clinics in
Quebec - a French-speaking province in eastern Canada - from 2005 through 2009.
found that more than one in 10 prescriptions in the study were for off-label
use. Also, more than 80% were for off-label uses lacking authentic scientific
evidence. The authors identified 3,484 adverse drug events. However, the study
might not have identified all medication-related events, if doctors had failed
to record all of the symptoms in patients.
The study was
published in the journal JAMA Internal Medicine
Area of Healthcare Concern in India
The drug controller general of India (DCGI) grants approval for new drugs in India. But, unfortunately, there is no definite guideline on the off-label use of drugs. Currently, laws
in the country don't permit drugs to be prescribed for indications for which they have not been approved. Amendments to the Indian Medical Council Act made off-label prescribing illegal.
marketing of pharmaceuticals are considered as a violation of the law, and it
is crime under the Drug and Magic Remedies (objectionable advertisements) act
A review article
'Regulating Off-label Drug Use in India: The Arena for Concern', recently
published in the journal Perspectives in Clinical Research
considering the advantages of off-label use the Indian government in close
association with the drug controller general of India (DCGI) should look at
ways and means to streamline the practice.
The review also
stresses that states and other jurisdictions in the country have a duty to
protect the health of the public. Permitting off-label promotion of drugs for
unproven benefits boosts industry profits at the expense of public health. A
risk - benefit ratio cannot be determined without knowing whether advantages
exist. Where no advantages benefits exist, no risk is acceptable.
However, many in
the country are of the opinion that authorizing off-label prescribing will set
a bad example because of the lack of awareness about medical conditions among
patients and domination of the pharmaceutical industry in India.
Eguale, M.D., Ph.D., adjunct professor, McGill University, Montreal, and
associate professor, Massachusetts College of Pharmacy and Health Sciences,
Boston; Randall Stafford, M.D., Ph.D., associate professor, medicine, and
director, Program on Prevention Outcomes and Practices, Stanford Prevention
Research Center, Palo Alto, Calif.; Nov. 2, 2015, JAMA Internal Medicine,
Sukhvinder Singh Oberoi Department of Public Health Dentistry, Sudha College of
Dental Sciences and Research, Faridabad, Haryana, India DOI: