Off-label Drug Use Poses Safety Risks: Experts

by Vishnuprasad on  November 6, 2015 at 3:49 PM Health In Focus   - G J E 4
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.
Off-label Drug Use Poses Safety Risks: Experts
Off-label Drug Use Poses Safety Risks: Experts

Off-label use 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.’
Clinicians 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.

However, the 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.

Among drugs commonly prescribed off-label, the antidepressant trazodone (Oleptro), often ordered to treat insomnia was linked to hallucinations. The schizophrenia drug Zyprexa (olanzapine), which is frequently suggested for depression, was associated with weight gain.

The researcher said that the off-label drug suggestion should be part of the discussion between physicians and their patients.

Clinicians have 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 options.

"Off-label 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, California.

He said the U.S. FDA confirms a medication's safety and efficacy for a single clinical condition.

However, many 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.

Amitriptyline (Elavil) 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.

Quinine 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.

Investigators 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.

Off-label marketing of pharmaceuticals are considered as a violation of the law, and it is crime under the Drug and Magic Remedies (objectionable advertisements) act 1954.

A review article 'Regulating Off-label Drug Use in India: The Arena for Concern', recently published in the journal Perspectives in Clinical Research suggests that 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.


1. Tewodros 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, online

2. Sukhvinder Singh Oberoi Department of Public Health Dentistry, Sudha College of Dental Sciences and Research, Faridabad, Haryana, India DOI: 10.4103/2229-3485.159935

Source: Medindia

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