What patients should know about off-label drug use

Staving off stage fright and controlling high blood pressure are two different things. Yet the same drug is sometimes prescribed for either problem. Propranolol, or Inderal, is approved by the Food and Drug Administration to treat conditions including hypertension, an irregular heart rhythm called atrial fibrillation and migraines. Performance anxiety, however, does not appear in the package insert.

Off-label drug use is common, and it often involves taking a drug for a different medical condition than it's meant for. Or, it can be taking drugs in a non-approved dosage or form. It might be children receiving drugs only FDA-approved for adults.

While estimates vary, some studies suggest that 1 in 5 prescriptions of common medications involves an off-label use. In some cases, experts say, there's a place for off-label use if it's done in a cautious and thoughtful way.

[See: 8 Questions to Ask Your Pharmacist.]

Not Without Risk

All off-label drug uses are not created equal. A study published in November 2015 in JAMA Internal Medicine compared prescription drugs used for off-label indications with and without strong scientific evidence to back the alternative use. When that evidence is lacking, there's a 54 percent increase in adverse drug events, found researchers led by Dr. Tewodros Eguale, an associate professor with MCPHS University in Massachusetts.

"What we reported was around 11 to 12 percent of prescriptions are for off-label use," Eguale says. "Out of these, four in five don't have scientific evidence to back them up. They lack the scientific evidence which says, you can use this particular drug for this particular indication for this condition."

One example of a dangerous off-label use, Eguale says, is taking the drug quinine, intended to treat severe forms of malaria, to instead address chronic nighttime leg pain from restless leg syndrome. Quinine is meant to be used only for short periods, he says, because of the number of known adverse drug reactions.

Reasonable off-label medication uses do exist, Eguale says. "For some conditions, there may not be a drug out there," he says. "And the physician has to use something." A good example, he says, is the antidepressant drug amitriptyline. It's now used off-label to treat pain from fibromyalgia, among other conditions, and there is evidence that shows it can be safely used.

The cornerstone of safe off-label drug treatment is discussion between the patient and physician, Eguale says. There's now a push for physicians to include treatment indications in electronic prescribing, he adds, which would allow pharmacists to more easily pick up medication errors.

Few Other Options

One controversy is the use of antipsychotic medications for people with Alzheimer's disease. Sometimes there's little choice, says Dr. David Knopman, a professor of neurology at the Mayo Clinic College of Medicine and vice chair of the Alzheimer's Association Medical and Scientific Advisory Council.

While four drugs are FDA-approved to treat the cognitive symptoms of Alzheimer's disease, they don't relieve the behavioral disturbances that can occur among some people with dementia, says Knopman, who's also a consultant in neurology at the Mayo Clinic. "Virtually all of that treatment is off-label," he says.

For patients with dementia with significant physical aggressiveness and agitation, non-pharmacological approaches should be exhausted first, Knopman says. When that fails, he says, antipsychotic drugs that are FDA-approved to treat schizophrenia and psychotic disorders are what practicing physicians have found effective.

However, several of these drugs, such as Abilify, Haldol and Risperdal, have a "very unfavorable side-effect profile," Knopman says, including symptoms seen in Parkinson's disease, such as stiffness, tremors and balance problems. Therefore, he says, he would not use those drugs to treat patients with dementia.

Instead, Knopman says, a better choice would be quetiapine, or Seroquel, which treats agitation but doesn't cause Parkinsonism. "But it's off-label," he says. "There's never been a study that showed Seroquel was effective in treating people with dementia." Another caveat is that, like other antipsychotic drugs, it has an FDA black box warning of increased risk of death in elderly patients with dementia-related psychosis.

"When we are forced to resort to a medication like quetiapine to treat physical aggressiveness, it's because family members are up against the wall because of the difficulty of managing somebody," Knopman says. "They can't be cared for at home because they're striking out at relatives. They can't be cared for in a facility because they're striking out at the caregivers. So it's a big deal – it's not a trivial matter."

[See: 5 Common Preventable Medical Errors.]

Parents Should Know

Kids are often excluded from drug studies required for the FDA approval process. So children are "definitely" more likely to be prescribed off-label drug use, says Dr. Kathleen Neville, a professor of pediatrics at the University of Arkansas for Medical Sciences/Arkansas Children's Hospital.

A 2007 study of children discharged from pediatric hospitals found that nearly 79 percent were taking one or more off-label medications. Two recent laws, the Best Pharmaceuticals for Children Act and the Pediatric Research Equity Act have improved "rational prescribing" for children and resulted in more than 500 labeling changes, according to the American Academy of Pediatrics.

Parents should realize that "off-label" doesn't mean "no evidence," Neville says. "It might be labeled for one use in adults but there's something similar in kids and it's never been studied. Or, it hasn't been studied to the extent that the FDA can use the evidence to label it."

Neville is the director of the experimental therapeutics program at ACH, where she sees kids with hard-to-treat pediatric cancers. "Then, we don't have the information," she says. "We're doing the study to get it."

The FDA has done a "wonderful" job in trying to maximize what it can do with the legislative authority it has, Neville says. Her advice is: "Parents should push, when they're electing people, that kids don't get left behind."

Case-by-Case Conversations

Polycystic ovary syndrome, or PCOS, is the leading cause of female infertility. PCOS puts women at risk for diabetes, heart disease and other serious medical conditions, as well as a variety of symptoms affecting their quality of life.

"There are no drugs approved by the FDA for PCOS," says Dr. Kathleen Hoeger, a professor of obstetrics and gynecology and director of the reproductive endocrine division at the University of Rochester Medical Center. "So that's a real deficit we have in our drug pool."

However, there are FDA-approved drug indications for treating individual PCOS symptoms, Hoeger explains. "We use birth control pills, which are approved for irregular periods, which PCOS women often have," she says. "And we use things like metformin, which is approved for the treatment of diabetes and prevention of diabetes in women with PCOS, even though they don't necessarily have diabetes, to help with the insulin resistance."

Insurance coverage for drugs like metformin can be a challenge, Hoeger says, as there is no PCOS indication on the label. Newer formulations of the drug, like Glumetza, which is approved for Type 2 diabetes, can be quite expensive, she adds.

Although the FDA hasn't approved a drug for a specific use, it could have value, Hoeger says. "Because the FDA approval has to do with the pharmaceutical company being willing to do all the studies and put in all the costs to make all the hurdles the FDA puts in front of the drug," she says.

For women taking off-label drugs for PCOS-related conditions, Hoeger says, "It's important for them to be educated that it is for a non-approved indication. It's important for them to have a conversation with their prescriber as to why they think this drug might be appropriate for them. But also to understand that in many situations, a risk-benefit analysis is something that the patient and the doctor do together."

[See: 14 Ways to Protect Seniors From Falls.]

Check With Your Pharmacist

Before dispensing medications for off-label use, Heather Free, a practicing pharmacist in the District of Columbia, has talked to the doctor or other health provider to determine why he or she is prescribing the drug this way and whether the dose is appropriate. She has also asked about the drug's overall safety for the individual patient.

"It's knowing that patient and their other health risks," says Free, who is a spokesperson for the American Pharmacists Association. For instance, for someone planning to take propranolol to stay calm before public speaking, she'd consider the drug's effect on their health. "So if they don't have a blood-pressure issue and they're taking a beta-blocker, what are the risks?" Free says. "Do they already have a low pulse? Because this is going to drop their pulse even more."

It's important for patients to empower themselves by understanding the medication and side effects as much as possible, Free says. And it's crucial for patients to alert all their prescribers about the new drug. "They may be seeing a neurologist for their migraine and getting this medication," she says. "But they also should be telling their primary care doctor so there's no duplication or very similar medications prescribed that can interfere more with the patient's condition than help."

You can do an FDA label searchto learn about a drug's approved indications, dosage and administration guideline and side effects.