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Is It Safe to Take Off Label Drugs for Unapproved Purposes?

There is a good chance you are taking off label drugs. Do you know the risks and benefits? Doctors may not reveal they are prescribing without FDA approval.

Are you taking a medication off label? By that we mean, has your physician prescribed a drug for an unapproved indication? Off label drugs are prescribed far more often than most patients realize. One study of physician prescribing patterns concluded (JAMA Internal Medicine, May 8, 2006):

“Off-label medication use is common in outpatient care, and most occurs without scientific support.”

What Are Off Label Drugs?

The FDA approves medications for specific purposes based on rigorous scientific evidence. In the official prescribing information these are listed as “indications.” You can go to DailyMed and put the name of your medicine into the search window. You are looking at the official FDA prescribing information. Scan down to INDICATIONS and USAGE to learn what the FDA says is sanctioned usage.

The Flomax Example of Off-Label Prescribing:

The official label for Tamsulosin (Flomax) states:

“FLOMAX (tamsulosin hydrochloride, USP) capsules are indicated for the treatment of the signs and symptoms of benign prostatic hyperplasia (BPH).”

In other words, the FDA has only approved the use of tamsulosin for an enlarged prostate gland. When a man’s prostate reaches a certain size it may be harder to pee. Guys who have to get up a few times at night to go to the bathroom frequently get a prescription for this drug.

Sometimes, though, doctors prescribe tamsulosin for off-label indications. It is estimated that 300,000 people end up in the ER with kidney stones (urolithiasis). The pain can be excruciating. Emergency physicians may prescribe tamsulosin to relax muscles within the urinary tract in the hopes of easing the passage of the stone(s).

A review in the American Journal of Emergency Medicine (Nov. 2016) notes that:

“tamsulosin has not been proven effective for increasing ureteral stone passage and is not approved by the Food and Drug Administration for this indication.”

The authors go on to note that while several studies suggest the drug could be helpful in passing kidney stones, others provide conflicting results:

“…one of the largest and most comprehensive randomized control trials has shown that tamsulosin is not more effective than a placebo at increasing the likelihood of stone expulsion. This study published in 2015 with 1136 patients had 81% spontaneous stone passage in the tamsulosin group compared with 80% spontaneous stone passage in the placebo group.”

Patients suffering from the unbearable pain of a kidney stone are unlikely to ask the ER doc if a medicine has FDA approval for that indication. They want relief and they want it fast. Will the emergency physician mention that tamsulosin is an off label drug for passage of kidney stones? Probably not. Will the doctor mention that the data are equivocal regarding effectiveness. We leave that to your imagination.

Prozac (Fluoxetine) and Premature Ejaculation:

Some doctors have heard that antidepressants like fluoxetine (Prozac) work well for premature ejaculation. This is definitely an off-label use that the FDA has not sanctioned.

We don’t doubt that fluoxetine might work for this purpose. It can also cause lowered libido, erectile dysfunction, difficulty achieving orgasm as well as other symptoms of sexual dysfunction.

The point is that many times off label drug prescribing happens by word of mouth. One doctor shares her experience with another doctor. Off label drug use might be mentioned at a luncheon. The quality of the evidence may not be revealed.

Where Does the FDA Stand on Off Label Drugs?

The agency has no authority over how doctors actually prescribe medicines. Read that sentence again please. NO authority! Zip, zero, nada. A doctor can prescribe any approved drug for just about any purpose.

What that means in practicality is that once the FDA gives a drug the green light for condition X, doctors can prescribe it to patients for condition Y or Z, even if there is little or no data to support the other uses. A doctor is under no obligation to mention that she is prescribing a medicine off label.

How Common is Off-Label Prescribing?

One study that asked this question and analyzed a large database reported that one out of five medications are prescribed off label (JAMA Internal Medicine, May 8, 2006). That’s disconcerting, but far more worrisome is this stat:

“15% of all estimated uses lacked scientific evidence of therapeutic efficacy…No more than 30% of the off-label practices we observed were supported by strong scientific evidence.”

That is damn worrisome. It means that patients are taking substantial risks that the off label drugs they are swallowing won’t work. The meds have not lost their side effects, however.

Off-Label Prescriptions Linked to Problems:

An analysis of 46,000 medical records of primary care patients revealed why off label drugs are potentially problematic (JAMA Internal Medicine, online, Nov. 2, 2015). Patients taking drugs for an off-label use were 44 percent more likely to experience an adverse drug reactions. If there was little scientific support for the use, the rate of side effects was even higher.

Beta Blockers and Stage Fright:

Beta blockers like atenolol and metoprolol are approved to treat high blood pressure and heart problems. Some doctors prescribe these drugs for stage fright or performance anxiety even though there is not a lot of high-quality research supporting this use.

We heard from one person who experienced an unpleasant reactions to a beta blocker:

“I love acting, but I suffer from stage fright. My doctor prescribed propranolol to ease my anxiety during a play.
Fortunately, I experimented during the final days of rehearsal. The first night, I couldn’t remember where I put my clothes during a scene change. The second night, I couldn’t recall my lines. It was a very strange and frightening experience.”

Some physicians prescribe beta blockers off label for “social anxiety disorder.” It helps control adrenaline surges. But someone with a susceptibility to asthma could end up in serious trouble because of a beta blocker. We heard from one reader who actually passed out from a severe asthma attack while taking atenolol.

Scary Off Label Drug Usage:

A recent analysis of off-label antidepressant prescribing in Canada uncovered some disconcerting trends (BMJ, Feb. 21, 2017).  The researchers reviewed 106,850 antidepressant prescriptions written by 174 physicians. Roughly one third of the prescribed drugs were for off label problems such as pain, insomnia or migraines.

Amitriptyline Often Prescribed Off Label:

Amitriptyline, for example, was prescribed far more often to treat pain and insomnia than depression. The authors point out that the evidence for such off-label uses was not great. Another old-fashioned antidepressant, trazodone, was also prescribed frequently for insomnia, even though it was never approved for this indication.

Then there is the whole issue of side effects. Amitriptyline is considered a strong anticholinergic drug. That means it affects the brain chemical acetylcholine. Drugs in this class have been linked to confusion, memory problems and dementia (JAMA Internal Medicine, online, March, 2015). Many experts in geriatric medicine consider amitriptyline inappropriate for people over 65, even if prescribed “on label.”

If you would like to learn more about drugs that have anticholinergic activity, here is an article that lists a surprising number of such drugs. You might be surprised at how many meds are on the list.

The Shocking Story of Gabapentin:

The antiseizure drug Neurontin (gabapentin) was approved by the FDA to treat epilepsy in 1993. The company that developed this drug got into trouble with the FDA for off-label marketing. Sales reps promoted Neurontin for conditions like ADHD, bipolar disorder, alcohol withdrawal, migraines and pain.

As already mentioned, physicians can prescribe medications off label. But drug companies have not been allowed to promote their medicines for unapproved uses. Pfizer ultimately pleaded guilty to fraudulent promotion and paid over $400 million in penalties.

Gabapentin is only approved by the FDA for treating epilepsy and for nerve pain brought on by a shingles attack (postherpetic neuralgia). Nevertheless, many doctors prescribe gabapentin off label for neuropathy, fibromyalgia, migraines and hot flashes.

Gabapentin side effects may include dizziness, fatigue, confusion, depression, dry mouth, indigestion and visual disturbances. If stopped suddenly, withdrawal symptoms may be triggered. They include anxiety, insomnia, nausea, pain and sweating.

Using Off Label Drugs Prudently:

There is nothing intrinsically wrong with off-label prescribing as long as the scientific evidence is strong and the benefits of the drug outweigh the risks. Patients should always be told when a medicine is being prescribed for an unapproved use.

Share your own experience with off label prescribing in the comment section below.

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About the Author
Joe Graedon is a pharmacologist who has dedicated his career to making drug information understandable to consumers. His best-selling book, The People’s Pharmacy, was published in 1976 and led to a syndicated newspaper column, syndicated public radio show and web site. In 2006, Long Island University awarded him an honorary doctorate as “one of the country's leading drug experts for the consumer.”.
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