Arthritis Today

Afraid of Drug Side Effects?

Side effects can occur, but the risk also can be overestimated.


It’s understandable that some people are uneasy about taking medication. These days, it seems you hear as much about risks from drugs as you do about benefits. Even some drugs that have been around for years and used by millions now seem too risky, or so the headlines suggest.

Side effects can occur with any drug, says Stanley Cohen, MD, a rheumatologist and clinical professor at the University of Texas Southwestern Medical School in Dallas. As a prime example he points to acetaminophen, an ingredient in hundreds of over-the-counter remedies and prescription painkillers. Yet, liver damage can occur from taking too much acetaminophen, which can happen if someone doesn’t recognize it on a drug label (sometimes it’s listed as “APAP” or “paracetamol”) or isn’t aware that the maximum safe dose is a combined total of 4,000 mg per day.

Taking medication does involve risk – even for the “safest” of medicines. The goal is to get the most good with the least harm. When deciding whether to take a medication, don’t rely just on the information you get from the news and in drug ads. It’s crucial to share your concerns with your doctor, who can talk about the likely benefits and potential risks specifically for you.

Here, we help lay the groundwork for these discussions – and perhaps reduce some of your fears about side effects, too.

Why You’re Worried

Here are four common reasons for patient concerns, and some objective reassurance from leading experts.

The risks aren’t clear.  On the laundry list of side effects, common and less serious problems are lumped with rare and more serious ones. Patients don’t know which on the list are likely to occur to them and often assume the worst. For example, with bisphosphonates – a medicine used in the treatment of osteoporosis and a complication of cancer – two rare side effects that have caused a lot of concern are osteonecrosis of the jaw and atypical fractures of the femur.

“Patients express worry about ‘that jawbone problem’ or ‘those funny fractures’ they’ve heard about on TV or read about in the paper,” says Jeffrey Curtis, MD, an associate professor of medicine and director of the Arthritis Clinical Intervention Program at the University of Alabama in Birmingham. “But when I ask how likely they think those problems are, they don’t have a clue.”

In this case, it’s partly because the numbers aren’t available. Sometimes the numbers aren’t clear or aren’t easy for the consumer to understand. Have your doctor or pharmacist put the available data into context for you.

The numbers can fool you. How numbers are presented makes a difference in a patient’s perception. For example, the risk for tuberculosis (TB) in the general U.S. population is 2.8 in 100,000; among people taking TNF inhibitors it is 49 in 100,000, according to one study. “TNF inhibitors cause a 17.5-fold increase in risk for TB,” is a way of describing the relative risk, and it sounds a lot scarier than “The risk of TB is 0.05 percent among people taking TNF inhibitors,” a way of describing the absolute – or actual – risk.

Here’s another example: Methotrexate, a mainstay disease-modifying antirheumatic drug (DMARD) for treating rheumatoid arthritis (RA) and juvenile arthritis, is associated with a 3 percent risk of serious infection, meaning 3 in 100 people treated with the drug for a year get a serious infection. If a biologic drug, specifically a TNF-alpha inhibitor, is added to methotrexate, the risk increases to 5 percent – meaning 5 in 100 people treated with both drugs get a serious infection.

This can be reported in terms of relative risk: “a 60 percent increase in the risk of a serious infection.” Or it can be reported as absolute risk: “An additional 2 in 100 people, or 2 percent, develop a serious infection.” Again, the former example is more intimidating.

“Just knowing there is a ‘significantly increased risk of infection,’ doesn’t provide much context,” says Dr. Curtis. But it can make some patients hesitant about adding a biologic to their methotrexate therapy, although the more aggressive approach could be key to shutting down pain and preventing joint deformity.

The drug seems worse than the disease. For many serious side effects, it’s unclear exactly what role the drug plays. Sometimes, the disease itself puts a person at risk for certain problems, with more severe disease equaling bigger risk. RA increases the risk of serious infection, including infections that require hospitalization, making it difficult to determine to what extent biologic agents, like TNF inhibitors, may further increase the risk.

Age, other health problems and other medications also can increase the risk of certain side effects. Studies show that having diabetes or chronic lung disease or taking corticosteroids also worsens the risk of serious infection in people taking biologic agents.

“There’s much uncertainty about the rare side effects that we blame on drugs, but truthfully, we don’t know if there is a causal association,” says Liana Fraenkel, MD, an associate professor of medicine, practicing rheumatologist and researcher at Yale School of Medicine in New Haven, CT. Some of Dr. Fraenkel’s research on this has been funded by the Arthritis Foundation.

Newer drugs list more risks. In recent years, the FDA has made sweeping changes to its drug safety program in an effort to better inform consumers about possible risks. Some of these changes were made possible by 2007 legislation authorizing the FDA to monitor and report on the safety of new drugs more rigorously. From 2000 to 2010, the FDA’s public database of reported side effects grew from 200,000 to nearly 700,000. As a result, newer drugs may have a longer list of side effects than older ones – but that doesn’t mean that newer drugs are more risky.

Progressive multifocal leukoencephalopathy (PML), a life-threatening brain disease caused by activation of an otherwise harmless virus, is an example. Dr. Fraenkel says that a handful of people with RA have developed PML on the biologic drug rituximab (Rituxan). She estimates the risk to be about 3 in 100,000. However, she notes, “just as many people with lupus have developed PML and have never been on biologics, but have been treated with cyclophosphamide,” a drug to treat kidney disease and other conditions. 

The occurrence of PML with rituximab has resulted in a black box warning due to the way serious side effects are now reported to the Food and Drug Administration. Cyclophosphamide, an older drug that predates the new safety reporting procedures, doesn’t carry the warning.

“Patients are much more frightened by newer drugs that are associated with these rare, serious side effects because of the different ways of reporting,” says Dr. Fraenkel. “But the uncertainties surrounding the side effects are the same.”

Take Steps to Reduce Risks

Just because a drug comes with certain risks doesn’t mean there’s nothing you can do about them. Many serious side effects can be reduced or prevented through smart strategies and a collaborative effort between you and your doctor.

Some side effects are silent. Others may start out so small they aren’t noticed. Simple lab tests and exams often can spot early signs of a problem so measures can be taken to avoid or minimize the problem. For example:

  • Because methotrexate can affect the liver, RA treatment guidelines recommend testing for liver problems before starting and regularly while using methotrexate. To reduce the risk of liver problems, talk to your doctor about supplementing with folic acid.
  • Osteoporosis is a major risk of long-term corticosteroid use. Guidelines recommend assessing total risk for bone loss (from all causes, including corticosteroids) and monitoring bone mineral density when corticosteroids are used for three months or longer. If corticosteroids cannot be stopped and you are at risk for complications from bone loss, talk with your doctor about options for supporting bone health, such as medications, supplements and lifestyle changes.
  • There is now good evidence that biologic agents do not increase the risk of most cancers, including lymphoma. However, they do appear to increase the risk of skin cancer, so people taking biologics should see a dermatologist at least yearly for a thorough exam.
  • To help reduce the risk of serious infections with biologic agents, make sure you are up to date on all recommended vaccinations, such as those against pneumonia and the flu. Also, be vigilant about reporting anything more than the sniffles, as early treatment of airway infections can help prevent a more serious problem requiring hospitalization. A fever that lasts longer than a day or signs of a skin or urinary tract infection also should be evaluated promptly.
  • If you use pain medications, know what dose is safe for you and how to recognize acetaminophen as an ingredient.

Speak Your Mind

Even the most informed patient may worry about starting a new drug or continuing with a therapy that causes bothersome side effects. It’s important that you let your doctor know your concerns; there may be alternative treatments or dosages you can try.

“Doctors and patients often approach decisions about medications differently,” says Dr. Fraenkel. Doctors focus on finding the best treatment plan and may classify some side effects as less serious when weighing drug risks against disease risks. But to move ahead with a plan, a doctor needs to understand a patient’s perspective.

“It’s not in your best interest to keep quiet,” says Dr. Fraenkel. “It’s much better to tell your doctor what worries you and why.” Then your doctor can begin to put what is important to you in context with what is important medically.

If, after an honest discussion with your doctor, you decide you no longer want to take prescription drugs for your condition, make sure to tell your doctor. Stopping suddenly can have its own side effects, and it’s important for you to make the decision fully informed about what the disease, untreated, can do to your body over the long-term.

“People often don’t think about things getting worse over time if their disease isn’t optimally treated,” says Dr. Fraenkel. “Refusal of therapy is not just refusing a risk. It’s also accepting, theoretically, increased risk of damage over time. That is why doctors feel strongly about pushing treatment, whereas patients may be more reluctant.” She recommends always discussing with your doctor what your life would be like if you chose not to take medication.

Dr. Curtis agrees. “The flip side of the coin – the risks of doing nothing or staying the course – often is missed.”