There’s no shortage of medications that can offer relief to people with arthritis. But with so many options to choose from, it’s important that you get the right medication for your particular situation. Each drug has potential drawbacks to go along with the benefits. No matter what medication your doctor recommends, make sure you understand the risks and follow the instructions exactly. Different types of arthritis require different medical approaches.
Osteoarthritis is the most common form of arthritis. The main problem in osteoarthritis is that cartilage (the stiff, rubbery substance that provides a cushion between two bones) starts wearing down after years of hard use, causing pain and stiffness. Physical therapy, gentle exercise, and weight loss can help relieve symptoms, but in some cases joint surgery or injections may be necessary. Drugs to treat this condition focus mainly on pain relief.
Rheumatoid arthritis works differently: It’s an autoimmune disorder, which means that the immune system is mistakenly attacking your own body’s tissue, in this case your joints. It can strike at an earlier age than osteoarthritis, and may even show up in children. Like other autoimmune conditions, rheumatoid arthritis is more common in women. In rheumatoid arthritis, the synovial membranes of your joints get inflamed. The immune cells also release certain enzymes that eventually chew away the cartilage. New studies suggest that rheumatoid arthritis needs to be treated aggressively early on for the best long-term results. Some rheumatoid arthritis medications target the wayward immune response in addition to controlling the pain.
Examples: Tylenol, generics
Doctors have known for a long time that acetaminophen — when used correctly — is one of the safest pain relievers around. For this reason, it’s often doctors’ first choice for treating chronic osteoarthritis pain. Since it doesn’t help reduce inflammation, people with rheumatic arthritis aren’t likely to benefit from taking acetaminophen alone.
Possible side effects: Too much acetaminophen can damage your liver, and taking more than 500 mg a day has been shown to raise blood pressure. Because acetaminophen is an ingredient in many over-the-counter preparations like cold medicines, it’s not always easy to be sure how much you’re getting in a day, so be sure to read labels carefully. Also, the Food and Drug Administration (FDA) estimates that 14,000 people wind up in the emergency room each year with accidental acetaminophen overdoses. So even if you don’t have to worry about high blood pressure, the FDA advises that you never take more than 4 grams — or 4,000 milligrams — a day. Too much acetaminophen can cause severe liver damage, which is why the American Liver Foundation recommends a maximum dose of no more than 3 grams (3,000 milligrams) a day if you are taking it on a long-term basis.
Possible cautions: You should not take acetaminophen if you’re a heavy drinker (you regularly have three or more alcoholic drinks a day), and your doctor should also know if you have a history of liver disease. Large doses of acetaminophen can overload and damage your liver — especially if it has to detoxify alcohol as well.
But whether you drink alcohol regularly or not, it’s a good idea to keep tabs on the amount of acetaminophen you take every day. A study reported in the journal Hepatology followed 662 patients with acute liver failure over a period of six years and found that acetaminophen was the most common cause of liver poisoning. Almost half of those cases were unintentional overdoses. Regularly using this drug can also enhance the action of the blood thinning drug warfarin (Coumadin), possibly leading to internal bleeding.
Aspirin and common NSAIDs
Examples: Anacin, Bayer, and Bufferin (aspirin), Advil, Motrin (ibuprofen), Aleve (naproxen), Nalfon (fenoprofen)
For decades, NSAIDs (non-steroidal anti-inflammatory drugs) have been the cornerstone of treatment for many different kinds of arthritis. But just because something is available over the counter doesn’t mean it’s perfectly safe. Large doses of NSAIDs — or smaller doses over a long time — can cause bleeding stomach ulcers, as well as kidney and liver damage. This is often more of a concern for people with rheumatoid arthritis. If your doctor recommends any NSAID, you’ll need to have regular checkups to make sure the drugs aren’t harming you. Taking a proton pump inhibitor like Nexium (esomeprazole) with NSAIDs lowers the risk of developing stomach ulcers. Taking an NSAID with food will also help to reduce the chances of having an upset stomach.
Possible side effects: The FDA requires that manufacturers of prescription NSAIDs warn consumers of the possible side effects, which include potentially life-threatening stomach bleeding and increased risk of heart attack or stroke.The agency also recommended that NSAIDs not be prescribed for anyone who has recently undergone coronary artery bypass surgery.
The FDA says that available evidence doesn’t indicate an increased risk for cardiovascular problems with short-term use of OTC NSAIDs, but it’s important to discuss possible side effects with your doctor. The agency also wants manufacturers to emphasize the importance of sticking to the recommended dosage and duration of use. One important note: The FDA advises that if your doctor has instructed you to take a daily aspirin to reduce the risk of heart problems, you should NOT stop taking it unless your doctor says so. Aspirin has been shown to have certain heart-protective properties. If you have any questions about your regular aspirin dose, call your doctor, but continue taking it in the meantime.
Here are some other things to be aware of if you take NSAIDs. A study found that women taking a moderate high dose of various NSAIDs per day were up to 78 percent more likely to develop high blood pressure than women who didn’t take the medication. So if you take NSAIDs every day, keep tabs on your blood pressure. Let your doctor know if you have an allergy to aspirin or similar drugs. You should tell your doctor if you take a blood thinner such as Coumadin (warfarin) because aspirin is also a blood thinner. High doses of aspirin can cause ringing in the ears. NSAIDs and aspirin can also cause or aggravate asthma.
Other side effects can include stomach cramps, diarrhea, indigestion, vomiting, and headache. Because internal bleeding can occur without pain, call your doctor immediately if you notice black stools. If you vomit blood or any substance that looks like coffee grounds, or suddenly feel weak, sweaty, and dizzy, get emergency help.
Like many drugs, NSAIDs are processed in the liver and excreted through the kidneys, so these organs should be monitored carefully. Drinking alcohol can overwhelm and damage your liver, so it’s best to cut down. NSAIDs can enhance the action of diabetes medicines and lead to low blood sugar, so diabetics need extra attention. In large doses, these drugs (except for aspirin) can also worsen high blood pressure over time.
Examples: Celebrex (celecoxib)
Doctors had high hopes for this class of drugs for their arthritis patients who needed long-term pain relief, but worries about heart problems prompted a 10-year study involving more than 24,000 patients. However, the study, published in November 2016 in the New England Journal of Medicine, found that Celebrex was no more harmful to the heart than were ibuprofen and naproxen. An FDA panel reiterated that conclusion again in 2018.
Celebrex is a type of NSAID called a COX-2 inhibitor because it targets that particular component of the inflammation process. (Other NSAIDs target both COX-1, which is found everywhere in the body, and COX-2, which is concentrated in inflamed areas.) Celebrex was also found to be safer for kidney function.
Possible side effects: The Celebrex label includes information about an earlier study that found an increased risk of heart problems in some participants. The American Heart Association also cautions that the drug was used for arthritis patients rather than heart patients and questions whether the study proved the drug safe for patients with heart problems. For this reason, some experts warn against giving Celebrex to arthritis patients who also have heart problems.
The FDA is encouraging doctors to prescribe the lowest effective dosage of Celebrex possible for the shortest duration possible to help prevent side effects.
There are a variety of other NSAIDs available by prescription, including Relafen (nabumetone), Mobic (meloxicam), Ponstel (meclofenamate sodium), Indocin (indomethacin), and Arthrotec (diclofenac sodium/misoprostol). Some of these are gentler on the stomach than aspirin, but each has its own set of side effects, often serious. Their prices range between the over-the-counter NSAIDs and the COX-2 inhibitors.
Non-biologic disease-modifying anti-rheumatic drugs (DMARDs)
These are usually slow-acting and work by interrupting the complex immune response that damages your joints in rheumatoid arthritis and other rheumatic conditions. Each works a little differently and side effects vary slightly, but all interfere with your immune system. The idea is that improving your rheumatoid arthritis will be worth the toll on your body — weakened immunity against infection and other side effects. These drugs often take one to six months to take full effect, so they are also called slow-acting anti-rheumatic drugs. Many rheumatologists start their patients off on one of the first three drugs listed below. Finding the right drug (or combination) for a person can be a long process of trial and error.
Xeljanz, one of the newer drugs in this class, is used to treat moderate to severe rheumatoid arthritis, particularly in adults who have tried methotrexate without success. It is also used for treating psoriatic arthritis.
Xeljanz targets a specific cellular process involving immune respose and is often given to patients who are not responding to other frontline drugs. A 2013 analysis of clinical studies showed that Xeljanz was more effective than placebo and also worked better for patients than a competing drug Humira (adalimuumab).
Possible side effects: upper respiratory tract infections, headache, diarrhea, and cold symtoms such as a sore throat or stuffy or runny nose. Xeljanz may interact with some supplements such as St. John’s wort, and some antidepressants, antifungals, and Hepatitis C medications.
Antimalarial drugs are commonly used to treat immune disorders, and the most commonly prescribed one is Plaquenil (hydroxychloroquine). It helps 30 to 40 percent of all rheumatoid arthritis patients who try it, but takes a long time to show improvement — one to six months. Hydroxychloroquine is a common first choice because it causes fewer side effects.
Possible side effects: The most common side effects include nausea, vomiting, diarrhea, and headache. In rare cases, it can damage the muscles of the heart. At higher doses it can sometimes cause retinal damage over time, so regular eye exams are important.
This drug suppresses the immune reaction in rheumatoid arthritis and is also an anti-inflammatory. About 60 percent of people with rheumatoid arthritis respond to this drug, but it often causes side effects. It takes at least one month to see improvement while on this drug.
Possible side effects: Patients are usually monitored closely for the first three months because of side effects, which include skin rash, headache, nausea, vomiting, and reduced sperm count. Some less common side effects are anemia, reduced white blood cell counts, fever, itching, and skin problems.
First used to treat various kinds of cancers, methotrexate is now commonly prescribed — usually in combination with NSAIDs — to treat rheumatoid arthritis. For active rheumatoid arthritis that doesn’t respond to NSAIDs, methotrexate is often the next treatment of choice. It can start to work within a month, which is much sooner than some other options such as antimalarials or gold salts. A recent study found that the sooner methotrexate treatment is started, the more it helps. This finding may be true for other drugs as well, so rheumatologists are likely to treat rheumatoid arthritis early and more aggressively.
Like most drugs used to treat rheumatoid arthritis, methotrexate works by mildly weakening the immune system. Patients who don’t respond to methotrexate alone may be prescribed the drug in combination with other drugs such as cyclosporine. Taking folic acid can help protect against some side effects of methotrexate. While you’re on this drug, your doctor will monitor your liver function and possibly your blood cell counts, too.
Possible side effects: Methotrexate can cause an upset stomach, nausea, vomiting, diarrhea, and unusual bleeding (vomiting blood, as well as blood in the urine or stool). It can cause liver problems, so you should tell your doctor if you have a history of liver disease or alcoholism. Rarely, it can also cause lung problems. Because methotrexate weakens immunity and can lower white blood cell counts, you’re more at risk for infections and will have a harder time fighting them off. Be sure to tell your doctor if you have an infection or a weakened immune system. Also, talk to your doctor if you’re planning to have a child. Methotrexate can impair fertility in both men and women, and has the potential to cause birth defects.
Leflunomide is an option for people who can’t take methotrexate or who don’t respond to it, and improvement takes one to two months.
Possible side effects: This drug causes liver enzymes to be higher than normal in 5 percent of users (60 percent of those on combination methotrexate and leflunomide) indicating possible liver damage. Leflunomide can cause diarrhea, skin rashes, hair loss, and birth defects. Leflunomide can stay in the body for up to two years, so if you’re a woman on this drug and you want to have a baby, you’ll need to talk to your doctor before you try to conceive.
Example: Enbrel (etanercept), Remicade (infliximab), Humira (adalimumab), Kineret (anakinra).
These high-tech drugs — products of genetic engineering — work by targeting particular parts of the inflammation reaction. The first three drugs target tumor necrosis factor-alpha (TNF-alpha), a naturally occurring protein that plays a key role in checking tumor growth, and is also involved in joint inflammation. Anakinra is another genetically engineered drug. It blocks a different agent in the synovial inflammation process. It’s an IL-1 receptor antagonist, which means it blocks the receptor for IL-1 on certain immune cells, sort of like jamming a lock. This keeps unwanted immune proteins from doing their inflammatory work.
Biologic response modifiers are especially helpful for people with mild to moderate rheumatoid arthritis who aren’t responding to other drugs. However, they can dampen the immune system significantly, and if you suffer from chronic infections, have a history of exposure to tuberculosis, or are otherwise at risk for infections, you should probably not take this drug.
TNF-alpha blockers are often prescribed in combination with methotrexate. Infliximab is taken intravenously, and etanercept and adalimumab are injectable drugs, so are fairly inconvenient and very expensive. On the bright side, they usually start to take effect within two weeks, and work for more than half of all people who try them. These drugs can also slow the damage of rheumatoid arthritis better than methotrexate alone.
Possible side effects: All can raise the risk of serious infections because they suppress your immune system in a specific way. Your doctor should know if you have an active infection or have been exposed to tuberculosis in the past. If you notice any signs of an infection, see your doctor right away. Etanercept, adalimumab, and anakinra can commonly cause mild to moderate reactions at the injection site consisting of pain, swelling, and redness. Infliximab may aggravate heart disease and increase the likelihood of congestive heart failure. Because these drugs interfere with the way your body fights cancer they pose a potential cancer risk. In fact, the FDA mentioned an increase in lymphoma among some patients taking Remicade in controlled studies, leading the agency to order manufacturers of all TNF blockers to cite the risk in their warning labels. Patients with asthma or chronic obstructive pulmonary disease have higher rates of lung infections on anakinra.
Examples: prednisone (Deltasone, Orasone), methylprednisolone (Medrol) These powerful medications — either taken orally or sometimes injected into a joint — ease inflammation and put the brakes on the immune system. They offer rapid, dramatic relief of rheumatoid arthritis, but are not a good choice for long-term therapy because of their wide range of serious side effects. Corticosteroids are often prescribed during severe flare-ups or when other drugs aren’t working. Your doctor will start lowering your dosage as soon as the disease seems to be under control. You’ll need regular checkups to make sure the benefits of the drugs outweigh the risks.
Possible side effects: Corticosteroids can be very hard on the body, especially when taken at high doses for long periods of time. Side effects can include weakened immunity (and increased risk of infection), mood changes, weight gain, and ulcers of the esophagus. Corticosteroid use impairs wound healing of the skin, and can lead to increased bruising, sweating, and stretch marks. Acne, increased body hair, and “moon face” are other cosmetic problems with corticosteroids. Potential long-term complications include osteoporosis, diabetes, cataracts, and hypertension (which increases the risk of heart disease, kidney damage, and stroke). People on these drugs are monitored for a variety of complications.
Examples: Imuran (azathioprine), Neoral (cyclosporine), Cytoxan (cyclophosphamide), Cuprimine (penicillamine)
Often used to prevent rejection after organ transplant, Imuran (azathioprine) and Neoral (cyclosporine) are immune suppressants that are sometimes used to treat arthritis when other drugs have failed. They’re not a first choice treatment because of their side effects, and because broadly suppressing the immune system also leaves you prone to infections. Cytoxan (cyclophosphamide) is an anticancer drug with a wide range of serious side effects, so it is rarely used for rheumatoid arthritis.
Penicillamine is an older drug derived from the antibiotic penicillin. Once commonly used for treating rheumatoid arthritis, now it’s rarely used because the dose needs to be increased slowly each month, and it takes four to six months to start working. Researchers are also studying minocycline (a tetracycline antibiotic) because it may be useful in combination with methotrexate at a lower cost than some of the new biologic drugs.
Possible side effects: These vary by drug. Immune-suppressing drugs can increase your risk of infections. Imuran (azathioprine) can cause digestive system problems including nausea and vomiting. Cyclosporine is highly toxic and can cause high blood pressure and kidney damage, but its more common side effects include headache, swollen gums, sensitivity to sunlight, and tremors. Cyclophosphamide can cause nausea, vomiting, rash, hair loss, temporary sterility (in men), and bladder toxicity (rarely). Side effects from penicillamine include nausea, upset stomach, and kidney damage.
Johns Hopkins Arthritis Center, Rheumatoid Arthritis Treatment
Graedon, J. Are All Arthritis Drugs Including Celebrex Right for the Heart? The People’s Pharmacy, November 14, 2016.
U.S. Food and Drug Administration. FDA approves new drug for rheumatoid arthritis.
Saag KG et al. American College of Rheumatology 2008 Recommendations for the Use of Nonbiologic and Biologic Disease-Modifying Antirheumatic Drugs in Rheumatoid Arthritis. Arthritis and Rheumatism (Arthritis Care and Research). Vol. 59, No. 6, pp 762784.
American Liver Foundation. The American Liver Foundation Issues Warning on Dangers of Excess Acetaminophen.
Mayo Clinic. Peptic ulcer: Treatment and drugs.
Suh DC et al. Co-prescribing of proton pump inhibitors among chronic users of NSAIDs in the UK. Rheumatology. 47(4):458-463.
Food and Drug Administration. Early Communication About an Ongoing Safety Review of Tumor Necrosis Factor (TNF) Blockers (marketed as Remicade, Enbrel, Humira, and Cimzia.
American Academy of Family Physicians. Prescription non-steroidal anti-inflammatory drugs.