A shortage of an injectable version of the drug methotrexate has been all over the news in 2012, sparking outrage and concern on behalf of children with a certain type of leukemia who can’t get their life-saving medication. But some people who have inflammatory types of arthritis and rely on the drug to keep their disease under control are also concerned about access to methotrexate.

“For the most part, this should be a manageable situation for arthritis patients,” says Donald Miller, PharmD, a professor of pharmacy practice at North Dakota State University, in Fargo. That’s because the majority of people with arthritis who take methotrexate – which is used in the treatment of rheumatoid arthritis, psoriatic arthritis, lupus and certain types of juvenile arthritis – use the pill form. There is no shortage of that right now.  

The root of the problem lies with the preservative-free, injectable form of methotrexate. Very high doses of it are used to treat pediatric cancer patients, and that is the form of the medication that is running dangerously low.

And now that shortage is increasing demand on other, injectable forms of methotrexate. “When you get shortages with even one product, it does have a ripple effect on everything else,” Miller says.

In this case, the form of injectable methotrexate with preservatives is being affected. It is used by arthritis patients (at much lower doses than cancer patients) when methotrexate pills don’t provide enough relief or cause unpleasant side effects. Some people may still be able to fill their prescriptions for injectable methotrexate at certain locations. For those who can’t, there are other options that may work for them until the shortage is resolved – which could be within two weeks, federal health officials said Thursday.

The shortage developed after one of the major suppliers of the preservative-free injectable medication, Ben Venue Laboratories, shut down an Ohio plant in November because of manufacturing problems identified during inspections by the Food and Drug Administration, or FDA, and other global regulatory agencies. Manufacturers of the type with preservatives are now reporting shortages due to increased demand.

In response to growing concerns that the medication shortage will worsen, the FDA said that Ben Venue will now release its emergency supplies of the injectable, which were produced before the shutdown, and two other manufacturers will step up production.
 

“The issue of methotrexate is and has been of the highest priority for the FDA, and we’ve been working hard to make sure that patients continue to get the medicine they need when they need it,” writes Patricia El-Hinnawy, a public affairs officer with the FDA, in an email response to questions from Arthritis Today.  

The Impact on Arthritis Patients

Although the impact of the shortage is greatest on cancer patients, arthritis patients around the country are feeling it, too.  

One reason is that “simply switching” from injectable to oral methotrexate isn’t always so simple. “We have switched everyone back to oral methotrexate. Most have done well, but there are some patients that were on injections because they could not tolerate pills – usually [due to] nausea. For these patients, the shortage could be a big problem,” says Leslie J. Crofford, MD, chief of the division of rheumatology at the University of Kentucky, in Lexington.

Some patients who are trying to fill or refill prescriptions for the injectable form are striking out. “We have had some patients from outside our area who [have called us for help because] they have not been able to obtain methotrexate at local pharmacies in some places,” says Eric Matteson, MD, chair of the division of rheumatology at the Mayo Clinic in Rochester, Minn.

People with arthritis in larger cities with many pharmacies may have better luck. “I had a patient who had some difficulty getting her injected methotrexate at her usual pharmacy. However, she was able to find another pharmacy close by that had available stock,” says Jon T. Giles, MD, a rheumatologist and an assistant professor of medicine in the division of rheumatology at Columbia University in New York City.

If you don’t find an alternate pharmacy that has the medication in stock, experts suggest asking your doctor if he or she knows of other suppliers. If not, your best option may be to talk with your doctor about the pills – even if you’ve tried them before and could not tolerate them well. Dr. Giles says there are certain “tricks” that can help, such spreading the pills out over a single day, taking them with food and/or taking them at night.

If the methotrexate shortage continues, and patients are having an especially difficult time on the oral form, alternative treatments – such as other disease-modifying antirheumatic drugs and corticosteroids – may need to be explored.
 

For most people on methotrexate, however, the pills are well tolerated. David Pisetsky, MD, PhD, a rheumatologist and professor of medicine at Duke University in Durham, N.C., says the shortage hasn’t yet affected his patients, but if it does, he would prescribe the pills.

“If I couldn’t get them the injection, I’d put them on the oral. It’s the same drug,” he says. It might not be as desirable for some patients, but he thinks it would work for most on a short-term, temporary basis.

Addressing Other Shortages

Methotrexate isn’t the only arthritis medication currently affected by shortages. Voltaren Gel, or topical diclofenac – a rub-on nonsteroidal anti-inflammatory medication – was also on the FDA's drug shortage list in early February 2012.

The FDA says there is no easy answer to these shortages.

“The problem of drug shortages is complex and stems from economic, legal, regulatory, policy and clinical decisions that are deeply interconnected,” El-Hinnawy explains. “However, the most common cause underlying most drug shortages relates to problems maintaining high quality manufacturing. While there is no simple solution to resolving drug shortages, we are doing all that we can to make sure patients have access to the critical medicines they need when they need them.”

Late last year, the Government Accounting Office in Washington, D.C., released a report saying the FDA should have more authority to require companies to disclose impending shortages.

“One thing that would be really important is if a company producing the drug [foresees] difficulty with production or distribution, it would be nice to let the FDA and public know that could be a concern,” Dr. Matteson says.

The FDA says there has been progress on this front as a result of an Executive Order the President signed in October. Among other things, it directs the FDA to require drug manufacturers to provide adequate notice of manufacturing discontinuances or other actions that could lead to critical shortages, and it encourages companies to voluntarily notify the FDA about potential shortages. The FDA says it has prevented 114 drug shortages since then, which it attributes to increased voluntary notifications from drug makers. Before the Executive Order went into effect, the FDA says it got about 10 voluntary notifications a month. The month after it was instituted, it received six times as many.