Critical drug shortages caused by COVID-19

First, it was toilet paper and antibacterial wipes. Then, medical masks and respirators. And for a while now, the COVID-19 pandemic has sparked a shortage of many essential drugs.

As you might expect, the drugs needed to treat patients with the novel virus were the first ones to disappear. But now, drugs that are only remotely related to the pandemic are becoming scarce.

“The active pharmaceutical ingredients for many commonly used medications come from China, and many of our generics are manufactured and imported from other countries, including India. Since the pandemic has affected manufacturing and exports worldwide, the shortages exemplified by antimicrobials and sedatives will soon impact numerous medications unrelated to the treatment of COVID-19,” predicted researchers in a commentary published in Mayo Clinic Proceedings.

Drug shortages are tracked by both the FDA and the American Society of Health-System Pharmacists (ASHP). Here are seven notable drugs now in short supply, according to the FDA and ASHP.

Hydroxychloroquine

Hydroxychloroquine sulfate tablets are in short supply, despite being an unsuccessful treatment for COVID-19.

In March, results of a small (n=36), open-label, non-randomized clinical trial in France showed that hydroxychloroquine (plus azithromycin) reduced viral load. Between February and March, prescriptions spiked 86%, according to researchers. The therapy was further touted by the media and President Trump. However, no rigorous clinical studies have since shown that hydroxychloroquine is an effective treatment for COVID-19. At least three controlled, large trials showed no efficacy in patients receiving the drug. In fact, it caused a higher risk of cardiovascular complications in COVID-19 patients.

Hydroxychloroquine is effective for lupus, rheumatoid arthritis, and other autoimmune diseases, for which it’s commonly prescribed. A shortage of this drug poses a danger for these patients. Without hydroxychloroquine refills, many patients with lupus will experience flare-ups and may develop irreversible organ damage, noted authors from Weill Cornell Medicine in a JAMA Health Forum article.

“As we have learned from consumer behavior with toilet paper, hand sanitizers, and masks during the COVID-19 crisis, even as the supply of hydroxychloroquine increases, barriers for patients with lupus who are vulnerable may persist. Stockpiling of hydroxychloroquine to prevent or treat COVID-19, despite very limited evidence of benefit, thus exposes these patients to enormous risks,” they wrote.

Manufacturers that make hydroxychloroquine, like Sandoz and Teva, have the drug on back order and can’t estimate a release date for more supply.

Azithromycin

There’s currently a shortage of azithromycin tablets and injections, according to the FDA and ASHP.

Azithromycin is indicated for treating a wide range of bacterial infections, but it’s also been used in patients with respiratory infections because of its potential immunomodulatory effects. As noted above, azithromycin has been used in conjunction with hydroxychloroquine for treating COVID-19. Between February and March 2020, the number of patients who received both hydroxychloroquine and azithromycin prescriptions skyrocketed a staggering 1044%.

Fortunately, the shortage of this highly useful antibacterial drug may soon be coming to an end, as the FDA recently noted that several pharma manufacturers have it available again.

Albuterol

Supplies of albuterol sulfate inhalers are low due to high demand. “The shortage is occurring because of the increased use of albuterol inhalers in hospitals for COVID-19 and suspected COVID-19 patients to help with respiratory issues,” warned the American College of Allergy, Asthma and Immunology.

Instead of using nebulizers—which could transport coronavirus droplets in the air—hospitals have been buying albuterol inhalers for individual patients. But this strategy has strained supplies of the inhalers for people who typically use them, such as those with asthma or chronic obstructive pulmonary disease.

“Albuterol is the primary rescue medication to treat asthma attacks and without albuterol, people are more likely to experience asthma attacks that they can’t control,” said Kenneth Mendez, president and CEO of the Asthma and Allergy Foundation of America. “This could potentially increase hospitalizations.”

In early April, the FDA approved the first generic albuterol inhaler to help increase the supply of the medicine.

Midazolam

The shortage of midazolam is due directly to the COVID-19 pandemic. Midazolam is a benzodiazepine sedative used to sedate patients having minor surgery, dental work, or other medical procedure—including critical care patients with COVID-19 who need to be intubated for mechanical ventilation.

According to the FDA Drug Shortages database, several manufacturers have midazolam on back order or are attempting to ramp up production to meet demand. To further increase supply, the FDA has also allowed Pfizer’s midazolam to be used past its labelled expiration date.

Fentanyl

Illegal fentanyl is one of the main drivers of the current opioid epidemic. But legally manufactured fentanyl is now in high demand for patients with COVID-19.

Shortly before the coronavirus pandemic struck, the US Drug Enforcement Agency called for cutting authorized fentanyl production by 31%. But the agency reversed that in early April when it ordered a 15% increase in the production of fentanyl and other controlled substances used in COVID-19 treatment.

Fentanyl injection is a first-line agent for pain relief in non-intubated patients with COVID-19. In intubated patients, fentanyl infusion is often the initial therapy for analgesia. Long-term use of fentanyl is avoided due to potential opioid addiction.

Several drug makers have fentanyl available in limited supply or on back order.

Dexamethasone

Last month, UK researchers released the results of the RECOVERY trial, in which they showed that a daily 6 mg dose of dexamethasone (either oral or intravenous) reduced deaths by 36% in COVID-19 patients on ventilators, and by 18% in patients on oxygen but not on ventilators. (The researchers found that dexamethasone offered no benefit—and possibly harm—in patients who didn’t require oxygen.)

The injection form of this common steroid has been in short supply ever since those results came out. That could be a problem because clinicians typically prefer intravenous dexamethasone in sicker patients, such as those on ventilators, because the oral form is less consistent and more difficult to administer in this population. Also, the injectable form is more complicated to produce than the pill form.

Consequently, most manufacturers of injectable dexamethasone have the drug on back order, with new supplies coming in late summer or date unknown. 

Famotidine

Could a popular over-the-counter heartburn medication reduce COVID-19 deaths? That’s what the American Journal of Gastroenterology recently reported in a new preprint article.

“The main finding of our single-center, retrospective study of hospitalized COVID-19 patients is that use of famotidine is associated with improved clinical outcomes including lower in-hospital mortality and a lower composite endpoint of death and/or intubation,” wrote researchers from Hartford Hospital, in Hartford, CT.

An additional finding was that COVID-19 patients taking famotidine also had lower levels of serum markers for serious disease, including serum ferritin, CRP, and procalcitonin levels.

How does a heartburn medication attack a viral respiratory infection like COVID-19? The researchers speculated that “famotidine’s effect is achieved via its antagonism or inverse-agonism of the histamine-2 receptor, inferring that the SARS-CoV-2 infection that results in COVID-19 is at least partially mediated by pathological histamine release and perhaps dysfunctional mast cell activation,” the authors wrote.

“Lower levels of ferritin, CRP, and procalcitonin in famotidine-treated patients in this study are compatible with the hypothesis that the drug may limit the abnormal excessive cytokine release from an uncontrolled immune activation,” they added.

The drug, with the brand name Pepcid, has been flying off the shelves since an observational study, which reached similar conclusions, was published in Gastroenterology in late May. Although it’s an over-the-counter drug, hospitals still order it, and both tablet and injection forms are now in shortage, according to the FDA.

More shortages

The seven drugs listed above aren’t the only ones experiencing shortages. Dozens of drugs—like heparin, furosemide, propofol, and norepinephrine injections—are all in short supply due to the pandemic.