Fluoroquinolones Safety Concerns and Warnings (Part I) – Blog Post by Asrar Qureshi

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FLUOROQUINOLONES

Fluoroquinolones class of drugs was introduced in 1980s. Quinolones such as nalidixic acid (Negram®) had been available much before that. Later pipemidic acid (Urixin®) was added. The first major fluoroquinolone was norfloxacin (Noroxin®). A battery of fluoroquinolones was then introduced on the world market in quick succession.

Pakistan also boasts a large market share captured by quinolones. Almost all products from this category have sold very well in Pakistan market, some more than others. Ofloxacin, Ciprofloxacin, Levofloxacin and Moxifloxacin are the most-selling fluoroquinolones; the cumulative sales running into billions of rupees.

Even at the time of introduction, several serious side effects were known; for examples, effects on central nervous system. Couple of years later, a new side effect was added, which was effect on blood sugar level. Fluoroquinolones could sway the blood sugar on either side; reduce it or increase it. With the passage of time and increased world-wide usage, more new side effects were reported.

We shall see how the side effect profile of fluoroquinolones has emerged over time.¹

• [July 2008] The FDA first added a Boxed Warning to fluoroquinolones for the increased risk of tendinitis and tendon rupture. ¹
• [February 2011] The risk of worsening symptoms for those with myasthenia gravis was added to the Boxed Warning. ¹
• [August 2013] The agency required updates to the labels to describe the potential for irreversible peripheral neuropathy (serious nerve damage). ¹
• [November 2015] An FDA Advisory Committee discussed the risks and benefits of fluoroquinolones for the treatment of acute bacterial sinusitis, acute bacterial exacerbation of chronic bronchitis and uncomplicated urinary tract infections based on new safety information. The new information focused on two or more side effects occurring at the same time and causing the potential for irreversible impairment. The advisory committee concluded that the serious risks associated with the use of fluoroquinolones for these types of uncomplicated infections generally outweighed the benefits for patients with other treatment options. ¹
• [12 May 2016]drug safety communication advised that fluoroquinolones should be reserved for these conditions only when there are no other options available due to potentially permanent, disabling side effects occurring together. ¹
• [26 July 2016] The U.S. Food and Drug Administration (FDA) approved changes to the labels of fluoroquinolone antibacterial drugs for systemic use (i.e., taken by mouth or by injection). These medicines are associated with disabling and potentially permanent side effects of the tendons, muscles, joints, nerves, and central nervous system that can occur together in the same patient. As a result, it revised the Boxed Warning, FDA’s strongest warning, to address these serious safety issues. FDA determined that fluoroquinolones should be reserved for use in patients who have no other treatment options for acute bacterial sinusitis, (ABS), acute bacterial exacerbation of chronic bronchitis (ABECB), and uncomplicated urinary tract infections (UTI) because the risk of these serious side effects generally outweighs the benefits in these patients. For some serious bacterial infections, the benefits of fluoroquinolones outweigh the risks, and it is appropriate for them to remain available as a therapeutic option.²
• [07 October 2018] The Food and Drug Administration (FDA) is strengthening the current warnings in the prescribing information that fluoroquinolone antibiotics may cause significant decreases in blood sugar and certain mental health side effects.³
• [20 December 2018]A U.S. Food and Drug Administration (FDA) review found that fluoroquinolone antibiotics can increase the occurrence of rare but serious events of ruptures or tears in the main artery of the body, called the aorta.  These tears, called aortic dissections, or ruptures of an aortic aneurysm can lead to dangerous bleeding or even death.  They can occur with fluoroquinolones for systemic use given by mouth or through an injection. Fluoroquinolones should not be used in patients at increased risk unless there are no other treatment options available.  People at increased risk include those with a history of blockages or aneurysms (abnormal bulges) of the aorta or other blood vessels, high blood pressure, certain genetic disorders that involve blood vessel changes, and the elderly.⁴

To be continued…..

Reference:

1. https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm513183.htm
2. https://www.fda.gov/Drugs/DrugSafety/ucm511530.htm
3. https://www.fda.gov/downloads/Drugs/DrugSafety/UCM612834.pdf
4. https://www.fda.gov/Drugs/DrugSafety/ucm628753.htm