Enter drug name:

Check the interactive ADRS Chart!

Risk of Tendon Rupture with Fluoroquinolones antibiotics

Levaquin (Levofloxacin) is in a group of antibiotics called fluoroquinolones. Levofloxacin is used to treat bacterial infections that cause bronchitis, pneumonia, chlamydia, gonorrhea, skin infections, urinary tract infections, and infections of the prostate.

Levaquin has been implicated in cases of Tendon Rupture. While the label of Levaquin lists Tendon Rupture as one of the reported adverse events in post marketing surveillance, no special warning is reflected in the label. Growing awareness of this adverse drug reaction, also associated with other drugs in the same class, has triggered the Office of the Illinois Attorney General, and later Public Citizen (www.citizen.org) to file a petition with the FDA to add a black box warning regarding the risks of Tendinopathy and Tendon Rupture to the product labels of all fluoroquinolone antibiotics.

In their petition, Public Citizen analyzed the FDA's AERS database showing that Tendon Rupture and Tendonitis were associated (relatively) more with fluoroquinolone antibiotics than any other class of drugs. To date, black box warning has not been added to the fluoroquinolones labels.  

We have undertaken a similar analysis of more recent data. The AERS is reported on a quarterly basis but may include reports from previous periods. To make our analysis as independent as possible from that of Public Citizen, we chose the most recent quarter available to us, namely, Q2 2007.

Table 1 shows the prevelance of Tendon disorder reports in the AERS database in Q2 2007. Table 2 shows the distribution of Tendonitis/Tendon Rupture in relationship to Fluroquinolones and other drugs for reports that listed these drugs as 'Primary Suspect'.

 Table 1.   Types of Tendon Pathology

 

 

Table 2.   Tendon Ruptures/Tendonitis by Drug

 

Note: reports in the AERS system are given unique numbers (ISRs). An ISR may consist of several reactions (PTs) which may include both Tendon Rupture and Tendonitis. We have only used one term per ISR. If the different terms were reported for the same patient in two separate ISRs, then both reports were included. Also note that in the AERS, the term ‘TENDONITIS’ appears multiple times in Q4 2007, while there is no ‘TENDINITIS’ in the same quarter. This might be due to the way the FDA codes this term. It seems however that both terms are used in the literature. Thus it is important to use the coded term whenever analyzing the AERS database.

It is quite evident that fluoroquinolones are associated with a relatively large number of Tendon related adverse reactions. The highest number of events on Levaquin might be due to a higher prescription rate for this drug.

More insight into the incidence of adverse reactions of fluoroquinolones can be gleaned by evaluating the profile of adverse drug reactions in terms of percent of total reaction for fluoroquinolones vs. all other drugs. The chart below shows the percent of total adverse reaction reports (approximately 7600 distinct terms) for each adverse reaction term in the AERS database for Q2/2007. The circles represent the percent of each of the fluoroquinolones reactions relative to the total reactions for this class of drugs. The stars represent each of the other drugs' reactions relative to the total reactions of all other drugs. The percentages are sorted from smallest to highest based on all other drugs. We call this chart: ADRS (Adverse Drug Reaction Standard) Chart. In theory, the ADRS chart should be similar to a chart plotted for a population of people that use placebo (or no drug at all) but are askded to report adverse events. Assuming most drugs are only associated with a small and specific reactions, these reactions are diluted when pooled together as in the ADRS chart. Thus the ADRS chart will approximate a placebo chart.

We have noted the reactions associated with Tendon Rupture and Tendonitis. Both are in the range of 1% of all adverse reactions associated with fluoroquinolones. In contrast, these adverse reactions are of relatively low percent (0.01% and 0.03% respectevely) of the total adverse events of all other drugs. In addition, Tendon Pain has high (0.85%) rate for fluoroquinolones as compared with all other drugs (0.003%). Lastly, Arthralgia (pain in the joint) has the highest rate (>2.5%) for fluoroquinolones, where as this event occurs only about 0.3% in all other drugs.

Check the interactive beta version of ADRS!

Read about the case study of the increased cardiovascular risk with Cox-2 Inhibitors