FDA Safety Changes: Fluoroquinolones and Other Antimicrobial Drugs

- Medscape Medical News

09/26/2007 - The US Food and Drug Administration (FDA) has approved safety labeling revisions to advise of the risk for tendon effects in elderly patients receiving fluoroquinolone antibiotics, particularly those receiving concomitant corticosteroids; the risk for potentially fatal hypersensitivity reactions after multiple doses of fluoroquinolone antimicrobials; and the potential of developing Clostridium difficile–associated diarrhea more than 2 months after completion of antimicrobial therapy.

Elderly People at Increased Risk for Fluoroquinolone-Related Tendon Effects

The FDA approved safety labeling revisions in June for certain fluoroquinolone antibiotics to warn of the risk for tendon effects in elderly people, especially those receiving concomitant treatment with corticosteroids, and the rare risk for serious and potentially fatal adverse events that may occur after repeated doses.

Updated product monographs include those for second-generation quinolones ciprofloxacin (Cipro [tablets/oral suspension], intravenous injection [Cipro IV], and extended-release tablets [Cipro XR]; Schering-Plough Corp) and ofloxacin (Floxin tablets; Ortho-McNeil Pharmaceutical, Inc) and the third-generation quinolone levofloxacin (Levaquin tablets, oral solution, injection, and injection in 5% dextrose; Ortho-McNeil).

The FDA previously warned that ruptures of the shoulder, hand, Achilles, and other tendons can occur during therapy or up to a few months after its discontinuation; some reported cases of patients have required surgical repair or resulted in prolonged disability.

Updated information now states that patients older than 65 years are at increased risk for severe tendon disorders and that this risk is further increased by concomitant use of corticosteroids. Therefore, caution is advised when prescribing fluoroquinolones in elderly patients, particularly in those receiving concomitant corticosteroids. Patients should be advised to discontinue therapy if they experience related symptoms and to rest and avoid exercise until tendonitis and tendon rupture have been ruled out.

The agency also previously warned of the risk for serious and occasionally fatal hypersensitivity reactions that often occur after the first dose of a quinolone. These have included cardiovascular collapse, hypotension or shock, seizure, loss of consciousness, tingling, angioedema, airway obstruction, dyspnea, urticaria, and other serious skin reactions.

The FDA now warns of the rare risk for serious and sometimes fatal events after multiple doses. Clinical manifestations may include 1 or more of the following: fever, rash, or severe dermatologic reactions (eg, toxic epidermal necrolysis and Stevens-Johnson syndrome); vasculitis, arthralgia, myalgias, and serum sickness; allergic pneumonitis; interstitial nephritis and acute renal insufficiency or failure; hepatitis, jaundice, acute hepatic necrosis or failure; and anemia (including hemolytic and aplastic), thrombocytopenia (including thrombocytopenic purpura), leukopenia, agranulocytosis, pancytopenia, and other hematologic abnormalities.

Treatment should be discontinued at the first appearance of a skin rash, jaundice, or any other sign of hypersensitivity, and supportive measures should be instituted.

Fluoroquinolones are a group of broad-spectrum antibiotics with good gram-positive and gram-negative coverage indicated for the treatment of infections caused by susceptible strains of designated microorganisms.

Antibiotics Linked to Risk for Clostridium difficile–Associated Diarrhea

The FDA approved safety labeling revisions in June for certain antimicrobials to warn of the risk for Clostridium difficile–associated diarrhea (CDAD).

Updated product monographs include those for sulfamethoxazole/trimethoprim tablets and double-strength tablets (Bactrim and Bactrim DS; Mutual Pharmaceutical Co, Inc); cefadroxil monohydrate tablets, capsules, and oral suspension (Duricef; Warner Chilcott Co, Inc); nitrofurantoin monohydrate/macrocrystals capsules (Macrobid; Proctor & Gamble Pharmaceuticals, Inc); cefpodoxime proxetil tablets and oral suspension (Vantin; Pfizer Global Pharmaceuticals, Inc); ciprofloxacin tablets and oral suspension, intravenous injection, and extended-release tablets (Cipro, Cipro IV, and Cipro XR; Schering-Plough Corp); ofloxacin tablets (Floxin; Ortho-McNeil Pharmaceutical, Inc); and levofloxacin tablets, oral solution, injection, and injection in 5% dextrose (Levaquin; Ortho-McNeil).

Treatment with antibacterial agents such as these can alter the colon's normal flora, leading to overgrowth of C difficile and subsequent release of toxins A and B that contribute to the development of CDAD. Nearly all antibiotics have been implicated in CDAD, which may range in severity from mild diarrhea to fatal colitis.

Because hypertoxin-producing strains of C difficile can be refractory to antimicrobial therapy, they are associated with increased morbidity and mortality and may require colectomy. The FDA advises that CDAD be considered in all patients who present with diarrhea after antibiotic use. Careful examination of medical history is required because of the potential for late-onset disease; cases of CDAD have been reported more than 2 months after completion of an antimicrobial course of therapy.

The FDA notes that current antibiotic therapy for the primary infection may need to be discontinued in patients with known or suspected CDAD. Appropriate fluid and electrolyte management, protein supplementation, antibiotic therapy for C difficile, and surgical evaluation also may be required.

Patients should be advised that diarrhea is a common problem caused by antibiotics and usually ceases after completion of therapy. Watery and bloody stools (with or without stomach cramps and fever) can occur after initiation of therapy, sometimes as late as 2 or more months after the last dose has been taken. Patients should also be instructed to contact their clinician as soon as possible if symptoms occur.

Sulfamethoxazole/trimethoprim, cefadroxil monohydrate, nitrofurantoin monohydrate, cefpodoxime proxetil, ciprofloxacin, ofloxacin, and levofloxacin are indicated for the treatment of infections caused by susceptible strains of designated microorganisms.

http://www.fda.gov/medwatch/SAFETY/2007/jun07_quickview.htm

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