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Drug Profile

Do NOT stop taking this or any drug without the advice of your physician. Some drugs can cause severe adverse effects when they are stopped suddenly.

Do Not Use [what does this mean?]
Generic drug name: gemifloxacin (gem i FLOX a sin)
Brand name(s): FACTIVE
GENERIC: not available FAMILY: Fluoroquinolones
Find the drug label by searching at DailyMed.

Alternative Treatment [top]

Numerous other, safer antibiotics are approved to treat the same infections as this drug (see Fluoroquinolones).

Safety Warnings For This Drug [top]

FDA-Required Black-Box Warnings

WARNING: SERIOUS ADVERSE REACTIONS INCLUDING TENDINITIS, TENDON RUPTURE, PERIPHERAL NEUROPATHY, CENTRAL NERVOUS SYSTEM EFFECTS and EXACERBATION OF MYASTHENIA GRAVIS

  • Fluoroquinolones, including FACTIVE, have been associated with disabling and potentially irreversible serious adverse reactions that have occurred together, including:
    • Tendinitis and tendon rupture
    • Peripheral neuropathy (nerve damage)
    • Central nervous system effects

Discontinue FACTIVE immediately and avoid the use of fluoroquinolones, including FACTIVE, in patients who experience any of these serious adverse reactions.

  • Fluoroquinolones, including FACTIVE, may exacerbate muscle weakness in patients with myasthenia gravis. Avoid FACTIVE in patients with known history of myasthenia gravis.
  • Because fluoroquinolones, including FACTIVE, have been associated with serious adverse reactions, reserve FACTIVE for use in patients who have no alternative treatment options for the acute bacterial exacerbation of chronic bronchitis.

Antibiotic-Associated Diarrhea

Antibiotic-associated diarrhea (AAD) is quite common and its incidence varies from 5% to 20% of patients depending on which antibiotic they are taking, although practically all antibiotics have been associated with AAD. Fortunately, most cases are mild and self-limited, ending with the cessation of use of the offending antibiotic. The antibiotics most commonly associated with this mild form of AAD include ampicillin, amoxicillin, cephalosporins and clindamycin.[1] There have been studies in children or adults in which the use of prophylactic yogurt in people using antibiotics has significantly reduced the occurrence or severity of AAD.[2],[3] However, 10% to 20% of all patients who get AAD (0.5% to 4% of patients using antibiotics) will get the more severe form of AAD known as pseudomembranous colitis (see below). If you are taking any antibiotic and develop diarrhea after starting to use the drug, call your physician to discuss whether another antibiotic should be used and to discuss the need for rehydration due to the fluid loss from the diarrhea.

Pseudomembranous colitis has been reported with nearly all antibacterial agents and may range in severity from mild to life-threatening. Therefore, it is important to consider this diagnosis in patients who present with diarrhea subsequent to the administration of antibacterial agents.

Because antibiotic therapy has been associated with severe colitis, which may end fatally, it should be reserved for serious infections where less toxic antimicrobial agents are inappropriate, as described in the INDICATIONS AND USAGE section. It should not be used in patients with nonbacterial infections such as most upper respiratory tract infections. Treatment with antibacterial agents alters the normal flora of the colon and may permit over-growth of clostridia. Studies indicate that a toxin produced by Clostridium difficile is one primary cause of "antibiotic-associated colitis."

After the diagnosis of pseudomembranous colitis has been established, therapeutic measures should be initiated. Mild cases of pseudomembranous colitis usually respond to drug discontinuation alone. In moderate to severe cases, consideration should be given to management with fluids and electrolytes, protein supplementation, and treatment with an antibacterial drug that is clinically effective against C. difficile colitis.

Diarrhea, colitis, and pseudomembranous colitis have been observed to begin up to several weeks following cessation of therapy.

Facts About This Drug [top]

Gemifloxacin (FACTIVE) was approved by the Food and Drug Administration (FDA) in April 2003. Gemifloxacin is a drug that should not have been approved and should not be used.

Marketing rights for the drug in North America belong to GeneSoft Pharmaceuticals Inc. of California, which licensed gemifloxacin from LG Life Sciences Ltd., based in Korea.

GeneSoft originally submitted its application to the FDA for gemifloxacin in December 1999. In the original application, the company sought...

Gemifloxacin (FACTIVE) was approved by the Food and Drug Administration (FDA) in April 2003. Gemifloxacin is a drug that should not have been approved and should not be used.

Marketing rights for the drug in North America belong to GeneSoft Pharmaceuticals Inc. of California, which licensed gemifloxacin from LG Life Sciences Ltd., based in Korea.

GeneSoft originally submitted its application to the FDA for gemifloxacin in December 1999. In the original application, the company sought approval for the treatment of adults for three types of respiratory tract infections: community-acquired pneumonia, acute bacterial exacerbation (worsening) of chronic bronchitis and acute bacterial sinusitis (sinus infection). In addition, GeneSoft wanted the drug approved for two types of urinary tract infections: uncomplicated urinary tract infection and complicated urinary tract infection.

Ultimately, gemifloxacin was approved for only two types of infection: community-acquired pneumonia and acute bacterial exacerbation of chronic bronchitis. Treatment is limited to seven days for community-acquired pneumonia and five days for acute bacterial exacerbation of chronic bronchitis because of the increased risk of adverse drug reactions with a longer duration of treatment.[4]

During the course of the FDA’s review of gemifloxacin, significant questions arose regarding the drug’s safety. Questions involved the higher-than-expected rate of rash reported in patients receiving gemifloxacin and the relationship between the drug and reported rashes, the potential for cross-sensitization with other fluoroquinolone antibiotics, and the possibility that the frequent occurrence of rash may foreshadow a risk of more serious skin reactions. Also, there were unresolved questions regarding gemifloxacin’s liver safety and concern over the potential for the drug to alter the heart’s electrical conduction, which could lead to dangerous heart rhythm disturbances.

Adverse effects

Peripheral neuropathy / tendon ruptures

Peripheral neuropathy and tendon ruptures have been reported in patients receiving fluoroquinolones. The FDA now requires that the product labels for all fluoroquinolone antibiotics must warn about the possibility of peripheral neuropathy (nerve damage) and tendon rupture.

Antibiotic-associated diarrhea

Antibiotic-associated diarrhea (AAD) is a common adverse effect of antibiotic treatment. A report appearing in the Oct. 25, 2005, Canadian Medical Association Journal estimated that as many as 2,000 patients may have died from AAD in Quebec hospitals since 2003.[5] Many different types of antibiotics can cause AAD, but reports have recently implicated the use of fluoroquinolone antibiotics as an important risk factor in the development of a potentially life-threatening form of AAD called pseudomembranous colitis, which is caused by a type of bacteria called Clostridium difficile.

Rash

As mentioned above, during the initial review of gemifloxacin, a higher-than-expected rate of rash was noted in the clinical trials. The rates of rash ranged from less than 1% to higher than 25%, depending upon the population or subset of patients being analyzed. Analyses of the rash data have shown that being a woman younger than 40 and having a duration of treatment longer than seven days are associated with an increased risk of rash.

GeneSoft addressed the rash issue by conducting an additional study that compared gemifloxacin with ciprofloxacin (an older, very popular fluoroquinolone) in healthy women who appeared to be at the greatest risk of developing a rash: those under 40 years of age and taking the drug for longer than 10 days. Public Citizen has serious questions about the ethics of conducting a clinical trial in healthy women to see how many rashes could be induced.

At the end of the study, rash had appeared in 31.7% of women given gemifloxacin and in 4.3% of women receiving ciprofloxacin. This is a greater than sevenfold difference in the risk of rash between the two drugs.

Results showed that 80% of the gemifloxacin-treated women who developed a rash did so on days 8, 9 or 10 of the study. More than 25% of these women had rashes covering more than 60% of their bodies, and 7.3% were classified as having a severe rash, whereas none of the women taking ciprofloxacin had a rash classified as severe. In addition, there were 16 cases of mucous membrane involvement (such as the lining of the mouth or throat) among the 260 women who developed a rash from gemifloxacin (6.2%) and none in the seven women who developed a rash from ciprofloxacin.

Gemifloxacin’s professional product labeling instructs physicians to warn patients to stop taking the drug and call the prescribing physician if a rash develops.[4]

Potential for liver toxicity

In doses greater than the FDA-approved daily dose of 320 milligrams (mg), gemifloxacin produced elevations of liver enzymes in the blood. Such elevations can be an early sign of liver toxicity. In studies submitted to the FDA, women who received a single dose of 640 mg of gemifloxacin, double the approved dose, were more likely to develop elevations of liver enzymes than were women who received ciprofloxacin.

Gemifloxacin’s product label carries the following precautionary warning: “The recommended dose of gemifloxacin 320 mg daily should not be exceeded and the recommended length of therapy should not be exceeded.”[4]

QT prolongation

QT prolongation, a change in the electrical activity of the heart that can lead to a fatal heart rhythm disturbance called torsades de pointes, is seen with other fluoroquinolone antibiotics, and there was enough concern at the FDA that the following bolded warning was required in the product label for gemifloxacin:

WARNINGS

THE SAFETY AND EFFECTIVENESS OF FACTIVE IN CHILDREN, ADOLESCENTS (LESS THAN 18 YEARS OF AGE), PREGNANT WOMEN, AND LACTATING WOMEN HAVE NOT BEEN ESTABLISHED. QT EFFECTS: FACTIVE MAY PROLONG THE QT INTERVAL IN SOME PATIENTS. FACTIVE SHOULD BE AVOIDED IN PATIENTS WITH A HISTORY OF PROLONGATION OF THE QTc INTERVAL, PATIENTS WITH UNCORRECTED ELECTROLYTE DISORDERS (HYPOKALEMIA [low blood levels of potassium] OR HYPOMAGNESEMIA [low blood levels of magnesium]), AND PATIENTS RECEIVING IA (E.G., QUINIDINE, PROCAINAMIDE) OR III (E.G., AMIODARONE, SOTALOL) ANTIARRHYTHMIC AGENTS.

The table below lists the generic names (brand names in parentheses) of the drugs for heart rhythm disturbances (antiarrhythmics) referred to in the warning above.

Class IA Antiarrhythmic Drugs

  • disopyramide (NORPACE)
  • procainamide (PROCANBID)
  • moricizine (ETHMOZINE)
  • quinidine (DURAQUIN, QUINIDEX, QUINAGLUTE)

Class III Antiarrhythmic Drugs

  • bretylium
  • amiodarone (CORDARONE)
  • sotalol (BETAPACE)

Retinal detachment

A study in the Journal of the American Medical Association found that patients taking oral fluoroquinolones appear to have an increased risk of developing retinal detachment, a medical emergency that can result in permanent vision loss unless promptly treated by an ophthalmologist. The authors of this study estimated that as many as 1,400 cases of retinal detachment each year in the U.S. may be caused by the use of these drugs.[6]

In 2013, a study conducted in diabetic patients found an increased risk of abnormal blood sugar levels in diabetic patients using oral fluoroquinolones.[7]

In March 2018, the BMJ published a study on the increased risk of aortic aneurysm or aortic dissection with fluoroquinolone use.[8]

Interactions

As of Jan. 15, 2004, Health Canada, an agency similar to the FDA, received 57 reports of suspected interactions associated with fluoroquinolones and the oral anticoagulant warfarin. If you take warfarin and are prescribed a fluoroquinolone antibiotic, ask your doctor what tests should be performed to monitor your blood coagulation levels.[9]

Regulatory actions surrounding gemifloxacin

2006: Public Citizen filed a petition with the FDA on Aug. 29, 2006, urging the agency to immediately warn consumers about the risks of tendinitis and tendon rupture associated with the use of fluoroquinolone antibiotics.

The petition called on the FDA to add a black-box warning, the strongest type of warning the FDA can require, to the product labels of all fluoroquinolone antibiotics, alerting health care professionals to the risks of using the drugs.

In addition, Public Citizen’s petition asked that a “Dear Doctor" letter be sent to warn physicians about these potentially serious adverse drug reactions. The petition also asked the FDA to require pharmacists to distribute FDA-approved Medication Guides informing consumers about the potential tendon damage that can result from using these antibiotics and what steps to take if unexplained tendon pain should develop.[10]

2008: The FDA updated the product labels for all fluoroquinolones to include a black-box warning with information about the increased risk of developing tendinitis and tendon rupture. The FDA also required manufacturers to develop a Medication Guide for patients.[11]

2011: The FDA added a black-box warning to the fluoroquinolone group of drugs stating that, when fluoroquinolones are used in patients with myasthenia gravis (a disease that causes muscle weakness), the drugs may exacerbate muscle weakness.[12]

The 2011 warning also requires that a Medication Guide about this risk be provided to patients.

This is one of a limited number of drugs for which the FDA requires an FDA-approved Medication Guide to be dispensed when the prescription is filled. An FDA advisory committee has unanimously recommended that all prescription drugs be accompanied by such Medication Guides, but at present, fewer than 5% of drugs are. The other 95% of drugs are accompanied by unregulated, often dangerously incomplete information leaflets that are not approved by the FDA.

2016: The FDA updated the drug product label for fluoroquinolones, stating that these drugs are associated with disabling and potentially permanent adverse effects of the tendons, muscles, joints, nerves and central nervous system.[13] The FDA also required that the new black-box warnings and other sections of the labeling for all oral and intravenous fluoroquinolones advise doctors not to prescribe the antibiotics to patients who have other treatment options for the following three common infections:

  • Acute bacterial exacerbation of chronic bronchitis (a type of chronic obstructive pulmonary disease, or COPD)
  • Acute uncomplicated bladder infection
  • Acute sinusitis

2018: The FDA strengthened the warning on the drug product labels of fluoroquinolones to warn that these drugs can cause low blood sugar (hypoglycemia) and psychiatric adverse effects.[14]

The FDA updated the product labels of fluoroquinolones to warn that fluoroquinolone use was associated with an increased risk of aortic aneurysm or dissection, which can lead to bleeding and death.[15]

2020: In December, the Medicines and Healthcare products Regulatory Agency (MHRA, a regulatory agency in the U.K. similar to the FDA) issued an advisory that fluoroquinolones are associated with a small risk of a heart valve defect called heart valve regurgitation, which occurs when the heart valves do not close completely, allowing blood to flow in the wrong direction.[16] Such heart valve problems may lead to heart failure.

last reviewed April 30, 2021