Prulifloxacin
Encyclopedia
Prulifloxacin is an older synthetic chemotherapeutic antibiotic
of the fluoroquinolone
drug class currently undergoing clinical trials prior to a possible NDA (New Drug Application) submission to the U.S. Food and Drug Administration (FDA). It is a prodrug
which is metabolized in the body to the active compound ulifloxacin. It was developed over two decades ago by Nippon Shinyaku Co. and was patented in Japan in 1987 and in the United States in 1989.
It has been approved for the treatment of uncomplicated and complicated urinary tract infections, community-acquired respiratory tract infections in Italy and gastroenteritis, including infectious diarrheas, in Japan. Prulifloxacin has not been approved for use in the United States.
In more recent times, Angelini ACRAF SpA, under license from Nippon Shinyaku, has fully developed prulifloxacin, for the European market.
Angelini is the licensee for the product in Italy. Following its launch in Italy, Angelini launched prulifloxacin in Portugal (January 2007) and it has been stated that further approvals will be sought in other European countries.
Prulifloxacin is currently marketed in Japan and Italy as Quisnon (Nippon Shinyaku); Sword (Meiji); Unidrox (Angelini) and generic as Pruquin.
In 1989 and 1992 United States patents (US 5086049) were issued to Nippon Shinyaku for prulifloxacin. It was not until June 2004, when Optimer Pharmaceuticals acquired exclusive rights to discover, develop and commercialize prulifloxacin (Pruvel) in the U.S. from Nippon Shinyaku Co., Ltd., that there were any attempts to seek FDA approval to market the drug in the United States. Optimer Pharmaceuticals
expects to file an NDA (new drug application) for prulifloxacin some time in 2010. As the patent for prulifloxacin has already expired, Optimer Pharmaceuticals has stated that this may have an effect on the commercial prospects of prulifloxacin within the United States market.
Italy
Japan
Other countries
In most countries, all formulations require a prescription.
Quinolones and fluoroquinolones are chemotherapeutic bactericidal drugs, eradicating bacteria by interfering with DNA replication
. The other antibiotic
s used today, (e.g., tetracyclines, lincomycin, erythromycin, and chloramphenicol) do not interact with components of eukaryotic ribosomal particle and, thus, have proven not to be toxic to eukaryotes, as opposed to the fluoroquinolone class of drugs. Safer drugs used to treat bacterial infections, such as penicillin
s and cephalosporin
s, inhibit cell wall biosynthesis, thereby causing bacterial cell death, as opposed to the interference with DNA replication as seen within the fluoroquinolone class of drugs.
Quinolones are synthetic chemotherapeutic agents that have a broad spectrum of antimicrobial activity as well as a unique mechanism of action, resulting in inhibition of bacterial DNA gyrase
and topoisomerase IV
. Quinolones inhibit the bacterial DNA gyrase
or the topoisomerase IV
enzyme, thereby inhibiting DNA
replication and transcription
. Quinolones can enter cells easily via porins
and, therefore, are often used to treat intracellular
pathogen
s such as Legionella pneumophila
and Mycoplasma pneumoniae
. For many gram-negative bacteria, DNA gyrase is the target, whereas topoisomerase IV is the target for many gram-positive bacteria. It is believed that eukaryotic cells do not contain DNA gyrase or topoisomerase IV. However, there is debate concerning whether the quinolones still have such an adverse effect on the DNA of healthy cells, in the manner described above, hence contributing to their adverse safety profile. This class has been shown to damage mitochondrial DNA
.
The fluoroquinolones rapidly cross the blood-placenta and blood-milk barrier, and are extensively distributed into the fetal tissues. For this reason the fluoroquinolones are contraindicated during pregnancy due to the risk of spontaneous abortions and birth defects. The fluoroquinolones have also been reported as being present in the mother’s milk and are passed on to the nursing child, which may increases the risk of the child suffering from this syndrome as well, even though the child had never been prescribed or taken any of the drugs found within this class.
Fluoroquinolones are not licensed by the U.S. FDA for use in children due to the risk of fatalities as well as permanent injury to the musculoskeletal system, with two exceptions. However, the fluoroquinolones are licensed to treat lower respiratory infections in children with cystic fibrosis in the UK.
Within the United States, the FDA has stated that it is their intention to pursue the licensing of the fluoroquinolones for pediatric use in spite of the evidence presented at that 62 Meeting of the Anti-Infective Drugs Advisory Committee that the fluoroquinolones cause irreversible joint damage in the pediatric population.
Prulifloxacin has highly pronounced side-effects in people suffering from panic disorder
or/and depression. There have been reported cases of psychosis, suicide attempts, panic attacks and acute anxiety, all occurring during or shortly after fluoroquinolone treatment. Patients with previous or current psychiatric conditions, are prone to experiencing this type of side-effect. Caution is highly advised.
phototoxicity reactions in patients treated with prulifloxacin."
"When treated with antibacterial agents of the quinolone group, patients with latent or known deficiencies for the glucose-6-phosphate dehydrogenase activity are predisposed to hemolytic reactions."
Within one review prulifloxacin was stated to have a similar tolerability profile to that of ciprofloxacin.
Within another study it was found that prulifloxacin patients experienced a larger number of adverse reactions as compared to those in the ciprofloxacin group (16% vs 12.5%). Of the four serious adverse events in the prulifloxacin group one was diagnosed as cardiorespiratory insufficiency which resulted in the death of the patient, although this death was not believed to be related to prulifloxacin. Ciprofloxacin has an adverse drug reaction rate (one or more reactions) of 16.5% as well as a Black Box Warning concerning spontaneous tendon ruptures. The FDA has requested that all drugs within this class carry such a Black Box Warning, and prulifloxacin would be no exception should it be approved for use in the United States in the future.
As previously noted the FDA had recommended that sponsor conduct a study to determine the effect of prulifloxacin on the prolongation of the QT interval, a condition that is associated with potentially life-threatening cardiac arrhythmias and death.
The results of one such cardiac study stated that "...prulifloxacin at steady state after therapeutic doses has no significant effects on the QTc interval and thus should prove to have no cardiac liability." The results of this trial were challenged by Malik et al. who questioned the validity of using an ECG study to prove the cardiac safety of the drug.
Other drugs within this class (i.e. grepafloxacin, sparfloxacin, moxifloxacin, levofloxacin, gatifloxacin, gemifloxacin) have also been associated with QT interval prolongation, resulting in sudden death of the patient. Grepafloxacin and Sparfloxacin were removed from clinical use due to this adverse event.
The United States sponsor reports that patients treated with prulifloxacin have experienced serious drug-related side effects including renal toxicities, cardiac arrhythmias, photosensitivity, and central nervous system effects, such as seizures.
Future clinical trials, which will involve testing in larger patient populations, may reveal a high prevalence of these or other side effects. In such an event, clinical trials would be interrupted, delayed or halted by the U.S. FDA or comparable foreign regulatory authorities. Such regulatory agencies could then prevent further development of prulifloxacin or ultimately deny its approval. The sponsor of prulifloxacin has stated that such a delay or denial would significantly harm the commercial prospects of prulifloxacin.
. Rheumatic disease after use of a fluoroquinolone (norfloxacin
) was first reported eleven years later. In response to a 1995 letter published in the New England Journal of Medicine
, representatives of the U.S. Food and Drug Administration (FDA) stated that the agency would "update the labeling [package insert] for all marketed fluoroquinolones to include a warning about the possibility of tendon rupture."
By August 1996, the FDA had not taken action, and the consumer advocacy group Public Citizen
filed a petition with the FDA prompting the agency to act. Two months later, the FDA published an alert in the FDA Medical Bulletin and requested that fluoroquinolone package inserts be amended to include information on this risk.
Nine years later, in 2005, the Illinois Attorney General
filed a second petition with the FDA again seeking Black Box Warning
s and "Dear Doctor" letters emphasizing the risk of tendon rupture; the FDA responded that it had not yet been able to reach a decision on the matter. In 2006, Public Citizen, supported by the Illinois Attorney General, renewed its demand of ten years prior for Black Box Warnings by filing a third petition requesting such changes be made. When the FDA failed to respond to these two petitions as required by law Public Citizen, in January 2008, filed suit to compel the FDA to respond to their 2006 petition. On July 7, 2008 the FDA requested that the makers of systemic-use fluoroquinolones add a boxed warning regarding spontaneous tendon ruptures, and to develop a Medication Guide for patients. The package inserts for Ciprofloxacin, Avelox (moxifloxacin
), Proquin XR, Factive (gemifloxacin
), Floxin (ofloxacin
), Noroxin (norfloxacin
) and Levaquin (levofloxacin
) were amended on September 8, 2008 to include these new warnings. Bayer
, which manufactures Cipro, Avelox and Proquin XR, issued a Dear Healthcare Professional letter on October 22 concerning these changes. Ortho-McNeil, the manufacturers of Levaquin, issued a similar letter in November. through the Health Care Notification Network, a registration-only website that distributes drug alerts to licensed healthcare professionals.
Antibiotic
An antibacterial is a compound or substance that kills or slows down the growth of bacteria.The term is often used synonymously with the term antibiotic; today, however, with increased knowledge of the causative agents of various infectious diseases, antibiotic has come to denote a broader range of...
of the fluoroquinolone
Quinolone
The quinolones are a family of synthetic broad-spectrum antibiotics. The term quinolone refers to potent synthetic chemotherapeutic antibacterials....
drug class currently undergoing clinical trials prior to a possible NDA (New Drug Application) submission to the U.S. Food and Drug Administration (FDA). It is a prodrug
Prodrug
A prodrug is a pharmacological substance administered in an inactive form. Once administered, the prodrug is metabolised in vivo into an active metabolite, a process termed bioactivation. The rationale behind the use of a prodrug is generally for absorption, distribution, metabolism, and...
which is metabolized in the body to the active compound ulifloxacin. It was developed over two decades ago by Nippon Shinyaku Co. and was patented in Japan in 1987 and in the United States in 1989.
It has been approved for the treatment of uncomplicated and complicated urinary tract infections, community-acquired respiratory tract infections in Italy and gastroenteritis, including infectious diarrheas, in Japan. Prulifloxacin has not been approved for use in the United States.
History
In 1987 a European Patent (EP 315828) for prulifloxacin (Quisnon ) was issued to the Japanese based pharmaceutical company, Nippon Shinyaku Co., Ltd (Nippon). Ten years after the issuance of the European patent, marketing approval was applied for and granted in Japan (March 1997). Subsequent to being approved by the Japanese authorities in 1997 prulifloxacin (Quisnon) was co-marketed and jointly developed in Japan with Meiji Seika as licensee (Sword).In more recent times, Angelini ACRAF SpA, under license from Nippon Shinyaku, has fully developed prulifloxacin, for the European market.
Angelini is the licensee for the product in Italy. Following its launch in Italy, Angelini launched prulifloxacin in Portugal (January 2007) and it has been stated that further approvals will be sought in other European countries.
Prulifloxacin is currently marketed in Japan and Italy as Quisnon (Nippon Shinyaku); Sword (Meiji); Unidrox (Angelini) and generic as Pruquin.
In 1989 and 1992 United States patents (US 5086049) were issued to Nippon Shinyaku for prulifloxacin. It was not until June 2004, when Optimer Pharmaceuticals acquired exclusive rights to discover, develop and commercialize prulifloxacin (Pruvel) in the U.S. from Nippon Shinyaku Co., Ltd., that there were any attempts to seek FDA approval to market the drug in the United States. Optimer Pharmaceuticals
expects to file an NDA (new drug application) for prulifloxacin some time in 2010. As the patent for prulifloxacin has already expired, Optimer Pharmaceuticals has stated that this may have an effect on the commercial prospects of prulifloxacin within the United States market.
Licensed uses
Prulifloxacin has been approved in Italy and Japan, (as indicated), for treatment of infections caused by susceptible bacteria, in the following conditions:Italy
- Acute uncomplicated lower urinary tract infections (simple cystitis)
- Complicated lower urinary tract infections
- Acute exacerbation of chronic bronchitis
Japan
- Gastroenteritis, including infectious diarrheas
Other countries
- Prulifloxacin has not been approved for use in the United States, but may have been approved in other Countries, other than that which is indicated above.
Availability
Prulifloxacin is available as:- Tablets (250 mg, 450 mg or 600 mg)
In most countries, all formulations require a prescription.
Mechanism of action
Like other fluoroquinolones, Prulifloxacin prevents bacterial DNA replication, transcription, repair and recombination through inhibition of bacterial DNA gyrase.Quinolones and fluoroquinolones are chemotherapeutic bactericidal drugs, eradicating bacteria by interfering with DNA replication
DNA replication
DNA replication is a biological process that occurs in all living organisms and copies their DNA; it is the basis for biological inheritance. The process starts with one double-stranded DNA molecule and produces two identical copies of the molecule...
. The other antibiotic
Antibiotic
An antibacterial is a compound or substance that kills or slows down the growth of bacteria.The term is often used synonymously with the term antibiotic; today, however, with increased knowledge of the causative agents of various infectious diseases, antibiotic has come to denote a broader range of...
s used today, (e.g., tetracyclines, lincomycin, erythromycin, and chloramphenicol) do not interact with components of eukaryotic ribosomal particle and, thus, have proven not to be toxic to eukaryotes, as opposed to the fluoroquinolone class of drugs. Safer drugs used to treat bacterial infections, such as penicillin
Penicillin
Penicillin is a group of antibiotics derived from Penicillium fungi. They include penicillin G, procaine penicillin, benzathine penicillin, and penicillin V....
s and cephalosporin
Cephalosporin
The cephalosporins are a class of β-lactam antibiotics originally derived from Acremonium, which was previously known as "Cephalosporium".Together with cephamycins they constitute a subgroup of β-lactam antibiotics called cephems.-Medical use:...
s, inhibit cell wall biosynthesis, thereby causing bacterial cell death, as opposed to the interference with DNA replication as seen within the fluoroquinolone class of drugs.
Quinolones are synthetic chemotherapeutic agents that have a broad spectrum of antimicrobial activity as well as a unique mechanism of action, resulting in inhibition of bacterial DNA gyrase
DNA gyrase
DNA gyrase, often referred to simply as gyrase, is an enzyme that relieves strain while double-stranded DNA is being unwound by helicase. This causes negative supercoiling of the DNA...
and topoisomerase IV
Topoisomerase IV
Topoisomerase IV is one of two type-II topoisomerases in bacteria, the other being DNA gyrase. Like gyrase, topoisomerase IV is able to pass one double-strand of DNA through another double-strand of DNA, thereby changing the linking number of DNA by two in each enzymatic...
. Quinolones inhibit the bacterial DNA gyrase
DNA gyrase
DNA gyrase, often referred to simply as gyrase, is an enzyme that relieves strain while double-stranded DNA is being unwound by helicase. This causes negative supercoiling of the DNA...
or the topoisomerase IV
Topoisomerase IV
Topoisomerase IV is one of two type-II topoisomerases in bacteria, the other being DNA gyrase. Like gyrase, topoisomerase IV is able to pass one double-strand of DNA through another double-strand of DNA, thereby changing the linking number of DNA by two in each enzymatic...
enzyme, thereby inhibiting DNA
DNA
Deoxyribonucleic acid is a nucleic acid that contains the genetic instructions used in the development and functioning of all known living organisms . The DNA segments that carry this genetic information are called genes, but other DNA sequences have structural purposes, or are involved in...
replication and transcription
Transcription (genetics)
Transcription is the process of creating a complementary RNA copy of a sequence of DNA. Both RNA and DNA are nucleic acids, which use base pairs of nucleotides as a complementary language that can be converted back and forth from DNA to RNA by the action of the correct enzymes...
. Quinolones can enter cells easily via porins
Porin (protein)
Porins are beta barrel proteins that cross a cellular membrane and act as a pore through which molecules can diffuse. Unlike other membrane transport proteins, porins are large enough to allow passive diffusion, i.e., they act as channels that are specific to different types of molecules...
and, therefore, are often used to treat intracellular
Intracellular
Not to be confused with intercellular, meaning "between cells".In cell biology, molecular biology and related fields, the word intracellular means "inside the cell".It is used in contrast to extracellular...
pathogen
Pathogen
A pathogen gignomai "I give birth to") or infectious agent — colloquially, a germ — is a microbe or microorganism such as a virus, bacterium, prion, or fungus that causes disease in its animal or plant host...
s such as Legionella pneumophila
Legionella pneumophila
Legionella pneumophila is a thin, ærobic, pleomorphic, flagellated, non-spore forming, Gram-negative bacterium of the genus Legionella. L. pneumophila is the primary human pathogenic bacterium in this group and is the causative agent of legionellosis or Legionnaires' disease.-Characterization:L...
and Mycoplasma pneumoniae
Mycoplasma pneumoniae
Mycoplasma pneumoniae is a very small bacterium in the class Mollicutes.It causes the disease mycoplasma pneumonia, a form of atypical bacterial pneumonia, and is related to cold agglutinin disease.-Cell wall/Treatment:...
. For many gram-negative bacteria, DNA gyrase is the target, whereas topoisomerase IV is the target for many gram-positive bacteria. It is believed that eukaryotic cells do not contain DNA gyrase or topoisomerase IV. However, there is debate concerning whether the quinolones still have such an adverse effect on the DNA of healthy cells, in the manner described above, hence contributing to their adverse safety profile. This class has been shown to damage mitochondrial DNA
Mitochondrial DNA
Mitochondrial DNA is the DNA located in organelles called mitochondria, structures within eukaryotic cells that convert the chemical energy from food into a form that cells can use, adenosine triphosphate...
.
Contraindications
There are only four contraindications found within the package insert:- “Prulifloxacin is contraindicated in patients with anamnesis of tendon diseases related to the administration of quinolones.”
- “Prulifloxacin is contraindicated in persons with a history of hypersensitivity to Prulifloxacin, any member of the quinolone class of antimicrobial agents, or any of the product components.”
- “Prulifloxacin is contraindicated in subjects with celiac disease.”'
- ”Prulifloxacin is also considered to be contraindicated within the pediatric population, pregnancyPregnancyPregnancy refers to the fertilization and development of one or more offspring, known as a fetus or embryo, in a woman's uterus. In a pregnancy, there can be multiple gestations, as in the case of twins or triplets...
, nursing mothers, and in patients with epilepsyEpilepsyEpilepsy is a common chronic neurological disorder characterized by seizures. These seizures are transient signs and/or symptoms of abnormal, excessive or hypersynchronous neuronal activity in the brain.About 50 million people worldwide have epilepsy, and nearly two out of every three new cases...
or other seizure disorders.”
- Pregnancy
The fluoroquinolones rapidly cross the blood-placenta and blood-milk barrier, and are extensively distributed into the fetal tissues. For this reason the fluoroquinolones are contraindicated during pregnancy due to the risk of spontaneous abortions and birth defects. The fluoroquinolones have also been reported as being present in the mother’s milk and are passed on to the nursing child, which may increases the risk of the child suffering from this syndrome as well, even though the child had never been prescribed or taken any of the drugs found within this class.
- Pediatric population
Fluoroquinolones are not licensed by the U.S. FDA for use in children due to the risk of fatalities as well as permanent injury to the musculoskeletal system, with two exceptions. However, the fluoroquinolones are licensed to treat lower respiratory infections in children with cystic fibrosis in the UK.
Within the United States, the FDA has stated that it is their intention to pursue the licensing of the fluoroquinolones for pediatric use in spite of the evidence presented at that 62 Meeting of the Anti-Infective Drugs Advisory Committee that the fluoroquinolones cause irreversible joint damage in the pediatric population.
- Depression and anxiety disorders
Prulifloxacin has highly pronounced side-effects in people suffering from panic disorder
Panic disorder
Panic disorder is an anxiety disorder characterized by recurring severe panic attacks. It may also include significant behavioral change lasting at least a month and of ongoing worry about the implications or concern about having other attacks. The latter are called anticipatory attacks...
or/and depression. There have been reported cases of psychosis, suicide attempts, panic attacks and acute anxiety, all occurring during or shortly after fluoroquinolone treatment. Patients with previous or current psychiatric conditions, are prone to experiencing this type of side-effect. Caution is highly advised.
Special precautions
"As with other quinolones, exposure to the sun or ultra-violet rays may causephototoxicity reactions in patients treated with prulifloxacin."
"When treated with antibacterial agents of the quinolone group, patients with latent or known deficiencies for the glucose-6-phosphate dehydrogenase activity are predisposed to hemolytic reactions."
Adverse Eevents
There is limited data to be found within the literature, (other than older animal studies) regarding the tolerability of prulifloxacin and what is stated appears to be contradictory.Within one review prulifloxacin was stated to have a similar tolerability profile to that of ciprofloxacin.
Within another study it was found that prulifloxacin patients experienced a larger number of adverse reactions as compared to those in the ciprofloxacin group (16% vs 12.5%). Of the four serious adverse events in the prulifloxacin group one was diagnosed as cardiorespiratory insufficiency which resulted in the death of the patient, although this death was not believed to be related to prulifloxacin. Ciprofloxacin has an adverse drug reaction rate (one or more reactions) of 16.5% as well as a Black Box Warning concerning spontaneous tendon ruptures. The FDA has requested that all drugs within this class carry such a Black Box Warning, and prulifloxacin would be no exception should it be approved for use in the United States in the future.
As previously noted the FDA had recommended that sponsor conduct a study to determine the effect of prulifloxacin on the prolongation of the QT interval, a condition that is associated with potentially life-threatening cardiac arrhythmias and death.
The results of one such cardiac study stated that "...prulifloxacin at steady state after therapeutic doses has no significant effects on the QTc interval and thus should prove to have no cardiac liability." The results of this trial were challenged by Malik et al. who questioned the validity of using an ECG study to prove the cardiac safety of the drug.
Other drugs within this class (i.e. grepafloxacin, sparfloxacin, moxifloxacin, levofloxacin, gatifloxacin, gemifloxacin) have also been associated with QT interval prolongation, resulting in sudden death of the patient. Grepafloxacin and Sparfloxacin were removed from clinical use due to this adverse event.
The United States sponsor reports that patients treated with prulifloxacin have experienced serious drug-related side effects including renal toxicities, cardiac arrhythmias, photosensitivity, and central nervous system effects, such as seizures.
Future clinical trials, which will involve testing in larger patient populations, may reveal a high prevalence of these or other side effects. In such an event, clinical trials would be interrupted, delayed or halted by the U.S. FDA or comparable foreign regulatory authorities. Such regulatory agencies could then prevent further development of prulifloxacin or ultimately deny its approval. The sponsor of prulifloxacin has stated that such a delay or denial would significantly harm the commercial prospects of prulifloxacin.
History of the black box warnings
Musculoskeletal disorders attributed to use of quinolone antibiotics were first reported in the medical literature in 1972, as an adverse reaction to nalidixic acidNalidixic acid
Nalidixic acid is the first of the synthetic quinolone antibiotics...
. Rheumatic disease after use of a fluoroquinolone (norfloxacin
Norfloxacin
Norfloxacin is a synthetic chemotherapeutic antibacterial agent occasionally used to treat common as well as complicated urinary tract infections. It is sold under various brand names with the most common being Noroxin. In form of ophthalmic solutions it is known as Chibroxin...
) was first reported eleven years later. In response to a 1995 letter published in the New England Journal of Medicine
New England Journal of Medicine
The New England Journal of Medicine is an English-language peer-reviewed medical journal published by the Massachusetts Medical Society. It describes itself as the oldest continuously published medical journal in the world.-History:...
, representatives of the U.S. Food and Drug Administration (FDA) stated that the agency would "update the labeling [package insert] for all marketed fluoroquinolones to include a warning about the possibility of tendon rupture."
By August 1996, the FDA had not taken action, and the consumer advocacy group Public Citizen
Public Citizen
Public Citizen is a non-profit, consumer rights advocacy group based in Washington, D.C., United States, with a branch in Austin, Texas. Public Citizen was founded by Ralph Nader in 1971, headed for 26 years by Joan Claybrook, and is now headed by Robert Weissman.-Lobbying Efforts:Public Citizen...
filed a petition with the FDA prompting the agency to act. Two months later, the FDA published an alert in the FDA Medical Bulletin and requested that fluoroquinolone package inserts be amended to include information on this risk.
Nine years later, in 2005, the Illinois Attorney General
Illinois Attorney General
The Illinois Attorney General is the highest legal officer of the state of Illinois in the United States. Originally an appointed office, it is now an office filled by election through universal suffrage...
filed a second petition with the FDA again seeking Black Box Warning
Black box warning
In the United States, a black box warning is a type of warning that appears on the package insert for prescription drugs that may cause serious adverse effects...
s and "Dear Doctor" letters emphasizing the risk of tendon rupture; the FDA responded that it had not yet been able to reach a decision on the matter. In 2006, Public Citizen, supported by the Illinois Attorney General, renewed its demand of ten years prior for Black Box Warnings by filing a third petition requesting such changes be made. When the FDA failed to respond to these two petitions as required by law Public Citizen, in January 2008, filed suit to compel the FDA to respond to their 2006 petition. On July 7, 2008 the FDA requested that the makers of systemic-use fluoroquinolones add a boxed warning regarding spontaneous tendon ruptures, and to develop a Medication Guide for patients. The package inserts for Ciprofloxacin, Avelox (moxifloxacin
Moxifloxacin
Moxifloxacin is a fourth-generation synthetic fluoroquinolone antibacterial agent developed by Bayer AG . It is marketed worldwide under the brand names Avelox, Avalox, and Avelon for oral treatment. In most countries, the drug is also available in parenteral form for intravenous infusion...
), Proquin XR, Factive (gemifloxacin
Gemifloxacin
Gemifloxacin mesylate is an oral broad-spectrum quinolone antibacterial agent used in the treatment of acute bacterial exacerbation of chronic bronchitis and mild-to-moderate pneumonia....
), Floxin (ofloxacin
Ofloxacin
Ofloxacin is a synthetic chemotherapeutic antibiotic of the fluoroquinolone drug class considered to be a second-generation fluoroquinolone. The original brand, Floxin, has been discontinued by the manufacturer in the United States on 18 June 2009, though generic equivalents continue to be...
), Noroxin (norfloxacin
Norfloxacin
Norfloxacin is a synthetic chemotherapeutic antibacterial agent occasionally used to treat common as well as complicated urinary tract infections. It is sold under various brand names with the most common being Noroxin. In form of ophthalmic solutions it is known as Chibroxin...
) and Levaquin (levofloxacin
Levofloxacin
Levofloxacin is a synthetic chemotherapeutic antibiotic of the fluoroquinolone drug class and is used to treat severe or life-threatening bacterial infections or bacterial infections that have failed to respond to other antibiotic classes. It is sold under various brand names, such as Levaquin and...
) were amended on September 8, 2008 to include these new warnings. Bayer
Bayer
Bayer AG is a chemical and pharmaceutical company founded in Barmen , Germany in 1863. It is headquartered in Leverkusen, North Rhine-Westphalia, Germany and well known for its original brand of aspirin.-History:...
, which manufactures Cipro, Avelox and Proquin XR, issued a Dear Healthcare Professional letter on October 22 concerning these changes. Ortho-McNeil, the manufacturers of Levaquin, issued a similar letter in November. through the Health Care Notification Network, a registration-only website that distributes drug alerts to licensed healthcare professionals.
Interactions
- Probenecid: Prulifloxacin urinary excretion decreases when concomitantly administered with probenecid.
- Fenbufen: The concomitant administration of fenbufen can cause increased risk of convulsions.
- Hypoglycemic agents: May cause hypoglycemia in diabetic patients under treatment with hypoglycemic agents.
- Theophylline: May cause a decreased theophylline clearance.
- Warfarin: May enhance the effects of oral anticoagulants such as warfarin and its derivatives.
- Nicardipine: May potentiate the phototoxicity of prulifloxacin.