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Any CNS side-effect occurs with an incidence of 1–2%.<ref name=Robert05/> Adverse event reporting for antibiotics found that 12.2% of adverse reaction reports concerning fluoroquinolones involved the CNS versus 3.6% for other antibiotics.<ref name=Robert05/> Newer agents to have a lower risk of side-effects have been found.<ref name=Bell1999/> Seizures are rare, and usually occur when they do in those with an underlying CNS disorder.<ref name=Robert05/> However, caution use in patient with epilepsy is still advised.<ref name=Robert05/> Very rare cases of suicidal behavior have been reported to occur, sometimes after a single dose.<ref>{{cite web |url=http://www.sanofi-aventis.co.uk/products/Tavanic500mgTabs_SPC.pdf |title=Tavanic SPC |work=Sanofi-aventis |accessdate=}}</ref> Drugs that induce suicidal ideation, including antibiotics, are associated with an increased risk of suicide attempts.<ref>{{Cite journal | last1 = Robertson | first1 = HT. | last2 = Allison | first2 = DB. | title = Drugs Associated with More Suicidal Ideations Are also Associated with More Suicide Attempts | journal = PLoS ONE | volume = 4 | issue = 10 | pages = e7312 | month = | year = 2009 | doi = 10.1371/journal.pone.0007312 | pmid = 19798416 |url=http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0007312 | pmc = 2749439 | last3 = Wright | first3 = James M. | editor1-last = Wright | editor1-first = James M. }}</ref>
Any CNS side-effect occurs with an incidence of 1–2%.<ref name=Robert05/> Adverse event reporting for antibiotics found that 12.2% of adverse reaction reports concerning fluoroquinolones involved the CNS versus 3.6% for other antibiotics.<ref name=Robert05/> Newer agents to have a lower risk of side-effects have been found.<ref name=Bell1999/> Seizures are rare, and usually occur when they do in those with an underlying CNS disorder.<ref name=Robert05/> However, caution use in patient with epilepsy is still advised.<ref name=Robert05/> Very rare cases of suicidal behavior have been reported to occur, sometimes after a single dose.<ref>{{cite web |url=http://www.sanofi-aventis.co.uk/products/Tavanic500mgTabs_SPC.pdf |title=Tavanic SPC |work=Sanofi-aventis |accessdate=}}</ref> Drugs that induce suicidal ideation, including antibiotics, are associated with an increased risk of suicide attempts.<ref>{{Cite journal | last1 = Robertson | first1 = HT. | last2 = Allison | first2 = DB. | title = Drugs Associated with More Suicidal Ideations Are also Associated with More Suicide Attempts | journal = PLoS ONE | volume = 4 | issue = 10 | pages = e7312 | month = | year = 2009 | doi = 10.1371/journal.pone.0007312 | pmid = 19798416 |url=http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0007312 | pmc = 2749439 | last3 = Wright | first3 = James M. | editor1-last = Wright | editor1-first = James M. }}</ref>


Fluoroquinolones can induce a wide range of serious adverse psychiatric effects. These reactions may manifest as extreme [[anxiety]], [[panic attacks]], [[Depression (mood)|depression]], [[anhedonia]], [[cognitive dysfunction]] (or brain fog), [[depersonalization]], [[paranoia]], [[hallucinations]], [[toxic psychosis]], [[seizures]], [[tremors]], taste perversions, abnormal dreams, chronic [[insomnia]], [[Vertigo (medical)|vertigo]], [[delirium]], [[suicidal thoughts]], and usually involves all five senses. For some people the symptoms resolve relatively soon after discontinuing the fluoroquinolone; for others, in the case of a [[neurotoxic]] effect, symptomatology may persist for months or even years after discontinuation.<ref name="pmid11172695"/><ref name="pnawf">{{cite journal | author =Cohen JS | year =2001 | month =December | title =Peripheral Neuropathy Associated with Fluoroquinolones | journal =Annals of Pharmacotherapy | volume =35 | issue =12 | pages =1540–7 | pmid =11793615 | url =http://fqvictims.org/fqvictims/News/neuropathy/Neuropathy.pdf | format =PDF | doi =10.1345/aph.1Z429 }}</ref> Fluoroquinolones are associated with a significant number of serious psychiatric events.<ref>{{cite journal |author=Doussau de Bazignan A, Thiessard F, Miremont-Salamé G, Conri C, Haramburu F |title=[Psychiatric adverse effects of fluoroquinolone: review of cases from the French pharmacologic surveillance database] |language=French |journal=Rev Med Interne |volume=27 |issue=6 |pages=448–52 |year=2006 |month=June |pmid=16580096 |doi=10.1016/j.revmed.2006.02.003 |url=}}</ref>
Fluoroquinolones can induce a wide range of serious adverse psychiatric effects. These reactions may manifest as extreme [[anxiety]], [[panic attacks]], [[Depression (mood)|depression]], [[anhedonia]], [[cognitive dysfunction]] (or brain fog), [[depersonalization]], [[paranoia]], [[hallucinations]], [[toxic psychosis]], [[seizures]], [[tremors]], taste perversions, abnormal dreams, chronic [[insomnia]], [[Vertigo (medical)|vertigo]], [[delirium]], [[suicidal thoughts]].


In addition, the fluoroquinolones may show depressant activity on the CNS, as was indicated by the depressant syndrome, decreased spontaneous motor activity, and hypothermia found in animal studies. Concomitant use of NSAIDs may increase seizure risk.<ref>{{cite journal |author=Rollof J, Vinge E |title=Neurologic adverse effects during concomitant treatment with ciprofloxacin, NSAIDS, and chloroquine: possible drug interaction |journal=Annals of Pharmacotherapy |volume=27 |issue=9 |pages=1058–9 |year=1993 |month=September |pmid=8219437 |doi= |url=}}</ref>
In addition, the fluoroquinolones may show depressant activity on the CNS, as was indicated by the depressant syndrome, decreased spontaneous motor activity, and hypothermia found in animal studies. Concomitant use of NSAIDs may increase seizure risk.<ref>{{cite journal |author=Rollof J, Vinge E |title=Neurologic adverse effects during concomitant treatment with ciprofloxacin, NSAIDS, and chloroquine: possible drug interaction |journal=Annals of Pharmacotherapy |volume=27 |issue=9 |pages=1058–9 |year=1993 |month=September |pmid=8219437 |doi= |url=}}</ref>

Revision as of 05:03, 4 January 2014

Adverse effects of fluoroquinolones

In general, fluoroquinolones are well tolerated, with most side effects being mild to moderate.[1] On occasion, serious adverse effects occur.[2]Common side effects include gastrointestinal effects such as nausea, vomiting and diarrhea, as well as headache and insomnia.

The overall rate of adverse events in patients treated with fluoroquinolones is roughly similar to that seen in patients treated with other antibiotic classes.[3][4][5][6] A U.S. Centers for Disease Control study found patients treated with fluoroquinolones experienced adverse events severe enough to lead to an emergency department visit more frequently than those treated with cephalosporins or macrolides, but less frequently than those treated with penicillins, clindamycin, sulfonamides, or vancomycin.[7]

Post-marketing surveillance has revealed a variety of relatively rare but serious adverse effects that are associated with all members of the fluoroquinolone antibacterial class. Among these, tendon problems and exacerbation of the symptoms of the neurological disorder myasthenia gravis are the subject of "black box" warnings in the United States. The most severe form of tendonopathy associated with fluoroquinolone administration is tendon rupture, which in the great majority of cases involves the Achilles tendon. Younger people typically experience good recovery, but permanent disability is possible, and is more likely in older patients.[8] The overall frequency of fluoroquinolone-associated Achilles tendon rupture in patients treated with ciprofloxacin or levofloxacin is has been estimated at 17 per 100,000 treatments.[9][10] Risk is substantially elevated in the elderly and in those with recent exposure to topical or systemic corticosteroid therapy. Simultaneous use of corticosteroids is present in almost one-third of quinolone-associated tendon rupture.[11] Tendon damage may manifest during, as well as up to a year after fluoroquinolone therapy has been completed.[12]

FQs prolong the QT interval by blocking voltage-gated potassium channels.[13] Prolongation of the QT interval can lead to torsades de pointes, a life threatening arrhythmia, but this appears relatively uncommon in part because the most widely prescribed fluoroquinolones (ciprofloxacin and levofloxacin) only minimally prolong the QT interval.[14]

Clostridium difficile associated diarrhea may occur in connection with the use of any antibacterial drug, especially those with a broad spectrum of activity such as clindamycin, cephalosporins, and fluoroquinolones. Fluoroquinoline treatment is associated with risk that is simlar to[15] or less [16][17] than that associated with broad spectrum cephalosporins.

Studies examining nervous system effects have estimated that neurotoxicity occurs in approximately 1% to 4.4% of patients taking FQs, with serious adverse effects occurring less than 0.5% of the time.[14] The most important of these may be peripheral neuropathy, which can be permanent.[18] Other nervous system effects include insomnia, restlessness, and rarely, seizure, convulsions, and psychosis[19] Other rare and serious adverse events have been observed with varying degrees of evidence for causation.[20][21][22][23]

Events that may occur in acute overdose are rare, and include renal failure and seizure.[24] Susceptible groups of patients, such as children and the elderly, are at greater risk of adverse reactions during therapeutic use.[1][25][26]

Other quinolones have had their licensed indications restricted in certain countries due to toxicity issues. These include sparfloxacin in 1995,[27] norfloxacin in 2008[28] and moxifloxacin in 2008.[29]


Background

Fluoroquinolones are often effective as antibacterial agents. They are recommended for a number of serious bacterial infections, and, in some cases of life-threatening infections, they can be life-saving.[30][31] The distinction between a quinolone drug and a fluoroquinolone drug is the addition of the fluorine atom to the basic pharmacophore, resulting in a fluorinated drug.[32] The terms fluoroquinolone and quinolone are often used interchangeably, without regard to this distinction.

Risk factors and interactions

Certain patient groups are at increased risk of fluoroquinolone ADRs. A 1998 retrospective survey of the use of the fluoroquinolones in the pediatric population showed that the fluoroquinolones were oftentimes prescribed in children, and that numerous serious side effects had been recorded.[33] Fluoroquinolones are not recommended in patient groups that are predisposed to adverse events (for example, because of diabetes, G6PD deficiency, renal impairment, myasthenia gravis, previous psychiatric, seizure disorder, or children (under 18)). An alternative antibiotic class should be used wherever possible in such patients, and,if used, special caution is advised; for example, possible dosage reduction may be required as well as extra vigilance for adverse reactions. There is also an increased risk of adverse events in the elderly, including tendon ruptures and seizures. Use in children or pregnant or breast-feeding women is not recommended and should be avoided. In the UK, the prescribing indications for fluoroquinolones for children is severely restricted. Only inhalant anthrax and pseudomonal infections in cystic fibrosis infections are licensed indications in the UK due to ongoing safety concerns. At the first sign of psychiatric, neurological, peripheral neuropathy, tendonitis, or hypersensitivity reactions, fluoroquinolones should be discontinued. Quinolones are contraindicated in patients having had previous quinolone-related tendinopathy. Dose, length of time, and number of exposures to fluoroquinolones, as well as combination with corticosteroids, NSAIDs, or theophylline, increase the risk adverse reactions. Concurrent use of corticosteroids increases the risk of multiskeletal injury, manifesting as chronic tendonitis or spontaneous ruptures of tendons, muscles, and cartilage. Concurrent use of NSAIDs may induce severe and prolonged seizures including status epilepticus.[34][35][36][37][22][38] Most cases of fluoroquinolone-precipitated seizures occur in the elderly or those with severe cerebral arteriosclerosis, epilepsy, brain tumour, anoxia, and alcohol dependence, as well as those taking theophylline or the NSAIDs.[2] Those who are benzodiazepine-dependent or in benzodiazepine withdrawal have a higher rate of adverse severe CNS effects possibly due to fluoroquinolones' displacement of benzodiazepines from their receptor site or pre-existing GABA underactivity due to withdrawal, thus leading to an increased sensitivity to fluoroquinolone toxicity.[39][40][41][42] Articaine may worsen certain symptoms in an individual with fluoroquinolone toxicity. There have been persistent reports of unexplained paresthesia following the use of articaine (burning, tingling, and sometimes sharp shooting pains in tissues previously anesthetized with this anesthetic) during dental procedures involving patients having had adverse reactions to the fluoroquinolones.[43] Broad spectrum antibacterials including cephalosporins, Fluoroquinolones (and clindamycin) have been associated with Clostridium difficile, a potentially life-threatening super-infection.[44] Use of quinolones is also highly associated with colonisation with MRSA compared to some other antibiotic classes.[45][46] Shigella toxin expression in EHEC infections has been shown to be upregulated following fluoroquinolone administration.[47] Fluoroquinolones can have serious and potential fatal reaction when taken with certain other drugs. Some agents decrease theophylline clearance and thus increase toxicity.[48] Warfarin is affected by many many drugs including fluoroquinolones and frequency of INR monitoring needs to be increased in those prescribed both agents.[49]

Adverse reactions and toxicities

Adverse reactions

The most common adverse effects of the fluoroquinolones involve the gastrointestinal tract, skin, CNS, and PNS. They are for most patients mild and reversible.[48] Severe adverse events such as hepatitis (trovafloxacin), hemolytic uremic syndrome (temafloxacin), and eosinophilic pneumonitis are thought to be specific to individual agents and as such not considered to be a class effect.[34] However, levofloxacin, ofloxacin, ciprofloxacin, and moxifloxacin have all been reported to be associated with liver injuries such as hepatotoxicity, hepatic failure, and delayed and prolonged cholestatic hepatitis.[50][51][52]

Mechanism of toxicity

The mechanisms of the toxicity of fluoroquinolones has been attributed to their interactions with different receptor complexes such as blockade of the GABAa receptor complex within the central nervous system, leading to excitotoxic type effects[2] and oxidative stress.[53]

Gastrointestinal

Nausea and vomiting are the most common side-effect of the fluoroquinolones.[48] The group of side-effects includes nausea, vomiting, abdominal pain, diarrhea, and taste disturbance, which occur in about 2-20% of people taking fluoroquinolones.[34] This rate is similar to those seen with azithromycin and cefixime.[48] The highest rates occurred among older agents, which have been discontinued. Newer agents have lower rate of GI side-effects.[34] C. difficile-associated diarrhea (CDAD) has been associated with all antibiotics.[34][22] When compared to other antibiotics, however, the risk of CDAD was found to be 2.5 times greater with fluoroquinolones.[22][54] Fluoroquinolones are associated with an increased risk of pseudomembranous colitis[55][56][57][58]

The spectrum of this disease ranges from asymptomatic carrier state to life-threatening pseudomembranous colitis and toxic megacolon. Pathogenesis of pseudomembranous colitis results from the suppression of the natural microflora of the colon by broad spectrum antibiotics, which creates an environment favorable for C. difficile proliferation. A Clostridium difficile infection is the principal cause of nosocomial, antibiotic-associated diarrhea, and pseudomembranous colitis. C. difficile can be fatal if left untreated.[59][60][61][62]

Like many antibiotics, fluoroquinolones increase the colonisation of Candida albicans, a yeast infection. Fluoroquinolones are associated with predisposing patients to an increased risk of C. difficile infections, and careful use, especially in acute hospitals, has been suggested.[63][64][65]

Musculoskeletal System

Joint pain and swelling occurs in approximately 1% of people taking fluoroquinolones and usually remits within days of stopping treatment.[34] A rare but serious adverse reaction with fluoroquinolones involves spontaneous tendon ruptures. Such injury to the patient include ruptures of various tendons (other than just the Achilles) and muscles, as well as damage to the cartilage and ligaments.[12][66] Fluoroquinolones also have adverse effects on cartilage.[67] The risk of tendon disorders with fluoroquinolone use is 0.1% to 0.4%[22] or 3 cases per 1000 patient-years of exposure.[68] These problems usually start 13 days after treatment was started and may possibly persist for a month.[34] Risk of tendon rupture is even less with only 38 of 46,000 people treated with fluoroquinolone suffering a rupture of the achilles. This is 1.9 times the rate seen in the general population.[69] The achilles is the most common tendon affected.[22] This risk is greatest in those older than 60, in those taking corticosteroid drugs, and in kidney, heart, and lung transplant recipients.[70] Because of their possible negative effect on cartilage, they are not recommended for use in pregnant women or children.[71] The FDA recommends stopping treatment, contacting a physician and resting affected limbs if these adverse events occur.[34]

As with any number of other drugs, drug induced fibromyalgia like symptoms are found with the fluoroquinolones. The multiskeletal adverse reactions of the fluoroquinolones may resemble rheumatological disease states, in particular, fibromyalgia, hypothyroidism, or rheumatoid arthritis. There have been numerous reports of fluoroquinolone-induced fibromyalgia.[72][73] Fluoroquinolone-induced fibromyalgia may be conceptualized as impaired sensory information processing in a neural network, resulting in dysfunctional responses resulting from the CNS and PNS damage outlined above.[74]

One of the most disabling adverse reactions is spontaneous rupture of multiple tendons, which may occur during therapy, as well as up to 6 months after therapy has been discontinued.[75][76] Although the onset of symptoms typically occurs within 12 weeks, injury was also described within hours to as long as months after the initiation of treatment, and even after discontinuation. Tendon injury was reported to occur as early as two hours after receipt of the first dose of a fluoroquinolone (ciprofloxacin)[77] to as late as 6 months after treatment had been terminated.[78][79] Tendinitis, arthralgia, myalgia, as well as severe joint, muscle, and tendon pain, are found to be the top-three adverse reactions reported to the FDA via the Adverse Event Reporting System (AERS)[80] for all the drugs within this class. For example:

November 1997 – November 2001—Ciprofloxacin 1,558 events

Bone, Tendon, Muscle and Ligament Damage

  • Pain in the Extremity (153)
  • Myalgia (148)
  • Tendonitis (122)

November 1997 – November 2001—Levofloxacin 2,898 events

Bone, Tendon, Muscle and Ligament Damage

  • Arthralgia (368)
  • Tendon Disorders (318)
  • Tendonitis (232)

The odds ratios (ORs) of suffering a spontaneous rupture of the achilles tendon are 4.3, for current exposure 2.4, recent exposure and 1.4 for past exposure to a fluoroquinolone drug, respectively, compared with non-exposure.[81] Within the Netherlands,[82] a large simultaneous increase in non-traumatic tendon ruptures and fluoroquinolone use was observed in the period between 1991 to 1996 following the introduction of the fluoroquinolones. The incidence of spontaneous tendon rupture within the kidney recipient population is even more common.[83] In the renal transplant population, an incidence of 12.2%–15.6% is reported, compared with 0.6%–3.6% for transplant recipients not receiving fluoroquinolones.[84][85] In one study of 149 heart transplant patients,[86] fourteen (9.5%) patients developed Achilles tendinopathy, which in three patients (2.25%) progressed to tendon rupture.

CNS effects

Any CNS side-effect occurs with an incidence of 1–2%.[34] Adverse event reporting for antibiotics found that 12.2% of adverse reaction reports concerning fluoroquinolones involved the CNS versus 3.6% for other antibiotics.[34] Newer agents to have a lower risk of side-effects have been found.[48] Seizures are rare, and usually occur when they do in those with an underlying CNS disorder.[34] However, caution use in patient with epilepsy is still advised.[34] Very rare cases of suicidal behavior have been reported to occur, sometimes after a single dose.[87] Drugs that induce suicidal ideation, including antibiotics, are associated with an increased risk of suicide attempts.[88]

Fluoroquinolones can induce a wide range of serious adverse psychiatric effects. These reactions may manifest as extreme anxiety, panic attacks, depression, anhedonia, cognitive dysfunction (or brain fog), depersonalization, paranoia, hallucinations, toxic psychosis, seizures, tremors, taste perversions, abnormal dreams, chronic insomnia, vertigo, delirium, suicidal thoughts.

In addition, the fluoroquinolones may show depressant activity on the CNS, as was indicated by the depressant syndrome, decreased spontaneous motor activity, and hypothermia found in animal studies. Concomitant use of NSAIDs may increase seizure risk.[89]

A positive correlation exists between the doses of fluoroquinolones and the prolongation (increases) in the caffeine elimination half-life. (In one case a sixfold increase).[90][91]

Electrolyte imbalances are common with previous reports of fluoroquinolone-induced seizures.[37]

The CNS ADRs are a combination of the interference with neurotransmissions (gamma-Aminobutyric acid or GABA), inhibiting of the clearance of other drugs (such as caffeine),[92] reduction of brain glucose uptake,[93] electrolyte imbalances,[37] neuronal dysfunction[94] or degeneration and inflammation. The fluoroquinolones are known as GABA inhibitors and as such have the ability to bind to neuroreceptor sites within the brain that appear to play a role in CNS adverse events. In recent years, extensive in vivo and in vitro experiments have been performed, and several mechanisms are thought to be responsible. The involvement of GABA and excitatory amino acid (EAA) neurotransmission as well as the kinetics of fluoroquinolone distribution in brain tissue are thought to be responsible.[2][95]

Dermatological effects

Photosensitivity reactions as well as life-threatening cutaneous reactions have been reported with the fluoroquinolone class. Such reactions include Stevens–Johnson syndrome, Sweet's syndrome, toxic epidermal necrolysis (TEN), and painful and disfiguring rashes. In 2008, Bayer issued a European "Dear Doctor Letter" advising physicians of the risk of potentially life-threatening bullous skin reactions like Stevens-Johnson-Syndrome (SJS) or toxic epidermal necrolysis (TEN) associated with moxifloxacin (Avelox).[50]

Ciprofloxacin-induced toxic epidermal necrolysis was first reported in 1991[96] with numerous other cases in the following years.[97][98][99][100] Levofloxacin,[99][101][102] Norfloxacin,[103] Ofloxacin,[104] and Trovan[105] have also been associated with toxic epidermal necrolysis.

There have been reports of the association between Steven-Johnson's syndrome and ciprofloxacin, with one case reporting that the syndrome was induced by a single dose of ciprofloxacin.[106] To our knowledge, as of 1997, a total of 6 cases have been reported in the literature documenting an association between oral ciprofloxacin administration and toxic epidermal necrolysis (TEN) or Stevens–Johnson syndrome.[107] A review performed in Sweden (circa 2003) found a total of nine cases. Together with previous data from the literature, these reports support the view that ciprofloxacin, as well as other fluoroquinolones, has the potential to cause fatal or severe adverse cutaneous events.[108]

Photosensitivity reactions reported with the fluoroquinolones mimic those of sunburn, with erythema and edema in the milder forms, and painful blistering with subsequent peeling when severe. A wide spectrum of cutaneous ADRs are reported with fluoroquinolones.

The phototoxic potentials of fluoroquinolones are influenced not only by the substituent at position 8 (Halogenation at position C8) but also by those at position 1. Drugs such as Lomefloxacin and Sparfloxcacin, with a C8-fluorine substituent, and Clinafloxacin, with a C8-chlorine substituent, exhibit a greater incidence of phototoxic reactions than drugs without this substituent.[109] Clinafloxacin was subsequently removed from clinical use due to severe phototoxicity reactions and in June 1995 The Medicines Agency restricted the use of Sparfloxacin due to the large number of reports of phototoxicity associated with its use.[110]

A previous dematologic ADR to a fluoroquinolone can sensitize a patient to more severe adverse reactions (with onset after only a single dose of the subsequent fluoroquinolone), as noted earlier in this presentation.[99] This is also true of other commonly used antibacterial classes, including the penicillins and cephalosporins. Patients having developed any kind of rash to a fluoroquinolone in the past have a potential to develop life-threatening photoallergic reactions when re-challenged with a fluoroquinolone drug later on in life.

PNS effects

Peripheral neuropathy has been rarely reported. Symptoms may include paresthesia (tingling), hypoesthesia (numbness), dysesthesia (pain), and weakness.[111] Therapy should be discontinued if any neurological symptoms develop in order to prevent the occurrence of a possible irreversible condition.[111] Rare cases of sensory impairment involving taste or smell have been reported with a number of fluoroquinolones and may last for up to several months.[112]

Fluoroquinolones have been shown since 1998 to cause irreversible peripheral neuropathy. Typical symptoms involve fasciculations (muscle twitches), paresthesia, tinnitus (ringing in the ear), hyperacusis (hypersensitivity to certain sounds), and other sensorimotor problems. Symptoms usually occur after a delayed onset, and continue to worsen. Quinolone-induced peripheral neuropathy usually presents as burning pain and numbness, and in some cases this becomes an irreversible condition that disables the patient for life. Most often this is the result of quinolone-induced damage to the peripheral nervous system (as noted above), manifesting as painful burning, cold, stinging, tingling paresthesias, or numbness. This may also result from muscle and tendon damage as well if the pain is of a burning or stabbing nature upon use of the limb affected. The exact manner in which the fluoroquinolones cause such PNS damage remains elusive. Several theories point to direct toxicity or vascular involvement. Peripheral neuropathy has been associated with the fluoroquinolone class since 1988 and has been reported in the leading medical journals for over two decades.[113][114][115]

In 2004, the FDA added warnings to the package inserts about the possibility of irreversible fluoroquinolone-innduced peripheral neuropathy.

Cardiac

Fluoroquinolones can cause QT prolongation and, thus, predispose a person to Torsades de Pointes which is sometimes fatal.[24] Some members of the quinolone family are more likely to causes an increased QT than others.[116] Grepafloxacin was removed from the market due to frequent QT prolongation. Of the currently available agents, moxifloxacin causes the greatest QT prolongation, while ciprofloxacin is associated with a lowest risk of QT prolongation.[116]

Blood disorders

Blood abnormalities are believed to occur in less than one percent of patients.[117] However, Temafloxacin was removed from clinical use in 1992 due to its side-effects of hemolytic anemia (destruction of red blood cells) and other blood cell abnormalities; kidney dysfunction requiring renal dialysis (in 50% of patients affected); and severe liver dysfunction.[118]

Blood sugar abnormalities

Changes in blood sugar levels may occur with fluoroquinolones. Risks for this complication includes diabetes, old age, renal failure, and sepsis. Gatifloxacin was removed from the market in the US and Canada partly due to its negative effects on blood sugar.[22] Temafloxacin was removed from clinical use in 1992 partially due to several cases of low blood sugar as well.[119]

Ocular toxicity

  • Oral and IV use

Oral use and I.V. use of the fluoroquinolones are associated with a significant number of serious visual disturbances. Patients receiving fluoroquinolones have been reported to have developed visual disturbances, which include color distortion and diplopia (double vision).[120] Such disturbances may present as blurred and dim vision, disturbed vision, flashing lights, diplopia, floaters,as well as decreased visual acuity and cataracts.[121] Norfloxacin, ProQuin XR and Ciprofloxacin have also been associated with diplopia.,[122][123][124] as well as Iquix (levofloxacin ophthalmic solution).[125][126] There are spontaneous reports of cases of double vision (diplopia) becoming permanent, as well as reports of floaters that never resolved in some patients.[127]

There have also been isolated reports of reversible vision loss and irreversible blindness associated with oral fluoroquinolone therapy.[128][129] Retinal degeneration has also been observed in animals.[130] These reports, while uncommon, include blindness, temporary blindness, partial blindness, and mydriasis.[131] There have also been three reports of serious macular detachment of the neuro-epithelium involving flumequine.[132]

Fluoroquinolones displayed the potential to be cytotoxic to human corneal keratocytes and endothelial cells, depending on drug concentration and duration of exposure. The potential for cytotoxicity may differ among fluoroquinolones.[133]

Hearing effects

  • Oral and IV use

Hearing loss appears to be a very rare event, while fluoroquinolone-induced tinnitus appears to be far more common. Both oral use and IV use of the fluoroquinolones have been reported to cause hearing loss, decreased hearing acuity, hypoacusis, and tinnitus.[134][135] The package inserts for the majority of the fluoroquinolones in use today[134] all list tinnitus as post marketing events. Specific fluoroquinolones[136] list the loss of hearing as reported events. Within the AERS maintained by the FDA, hearing loss, tinnitus, decreased hearing acuity, and hypoacusis have all been reported with the fluoroquinolone class.[137] There have also been isolated case reports of ototoxicity leading to reversible and irreversible deafness as a result of oral or IV therapy.[138] There have been spontaneous reports of fluoroquinlone-induced tinnitus being permanent, together with loss of hearing in the higher frequencies.

  • Otic use (ear drops)

There have been studies showing some in vitro ototoxicity potential in fluoroquinolones.[139] Within a 1992 animal study involving Long Evan rats, nalidixic acid showed partial loss of the outer hair cells of the organ of Corti in the cochlea, suggesting that nalidixic acid has slight ototoxicity.[140] The package insert for Ofloxacin otic solution list the loss of hearing as reported events. There has also been a case report associating the use of Ciprofloxacin ear drops and seizures.[141] Nevertheless, the fluoroquinolone eardrop solutions are believed to be non-ototoxic and are preferred over the known ototoxic aminoglycoside antibiotics, in the topical treatment of ear infections.[142]

DNA effects

The fluoroquinolones exert their therapeutic effects by interfering with bacterial DNA replication by inhibiting an enzyme complex called DNA gyrase. Research has indicated that fluoroquinolones at therapeutically used doses have little effect on enzymes involved in DNA replication in mammalian cells including human cells; however, not all subtypes of eucaryotic topoisomerases have been routinely studied in clinical studies.[143][144][145] In vitro studies in human fibroblast cells have shown that nalidixic acid can impair repair type DNA synthesis at a relatively low dosage (5 ug/ml), but this effect is seen only at very high doses (at least 50 ug/ml) of other quinolones (ciprofloxacin, norfloxacin, and ofloxacin) tested.[146] Fluoroquinolones increase the uptake of deoxyuridine, uridine, and thymidine into the DNA of human lymphocytes and decrease pyrimidine production. A reduction in leucine occurs. With some quinolones, these effects appear to occur at therapeutic dose levels. Quinolones also appear to effect the growth of eucaryotic cells and HeLa cells. However, relatively high doses of quinolones (20 ug/ml) are required to impair eucaryotic cell growth. At doses that are achievable in therapeutic dosing of (5 ug/ml), a 50% reduction in lymphocyte immunogloblin production occurs. DNA damage such as strand breaks, occurs only at extremely high doses of fluoroquinolones (above 100 ug/ml). DNA polymerase a, topoisomerase I, topoisomerase II, and mitochondrial function are inhibited only at high doses of quinolones above the dosages that would be seen in clinical practice.[147][148][149][150][151] Some quinolones have been shown to be capable of causing injury to the chromosome of eukaryotic cells.[152] As such, some fluoroquinolones may cause injury to the chromosome of eukaryotic cells. There is some debate in the medical literature as to whether these DNA effects are to be considered one of the mechanisms of action concerning some of the severe ADRs and toxicities experienced by some patients following fluoroquinolone therapy. It has been speculated that the effects of fluoroquinolones on human eukaryotic topoisomerases have potential to cause cytotoxicity. Fluoroquinolones may have the potential to cause clastogenicity and the induction of micronuclei.[153][154] Retinal pigment epithelial cells are critical to the functioning of the eye and are involved in many eye diseases. In one study, DNA damage to RPE cells was observed with Sparfloxacin.[155]

References

  1. ^ a b Owens RC, Ambrose PG (2005). "Antimicrobial safety: focus on fluoroquinolones". Clin. Infect. Dis. 41 Suppl 2: S144–57. doi:10.1086/428055. PMID 15942881. {{cite journal}}: Unknown parameter |month= ignored (help)
  2. ^ a b c d De Sarro A, De Sarro G (2001). "Adverse reactions to fluoroquinolones. an overview on mechanistic aspects". Curr. Med. Chem. 8 (4): 371–84. PMID 11172695. {{cite journal}}: Unknown parameter |month= ignored (help)
  3. ^ "www.fda.gov".
  4. ^ Skalsky K, Yahav D, Lador A, Eliakim-Raz N, Leibovici L, Paul M (2013). "Macrolides vs. quinolones for community-acquired pneumonia: meta-analysis of randomized controlled trials". Clin. Microbiol. Infect. 19 (4): 370–8. doi:10.1111/j.1469-0691.2012.03838.x. PMID 22489673. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  5. ^ Falagas ME, Matthaiou DK, Vardakas KZ (2006). "Fluoroquinolones vs beta-lactams for empirical treatment of immunocompetent patients with skin and soft tissue infections: a meta-analysis of randomized controlled trials". Mayo Clin. Proc. 81 (12): 1553–66. PMID 17165634. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  6. ^ Van Bambeke F, Tulkens PM (2009). "Safety profile of the respiratory fluoroquinolone moxifloxacin: comparison with other fluoroquinolones and other antibacterial classes". Drug Saf. 32 (5): 359–78. PMID 19419232.
  7. ^ Shehab N, Patel PR, Srinivasan A, Budnitz DS (2008). "Emergency department visits for antibiotic-associated adverse events". Clin. Infect. Dis. 47 (6): 735–43. doi:10.1086/591126. PMID 18694344. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  8. ^ Kim GK (2010). "The Risk of Fluoroquinolone-induced Tendinopathy and Tendon Rupture: What Does The Clinician Need To Know?". J Clin Aesthet Dermatol. 3 (4): 49–54. PMC 2921747. PMID 20725547. {{cite journal}}: Unknown parameter |month= ignored (help)
  9. ^ Sode J, Obel N, Hallas J, Lassen A (2007). "Use of fluroquinolone and risk of Achilles tendon rupture: a population-based cohort study". Eur. J. Clin. Pharmacol. 63 (5): 499–503. doi:10.1007/s00228-007-0265-9. PMID 17334751. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  10. ^ Owens RC, Ambrose PG (2005). "Antimicrobial safety: focus on fluoroquinolones". Clin. Infect. Dis. 41 Suppl 2: S144–57. doi:10.1086/428055. PMID 15942881. {{cite journal}}: Unknown parameter |month= ignored (help)
  11. ^ Khaliq Y, Zhanel GG (2005). "Musculoskeletal injury associated with fluoroquinolone antibiotics". Clin Plast Surg. 32 (4): 495–502, vi. doi:10.1016/j.cps.2005.05.004. PMID 16139623. {{cite journal}}: Unknown parameter |month= ignored (help)
  12. ^ a b Saint F, Gueguen G, Biserte J, Fontaine C, Mazeman E (2000). "[Rupture of the patellar ligament one month after treatment with fluoroquinolone]". Rev Chir Orthop Reparatrice Appar Mot (in French). 86 (5): 495–7. PMID 10970974. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  13. ^ Heidelbaugh JJ, Holmstrom H (2013). "The perils of prescribing fluoroquinolones". J Fam Pract. 62 (4): 191–7. PMID 23570031. {{cite journal}}: Unknown parameter |month= ignored (help)
  14. ^ a b Rubinstein E, Camm J (2002). "Cardiotoxicity of fluoroquinolones". J. Antimicrob. Chemother. 49 (4): 593–6. PMID 11909831. {{cite journal}}: Unknown parameter |month= ignored (help)
  15. ^ Deshpande A, Pasupuleti V, Thota P; et al. (2013). "Community-associated Clostridium difficile infection and antibiotics: a meta-analysis". J. Antimicrob. Chemother. 68 (9): 1951–61. doi:10.1093/jac/dkt129. PMID 23620467. {{cite journal}}: Explicit use of et al. in: |author= (help); Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  16. ^ Slimings C, Riley TV (2013). "Antibiotics and hospital-acquired Clostridium difficile infection: update of systematic review and meta-analysis". J. Antimicrob. Chemother. doi:10.1093/jac/dkt477. PMID 24324224. {{cite journal}}: Unknown parameter |month= ignored (help)
  17. ^ "Data Mining Analysis of Multiple Antibiotics in AERS".
  18. ^ "FDA Drug Safety Communication: FDA requires label changes to warn of risk for possibly permanent nerve damage from antibacterial fluoroquinolone drugs taken by mouth or by injection".
  19. ^ Galatti L, Giustini SE, Sessa A; et al. (2005). "Neuropsychiatric reactions to drugs: an analysis of spontaneous reports from general practitioners in Italy". Pharmacol. Res. 51 (3): 211–6. doi:10.1016/j.phrs.2004.08.003. PMID 15661570. {{cite journal}}: Explicit use of et al. in: |author= (help); Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  20. ^ Babar, S. (2013). "SIADH Associated With Ciprofloxacin" (PDF). The Annals of Pharmacotherapy. 47 (10). Sage Publishing: 1359-1363. doi:10.1177/1060028013502457. ISSN 1060-0280. Retrieved November 139,2013. {{cite journal}}: Check date values in: |accessdate= (help); Unknown parameter |month= ignored (help)
  21. ^ Rouveix, B. (2006). "[Clinically significant toxicity and tolerance of the main antibiotics used in lower respiratory tract infections]". Med Mal Infect. 36 (11–12): 697–705. doi:10.1016/j.medmal.2006.05.012. PMID 16876974. {{cite journal}}: Unknown parameter |month= ignored (help)
  22. ^ a b c d e f g Mehlhorn AJ, Brown DA (2007). "Safety concerns with fluoroquinolones". Annals of Pharmacotherapy. 41 (11): 1859–66. doi:10.1345/aph.1K347. PMID 17911203. {{cite journal}}: Unknown parameter |month= ignored (help) Cite error: The named reference "pmid17911203" was defined multiple times with different content (see the help page).
  23. ^ Jones SF, Smith RH (1997). "Quinolones may induce hepatitis". BMJ. 314 (7084): 869. doi:10.1136/bmj.314.7084.869. PMC 2126221. PMID 9093098. {{cite journal}}: Unknown parameter |month= ignored (help)
  24. ^ a b Cite error: The named reference Gold2006 was invoked but never defined (see the help page).
  25. ^ Iannini PB (2007). "The safety profile of moxifloxacin and other fluoroquinolones in special patient populations". Curr Med Res Opin. 23 (6): 1403–13. doi:10.1185/030079907X188099. PMID 17559736. {{cite journal}}: Unknown parameter |month= ignored (help)
  26. ^ Farinas, Evelyn R (1 March 2005). "Consult: One-Year Post Pediatric Exclusivity Postmarketing Adverse Events Review" (PDF). USA: FDA. Retrieved 31 August 2009. {{cite web}}: Unknown parameter |coauthor= ignored (|author= suggested) (help)
  27. ^ "Consolidated List of Products" (PDF). United Nations. 2005. {{cite web}}: Cite has empty unknown parameter: |coauthors= (help)
  28. ^ The European Medicines Agency (24 July 2008). "EMEA Restricts Use of Oral Norfloxacin Drugs in UTIs". United Kingdom: Doctor's Guide.
  29. ^ The European Medicines Agency (EMEA) (24 July 2008). "EMEA recommends restricting the use of oral moxifloxacin-containing medicines". {{cite web}}: Unknown parameter |coauthors= ignored (|author= suggested) (help)
  30. ^ de Castro FR, Torres A (2003). "Optimizing treatment outcomes in severe community-acquired pneumonia". Am J Respir Med. 2 (1): 39–54. PMID 14720021.
  31. ^ Niyogi SK (2005). "Shigellosis". J. Microbiol. 43 (2): 133–43. PMID 15880088. {{cite journal}}: Unknown parameter |month= ignored (help)
  32. ^ R. Schaumann (2007). "Activities of Quinolones Against Obligately Anaerobic Bacteria" (PDF). Anti-Infective Agents in Medicinal Chemistry. 6: 49–56. {{cite journal}}: Unknown parameter |coauthors= ignored (|author= suggested) (help)
  33. ^ Pariente-Khayat, A.; Vauzelle-Kervroedan, F.; d'Athis, P.; Bréart, G.; Gendrel, D.; Aujard, Y.; Olive, G.; Pons, G. (1998). "[Retrospective survey of fluoroquinolone use in children]". Arch Pediatr. 5 (5): 484–8. doi:10.1016/S0929-693X(99)80311-X. PMID 9759180. {{cite journal}}: Unknown parameter |month= ignored (help)
  34. ^ a b c d e f g h i j k l Owens RC, Ambrose PG (2005). "Antimicrobial safety: focus on fluoroquinolones". Clin. Infect. Dis. 41 (Suppl 2): S144–57. doi:10.1086/428055. PMID 15942881. {{cite journal}}: Unknown parameter |month= ignored (help)
  35. ^ Committee on Safety of Medicines (2008). "Quinolones". United Kingdom: British National Formulary. Retrieved 16 February 2009. {{cite web}}: Unknown parameter |coauthors= ignored (|author= suggested) (help)
  36. ^ Bayer HealthCare Pharmaceuticals Inc (2008). "CIPRO (ciprofloxacin hydrochloride) TABLETS CIPRO,(ciprofloxacin*) ORAL SUSPENSION" (PDF). USA: FDA. Retrieved 31 August 2009. {{cite web}}: Cite has empty unknown parameter: |coauthors= (help); Unknown parameter |month= ignored (help)
  37. ^ a b c Kushner JM, Peckman HJ, Snyder CR (2001). "Seizures associated with fluoroquinolones". Annals of Pharmacotherapy. 35 (10): 1194–8. doi:10.1345/aph.10359. PMID 11675843. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  38. ^ "(WO/2002/093162) INDIVIDUALIZATION OF THERAPY WITH ANTIBIOTIC AGENTS". World Health Organisation. 21 November 2002.
  39. ^ Professor Heather Ashton (2002). "Benzodiazepines: How They Work and How to Withdraw".
  40. ^ McConnell JG (2008). "Benzodiazepine tolerance, dependency, and withdrawal syndromes and interactions with fluoroquinolone antimicrobials". British Journal of General Practice. 58 (550). Royal College of General Practitioners: 365–366. doi:10.3399/bjgp08X280317. PMC 2435654. PMID 18482496. {{cite journal}}: Unknown parameter |month= ignored (help)
  41. ^ Unseld E (1990). "Possible interaction of fluoroquinolones with the benzodiazepine-GABAA-receptor complex". Br J Clin Pharmacol. 30 (1): 63–70. doi:10.1111/j.1365-2125.1990.tb03744.x. PMC 1368276. PMID 2167717. {{cite journal}}: Unknown parameter |coauthors= ignored (|author= suggested) (help); Unknown parameter |month= ignored (help)
  42. ^ Sternbach H, State R (1997). "Antibiotics: neuropsychiatric effects and psychotropic interactions". Harv Rev Psychiatry. 5 (4): 214–26. doi:10.3109/10673229709000304. PMID 9427014.
  43. ^ Martin S. Spiller, D.M.D. "The Local Anesthetics". Archived from the original on 18 January 2009. Retrieved 30 January 2009. {{cite web}}: Unknown parameter |deadurl= ignored (|url-status= suggested) (help)
  44. ^ Cite error: The named reference cdacfh09 was invoked but never defined (see the help page).
  45. ^ Cite error: The named reference Muto-2003 was invoked but never defined (see the help page).
  46. ^ Cite error: The named reference Tacconelli-2008 was invoked but never defined (see the help page).
  47. ^ "Toxin Gene Expression by Shiga Toxin-Producing Escherichia coli: the Role of Antibiotics and the Bacterial SOS Response". Cdc.gov. 2009-03-05. Retrieved 2011-03-29.
  48. ^ a b c d e Ball P, Mandell L, Niki Y, Tillotson G (1999). "Comparative tolerability of the newer fluoroquinolone antibacterials". Drug Saf. 21 (5): 407–21. doi:10.2165/00002018-199921050-00005. PMID 10554054. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  49. ^ Borcherding SM, Stevens R, Nicholas RA, Corley CR, Self T (1996). "Quinolones: a practical review of clinical uses, dosing considerations, and drug interactions". J Fam Pract. 42 (1): 69–78. PMID 8537808. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  50. ^ a b Bayer Schering Pharma, Bayer plc (2008). "IMPORTANT INFORMATION REGARDING SERIOUS ADVERSE REACTIONS AND SAFETY MEASURES" (PDF). United Kingdom: Medicines and Healthcare products Regulatory Agency (MHRA). {{cite web}}: Unknown parameter |month= ignored (help)
  51. ^ Zimpfer, Annette; Propst, Albert; Mikuz, Gregor; Vogel, Wolfgang; Terracciano, Luigi; Stadlmann, Sylvia (2004). "Ciprofloxacin-induced acute liver injury: case report and review of literature". Virchows Archiv. 1. 444 (1): 87–9. doi:10.1007/s00428-003-0917-9. ISSN 0945-6317. PMID 14994731.
  52. ^ Renata Albrecht (19 June 2007). "NDA 20-634/S-045, NDA 20-635/S-048, NDA 21-721/S-013" (PDF). USA: FDA.
  53. ^ Saint F, Salomon L, Cicco A, de la Taille A, Chopin D, Abbou CC (2001). "[Tendinopathy associated with fluoroquinolones: individuals at risk, incriminated physiopathologic mechanisms, therapeutic management]". Prog. Urol. (in French). 11 (6): 1331–4. PMID 11859676. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  54. ^ Fashner J, Garcia M, Ribble L, Crowell K (September 2011). "Clinical inquiry: what risk factors contribute to C difficile diarrhea?". J Fam Pract. 60 (9): 545–7. PMID 21901182.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  55. ^ McCusker ME, Harris AD, Perencevich E, Roghmann MC (2003). "Fluoroquinolone Use and Clostridium difficile–Associated Diarrhea". Emerging Infect. Dis. 9 (6): 730–3. doi:10.3201/eid0906.020385. PMC 3000134. PMID 12781017. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  56. ^ Deshpande A, Pant C, Jain A, Fraser TG, Rolston DD (2008). "Do fluoroquinolones predispose patients to Clostridium difficile associated disease? A review of the evidence". Curr Med Res Opin. 24 (2): 329–33. doi:10.1185/030079908X253735. PMID 18067688. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  57. ^ Walbrown MA, Aspinall SL, Bayliss NK; et al. (2008). "Evaluation of Clostridium difficile-associated diarrhea with a drug formulary change in preferred fluoroquinolones" (PDF). J Manag Care Pharm. 14 (1): 34–40. PMID 18240880. {{cite journal}}: Explicit use of et al. in: |author= (help)CS1 maint: multiple names: authors list (link)
  58. ^ Muto CA, Pokrywka M, Shutt K; et al. (2005). "A large outbreak of Clostridium difficile-associated disease with an unexpected proportion of deaths and colectomies at a teaching hospital following increased fluoroquinolone use". Infect Control Hosp Epidemiol. 26 (3): 273–80. doi:10.1086/502539. PMID 15796280. {{cite journal}}: Explicit use of et al. in: |author= (help); Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  59. ^ Cain DB, O'Connor ME (1990). "Pseudomembranous colitis associated with ciprofloxacin". Lancet. 336 (8720): 946. doi:10.1016/0140-6736(90)92320-H. PMID 1976960. {{cite journal}}: Unknown parameter |month= ignored (help)
  60. ^ Pérez-Calvo JI, Matamala C, Sanjoaquín I, Amores M, Castillo J, Bueno-Gómez J (1993). "[Diarrhea following antibiotic treatment, Clostridium difficile, and quinolones]". Enferm. Infecc. Microbiol. Clin. (in Spanish; Castilian). 11 (6): 345. PMID 8347715.{{cite journal}}: CS1 maint: multiple names: authors list (link) CS1 maint: unrecognized language (link)
  61. ^ Ozawa TT, Valadez T (2002). "Clostridium difficile infection associated with levofloxacin treatment". Tenn Med. 95 (3): 113–5. PMID 11898264. {{cite journal}}: Unknown parameter |month= ignored (help)
  62. ^ Ortiz-de-Saracho J, Pantoja L, Romero MJ, López R (2003). "Moxifloxacin-induced Clostridium difficile diarrhea". Annals of Pharmacotherapy. 37 (3): 452–3. doi:10.1345/aph.1C325. PMID 12639182. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  63. ^ Mavromanolakis E, Maraki S, Cranidis A, Tselentis Y, Kontoyiannis DP, Samonis G (2001). "The impact of norfloxacin, ciprofloxacin and ofloxacin on human gut colonization by Candida albicans". Scand. J. Infect. Dis. 33 (6): 477–8. doi:10.1080/00365540152030006. PMID 11450873.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  64. ^ Yip C, Loeb M, Salama S, Moss L, Olde J (2001). "Quinolone use as a risk factor for nosocomial Clostridium difficile-associated diarrhea". Infect Control Hosp Epidemiol. 22 (9): 572–5. doi:10.1086/501954. PMID 11732787. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  65. ^ Meyers JS, Ehrenpreis ED, Craig RM (2001). "Small Intestinal Bacterial Overgrowth Syndrome". Curr Treat Options Gastroenterol. 4 (1): 7–14. doi:10.1007/s11938-001-0042-2. PMID 11177677. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  66. ^ Cottrell WC, Pearsall AW, Hollis MJ (2002). "Simultaneous tears of the Achilles tendon and medial head of the gastrocnemius muscle". Orthopedics. 25 (6): 685–7. PMID 12083581. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  67. ^ Bertin P, Gillet P, Treves R, Netter P (1998). "[Do some drugs have adverse effects on cartilage?]". Therapie (in French). 53 (1): 17–20. PMID 9773095.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  68. ^ "UpToDate Inc".
  69. ^ Cite error: The named reference pmid12039823 was invoked but never defined (see the help page).
  70. ^ "FDA News Release". Food and Drug Administration (United States).
  71. ^ Lipsky BA, Baker CA (1999). "Fluoroquinolone toxicity profiles: a review focusing on newer agents". Clin. Infect. Dis. 28 (2): 352–64. doi:10.1086/515104. PMID 10064255. {{cite journal}}: Unknown parameter |month= ignored (help)
  72. ^ di Fazano CS, Bertin P (2001). "The pharmacological management of drug-induced rheumatic disorders". Expert Opin Pharmacother. 2 (10): 1623–31. doi:10.1517/14656566.2.10.1623. PMID 11825305. {{cite journal}}: Unknown parameter |month= ignored (help)
  73. ^ Vergne P, Bertin P, Bonnet C, Scotto C, Trèves R (2000). "Drug-induced rheumatic disorders: incidence, prevention and management". Drug Saf. 23 (4): 279–93. doi:10.2165/00002018-200023040-00002. PMID 11051216. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  74. ^ Wahle M, Krause A, Pierer M, Hantzschel H, Baerwald CG (2002). "Immunopathogenesis of rheumatic diseases in the context of neuroendocrine interactions". Annals of the New York Academy of Sciences. 966: 355–64. doi:10.1111/j.1749-6632.2002.tb04235.x. PMID 12114292. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  75. ^ Bailey RR, Natale R, Linton AL (1972). "Nalidixic acid arthralgia". Can Med Assoc J. 107 (7): 604 passim. PMC 1940945. PMID 4541768. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  76. ^ Harrell RM (1999). "Fluoroquinolone-induced tendinopathy: what do we know?". South. Med. J. 92 (6): 622–5. doi:10.1097/00007611-199906000-00014. PMID 10372859. {{cite journal}}: Unknown parameter |month= ignored (help)
  77. ^ Jagose JT, McGregor DR, Nind GR, Bailey RR (1996). "Achilles tendon rupture due to ciprofloxacin". N. Z. Med. J. 109 (1035): 471–2. PMID 9006634. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  78. ^ Casparian JM, Luchi M, Moffat RE, Hinthorn D (2000). "Quinolones and tendon ruptures". South. Med. J. 93 (5): 488–91. PMID 10832946. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  79. ^ Khaliq Y, Zhanel GG (2003). "Fluoroquinolone-associated tendinopathy: a critical review of the literature". Clin. Infect. Dis. 36 (11): 1404–10. doi:10.1086/375078. PMID 12766835. {{cite journal}}: Unknown parameter |month= ignored (help)
  80. ^ Summaries received from the FDA under the Freedom of Information Act. Accessed November of 2001
  81. ^ "Avoiding Achilles Tendon Ruptures in the Elderly". Clinical Reviews. Retrieved 22 February 2009.
  82. ^ van der Linden PD, Nab HW, Simonian S, Stricker BH, Leufkens HG, Herings RM (2001). "Fluoroquinolone use and the change in incidence of tendon ruptures in the Netherlands" (PDF). Pharm World Sci. 23 (3): 89–92. doi:10.1023/A:1011254030271. PMID 11468881. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  83. ^ Muzi F, Gravante G, Tati E, Tati G (2007). "Fluoroquinolones-induced tendinitis and tendon rupture in kidney transplant recipients: 2 cases and a review of the literature". Transplant. Proc. 39 (5): 1673–5. doi:10.1016/j.transproceed.2007.01.077. PMID 17580216. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  84. ^ Donck JB, Segaert MF, Vanrenterghem YF (1994). "Fluoroquinolones and Achilles tendinopathy in renal transplant recipients". Transplantation. 58 (6): 736–7. doi:10.1097/00007890-199409270-00021. PMID 7940700. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  85. ^ Leray H, Mourad G, Chong G, Marcelli C, Borderie P, Mion C (1993). "[Spontaneous ruptures of the Achilles tendon after kidney transplantation: use of fluoroquinolones]". Presse Med (in French). 22 (36): 1834. PMID 8309916. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  86. ^ Barge-Caballero E, Crespo-Leiro MG, Paniagua-Martín MJ; et al. (2008). "Quinolone-related Achilles tendinopathy in heart transplant patients: incidence and risk factors". J. Heart Lung Transplant. 27 (1): 46–51. doi:10.1016/j.healun.2007.09.021. PMID 18187086. {{cite journal}}: Explicit use of et al. in: |author= (help); Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  87. ^ "Tavanic SPC" (PDF). Sanofi-aventis.
  88. ^ Robertson, HT.; Allison, DB.; Wright, James M. (2009). Wright, James M. (ed.). "Drugs Associated with More Suicidal Ideations Are also Associated with More Suicide Attempts". PLoS ONE. 4 (10): e7312. doi:10.1371/journal.pone.0007312. PMC 2749439. PMID 19798416. {{cite journal}}: Cite has empty unknown parameter: |month= (help)CS1 maint: unflagged free DOI (link)
  89. ^ Rollof J, Vinge E (1993). "Neurologic adverse effects during concomitant treatment with ciprofloxacin, NSAIDS, and chloroquine: possible drug interaction". Annals of Pharmacotherapy. 27 (9): 1058–9. PMID 8219437. {{cite journal}}: Unknown parameter |month= ignored (help)
  90. ^ Lamarine RJ (1994). "Selected health and behavioral effects related to the use of caffeine". J Community Health. 19 (6): 449–66. doi:10.1007/BF02260326. PMID 7844249. {{cite journal}}: Unknown parameter |month= ignored (help)
  91. ^ Harder S, Fuhr U, Staib AH, Wolff T (1989). "Ciprofloxacin-caffeine: a drug interaction established using in vivo and in vitro investigations". Am. J. Med. 87 (5A): 89S–91S. doi:10.1016/0002-9343(89)90031-4. PMID 2589393. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  92. ^ Harder S, Staib AH, Beer C, Papenburg A, Stille W, Shah PM (1988). "4-quinolones inhibit biotransformation of caffeine". Eur. J. Clin. Pharmacol. 35 (6): 651–6. doi:10.1007/BF00637602. PMID 2853056.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  93. ^ Ge DT, Law PY, Kong SK, Ho YY (2009). "Disturbance of cellular glucose transport by two prevalently used fluoroquinolone antibiotics ciprofloxacin and levofloxacin involves glucose transporter type 1". Toxicol. Lett. 184 (2): 81–4. doi:10.1016/j.toxlet.2008.10.017. PMID 19022360. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  94. ^ Roos K (2006). "Inflammatory diseases and infection". Current Opinion in Neurology. 19 (4): 339–40. doi:10.1097/01.wco.0000236611.28721.5d. PMID 16914970. {{cite journal}}: Unknown parameter |month= ignored (help)
  95. ^ Dodd PR, Davies LP, Watson WE; et al. (1989). "Neurochemical studies on quinolone antibiotics: effects on glutamate, GABA and adenosine systems in mammalian CNS". Pharmacol. Toxicol. 64 (5): 404–11. doi:10.1111/j.1600-0773.1989.tb00676.x. PMID 2771865. {{cite journal}}: Explicit use of et al. in: |author= (help); Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  96. ^ Tham TC, Allen G, Hayes D, McGrady B, Riddell JG (1991). "Possible association between toxic epidermal necrolysis and ciprofloxacin". Lancet. 338 (8765): 522. doi:10.1016/0140-6736(91)90602-L. PMID 1678488. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  97. ^ Urbina, F; Barrios, M; Sudy, E (2006). "Photolocalized purpura during ciprofloxacin therapy". Photodermatology, photoimmunology & photomedicine. 22 (2): 111–2. doi:10.1111/j.1600-0781.2006.00210.x. ISSN 0905-4383. PMID 16606417. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  98. ^ Rodríguez-Morales, A; Llamazares, Aa; Benito, Rp; Cócera, Cm (2001). "Fixed drug eruption from quinolones with a positive lesional patch test to ciprofloxacin". Contact dermatitis. 44 (4): 255. doi:10.1034/j.1600-0536.2001.440409-10.x. ISSN 0105-1873. PMID 11336009. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  99. ^ a b c Christie, Mj; Wong, K; Ting, Rh; Tam, Py; Sikaneta, Tg (2005). "Generalized seizure and toxic epidermal necrolysis following levofloxacin exposure". Annals of Pharmacotherapy. 39 (5): 953–5. doi:10.1345/aph.1E587. ISSN 1060-0280. PMID 15827068. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  100. ^ Moshfeghi, M; Mandler, Hd (1993). "Ciprofloxacin-induced toxic epidermal necrolysis". Annals of Pharmacotherapy. 27 (12): 1467–9. ISSN 1060-0280. PMID 8305780. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  101. ^ Digwood-Lettieri S, Reilly KJ, Haith LR; et al. (2002). "Levofloxacin-induced toxic epidermal necrolysis in an elderly patient". Pharmacotherapy. 22 (6): 789–93. doi:10.1592/phco.22.9.789.34074. PMID 12066972. {{cite journal}}: Explicit use of et al. in: |author= (help); Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  102. ^ Digwood-Lettieri, S; Reilly, Kj; Haith, Lr, Jr; Patton, Ml; Guilday, Rj; Cawley, Mj; Ackerman, Bh (2002). "Levofloxacin-induced toxic epidermal necrolysis in an elderly patient". Pharmacotherapy. 22 (6): 789–93. doi:10.1592/phco.22.9.789.34074. ISSN 0277-0008. PMID 12066972. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  103. ^ Sahin, Mt; Ozturkcan, S; Inanir, I; Filiz, Ee (2005). "Norfloxacin-induced toxic epidermal necrolysis". Annals of Pharmacotherapy. 39 (4): 768–70. doi:10.1345/aph.1E530. ISSN 1060-0280. PMID 15713789. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  104. ^ Melde, Sl (2001). "Ofloxacin: a probable cause of toxic epidermal necrolysis". Annals of Pharmacotherapy. 35 (11): 1388–90. doi:10.1345/aph.1Z433. ISSN 1060-0280. PMID 11724089. {{cite journal}}: Unknown parameter |month= ignored (help)
  105. ^ Matthews MR, Caruso DM, Phillips BJ, Csontos LG (1999). "Fulminant toxic epidermal necrolysis induced by trovafloxacin". Arch. Intern. Med. 159 (18): 2225. doi:10.1001/archinte.159.18.2225. PMID 10527301. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  106. ^ Gohel DR, Oza JJ (1994). "Steven-Johnson's syndrome following single dose of ciprofloxacin". J Assoc Physicians India. 42 (8): 665. PMID 7868575. {{cite journal}}: Unknown parameter |month= ignored (help)
  107. ^ Livasy, Ca; Kaplan, Am (1997). "Ciprofloxacin-induced toxic epidermal necrolysis: a case report". Dermatology (Basel, Switzerland). 195 (2): 173–5. doi:10.1159/000245726. ISSN 1018-8665. PMID 9310730. {{cite journal}}: Cite has empty unknown parameter: |month= (help)CS1 maint: multiple names: authors list (link)
  108. ^ Hällgren, J; Tengvall-Linder, M; Persson, M; Wahlgren, Cf (2003). "Stevens–Johnson syndrome associated with ciprofloxacin: a review of adverse cutaneous events reported in Sweden as associated with this drug". Journal of the American Academy of Dermatology. 49 (5 Suppl): S267–9. doi:10.1016/S0190-9622(03)00478-X. ISSN 0190-9622. PMID 14576649. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  109. ^ Domagala, Jm (1994). "Structure-activity and structure-side-effect relationships for the quinolone antibacterials". The Journal of antimicrobial chemotherapy. 33 (4): 685–706. doi:10.1093/jac/33.4.685. ISSN 0305-7453. PMID 8056688. {{cite journal}}: Unknown parameter |month= ignored (help)
  110. ^ "products_0_Start" (PDF). Retrieved 2011-03-29.
  111. ^ a b "MedWatch - July 2004 Safety-Related Drug Labeling Changes - Detailed". Food and Drug Administration (United States).
  112. ^ "Safety profile of grepafloxacin compared with other fluoroquinolones" (PDF). Ralf Stahlmann and Rudolf Schwabe.
  113. ^ Cite error: The named reference Hedenmalm96 was invoked but never defined (see the help page).
  114. ^ Aoun M, Jacquy C, Debusscher L; et al. (1992). "Peripheral neuropathy associated with fluoroquinolones". Lancet. 340 (8811): 127. doi:10.1016/0140-6736(92)90460-K. PMID 1352007. {{cite journal}}: Explicit use of et al. in: |author= (help); Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  115. ^ Cohen JS (2001). "Peripheral neuropathy associated with fluoroquinolones". Annals of Pharmacotherapy. 35 (12): 1540–7. doi:10.1345/aph.1Z429. PMID 11793615. {{cite journal}}: Unknown parameter |month= ignored (help)
  116. ^ a b Falagas ME, Rafailidis PI, Rosmarakis ES (2007). "Arrhythmias associated with fluoroquinolone therapy". Int. J. Antimicrob. Agents. 29 (4): 374–9. doi:10.1016/j.ijantimicag.2006.11.011. PMID 17241772. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  117. ^ "UpToDate Inc". Uptodate.
  118. ^ Cite error: The named reference fda.gov was invoked but never defined (see the help page).
  119. ^ http://www.fda.gov/ohrms/dockets/ac/98/briefingbook/1998-3454B1_03_WL49.pdf
  120. ^ Ball P (1989). "Adverse reactions and interactions of fluoroquinolones". Clin Invest Med. 12 (1): 28–34. PMID 2646053. {{cite journal}}: Unknown parameter |month= ignored (help)
  121. ^ The antimicrobial drugs By Eric Michael Scholar, William B. Pratt Edition: 2, illustrated Published by Oxford University Press US, 2000 ISBN 0-19-512529-0, ISBN 978-0-19-512529-0 607 pages citing to page 271 and reference [160], to wit: W. Christ and B. Esch, Adverse reactions to fluoroquinolones in adults and children. Infect Dis Clin Pract 1994;3 (Suppl 3). S168-S176 http://books.google.com/books?id=gACeB8XCnpgC&pg=PA271&lpg=PA271&dq=%22diplopia%22+%22quinolone%22&source=bl&ots=5Mcj9Hc-jm&sig=eZXYD15q5LPQ8EpFtsZgLeDrRMA&hl=en&ei=PTe0SbvYLIGCtwfZvpmtCQ&sa=X&oi=book_result&resnum=9&ct=result
  122. ^ Poisoning and toxicology handbook By Jerrold B. Leikin, Frank P. Paloucek Edition: 4, illustrated Published by Informa Health Care, 2007 ISBN 1-4200-4479-6, ISBN 978-1-4200-4479-9 Page 503-504 / page 194
  123. ^ "MedWatch Safety Alerts for Human Medical Products" (PDF). Fda.gov. 2008-11-06. Retrieved 2011-03-29.
  124. ^ [1][dead link‍]
  125. ^ http://vistakonpharmaceutical.com/pdf/iquix_pi.pdf
  126. ^ http://www.accessdata.fda.gov/drugsatfda_docs/label/2004/21571_iquix_lbl.pdf
  127. ^ Fraunfelder, Fw; Fraunfelder, Ft (2009). "Diplopia and Fluoroquinolones". Ophthalmology. 116 (9): 1814–7. doi:10.1016/j.ophtha.2009.06.027. ISSN 0161-6420. PMID 19643481. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  128. ^ Vrabec TR, Sergott RC, Jaeger EA, Savino PJ, Bosley TM (1990). "Reversible visual loss in a patient receiving high-dose ciprofloxacin hydrochloride (Cipro)". Ophthalmology. 97 (6): 707–10. PMID 2374675. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  129. ^ "Case Presentation - Moxifloxacin (Avelox)". written at Canada (PDF). Canadian Adverse Drug Reaction Newsletter. October 2002. http://www.hc-sc.gc.ca/dhp-mps/alt_formats/hpfb-dgpsa/pdf/medeff/carn-bcei_v12n4-eng.pdf. Retrieved on 30 January 2009.
  130. ^ Gelatt KN, van der Woerdt A, Ketring KL; et al. (2001). "Enrofloxacin-associated retinal degeneration in cats". Vet Ophthalmol. 4 (2): 99–106. doi:10.1046/j.1463-5224.2001.00182.x. PMID 11422990. {{cite journal}}: Explicit use of et al. in: |author= (help); Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  131. ^ Shimoda K, Okawara S, Kato M (2001). "Phototoxic retinal degeneration and toxicokinetics of sitafloxacin, a quinolone antibacterial agent, in mice". Arch. Toxicol. 75 (7): 395–9. doi:10.1007/s002040100263. PMID 11693179. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  132. ^ Sirbat D, Saudax E, Hurault de Ligny B, Hachet E, Raspiller A (1983). "[Serous macular detachment of the neuro-epithelium and flumequine]". J Fr Ophtalmol (in French). 6 (10): 829–36. PMID 6672059.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  133. ^ Bezwada P, Clark LA, Schneider S (2008). "Intrinsic cytotoxic effects of fluoroquinolones on human corneal keratocytes and endothelial cells". Curr Med Res Opin. 24 (2): 419–24. doi:10.1185/030079908X261005. PMID 18157922. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  134. ^ a b Moxifloxacin (Avelox) package insert: http://www.accessdata.fda.gov/drugsatfda_docs/label/2008/021085s039,021277s033lbl.pdf Ciprofloxacin (Cipro) package insert: http://www.accessdata.fda.gov/drugsatfda_docs/label/2008/019537s68,19847s42,19857s49,20780s26,21473s24lbl.pdf Ofloxacin (Floxin) package insert: http://www.accessdata.fda.gov/drugsatfda_docs/label/2008/019735s059lbl.pdf Levofloxacin (Levaquin) package insert: http://www.accessdata.fda.gov/drugsatfda_docs/label/2008/021721s020_020635s57_020634s52_lbl.pdf Norfloxacin (Noroxin) package insert: http://www.accessdata.fda.gov/drugsatfda_docs/label/2008/019384s052lbl.pdf Proquin XR package insert: http://www.accessdata.fda.gov/drugsatfda_docs/label/2008/021744s008lbl.pdf Sparfloxacin (Zagam) package insert: http://www.accessdata.fda.gov/drugsatfda_docs/label/2003/020677s006lbl.pdf Cinoxacin (Cinobac) package insert: http://www.accessdata.fda.gov/drugsatfda_docs/label/2002/18067s29lbl.pdf Equin (Solage) package insert: http://www.accessdata.fda.gov/drugsatfda_docs/label/2007/020922s003lbl.pdf Ofloxacin otic package insert: http://www.accessdata.fda.gov/drugsatfda_docs/label/2008/019735s059lbl.pdf
  135. ^ Paul J, Brown NM (1995). "Tinnitus and ciprofloxacin". BMJ. 311 (6999): 232. PMC 2550285. PMID 7627041. {{cite journal}}: Unknown parameter |month= ignored (help)
  136. ^ Ciprofloxacin (Cipro) package insert:http://www.accessdata.fda.gov/drugsatfda_docs/label/2008/019537s68,19847s42,19857s49,20780s26,21473s24lbl.pdf Ofloxacin otic package insert: http://www.accessdata.fda.gov/drugsatfda_docs/label/2003/20799slr012_floxin_lbl.pdf Norfloxacin (Noroxin) package insert: http://www.accessdata.fda.gov/drugsatfda_docs/label/2008/019384s052lbl.pdf Proquin XR package insert: http://www.accessdata.fda.gov/drugsatfda_docs/label/2008/021744s008lbl.pdf
  137. ^ http://www.fdable.com/basic_query/aers/7e829e140dd289c9dec44e9541ca7846 (ciprofloxacin) http://www.fdable.com/basic_query/aers/cf0caad8d6cdfcab19e88d5f0bec72a0 (moxifloxacin) http://www.fdable.com/basic_query/aers/4d2af494063504d3bf8c9559180915cc (ofloxacin) http://www.fdable.com/basic_query/aers/5fc512f95c82788f16456a4a4853dfcd (levofloxacin) http://www.fdable.com/basic_query/aers/97cfd7d5bcdeabe2bbaf89d4d2c7a3da (norfloxacin) http://www.fdable.com/basic_query/aers/714e096436dd911b78b410cb28b1a07e (cinoxacin)
  138. ^ ^ "Ciprofloxacin: suspected association with deafness and reduced hearing" (PDF). Canadian Adverse Reaction Newsletter (Health Canada) 14 (1). January 2004. http://www.hc-sc.gc.ca/dhp-mps/alt_formats/hpfb-dgpsa/pdf/medeff/carn-bcei_v14n1-eng.pdf. Retrieved on 18 February 2009.
  139. ^ Russell PT, Church CA, Jinn TH, Kim DJ, John EO, Jung TT (2001). "Effects of common topical otic preparations on the morphology of isolated cochlear outer hair cells". Acta Otolaryngol. 121 (2): 135–9. doi:10.1080/000164801300043208. PMID 11349764. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  140. ^ Ophthalmotoxicity and ototoxicity of the new quinolone antibacterial agent levofloxacin in Long Evans rats. Nomura M, Yamada M, Yamamura H, Kajimura T, Takayama S. Drug Safety Research Center, Daiichi Pharmaceutical Co., Ltd., Tokyo, Japan.
  141. ^ Orr, Cf; Rowe, Db (2003). "Eardrop attacks: seizures triggered by ciprofloxacin eardrops". The Medical journal of Australia. 178 (7): 343. ISSN 0025-729X. PMID 12670280. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  142. ^ ^ Coats H (April 2008). "Ear drops and ototoxicity". Australian Prescriber 31 (2): 40–1. http://www.australianprescriber.com/magazine/31/2/40/1/
  143. ^ Gootz TD, Barrett JF, Sutcliffe JA (1990). "Inhibitory effects of quinolone antibacterial agents on eucaryotic topoisomerases and related test systems". Antimicrob. Agents Chemother. 34 (1): 8–12. doi:10.1128/AAC.34.1.8. PMC 171510. PMID 2158274. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  144. ^ Thomas A, Tocher J, Edwards DI (1990). "Electrochemical characteristics of five quinolone drugs and their effect on DNA damage and repair in Escherichia coli". J. Antimicrob. Chemother. 25 (5): 733–44. doi:10.1093/jac/25.5.733. PMID 2165050. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  145. ^ "Fluoroquinolones and Quinolones". The American Academy of Optometry (British Chapter). Archived from the original on 12 March 2009. Retrieved 29 January 2009. {{cite web}}: Unknown parameter |deadurl= ignored (|url-status= suggested) (help)
  146. ^ Hussy P, Maass G, Tümmler B, Grosse F, Schomburg U (1986). "Effect of 4-quinolones and novobiocin on calf thymus DNA polymerase alpha primase complex, topoisomerases I and II, and growth of mammalian lymphoblasts" (PDF). Antimicrob. Agents Chemother. 29 (6): 1073–8. doi:10.1128/AAC.29.6.1073. PMC 180502. PMID 3015015. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  147. ^ Forsgren A, Bredberg A, Pardee AB, Schlossman SF, Tedder TF (1987). "Effects of ciprofloxacin on eucaryotic pyrimidine nucleotide biosynthesis and cell growth" (PDF). Antimicrob. Agents Chemother. 31 (5): 774–9. doi:10.1128/AAC.31.5.774. PMC 174831. PMID 3606077. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  148. ^ Yaseen A. Al-Soud; Najim A. Al-Masoudi (2003). "A new class of dihaloquinolones bearing N'-aldehydoglycosylhydrazides, mercapto-1,2,4-triazole, oxadiazoline and a-amino ester precursors: synthesis and antimicrobial activity". J. Braz. Chem. Soc. 14 (5): 790. doi:10.1590/S0103-50532003000500014. Nevertheless, some quinolones cause injury to the chromosome of eukaryotic cells.21,22 These findings prompted us to optimize the substituent at C-3, by... {{cite journal}}: Cite has empty unknown parameter: |month= (help)CS1 maint: multiple names: authors list (link)
  149. ^ Elsea SH, Osheroff N, Nitiss JL (1992). "Cytotoxicity of quinolones toward eukaryotic cells. Identification of topoisomerase II as the primary cellular target for the quinolone CP-115,953 in yeast". J. Biol. Chem. 267 (19): 13150–3. PMID 1320012. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  150. ^ Lawrence JW, Darkin-Rattray S, Xie F, Neims AH, Rowe TC (1993). "4-Quinolones cause a selective loss of mitochondrial DNA from mouse L1210 leukemia cells". J. Cell. Biochem. 51 (2): 165–74. doi:10.1002/jcb.240510208. PMID 8440750. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  151. ^ Enzmann H, Wiemann C, Ahr HJ, Schlüter G (1999). "Damage to mitochondrial DNA induced by the quinolone Bay y 3118 in embryonic turkey liver". Mutat. Res. 425 (2): 213–24. doi:10.1016/S0027-5107(99)00044-5. PMID 10216214. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  152. ^ Yaseen A. Al-Soud a and Najim A. Al-Masoudi (2003). "A New Class of Dihaloquinolones Bearing N'-Aldehydoglycosylhydrazides, Mercapto-1,2,4-triazole, Oxadiazoline and α-Amino Ester Precursors: Synthesis and Antimicrobial Activity" (PDF). J. Braz. Chem. Soc. 14 (5): 790–796. doi:10.1590/S0103-50532003000500014. Although the current quinolones are not considered to be potent inhibitors of eucaryotic topoisomerases, some effects on these and other enzymes involved with DNA replication have been observed
  153. ^ Suto MJ, Domagala JM, Roland GE, Mailloux GB, Cohen MA (1992). "Fluoroquinolones: relationships between structural variations, mammalian cell cytotoxicity, and antimicrobial activity". Journal of Medicinal Chemistry. 35 (25): 4745–50. doi:10.1021/jm00103a013. PMID 1469702. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  154. ^ Kashida Y, Sasaki YF, Ohsawa K; et al. (2002). "Mechanistic study on flumequine hepatocarcinogenicity focusing on DNA damage in mice". Toxicol. Sci. 69 (2): 317–21. doi:10.1093/toxsci/69.2.317. PMID 12377980. {{cite journal}}: Explicit use of et al. in: |author= (help); Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  155. ^ Verna LK, Holman SA, Lee VC, Hoh J (2000). "UVA-induced oxidative damage in retinal pigment epithelial cells after H2O2 or sparfloxacin exposure" (PDF). Cell Biol. Toxicol. 16 (5): 303–12. doi:10.1023/A:1026798314217. PMID 11201054.{{cite journal}}: CS1 maint: multiple names: authors list (link)
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