Nitroimidazole

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5-Nitroimidazole[1]

Names

IUPAC name

5-Nitro-1H-imidazole

Identifiers

CAS Number  3034-38-6 

3D model (JSmol)  Interactive image

ChemSpider  10637918 

ECHA InfoCard 100.019.296 

PubChem CID  18208

UNII  Y8U32AZ5O7 

CompTox  DTXSID9062803 
Dashboard (EPA)

InChI[show]

SMILES[show]

Properties

Chemical formula C3H3N3O2

Molar mass 113.076 g·mol−1

Melting point 303 °C (577 °F; 576 K) (decomposes)

 Hazards

Main hazards Xn

R-phrases (outdated) R20/21/22 R36/37/38

S-phrases (outdated) S26 S36/37

Except where otherwise noted, data are given for materials in

their standard state (at 25 °C [77 °F], 100 kPa).

 verify (what is   ?)

Infobox references

5-Nitroimidazole is an organic compound with the formula O2NC3H2N2H. The nitro

group at position 5 on the imidazole ring is the most common positional isomer. The
term nitroimidazole also refers to a class of antibiotics that share similar chemical
structures.[2]

Synthesis[edit]
Imidazole undergoes a nitration reaction with a mixture of nitric acid and sulfuric acid to
give 5-nitroimidazole:
C3H3N2H + HNO3 + H2SO4 → O2NC3H2N2H + H2O

Nitroimidazole antibiotics[edit]

Position numbers on the ring

From the chemistry perspective, nitroimidazole antibiotics

can be classified according to the location of the
nitro functional group. Structures with names 4- and 5-
nitroimidazole are equivalent from the perspective of drugs
since these tautomers readily interconvert. Drugs of the 5-
nitro variety
include metronidazole, tinidazole, nimorazole, dimetridazol
e, pretomanid, ornidazole, megazol, and azanidazole.
Drugs based on 2-nitromidazoles include benznidazole.
Nitroimidazole antibiotics have been used to
combat anaerobic bacterial and parasitic infections.[3] Perha
 ps the most common example is metronidazole. Other
heterocycles such as nitrothiazoles (thiazole) are also used
for this purpose. Nitroheterocycles may
be reductively activated in hypoxic cells, and then
undergo redox recycling or decompose to toxic products.[4]

Three nitroimidazole antibiotics: metronidazole, tinidazole, and nimorazole

References[edit]
1. ^ 4-Nitroimidazole at Sigma-Aldrich
2. ^ Edwards, David I. (1993). "Nitroimidazole drugs-action
and resistance mechanisms I. Mechanism of
action". Journal of Antimicrobial Chemotherapy. 31 (1):
9–20.  doi:10.1093/jac/31.1.9. PMID 8444678.
3. ^ Mital A (2009).  "Synthetic Nitroimidazoles: Biological
Activities and Mutagenicity Relationships". Sci
Pharm. 77 (3): 497–520. doi:10.3797/scipharm.0907-14.
4. ^ Juchau, MR (1989). "Bioactivation in chemical
teratogenesis". Annu. Rev. Pharmacol. Toxicol. 29: 165–
167.  doi:10.1146/annurev.pa.29.040189.001121. PMID 
2658769.

show

Antiparasitics directed at excavata parasites (P01)

show

Antiparasitics – antiprotozoal agents – agents against amoebozoa/amebicide (P01)

show
 Antibacterials that inhibit nucleic acid (J01E, J01M)
Categories: 
 Disulfiram-like drugs
 Nitroimidazoles
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Ciprofloxacin
From Wikipedia, the free encyclopedia
Jump to navigationJump to search
"Cipro" redirects here. For the Rome Metro station, see Cipro (Rome Metro).
Not to be confused with Ciproxifan.

Ciprofloxacin

Clinical data

Trade Ciloxan, Cipro, Neofloxin, others

names
AHFS/ Monograph
Drugs.c
om

Medline a688016
Plus

License  US DailyMed: Ciprofloxacin

data  US FDA: Ciprofloxacin

Pregna  AU: B3[1]
ncy
 US: C (Risk not ruled out)[1]
categor
y

Routes By mouth, intravenous, topical (ear drops, eye drops)

of
adminis
tration

Drug Fluoroquinolone
class

ATC  J01MA02 (WHO) S01AE03 (WHO) S02AA15 (WH
code
O) S03AA07 (WHO) J01RA10 (WHO) J01RA11 (

WHO) J01RA12 (WHO)

Legal status

Legal  AU: S4 (Prescription only)

status
 CA: ℞-only

 UK: POM (Prescription only)

 US: ℞-only

Pharmacokinetic data

Bioavail 70%[2]
ability

Protein 30%[2]
binding

Metabo Liver (incl. CYP1A2)
lism

Elimina 3.5 hours[2]

tion hal
f-life
Excreti Kidney
on

Identifiers

IUPAC name[show]

CAS  85721-33-1 
Numbe
r

PubChe  2764
m CID

PubChe  46504733
m SID

DrugBa  DB00537 
nk

ChemS  2662 
pider

UNII  5E8K9I0O4U

KEGG  D00186 

 as HCl: D02216 

ChEBI  CHEBI:100241 

ChEM  ChEMBL8 
BL

NIAID  001992
ChemD
B

CompT  DTXSID8022824 
ox
Dashbo
ard (EP
A)

ECHA 100.123.026 
InfoCar
d

Chemical and physical data

Formul C17H18FN3O3
a

Molar 331.347 g·mol−1
mass
 3D  Interactive image
model
(JSmol)

SMILES[show]

InChI[show]

  (verify)

Ciprofloxacin is an antibiotic used to treat a number of bacterial infections.[3] This

includes bone and joint infections, intra abdominal infections, certain type of infectious
diarrhea, respiratory tract infections, skin infections, typhoid fever, and urinary tract
infections, among others.[3] For some infections it is used in addition to other antibiotics.
[3]
 It can be taken by mouth, as eye drops, as ear drops, or intravenously. [3][4]
Common side effects include nausea, vomiting, diarrhea and rash. [3] Severe side effects
include an increased risk of tendon rupture, hallucinations, and nerve damage.[3] In
people with myasthenia gravis, there is worsening muscle weakness.[3] Rates of side
effects appear to be higher than some groups of antibiotics such as cephalosporins but
lower than others such as clindamycin.[5] Studies in other animals raise concerns
regarding use in pregnancy.[6] No problems were identified, however, in the children of a
small number of women who took the medication. [6] It appears to be safe
during breastfeeding.[3] It is a second-generation fluoroquinolone with a broad spectrum
of activity that usually results in the death of the bacteria.[3][7][8]
Ciprofloxacin was patented in 1980 and introduced in 1987. [9][10] It is on the World Health
Organization's List of Essential Medicines.[11] The World Health Organization classifies
ciprofloxacin as critically important for human medicine. [12] It is available as a generic
medication.[3][13] In 2017, it was the 107th most commonly prescribed medication in the
United States, with more than six million prescriptions. [14][15]

Contents

 1Medical uses
o 1.1Pregnancy
o 1.2Breastfeeding
o 1.3Children
o 1.4Spectrum of activity
o 1.5Bacterial resistance
 2Contraindications
 3Adverse effects
o 3.1Tendon problems
o 3.2Cardiac arrhythmia
o 3.3Nervous system
o 3.4Cancer
o 3.5Other
  4Overdose
 5Interactions
 6Mechanism of action
 7Pharmacokinetics
 8Chemical properties
 9Usage
 10History
 11Society and culture
o 11.1Cost
o 11.2Generic equivalents
o 11.3Available forms
o 11.4Litigation
 12Research
 13References
 14External links

Medical uses[edit]
Ciprofloxacin is used to treat a wide variety of infections, including infections of bones
and joints, endocarditis, gastroenteritis, malignant otitis externa, respiratory tract
infections, cellulitis, urinary tract infections, prostatitis, anthrax, and chancroid.[3]
Ciprofloxacin only treats bacterial infections; it does not treat viral infections such as
the common cold. For certain uses including acute sinusitis, lower respiratory tract
infections and uncomplicated gonorrhea, ciprofloxacin is not considered a first-line
agent.
Ciprofloxacin occupies an important role in treatment guidelines issued by major
medical societies for the treatment of serious infections, especially those likely to be
caused by Gram-negative bacteria, including Pseudomonas aeruginosa. For example,
ciprofloxacin in combination with metronidazole is one of several first-line antibiotic
regimens recommended by the Infectious Diseases Society of America for the treatment
of community-acquired abdominal infections in adults. [16] It also features prominently in
treatment guidelines for acute pyelonephritis, complicated or hospital-acquired urinary
tract infection, acute or chronic prostatitis, [17] certain types of endocarditis,[18] certain skin
infections,[19] and prosthetic joint infections.[20]
In other cases, treatment guidelines are more restrictive, recommending in most cases
that older, narrower-spectrum drugs be used as first-line therapy for less severe
infections to minimize fluoroquinolone-resistance development. For example, the
Infectious Diseases Society of America recommends the use of ciprofloxacin and other
fluoroquinolones in urinary tract infections be reserved to cases of proven or expected
resistance to narrower-spectrum drugs such
as nitrofurantoin or trimethoprim/sulfamethoxazole.[21] The European Association of
Urology recommends ciprofloxacin as an alternative regimen for the treatment of
uncomplicated urinary tract infections, but cautions that the potential for "adverse events
have to be considered".[17]
Although approved by regulatory authorities for the treatment of respiratory infections,
ciprofloxacin is not recommended for respiratory infections by most treatment guidelines
due in part to its modest activity against the common respiratory
pathogen Streptococcus pneumoniae.[22][23][24] "Respiratory quinolones" such
as levofloxacin, having greater activity against this pathogen, are recommended as first
line agents for the treatment of community-acquired pneumonia in patients with
important co-morbidities and in patients requiring hospitalization (Infectious Diseases
Society of America 2007). Similarly, ciprofloxacin is not recommended as a first-line
treatment for acute sinusitis.[25][26]
Ciprofloxacin is approved for the treatment of gonorrhea in many countries, but this
recommendation is widely regarded as obsolete due to resistance development. [27][28][29]
Pregnancy[edit]
In the United States ciprofloxacin is pregnancy category C.[30][1] This category includes
drugs for which no adequate and well-controlled studies in human pregnancy exist, and
for which animal studies have suggested the potential for harm to the fetus, but potential
benefits may warrant use of the drug in pregnant women despite potential risks. An
expert review of published data on experiences with ciprofloxacin use during pregnancy
by the Teratogen Information System concluded therapeutic doses during pregnancy
are unlikely to pose a substantial teratogenic risk (quantity and quality of data=fair), but
the data are insufficient to state no risk exists.[31] Exposure to quinolones, including
levofloxacin, during the first-trimester is not associated with an increased risk of
stillbirths, premature births, birth defects, or low birth weight. [32]
Two small post-marketing epidemiology studies of mostly short-term, first-trimester
exposure found that fluoroquinolones did not increase risk of major malformations,
spontaneous abortions, premature birth, or low birth weight. [33][34] The label notes,
however, that these studies are insufficient to reliably evaluate the definitive safety or
risk of less common defects by ciprofloxacin in pregnant women and their developing
fetuses.
Breastfeeding[edit]
Fluoroquinolones have been reported as present in a mother's milk and thus passed on
to the nursing child.[35][36] The U.S. Food and Drug Administration (FDA) recommends that
because of the risk of serious adverse reactions (including articular damage) in infants
nursing from mothers taking ciprofloxacin, a decision should be made whether to
discontinue nursing or discontinue the drug, taking into account the importance of the
drug to the mother.
Children[edit]
Oral and intravenous ciprofloxacin are approved by the FDA for use in children for only
two indications due to the risk of permanent injury to the musculoskeletal system:

1. Inhalational anthrax (postexposure)[37]
 2. Complicated urinary tract infections
and pyelonephritis due to Escherichia coli,[38] but
never as first-line agents.
Current[when?] recommendations by the American Academy of Pediatrics note the systemic
use of ciprofloxacin in children should be restricted to infections caused by multidrug-
resistant pathogens or when no safe or effective alternatives are available. [39]
Spectrum of activity[edit]
Its spectrum of activity includes most strains of bacterial pathogens responsible
for community-acquired pneumonias, bronchitis, urinary tract infections,
and gastroenteritis.[40] Ciprofloxacin is particularly effective against Gram-negative
bacteria (such as Escherichia coli, Haemophilus influenzae, Klebsiella
pneumoniae, Legionella pneumophila, Moraxella catarrhalis, Proteus mirabilis,
and Pseudomonas aeruginosa), but is less effective against Gram-positive
bacteria (such as methicillin-sensitive Staphylococcus aureus, Streptococcus
pneumoniae, and Enterococcus faecalis) than newer fluoroquinolones.[41]
Bacterial resistance[edit]
See also: Antibiotic abuse and Antibiotic resistance
As a result of its widespread use to treat minor infections readily treatable with older,
narrower spectrum antibiotics, many bacteria have developed resistance to this drug in
recent years, leaving it significantly less effective than it would have been otherwise. [42][43]
Resistance to ciprofloxacin and other fluoroquinolones may evolve rapidly, even during
a course of treatment. Numerous pathogens, including enterococci, Streptococcus
pyogenes and Klebsiella pneumoniae (quinolone-resistant) now exhibit resistance.
[44]
 Widespread veterinary usage of the fluoroquinolones, particularly in Europe, has been
implicated.[45] Meanwhile, some Burkholderia cepacia, Clostridium
innocuum and Enterococcus faecium strains have developed resistance to ciprofloxacin
to varying degrees.[46]
Fluoroquinolones had become the class of antibiotics most commonly prescribed to
adults in 2002.[47] Nearly half (42%) of those prescriptions in the U.S. were for conditions
not approved by the FDA, such as acute bronchitis, otitis media, and acute upper
respiratory tract infection, according to a study supported in part by the Agency for
Healthcare Research and Quality.[47] Additionally, they were commonly prescribed for
medical conditions that were not even bacterial to begin with, such as viral infections, or
those to which no proven benefit existed.

Contraindications[edit]
Contraindications include:[48]

 Taking tizanidine at the same time

 Use by those who are hypersensitive to any member
of the quinolone class of antimicrobial agents
Ciprofloxacin is also considered to be contraindicated in children (except for the
indications outlined above), in pregnancy, to nursing mothers, and in people
with epilepsy or other seizure disorders.

Adverse effects[edit]
Adverse effects can involve the tendons, muscles, joints, nerves, and the central
nervous system.[49][50]
Rates of adverse effects appear to be higher than with some groups of antibiotics such
as cephalosporins but lower than with others such as clindamycin.[5] Compared to other
antibiotics some studies find a higher rate of adverse effects [51][52] while others find no
difference.[53]
In clinical trials most of the adverse events were described as mild or moderate in
severity, abated soon after the drug was discontinued, and required no treatment.
[30]
 Some adverse effects may be permanent.[49] Ciprofloxacin was stopped because of an
adverse event in 1% of people treated with the medication by mouth. The most
frequently reported drug-related events, from trials of all formulations, all dosages, all
drug-therapy durations, and for all indications, were nausea (2.5%), diarrhea (1.6%),
abnormal liver function tests (1.3%), vomiting (1%), and rash (1%). Other adverse
events occurred at rates of <1%.[54]
Tendon problems[edit]
Ciprofloxacin includes a boxed warning in the United States due to an increased risk
of tendinitis and tendon rupture, especially in people who are older than 60 years,
people who also use corticosteroids, and people with kidney, lung, or heart transplants.
[55]
 Tendon rupture can occur during therapy or even months after discontinuation of the
medication.[56] One study found that fluoroquinolone use was associated with a 1.9-fold
increase in tendon problems. The risk increased to 3.2 in those over 60 years of age
and to 6.2 in those over the age of 60 who were also taking corticosteroids. Among the
46,766 quinolone users in the study, 38 (0.08%) cases of Achilles tendon rupture were
identified.[57]
Cardiac arrhythmia[edit]
The fluoroquinolones, including ciprofloxacin, are associated with an increased risk of
cardiac toxicity, including QT interval prolongation, torsades de pointes, ventricular
arrhythmia, and sudden death.[58][50]
Nervous system[edit]
Because Ciprofloxacin is lipophilic, it has the ability to cross the blood-brain barrier.
[59]
 The 2013 FDA label warns of nervous system effects. Ciprofloxacin, like other
fluoroquinolones, is known to trigger seizures or lower the seizure threshold, and may
cause other central nervous system adverse effects. Headache, dizziness, and
insomnia have been reported as occurring fairly commonly in postapproval review
articles, along with a much lower incidence of serious CNS adverse effects such as
tremors, psychosis, anxiety, hallucinations, paranoia, and suicide attempts, especially at
higher doses.[5] Like other fluoroquinolones, it is also known to cause peripheral
neuropathy that may be irreversible, such as weakness, burning pain, tingling or
numbness.[60]
Cancer[edit]
Ciprofloxacin is active in six of eight in vitro assays used as rapid screens for the
detection of genotoxic effects, but is not active in in vivo assays of genotoxicity.[30] Long-
term carcinogenicity studies in rats and mice resulted in no carcinogenic or tumorigenic
effects due to ciprofloxacin at daily oral dose levels up to 250 and 750 mg/kg to rats and
mice, respectively (about 1.7 and 2.5 times the highest recommended therapeutic dose
based upon mg/m2). Results from photo co-carcinogenicity testing indicate ciprofloxacin
does not reduce the time to appearance of UV-induced skin tumors as compared to
vehicle control.[citation needed]
Other[edit]
The other black box warning is that ciprofloxacin should not be used in people
with myasthenia gravis due to possible exacerbation of muscle weakness which may
lead to breathing problems resulting in death or ventilator support. Fluoroquinolones are
known to block neuromuscular transmission. [30] There are concerns that fluoroquinolones
including ciprofloxacin can affect cartilage in young children. [61]
Clostridium difficile-associated diarrhea is a serious adverse effect of ciprofloxacin and
other fluoroquinolones; it is unclear whether the risk is higher than with other broad-
spectrum antibiotics.[62]
A wide range of rare but potentially fatal adverse effects reported to the U.S. FDA or the
subject of case reports includes aortic dissection,[63] toxic epidermal necrolysis, Stevens–
Johnson syndrome, low blood pressure, allergic pneumonitis, bone marrow
suppression, hepatitis or liver failure, and sensitivity to light. [30][64] The medication should
be discontinued if a rash, jaundice, or other sign of hypersensitivity occurs. [30]
Children and the elderly are at a much greater risk of experiencing adverse reactions. [65]
[66]

Overdose[edit]
Overdose of ciprofloxacin may result in reversible renal toxicity. Treatment of overdose
includes emptying of the stomach by induced vomiting or gastric lavage, as well as
administration of antacids containing magnesium, aluminum, or calcium to reduce drug
absorption. Renal function and urinary pH should be monitored. Important support
includes adequate hydration and urine acidification if necessary to prevent
crystalluria. Hemodialysis or peritoneal dialysis can only remove less than 10% of
ciprofloxacin.[67] Ciprofloxacin may be quantified in plasma or serum to monitor for drug
accumulation in patients with hepatic dysfunction or to confirm a diagnosis of poisoning
in acute overdose victims.[68]

Interactions[edit]
Ciprofloxacin interacts with certain foods and several other drugs leading to undesirable
increases or decreases in the serum levels or distribution of one or both drugs.
Ciprofloxacin should not be taken with antacids containing magnesium or aluminum,
highly buffered drugs (sevelamer, lanthanum carbonate, sucralfate, didanosine), or with
supplements containing calcium, iron, or zinc. It should be taken two hours before or six
hours after these products. Magnesium or aluminum antacids turn ciprofloxacin into
insoluble salts that are not readily absorbed by the intestinal tract, reducing peak serum
concentrations by 90% or more, leading to therapeutic failure. Additionally, it should not
be taken with dairy products or calcium-fortified juices alone, as peak serum
concentration and the area under the serum concentration-time curve can be reduced
up to 40%. However, ciprofloxacin may be taken with dairy products or calcium-fortified
juices as part of a meal.[67][69][70]
Ciprofloxacin inhibits the drug-metabolizing enzyme CYP1A2 and thereby can reduce
the clearance of drugs metabolized by that enzyme. CYP1A2 substrates that exhibit
increased serum levels in ciprofloxacin-treated patients
include tizanidine, theophylline, caffeine, methylxanthines, clozapine, olanzapine,
and ropinirole. Co-administration of ciprofloxacin with the CYP1A2 substrate tizanidine
(Zanaflex) is contraindicated due to a 583% increase in the peak serum concentrations
of tizanidine when administered with ciprofloxacin as compared to administration of
tizanidine alone. Use of ciprofloxacin is cautioned in patients on theophylline due to its
narrow therapeutic index. The authors of one review recommended that patients being
treated with ciprofloxacin reduce their caffeine intake. Evidence for significant
interactions with several other CYP1A2 substrates such as cyclosporine is equivocal or
conflicting.[70][71][72]
The Committee on Safety of Medicines and the FDA warn that central nervous
system adverse effects, including seizure risk, may be increased when NSAIDs are
combined with quinolones.[71][73] The mechanism for this interaction may involve
a synergistic increased antagonism of GABA neurotransmission.[74][75]
Altered serum levels of the antiepileptic drugs phenytoin and carbamazepine (increased
and decreased) have been reported in patients receiving concomitant ciprofloxacin. [71][76][77]
Ciprofloxacin is a potent inhibitor of CYP1A2, CYP2D6, and CYP3A4.[78]

Mechanism of action[edit]
Ciprofloxacin is a broad-spectrum antibiotic of the fluoroquinolone class. It is active
against some Gram-positive and many Gram-negative bacteria.[79] It functions by
inhibiting a type II topoisomerase (DNA gyrase) and topoisomerase IV,[80][81] necessary to
separate bacterial DNA, thereby inhibiting cell division.

Pharmacokinetics[edit]
Ciprofloxacin for systemic administration is available as immediate-release tablets,
extended-release tablets, an oral suspension, and as a solution for intravenous
administration. When administered over one hour as an intravenous infusion,
[30]
 ciprofloxacin rapidly distributes into the tissues, with levels in some tissues exceeding
those in the serum. Penetration into the central nervous system is relatively modest,
with cerebrospinal fluid levels normally less than 10% of peak serum concentrations.
The serum half-life of ciprofloxacin is about 4–6 hours, with 50–70% of an administered
dose being excreted in the urine as unmetabolized drug. An additional 10% is excreted
in urine as metabolites. Urinary excretion is virtually complete 24 hours after
administration. Dose adjustment is required in the elderly and in those with renal
impairment.[citation needed]
Ciprofloxacin is weakly bound to serum proteins (20–40%), but is an inhibitor of the
drug-metabolizing enzyme cytochrome P450 1A2, which leads to the potential for
clinically important drug interactions with drugs metabolized by that enzyme. [medical citation needed]
Ciprofloxacin is about 70% orally available when administered orally, so a slightly higher
dose is needed to achieve the same exposure when switching from IV to oral
administration[30]
The extended release oral tablets [82] allow once-daily administration by releasing the
drug more slowly in the gastrointestinal tract. These tablets contain 35% of the
administered dose in an immediate-release form and 65% in a slow-release matrix.
Maximum serum concentrations are achieved between 1 and 4 hours after
administration. Compared to the 250- and 500-mg immediate-release tablets, the 500-
mg and 1000-mg XR tablets provide higher C max, but the 24-hour AUCs are equivalent.
Ciprofloxacin immediate-release tablets contain ciprofloxacin as the hydrochloride salt,
and the XR tablets contain a mixture of the hydrochloride salt as the free base. [83]

Chemical properties[edit]
Ciprofloxacin is 1-cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-7-(1-piperazinyl)-3-
quinolinecarboxylic acid. Its empirical formula is C17H18FN3O3 and its molecular weight is
331.4 g/mol. It is a faintly yellowish to light yellow crystalline substance. [67]
Ciprofloxacin hydrochloride (USP) is the monohydrochloride monohydrate salt of
ciprofloxacin. It is a faintly yellowish to light yellow crystalline substance with a
molecular weight of 385.8 g/mol. Its empirical formula is C 17H18FN3O3HCl•H2O.[67]

Usage[edit]
Ciprofloxacin is the most widely used of the second-generation quinolones. [84][85] In 2010,
over 20 million prescriptions were written, making it the 35th-most commonly prescribed
generic drug and the 5th-most commonly prescribed antibacterial in the U.S. [86]

History[edit]
Ciprofloxacin 250-mg tablets from Ukraine

The first members of the quinolone antibacterial class were relatively low-potency drugs
such as nalidixic acid, used mainly in the treatment of urinary tract infections owing to
their renal excretion and propensity to be concentrated in urine. [87] In 1979, the
publication of a patent[88] filed by the pharmaceutical arm of Kyorin Seiyaku Kabushiki
Kaisha disclosed the discovery of norfloxacin, and the demonstration that certain
structural modifications including the attachment of a fluorine atom to the quinolone ring
leads to dramatically enhanced antibacterial potency. [89] In the aftermath of this
disclosure, several other pharmaceutical companies initiated research and development
programs with the goal of discovering additional antibacterial agents of the
fluoroquinolone class.
The fluoroquinolone program at Bayer focused on examining the effects of very minor
changes to the norfloxacin structure.[90][91] In 1983, the company published in vitro potency
data for ciprofloxacin, a fluoroquinolone antibacterial having a chemical structure
differing from that of norfloxacin by the presence of a single carbon atom. [92] This small
change led to a two- to 10-fold increase in potency against most strains of Gram-
negative bacteria. Importantly, this structural change led to a four-fold improvement in
activity against the important Gram-negative pathogen Pseudomonas aeruginosa,
making ciprofloxacin one of the most potent known drugs for the treatment of this
intrinsically antibiotic-resistant pathogen.[medical citation needed]
The oral tablet form of ciprofloxacin was approved in October 1987, [93] just one year after
the approval of norfloxacin.[94] In 1991, the intravenous formulation was introduced.
Ciprofloxacin sales reached a peak of about 2 billion euros in 2001, before Bayer's
patent expired in 2004, after which annual sales have averaged around €200 million. [95][96]
The name probably originates from the International Scientific Nomenclature: ci-
(alteration of cycl-) + propyl + fluor- + ox- + az- + -mycin.[97]

Society and culture[edit]

Cost[edit]
It is available as a generic medication and not very expensive. [3][13]
Generic equivalents[edit]
On 24 October 2001, the Prescription Access Litigation (PAL) project filed suit to
dissolve an agreement between Bayer and three of its competitors which
produced generic versions of drugs (Barr Laboratories, Rugby Laboratories,
and Hoechst-Marion-Roussel) that PAL claimed was blocking access to adequate
supplies and cheaper, generic versions of ciprofloxacin. The plaintiffs charged that
Bayer Corporation, a unit of Bayer AG, had unlawfully paid the three competing
companies a total of $200 million to prevent cheaper, generic versions of ciprofloxacin
from being brought to the market, as well as manipulating its price and supply.
Numerous other consumer advocacy groups joined the lawsuit. On 15 October 2008,
five years after Bayer's patent had expired, the United States District Court for the
Eastern District of New York granted Bayer's and the other defendants' motion for
summary judgment, holding that any anticompetitive effects caused by the settlement
agreements between Bayer and its codefendants were within the exclusionary zone of
the patent and thus could not be redressed by federal antitrust law, [98] in effect upholding
Bayer's agreement with its competitors.
Available forms[edit]
Ciprofloxacin for systemic administration is available as immediate-release tablets, as
extended-release tablets, as an oral suspension, and as a solution for intravenous
infusion. It is also available for local administration as eye drops and ear drops.
Litigation[edit]
A class action was filed against Bayer AG on behalf of employees of the Brentwood
Post Office in Washington, D.C., and workers at the U.S. Capitol, along with employees
of American Media, Inc. in Florida and postal workers in general who alleged they
suffered serious adverse effects from taking ciprofloxacin in the aftermath of the anthrax
attacks in 2001. The action alleged Bayer failed to warn class members of the potential
side effects of the drug, thereby violating the Pennsylvania Unfair Trade Practices and
Consumer Protection Laws. The class action was defeated and the litigation abandoned
by the plaintiffs.[99] A similar action was filed in 2003 in New Jersey by four New Jersey
postal workers but was withdrawn for lack of grounds, as workers had been informed of
the risks of ciprofloxacin when they were given the option of taking the drug. [100][101]

Research[edit]
As resistance to ciprofloxacin has grown since its introduction, research has been
conducted to discover and develop analogs that can be effective against resistant
bacteria; some have been looked at in antiviral models as well. [102]
A study showed ciprofloxacin demonstrated activity against severe acute respiratory
syndrome coronavirus 2 (SARS-CoV-2) in Vero E6 cells, consistent with previous
reports of its unexpected antiviral effects. [103]

References[edit]
1. ^ Jump up to:      "Ciprofloxacin Use During
a b c

Pregnancy". Drugs.com. 7 January 2019. Retrieved 19

December 2019.
2. ^ Jump up to:a b c Zhanel GG, Fontaine S, Adam H, Schurek K,
Mayer M, Noreddin AM, Gin AS, Rubinstein E, Hoban DJ
(2006). "A Review of New Fluoroquinolones : Focus on their
Use in Respiratory Tract Infections". Treatments in
Respiratory Medicine.  5 (6): 437–65. doi:10.2165/00151829-
200605060-00009.  PMID  17154673. S2CID  26955572.
3. ^ Jump up to:a b c d e f g h i j k l "Ciprofloxacin Hydrochloride". The
American Society of Health-System
Pharmacists.  Archived  from the original on 23 September
2015. Retrieved  23 August 2015.
4. ^ "Ciprofloxacin Hcl Drops". WebMD. 22 February 2018.
Retrieved 22 February 2018.
5. ^ Jump up to:      Heidelbaugh JJ, Holmstrom H (April 2013). "The
a b c

perils of prescribing fluoroquinolones". The Journal of Family

Practice. 62 (4): 191–7. PMID 23570031.
6. ^ Jump up to:a b "Prescribing medicines in pregnancy
database".  Australian Government. 23 August
2015.  Archived  from the original on 8 April 2014.
7. ^ Ball P (July 2000).  "Quinolone generations: natural history
or natural selection?".  The Journal of Antimicrobial
Chemotherapy. 46 Suppl T1: 17–
24.  doi:10.1093/oxfordjournals.jac.a020889.  PMID  10997595
.
8. ^ Oliphant CM, Green GM (February 2002). "Quinolones: a
comprehensive review". American Family Physician. 65 (3):
455–64. PMID 11858629.
9. ^ Oxford Handbook of Infectious Diseases and Microbiology.
OUP Oxford. 2009. p. 56.  ISBN  978-0-19-103962-
1. Archived from the original on 8 September 2017.
10. ^ Fischer, Jnos; Ganellin, C. Robin (2006).  Analogue-based
Drug Discovery. John Wiley & Sons.
p. 500.  ISBN  9783527607495.
11. ^ World Health Organization  (2019). World Health
Organization model list of essential medicines: 21st list 2019.
Geneva: World Health Organization.  hdl:10665/325771.
WHO/MVP/EMP/IAU/2019.06. License: CC BY-NC-SA 3.0
IGO.
12. ^ World Health Organization  (2019). Critically important
antimicrobials for human medicine(6th revision ed.). Geneva:
World Health
Organization.  hdl:10665/312266.  ISBN  9789241515528.
13. ^ Jump up to:a b Hamilton, Richard J. (2014).  Tarascon
pharmacopoeia  (15 ed.). Jones & Bartlett Publishers.
p. 85.  ISBN  978-1-284-05671-6. Archived from the original
on 8 September 2017.
14. ^ "The Top 300 of 2020".  ClinCalc. Retrieved 11 April  2020.
15. ^ "Ciprofloxacin – Drug Usage Statistics".  ClinCalc.
Retrieved 11 April  2020.
16. ^ Solomkin JS, Mazuski JE, Bradley JS, Rodvold KA,
Goldstein EJ, Baron EJ, O'Neill PJ, Chow AW, Dellinger EP,
Eachempati SR, Gorbach S, Hilfiker M, May AK, Nathens AB,
Sawyer RG, Bartlett JG (January 2010). "Diagnosis and
management of complicated intra-abdominal infection in
adults and children: guidelines by the Surgical Infection
Society and the Infectious Diseases Society of
America". Clinical Infectious Diseases. 50 (2): 133–
64.  doi:10.1086/649554. PMID 20034345.
17. ^ Jump up to:a b Grabe M, Bjerklund-Johansen TE, Botto H, Çek
M, Naber KG, Pickard RS, Tenke P, Wagenlehner F, Wullt B
(2013).  "Guidelines on Urological Infections"  (PDF).
European Association of Urology. Archived from the
original  (PDF)  on 31 December 2013.
18. ^ Baddour LM, Wilson WR, Bayer AS, Fowler VG, Bolger AF,
Levison ME, et al. (June 2005).  "Infective endocarditis:
diagnosis, antimicrobial therapy, and management of
complications: a statement for healthcare professionals from
 the Committee on Rheumatic Fever, Endocarditis, and
Kawasaki Disease, Council on Cardiovascular Disease in the
Young, and the Councils on Clinical Cardiology, Stroke, and
Cardiovascular Surgery and Anesthesia, American Heart
Association: endorsed by the Infectious Diseases Society of
America". Circulation.  111  (23): e394–
434.  doi:10.1161/CIRCULATIONAHA.105.165564.  PMID  159
56145.
19. ^ Stevens DL, Bisno AL, Chambers HF, Everett ED, Dellinger
P, Goldstein EJ, Gorbach SL, Hirschmann JV, Kaplan EL,
Montoya JG, Wade JC (November 2005).  "Practice
guidelines for the diagnosis and management of skin and
soft-tissue infections".  Clinical Infectious Diseases.  41  (10):
1373–406.  doi:10.1086/497143. PMID 16231249.
20. ^ Osmon DR, Berbari EF, Berendt AR, Lew D, Zimmerli W,
Steckelberg JM, Rao N, Hanssen A, Wilson WR (January
2013). "Diagnosis and management of prosthetic joint
infection: clinical practice guidelines by the Infectious
Diseases Society of America". Clinical Infectious
Diseases.  56  (1): e1–
e25.  doi:10.1093/cid/cis803.  PMID  23223583.
21. ^ Gupta K, Hooton TM, Naber KG, Wullt B, Colgan R, Miller
LG, Moran GJ, Nicolle LE, Raz R, Schaeffer AJ, Soper DE
(March 2011). "International clinical practice guidelines for the
treatment of acute uncomplicated cystitis and pyelonephritis
in women: A 2010 update by the Infectious Diseases Society
of America and the European Society for Microbiology and
Infectious Diseases".  Clinical Infectious Diseases.  52  (5):
e103–20. doi:10.1093/cid/ciq257. PMID 21292654.
22. ^ Hoogkamp-Korstanje JA, Klein SJ (September 1986).
"Ciprofloxacin in acute exacerbations of chronic
bronchitis".  The Journal of Antimicrobial
Chemotherapy. 18 (3): 407–
13.  doi:10.1093/jac/18.3.407.  PMID  3490468.
23. ^ Vardakas KZ, Siempos II, Grammatikos A, Athanassa Z,
Korbila IP, Falagas ME (December 2008). "Respiratory
fluoroquinolones for the treatment of community-acquired
pneumonia: a meta-analysis of randomized controlled
trials".  CMAJ. 179 (12): 1269–
77.  doi:10.1503/cmaj.080358. PMC  2585120.  PMID  190476
08.
24. ^ Donaldson PM, Pallett AP, Carroll MP (May
1994). "Ciprofloxacin in general practice".  BMJ.  308  (6941):
1437.  doi:10.1136/bmj.308.6941.1437.  PMC 2540361. PMID 
8019264.
25. ^ Karageorgopoulos DE, Giannopoulou KP, Grammatikos
AP, Dimopoulos G, Falagas ME (March
2008). "Fluoroquinolones compared with beta-lactam
antibiotics for the treatment of acute bacterial sinusitis: a
meta-analysis of randomized controlled
trials".  CMAJ. 178 (7): 845–
54.  doi:10.1503/cmaj.071157. PMC  2267830.  PMID  183623
80.
26. ^ Chow AW, Benninger MS, Brook I, Brozek JL, Goldstein EJ,
Hicks LA, Pankey GA, Seleznick M, Volturo G, Wald ER, File
TM (April 2012). "IDSA clinical practice guideline for acute
 bacterial rhinosinusitis in children and adults".  Clinical
Infectious Diseases.  54  (8): e72–
e112.  doi:10.1093/cid/cir1043.  PMID  22438350. S2CID  1946
193.
27. ^ Department of Health and Human Services;  Centers for
Disease Control and Prevention(November
2004). "Gonococcal Isolate Surveillance Project (GISP)
Annual Report – 2003"  (PDF). USA: Center for Disease
Controlo. Archived  (PDF)  from the original on 24 April 2009.
Retrieved 31 August  2009.
28. ^ Young H, Palmer H, Winter A (22 July 2003). "Ciprofloxacin
resistant gonorrhoea: the situation in Scotland and
implications for therapy"  (PDF). SCIEH Weekly
Report. 37.  ISSN  1357-4493. Archived from  the
original  (PDF)  on 22 July 2011. Retrieved  30 August 2009.
29. ^ Centers for Disease Control Prevention (CDC) (April
2007). "Update to CDC's sexually transmitted diseases
treatment guidelines, 2006: fluoroquinolones no longer
recommended for treatment of gonococcal
infections". MMWR. Morbidity and Mortality Weekly
Report. 56 (14): 332–6. PMID 17431378.  Archived  from the
original on 8 December 2016.
30. ^ Jump up to:a b c d e f g h "US Cipro label"  (PDF). U.S.  Food and
Drug Administration (FDA). July 2017. For label updates
see FDA Index page for NDA 019537
31. ^ Barolin GS (May 1995).  "[Illness, anxiety and the physician.
An example from neurology and neurorehabilitation]". Wiener
Medizinische Wochenschrift.  141  (22): 512–
25.  PMC 1801454. PMID 1801454.
32. ^ Ziv A, Masarwa R, Perlman A, Ziv D, Matok I (March 2018).
"Pregnancy Outcomes Following Exposure to Quinolone
Antibiotics – a Systematic-Review and Meta-
Analysis".  Pharm. Res. 35 (5): 109.  doi:10.1007/s11095-018-
2383-8. PMID 29582196.  S2CID 4724821.
33. ^ Loebstein R, Addis A, Ho E, Andreou R, Sage S,
Donnenfeld AE, Schick B, Bonati M, Moretti M, Lalkin A,
Pastuszak A, Koren G (June 1998). "Pregnancy outcome
following gestational exposure to fluoroquinolones: a
multicenter prospective controlled study".  Antimicrobial
Agents and Chemotherapy. 42 (6): 1336–
9. doi:10.1128/AAC.42.6.1336.  PMC 105599. PMID 962447
1.
34. ^ Schaefer C, Amoura-Elefant E, Vial T, Ornoy A, Garbis H,
Robert E, Rodriguez-Pinilla E, Pexieder T, Prapas N, Merlob
P (November 1996). "Pregnancy outcome after prenatal
quinolone exposure. Evaluation of a case registry of the
European Network of Teratology Information Services
(ENTIS)".  European Journal of Obstetrics, Gynecology, and
Reproductive Biology.  69  (2): 83–9. doi:10.1016/0301-
2115(95)02524-3. PMID 8902438.
35. ^ Shin HC, Kim JC, Chung MK, Jung YH, Kim JS, Lee MK,
Amidon GL (September 2003). "Fetal and maternal tissue
distribution of the new fluoroquinolone DW-116 in pregnant
rats". Comparative Biochemistry and Physiology. Toxicology
& Pharmacology. 136 (1): 95–
102.  doi:10.1016/j.cca.2003.08.004. PMID 14522602.
36. ^ Dan M, Weidekamm E, Sagiv R, Portmann R, Zakut H
(February 1993). "Penetration of fleroxacin into breast milk
and pharmacokinetics in lactating women". Antimicrobial
Agents and Chemotherapy. 37 (2): 293–
6. doi:10.1128/AAC.37.2.293. PMC  187655.  PMID  8452360.
37. ^ Dianne Murphy (30 August 2000).  "Cipro Labeling Revision
Letter 08/30/2000 Supplement 008 New or Modified
Indication"  (PDF). U.S. Food and Drug
Administration  (FDA).  Archived  (PDF) from the original on 18
October 2012.
38. ^ Renata Albrecht (25 March 2004). "Cipro Labeling Revision
Letter 03/25/2004 Supplement 049 Patient Population
Altered"  (PDF). U.S.  Food and Drug
Administration  (FDA).  Archived  (PDF) from the original on 18
October 2012. Retrieved  7 September 2009.
39. ^ Choi SH, Kim EY, Kim YJ (May 2013). "Systemic use of
fluoroquinolone in children". Korean Journal of
Pediatrics. 56 (5): 196–
201.  doi:10.3345/kjp.2013.56.5.196.  PMC 3668199. PMID 2
3741232.
40. ^ Johannsen EC, Sabatine MS (2010). Pharmcards review
cards for medical students  (4th ed.). Philadelphia: Wolters
Kluwer|Lippincott Williams & Wilkins.  ISBN  978-0-7817-8741-
3. OCLC  893525059.[page  needed]
41. ^ Hooper D (12 February 2018).  "Fluoroquinolones –
UpToDate".  UpToDate. Retrieved  26 February  2018.
42. ^ Vatopoulos AC, Kalapothaki V, Legakis NJ
(1999).  "Bacterial resistance to ciprofloxacin in Greece:
results from the National Electronic Surveillance System.
Greek Network for the Surveillance of Antimicrobial
Resistance".  Emerging Infectious Diseases. 5  (3): 471–
6. doi:10.3201/eid0503.990325. PMC  2640758.  PMID  10341
191.
43. ^ "Bacterial resistance prompts concern among health
officials". Minnesota Department of Health. 26 February 2009.
Archived from  the original on 5 March 2009.
44. ^ M Jacobs, Worldwide Overview of Antimicrobial Resistance.
International Symposium on Antimicrobial Agents and
Resistance 2005.
45. ^ "Update on Extra-Label Use of Fluoroquinolones" (Press
release). Center for Veterinary Medicine (CVM). 16 July
1996.  Archived  from the original on 9 March 2010.
Retrieved 12 August  2009.
46. ^ "Ciprofloxacin Data Sheet"  (PDF). Toku-E. 1 December
2010. Archived from the original  (PDF) on 9 October 2013.
Retrieved 20 June  2012.
47. ^ Jump up to:a b Linder JA, Huang ES, Steinman MA, Gonzales R,
Stafford RS (March 2005). "Fluoroquinolone prescribing in the
United States: 1995 to 2002".  The American Journal of
Medicine. 118 (3): 259–
68.  doi:10.1016/j.amjmed.2004.09.015. PMID 15745724.
48. ^ "Cipro Labeling Revision 02/25/2011 Supplement
075"  (PDF). U.S. Food and Drug Administration  (FDA). 25
February 2011. Archived  (PDF)  from the original on 17
October 2012. Retrieved  1 April  2011.
49. ^ Jump up to:    "Drug Safety and Availability – FDA Drug Safety
a b

Communication: FDA updates warnings for oral and

injectable fluoroquinolone antibiotics due to disabling side
effects".  U.S. Food and Drug Administration  (FDA).
Retrieved 10 January  2018.
50. ^ Jump up to:a b Liu X, Ma J, Huang L, Zhu W, Yuan P, Wan R,
Hong K (November 2017).  "Fluoroquinolones increase the
risk of serious arrhythmias: A systematic review and meta-
analysis". Medicine (Baltimore). 96 (44):
e8273. doi:10.1097/MD.0000000000008273. PMC  5682775. 
PMID 29095256.
51. ^ Brown KA, Khanafer N, Daneman N, Fisman DN (May
2013). "Meta-analysis of antibiotics and the risk of
community-associated Clostridium difficile
infection".  Antimicrobial Agents and Chemotherapy. 57 (5):
2326–32. doi:10.1128/AAC.02176-12.  PMC 3632900. PMID 
23478961.
52. ^ Falagas ME, Matthaiou DK, Vardakas KZ (December
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 Clinic Proceedings. 81(12): 1553–
66.  doi:10.4065/81.12.1553.  PMID  17165634.
53. ^ Knottnerus BJ, Grigoryan L, Geerlings SE, Moll van
Charante EP, Verheij TJ, Kessels AG, ter Riet G (December
2012). "Comparative effectiveness of antibiotics for
uncomplicated urinary tract infections: network meta-analysis
of randomized trials". Family Practice. 29(6): 659–
70.  doi:10.1093/fampra/cms029.  PMID  22516128.
54. ^ "Cipro IV Meta-analysis"  (PDF). U.S.  Food and Drug
Administration  (FDA). November 2011.
55. ^ Stephenson AL, Wu W, Cortes D, Rochon PA (September
2013). "Tendon Injury and Fluoroquinolone Use: A Systematic
Review". Drug Saf. 36 (9): 709–21. doi:10.1007/s40264-013-
0089-8. PMID 23888427.  S2CID 24948660.
56. ^ Saint F, Gueguen G, Biserte J, Fontaine C, Mazeman E
(September 2000). "[Rupture of the patellar ligament one
month after treatment with fluoroquinolone]"  [Rupture of the
patellar ligament one month after treatment with
fluoroquinolone]. Revue de Chirurgie Orthopedique et
Reparatrice de l'Appareil Moteur (in French).  86  (5): 495–
7. PMID 10970974.
57. ^ Corrao G, Zambon A, Bertù L, Mauri A, Paleari V, Rossi C,
Venegoni M (2006). "Evidence of tendinitis provoked by
fluoroquinolone treatment: a case-control study".  Drug
Safety.  29(10): 889–96. doi:10.2165/00002018-200629100-
00006. PMID 16970512.  S2CID 21513856.
58. ^ Gorelik E, Masarwa R, Perlman A, Rotshild V, Abbasi M,
Muszkat M, Matok I (October 2018). "Fluoroquinolones and
Cardiovascular Risk: A Systematic Review, Meta-analysis
and Network Meta-analysis".  Drug Saf.  42  (4): 529–
538.  doi:10.1007/s40264-018-0751-2. PMID 30368737.  S2CI
D 53105534.
59. ^ Babar SM (October 2013). "SIADH associated with
ciprofloxacin".  The Annals of Pharmacotherapy. 47 (10):
 1359–63. doi:10.1177/1060028013502457.  PMID  24259701. 
S2CID  36759747.
60. ^ "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". U.S.  Food and Drug Administration (FDA).
Archived from  the original on 28 May 2016.
61. ^ "CIPRO (ciprofloxacin hydrochloride)
TABLETS"  (PDF).  U.S. Food and Drug Administration  (FDA).
Retrieved 13 October  2018.
62. ^ Deshpande A, Pant C, Jain A, Fraser TG, Rolston DD
(February 2008). "Do fluoroquinolones predispose patients to
Clostridium difficile associated disease? A review of the
evidence". Current Medical Research and Opinion.  24  (2):
329–33. doi:10.1185/030079908X253735. PMID 18067688. 
S2CID  280563.
63. ^ "Drug Safety and Availability – FDA warns about increased
risk of ruptures or tears in the aorta blood vessel with
fluoroquinolone antibiotics in certain patients".  U.S. Food and
Drug Administration (FDA). Retrieved 4 January 2019.
64. ^ Alshammari TM, Larrat EP, Morrill HJ, Caffrey AR, Quilliam
BJ, LaPlante KL (January 2014). "Risk of hepatotoxicity
associated with fluoroquinolones: a national case-control
safety study".  American Journal of Health-System
Pharmacy.  71  (1): 37–
43.  doi:10.2146/ajhp130165.  PMID  24352180.
65. ^ Iannini PB (June 2007). "The safety profile of moxifloxacin
and other fluoroquinolones in special patient
populations".  Current Medical Research and Opinion. 23 (6):
1403–13. doi:10.1185/030079907X188099. PMID 17559736. 
S2CID  34091286.
66. ^ Owens RC, Ambrose PG (July 2005).  "Antimicrobial safety:
focus on fluoroquinolones".  Clinical Infectious Diseases. 41
Suppl 2: S144–57.  doi:10.1086/428055. PMID 15942881.
67. ^ Jump up to:a b c d "Cipro Labeling Revision 04/06/2009
Supplement 073"  (PDF). U.S. Food and Drug
Administration  (FDA). 6 April 2009.  Archived  (PDF) from the
original on 5 July 2010. Retrieved  8 September 2009.
68. ^ R. Baselt, Disposition of Toxic Drugs and Chemicals in
Man, 8th edition, Biomedical Publications, Foster City, CA,
2008, pp. 313–315. ISBN 978-0-9626523-7-0.
69. ^ Rodvold KA, Piscitelli SC (August 1993). "New oral
macrolide and fluoroquinolone antibiotics: an overview of
pharmacokinetics, interactions, and safety". Clinical Infectious
Diseases. 17 Suppl 1: S192–
9. doi:10.1093/clinids/17.supplement_1.s192. PMID 8399914
.
70. ^ Jump up to:a b Bolhuis MS, Panday PN, Pranger AD, Kosterink
JG, Alffenaar JW (November 2011). "Pharmacokinetic drug
interactions of antimicrobial drugs: a systematic review on
oxazolidinones, rifamycines, macrolides, fluoroquinolones,
and Beta-lactams". Pharmaceutics.  3 (4): 865–
913.  doi:10.3390/pharmaceutics3040865.  PMC 3857062. P
MID  24309312.
71. ^ Jump up to:      "Cipro Labeling Revision 10/03/2008
a b c

Supplement 068"  (PDF). U.S. Food and Drug

Administration  (FDA). 3 October 2008.  Archived  (PDF) from
the original on 14 December 2010. Retrieved  31
August  2009.
72. ^ Janknegt R (November 1990). "Drug interactions with
quinolones". The Journal of Antimicrobial Chemotherapy. 26
Suppl D: 7–
29.  doi:10.1093/jac/26.suppl_D.7.  PMID  2286594.
73. ^ Royal Pharmaceutical Society of Great Britain (2009). "5
Infections".  British National Formulary (BNF 57). BMJ Group
and RPS Publishing. ISBN 978-0-85369-845-6.
74. ^ De Sarro A, De Sarro G (March 2001). "Adverse reactions
to fluoroquinolones. an overview on mechanistic
aspects". Current Medicinal Chemistry.  8 (4): 371–
84.  doi:10.2174/0929867013373435. PMID 11172695.
75. ^ Brouwers JR (1992). "Drug interactions with quinolone
antibacterials".  Drug Safety. 7  (4): 268–
81.  doi:10.2165/00002018-199207040-00003.  PMID  152469
9. S2CID  6701544.
76. ^ Shahzadi A, Javed I, Aslam B, Muhammad F, Asi MR,
Ashraf MY (January 2011). "Therapeutic effects of
ciprofloxacin on the pharmacokinetics of carbamazepine in
healthy adult male volunteers".  Pakistan Journal of
Pharmaceutical Sciences.  24  (1): 63–8. PMID 21190921.
77. ^ Springuel P (January 1998). "Risk of seizures from
concomitant use of ciprofloxacin and phenytoin in patients
with epilepsy".  CMAJ. 158 (1): 104–5, 108–
9. PMID 9475922.
78. ^ Haddad A, Davis M, Lagman R (March 2007). "The
pharmacological importance of cytochrome CYP3A4 in the
palliation of symptoms: review and recommendations for
avoiding adverse drug interactions". Supportive Care in
Cancer. 15 (3): 251–7. doi:10.1007/s00520-006-0127-
5. PMID 17139496.  S2CID 9186457.
79. ^ First aid for the USMLE step 2 CK  (6th ed.). McGraw-Hill
Medical. June 2007. ISBN 9780071487955.
80. ^ Drlica K, Zhao X (September 1997). "DNA gyrase,
topoisomerase IV, and the 4-quinolones".  Microbiology and
Molecular Biology Reviews. 61 (3): 377–
92.  doi:10.1128/.61.3.377-392.1997. PMC  232616.  PMID  92
93187.
81. ^ Pommier Y, Leo E, Zhang H, Marchand C (May
2010). "DNA topoisomerases and their poisoning by
anticancer and antibacterial drugs". Chemistry &
Biology.  17  (5): 421–
33.  doi:10.1016/j.chembiol.2010.04.012.  PMC 7316379. PMI
D 20534341.
82. ^ "Cipro XR Prescribing Information"  (PDF). U.S.  Food and
Drug Administration (FDA). Archived  (PDF)  from the original
on 30 December 2013.
83. ^ "CIPRO® (ciprofloxacin hydrochloride)
TABLETS"  (PDF).  Food and Drug Administration. 2008.
84. ^ Goossens H, Ferech M, Coenen S, Stephens P (April
2007). "Comparison of outpatient systemic antibacterial use
in 2004 in the United States and 27 European
countries".  Clinical Infectious Diseases.  44  (8): 1091–
5. doi:10.1086/512810.  PMID  17366456.
85. ^ "British Columbia Annual Summary of Antibiotics Utilization
2010"  (PDF). Archived from the original  (PDF) on 30
December 2013.
86. ^ "2010 Top 200 generic drugs by total prescriptions"  (PDF).
Archived from  the original  (PDF)  on 15 December 2012.
Retrieved 2 November 2012.
87. ^ Mayrer AR, Andriole VT (January 1982). "Urinary tract
antiseptics".  The Medical Clinics of North America. 66 (1):
199–208. doi:10.1016/s0025-7125(16)31453-5. PMID 70383
29.
88. ^ "Patent US4146719 - Piperazinyl derivatives of quinoline
carboxylic acids - Google Patents".
89. ^ Khan MY, Gruninger RP, Nelson SM, Klicker RE (May
1982). "Comparative in vitro activity of norfloxacin (MK-0366)
and ten other oral antimicrobial agents against urinary
bacterial isolates".  Antimicrobial Agents and
Chemotherapy. 21 (5): 848–
51.  doi:10.1128/AAC.21.5.848.  PMC 182027. PMID 621320
0.
90. ^ "Patent US4547503 – 1-Cyclopropyl-6-fluoro-1,4-dihydro-4-
oxo-7-[4-(oxo-alkyl)-1-piperazinyl ... – Google Patents".
91. ^ "Patent US4544658 – 1-Cyclopropyl-6-fluoro-1,4-dihydro-4-
oxo-7-(alkyl-1-piperazinyl)quinoline-3 ... – Google Patents".
92. ^ Wise R, Andrews JM, Edwards LJ (April 1983). "In vitro
activity of Bay 09867, a new quinoline derivative, compared
with those of other antimicrobial agents".  Antimicrobial
Agents and Chemotherapy. 23 (4): 559–
64.  doi:10.1128/aac.23.4.559.  PMC 184701. PMID 6222695.
93. ^ "Orange Book: Approved Drug Products with Therapeutic
Equivalence Evaluations N019537". U.S. Food and Drug
Administration  (FDA).  Archived  from the original on 6
January 2014. Retrieved  5 January  2014.
94. ^ "Orange Book Detail Record Search". U.S.  Food and Drug
Administration  (FDA).  Archived  from the original on 6
January 2014.
95. ^ "www.sec.gov". Archived from the original on 9 July 2017.
96. ^ Dan Prochilo for Law360 18 November 2013 Bayer's $74M
Cipro Pay-For-Delay Deal Approved In Calif. Archived 18
March 2015 at the Wayback Machine
97. ^ merriam-webster.com[full citation needed]
98. ^ United States Court of Appeals for the Federal Circuit
(2008).  "United States Court of Appeals for the Federal
Circuit"  (PDF). USA. Archived from the original  (PDF) on 27
August 2009. Retrieved  4 September 2009.
99. ^ "Legal Brief of Postal Employees Cases (EEOC, MSPB,
District Courts)". USA: Postal Reporter. Archived from  the
original on 21 October 2007. Retrieved 9 September  2009.
 100. ^ Los Angeles Times, from wire service reports. 19 October
2003 Postal Workers Sue Over Anthrax Scare
Antibiotic Archived 5 December 2014 at the Wayback
Machine
101. ^ Bill Lewis, President of Trenton Metro Area Local,
American Postal Workers Union, AFL-CIO. 7 December
2003 Trenton Metro Area Local: Welcome to Bill's
Corner Archived23 October 2014 at the Wayback
Machine Page accessed 23 October 2014
102. ^ Zhang GF, Liu X, Zhang S, Pan B, Liu ML (February
2018). "Ciprofloxacin derivatives and their antibacterial
activities". European Journal of Medicinal Chemistry.  146:
599–612. doi:10.1016/j.ejmech.2018.01.078. PMID 2940798
4.
103. ^ Ambroxol and Ciprofloxacin Show Activity Against SARS-
CoV2 in Vero E6 Cells at Clinically-Relevant Concentrations.
Bradfute et al.
BioRxiv https://doi.org/10.1101/2020.08.11.245100

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