Ciprofloxacin is a fluoroquinolone antibiotic used to treat a number of bacterial infections.[4] This includes bone and joint infections, intra-abdominal infections, certain types of infectious diarrhea, respiratory tract infections, skin infections, typhoid fever, and urinary tract infections, among others.[4] For some infections it is used in addition to other antibiotics.[4] It can be taken by mouth, as eye drops, as ear drops, or intravenously.[4][5]
Common side effects include nausea, vomiting, and diarrhea.[4] Severe side effects include tendon rupture, hallucinations, and nerve damage.[4] In people with myasthenia gravis, there is worsening muscle weakness.[4] Rates of side effects appear to be higher than some groups of antibiotics such as cephalosporins but lower than others such as clindamycin.[6] Studies in other animals raise concerns regarding use in pregnancy. No problems were identified, however, in the children of a small number of women who took the medication.[7] It appears to be safe during breastfeeding.[4] It is a second-generation fluoroquinolone with a broad spectrum of activity that usually results in the death of the bacteria.[4][8][9]
Ciprofloxacin was patented in 1980 and introduced by Bayer in 1987.[10][11] It is on the World Health Organization's List of Essential Medicines.[12] The World Health Organization classifies ciprofloxacin as critically important for human medicine.[13] It is available as a generic medication.[4][14] In 2023, it was the 155th most commonly prescribed medication in the United States, with more than 3million prescriptions.[15][16]
Medical uses
Ciprofloxacin is used to treat a wide variety of infections, including infections of bones and joints, endocarditis, bacterial gastroenteritis, malignant otitis externa, bubonic plague, respiratory tract infections, cellulitis, urinary tract infections, prostatitis, anthrax, and chancroid.[4]
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.[17] It also features prominently in treatment guidelines for acute pyelonephritis, complicated or hospital-acquired urinary tract infection, acute or chronic prostatitis,[18] certain types of endocarditis,[19]
Contraindications
Contraindications include:[2]
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.
Caution may be required in people with Marfan syndrome or Ehlers–Danlos syndrome.[48]
- Taking tizanidine at the same time
- Use by those who are hypersensitive to any member of the quinolone class of antimicrobial agents
- Use by those who are diagnosed with myasthenia gravis, as muscle weakness may be exacerbated[47]
Adverse effects
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.[6] 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.
Overdose
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, aluminium, 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.[66] 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.[67]
Interactions
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.[66][68][69]
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,
Mechanism of action
Ciprofloxacin is a broad-spectrum antibiotic of the fluoroquinolone class. It is active against some Gram-positive and many Gram-negative bacteria.[77] It functions by inhibiting a type II topoisomerase (DNA gyrase) and topoisomerase IV,[78][79] necessary to separate bacterial DNA, thereby inhibiting cell division. Bacterial DNA fragmentation will occur as a result of inhibition of the enzymes.
Pharmacokinetics
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,[2] 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.[2]
Ciprofloxacin is weakly bound to serum proteins (20–40%). It 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.[4] Ciprofloxacin is about 70% available when administered orally.[2]
Chemical properties
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.[66]
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 C17H18FN3O3HCl•H2O.[66]
Usage
Ciprofloxacin is the most widely used of the second-generation quinolones.[81][82] 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 US.[83]
History
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.[84] In 1979, the publication of a patent[85] 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.[86] 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.[87][88]
Society and culture
Economics
Generic equivalents
In 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,
Research
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.[100]
External links
References
- Ciprofloxacin Use During Pregnancy Drugs.com, 7 January 2019, retrieved 19 December 2019^
- Cipro- ciprofloxacin hydrochloride tablet, film coated; Cipro- ciprofloxacin kit DailyMed, 31 January 2023, retrieved 9 February 2024^
- A Review of New Fluoroquinolones: Focus on their Use in Respiratory Tract Infections Treatments in Respiratory Medicine, 2006^