Ciprofloxacin: Uses, Dosage, Side Effects and Warnings

What is ciprofloxacin?

Ciprofloxacin hydrochloride, usually referred to simply as ciprofloxacin, is an antibiotic in the fluoroquinolone family, which also includes medications such as norfloxacin, ofloxacin, levofloxacin, and moxifloxacin.

Ciprofloxacin works by inhibiting bacterial enzymes called DNA gyrase and topoisomerase IV, which are essential for bacterial replication and survival.

This antibiotic has good activity against several gram-negative bacteria and remains useful for treating certain complicated urinary tract infections, bacterial prostatitis, and other infections caused by susceptible organisms.

However, its use has become more restricted in recent years because of increasing bacterial resistance and the risk, although uncommon, of serious and potentially persistent adverse effects. For this reason, ciprofloxacin is not usually a first-line option for uncomplicated infections when safer and equally effective antibiotics are available.

In children, ciprofloxacin is also not a first-line antibiotic, mainly because of the higher risk of musculoskeletal adverse effects. However, it may be used in certain specific situations. Pediatric indications vary among countries and are explained later in this article.

Attention: this article is not intended to be a complete ciprofloxacin package insert. Our goal is to provide information that is less technical than the official prescribing information and more useful to patients looking for information about this medication. What follows is a summary of the most relevant information from the medical literature and ciprofloxacin prescribing information available in different countries.

What is ciprofloxacin used for?

Ciprofloxacin is a second-generation fluoroquinolone with activity against several types of bacteria, especially gram-negative bacteria.

Depending on the causative bacteria and their susceptibility profile, ciprofloxacin may be used to treat:

• Cystitis, in selected situations when the antibiotics usually recommended are not appropriate.
• Pyelonephritis.
• Complicated urinary tract infections.
• Bacterial prostatitis.
• Gonorrhea in selected situations when susceptibility to ciprofloxacin has been documented.
• Certain types of bacterial diarrhea.
• Typhoid fever.
• Certain intra-abdominal infections, usually in combination with another antibiotic when coverage against anaerobic bacteria is also required.
• Certain respiratory tract infections caused by gram-negative bacteria.
• Bone and joint infections caused by susceptible bacteria.
• Certain skin and soft tissue infections caused by gram-negative bacteria.
• Pseudomonas aeruginosa infections in selected situations.
• Inhalational anthrax, including post-exposure prophylaxis.
• Plague.
• Prophylaxis of meningococcal disease in certain situations.

The fact that a bacterium may be susceptible to ciprofloxacin does not mean that this antibiotic is always a good choice for treating it. The decision depends on the site and severity of the infection, local bacterial resistance patterns, and, when available, culture and antibiotic susceptibility testing results.

This is particularly important for urinary tract infections. Resistance of Escherichia coli to fluoroquinolones has increased substantially in many regions, which is why ciprofloxacin is no longer one of the first choices for uncomplicated cystitis.

The same reasoning applies to gonorrhea. Because of resistance in Neisseria gonorrhoeae, ciprofloxacin should not be used empirically to treat gonorrhea except in specific situations in which susceptibility to the drug has been demonstrated.

Activity against gram-negative bacteria

Gram-negative bacteria that may be susceptible to ciprofloxacin include Escherichia coli, Klebsiella pneumoniae, Klebsiella oxytoca, Proteus mirabilis, Proteus vulgaris, Enterobacter spp., Citrobacter freundii, Morganella morganii, Serratia marcescens, Haemophilus influenzae, Moraxella catarrhalis, Shigella spp., Campylobacter spp., and Pseudomonas aeruginosa.

Activity against gram-positive bacteria

Its spectrum against gram-positive bacteria is more limited. Some methicillin-susceptible strains of Staphylococcus aureus may be susceptible, but ciprofloxacin has insufficient activity against several streptococci, including Streptococcus pneumoniae, and is therefore not a good choice when these organisms are the main suspected pathogens.

Ciprofloxacin also does not provide adequate coverage against many anaerobic bacteria. For this reason, certain intra-abdominal, pelvic, or mixed infections require combination therapy with other antibiotics.

Brand names and formulations

Ciprofloxacin has been available for many years and is widely available as a generic medication.

Brand names vary considerably between countries and manufacturers. In the United States, the best-known brand name is Cipro.

Formulations

Available formulations also vary by country and manufacturer.

Immediate-release tablets are most commonly available in 250 mg, 500 mg, and 750 mg strengths. Extended-release formulations, including 500 mg and 1000 mg strengths, have also been marketed.

Ciprofloxacin may also be available as an oral suspension and as a solution for intravenous administration.

Immediate-release and extended-release formulations are not interchangeable, as their dosing schedules may differ.

Dosage

As with most antibiotics, the dose and duration of treatment depend on the type and severity of the infection, the causative bacteria, antibiotic susceptibility testing results, and the patient’s kidney function.

For immediate-release tablets, adult doses generally range from 250 to 750 mg every 12 hours, with a usual maximum dose of 1500 mg per day.

Some dosing regimens used in adults are described below. Exact doses and treatment durations may differ between national prescribing information and clinical guidelines, so the prescribed regimen and current recommendations in the patient’s country should always take precedence.

Cystitis

Ciprofloxacin is currently not one of the first-line antibiotics for uncomplicated cystitis, particularly in women.

When its use is necessary because the usually recommended options are unsuitable and the bacteria are susceptible, one regimen used for acute uncomplicated cystitis in women is:

• Ciprofloxacin 250 mg every 12 hours for 3 days.

The dose and duration may differ in men or in patients with complicated urinary tract infections. In men, possible prostate involvement should also be considered, as this may require a longer course of treatment.

For currently recommended treatment options for urinary tract infections, read: Treatment of Urinary Tract Infection (UTI) With Antibiotics.

Pyelonephritis

When ciprofloxacin is appropriate and the bacteria are susceptible, a commonly used regimen for acute pyelonephritis in adults is:

• Ciprofloxacin 500 mg every 12 hours for 7 days.

For more complicated infections, doses of 500 to 750 mg every 12 hours and longer courses of treatment may be necessary.

Patients with severe pyelonephritis, sepsis, persistent vomiting, or inability to take oral medication may need to begin treatment intravenously.

In men with febrile urinary tract infection, recurrent pyelonephritis, or suspected prostate involvement, longer treatment courses, often at least 14 days, may be necessary.

Acute bacterial prostatitis

In acute bacterial prostatitis, the total duration of treatment is usually 2 to 4 weeks.

Ciprofloxacin 500 to 750 mg every 12 hours is one of the options when the bacteria are susceptible.

In patients with a severe systemic infection, treatment may initially be given intravenously. Once the patient improves clinically, treatment can be changed to an appropriate oral antibiotic to complete the full course.

Chronic bacterial prostatitis

For chronic bacterial prostatitis caused by susceptible organisms, a commonly used regimen is:

• Ciprofloxacin 500 to 750 mg every 12 hours for 4 to 6 weeks.

Fluoroquinolones have the advantage of achieving good concentrations in prostate tissue, but the choice of antibiotic should always take culture and antibiotic susceptibility testing into account.

Other dosing regimens

Other regimens used in adults, depending on the infection and bacterial susceptibility, include:

• Skin and soft tissue infections: 500 to 750 mg every 12 hours, usually for 7 to 14 days.
• Bone and joint infections: 500 to 750 mg every 12 hours, usually for 4 to 8 weeks. Duration depends on the type of infection, the causative bacteria, and adequate control of the source of infection.
• Complicated intra-abdominal infections: 500 mg every 12 hours for 7 to 14 days, usually in combination with metronidazole or another antibiotic with adequate activity against anaerobic bacteria.
• Certain bacterial diarrheas: 500 mg every 12 hours. Duration varies depending on the causative bacteria, local resistance patterns, and current recommendations. When ciprofloxacin is an appropriate treatment for travelers’ diarrhea, one regimen is 500 mg every 12 hours for 3 days.
• Typhoid fever: 500 mg every 12 hours, generally for 7 to 10 days, when the bacteria are susceptible to ciprofloxacin.
• Plague: 500 to 750 mg every 12 hours for 14 days.
• Meningococcal disease prophylaxis in adults: 500 mg as a single dose when ciprofloxacin is considered appropriate according to local resistance patterns.
• Inhalational anthrax after exposure: 500 mg every 12 hours for 60 days.
• Cholera: ciprofloxacin regimens vary among guidelines and should only be used when the strain is susceptible.

These doses are reference regimens for adults with preserved kidney function. The decision to use ciprofloxacin and the duration of treatment must take into account the site and severity of the infection, identification of the causative bacteria, and, whenever available, antibiotic susceptibility testing.

How to take ciprofloxacin

Ciprofloxacin may be taken with or without food. When taken on an empty stomach, absorption may occur slightly faster.

However, the medication should not be taken at the same time as milk, yogurt, or calcium-fortified beverages alone, because these products can reduce its absorption. This does not mean that dairy products must be completely avoided during treatment: ciprofloxacin may be taken with a meal that contains these foods.

Antacids and products containing calcium, iron, magnesium, aluminum, or zinc can also significantly reduce ciprofloxacin absorption. Sucralfate and phosphate binders such as sevelamer or lanthanum can have the same effect.

For oral ciprofloxacin in the United States, the practical recommendation is to take the antibiotic at least 2 hours before or 6 hours after these products.

Adequate hydration is recommended during treatment.

Dose adjustment in kidney impairment

Ciprofloxacin is eliminated primarily through the kidneys. In patients with chronic kidney disease, the dose may need to be reduced or the interval between doses increased.

Dose adjustment should be based on creatinine clearance.

According to U.S. prescribing information for immediate-release ciprofloxacin tablets:

• Creatinine clearance above 50 mL/min: usual dose.
• Creatinine clearance between 30 and 50 mL/min: 250 to 500 mg every 12 hours.
• Creatinine clearance between 5 and 29 mL/min: 250 to 500 mg every 18 hours.
• Hemodialysis: 250 to 500 mg every 24 hours, administered after dialysis.
• Peritoneal dialysis: 250 to 500 mg every 24 hours.

Recommendations may differ slightly in prescribing information from other countries, especially regarding the dose interval in patients with severe kidney impairment. Therefore, patients with reduced kidney function should follow the locally approved prescribing information and the regimen prescribed by their physician.

Effectiveness and bacterial resistance

The effectiveness of ciprofloxacin depends primarily on whether the bacteria causing the infection are susceptible to the antibiotic. When the organism is susceptible and the medication is used at the appropriate dose and for the appropriate duration, ciprofloxacin can be highly effective for infections in which it is indicated.

Response to treatment also depends on the site and severity of the infection, the presence of abscesses or obstructions, the patient’s clinical condition, and, in some cases, the need for additional antibiotics or procedures to control the source of infection.

An important problem is that bacterial resistance to ciprofloxacin has increased over recent decades. This is particularly relevant in urinary tract infections caused by Escherichia coli, gonorrhea, and certain gastrointestinal infections.

For this reason, when culture and antibiotic susceptibility testing are available, the results help determine whether ciprofloxacin is an appropriate choice. If the bacteria are resistant to ciprofloxacin, treatment should be changed to an antibiotic to which the organism is susceptible.

Ciprofloxacin side effects

Ciprofloxacin is generally well tolerated by most patients. The most common adverse effects are nausea and diarrhea. Vomiting, abdominal discomfort, loss of appetite, headache, and dizziness may also occur.

Rarely, fluoroquinolones can cause serious, disabling, and potentially irreversible adverse effects, even in people without known risk factors.

The most important of these effects primarily involve the tendons, peripheral nerves, and central nervous system.

Tendinitis and tendon rupture

Fluoroquinolones are associated with an increased risk of tendinitis and tendon rupture, particularly involving the Achilles tendon.

The problem may develop within the first hours or days of treatment, but cases have also been reported several months after the medication has been discontinued.

The risk is higher in:

• People older than 60 years.
• Patients taking corticosteroids.
• Transplant recipients.
• People with kidney impairment.
• Patients with a previous history of tendon disorders.
• People who engage in strenuous physical activity.

Pain, swelling, or inflammation in a tendon during treatment are warning signs. In these situations, ciprofloxacin should be discontinued and the patient should seek medical advice before returning to exercise or placing stress on the affected area.

Peripheral neuropathy

Ciprofloxacin can also cause peripheral neuropathy, which may develop rapidly after treatment begins and, in some patients, may result in persistent symptoms.

Burning, tingling, numbness, altered sensation, or weakness in the arms or legs should be reported promptly to a physician.

Neurologic and psychiatric effects

Fluoroquinolones can cause central nervous system effects, sometimes even after the first dose.

Possible symptoms include:

• Agitation.
• Anxiety.
• Insomnia.
• Confusion or delirium.
• Disorientation.
• Memory problems.
• Hallucinations.
• Tremors.
• Depression.
• Seizures.

Ciprofloxacin may lower the seizure threshold and should be used with caution in patients with epilepsy or other conditions that increase the risk of seizures.

Blood glucose changes

Fluoroquinolones can cause both hyperglycemia and hypoglycemia.

This risk is particularly important in patients with diabetes mellitus who use insulin or certain glucose-lowering medications.

Rare cases of severe hypoglycemia, including coma, have been reported.

Other important adverse effects

Other relevant adverse effects of ciprofloxacin include:

• Severe allergic reactions.
• Photosensitivity.
• Abnormal heart rhythms due to QT interval prolongation.
• Liver injury.
• Diarrhea associated with Clostridioides difficile.
• Worsening of myasthenia gravis symptoms.
• Increased risk of aortic aneurysm or dissection in predisposed individuals.

Sudden, severe pain in the chest, abdomen, or back during or after the use of a fluoroquinolone requires urgent medical evaluation, especially in patients with a known aortic aneurysm or other major vascular risk factors.

Because of the risk of serious adverse effects, even though they are uncommon, fluoroquinolones should be avoided for mild infections when safer, appropriate alternatives are available.

Contraindications and precautions

Ciprofloxacin is contraindicated in people who are allergic to ciprofloxacin itself or to other quinolones.

Another important contraindication is simultaneous use with tizanidine. Ciprofloxacin can substantially increase blood levels of tizanidine, potentially causing excessive sedation and a significant drop in blood pressure.

In addition to these formal contraindications, ciprofloxacin should be avoided or used only after careful assessment of the risks and benefits in people with:

• A history of quinolone-associated tendinitis or tendon rupture.
• Peripheral neuropathy.
• Myasthenia gravis.
• Epilepsy or other important risk factors for seizures.
• QT interval prolongation or a high risk of cardiac arrhythmias.
• A known aortic aneurysm or an increased risk of aneurysm or dissection.
• Significant kidney impairment requiring dose adjustment.

Blood donation rules vary between countries and blood collection services. In the United States, ciprofloxacin itself does not require a fixed seven-day waiting period after the last dose. However, a person with an active infection should not donate blood. Eligibility after antibiotic treatment depends primarily on the reason the antibiotic was prescribed and whether the person has recovered. Anyone currently taking ciprofloxacin or who has recently completed treatment should confirm eligibility with the blood donation center before donating.

Ciprofloxacin in children

Ciprofloxacin is not a first-line antibiotic in pediatric patients because of the higher risk of musculoskeletal adverse effects. Nevertheless, its use is not absolutely contraindicated in children.

Approved pediatric indications vary among countries.

In the United States, oral ciprofloxacin is approved for selected situations, including:

• Complicated urinary tract infections and pyelonephritis caused by Escherichia coli in children and adolescents 1 to 17 years of age.
• Post-exposure prophylaxis and treatment of inhalational anthrax in pediatric patients from birth through 17 years of age.
• Treatment and prophylaxis of plague in pediatric patients from birth through 17 years of age.

Other countries may authorize additional pediatric indications, including selected severe infections caused by Pseudomonas aeruginosa, such as bronchopulmonary infections in patients with cystic fibrosis.

Pediatric treatment should be prescribed by a physician experienced in managing these infections.

Ciprofloxacin during pregnancy and breastfeeding

Pregnancy

As a precaution, ciprofloxacin is usually avoided during pregnancy when more appropriate antibiotics are available.

Available observational studies in humans have not shown a clear increase in the risk of major congenital malformations, miscarriage, or other adverse pregnancy outcomes.

However, because cartilage abnormalities have been observed in young animals exposed to quinolones and because other antibiotics have been more extensively studied during pregnancy, ciprofloxacin is usually not considered a first-line antibiotic for pregnant women.

Breastfeeding

Ciprofloxacin passes into breast milk.

Recommendations regarding its use during breastfeeding are not entirely uniform. U.S. prescribing information recommends avoiding breastfeeding during treatment and for two days after the final dose, with pumping and discarding of breast milk during this period when appropriate.

On the other hand, the U.S. National Library of Medicine’s LactMed database considers ciprofloxacin acceptable during breastfeeding because the amount transferred into breast milk is low. It recommends monitoring the infant for possible effects on intestinal flora, such as diarrhea, oral thrush, or diaper rash.

Therefore, when ciprofloxacin treatment is necessary, the physician should assess the clinical situation, whether an equally effective alternative antibiotic is available, and the most appropriate approach to breastfeeding.

Drug interactions

Ciprofloxacin can interact with several medications.

The combination with tizanidine is contraindicated because ciprofloxacin can substantially increase blood concentrations of tizanidine, causing hypotension and excessive sedation.

Antacids containing magnesium or aluminum, sucralfate, sevelamer, and supplements or multivitamins containing calcium, iron, or zinc can significantly reduce ciprofloxacin absorption.

The same precaution applies to large amounts of calcium taken alone. Ciprofloxacin should not be taken with milk, yogurt, or calcium-fortified beverages alone, although it may be taken with a meal containing these foods.

In patients taking anticoagulants, ciprofloxacin may increase the effect of warfarin, resulting in an increased INR and a higher risk of bleeding. When the combination is necessary, INR should be monitored.

Ciprofloxacin also inhibits an enzyme called CYP1A2 and can increase the blood concentration of certain medications.

Important interactions include:

• Theophylline: blood concentrations may increase substantially, raising the risk of serious adverse effects. The combination should be avoided whenever possible.
• Duloxetine: drug levels may increase.
• Clozapine: blood concentrations may increase.
• Ropinirole: drug levels may increase.
• Caffeine: its elimination may be slower, increasing its stimulant effects.
• Phenytoin: blood levels may increase or decrease, so monitoring may be necessary when the medications are used together.
• Methotrexate: blood concentrations and toxicity may increase.
• Cyclosporine: a transient increase in creatinine may occur.
• Diabetes medications: there may be an increased risk of hypoglycemia, particularly with certain sulfonylureas.
• Nonsteroidal anti-inflammatory drugs: animal studies have shown that high doses of quinolones combined with certain NSAIDs, except aspirin, may increase the risk of seizures. The combination is not formally contraindicated, but caution is recommended, particularly in people predisposed to seizures.
• Medications that prolong the QT interval, including certain antiarrhythmics, antidepressants, macrolides, and antipsychotics: the combination may increase the risk of arrhythmias.

As with most antibiotics, ciprofloxacin does not directly reduce the effectiveness of birth control pills. However, severe vomiting or diarrhea may interfere with the absorption of oral contraceptives.

Because the complete list of interactions is extensive, patients who take several medications should tell their physician or pharmacist everything they are taking before starting ciprofloxacin.

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