Ciprofloxacin
1. Drug Name
Generic Name: Ciprofloxacin
Brand Names: Cipro, Proquin XR, Cipro XR, and others.
2. Drug Classification
Class: Antibiotic, Fluoroquinolone
Subclass: None (Fluoroquinolone class)
3. Mechanism of Action
Primary Action: Ciprofloxacin is a broad-spectrum bactericidal antibiotic that works by inhibiting bacterial DNA synthesis. It primarily targets two bacterial enzymes: DNA gyrase and topoisomerase IV. These enzymes are responsible for the supercoiling and untangling of bacterial DNA during replication. Inhibition of these enzymes results in the stabilization of DNA strand breaks, ultimately leading to bacterial cell death.
Spectrum of Activity: Ciprofloxacin has potent activity against a wide range of both gram-negative and gram-positive bacteria, including:
Gram-negative organisms: Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Haemophilus influenzae, Neisseria gonorrhoeae, Salmonella species, Shigella species.
Gram-positive organisms: Streptococcus pneumoniae, Staphylococcus aureus (including some MRSA strains), Enterococcus species.
Atypical pathogens: Mycoplasma pneumoniae, Chlamydia pneumoniae, Legionella pneumophila.
Resistance Mechanisms: Bacterial resistance to ciprofloxacin occurs mainly through mutations in the DNA gyrase and topoisomerase IV genes, leading to reduced binding affinity for the drug. Additionally, efflux pumps may expel ciprofloxacin from bacterial cells, contributing to resistance.
4. Pharmacokinetics
Absorption: Ciprofloxacin is well absorbed after oral administration, with a bioavailability of approximately 70-80%. The presence of food may slightly decrease the absorption, but it is not significantly affected.
Distribution: Ciprofloxacin is widely distributed throughout the body, including the lungs, liver, kidneys, bones, and soft tissues. It also achieves therapeutic concentrations in the urine, making it highly effective in treating urinary tract infections.
Metabolism: Ciprofloxacin is partially metabolized in the liver via the CYP450 enzyme system (primarily CYP1A2). However, most of the drug remains unchanged and is excreted via the kidneys.
Excretion: The half-life of ciprofloxacin is approximately 4 hours. It is primarily eliminated unchanged via the kidneys (approximately 40-50% of the dose) and to a lesser extent via feces.
Special Considerations: Ciprofloxacin dosing must be adjusted in patients with renal impairment, especially in cases of significant renal dysfunction (creatinine clearance <30 mL/min).
5. Indications
Primary Indications:
Urinary Tract Infections (UTIs): Acute uncomplicated cystitis, complicated UTIs, pyelonephritis.
Respiratory Tract Infections: Community-acquired pneumonia, chronic obstructive pulmonary disease (COPD) exacerbations, acute bacterial sinusitis.
Intra-abdominal Infections: Bacterial infections such as peritonitis and abscesses.
Gastrointestinal Infections: Diarrhea caused by Shigella and Salmonella species, as well as cholera.
Bone and Joint Infections: Osteomyelitis and septic arthritis.
Anthrax: Ciprofloxacin is used in post-exposure prophylaxis and treatment of inhalational anthrax.
Off-label Uses:
Chronic prostatitis: Ciprofloxacin can be used in treating chronic prostatitis caused by susceptible bacteria.
Plague: It is also effective against Yersinia pestis, the causative agent of plague.
Tularemia: For the treatment of Francisella tularensis infections.
Specific Populations: Ciprofloxacin is generally safe for adults and older children. However, its use in pediatric populations is limited due to concerns about joint and cartilage toxicity, especially in young children.
6. Dosage and Administration
Adult Dosing:
Urinary Tract Infections: 250-500 mg every 12 hours for 3 to 14 days, depending on the severity of the infection.
Respiratory Tract Infections: 500-750 mg every 12 hours for 7-14 days.
Intra-abdominal Infections: 400 mg IV every 8 hours, or 500 mg orally every 12 hours.
Anthrax (Post-exposure Prophylaxis): 500 mg every 12 hours for 60 days.
Bone and Joint Infections: 500 mg to 750 mg every 12 hours for 4 to 6 weeks, depending on the severity and organism.
Pediatric Dosing: For pediatric patients (age ≥1 year), the typical dose is 10-20 mg/kg every 12 hours for infections like UTIs and pneumonia. However, the maximum dose for children should not exceed 500 mg per dose.
Renal Adjustments: Dose reductions are necessary in patients with renal impairment. For patients with a creatinine clearance less than 30 mL/min, the dosing interval should be extended (e.g., every 24 hours).
Route of Administration: Ciprofloxacin is available in oral tablets, oral suspension, and intravenous formulations.
7. Contraindications
Absolute Contraindications:
Hypersensitivity to ciprofloxacin, other fluoroquinolones, or any component of the formulation.
Relative Contraindications:
Tendon Disorders: Ciprofloxacin can cause tendonitis and tendon rupture, particularly in elderly patients and those on corticosteroid therapy.
QT Prolongation: Should be used with caution in patients with a history of arrhythmias or those taking other drugs that prolong the QT interval.
Pregnancy and Lactation: Ciprofloxacin should be used during pregnancy only if the potential benefits outweigh the risks (Category C). It is excreted in breast milk, so it should be used cautiously in breastfeeding mothers.
8. Warnings and Precautions
Tendonitis and Tendon Rupture: Fluoroquinolones, including ciprofloxacin, are associated with an increased risk of tendonitis and tendon rupture, especially in older adults and those receiving corticosteroid treatment.
CNS Effects: Ciprofloxacin may cause CNS effects such as seizures, dizziness, and confusion. Caution should be exercised in patients with a history of seizures or other CNS disorders.
QT Prolongation: Ciprofloxacin can prolong the QT interval, which can lead to life-threatening arrhythmias, particularly in patients with pre-existing heart conditions or electrolyte imbalances.
C. difficile-Associated Diarrhea: Ciprofloxacin may cause a severe form of diarrhea due to Clostridium difficile overgrowth. Discontinue use if significant diarrhea occurs.
Glucose Abnormalities: Ciprofloxacin has been associated with both hypoglycemia and hyperglycemia, particularly in diabetic patients.
Photosensitivity: Patients should be advised to avoid excessive sunlight or tanning beds, as ciprofloxacin may increase the risk of sunburn or photosensitivity reactions.
9. Adverse Effects
Common Adverse Effects (≥10%):
Gastrointestinal upset (nausea, diarrhea, vomiting).
Less Common but Clinically Significant:
Musculoskeletal: Tendonitis, tendon rupture, arthralgia, and myalgia.
CNS Effects: Headache, dizziness, confusion, seizures.
Cardiovascular: QT prolongation, arrhythmias.
Hematologic: Leukopenia, thrombocytopenia.
Serious Adverse Reactions:
Tendon rupture (especially Achilles tendon): Particularly in older adults, patients on corticosteroids, and those with renal impairment.
Severe allergic reactions such as anaphylaxis, Stevens-Johnson syndrome, and toxic epidermal necrolysis.
Seizures and CNS toxicity: Especially in patients with a history of epilepsy or those taking drugs that lower the seizure threshold.
10. Drug Interactions
Major Drug Interactions:
Antacids and Cationic Compounds: Antacids containing aluminum, magnesium, or calcium may decrease the absorption of ciprofloxacin. These should be taken 2 hours before or after ciprofloxacin.
CYP450 Inhibitors (e.g., fluvoxamine, cimetidine): Ciprofloxacin is metabolized by CYP1A2; drugs that inhibit this enzyme can lead to elevated ciprofloxacin levels.
Warfarin: Ciprofloxacin may potentiate the anticoagulant effects of warfarin, increasing the risk of bleeding. Monitoring of INR is recommended.
QT Prolonging Drugs: Concurrent use with drugs that prolong the QT interval (e.g., antiarrhythmics, antipsychotics) may increase the risk of arrhythmias.
Theophylline: Ciprofloxacin may increase the serum concentration of theophylline, leading to toxicity.
Food-Drug Interactions: Ciprofloxacin absorption is reduced by dairy products and calcium-fortified juices, so these should be avoided within 2 hours of taking the drug.
11. Clinical Pharmacology
Pharmacodynamics: Ciprofloxacin exhibits concentration-dependent bactericidal activity. The therapeutic concentration required for bacterial eradication is determined by the AUC (Area Under the Curve) to MIC (Minimum Inhibitory Concentration) ratio.
Additional Pharmacological Effects: Ciprofloxacin also possesses anti-inflammatory effects, which may contribute to its efficacy in treating certain respiratory infections.
12. Special Populations
Pregnancy: Ciprofloxacin is a Category C drug. It should only be used during pregnancy when the potential benefit outweighs the risks, as it has been shown to cause cartilage damage in animal studies.
Lactation: Ciprofloxacin is excreted in breast milk in low amounts, but its use during lactation should be weighed against the potential risks to the infant.
Pediatrics: Ciprofloxacin is contraindicated in children under 18 years of age unless absolutely necessary due to concerns about joint and cartilage toxicity.
Geriatrics: Elderly patients are at increased risk for tendonitis, tendon rupture, CNS effects, and renal dysfunction. Renal dosing adjustments are often required.
13. Therapeutic Uses
First-Line Therapy: Ciprofloxacin is used as first-line therapy for UTIs, traveler's diarrhea, and certain respiratory infections.
Second-Line Therapy: It is used in multi-drug-resistant infections and in combination with other antibiotics for resistant tuberculosis or complicated infections.
Combination Therapy: Ciprofloxacin can be used in combination with beta-lactam antibiotics for serious infections like pneumonia, sepsis, and intra-abdominal infections.
14. Monitoring and Follow-Up
Lab Tests: Monitoring of renal function (creatinine, blood urea nitrogen), liver enzymes (AST, ALT), and complete blood count (CBC) is recommended during prolonged therapy.
Electrocardiogram (ECG): For patients with a risk of QT prolongation or those on medications affecting cardiac rhythm.
Tendon Assessment: Clinicians should monitor for signs of tendonitis and tendon rupture, especially in high-risk populations.
15. Overdose Management
Symptoms of Overdose: Nausea, vomiting, dizziness, confusion, and seizures.
Treatment Protocols: There is no specific antidote for ciprofloxacin overdose. Symptomatic treatment should be initiated, including hydration, antiemetics, and seizure control.
Supportive Measures: Activated charcoal may be considered in the case of recent overdose, along with general supportive measures.
16. Patient Counseling Information
Key Points to Discuss with Patients:
Take ciprofloxacin exactly as prescribed, even if you start feeling better before finishing the entire course.
Avoid dairy products or antacids within 2 hours of taking ciprofloxacin.
Report any symptoms of tendon pain or swelling, as these may indicate tendonitis or tendon rupture.
Avoid prolonged exposure to sunlight or tanning beds.
Signs/Symptoms to Watch For:
Pain, swelling, or inflammation in the tendons.
Difficulty breathing, rash, or other signs of an allergic reaction.
Severe diarrhea or abdominal pain.