Cipro - Drug Monograph

Introduction

Cipro (ciprofloxacin) is a broad-spectrum fluoroquinolone antibiotic that has been widely used in clinical practice since its approval in 1987. As a second-generation fluoroquinolone, it demonstrates potent activity against both Gram-positive and Gram-negative bacteria, particularly aerobic organisms. Ciprofloxacin remains an important therapeutic option for various bacterial infections, though its use has become more restricted in recent years due to safety concerns and antimicrobial stewardship considerations.

Mechanism of Action

Ciprofloxacin exerts its bactericidal effect by inhibiting bacterial DNA gyrase (topoisomerase II) and topoisomerase IV. DNA gyrase is essential for DNA replication, transcription, and repair, while topoisomerase IV is crucial for chromosome partitioning during cell division. By binding to these enzymes, ciprofloxacin creates stable DNA-enzyme complexes that block DNA replication, leading to rapid bacterial cell death. This dual mechanism provides concentration-dependent killing activity against susceptible organisms.

Indications

FDA-approved indications include:

• Complicated urinary tract infections
• Acute uncomplicated cystitis
• Chronic bacterial prostatitis
• Lower respiratory tract infections (including pneumonia)
• Acute exacerbations of chronic bronchitis
• Skin and skin structure infections
• Bone and joint infections
• Infectious diarrhea
• Typhoid fever
• Complicated intra-abdominal infections (in combination with metronidazole)
• Plague
• Post-exposure inhalation anthrax

Off-label uses (with appropriate clinical justification) may include certain sexually transmitted infections and mycobacterial infections.

Dosage and Administration

• Oral: 250-750 mg every 12 hours
• IV: 200-400 mg every 12 hours

• Urinary tract infections: 250-500 mg every 12 hours for 7-14 days
• Respiratory infections: 500-750 mg every 12 hours for 7-14 days
• Bone/joint infections: 500-750 mg every 12 hours for 4-6 weeks

• Renal impairment: Dose adjustment required for CrCl <50 mL/min
• Hepatic impairment: No significant adjustment needed
• Elderly: Consider reduced dosing based on renal function
• Pediatrics: Generally contraindicated except for specific indications (plague, anthrax)

• Oral administration should occur 2 hours before or 4 hours after antacids, sucralfate, or products containing calcium, iron, or zinc
• IV infusion should be administered over 60 minutes

Pharmacokinetics

Contraindications

• Known hypersensitivity to ciprofloxacin or other quinolones
• Concomitant administration with tizanidine
• History of tendon disorders associated with quinolone use

Warnings and Precautions

• Tendinitis and tendon rupture
• Exacerbation of myasthenia gravis
• Peripheral neuropathy

• CNS effects: seizures, increased intracranial pressure, psychosis
• QT prolongation and arrhythmias
• Photosensitivity reactions
• Hepatotoxicity
• Clostridioides difficile-associated diarrhea
• Aortic aneurysm and dissection
• Hypoglycemia (especially in diabetic patients)
• Musculoskeletal disorders in pediatric patients

Drug Interactions

• Antacids, sucralfate, iron, calcium, zinc: Decreased absorption
• Theophylline: Increased theophylline levels
• Warfarin: Enhanced anticoagulant effect
• Tizanidine: Contraindicated combination
• CYP1A2 substrates: Increased levels of drugs like caffeine, clozapine, olanzapine
• QT-prolonging agents: Additive effect on cardiac repolarization
• NSAIDs: Increased risk of CNS stimulation
• Probenecid: Decreased renal clearance of ciprofloxacin
• Corticosteroids: Increased risk of tendon rupture

Adverse Effects

• Nausea (5-10%)
• Diarrhea (2-8%)
• Headache (1-5%)
• Dizziness (1-3%)
• Rash (1-2%)

• Tendinitis and tendon rupture
• Peripheral neuropathy
• QT prolongation and torsades de pointes
• Hepatotoxicity
• Seizures
• Psychotic reactions
• Photosensitivity
• Blood dyscrasias
• Stevens-Johnson syndrome
• Aortic aneurysm/dissection

Monitoring Parameters

• Clinical response to therapy
• Renal function (baseline and during prolonged therapy)
• Liver function tests (prolonged therapy)
• Signs of tendon inflammation or rupture
• Neurological symptoms
• Blood glucose in diabetic patients
• ECG monitoring in patients at risk for QT prolongation
• Signs of C. difficile infection

Patient Education

• Complete the full course of therapy unless directed otherwise by healthcare provider
• Take with water 2 hours before or 4 hours after antacids, dairy products, or mineral supplements
• Maintain adequate hydration
• Immediately report tendon pain, swelling, or inflammation
• Report any numbness, tingling, or burning sensations
• Avoid excessive sun exposure and use sunscreen
• Be aware of potential dizziness and avoid driving if affected
• Inform all healthcare providers of ciprofloxacin use
• Diabetic patients should monitor blood glucose closely
• Report any unusual muscle pain or weakness
• Immediately seek medical attention for any signs of allergic reaction

References

1. FDA Prescribing Information: Cipro (ciprofloxacin). 2023 2. Gilbert DN, et al. The Sanford Guide to Antimicrobial Therapy. 52nd ed. 2022 3. Owens RC Jr, Ambrose PG. Antimicrobial safety: focus on fluoroquinolones. Clin Infect Dis. 2005;41 Suppl 2:S144-S157 4. Rubinstein E, et al. Safety profile of quinolones. Expert Opin Drug Saf. 2014;13(10):1321-1333 5. Mandell LA, et al. Infectious Diseases Society of America/American Thoracic Society consensus guidelines on the management of community-acquired pneumonia in adults. Clin Infect Dis. 2007;44 Suppl 2:S27-S72 6. Clinical and Laboratory Standards Institute. Performance Standards for Antimicrobial Susceptibility Testing. 33rd ed. 2023 7. Lee CC, et al. Risk of aortic dissection and aortic aneurysm in patients taking oral fluoroquinolone. JAMA Intern Med. 2018;178(12):1589-1597 8. FDA Drug Safety Communication: FDA updates warnings for oral and injectable fluoroquinolone antibiotics due to disabling side effects. July 2016