BLACK BOX WARNING
- tendinitis and tendon rupture — increased in elderly and with corticosteroid use; peripheral neuropathy — may be irreversible; CNS effects; myasthenia gravis exacerbation; aortic aneurysm and aortic dissection
ciprofloxacin
Brand: Cipro, Cipro XR
⚠ BBW Prototype Drug
Drug Class: antibiotic
Drug Family: antibiotic
Subclass: fluoroquinolone / second-generation
Organ Systems: infectious-disease
Mechanism of Action
Inhibits bacterial DNA gyrase (gram-negatives) and topoisomerase IV (gram-positives), enzymes required to relieve DNA supercoiling during replication; bactericidal; concentration-dependent killing.
DNA gyrase (topoisomerase II)topoisomerase IV
Indications
- complicated UTI and pyelonephritis
- anthrax (drug of choice)
- typhoid fever
- gonorrhea (no longer first-line due to resistance)
- traveler's diarrhea
- prostatitis
- bone/joint infections (Pseudomonas)
- febrile neutropenia (with beta-lactam)
Contraindications
- concurrent tizanidine (CYP1A2 inhibition — severe hypotension)
- myasthenia gravis (fluoroquinolone may exacerbate)
- children <18 (except anthrax/inhalation therapy)
Adverse Effects
Common
- nausea
- diarrhea
- headache
- rash
- QTc prolongation
Serious
- tendinopathy / tendon rupture (Achilles — especially elderly, corticosteroid use)
- peripheral neuropathy (potentially irreversible)
- CNS effects (dizziness, seizures, psychosis)
- hypoglycemia (especially in diabetics on oral hypoglycemics)
- aortic aneurysm/dissection (FDA warning 2018)
Pharmacokinetics (ADME)
| Absorption | Oral bioavailability ~70%; reduced by divalent cations (antacids, calcium, iron, zinc) |
| Distribution | Protein binding 20–40%; Vd ~2–3.5 L/kg; excellent tissue penetration including prostate and bone |
| Metabolism | CYP1A2 inhibitor; hepatic partial metabolism to active desethylene-ciprofloxacin |
| Excretion | Renal 40–50%; fecal; dose adjustment for CrCl <30 mL/min |
| Half-life | 3.5–5 hours |
| Onset | 1–2 hours |
| Peak | 1–2 hours |
| Duration | 12 hours (q12h dosing) |
| Protein Binding | 20–40% |
| Vd | 2–3.5 L/kg |
Drug Interactions
| Drug / Agent | Mechanism | Severity |
|---|---|---|
| multivalent cations (antacids, calcium, iron, sucralfate, dairy) | chelation reduces ciprofloxacin oral absorption by 50–90%; separate by 2–4 hours | major |
| theophylline | CYP1A2 inhibition increases theophylline levels; risk of toxicity | major |
| warfarin | CYP1A2 inhibition reduces warfarin metabolism; INR elevation | major |
Nursing Considerations
- Administer oral ciprofloxacin at least 2 hours before or 6 hours after antacids, calcium supplements, iron, zinc, sucralfate, or dairy products — chelation dramatically reduces absorption
- Instruct patients to report tendon pain or swelling immediately — discontinue and restrict activity; risk is highest in elderly patients and those on corticosteroids
- Monitor blood glucose in diabetic patients on antidiabetic medications — fluoroquinolones can cause hypoglycemia (especially with sulfonylureas) or hyperglycemia
- Avoid fluoroquinolones when alternatives are appropriate — reserve for serious gram-negative infections to preserve efficacy and minimize serious adverse effects
Clinical Pearls
- Ciprofloxacin has the strongest gram-negative activity of the fluoroquinolones including activity against Pseudomonas aeruginosa — but fluoroquinolone resistance in Pseudomonas has become common in many hospitals, limiting empiric use
- The FDA's 2016 boxed warning revision and 2018 aortic aneurysm warning reflect growing evidence that fluoroquinolones have serious systemic toxicities — they should not be used for uncomplicated UTIs, sinusitis, or bronchitis when safer alternatives exist
Safety Profile
Pregnancy avoid
Lactation avoid
Renal Adjustment Required
Hepatic Adjustment Not required
TDM Not required
Guideline Update pending
Concordance Terms
Cross-referenced clinical concepts — click any term to see all content where it appears.