Ciprofloxacin

Usage

Ciprofloxacin, a synthetic broad-spectrum antibiotic belonging to the fluoroquinolone class, is prescribed for various bacterial infections. These include urinary tract infections (UTIs), respiratory tract infections, skin and soft tissue infections, bone and joint infections, gastrointestinal infections, and certain sexually transmitted infections (STIs) like gonorrhea. It is also used for prophylaxis and treatment of anthrax and plague.

Pharmacological Classification: Fluoroquinolone antibiotic.

Mechanism of Action: Ciprofloxacin inhibits bacterial DNA gyrase and topoisomerase IV, enzymes essential for bacterial DNA replication and repair, ultimately leading to bacterial cell death.

Alternate Names

Ciprofloxacin is also known internationally by its generic name.

Brand Names: Cipro, Cipro XR, Proquin XR.

How It Works

Pharmacodynamics: Ciprofloxacin exhibits bactericidal activity by disrupting bacterial DNA replication and repair. It achieves high concentrations in various tissues and fluids, including urine, lungs, and bone.

Pharmacokinetics:

• Absorption: Ciprofloxacin is well-absorbed orally, with bioavailability around 70%. Food can slightly delay absorption but does not significantly affect overall bioavailability.
• Distribution: It is widely distributed throughout the body, reaching therapeutic concentrations in various tissues and fluids.
• Metabolism: Ciprofloxacin undergoes minimal hepatic metabolism.
• Elimination: Primarily eliminated renally (glomerular filtration and tubular secretion) with a small portion excreted in feces. The half-life is approximately 4 hours in individuals with normal renal function but is prolonged in patients with renal impairment.

Mode of Action: Ciprofloxacin targets bacterial DNA gyrase and topoisomerase IV. These enzymes introduce negative supercoils into DNA, relieving torsional stress during DNA replication. By binding to the enzyme-DNA complex, ciprofloxacin stabilizes the complex, creating double-strand DNA breaks and inhibiting DNA replication and repair.

Elimination Pathways: Predominantly renal excretion (glomerular filtration and tubular secretion) of unchanged drug, with a minor contribution from fecal excretion.

Dosage

Standard Dosage

Adults:

• Immediate-release: 250-750 mg every 12 hours.
• Extended-release: 500-1000 mg every 24 hours (for UTIs only). Duration depends on infection type and severity, typically 3-14 days or longer for severe infections like bone and joint infections.

Children:

• Complicated UTIs/Pyelonephritis: 10-20 mg/kg every 12 hours (max 750 mg/dose).
• Other Infections: Dosing varies depending on infection, refer to specific guidelines. Pediatric dosage is often weight-based.

Special Cases:

• Elderly Patients: Adjust dose based on creatinine clearance.
• Patients with Renal Impairment: Dosage adjustment is crucial.
  • CrCl 30-50 mL/min: Reduce dose or increase interval.
  • CrCl <30 mL/min: Significant dose reduction required.
• Patients with Hepatic Dysfunction: No dose adjustment is typically necessary.
• Patients with Comorbid Conditions: Assess case-by-case for potential interactions or contraindications.

Clinical Use Cases

Dosage may vary based on infection severity and clinical context. Consultation with an infectious disease specialist is advisable for specific recommendations.

Dosage Adjustments:

Renal or hepatic impairment necessitates dose modification based on creatinine clearance or Child-Pugh score. Monitor drug levels in patients with severe renal impairment for optimal dosage adjustments.

Side Effects

Common Side Effects:

Nausea, diarrhea, abdominal pain, vomiting, headache, dizziness.

Rare but Serious Side Effects:

• Tendinitis, tendon rupture (especially Achilles tendon).
• Peripheral neuropathy.
• Seizures.
• Clostridioides difficile-associated diarrhea.
• QT interval prolongation.
• Hepatotoxicity (rare but potentially fatal).
• Hypersensitivity reactions (including anaphylaxis).

Long-Term Effects:

Peripheral neuropathy may persist after discontinuation.

Adverse Drug Reactions (ADR):

Anaphylaxis, Stevens-Johnson syndrome, toxic epidermal necrolysis, hepatic necrosis, Clostridioides difficile colitis.

Contraindications

Hypersensitivity to ciprofloxacin or other fluoroquinolones. Concomitant use with tizanidine. Patients with a history of QT prolongation.

Drug Interactions

• Theophylline: Increased risk of theophylline toxicity. Monitor serum levels closely.
• Warfarin: Enhanced anticoagulant effect. Monitor INR closely.
• NSAIDs: Increased risk of seizures.
• Antacids, multivitamins containing iron, zinc, magnesium, or calcium: Reduced ciprofloxacin absorption. Administer several hours apart.
• Drugs that prolong QT interval: Avoid concomitant use due to increased risk of torsades de pointes.

Pregnancy and Breastfeeding

Ciprofloxacin crosses the placenta and is present in breast milk. Data on human pregnancy is limited, but animal studies suggest potential for fetal harm. Avoid during pregnancy unless benefits outweigh risks. Use caution during breastfeeding due to potential cartilage development effects.

Drug Profile Summary

• Mechanism of Action: Inhibits bacterial DNA gyrase and topoisomerase IV.
• Side Effects: Nausea, diarrhea, headache, tendinitis, seizures (rare), QT prolongation (rare).
• Contraindications: Hypersensitivity, concomitant tizanidine use, history of QT prolongation.
• Drug Interactions: Theophylline, warfarin, NSAIDs, antacids.
• Pregnancy & Breastfeeding: Use with caution if benefits outweigh risks.
• Dosage: 250-750 mg every 12 hours (IR), 500-1000 mg every 24 hours (XR).
• Monitoring Parameters: Renal function, liver function (if indicated), theophylline levels (if co-administered), INR (if co-administered with warfarin), signs of tendinitis, cardiac rhythm.

Popular Combinations

Ciprofloxacin is sometimes used in combination with metronidazole for intra-abdominal infections.

Precautions

Obtain detailed patient history regarding allergies, renal/hepatic function, and concomitant medications. Pre-existing conditions like myasthenia gravis and epilepsy require careful monitoring. Advise patients to avoid excessive sun exposure. Counsel patients on the risk of tendon rupture and to promptly report any musculoskeletal symptoms.

FAQs (Frequently Asked Questions)

Q1: What is the recommended dosage for Ciprofloxacin?

A: The recommended dosage for adults is 250-750 mg of immediate-release Ciprofloxacin every 12 hours or 500-1000 mg of extended-release Ciprofloxacin every 24 hours. Pediatric dosing is weight-based (10-20 mg/kg every 12 hours). Dosage adjustments are required for patients with renal impairment.

Q2: What are the common side effects of Ciprofloxacin?

A: Common side effects include nausea, diarrhea, vomiting, abdominal pain, headache, and dizziness.

Q3: What are the serious side effects of Ciprofloxacin?

A: Rare but serious side effects include tendinitis, tendon rupture, peripheral neuropathy, seizures, C. difficile-associated diarrhea, QT interval prolongation, hepatotoxicity, and hypersensitivity reactions.

Q4: What are the contraindications for Ciprofloxacin?

A: Contraindications include hypersensitivity to ciprofloxacin or other fluoroquinolones, concomitant use of tizanidine, and a history of QT prolongation.

Q5: What are the major drug interactions with Ciprofloxacin?

A: Ciprofloxacin interacts with theophylline, warfarin, NSAIDs, antacids, and drugs that prolong the QT interval.

Q6: Can Ciprofloxacin be used during pregnancy and breastfeeding?

A: Ciprofloxacin should be used with caution during pregnancy and breastfeeding, only if the potential benefit outweighs the risks. It can cross the placenta and is present in breast milk.

Q7: What monitoring parameters are important for patients taking Ciprofloxacin?

A: Monitor renal and liver function, theophylline levels (if co-administered), INR (if taking warfarin), and cardiac rhythm. Look for signs of tendinitis.

Q8: How does Ciprofloxacin work against bacterial infections?

A: Ciprofloxacin inhibits bacterial DNA gyrase and topoisomerase IV, essential enzymes for bacterial DNA replication and repair. This inhibition leads to bacterial cell death.

Q9: What are some common infections that Ciprofloxacin is used to treat?

A: Ciprofloxacin is prescribed for UTIs, respiratory tract infections, skin and soft tissue infections, bone and joint infections, gastrointestinal infections, and certain STIs. It is also used for prophylaxis and treatment of anthrax and plague.

Q10: What are the considerations for prescribing Ciprofloxacin to elderly patients?

A: Dose adjustments based on creatinine clearance are required in elderly patients due to age-related decline in renal function.