Pefloxacin Mesylate Dihydrate

Approved Indications:

• Urinary Tract Infections (UTIs): Including uncomplicated and complicated infections.
• Lower Respiratory Tract Infections: Including chronic bronchitis and pneumonia caused by susceptible bacteria.
• Gastrointestinal Infections: Including typhoid fever, enteritis, and bacterial diarrhea.
• Sexually Transmitted Infections (STIs): Including gonorrhea and prostatitis.
• Gynecological Infections: Such as pelvic inflammatory disease.
• Skin and Soft Tissue Infections: Including infected wounds, cellulitis, and abscesses.
• Bone and Joint Infections: Such as osteomyelitis and septic arthritis.
• Bacteremia and Septicemia: Caused by gram-negative or gram-positive pathogens.
• Prophylaxis in Surgery: Especially for urological and gastrointestinal procedures.
• Typhoid Carriers: For eradication in chronic carriers of Salmonella typhi.

Clinically Accepted Off-Label Uses:

• Multidrug-resistant gram-negative infections: In select clinical scenarios, especially where other fluoroquinolones are not effective.
• Hospital-acquired infections (HAIs): Including ventilator-associated pneumonia or catheter-related infections caused by sensitive organisms.

Route of Administration: Oral and Intravenous (IV)

Dosage Forms:

• Tablets: 400 mg
• IV Infusion: 400 mg/100 ml

Adults:

• Standard Dose (Oral or IV):
  400 mg twice daily (every 12 hours)
• Typhoid Fever or Bone Infections:
  400 mg every 12 hours for 14 days
• Chronic Carriers of Typhoid:
  400 mg twice daily for 28 days
• Severe Infections (IV Route):
  Initial IV therapy may be started at 400 mg every 12 hours, then switched to oral when appropriate.

Elderly:

• Use with caution due to increased risk of CNS effects and tendinopathy.
• Renal function should be assessed; dose adjustment may be required in severe renal impairment.

Pediatric Use:

• Not recommended in children under 15 years due to potential joint toxicity.

Renal Impairment:

• Creatinine clearance <20 mL/min: Reduce dose to 400 mg once daily

Hepatic Impairment:

• Use cautiously in severe hepatic impairment as pefloxacin is primarily metabolized in the liver.

Administration Notes:

• Oral: Take with water, preferably on an empty stomach.
• IV: Infuse over 60 minutes; do not administer as bolus.
• Maintain adequate hydration to prevent crystalluria.

Pefloxacin is a synthetic broad-spectrum fluoroquinolone antibiotic. It acts by inhibiting bacterial DNA gyrase (topoisomerase II) and topoisomerase IV, enzymes essential for bacterial DNA replication, transcription, repair, and recombination. Inhibition of these enzymes leads to disruption of bacterial cell division and ultimately bacterial cell death. It is bactericidal and exhibits concentration-dependent killing against both gram-negative and some gram-positive bacteria.

• Absorption: Rapidly absorbed after oral administration with ~80–100% bioavailability.
• Peak Plasma Time: 1.5 to 2 hours after oral administration.
• Distribution: Wide distribution in tissues and body fluids, including bone, lung, and prostate. Crosses the blood-brain barrier and placenta.
• Protein Binding: ~25–30%
• Metabolism: Extensively metabolized in the liver; main active metabolite is norfloxacin (less active).
• Half-life: Approximately 8–12 hours
• Excretion: Primarily via renal and fecal routes. Approximately 60% is excreted unchanged in urine.

• Pregnancy:
  Not recommended during pregnancy due to risk of cartilage damage observed in animal studies. Should only be used if no safer alternative is available and the potential benefit outweighs the risk.
• Lactation:
  Pefloxacin is excreted in breast milk. Due to the risk of joint toxicity in infants, breastfeeding should be avoided during treatment.

• Primary Class: Antibacterial agent
• Subclass: Fluoroquinolone antibiotic
• Generation: Second-generation fluoroquinolone

• Known hypersensitivity to pefloxacin, other quinolones, or formulation excipients
• History of tendinitis or tendon rupture associated with fluoroquinolone use
• Epilepsy or seizure disorders
• Children and adolescents under 15 years of age
• Pregnancy and breastfeeding
• Severe hepatic impairment (without dose monitoring or adjustment)

• Tendinopathy and Tendon Rupture: Risk increased in elderly and corticosteroid users; discontinue at first sign of tendon pain or inflammation.
• CNS Effects: May cause seizures, confusion, tremor, hallucinations; avoid in patients with CNS disorders.
• Photosensitivity: Advise sun protection; avoid direct sunlight and tanning beds.
• QT Prolongation: Caution in patients with known QT abnormalities or on QT-prolonging drugs.
• Peripheral Neuropathy: Discontinue if symptoms such as pain, burning, tingling, or numbness occur.
• Hepatotoxicity: Monitor liver enzymes periodically during prolonged use.
• Superinfection: Risk of fungal or resistant bacterial overgrowth with prolonged use.

Common Side Effects:

• Gastrointestinal: Nausea, vomiting, diarrhea, abdominal pain
• Central Nervous System: Headache, dizziness, insomnia, agitation
• Dermatologic: Rash, pruritus, photosensitivity reactions
• Musculoskeletal: Arthralgia, tendon pain

Serious Side Effects:

• Tendon rupture (Achilles tendon most commonly affected)
• Seizures
• Hepatitis and liver enzyme elevation
• QT interval prolongation and arrhythmias
• Anaphylaxis or severe hypersensitivity reactions
• Peripheral neuropathy
• Clostridioides difficile–associated diarrhea

Onset & Dose-dependence:
CNS and tendon effects may appear within days of starting therapy and may be dose-related.

• Antacids and Sucralfate: Reduce absorption; administer pefloxacin 2–4 hours before or after.
• Theophylline: Increased serum levels and risk of toxicity due to CYP1A2 inhibition.
• NSAIDs: Increased risk of seizures when combined with fluoroquinolones.
• Oral Anticoagulants (e.g., warfarin): Potentiated anticoagulant effect; monitor INR.
• CYP450 Interactions: Inhibits CYP1A2—may increase levels of drugs metabolized by this enzyme.
• Alcohol: May increase CNS side effects such as dizziness and confusion; avoid during therapy.

• Fluoroquinolone Class Warning (Regulatory Agencies): Reinforced safety warnings regarding risk of tendon rupture, peripheral neuropathy, and CNS effects; caution advised especially in elderly and those on corticosteroids.
• EMA and WHO Alerts: Recommend restricted use of fluoroquinolones for non-serious infections to prevent resistance and severe adverse effects.
• Use in Children: Strongly discouraged unless no alternative is available and benefits outweigh risks.

• Tablets:
  Store below 25°C in a dry place, protected from light and moisture.
  Keep in original packaging.
• IV Infusion:
  Store at 2°C to 8°C (refrigerated).
  Do not freeze. Protect from light.
  Once opened, use immediately or discard if discolored or cloudy.
• Handling:
  Do not crush tablets. Shake IV container before use. Use aseptic technique for IV preparation.