Cefpodoxime Proxetil + Clavulanic Acid

Cefpodoxime Proxetil + Clavulanic Acid is a broad-spectrum antibacterial combination indicated for the treatment of a wide range of bacterial infections caused by β-lactamase-producing organisms. Its indications include:

Respiratory Tract Infections:

• Acute bacterial sinusitis
• Acute exacerbation of chronic bronchitis
• Community-acquired pneumonia (mild to moderate)

Ear, Nose & Throat (ENT) Infections:

• Otitis media
• Pharyngitis and tonsillitis

Genitourinary Tract Infections:

• Uncomplicated urinary tract infections (including cystitis)

Skin & Soft Tissue Infections:

• Cellulitis
• Impetigo
• Wound infections

Gynecological Infections (off-label):

• Pelvic inflammatory disease (mild to moderate)

Gastrointestinal Infections (off-label):

• Bacterial gastroenteritis (when resistant pathogens are identified)

Route: Oral
Dosage forms available: Tablets (e.g., 200 mg Cefpodoxime + 125 mg Clavulanic Acid), Suspensions (e.g., 100 mg/5 mL Cefpodoxime + Clavulanate proportionally)

Adults:

• Mild to moderate infections: 200 mg Cefpodoxime + 125 mg Clavulanic Acid orally twice daily for 5–14 days depending on severity and site.
• Severe infections: Dose duration may be extended up to 14 days under supervision.

Pediatric Dosing (Suspension):

• 5 mg/kg/day of Cefpodoxime component divided into two doses. Adjust based on severity and age.
• Example: For a child weighing 15 kg, 3 mL of 100 mg/5 mL suspension every 12 hours.

Elderly:

• No dosage adjustment required unless renal function is impaired.

Renal Impairment:

• CrCl 30–50 mL/min: Administer every 12 hours.
• CrCl <30 mL/min: Administer once daily.
• Hemodialysis patients: Administer dose after dialysis session.

Hepatic Impairment:

• No dosage adjustment generally required; monitor liver function tests in prolonged therapy.

Administration Notes:

• Administer with food to enhance absorption.
• Shake suspension well before use.
• Complete the full course even if symptoms improve early.

Cefpodoxime is a third-generation cephalosporin that inhibits bacterial cell wall synthesis by binding to penicillin-binding proteins (PBPs), leading to cell lysis and death. Clavulanic acid, a β-lactamase inhibitor, irreversibly binds and inactivates β-lactamase enzymes produced by resistant bacteria, thereby protecting cefpodoxime from enzymatic degradation. This synergistic combination effectively restores cefpodoxime’s activity against β-lactamase-producing Gram-positive and Gram-negative bacteria.

Absorption:

• Cefpodoxime proxetil is a prodrug, hydrolyzed to active cefpodoxime during absorption.
• Bioavailability of cefpodoxime increases to ~50% when taken with food.
• Clavulanic acid is also well absorbed orally.

Distribution:

• Widely distributed to tissues and fluids including lungs, tonsils, urine, and skin.
• Protein binding: Cefpodoxime ~22–33%; Clavulanic acid ~25%.

Metabolism:

• Clavulanic acid is partially metabolized in the liver.
• Cefpodoxime undergoes minimal metabolism.

Elimination:

• Primarily eliminated via the kidneys (unchanged cefpodoxime).
• Half-life: Cefpodoxime ~2.2 hours; Clavulanic acid ~1 hour.
• Excretion: ~80% (cefpodoxime) and ~50% (clavulanic acid) via urine within 6 hours.

Pregnancy:

• FDA Category B
  Animal studies have not demonstrated fetal harm; however, no adequate human studies exist. Use only if clearly needed.

Lactation:

• Excreted in low concentrations in breast milk.
  Although generally considered safe, monitor the infant for signs of gastrointestinal disturbances (e.g., diarrhea, candidiasis).

Caution:

• Limited human data; use with caution in lactating mothers and avoid prolonged use.

• Primary Class: Third-Generation Cephalosporin (Antibiotic)
• Subclass: β-lactam/β-lactamase inhibitor combination

• Known hypersensitivity to cephalosporins, clavulanic acid, or any formulation components
• History of severe hypersensitivity (e.g., anaphylaxis) to penicillins or other β-lactam antibiotics
• Severe hepatic dysfunction with prior clavulanic acid exposure
• Patients with phenylketonuria (if using certain formulations containing aspartame)

• Hypersensitivity Reactions: Risk of cross-sensitivity with penicillins; monitor closely.
• Clostridioides difficile–Associated Diarrhea (CDAD): Can occur; consider in cases of persistent diarrhea.
• Hepatic Dysfunction: Monitor liver enzymes during prolonged therapy; discontinue if transaminase elevations persist.
• Renal Impairment: Adjust dose as necessary; monitor renal function.
• Superinfection: Prolonged use may lead to fungal or bacterial superinfection, including candidiasis.
• Seizures: High doses or renal impairment may increase seizure risk.

Common (≥1%):

• Gastrointestinal: Diarrhea, nausea, vomiting, abdominal pain
• Skin: Rash, pruritus
• Neurological: Headache, dizziness

Less Common:

• Hematologic: Eosinophilia, thrombocytopenia, leukopenia
• Hepatic: Elevated ALT, AST, bilirubin
• Renal: Mild transient increases in serum creatinine or BUN

Serious (Rare):

• Anaphylaxis
• Stevens-Johnson syndrome (SJS)
• Toxic epidermal necrolysis (TEN)
• Hepatotoxicity
• Seizures (especially in renal impairment)

• Probenecid: Reduces renal clearance of cefpodoxime; increases serum levels.
• Antacids (aluminum/magnesium) or H2-blockers: May reduce cefpodoxime absorption.
• Oral anticoagulants (e.g., warfarin): Enhanced anticoagulant effect possible.
• Live vaccines (e.g., typhoid): Antibiotic may reduce vaccine efficacy.
• CYP Interactions: Not primarily metabolized by CYP450; negligible enzyme involvement.

• WHO and IDSA emphasize judicious use of β-lactam + β-lactamase inhibitor combinations to prevent resistance development.
• EMA has reiterated safety during pregnancy and lactation as generally acceptable, but warns against indiscriminate use due to rising resistance.
• Recent Update: New formulations approved in pediatric suspensions with improved palatability and stability.

• Tablets: Store below 25°C, protect from moisture and light.
• Dry powder for suspension: Store in a tightly closed container below 25°C.
• After reconstitution: Refrigerate at 2°C to 8°C; use within 7–10 days.
• Do not freeze.
• Shake well before use.
• Keep out of reach of children.