Orobac

Approved Indications:

• Acute Bacterial Exacerbation of Chronic Bronchitis (ABECB): Caused by Haemophilus influenzae, Streptococcus pneumoniae (penicillin-susceptible strains), and Moraxella catarrhalis.
• Community-Acquired Pneumonia (Mild to Moderate): Caused by Streptococcus pneumoniae (penicillin-susceptible strains), Haemophilus influenzae (including β-lactamase–producing strains), and Haemophilus parainfluenzae.
• Pharyngitis/Tonsillitis: Caused by Streptococcus pyogenes.
• Uncomplicated Skin and Skin Structure Infections: Caused by Staphylococcus aureus (methicillin-susceptible strains) and Streptococcus pyogenes.

Clinically Accepted Off-label Uses:

• Sinusitis (when caused by susceptible organisms).
• Urinary tract infections (UTIs) in select cases, though not typically first-line.
• Otitis media in some resistant pediatric infections (clinical discretion advised).

Adults and Adolescents (≥12 years):

• Pharyngitis/Tonsillitis: 200 mg orally twice daily for 10 days
• ABECB: 200 mg orally twice daily for 10 days
• Community-Acquired Pneumonia: 400 mg orally twice daily for 14 days
• Skin/Skin Structure Infections: 400 mg orally twice daily for 10 days

Pediatric Use:

• Safety and efficacy not established in children <12 years.

Geriatric Patients:

• No dose adjustment necessary unless renal function is impaired.

Renal Impairment:

• CrCl ≥50 mL/min: No adjustment
• CrCl 30–49 mL/min: 200 mg twice daily
• CrCl <30 mL/min: Not recommended due to increased drug exposure

Hepatic Impairment:

• No dose adjustment needed in mild-to-moderate hepatic impairment.

Administration Guidelines:

• Should be taken with meals to enhance absorption.
• Tablets must not be split or crushed.

Cefditoren is a third-generation oral cephalosporin antibiotic that exerts bactericidal activity by inhibiting bacterial cell wall synthesis. It binds to penicillin-binding proteins (PBPs), which are essential enzymes involved in the final stages of peptidoglycan synthesis within the bacterial cell wall. Inhibition of PBPs weakens the structural integrity of the cell wall, leading to cell lysis and death. Cefditoren is active against a wide range of Gram-positive and Gram-negative bacteria, including strains that produce β-lactamase.

• Absorption: Oral bioavailability is approximately 14–16% when taken with food. High-fat meals significantly enhance absorption.
• Distribution: Volume of distribution ~9.3–9.5 L; ~88% protein-bound, primarily to albumin.
• Metabolism: Minimal hepatic metabolism. The prodrug form (cefditoren pivoxil) is hydrolyzed to the active form, cefditoren, by esterases in the intestinal wall.
• Elimination: Primarily excreted unchanged via the urine (~70% within 24 hours).
• Half-life: Approximately 1.5 hours
• Peak Plasma Time: 1.5–3 hours post-dose (with food)

• Pregnancy: Cefditoren is categorized as Pregnancy Category B. Animal studies have shown no fetal harm, but adequate human studies are lacking. Use only if clearly needed.
• Lactation: It is unknown whether cefditoren is excreted in human breast milk. However, due to potential adverse reactions in nursing infants (e.g., gastrointestinal flora alteration), caution is advised. Monitor infant for diarrhea or candidiasis.

• Primary Class: Third-generation cephalosporin antibiotic
• Subclass: Oral β-lactam antibacterial
• Prodrug: Cefditoren pivoxil (converted to active cefditoren in vivo)

• Known hypersensitivity to cefditoren, cephalosporins, penicillins, or any formulation excipients
• Carnitine Deficiency or Inborn Errors of Metabolism affecting carnitine synthesis/utilization
• Severe renal impairment (CrCl <30 mL/min)
• History of anaphylaxis to β-lactam antibiotics

• Serious Hypersensitivity Reactions: Including anaphylaxis and Stevens-Johnson syndrome.
• Clostridioides difficile–Associated Diarrhea (CDAD): Monitor for severe or prolonged diarrhea.
• Seizure Risk: Especially in patients with renal impairment or those receiving high doses.
• Superinfection Risk: Long-term use may promote overgrowth of non-susceptible organisms including fungi.
• Carnitine Depletion: Cefditoren pivoxil contains a pivaloyl group which can reduce serum carnitine levels with long-term use.
• Use in Children: Not recommended below 12 years of age due to lack of safety data.

Common Adverse Effects:

• Gastrointestinal: Diarrhea, nausea, abdominal pain, dyspepsia
• Nervous System: Headache, dizziness
• Skin: Rash, pruritus

Serious/Rare Adverse Effects:

• Hematologic: Thrombocytopenia, leukopenia
• Hepatic: Elevated liver enzymes (ALT, AST)
• Renal: Interstitial nephritis (rare)
• Allergic: Anaphylaxis, Stevens-Johnson syndrome
• Gastrointestinal: CDAD, pseudomembranous colitis

• Probenecid: Inhibits renal excretion of cefditoren, increasing plasma concentrations.
• Antacids/H2-receptor blockers/PPIs: May reduce cefditoren absorption; avoid co-administration.
• Iron Supplements: Decrease oral bioavailability of cefditoren; administer at different times.
• CYP450: Cefditoren is not metabolized by or an inducer/inhibitor of CYP enzymes; minimal drug interactions via this route.

• EMA & FDA Advisory: Confirmed continued efficacy in treating ABECB and pharyngitis, but recommend antibiotic stewardship to limit resistance.
• Guideline Shifts: Increasing preference for narrow-spectrum agents where possible; cefditoren use should be guided by susceptibility testing.
• No new black box warnings or contraindications have been issued as of 2024–2025.

• Temperature: Store at 20°C to 25°C (68°F to 77°F); excursions permitted between 15°C and 30°C.
• Humidity: Store in a dry place; avoid exposure to high humidity.
• Light: Protect from excessive light exposure.
• Handling: Keep tablets in original packaging until use. Do not split or crush tablets.
• Reconstitution: Not applicable—solid oral formulation only.