Clarocin

Approved Indications:

• Respiratory Tract Infections:
• Acute bacterial exacerbation of chronic bronchitis (ABECB)
• Community-acquired pneumonia (mild to moderate)
• Pharyngitis or tonsillitis due to Streptococcus pyogenes
• Acute maxillary sinusitis
• Skin and Skin Structure Infections:
• Uncomplicated skin infections (e.g., folliculitis, cellulitis)
• Mycobacterial Infections:
• Disseminated Mycobacterium avium complex (MAC) disease in HIV patients (prevention and treatment)
• Helicobacter pylori Eradication:
• As part of triple or quadruple therapy for active duodenal ulcer disease
• Otitis Media:
• In children aged ≥6 months

Clinically Accepted Off-Label Uses:

• Rheumatic Fever Prophylaxis: In patients allergic to penicillin
• Legionnaires’ Disease: Alternative therapy
• Pertussis: Treatment and post-exposure prophylaxis
• Nontuberculous Mycobacterial Lung Disease: Chronic treatment (with ethambutol and rifamycins)
• Rosacea: Off-label topical/oral use for inflammatory lesions (limited cases)

Adults:

• Typical Infections (respiratory/skin):
  250–500 mg orally every 12 hours for 7–14 days.
• Acute maxillary sinusitis:
  500 mg orally every 12 hours for 14 days.
• Mycobacterial infections (MAC):
• Treatment: 500 mg orally twice daily (with ethambutol ± rifabutin).
• Prophylaxis: 500 mg orally once daily.
• H. pylori Eradication (triple therapy):
• Clarithromycin 500 mg twice daily
• Plus amoxicillin 1 g twice daily
• Plus a proton pump inhibitor (e.g., omeprazole 20 mg twice daily) for 14 days.

Pediatrics:

• General dosing:
  7.5 mg/kg orally every 12 hours (max 500 mg/dose) for 10 days.
• Otitis media/sinusitis:
  May require up to 15 mg/kg/day in divided doses.

Elderly:

• Same adult dosage; consider renal and hepatic function.

Renal Impairment:

• CrCl <30 mL/min: Reduce dose by 50%.
  If 500 mg twice daily is standard, reduce to 250 mg twice daily.

Hepatic Impairment:

• Mild to moderate impairment: No dose adjustment.
• Severe: Use with caution and monitor.

Route: Oral (tablet, suspension); IV formulation available for hospital use.

Administration Notes:

• With or without food (preferably with food to reduce GI upset).
• Extended-release tablets: Swallow whole; do not crush or chew.

Clarithromycin is a macrolide antibiotic that inhibits bacterial protein synthesis by binding to the 50S ribosomal subunit of susceptible bacteria. This action blocks translocation of aminoacyl tRNA, thereby inhibiting peptide chain elongation. The result is a bacteriostatic effect, though at higher concentrations or against highly susceptible organisms, it may exert bactericidal activity. Clarithromycin also has immunomodulatory effects, which may contribute to its benefit in respiratory diseases and mycobacterial infections.

• Absorption: Well absorbed orally; food delays peak levels but not overall absorption.
• Bioavailability: ~50% (increased with food).
• Peak Plasma Time: 2–3 hours after oral dose.
• Distribution: Widely distributed in tissues; high intracellular concentrations.
• Protein Binding: ~70%.
• Metabolism: Hepatic metabolism via CYP3A4 to the active metabolite 14-hydroxyclarithromycin.
• Half-life:
• Clarithromycin: 3–7 hours
• 14-hydroxyclarithromycin: 5–9 hours
• Elimination:
• ~20–40% excreted unchanged in urine
• Remainder excreted as metabolites in urine and feces

• Pregnancy:
  FDA Category C. Animal studies have shown fetal harm at high doses, but adequate and well-controlled studies in humans are lacking. Use only if benefits outweigh risks.
• Lactation:
  Clarithromycin is excreted in human milk. The effect on breastfed infants is unknown but may include diarrhea, rash, or fungal infections. Use with caution or consider alternative agents during breastfeeding.
• Recommendation:
  Avoid use in pregnancy unless clearly needed. Monitor breastfed infants for side effects if maternal therapy is necessary.

• Primary Class: Macrolide Antibiotic
• Subclass: 14-membered ring macrolide (second-generation macrolide)

• Known hypersensitivity to clarithromycin, erythromycin, or other macrolides
• Concomitant use with:
• Cisapride
• Pimozide
• Colchicine (in renal or hepatic impairment)
• Ergotamine or dihydroergotamine
• History of cholestatic jaundice/hepatic dysfunction associated with prior clarithromycin use
• Severe liver failure with concurrent renal impairment

• QT Prolongation: May cause arrhythmias, especially torsades de pointes; avoid in patients with prolonged QT, bradycardia, or electrolyte disturbances.
• Hepatotoxicity: Risk of severe hepatocellular or cholestatic hepatitis; monitor liver enzymes.
• Serious Allergic Reactions: Rare but possible (anaphylaxis, Stevens-Johnson Syndrome).
• Superinfection Risk: Prolonged use may result in fungal or bacterial superinfection, including Clostridioides difficile–associated diarrhea (CDAD).
• Use in Myasthenia Gravis: May exacerbate symptoms.
• Renal Impairment: Adjust dose to avoid toxicity.

Common:

• Gastrointestinal: Nausea, vomiting, diarrhea, abdominal pain, dyspepsia
• Taste: Metallic or bitter taste
• Nervous System: Headache, dizziness
• Skin: Rash

Less Common:

• Hepatic: Elevated liver enzymes, cholestatic jaundice
• Musculoskeletal: Arthralgia, myalgia

Serious/Rare:

• QT prolongation and arrhythmias
• Anaphylaxis
• Stevens-Johnson Syndrome, toxic epidermal necrolysis
• Pancreatitis
• Hearing loss (reversible)
• CDAD

Timing & Severity:

• GI effects typically occur within first few days
• Serious effects may be delayed and require immediate discontinuation

Major Drug-Drug Interactions (CYP3A4-related):

• Inhibits CYP3A4, increasing levels of:
• Statins (e.g., simvastatin, lovastatin): Risk of myopathy/rhabdomyolysis
• Calcium channel blockers: Hypotension, bradycardia
• Benzodiazepines (e.g., midazolam, triazolam): CNS depression
• Colchicine: Toxicity, especially in renal/hepatic impairment
• Warfarin: Enhanced anticoagulant effect (monitor INR)

Drug–Food Interaction:

• Food delays absorption but does not reduce overall bioavailability.

Drug–Alcohol Interaction:

• No direct interaction, but alcohol may worsen GI side effects.

Enzyme Systems:

• Strong CYP3A4 inhibitor
• Moderate CYP1A2 interactions possible

• Updated H. pylori Guidelines (ACG 2022): Clarithromycin resistance is rising; use only when regional resistance is low or susceptibility is confirmed.
• EMA Safety Updates: Reinforced warnings on QT prolongation and contraindications with interacting drugs (e.g., colchicine).
• MAC Management Guidelines: Clarithromycin remains cornerstone agent in combination regimens, though rifamycins and newer macrolides may be preferred in resistance cases.

• Tablets and Oral Suspension:
• Store at 20°C to 25°C (68°F to 77°F)
• Protect from moisture and light
• Do not freeze suspension
• Powder for Suspension:
• After reconstitution, store at room temperature (below 25°C)
• Use within 14 days; do not refrigerate
• IV Form (if used):
• Store dry vials at controlled room temperature
• Reconstituted solution must be used promptly or stored per manufacturer’s guidelines
• Handling Precautions:
• Shake suspension well before each use
• Keep out of reach of children
• Avoid exposure to excessive heat