Introduction
Clarithromycin is a semi-synthetic macrolide antibiotic derived from erythromycin. It is widely used in clinical practice for its broad-spectrum antibacterial activity against both Gram-positive and Gram-negative organisms, as well as atypical pathogens. As a key member of the macrolide class, clarithromycin has become an essential therapeutic agent for respiratory tract infections, skin and soft tissue infections, and Helicobacter pylori eradication regimens.
Mechanism of Action
Clarithromycin exerts its antibacterial effects by binding to the 50S ribosomal subunit of susceptible microorganisms, thereby inhibiting protein synthesis. This binding prevents translocation of aminoacyl tRNA and inhibits the formation of initiation complexes. The drug demonstrates concentration-dependent bactericidal activity against some organisms while exhibiting bacteriostatic effects against others. Its active metabolite, 14-hydroxyclarithromycin, contributes significantly to its antimicrobial activity, particularly enhancing its effectiveness against Haemophilus influenzae.
Indications
FDA-approved indications include:
- Acute bacterial exacerbation of chronic bronchitis
- Community-acquired pneumonia
- Pharyngitis/tonsillitis
- Acute maxillary sinusitis
- Uncomplicated skin and skin structure infections
- Helicobacter pylori eradication (in combination with other agents)
- Mycobacterium avium complex (MAC) prophylaxis and treatment in HIV patients
Off-label uses include:
- Pertussis prophylaxis and treatment
- Lyme disease
- Legionnaires' disease
- Bartonella infections
Dosage and Administration
Adults:- Respiratory tract infections: 250-500 mg every 12 hours for 7-14 days
- Skin and skin structure infections: 250 mg every 12 hours for 7-14 days
- H. pylori eradication: 500 mg twice daily with amoxicillin and proton pump inhibitor
- MAC prophylaxis: 500 mg twice daily
- 7.5 mg/kg every 12 hours (maximum 500 mg/dose)
- CrCl <30 mL/min: Reduce dose by 50% or extend dosing interval
- May be taken with or without food
- Tablets should be swallowed whole
- Extended-release tablets must not be crushed or chewed
Pharmacokinetics
Absorption: Rapidly absorbed with bioavailability of approximately 50%; food slightly delays absorption but does not affect overall bioavailability Distribution: Widely distributed throughout body tissues and fluids; volume of distribution ~4 L/kg; penetrates well into respiratory tissues and fluids Metabolism: Extensive hepatic metabolism via CYP3A4 to active 14-hydroxy metabolite Elimination: Primarily hepatic elimination with biliary excretion; elimination half-life 3-7 hours; 20% excreted unchanged in urine Protein binding: Approximately 70%Contraindications
- Known hypersensitivity to clarithromycin, other macrolides, or any component of the formulation
- Concomitant use with cisapride, pimozide, ergot alkaloids, or colchicine (in patients with renal or hepatic impairment)
- History of QT prolongation or ventricular arrhythmias
- Hypokalemia or hypomagnesemia
- Concomitant use with HMG-CoA reductase inhibitors extensively metabolized by CYP3A4
Warnings and Precautions
Black Box Warning: Clarithromycin may prolong the QT interval and increase risk of cardiovascular mortality in patients with coronary artery disease- May cause exacerbation of myasthenia gravis
- Risk of Clostridium difficile-associated diarrhea
- Potential for hepatic dysfunction including hepatitis and hepatic failure
- May cause hearing loss (usually reversible)
- Risk of superinfection including fungal and bacterial pathogens
- Use caution in patients with severe renal impairment (CrCl <30 mL/min)
- Monitor for drug interactions involving CYP3A4 and P-glycoprotein
Drug Interactions
Major interactions:- CYP3A4 inhibitors: Increased clarithromycin levels
- CYP3A4 substrates: Increased levels of co-administered drugs
- Warfarin: Enhanced anticoagulant effect (monitor INR)
- Digoxin: Increased digoxin levels
- Theophylline: Increased theophylline levels
- Colchicine: Increased risk of colchicine toxicity
- Statins (simvastatin, lovastatin, atorvastatin): Increased risk of rhabdomyolysis
- Protease inhibitors: Altered pharmacokinetics
- Oral hypoglycemics: Enhanced hypoglycemic effect
Adverse Effects
Common (≥1%):- Diarrhea (3%)
- Nausea (3%)
- Abnormal taste (3%)
- Dyspepsia (2%)
- Abdominal pain (2%)
- Headache (2%)
- QT prolongation and torsades de pointes
- Hepatotoxicity
- Stevens-Johnson syndrome
- Acute pancreatitis
- Hearing loss
- Pseudomembranous colitis
- Severe skin reactions
Monitoring Parameters
- Clinical response to therapy
- Signs of superinfection
- Liver function tests (baseline and during prolonged therapy)
- Renal function in patients with pre-existing impairment
- ECG monitoring in patients with cardiac risk factors
- INR in patients taking warfarin
- Serum drug levels of interacting medications
- Signs of ototoxicity in elderly patients or those receiving high doses
Patient Education
- Complete the full course of therapy even if feeling better
- Take exactly as prescribed; do not skip doses
- May be taken with food to minimize gastrointestinal upset
- Report any signs of allergic reaction (rash, itching, swelling)
- Report severe diarrhea, abdominal pain, or bloody stools
- Inform all healthcare providers about clarithromycin use
- Avoid grapefruit juice during therapy
- Use non-hormonal contraception as clarithromycin may reduce effectiveness of oral contraceptives
- Report any palpitations, dizziness, or fainting
- Be aware of potential taste disturbances
References
1. FDA Prescribing Information: Biaxin (clarithromycin). Revised 2022 2. Gilbert DN, et al. The Sanford Guide to Antimicrobial Therapy. 52nd edition 3. Lexicomp Online: Clarithromycin monograph. Wolters Kluwer Clinical Drug Information 4. Thorne Pharmaceuticals: Clarithromycin clinical pharmacology 5. American Thoracic Society Guidelines for Community-Acquired Pneumonia. Am J Respir Crit Care Med. 2019 6. Clinical and Laboratory Standards Institute (CLSI). Performance Standards for Antimicrobial Susceptibility Testing 7. Micromedex Solutions: Clarithromycin drug information 8. PubMed Central: Clarithromycin pharmacokinetic studies 9. Infectious Diseases Society of America (IDSA) Guidelines 10. Drug Interaction Facts: Facts & Comparisons
Note: This information is intended for educational purposes only and should not replace professional medical advice. Always consult with a healthcare provider for personalized medical guidance.