Clarithromycin tablets for treatment of bacterial infections and H. pylori eradication

Clarithromycin tablets are oral antibiotics belonging to the macrolide class. They are approved for treating mild to moderate bacterial infections caused by susceptible bacteria. In adults, they are also used in combination therapy to eradicate Helicobacter pylori infection associated with duodenal ulcer disease. Clarithromycin tablets come in 250 mg and 500 mg strengths.

Clarithromycin tablets are indicated for the treatment of mild to moderate infections caused by certain susceptible bacteria in both adults and pediatric patients. Approved infections include:

• Acute bacterial exacerbation of chronic bronchitis in adults
• Acute maxillary sinusitis in adults
• Community-acquired pneumonia in adults and pediatric patients
• Pharyngitis and tonsillitis as an alternative for individuals who cannot use first-line therapy
• Uncomplicated skin and skin structure infections
• Acute otitis media in pediatric patients
• Treatment and prophylaxis of disseminated Mycobacterium avium complex infections in patients with advanced HIV infection

Additionally, clarithromycin is used in adults as part of combination regimens with amoxicillin and a proton pump inhibitor (lansoprazole or omeprazole) to eradicate Helicobacter pylori infection and reduce the risk of duodenal ulcer recurrence.

Important limitation: Clarithromycin should only be used to treat infections proven or strongly suspected to be caused by susceptible bacteria, to reduce the development of resistant bacteria.

Clarithromycin

Clarithromycin is a macrolide antibiotic that works by inhibiting bacterial protein synthesis. It binds to the 50S ribosomal subunit of susceptible bacteria, preventing the growth and replication of the bacteria that cause infections.

Adults

For mild to moderate infections, clarithromycin tablets are taken orally every 12 hours for 7 to 14 days, depending on the infection. Typical doses are:

• 250 to 500 mg every 12 hours for acute bacterial exacerbation of chronic bronchitis (7 to 14 days)
• 500 mg every 12 hours for acute maxillary sinusitis (14 days)
• 250 mg every 12 hours for community-acquired pneumonia (7 to 14 days)
• 250 mg every 12 hours for pharyngitis/tonsillitis (10 days)
• 250 mg every 12 hours for uncomplicated skin and skin structure infections (7 to 14 days)
• 500 mg every 12 hours for treatment and prophylaxis of disseminated Mycobacterium avium complex infections (duration based on clinical response)

H. pylori eradication in adults

• Triple therapy with clarithromycin 500 mg, amoxicillin 1 gram, and lansoprazole 30 mg every 12 hours for 10 or 14 days
• Triple therapy with clarithromycin 500 mg, amoxicillin 1 gram, and omeprazole 20 mg every 12 hours for 10 days, followed by an additional 18 days of omeprazole 20 mg once daily if an ulcer is present
• Dual therapy with clarithromycin 500 mg every 8 hours and omeprazole 40 mg once daily for 14 days, followed by 14 days of omeprazole 20 mg once daily for ulcer healing

Pediatric patients

• 15 mg/kg/day divided every 12 hours for 10 days for mild to moderate infections (up to adult dose)
• Mycobacterial infections: 7.5 mg/kg every 12 hours up to 500 mg every 12 hours

Dosage adjustments

• Reduce dose by 50% in patients with severe renal impairment (creatinine clearance less than 30 mL/min)
• Reduce dose by 50% in moderate renal impairment (30 to 60 mL/min) when coadministered with atazanavir or ritonavir-containing regimens
• Reduce dose by 75% in severe renal impairment with atazanavir or ritonavir-containing regimens

Clarithromycin tablets may be taken with or without food.

• Known hypersensitivity to clarithromycin, erythromycin, or other macrolide antibacterial drugs
• Concomitant use with cisapride or pimozide
• History of cholestatic jaundice or hepatic dysfunction with prior clarithromycin use
• Co-administration with colchicine in patients with renal or hepatic impairment
• Co-administration with lomitapide
• Co-administration with lovastatin or simvastatin
• Co-administration with ergotamine or dihydroergotamine
• Co-administration with lurasidone

Severe allergic reactions

Discontinue clarithromycin if signs of severe hypersensitivity, such as anaphylaxis, Stevens-Johnson syndrome, or toxic epidermal necrolysis occur.

QT interval prolongation and arrhythmias

Avoid use in patients with known QT prolongation, those taking drugs that prolong the QT interval, uncorrected electrolyte abnormalities, significant bradycardia, or receiving class IA or III antiarrhythmics. Fatal cases of ventricular arrhythmias including torsades de pointes have been reported.

Hepatotoxicity

Reports of reversible but sometimes severe liver dysfunction including hepatitis and jaundice have occurred. Monitor liver function and discontinue if hepatic injury develops.

Drug interactions and related serious adverse reactions

Clarithromycin can interact with colchicine, certain lipid-lowering agents, calcium channel blockers, and other drugs, potentially causing serious adverse effects. Dose adjustments or avoidance may be needed.

Mortality risk in coronary artery disease

In patients with coronary artery disease, there may be an increased risk of all-cause mortality one year or more after treatment. Balance risks and benefits.

Clostridium difficile-associated diarrhea

Evaluate patients who develop diarrhea during or after treatment for possible C. difficile infection.

Embryo-fetal toxicity

Based on animal data, clarithromycin is generally not recommended during pregnancy unless no alternative is appropriate.

Myasthenia gravis

Exacerbation of symptoms has been reported. Use with caution in affected patients.

Common side effects include gastrointestinal disturbances such as nausea, vomiting, diarrhea, and abdominal pain. Serious but rare reactions include severe hypersensitivity (e.g., Stevens-Johnson syndrome), liver dysfunction, QT prolongation with arrhythmias, and Clostridium difficile-associated diarrhea.

• Cisapride and pimozide: Contraindicated due to risk of fatal cardiac arrhythmias from CYP3A4 metabolism inhibition.
• Colchicine: Contraindicated in patients with renal or hepatic impairment.
• HMG-CoA reductase inhibitors (lovastatin, simvastatin): Contraindicated due to increased risk of myopathy, including rhabdomyolysis.
• Lomitapide: Contraindicated due to potential for markedly increased liver enzymes.
• Ergot alkaloids (ergotamine, dihydroergotamine): Contraindicated due to serious reactions.
• Lurasidone: Contraindicated due to increased exposure and risk of serious adverse reactions.
• Atazanavir and ritonavir-containing regimens: Require clarithromycin dose reduction; clarithromycin also affects metabolism of these drugs.

Pregnancy

Clarithromycin is not recommended during pregnancy unless no appropriate alternative therapy is available, based on animal toxicity data.

Lactation