Drugs>Antimicrobial Agents>

INDICATIONS

• Pharyngitis and tonsillitis
• Acute maxillary sinusitis
• Acute bacterial exacerbation of chronic bronchitis
• Community acquired pneumonia 
• Acute otitis media
• Uncomplicated skin and skin structure infections
• Treatment of disseminated mycobacterial infections due to Mycobacterium avium complex
• Prophylaxis of Mycobacterium avium complex
• Treatment of active duodenal ulcer associated with H. pylori infection (in combination with omeprazole or ranitidine bismuth citrate)

• Bartonella infection 

FORMS

*Prices represent cost per unit specified and are representative of "Average Wholesale Price" (AWP). AWP Prices were obtained and gathered by Lakshmi Vasist Pharm D using the Red Book, manufacturer's information, and the McKesson database.

^Dosage is indicated in mg unless otherwise noted.

USUAL ADULT DOSING

• MAC prophylaxis: 500 mg PO bid (azithromycin 1200 mg q wk preferred)
• MAC treatment: 500 mg PO bid or 1000 mg XL qd (in combination with ethambutol) x 1 yr and treat until immune reconstitution (CD4 >100 x 6 mos)
• Infections due to H influenzae and H. parainfluenzae: 500 mg bid x 7-14d.
• Community acquired pneumonia, pharyngitis, tonsillitis, otitis media, and uncomplicated soft tissue infections: 250-500 mg bid or 1000 mg XL qd x 7d.
• Peptic ulcer disease due to H. pylori: 500 mg in combination with PPI and amoxicillin bid x 10-14 d.
• Acute bacterial sinusitis: 500 mg bid or 1000 mg XL qd w/ food x 7-14d
• Acute exacerbation of chronic bronchitis: 500 mg bid or 1000 mg XLqd w/ food x 7d

RENAL DOSING

ADVERSE DRUG REACTIONS

• GI intolerance (diarrhea, nausea, vomiting)
• Metalic taste
• Transaminases elevation

• Headache
• Reversible hearing loss and tinnitus
• C. difficile colitis
• Rash

DRUG INTERACTIONS

• APV or FPV: APV AUC increased by 18% (studied with APV). Clarithromycin not affected by unboosted APV. No dose adjustment needed. See RTV for dose adjustment with FPV/r.
• ATV: ATV AUC increased by 28%. Clarithromycin AUC increased by 94%. QTc prolongation observed with co-administration. 50% of clarithromycin dose recommended when co-administered with ATV. Use azithromycin. Further dose adjustment needed with moderate to severe renal insufficiency and ESRD, no specific dosing guidelines consider:Cr clearance 30-60ml/min: 250 mg qd. Cr clearance <30ml/min: 250 mg every other day.
• DLV: Clarithromycin AUC increased by 100%. DLV AUC increased by 44%. Dose adjustment recommended with impaired renal function. Clarithromycin dose: Cr clearance 30-60ml/min=500 mg qd. Cr clearance <30ml/min=250 mg qd.  
• EFV: clarithromycin AUC decreased by 39%. Clinical significance unknown. High incidence of rash seen in healthy volunteer receiving this combination. Consider azithromycin.
• NVP: clarithromycin AUC decreased by 29% but 14-hydroxy clarithromycin (active metabolite) AUC increased by 27%. NVP AUC increased by 26%. No dose adjustment needed.
• RTV: clarithromycin AUC increased by 77%, Cmin increased by 182%. Reduce clarithromycin dose by 50% in end stage renal disease. Consider using azithromycin.
• SQV: clarithromycin increases SQV AUC by 177% and SQV increases clarithromycin AUC by 45%.  See RTV for dose adjustment with SQV/r.
• LPV/r: may increase clarithromycin serum level. Decrease dose of clarithromycin by 50% in ESRD.
• Theophylline: may increase theophylline serum levels. Monitor serum level with dose adjustment.
• Pimozide, cisapride, astemizole and terfenadine: contraindicated
• Ergot Alkaloid: avoid co-administration
• Warfarin: may increase anticoagulant effect of warfarin. Monitor INR closely.
• Cyclosporine: may increase cyclosporine serum levels. Monitor closely.
• Benzodiazepines (alprazolam, diazepam, midazolam, triazolam): may increase benzodiazepines serum concentrations. Use alternative benzodiazepines (i.e lorazepam, oxazepam, temazepam).
• Carbamazepine: carbamazepine serum levels increased by 60%. Avoid or use with close monitoring of carbamazepine levels with appropriate dose adjustment.
• Rifampin: contraindicated
• Rifabutin: clarithromycin AUC decreased by 44% and 14-hydroxy-clarithromycin increased by 57%. 14-hydroxy metabolite has less activity against MAC. Rifabutin AUC increased by 56%. Consider using azithromycin.
• Digoxin: case reports of digoxin toxicity. Monitor closely with co-administration.
• Amiodarone: may increase amiodarone serum levels. Monitor closely with proper dose adjustment.
• TPV/r: clarithromycin increases TPV AUC by 66% and TPV/r increases clarithromycin AUC by 19%. Adjust clarithromycin dose according to renal function: CrCl >60 ml/min=500 mg bid; CrCl 30-60 ml/min=500 mg po qd; CrCl <30 ml.min=250 mg po qd. Consider azithromycin.
• DRV/r: clarithromycin did not affect DRV AUC, but DRV increases clarithromycin AUC by 57%. Adjust clarithromycin dose according to renal function: CrCl >60 ml/min=500 mg bid; CrCl 30-60 ml/min=500 mg po qd; CrCl <30 ml.min=250 mg po qd. Consider azithromycin.
• Lovastatin and simvastatin: may significantly increase lovastatin and simvastatin serum concentrations. Consider pravastatin with co-administration.
• Fentanyl: may significantly increase fentanyl serum concentrations. Avoid co-administration. Consider morphine.
• Tacrolimus, sirolimus, cyclosporine: may significantly increase immunosuppressants serum concentrations. Monitor closely with dose adjustments.

SPECTRUM

Detailed Spectrum of Activity

RESISTANCE

• S. pneumoniae macrolide resistance ~26% but clinical significance unclear; treatment failures reported.
• Use of clarithromycin monotherapy for MAC infection in HIV associated with high rates of resistance. Combination therapy (usually with ethambutol) recommended. Drug sensitivity testing may help guide therapy but clinical significance is unclear.

PHARMACOLOGY

Pharmacology

COMMENTS

REFERENCES

REFERENCED WITHIN THIS GUIDE

• Cryptosporidiosis
• Ethambutol
• Sinusitis