No

Antibiotic, Macrolide

Dental: Alternate antibiotic in the treatment of common orofacial infections caused by aerobic gram-positive cocci and susceptible anaerobes; alternate antibiotic for the prevention of bacterial endocarditis in patients undergoing dental procedures

Medical: In adults, for treatment of pharyngitis/tonsillitis, acute maxillary sinusitis, acute exacerbation of chronic bronchitis, pneumonia, uncomplicated skin/skin structure infections due to susceptible S. pyogenes, S. pneumoniae, S. agalactiae, viridans Streptococcus, M. catarrhalis, C. trachomatis, Legionella sp, Mycoplasma pneumoniae, S. aureus, H. influenzae; has activity against M. avium and M. intracellulare infection and is indicated for treatment of and prevention of disseminated mycobacterial infections due to M. avium complex disease (eg, patients with advanced HIV infection); indicated for the treatment of duodenal ulcer disease due to H. pylori in regimens with other drugs including amoxicillin and lansoprazole or omeprazole, ranitidine, bismuth citrate, bismuth subsalicylate, tetracycline and/or an H₂-antagonist; also indicated for prophylaxis of bacterial endocarditis in patients who are allergic to penicillin and undergoing surgical or dental procedures

In children, for treatment of pharyngitis/tonsillitis, acute maxillary sinusitis, acute otitis media, uncomplicated skin/skin structure infections due to the above organisms; treatment of and prevention of disseminated mycobacterial infections due to M. avium complex disease (eg, patients with advanced HIV infection)

Exhibits the same spectrum of in vitro activity as erythromycin, but with significantly increased potency against those organisms

C

Hypersensitivity to clarithromycin, erythromycin, or any macrolide antibiotic; use with pimozide, astemizole, cisapride, terfenadine

In presence of severe renal impairment with or without coexisting hepatic impairment, decreased dosage or prolonged dosing interval may be appropriate; antibiotic-associated colitis has been reported with use of clarithromycin; elderly patients have experienced increased incidents of adverse effects due to known age-related decreases in renal function

1% to 10%:

Central nervous system: Headache

Gastrointestinal: Diarrhea, nausea, abnormal taste, heartburn, abdominal pain

<1% (limited to important or life-threatening symptoms): Ventricular tachycardia, QT prolongation, torsade de pointes, Clostridium difficile colitis, leukopenia, elevated prothrombin time, thrombocytopenia; elevated AST, alkaline phosphatase, and bilirubin; elevated BUN/serum creatinine, shortness of breath, leukopenia, neutropenia, manic behavior, tremor, hypoglycemia, anaphylaxis, Stevens-Johnson syndrome, toxic epidermal necrolysis, anxiety, hallucinations, anorexia, vomiting, tongue discoloration, glossitis, dizziness

Symptoms of overdose include nausea, vomiting, diarrhea, prostration, reversible pancreatitis, hearing loss with or without tinnitus or vertigo

Treatment includes symptomatic and supportive care

CYP3A3/4 enzyme substrate; CYP1A2 and 3A3/4 enzyme inhibitor

Clarithromycin increases serum theophylline levels by as much as 20%

Increased concentration of HMG CoA-reductase inhibitors (lovastatin and simvastatin)

Amprenavir's serum concentration may be increased.

Significantly increases carbamazepine levels and those of cyclosporine, digoxin, ergot alkaloid, tacrolimus, omeprazole and triazolam

Peak levels (but not AUC) of zidovudine are often increased; terfenadine and astemizole should be avoided with use of clarithromycin since plasma levels may be increased by >3 times; serious arrhythmias have occurred with cisapride and other drugs which inhibit cytochrome P-450 3A4 (eg, clarithromycin)

Fluconazole increases clarithromycin levels and AUC by ~25%; death has been reported with administration of pimozide and clarithromycin. Concurrent use is contraindicated.

Note: While other drug interactions (bromocriptine, disopyramide, lovastatin, phenytoin, and valproate) known to occur with erythromycin have not been reported in clinical trials with clarithromycin, concurrent use of these drugs should be monitored closely

Reconstituted oral suspension should not be refrigerated because it might gel; microencapsulated particles of clarithromycin in suspension is stable for 14 days when stored at room temperature

Exerts its antibacterial action by binding to 50S ribosomal subunit resulting in inhibition of protein synthesis. The 14-OH metabolite of clarithromycin is twice as active as the parent compound against certain organisms.

Absorption: Highly stable in the presence of gastric acid (unlike erythromycin)

Distribution: Widely distributes into most body tissues with the exception of the CNS

Metabolism: Partially converted to the microbiologically active metabolite, 14-OH clarithromycin

Bioavailability: 50%; food delays but does not affect extent of bioavailability; T_max: 2-4 hours

Half-life: 5-7 hours

Elimination: Primarily renal excretion; clearance approximates normal GFR

Safe use in children has not been established

Adults: Oral:

Usual dose: 250-500 mg every 12 hours or 1000 mg (2 x 500 mg extended release tablets) once daily for for 7-14 days

Upper respiratory tract: 250-500 mg every 12 hours for 10-14 days

Pharyngitis/tonsillitis: 250 mg every 12 hours for 10 days

Acute maxillary sinusitis: 500 mg every 12 hours or 1000 mg (2 x 500 mg extended release tablets) once daily for 14 days

Lower respiratory tract: 250-500 mg every 12 hours for 7-14 days

Acute exacerbation of chronic bronchitis due to:

M. catarrhalis and S. pneumoniae: 250 mg every 12 hours or 1000 mg (2 x 500 mg extended release tablets) once daily for 7-14 days

H. influenzae: 500 mg every 12 hours for 7-14 days

Pneumonia due to M. pneumoniae and S. pneumoniae: 250 mg every 12 hours for 7-14 days

Mycobacterial infection (prevention and treatment): 500 mg twice daily (use with other antimycobacterial drugs, eg, ethambutol, clofazimine, or rifampin)

Prophylaxis of bacterial endocarditis: 500 mg 1 hour prior to procedure

Uncomplicated skin and skin structure: 250 mg every 12 hours for 7-14 days

Helicobacter pylori: Combination regimen with bismuth subsalicylate, tetracycline, clarithromycin, and an H₂-receptor antagonist; or combination of omeprazole and clarithromycin; 250 mg twice daily to 500 mg 3 times/day

Dosing adjustment in renal impairment: Adults: Oral:

Cl_cr <30 mL/minute: 500 mg loading dose, then 250 mg once or twice daily

Dosing adjustment in severe renal impairment: Decreased doses or prolonged dosing intervals are recommended

May be taken with or without meals; may be taken with milk; food delays absorption; total absorption remains unchanged

Macrolides have been reported to cause nightmares, confusion, anxiety, and mood lability

Contraindicated with pimozide; increases carbamazepine and triazolam levels; monitor for signs of toxicity

No information available to require special precautions

No effects or complications reported

Take full course of therapy; do not discontinue without consulting prescriber. Maintain adequate hydration (2-3 L/day of fluids unless instructed to restrict fluid intake). You may experience nausea (small frequent meals, or sucking lozenges may help); abnormal taste (frequent mouth care or chewing gum may help); diarrhea, headache, or abdominal cramps (medication may be ordered). Report persistent fever or chills, easy bruising or bleeding, or joint pain. Report severe persistent diarrhea, skin rash, sores in mouth, foul-smelling urine, rapid heartbeat or palpitations, or difficulty breathing. Do not refrigerate oral suspension (more palatable at room temperature). Pregnancy/breast-feeding precautions: Inform prescriber if you are or intend to be pregnant. Consult prescriber if breast-feeding.

Administer every 12 hours rather than twice daily to avoid peak and trough variation

Monitor patients receiving clarithromycin and drugs known to interact with erythromycin (ie, theophylline, digoxin, anticoagulants, triazolam) since there are still very few studies examining drug-drug interactions with clarithromycin; liver function tests

Granules for oral suspension: 125 mg/5 mL (50 mL, 100 mL); 250 mg/5 mL (50 mL, 100 mL)

Tablet, film coated: 250 mg, 500 mg

Tablet, film-coated, extended release: 500 mg

"1997 USPHS/IDSA Guidelines for the Prevention of Opportunistic Infections in Persons Infected With Human Immunodeficiency Virus. USPHS/IDSA Prevention of Opportunistic Working Group," MMWR Morb Mortal Wkly Rep, 1997, 46(RR-12):1-46.

American Thoracic Society, "Guidelines for the Initial Management of Adults With Community-Acquired Pneumonia: Diagnosis, Assessment of Severity, and Initial Antimicrobial Therapy," Am Rev Respir Dis, 1993, 148(5):1418-26.

Amsden GW, "Erythromycin, Clarithromycin, and Azithromycin: Are the Differences Real?" Clin Ther, 1996, 18(1):56-72.

Aspin MM, Hoberman A, McCarty J, et al, "Comparative Study of the Safety and Efficacy of Clarithromycin and Amoxicillin-Clavulanate in the Treatment of Acute Otitis Media in Children," J Pediatr, 1994, 125(1):136-41.

Barradell LB, Plosker GL, and McTavish D, "Clarithromycin. A Review of Its Pharmacological Properties and Therapeutic Use in Mycobacterium avium-intracellulare Complex Infection in Patients With Acquired Immune Deficiency Syndrome," Drugs, 1993, 46(2):289-312.

Chu SY, Wilson DS, Guay DR, et al, "Clarithromycin Pharmacokinetics in Healthy Young and Elderly Volunteers," J Clin Pharmacol, 1992, 32(11):1045-9.

Dajani AS, Taubert KA, Wilson W, et al, "Prevention of Bacterial Endocarditis Recommendations by the American Heart Association," JAMA 1997, 277(22):1794-801.

Goldman MP and Longworth DL, "The Role of Azithromycin and Clarithromycin in Clinical Practice," Cleve Clin J Med, 1993, 60(5):359-64.

Guay DR, "Pharmacokinetics of New Macrolides," Infect Med, 1992, 9(Suppl A):9-13.

Guay DR and Craft JC, "Overview of the Pharmacology of Clarithromycin Suspension in Children and a Comparison With That in Adults," Pediatr Infect Dis J, 1993, 12(12 Suppl 3):S106-11.

Husson RN, Ross LA, Sandelli S, et al, "Orally Administered Clarithromycin for the Treatment of Systemic Mycobacterium avium Complex Infection in Children With Acquired Immunodeficiency Syndrome," J Pediatr, 1994, 124(5 Pt 1):807-14.

Langtry HD and Brogden RN, "Clarithromycin. A Review of Its Efficacy in the Treatment of Respiratory Tract Infections in Immunocompetent Patients," Drugs, 1997, 53(6):973-1004.

McConnell SA and Amsden GW, "Review and Comparison of Advanced-Generation Macrolides Clarithromycin and Dirithromycin," Pharmacotherapy, 1999, 19(4):404-15.

Neu HC, "The Development of Macrolides: Clarithromycin in Perspective," J Antimicrob Chemother, 1991, 27(Suppl A):1-9.

Nightingale SD, Koster FT, Mertz GJ, et al, "Clarithromycin-Induced Mania in Two Patients With AIDS," Clin Infect Dis, 1995, 20(6):1563-4.

Oteo JA, Gomez-Cadinanos RA, Rosel L, et al, "Clarithromycin-Induced Thrombocytopenic Purpura," Clin Infect Dis, 1994, 19(6):1170-1.

Peters DH and Clissold SP, "Clarithromycin: A Review of its Antimicrobial Activity, Pharmacokinetic Properties, and Therapeutic Potential," Drugs, 1992, 44(1):117-64.

"Pimozide (Orap) Contraindicated With Clarithromycin (Biaxin) and Other Macrolide Antibiotics," FDA Medical Bulletin, October 1996, 3.

Pollak PT, Sketris IS, MacKenzie SL, et al, "Delirium Probably Induced by Clarithromycin in a Patient Receiving Fluoxetine," Ann Pharmacother, 1995, 29(5):486-8.

Public Health Service Task Force on Prophylaxis and Therapy for Mycobacterium avium Complex, "Recommendations on Prophylaxis and Therapy for Disseminated Mycobacterium avium Complex Disease in Patients Infected With the Human Immunodeficiency Virus," N Engl J Med, 1993, 329(12):898-904.

Stafstrom CE, Nohria V, Loganbill H, et al, "Erythromycin-induced Carbamazepine Toxicity: A Continuing Problem," Arch Pediatr Adolesc Med, 1995, 149(1):99-101.

Tartaglione TA, "Therapeutic Options for the Management and Prevention of Mycobacterium avium Complex Infection in Patients With the Acquired Immunodeficiency Syndrome," Pharmacotherapy, 1996, 16(2):171-82.

Teare JP, Booth JC, Brown JL, et al, "Pseudomembranous Colitis Following Clarithromycin Therapy," Eur J Gastroenterol Hepatol, 1995, 7(3):275-7.

Wallace RJ Jr, Brown BA, and Griffith DE, "Drug Intolerance to High-Dose Clarithromycin Among Elderly Patients," Diagn Microbiol Infect Dis, 1993, 16(3):215-21.

Wynn RL, "New Erythromycins," Gen Dent, 1996, 44(4):304-7.

Zuckerman JM and Kaye KM, "The Newer Macrolides. Azithromycin and Clarithromycin," Infect Dis Clin North Am, 1995, 9(3):731-45.