CLARITHROMYCIN

• INTRODUCTION
• ANTOMICROBIAL ACTIVITY
• CLINICAL PHARMACOKINETICS
• CLINICAL EFFICACY
• OTHER INFECTIONS
• TOLERABILITY PROFILE
• ADVERSE EFFECTS & DRUG INTERACTIONS
• PHARMACOECONOMIC CONSIDERATIONS
• CHOOSING MACROLIDES
• CONCLUDING SUMMARY
• BRIGHTER SIDE OF CLARITHROMYCIN
• DARKER SIDE OF CLARITHROMYCIN
• CURRENT TRENDS IN MACROLIDE USE

CLINICAL EFFICACY:

Adult dose of Clarithromycin 0.25 to 0.5 g b.d for 10 -14 days.
Children 7.5mg/kg b.d I.V 500mg b.d diluted to 2mg/ml concentration in 250ml of dextrose or normal saline.

CONCURRENT ADMINISTATION OF TERFINADINE OR ASTEMIZOLE OR CISAPRIDE IS CONTRAINDICATED .

In Streptococcal pharyngitis:

 In patients allergic to betalactams or intolerant to erythromycin , clarithromycin is the better choice since it has better activity that erythromycin (greater tolerability and less GIT manifestations) but is expensive.

Sinusitis:

Most often the pathogens involved are S.pneumoniae, H.influenzae, and anaerobes and less often staphylo , S.pyogenes, M.catarrhalis. There is no clear advantage of newer macrolides over amoxycillin except in H.influenzae. Azithromycin has also been studied and found to be equiv. effective with clarithromycin and amoxycillins.

Acute otitis media:

Organisms implicated are S.pneumoniae, H.influenzae, and M.catarrhalis. More recent trials suggest even shorter course of clarithromycin (5 days), Azithromycin (3days) are effective for acute otitis media. Alper et al showed that clarithromycin was more effective than amoxycillin in eradicating high-level penicillin resistant pneumococcci. Both clarithromycin and Azithromycin are suitable for acute otitis media.

Chest infections:

Acute bronchitis is an inflammatory condition of tracheobronchial tree that is usually viral in origin; Rhinovirus, influenza, adenovirus, M.pneumoniae, C.pneumoniae, and M.catarrhalis may be seen in acute bronchitis. Role of secondary bacterial invasion by S.pneumoniae and H.influenzae is unclear. Therefore there is no clear benefit in treating acute bronchitis with antibiotics in patients who are otherwise healthy. Patients with underlying chronic disease, however, might benefit from antibiotics with improvement of symptoms. If antibiotics are used, a macrolide or a betalactam should be used. Erythromycin, Azithromycin and clarithromycin are all reasonable choices.

In chronic bronchitis, a clinical syndrome characterized by cough and sputum production , the symptoms are most often directed to chronic bronchial irritation with inflammatory changes in the airways. For treatment of Acute Exacerbation of Chronic Bronchitis (AECB), Short-term antibiotic therapy is useful in patients with increased sputum production with purulence. Both clarithromycin and Azithromycin are reasonable choices alternative to cephalosporins.

Community Acquired Pneumonia:

Treatment is empirical and newer macrolides are active against many major pathogens of Community Acquired Pneumoniae including S.pneumoniae, H.influenzae, M.pneumoniae, L.pneumophiliae, and C.pneumoniae. Clarithromycin is an ideal choice in case of pneumoccal pneumonia, H.influenzae and Legionellae pneumonia. Hammedani et al determined that clarithromycin was very effective in the treatment legionellair’s disease.

Results of comparator trials have shown similar efficacy for clarithromycin and other antibacterial agents in treatment of community acquired pneumonia, Acute bronchitis, ACEB, sinusitis, pharyngitis and otitis media. Comparators include betalactams, with combination of clauvulanic acid, Penicillin V, Cefaclor, Cefuroxime axetil, Cefpodoxime, Ceftibuten, Cefixime, Erythromycin, Azithromycin, Dirithromycin, Roxithromycin, and Josamycin. The study revealed hat CLARITHROMYCIN produced better clinical success and bacterial eradication.

Skin & soft tissue infection:

For most of the skin infections where erythromycin is indicated clarithromycin not only substitutes but produced better clinical eradication rates.

In opportunistic infections associated with AIDS:

Recently clarithromycin has been considered to be an important agent prophylactically (single agent) in the treatment of preventive strategies of disseminated MAC in AIDS. Macrolides are especially attractive treatment options for MAC bacteremia in disseminated advances AIDS and thanks to the Excellent Tolerability (Clarithromycin in particular), ease of administration and lack of recognizable interactions by clarithromycin with anti HIV agents like protease inhibitors.

Clarithromycin is one of the single agent in the long term prophylaxis against opportunistic MAC infection in AIDS patients. Chemoprophylaxis is one of the most effective preventive strategic agent in disseminated MAC disease and this strategy improves quality of life (QOL) and reduce the risk of death associated with this disease in AIDS patients. Antimicrobial spectrum of macrolides encompasses atypical mycobacteriae together with gram-positive bacteriae and even some protozoae while it has been shown that clarithromycin confers survival benefits compared with placebo. Prolonged per oral clarithromycin as a single agent (others Azithromycin & Rifabutin) in Chemoprophylaxis for disseminated MAC infection in AIDS. In contrast to Rifabutin , macrolides are associated with bacterial resistance and offer no protection against tuberculosis. Although Rifabutin, Azithromycin, and clarithromycin have similar effects as prophylactic agents in disseminated MAC infection in AIDS, Clarithromycin produced significant survival benefits. Clinically clarithromycin interacts with Rifabutin because of their hepatic enzyme effects. Clarithromycin demonstrated significant survival benefit over azithromycin and rifabutin. With clarithromycin, rifabutin there is increased incidences of uveitis (PCK Interaction)

Efficacy Data:

Either clarithromycin or azithromycin can be used in preference to rifabutin and macrolides are less likely to interact with anti HIV protease inhibitors whereas emergence of resistance is lower with rifabutin and rifabutin prevents tuberculosis while macrolides cannot. Mycobacterium Chelonae is noted for antimicrobial resistance, with limited and potential toxic therapeutic options. clarithromycin is much more active than erythromycin or azithromycin against M.chelonae and has been used successfully as monotherapy for the treatment of disseminated cutaneous disease.

Mycobacterium leprea - Clarithromycin alone or in combination with minocycline is highly beneficial in M.leprae.

NEITHER CLARITHROMYCIN NOR AZITHROMYCIN HAS ANY EFFECT ON M. TUBERCULOSIS

OTHER INFECTIONS:

Urogenital infections with C.trachomatis both azithromycin and clarithromycin are very effective. Azithromycin is preferable and is given as a single dose of 1 H which is curative.

H.pylori infections, Clarithromycin is preferred over azithromycin since the latter may manifest high level of post therapy resistance. Clarithromycin acts slowly and exhibit synergy with omeprazole and Lansoprazole and enhance H pylori eradication rapidly and moreover clarithromycin with Omeprazole show beneficial interaction for rapid synergistic efficacy.

T.gondii infection and in Cryptosporidiosis associated with AIDS, clarithromycin in combination with pyrimethamine is effective.

In Lyme disease, a most common tick borne infection with arthritis caused by B.burgedorferi, clarithromycin produced significant results in recent studies (Azithromycin is also effective)

TOLERABILITY PROFILE:

Various comparative trials have indicated that clarithromycin is generally well tolerated and has better tolerability than erythromycin etc., which are noted for their high GIT irritant effects. The most common events associated with the use of clarithromycin are diarrhea, abnormal taste, nausea, dyspepsia, headache, and very low withdrawal rate both in adults and children. Fewer adverse GIT events and better tolerability over erythromycin and even amoxycillin-clauvulanic acid combination. Hypersensitive reactions do occur but rare may range from mild rashes to erythema nodosum. Isolated incidence of cholestatic hepatitis may occur rarely.