Azithromycin  Zmax

 

Antibiotic Class

Macrolide

Antimicrobial Spectrum

Staphylococcus aureus, Bacillus cereus, Bordetella pertussis, Chlamydia trachomatis, Corynebacterium diphtheriae, Gardnerella vaginalis, H. influenzae, Legionella pneumophila, Moraxella catarrhalis, Mycobacterium spp., Mycoplasma pneumoniae, Pasteurella multocida, S. pneumoniae, S. pyogenes.

Mechanism of Action

Macrolides inhibit protein synthesis. They impair the elongation cycle of the peptidyl chain by specifically binding to the 50 S subunit of the ribosome. 

Pharmacodynamics

Macrolides produce time-dependent killing

Pharmacokinetics

500mg dose: Cmax: 0.4mg/L; Half-life: 35-40 hours; Volume of distribution: 23-31 L/kg; Table 3

Adverse Effects

Gastrointestinal: abdominal cramps, nausea, diarrhea, anorexia, pancreatitis

Genitourinary: vulvovaginal candidiasis, renal failure

Cardiovascular System: prolongation of QT interval

Hepatic: hepatotoxicity, jaundice

Hematologic: eosinophilia, thrombocytosis, lymphopenia

Central Nervous System: headache, fatigue

Endocrine/Metabolic: hyperglycemia

Dermatologic: itching, nail discoloration

Dosage

Oral: 250mg, 600mg tablet

         1gram packet

         100mg/5ml, 200mg/5ml powder for reconstitution to suspension

IV:    500mg vial

Dosing in adults

Acute bacterial exacerbations of COPD: 500mg PO q24h x 3 days, or 500mg on day 1, 250 mg q24h on days 2-5

Acute bacterial sinusitis 500mg PO q24h x 3 days

Cervicitis due to Chlamydia trachomatis: 1 gram PO x 1 dose

Cervicitis due to Neisseria gonorrhoeae: 2 gram PO x 1 dose

Chancroid (genital ulcer disease due to Haemophilus ducreyi): 1 gram PO x 1

Mycobacterium avium complex, prophylaxis: 1200mg PO q weekly

Mycobacterium avium complex, treatment: 500 mg PO q24h (in combination with ethambutol)

Pharyngitis/tonsillitis: 500mg PO day 1, then 250mg q24h on days 2-5

Community acquired pneumonia (mild severity): 500mg PO day 1, then 250mg q24h on days 2-5

Skin and skin structure infections (uncomplicated): 500mg PO day 1, 250mg q24h on days 2-5

Urethritis due to Chlamydia trachomatis: 1 gram PO x 1

Urethritis due to Neisseria gonorrhoeae: 2 gram PO x 1

Pelvic inflammatory disease: 500mg IV q24h for at least 2 days, then 250 mg PO q24h x 7 days total

Community acquired pneumonia: 500mg IV q24h x at least 2 days, followed by 500mg PO q24h x 7-10 days total.

Dosing in pediatrics

Acute bacterial sinusitis (> 6 months): 10 mg/kg PO q24h x 3 days

Mycobacterium avium complex disease, primary prevention: 20 mg/kg PO q weekly (maximum per dose 1200 mg)

Mycobacterium avium complex disease, secondary prevention: 5 mg/kg q24h (maximum dose 250mg) PO combined with ethambutol

Mycobacterium avium complex disease, treatment: 5 mg/kg up to 20 mg/kg PO x 1 month or longer

Otitis media, acute (> 6 months): 30mg/kg PO x 1, or 10mg/kg PO q24h x 3 days, or 10 mg/kg PO on day 1 followed by 5 mg/kg PO q24h on days 2-5

Pharyngitis, tonsillitis (>2 years old): 12 mg/kg PO q24h x 5 days

Pharyngitis/tonsillitis (second-line therapy): (>16 years) 500 mg PO day 1, then 250 mg q24h on days 2-5

Pneumonia, community-acquired (>6 months): 10 mg/kg PO day 1, then 5 mg/kg q24h on days 2-5

Pneumonia, community-acquired (mild severity): (>16 years) 500mg PO day 1, then 250 mg q24h on days 2-5

Skin and skin structure infections (uncomplicated): (>16 years) 500mg PO on day 1, then 250mg q24h on days 2-5

Disease state based dosing

Hepatic failures: No adjustment necessary

Renal failures: No adjustment necessary, however should be used with caution in patients with CrCl < 10ml/min. No supplemental doses needed after dialysis.

Contraindications/Warnings/Precautions

Contraindicated: Coadministration with astemizole, cisapride, ergotamine, terfenadine

Precautions: May prolong the QTc interval

Drug Interactions

Due to its hepatic metabolism, caution should be exercised when administering this agent with other drugs metabolized in the liver. The following drug interactions are clinically relevant but do not represent the comprehensive list of documented or potential drug-drug interactions.

Amiodarone: Incereased risk of cardiotoxicity (QTc prolongation)

Cyclosporine: Concomitant administration may increase cyclosporine levels. Close monitoring of cyclosporine levels is recommended

Nelfinavir: Coadministration may lead to increased azithromycin levels

Phenytoin: Concomitant administration may increase phenytoin levels. Close monitoring of phenytoin levels is recommended

Pregnancy

Category B: No evidence of risk in humans but studies inadequate.

Monitoring Requirements

Therapeutic: Periodic WBC, chest X-ray if pneumonia, cultures, temperature

Brand names/Manufacturer

ZITHROMAX (Pfizer MALAYSIA, THAILAND, SINGAPORE, FINLAND, NEW ZEALAND, ISRAEL, GREECE, CHILE, UNITED KINGDOM, USA, FRANCE, NETHERLANDS, AUSTRIA, AUSTRALIA, GERMANY, SWITZERLAND, SOUTH AFRICA, IRELAND, CANADA, PORTUGAL, HONG KONG)

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