II. Pharmacokinetics: Half Life

  1. Clarithromycin: 5 hours
  2. Telithromycin: 10 hours
  3. Azithromycin: 68 hours

III. Precautions

  1. Increasing Macrolide resistance for most indications (see below)
  2. QT Prolongation with Azithromycin (see below)
  3. Calcium Channel Blocker interaction with Clarithromycin (see below)
  4. Macrolides in general (including Azithromycin) may increase heart defects with first trimester exposure of 5-7 days
    1. Previously only Clarithromycin was considered a potential Teratogen (Cleft Lip association)
    2. Fan (2020) BMJ 368: m331 +PMID:32075790 [PubMed]

IV. Dosing: Azithromycin (Zithromax)

  1. Directions
    1. Take more than 1 hour before or 2 hours after food
    2. Adult
      1. Day 1: 500 mg PO qd
      2. Day 2 to 5: 250 mg PO qd
    3. Child
      1. Day 1: 10 mg/kg PO qd (maximum: 500 mg)
      2. Day 2 to 5: 5 mg/kg PO qd (maximum: 250 mg)
    4. Infant under age 6 months
      1. 10 mg/kg/day for 5 days
  2. New preparations
    1. ZMax 2 grams orally x1 dose (Available in 2005)
      1. For uncomplicated Community Acquired Pneumonia
      2. Vomiting >1 hour after dose - no additional med
      3. Use within 12 hours of reconstituting
    2. References
      1. (2005) Prescribers Letter 12(8):44

V. Dosing: Clarithromycin (Biaxin)

  1. May take with or without food
  2. Adult: 250 to 500 mg PO bid
  3. Child: 7.5 mg/kg PO bid

VI. Dosing: Telithromycin

VII. Adverse Effects

  1. Class
    1. Less Nausea and Vomiting than with Erythromycin
    2. QT Prolongation (see below)
      1. Three fold increased risk of Sudden Cardiac Death while on Azithromycin
      2. Ray (2013) N Engl J Med 366(20): 1881-90 [PubMed]
  2. Clarithromycin
    1. Dysgeusia or distorted taste (20%)
    2. Calcium Channel BlockerDrug Interaction (see below)
    3. Increased cardiovascular deaths
      1. Observation in some studies as of 2018, but needs confirmation
      2. Inghammer (2017) Am J Epidemiol +PMID:29155931 [PubMed]
      3. Svanström (2014) BMJ 349:g4930 +PMID:25139799 [PubMed]

VIII. Drug Interactions: Clarithromycin

  1. Calcium Channel Blockers
    1. Clarithromycin increases Calcium Channel Blocker levels via CYP3A4 inhibition
    2. Highest risk with Dihydropyridine Calcium Channel Blockers (Nifedipine, Felodipine)
    3. Highest risk in age over 65 years old
    4. Provokes Hypotension and Bradycardia
    5. Risk of Acute Kidney Injury (often requiring hospitalization)
      1. Number needed to harm: 1 in 465 for over age 65 years
    6. References
      1. Gandhi (2013) JAMA 310(23):2544-53 [PubMed]

IX. Indications: Major indications for broad spectrum Macrolides

  1. Single dose Chlamydia trachomatis treatment
  2. Respiratory infections
    1. Otitis Media (Azithromycin)
      1. Not recommended due to increased resistance rates
    2. Community Acquired Pneumonia
      1. Limit to suspected Mycoplasma pneumonia or Legionella pneumonia
      2. Macrolide resistant pneumococcus is common
      3. Consider Doxycycline as alternative
    3. Acute Sinusitis (Azithromycin)
      1. Not recommended due to growing resistance rates
    4. Streptococcal Pharyngitis
      1. Macrolides are only indicated in significant allergy to beta-lactams
    5. Non-tuberculous Mycobacterial infections
    6. Helicobacter infections
  3. References
    1. (2013) Presc Lett 20(8): 44

X. Contraindications

  1. Telithromycin (Ketek) may cause repiratory failure in Myasthenia Gravis (FDA Black Box Warning)

XI. Preparations: Activity Spectrum

  1. Macrolide resistance is increasing
    1. Resistance to one Macrolide is resistance to all
  2. Spectrum includes organisms covered by Erythromycin
  3. Clarithromycin
    1. Streptococcus Pneumoniae (Pneumococcus)
    2. Staphylococcus aureus
    3. Toxoplasmosis gondii
    4. Mycobacterium leprae
    5. Mycobacterium Avium Complex
    6. Borrelia Burgdorferi
  4. Azithromycin
    1. HaemophilusInfluenzae
    2. Moraxella catarrhalis
    3. Toxoplasmosis gondii
    4. Mycobacterium Avium Complex (Clarithromycin better)
    5. Borrelia Burgdorferi
  5. Telithromycin
    1. Avoid in patients with Myasthenia Gravis due to risk of Respiratory Failure (FDA Black Box Warning)
    2. Similar to other Extended Spectrum Macrolides
    3. Appears to have greater activity for pneumococcus
    4. May be used in place of other broad spectrum agents
      1. Augmentin
      2. Extended spectrum Fluoroquinolones
    5. References
      1. Fogarty (2003) J Antimicrob Chemother 51:947-55 [PubMed]

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Cost: Medications

azithromycin (on 12/21/2022 at Medicaid.Gov Survey of pharmacy drug pricing)
AZITHROMYCIN 1 GM PWD PACKET Generic $19.97 each
AZITHROMYCIN 100 MG/5 ML SUSP Generic $0.48 per ml
AZITHROMYCIN 200 MG/5 ML SUSP Generic $0.41 per ml
AZITHROMYCIN 250 MG TABLET Generic $0.33 each
AZITHROMYCIN 500 MG TABLET Generic $0.64 each
AZITHROMYCIN 600 MG TABLET Generic $1.29 each
zithromax (on 2/23/2022 at Medicaid.Gov Survey of pharmacy drug pricing)
ZITHROMAX 250 MG TABLET Generic $0.33 each
ZITHROMAX 250 MG Z-PAK TABLET Generic $0.33 each
clarithromycin (on 12/21/2022 at Medicaid.Gov Survey of pharmacy drug pricing)
CLARITHROMYCIN 125 MG/5 ML SUS Generic $0.86 per ml
CLARITHROMYCIN 250 MG TABLET Generic $0.47 each
CLARITHROMYCIN 250 MG/5 ML SUS Generic $1.43 per ml
CLARITHROMYCIN 500 MG TABLET Generic $0.41 each
CLARITHROMYCIN ER 500 MG TAB Generic $4.32 each