Pharm

Clarithromycin

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Clarithromycin, Biaxin

  • Indications
  1. Conditions
    1. Community Acquired Pneumonia
      1. Limit to suspected Mycoplasma pneumonia or Legionella pneumonia
      2. Macrolide resistant pneumococcus is common
      3. Consider Doxycycline as alternative
    2. Streptococcal Pharyngitis
      1. Macrolides are only indicated in significant allergy to beta-lactams
    3. Non-tuberculous Mycobacterial infections
    4. Helicobacter infections
  2. Activity
    1. Macrolide resistance is increasing
      1. Resistance to one Macrolide is resistance to all
    2. Spectrum includes organisms covered by Erythromycin
    3. Streptococcus Pneumoniae (Pneumococcus)
    4. Staphylococcus aureus
    5. Toxoplasmosis gondii
    6. Mycobacterium leprae
    7. Mycobacterium Avium Complex
    8. Borrelia Burgdorferi
  • Medications
  1. Tablets: 250 and 500 mg
  2. Suspension: 125 and 250 mg/5 ml
  • Dosing
  1. See Pertussis
  2. May take with or without food
  3. General
    1. Adult: 250 to 500 mg orally twice daily
    2. Child: 7.5 mg/kg orally twice daily
  4. Group A Streptococcal Pharyngitis (second line agent in beta lactam allergy)
    1. Adult: Take 250 mg orally twice daily for 10 days
    2. Child: 7.5 mg orally twice daily for 10 days
  5. Acute Exacerbation of Chronic Bronchitis
    1. Adult: Take 250 mg orally twice daily for 7 to 14 days
  6. Mycobacterium Avium Complex Disease (e.g. AIDS)
    1. Adult: 500 mg orally twice daily
    2. Active disease is treated with at least 2 drugs
  7. Renal Dosing
    1. eGFR 30 to 60 ml/min: Decrease dose by 50%
    2. eGFR <30 ml/min: Decrease dose by 75%
  • Pharmacokinetics
  1. Half Life: 5 hours
  • Adverse Effects
  1. See Macrolide
  2. Dysgeusia or Distorted Taste (20%)
  3. Calcium Channel Blocker Drug Interaction (see below)
  4. Myasthenia Gravis (risk of exacerbation)
  5. QT Prolongation
    1. Appears to be a class effect of Macrolides, but seen more with Azithromycin
    2. Higher risk with known QTc Prolongation, Hypokalemia, Hypomagnesemia, Class IA or III Antiarrhythmics
  6. 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]
  • Safety
  1. Considered safe in Lactation
  2. Pregnancy Category C
    1. Clarithromycin is considered a potential Teratogen (Cleft Lip association)
    2. Macrolides in general may increase heart defects with first trimester exposure of 5-7 days
    3. Fan (2020) BMJ 368: m331 +PMID:32075790 [PubMed]
  • Drug Interactions
  1. Clarithromycin is a strong CYP3A4 inhibitor
    1. Includes Calcium Channel Blockers as below
    2. Numerous interactions including Carbamazepine, Quetiapine, Simvastatin
    3. Toxicity risks with Ergotamines and Colchicine
  2. Warfarin
    1. May increase INR
  3. 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]