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clarithromycin (Biaxin)

Tradename: Biaxin. Indications: - treatment of non life-threatening bacterial infections due to susceptible organisms - skin or soft tissue infections - Lyme disease - lower espiratory tract infection - community-acquired pneumonia - pneumonia in patients with COPD - Legionnaire's disease - pertussis - adjunctive treatment of inhalation anthrax - acute otitis media [11] - gastrointestinal infections - adjunctive treatment of gastritis due to H pylori - boutonneuse fever - endocarditis prophylaxis prior to procedure Dosage: 1) 500 mg PO BID 2) should be taken with meals 3) 500 mg QD when creatinine clearance is < 30 mL/min 4) 500 mg PO 1 hour prior to procedure (endocarditis prophylaxis) Pharmacokinetics: 1) oral bioavailability is 70-80% 2) 1/2life is 2-6 hours (22 hours ESRD) 3) metabolized by the liver by cyt P450 3A4 4) eliminated in the urine 5) well distributed to most body tissues 6) highly concentrated in pulmonary tissue Antimicrobial activity: Gram positive - Streptococcus - Streptococcus group A - Streptococcus group B - Streptococcus group C - Streptococcus group G - Streptococcus pneumonia* - Staphylococcus aureus (MSSA) (+/-) Gram negative - Neisseria gonorrhoeae - Moraxella catarrhalis - Haemophilus influenzae - Haemophilus parainfluenzae [11] - Legionella - Chlamydophila pneumoniae [11] Atypical bacteria - Chlamydia species - Mycoplasma pneumonia - Mycobacterium avium complex Anaerobes - Actinomyces - Bacteroides melaninogenicus - Clostridium species * community-acquired resistant pneumococcus has been reported [6] Adverse effects: 1) adverse GI effects of nausea, vomiting, cramps, diarrhea, increased aspartate transaminase (AST), & cholestatic jaundice less than erythromycin 3) phlebitis 4) transient deafness 5) rash 6) increased INR 7) hypersensitivity reactions (rare) 8) increased cardiovascular mortality noted 1 year after 14 day course [9,18] (see CLARICOR study) - increased cardiovascular mortality noted 1 year after treatment of COPD exacerbation with clarithromycin [10] - 2-fold increased risk of sudden cardiac death (relative to penicillin) [13] - absolute risk is small: 5.3 per 1000 patient years [13] - current clarithromycin use associated with excess risk for MI, cardiac arrhythmia, & death [15] - QT prolongation (case reports) 9) 2-fold increased risk of miscarriage [17] Drug interactions: 1) QT prolongation associated with concurrent administration of: a) astemizole b) terfenadine c) cisapride 2) clarithromycin & erythromycin increase serum levels of: a) theophylline b) carbamazepine c) digoxin d) colchicine (potentially fatal) [5,19] e) glipizide f) gliburide [16] 3) may decrease metabolism of warfarin 4) rifabutin in combination a) decreased levels of clarithromycin b) increased levels of rifabutin 5) ritonavir in combination increases clarithromycin levels 6) any drug that inhibits cyt P450 3A4, including clarithromycin itself, may increase levels of clarithromycin 7) any drug that induces cyt P450 3A4 may diminish levels of clarithromycin 8) clarithromycin inhibits cyt P450 3A4, thus inhibits its own metabolism & metabolism of other cyt P450 3A4 substrates 7) inhibits P-glycoprotein - increases intracellular concentration of drugs pumped out of cells by P-glycoprotein [8] 8) clarithromycin inhibits OATP1B1 & OATP1B3 thus increases toxicity of rosuvastatin, fluvastatin, & pravastatin [14] - increased risk for hospitalization for acute kidney injury (RR=1.65), hyperkalemia (RR=2.2), mortality (RR=1.4) - absolute risk likely under 1% [14] 9) combination with calcium channel blocker, linked to hypotension & acute renal failure (RR=2) [12,16] Laboratory: - clarithromycin in specimen - clarithromycin in CSF - clarithromycin in dried blood spot - clarithromycin in serum/plasma Mechanism of action: 1) binds to 50S ribosomal subunit inhibiting bacterial protein synthesis 2) bacteriostatic

Interactions

drug interactions drug adverse effects of macrolide(s)

Related

CLARICOR trial cytochrome P450 3A4 (cytochrome P450 C3, nifedipine oxidase, P450-PCN1, NF-25, CYP3A4)

General

macrolide (macrolide antibiotic)

Properties

MISC-INFO: elimination route LIVER 1/2life 2-6 HOURS pregnancy-category C safety in lactation ?

Database Correlations

PUBCHEM correlations

References

  1. The Pharmacological Basis of Therapeutics, 9th ed. Gilman et al, eds. Permagon Press/McGraw Hill, 1996
  2. Sanford Guide to antimicrobial therapy 1997, 2001
  3. Harrison's Principles of Internal Medicine, 13th ed. Companion Handbook. Isselbacher et al (eds), McGraw-Hill Inc. NY, 1995, pg 164
  4. Drug Information & Medication Formulary, Veterans Affairs, Central California Health Care System, 1st ed., Ravnan et al eds, 1998
  5. Medical Knowledge Self Assessment Program (MKSAP) 11, 19. American College of Physicians, Philadelphia 1998, 2018.
  6. Journal Watch 20(24):194, 2000 Kelley et al, Clin Infect Dis Oct 31:1008, 2000
  7. Prescriber's Letter 13(3): 2006 Cytochrome P450 drug interactions Detail-Document#: 220233 (subscription needed) http://www.prescribersletter.com
  8. Prescriber's Letter 12(9): 2005 Fatal Interaction Between Clarithromycin and Colchicine Detail-Document#: 211004 (subscription needed) http://www.prescribersletter.com
  9. Prescriber's Letter 13(1): 2006 Clarithromycin mortality alert for patients with heart disease Detail-Document#: 220110 (subscription needed) http://www.prescribersletter.com
  10. Schembri S et al Cardiovascular events after clarithromycin use in lower respiratory tract infections: analysis of two prospective cohort studies. BMJ 2013;346:f1235 PMID: 23525864 http://www.bmj.com/content/346/bmj.f1235
  11. Deprecated Reference
  12. Gandhi S et al Calcium-channel blocker - Clarithromycin Drug Interactions and Acute Kidney Injury. JAMA. Published online November 9, 2013 PMID: 24346990 http://jama.jamanetwork.com/article.aspx?articleid=1769739
  13. Svanstrom H et al Use of clarithromycin and roxithromycin and risk of cardiac death: cohort study. BMJ 2014;349:g4930 PMID: 25139799 http://www.bmj.com/content/349/bmj.g4930
  14. Li DQ, Kim R, McArthur E et al Risk of adverse events among older adults following co- prescription of clarithromycin and statins not metabolized by cytochrome P450 3A4. CMAJ. Dec 22, 2014 PMID: 25534598 http://www.cmaj.ca/content/early/2014/12/22/cmaj.140950.full.pdf+html
  15. Wong AYS et al. Cardiovascular outcomes associated with use of clarithromycin: Population based study. BMJ 2016 Jan 13; 352:h6926 PMID: 26768836 http://www.bmj.com/content/352/bmj.h6926
  16. Paauw DS Dangerous and Deadly Drug Combinations Medscape. June 30, 2016 http://www.medscape.com/features/slideshow/dangerous-drug-combinations
  17. Muanda FT, Sheehy O, Berard A Use of antibiotics during pregnancy and risk of spontaneous abortion. CMAJ 2017 May 1;189:E625-33 PMID: 28461374 http://www.cmaj.ca/content/189/17/E625.full.pdf+html
  18. Brooks M FDA Alert: Clarithromycin Risky in Patients With Heart Disease. Medscape - Feb 22, 2018. https://www.medscape.com/viewarticle/893025 - FDA Safety Alert. Feb 22, 2018 Clarithromycin (Biaxin): Drug Safety Communication - Potential Increased Risk of Heart Problems or Death in Patients With Heart Disease. https://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm597862.htm
  19. Hung IF, Wu AK, Cheng VC et al Fatal interaction between clarithromycin and colchicine in patients with renal insufficiency: a retrospective study. Clin Infect Dis. 2005 Aug 1;41(3):291-300. Epub 2005 Jun 23. PMID: 16007523

Component-of

amoxicillin/clarithromycin/lansoprazole (PrevPak, ACL) amoxicillin/clarithromycin/omeprazole amoxicillin/clarithromycin/vonoprazan