clarithromycin (Biaxin)
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Introduction
Tradename: Biaxin.
Indications
- treatment of non life-threatening bacterial infections due to susceptible organisms
- skin or soft tissue infections
- 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
- 500 mg PO BID
- should be taken with meals
- 500 mg QD when creatinine clearance is < 30 mL/min
- 500 mg PO 1 hour prior to procedure (endocarditis prophylaxis)
Pharmacokinetics
- oral bioavailability is 70-80%
- 1/2life is 2-6 hours (22 hours ESRD)
- metabolized by the liver by cyt P450 3A4
- eliminated in the urine
- well distributed to most body tissues
- highly concentrated in pulmonary tissue
elimination via liver
1/2life = 2-6 hours
Antimicrobial activity
- Neisseria gonorrhoeae
- Moraxella catarrhalis
- Haemophilus influenzae
- Haemophilus parainfluenzae[11]
- Legionella
- Chlamydophila pneumoniae[11]
* community-acquired resistant pneumococcus has been reported[6]
Adverse effects
- adverse GI effects of nausea, vomiting, cramps, diarrhea, increased aspartate transaminase (AST), & cholestatic jaundice less than erythromycin
- phlebitis
- transient deafness
- rash
- increased INR
- hypersensitivity reactions (rare)
- 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)
- 2-fold increased risk of miscarriage[17]
Drug interactions
- QT prolongation associated with concurrent administration of:
- clarithromycin & erythromycin increase serum levels of:
- theophylline
- carbamazepine
- digoxin
- colchicine (potentially fatal)[5][19]
- glipizide
- gliburide[16]
- may decrease metabolism of warfarin
- rifabutin in combination
- decreased levels of clarithromycin
- increased levels of rifabutin
- ritonavir in combination increases clarithromycin levels
- any drug that inhibits cyt P450 3A4, including clarithromycin itself, may increase levels of clarithromycin
- any drug that induces cyt P450 3A4 may diminish levels of clarithromycin
- clarithromycin inhibits cyt P450 3A4, thus inhibits its own metabolism & metabolism of other cyt P450 3A4 substrates
- inhibits P-glycoprotein
- increases intracellular concentration of drugs pumped out of cells by P-glycoprotein[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]
- combination with calcium channel blocker, linked to hypotension & acute renal failure (RR=2)[12][16]
- drug interaction(s) anticonvulsants with anti-bacterial agents
- drug interaction(s) of digoxin in combination with macrolides
- drug interaction(s) of calcium channel blockers with clarithromycin
- drug interaction(s) of statins with macrolide
- drug interaction(s) of antibiotics with warfarin
- drug interaction(s) of theophylline with macrolide
- drug interaction(s) of macrolides with sulfonylureas
- drug interaction(s) of eplerenone with clarithromycin
Laboratory
Mechanism of action
- binds to 50S ribosomal subunit inhibiting bacterial protein synthesis
- bacteriostatic
More general terms
Additional terms
- CLARICOR trial
- cytochrome P450 3A4 (cytochrome P450 C3, nifedipine oxidase, P450-PCN1, NF-25, CYP3A4)
Component of
- amoxicillin/clarithromycin/vonoprazan
- amoxicillin/clarithromycin/omeprazole
- amoxicillin/clarithromycin/lansoprazole (PrevPak, ACL)
References
- ↑ The Pharmacological Basis of Therapeutics, 9th ed. Gilman et al, eds. Permagon Press/McGraw Hill, 1996
- ↑ Sanford Guide to antimicrobial therapy 1997, 2001
- ↑ Harrison's Principles of Internal Medicine, 13th ed. Companion Handbook. Isselbacher et al (eds), McGraw-Hill Inc. NY, 1995, pg 164
- ↑ Drug Information & Medication Formulary, Veterans Affairs, Central California Health Care System, 1st ed., Ravnan et al eds, 1998
- ↑ Jump up to: 5.0 5.1 Medical Knowledge Self Assessment Program (MKSAP) 11, 19. American College of Physicians, Philadelphia 1998, 2018.
- ↑ Jump up to: 6.0 6.1 Journal Watch 20(24):194, 2000 Kelley et al, Clin Infect Dis Oct 31:1008, 2000
- ↑ Prescriber's Letter 13(3): 2006 Cytochrome P450 drug interactions Detail-Document#: http://prescribersletter.com/(5bhgn1a4ni4cyp2tvybwfh55)/pl/ArticleDD.aspx?li=1&st=1&cs=&s=PRL&pt=3&fpt=25&dd=220233&pb=PRL (subscription needed) http://www.prescribersletter.com
- ↑ Jump up to: 8.0 8.1 Prescriber's Letter 12(9): 2005 Fatal Interaction Between Clarithromycin and Colchicine Detail-Document#: http://prescribersletter.com/(5bhgn1a4ni4cyp2tvybwfh55)/pl/ArticleDD.aspx?li=1&st=1&cs=&s=PRL&pt=3&fpt=25&dd=211004&pb=PRL (subscription needed) http://www.prescribersletter.com
- ↑ Jump up to: 9.0 9.1 Prescriber's Letter 13(1): 2006 Clarithromycin mortality alert for patients with heart disease Detail-Document#: http://prescribersletter.com/(5bhgn1a4ni4cyp2tvybwfh55)/pl/ArticleDD.aspx?li=1&st=1&cs=&s=PRL&pt=3&fpt=25&dd=220110&pb=PRL (subscription needed) http://www.prescribersletter.com
- ↑ Jump up to: 10.0 10.1 Schembri S et al Cardiovascular events after clarithromycin use in lower respiratory tract infections: analysis of two prospective cohort studies. BMJ 2013;346:f1235 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/23525864 <Internet> http://www.bmj.com/content/346/bmj.f1235
- ↑ Jump up to: 11.0 11.1 11.2 11.3 Deprecated Reference
- ↑ Jump up to: 12.0 12.1 Gandhi S et al Calcium-channel blocker - Clarithromycin Drug Interactions and Acute Kidney Injury. JAMA. Published online November 9, 2013 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/24346990 <Internet> http://jama.jamanetwork.com/article.aspx?articleid=1769739
- ↑ Jump up to: 13.0 13.1 13.2 Svanstrom H et al Use of clarithromycin and roxithromycin and risk of cardiac death: cohort study. BMJ 2014;349:g4930 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/25139799 <Internet> http://www.bmj.com/content/349/bmj.g4930
- ↑ Jump up to: 14.0 14.1 14.2 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 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/25534598 <Internet> http://www.cmaj.ca/content/early/2014/12/22/cmaj.140950.full.pdf+html
- ↑ Jump up to: 15.0 15.1 Wong AYS et al. Cardiovascular outcomes associated with use of clarithromycin: Population based study. BMJ 2016 Jan 13; 352:h6926 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/26768836 <Internet> http://www.bmj.com/content/352/bmj.h6926
- ↑ Jump up to: 16.0 16.1 16.2 Paauw DS Dangerous and Deadly Drug Combinations Medscape. June 30, 2016 http://www.medscape.com/features/slideshow/dangerous-drug-combinations
- ↑ Jump up to: 17.0 17.1 Muanda FT, Sheehy O, Berard A Use of antibiotics during pregnancy and risk of spontaneous abortion. CMAJ 2017 May 1;189:E625-33 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/28461374 <Internet> http://www.cmaj.ca/content/189/17/E625.full.pdf+html
- ↑ Jump up to: 18.0 18.1 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 - ↑ Jump up to: 19.0 19.1 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: https://www.ncbi.nlm.nih.gov/pubmed/16007523
Database
- PubChem: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=84029
- PubChem: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=54688
- PubChem: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=5311050
- PubChem: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=5284534
- PubChem: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=370512
- PubChem: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=2778