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Clarithromycin

Clarithromycin
Systematic (IUPAC) name
(3R,4S,5S,6R,7R,9R,11S,12R,13S,14S)-6-{[(2S,3R,4S,6R) -4-(dimethylamino)-3-hydroxy-6-methyloxan-2-yl]oxy} -14-ethyl-12,13-dihydroxy-4-{[(2R,4S,5S,6S)-5-hydroxy -4-methoxy-4,6-dimethyloxan-2-yl]oxy}-7 -methoxy-3,5,7,9,11,13-hexamethyl -1-oxacyclotetradecane-2,10-dione
Clinical data
Trade names Biaxin
AHFS/Drugs.com
MedlinePlus
Pregnancy
category
Legal status
  • prescription only
Routes of
administration
oral, intravenous
Pharmacokinetic data
Bioavailability 50%
Protein binding low binding
Metabolism hepatic
Biological half-life 3–4 h
Identifiers
CAS Registry Number  Y
ATC code J01
PubChem CID:
DrugBank  Y
ChemSpider  N
UNII  Y
KEGG  Y
ChEMBL  N
Chemical data
Formula C38H69NO13
Molecular mass 747.953 g/mol
 N   

Clarithromycin, sold under the brand name Biaxin among others, is an health system.[3] It is available as a generic medication.[1] The wholesale cost is between 0.13 and 0.79 USD per dose.[4] In the United States it is moderately expensive at 50 to 100 USD for a course of treatment.[5] It is made from erythromycin and is chemically known as "6-O-methylerythromycin".[6]

Contents

  • Medical uses 1
    • Spectrum of resistance and susceptibility 1.1
  • Contraindications 2
  • Side effects 3
    • Cardiac 3.1
    • Liver and kidney 3.2
    • Central nervous system 3.3
    • Infection 3.4
    • Pregnancy 3.5
  • Interactions 4
    • Statins 4.1
    • Calcium channel blockers 4.2
    • Carbamazepine 4.3
    • HIV medications 4.4
    • Buspirone 4.5
  • Mechanism of action 5
  • Pharmacokinetics 6
  • Metabolism 7
  • History 8
  • Society and culture 9
    • Cost 9.1
    • Brand names 9.2
  • References 10
  • External links 11

Medical uses

Clarithromycin is primarily used to treat a number of bacterial infections including: pneumonia, Helicobacter pylori and as an alternative to penicillin in strep throat.[1] Other uses include: cat scratch disease and other infections due to bartonella, cryptosporidiosis, as a second line agent in Lyme disease and toxoplasmosis.[1] It may also be used to prevent bacterial endocarditis in those who cannot take penicillin.[1]

Spectrum of resistance and susceptibility

Clarithromycin covers

  • "Biaxin XL (labeling)" (pdf).  
  • US patent 4331803, Watanabe, Y.; Morimoto, S. & Omura, S., "Novel erythromycin compounds", issued 1981-05-19, assigned to Taisho Pharmaceutical 

External links

  1. ^ a b c d e f g h "Vancocin". The American Society of Health-System Pharmacists. Retrieved September 4, 2015. 
  2. ^ a b Greenwood, David (2008). Antimicrobial drugs : chronicle of a twentieth century medical triumph (1 ed.). Oxford: Oxford University Press. p. 239.  
  3. ^ "WHO Model List of EssentialMedicines" (PDF). World Health Organization. October 2013. Retrieved 22 April 2014. 
  4. ^ a b "Clarithromycin". International Drug Price Indicator Guide. Retrieved 7 September 2015. 
  5. ^ a b Hamilton, Richart (2015). Tarascon Pocket Pharmacopoeia 2015 Deluxe Lab-Coat Edition. Jones & Bartlett Learning. p. 92.  
  6. ^ Kirst, Herbert A. (2012). Macrolide Antibiotics (2 ed.). Basel: Birkhäuser Basel. p. 53.  
  7. ^ http://www.toku-e.com/Assets/MIC/Clarithromycin%20USP.pdf
  8. ^ Malhotra-Kumar, S.; Lammens, C.; Coenen, S.; Van Herck, K.; Goossens, H. (2007). "Effect of azithromycin and clarithromycin therapy on pharyngeal carriage of macrolide-resistant streptococci in healthy volunteers: A randomised, double-blind, placebo-controlled study". The Lancet 369 (9560): 482–490.  
  9. ^ Yamaguchi S, Kaneko Y, Yamagishi T, et al. [Clarithromycin-induced torsades de pointes]. Nippon Naika Gakkai Zasshi. 2003;92(1):143–5.
  10. ^ Winkel, P.; Hilden, J. R.; Fischer Hansen, J. R.; Hildebrandt, P.; Kastrup, J.; Kolmos, H. J. R.; Kjøller, E.; Jespersen, C. M.; Gluud, C.; Jensen, G. B.; Claricor Trial, G. (2011). "Excess Sudden Cardiac Deaths after Short-Term Clarithromycin Administration in the CLARICOR Trial: Why is This So, and Why Are Statins Protective". Cardiology 118 (1): 63–67.  
  11. ^ Tietz, A.; Heim, M. H.; Eriksson, U.; Marsch, S.; Terracciano, L.; Krähenbühl, S. (2003). "Fulminant liver failure associated with clarithromycin". The Annals of Pharmacotherapy 37 (1): 57–60.  
  12. ^ Andersen JT, Petersen M, Jimenez-Solem E, Broedbaek K, Andersen NL, et al. (2013) Clarithromycin in Early Pregnancy and the Risk of Miscarriage and Malformation: A Register Based Nationwide Cohort Study. PLoS ONE 8(1): e53327. doi:10.1371/journal.pone.0053327
  13. ^ Patel AM, Shariff S, Bailey DG, et al. Statin toxicity from macrolide antibiotic coprescription: a population-based cohort study. Ann Intern Med. 2013;158(12):869–76.
  14. ^ [4]
  15. ^ Demir S, Akin S, Tercan F, Ariboğan A, Oğuzkurt L. Ergotamine-induced lower extremity arterial vasospasm presenting as acute limb ischemia. Diagn Interv Radiol. 2010;16(2):165–7.
  16. ^ Sekar VJ, Spinosa-guzman S, De paepe E, et al. Darunavir/ritonavir pharmacokinetics following coadministration with clarithromycin in healthy volunteers. J Clin Pharmacol. 2008;48(1):60–5.
  17. ^ Ferrero JL, Bopp BA, Marsh KC, et al. Metabolism and Disposition of Clarithromycin in Man. Drug Metab Dispos. 1990;18(4):441–446. [PubMed 1976065]

References

Clarithromycin is available under several brand names, for example Binoclar, Biclar, Bioclar, Biaxin, Crixan, Claritron, Clarihexal, Clacid, Claritt, Clacee, Clarac, Clariwin, Claripen, Clarem, Claridar, Fromilid, Infex, Kalixocin, Karicin, Klaricid, Klacid, Klaram, Klabax, Monoclar, Resclar, Truclar, and Vikrol.

In Pakistan, it is available under the brand name Rithmo, and is manufactured and marketed by SAMI Pharmaceuticals and used by many pharmaceuticals companies such as CCL Pharmaceuticals. In Bangladesh, it is available as Binoclar by Sandoz, Claricin by the Acme Laboratories Ltd. In the United States, generic clarithromycin is available from Andrx, Genpharm, Ivax, Ranbaxy Laboratories, Roxane, Sandoz, Teva, and Wockhardt. In the Middle East, it is available as Claridar, produced by Dar al Dawa. In India, Acnesol-CL gel, containing 1% clarithromycin, marketed by Systopic, is used to treat acne vulgaris.

Brand names

It is available as a generic medication.[1] The wholesale cost is between 0.13 and 0.79 USD per dose.[4] In the United States it is moderately expensive at 50 to 100 USD for a course of treatment.[5]

Cost

Society and culture

Clarithromycin was invented by researchers at the Japanese drug company Taisho Pharmaceutical in 1980.[2] The product emerged through efforts to develop a version of the antibiotic erythromycin that did not experience acid instability in the digestive tract, causing side effects, such as nausea and stomachache. Taisho filed for patent protection for the drug around 1980 and subsequently introduced a branded version of its drug, called Clarith, to the Japanese market in 1991. In 1985, Taisho partnered with the American company Abbott Laboratories for the international rights, and Abbott also gained FDA approval for Biaxin in October 1991. The drug went generic in Europe in 2004 and in the US in mid-2005.

History

Clarithromycin has a fairly rapid first-pass metabolism in the liver. Its major metabolites include an inactive metabolite, N-desmethylclarithromycin, and an active metabolite, 14-(R)-hydroxyclarithromycin. Compared to clarithromycin, 14-(R)-hydroxyclarithromycin is less potent against mycobacterial tuberculosis and the Mycobacterium avium complex. Clarithromycin (20%-40%) and its active metabolite (10%-15%) are excreted in urine. Of all the drugs in its class, clarithromycin has the best bioavailability at 50%, which makes it amenable to oral administration. Its elimination half-life is about 3 to 4 hours with 250 mg administered every 12 h, but increased to 5 to 7 h with 500 mg administered every 8 to 12 h. With any of these dosing regimens, the steady-state concentration of this metabolite is generally attained within 3 to 4 days.[17]

Metabolism

Unlike erythromycin, clarithromycin is acid-stable, so can be taken orally without having to be protected from gastric acids. It is readily absorbed, and diffuses into most tissues and phagocytes. Due to the high concentration in phagocytes, clarithromycin is actively transported to the site of infection. During active phagocytosis, large concentrations of clarithromycin are released; its concentration in the tissues can be over 10 times higher than in plasma. Highest concentrations are found in liver, lung tissue, and stool.

Pharmacokinetics

Clarithromycin prevents bacteria from growing by interfering with their protein synthesis. It binds to 23S rRNA, a component of the 50S subunit of the bacterial ribosome, thus inhibiting the translation of peptides.

Mechanism of action

It can also cause serotonin syndrome symptoms when taken in conjunction with buspirone.

Buspirone

Depending on the combination of medications, clarithromycin therapy could be contraindicated, require changing doses of some medications, or be acceptable without dose adjustments.[16]

HIV medications

Clarithromycin almost doubles the level of carbamazepine in the body by reducing its clearance, inducing toxic symptoms of carbamazepine, including diplopia and nausea, as well as hyponatremia.

Carbamazepine

When ergotamine migraine medications are taken with clarithromycin, the risk of acute ergot toxicity is increased, including vasospasm and ischemia of the extremities.[15]

Patients on a calcium channel blocker who were also given clarithromycin have a higher risk of critically low blood pressure, kidney failure, and death, compared to pairing calcium channel blockers with azithromycin, a drug similar to clarithromycin but without CYP3A4 inhibition.[14]

Calcium channel blockers

When it is taken with certain statins (a class of drugs used to reduce blood serum cholesterol levels), the risk of side effects is increased, including muscle aches and rhabdomyolysis.[13]

Statins

Clarithromycin inhibits an important enzyme, CYP3A4, involved in the metabolism of many other commonly prescribed drugs. Taking clarithromycin with these other drugs may lead to unexpected increases or decreases in drug levels.

Interactions

Clarithromycin has been shown to induce miscarriage in animals, and a recent study found an increased risk of miscarriage in women exposed to it in early pregnancy.[12]

Pregnancy

A risk of oral candidiasis, due to the elimination of the yeast's natural bacterial competitors by the antibiotic, is also incurred.

Infection

Common adverse effects of clarithromycin in the central nervous system include dizziness, headaches. Rarely, it can cause ototoxicity, delirium and mania.

Central nervous system

Clarithromycin has been known to cause jaundice, cirrhosis, and kidney problems, including renal failure.

Liver and kidney

In one trial, the use of short-term clarithromycin treatment was correlated with an increased incidence of deaths classified as sudden cardiac deaths in stable coronary heart disease patients not using statins.[10] Some case reports suspect it of causing liver disease.[11]

Clarithromycin can lead to a prolonged QT interval. In patients with long QT syndrome, cardiac disease, or patients taking other QT-prolonging medications, this can increase risk for life-threatening arrhythmias.[9]

Cardiac

The most common (>1%) side effects are gastrointestinal: diarrhea, nausea, abdominal pain, and vomiting. It also can cause headaches, insomnia, and abnormal liver function tests. Allergic reactions include rashes and anaphylaxis. Less common side effects include extreme irritability, hallucinations (auditory and visual), dizziness/motion sickness, and alteration in senses of smell and taste, including a metallic taste. Dry mouth, panic attacks, and nightmares have also been reported, albeit less frequently.[3]

Side effects

Clarithromycin should be used with caution if the person has liver or kidney disease, certain heart problems, or takes drugs that might cause certain heart problems (e.g., QT prolongation or bradycardia), or an electrolyte imbalance (e.g., low potassium or sodium levels).

Contraindications

Its antibacterial spectrum is the same as erythromycin, but it is also active against Mycobacterium avium complex MAV, M. leprae, and atypical mycobacteria.

Many Gram-positive microbes quickly develop resistance to clarithromycin after standard courses of treatment, most frequently by acquisition of the erm(B) gene, which confers high-level resistance to all macrolides.[8]

  • Haemophilus influenzae: 0.008→256 μg/ml
  • Streptococcus pneumoniae: 0.001→256 μg/ml
  • Streptococcus pyogenes: 0.001→128 μg/ml

[7]

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