Clarithromycin

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Clarithromycin is a macrolide antibiotic used to treat a variety of different infections. These include infections of the skin and soft tissue or the respiratory system (pharyngitis, tonsillitis, sinusitis, pneumonia).

Clarithromycin can also be used (along with other medicines) to treat the infection H. pylori in patients with duodenal ulcers.

Contents

[edit] BRAND NAMES

[edit] STRUCTURE

Clarithromycin.jpg

[edit] MECHANISM OF ACTION

Clarithromycin is a macrolide antibiotic. Like other macrolides, Clarithromycin binds to the 50S subunit of the ribosome of the bacteria, blocking RNA-mediated bacterial protein synthesis.

[edit] INDICATIONS

Adults:

  • Community-acquired pneumonia due to Chlamydophila pneumoniae, Haemophilus influenzae, Mycoplasma pneumoniae or Streptococcus pneumoniae
  • Pharyngitis and tonsillitis caused by Streptococcus pyogenes as an alternative to first-line therapy (Penicillin by either the intramuscular or the oral route is the usual drug of choice in the treatment of Streptococcus pyogenes infection)
  • Acute bacterial exacerbations of chronic bronchitis and Acute bacterial sinusitis, due to Haemophilus influenzae, Moraxella catarrhalis or Streptococcus pneumoniae.
  • Uncomplicated skin infections due to Staphylococcus aureus and Streptococcus pyogenes
  • Disseminated mycobacterial infections due to Mycobacterium avium, or Mycobacterium intracellulare
  • Prevention of disseminated Mycobacterium avium complex (MAC) disease in patients with advanced HIV infection
  • In combination with Amoxicillin and one of Lansoprazole, omeprazole or esomeprazole, as triple therapy, are indicated to eradicate H. pylori.


Pediatric Patients

  • Acute otitis media caused by Haemophilus influenzae, Moraxella catarrhalis or Streptococcus pneumoniae
  • Community-acquired pneumonia due to Chlamydophila pneumoniae, Mycoplasma pneumoniae or Streptococcus pneumoniae
  • Pharyngitis/tonsillitis caused by Streptococcus pyogenes
  • Acute sinusitis due to Haemophilus influenzae, Moraxella catarrhalis, or Streptococcus pneumoniae
  • Uncomplicated skin and skin structure infections due to Staphylococcus aureus, or Streptococcus pyogenes
  • Disseminated mycobacterial infections due to Mycobacterium avium, or Mycobacterium intracellulare

[edit] DOSAGE

Adults:

To treat a respiratory, skin or soft tissue infection

  • Adults, Elderly and children over 12 years old: The usual dose is 250 mg twice a day for 7 days. For severe infections the dose may be increased to 500 mg twice a day for up to 14 days.

To treat H. pylori infection in adults with duodenal ulcers: Clarithromycin (500 mg) Twice Daily is usually combined with Omeprazole (20 mg) twice daily and Amoxicillin (1000 mg) Twice Daily to treat H.pylori infection in adults with duodenal ulcers.


Children:

Community-Acquired Pneumonia, Sinusitis, Bronchitis, Skin Infections: The usual recommended daily dosage is 7,5 mg/kg twice a day for 10 days.

[edit] CONTRAINDICATIONS

  • Known hypersensitivity to clarithromycin
  • History of cholestatic jaundice or hepatic dysfunction associated with prior use of clarithromycin.
  • Coadministration with: Cisapride, pimozide, astemizole, terfenadine because of a risk for cardiac arrhythmias (QT prolongation, ventricular tachycardia, ventricular fibrillation, and torsades de pointes) most likely due to inhibition of metabolism of these drugs by clarithromycin.
  • Coadministration with colchicine in patients with renal or hepatic impairment
  • Arrhythmia: Clarithromycin should not be given to patients with history of QT prolongation or ventricular cardiac arrhythmia, including torsades de pointes
  • Coadministration with statins that are extensively metabolized by CYP3A4 (ie, lovastatin, simvastatin), due to the risk of myopathy, including rhabdomyolysis.
  • Ergot preparations (ergotamine or dihydroergotamine) should be avoided in patients who are taking clarithromycin due to inhibition of metabolism of these drugs by clarithromycin with a risk of developing clinical ergotism (i.e., hypertension, lingual ischemia, and peripheral cyanosis)[1]

[edit] PRECAUTIONS

  • Significant renal impairment with or without coexisting hepatic impairment: decreased dosage or prolonged dosing intervals may be appropriate.
  • Clarithromycin can cause abnormal liver function tests, jaundice, cirrhosis. Discontinue it immediately if signs and symptoms of hepatitis occur, such as anorexia, jaundice, dark urine, pruritus, or tender abdomen.

[edit] INTERACTIONS

Clarithromycin inhibits the hepatic microsomal CYP3A4 isoenzyme. The following are examples of some clinically significant CYP3A4 based drug interactions (Increased serum concentrations):

  • Carbamazepine: Blood level monitoring of carbamazepine may be considered.
  • Colchicine (Contraindicated)
  • Sildenafil, Tadalafil, or Vardenafil (Co-administration is not recommended)
  • Triazolam or Alprazolam: Caution and appropriate dose adjustments should be considered. For benzodiazepines which are not metabolized by CYP3A (e.g., temazepam, nitrazepam, lorazepam), a clinically important interaction with clarithromycin is unlikely.
  • Atazanavir: Doses of clarithromycin greater than 1000 mg per day should not be co-administered with Atazanavir
  • Ergotamine or dihydroergotamine: Concomitant administration of clarithromycin and ergotamine or dihydroergotamine is contraindicated, as this may result in ergot toxicity.
  • Antiarrhythmics: There have been post-marketing reports of torsades de pointes occurring with concurrent use of clarithromycin and quinidine or disopyramide. Electrocardiograms should be monitored for QTc prolongation during coadministration of clarithromycin with these drugs. Serum concentrations of these medications should also be monitored.
  • Statins: Concomitant administration of clarithromycin with lovastatin or simvastatin is contraindicated. Rhabdomyolysis have also been reported in patients taking atorvastatin or rosuvastatin concomitantly with clarithromycin. When used with clarithromycin, atorvastatin or rosuvastatin should be administered in the lowest possible doses or use of a statin that is not dependent on CYP3A metabolism (e.g. fluvastatin or pravastatin) should be considered.
  • Hypoglycemic agents and/or insulin: The concomitant use of clarithromycin with these drugs can result in significant hypoglycemia. With certain hypoglycemic drugs such as nateglinide, pioglitazone, repaglinide and rosiglitazone, inhibition of CYP3A enzyme by clarithromycin may be involved and could cause hypoglycemia when used concomitantly. Careful monitoring of glucose is recommended.

Other interactions

  • Verapamil: Hypotension, bradyarrhythmias, and lactic acidosis have been observed in patients receiving concurrent verapamil
  • Zidovudine: Administration of clarithromycin and zidovudine should be separated by at least two hours.
  • Digoxin: Elevated digoxin serum concentrations in patients receiving clarithromycin and digoxin concomitantly have been reported in post-marketing surveillance. Some patients have shown clinical signs consistent with digoxin toxicity, including potentially fatal arrhythmias. Monitoring of serum digoxin concentrations should be considered, especially for patients with digoxin concentrations in the upper therapeutic range.
  • Anticoagulants: Clarithromycin may potentiate oral anticoagulants (monitor prothrombin time)
  • Clarithromycin increase cyclosporine levels with increased toxicity.
  • Clarithromycin increase theophylline levels.

[edit] PREGNANCY AND LACTATION

  • Pregnancy Category B3 (AU)
  • Pregnancy Category C (US). Clarithromycin should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
  • Nursing Mothers: caution should be exercised when clarithromycin is administered to a nursing woman.

[edit] SIDE EFFECTS

The most frequently reported events in adults were diarrhea (3%), nausea (3%), abnormal taste (3%), dyspepsia (2%), abdominal pain/discomfort (2%), headache (2%) and abnormal liver function tests

In pediatric patients, the most frequently reported events were diarrhea (6%), vomiting (6%), abdominal pain (3%), rash (3%), and headache (2%).

Most of these events were described as mild or moderate in severity.

More serious side effects are described in Contraindication and Precaution sections

[edit] RELATED LINKS

Macrolides: Mechanisms of Action
Study Links Heart Deaths To Clarithromycin

Macrolides Mechanisms of Action - Medvideos.org

[edit] BIBLIOGRAPHY

[edit] REFERENCES

  1. http://www.ncbi.nlm.nih.gov/pubmed/8607732