grepafloxacin (Raxar)

Introduction

Tradename: Raxar. Galaxo Wellcome is voluntarily withdrawing grepafloxaxcin due to safety concerns (November 1999). A small number of severe cardiovascular events (QT prolongation) have been reported. Due to the availability of other agents in this class, grepafloxacin is being withdrawn.

Indications

• bacterial infections due to susceptible organisms
  • acute bacterial exacerbations of chronic bronchitis
  • community acquired pneumonia
    • Haemophilus influenza
    • Streptococcus pneumonia
    • Moraxella catarrhalis
• uncomplicated gonorrhea (urethral in male, endocervical & rectal in females) caused by Neisseria gonorrhea
• non-gonococcal urethritis & cervicitis caused by Chlamydia trachomatis

Dosage

400-600 mg PO QD

Tabs: 200 mg

Dosage adjustment in renal failure

none necessary

Pharmacokinetics

• metabolized in the liver by cyt P450 1A2

elimination via liver

elimination via kidney

1/2life = 12-16 hours

Antimicrobial activity

Gram positive

• Streptococcus pneumonia (penicillin susceptible)
• Streptococcus pyogenes
• Streptococcus agalactiae
• Staphylococcus aureus (MSSA)
• Staphylococcus epidermidis (methicillin-sensitive)

Gram negative

• Neisseria gonorrhoeae
• Moraxella catarrhalis
• Haemophilus influenzae
• Escherichia coli
• Klebsiella species
• Enterobacter species
• Proteus mirabilis
• Proteus vulgaris

Morganella species

• Citrobacter species

Atypical bacteria

• Chlamydia trachomatis
• Mycoplasma pneumonia

Adverse effects

• common > 10%
  • nausea
  • taste aversion
• less common 1-9%
  • headache, dizziness, diarrhea, vaginitis, abdominal pain, vomiting, pruritus, dyspepsia, leukorrhea, asthenia, insomnia, rash, anorexia, somnolence, dry mouth, photosensitivity, constipation, pain, nervousness
• uncommon <1%
  • many, including prolongation of the QT interval

• drug adverse effects of fluoroquinolones

Drug interactions

• any drug which inhibits cyt P450 1A2 (including grepafloxacin itself) can increase grepafloxacin levels
• any drug which induces cyt P450 1A2 can diminish grepafloxacin levels
• grepafloxacin inhibits cyt P450 1A2, thus inhibits its own metabolism & metabolism of other drugs metabolized by cyt P450 1A2

• drug interaction(s) anticonvulsants with anti-bacterial agents
• drug interaction(s) of antibiotics with warfarin
• drug interaction(s) of theophylline with fluoroquinolone
• drug interaction(s) of beta-adrenergic receptor antagonists with quinolones
• drug interaction(s) of fluroquinolones with amiodarone
• drug interaction(s) of fluroquinolones with sulfonylureas
• drug interaction(s) of fluoroquinolones with hypoglycemic agents

More general terms

• fluoroquinolone

Additional terms

• cytochrome p450 1A2 (cytochrome P3-450, phenacetin deethylase, cytochrome p450-4, CYP1A2)

Database

• PubChem: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=72474
• PubChem: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=115008
• PubChem: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=656829
• PubChem: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=