erythromycin (Eryc, Eryctte, E-mycin, Ilotycin, AK-Mycin, A/T/S, T-stat)

Introduction

Tradename: Eryc, E-mycin, Erycette (topical), Ilotycin, AK-Mycin (ophthalmic)

Indications

• treatment of non life threatening bacterial infections
  • skin or soft tissue infection
    • ecthyma, erysipeloid, erysepelas, erythrasma
    • moderate-severe inflammatory acne
  • respiratory tract infection
    • pertussis
    • pneumonia
  • gastrointestinal infection
    • proctitis
  • urogenital infection
    • urethritis
    • syphilis, trachoma, gonorrhea, chancroid, lymphogranuloma venereum, donovanosis
  • acute otitis media
  • rheumatic fever
  • Lyme disease, borreliosis
• anthrax, cutaneous anthrax, inhalation anthrax
• listeriosis, diptheria, actinomycosis, Legionnaire's disease,
• prophylaxis before bowel surgery, upper GI endoscopy
• stimulate intestinal motility
  • GERD, gastroparesis, bowel preparation
• topical: treatment of acne, rosacea:
• eye infections
  • blepharoconjunctivitis
  • ophthalmia neonatorum
  • eyelid disease
    • meibomitis

Contraindications

Caution: avoid in infants < 2 weeks of age

pregnancy category = b

safety in lactation = +

Dosage

• systemic
  • 250-500 mg PO QID.
  • 333 mg PO TID.
  • 500 mg PO BID.
  • 10-20 mg/kg/day IV divided every 6 hours, max 4 g/day.
  • Legionella dose: 1 g IV every 6 hours
• topical: apply BID after cleansing
• ophthalmic
  • apply BID-QID
  • Chlamydia: 1 strip BID for 2 months, or BID for the 1st 5 days of the month for 6 months

Tabs: 250, 333, 500 mg.

Injection: IV form: erythromycin lactobionate.

Solution: 60 mL

Ointment: 0.5%

Dosage adjustment in renal failure

Table

creatinine clearance	dosage
10-50 mL/min	100%
< 10 mL/min	50-75% dosing
hemodialysis	no post-hemodialysis dosing

Pharmacokinetics

• oral dose absorbed primarily in the duodenum
• oral bioavailability 18-45%
• well distributed to most tissues
  • does not penetrate CSF well
  • crosses placenta
• protein-binding 75-90%
• metabolized by demethylation in the liver by cyt P450 3A4
• eliminated in the bile
• 1/2life is 1-2 hours (5-6 hours ESRD)

elimination via liver

1/2life = 1-2 hours

protein binding = 75-90 %

Antimicrobial activity

Gram positive

• Streptococcus
  • Streptococcus group A
  • Streptococcus group B
  • Streptococcus group C
  • Streptococcus group G
  • Streptococcus pneumonia
• Staphylococcus aureus (MSSA) (+/-)
• Staphylococcus epidermidis (+/-)
• Corynebacterium diphtheriae

Gram negative

• Neisseria gonorrhoeae
• Moraxella catarrhalis
• Haemophilus influenzae (+/-)
• Legionella
• Haemophilus ducreyi
• Bordetella pertussis
• Chlamydophila pneumoniae
• Campylobacter

Atypical bacteria

• Chlamydia species
• Mycoplasma pneumonia
• Rickettsia (+/-)
• Ureaplasma

Anaerobes

• Actinomyces
• Clostridium species (+/-)

Adverse effects

• common & less common (> 1%)
  • nausea/vomiting
  • diarrhea, cramps*
  • increased aspartate transaminase (AST)
  • cholestatic jaundice
  • phlebitis at injection site & thrombophlebitis
  • oral candidiasis
• uncommon (< 1%)
  • hypertrophic pyloric stenosis#, ventricular arrhythmias, fever, skin rash, diarrhea, eosinophilia, hypersensitivity reaction (rare)
• other
  • increased PT & INR
  • ototoxicity (tinnitus, transient deafness)
    • high doses IV, i.e. 4 g/day
    • generally reversible
  • QT prolongation, torsades de pointes
• as topical agent
  • local dryness
  • erythema
  • tenderness
  • burning
  • irritation
  • hypersensitivity (rare)

* GI intolerance due to hepatic reduction to ketal analogous to motilin.

# Incidence of hypertrophic pyloric stenosis 1-2.6% in infants given erythromycin within 1st 2 weeks of life

• drug adverse effects of macrolide(s)

Drug interactions

• QT prolongation associated with concurrent administration of cyt P450 3A4 inhibitors:
  • astemizole
  • terfenadine
  • cisapride
  • ketoconazole
  • itraconazole
  • nefazodone
  • antiretroviral protease inhibitors
• erythromycin inhibits metabolism of:
  • theophylline
  • carbamazepine
  • warfarin
  • cyclosporine
  • benzodiazepines
  • phenytoin
  • triazolam
  • diltiazem
  • verapamil
• do NOT administer in combination with clindamycin
• any drug that inhibits cyt P450 3A4 may increase levels of erythromycin
• any drug that induces cyt P450 3A4 may diminish levels of erythromycin
• erythromycin inhibits cyt P450 1A2 & cyt P450 3A4
  • inhibits its own metabolism & metabolism of other cyt P450 3A4 substrates
  • inhibits metabolism of cyt P450 1A2 substrates
• inhibits P-glycoprotein
  • increases intracellular concentration of drugs pumped out of cells by P-glycoprotein
• erythromycin in combination with calcium channel blocker may increase risk of hypotension & acute renal failure

• 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 erythromycin
• 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

Mechanism of action

• bacteriostatic
• binds to 50S ribosomal subunits
• inhibits bacterial protein synthesis
• may have anti-inflammatory properties
• enhances GI motility, peristalsis

More general terms

• macrolide (macrolide antibiotic)

More specific terms

• erythromycin estolate (Ilosone)
• erythromycin ethyl succinate (EES, Pediamycin)
• erythromycin lactobionate (Erythrocin)
• Erythromycin Ophthalmic (Romycin)

Additional terms

• cytochrome p450 1A2 (cytochrome P3-450, phenacetin deethylase, cytochrome p450-4, CYP1A2)
• cytochrome P450 3A4 (cytochrome P450 C3, nifedipine oxidase, P450-PCN1, NF-25, CYP3A4)

Component of

• benzoyl peroxide/erythromycin (Benzamycin)

Database

• PubChem: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=12560
• PubChem: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=3255
• PubChem: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=8233