nafcillin (Nafcil, Unipen, Nallpen)

Introduction

Tradenames: Nafcil, Unipen. 2nd generation penicillin.

Indications

• treatment of serious bacterial infections
  • infectious arthritis, osteomyelitis
  • skin or soft tissue infection
  • urinary tract infection
  • respiratory tract infection
  • bacteremia
• empiric treatment for fever of unknown origin
• mainly indicated for penicillinase-producing Staphylococci

Contraindications

• avoid in patients with hypersensitivity to penicillin

pregnancy category = b

safety in lactation = ?

Dosage

1-2 g IV/IM every 4 hours

• 250-500 mg PO every 4-6 hours.

Pediatrics: 50 mg/kg/day divided every 4-6 hours

Tabs: 250 & 500 mg.

Suspension: 250 mg/5 mL.

Powder for injection: 500 mg, 1 g, 2 g.

Pharmacokinetics

• well distributed to most tissues & fluids
• minimal CSF penetration
• elimination 1/2life is 1 hour with normal or moderately impaired renal function
• protein binding 90%
• 60% is metabolized in the liver
• most is eliminated in the bile, small amounts in the urine
• dosage adjustment not necessary with renal insufficiency
• minimally removed by hemodialysis
• dose adjustment may be warranted in patients with both hepatic & renal insufficiency

elimination via liver

elimination via kidney

protein binding = 90 %

elimination by hemodialysis = -

Monitor

• weekly monitoring for outpatients on parenteral nafcillin
  • liver function tests
  • renal function tests
  • complete blood count

Antimicrobial activity

• Staphylococcus aureus (but not methicillin-resistant S. aureus {MRSA})
• less active than other penicillins against Streptococcus sp.
• lacks enterococcus & anaerobic coverage

Adverse effects

• common (> 10%)
  • phlebitis or irritation at IV site
• uncommon (< 1%)
  • thrombophlebitis, fever, rash, nausea, diarrhea, neutropenia, pain, acute interstitial nephritis, hypersensitivity reactions
• other
• blood dyscrasia (rare)
• elevated serum transaminases
• seizures (rare)

Drug interactions

• probenecid increases & prolongs the 1/2life of nafcillin
• nafcillin induces cyt P450 3A4
  • may diminish levels of drugs metabolized by cyt P450 3A4

• drug interaction(s) anticonvulsants with anti-bacterial agents
• drug interaction(s) of antibiotics with warfarin

Mechanism of action

• inhibition of bacterial wall synthesis
• active against penicillinase-producing organisms

More general terms

• 2nd generation penicillin (penicillinase-resistant)

Additional terms

• cytochrome P450 3A4 (cytochrome P450 C3, nifedipine oxidase, P450-PCN1, NF-25, CYP3A4)

Database

• PubChem: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=8982
• PubChem: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=64712
• PubChem: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=23567
• PubChem: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=23568
• PubChem: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=4414
• PubChem: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=5282391