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Pronunciation
(naf SIL in)
Index Terms
Generic Available
Yes
Canadian Brand Names
Pharmacologic Category
Pharmacologic Category Synonyms
Use: Labeled Indications
Treatment of infections such as osteomyelitis, septicemia, endocarditis, and CNS infections caused by susceptible strains of staphylococci species
Pregnancy Risk Factor
B
Pregnancy Considerations
Adverse events have not been observed in animal studies; therefore, nafcillin is classified as pregnancy category B. There is no available data on the placental transfer of nafcillin. Human experience with the penicillins during pregnancy has not shown any positive evidence of adverse effects on the fetus.
Lactation
Enters breast milk/use caution
Breast-Feeding Considerations
It is not known if nafcillin crosses into human milk. The manufacturer recommends that caution be exercised when administering nafcillin to nursing women. Other penicillins distribute into human milk and are considered safe for use during breast-feeding. Nondose-related effects could include modification of bowel flora.
Contraindications
Hypersensitivity to nafcillin, or any component of the formulation, or penicillins; premixed injection may contain corn-derived dextrose and its use is contraindicated in patients with allergy to corn-related products
Warnings/Precautions
Concerns related to adverse effects:
• Anaphylactoid/hypersensitivity reactions: Serious and occasionally severe or fatal hypersensitivity (anaphylactoid) reactions have been reported in patients on penicillin therapy, especially with a history of beta-lactam hypersensitivity, history of sensitivity to multiple allergens, or previous IgE-mediated reactions (eg, anaphylaxis, angioedema, urticaria). Use with caution in asthmatic patients.
• Superinfection: Prolonged use may result in fungal or bacterial superinfection, including C. difficile-associated diarrhea (CDAD) and pseudomembranous colitis; CDAD has been observed >2 months postantibiotic treatment.
Disease-related concerns:
• Hepatic/renal impairment: Use with caution in patients with concomitant hepatic and renal impairment; dosage adjustment recommended.
Special populations:
• Neonates: Use with caution in neonates; elimination of drug is slow.
Other warnings/precautions:
• Extravasation: Avoid extravasation of I.V. infusions.
Adverse Reactions
Frequency not defined.
Central nervous system: Neurotoxicity (high doses)
Gastrointestinal: Pseudomembranous colitis
Hematologic: Agranulocytosis, bone marrow depression, neutropenia
Local: Inflammation, pain, phlebitis, skin sloughing, swelling, and thrombophlebitis at the injection site; oxacillin (less likely to cause phlebitis) is often preferred in pediatric patients; tissue necrosis with sloughing (SubQ extravasation)
Renal: Interstitial nephritis (rare), renal tubular damage (rare)
Miscellaneous: Anaphylaxis, hypersensitivity reactions (immediate and delayed; general incidence of 1% to 10% for penicillins), serum sickness
Metabolism/Transport Effects
Induces CYP3A4 (strong)
Drug Interactions
Calcium Channel Blockers: Nafcillin may increase the metabolism of Calcium Channel Blockers. Exceptions: Clevidipine. Risk D: Consider therapy modification
CycloSPORINE: Nafcillin may increase the metabolism of CycloSPORINE. Risk C: Monitor therapy
CYP3A4 Substrates: CYP3A4 Inducers (Strong) may increase the metabolism of CYP3A4 Substrates. Risk C: Monitor therapy
Dronedarone: CYP3A4 Inducers (Strong) may decrease the serum concentration of Dronedarone. Risk X: Avoid combination
Everolimus: CYP3A4 Inducers (Strong) may decrease the serum concentration of Everolimus. Management: Avoid concurrent use of strong CYP3A4 inducers, but if strong CYP3A4 inducers cannot be avoided, consider gradually (in 5 mg increments) increasing the everolimus dose from 10 mg/day to 20 mg/day (adult doses). Risk X: Avoid combination
Fusidic Acid: May diminish the therapeutic effect of Penicillins. Risk D: Consider therapy modification
Maraviroc: CYP3A4 Inducers (Strong) may decrease the serum concentration of Maraviroc. Management: Maraviroc adult dose should be increased to 600 mg twice daily when used with strong CYP3A4 inducers. This recommendation only applies in the absence of a concurrent strong CYP3A4 inhibitor (e.g., most protease inhibitors). Risk D: Consider therapy modification
Methotrexate: Penicillins may decrease the excretion of Methotrexate. Risk C: Monitor therapy
Mycophenolate: Penicillins may decrease serum concentrations of the active metabolite(s) of Mycophenolate. This effect appears to be the result of impaired enterohepatic recirculation. Risk C: Monitor therapy
Nilotinib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Nilotinib. Risk X: Avoid combination
Oral Contraceptive (Estrogens): Nafcillin may increase the metabolism of Oral Contraceptive (Estrogens). Risk D: Consider therapy modification
Pazopanib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Pazopanib. Risk X: Avoid combination
Ranolazine: CYP3A4 Inducers (Strong) may decrease the serum concentration of Ranolazine. Risk X: Avoid combination
Saxagliptin: CYP3A4 Inducers may decrease the serum concentration of Saxagliptin. Risk C: Monitor therapy
Sorafenib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Sorafenib. Risk D: Consider therapy modification
Tadalafil: CYP3A4 Inducers (Strong) may decrease the serum concentration of Tadalafil. Management: Erectile dysfunction: monitor for decreased effectiveness - no standard dose adjustments recommended. Avoid use of tadalafil for pulmonary arterial hypertension in patients receiving a strong CYP3A4 inducer. Risk D: Consider therapy modification
Tetracycline Derivatives: May diminish the therapeutic effect of Penicillins. Risk D: Consider therapy modification
Tolvaptan: CYP3A4 Inducers (Strong) may decrease the serum concentration of Tolvaptan. Management: If concurrent use is necessary, increased doses of tolvaptan (with close monitoring for toxicity and clinical response) may be needed. Risk X: Avoid combination
Typhoid Vaccine: Antibiotics may diminish the therapeutic effect of Typhoid Vaccine. Only the live attenuated Ty21a strain is affected. Risk D: Consider therapy modification
Uricosuric Agents: May decrease the excretion of Penicillins. Risk C: Monitor therapy
Vitamin K Antagonists (eg, warfarin): Nafcillin may diminish the anticoagulant effect of Vitamin K Antagonists. Risk D: Consider therapy modification
Storage
Premixed infusions: Store in a freezer at -20°C (4°F). Thaw at room temperature or under refrigeration only. Thawed bags are stable for 21 days under refrigeration or 72 hours at room temperature. Do not refreeze.
Vials: Reconstituted parenteral solution is stable for 3 days at room temperature and 7 days when refrigerated or 12 weeks when frozen. For I.V. infusion in NS or D5W, solution is stable for 24 hours at room temperature and 96 hours when refrigerated.
Compatibility
Stable in dextran 40 10% in dextrose, D5LR, D51/4NS, D51/2NS, D5NS, D5W, D10NS, D10W, LR, NS; variable stability (consult detailed reference) in peritoneal dialysis solution, TPN.
Y-site administration: Compatible: Acyclovir, atropine, cyclophosphamide, diazepam, enalaprilat, esmolol, famotidine, fentanyl, fluconazole, foscarnet, heparin, hydromorphone, magnesium sulfate, morphine, nicardipine, perphenazine, propofol, theophylline, zidovudine. Incompatible: Droperidol, fentanyl and droperidol, insulin (regular), labetalol, midazolam, nalbuphine, pentazocine, verapamil. Variable (consult detailed reference): Diltiazem, meperidine, TPN, vancomycin.
Compatibility in syringe: Compatible: Cimetidine, heparin.
Compatibility when admixed: Compatible: Chloramphenicol, chlorothiazide, dexamethasone sodium phosphate, diphenhydramine, ephedrine, heparin, hydroxyzine, lidocaine, potassium chloride, prochlorperazine edisylate, sodium bicarbonate, sodium lactate. Incompatible: Ascorbic acid injection, aztreonam, bleomycin, cytarabine, gentamicin, hydrocortisone sodium succinate, methylprednisolone sodium succinate, promazine. Variable (consult detailed reference): Aminophylline, verapamil, vitamin B complex with C.
Mechanism of Action
Interferes with bacterial cell wall synthesis during active multiplication, causing cell wall death and resultant bactericidal activity against susceptible bacteria
Pharmacodynamics/Kinetics
Distribution: Widely distributed; CSF penetration is poor but enhanced by meningeal inflammation
Protein binding: ~90%; primarily to albumin
Metabolism: Primarily hepatic; undergoes enterohepatic recirculation
Half-life elimination:
Neonates: <3 weeks: 2.2-5.5 hours; 4-9 weeks: 1.2-2.3 hours
Children 3 months to 14 years: 0.75-1.9 hours
Adults: Normal renal/hepatic function: 30-60 minutes
Time to peak, serum: I.M.: 30-60 minutes
Excretion: Primarily feces; urine (10% to 30% as unchanged drug)
Dosage
Usual dosage range:
Neonates: I.M., I.V.:
1200-2000 g, <7 days: 50 mg/kg/day divided every 12 hours
>2000 g, <7 days: 75 mg/kg/day divided every 8 hours
1200-2000 g, ?7 days: 75 mg/kg/day divided every 8 hours
>2000 g, ?7 days: 100-140 mg/kg/day divided every 6 hours
Children:
I.M.: 25 mg/kg twice daily
I.V.: 50-200 mg/kg/day in divided doses every 4-6 hours (maximum: 12 g/day)
Adults:
I.M.: 500 mg every 4-6 hours
I.V.: 500-2000 mg every 4-6 hours
Indication-specific dosing:
Children:
Mild-to-moderate infections: I.M., I.V.: 50-100 mg/kg/day in divided doses every 6 hours
Severe infections: I.M., I.V.: 100-200 mg/kg/day in divided doses every 4-6 hours (maximum dose: 12 g/day)
Staphylococcal endocarditis: I.V.:
Native valve: 200 mg/kg/day in divided doses every 4-6 hours for 6 weeks
Prosthetic valve: 200 mg/kg/day in divided doses every 4-6 hours for ?6 weeks (use with rifampin and gentamicin)
Adults: I.V.:
Endocarditis: MSSA:
Native valve: 12 g/24 hours in 4-6 divided doses for 6 weeks
Prosthetic valve: 12 g/24 hours in 6 divided doses for ?6 weeks (use with rifampin and gentamicin)
Joint:
Bursitis, septic: 2 g every 4 hours
Prosthetic: 2 g every 4-6 hours with rifampin for 6 weeks
Staphylococcus aureus,
methicillin-susceptible infections, including brain abscess, empyema, erysipelas, mastitis, myositis, orbital cellulitis, osteomyelitis, pneumonia, splenic abscess, toxic shock, urinary tract (perinephric abscess): 2 g every 4 hours
Dosing adjustment in renal impairment: Not necessary unless renal impairment is in the setting of concomitant hepatic impairment
Dialysis: Not dialyzable (0% to 5%) via hemodialysis; supplemental dosage not necessary with hemo- or peritoneal dialysis or continuous arteriovenous or venovenous hemofiltration
Dosing adjustment in hepatic impairment: In patients with both hepatic and renal impairment, modification of dosage may be necessary; no data available.
Administration: I.M.
Rotate injection sites.
Administration: I.V.
Vesicant. Administer around-the-clock to promote less variation in peak and trough serum levels. Infuse over 30-60 minutes.
Administration: I.V. Detail
Extravasation management: Use cold packs.
Hyaluronidase: Add 1 mL NS to 150 unit vial to make 150 units/mL of concentration; mix 0.1 mL of above with 0.9 mL NS in 1 mL syringe to make final concentration = 15 units/mL.
pH: 6.0-8.5
Monitoring Parameters
Baseline and periodic CBC with differential; periodic urinalysis, BUN, serum creatinine, AST and ALT; observe for signs and symptoms of anaphylaxis during first dose
Test Interactions
Positive Coombs' test (direct), false-positive urinary and serum proteins; may inactivate aminoglycosides in vitro
Dietary Considerations
Premixed injection may contain corn-derived dextrose and its use is contraindicated in patients with allergy to corn-related products. Sodium content of 1 g: 76.6 mg (3.33 mEq).
Patient Education
Do not take any new medication during therapy unless approved by prescriber. This medication can only be administered by infusion or injection. Report immediately any redness, swelling, burning, or pain at injection/infusion site; respiratory difficulty or swallowing; chest pain; persistent diarrhea; or rash. May cause nausea (small, frequent meals, frequent mouth care, chewing gum, or sucking lozenges may help); or opportunistic infection (eg, fever, chills, sore throat, burning urination, fatigue). Report persistent side effects or if condition does not respond to treatment. Breast-feeding precaution: Consult prescriber if breast-feeding.
Geriatric Considerations
Nafcillin has not been studied exclusively in the elderly, however, given its route of elimination, dosage adjustments based upon age and renal function is not necessary
Dental Health: Effects on Dental Treatment
Key adverse event(s) related to dental treatment: Prolonged use of penicillins may lead to the development of oral candidiasis.
Dental Health: Vasoconstrictor/Local Anesthetic Precautions
No information available to require special precautions
Mental Health: Effects on Mental Status
Penicillins reported to cause apprehension, illusions, hallucinations, depersonalization, agitation, insomnia, and encephalopathy
Mental Health: Effects on Psychiatric Treatment
May cause neutropenia; use caution with clozapine and carbamazepine
Nursing: Physical Assessment/Monitoring
Assess results of culture and sensitivity tests and allergy history prior to starting therapy. Assess potential for interactions with other pharmacological agents patient may be taking (eg, increased [toxic] or decreased [subtherapeutic] levels/effects. Infusion/Injection site must be monitored closely to prevent extravasation (use ice packs). Assess for therapeutic effect (resolution of infection) and adverse reactions (eg, hypersensitivity, opportunistic infection [eg, fever, chills, unhealed sores, white plaques in mouth or vagina, purulent vaginal discharge, fatigue)]. Teach patient possible side effects/appropriate interventions and adverse symptoms to report.
Oncology: Emetic Potential
Very low (<10%)
Oncology: Vesicant
Yes; see Management of Drug Extravasations.
Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Infusion [premixed iso-osmotic dextrose solution]: 1 g (50 mL); 2 g (100 mL)
Injection, powder for reconstitution, as sodium: 1 g, 2 g, 10 g
References
Baddour LM, Wilson WR, Bayer AS, et al, “Infective Endocarditis. Diagnosis, Antimicrobial Therapy, and Management of Complications. A Statement for Healthcare Professionals from the Committee on Rheumatic Fever, Endocarditis, and Kawasaki Disease, Council on Cardiovascular Disease in the Young, and the Councils on Clinical Cardiology, Stroke, and Cardiovascular Surgery and Anesthesia, American Heart Association,” Circulation, 2005, 111(23):e394-434.
Banner W Jr, Gooch WM 3d, Burckart G, et al, “Pharmacokinetics of Nafcillin in Infants With Low Birth Weights,” Antimicrob Agents Chemother, 1980, 17(4):691-4.
Donowitz GR and Mandell GL, “Beta-Lactam Antibiotics,” N Engl J Med, 1988, 318(7):419-26 and 318(8):490-500.
Wright AJ, “The Penicillins,” Mayo Clin Proc, 1999, 74(3):290-307.
Zenk KE, Dungy CL, and Greene CR, “Nafcillin Extravasation Injury: Use of Hyaluronidase as an Antidote,” Am J Dis Child, 1981, 135(12):1113-4.
Lexi-Comp.com
Last full review/revision November 2009
Content last modified November 2009
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