This information has been developed and provided by an independent third-party source. Merck & Co., Inc. does not endorse and is not responsible for the accuracy of the content, or for practices or standards of non-Merck sources.

Pronunciation

(naf SIL in)

Generic Available (U.S.)

Yes

Index Terms

• Ethoxynaphthamido Penicillin Sodium
• Nafcillin Sodium
• Nallpen
• Sodium Nafcillin

Canadian Brand Names

• Nallpen®
• Unipen®

Pharmacologic Category

• Antibiotic, Penicillin

Pharmacologic Category Synonyms

• Penicillin Derivative Antibiotic

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

BCG: Antibiotics may diminish the therapeutic effect of BCG. Risk X: Avoid combination

Calcium Channel Blockers: Nafcillin may increase the metabolism of Calcium Channel Blockers. Exceptions: Clevidipine. Risk D: Consider therapy modification

Contraceptives (Estrogens): Nafcillin may increase the metabolism of Contraceptives (Estrogens). Management: Use of an alternative, nonhormonal form of contraception during nafcillin therapy is recommended. Risk D: Consider therapy modification

CycloSPORINE: Nafcillin may increase the metabolism of CycloSPORINE. Risk C: Monitor therapy

CycloSPORINE (Systemic): Nafcillin may increase the metabolism of CycloSPORINE (Systemic). Risk C: Monitor therapy

CYP3A4 Substrates: CYP3A4 Inducers (Strong) may increase the metabolism of CYP3A4 Substrates. Risk C: Monitor therapy

Dienogest: CYP3A4 Inducers (Strong) may decrease the serum concentration of Dienogest. Management: Avoid use of dienogest for contraception when using medications that induce CYP3A4 and for at least 28 days after discontinuation of a CYP3A4 inducer. An alternative form of contraception should be used during this time. Risk X: Avoid combination

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

Exemestane: CYP3A4 Inducers (Strong) may decrease the serum concentration of Exemestane. Management: Exemestane prescribing information recommends using an increased dose (50 mg/day) in patients receiving concurrent strong CYP3A4 inducers. Monitor patients closely for evidence of toxicity and/or inadequate clinical response. Risk D: Consider therapy modification

Fusidic Acid: May diminish the therapeutic effect of Penicillins. Risk D: Consider therapy modification

Gefitinib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Gefitinib. Management: In the absence of severe adverse drug reactions, consider increasing gefitinib dose to 500 mg daily in patients receiving strong CYP3A4 inducers. Carefully monitor clinical response and development of adverse reactions. Risk D: Consider therapy modification

GuanFACINE: CYP3A4 Inducers (Strong) may decrease the serum concentration of GuanFACINE. Management: Consider increasing the guanfacine dose (within the labeled dosage range) when such a combination is used. Risk D: Consider therapy modification

Imatinib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Imatinib. Management: Avoid concurrent use of imatinib with strong CYP3A4 inducers when possible. If such a combination must be used, increase imatinib dose by at least 50% and monitor the patient's clinical response closely. Risk D: Consider therapy modification

Ixabepilone: CYP3A4 Inducers (Strong) may decrease the serum concentration of Ixabepilone. Management: Avoid this combination whenever possible. If this combination must be used, a gradual increase in ixabepilone dose from 40 mg/m² to 60 mg/m² (given as a 4-hour infusion), as tolerated, should be considered. Risk D: Consider therapy modification

Linagliptin: CYP3A4 Inducers (Strong) may decrease the serum concentration of Linagliptin. Management: Strongly consider using an alternative to any strong CYP3A4 inducer in patients who are being treated with linagliptin. If this combination is used, monitor patients closely for evidence of reduced linagliptin effectiveness. Risk D: Consider therapy modification

Lurasidone: CYP3A4 Inducers (Strong) may decrease the serum concentration of Lurasidone. Risk X: Avoid combination

Maraviroc: CYP3A4 Inducers (Strong) may decrease the serum concentration of Maraviroc. Management: Increase maraviroc adult dose to 600 mg twice daily when used with strong CYP3A4 inducers. This does not apply to patients also receiving strong CYP3A4 inhibitors. Do not use maraviroc with strong CYP3A4 inducers in patients with Clcr less than 30 mL/min. 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

Pazopanib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Pazopanib. Risk X: Avoid combination

Praziquantel: CYP3A4 Inducers (Strong) may decrease the serum concentration of Praziquantel. Management: Avoid concomitant use of praziquantel with strong CYP3A4 inducers. Discontinue rifampin 4 weeks prior to initiation of praziquantel therapy. Rifampin may be resumed the day following praziquantel completion. Risk X: Avoid combination

Probenecid: May increase the serum concentration of Penicillins. Risk C: Monitor therapy

Ranolazine: CYP3A4 Inducers (Strong) may decrease the serum concentration of Ranolazine. Risk X: Avoid combination

Roflumilast: CYP3A4 Inducers (Strong) may decrease the serum concentration of Roflumilast. Management: Roflumilast U.S. prescribing information recommends against combining strong CYP3A4 inducers with roflumilast. The Canadian product monograph makes no such recommendation but notes that such agents may reduce roflumilast therapeutic effects. Risk X: Avoid combination

RomiDEPsin: CYP3A4 Inducers (Strong) may decrease the serum concentration of RomiDEPsin. 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. Management: Vaccination with live attenuated typhoid vaccine (Ty21a) should be avoided in patients being treated with systemic antibacterial agents. Use of this vaccine should be postponed until at least 24 hours after cessation of antibacterial agents. Risk D: Consider therapy modification

Ulipristal: CYP3A4 Inducers (Strong) may decrease the serum concentration of Ulipristal. Risk C: Monitor therapy

Vandetanib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Vandetanib. Risk X: Avoid combination

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

Poorly dialyzed; no supplemental dose or dosage adjustment necessary, including patients on intermittent hemodialysis, peritoneal dialysis, or continuous renal replacement therapy (eg, CVVHD).

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. Some products may contain sodium.

Patient Education

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 or opportunistic infection (eg, fever, chills, sore throat, burning urination). Report persistent side effects or if condition does not respond to treatment.

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. Infusion/Injection site must be monitored closely to prevent extravasation (use ice packs). Monitor for hypersensitivity and opportunistic infection (eg, fever, chills, unhealed sores, white plaques in mouth or vagina, purulent vaginal discharge).

Oncology: Vesicant

Vesicant; 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: 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 - Executive Summary: Endorsed by the Infectious Diseases Society of America,” Circulation, 2005, 111(23):3167-184.

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 May 2011