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Here’s what to ask a doctor about hereditary angioedema

Nafcillin

Pronunciation

Pronunciation

(naf SIL in)

Index Terms

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

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Solution, Intravenous:

Generic: 1 g/50 mL (50 mL); 2 g/100 mL (100 mL)

Solution Reconstituted, Injection:

Generic: 1 g (1 ea); 2 g (1 ea); 10 g (1 ea)

Solution Reconstituted, Injection [preservative free]:

Generic: 1 g (1 ea); 2 g (1 ea); 10 g (1 ea)

Solution Reconstituted, Intravenous:

Generic: 1 g (1 ea); 2 g (1 ea)

Pharmacologic Category

  • Antibiotic, Penicillin

Pharmacology

Interferes with bacterial cell wall synthesis during active multiplication, causing cell wall destruction and resultant bactericidal activity against susceptible bacteria; resistant to inactivation by staphylococcal penicillinase

Distribution

Widely distributed; CSF penetration is poor but enhanced by meningeal inflammation

Vd: Neonates: 0.24 to 0.53 L/kg; Children: 0.85 to 0.91 L/kg; Adults: 0.57 to 1.55 L/kg

Metabolism

Primarily hepatic; undergoes enterohepatic recirculation

Excretion

Primarily feces; urine (~30% as unchanged drug)

Time to Peak

Serum: IM: 30-60 minutes

Half-Life Elimination

Neonates <3 weeks: 2.2 to 5.5 hours; 4 to 9 weeks: 1.2 to 2.3 hours

Infants and Children 1 month to 14 years: 0.75 to 1.9 hours

Adults: Normal renal/hepatic function: 33 to 61 minutes

Protein Binding

~90%; primarily to albumin

Special Populations: Hepatic Function Impairment

Plasma clearance is significantly decreased and excretion in urine was significantly increased from approximately 30% to 50% in patients with biliary obstruction and cirrhosis.

Use: Labeled Indications

Staphylococcal infections: Treatment of infections caused by susceptible penicillinase-producing staphylococci; empiric therapy in suspected cases of resistant staphylococcal infections.

Contraindications

Hypersensitivity to nafcillin, or any component of the formulation, or penicillins

Dosing: Adult

Endocarditis, treatment: Methicillin-susceptible Staphylococcus aureus (MSSA) (off-label dose): IV:

Native valve: 12 g/day in 4 or 6 divided doses (ie, 2 g every 4 hours or 3 g every 6 hours) for 6 weeks. Note: Dosing intended for complicated right-sided infective endocarditis (IE) or left-sided IE. For uncomplicated right-sided IE, 2 weeks of therapy may be adequate (AHA [Baddour 2015]).

Prosthetic valve: 12 g/day in 6 divided doses (ie, 2 g every 4 hours) for ≥6 weeks (use with rifampin for entire course and gentamicin for first 2 weeks) (AHA [Baddour 2015])

Prosthetic joint infections (off-label dose): Staphylococci (oxacillin-susceptible): 1.5 to 2 g every 4 to 6 hours for 4 to 6 weeks (2 to 6 weeks if in combination with rifampin), followed by oral antibiotic treatment and suppressive regimens (Osmon 2013)

Skin and soft tissue infections (IDSA [Stevens 2014]):

Due to methicillin-susceptible Staphylococcus aureus (MSSA) (off-label dose): IV: 1 to 2 g every 4 hours for 7 to 14 days

Necrotizing infection due to MSSA (off-label use): IV: 1 to 2 g every 4 hours; continue until further debridement is not necessary, patient has clinically improved, and patient is afebrile for 48 to 72 hours

Streptococcal skin infections (off-label use): IV: 1 to 2 g every 4 to 6 hours (IDSA [Stevens 2014])

Surgical site infections (trunk or extremity [away from axilla or perineum]) (off-label use): IV: 2 g every 6 hours (IDSA [Stevens 2014])

Dosing: Geriatric

Refer to adult dosing.

Dosing: Pediatric

Mild-to-moderate infections: IM, IV: 100 to 150 mg/kg/day in divided doses every 6 hours (maximum dose: 4,000 mg daily) (Red Book [AAP 2015])

Severe infections: IM, IV: 150 to 200 mg/kg/day in divided doses every 4 to 6 hours (Red Book [AAP 2015]); for life-threatening infection (eg, meningitis), 200 mg/kg/day in divided doses every 6 hours (maximum dose: 12 g daily) (Tunkel 2004)

Skin and soft tissue infections (IDSA [Stevens 2014]):

Due to methicillin-susceptible Staphylococcus aureus (MSSA): IV: 100 to 150 mg/kg/day in divided doses every 6 hours for 7 to 14 days

Necrotizing infection due to MSSA (off-label use): IV: 200 mg/kg/day in divided doses every 6 hours; continue until further debridement is not necessary, patient has clinically improved, and patient is afebrile for 48 to 72 hours

Streptococcal skin infections (off-label use): IV: 200 mg/kg/day in divided doses every 6 hours (IDSA [Stevens 2014])

Dosing: Renal Impairment

No dosage adjustment is necessary unless in the setting of concomitant hepatic impairment; however, manufacturer labeling does not provide specific dosage adjustments.

Poorly dialyzed. No supplemental dose or dosage adjustment necessary, including patients on intermittent hemodialysis, peritoneal dialysis, or continuous renal replacement therapy (eg, CVVHD) (Aronoff 2007; Heintz 2009).

Dosing: Hepatic Impairment

There are no dosage adjustments provided in the manufacturer's labeling. Nafcillin primarily undergoes hepatic metabolism; dosage adjustment may be necessary, particularly in the setting of concomitant renal impairment.

Administration

IM: Administer as a deep intragluteal injection; rotate injection sites.

IV: Infuse over 30-60 minutes. Vesicant; ensure proper needle or catheter placement prior to and during IV infusion. Avoid extravasation.

Extravasation management: If extravasation occurs, stop infusion immediately and disconnect (leave needle/cannula in place); gently aspirate extravasated solution (do NOT flush the line); initiate hyaluronidase antidote; remove needle/cannula (if not using IV hyaluronidase antidote), apply dry cold compresses (Hurst 2004); elevate extremity.

Hyaluronidase: Intradermal or SubQ: Inject a total of 1 mL (15 units/mL) as five separate 0.2 mL injections (using a 25-gauge needle) into area of extravasation at the leading edge in a clockwise manner (MacCara, 1983; Zenk, 1981).

Dietary Considerations

Some products may contain sodium.

Compatibility

Stable in dextran 40 10% in dextrose, D5LR, D51/4NS, D51/2NS, D5NS, D5W, D10NS, D10W, LR, NS.

Y-site administration: Incompatible with caspofungin acetate, diltiazem, insulin (regular), labetalol, midazolam, verapamil.

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: Store at 20°C to 25°C (68°F to 77°F). Reconstituted parenteral solution is stable for 3 days at room temperature and 7 days when refrigerated. For IV infusion in NS or D5W, solution is stable for 24 hours at room temperature and 7 days when refrigerated.

Solutions for ambulatory IV infusion reservoirs (eg, >24-hour supply) may be subject to inadvertent exposure to temperatures higher than recommended due to heat radiation from patient's skin; lower concentrations of preparation may be needed to prevent precipitation of solution in some circumstances (Chan 2005).

Drug Interactions

Antihepaciviral Combination Products: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Antihepaciviral Combination Products. Avoid combination

ARIPiprazole: CYP3A4 Inducers may decrease the serum concentration of ARIPiprazole. Management: Double the oral aripiprazole dose and closely monitor response. Reduce oral aripiprazole dose to 10-15 mg/day (for adults) if the inducer is discontinued. Avoid use of CYP3A4 inducers for more than 14 days with extended-release injectable aripiprazole. Consider therapy modification

Asunaprevir: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Asunaprevir. Avoid combination

Axitinib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Axitinib. Avoid combination

BCG (Intravesical): Antibiotics may diminish the therapeutic effect of BCG (Intravesical). Avoid combination

BCG Vaccine (Immunization): Antibiotics may diminish the therapeutic effect of BCG Vaccine (Immunization). Monitor therapy

Bedaquiline: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Bedaquiline. Avoid combination

Bosutinib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Bosutinib. Avoid combination

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

Cholera Vaccine: Antibiotics may diminish the therapeutic effect of Cholera Vaccine. Avoid combination

Clarithromycin: CYP3A4 Inducers (Moderate) may increase serum concentrations of the active metabolite(s) of Clarithromycin. CYP3A4 Inducers (Moderate) may decrease the serum concentration of Clarithromycin. Management: Consider alternative antimicrobial therapy for patients receiving a CYP3A inducer. Drugs that enhance the metabolism of clarithromycin into 14-hydroxyclarithromycin may alter the clinical activity of clarithromycin and impair its efficacy. Consider therapy modification

Cobimetinib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Cobimetinib. Avoid combination

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

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

CYP3A4 Substrates: CYP3A4 Inducers (Moderate) may decrease the serum concentration of CYP3A4 Substrates. Monitor therapy

Daclatasvir: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Daclatasvir. Management: Increase the daclatasvir dose to 90 mg once daily if used with a moderate CYP3A4 inducer. Consider therapy modification

Elbasvir: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Elbasvir. Avoid combination

Estriol (Systemic): CYP3A4 Inducers (Moderate) may decrease the serum concentration of Estriol (Systemic). Monitor therapy

Estriol (Topical): CYP3A4 Inducers (Moderate) may decrease the serum concentration of Estriol (Topical). Monitor therapy

FentaNYL: CYP3A4 Inducers (Moderate) may decrease the serum concentration of FentaNYL. Monitor therapy

Flibanserin: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Flibanserin. Avoid combination

Grazoprevir: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Grazoprevir. Avoid combination

GuanFACINE: CYP3A4 Inducers (Moderate) may decrease the serum concentration of GuanFACINE. Management: Increase the guanfacine dose by up to double when initiating concomitant therapy with moderate CYP3A4 inducers. Increase guanfacine dose gradually over 1-2 weeks if moderate CYP3A4 inducer therapy is just beginning. Consider therapy modification

HYDROcodone: CYP3A4 Inducers (Moderate) may decrease the serum concentration of HYDROcodone. Monitor therapy

Ibrutinib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Ibrutinib. Management: Although moderate CYP3A inducers are not specifically contraindicated with ibrutinib, prescribing information indicates that they may decrease AUC up to 3-fold. If possible, alternatives with less CYP3A induction should be considered. Consider therapy modification

Ifosfamide: CYP3A4 Inducers (Moderate) may decrease serum concentrations of the active metabolite(s) of Ifosfamide. CYP3A4 Inducers (Moderate) may increase serum concentrations of the active metabolite(s) of Ifosfamide. Monitor therapy

Lactobacillus and Estriol: Antibiotics may diminish the therapeutic effect of Lactobacillus and Estriol. Monitor therapy

Methotrexate: Penicillins may increase the serum concentration of Methotrexate. Monitor therapy

Mirodenafil: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Mirodenafil. 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. Monitor therapy

Nisoldipine: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Nisoldipine. Avoid combination

Olaparib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Olaparib. Avoid combination

Palbociclib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Palbociclib. Management: The US label does not provide specific recommendations concerning use with moderate CYP3A4 inducers, but the Canadian label recommends avoiding use of moderate CYP3A4 inducers. Consider therapy modification

Probenecid: May increase the serum concentration of Penicillins. Management: Avoid the routine use of penicillins and probenecid, but this combination may be used advantageously in select cases with careful monitoring. Monitor for toxic effects of penicillins if probenecid is initiated or the dose is increased. Consider therapy modification

Ranolazine: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Ranolazine. Avoid combination

Rolapitant: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Rolapitant. Management: Monitor for reduced rolapitant response. Recommended dexamethasone regimens should be used with rolapitant. Higher dexamethasone doses or more prolonged use may increase the potential for a significant interaction. Monitor therapy

SAXagliptin: CYP3A4 Inducers may decrease the serum concentration of SAXagliptin. Monitor therapy

Simeprevir: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Simeprevir. Avoid combination

Sodium Picosulfate: Antibiotics may diminish the therapeutic effect of Sodium Picosulfate. Management: Consider using an alternative product for bowel cleansing prior to a colonoscopy in patients who have recently used or are concurrently using an antibiotic. Consider therapy modification

Sonidegib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Sonidegib. Avoid combination

Tetracycline Derivatives: May diminish the therapeutic effect of Penicillins. Consider therapy modification

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 3 days after cessation of antibacterial agents. Consider therapy modification

Velpatasvir: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Velpatasvir. Avoid combination

Venetoclax: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Venetoclax. Avoid combination

Vitamin K Antagonists (eg, warfarin): Nafcillin may diminish the anticoagulant effect of Vitamin K Antagonists. Management: Consider choosing an alternative antibiotic. Monitor for decreased therapeutic effects and need for dose adjustments of oral anticoagulants if nafcillin is initiated/dose increased, or increased effects if nafcillin is discontinued/dose decreased. Consider therapy modification

Zolpidem: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Zolpidem. Monitor therapy

Test Interactions

Positive Coombs' test (direct), false-positive urinary and serum proteins; may inactivate aminoglycosides in vitro

Adverse Reactions

Frequency not always defined.

Central nervous system: Neurotoxicity (high doses)

Gastrointestinal: C. difficile-associated diarrhea

Hematologic: Agranulocytosis, bone marrow depression, neutropenia

Local: Inflammation, pain, phlebitis, skin sloughing, swelling, and thrombophlebitis at the injection site; 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

<1% (Limited to important or life-threatening): ALT increased, AST increased, bilirubin increased, cholestatic hepatitis, diarrhea, drug-induced lupus erythematosus, fever, hypokalemia, itching, nausea, rash (including bullous skin eruptions), vomiting

Warnings/Precautions

Concerns related to adverse effects:

• Anaphylactic/hypersensitivity reactions: Serious and occasionally severe or fatal hypersensitivity (anaphylactic) 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 patients with a history of significant allergies and/or asthma; discontinue treatment and institute appropriate therapy if an allergic reaction occurs.

• Neurotoxic effects: Large IV or intraventricular doses have been associated with neurotoxicity; use caution, especially in patients with concomitant renal and hepatic dysfunction.

• 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:

• Heart failure: May contain a significant amount of sodium; use with caution in patients with heart failure.

• Hepatic/renal impairment: Use with caution in patients with concomitant hepatic and renal impairment; dosage adjustment recommended.

Concurrent drug therapy issues:

• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

Special populations:

• Pediatric: Use with caution in pediatric patients; elimination of drug may be decreased.

Other warnings/precautions:

• Extravasation: Vesicant; avoid extravasation of IV infusions; ensure proper catheter or needle position prior to and during infusion.

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

Pregnancy Risk Factor

B

Pregnancy Considerations

Adverse events have not been observed in animal reproduction studies. Information specific to nafcillin use in pregnancy is limited. Maternal use of penicillins has generally not resulted in an increased risk of birth defects.

Patient Education

• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

• Patient may experience nausea, vomiting, or diarrhea. Have patient report immediately to prescriber muscle weakness, muscle pain, joint pain, abdominal pain, bruising, bleeding, severe dizziness, passing out, chills, pharyngitis, severe loss of strength and energy, severe injection site pain, redness, burning, edema, or irritation, or signs of Clostridium difficile (C. diff)-associated diarrhea (stomach pain or cramps, very loose or watery stools, or bloody stools) (HCAHPS).

• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for healthcare professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience and judgment in diagnosing, treating and advising patients.

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