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Nafcillin

Medically reviewed by Drugs.com. Last updated on Nov 6, 2020.

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. [DSC] = Discontinued product

Solution, Intravenous:

Generic: 2 g/100 mL (100 mL)

Solution, Intravenous [preservative free]:

Generic: 1 g/50 mL (50 mL)

Solution Reconstituted, Injection:

Generic: 1 g (1 ea); 2 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: 2 g (1 ea [DSC])

Solution Reconstituted, Intravenous [preservative free]:

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

Off Label Uses

Catheter-related bloodstream infections

Based on the Infectious Diseases Society of America (IDSA) clinical practice guidelines for the diagnosis and management of intravascular catheter-related infections, nafcillin is effective and recommended for the treatment of catheter-related bloodstream infections caused by methicillin-susceptible S. aureus or methicillin-susceptible coagulase-negative Staphylococcus species.

Skin and soft tissue necrotizing infection

Based on the IDSA guidelines for the diagnosis and management of skin and soft tissue infections (SSTI), nafcillin is an effective and recommended option for treatment of necrotizing infections of the skin, fascia, and muscle due to methicillin-sensitive Staphylococcus aureus.

Streptococcal skin infections

Based on the IDSA guidelines for the diagnosis and management of skin and soft tissue infections (SSTI), nafcillin is an effective and recommended option for treatment of streptococcal skin infections.

Surgical site infections

Based on the IDSA guidelines for the diagnosis and management of SSTIs, nafcillin is an effective and recommended option for treatment of surgical site infections occurring after surgery of the trunk or extremity (away from the axilla or perineum). Systemic antibacterials are not routinely indicated for surgical site infections, but may be beneficial (in conjunction with suture removal plus incision and drainage) in patients with significant systemic response (eg, temperature >38.5ºC, heart rate >110 beats per minute, erythema/induration extending >5 cm from incision, WBC >12,000/mm3).

Contraindications

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

Documentation of allergenic cross-reactivity for beta-lactams (eg, penicillins and cephalosporins) is limited. However, because of similarities in chemical structure and/or pharmacologic actions, the possibility of cross-sensitivity cannot be ruled out with certainty.

Dosing: Adult

Catheter-related bloodstream infections (off-label use): IV: 2 g every 4 hours (IDSA [Mermel 2009])

Endocarditis: 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: Duration 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])

Meningitis, bacterial: Methicillin-susceptible S. aureus (off-label dose): IV: 2 g every 4 hours; consider addition of rifampin if organism is susceptible and prosthetic material is present (IDSA [Tunkel 2004]; IDSA [Tunkel 2017])

Osteomyelitis: Methicillin-susceptible S. aureus (MSSA) (off-label dose): IV: 1.5 to 2 g every 4 to 6 hours or via continuous infusion (IDSA [Berbari 2015])

Prosthetic joint infections: Methicillin-susceptible S. aureus (MSSA) (off-label dose): 1.5 to 2 g every 4 to 6 hours (IDSA [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])

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Geriatric

Refer to adult dosing.

Dosing: Pediatric

General dosing, susceptible infection:

Traditional (intermittent) dosing: Infants, Children, and Adolescents: IM, IV: 100 to 200 mg/kg/day in divided doses every 4 to 6 hours; maximum daily dose: 12 g/day divided every 4 hours; usual maximum dose: 2,000 mg/dose; for severe infections, doses at the higher end of the range should be considered (Bradley 2019; Red Book [AAP 2018]).

Continuous infusion dosing: Limited data available: Children and Adolescents: IV: 150 to 200 mg/kg/day infused continuously over 24 hours; maximum daily dose: 12 g/day. Dosing based on a retrospective case series in 40 pediatric patients (median age: 9 years; interquartile range: 2.3 to 12 years); the reported mean dose was 190 ± 36.4 mg/kg/day; the majority of infections treated were methicillin-susceptible Staphylococcus aureus (MSSA) (87.2% of patients) and coagulase negative staphylococcal species (7.7%); infection sites were primarily bloodstream, musculoskeletal, and skin and soft tissue (Knoderer 2017).

Endocarditis, treatment (AHA [Baltimore 2015]): Children and Adolescents: IV: 200 mg/kg/day in divided doses every 4 to 6 hours; maximum daily dose: 12 g/day divided every 4 hours; treat for at least 4 weeks; longer durations may be necessary; may use in combination with gentamicin for some resistant organisms (AHA [Baltimore 2015]).

Meningitis, including healthcare associated ventriculitis/meningitis; MSSA: Infants, Children, and Adolescents: IV: 200 mg/kg/day in divided doses every 6 hours; maximum daily dose: 12 g/day; usual maximum dose: 2,000 mg/dose (IDSA [Tunkel 2004]; IDSA [Tunkel 2017]).

Skin and soft tissue infections (IDSA [Stevens 2014]): Infants, Children, and Adolescents:

MSSA: IV: 100 to 150 mg/kg/day in divided doses every 6 hours; maximum daily dose: 12 g/day; usual maximum dose: 2,000 mg/dose.

Necrotizing infection due to MSSA: IV: 200 mg/kg/day in divided doses every 6 hours; maximum daily dose: 12 g/day; usual maximum dose: 2,000 mg/dose; continue until further debridement is not necessary, patient has clinically improved, and patient is afebrile for 48 to 72 hours.

Streptococcal skin infections: Infants, Children, and Adolescents: IV: 200 mg/kg/day in divided doses every 6 hours; maximum daily dose: 12 g/day; usual maximum dose: 2,000 mg/dose.

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Reconstitution

Parenteral:

IM: Reconstitute with NS, SWFI or bacteriostatic water for injection; resultant concentration is 250 mg/mL

IV: Reconstitute powder for injection with NS, or SWFI, resultant concentration dependent upon product (see manufacturer's labeling for specific details)

Direct IV injection: Further dilute dose in 15 to 30 mL of NS or SWFI

Intermittent IV infusion: Further dilute in an appropriate fluid, final concentration should not exceed 40 mg/mL (Klaus 1989); in fluid-restricted patients, a higher concentration may be used depending on the diluent (D5W: 71 mg/mL; NS: 62 mg/mL; SWI: 125 mg/mL) (Robinson 1987)

Administration

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

IV: Infuse over 30 to 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, Reynolds 2014); elevate extremity.

Hyaluronidase: Intradermal or SubQ: Inject a total of 1 to 1.7 mL (15 units/mL) as 5 separate 0.2 to 0.3 mL injections (using a 25-gauge needle) into area of extravasation at the leading edge in a clockwise manner (MacCara 1983, Reynolds 2014, Zenk 1981).

Dietary Considerations

Some products may contain sodium.

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

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

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

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

Acemetacin: May increase the serum concentration of Penicillins. Monitor therapy

Alfentanil: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Alfentanil. Management: If concomitant use of alfentanil and moderate CYP3A4 inducers is necessary, consider dosage increase of alfentanil until stable drug effects are achieved. Monitor patients for signs of opioid withdrawal. Consider therapy modification

Aminoglycosides: Penicillins may decrease the serum concentration of Aminoglycosides. Primarily associated with extended spectrum penicillins, and patients with renal dysfunction. Monitor therapy

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

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

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

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

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

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

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

Avapritinib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Avapritinib. 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

Benzhydrocodone: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Benzhydrocodone. Specifically, the serum concentrations of hydrocodone may be reduced. Monitor therapy

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

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

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

Brigatinib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Brigatinib. Management: Avoid concurrent use of brigatinib with moderate CYP3A4 inducers when possible. If combined, increase the daily dose of brigatinib in 30 mg increments after 7 days of treatment with the current brigatinib dose, up to maximum of twice the dose. Consider therapy modification

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

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

Cholera Vaccine: Antibiotics may diminish the therapeutic effect of Cholera Vaccine. Management: Avoid cholera vaccine in patients receiving systemic antibiotics, and within 14 days following the use of oral or parenteral antibiotics. 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

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

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

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

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

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

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

CYP3A4 Substrates (High risk with Inducers): CYP3A4 Inducers (Moderate) may decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). 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

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

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

Deflazacort: CYP3A4 Inducers (Moderate) may decrease serum concentrations of the active metabolite(s) of Deflazacort. Avoid combination

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

Dichlorphenamide: Penicillins may enhance the hypokalemic effect of Dichlorphenamide. Monitor therapy

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

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

Elexacaftor, Tezacaftor, and Ivacaftor: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Elexacaftor, Tezacaftor, and Ivacaftor. Monitor therapy

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

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

Erdafitinib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Erdafitinib. Management: Dose modifications of erdafitinib may be required. See full monograph for details. Consider therapy modification

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

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

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

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

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

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

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

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

Fosaprepitant: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Fosaprepitant. Specifically, CYP3A4 Inducers (Moderate) may decrease serum concentrations of the active metabolite aprepitant. Monitor therapy

Glasdegib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Glasdegib. Management: Avoid use of glasdegib and moderate CYP3A4 inducers whenever possible. If combined, increase glasdegib dose from 100 mg daily to 200 mg daily or from 50 mg daily to 100 mg daily. Resume previous glasdegib dose 7 days after discontinuation of the inducer. Consider therapy modification

Glecaprevir and Pibrentasvir: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Glecaprevir and Pibrentasvir. Monitor therapy

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 extended-release guanfacine dose by up to double when initiating guanfacine in patients taking CYP3A4 inducers or if initiating a CYP3A4 inducer in a patient already taking extended-release guanfacine. Monitor for reduced guanfacine efficacy. Consider therapy modification

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

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

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

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

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

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

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

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

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

Lefamulin: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Lefamulin. Management: Avoid concomitant use of lefamulin with moderate CYP3A4 inducers unless the benefits outweigh the risks. Consider therapy modification

Lefamulin (Intravenous): CYP3A4 Inducers (Moderate) may decrease the serum concentration of Lefamulin (Intravenous). Management: Avoid concomitant use of lefamulin (intravenous) with moderate CYP3A4 inducers unless the benefits outweigh the risks. Consider therapy modification

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

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

Letermovir: Nafcillin may decrease the serum concentration of Letermovir. Avoid combination

Lorlatinib: CYP3A4 Inducers (Moderate) may enhance the hepatotoxic effect of Lorlatinib. CYP3A4 Inducers (Moderate) may decrease the serum concentration of Lorlatinib. Management: Avoid use of lorlatinib with moderate CYP3A4 inducers. If such a combination must be used, monitor AST, ALT, and bilirubin within 48 hours of starting the combination and at least three times within the first week of combined use. Consider therapy modification

Lumacaftor and Ivacaftor: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Lumacaftor and Ivacaftor. Monitor therapy

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

Lurasidone: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Lurasidone. Management: Monitor for decreased lurasidone effects if combined with moderate CYP3A4 inducers and consider increasing the lurasidone dose if coadministered with a moderate CYP3A4 inducer for 7 or more days. Consider therapy modification

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

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

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

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

MethylPREDNISolone: CYP3A4 Inducers (Moderate) may decrease the serum concentration of MethylPREDNISolone. 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

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

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

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

NIFEdipine: Nafcillin may decrease the serum concentration of NIFEdipine. Management: Consider alternative antibiotic therapy in patients receiving nifedipine. Monitor for decreased therapeutic effects of nifedipine if nafcillin is initiated/dose increased, or increased effects if nafcillin is discontinued/dose decreased. Consider therapy modification

NiMODipine: CYP3A4 Inducers (Moderate) may decrease the serum concentration of NiMODipine. 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

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

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

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

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

Perampanel: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Perampanel. Management: Increase the perampanel starting dose to 4 mg/day when perampanel is used concurrently with moderate and strong CYP3A4 inducers. Monitor perampanel response closely, particularly with changes to CYP3A4 inducer therapy. Consider therapy modification

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Tetracyclines: May diminish the therapeutic effect of Penicillins. Monitor therapy

Tezacaftor and Ivacaftor: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Tezacaftor and Ivacaftor. Monitor therapy

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

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

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

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

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

Typhoid Vaccine: Antibiotics may diminish the therapeutic effect of Typhoid Vaccine. Only the live attenuated Ty21a strain is affected. Management: Avoid use of live attenuated typhoid vaccine (Ty21a) in patients being treated with systemic antibacterial agents. Postpone vaccination until 3 days after cessation of antibiotics and avoid starting antibiotics within 3 days of last vaccine dose. Consider therapy modification

Ubrogepant: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Ubrogepant. Management: Use an initial ubrogepant dose of 100 mg and second dose (if needed) of 100 mg when used with a moderate CYP3A4 inducer. Consider therapy modification

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

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

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

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

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

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

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

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

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

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

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

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

Voxelotor: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Voxelotor. Management: Avoid concomitant use of voxelotor and moderate CYP3A4 inducers. If concomitant use is unavoidable, increase the voxelotor dose to 2,500 mg once daily. Consider therapy modification

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

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

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

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

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

Test Interactions

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

Adverse Reactions

The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.

Frequency not defined.

Cardiovascular: Local thrombophlebitis

Central nervous system: Neurotoxicity (high doses)

Gastrointestinal: Cholestasis, Clostridioides (formerly Clostridium) difficile-associated diarrhea

Hematologic & oncologic: Agranulocytosis, bone marrow depression, neutropenia

Hepatic: Increased serum transaminases

Hypersensitivity: Anaphylaxis

Local: Inflammation at injection site, injection site phlebitis, local skin exfoliation (at injection site), pain at injection site, swelling at injection site

Renal: Interstitial nephritis, renal tubular disease

<1%, postmarketing, and/or case reports: Cholestatic hepatitis

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 or a history of sensitivity to multiple allergens. 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.

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

• Hepatic effects: Elevation of liver transaminases and/or cholestasis may occur, specifically with high doses. Reevaluate use in patients who develop worsening hepatic function.

• Hypokalemia: Hypokalemia has been observed in pediatric and adult patients. In a retrospective cohort study comparing tolerability of maximum daily dosing (12 g) of nafcillin and oxacillin in adults (n=224; median age: 56 years; range: 19 to 90 years), the observed incidences of hypokalemia (≤3.3 mmol/L), severe hypokalemia (≤2.9 mmol/L), and acute decreases (≥0.5 mmol/L) from baseline of serum potassium were significantly higher in the nafcillin group compared to oxacillin; median time to onset was 3 to 4 days (Viehman 2016). While a similar level of comparison has not been reported in pediatric patients, hypokalemia has been observed with nafcillin therapy in pediatric patients. In a study of children and adolescents receiving continuous infusion nafcillin at a mean dose of 190 ± 36.4 mg/kg/day, hypokalemia developed in 3 (7.5%) subjects (Knoderer 2017). Hypokalemia was also reported in a retrospective review of 30 pediatric patients with malignancies who received nafcillin in combination with carbenicillin and gentamicin; hypokalemia was reported in 50% (24/48) of antibiotic courses and usual reported onset was 4 days of therapy (Stapleton 1976). Consider serum potassium monitoring with high doses or prolonged therapy.

• 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.

Monitoring Parameters

Baseline and periodic CBC with differential, urinalysis, BUN, serum creatinine; baseline and periodic serum bilirubin, AST, ALT, alkaline phosphatase and gamma glutamyl transferase (especially when using high doses); observe for signs and symptoms of anaphylaxis during first dose. Monitor infusion site.

Pregnancy Risk Factor

B

Pregnancy Considerations

Penicillin class antibiotics cross the placenta in varying degrees. Nafcillin is highly protein bound which may limit fetal exposure (Nau 1987).

As a class, penicillin antibiotics are widely used in pregnant women. Based on available data, penicillin antibiotics are generally considered compatible for use during pregnancy (Ailes 2016; Bookstaver 2015; Crider 2009; Damkier 2019; Lamont 2014; Muanda 2017a; Muanda 2017b).

Patient Education

What is this drug used for?

• It is used to treat bacterial infections.

All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:

• Nausea

• Vomiting

• Diarrhea

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

• Kidney problems like unable to pass urine, blood in the urine, change in amount of urine passed, or weight gain.

• Liver problems like dark urine, fatigue, lack of appetite, nausea, abdominal pain, light-colored stools, vomiting, or yellow skin.

• Muscle weakness

• Muscle pain

• Joint pain

• Abdominal pain

• Infection

• Bruising

• Bleeding

• Severe dizziness

• Passing out

• Severe loss of strength and energy

• Twitching

• Seizure

• Burning or numbness feeling

• Severe injection site pain, redness, burning, swelling, or irritation

Clostridioides (formerly Clostridium) difficile-associated diarrhea like stomach pain or cramps, very loose or watery stools, or bloody stools.

• Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing, swallowing, or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.

Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.

Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a limited summary of general information about the medicine’s uses from the patient education leaflet and is not intended to be comprehensive. This limited summary does NOT include all information available about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not intended to provide medical advice, diagnosis or treatment and does not replace information you receive from the healthcare provider. For a more detailed summary of information about the risks and benefits of using this medicine, please speak with your healthcare provider and review the entire patient education leaflet.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.