Nafcillin: Pediatric drug information

(For additional information see "Nafcillin: Drug information" and see "Nafcillin: Patient drug information")

For abbreviations, symbols, and age group definitions used in Lexicomp (show table)

Therapeutic Category

Antibiotic, Penicillin (Antistaphylococcal)

Dosing: Neonatal

General dosing, susceptible infection (non-CNS): Limited data available: Note: Duration of therapy is dependent on several factors including infection site and severity, adequacy of source control, culture/susceptibility of organism (if known), and clinical response.

Gestational age-directed dosing (Ref): IM, IV:

Gestational Age	Postnatal Age	Dose
≤34 weeks	≤7 days	25 mg/kg/dose every 12 hours
≤34 weeks	8 to 28 days	25 mg/kg/dose every 8 hours
>34 weeks	≤7 days	25 mg/kg/dose every 8 hours
>34 weeks	8 to 28 days	25 mg/kg/dose every 6 hours

Weight-directed dosing (Ref): IM, IV:

Body Weight	Postnatal Age	Dose
<1 kg	≤14 days	25 mg/kg/dose every 12 hours
	15 to 28 days	25 mg/kg/dose every 8 hours
	29 to 60 days	37.5 mg/kg/dose every 6 hours
1 to 2 kg	≤7 days	25 mg/kg/dose every 12 hours
	8 to 28 days	25 mg/kg/dose every 8 hours
	29 to 60 days	37.5 mg/kg/dose every 6 hours
>2 kg	≤7 days	25 mg/kg/dose every 8 hours
	8 to 28 days	25 mg/kg/dose every 6 hours
	29 to 60 days	37.5 mg/kg/dose every 6 hours

Meningitis

Meningitis: Limited data available:

Age-directed dosing:

PNA 0 to 7 days: IV: 75 mg/kg/day in divided doses every 8 to 12 hours for 14 to 21 days (Ref).

PNA 8 to 28 days: IV: 100 to 150 mg/kg/day in divided doses every 6 to 8 hours for 14 to 21 days (Ref).

Weight-directed dosing (Ref): Expert recommendations suggest higher dosing (eg, in some cases, approximately doubling the dose) to ensure adequate CNS penetration: IV:

Body Weight	Postnatal Age	Dose (IV)
<1 kg	≤14 days	50 mg/kg/dose every 12 hours
	15 to 28 days	50 mg/kg/dose every 8 hours
	29 to 60 days	50 mg/kg/dose every 6 hours
1 to 2 kg	≤7 days	50 mg/kg/dose every 12 hours
	8 to 28 days	50 mg/kg/dose every 8 hours
	29 to 60 days	50 mg/kg/dose every 6 hours
>2 kg	≤7 days	50 mg/kg/dose every 8 hours
>2 kg	8 to 60 days	50 mg/kg/dose every 6 hours

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 (Ref).

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 (Ref).

Endocarditis, treatment

Endocarditis, treatment (Ref): 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 (Ref).

Meningitis, including healthcare associated ventriculitis/meningitis; MSSA

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 (Ref).

Skin and soft tissue infections

Skin and soft tissue infections (Ref): 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.

Dosing: Kidney Impairment: Pediatric

Infants, Children, and Adolescents: No dosage adjustment is necessary unless renal impairment is in the setting of concomitant hepatic impairment then use with caution; specific adjustment for combined renal and hepatic impairment is not provided in the manufacturer's labeling.

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

Dosing: Hepatic Impairment: Pediatric

Infants, Children, and Adolescents: There are no dosage adjustments provided in the manufacturer's labeling; however, dosage adjustment may be necessary particularly in the setting of concomitant renal impairment; nafcillin primarily undergoes hepatic metabolism. In patients with both hepatic and renal impairment, monitoring of serum drug concentrations and modification of dosage may be necessary.

Dosing: Adult

(For additional information see "Nafcillin: Drug information")

Usual dosage range: IV: 1 to 2 g every 4 to 6 hours; may also administer total daily dose as a continuous infusion over 24 hours (eg, for a dose of 2 g every 4 hours, administer 12 g over 24 hours) (Ref).

Bloodstream infection

Bloodstream infection: Pathogen-directed therapy for methicillin-susceptible staphylococci (off label): IV: 2 g every 4 hours; treat uncomplicated bacteremia for ≥14 days starting from day of first negative blood culture, with longer courses warranted for endocarditis or metastatic sites of infection (Ref).

Endocarditis, treatment

Endocarditis, treatment: Pathogen-directed therapy for methicillin-susceptible staphylococci (off label):

Native valve: IV: 12 g/day in 4 or 6 divided doses (ie, 2 g every 4 hours or 3 g every 6 hours) for 6 weeks. For uncomplicated right-sided IE, 2 weeks of therapy may be adequate (Ref).

Prosthetic valve: IV: 12 g/day in 6 divided doses (ie, 2 g every 4 hours) for ≥6 weeks (use with rifampin for entire duration of therapy and gentamicin for first 2 weeks) (Ref).

Meningitis, bacterial

Meningitis, bacterial: Pathogen-directed therapy for methicillin-susceptible staphylococci (off label) : IV: 2 g every 4 hours; consider addition of rifampin if organism is susceptible and prosthetic material is present. Treatment duration is 10 to 14 days, depending on causative pathogen(s) and clinical response (Ref).

Osteomyelitis and/or discitis

Osteomyelitis and/or discitis: Pathogen-directed therapy for methicillin-susceptible staphylococci (off label): IV: 1.5 to 2 g every 4 to 6 hours or via continuous infusion for ≥6 weeks depending on extent of infection, debridement, and clinical response (Ref).

Pneumonia

Pneumonia: Pathogen-directed therapy for methicillin-susceptible staphylococci (off label) : IV: 2 g every 4 hours (Ref). Minimum duration is generally 5 days for community-acquired pneumonia and 7 days for hospital-acquired or ventilator-associated pneumonia; patients should be clinically stable with normal vital signs before therapy is discontinued (Ref).

Prosthetic joint infection

Prosthetic joint infection: Pathogen-directed therapy for methicillin-susceptible staphylococci (off label): IV: 1.5 to 2 g every 4 to 6 hours; duration ranges from 2 to 6 weeks depending on prosthesis management, use of rifampin, and other patient-specific factors (Ref).

Skin and soft tissue infection

Skin and soft tissue infection:

Cellulitis (nonpurulent) in patients without risk for methicillin-resistant S. aureus: IV: 1 to 2 g every 4 hours. Total duration of therapy is ≥5 days (including oral step-down therapy); may extend up to 14 days depending on severity and clinical response (Ref).

Necrotizing infection due to methicillin-susceptible S. aureus (MSSA) (off label): 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 (Ref).

Surgical site incisional infection (trunk or extremity, not involving axilla or perineum) (off label): IV: 2 g every 6 hours; duration is dependent upon severity, need for debridement, and clinical response (Ref).

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

Dosing: Kidney Impairment: Adult

No dosage adjustment necessary; use with caution in patients with 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) (Ref).

Dosing: Hepatic Impairment: Adult

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.

Dosage Forms: US

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

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)

Solution Reconstituted, Intravenous [preservative free]:

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

Generic Equivalent Available: US

Yes

Dosage Forms Considerations

Nafcillin lyophilized powder contains sodium approximately 66 mg [2.9 mEq] per gram of nafcillin.

Nafcillin in Dextrose (iso-osmotic) contains sodium 76.6 mg [3.33 mEq] per gram of nafcillin.

Administration: Pediatric

Parenteral:

IM: Administer reconstituted solution as deep intragluteal injection; rotate injection sites.

IV:

Direct IV injection: Further dilute, and administer over 5 to 10 minutes.

Intermittent IV infusion: Infuse over 30 to 60 minutes.

Continuous IV infusion: Children and Adolescents: Infuse daily dose over 24 hours (Ref).

Vesicant; ensure proper needle or catheter placement prior to and during IV infusion. Avoid extravasation. 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 (see Management of Drug Extravasations for more details); remove needle/cannula; apply dry cold compresses (Ref); elevate extremity.

Administration: Adult

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

IV: Infuse over 30 to 60 minutes; may administer as a direct injection over 5 to 10 minutes. Total daily dose may also be administered over 24 hours as a continuous infusion (Ref). 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 (Ref); 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 (Ref).

Storage/Stability

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).

Use

Treatment of bacterial infections such as osteomyelitis, septicemia, endocarditis, and CNS infections due to susceptible strains of Staphylococcus (FDA approved in pediatric patients [IM] and adults [IM and IV]).

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 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

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.

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).

• 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.

Warnings: Additional Pediatric Considerations

In a study of pediatric patients (5 to 19 years) receiving outpatient nafcillin for >3 weeks, significantly less rash was reported in the nafcillin group (10.3%) compared to oxacillin group (31.7%) (Maraqa 2002).

Metabolism/Transport Effects

Substrate of OAT1/3; Induces CYP3A4 (moderate)

Drug Interactions

Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.

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

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

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

Acemetacin: May increase the serum concentration of Penicillins. Risk C: 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. Risk D: Consider therapy modification

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

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

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

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

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

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

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

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

Artemether and Lumefantrine: CYP3A4 Inducers (Moderate) may decrease serum concentrations of the active metabolite(s) of Artemether and Lumefantrine. Specifically, concentrations of dihydroartemisinin (DHA), the active metabolite of artemether may be decreased. CYP3A4 Inducers (Moderate) may decrease the serum concentration of Artemether and Lumefantrine. Risk C: Monitor therapy

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

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

Atogepant: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Atogepant. Management: The recommended dose of atogepant is 30 mg once daily or 60 mg once daily when combined with strong or moderate CYP3A4 inducers. Risk D: Consider therapy modification

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

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

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

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

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

Bacillus clausii: Antibiotics may diminish the therapeutic effect of Bacillus clausii. Management: Bacillus clausii should be taken in between antibiotic doses during concomitant therapy. Risk D: Consider therapy modification

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

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

Bedaquiline: CYP3A4 Inducers (Moderate) may decrease serum concentrations of the active metabolite(s) of Bedaquiline. CYP3A4 Inducers (Moderate) may decrease the serum concentration of Bedaquiline. Risk X: Avoid combination

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

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

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

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

Brexpiprazole: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Brexpiprazole. Risk C: 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. Risk D: Consider therapy modification

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

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

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

Cannabis: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Cannabis. More specifically, tetrahydrocannabinol and cannabidiol serum concentrations may be decreased. Risk C: Monitor therapy

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

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

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

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

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. Risk X: 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 CYP3A4 inducer. Drugs that enhance the metabolism of clarithromycin into 14-hydroxyclarithromycin may alter the clinical activity of clarithromycin and impair its efficacy. Risk D: Consider therapy modification

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

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

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

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

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

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

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

CycloSPORINE (Systemic): CYP3A4 Inducers (Moderate) may decrease the serum concentration of CycloSPORINE (Systemic). Risk C: 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. Risk D: Consider therapy modification

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

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

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

Dasatinib: CYP3A4 Inducers (Moderate) may increase the serum concentration of Dasatinib. Risk C: Monitor therapy

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

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

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

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

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

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

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

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

DOXOrubicin (Conventional): CYP3A4 Inducers (Moderate) may decrease the serum concentration of DOXOrubicin (Conventional). Risk X: Avoid combination

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

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

Duvelisib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Duvelisib. Management: Avoid if possible. If used, on day 12 of combination increase duvelisib from 25 mg twice daily to 40 mg twice daily or from 15 mg twice daily to 25 mg twice daily. Resume prior duvelisib dose 14 days after stopping moderate CYP3A4 inducer. Risk D: Consider therapy modification

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

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

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

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

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

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

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

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

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

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

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

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

Estrogen Derivatives: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Estrogen Derivatives. Risk C: Monitor therapy

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

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

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

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

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

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

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

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

Fexinidazole: CYP3A4 Inducers (Moderate) may increase serum concentrations of the active metabolite(s) of Fexinidazole. Risk X: Avoid combination

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

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

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

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

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

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

Ganaxolone: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Ganaxolone. Management: Avoid concomitant use of ganaxolone and moderate CYP3A4 inducers whenever possible. If combined, consider increasing the dose of ganaxolone, but do not exceed the maximum recommended daily dose. Risk D: Consider therapy modification

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

Gemigliptin: CYP3A4 Inducers (Moderate) may decrease serum concentrations of the active metabolite(s) of Gemigliptin. CYP3A4 Inducers (Moderate) may decrease the serum concentration of Gemigliptin. Risk C: 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. Risk D: Consider therapy modification

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

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. Risk D: Consider therapy modification

Hormonal Contraceptives: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Hormonal Contraceptives. Management: Advise patients to use an alternative method of contraception or a back-up method during coadministration, and to continue back-up contraception for 28 days after discontinuing a moderate CYP3A4 inducer to ensure contraceptive reliability. Risk D: Consider therapy modification

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

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

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

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

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

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

Immune Checkpoint Inhibitors: Antibiotics may diminish the therapeutic effect of Immune Checkpoint Inhibitors. Risk C: Monitor therapy

Indinavir: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Indinavir. Management: Consider avoiding the combination of indinavir and moderate CYP3A4 inducers whenever possible due to the risk for decreased indinavir concentrations, reduced efficacy, and development of resistance. If combined, monitor for indinavir treatment failure. Risk D: Consider therapy modification

Infigratinib: CYP3A4 Inducers (Moderate) may decrease serum concentrations of the active metabolite(s) of Infigratinib. CYP3A4 Inducers (Moderate) may decrease the serum concentration of Infigratinib. Risk X: Avoid combination

Irinotecan Products: CYP3A4 Inducers (Moderate) may decrease serum concentrations of the active metabolite(s) of Irinotecan Products. Specifically, concentrations of SN-38 may be reduced. Risk C: Monitor therapy

Isavuconazonium Sulfate: CYP3A4 Inducers (Moderate) may decrease serum concentrations of the active metabolite(s) of Isavuconazonium Sulfate. Specifically, CYP3A4 Inducers (Moderate) may decrease isavuconazole serum concentrations. Risk C: Monitor therapy

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

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

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

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

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

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

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

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

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

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

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

Larotrectinib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Larotrectinib. Management: Double the larotrectinib dose if used together with a moderate CYP3A4 inducer. Following discontinuation of the moderate CYP3A4 inducer, resume the previous dose of larotrectinib after a period of 3 to 5 times the inducer's half-life. Risk D: Consider therapy modification

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. Risk D: 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. Risk D: Consider therapy modification

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

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

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

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

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

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

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

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

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

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

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, increase lorlatinib to 125 mg daily. Monitor for reduced lorlatinib efficacy and consider closer monitoring of AST, ALT, and bilirubin. Risk D: Consider therapy modification

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

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

Lumateperone: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Lumateperone. Risk X: 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. Risk D: Consider therapy modification

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

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

Maraviroc: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Maraviroc. Management: Increase maraviroc adult dose to 600 mg twice/day, but only if not receiving a strong CYP3A4 inhibitor. Not recommended for pediatric patients not also receiving a strong CYP3A4 inhibitor. Contraindicated in patients with CrCl less than 30 mL/min. Risk D: Consider therapy modification

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

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

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

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

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

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

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

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

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

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

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

Mitapivat: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Mitapivat. Management: Consider alternatives to this combination when possible. If combined, monitor hemoglobin and titrate mitapivat beyond 50 mg twice daily, if needed, but do not exceed doses of 100 mg twice daily. Risk D: Consider therapy modification

Mobocertinib: CYP3A4 Inducers (Moderate) may decrease serum concentrations of the active metabolite(s) of Mobocertinib. CYP3A4 Inducers (Moderate) may decrease the serum concentration of Mobocertinib. Risk X: Avoid combination

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

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

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

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

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

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

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

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

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

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

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

Nirmatrelvir and Ritonavir: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Nirmatrelvir and Ritonavir. Risk C: Monitor therapy

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

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

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

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

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

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

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

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

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

PACLitaxel (Conventional): CYP3A4 Inducers (Moderate) may decrease the serum concentration of PACLitaxel (Conventional). Risk C: Monitor therapy

PACLitaxel (Protein Bound): CYP3A4 Inducers (Moderate) may decrease the serum concentration of PACLitaxel (Protein Bound). Risk C: Monitor therapy

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

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

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

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

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

Perampanel: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Perampanel. Management: Increase perampanel starting dose to 4 mg/day if used with moderate CYP3A4 inducers. Increase perampanel dose by 2 mg/day no more than once weekly based on response and tolerability. Dose adjustments may be needed if the inducer is discontinued. Risk D: Consider therapy modification

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

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

Pirtobrutinib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Pirtobrutinib. Management: Avoid concomitant use if possible. If combined, if the current pirtobrutinib dose is 200 mg once daily, increase to 300 mg once daily. If current pirtobrutinib dose is 50 mg or 100 mg once daily, increase the dose by 50 mg. Risk D: Consider therapy modification

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

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

Praziquantel: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Praziquantel. Management: Consider alternatives to this combination when possible. If combined, monitor for reduced praziquantel efficacy if combined with moderate CYP3A4 inducers. Risk D: Consider therapy modification

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

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

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

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

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

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

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

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

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

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

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

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

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

Ripretinib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Ripretinib. Management: Avoid this combination if possible. If concomitant use is required, increase ripretinib to 150 mg twice daily. Decrease ripretinib to 150 mg once daily 14 days after stopping a moderate CYP3A4 inducer. Monitor patients for ripretinib response and toxicity Risk D: Consider therapy modification

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

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

Roflumilast (Systemic): CYP3A4 Inducers (Moderate) may decrease serum concentrations of the active metabolite(s) of Roflumilast (Systemic). CYP3A4 Inducers (Moderate) may decrease the serum concentration of Roflumilast (Systemic). Risk C: Monitor therapy

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

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

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

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

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

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

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

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

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

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

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

Sodium Benzoate: Penicillins may diminish the therapeutic effect of Sodium Benzoate. Risk C: 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. Risk D: Consider therapy modification

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

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

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

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

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

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

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

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

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

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

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

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

Temsirolimus: CYP3A4 Inducers (Moderate) may decrease serum concentrations of the active metabolite(s) of Temsirolimus. Specifically, sirolimus concentrations may be decreased. CYP3A4 Inducers (Moderate) may decrease the serum concentration of Temsirolimus. Risk C: Monitor therapy

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

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

Tetrahydrocannabinol and Cannabidiol: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Tetrahydrocannabinol and Cannabidiol. Risk C: Monitor therapy

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

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

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

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

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

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

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

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

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

Tucatinib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Tucatinib. Risk C: 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. Risk D: 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. Risk D: Consider therapy modification

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

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

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

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

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

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

Vilazodone: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Vilazodone. Risk C: 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. Risk D: Consider therapy modification

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

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

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

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

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

Voxelotor: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Voxelotor. Management: Avoid concomitant use of voxelotor and moderate CYP3A4 inducers. If unavoidable, increase the voxelotor dose to 2,000 mg once daily. For children ages 4 to less than 12 years, weight-based dose adjustments are required. See full monograph for details. Risk D: Consider therapy modification

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

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

Zanubrutinib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Zanubrutinib. Management: Avoid this combination if possible. If coadministration of zanubrutinib and a moderate CYP3A4 inducer is required, increase the zanubrutinib dose to 320 mg twice daily. Risk D: Consider therapy modification

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

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

Dietary Considerations

Some products may contain sodium.

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).

Monitoring Parameters

CBC with differential, urinalysis, BUN, SCr (baseline and periodic during prolonged therapy); serum potassium (baseline and periodic) (Knoderer 2017; Viehman 2016); serum bilirubin, AST, ALT, alkaline phosphatase, and gamma glutamyl transferase (especially when using high doses or during prolonged therapy) (baseline and periodic). Observe for signs and symptoms of anaphylaxis during first dose. Monitor IV site for extravasation.

Mechanism of Action

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

Pharmacokinetics (Adult Data Unless Noted)

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

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

Protein binding: ~90%; primarily to albumin

Metabolism: Primarily hepatic; undergoes enterohepatic recirculation

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

Time to peak, serum: IM: 30 to 60 minutes

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

Pharmacokinetics: Additional Considerations (Adult Data Unless Noted)

Hepatic function impairment: Plasma clearance is significantly decreased and excretion in urine was significantly increased from ~30% to 50% in patients with biliary obstruction and cirrhosis.

Anti-infective considerations:

Parameters associated with efficacy: Time dependent, associated with time free drug concentration (fT) > minimum inhibitory concentration (MIC); goal: ≥50% fT > MIC (bactericidal) (Drusano 2003; Turnidge 1998).

Critically ill patients in the ICU: Minimum goal: ≥50% fT > MIC; preferred goal: ≥100% fT > MIC (Abdul-Aziz 2020; Al-Shaer 2020; Roberts 2014); some experts favor ≥100% fT > 4 times the MIC (Guilhaumou 2019).

Expected drug exposure in normal renal function:

C_max(peak): Single dose: IV:

Infants, children, and adolescents ≤13 years of age: 37.5 mg/kg (infused over 15 minutes): 48.1 ± 3.5 mg/L (Feldman 1978).

Adults: 500 mg (infused over 7 minutes): ~30 mg/L.

Postantibiotic effect: Minimal bacterial killing continues after concentration of penicillins fall below the MIC of targeted pathogen and varies based on the organism:

Gram-positive cocci: 1.5 to 3.5 hours (Craig 1991).

Gram-negative bacilli: 0 to 1.5 hours (Craig 1991).

Parameters associated with toxicity: Continuous infusion: Hospitalized adults: In a retrospective study, steady-state nafcillin concentrations were significantly higher in patients who experienced an adverse drug event compared to those who did not (66 vs 25.5 mg/L). Specifically, concentrations were higher in patients who experienced hepatotoxicity (62.8 vs 27 mg/L), nausea/vomiting (80 vs 28.5 mg/L), and diarrhea (66.5 vs 26.5 mg/L) (Benefield 2016).

Pricing: US

Solution (Nafcillin Sodium in Dextrose Intravenous)

1 gm/50 mL (per mL): $0.41

2 g/100 mL (per mL): $0.29

Solution (reconstituted) (Nafcillin Sodium Injection)

1 g (per each): $13.20 - $17.87

2 g (per each): $9.85 - $34.67

Solution (reconstituted) (Nafcillin Sodium Intravenous)

1 g (per each): $17.52 - $19.25

2 g (per each): $33.99 - $37.35

10 g (per each): $120.00 - $174.00

Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.

Abdul-Aziz MH, Alffenaar JC, Bassetti M, et al; Infection Section of European Society of Intensive Care Medicine (ESICM); Pharmacokinetic/pharmacodynamic and critically ill patient study groups of European Society of Clinical Microbiology and Infectious Diseases (ESCMID); Infectious Diseases Group of International Association of Therapeutic Drug Monitoring and Clinical Toxicology (IATDMCT); infections in the ICU and Sepsis Working Group of International Society of Antimicrobial Chemotherapy (ISAC). Antimicrobial therapeutic drug monitoring in critically ill adult patients: a position paper. Intensive Care Med. 2020;46(6):1127-1153. doi:10.1007/s00134-020-06050-1 [PubMed 32383061]
Ailes EC, Gilboa SM, Gill SK, et al; The National Birth Defects Prevention Study. Association between antibiotic use among pregnant women with urinary tract infections in the first trimester and birth defects, National Birth Defects Prevention Study 1997 to 2011. Birth Defects Res A Clin Mol Teratol. 2016;106(11):940-949. doi:10.1002/bdra.23570 [PubMed 27891788]
Alam MB, Kadoura A, Sathaiah M. A Fatal Case of Nafcillin-Induced Hepatotoxicity: A Case Report and the Literature Review. Case Report Med. 2012;2012:953714. [PubMed 22844299]
Al-Shaer MH, Rubido E, Cherabuddi K, Venugopalan V, Klinker K, Peloquin C. Early therapeutic monitoring of β-lactams and associated therapy outcomes in critically ill patients. J Antimicrob Chemother. 2020;75(12):3644-3651. doi:10.1093/jac/dkaa359 [PubMed 32910809]
American Academy of Pediatrics (AAP). In: Kimberlin DW, Brady MT, Jackson MA, Long SA, eds. Red Book: 2018 Report of the Committee on Infectious Diseases. 31st ed. American Academy of Pediatrics; 2018.
Aronoff GR, Bennett WM, Berns JS, et al. Drug Prescribing in Renal Failure: Dosing Guidelines for Adults and Children. 5th ed. American College of Physicians; 2007.
Baddour LM, Wilson WR, Bayer AS, et al; American Heart Association Committee on Rheumatic Fever, Endocarditis, and Kawasaki Disease of the Council on Cardiovascular Disease in the Young, Council on Clinical Cardiology, Council on Cardiovascular Surgery and Anesthesia, and Stroke Council. Infective endocarditis in adults: diagnosis, antimicrobial therapy, and management of complications: a scientific statement for healthcare professionals from the American Heart Association. Circulation. 2015;132(15):1435-1486. doi: 10.1161/CIR.0000000000000296. [PubMed 26373316]
Baltimore RS, Gewitz M, Baddour LM, et al; American Heart Association Rheumatic Fever, Endocarditis, and Kawasaki Disease Committee of the Council on Cardiovascular Disease in the Young and the Council on Cardiovascular and Stroke Nursing. Infective endocarditis in childhood: 2015 update: a scientific statement from the American Heart Association. Circulation. 2015;132(15):1487-1515. doi:10.1161/CIR.0000000000000298 [PubMed 26373317]
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):691-694. [PubMed 7396459]
Bauer KA, West JE, Shidham G. An antimicrobial stewardship program’s evaluation of the safety and efficacy of continuous infusion of nafcillin in the treatment of methicillin-sensitive Staphylococcus aureus bacteremia. Infect Dis Clin Pract. 2013;21(2):111-113.
Benefield RJ, Barker BC, Gast CM, Alexander DP. Patient variables associated with nafcillin plasma concentrations and toxicity. Pharmacotherapy. 2016;36(9):994-1002. doi:10.1002/phar.1805 [PubMed 27485941]
Berbari EF, Kanj SS, Kowalski TJ, et al. 2015 Infectious Diseases Society of America (IDSA) Clinical Practice Guidelines for the diagnosis and treatment of native vertebral osteomyelitis in adults. Clin Infect Dis. 2015;61(6):e26-e46. [PubMed 26229122]
Blazes DL, Martin GJ. Drug Induced Lupus Erythematosus Secondary to Nafcillin: The First Reported Case. Rheumatol Int. 2004;24(4):242-243. [PubMed 14658003]
Bookstaver PB, Bland CM, Griffin B, Stover KR, Eiland LS, McLaughlin M. A review of antibiotic use in pregnancy. Pharmacotherapy. 2015;35(11):1052-1062. doi:10.1002/phar.1649 [PubMed 26598097]
Bradley JS, Byington CL, Shah SS, et al. The Management of Community-Acquired Pneumonia in Infants and Children Older Than 3 Months of Age: Clinical Practice Guidelines by the Pediatric Infectious Diseases Society and the Infectious Diseases Society of America. Clin Infect Dis. 2011;53(7):e25-e76. [PubMed 21880587]
Bradley JS, Nelson JD, eds. Nelson's Pediatric Antimicrobial Therapy. 25th ed. American Academy of Pediatrics; 2019.
Carek PJ, Dickerson LM, Sack JL. Diagnosis and Management of Osteomyelitis. Am Fam Physician. 2001;63(12):2413-2420. [PubMed 11430456]
Chan V. Influence of temperature and drug concentration on nafcillin precipitation. Am J Health Syst Pharm. 2005;62(13):1347-1348. [PubMed 15972371]
Chang M, Koh ES, Kim MJ, et al. Nafcillin-Induced Bullous Skin Eruption With Granulocytopenia in a Patient With End Stage Renal Disease. Intern Med. 2012;51(3):287-289. [PubMed 22293804]
Cone LA, Lopez C, O’Connell SJ, et al. Staphylococcal Septic Synovitis of the Sternoclavicular Joint With Retrosternal Extension. J Clin Rheumatol. 2006;12(4):187-189. [PubMed 16891922]
Craig WA. The postantibiotic effect. Clin Microbiology Newsletter. 1991;13(16):121-124. doi:10.1016/0196-4399(91)90030-Y [PubMed 1938689]
Crider KS, Cleves MA, Reefhuis J, Berry RJ, Hobbs CA, Hu DJ. Antibacterial medication use during pregnancy and risk of birth defects: National Birth Defects Prevention Study. Arch Pediatr Adolesc Med. 2009;163(11):978-985. doi:10.1001/archpediatrics.2009.188 [PubMed 19884587]
Dahlgren AF. Adverse Drug Reactions in Home Care Patients Receiving Nafcillin or Oxacillin. Am J Health Syst Pharm. 1997;54(10):1176-1179. [PubMed 9161625]
Damkier P, Brønniche LMS, Korch-Frandsen JFB, Broe A. In utero exposure to antibiotics and risk of congenital malformations: a population-based study. Am J Obstet Gynecol. 2019;221(6):648.e1-648.e15. doi:10.1016/j.ajog.2019.06.050 [PubMed 31260651]
Donowitz GR, Mandell GL. Beta-Lactam Antibiotics. N Engl J Med. 1988;318(7):419-26 and 318(8):490-500. [PubMed 3277054]
Drusano GL. Prevention of resistance: a goal for dose selection for antimicrobial agents. Clin Infect Dis. 2003;36(suppl 1):S42-S50. doi:10.1086/344653 [PubMed 12516029]
Feldman WE, Nelson JD, Stanberry LR. Clinical and pharmacokinetic evaluation of nafcillin in infants and children. J Pediatr. 1978;93(6):1029-1033. doi:10.1016/s0022-3476(78)81251-7 [PubMed 722420]
Gould FK, Denning DW, Elliott TS, et al.G uidelines for the Diagnosis and Antibiotic Treatment of Endocarditis in Adults: A Report of the Working Party of the British Society for Antimicrobial Chemotherapy. J Antimicrob Chemother. 2012;67(2):269-289. [PubMed 22086858]
Guilhaumou R, Benaboud S, Bennis Y, et al. Optimization of the treatment with beta-lactam antibiotics in critically ill patients-guidelines from the French Society of Pharmacology and Therapeutics (Société Française de Pharmacologie et Thérapeutique-SFPT) and the French Society of Anaesthesia and Intensive Care Medicine (Société Française d'Anesthésie et Réanimation-SFAR). Crit Care. 2019;23(1):104. doi:10.1186/s13054-019-2378-9 [PubMed 30925922]
Heintz BH, Matzke GR, Dager WE. Antimicrobial Dosing Concepts and Recommendations for Critically Ill Adult Patients Receiving Continuous Renal Replacement Therapy or Intermittent Hemodialysis. Pharmacotherapy. 2009;29(5):562-577. [PubMed 19397464]
Hurst S, McMillan M. Innovative solutions in critical care units: extravasation guidelines. Dimens Crit Care Nurs. 2004;23(3):125-128. [PubMed 15192356]
Kalil AC, Metersky ML, Klompas M, et al. Management of adults with hospital-acquired and ventilator-associated pneumonia: 2016 clinical practice guidelines by the Infectious Diseases Society of America and the American Thoracic Society. Clin Infect Dis. 2016;63(5):e61-e111. doi:10.1093/cid/ciw353 [PubMed 27418577]
Klaus JR, Knodel LC, Kavanagh RE. Administration guidelines for parenteral drug therapy. Part I: pediatric patients. J Pharm Technol. 1989;5(3):101-128. [PubMed 10318297]
Klompas M. Treatment of hospital-acquired and ventilator-associated pneumonia in adults. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed January 20, 2022.
Knoderer CA, Karmire LC, Nichols KR. Clinical outcomes with continuous nafcillin infusions in children. J Pediatr Pharmacol Ther. 2017;22(4):261-265. [PubMed 28943820]
Lamont HF, Blogg HJ, Lamont RF. Safety of antimicrobial treatment during pregnancy: a current review of resistance, immunomodulation and teratogenicity. Expert Opin Drug Saf. 2014;13(12):1569-1581. doi:10.1517/14740338.2014.939580 [PubMed 25189188]
MacCara ME. Extravasation - A Hazard of Intravenous Therapy. Drug Intell Clin Pharm. 1983;17(10):713. [PubMed 6628223]
Mandell LA, Wunderink RG, Anzueto A, et al .Infectious Diseases Society of America/American Thoracic Society Consensus Guidelines on the Management of Community-Acquired Pneumonia in Adults. Clin Infect Dis. 2007;44(suppl 2):27-72. [PubMed 17278083]
Maraqa NF, Gomez MM, Rathore MH, et al. Higher Occurrence of Hepatotoxicity and Rash in Patients Treated With Oxacillin, Compared With Those Treated With Nafcillin and Other Commonly Used Antimicrobials. Clin Infect Dis. 2002;34(1):50-54. [PubMed 11731945]
Mermel LA, Allon M, Bouza E, et al. Clinical practice guidelines for the diagnosis and management of intravascular catheter-related infection: 2009 update by the Infectious Diseases Society of America. Clin Infect Dis. 2009;49(1):1-45. [PubMed 19489710]
Metlay JP, Waterer GW, Long AC, et al. Diagnosis and treatment of adults with community-acquired pneumonia. An official clinical practice guideline of the American Thoracic Society and Infectious Diseases Society of America. Am J Resp Crit Care Med. 2019;200(7):e45-e67. doi:10.1164/rccm.201908-1581ST. [PubMed 31573350]
Muanda FT, Sheehy O, Bérard A. Use of antibiotics during pregnancy and the risk of major congenital malformations: a population based cohort study. Br J Clin Pharmacol. 2017a;83(11):2557-2571. doi:10.1111/bcp.13364 [PubMed 28722171]
Muanda FT, Sheehy O, Bérard A. Use of antibiotics during pregnancy and risk of spontaneous abortion. CMAJ. 2017b;189(17):E625-E633. doi:10.1503/cmaj.161020 [PubMed 28461374]
Nafcillin [prescribing information]. Princeton, NJ: Sandoz Inc; November 2015.
Nafcillin in Dextrose [prescribing information]. Deerfield, IL: Baxter Healthcare Corporation; July 2017.
Nafcillin pharmacy bulk package [prescribing information]. Princeton, NJ: Sandoz Inc; November 2015.
Nau H. Clinical pharmacokinetics in pregnancy and perinatology. II. Penicillins. Dev Pharmacol Ther. 1987;10(3):174-198. doi:10.1159/000457744 [PubMed 3301235]
Osmon DR, Berbari EF, Berendt AR, et al. Diagnosis and Management of Prosthetic Joint Infection: Clinical Practice Guideline by the Infectious Diseases Society of America. Clin Infect Dis. 2013;56(1):e1-e25. [PubMed 23223583]
Qua DA, Tan MJ. Hypokalemia Associated With Nafcillin Treatment. Infect Dis Clin Pract. 2009;17(2):130-131.
Refer to manufacturer's labeling.
Reynolds PM, Maclaren R, Mueller SW, Fish DN, Kiser TH. Management of extravasation injuries: a focused evaluation of noncytotoxic medications. Pharmacotherapy. 2014;34(6):617-632. doi:10.1002/phar.1396 [PubMed 24420913]
Roberts JA, Paul SK, Akova M, et al; DALI Study. DALI: defining antibiotic levels in intensive care unit patients: are current β-lactam antibiotic doses sufficient for critically ill patients? Clin Infect Dis. 2014;58(8):1072-1083. doi:10.1093/cid/ciu027 [PubMed 24429437]
Robinson DC, Cookson TL, Grisafe JA. Concentration Guidelines for Parenteral Antibiotics in Fluid-Restricted Patients. Drug Intell Clin Pharm. 1987;21(12):985-989. [PubMed 3428165]
Schulmeister L. Extravasation Management. Semin Oncol Nurs. 2007;23(3):184-190. [PubMed 17693345]
Spelman D, Baddour LM. Acute cellulitis and erysipelas in adults: Treatment. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed June 17, 2022.
Stapleton FB, Nelson B, Vats TS, Linshaw MA. Hypokalemia associated with antibiotic treatment. Evidence in children with malignant neoplasms. Am J Dis Child. 1976;130(10):1104-1108. [PubMed 1067752]
Stevens DL, Bisno AL, Chambers HF, et al. Practice guidelines for the diagnosis and management of skin and soft tissue infections: 2014 update by the Infectious Diseases Society of America. Clin Infect Dis. 2014;59(2):e10-e52. doi:10.1093/cid/ciu444 [PubMed 24973422]
Trotman RL, Williamson JC, Shoemaker DM, et al. Antibiotic Dosing in Critically Ill Adult Patients Receiving Continuous Renal Replacement Therapy. Clin Infect Dis. 2005;41(8):1159-1166. [PubMed 16163635]
Tunkel AR, Hartman BJ, Kaplan SL, et al. Practice guidelines for the management of bacterial meningitis. Clin Infect Dis. 2004;39(9):1267-1284. [PubMed 15494903]
Tunkel AR, Hasbun R, Bhimraj A, et al. 2017 Infectious Diseases Society of America's clinical practice guidelines for healthcare-associated ventriculitis and meningitis. Clin Infect Dis. Published online February 14, 2017. doi:10.1093/cid/ciw861 [PubMed 28203777]
Turnidge JD. The pharmacodynamics of beta-lactams. Clin Infect Dis. 1998;27(1):10-22. doi:10.1086/514622 [PubMed 9675443]
Viehman JA, Oleksiuk LM, Sheridan KR, et al. Adverse events lead to drug discontinuation more commonly among patients who receive nafcillin than among those who receive oxacillin. Antimicrob Agents Chemother. 2016;60(5):3090-3095. [PubMed 26976858]
World Health Organization (WHO). Breastfeeding and maternal medication, recommendations for drugs in the eleventh WHO model list of essential drugs. http://www.who.int/maternal_child_adolescent/documents/55732/en/. Published 2002. Accessed May 28, 2020.
Wright AJ. The Penicillins. Mayo Clin Proc. 1999;74(3):290-307. [PubMed 10090000]
Zenk KE. Management of intravenous extravasations. Infusion. 1981;5(4):77-79.
Zenk KE, Dungy CL, Greene CR.N afcillin Extravasation Injury: Use of Hyaluronidase as an Antidote. Am J Dis Child. 1981;135(12):1113-1114. [PubMed 7315807]

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Nafcillin: Pediatric drug information