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 |
8 to 28 days |
25 mg/kg/dose every 8 hours | |
>34 weeks |
≤7 days |
25 mg/kg/dose every 8 hours |
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: 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 |
8 to 60 days |
50 mg/kg/dose every 6 hours |
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 (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: 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 (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.
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).
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.
(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: 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: 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: 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: 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: 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: 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:
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.
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).
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.
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)
Yes
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.
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.
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).
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).
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]).
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
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.
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.
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).
Substrate of OAT1/3; Induces CYP3A4 (moderate)
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
Some products may contain sodium.
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).
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.
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
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)
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:
Cmax (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).
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
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