NAFCILLIN SODIUM
  • NAFCILLIN SODIUM

  • QTY 1 • 1 G • VIAL • Near 77381

NAFCILLIN (naf SILL in) is a penicillin antibiotic. It treats some infections caused by bacteria. It will not work for colds, the flu, or other viruses.

NAFCILLIN SODIUM Pediatric Monographs
  • General Administration Information
    For storage information, see the specific product information within the How Supplied section.

    Route-Specific Administration

    Injectable Administration
    -Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit.
    Intravenous Administration
    Reconstitution
    -Vials: Reconstitute with Sterile Water for Injection or 0.9% Sodium Chloride Injection. Review the reconstitution instructions for the particular product and package size, as the amount of diluent required for reconstitution may vary by manufacturer.
    -Storage: Reconstituted solutions are stable for 3 days at room temperature or 7 days under refrigeration.
    -Pharmacy bulk package: Reconstitute 10 g vial with 93 mL of Sterile Water for Injection or 0.9% Sodium Chloride Injection for a resultant concentration of 100 mg/mL.
    -Storage: Use reconstituted pharmacy bulk package within 4 hours from initial entry.

    Dilution
    -For Intermittent IV Injection: Further dilute the reconstituted solution in 15 to 30 mL of Sterile Water for Injection or 0.9% Sodium Chloride Injection.
    -For Intermittent IV Infusion: Further dilute reconstituted solution in 0.9% Sodium Chloride Injection or 5% Dextrose Injection to a usual concentration of 10 to 40 mg/mL.-For peripheral vein infusion, a concentration of 20 mg/mL or less is preferred to lessen the risk of phlebitis ; however, some patients cannot tolerate the fluid load and need a more concentrated solution.
    -For fluid restricted patients, higher concentrations may be used depending on the diluent (5% Dextrose Injection: up to 71 mg/mL; 0.9% Sodium Chloride Injection: up to 64 mg/mL; Sterile Water for Injection: up to 128 mg/mL). These higher concentrations may increase the risk of phlebitis.

    -Storage:-Solutions diluted in 0.9% Sodium Chloride Injection or Sterile Water for Injection to a concentration of 10 to 200 mg/mL are stable for 24 hours at room temperature (25 degrees C) or 7 days under refrigeration (4 degrees C).
    -Solutions diluted in 5% Dextrose Injection to a concentration of 2 to 30 mg/mL are stable for 24 hours at room temperature (25 degrees C). Solutions diluted in 5% Dextrose Injection to a concentration of 10 to 30 mg/mL are stable for 7 days under refrigeration (4 degrees C).

    -GALAXY bags: No further dilution is required.

    Thawing Frozen Pre-mixed Bags
    -Frozen GALAXY bags: Thaw frozen container at room temperature or under refrigeration. Do not force thaw by immersion in water baths or by microwave irradiation.
    -Components of the solution may precipitate in the frozen state and will dissolve upon reaching room temperature; potency is not affected. If the solution remains cloudy or if an insoluble precipitate remains after the solution has reached room temperature and has been agitated, discard the product.
    -Storage: The thawed solution remains stable for 21 days under refrigeration or for 3 days at room temperature. Do not refreeze.

    Intermittent IV Injection
    -Inject slowly over 5 to 10 minutes into the tubing of a free-flowing compatible IV solution. To minimize vein irritation, inject as slowly as possible. Compatible solutions include 5% Dextrose Injection, 0.9% Sodium Chloride Injection, 5% Dextrose and 0.45% Sodium Chloride Injection, and Lactated Ringer's Injection.

    Intermittent IV Infusion
    -Infuse IV slowly over 30 to 60 minutes to reduce the risk for phlebitis and extravasation. For peripheral vein infusion, consider infusion over 60 minutes. Shorter infusions (15 to 30 minutes) have been tolerated by children ; however, in general, more rapid infusions are associated with a higher risk of infusion site reactions.

    Intramuscular Administration
    Reconstitution
    -Vials: Reconstitute with Sterile Water for Injection, Bacteriostatic Water for Injection with Parabens or Benzyl Alcohol, or 0.9% Sodium Chloride Injection for a resultant concentration of 250 mg/mL. Review the reconstitution instructions for the particular product and package size, as the amount of diluent required for reconstitution may vary by manufacturer. For neonates, use Sterile Water for Injection or 0.9% Sodium Chloride Injection to avoid the administration of benzyl alcohol.
    -Storage: Reconstituted solutions are stable for 3 days at room temperature or 7 days under refrigeration.

    Intramuscular Injection
    -Inject deeply into a large muscle (i.e., upper outer quadrant of the gluteus maximus or lateral part of the thigh). Care should be taken to avoid sciatic nerve injury.
    -In general, IM administration of antibiotics in very low birth weight premature neonates is not practical due to small muscle mass, and absorption is unreliable due to hemodynamic instability that is relatively common in this population.

    Both IM and IV injection of nafcillin can be painful and can cause an injection site reaction. A local reaction, including pain, induration, swelling, inflammation, phlebitis, thrombophlebitis, and occasional skin sloughing can occur. Phlebitis proximal to the administration site occurs frequently in patients receiving intravenous nafcillin, particularly with longer treatment courses and the use of peripheral access. Administration via a central venous line is preferred when available. If a peripheral venous line must be used for administration, the following recommendations have been suggested to minimize the risk of severe phlebitis: rotation of the peripheral IV site every 72 hours, limit the nafcillin concentration to 20 mg/ml unless the patient is fluid-restricted, and infuse each dose over 60 minutes. In addition to phlebitis, severe tissue necrosis with sloughing secondary to subcutaneous extravasation of nafcillin has been reported, including in infants and children. Hyaluronidase treatment (15 units in 1 ml of NS) has been successfully used for nafcillin extravasation in pediatric case reports (including neonates) and has resulted in decreased tissue damage and destruction.

    Interstitial nephritis, a hypersensitivity reaction, with renal tubular necrosis (damage) has been reported with nafcillin therapy. Manifestations of interstitial nephritis include rash, pyrexia, increased eosinophils, hematuria, proteinuria, and renal insufficiency. Most cases have resolved upon discontinuation of nafcillin; however, some patients may require dialysis treatment and may develop permanent renal damage. Increased creatinine (1 mg/dL or more) was reported in approximately 5% of children receiving nafcillin in a clinical study (n = 74). Microscopic hematuria and leukocyturia were also reported in 2 patients.

    Neutropenia and eosinophilia are the most common hematologic adverse effects reported in pediatric patients receiving nafcillin. Two safety studies in pediatric patients reported neutropenia in 6-8% of patients. In a retrospective review of outpatients (ages 2 days to 19 years) who received antimicrobial therapy, 9 of the 58 patients (15.5%) who received nafcillin developed neutropenia. Neutropenia typically develops after several days to weeks of therapy and resolves after discontinuation of nafcillin. Eosinophilia has been reported in 9-24% pediatric patients who received nafcillin during clinical trials. In addition to being an independent adverse reaction, eosinophilia may also be one of several presenting signs of interstitial nephritis; evaluate all patients presenting with eosinophilia for other signs of this reaction (e.g. rash, increased temperature, hematuria, proteinuria, renal insufficiency). Agranulocytosis and bone marrow depression have also been less commonly associated with nafcillin therapy.

    Although penicillin allergy has been reported in up to 20% of patients in the general population, up to 90% of those patients lack penicillin-specific IgE antibodies and can safely tolerate the antibiotic. Careful assessment of patients who report a penicillin allergy is critical; while many of these reports are not real hypersensitivity reactions, those patients with a true allergy to penicillins are at risk for severe reactions upon re-exposure to a drug in the penicillin class, such as nafcillin. The actual prevalence of penicillin allergy in the general population is most likely <= 5%. Severe immediate anaphylactoid reactions are very rare and usually occur within 20 minutes of administration; these reaction may include anaphylactic shock, angioedema, laryngospasm, laryngeal edema, bronchospasm, hypotension, vascular collapse, and even death. Other immediate reactions that occur between 20 minutes and 48 hours after administration include urticaria, pruritus, fever, and occasionally laryngeal edema, laryngospasm, and hypotension. Serum sickness-like symptoms (fever, malaise, myalgia, arthralgia) are delayed and typically occur > 48 hours and sometimes 2-4 weeks after administration. While rash may be a presenting sign of a hypersensitivity reaction, non-allergic macular rashes are also associated with penicillin antibiotics. In patients who have not received a penicillin previously, this type of rash typically begins at least 4-5 days after treatment is started ; the rash may be extensive, covering the entire body, and usually disappears in 3-7 days. Rash (unspecified) was reported in approximately 10% of pediatric patients receiving nafcillin (n = 58) in a retrospective review of outpatient parenteral antimicrobial therapy; the incidence of rash was higher with oxacillin (32%). Other skin reactions that occur infrequently, but can be serious, include Stevens-Johnson syndrome, exfoliative dermatitis, and toxic epidermal necrolysis.

    In 2 clinical trials of nafcillin use in children, mildly elevated hepatic enzymes (ALT and/or AST) were reported in approximately 3% (1 of 32) and 16% (12 of 74) of patients. Increased alkaline phosphatase was also reported rarely. Cholestasis may also occur, particularly with administration of high doses of nafcillin.

    In the general population, gastrointestinal adverse events may occur in 2-5% of patients receiving penicillins. Side effects reported with nafcillin include nausea, vomiting, diarrhea, abdominal pain, stomatitis, black or hair tongue (tongue discoloration), or other symptoms of gastrointestinal irritation. Persistent or severe diarrhea may also be a sign of Clostridium difficile associated diarrhea (CDAD); carefully evaluate all patients who develop significant diarrhea.

    Neurotoxic reactions such as seizures have been reported when large doses of penicillins were administered to patients with renal impairment. Unlike most penicillins, nafcillin is not renally eliminated; however, hepatic impairment may present a similar risk for patients receiving nafcillin. Patients with concomitant renal and hepatic impairment are at particular risk; appropriate nafcillin dosage adjustments should be observed in patients with renal and hepatic insufficiency.

    Prolonged use of antimicrobials, including nafcillin, may lead to overgrowth of non-susceptible pathogens or superinfection. Pseudomembranous colitis can also occur during or after treatment. Prolonged antibiotic use is more likely to result in an overgrowth of non-susceptible organisms such as Candida and Clostridium difficile. Diarrhea may be indicative of an antibiotic-associated colitis, and the possible development of pseudomembranous colitis from toxins produced by Clostridium difficile should be considered. Clostridium difficile associated diarrhea (CDAD) may range in severity from mild diarrhea to fatal colitis. If CDAD is suspected or confirmed, ongoing antibiotic use not directed against C. difficile may need to be discontinued. Appropriate fluid and electrolyte management, protein supplementation, antibiotic treatment of C. difficile, and surgical evaluation should be instituted as clinically indicated.

    A false-positive reaction for glucose in the urine has been observed in patients receiving penicillin antibiotics, such as nafcillin, and using copper-reduction tests (e.g., Benedict's solution, Fehling's solution, and Clinitest tablets). This reaction, however, has not been observed with glucose oxidase tests (e.g., Tes-tape, Clinistix, Diastix).

    Nafcillin is a penicillin and is contraindicated in patients with serious (anaphylactic) penicillin hypersensitivity. Nafcillin should be used cautiously in patients with carbapenem hypersensitivity or cephalosporin hypersensitivity because its structural similarity to the cephalosporins and carbapenems causes these patients to be more susceptible to hypersensitivity reactions. Patients with allergies or allergic conditions including asthma, eczema, hives, or hay fever may have a greater risk for hypersensitivity reactions to penicillins.

    Use nafcillin with caution in patients with hepatic disease and in infants with jaundice because the drug is eliminated primarily via the bile. In patients with concomitant hepatic impairment and renal impairment, neurotoxic reactions may occur.

    Almost all antibacterial agents, including nafcillin, have been associated with pseudomembranous colitis (antibiotic-associated colitis), which may range in severity from mild to life-threatening. In the colon, overgrowth of Clostridia may occur when normal flora is altered subsequent to antibacterial administration. The toxin produced by Clostridium difficile is a primary cause of pseudomembranous colitis. Consider pseudomembranous colitis as a potential diagnosis in patients presenting with diarrhea after antibacterial administration. Systemic antibiotics should be prescribed with caution to patients with inflammatory bowel disease such as ulcerative colitis or other GI disease. If diarrhea develops during therapy, discontinue the drug. After a diagnosis of pseudomembranous colitis, institute therapeutic measures. Practitioners should be aware that antibiotic-associated colitis can occur over 2 months or more after discontinuation of systemic antibiotic therapy; a careful medical history should be taken.

    Use nafcillin cautiously in patients with fluid and electrolyte imbalance and those who are particularly sensitive to sodium intake (e.g., newborns, patients with heart failure or hypertension). Nafcillin contains approximately 2.9-3.33 mEq of sodium per gram depending on the particular product; consult specific product labeling for precise sodium content.

    Extravasation of nafcillin can be very painful and cause serious tissue damage, including local tissue necrosis. Do not exceed recommended infusion rates and monitor the administration site frequently. Hyaluronidase treatment (15 units in 1 ml of NS) has been successfully used for nafcillin extravasation in pediatric case reports (including neonates) and has resulted in decreased tissue damage and destruction.

    Description: Nafcillin is a semisynthetic antistaphylococcal penicillin. Unlike penicillin, ampicillin, and the extended-spectrum penicillins, nafcillin resists hydrolysis by penicillinase. As a result, nafcillin, along with other agents in the same group (e.g., oxacillin, dicloxacillin), is active against penicillinase-producing S. aureus. Nafcillin is commonly used for skin and soft-tissue infections in pediatric patients; it is also used for bacteremia, meningitis, endocarditis, respiratory tract infections, and bone and joint infections due to methicillin-susceptible Staphylococcus aureus. Unlike other penicillins, nafcillin is excreted primarily in the bile and undergoes enterohepatic circulation. Therefore, particular caution should be exercised in patients with hepatic impairment and in neonates with jaundice. A lower incidence of adverse effects (hepatotoxicity and rash) has been reported in children receiving therapy with nafcillin compared to those receiving oxacillin. Intramuscular use of nafcillin is FDA-approved for use in pediatric patients as young as neonates. Although not FDA-approved, the IV route of nafcillin is widely used off-label in pediatric patients as young as neonates.

    General dosing information:
    -Nafcillin is FDA-approved for the treatment of moderate to severe infections due to penicillinase-producing Staphylococcus sp. only.

    Per the manufacturer, this drug has been shown to be active against most strains of the following microorganisms either in vitro and/or in clinical infections: Staphylococcus aureus (MSSA), Staphylococcus sp.
    NOTE: The safety and effectiveness in treating clinical infections due to organisms with in vitro data only have not been established in adequate and well-controlled clinical trials.

    For the treatment of bacteremia, skin and skin structure infections (e.g., cellulitis), and bone and joint infections (e.g., osteomyelitis, infectious arthritis) caused by penicillinase-producing Staphylococcus sp.:
    Intravenous dosage*:
    Neonates 34 weeks gestation and younger and 0 to 7 days: 25 mg/kg/dose IV every 12 hours.
    Neonates 34 weeks gestation and younger and older than 7 days: 25 mg/kg/dose IV every 8 hours.
    Neonates older than 34 weeks gestation and 0 to 7 days: 25 mg/kg/dose IV every 8 hours.
    Neonates older than 34 weeks gestation and older than 7 days: 25 mg/kg/dose IV every 6 hours.
    Infants, Children, and Adolescents: 100 to 200 mg/kg/day IV divided every 4 to 6 hours (Max: 12 g/day).

    Intramuscular dosage:
    Neonates 34 weeks gestation and younger and 0 to 7 days: 25 mg/kg/dose IM every 12 hours is recommended by the American Academy of Pediatrics (AAP). The FDA-approved dosage is 10 mg/kg/dose IM every 12 hours.
    Neonates 34 weeks gestation and younger and older than 7 days: 25 mg/kg/dose IM every 8 hours is recommended by the American Academy of Pediatrics (AAP). The FDA-approved dosage is 10 mg/kg/dose IM every 12 hours.
    Neonates older than 34 weeks gestation and 0 to 7 days: 25 mg/kg/dose IM every 8 hours is recommended by the American Academy of Pediatrics (AAP). The FDA-approved dosage is 10 mg/kg/dose IM every 12 hours.
    Neonates older than 34 weeks gestation and older than 7 days: 25 mg/kg/dose IM every 6 hours is recommended by the American Academy of Pediatrics (AAP). The FDA-approved dosage is 10 mg/kg/dose IM every 12 hours.
    Infants, Children, and Adolescents: 100 to 200 mg/kg/day IM divided every 4 to 6 hours (Max: 12 g/day) is recommended by the American Academy of Pediatrics (AAP). Alternately, for patients weighing less than 40 kg, the FDA-approved dosage is 25 mg/kg/dose IM every 12 hours. For patients weighing more than 40 kg, the FDA-approved dosage is 500 mg IM every 4 to 6 hours for most infections and up to 1 g IM or IV every 4 hours for severe infections.

    For the treatment of infective endocarditis:
    Intravenous dosage*:
    Neonates 34 weeks gestation and younger and 0 to 7 days: 25 mg/kg/dose IV every 12 hours.
    Neonates 34 weeks gestation and younger and older than 7 days: 25 mg/kg/dose IV every 8 hours.
    Neonates older than 34 weeks gestation and 0 to 7 days: 25 mg/kg/dose IV every 8 hours.
    Neonates older than 34 weeks gestation and older than 7 days: 25 mg/kg/dose IV every 6 hours.
    Infants: 100 to 200 mg/kg/day IV divided every 4 to 6 hours.
    Children and Adolescents: 200 mg/kg/day IV divided every 4 to 6 hours (Max: 12 g/day) is recommended by guidelines. Nafcillin is an alternative therapy for penicillin-susceptible staphylococcal native valve endocarditis (NVE). Nafcillin is a preferred therapy for penicillin-resistant, methicillin-sensitive S. aureus (MSSA) NVE; may consider adding gentamicin for the first 3 to 5 days. Treat NVE for at least 4 to 6 weeks. For MSSA prosthetic valve endocarditis (PVE), treat with nafcillin plus rifampin for 6 weeks; add gentamicin for the first 2 weeks.

    For the treatment of bacterial meningitis:
    Intravenous dosage*:
    Neonates 0 to 7 days weighing 2 kg or less: 50 mg/kg/dose IV every 12 hours.
    Neonates 0 to 7 days weighing more than 2 kg: 50 mg/kg/dose IV every 8 hours. Alternately, clinical practice guidelines recommend 75 mg/kg/day IV divided every 8 to 12 hours for methicillin-sensitive S. aureus meningitis.
    Neonates older than 7 days weighing 2 kg or less: 50 mg/kg/dose IV every 8 hours.
    Neonates older than 7 days weighing more than 2 kg: 50 mg/kg/dose IV every 6 hours. Alternately, clinical practice guidelines recommend 100 to 150 mg/kg/day IV divided every 6 to 8 hours for methicillin-sensitive S. aureus meningitis.
    Infants, Children, and Adolescents: 200 mg/kg/day IV divided every 6 hours (Max: 12 g/day) is recommended for methicillin-sensitive S. aureus meningitis by clinical practice guidelines.

    For the treatment of lower respiratory tract infections (LRTIs), including community-acquired pneumonia (CAP):
    -for the treatment of nonspecific lower respiratory tract infections (LRTIs):
    Intravenous dosage*:
    Neonates 34 weeks gestation and younger and 0 to 7 days: 25 mg/kg/dose IV every 12 hours.
    Neonates 34 weeks gestation and younger and older than 7 days: 25 mg/kg/dose IV every 8 hours.
    Neonates older than 34 weeks gestation and 0 to 7 days: 25 mg/kg/dose IV every 8 hours.
    Neonates older than 34 weeks gestation and older than 7 days: 25 mg/kg/dose IV every 6 hours.
    Infants, Children, and Adolescents: 150 to 200 mg/kg/day IV divided every 4 to 6 hours (Max: 2 g/dose).
    Intramuscular dosage:
    Neonates 34 weeks gestation and younger and 0 to 7 days: 25 mg/kg/dose IM every 12 hours is recommended by the American Academy of Pediatrics (AAP). The FDA-approved dose is 10 mg/kg/dose IM every 12 hours.
    Neonates 34 weeks gestation and younger and older than 7 days: 25 mg/kg/dose IM every 8 hours is recommended by the American Academy of Pediatrics (AAP). The FDA-approved dose is 10 mg/kg/dose IM every 12 hours.
    Neonates older than 34 weeks gestation and 0 to 7 days: 25 mg/kg/dose IM every 8 hours is recommended by the American Academy of Pediatrics (AAP). The FDA-approved dose is 10 mg/kg/dose IM every 12 hours.
    Neonates older than 34 weeks gestation and older than 7 days: 25 mg/kg/dose IM every 6 hours is recommended by the American Academy of Pediatrics (AAP). The FDA-approved dose is 10 mg/kg/dose IM every 12 hours.
    Infants, Children, and Adolescents weighing less than 40 kg: 150 to 200 mg/kg/day IM divided every 4 to 6 hours (Max: 2 g/dose) is recommended by the American Academy of Pediatrics (AAP). The FDA-approved dose is 25 mg/kg/dose IM every 12 hours.
    Children and Adolescents weighing 40 kg or more: 150 to 200 mg/kg/day IM divided every 4 to 6 hours (Max: 2 g/dose) is recommended by the American Academy of Pediatrics (AAP). The FDA-approved dose is 500 mg IM every 4 to 6 hours for mild to moderate infections and 1 g IM every 4 hours for severe infections.
    -for the treatment of community-acquired pneumonia (CAP):
    Intravenous dosage*:
    Infants 4 to 11 months, Children, and Adolescents: 150 to 200 mg/kg/day IV divided every 4 to 8 hours (Max: 2 g/dose) for 10 days. Guidelines recommend a semisynthetic penicillin for hospitalized patients with infections due to methicillin-susceptible S. aureus.
    Intramuscular dosage:
    Infants 4 to 11 months, Children, and Adolescents: 150 to 200 mg/kg/day IM divided every 4 to 8 hours (Max: 2 g/dose) for 10 days. Guidelines recommend a semisynthetic penicillin for hospitalized patients with infections due to methicillin-susceptible S. aureus.

    For the treatment of neonatal mastitis*:
    Intravenous dosage:
    Neonates 34 weeks gestation and younger and 0 to 7 days: 25 mg/kg/dose IV every 12 hours.
    Neonates 34 weeks gestation and younger and older than 7 days: 25 mg/kg/dose IV every 8 hours.
    Neonates older than 34 weeks gestation and 0 to 7 days: 25 mg/kg/dose IV every 8 hours.
    Neonates older than 34 weeks gestation and older than 7 days: 25 mg/kg/dose IV every 6 hours.
    Infants 1 to 2 months: 100 to 200 mg/kg/day IV divided every 4 to 6 hours.

    Maximum Dosage Limits:
    -Neonates
    20 mg/kg/day IM is the FDA-approved dosage for all neonates; however, this dose is not typically used in current clinical practice. Safety and efficacy of IV route have not been established; however, the following doses have been used off-label:
    0 to 7 days weighing 2 kg or less : up to 100 mg/kg/day IV/IM.
    0 to 7 days weighing more than 2 kg : up to 150 mg/kg/day IV/IM.
    older than 7 days weighing 2 kg or less : up to 150 mg/kg/day IV/IM.
    older than 7 days weighing more than 2 kg : up to 200 mg/kg/day IV/IM.
    -Infants
    50 mg/kg/day IM is the FDA-approved dosage; up to 200 mg/kg/day IV/IM has been used off-label.
    -Children
    weight less than 40 kg: 50 mg/kg/day IM is the FDA-approved dosage; up to 200 mg/kg/day IV/IM has been used off-label.
    weight 40 kg or more: 6 g/day IM is the FDA-approved dosage; up to 200 mg/kg/day (Max: 12 g/day) IV/IM has been used off-label.
    -Adolescents
    weight less than 40 kg: 50 mg/kg/day IM is the FDA-approved dosage; up to 200 mg/kg/day IV/IM has been used off-label.
    weight 40 kg or more: 6 g/day IM is the FDA-approved dosage; up to 200 mg/kg/day (Max: 12 g/day) IV/IM has been used off-label.

    Patients with Hepatic Impairment Dosing
    Specific guidelines for dosage adjustments in patients with hepatic impairment are not available; however, nafcillin clearance is significantly decreased in patients with hepatic dysfunction.

    Patients with Renal Impairment Dosing
    Dosage adjustments are not necessary.

    *non-FDA-approved indication

    Monograph content under development

    Mechanism of Action: Nafcillin, a beta-lactam antibiotic, is mainly bactericidal. It inhibits the third and final stage of bacterial cell wall synthesis by preferentially binding to specific penicillin-binding proteins (PBPs) that are located inside the bacterial cell wall. Penicillin-binding proteins are responsible for several steps in cell wall synthesis and are found in quantities of several hundred to several thousand molecules per bacterial cell. Penicillin-binding proteins vary among different bacterial species. Thus, the intrinsic activity of nafcillin and other beta-lactams against a particular organism depends on their ability to gain access to and bind with the necessary PBP. Like all beta-lactam antibiotics, nafcillin's ability to interfere with PBP-mediated cell wall synthesis ultimately leads to cell lysis. Lysis is mediated by bacterial cell wall autolytic enzymes (i.e., autolysins). The relationship between PBPs and autolysins is unclear, but it is possible that the beta-lactam antibiotic interferes with an autolysin inhibitor. Prevention of the autolysin response to beta-lactam antibiotic exposure through loss of autolytic activity (mutation) or inactivation of autolysin (low-medium pH) by the microorganism can lead to tolerance to the beta-lactam antibiotic resulting in bacteriostatic activity.

    Nafcillin, because of its side chain, resists destruction by beta-lactamases. This makes it useful for treating bacteria that resist penicillin due to the presence of penicillinase. Nafcillin is ineffective, however, against methicillin-resistant S. aureus (MRSA). These organisms appear to resist nafcillin and related antistaphylococcal penicillins due to the presence of a relatively insensitive PBP, although this mechanism is not fully understood.

    Beta-lactams, including nafcillin, exhibit concentration-independent or time-dependent killing. In vitro and in vivo animal studies have demonstrated that the major pharmacodynamic parameter that determines efficacy for beta-lactams is the amount of time free (non-protein bound) drug concentrations exceed the minimum inhibitory concentration (MIC) of the organism (free T > MIC). This microbiological killing pattern is due to the mechanism of action, which is acylation of PBPs. There is a maximum proportion of PBPs that can be acylated; therefore, once maximum acylation has occurred, killing rates cannot increase. Free beta-lactam concentrations do not have to remain above the MIC for the entire dosing interval. The percentage of time required for both bacteriostatic and maximal bactericidal activity is different for the various classes of beta-lactams. Penicillins require free drug concentrations to exceed the MIC for 30% of the dosing interval to achieve bacteriostatic activity and 50% of the dosing interval to achieve bactericidal activity. Cephalosporins require free drug concentrations to be above the MIC for 35-40% of the dosing interval for bacteriostatic activity and 60-70% of the dosing interval for bactericidal activity. Carbapenems require free drug concentrations to exceed the MIC for 20% of the dosing interval for bacteriostatic activity and 40% of the dosing interval for maximal bactericidal activity.

    Pharmacokinetics: Nafcillin is administered intravenously and intramuscularly. Protein binding is approximately 90%; binding is primarily to serum albumin. Nafcillin is widely distributed into liver; bone; bile; and pleural, pericardial, peritoneal, and synovial fluids. Although it generally reaches low concentrations in cerebrospinal fluid (CSF), higher concentrations are obtained when the meninges are inflamed making nafcillin effective in the treatment of meningitis when appropriate doses are used. In the absence of meningeal inflammation, nafcillin has been associated with sub-therapeutic CSF concentrations ; however, in 14 pediatric patients with suspected ventriculoperitoneal shunt infections, nafcillin 200 mg/kg/day IV achieved adequate concentrations in ventricular fluid. Approximately 70-90% of a dose is metabolized in the liver to inactive metabolites; <= 30% of a dose is excreted unchanged in the urine. Unlike other penicillins, nafcillin is excreted primarily in the bile and undergoes enterohepatic circulation. The elimination half-life of nafcillin in adults is approximately 30-60 minutes.

    Affected cytochrome P450 isoenzymes: CYP3A4
    In vitro data suggest that nafcillin may induce the CYP3A4 isoenzyme.


    -Route-Specific Pharmacokinetics
    Intravenous Route
    Peak blood concentrations are reached at the end of an IV infusion. In 14 pediatric patients with suspected VP shunt infections, the peak ventricular fluid concentrations were reached approximately 120-180 minutes after the end of the infusion.

    Intramuscular Route
    Peak concentrations are reached within 1 hour after IM administration in most patients. Bioavailability of the IM route relative to the IV route is approximately 95-100%. In a small pharmacokinetic study in newborns (< 1 day old) and children (1-5 years), peak concentrations at 1 hour were significantly higher in the newborns compared with children (25.34 vs. 6.64 mcg/ml, respectively). The rate of nafcillin elimination was also slower in newborns compared with children.


    -Special Populations
    Pediatrics
    Neonates
    Nafcillin clearance increases with postnatal age; immature hepatic and renal function lead to slower elimination compared to older children. In a pharmacokinetic study in 13 premature neonates (29-33 weeks gestational age; mean weight 1.19 kg), the mean volume of distribution and elimination half-life of nafcillin were 0.33 L/kg and 3.2 hours, respectively. The elimination half-life was approximately 3-4.5 hours in patients <= 7 days, 2.5-3.5 hours in patients 8-21 days, and 1-2 hours in patients > 21 days.

    Infants, Children, and Adolescents
    The pharmacokinetics of nafcillin in infants and children are comparable to those of adults. In a pharmacokinetic study in infants and children (n = 46; 1 month to 13.5 years) the mean volume of distribution and elimination half-life of nafcillin were 0.89 L/kg and 0.76 hours, respectively. No significant differences in pharmacokinetic parameters were found between age groups included in the study.

    Hepatic Impairment
    Pharmacokinetic data are unavailable in pediatric patients with hepatic impairment; however, adult data have shown that the clearance of nafcillin is significantly decreased in patients with hepatic dysfunction. In these patients, the renal elimination of nafcillin is significantly increased from 30% to approximately 50%, indicating that concomitant renal disease may further decrease nafcillin clearance. Dosage adjustments are recommended in patients with concomitant hepatic and renal impairment.

    Renal Impairment
    The clearance of nafcillin is not significantly affected by renal impairment alone. Dosage adjustments are only recommended in patients with concomitant liver impairment.

    Hemodialysis
    Nafcillin is not removed by hemodialysis.

DISCLAIMER: This drug information content is provided for informational purposes only and is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Patients should always consult their physician with any questions regarding a medical condition and to obtain medical advice and treatment. Drug information is sourced from GSDD (Gold Standard Drug Database ) provided by Elsevier.

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