nafcillin

414.48

414.47

205-690-9

4CNZ27M7RV

DTXSID8023343

C62053

J - Antiinfectives for systemic use

3.3

1.42±0.1 g/cm3(Predicted)

714.1±60.0 °C(Predicted)

Soluble|NOT MORE THAN SLIGHT CHARACTERISTIC ODOR; WHITE TO YELLOWISH WHITE POWDER; FREELY SOL IN WATER & CHLOROFORM, SOL IN ALCOHOL /NAFCILLIN SODIUM/|1.72e-02 g/L

Commercially available nafcillin sodium capsules and tablets should be stored in tight containers at a temperature less than 40 °C, preferably between 15-30 °C; the tablets should also be protected from light. /Nafcillin sodium/|Nafcillin sodium powder for injection should be stored @ room temperature or colder. /Nafcillin sodium/

2.44±0.50(Predicted)

196.1 Ų [M+H]+ [CCS Type: TW, Method: calibrated with Waters Major Mix]|202 Ų [M+Na]+ [CCS Type: TW, Method: calibrated with Waters Major Mix]

STABLE @ ROOM TEMP FOR 2-4 YR /DRY STATE/ DEPENDING ON DOSAGE FORM|ORAL SOLN AFTER RECONSTITUTION WITH DILUENT SHOULD BE STORED @ 2-8 °C /DISCARD UNUSED SOLN AFTER 1 WK/|STABLE FOR 24 HR IN 1/6 MOLAR SODIUM LACTATE INJECTION WHEN STORED @ ROOM TEMP IN CONCN OF 30 MG/ML|LESS THAN 10% ACTIVITY LOST @ ROOM TEMP IN 24 HR (0.905% SODIUM CHLORIDE, 5% DEXTROSE IN 0.45% SODIUM CHLORIDE OR RINGER SOLN)|For more Stability/Shelf Life (Complete) data for NAFCILLIN (10 total), please visit the HSDB record page.

SRP: At the time of review, criteria for land treatment or burial (sanitary landfill) disposal practices are subject to significant revision. Prior to implementing land disposal of waste residue (including waste sludge), consult with environmental regulatory agencies for guidance on acceptable disposal practices.

Manufacturers, packers, and distributors of drug and drug products for human use are responsible for complying with the labeling, certification, and usage requirements as prescribed by the Federal Food, Drug, and Cosmetic Act, as amended (secs 201-902, 52 Stat. 1040 et seq., as amended; 21 U.S.C. 321-392).

Serious toxicity is unlikely following large doses of nafcillin. Acute ingestion of large doses of nafcillin may cause nausea, vomiting, diarrhea and abdominal pain. Acute oliguric renal failure and hematuria may occur following large doses. The oral LD50 in rats is >5000mg/kg and the intravenous LD50 in rats is >1000mg/kg [MSDS].

The serum aminotransferase elevations that appear during high dose intravenous therapy with oxacillin do not appear to occur with high doses of nafcillin, and patients who develop elevated serum aminotransferase levels while on high dose oxacillin can be safety switched to intravenous nafcillin or other penicillin antibiotics. Only rare instances of clinically apparent hepatotoxicity have been linked to use of nafcillin. Typically, the injury has been a cholestatic hepatitis that arises 1 to 6 weeks after starting nafcillin and can be prolonged, but ultimately resolves. Rash, fever and eosinophilia are uncommon but can occur (Case 1). The injury is similar to that described with flucloxacillin and cloxacillin but is far less frequent with nafcillin. Autoantibodies are uncommon.|Three forms of liver injury have been attributed to the penicillinase-resistant and other penicillins. The first is a transient and usually asymptomatic elevation in serum aminotransferase levels that occurs with high dose intravenous therapy with oxacillin (Case 1, Oxacillin) and rarely with standard penicillins (Case 1, Penicillin G). This reaction has not been described with nafcillin or dicloxacillin and patients can be safety switched to these or other forms of penicillin in the face of oxacillin injury. This form of penicillin-induced liver injury occurs only with high dose therapy that is likely due to direct hepatotoxicity.

SERUM BINDING OF...NAFCILLIN...IS REDUCED WHEN ADMIN CONCURRENTLY WITH ASPIRIN.|CHLORAMPHENICOL MAY ANTAGONIZE ACTION OF PENICILLINS. /PENICILLINS/|...ALL...PENICILLINS & ERYTHROMYCINS MAY THEORETICALLY BE EXPECTED TO.../EXHIBIT SYNERGISTIC ANTIBACTERIAL ACTIVITY/. /PENICILLINS/|TETRACYCLINE MAY ANTAGONIZE BACTERICIDAL EFFECT OF PENICILLIN /G/...ANTAGONISM OF ACTION OF ALL...PENICILLINS MIGHT BE EXPECTED. /PENICILLINS/|For more Interactions (Complete) data for NAFCILLIN (14 total), please visit the HSDB record page.

The degree of nafcillin binding to serum proteins is 89.9 ± 1.5%, where it is mainly bound to albumin.

Indicated in the treatment of infections caused by penicillinase-producing staphylococci which have demonstrated susceptibility to the drug.|FDA Label

Nafcillin is a parenteral, second generation penicillinase-resistant penicillin antibiotic used largely to treat moderate to severe staphylococcal infections. Nafcillin has been linked to rare occurrences of clinically apparent, idiosyncratic liver injury.

Penicillin (Penicillinase-Resistant)

Penicillins|NAFCILLIN IS SIMILAR TO OXACILLIN IN ITS POTENCY AGAINST /PENICILLINASE-PRODUCING/ PENICILLIN G-RESISTANT STAPH AUREUS, BUT NOT AS ACTIVE AS PENICILLIN G AGAINST STAPHYLOCOCCI SENSITIVE TO THE LATTER AGENT. NAFCILLIN IS INACTIVATED TO A VARIABLE DEGREE IN ACIDIC MEDIUM OF GASTRIC CONTENTS.|ALTHOUGH...ALSO EFFECTIVE AGAINST NON-PENICILLINASE-PRODUCING STREPTOCOCCI, PNEUMOCOCCI, & GONOCOCCI, IT IS USUALLY NOT USED TO TREAT INFECTIONS CAUSED BY THESE BACTERIA UNLESS THEY ARE PART OF A MIXED INFECTION WITH PENICILLIN G-RESISTANT STAPHYLOCOCCI. /NAFCILLIN SODIUM/|NAFCILLIN...SUPPRESSES GROWTH OF E COLI & CERTAIN OTHER ORGANISMS THAT CAUSE URINARY TRACT INFECTIONS, &...IS SOMETIMES USED TO TREAT SUCH INFECTIONS; HOWEVER, AFTER ORAL ADMIN, ESP, URINE LEVELS OF DRUG ARE GENERALLY LOWER THAN WITH...OTHER PENICILLINS OR TOO ERRATIC, SO PARENTERAL ADMIN OF OTHER PENICILLINS...PREFERRED.|For more Therapeutic Uses (Complete) data for NAFCILLIN (14 total), please visit the HSDB record page.

3 PEDIATRIC PATIENTS ON 100-180 MG/KG/DAY NAFCILLIN DEVELOPED NEUTROPENIA. RECOMMENDED THAT ABSOLUTE NEUTROPHIL COUNT LESS THAN 1000/ML INDICATES CHANGE TO NON-PENICILLIN ANTIBIOTIC. CHILDREN ON IV PENICILLINS SHOULD HAVE WBC COUNTS WITH DIFFERENTIAL ANALYSIS 2-3 TIMES/WK.|UNUSUALLY HIGH OCCURRENCE OF DRUG REACTIONS WITH NAFCILLIN.|Because penicillins are distributed into milk, nafcillin should be used with caution in nursing women.|Penicillins are distributed into breast milk, some in low concentrations. Although significant problems in humans have not been documented, the use of penicillins by nursing mothers may lead to sensitization, diarrhea, candidiasis, and skin rash in the infant. /Penicillins/|For more Drug Warnings (Complete) data for NAFCILLIN (17 total), please visit the HSDB record page.

/IN HAMSTERS/ TOLERANCE DEVELOPED TO MULTIPLE DOSING. /PENICILLINS/

Nafcillin is a semisynthetic antibiotic substance derived from 6-amino-penicillanic acid. The drugs in this class are highly resistant to inactivation by staphylococcal penicillinase and are active against penicillinase-producing and non penicillinase-producing strains of Staphylococcus species.

Substances that inhibit the growth or reproduction of BACTERIA. (See all compounds classified as Anti-Bacterial Agents.)

Following intravenous administration of 500mg nafcillin, the mean plasma concentration was approximately 30 µg/mL. This value was reached after 5 minutes of injection.|Nafcillin is primarily eliminated by non-renal routes, namely hepatic inactivation and excretion in the bile.|Nafcillin is reported to be widely distributed in various body fluids, including bile, pleural, amniotic and synovial fluids.|...ABSORPTION AFTER ORAL ADMIN IS IRREGULAR...WHETHER...TAKEN WITH MEALS OR ON EMPTY STOMACH. AFTER PARENTERAL ADMIN, PLASMA CONCN OF NAFCILLIN IS LOWER THAN...EQUIV DOSE OXACILLIN. THIS IS ASSOC WITH...LARGER APPARENT VOL DISTRIBUTION OF NAFCILLIN, RESULTING FROM SELECTIVE SEQUESTRATION...IN LIVER & POSSIBLY OTHER TISSUE|...BOUND TO PLASMA PROTEIN TO EXTENT OF ABOUT 90%. ONLY APPROX 10% OF ORAL DOSE...RECOVERABLE IN URINE. PROBENECID FURTHER REDUCES EXCRETION IN URINE. MAJOR CHANNEL OF ELIMINATION...IS BILE...ABOUT 90% OF SINGLE IV DOSE... ACCOUNTED FOR BY BILIARY EXCRETION; THERE IS SOME REABSORPTION OF DRUG FROM SMALL INTESTINE.|PEAK CONCN OF NAFCILLIN IN BILE ARE WELL ABOVE THOSE FOUND IN PLASMA.|A 1 G ORAL DOSE NAFCILLIN SODIUM REACHED BLOOD CONCN 0.7 MG% @ 1 HR; 0.5 G IM DOSE REACHED CONCN 0.6 MG% @ 1 HR. 17% OF AN ORAL DOSE WAS EXCRETED IN URINE; 36% OF IM DOSE WAS EXCRETED IN URINE. /NAFCILLIN SODIUM/|For more Absorption, Distribution and Excretion (Complete) data for NAFCILLIN (19 total), please visit the HSDB record page.

Hepatic metabolism accounts for less than 30% of the biotransformation of most penicillins.|...PROTON-CATALYZED HYDROLYSIS /OF PENICILLINS/ TO YIELD PENICILLOIC ACIDS IS WELL DOCUMENTED...CATALYZED BY BACTERIAL BETA-LACTAMASE & BY MAMMALIAN ENZYMES. /PENICILLINS/|NAFCILLIN GIVES 2-ETHOXY-1-NAPHTHAMIDOPENICILLOIC ACID IN BACILLUS. /FROM TABLE/|Approx 60% of a dose of nafcillin is metabolized in the liver to inactive metabolites.

The serum half-life of nafcillin administered by the intravenous route ranged from 33 to 61 minutes as measured in three separate studies.|NORMAL T1/2 OF NAFCILLIN IS 0.5 HR. /FROM TABLE/|The serum half-life of nafcillin in adults with normal renal and hepatic function averages 0.5-1.5 hr. In one study in healthy adults, nafcillin had a distribution half-life ... of 0.17 hr and an elimination half-life ... of 1.02 hr.|The serum half-life of ... /nafcillin/ is reportedly 1.2-1.9 hr in patients with creatinine clearances of 3-59 ml/min per 1.73 sq meters and 1.8-2.8 hr in patients with creatinine clearances less than 3 ml/min per 1.73 sq meters.|In one study in patients with cirrhosis or extrahepatic biliary obstruction, the t1/2alpha of nafcillin averaged 0.26 or 0.29 hr, respectively, and the t1/2beta averaged 1.2 and 1.7 hr, respectively. Serum clearance of the drug in these patients was lower than in patients with normal renal and hepatic function and averaged 291.5 ml/min in those with cirrhosis and 163.4 ml/min in those with extrahepatic obstruction.|In children 1 mo to 14 yr of age, the serum half-life of nafcillin ranges from 0.75-1.9 hr. Serum concn of nafcillin are generally higher and the serum half-life is longer in neonates than in older children. In one study, the serum half-life of nafcillin ranged from 2.2-5.5 hr in neonates 3 wk of age or younger and 1.2-2.3 hr in neonates 4-9 wk of age.

Like other penicillins, nafcillin exerts a bactericidal action against penicillin-susceptible microorganisms during the state of active multiplication in the bacterial cell wall synthesis. It inhibits the biosynthesis of the bacterial cell wall by forming covalent bonds with penicillin-binding proteins that play a critical role in the final transpeptidation process. Binding to penicillin-binding proteins inhibits the transpeptidase and carboxypeptidase activities conferred by these proteins and prevents the formation of the crosslinks.|SODIUM NAFCILLIN & METHICILLIN ARE GOOD EXAMPLES OF A STRUCTURAL DESIGN THAT INHIBITS BETA-LACTAM HYDROLYSIS BY STERIC CROWDING. /SODIUM NAFCILLIN/|The penicillins and their metabolites are potent immunogens because of their ability to combine with proteins and act as haptens for acute antibody-mediated reactions. The most frequent (about 95 percent) or "major" determinant of penicillin allergy is the penicilloyl determinant produced by opening the beta-lactam ring of the penicillin. This allows linkage of the penicillin to protein at the amide group. "Minor" determinants (less frequent) are the other metabolites formed, including native penicillin and penicilloic acids. /Penicillins/|Bactericidal; inhibit bacterial cell wall synthesis. Action is dependent on the ability of penicillins to reach and bind penicillin-binding proteins (PBPs) located on the inner membrane of the bacterial cell wall. Penicillin-binding proteins (which include transpeptidases, carboxypeptidases, and endopeptidases) are enzymes that are involved in the terminal stages of assembling the bacterial cell wall and in reshaping the cell wall during growth and division. Penicillins bind to, and inactivate, penicillin-binding proteins, resulting in the weakening of the bacterial cell wall and lysis. /Penicillins/

SEE PENICILLINS. MASSIVE IV DOSES...(20-60 MILLION UNITS/DAY...) MAY RESULT IN ENCEPHALOPATHY WITH MUSCULAR HYPERIRRITABILITY, MYOCLONUS, VISUAL & AUDITORY HALLUCINATIONS & GENERALIZED CONVULSIONS. /PENICILLINS/|OF 29 STAPH AUREUS PATIENTS TREATED WITH 12 G/DAY IV NAFCILLIN, 4 HAD FEVER, RASH, & LEUKOPENIA; 1 HAD ABSOLUTE NEUTROPENIA.|EFFECT IS MOST LIKELY DUE TO DIRECT TOXIC EFFECT ON BONE MARROW. USUALLY OCCURS DURING 3RD WK THERAPY & REMITS WITH DRUG CESSATION.|HYPOKALEMIA WAS ASSOCIATED WITH NAFCILLIN ADMINISTRATION.|For more Human Toxicity Excerpts (Complete) data for NAFCILLIN (46 total), please visit the HSDB record page.

Nafcil

POWDER FOR INJECTION IS BUFFERED WITH 40 MG SODIUM CITRATE/G OF DRUG; CAPSULES & TABLETS ARE BUFFERED WITH CALCIUM CARBONATE.|NAFCILLIN SODIUM, USP (UNIPEN)...AVAILABLE FOR ORAL & PARENTERAL USE. CAPSULES USUALLY CONTAIN 250 MG...DRUG. SOLN IS ALSO MARKETED FOR ORAL USE. STERILE PREPN FOR INJECTION...AMPULS CONTAINING 500 MG, 1 G, OR 2 G OF SALT. /NAFCILLIN SODIUM/

...A SEMISYNTHETIC PENICILLIN, DERIVED FROM 6-AMINOPENICILLANIC ACID, IS HIGHLY RESISTANT TO PENICILLINASE...|PATENTS: US PATENT 3,157,639. /NAFCILLIN SODIUM/|POTENCY: NOT LESS THAN 820 UG OF NAFCILLIN/MG. /NAFCILLIN SODIUM/|Doyle et al. Brit pat 880,400 (1961 to Beecham) /Nafcillin sodium/

PYROLYSIS GLC PROVIDED REPRODUCIBLE PYROGRAMS FOR 14 PENICILLINS & CEPHALOSPORINS AS FOOD & DRUG INGREDIENTS.

A NEW, RAPID METHOD FOR MEASURING NAFCILLIN IS DESCRIBED. THE RESULTS OBTAINED BY THIS SPECTROFLUOROMETRIC TECHNIQUE WERE IN COMPLETE ACCORD WITH THOSE OBTAINED BY THE CONVENTIONAL ASSAY USING STAPHYLOCOCCUS AUREUS ATCC 6538P.

Human Drugs -> FDA Approved Drug Products with Therapeutic Equivalence Evaluations (Orange Book) -> Active Ingredients|Pharmaceuticals