Nafcillin Sodium - Nafcillin Sodium injection, Powder, For Solution prescribing information
INDICATIONS AND USAGE
Nafcillin is indicated in the treatment of infections caused by penicillinase-producing staphylococci which have demonstrated susceptibility to the drug. Culture and susceptibility tests should be performed initially to determine the causative organism and its susceptibility to the drug (see CLINICAL PHARMACOLOGY — Susceptibility Test Methods .
Nafcillin should not be used in infections caused by organisms susceptible to penicillin G. If the susceptibility tests indicate that the infection is due to methicillin-resistant Staphylococcus sp., therapy with Nafcillin for Injection, USP should be discontinued and alternative therapy provided.
To reduce the development of drug-resistant bacteria and maintain the effectiveness of Nafcillin for Injection, USP and other antibacterial drugs, Nafcillin for Injection, USP should be used only to treat or prevent infections that are proven or strongly suspected to be caused by susceptible bacteria. When culture and susceptibility information are available, they should be considered in selecting or modifying antibacterial therapy. In the absence of such data, local epidemiology and susceptibility patterns may contribute to the empiric selection of therapy.
DOSAGE AND ADMINISTRATION
Nafcillin for Injection is available for intramuscular and intravenous use.
The usual I.V dosage for adults is 500 mg every 4 hours. For severe infections, 1 gram every 4 hours is recommended. Administer slowly over at least 30 to 60 minutes to minimize the risk of vein irritation and extravasation.
Drug | Adults | Infants and Children <40 kg (88 lbs) | Other Recommendations |
Nafcillin | 500 mg IM every 4 to 6 hours. IV every 4 hours | 25 mg/kg IM twice daily | Neonates 10 mg/kg IM twice daily |
Nafcillin | 1 gram IM or IV every 4 hours (severe infections) |
Bacteriologic studies to determine the causative organisms and their susceptibility to nafcillin should always be performed. Duration of therapy varies with the type and severity of infection as well as the overall condition of the patient; therefore, it should be determined by the clinical and bacteriological response of the patient. In severe staphylococcal infections, therapy with nafcillin should be continued for at least 14 days. The treatment of endocarditis and osteomyelitis may require a longer duration of therapy.
No dosage alterations are necessary for patients with renal dysfunction, including those on hemodialysis. Hemodialysis does not accelerate nafcillin clearance from the blood.
With intravenous administration, particularly in elderly patients, care should be taken because of the possibility of thrombophlebitis.
Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration whenever solution and container permit. Do not add supplementary medication to Nafcillin.
DIRECTIONS FOR USE
For Intramuscular Use
Reconstitute with Sterile Water for Injection, USP, 0.9% Sodium Chloride Injection, USP or Bacteriostatic Water for Injection, USP (with benzyl alcohol or parabens); add 3.4 mL to the 1 g vial for 4 mL resulting solution and 6.6 mL to the 2 g vial for 8 mL resulting solution. All reconstituted vials have a concentration of 250 mg per mL.
The clear solution should be administered by deep intragluteal injection immediately after reconstitution.
Reconstituted Stability
Reconstitute with the required amount of Sterile Water for Injection, USP, 0.9% Sodium Chloride Injection, USP or Bacteriostatic Water for Injection, USP (with benzyl alcohol or parabens). The resulting solutions are stable for 3 days at room temperature or 7 days under refrigeration and 90 days frozen.
For Direct Intravenous Use
The required amount of drug should be diluted in 15 to 30 mL of Sterile Water for Injection, USP or Sodium Chloride Injection, USP and injected over a 5- to 10- minute period. This may be accomplished through the tubing of an intravenous infusion if desirable.
For Administration by Intravenous Drip
Reconstitute as directed above (For Intravenous Use) prior to diluting with intravenous solution.
| •IMPORTANT: This chemical stability information in no way indicates that it would be acceptable practice to use this product well after the preparation time. Good professional practice suggests that a product should be used as soon after preparation as feasible. | |||||||
Concentration mg/mL | Sterile water for Injection , USP | Sodium Chloride Injection USP (0.9%) | Sodium Lactate Solution USP (M/6 Molar) | Dextrose injection USP (5%) | Dextrose and sodium chloride injection USP (5% Dextrose and 0.45% Sodium Chloride) | Invert Sugar Injection USP (10%) | Lactated Ringer’s Injection USP |
ROOM TEMPERATURE (25° C) | |||||||
10-200 | 24 Hrs | 24 Hrs | |||||
30 | 24 Hrs | ||||||
2-30 | 24 Hrs | 24 Hrs | |||||
10-30 | 24 Hrs | 24 Hrs | |||||
REFRIGERATION (4° C) | |||||||
10-200 | 7 Days | 7 Days | |||||
10-30 | 7 Days | 7 Days | 7 Days | 7 Days | 7 Days | ||
FROZEN (-15° C) | |||||||
250 | 90 Days | 90 Days | |||||
10-250 | 90 Days | 90 Days | 90 Days | 90 Days | 90 Days | ||
Only those solutions listed above should be used for the intravenous infusion of nafcillin sodium, USP. The concentration of the antibiotic should fall within the range specified. The drug concentration and the rate and volume of the infusion should be adjusted so that the total dose of nafcillin is administered before the drug loses its stability in the solution in use.
There is no clinical experience available on the use of this agent in neonates or infants for this route of administration.
This route of administration should be used for relatively short-term therapy (24 to 48 hours) because of the occasional occurrence of thrombophlebitis particularly in elderly patients.
If another agent is used in conjunction with nafcillin therapy, it should not be physically mixed with nafcillin but should be administered separately.
CONTRAINDICATIONS
A history of a hypersensitivity (anaphylactic) reaction to any penicillin is a contraindication.
ADVERSE REACTIONS
Body as a Whole
The reported incidence of allergic reactions to penicillin ranges from 0.7 to 10 percent (see WARNINGS ). Sensitization is usually the result of treatment, but some individuals have had immediate reactions to penicillin when first treated. In such cases, it is thought that the patients may have had prior exposure to the drug via trace amounts present in milk or vaccines. Two types of allergic reactions to penicillins are noted clinically, immediate and delayed.
Immediate reactions usually occur within 20 minutes of administration and range in severity from urticaria and pruritus to angioedema, laryngospasm, bronchospasm, hypotension, vascular collapse, and death. Such immediate anaphylactic reactions are very rare (see WARNINGS ) and usually occur after parenteral therapy but have occurred in patients receiving oral therapy. Another type of immediate reaction, an accelerated reaction, may occur between 20 minutes and 48 hours after administration and may include urticaria, pruritus, and fever.
Although laryngeal edema, laryngospasm, and hypotension occasionally occur, fatality is uncommon. Delayed allergic reactions to penicillin therapy usually occur after 48 hours and sometimes as late as 2 to 4 weeks after initiation of therapy. Manifestations of this type of reaction include serum sickness-like symptoms ( i.e. , fever, malaise, urticaria, myalgia, arthralgia, abdominal pain) and various skin rashes. Nausea, vomiting, diarrhea, stomatitis, black or hairy tongue, and other symptoms of gastrointestinal irritation may occur, especially during oral penicillin therapy.
Local Reactions
Pain, swelling, inflammation, phlebitis, thrombophlebitis, and occasional skin sloughing at the injection site have occurred with intravenous administration of nafcillin. (See DOSAGE AND ADMINISTRATION ) Severe tissue necrosis with sloughing secondary to subcutaneous extravasation of nafcillin has been reported.
Nervous System Reactions
Neurotoxic reactions similar to those observed with penicillin G could occur with large intravenous or intraventricular doses of nafcillin especially in patients with concomitant hepatic insufficiency and renal dysfunction. (See PRECAUTIONS ).
Urogenital Reactions
Renal tubular damage and interstitial nephritis have been associated with the administration of nafcillin. Manifestations of this reaction may include rash, fever, eosinophilia, hematuria, proteinuria, and renal insufficiency.
Hepatic Reactions
Elevation of liver transaminases and/or cholestasis may occur, especially with administration of high doses of nafcillin.
Gastrointestinal Reactions
Pseudomembranous colitis has been reported with the use of nafcillin. The onset of pseudomembranous colitis symptoms may occur during or after antibiotic treatment (see WARNINGS ).
Metabolic Reactions
Agranulocytosis, neutropenia, and bone marrow depression have been associated with the use of nafcillin.
To report SUSPECTED ADVERSE REACTIONS , contact Onesource at 1-888-217-8103 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch
OVERDOSAGE
Neurotoxic reactions similar to those observed with penicillin G may arise with intravenous doses of nafcillin especially in patients with concomitant hepatic insufficiency and renal dysfunction (see PRECAUTIONS ).
In the case of overdosage, discontinue nafcillin, treat symptomatically and institute supportive measures as required. Hemodialysis does not increase the rate of clearance of nafcillin from the blood.
DESCRIPTION
Nafcillin for Injection, USP is semisynthetic penicillin derived from the penicillin nucleus, 6-aminopenicillanic acid. The chemical name of nafcillin sodium is Monosodium (2 S ,5 R ,6 R )-6-(2-ethoxy-1-naphthamido)-3,3-dimethyl-7-oxo-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylate monohydrate. It is resistant to inactivation by the enzyme penicillinase (beta-lactamase). The structural formula is as follows:
Nafcillin for Injection, USP for the intramuscular or intravenous route of administration, contains nafcillin sodium as a sterile white to yellowish white powder for reconstitution. The pH of the reconstituted solution is 6 to 8.5. Nafcillin for Injection, USP contains nafcillin sodium as the monohydrate equivalent to 1 gram or 2 grams of nafcillin per vial and is buffered with 40 mg sodium citrate per gram. The sodium content is 63.39 mg [2.76 mEq] per gram.
CLINICAL PHARMACOLOGY
In a study of five healthy adults administered a single 500 mg dose of nafcillin by intravenous injection over seven minutes, the mean plasma concentration of the drug was approximately 30 mcg/mL at 5 minutes after injection. The mean area under the plasma concentration-versus-time curve (AUC) for nafcillin in this study was 18.06 mcg.h/mL.
The serum half-life of nafcillin administered by the intravenous route ranged from 33 to 61 minutes as measured in three separate studies.
In contrast to the other penicillinase-resistant penicillins, only about 30% of nafcillin is excreted as unchanged drug in the urine of normal volunteers, and most within the first six hours. Nafcillin is primarily eliminated by nonrenal routes, namely hepatic inactivation and excretion in the bile.
Nafcillin binds to serum proteins, mainly albumin. The degree of protein binding reported for nafcillin is 89.9 ± 1.5%. Reported values vary with the method of study and the investigator.
The concurrent administration of probenecid with nafcillin increases and prolongs plasma concentrations of nafcillin. Probenecid significantly reduces the total body clearance of nafcillin with renal clearance being decreased to a greater extent than nonrenal clearance.
The penicillinase-resistant penicillins are widely distributed in various body fluids, including bile, pleural, amniotic and synovial fluids. With normal doses insignificant concentrations are found in the aqueous humor of the eye. High nafcillin CSF levels have been obtained in the presence of inflamed meninges.
Renal failure does not appreciably affect the serum half-life of nafcillin; therefore, no modification of the usual nafcillin dosage is necessary in renal failure with or without hemodialysis. Hemodialysis does not accelerate the rate of clearance of nafcillin from the blood.
A study which assessed the effects of cirrhosis and extrahepatic biliary obstruction in man demonstrated that the plasma clearance of nafcillin was significantly decreased in patients with hepatic dysfunction. In these patients with cirrhosis and extrahepatic obstruction, nafcillin excretion in the urine was significantly increased from about 30 to 50% of the administered dose, suggesting that renal disease superimposed on hepatic disease could further decrease nafcillin clearance.
PHARMACOKINETICS
Intramuscular injections of nafcillin sodium, USP 1 gram produced peak serum levels in 0.5 to 1 hour of 7.61 mcg/mL. The degree of protein binding reported has been 89.9 +/-1.5%. With normal doses nafcillin is found in therapeutic concentrations in the pleural, bile, and amniotic fluids. Insignificant concentrations are found in the cerebrospinal fluid and aqueous humor. Blood concentrations may be tripled by the concurrent use of probenecid. Clinical studies with nafcillin sodium in infants under three days of age and prematures have revealed higher blood levels and slower rates of urinary excretion than in older children and adults. A high concentration of nafcillin sodium is excreted via the bile. About 30% of an intramuscular dose is excreted in the urine.
MICROBIOLOGY
Penicillinase-resistant penicillins exert a bactericidal action against penicillin-susceptible microorganisms during the state of active multiplication. All penicillins inhibit the biosynthesis of the bacterial cell wall. Nafcillin sodium has been shown to be active against most isolates of the following microorganism, both in vitro and in clinical infections as described in the INDICATIONS AND USAGE section.
Gram-Positive Bacteria
Staphylococcus aureus (Methicillin-susceptible isolates only)
Susceptibility Test Methods
For specific information regarding susceptibility test interpretive criteria, and associated test methods and quality control standards recognized by FDA for nafcillin for injection, please see: https://www.fda.gov/STIC.
HOW SUPPLIED
Each Nafcillin for Injection, USP vial contains nafcillin sodium,USP equivalent to 1 gram or 2 grams of nafcillin.
| • Vial stoppers are not made with natural rubber latex. Store dry powder at 20° to 25°C (68° to 77°F). [See USP Controlled Room Temperature.] | ||
NDC | Nafcillin for Injection , USP | Package factor |
72485-405-10 | 1 gram vial • | 10s |
72485-406-10 | 2 grams vial • | 10s |
