NAFCILLIN

Nafcillin for Injection, USP is semisynthetic penicillin derived from the penicillin nucleus, 6-aminopenicillanic acid. The chemical name of nafcillin sodium is Monosodium (2S,5R,6R)-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 is a sterile white to yellowish-white powder for reconstitution and is supplied in 10 gram Pharmacy Bulk Package bottles. Each Pharmacy Bulk Package contains nafcillin sodium as the monohydrate equivalent to 10 grams of nafcillin. Sodium citrate is added to optimize pH. The sodium content is not more than 65.78 mg [2.9 mEq] per gram of nafcillin. A pharmacy bulk package is a container of a sterile preparation for parenteral use that contains many single doses. The contents of this pharmacy bulk package are intended for use by a pharmacy admixture service for addition to suitable parenteral fluids in the preparation of admixtures for intravenous infusion (See DOSAGE AND ADMINISTRATION, Directions for Proper Use of Pharmacy Bulk Package .) FURTHER DILUTION IS REQUIRED. NOT FOR DIRECT INFUSION. Chemical Structure

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 a 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.

The intent of the pharmacy bulk package for this product is for preparation of solutions for IV infusion only. Nafcillin for Injection is available for 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. 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 Administration by Intravenous Drip Refer to Directions for Proper Use of a Pharmacy Bulk Package Bottle. Add 93 mL Sterile Water for Injection, USP, or 0.9% Sodium Chloride Injection, USP. The resulting solution will contain 100 mg nafcillin activity per mL and will require further dilution. CAUTION: NOT TO BE DISPENSED AS A UNIT. Directions for Proper Use of Pharmacy Bulk Package a. The container closure may be penetrated only one time after reconstitution, utilizing a suitable sterile dispensing set which allows measured distribution of the contents. b. Use of this product is restricted to a suitable work area, such as a laminar flow hood. c. Once this container closure has been punctures, withdrawal of the contents should be completed without delay. If prompt fluid transfer cannot be accomplished, discard the contents no later than 4 HOURS after initial closure puncture. This time limit should begin with the introduction of solvent for diluent into the Pharmacy Bulk Package. 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 for Injection, USP. STABILITY PERIODS FOR NAFCILLIN FOR INJECTION, USP* 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 * 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. ROOM TEMPERATURE (25ºC) 10 to 200 24 Hrs 24 Hrs 30 24 Hrs 2 to 30 24 Hrs 24 Hrs 10 to 30 24 Hrs 24 Hrs REFRIGERATION (4ºC) 10 to 200 7 Days 7 Days 10 to 30 7 Days 7 Days 7 Days 7 Days 7 Days FROZEN (-15ºC) 250 90 Days 90 Days 10 to 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.

A history of a hypersensitivity (anaphylactic) reaction to any penicillin is a contraindication.

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 EVENTS, contact FDA at 1-800-FDA-1088 or www.fda.gov

Tetracycline, a bacteriostatic antibiotic, may antagonize the bactericidal effect of penicillin, and concurrent use of these drugs should be avoided. Nafcillin in high dosage regimens, i.e., 2 grams every 4 hours, has been reported to decrease the effects of warfarin. When nafcillin and warfarin are used concomitantly, the prothrombin time should be closely monitored and the dose of warfarin adjusted as necessary. This effect may persist for up to 30 days after nafcillin has been discontinued. Nafcillin when administered concomitantly with cyclosporine has been reported to result in subtherapeutic cyclosporine levels. The nafcillin-cyclosporine interaction was documented in a patient during two separate courses of therapy. When cyclosporine and nafcillin are used concomitantly in organ transplant patients, the cyclosporine levels should be monitored.