nafcillin 250 MG Oral Capsule

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 may be used to initiate therapy in suspected cases of resistant staphylococcal infections prior to the availability of susceptibility test results. 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 an organism other than a resistant Staphylococcus , therapy should not be continued with Nafcillin. To reduce the development of drug-resistant bacteria and maintain the effectiveness of Nafcillin for Injection and other antibacterial drugs, Nafcillin for Injection 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 IV 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. Recommended Dosage for Nafcillin for Injection, USP 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 for Injection, USP. 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 gram vial for 4 mL resulting solution and 6.6 mL to the 2 grams 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 intra- venous infusion if desirable. For Administration by Intravenous Drip Reconstitute as directed above (For Intravenous Use) prior to diluting with intravenous solutions. STABILITY PERIODS FOR NAFCILLIN FOR 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. 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 (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 intra- venous infusion of Nafcillin for Injection, USP. The concentrations 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.

WARNINGS SERIOUS AND OCCASIONALLY FATAL HYPERSENSITIVITY (ANAPHYLACTIC) REACTIONS HAVE BEEN REPORTED IN PATIENTS ON PENICILLIN THERAPY. THESE REACTIONS ARE MORE LIKELY TO OCCUR IN INDIVIDUALS WITH A HISTORY OF PENICILLIN HYPERSENSITIVITY AND/OR A HISTORY OF SENSITIVITY TO MULTIPLE ALLERGENS. THERE HAVE BEEN REPORTS OF INDIVIDUALS WITH A HISTORY OF PENICILLIN HYPERSENSITIVITY WHO HAVE EXPERIENCED SEVERE REACTIONS WHEN TREATED WITH CEPHALOSPORINS. BEFORE INITIATING THERAPY WITH NAFCILLIN, CAREFUL INQUIRY SHOULD BE MADE CONCERNING PREVIOUS HYPERSENSITIVITY REACTIONS TO PENICILLINS, CEPHALOSPORINS, OR OTHER ALLERGENS. IF AN ALLERGIC REACTION OCCURS, NAFCILLIN SHOULD BE DISCONTINUED AND APPROPRIATE THERAPY INSTITUTED. SERIOUS ANAPHYLACTIC REACTIONS REQUIRE IMMEDIATE EMERGENCY TREATMENT WITH EPINEPHRINE. OXYGEN, INTRAVENOUS STEROIDS, AND AIRWAY MANAGEMENT, INCLUDING INTUBATION, SHOULD ALSO BE ADMINISTERED AS INDICATED. Clostridium difficile associated diarrhea (CDAD) has been reported with use of nearly all antibacterial agents, including Nafcillin for Injection, and may range in severity from mild diarrhea to fatal colitis. Treatment with antibacterial agents alters the normal flora of the colon leading to overgrowth of C. difficile . C. difficile produces toxins A and B which contribute to the development of CDAD. Hypertoxin producing strains of C. difficile cause increased morbidity and mortality, as these infections can be refractory to antimicrobial therapy and may require colectomy. CDAD must be considered in all patients who present with diarrhea following antibiotic use. Careful medical history is necessary since CDAD has been reported to occur over two months after the administration of antibacterial agents. 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.

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

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.