Neurotoxic reactions similar to those observed with penicillin G may arise with intravenous doses of Nafcillin Sodium Sandoz especially in patients with concomitant hepatic insufficiency and renal dysfunction (see PRECAUTIONS).
In the case of overdosage, discontinue Nafcillin Sodium Sandoz, treat symptomatically and institute supportive measures as required. Hemodialysis does not increase the rate of clearance of Nafcillin Sodium Sandoz from the blood.
A history of a hypersensitivity (anaphylactic) reaction to any penicillin is a contraindication.
Solutions containing dextrose may be contraindicated in patients with known allergy to corn or corn products.
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 ReactionsPain, swelling, inflammation, phlebitis, thrombophlebitis, and occasional skin sloughing at the injection site have occurred with intravenous administration of Nafcillin Sodium Sandoz (see DOSAGE AND ADMINISTRATION). Severe tissue necrosis with sloughing secondary to subcutaneous extravasation of Nafcillin Sodium Sandoz has been reported.
Nervous System ReactionsNeurotoxic reactions similar to those observed with penicillin G could occur with large intravenous or intraventricular doses of Nafcillin Sodium Sandoz especially in patients with concomitant hepatic insufficiency and renal dysfunction (see PRECAUTIONS).
Urogenital ReactionsRenal tubular damage and interstitial nephritis have been associated with the administration of Nafcillin Sodium Sandoz. Manifestations of this reaction may include rash, fever, eosinophilia, hematuria, proteinuria, and renal insufficiency.
Hepatic ReactionsElevation of liver transaminases and/or cholestasis may occur, specifically with administration of high doses of Nafcillin Sodium Sandoz.
Gastrointestinal ReactionsPseudomembranous colitis has been reported with the use of Nafcillin Sodium Sandoz. The onset of pseudomembranous colitis symptoms may occur during or after antibiotic treatment (see WARNINGS).
Metabolic ReactionsAgranulocytosis, neutropenia, and bone marrow depression have been associated with the use of Nafcillin Sodium Sandoz.
Nafcillin Sodium Sandoz 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 Sodium Sandoz 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 species, therapy with Nafcillin Sodium Sandoz Injection, USP should be discontinued and alternative therapy provided.
To reduce the development of drug-resistant bacteria and maintain the effectiveness of Nafcillin Sodium Sandoz Injection, USP and other antibacterial drugs, Nafcillin Sodium Sandoz 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.
Serious and occasionally fatal hypersensitivity (anaphylactic) reactions have been reported in patients receiving beta-lactam antibacterial drugs. These reactions are more likely to occur in individuals with a history of penicillin hypersensitivity and/or a history of sensitivity to multiple allergens. Before initiating therapy with Nafcillin Sodium Sandoz, inquire about previous hypersensitivity reactions to penicillins, cephalosporins, or other allergens. If an allergic reaction occurs, discontinue Nafcillin Sodium Sandoz and institute appropriate therapy.
Clostridium difficile associated diarrhea (CDAD) has been reported with use of nearly all antibacterial agents, including Nafcillin Sodium Sandoz Injection, USP, 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.
PRECAUTIONS GeneralNafcillin Sodium Sandoz should generally not be administered to patients with a history of sensitivity to any penicillin.
Penicillin should be used with caution in individuals with histories of significant allergies and/or asthma. Whenever allergic reactions occur, penicillin should be withdrawn unless, in the opinion of the physician, the condition being treated is life-threatening and amenable only to penicillin therapy. The use of antibiotics may result in overgrowth of nonsusceptible organisms. If new infections due to bacteria or fungi occur, the drug should be discontinued and appropriate measures taken.
The liver/biliary tract is the primary route of Nafcillin Sodium Sandoz clearance. Caution should be exercised when patients with concomitant hepatic insufficiency and renal dysfunction are treated with Nafcillin Sodium Sandoz.
Prescribing Nafcillin Sodium Sandoz Injection, USP in the absence of a proven or strongly suspected bacterial infection or a prophylactic indication is unlikely to provide benefit to the patient and increases the risk of the development of drug-resistant bacteria.
Laboratory TestsBacteriologic studies to determine the causative organisms and their susceptibility to the penicillinaseresistant penicillins should be performed (see CLINICAL PHARMACOLOGY - Microbiology). In the treatment of suspected staphylococcal infections, therapy should be changed to another active agent if culture tests fail to demonstrate the presence of staphylococci.
Periodic assessment of organ system function including renal, hepatic, and hematopoietic should be made during prolonged therapy with Nafcillin Sodium Sandoz. White blood cell and differential cell counts should be obtained prior to initiation of therapy and periodically during therapy with Nafcillin Sodium Sandoz. Urinalysis, serum blood urea nitrogen, and creatinine determinations should be performed at baseline and periodically during therapy with Nafcillin Sodium Sandoz. Serum bilirubin, aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase, and gamma glutamyl transferase should be obtained at baseline and periodically during therapy, especially when using high Nafcillin Sodium Sandoz doses. In patients with worsening hepatic function, the risk versus benefit of continued Nafcillin Sodium Sandoz use should be re-evaluated.
Drug/Laboratory Test InteractionsNafcillin Sodium Sandoz in the urine can cause a false-positive urine reaction for protein when the sulfosalicyclic acid test is used, but not with the dipstick.
Carcinogenesis, Mutagenesis, Impairment Of FertilityNo long term animal studies have been conducted with these drugs. Studies on reproduction (Nafcillin Sodium Sandoz) in rats and mice reveal no fetal or maternal abnormalities before conception and continuously through weaning (one generation).
PregnancyReproduction studies have been performed in the mouse with oral doses up to 20 times the human dose and orally in the rat at doses up to 40 times the human dose and have revealed no evidence of impaired fertility or harm to the rodent fetus due to Nafcillin Sodium Sandoz. There are, however, no adequate or well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, Nafcillin Sodium Sandoz should be used during pregnancy only if clearly needed.
Nursing MothersPenicillins are excreted in human milk. Caution should be exercised when penicillins are administered to a nursing woman.
Pediatric UseThe liver/biliary tract is the principal route of Nafcillin Sodium Sandoz elimination. Because of immature hepatic and renal function in pediatric patients, Nafcillin Sodium Sandoz excretion may be impaired. Safety and effectiveness in pediatric patients have not been established for the use of intravenous Nafcillin Sodium Sandoz.
The potential for toxic effects in pediatric patients from chemicals that may leach from the single dose premixed intravenous preparation in plastic containers has not been determined.
Geriatric UseClinical studies of Nafcillin Sodium Sandoz Injection, USP did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.
Nafcillin Sodium Sandoz Injection, USP contains 76.6 mg (3.33 mEq) of sodium per gram. At the usual recommended doses, patients would receive between 230 and 460 mg/day (10.0 and 20.0 mEq) of sodium. The geriatric population may respond with a blunted natriuresis to salt loading. This may be clinically important with regard to such diseases as congestive heart failure.
Nafcillin Sodium Sandoz Injection, USP supplied as a premixed frozen solution is to be administered as an intravenous infusion. The usual I.V. dosage for adults is 500 mg every 4 hours. For severe infections, 1 g 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 Sodium Sandoz 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 Sodium Sandoz 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 Sodium Sandoz 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 Sodium Sandoz Injection, USP.
Store in a freezer capable of maintaining a temperature of -20°C (-4°F) or less.
Directions For Use Of Galaxy Container (PL 2040 Plastic)Nafcillin Sodium Sandoz Injection, USP in GALAXY container (PL 2040 Plastic) is for intravenous administration using sterile equipment.
StorageStore in a freezer capable of maintaining a temperature of -20°C/-4°F.
Thawing Of Plastic ContainersThaw frozen container at room temperature (25°C/77°F) or under refrigeration (5°C/41°F). [DO NOT FORCE THAW BY IMMERSION IN WATER BATHS OR BY MICROWAVE IRRADIATION.]
Check for minute leaks by squeezing bag firmly. If leaks are detected, discard solution as sterility may be impaired.
Do not add supplementary medication.
Visually inspect the container. If the outlet port protector is damaged, detached, or not present, discard container as solution path sterility may be impaired. Components of the solution may precipitate in the frozen state and will dissolve upon reaching room temperature with little or no agitation. Potency is not affected. Agitate after solution has reached room temperature. If after visual inspection the solution remains cloudy or if an insoluble precipitate is noted or if any seals are not intact, the container should be discarded.
The thawed 1 g and 2 g solutions are stable for 21 days under refrigeration (5°C/41°F) or 72 hours at room temperature (25°C/77°F). Do not refreeze.
Caution: Do not use plastic containers in series connections. Such use could result in air embolism due to residual air being drawn from the primary container before administration of the fluid from the secondary container is complete.
Preparation For Intravenous Administration
