Claforan Information
Claforan ()
Claforan () Description
Sterile Claforan () (cefotaxime sodium) is a semisynthetic, broad spectrum cephalosporin antibiotic for parenteral administration. It is the sodium salt of 7-[2-(2-amino-4-thiazolyl) glyoxylamido]-3-(hydroxymethyl)-8-oxo-5-thia-1-azabicyclo [4.2.0] oct-2-ene-2-carboxylate 7 (Z)-(o-methyloxime), acetate (ester). Claforan () contains approximately 50.5 mg (2.2 mEq) of sodium per gram of cefotaxime activity. Solutions of Claforan () range from very pale yellow to light amber depending on the concentration and the diluent used. The pH of the injectable solutions usually ranges from 5.0 to 7.5. The CAS Registry Number is 64485-93-4.
Claforan () is supplied as a dry powder in conventional and ADD-Vantage System compatible vials, infusion bottles, pharmacy bulk package bottles, and as a frozen, premixed, iso-osmotic injection in a buffered diluent solution in plastic containers. Claforan () , equivalent to 1 gram and 2 grams cefotaxime, is supplied as frozen, premixed, iso-osmotic injections in plastic containers. Solutions range from very pale yellow to light amber. Dextrose Hydrous, USP has been added to adjust osmolality (approximately 1.7 g and 700 mg to the 1 g and 2 g cefotaxime dosages, respectively). The injections are buffered with sodium citrate hydrous, USP. The pH is adjusted with hydrochloric acid and may be adjusted with sodium hydroxide.
The plastic container is fabricated from a specially designed multilayer plastic (PL 2040). Solutions are in contact with the polyethylene layer of this container and can leach out certain chemical components of the plastic in very small amounts within the expiration period. The suitability of the plastic has been confirmed in tests in animals according to the USP biological tests for plastic containers, as well as by tissue culture toxicity studies.
Claforan () Clinical Pharmacology
Following IM administration of a single 500 mg or 1 g dose of Claforan () to normal volunteers, mean peak serum concentrations of 11.7 and 20.5 mcg/mL respectively were attained within 30 minutes and declined with an elimination half-life of approximately 1 hour. There was a dose-dependent increase in serum levels after the IV administration of 500 mg, 1 g, and 2 g of Claforan () (38.9, 101.7, and 214.4 mcg/mL respectively) without alteration in the elimination half-life. There is no evidence of accumulation following repetitive IV infusion of 1 g doses every 6 hours for 14 days as there are no alterations of serum or renal clearance. About 60% of the administered dose was recovered from urine during the first 6 hours following the start of the infusion.
Approximately 20–36% of an intravenously administered dose of C-cefotaxime is excreted by the kidney as unchanged cefotaxime and 15–25% as the desacetyl derivative, the major metabolite. The desacetyl metabolite has been shown to contribute to the bactericidal activity. Two other urinary metabolites (M and M) account for about 20–25%. They lack bactericidal activity.
A single 50 mg/kg dose of Claforan () was administered as an intravenous infusion over a 10- to 15-minute period to 29 newborn infants grouped according to birth weight and age. The mean half-life of cefotaxime in infants with lower birth weights (≤1500 grams), regardless of age, was longer (4.6 hours) than the mean half-life (3.4 hours) in infants whose birth weight was greater than 1500 grams. Mean serum clearance was also smaller in the lower birth weight infants. Although the differences in mean half-life values are statistically significant for weight, they are not clinically important. Therefore, dosage should be based solely on age. (See section.)
Additionally, no disulfiram-like reactions were reported in a study conducted in 22 healthy volunteers administered Claforan () and ethanol.
Claforan () Indications And Usage
Claforan () is indicated for the treatment of patients with serious infections caused by susceptible strains of the designated microorganisms in the diseases listed below.
Efficacy for this organism, in this organ system, has been studied in fewer than 10 infections.
Although many strains of enterococci (e.g., ) and species are resistant to cefotaxime sodium , Claforan () has been used successfully in treating patients with infections caused by susceptible organisms.
Specimens for bacteriologic culture should be obtained prior to therapy in order to isolate and identify causative organisms and to determine their susceptibilities to Claforan () . Therapy may be instituted before results of susceptibility studies are known; however, once these results become available, the antibiotic treatment should be adjusted accordingly.
In certain cases of confirmed or suspected gram-positive or gram-negative sepsis or in patients with other serious infections in which the causative organism has not been identified, Claforan () may be used concomitantly with an aminoglycoside. The dosage recommended in the labeling of both antibiotics may be given and depends on the severity of the infection and the patient's condition. Renal function should be carefully monitored, especially if higher dosages of the aminoglycosides are to be administered or if therapy is prolonged, because of the potential nephrotoxicity and ototoxicity of aminoglycoside antibiotics. It is possible that nephrotoxicity may be potentiated if Claforan () is used concomitantly with an aminoglycoside.
The administration of Claforan () preoperatively reduces the incidence of certain infections in patients undergoing surgical procedures (e.g., abdominal or vaginal hysterectomy, gastrointestinal and genitourinary tract surgery) that may be classified as contaminated or potentially contaminated.
In patients undergoing cesarean section, intraoperative (after clamping the umbilical cord) and postoperative use of Claforan () may also reduce the incidence of certain postoperative infections. See section.
Effective use for elective surgery depends on the time of administration. To achieve effective tissue levels, Claforan () should be given 1/2 or 1 1/2 hours before surgery. See section.
For patients undergoing gastrointestinal surgery, preoperative bowel preparation by mechanical cleansing as well as with a non-absorbable antibiotic (e.g., neomycin) is recommended.
If there are signs of infection, specimens for culture should be obtained for identification of the causative organism so that appropriate therapy may be instituted.
To reduce the development of drug-resistant bacteria and maintain the effectiveness of Claforan () and other antibacterial drugs, Claforan () 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.
Claforan () Contraindications
Claforan () is contraindicated in patients who have shown hypersensitivity to cefotaxime sodium, or the cephalosporin group of antibiotics.
Claforan () Warnings
BEFORE THERAPY WITH Claforan () IS INSTITUTED, CAREFUL INQUIRY SHOULD BE MADE TO DETERMINE WHETHER THE PATIENT HAS HAD PREVIOUS HYPERSENSITIVITY REACTIONS TO CEFOTAXIME SODIUM, CEPHALOSPORINS, PENICILLINS, OR OTHER DRUGS. THIS PRODUCT SHOULD BE GIVEN WITH CAUTION TO PATIENTS WITH TYPE I HYPERSENSITIVITY REACTIONS TO PENICILLIN. ANTIBIOTICS SHOULD BE ADMINISTERED WITH CAUTION TO ANY PATIENT WHO HAS DEMONSTRATED SOME FORM OF ALLERGY, PARTICULARLY TO DRUGS. IF AN ALLERGIC REACTION TO Claforan () OCCURS, DISCONTINUE TREATMENT WITH THE DRUG. SERIOUS HYPERSENSITIVITY REACTIONS MAY REQUIRE EPINEPHRINE AND OTHER EMERGENCY MEASURES.
During post-marketing surveillance, a potentially life-threatening arrhythmia was reported in each of six patients who received a rapid (less than 60 seconds) bolus injection of cefotaxime through a central venous catheter. Therefore, cefotaxime should only be administered as instructed in the section.
If CDAD is suspected or confirmed, ongoing antibiotic use not directed against may need to be discontinued. Appropriate fluid and electrolyte management, protein supplementation, antibiotic treatment of and surgical evaluation should be instituted as clinically indicated.
Claforan () Precautions
Prescribing Claforan () 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.
Claforan () should be prescribed with caution in individuals with a history of gastrointestinal disease, particularly colitis.
Because high and prolonged serum antibiotic concentrations can occur from usual doses in patients with transient or persistent reduction of urinary output because of renal insufficiency, the total daily dosage should be reduced when Claforan () is administered to such patients. Continued dosage should be determined by degree of renal impairment, severity of infection, and susceptibility of the causative organism.
Although there is no clinical evidence supporting the necessity of changing the dosage of cefotaxime sodium in patients with even profound renal dysfunction, it is suggested that, until further data are obtained, the dose of cefotaxime sodium be halved in patients with estimated creatinine clearances of less than 20 mL/min/1.73 m.
When only serum creatinine is available, the following formula (based on sex, weight, and age of the patient) may be used to convert this value into creatinine clearance. The serum creatinine should represent a steady state of renal function.
Weight (kg) × (140 - age)
As with other antibiotics, prolonged use of Claforan () may result in overgrowth of nonsusceptible organisms. Repeated evaluation of the patient's condition is essential. If superinfection occurs during therapy, appropriate measures should be taken.
As with other beta-lactam antibiotics, granulocytopenia and, more rarely, agranulocytosis may develop during treatment with Claforan () , particularly if given over long periods. For courses of treatment lasting longer than 10 days, blood counts should therefore be monitored.
Claforan () , like other parenteral anti-infective drugs, may be locally irritating to tissues. In most cases, perivascular extravasation of Claforan () responds to changing of the infusion site. In rare instances, extensive perivascular extravasation of Claforan () may result in tissue damage and require surgical treatment. To minimize the potential for tissue inflammation, infusion sites should be monitored regularly and changed when appropriate.
Patients should be counseled that antibacterial drugs including Claforan () should only be used to treat bacterial infections. They do not treat viral infections (e.g., the common cold). When Claforan () is prescribed to treat a bacterial infection, patients should be told that although it is common to feel better early in the course of therapy, the medication should be taken exactly as directed. Skipping doses or not completing the full course of therapy may (1) decrease the effectiveness of the immediate treatment and (2) increase the likelihood that bacteria will develop resistance and will not be treatable by Claforan () or other antibacterial drugs in the future.
Diarrhea is a common problem caused by antibiotics which usually ends when the antibiotic is discontinued. Sometimes after starting treatment with antibiotics, patients can develop watery and bloody stools (with or without stomach cramps and fever) even as late as two or more months after having taken the last dose of the antibiotic. If this occurs, patients should contact their physician as soon as possible.
Increased nephrotoxicity has been reported following concomitant administration of cephalosporins and aminoglycoside antibiotics.
Probenecid interferes with the renal tubular transfer of cephalosporins, thereby delaying their excretion and increasing their plasma concentrations.
As with other cephalosporins, cefotaxime may potentiate the renal toxicity of nephrotoxic drugs. See section.
Cephalosporins, including cefotaxime sodium, are known to occasionally induce a positive direct Coombs' test.
Urinary glucose testing with non-specific reducing agents may yield a false-positive reaction in patients treated with cefotaxime. This phenomenon is not seen when a glucose-oxidase specific method is used.
Of the 1409 subjects in clinical studies of cefotaxime, 632 (45%) were 65 and over, while 258 (18%) were 75 and over. No overall differences in safety or effectiveness were observed between these subjects and younger subjects, and other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out.
This drug is known to be substantially excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function (see ).
Claforan () Adverse Reactions
Claforan () is generally well tolerated. The most common adverse reactions have been local reactions following IM or IV injection. Other adverse reactions have been encountered infrequently.
The most frequent adverse reactions (greater than 1%) are:
Local (4.3%) - Injection site inflammation with IV administration. Pain, induration, and tenderness after IM injection.
Hypersensitivity (2.4%) - Rash, pruritus, fever, eosinophilia.
Gastrointestinal (1.4%) - Colitis, diarrhea, nausea, and vomiting.
Symptoms of pseudomembranous colitis can appear during or after antibiotic treatment.
Nausea and vomiting have been reported rarely.
Less frequent adverse reactions (less than 1%) are:
Hematologic System - Neutropenia, transient leukopenia, have been reported. Some individuals have developed positive direct Coombs Tests during treatment with Claforan () and other cephalosporin antibiotics.
Genitourinary System - Moniliasis, vaginitis.
Central Nervous System - Headache.
Liver - Transient elevations in AST, ALT, serum LDH, and serum alkaline phosphatase levels have been reported.
Kidney - As with some other cephalosporins, transient elevations of BUN have been occasionally observed with Claforan () .
The following adverse reactions have been identified during post-approval use of Claforan () . Because these reactions were reported voluntarily from a population of uncertain size, it is not possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
Cardiovascular System - Potentially life-threatening arrhythmias following rapid (less than 60 seconds) bolus administration via central venous catheter have been observed.
Central Nervous System - Administration of high doses of beta-lactam antibiotics, including cefotaxime, particularly in patients with renal insufficiency may result in encephalopathy (e.g. impairment of consciousness, abnormal movements and convulsions).
Cutaneous - As with other cephalosporins, isolated cases of toxic epidermal necrolysis, Stevens-Johnson syndrome, and erythema multiforme have been reported.
Hematologic System - Hemolytic anemia, agranulocytosis, thrombocytopenia.
Hypersensitivity - Anaphylaxis (e.g., angioedema, bronchospasm, malaise possibly culminating in shock), urticaria.
Kidney - Interstitial nephritis, transient elevations of creatinine.
Liver - Hepatitis, jaundice, cholestasis, elevations of gamma GT and bilirubin.
In addition to the adverse reactions listed above which have been observed in patients treated with cefotaxime sodium, the following adverse reactions and altered laboratory tests have been reported for cephalosporin class antibiotics: allergic reactions, hepatic dysfunction including cholestasis, aplastic anemia, hemorrhage, and false-positive test for urinary glucose.
Several cephalosporins have been implicated in triggering seizures, particularly in patients with renal impairment when the dosage was not reduced. See and . If seizures associated with drug therapy occur, the drug should be discontinued. Anticonvulsant therapy can be given if clinically indicated.
Claforan () Overdosage
The acute toxicity of Claforan () was evaluated in neonatal and adult mice and rats. Significant mortality was seen at parenteral doses in excess of 6000 mg/kg/day in all groups. Common toxic signs in animals that died were a decrease in spontaneous activity, tonic and clonic convulsions, dyspnea, hypothermia, and cyanosis. Cefotaxime sodium overdosage has occurred in patients. Most cases have shown no overt toxicity. The most frequent reactions were elevations of BUN and creatinine. There is a risk of reversible encephalopathy in cases of administration of high doses of beta-lactam antibiotics including cefotaxime. No specific antidote exists. Patients who receive an acute overdosage should be carefully observed and given supportive treatment.
Claforan () Dosage And Administration
Dosage and route of administration should be determined by susceptibility of the causative organisms, severity of the infection, and the condition of the patient (see ). Claforan () may be administered IM or IV after reconstitution. Premixed Claforan () Injection is intended for IV administration after thawing. The maximum daily dosage should not exceed 12 grams.
If is a suspected pathogen, appropriate anti-chlamydial coverage should be added, because cefotaxime sodium has no activity against this organism.
To prevent postoperative infection in contaminated or potentially contaminated surgery, the recommended dose is a single 1 gram IM or IV administered 30 to 90 minutes prior to start of surgery.
The following dosage schedule is recommended:
Neonates (birth to 1 month):
0–1 week of age 50 mg/kg per dose every 12 hours IV 1–4 weeks of age 50 mg/kg per dose every 8 hours IV
It is not necessary to differentiate between premature and normal-gestational age infants.
Infants and Children (1 month to 12 years):
For body weights less than 50 kg, the recommended daily dose is 50 to 180 mg/kg IM or IV body weight divided into four to six equal doses. The higher dosages should be used for more severe or serious infections, including meningitis. For body weights 50 kg or more, the usual adult dosage should be used; the maximum daily dosage should not exceed 12 grams.
see .
NOTE:
Claforan () for IM or IV administration should be reconstituted as follows:
Shake to dissolve; inspect for particulate matter and discoloration prior to use. Solutions of Claforan () range from very pale yellow to light amber, depending on concentration, diluent used, and length and condition of storage.
Solutions of Claforan () Sterile reconstituted as described above remain chemically stable (potency remains above 90%) as follows when stored in original containers and disposable plastic syringes:
Reconstituted solutions stored in original containers and plastic syringes remain stable for 13 weeks frozen.
Reconstituted solutions may be further diluted up to 1000 mL with the following solutions and maintain satisfactory potency for 24 hours at or below 22°C, and at least 5 days under refrigeration (at or below 5°C): 0.9% Sodium Chloride Injection; 5 or 10% Dextrose Injection; 5% Dextrose and 0.9% Sodium Chloride Injection, 5% Dextrose and 0.45% Sodium Chloride Injection; 5% Dextrose and 0.2% Sodium Chloride Injection; Lactated Ringer's Solution; Sodium Lactate Injection (M/6); 10% Invert Sugar Injection, 8.5% TRAVASOL (Amino Acid) Injection without Electrolytes.
Solutions of Claforan () Sterile reconstituted in 0.9% Sodium Chloride Injection or 5% Dextrose Injection in Viaflex plastic containers maintain satisfactory potency for 24 hours at or below 22°C, 5 days under refrigeration (at or below 5°C) and 13 weeks frozen. Solutions of Claforan () Sterile reconstituted in 0.9% Sodium Chloride Injection or 5% Dextrose Injection in the ADD-Vantage flexible containers maintain satisfactory potency for 24 hours at or below 22°C. DO NOT FREEZE.
NOTE:
Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.
Claforan () How Supplied
Sterile Claforan () is a dry off-white to pale yellow crystalline powder supplied in vials and bottles containing cefotaxime sodium as follows:
500 mg cefotaxime (free acid equivalent) in vials in packages of 10 (NDC 0039-0017-10).
1 g cefotaxime (free acid equivalent) in vials in packages of 10 (NDC 0039-0018-10), packages of 25 (NDC 0039-0018-25), packages of 50 (NDC 0039-0018-50); infusion bottles in packages of 10 (NDC 0039-0018-11).
2 g cefotaxime (free acid equivalent) in vials in packages of 10 (NDC 0039-0019-10), packages of 25 (NDC 0039-0019-25), packages of 50 (NDC 0039-0019-50); infusion bottles in packages of 10 (NDC 0039-0019-11).
1 g cefotaxime (free acid equivalent) in ADD-Vantage System vials in packages of 25 (NDC 0039-0023-25) and 50 (NDC 0039-0023-50).
2 g cefotaxime (free acid equivalent) in ADD-Vantage System vials in packages of 25 (NDC 0039-0024-25) and 50 (NDC 0039-0024-50).
ADD-Vantage System diluents (5% Dextrose or 0.9% Sodium Chloride) are available from Abbott Laboratories.
Also available:
Pharmacy Bulk Package:
10g cefotaxime (free acid equivalent) in bottles (NDC 0039-0020-01)
Premixed Claforan () Injection is supplied as a frozen, iso-osmotic, sterile, nonpyrogenic solution in 50 mL single dose Galaxy containers (PL 2040 plastic) as follows:
1 g cefotaxime (free acid equivalent) in packages of 12 (NDC 0039-0037-05) 2G3518.
2 g cefotaxime (free acid equivalent) in packages of 12 (NDC 0039-0038-05) 2G3519.
Claforan () Injection supplied as a frozen, iso-osmotic, sterile, nonpyrogenic solution in Galaxy containers (PL 2040 plastic) is manufactured for sanofi-aventis U.S. LLC by Baxter Healthcare Corporation.
Claforan ()
Claforan () Principal Display Panel - Mg Vial
NDC 0039-0017-01
FOR IM/IV ADMINISTRATION
Claforan () Principal Display Panel - Mg Vial Carton
NDC 0039-0017-10
FOR IM/IV ADMINISTRATION
Claforan () Principal Display Panel - Pharmacy Bulk Pack
NDC 0039-0020-01
NOT FOR DIRECT INFUSION
Claforan () Principal Display Panel - Ml Bag Label
Claforan () Principal Display Panel - Ml Container Label
