Claforan

Mechanism of Action

Binds to penicillin-binding proteins and inhibits final transpeptidation step of peptidoglycan synthesis, resulting in cell-wall death; resists degradation by beta-lactamase; proper dosing and appropriate route of administration are determined by condition of patient, severity of infection, and susceptibility of microorganism

Absorption

Peak plasma time: IM, 30 min

Distribution

Distribution: widely distributed to body tissues and fluids, including aqueous humor, ascitic and prostatic fluids, bone, penetrates CSF when meninges inflamed

Widely distributed to body tissues and fluids, including aqueous humor, ascitic and prostatic fluids, and bone; penetrates CSF when meninges are inflamed

Metabolism

Partially metabolized in liver

Metabolite: Desacetylcefotaxime (active)

Elimination

Half-life: Parent drug, 1-1.5 hr; active metabolite, 1-1.9 hr

Excretion: Urine

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.

Common side effects of Claforan include:

• irritation at the site of injection
• diarrhea
• rash
• itching
• diarrhea
• nausea
• vomiting
• fever

This is not a complete list of Claforan side effects. Ask your doctor or pharmacist for more information.

Serious side effects have been reported with Claforan. See the “Drug Precautions” section.

Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

Take Claforan exactly as prescribed by your doctor. Follow the directions on your prescription label carefully.

The Claforan dose your doctor recommends will be based on (use any or all that apply):

• the condition being treated
• other medical conditions you have
• other medications you are taking
• how you respond to this medication
• your kidney function
• your weight
• your age

The recommended dose range for Claforan in adults is 0.5 grams once a day to 12 grams divided into multiple doses per day.

The recommended dose range for Claforan in children includes the following.

• 0 to 1 week of age – 50 mg/kg per dose every 12 hours IV
• 1 to 4 weeks of age – 50 mg/kg per dose every 8 hours IV
• If 1 month to 12 years old:
  • Less than 50 kg – 50 to 180 mg/kg IM or IV divided into four to six equal doses
  • Greater than or equal to 50 kg – use the usual adult dose (max dose of 12 grams)

Antibiotic medicines can cause diarrhea, which may be a sign of a new infection. If you have diarrhea that is watery or bloody, stop using cefotaxime and call your doctor. Do not use anti-diarrhea medicine unless your doctor tells you to.

You should not use this medicine if you are allergic to cefotaxime, or to other cephalosporin antibiotics, such as:

• cefaclor (Raniclor);

• cefadroxil (Duricef);

• cefazolin (Ancef);

• cefdinir (Omnicef);

• cefditoren (Spectracef);

• cefpodoxime (Vantin);

• cefprozil (Cefzil);

• ceftibuten (Cedax);

• cefuroxime (Ceftin);

• cephalexin (Keflex); or

• cephradine (Velosef).

To make sure cefotaxime is safe for you, tell your doctor if you have:

• an allergy to penicillin;

• kidney disease;

• liver disease;

• a stomach or intestinal disorder such as colitis;

• diabetes;

• a heart rhythm disorder; or

• if you also take furosemide.

This medicine is not expected to harm an unborn baby. Tell your doctor if you are pregnant or plan to become pregnant.

Cefotaxime can pass into breast milk and may harm a nursing baby. Tell your doctor if you are breast-feeding a baby.

Antibacterial; β-lactam antibiotic; third generation cephalosporin.a b

Storage

Parenteral

15–30°C;230 366 367 protect from light.230 366 367

Following reconstitution with sterile water for injection, IV solutions containing 50 or 95 mg/mL are stable for 24 hours at room temperature (≤22°C) or 7 days when refrigerated (≤5°C).230 IV solutions reconstituted with 0.9% sodium chloride injection or 5% dextrose injection and further diluted in a compatible IV solution are stable for 24 hours at room temperature (≤22°C) or at least 5 days when refrigerated (≤5°C).230

Following reconstitution with sterile or bacteriostatic water for injection, IM solutions containing 230–330 mg/mL are stable in their original containers for 12 hours at room temperature (≤22°C) or 10 days when refrigerated (≤5°C).230

Powder for injection and solutions may darken.230

Claforan ADD-Vantage vials: <30°C; protect from light.230 After reconstitution as directed in 0.9% sodium chloride injection or 5% dextrose injection, stable for 24 hours at ≤22°C;230 do not freeze.230

-20°C or lower.230 Thawed solution stable 24 hours at room temperature (≤22°C) or 7 days under refrigeration (≤5°C).230

Do not refreeze after thawing.230

Compatibility

For information on systemic interactions resulting from concomitant use, see Interactions.

Parenteral

Cefotaxime sodium is most stable at a pH of 5–7 and should not be diluted with IV solutions that have a pH >7.5 (e.g., sodium bicarbonate).230

• Advise patients that antibacterials (including cefotaxime) should only be used to treat bacterial infections and not used to treat viral infections (e.g., the common cold).230

• Importance of completing full course of therapy, even if feeling better after a few days.230

• Advise patients that skipping doses or not completing the full course of therapy may decrease effectiveness and increase the likelihood that bacteria will develop resistance and will not be treatable with cefotaxime or other antibacterials in the future.230

• Advise patients that diarrhea is a common problem caused by anti-infectives and usually ends when the drug is discontinued.230 Importance of contacting a clinician if watery and bloody stools (with or without stomach cramps and fever) occur during or as late as 2 months or longer after the last dose.230

• Importance of informing clinicians if an allergic reaction occurs.230

• Importance of informing clinicians of existing or contemplated therapy, including prescription and OTC drugs as well as any concomitant illnesses.230

• Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.230

• Importance of informing patients of other important precautionary information.230 (See Cautions.)

Cefotaxime injection is used to treat bacterial infections in many different parts of the body. This medicine is also given before, during, and after certain types of surgery to prevent infections.

Cefotaxime injection belongs to the class of medicines known as cephalosporin antibiotics. It works by killing bacteria or preventing their growth. However, this medicine will not work for colds, flu, or other virus infections.

This medicine is to be given only by or under the supervision of your doctor.

A nurse or other trained health professional will give you or your child this medicine. This medicine is given as a shot into a muscle or a vein.

Use this medicine as ordered by your doctor. Read all information given to you. Follow all instructions closely.

• To gain the most benefit, do not miss doses.
• Keep taking Claforan as you have been told by your doctor or other health care provider, even if you feel well.
• It is given as a shot into a muscle or vein.
• Your doctor may teach you how to use.
• Follow how to use carefully.
• Do not use if the solution is cloudy, leaking, or has particles.
• Do not use if solution changes color.
• Throw away needles in a needle/sharp disposal box. Do not reuse needles or other items. When the box is full, follow all local rules for getting rid of it. Talk with a doctor or pharmacist if you have any questions.

What do I do if I miss a dose?

• Take a missed dose as soon as you think about it.
• If it is close to the time for your next dose, skip the missed dose and go back to your normal time.
• Do not take 2 doses at the same time or extra doses.

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 72 (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, 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.

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 14C-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 (M2 and M3) 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 DOSAGE AND ADMINISTRATION section.)

Drug Interactions

A single intravenous dose and oral dose of probenecid (500 mg each) followed by two oral doses of probenecid 500 mg at approximately hourly intervals administered to three healthy male subjects receiving a continuous infusion of cefotaxime increased the steady-state plasma concentration of cefotaxime by approximately 80%. In another study, administration of oral probenecid 500 mg every 6 hours to six healthy male subjects with cefotaxime 1 gram infused over 5 minutes decreased the total clearance of cefotaxime by approximately 50%.

Additionally, no disulfiram-like reactions were reported in a study conducted in 22 healthy volunteers administered Claforan and ethanol.

Microbiology

Cefotaxime sodium is a bactericidal agent that acts by inhibition of bacterial cell wall synthesis. Cefotaxime has activity in the presence of some beta-lactamases, both penicillinases and cephalosporinases, of Gram-negative and Gram-positive bacteria.

Resistance to cefotaxime is primarily through hydrolysis by beta-lactamase, alteration of penicillin-binding proteins (PBPs), and decreased permeability.

Susceptibility to cefotaxime will vary geographically and may change over time; local susceptibility data should be consulted, if available. Cefotaxime has been shown to be active against most isolates of the following bacteria both in vitro and in clinical infections as described in the INDICATIONS AND USAGE section:

Gram-positive bacteria

Enterococcus spp.1
Staphylococcus aureus (methicillin-susceptible isolates only)
Staphylococcus epidermidis
Streptococcus pneumoniae
Streptococcus pyogenes (Group A beta-hemolytic streptococci)
Streptococcus spp. (Viridans group streptococci)

Gram-negative bacteria

Acinetobacter spp.
Citrobacter spp.2
Enterobacter spp.2
Escherichia coli 2
Haemophilus influenzae
Haemophilus parainfluenzae
Klebsiella spp. (including Klebsiella pneumoniae)2
Morganella morganii2
Neisseria gonorrhoeae (including beta-lactamase-positive and negative strains)
Neisseria meningitidis
Proteus mirabilis2
Proteus vulgaris2
Providencia rettgeri2
Providencia stuartii2
Serratia marcescens2

Anaerobic bacteria

Bacteroides spp., including some isolates of Bacteroides fragilis
Clostridium spp. (most isolates of Clostridium difficile are resistant)
Fusobacterium spp. (including Fusobacterium nucleatum)
Peptococcus spp.
Peptostreptococcus spp.

The following in vitro data are available, but their clinical significance is unknown. At least 90 percent of the following microorganisms exhibit an in vitro minimum inhibitory concentration (MIC) less than or equal to 1 mcg/mL. However, the efficacy of cefotaxime in treating clinical infections due to these microorganisms has not been established in adequate and well-controlled clinical trials.

Gram-negative bacteria

Providencia spp.
Salmonella spp. (including Salmonella typhi)
Shigella spp.

When available, the clinical microbiology laboratory should provide the results of in vitro susceptibility test results for antimicrobial drug products used in resident hospitals to the physician as periodic reports that describe the susceptibility profile of nosocomial and community-acquired pathogens. These reports should aid the physician in selecting an antibacterial drug product for treatment.

Dilution techniques

Quantitative methods are used to determine antimicrobial minimum inhibitory concentrations (MICs). These MICs provide estimates of the susceptibility of bacteria to antimicrobial compounds. The MICs should be determined using a standardized test method (broth or agar) 1,2. The MIC values should be interpreted according to the criteria provided in Table 1.

Diffusion techniques

Quantitative methods that require measurement of zone diameters also provide reproducible estimates of the susceptibility of bacteria to antimicrobial compounds. The zone size provides an estimate of the susceptibility of bacteria to antimicrobial compounds. The zone size should be determined using a standardized test method2,3. This procedure uses paper disks impregnated with 30 mcg cefotaxime to test the susceptibility of microorganisms to cefotaxime. The disk diffusion interpretive criteria are provided in Table 1.

Anaerobic techniques

For anaerobic bacteria, the susceptibility to cefotaxime as MICs can be determined by a standardized agar test method3,4. The MIC values obtained should be interpreted according to the criteria provided in Table 1.

A report of Susceptible indicates that the antimicrobial drug is likely to inhibit growth of the pathogen if the antimicrobial drug reaches the concentration at the site of infection. A report of Intermediate indicates that the result should be considered equivocal, and if the microorganism is not fully susceptible to alternative, clinically feasible drugs, the test should be repeated. This category implies possible clinical applicability in body sites where the drug is physiologically concentrated or in situations where a high dosage of drug can be used. This category also provides a buffer zone that prevents small uncontrolled technical factors from causing major discrepancies in interpretation. A report of Resistant indicates that the antimicrobial drug is not likely to inhibit growth of the pathogen if the antimicrobial drug reaches the concentrations usually achievable at the site of infection; other therapy should be selected.

Quality Control

Standardized susceptibility test procedures require the use of laboratory controls to monitor and ensure the accuracy and precision of supplies and reagents used in the assay, and the techniques of the individual performing the test1,2,3,4. Standard cefotaxime powder should provide the following range of MIC values noted in Table 2. For the diffusion technique using the 30 mcg disk, the criteria in Table 2 should be achieved.

Clinical Trials Experience

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, 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.

Post-Marketing Experience

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). Dizziness has also been reported.

Cutaneous - As with other cephalosporins, isolated cases of toxic epidermal necrolysis, Stevens-Johnson syndrome, and erythema multiforme have been reported. Acute generalized exanthematous pustulosis (AGEP) has also been reported.

General disorders and administration site conditions - Inflammatory reactions at the injection site, including phlebitis/thrombophlebitis.

Hematologic System - Hemolytic anemia, agranulocytosis, thrombocytopenia, pancytopenia, bone marrow failure.

Hypersensitivity - Anaphylaxis (e.g., angioedema, bronchospasm, malaise possibly culminating in shock), urticaria.

Kidney - Interstitial nephritis, transient elevations of creatinine, acute renal failure.

Liver - Hepatitis, jaundice, cholestasis, elevations of gamma GT and bilirubin.

Cephalosporin Class Labeling

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 DOSAGE AND ADMINISTRATION and OVERDOSAGE. If seizures associated with drug therapy occur, the drug should be discontinued. Anticonvulsant therapy can be given if clinically indicated.

Adults

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 table for dosage guideline). 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 C. trachomatis 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.

Cesarean Section Patients

The first dose of 1 gram is administered intravenously as soon as the umbilical cord is clamped. The second and third doses should be given as 1 gram intravenously or intramuscularly at 6 and 12 hours after the first dose.

Neonates, Infants, and Children

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.

Geriatric Use

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 PRECAUTIONS, General and PRECAUTIONS, Geriatric Use.)

Impaired Renal Function

see PRECAUTIONS, General.

NOTE: As with antibiotic therapy in general, administration of Claforan should be continued for a minimum of 48 to 72 hours after the patient defervesces or after evidence of bacterial eradication has been obtained; a minimum of 10 days of treatment is recommended for infections caused by Group A beta-hemolytic streptococci in order to guard against the risk of rheumatic fever or glomerulonephritis; frequent bacteriologic and clinical appraisal is necessary during therapy of chronic urinary tract infection and may be required for several months after therapy has been completed; persistent infections may require treatment of several weeks and doses smaller than those indicated above should not be used.

Preparation of Claforan Sterile

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.

Reconstitute VIALS with Sterile Water for Injection or Bacteriostatic Water for Injection as described above.

Reconstitute VIALS with at least 10 mL of Sterile Water for Injection. Reconstitute INFUSION BOTTLES with 50 or 100 mL of 0.9% Sodium Chloride Injection or 5% Dextrose Injection. For other diluents, see COMPATIBILITY AND STABILITY section.

NOTE: Solutions of Claforan must not be admixed with aminoglycoside solutions. If Claforan and aminoglycosides are to be administered to the same patient, they must be administered separately and not as mixed injection.

A SOLUTION OF 1 G Claforan IN 14 ML OF STERILE WATER FOR INJECTION IS ISOTONIC.

As with all IM preparations, Claforan should be injected well within the body of a relatively large muscle such as the upper outer quadrant of the buttock (i.e., gluteus maximus); aspiration is necessary to avoid inadvertent injection into a blood vessel. Individual IM doses of 2 grams may be given if the dose is divided and is administered in different intramuscular sites.

The IV route is preferable for patients with bacteremia, bacterial septicemia, peritonitis, meningitis, or other severe or life-threatening infections, or for patients who may be poor risks because of lowered resistance resulting from such debilitating conditions as malnutrition, trauma, surgery, diabetes, heart failure, or malignancy, particularly if shock is present or impending.

For intermittent IV administration, a solution containing 1 gram or 2 grams in 10 mL of Sterile Water for Injection can be injected over a period of three to five minutes. Cefotaxime should not be administered over a period of less than three minutes. (See WARNINGS). With an infusion system, it may also be given over a longer period of time through the tubing system by which the patient may be receiving other IV solutions. However, during infusion of the solution containing Claforan, it is advisable to discontinue temporarily the administration of other solutions at the same site.

For the administration of higher doses by continuous IV infusion, a solution of Claforan may be added to IV bottles containing the solutions discussed below.

Directions for use of Claforan Injection in Galaxy® Container (PL 2040 Plastic)

Claforan Injection in Galaxy® Containers (PL 2040 plastic) is for continuous or intermittent infusion using sterile equipment.

Store in a freezer capable of maintaining a temperature of -20°C/-4°F.

Thaw frozen container at room temperature or under refrigeration (at or below 5°C). [DO NOT FORCE THAW BY IMMERSION IN WATER BATHS OR BY MICROWAVE IRRADIATION.]

Check for minute leaks by squeezing container firmly. If leaks are detected, discard solution as sterility may be impaired.

DO NOT ADD SUPPLEMENTARY MEDICATION.

The container should be visually inspected. 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 or outlet ports are not intact, the container should be discarded.

The thawed solution is stable for 10 days under refrigeration (at or below 5°C) or 24 hours at or below 22°C. Do not refreeze thawed antibiotics.

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.

1. Suspend container from eyelet support.
2. Remove protector from outlet port at bottom of container.
3. Attach administration set. Refer to complete directions accompanying set.

Preparation of Claforan Sterile in ADD-Vantage System

Claforan Sterile 1 g or 2 g may be reconstituted in 50 mL or 100 mL of 5% Dextrose or 0.9% Sodium Chloride in the ADD-Vantage diluent container. Refer to enclosed, separate INSTRUCTIONS FOR ADD-VANTAGE SYSTEM.

Compatibility and Stability

Solutions of Claforan Sterile reconstituted as described above (Preparation of Claforan Sterile) 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: Claforan solutions exhibit maximum stability in the pH 5–7 range. Solutions of Claforan should not be prepared with diluents having a pH above 7.5, such as Sodium Bicarbonate Injection.

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.

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).

2 g cefotaxime (free acid equivalent) in vials in packages of 10 (NDC 0039-0019-10).

1 g cefotaxime (free acid equivalent) in ADD-Vantage System vials in packages of 25 (NDC 0039-0023-25).

2 g cefotaxime (free acid equivalent) in ADD-Vantage System vials in packages of 25 (NDC 0039-0024-25).

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)

NOTE: Claforan in the dry state should be stored below 30°C. The dry material as well as solutions tend to darken depending on storage conditions and should be protected from elevated temperatures and excessive light.

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) and packages of 24 (2 × 12) (NDC 0039-0037-24) 2G3518.

2 g cefotaxime (free acid equivalent) in packages of 12 (NDC 0039-0038-05) and packages of 24 (2 × 12) (NDC 0039-0038-24) 2G3519.

NOTE: Store Premixed Claforan Injection at or below -20°C/-4°F. [See Directions for use of Claforan Injection in Galaxy® Containers (PL 2040 Plastic)].

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.