Tazicef

Name: Tazicef

Pharmacology

Mechanism of Action

Third-generation cephalosporin with broad-spectrum gram-negative activity, including Pseudomonas; has lower efficacy against gram-positive organisms and higher efficacy against resistant organisms; arrests bacterial growth by binding to 1 or more penicillin-binding proteins, thereby, in turn, inhibiting final transpeptidation step of peptidoglycan synthesis in bacterial cell-wall synthesis and inhibiting cell-wall biosynthesis

Absorption

Peak plasma time: IM, 1 hr

Distribution

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

Protein bound: 5-24%

Metabolism

Not metabolized

Elimination

Half-life: 1-2 hr

Dialyzable: Hemodialysis, yes; peritoneal dialysis, yes

Excretion: Urine (80-90% as unchanged drug)

Side Effects of Tazicef

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

Common side effects include:

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

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

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

What is Tazicef (ceftazidime injection)?

Ceftazidime is a cephalosporin (SEF a low spor in) antibiotic. It works by fighting bacteria in your body.

Ceftazidime injection is used to treat many kinds of bacterial infections, including severe or life-threatening forms.

Ceftazidime may also be used for purposes not listed in this medication guide.

What should I discuss with my health care provider before using Tazicef (ceftazidime injection)?

You should not use this medicine if you have ever had a severe allergic reaction to ceftazidime or any other cephalosporin antibiotic, such as:

  • cefaclor (Raniclor);

  • cefadroxil (Duricef);

  • cefdinir (Omnicef);

  • cefazolin (Ancef);

  • cefditoren (Spectracef);

  • cefpodoxime (Vantin);

  • cefprozil (Cefzil);

  • ceftibuten (Cedax);

  • cefuroxime (Ceftin);

  • cephalexin (Keflex); or

  • cephradine (Velosef).

Before using ceftazidime, tell your doctor if you are allergic to any type of penicillin antibiotic, such as:

  • amoxicillin (Amoxil, Augmentin, Moxatag);

  • ampicillin (Principen, Unasyn);

  • dicloxacillin (Dycill, Dynapen);

  • oxacillin (Bactocill);

  • penicillin (Bicillin L-A, PC Pen VK, Pfizerpen); or

  • ticarcillin (Ticar, Timentin).

To make sure cefazolin is safe for you, tell your doctor if you have ever had:

  • kidney disease;

  • liver disease;

  • a stomach or intestinal disorder such as colitis;

  • seizures or epilepsy;

  • diabetes;

  • congestive heart failure; or

  • if you are malnourished.

It is not known whether this medicine will harm an unborn baby. Tell your doctor if you are pregnant or plan to become pregnant.

Ceftazidime can make birth control pills less effective. Ask your doctor about using non hormonal birth control (condom, diaphragm with spermicide) to prevent pregnancy.

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

Tazicef (ceftazidime injection) side effects

Get emergency medical help if you have signs of an allergic reaction: hives; difficult breathing; swelling of your face, lips, tongue, or throat.

Call your doctor at once if you have:

  • severe stomach pain, diarrhea that is watery or bloody; o

  • confusion, problems with speech or memory;

  • seizure (black-out or convulsions); or

  • a cold feeling, discoloration, or skin changes in your fingers.

Common side effects may include:

  • pain, swelling, burning, or irritation around the IV needle;

  • nausea, vomiting, diarrhea, stomach pain; or

  • vaginal itching or discharge.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Commonly used brand name(s)

In the U.S.

  • Fortaz
  • Tazicef

In Canada

  • Ceptaz

Available Dosage Forms:

  • Powder for Solution

Therapeutic Class: Antibiotic

Pharmacologic Class: 3rd Generation Cephalosporin

What are some side effects that I need to call my doctor about right away?

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

  • Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.
  • Any unexplained bruising or bleeding.
  • Irritation where the shot is given.
  • Not able to pass urine or change in how much urine is passed.
  • Fever or chills.
  • Sore throat.
  • Seizures.
  • Feeling very tired or weak.
  • Vaginal itching or discharge.
  • It is common to have diarrhea when taking Tazicef. Rarely, a very bad form of diarrhea called Clostridium difficile (C diff)–associated diarrhea (CDAD) may occur. Sometimes, this has led to a deadly bowel problem (colitis). CDAD may happen while you are taking this medicine or within a few months after you stop taking it. Call your doctor right away if you have stomach pain or cramps, very loose or watery stools, or bloody stools. Do not try to treat loose stools without first checking with your doctor.

Tazicef Description

Ceftazidime is a semisynthetic, broad-spectrum, beta-lactam antibiotic for parenteral administration. It is the pentahydrate of pyridinium, 1-[[7-[[(2-amino-4-thiazolyl)[(1-carboxy-1- methylethoxy) imino] acetyl]amino]-2-carboxy-8-oxo-5-thia-1-azabicyclo(4.2.0.)oct-2-en-3-yl] methyl]-, hydroxide, inner salt, [6R-[6α,7β (Z)]]. It has the following structure:

The empirical formula is C22H32N6O12S2, representing a molecular weight of 636.6.

Tazicef (ceftazidime for injection, USP) is a sterile, dry-powdered mixture of ceftazidime pentahydrate and sodium carbonate. The sodium carbonate at a concentration of 118 mg/g of ceftazidime activity has been admixed to facilitate dissolution. The total sodium content of the mixture is approximately 54 mg (2.3 mEq)/g of ceftazidime activity. Solutions of Tazicef range in color from light yellow to amber, depending on the diluent and volume used. The pH of freshly reconstituted solutions usually ranges from 5.0 to 7.5.

Tazicef is available in a 6 gram Pharmacy Bulk Package. 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. FURTHER DILUTION IS REQUIRED BEFORE USE. The 6 gram pharmacy bulk package can be reconstituted with 26 mL of Sterile Water for Injection; after reconstitution, each 5 mL of the resulting solution contains approximately 1g of ceftazidime.

Precautions

General

High and prolonged serum ceftazidime concentrations can occur from usual dosages in patients with transient or persistent reduction of urinary output because of renal insufficiency.

The total daily dosage should be reduced when ceftazidime is administered to patients with renal insufficiency (see DOSAGE AND ADMINISTRATION). Elevated levels of ceftazidime in these patients can lead to seizures, encephalopathy, coma, asterixis, neuromuscular excitability, and myoclonia. Continued dosage should be determined by degree of renal impairment, severity of infection, and susceptibility of the causative organisms.

As with other antibiotics, prolonged use of Tazicef (ceftazidime for injection, USP) 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.

Inducible type I beta-lactamase resistance has been noted with some organisms (e.g., Enterobacter spp., Pseudomonas spp., and Serratia spp.). As with other extended-spectrum beta-lactam antibiotics, resistance can develop during therapy, leading to clinical failure in some cases. When treating infections caused by these organisms, periodic susceptibility testing should be performed when clinically appropriate. If patients fail to respond to monotherapy, an aminoglycoside or similar agent should be considered.

Cephalosporins may be associated with a fall in prothrombin activity. Those at risk include patients with renal and hepatic impairment, or poor nutritional state, as well as patients receiving a protracted course of antimicrobial therapy. Prothrombin time should be monitored in patients at risk and exogenous vitamin K administered as indicated.

Tazicef should be prescribed with caution in individuals with a history of gastrointestinal disease, particularly colitis.

Distal necrosis can occur after inadvertent intra-arterial administration of ceftazidime.

Prescribing Tazicef (ceftazidime) 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.

Information for Patients

Patients should be counseled that antibacterial drugs, including Tazicef (ceftazidime), should only be used to treat bacterial infections. They do not treat viral infections (e.g., the common cold). When Tazicef (ceftazidime) 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 Tazicef (ceftazidime) 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 2 or more months after having taken the last dose of the antibiotic. If this occurs, patients should contact their physician as soon as possible.

Drug Interactions

Nephrotoxicity has been reported following concomitant administration of cephalosporins with aminoglycoside antibiotics or potent diuretics such as furosemide. 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. Nephrotoxicity and ototoxicity were not noted when ceftazidime was given alone in clinical trials.

Chloramphenicol has been shown to be antagonistic to beta-lactam antibiotics, including ceftazidime, based on in vitro studies and time kill curves with enteric gram-negative bacilli. Due to the possibility of antagonism in vivo, particularly when bactericidal activity is desired, this drug combination should be avoided.

In common with other antibiotics, ceftazidime may affect the gut flora, leading to lower estrogen reabsorption and reduced efficacy of combined oral estrogen/progesterone contraceptives.

Drug/Laboratory Test Interactions

The administration of ceftazidime may result in a false-positive reaction for glucose in the urine when using CLINITEST® tablets, Benedict's solution, or Fehling's solution.

It is recommended that glucose tests based on enzymatic glucose oxidase reactions (such as CLINISTIX®) be used.

Carcinogenesis, Mutagenesis, Impairment of Fertility

Long-term studies in animals have not been performed to evaluate carcinogenic potential. However, a mouse micronucleus test and an Ames test were both negative for mutagenic effects.

Pregnancy

Teratogenic Effects

Pregnancy Category B. Reproduction studies have been performed in mice and rats at doses up to 40 times the human dose and have revealed no evidence of impaired fertility or harm to the fetus due to Tazicef. There are, however, no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed.

Nursing Mothers

Ceftazidime is excreted in human milk in low concentrations. Caution should be exercised when Tazicef is administered to a nursing woman.

Pediatric Use

(see DOSAGE AND ADMINISTRATION).

Geriatric Use

Of the 2,221 subjects who received ceftazidime in 11 clinical studies, 824 (37%) were 65 and older while 391 (18%) were 75 and older. 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 susceptibility of some older individuals to drug effects 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 DOSAGE AND ADMINISTRATION).

Tazicef Dosage and Administration

PHARMACY BULK PACKAGE – NOT FOR DIRECT INFUSION

NOTE: The Pharmacy Bulk Package is intended for preparing IV admixtures only. Dosage recommendations for intramuscular or intravenous injection and intraperitoneal use are for informational purposes only.

Dosage: The usual adult dosage is 1 gram administered intravenously every 8 to 12 hours. The dosage and route should be determined by the susceptibility of the causative organisms, the severity of infection, and the condition and renal function of the patient.

The guidelines for dosage of Tazicef (ceftazidime for injection, USP) are listed in Table 5. The following dosage schedule is recommended. 

Table 5. Recommended Dosage Schedule
* Although clinical improvement has been shown, bacteriologic cures cannot be expected in patients with chronic respiratory disease and cystic fibrosis. † The higher dose should be reserved for immunocompromised pediatric patients or pediatric patients with cystic fibrosis or meningitis.

Dose

Frequency

Adults

Usual recommended dosage

1 gram IV or IM

q8-12hr

Uncomplicated urinary tract infections

250 mg IV or IM

q12hr

Bone and joint infections

2 grams IV

q12hr

Complicated urinary tract infections

500 mg IV or IM

q8-12hr

Uncomplicated pneumonia; mild skin and

skin-structure infections

500 mg to 1 gram

IV or IM

q8hr

Serious gynecologic and

intra-abdominal infections

2 grams IV

q8hr

Meningitis

2 grams IV

q8hr

Very severe life-threatening infections,

especially in immunocompromised patients

2 grams IV

q8hr

Lung infections caused by Pseudomonas

spp. in patients with cystic fibrosis with

normal renal function*

30 to 50 mg/kg IV

to a maximum

of 6 grams per day

q8hr
  

Neonates (0 – 4 weeks)

30 mg/kg IV

q12hr

Infants and children

(1 month – 12 years)
   

30 to 50 mg/kg IV

to a maximum

of 6 grams per day†

q8hr
   

Impaired Hepatic Function

No adjustment in dosage is required for patients with hepatic dysfunction.

Impaired Renal Function

Ceftazidime is excreted by the kidneys, almost exclusively by glomerular filtration. Therefore, in patients with impaired renal function (glomerular filtration rate [GFR] <50 mL/min), it is recommended that the dosage of ceftazidime be reduced to compensate for its slower excretion. In patients with suspected renal insufficiency, an initial loading dose of 1 gram of ceftazidime may be given. An estimate of GFR should be made to determine the appropriate maintenance dosage. The recommended dosage is presented in Table 6. 

Table 6. Recommended Maintenance Dosages of Tazicef (ceftazidime for injection, USP) in Renal Insufficiency

NOTE: IF THE DOSE RECOMMENDED IN TABLE 5 ABOVE IS LOWER THAN THAT RECOMMENDED FOR PATIENTS WITH RENAL INSUFFICIENCY AS OUTLINED IN TABLE 6, THE LOWER DOSE SHOULD BE USED.

Creatinine

Clearance

(mL/min)

Recommended

Unit Dose of

Tazicef

Frequency

of Dosing

50 to 31

30 to 16

15 to 6

<5

1 gram

1 gram

500 mg

500 mg

q12hr

q24hr

q24hr

q48hr

When only serum creatinine is available, the following formula (Cockcroft’s equation)4 may be used to estimate creatinine clearance. The serum creatinine should represent a steady state of renal function:

                                                                                 [Weight (kg) x (140 - age)]
Males: Creatinine clearance (mL/min) =                 ––––––––––––––––––––––––––
                                                                                 [72 x serum creatinine (mg/dL)]        

Females: 0.85 x male value 

In patients with severe infections who would normally receive 6 grams of Tazicef daily were it not for renal insufficiency, the unit dose given in the table above may be increased by 50% or the dosing frequency may be increased appropriately. Further dosing should be determined by therapeutic monitoring, severity of the infection, and susceptibility of the causative organism.

In pediatric patients as for adults, the creatinine clearance should be adjusted for body surface area or lean body mass, and the dosing frequency should be reduced in cases of renal insufficiency.

In patients undergoing hemodialysis, a loading dose of 1 gram is recommended, followed by 1 gram after each hemodialysis period.

Tazicef (ceftazidime for injection, USP) can also be used in patients undergoing intra-peritoneal dialysis and continuous ambulatory peritoneal dialysis. In such patients, a loading dose of 1 gram of Tazicef may be given, followed by 500 mg every 24 hours. In addition to IV use, Tazicef can be incorporated in the dialysis fluid at a concentration of 250 mg for 2 L of dialysis fluid.

Note: Generally Tazicef should be continued for 2 days after the signs and symptoms of infection have disappeared, but in complicated infections longer therapy may be required.

Administration

Pharmacy Bulk Package is for use in a pharmacy admixture service only. Refer to Table 7. See above NOTE concerning the proper use of Pharmacy Bulk Packages.

Intravenous Administration

The IV route is preferable for patients with bacterial septicemia, bacterial meningitis, peritonitis, 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 pending.

Intermittent IV infusion with a Y-type administration set can be accomplished with compatible solutions. However, during infusion of a solution containing ceftazidime, it is desirable to discontinue the other solution.

All vials of Tazicef as supplied are under reduced pressure. When Tazicef is dissolved, carbon dioxide is released and a positive pressure develops.

Solutions of Tazicef, like those of most beta-lactam antibiotics, should not be added to solutions of aminoglycoside antibiotics because of potential interaction.

However, if concurrent therapy with Tazicef and an aminoglycoside is indicated, each of these antibiotics can be administered separately to the same patient.

Directions for Use of Pharmacy Bulk Packages:

Reconstitute with Sterile Water for Injection according to Table 7. 

Table 7. Preparation of Solutions of Tazicef

Diluent to Be Added

Approx. Avail. Volume

Approx. Avg. Concentration

26 mL

56 mL

30 mL

60 mL

1 gram/5 mL

1 gram/10 mL

Note: The Pharmacy Bulk Package is for use in a pharmacy admixture service only. Using aseptic technique, the closure should be penetrated only 1 time after reconstitution using a sterile dispensing set which allows measured dispensing of the contents. Use of a syringe and needle is not recommended as it may cause leakage. The withdrawal of container contents should be accomplished without delay. THE ENTIRE CONTENTS OF THE VIAL SHOULD BE DISPENSED WITHIN 4 HOURS OF INITIAL ENTRY.

A plastic bail attached to the Pharmacy Bulk Package provides a suitable hanging device while dispensing in the pharmacy.

Reconstitute with Sterile Water for Injection according to Table 7.

The vacuum may assist entry of the diluent. SHAKE WELL.

Insert a gas relief needle through the vial closure to relieve the internal pressure. Remove the gas relief needle before extracting any solution.

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