Branded Medicine

 

Powdered for Injection

COMPOSITION
Each vial contains:
Ceftizoxime sodium  1145 mg
(equivalent to Ceftizoxime base 1 g)

PHARMACOLOGY
Ceftizoxime, like other cephalosporins, kills bacteria by interfering with the synthesis of the bacterial cell wall. Ceftizoxime binds with high affinity to penicillin-binding proteins in the bacterial cell wall, thus interfering with peptidoglycan synthesis. Peptidoglycan is a heteropolymeric structure that provides the cell wall with mechanical stability. The final stage in the synthesis of peptidoglycan involves the completion of the cross-linking and the terminal glycine residue of the pentaglycine bridge is linked to the fourth residue of the pentapeptide (D-alanine). The transpeptidase enzyme that performs this step is inhibited by cephalosporins and penicillins.
Ceftizoxime sodium has broad spectrum activity against gram positive and negative microorganisms. In particular, it has potent activity against gram positives, such as Streptococcus pneumoniae, Streptococcus sp. (excluding enterococci), and gram negatives, such as E. coli, Klebsiella sp., Proteus mirabilis, indole-positive Proteus sp., Haemophilus influenzae. It is also active against Citrobacter sp., Enterobacter sp., Serratia sp., and anaerobes including Bacteroides sp., which are resistant to many other cephalosporins. Its mode of action is bactericidal.
It is stable to β-lactamase produced by many organisms and is active against β-lactamase producing organisms.

PHARMACOKINETICS
1.Serum concentration
- Intravenous injection
Serum ceftizoxime concentration in healthy adults given 0.5 g or 1.0 g intravenously were, respectively, 58.9 μg/ml and 114.8 μg/ml at 5 minutes, and 1.0 μg/ml and 2.1 μg/ml at 6 hours. The serum half-lives of ceftizoxime were 1.21 hours (0.5 g IV) and 1.29 hours (1 g IV). Maximum serum concentrations were 57.9 μg/ml (after a 1 g, 1-hour drip infusion) and 34.6 μg/ml (after a 1 g, 2-hour drip infusion), 123.7 μg/ml (after a 2 g, 1 hour drip infusion) and 79.3 μg/ml (after a 2 g, 2-hour drip infusion).
Following an intravenous injection of 20 mg/kg or 30 mg/kg in pediatric patients with normal renal function, serum concentrations were 61.1 μg/ml and 95.9 μg/ml, respectively at 15 minutes after dosing, and 3.3 μg/ml and 1.9 μg/ml, respectively at 6 hours after administration. The serum half- lives were 1.40 hours (20 mg/kg, IV) and 1.06 hours (30 mg/kg, IV)
- Intramuscular injection
Maximum serum concentrations of ceftizoxime in healthy adults given 0.25 g or 0.5 g intramuscularly were, respectively 10.1 μg/ml at 15 minutes and 17.9 μg/ml at 30 minutes. The serum half-lives of ceftizoxime were 1.21 hours (0.25 g IM) and 1.51 hours (0.5 g IM). In patients with impaired renal function, the serum half-life was prolonged proportionate to the severity of renal impairment, with serum concentrations persisting for longer periods.

2.Tissue penetration (distribution)
Distribution into body fluids such as the sputum, pleural effusion, biliary fluid and cerebrospinal fluid, and penetration into tissues such as the tonsil, gall-bladder, uterus and prostate, is good.

3.Metabolism
No antibacterial metabolites are found in the urine.

4.Excretion
Ceftizoxime sodium is excreted primarily through the kidneys. The urine excretion rate (up to 6 hours after a dose) in healthy adults was 80 - 90% when given intravenously and 60 - 70%
intramuscularly. Ceftizoxime urine concentrations were 2.660 μg/ml (0-2 hours) and 1.175 μg/ml (2 - 4 hours) with 1 g IV, 1.179 μg/ml (0 - 2 hours) and 739 μg/ml (2 - 4 hours) with 0.5 g IM. Following an intravenous injection of 30 mg/kg in pediatric patients with normal renal function, 6 hours after a dose the urinary excretion rate was 77.5 %.
Urinary drug concentrations were 4.834 μg/ml (0 - 2 hours) and 1.154 μg/ml (2 - 4 hours)

INDICATIONS
The following infections caused by ceftizoxime susceptible Streptoccus sp. (excluding enterococci), Streptococcus pneumoniae, Haemophilus influenzae, Escherichia coli, Klebsiella sp., Proteus sp., Serratia sp., Enterobacter sp., Citrobacter sp., Peptococcus sp., Peptostreptococcus sp., and Bacteroides sp.:
Septicemia, bacterial endocarditis.
Secondary infections of wounds or burns.
Bronchitis, infected bronchiectasis, secondary infections of chronic respiratory tract diseases, pneumonia, pulmonary suppuration, pyothorax.
Cholangitis, cholecystitis.
Peritonitis
Pyelonephritis, cystitis, prostatitis.
Meningitis caused by H. influenzae

CONTRAINDICATION
Patients with:
A history of shock caused by ceftizoxime sodium and in patients who are hypersensitive to other cephalosporins.
A history of hypersensitivity to lidocaine or anilide type local anesthetics (if lidocaine is used for reconstitution before intramuscular administration).

DOSAGE AND ADMINISTRATION
1.Intravenous injection
For adults, usually 0.5-2 g/day of ceftizoxime is administered intravenously in 2-4 equally divided doses, increased to 4 g/day for severe or intractable infections, according to the age and condition of the patient. For children 6 months or older usually, 40-80 mg/kg/day of ceftizoxime in 2-4 equally divided doses, increased to 120 mg/kg/day for severe or intractable infections, according to the age and condition of the patient.
2.Intramuscular injection
For adults, usually, 0.5-2 g/day of ceftizoxime is administered intramuscularly in 2-4 equally divided doses, according to the age and condition of the patient.
(See 'Cautions in application')

RECONSTITUTION
1.Intravenous injection
Reconstitute with distilled water for injection, physiological saline (isotonic sodium chloride solution), or glucose injection, and inject slowly.
2.Intravenous drip infusion
Following reconstitution, dilute with intravenous solutions for infusion such as glucose solution, electrolyte or amino acid solutions, and inject over 30-120 minutes.
(Note : distilled water for injection should not be used for drip infusions as it is not isotonic)
3.Intramuscular injection
Reconstitute with 2 ml of either distilled water for injection or 0.5% w/v lidocaine injection.
(See 'Cautions in application')

PRECAUTIONS FOR USE
1.General precautions
Careful inquiry about any form of hypersensitivity should be made to avoid reactions such as shock. Prior to use, skin testing is recommended.
2.Careful administration
Patients with:
A history of hypersensitivity to penicillins or cephems.
A personal or familial history of some form of allergy such as bronchial asthma, rash or urticaria.
Serious renal function disorder;
As serum ceftizoxime concentrations persist for longer periods, the dosage of the drug should be decreased, and/or the administration interval should be lengthened, proportionate to the severity of renal impairment.
Poor oral nutrition, parenteral nutrition, the elderly or debilitated state;
Careful observation essential in these patients as vitamin K deficiency symptoms may develop.
3.Use in children
Safety in newborns or prematures and children less than six months has not been established.
4.Use during pregnancy
Safety during pregnancy has not been established; therefore, the drug should be administered to patients who are or may become pregnant only if the expected therapeutic benefit is thought to outweight any possible risk.
5.Effect on laboratory test
False-positive results with urine sugar tests using Benedicts test solution, Fehling test solution, and Clinitest- but not with Tes-Tape- may occur.
A positive direct Coombs- test may occur.
6.Cautions in application
Give intravenously as slowly as possible since vascular pain or thrombophlebitis after a large IV dose may occur.
In giving an intramuscular injection, the following cautions should be exercised:
The use of intramuscular injection should be minimized and used only when it can not be avoided.
Avoided repeated injections in the same site.
Do not administer the drug by the intramuscular route to newborns, prematures, sucklings (nursing infants), or pediatrics (young children)
Avoid injection into nerve pathways.
If patients complain of severe pain or if blood is aspirated into the syringe when the needle is inserted, the needle should be withdrawn immediately and new injection site selected.
Solutions of the drug prepared with lidocaine for intramuscular administration must not be used for intravenous injection.
Intramuscular administration may cause pain or induration at the injection site.
Use promptly after reconstitution. If a reconstituted solution must be stored, use within 6 hours (at room temperature) and 3 days (if refrigerated) to avoid possible precipitation which may happen with longer storage. The precipitate is ceftizoxime, the free acid of ceftizoxime sodium.
The drug can still be safely used even if reconstituted solutions sometime become slightly more yellow with a lapse of time.

SIDE EFFECTS
Shock
Adequate caution in administration should be used as shock symptoms may rarely occur. If any related signs or symptoms such as feeling unwell, oral cavity discomfort, stridor, dizziness, abnormal urge to defecate, tinnitus or diaphoresis occur, the drug must be discontinued immediately.
Hypersensitivity
If signs of hypersensitivity reactions such as rash, urticaria, erythema, pruritus, fever, lymph node enlargement or numbness occur, the drug should be discontinued and appropriate measures should be taken.
Haematologic
Granulocytopenia or eosinophilia in frequently may occur. Rarely erythrocytopenia, haemolytic anemia or thrombocytopenia may occur. The drug should be discontinued if any of these abnormalities is found.
Hepatic
Infrequently an increase in SGOT, SGPT, alkaline phosphatase or bilirubin may occur. Rarely jaundice may occur.
Renal
Infrequently renal impairment such as an increase in BUN or serum creatinine level, oliguria or proteinuria may occur. If urine abnormalities such as oliguria, proteinuria or hematuria, or findings of renal function disorder such as an increase in BUN or the serum creatinine level occur, appropriate measures such as discontinuation of the drug should be taken.
Gastrointestinal
In rare instances a serious colitis manifested by fever, abdominal pain, leukocytosis and severe diarrhea with mucus/blood in stools may occur. Upon endoscopy this may be diagnosed as pseudomembranous colitis.
Abdominal pain or frequent diarrhea requires appropriate measures, including prompt withdrawal of the drug. Infrequently diarrhea, and rarely nausea of vomiting, may occur.
Substituted microbism (Alteration in bacterial flora).
Rarely stomatitis or candidiasis may occur.
Vitamin deficiencies
Rarely vitamin K deficiencies (such as hypoprothrombinaemia or bleeding tendencies) or vitamin B group deficiencies (such as glossitis, stomatitis, anorexia or neuritis) may occur.
Others
Rarely headache may occur.

DRUG INTERACTIONS
Probenecid
Oral probenecid administered shortly before or concomitantly with ceftizoxime slows the rate of renal tubular secretion of ceftizoxime and produces higher and more prolonged serum concentrations of the drug.
Aminoglycosides
Concurrent use of aminoglycosides and certain cephalosphorins reportedly may increase the risk of nephrotoxicity during therapy. Although this effect has not been reported to date with ceftizoxime, the manufacturer states that the possibility that nephrotoxicity may be potentiated should be considered if the drug is used concomitantly with an aminoglycosides and renal function should be monitored.

Presentation and reg. no:
Box, 1 vial @ 1 gram; DKL0605041544A1

ON MEDICAL PRESCRIPTION ONLY

STORE AT ROOM TEMPERATURE BELOW 30oC.
PROTECT FROM LIGHT

Manufactured by:
Dexa Medica