Ezone

Sulbactam (Ezone) sodium/Cefoperazone (Ezone) sodium combination is available as a dry powder for reconstitution in both a 1:1 and 1:2 ratio in terms of free SBT/CPZ.

Sulbactam (Ezone) sodium is a derivative of the basic penicillin nucleus. It is an irreversible β-lactamase inhibitor for parenteral use only. Chemically it is sodium penicillinase sulfone. It contains sodium 92 mg sodium (4 mEq) per gram.

Sulbactam (Ezone) is an off-white crystalline powder which is highly soluble in water. The molecular weight is 255.22.

Cefoperazone (Ezone) sodium is a semisynthetic broad-spectrum cephalosporin antibiotic for parenteral use only. It contains sodium 34 mg (1.5 mEq)/g. Cefoperazone (Ezone) is a white crystalline powder which is freely soluble in water. The molecular weight is 667.65.

Formulation: Each vial contains Cefoperazone (Ezone) sodium equivalent to 1000 mg of Cefoperazone (Ezone) and Sulbactam (Ezone) sodium equivalent to 500 mg Sulbactam (Ezone).

Central Nervous System (CNS) Infections: Meningitis and ventriculitis caused by N. meningitidis, H. influenzae, S. pneumoniae, K. pnuemoniae and E. coli.

Bacteremia/septicemia caused by E. coli, Klebsiella spp, S. marcescens, S. aureus and Streptococcus spp (including S. pneumoniae).

Intra-abdominial infections including peritonitis caused by Streptococcus spp, E. coli, Klebsiella spp, Bacteroides spp and anaerobic cocci (including Peptostreptococcus spp and Peptococcus, P. mirabilis and Clostridium spp).

Lower Respiratory Tract Infections: Including pneumonia caused by S. pneumoniae (formerly Diplococcus pneumoniae), S. pyogenes (Group A streptococci) and other streptococci (excluding enterococci eg, S. faecalis), S. aureus (penicillinase-/non-penicillinase-producing), E. coli, Klebsiella spp, H. influenzae (including ampicillin-resistant strains), H. parainfluenzae, P. mirabilis, Serratia marcescens and Enterobacter spp, indole-positive Proteus and Pseudomonas spp (including P. aeruginosa).

Genitourinary Infections: Urinary tract infections caused by Enterococcus spp, S. epidermidis, S. aureus (penicillinase-/non-penicillinase-producing), Citrobacter spp, Enterobacter spp, E. coli, Klebsiella spp, P. mirabilis, P. vulgaris, P. inconstans group B, Morganella morganii, Providencia rettgeri, Serratia marcescens and Pseudomonas spp (including P. aeruginosa).

Also, uncomplicated gonorrhoea (cervical/urethral and rectal) caused by N. gonorrhoea, including penicillinase-producing strains.

Gynaecological Infections: Including pelvic inflammatory disease, endometritis and pelvic cellulitis caused by S. epidermidis, Streptococcus spp, Enterococcus spp, Enterobacter spp, Klebsiella spp, E. coli, P. mirabilis, Bacteroides spp (including B. fragilis), Clostridium spp and anaerobic cocci (including Peptostreptococcus spp and Peptococcus spp) and Fusobacterium spp (including F. nucleatum).

Skin and Skin Structure Infections: Caused by S. aureus (penicillinase-/non-penicillinase-producing), S. epidermidis, S. pyogenes (Group A streptococci) and other streptococci, Enterococcus spp, Acinetobacter spp, Citrobacter spp, E. coli, Enterobacter spp, Klebsiella spp, P. mirabilis, M. morganii, P. rettgeri, P. vulgaris, Pseudomonas spp, S. marcescens, Bacteroides spp, and anaerobic cocci (including Peptostreptococcus spp and Peptococcus spp).

Bone and/or Joint Infections: Caused by S. aureus (penicillinase-/non-penicillinase-producing strains), Streptococcus spp, Pseudomonas species and P. mirabilis.

Pre-Operative Prophylaxis: May reduce the incidence of certain post-operative infections in patients undergoing surgical procedures (eg, abdominal or vaginal hysterectomy, gastrointestinal and genitourinary surgery) that are classified as contaminated or potentially contaminated.

Cesarean Section: Intraoperative (after clamping the umbilical cord) and post-operative use may reduce the incidence of certain post-operative infections.

Concomitant Aminoglocoside Therapy: In certain cases of confirmed or suspected gram-positive or gram-negative species or other serious infections in which the causative organism has not been identified, Ezone may be used concomitantly with an aminoglycoside. The dosage recommended for both antibiotics may be given, and it depends on the severity of the infection and the patient's conditions. Monitor renal function, especially if higher dosages of the aminoglycosides are used, or therapy is prolonged because of the potential neprotoxicity and ototoxicity of aminoglycoside antibiotics. Some β-lactam antibiotics also have a certain degree of nephrotoxicity. Although not noted when Ezone was given alone, nephrotoxicity may be potentiated if it is used concomitantly with an aminoglycoside.

Adults: The maximum daily dosage should not exceed 12 g. The dosage and route of administration by susceptibility of the causative organisms, severity of the infection and the patient's condition is determined by the table as follows.

Pre-Operative Prophylaxis: 1 g IV or IM, 30-90 min prior to surgery.

Cesarean Section: Administer the first dose as 1 g IV as soon as the umbilical cord is clamped. Administer the 2nd and 3rd doses as l g IV or IM at 6- and 12-hr intervals after the 1st dose.

Gonorrhea: Disseminated Gonococcal Infection: 500 mg IV 4 times/day for at least 7 days.

Gonococcal Ophthalmia: 500mg IV 4 times/day for penicillinase-producing N. gonorrhoeae (PPNG).

Paediatric: It is not necessary to differentiate between premature and normal gestational age infants.

The following dosage recommendations may serve as a guide: See Table 2.

Renal Impairment: Determine dosage by degree of renal impairment severity of infection and susceptibility of the causative organism. In patients with estimated creatinine clearances of <20 mL/min/1.73 m², reduce dosage by ½. When only serum creatinine is available, the following formula may be used to convert this value into creatinine clearance. The serum creatinine should represent steady-state renal function.

Administration: Freshly prepared Ezone solutions should be used. A pale yellowish colour of the solution does not indicate an impairment of the antibiotic efficacy.

The duration of treatment depends on the patients response. It should be continued for at least 3 days after the body temperature has returned to normal.

IV Administration: Ezone is injected preferably by the IV route. The 250-mg dose is dissolved in at least 2 mL water for injection. The 500-mg and 1-g doses are dissolved in at least 4 mL water for injection and then injected over a period of 3-5 min either directly into a vein or into the distal part of a clamped infusion tube.

For intermittent IV administration, a solution containing 1 or 2 g in 10 mL sterile water for injection can be injected over a period of 3-5 min.

IM Administration: Ezone may also be injected IM. For this purpose, the contents of 1 vial of 250 mg are dissolved in 2 mL and of 500 mg and 1 g in 4 mL water or injections, respectively and should then be injected deep into the gluteus muscle.

Known allergy to any of the ingredients of Ezone.

The simultaneous use of Ezone Zota Pharmaceuticals with psychotropic, anticonvulsant medications and ethanol is observed enhancement inhibitory action alprazolam on the CNS.

The simultaneous use with blockers of histamine H2-receptor reduce the clearance of alprazolam and increase the inhibitory effect of alprazolam on the CNS; macrolide antibiotics reduce the clearance of alprazolam.

The simultaneous use with hormonal oral contraceptives increased T1/2 of alprazolam.

Simultaneous administration of Ezone Zota Pharmaceuticals with dextropropoxyphene observed a more pronounced CNS depression than in combination with other benzodiazepines, as may increase the concentration of alprazolam in blood plasma.

Simultaneous treatment with digoxin increases the risk of intoxication by cardiac glycosides.

Alprazolam increases the concentration of imipramine in plasma.

Simultaneous administration with itraconazole, ketoconazole increases the effects of alprazolam.

Simultaneous administration with paroxetine may increases the effects of alprazolam due to the inhibition of its metabolism.

Fluvoxamine increases the concentration of alprazolam in plasma and risk of its side effects.

Simultaneous administration of Ezone Zota Pharmaceuticals with fluoxetine may increase the concentration of alprazolam in plasma by decreasing its metabolism and clearance under the influence of fluoxetine which is accompanied by psychomotor disorders.

It can not be exclude the possibility of strengthening effect of alprazolam for simultaneous administration with erythromycin.

Sulbactam (Ezone)/Cefoperazone (Ezone) is generally well tolerated. The majority of adverse events are of mild or moderate severity and are tolerated with continued treatment.

The following adverse drug reactions (ADRs) were observed in clinical trials (comparative and non-comparative studies) and in the post-marketing.

All ADRs listed as follows are presented by MedDRA SOC. Within each frequency category, the ADRs are presented in the order of clinical importance.

CIOMS III Categories: Very Common: ≥1/10 (≥10%); common: ≥1/100 to <1/10 (≥1% and <10%); uncommon: ≥1/1000 to <1/100 (≥0.1% and <1%); not known: Frequency cannot be estimated from available data.

Blood and Lymphatic System Disorders: Very Common: Leucopenia^*, neutropenia^*, positive Coomb's direct test^*, decreased haemoglobin and haematocrit^*, thrombocytopenia^*, eosinophilia^*. Not Known: Hypoprothrombinaemia.

Immune System Disorders: Not Known: Anaphylactoid reaction including shock.

Nervous System Disorders: Uncommon: Headache.

Vascular Disorders: Not Known: Vasculitis, hypotension.

Gastrointestinal Disorders: Common: Diarrhoea, nausea, vomiting. Not Known: Pseudomembranous colitis.

Hepatobiliary Disorders: Very Common: Increased alanine aminotransferase, aspartate aminotransferase and blood alkaline phosphatase^*. Common: Increased blood bilirubin^*.

Skin and Subcutaneous Tissue Disorders: Uncommon: Pruritus, urticaria. Not Known: Stevens-Johnson syndrome, maculopapular rash.

Renal and Urinary Disorders: Not Known: Haematuria.

General Disorders and Administration Site Conditions: Uncommon: Infusion site phlebitis, injection site pain, pyrexia, chills.

^*In the calculation for laboratory abnormality ADR frequencies, all available laboratory values, including those of subjects with baseline abnormalities, were included. This conservative approach was taken because the raw data did not allow distinction between the subset of subjects with baseline abnormalities who had treatment-emergent significant laboratory changes from those subjects with baseline abnormalities who did not have treatment-emergent significant laboratory changes. For leucocytes, neutrophils, platelets, haemoglobin and haematocrit, only abnormalities are reported in studies. Increases and decreases are not differentiated.