Dorifast Tz

Uses

Cefoperazone is used for the treatment of the following infections when caused by susceptible organisms: Respiratory Tract Infections, Peritonitis & Other Intra-abdominal Infections, Bacterial Septicemia, Skin and Skin Structures Infections, Pelvic Inflammatory Disease, Endometritis & Other Infections of the Female Genital Tract, Urinary Tract Infections, Enterococcal Infections etc.

Tazobactam is a beta lactamase inhibitor administered with antibiotics such as piperacillin and ceftolozane to prevent their degradation, resulting in increased efficacy.

Tazobactam is used in combination with piperacillin or ceftolozane to broaden the spectrum of piperacillin antibacterial action, treating susceptible infections. As with any other antibiotic, tazobactam should only be used for infections that are either proven or strongly suspected to be susceptible to the tazobactam containing drug.

Tazobactam-piperacillin

When combined with piperacillin, it is used to treat a variety of infections, including those caused by aerobic and facultative gram-positive and gram-negative bacteria, in addition to gram-positive and gram-negative anaerobes. Some examples of infections treated with piperacillin-tazobactam include cellulitis, diabetic foot infections, appendicitis, and postpartum endometritis infections. Certain gram-negative bacilli infections with beta-lactamase producing organisms cannot be treated with piperacillin-tazobactam, due to a gene mutation conferring antibiotic resistance.

Tazobactam-ceftolozane

Tazobactam-ceftolozane combined with metronidazole is used to treat complicated urinary tract infections (UTI) and complicated intra-abdominal infections, as well as ventilator-associated bacterial pneumonia and hospital-acquired bacterial pneumonia.. This combination increases efficacy against infections with gram-negative bacilli.

Dorifast Tz is also used to associated treatment for these conditions: Bacterial Infections, Bloodstream Infections, Bone and Joint Infections, Intra-Abdominal Infections, Lower Respiratory Tract Infection (LRTI), Meningitis, Peritonitis, Postoperative Infections, Skin and Soft Tissue Infections, Upper Respiratory Tract Infection, Urinary Tract Infection, Genital tract infectionAnimal bite, Cellulitis, Complicated Appendicitis, Cutaneous Abscess, Diabetic Foot Ulcers (DFU), Pelvic Inflammatory Disease (PID), Peritonitis, Pneumonia, Hospital-Acquired, Postpartum Endometritis, Surgical Site Infections, Ventilator-Associated Pneumonia (VAP), Complicated Bacterial Urinary Tract Infections, Complicated Pyelonephritis, Complicated intra-abdominal bacterial infections, Moderate Bacterial Infections, Moderate Community acquired pneumonia, Moderate Nosocomial pneumonia, Severe Bacterial Infections, Severe Nosocomial pneumonia, Uncomplicated skin and subcutaneous tissue bacterial infections

How Dorifast Tz works

Like all beta-lactam antibiotics, cefoperazone binds to specific penicillin-binding proteins (PBPs) located inside the bacterial cell wall, causing the inhibition of the third and last stage of bacterial cell wall synthesis. Cell lysis is then mediated by bacterial cell wall autolytic enzymes such as autolysins.

Tazobactam broadens the spectrum of piperacillin and ceftolozane by making them effective against organisms that express beta-lactamase and would normally degrade them. This occurs through the irreversible inhibition of beta-lactamase enzymes. In addition, tazobactam may bind covalently to plasmid-mediated and chromosome-mediated beta-lactamase enzymes. Tazobactam is predominantly effective against the OHIO-1, SHV-1, and TEM groups of beta-lactamases, but may also inhibit other beta-lactamases.

Tazobactam shows little antibacterial activity by itself, and for this reason, is generally not administered alone.

Dosage

Dorifast Tz dosage

Sterile Cefoperazone Sodium can be administered by IM or IV injection (following dilution).

Adult: 2 to 4 grams per day administered in equally divided doses every 12 hours. In severe infections or infections caused by less sensitive organisms, the total daily dose and/or frequency may be increased. Patients have been successfully treated with a total daily dosage of 6-12 grams divided into 2,3, or 4 administrations ranging from 1.5 to 4 grams per dose. When treating infections caused by Streptococcus pyogenes, therapy should be continued for at least 10 days

Cefoperazone for intravenous or intramuscular use may be initially reconstituted with compatible solution. Solutions should be allowed to stand after reconstitution to allow any foaming to dissipate to permit visual inspection for complete solubilization. Vigorous and prolonged agitation may be necessary to solubilize Cefoperazone in higher concentrations (above 333 mg Cefoperazone/ml). The maximum solubility of Cefoperazone is approximately 475 mg Cefoperazone/ml of compatible diluent.

Side Effects

As with all Cephalosporins, hypersensitivity manifested by skin reactions (1 patient in 45), drug fever (1 in 260), or a change in Coombs' test (1 in 60) has been reported. These reactions are more likely to occur in patients with a history of allergies, particularly to Penicillin.

Toxicity

Symptoms of overdose include blood in the urine, diarrhea, nausea, upper abdominal pain, and vomiting.

Overdose

Post-marketing reports have been made of overdose cases with piperacillin/tazobactam. Nausea, vomiting, and diarrhea are frequent manifestations of an overdose. Neuromuscular excitability or seizures may also occur with high intravenous doses or renal failure. There is no specific antidote. Provide supportive measures in case of an overdose. Anticonvulsive agents may be indicated when neuromuscular excitability or seizures occur. If anaphylaxis occurs, traditional measures should be taken to manage hypersensitivity (for example, adrenaline, antihistamines, corticosteroids, and oxygen/airway maintenance). Similar measures should be taken after a ceftolozane-tazobactam overdose. Hemodialysis can be used to remove the drug from the circulation .

A note on nephrotoxicity

Cases of life-threatening nephrotoxicity have been seen in critically ill patients receiving piperacillin-tazobactam. Alternative therapy and/or renal monitoring should be considered in critically ill patients.

Carcinogenesis/Mutagenesis

Tazobactam tested negative for genotoxic effects in the Ames assay, an after in vitro chromosomal aberration and point mutation assay in the Chinese hamster, an various other assays.

Use in pregnancy

Tazobactam has been found cross the placenta in rats. No data on human studies are available, however, rat studies have shown no teratogenetic effects at doses 6-14 times the equivalent maximum recommended human dose.

Use in lactation

There are no data on the presence of tazobactam in human breastmilk. No data are currently available on the effects of tazobactam on the infant, or how it affects milk production. Use clinical judgement and consider the maternal need for the drug and the benefits of breastfeeding the infant before administration during lactation. Small concentrations of piperacillin-tazobactam have been found in the breastmilk and can lead to hypersensitivity in a breastfeeding infant. In some cases, breastfeeding may have to be discontinued temporarily.

Precaution

Cefoperazone is extensively excreted in bile. The serum half-life of Cefoperazone is increased 2-4 fold in patients with hepatic disease and/or biliary obstruction. In general, total daily dosage above 4 gm should not be necessary in such patients. If higher dosages are used, serum concentrations should be monitored.

Volume of Distribution

18.2 L when given with piperacillin

13.5-18.2 L when given with ceftolozane

Piperacillin-tazobactam is widely distributed in body tissues and fluids. These may include but are not limited to the intestine, gallbladder, lung, female reproductive organs, and the bile. Meningeal distribution of piperacillin-tazobactam increases with inflammation, but is otherwise low.

Elimination Route

Tazobactam is coadministered with piperacillin or ceftolozane, pharmacokinetic information will be provided for these combinations.

Piperacillin-tazobactam

Peak plasma concentrations occur immediately after the completion of intravenous infusion. Following several doses of piperacillin-tazobactam infusions every 6 hours, peak concentrations were similar to those that were measured after the initial dose.

Ceftolozane-piperacillin

AUC: 24.4-25 mcg•h/mL

Peak concentrations are reached on day 1 after the first dose and range from 18 to 18.4 mcg/mL.

Half Life

The mean serum half-life is approximately 2.0 hours, independent of the route of administration.

Piperacillin-tazobactam

After a single dose in healthy volunteers, the plasma half-life of piperacillin and tazobactam was in the range of 0.7 to 1.2 hours.

Ceftolozane-tazobactam

0.91-1.03 hours

Clearance

Because tazobactam is cleared by the kidneys and is a substrate of the transporters OAT1 and OAT3, inhibitors of these transporters should be avoided to ensure efficacy. Dosage adjustments of piperacillin-tazobactam and ceftolozane-tazobactam must be made for patients with impaired renal clearance.

The mean clearance rate of tazobactam was found to be 48.3-83.6 mL/min in patients admitted to the intensive care unit who were given renal replacement therapy and receiving intravenous piperacillin-tazobactam.

The clearance of tazobactam is dependent on renal function, as determined by renal clearance.

Elimination Route

Cefoperazone is excreted mainly in the bile.

Tazobactam and its metabolite are mainly eliminated by the kidneys with about 80% of the administered dose eliminated as unchanged drug. The remaining drug is excreted as a single metabolite.

Pregnancy & Breastfeeding use

Pregnancy Category B.This drug should be used during pregnancy only if clearly needed. Only low concentrations of Cefoperazone is excreted in human milk. Although Cefoperazone passes poorly into breast milk of nursing mothers, caution should be exercised when Cefoperazone is administered to a nursing woman.

Contraindication

Cefoperazone is contraindicated in patients with known allergy to the Cephalosporin-class of antibiotics.

Special Warning

Children use: Safety and effectiveness in children have not been established.

Geriatric use: Reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.

Storage Condition

Cefoperazone is to be stored in a dry place, below 25°C and protected from light prior to reconstitution. The reconstituted solution may be stored for 24 hours if kept in room temperature (below 25°C).

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