Cefoperazone

Cefoperazone belongs to the pharmacological class of Third-generation cephalosporin antibiotics.

Cefoperazone has been approved to relieve symptoms and also for the treatment and maintenance of Endometritis, Febrile Neutropenia, Intra Abdominal Infection, Joint Infection, Pelvic Inflammatory Disease, Peritonitis, Pneumonia, Pyelonephritis, Bacteremia, Skin or Soft Tissue Infection, Urinary Tract Infection.

Cefoperazone reaches high levels in the serum and bile after a single dose. The mean serum half-life is about 2 hours, independent of the route of administration. Steady-state serum concentrations of approximately 150 mcg/mL were observed in severely immunocompromised patients given a total daily dose of 16 g by constant infusion. The reversible protein binding of Cefoperazone varies with the serum concentration, with 93% binding observed at 25 mcg/mL and 82% binding at 500 mcg/mL. Cefoperazone is primarily excreted in the bile, with maximum bile concentrations generally achieved between one and three hours after administration. Following a single dose, 20-30% of Cefoperazone is recovered in urine over a 12-hour period, with no significant quantity of metabolites detected.

The common side effects which are involved in the use of Cefoperazone are nausea, headache, vomiting, rashes or itching at the site of injection , itching, diarrhea, headache,upset stomach, etc.

Cefoperazone is available in the form of Intramuscular, Intravenous Injections

Cefoperazone is approved in the U.S., U.K., Germany, Japan, Malaysia, India, and China.

Cefoperazone belongs to the pharmacological class of Third-generation cephalosporin antibiotics.

Cefoperazone, similar to other beta-lactam antibiotics, attaches to penicillin-binding proteins (PBPs) present in the bacterial cell wall, which obstructs the final stage of bacterial cell wall synthesis. Consequently, bacterial cell wall autolytic enzymes such as autolysins facilitate cell lysis.

Cefoperazone has been approved to relieve symptoms and also for the treatment and maintenance of Endometritis, Febrile Neutropenia, Intraabdominal Infection, Joint Infection, Pelvic Inflammatory Disease, Peritonitis, Pneumonia, Pyelonephritis, Bacteremia, Skin or Soft Tissue Infection, Urinary Tract Infection.

The maximum serum concentration (Cmax) of cefoperazone is typically achieved within 30 to 60 minutes after intravenous administration. The time to maximum concentration (tmax) ranges from 30 minutes to 3 hours.

The onset of action is generally rapid, with bacterial growth inhibition observed within 1 to 2 hours after administration. The duration of action varies depending on the dose and frequency of administration, as well as the severity and location of the infection being treated. Generally, cefoperazone has a half-life of 1 to 2 hours and is eliminated primarily by the kidneys, with approximately 70% of the drug excreted unchanged in the urine within 24 hours.

Cefoperazone is found to be available in the form of Intramuscular, Intravenous Injections.

Cefoperazone can be used in the following treatment:

• Endometritis
• Febrile Neutropenia
• Intraabdominal Infection
• Joint Infection
• Pelvic Inflammatory Disease
• Peritonitis
• Pneumonia
• Pyelonephritis
• Bacteremia
• Skin or Soft Tissue Infection
• Urinary Tract Infection

Cefoperazone can help to relieve symptoms and also for the treatment and maintenance of Endometritis, Febrile Neutropenia, Intraabdominal Infection, Joint Infection, Pelvic Inflammatory Disease, Peritonitis, Pneumonia, Pyelonephritis, Bacteremia, Skin or Soft Tissue Infection, Urinary Tract Infection.

Cefoperazone is approved for use in the following clinical indications:

● Endometritis

● Febrile Neutropenia

● Intraabdominal Infection

● Joint Infection

● Pelvic Inflammatory Disease

● Peritonitis

● Pneumonia

● Pyelonephritis

● Bacteremia

● Skin or Soft Tissue Infection

● Urinary Tract Infection

Endometritis: 2 g IV q12h

Febrile Neutropenia: 2 g IV q8h

Intraabdominal Infection: 1-2 g IV q12h

Joint Infection: 2 g IV q12h

Pelvic Inflammatory Disease: 2 g IV q12h

Peritonitis: 1-2 g IV q12h

Pneumonia: 1-2 g IV q12h

Pyelonephritis: 2 g IV q12h

Bacteremia: 1-2 g IV q12h

Skin or Soft Tissue Infection: 1-2 g IV q12h

Urinary Tract Infection: 2 g IV q12h

Cefoperazone is available in the following dosage forms 1g, 2g, 10g.

Intramuscular, Intravenous Injections.

• Dosage Adjustments in Kidney Patients:

Close monitoring of serum levels is recommended if doses higher than 4 g/24 hours are needed in patients with liver disease. For patients with both liver dysfunction and significant renal impairment, the dosage should not exceed 1 to 2 g/day, and serum levels should be closely monitored. This applies to patients with liver disease.

• Dosage Adjustments in Pediatric Patients:

The recommended dosage of cefoperazone is 100-150 mg/kg per day, which should be divided and administered every 8-12 hours.

There are no known specific dietary restrictions related to the use of cefoperazone. However, it is generally recommended to avoid excessive consumption of alcohol while taking cefoperazone, as it may increase the risk of side effects such as liver damage. Additionally, it is important to maintain a healthy and balanced diet to support overall health and help the body fight off infections. It is always advisable to consult with a healthcare provider or a registered dietitian for personalized dietary recommendations related to your specific health condition and treatment.

Cefoperazone may be contraindicated under the following conditions:

• Hypersensitivity or allergy to Cefoperazone or any other cephalosporin antibiotics.

The physician should closely monitor the patients as well as keep pharmacovigilance as follows:

Hypersensitivity Reactions:

Hypersensitivity reactions are a potential risk for patients receiving beta-lactam antibiotics, such as cefoperazone, and can be severe or even fatal. Patients with a history of hypersensitivity to cephalosporins, penicillins, carbapenems, or other drugs are at a higher risk for these reactions. It is important to conduct a thorough inquiry about previous allergic reactions before starting therapy with cefoperazone. Caution should be exercised when prescribing this product to patients with a known beta-lactam allergy. If an allergic reaction occurs, cefoperazone should be stopped immediately, and appropriate treatment should be initiated.

Clostridium difficile-Associated Diarrhea:

The use of antibacterial agents, including cefoperazone, can result in Clostridium difficile-associated diarrhea (CDAD) due to alterations in the normal colon flora that promote the growth of C. difficile. This can cause diarrhea ranging from mild to severe, including fatal colitis. Hypertoxin-producing strains of C. difficile can lead to significant morbidity and mortality, and treating such infections can be challenging and may require colectomy. As such, CDAD should be considered in any patient experiencing diarrhea following antibacterial drug use. If CDAD is suspected or confirmed, ongoing antibacterial treatment may need to be discontinued, and appropriate management, including fluid and electrolyte support, protein supplementation, antibacterial treatment for C. difficile, and surgical evaluation, should be initiated as necessary.

Hemorrhage:

Cefoperazone use can also increase the risk of hemorrhage, including severe or fatal cases. Thrombocytopenia, coagulopathy, and signs of bleeding should be monitored closely during therapy with cefoperazone. If persistent bleeding occurs, and no other explanation is identified, cefoperazone should be discontinued immediately.

There is no specific alcohol warning for cefoperazone, but it is generally recommended to avoid alcohol while taking antibiotics as it can interfere with the effectiveness of the medication and increase the risk of the side effects such as nausea, vomiting, and headache. It is always best to follow the advice of your healthcare provider regarding the use of alcohol while taking any medication.

Cefoperazone is excreted in low concentrations in human milk, and it passes poorly into the breast milk of nursing mothers. Although caution should be exercised when Cefoperazone is administered to a nursing woman.

Pregnancy Category B

The use of Cefoperazone in pregnant women is classified as Pregnancy Category B. Animal reproduction studies conducted on mice, rats, and monkeys at doses up to 10 times the human dose did not show evidence of impaired fertility or harm to the fetus due to Cefoperazone. However, there is found to be no adequate and well-controlled studies in pregnant women. Therefore, the drug should only be used during pregnancy if it is clearly needed.

There are no food warnings related to cefaperazone according to the USFDA. However, it is generally recommended to avoid consuming large amounts of alcohol while taking antibiotics, including cefaperazone, as it can increase the risk of certain side effects such as gastrointestinal upset and dizziness. Additionally, certain foods, particularly those high in calcium, may interfere with the absorption of cefoperazone if taken orally. Therefore, it is advisable to avoid consuming these foods at the same time as taking cefoperazone.

The adverse reactions related to Cefoperazone can be categorized as follows:

Common:

• Nausea
• Diarrhea
• Vomiting
• Skin rash
• Injection site reactions (such as pain or inflammation)
• Eosinophilia (increase in eosinophils, a type of white blood cell)
• Transient increase in liver enzymes
• Pain or phlebitis at the injection site

Less Common:

• Headache
• Dizziness
• Abdominal pain
• Flatulence
• Dysgeusia (distorted sense of taste)
• Leukopenia (decrease in white blood cells)
• Thrombocytosis (increase in platelets)

Rare:

• Seizures
• Anaphylaxis (serious allergic reaction)
• Stevens-Johnson syndrome (a severe skin reaction)
• Toxic epidermal necrolysis (a rare and serious skin reaction)
• Pseudomembranous colitis (a severe inflammation of the colon)
• Hemolytic anemia (decrease in red blood cells due to their destruction)

The clinically relevant drug interactions of Cefoperazone are briefly summarized here:

Aminoglycosides: Concurrent use of aminoglycosides and cefoperazone may increase the risk of nephrotoxicity and ototoxicity.

Probenecid: Probenecid can increase the serum concentration of cefoperazone by inhibiting its renal excretion.

Loop Diuretics: Cefoperazone can displace loop diuretics from protein binding sites, leading to increased free drug concentrations and potential ototoxicity.

Warfarin: Cefoperazone may increase the anticoagulant effect of warfarin by decreasing its metabolism.

Oral Contraceptives: Cefoperazone may decrease the effectiveness of oral contraceptives, leading to an unplanned pregnancy.

Methotrexate: Cefoperazone can increase the serum concentration of methotrexate, leading to increased toxicity.

Live Vaccines: Cefoperazone may decrease the effectiveness of live vaccines, such as measles, mumps, rubella, and varicella.

The following are the side effects involving Cefoperazone :

• Diarrhea
• Nausea and vomiting
• Abdominal pain
• Headache
• Dizziness
• Skin rash or itching
• Injection site reactions such as pain, swelling, or redness
• Fever or chills
• Blood disorders such as anemia, leukopenia, or thrombocytopenia
• Liver function abnormalities
• Kidney function abnormalities

Pregnancy

Pregnancy Category B

The use of Cefoperazone in pregnant women is classified as Pregnancy Category B. Animal reproduction studies conducted on mice, rats, and monkeys at doses up to 10 times the human dose did not show evidence of impaired fertility or harm to the fetus due to Cefoperazone. However, there is found to be no adequate and well-controlled studies in pregnant women. Therefore, the drug should only be used during pregnancy if it is clearly needed.

Nursing Mothers:

Cefoperazone is excreted in low concentrations in human milk, and it passes poorly into the breast milk of nursing mothers. Although caution should be exercised when Cefoperazone is administered to a nursing woman.

Pediatric Use:

The safety and effectiveness of Cefoperazone in children have not been established. Testicular changes in prepubertal rats have been reported. Therefore, the drug should not be used in pediatric patients unless it is deemed necessary.

Geriatric Use:

Clinical studies of Cefoperazone did not include a sufficient number of subjects aged 65 and over to determine whether they responded differently from younger patients. In general, caution is to be exercised when prescribing Cefoperazone to elderly patients, as they are more likely to have decreased hepatic, renal, or cardiac function, and concomitant diseases or other drug therapy. Therefore, dose selection for an elderly patient should be done cautiously, usually starting at the low end of the dosing range.

Physicians should be knowledgeable as well as vigilant about the treatment and identification of overdosage of Cefoperazone.

An overdose of cefoperazone may result in neurological symptoms such as seizures, confusion, and dizziness. It may also cause gastrointestinal symptoms such as nausea, vomiting, and diarrhea. In the case of an overdose, the patient should seek immediate medical attention.

Treatment for cefoperazone overdose typically involves supportive care and symptomatic management. In cases of seizures or neurological symptoms, anticonvulsants may be administered. In the case of severe gastrointestinal symptoms, antiemetic or antidiarrheal medications may be prescribed.

Since cefoperazone is primarily excreted through the urine, increasing urinary output may help in eliminating the drug from the body. Therefore, the patient may be given intravenous fluids to increase urine output and aid in the elimination of cefoperazone.

Hemodialysis is not effective in removing cefoperazone from the body. However, if the patient has renal insufficiency, hemodialysis may be indicated to manage the underlying condition.

Pharmacodynamics

Cefoperazone is classified as a third-generation cephalosporin antibiotic that works by inhibiting bacterial cell wall synthesis, resulting in a bactericidal effect.

Pharmacokinetics

After a single dose of Cefoperazone, high levels of the drug are detected in both serum and bile. Table 1 presents the serum concentrations of Cefoperazone in normal volunteers who received either a single intravenous infusion of 1, 2, 3 or 4 grams of the drug over 15 minutes or a single intramuscular injection of 1 or 2 grams. The mean serum half-life of Cefoperazone is approximately 2.0 hours, irrespective of the administration route.

In a pharmacokinetic study, severely immunocompromised patients received a total daily dose of 16 grams of Cefoperazone via constant infusion without any complications. These patients achieved steady-state serum concentrations of about 150 mcg/mL.

In vitro experiments using human serum demonstrate that reversible protein binding of Cefoperazone varies based on serum concentration, with 93% at 25 mcg/mL of Cefoperazone, 90% at 250 mcg/mL, and 82% at 500 mcg/mL. Following a single intramuscular or intravenous dose, the urinary recovery of Cefoperazone over a 12-hour period averages 20-30%. No significant metabolites have been found in the urine. Infusion of a 2g dose for 15 minutes can produce urinary concentrations greater than 2200 mcg/mL, while IM injection of 2g results in peak urine concentrations of almost 1000 mcg/mL, maintaining therapeutic levels for 12 hours.

Repeated administration of Cefoperazone every 12 hours does not cause drug accumulation in normal subjects. Peak serum concentrations, areas under the curve (AUCs), and serum half-lives in patients with severe renal insufficiency are not significantly different from those in normal volunteers. In patients with a hepatic dysfunction, the serum half-life is prolonged, and urinary excretion is increased. Cefoperazone may accumulate in the serum of patients with both renal and hepatic insufficiencies.

Cefoperazone has been used in pediatric patients, but its safety and efficacy in children have not been established. The half-life of Cefoperazone in serum is 6-10 hours in low birth-weight neonates.

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