Cefotetan

Cefotetan belongs to the pharmacological class of Second-generation cephalosporin antibiotics.

Cefotetan has been approved to relieve symptoms and also for the treatment and maintenance of Pelvic inflammatory disease, Skin and soft tissue infection, Surgical prophylaxis ,Urinary tract infection, Intra-abdominal infection, Pelvic inflammatory disease, Peritonitis, Surgical prophylaxis.

Cefotetan is a drug that is primarily administered intravenously or intramuscularly. The drug has a volume of distribution of 10.4 L in elderly patients with normal renal function and 10.3 L in healthy volunteers aged 25 to 28 years. Cefotetan is 88% plasma protein bound. The drug is minimally metabolized in the liver, and no active metabolites have been detected. However, small amounts which is less than 7% of cefotetan in plasma and urine may be converted to its tautomer, which has antimicrobial activity similar to the parent drug. Cefotetan is eliminated from the body primarily by the kidneys, with 51% to 81% of the administered dose excreted unchanged in the urine over a 24-hour period. This results in high and prolonged urinary concentrations of the drug.

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

Cefotetan is available in the form of Powder for injection, Injectable solution, Intravenous Infusion.

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

Cefotetan belongs to the pharmacological class of Second-generation cephalosporin antibiotics.

Cefotetan is a cephalosporin antibiotic that works by inhibiting bacterial cell wall synthesis. Specifically, it binds to and inhibits the activity of penicillin-binding proteins (PBPs) located on the bacterial cell wall, which are responsible for the final stages of peptidoglycan synthesis. This inhibition leads to the disruption of the bacterial cell wall, ultimately resulting in bacterial cell death. Additionally, Cefotetan also exhibits some degree of bactericidal activity by interfering with bacterial cell membrane permeability and inhibiting cell division.

Cefotetan has been approved to relieve symptoms and also for the treatment and maintenance of Pelvic inflammatory disease, Skin and soft tissue infection, Surgical prophylaxis ,Urinary tract infection, Intra-abdominal infection, Pelvic inflammatory disease, Peritonitis, Surgical prophylaxis.

The peak plasma concentration (Cmax) of cefotetan after intravenous administration ranges from 150 to 200 mcg/mL for a 1 g dose and 300 to 400 mcg/mL for a 2 g dose. The time to reach peak plasma concentration i.e. Tmax, is typically around 30 minutes to 1 hour after intravenous administration.

The elimination half-life of cefotetan is approximately 2 hours in patients with normal renal function. However, the half-life may be prolonged in patients with renal impairment.

The onset of action of cefotetan is relatively rapid, with clinical improvement often seen within 24 to 48 hours of initiating therapy. The duration of action of a single dose of cefotetan is typically 12 to 24 hours, depending on the severity of the infection as well as the patient's renal function.

Cefotetan is found to be available in the form of Powder for injection, Injectable solution, Intravenous Infusion.

Cefotetan can be used in the following treatment:

• Pelvic inflammatory disease
• Skin and soft tissue infection
• Surgical prophylaxis
• Urinary tract infection
• Intra-abdominal infection
• Pelvic inflammatory disease
• Peritonitis
• Surgical prophylaxis

Cefotetan can help to relieve symptoms and also for the treatment and maintenance of Pelvic inflammatory disease, Skin and soft tissue infection, Surgical prophylaxis, Urinary tract infection, Intra-abdominal infection, Pelvic inflammatory disease, Peritonitis, Surgical prophylaxis.

Cefotetan is approved for use in the following clinical indications:

● Pelvic inflammatory disease

● Skin and soft tissue infection

● Surgical prophylaxis

● Urinary tract infection

● Intra-abdominal infection

● Pelvic inflammatory disease

● Peritonitis

● Surgical prophylaxis

Pelvic inflammatory disease:

Cefotetan can be given intravenously at a dose of 2 g every 12 hours in combination with doxycycline. The total duration of therapy, which may include oral step-down therapy, is 14 days. Oral therapy can usually be initiated within 24 to 48 hours of clinical improvement.

Skin and soft tissue infection:

For mild to moderate infections, cefotetan can be given intramuscularly at a dose of 1 g every 12 hours. For intravenous administration, a dose of 1 g every 12 hours or 2 g every 24 hours can be given.

For severe infections, intravenous administration is recommended at a dose of 2 g every 12 hours.

Surgical prophylaxis:

For surgical prophylaxis, a dose of 2 g should be administered intravenously within 60 minutes prior to surgery. If the procedure is lengthy or if there is excessive blood loss, doses may be repeated in 6 hours.

Urinary tract infection:

For the treatment of urinary tract infections, cefotetan can be given intramuscularly or intravenously at a dose of 500 mg every 12 hours or 1 to 2 g every 12 to 24 hours.

Powder for injection: 1 g, 2 g

Premixed solution for injection: 1 g in 50 mL, 2 g in 50 mL

Powder for injection, Injectable solution, Intravenous Infusion.

• Dosage Adjustments in Kidney Patients:

For patients with creatinine clearance (CrCl) between 30-50 mL/min, the dose should be reduced by about 50%.

For patients with CrCl less than 30 mL/min, the dose should be reduced by 75%.

For patients on hemodialysis, a loading dose of 1 g should be given initially, followed by a maintenance dose of 0.5-1 g after each hemodialysis session.

• Dosage Adjustments in Pediatric Patients:

Intra-abdominal infection:

Due to high rates of resistant anaerobes, including Bacteroides fragilis, and potential for decreased efficacy, cefotetan is not recommended for empiric treatment.

Infants, Children, and Adolescents: IV: 20 to 40 mg/kg/dose every 12 hours.

Pelvic inflammatory disease:

Limited data is available. For children ≥45 kg and adolescents, IV: 2,000 mg every 12 hours in combination with doxycycline for 14 days is recommended. Oral step-down therapy can be initiated within 24 to 48 hours of clinical improvement and may be used to complete the 14-day treatment course.

Peritonitis, prophylaxis for patients receiving peritoneal dialysis undergoing GI or genitourinary procedures:

Limited data is available. For infants, children, and adolescents, IV: 30 to 40 mg/kg administered 30 to 60 minutes before the procedure; maximum dose: 2,000 mg/dose.

Surgical prophylaxis:

Limited data is available. For children and adolescents, IV: 40 mg/kg within 60 minutes prior to the procedure; the dose may be repeated in 6 hours for prolonged procedures or excessive blood loss; maximum dose: 2,000 mg/dose.

There are no specific dietary restrictions associated with the use of cefotetan. However, it is recommended to take cefotetan with food to reduce the risk of gastrointestinal side effects such as nausea, vomiting, and diarrhea. Patients should avoid taking cefotetan with products that contain calcium, magnesium, or aluminum such as antacids, as these may decrease the absorption of the drug. Patients should also avoid consuming alcohol while taking cefotetan as it may increase the risk of certain side effects such as dizziness, drowsiness, and headache.

Cefotetan may be contraindicated under the following conditions:

• In individuals with a history of hypersensitivity reactions to cefotetan, cephalosporins, penicillins, or any other component of the formulation.
• In patients with a history of bleeding disorders or a known allergy to sulfites.
• In premature infants and neonates because the product contains benzyl alcohol.

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

Before initiating therapy with cefotetan, it is important to inquire about the patient's history of hypersensitivity reactions to cefotetan, cephalosporins, penicillins, or other drugs. Caution should be exercised while administering this drug to penicillin-sensitive patients due to cross-hypersensitivity among beta-lactam antibiotics, which might occur in up to 10% of patients with a history of penicillin allergy. If an allergic reaction to cefotetan occurs, the drug should be discontinued. Serious acute hypersensitivity reactions might require treatment with epinephrine as well as other emergency measures, including oxygen, intravenous fluids, intravenous antihistamines, corticosteroids, pressor amines, as well as airway management, as clinically indicated.

An immune-mediated hemolytic anemia has been observed in patients receiving cephalosporin class antibiotics, including cefotetan. Severe cases of hemolytic anemia, including fatalities, had been reported in association with the administration of cefotetan. Although such reports are uncommon, there appears to be an increased risk of developing hemolytic anemia on the drug cefotetan relative to other cephalosporins of at least three fold. If a patient develops anemia within 2-3 weeks after receiving cefotetan, the diagnosis of a cephalosporin-associated anemia should be considered and the drug should be stopped until the etiology is determined with certainty. Blood transfusions may be considered as needed. Patients who receive courses of cefotetan for the treatment or prophylaxis of infections should have periodic monitoring for signs as well as symptoms of hemolytic anemia, which including a measurement of hematological parameters where appropriate.

Pseudomembranous colitis, a potentially life-threatening condition, had been reported with nearly all antibacterial agents, including cefotetan. It is important to consider this diagnosis in patients who present with diarrhea following the administration of antibacterial agents. Treatment with antibacterial agents is said to alter the normal flora of the colon and might permit overgrowth of clostridia, including Clostridium difficile, which produces a toxin that is a primary cause of "antibiotic-associated colitis." After the diagnosis of pseudomembranous colitis had been established, appropriate therapeutic measures should be initiated, including drug discontinuation, fluid and electrolyte management, protein supplementation, as well as treatment with an antibacterial drug clinically effective against Clostridium difficile colitis.

As with many other broad-spectrum antibiotics, cefotetan might be associated with a fall in prothrombin activity and, possibly, subsequent bleeding. Patients at increased risk include those with renal or hepatobiliary impairment, poor nutritional status, the elderly, as well as patients with cancer. Prothrombin time should be monitored, as well as exogenous vitamin K should be administered as indicated.

There is a moderate interaction between alcohol and Cefotetan. It is recommended to avoid drinking alcohol while taking Cefotetan because it may increase the risk of side effects for example dizziness, drowsiness, and gastrointestinal upset. Additionally, alcohol may also impair the body's ability to fight infections, which may reduce the effectiveness of Cefotetan in treating bacterial infections.

Cefotetan is excreted in low concentrations in human milk, and caution should be exercised when administering it to nursing women.

Pregnancy Category B

Cefotetan falls under Pregnancy Category B, as reproduction studies on rats and monkeys at doses up to 20 times the human dose have not shown any evidence of impaired fertility or harm to the fetus. However, as there are no adequate and well-controlled studies on pregnant women, the drug should only be used during pregnancy if it is clearly necessary.

There is found to be no sufficient scientific evidence regarding the use and safety of Cefotetan in concurrent use with any particular food.

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

Common:

• Diarrhea
• Nausea and vomiting
• Injection site reactions
• Headache
• Abdominal pain
• Increased liver enzymes
• Skin rash
• Fever

Less Common:

• Dizziness
• Fatigue
• Changes in taste or smell
• Thrush (yeast infection in the mouth)
• Vaginal itching or discharge
• Joint pain or swelling
• Anemia (low red blood cell count)

Rare:

• Allergic reaction, including anaphylaxis
• Kidney damage
• Clostridium difficile infection (a bacterial infection of the gut)
• Seizures or convulsions
• Stevens-Johnson syndrome (a serious skin condition)

The clinically relevant drug interactions of Cefotetan is briefly summarized here:

Aminoglycosides: Using cefotetan with aminoglycosides, such as gentamicin, can increase the risk of kidney damage.

Diuretics: Cefotetan can increase the risk of bleeding when used with diuretics such as furosemide.

Probenecid: Probenecid can increase the level of cefotetan in the blood, potentially leading to side effects.

Warfarin: Cefotetan can increase the effect of warfarin, which can increase the risk of bleeding.

Birth control pills: Cefotetan can reduce the effectiveness of birth control pills, increasing the risk of pregnancy.

Other antibiotics: Using cefotetan with other antibiotics, particularly other beta-lactam antibiotics such as penicillin, can increase the risk of allergic reactions.

The following are the side effects involving Cefotetan:

• Diarrhea
• Nausea and vomiting
• Allergic reactions
• Headache
• Injection site reactions
• Fever
• Chills
• Dizziness
• Fatigue
• Changes in blood counts.

• Pregnancy

Pregnancy Category B

Cefotetan falls under Pregnancy Category B, as reproduction studies on rats and monkeys at doses up to 20 times the human dose have not shown any evidence of impaired fertility or harm to the fetus. However, as there are no adequate and well-controlled studies on pregnant women, the drug should only be used during pregnancy if it is clearly necessary.

• Nursing Mothers: Cefotetan is excreted in low concentrations in human milk, and caution should be exercised when administering it to nursing women.

• Pediatric Use: The safety and effectiveness of cefotetan in children have not been established.

• Geriatric Use: Clinical studies on cefotetan have included 925 subjects, with 53% being 60 years or older and 8% being 80 years or older. No significant differences were observed in safety or effectiveness between these subjects and younger ones. However, as this drug is primarily excreted through the kidneys, elderly patients with decreased renal function may be at a higher risk of toxic reactions. Dose selection should be carefully monitored in such cases, and renal function should be monitored regularly.

Physicians should be knowledgeable as well as vigilant about the treatment and identification of over dosage of Cefotetan.

An overdose of cefotetan may lead to symptoms such as seizures, confusion, hallucinations, and tremors. In severe cases, an overdose may cause respiratory depression or cardiac arrest.

In the event of an overdose, treatment may include supportive care such as maintaining adequate airway and oxygenation, providing cardiovascular support, and monitoring renal and hepatic function. Hemodialysis can also be considered in patients with severely impaired renal function.

If an allergic reaction or anaphylaxis occurs, treatment may include the administration of epinephrine, corticosteroids, and antihistamines. In the case of severe allergic reactions, emergency medical attention should be sought immediately.

Pharmacodynamics

Cefotetan is an antibiotic belonging to the semisynthetic cephamycin class, and is administered intravenously or intramuscularly. The drug has a high degree of resistance to a broad spectrum of beta-lactamases, making it effective against a wide range of both aerobic and anaerobic gram-positive and gram-negative microorganisms.

Pharmacokinetics

Cefotetan is a drug that is primarily administered intravenously or intramuscularly. The drug has a volume of distribution of 10.4 L in elderly patients with normal renal function and 10.3 L in healthy volunteers aged 25 to 28 years. Cefotetan is 88% plasma protein bound. The drug is minimally metabolized in the liver, and no active metabolites have been detected. However, small amounts (less than 7%) of cefotetan in plasma and urine may be converted to its tautomer, which has antimicrobial activity similar to the parent drug. Cefotetan is eliminated from the body primarily by the kidneys, with 51% to 81% of the administered dose excreted unchanged in the urine over a 24-hour period. This results in high and prolonged urinary concentrations of the drug.

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