Cefotaxime

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

"Cefotaxime" has been approved to relieve symptoms and also for the treatment and maintenance of Acute bacterial rhinosinusitis, Bite wound, Brain abscess, Cesarean delivery, Chronic obstructive pulmonary disease, Gonococcal infection, Intra-abdominal infection, Lyme disease, Meningitis, Pneumonia, Salmonella species infection, Sepsis, Septic arthritis, Skin and soft tissue necrotizing infections, Spontaneous bacterial peritonitis. Surgical prophylaxis

Cefotaxime is administered parenterally, either intravenously or intramuscularly, and is rapidly absorbed into the bloodstream with a bioavailability of 100%. It has a large volume of distribution and penetrates well into most body tissues and fluids, including the cerebrospinal fluid. Cefotaxime is primarily excreted unchanged by the kidneys, with an elimination half-life of 1-2 hours in adults and up to 4 hours in neonates.

The common side effects of "Cefotaxime" are nausea, vomiting, gas, weakness, tiredness, itching, diarrhea, headache, upset stomach, etc.

"Cefotaxime" is available in the form of Injections, Intravenous Infusion.

"Cefotaxime" is approved in Germany, Japan, Malaysia, India, China, Canada, the U.S., U.K.

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

Cefotaxime exerts its bactericidal effect by inhibiting the synthesis of the cell wall through its interaction with penicillin-binding proteins (PBPs). Specifically, Cefotaxime exhibits a strong affinity towards PBPs located in the cell wall, such as PBP Ib and PBP III.

"Cefotaxime" has been approved to relieve symptoms and also for the treatment and maintenance of Acute bacterial rhinosinusitis, Bite wound, Brain abscess, Cesarean delivery, Chronic obstructive pulmonary disease, Gonococcal infection, Intra-abdominal infection, Lyme disease, Meningitis, Pneumonia, Salmonella species infection, Sepsis, Septic arthritis, Skin and soft tissue necrotizing infections, Spontaneous bacterial peritonitis. Surgical prophylaxis

Cmax and Tmax of Cefotaxime depend on the dose and route of administration. In general, after intravenous administration, the Cmax is achieved within 30 to 60 minutes. The onset of action is also rapid, with bactericidal effects observed within hours of administration.

The elimination half-life of Cefotaxime is approximately 1 to 2 hours in adults with normal renal function. The duration of action depends on the dose, frequency of administration, and the severity of the infection being treated. In general, Cefotaxime is given every 6 to 8 hours to maintain therapeutic concentrations in the bloodstream.

Cefotaxime is found to be available in the form of Injections and Intravenous Infusion.

"Cefotaxime" can be used in the following treatment:

• Acute bacterial rhinosinusitis
• Bite wound
• Brain abscess
• Cesarean delivery
• Chronic obstructive pulmonary disease
• Gonococcal infection
• Gonococcal infection
• Intra-abdominal infection
• Lyme disease
• Meningitis
• Pneumonia
• Salmonella species infection
• Sepsis
• Septic arthritis
• Skin and soft tissue necrotizing infections
• Spontaneous bacterial peritonitis
• Surgical prophylaxis

Cefotaxime can help to relieve symptoms and also for the treatment and maintenance of Acute bacterial rhinosinusitis, Bite wound, Brain abscess, Cesarean delivery, Chronic obstructive pulmonary disease, Gonococcal infection, Intra-abdominal infection, Lyme disease, Meningitis, Pneumonia, Salmonella species infection, Sepsis, Septic arthritis, Skin and soft tissue necrotizing infections, Spontaneous bacterial peritonitis. Surgical prophylaxis.

"Cefotaxime" is approved for use in the following clinical indications:

● Acute bacterial rhinosinusitis

● Bite wound

● Brain abscess

● Cesarean delivery

● Chronic obstructive pulmonary disease

● Gonococcal infection

● Intra-abdominal infection

● Lyme disease

● Meningitis

● Pneumonia

● Salmonella species infection

● Sepsis

● Septic arthritis

● Skin and soft tissue necrotizing infections

● Spontaneous bacterial peritonitis

● Surgical prophylaxis

Acute bacterial rhinosinusitis: IV or IM dosage strength of 1 to 2 grams every 8 hours

Bite wounds: IV or IM dosage strength of 1 to 2 grams every 12 hours

Brain abscess: IV dosage strength of 2 to 3 grams every 6 to 8 hours

Cesarean delivery: IV dosage strength of 1 gram every 6 to 8 hours

Chronic obstructive pulmonary disease, acute exacerbation: IV or IM dosage strength of 1 to 2 grams every 8 hours

Gonococcal infection, disseminated: IV dosage strength of 1 to 2 grams every 12 hours.

Gonococcal infection, uncomplicated: IV dosage strength of 1 gram as a single dose

Intra-abdominal infection, mild to moderate: IV dosage strength of 1 to 2 grams every 6 to 8 hours

Lyme disease: IV dosage strength of 2 grams every 24 hours

Meningitis, bacterial: IV dosage strength of 2 to 3 grams every 4 to 6 hours

Pneumonia, community-acquired: IV dosage strength of 1 to 2 grams every 8 hours.

Salmonella species infection: IV dosage strength of 1 to 2 grams every 6 to 8 hours

Sepsis: IV dosage strength of 1 to 2 grams every 6 to 8 hours

Septic arthritis: IV dosage strength of 1 to 2 grams every 8 hours

Skin and soft tissue necrotizing infections: IV dosage strength of 2 grams every 8 hours

Spontaneous bacterial peritonitis: IV dosage strength of 2 grams every 8 hours

Surgical prophylaxis: IV dosage strength of 1 to 2 grams within 30 to 60 minutes prior to surgical incision.

Powder for injection: 500 mg, 1 g, and 2 g vials

Powder for solution: 1 g and 2 g vials

Injection premix: 1 g, 2 g, and 10 g vials

Injection, Powder for injection.

• Dosage Adjustments in Kidney Patients:

For patients with kidney impairment, dosage adjustments of Cefotaxime may be necessary to prevent drug accumulation and potential toxicity. The dosage adjustments depend on the severity of kidney impairment, as determined by the patient's estimated glomerular filtration rate (eGFR) or creatinine clearance (CrCl) levels.

The following are general guidelines for dosage adjustments of Cefotaxime in patients with kidney impairment:

For patients with mild to moderate kidney impairment (eGFR or CrCl 30-90 mL/min/1.73m2), the usual adult dose of Cefotaxime can be given every 8 hours.

For patients with severe kidney impairment (eGFR or CrCl <30 mL/min/1.73m2), the usual adult dose of Cefotaxime can be given every 12-24 hours.

For patients on hemodialysis, a supplemental dose of Cefotaxime may be given after each dialysis session.

• Dosage Adjustments in Pediatric Patients:

Acute bacterial rhinosinusitis is a severe infection that may require hospitalization. The recommended dosage for children and adolescents is 100 to 200 mg/kg/day in divided doses every six hours for 10 to 14 days, with a maximum dose of 2,000 mg/dose.

Endocarditis treatment in children and adolescents involves a dosage of 200 mg/kg/day in divided doses every 6 hours, with a maximum daily dose of 12 g/day. The treatment should last for at least four weeks, depending on the pathogen and valve type. The duration may be longer, and other antibiotics may be used in combination depending on the pathogen.

For gonococcal infection, disseminated (arthritis and arthritis-dermatitis syndrome), adolescents should receive 1,000 mg every 8 hours intravenously. The total duration of therapy should be at least seven days, including oral step-down therapy. If chlamydia is not excluded, treatment for chlamydia should be given in combination.

Intra-abdominal infection treatment in infants, children, and adolescents requires a dosage of 150 to 200 mg/kg/day in divided doses every six to eight hours in combination with metronidazole. The maximum dose is 2,000 mg/dose, and the typical duration of therapy is 4 to 7 days.

Lyme disease treatment in infants, children, and adolescents requires a dosage of 150 to 200 mg/kg/day in divided doses every six to eight hours, with a maximum daily dose of 6,000 mg/day. The duration of therapy depends on the clinical syndrome, and meningitis or radiculopathy should be treated for 14 to 21 days.

Meningitis treatment in infants, children, and adolescents involves a dosage of 225 to 300 mg/kg/day in divided doses every six to eight hours, with a maximum dose of 2,000 mg/dose. Vancomycin should be used in combination for empiric coverage. Some experts recommend a higher dosage of 300 mg/kg/day divided every 4 to 6 hours with a maximum daily dose of 12 g/day.

For peritonitis (peritoneal dialysis), infants, children, and adolescents should receive intermittent intraperitoneal dosages of 30 mg/kg/dose every 24 hours in the extended dwell or a continuous loading dose of 500 mg per liter of dialysate and a maintenance dose of 250 mg per liter. A maintenance dose of 125 mg/liter is also an option.

Pneumonia, community-acquired in infants, children, and adolescents, requires a dosage of 150 to 200 mg/kg/day in divided doses every six to eight hours, with a maximum dose of 2,000 mg/dose. If methicillin-resistant Staphylococcus aureus or atypical pathogens are a concern, it should be used as part of an appropriate combination regimen.

Salmonellosis treatment in adolescents with HIV involves a dosage of 1,000 mg every 8 hours intravenously.

Skin and soft tissue infections that are necrotizing require immediate treatment with a combination of antibiotics like metronidazole or clindamycin, along with an intravenous dose of 200 mg/kg/day in divided doses every 6 hours. The treatment should continue until there is no further need for surgical removal of affected tissue, the patient shows clinical improvement, and the patient remains fever-free for 48 to 72 hours.

For surgical prophylaxis in children and adolescents, an intravenous dose of 50 mg/kg should be given within 60 minutes before the surgical incision. The dose may be repeated after 3 hours if the procedure takes longer than expected or if there is significant blood loss. The maximum dose should not exceed 1,000 mg, but a larger maximum dose of 2,000 mg is recommended for patients weighing more than 120 kg or with a BMI above 30 kg/m2.

In infants, children, and adolescents with urinary tract infections, an intravenous or intramuscular dose of 150 mg/kg/day in divided doses every six to eight hours is recommended. The maximum dose should not exceed 2,000 mg/dose, and the duration of treatment depends on the patient's age, response to therapy, and the extent of infection.

There are no specific dietary restrictions related to the use of Cefotaxime. However, it is important to maintain a healthy and balanced diet to support the body's natural immune system and promote overall health. Additionally, it is important to avoid consuming alcohol while taking Cefotaxime, as it may increase the risk of certain side effects such as stomach upset and dizziness.

"Cefotaxime" may be contraindicated under the following conditions:

• In individuals with a history of hypersensitivity reactions to cephalosporins, penicillin, or other drugs.
• In patients with type 1 hypersensitivity reactions to penicillin due to cross-allergy that exists between penicillin as well as cephalosporins in 5 to 10% of cases.
• In patients who have a history of cephalosporin-associated hemolytic anemia, the recurrence of hemolysis may be much more severe.
• Individuals who have a history of lower gastrointestinal disease, particularly colitis, should be cautiously prescribed.
• Patients with abnormal liver or kidney function should also be monitored closely.
• Lastly, Cefotaxime should only be administered as instructed in the dosage and administration section to avoid potential life-threatening arrhythmias.

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

Anaphylactic:

Before initiating therapy with Cefotaxime, it is important to determine whether the patient had previous hypersensitivity reactions to Cefotaxime, cephalosporins, penicillins, or any other drugs. Cross-allergy exists between penicillins and cephalosporins in 5 to 10% of cases, and Cefotaxime should be administered with caution to patients with type 1 hypersensitivity reactions to penicillin. If an allergic reaction to Cefotaxime occurs, it should be discontinued, and the patient should be treated with the usual agents such as epinephrine, antihistamines, pressor amines, or corticosteroids.

Speed of i.v. Injection:

A potentially life-threatening arrhythmia had been reported in very few patients who received a rapid bolus injection of Cefotaxime through a central venous catheter. Therefore, Cefotaxime should only be administered as instructed in the dosage and administration section.

Clostridium difficile -associated disease:

The use of Cefotaxime has been associated with Clostridium difficile-associated disease (CDAD), ranging in severity from mild diarrhea to fatal colitis. It is important to consider this diagnosis in the patients who suffer from diarrhea or symptoms of colitis, pseudomembranous colitis, toxic megacolon, or perforation of the colon following the administration of any antibacterial agent. CDAD can occur up to 2 months after the administration of antibacterial agents. Appropriate therapeutic measures should be initiated if the diagnosis of CDAD is suspected or confirmed.

Hemolytic anemia:

Cefotaxime should not be used in patients who have a history of cephalosporin-associated hemolytic anemia since the recurrence of hemolysis is much more severe. Patients might benefit from periodic monitoring for signs and symptoms of hemolytic anemia.

General:

Prolonged use of Cefotaxime might result in the overgrowth of nonsusceptible organisms. A Constant evaluation of the patient's condition is essential, therapy should be discontinued, as well as appropriate measures taken if superinfection occurs. Cefotaxime may be locally irritating to tissues, and infusion sites should be monitored regularly as well as changed when appropriate to minimize the potential for tissue inflammation.

Patients taking Cefotaxime should refrain from driving or operating machinery if experiencing side effects such as dizziness, as their ability to concentrate and react properly may be impaired.

Blood disorders:

As with other β-lactam antibiotics, blood disorders such as granulocytopenia, leukopenia, neutropenia, and, more rarely, bone marrow failure, pancytopenia, or agranulocytosis might develop during treatment with Cefotaxime. For courses of treatment lasting longer than ten days, blood counts should, therefore, be monitored, and also treatment discontinuation should be considered in case of abnormal results. Cefotaxime should be prescribed cautiously in individuals who have a history of lower gastrointestinal disease, particularly colitis.

There is a moderate interaction between alcohol and "Cefotaxime." It is generally recommended to avoid drinking alcohol while taking "Cefotaxime" 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 "Cefotaxime" in treating bacterial infections.

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

Pregnancy Category B

During reproduction studies, pregnant mice and rats were given Cefotaxime intravenously at doses up to 1200 mg/kg/day, which is 0.4 and 0.8 times the recommended human dose based on mg/m2, respectively. These studies did not show any evidence of embryotoxicity or teratogenicity. Although Cefotaxime can cross the placental barrier and appear in cord blood, its effect on the human fetus is not known, as there are no well-controlled studies in pregnant women. Therefore, Cefotaxime should only be used during pregnancy if it is clearly needed.

In the perinatal as well as postnatal studies with rats, the pups in the group given 1200 mg/kg/day of Cefotaxime had significantly lighter weight at birth and remained smaller than the control group during the twenty one days of nursing.

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

The adverse reactions related to "Cefotaxime" can be categorized as follows:

Common

• Diarrhea
• Nausea and vomiting
• Skin rash
• Swelling, pain or redness at the injection site
• Fever

Less common

• Headache
• Dizziness
• Insomnia
• Itching or hives
• Yeast infection
• Abdominal pain
• Joint pain
• Muscle pain

Rare

• Seizures
• Stevens-Johnson syndrome (a severe skin reaction)
• Clostridioides difficile infection (a type of bacterial infection that causes diarrhea and colitis)
• Hemolytic anemia (a type of anemia caused by the destruction of red blood cells)
• Agranulocytosis (a condition in which the body produces a very low number of white blood cells)

The clinically relevant drug interactions of "Cefotaxime" is briefly summarized here:

Three healthy male participants receiving a continuous infusion of Cefotaxime were given a single intravenous and oral dose of probenecid (500 mg each), followed by 2 oral doses of probenecid 500 mg at approximately hourly intervals. This resulted in an approximately 80% increase in the steady-state plasma concentration of Cefotaxime. In another study, six healthy male participants receiving Cefotaxime 1 gram infused over 5 minutes were administered oral probenecid 500 mg every 6 hours, which led to a decrease in the total clearance of Cefotaxime by approximately 50%.

In addition, a study conducted on 22 healthy volunteers who were administered Cefotaxime and ethanol reported no disulfiram-like reactions.

The following are the side effects involving "Cefotaxime":

• Diarrhea
• Nausea and vomiting
• Rash or itching
• Pain or swelling at the injection site
• Headache
• Dizziness
• Fever
• Increased liver enzymes

• Pregnancy

Pregnancy Category B

During reproduction studies, pregnant mice and rats were given Cefotaxime intravenously at doses up to 1200 mg/kg/day, which is 0.4 and 0.8 times the recommended human dose based on mg/m2, respectively. These studies did not show any evidence of embryotoxicity or teratogenicity. Although Cefotaxime can cross the placental barrier and appear in cord blood, its effect on the human fetus is not known, as there are no well-controlled studies in pregnant women. Therefore, Cefotaxime should only be used during pregnancy if it is clearly needed.

In perinatal as well as postnatal studies with rats, the pups in the group given 1200 mg/kg/day of Cefotaxime had significantly lighter weight at birth and remained smaller than the control group during the 21 days of nursing.

• Nursing Mothers:

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

• Pediatric Use:

Cefotaxime is approved for use in pediatric populations and has been shown to be effective in treating various bacterial infections in children. However, the potential for toxic effects in pediatric patients from chemicals that may leach from the plastic in single-dose Galaxy® Containers (premixed Cefotaxime Injection) has not been determined. Therefore, caution should be exercised when administering Cefotaxime to pediatric patients, and the benefits of treatment should be weighed against the potential risks. Additionally, healthcare providers should follow dosing guidelines specific to the patient's age, weight, and medical condition, as the appropriate dose may vary in pediatric patients. Monitoring renal function may also be necessary for pediatric patients, particularly those with impaired renal function.

• Geriatric Use:

In clinical studies of Cefotaxime, no overall differences in safety or effectiveness were observed between elderly patients (65 years and over) and younger patients. However, because this drug is excreted substantially by the kidney, the risk of toxic reactions may be greater in patients with impaired renal function, especially in elderly patients who are more likely to have decreased renal function. Therefore, careful dose selection and monitoring of renal function may be necessary for elderly patients.

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

An overdose of Cefotaxime can cause serious adverse effects and requires immediate medical attention. The treatment of cefotaxime overdose depends on the severity of the symptoms and may involve the following:

Discontinuation of Cefotaxime: The first step in treating cefotaxime overdose is to discontinue the drug immediately.

Supportive care: Depending on the severity of the symptoms, supportive care may be required. For example, if the patient experiences seizures, anticonvulsant medications may be administered. Other supportive measures may include monitoring vital signs, providing oxygen therapy, and maintaining fluid and electrolyte balance.

Gastric lavage: In some cases, gastric lavage may be necessary to remove any unabsorbed cefotaxime from the stomach.

Activated charcoal: Activated charcoal may be administered to prevent the absorption of any remaining cefotaxime in the gastrointestinal tract.

Hemodialysis: In severe cases of cefotaxime overdose, hemodialysis may be necessary to remove the drug from the bloodstream.

Pharmacodynamics

Cefotaxime is an intravenous antibiotic belonging to the third generation cephalosporin class, with broad-spectrum activity against both Gram-positive and Gram-negative bacteria, but not effective against Pseudomonas aeruginosa. The drug's mechanism of action involves the inhibition of bacterial cell wall biosynthesis. One of the positive attributes of Cefotaxime is its resistance to penicillinases, making it a useful treatment option for infections resistant to penicillin derivatives.

Pharmacokinetics

• Absorption:

Cefotaxime is administered intravenously (IV) or intramuscularly (IM). After IV administration, it reaches its peak plasma concentration within 30 minutes. The bioavailability of Cefotaxime after IM administration is around 95%.

• Distribution:

Cefotaxime has a volume of distribution of approximately 0.2 to 0.3 L/kg, indicating that it is distributed widely throughout the body. The drug crosses the blood-brain barrier and achieves therapeutic concentrations in cerebrospinal fluid. Cefotaxime also crosses the placenta and is found in breast milk.

• Metabolism:

Cefotaxime is not metabolized in the liver and is eliminated primarily unchanged in the urine. In patients with renal Impairment, the elimination half-life of Cefotaxime may be prolonged.

• Excretion:

The elimination half-life of Cefotaxime is around 1 to 1.5 hours in patients with normal renal function. Approximately 80% of the drug is excreted unchanged in the urine within 24 hours.

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