Cefixime

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

Cefixime has been approved to relieve symptoms and also for the treatment and maintenance of Gonococcal infection, Rhinosinusitis, Streptococcal pharyngitis, Typhoid fever, Urinary tract infection.

Cefixime is rapidly absorbed from the gastrointestinal tract, and its bioavailability is about 40-50%. The maximum concentration (Cmax) in the blood is achieved approximately 2-6 hours after oral administration, and its half-life is approximately 3-4 hours. Cefixime is excreted primarily through the kidneys, and approximately 50% of the administered dose is excreted unchanged in the urine. The pharmacokinetics of cefixime are not significantly affected by food, and it can be administered with or without food. The pharmacokinetic profile of cefixime supports its once-daily dosing regimen for most indications.

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

Cefixime is available in the form of Tablets , Capsules, Chewable Tablets, Oral suspensions.

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

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

Cefixime, 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.

Cefixime has been approved to relieve symptoms and also for the treatment and maintenance of Gonococcal infection, Rhinosinusitis, Streptococcal pharyngitis, Typhoid fever, Urinary tract infection.

The Cmax (maximum plasma concentration) of cefixime varies depending on the dosage form and strength. For example, in healthy adults receiving a single 400 mg oral dose of cefixime as a tablet, the Cmax was 2.1 µg/mL, and Tmax (time to maximum plasma concentration) was approximately 4 hours. The Cmax for a single 400 mg dose of cefixime suspension was slightly lower at 1.7 µg/mL, with a Tmax of approximately 3 hours.

The onset of action of cefixime is relatively rapid, with significant antibacterial activity observed within 2 to 4 hours of administration. The duration of action of cefixime varies depending on the indication being treated and the dosage regimen used. In general, the drug has a half-life of approximately 3 to 4 hours, and is typically given once daily for 7 to 14 days, depending on the indication.

Cefixime is found to be available in the form of Tablets , Capsules, Chewable Tablets, Oral suspensions.

Cefixime can be used in the following treatment:

• Gonococcal infection
• Rhinosinusitis
• Streptococcal pharyngitis
• Typhoid fever
• Urinary tract infection

Cefixime can help to relieve symptoms and also for the treatment and maintenance of Gonococcal infection, Rhinosinusitis, Streptococcal pharyngitis, Typhoid fever, Urinary tract infection.

Cefixime is approved for use in the following clinical indications:

● Gonococcal infection

● Rhinosinusitis

● Streptococcal pharyngitis

● Typhoid fever

● Urinary tract infection

• Uncomplicated gonococcal infections, cefixime can be administered orally as a single 800 mg dose. However, it should only be used as an alternative agent if ceftriaxone cannot be used, as it is not as effective. If treatment failure is suspected, an infectious diseases specialist should be consulted. For expedited partner therapy, the same dosage can be given as a single dose along with chlamydia treatment, but it should only be used when public health strategies are unavailable or impractical.

• Acute bacterial rhinosinusitis, cefixime can be used off-label as an alternative agent for patients with penicillin allergy who can tolerate cephalosporins. However, in uncomplicated cases, initial observation and symptom management without antibiotic therapy is appropriate for most patients, and antibiotic therapy should only be used if there is poor follow-up or lack of improvement over the observation period.

• Group A streptococcal pharyngitis, cefixime can be used as an alternative agent for mild, non-anaphylactic penicillin allergy. It is administered orally as a 400 mg dose once daily for 10 days.

• Typhoid fever, cefixime is used off-label and is administered orally as a 100 to 200 mg dose twice daily for 7 to 14 days.

• Urinary tract infections, cefixime is used as an alternative agent and should be used with caution only when recommended agents cannot be used. For acute uncomplicated cystitis, a 400 mg dose is given orally once daily for 7 days. For complicated UTIs, including pyelonephritis, a 400 mg dose is given orally once daily for 10 to 14 days, following appropriate parenteral therapy. For mild infections, a single dose of a long-acting parenteral agent is also acceptable for outpatient treatment.

Tablets: 200 mg, 400 mg

Capsules: 400 mg

Oral suspension: 100 mg/5 ml, 200 mg/5 ml

Chewable tablets: 100 mg, 200 mg

Tablets , Capsules, Chewable Tablets, Oral suspensions.

• Dosage Adjustments in Kidney Patients:

CrCl ≥60 mL/minute: No dosage adjustment necessary.

CrCl >20 to <60 mL/minute: 300 mg once daily.

CrCl ≤20 mL/minute: 200 mg once daily.

• Dosage Adjustments in Pediatric Patients:

Febrile neutropenia: Febrile neutropenia is a condition characterized by a low white blood cell count and fever. Limited data is available for the use of cefixime in treating low-risk febrile neutropenia in infants, children, and adolescents. The recommended dose is 8 mg/kg/day once daily or in divided doses every 12 hours. Cefixime therapy is usually initiated as step-down therapy after 48 to 72 hours of empiric parenteral antibiotic therapy, with the first cefixime dose administered at the end of the last IV infusion. In clinical trials, doses were repeated if the patient vomited within 2 hours.

Uncomplicated Gonococcal Infection: Cefixime can be used as an alternative agent in the treatment of uncomplicated gonococcal infections of the cervix, urethra, or rectum in children ≥45 kg and adolescents. The recommended dose is 800 mg as a single dose. If chlamydial infection has not been excluded, cefixime should be given as part of an appropriate combination regimen. Cefixime should only be used if ceftriaxone is unavailable.

Limited data is available for the use of cefixime in preventing diarrhea associated with irinotecan therapy in infants, children, and adolescents. The recommended dose is 8 mg/kg once daily, beginning 5 days before oral irinotecan therapy and continuing throughout the course.

Acute Otitis Media: Cefixime can be used as an alternative agent in the treatment of acute otitis media in infants, children, and adolescents. The recommended dose is 8 mg/kg/day once daily or in divided doses every 12 hours, with a maximum daily dose of 400 mg/day. Cefixime is not preferred therapy and should only be considered in combination with clindamycin in certain scenarios after failure of first-line agents.

Acute Bacterial Rhinosinusitis: Cefixime can be used as an alternative agent in the treatment of acute bacterial rhinosinusitis in infants, children, and adolescents. The recommended dose is 8 mg/kg/day once daily or in divided doses every 12 hours with concomitant clindamycin for 10 to 14 days, with a maximum daily dose of 400 mg/day. Cefixime is not first-line therapy and should only be considered after failure of initial therapy or in patients with non-type I penicillin allergy.

Streptococcus A Infection: Cefixime can be used as an alternative agent in the treatment of streptococcus group A pharyngitis/tonsillitis in infants, children, and adolescents with nonanaphylactic penicillin allergy. The recommended dose is 8 mg/kg/day once daily or in divided doses every 12 hours for 10 days, with a maximum daily dose of 400 mg/day. Narrow-spectrum cephalosporins, such as cephalexin, are preferred over broad-spectrum cephalosporins like cefixime.

Salmonella Typhi Infection: Limited data is available for the use of cefixime in treating typhoid fever caused by Salmonella typhi in infants, children, and adolescents. The recommended dose is 15 to 20 mg/kg/day in divided doses every 12 hours for 7 to 14 days. The usual adult dose is 100 to 200 mg twice daily.

Acute Urinary Tract Infection: Cefixime can be used in the treatment of acute urinary tract infections in infants ≥2 months, children, and adolescents. The recommended dose is 8 mg/kg/day once daily or in divided doses every 12 hours for 7 to 14 days. Shorter courses (1 to 3 days) have been shown to be inferior to longer durations of therapy.

There are no specific dietary restrictions related to the use of cefixime. However, it is recommended to take cefixime with food or milk to reduce the risk of stomach upset. Additionally, patients should avoid consuming alcohol while taking cefixime, as it may increase the risk of side effects such as dizziness, headache, and stomach upset.

Cefixime may be contraindicated under the following conditions:

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

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

Hypersensitivity Reactions:

For patients who are sensitive to penicillins, caution should be exercised when administering Cefixime (cefixime) as they may also be sensitive to cephalosporins like Cefixime, or to both. Medical literature suggests that patients who are sensitive to cephalosporins are highly likely to be penicillin sensitive as well. Antibiotics, including Cefixime, should be given with caution to patients who have displayed any form of allergy, especially to drugs.

Severe Cutaneous Adverse Reactions:

Severe cutaneous adverse reactions such as Stevens-Johnson syndrome, toxic epidermal necrolysis, and drug rash with eosinophilia and systemic symptoms (DRESS) have been reported in some patients who were taking Cefixime. When these reactions occur, Cefixime should be stopped immediately, and appropriate therapy or measures should be taken.

Clostridium difficile-Associated Diarrhea:

Clostridium difficile-associated disease (CDAD) has also been reported in patients using many antibacterial agents, including Cefixime. CDAD can range from mild diarrhea to fatal colitis. It is important to consider this diagnosis in patients who exhibit symptoms such as diarrhea, colitis, pseudomembranous colitis, toxic megacolon, or perforation of colon after being administered any antibacterial agent. CDAD has been reported to occur over two months after the use of antibacterial agents. Antibacterial agents can alter the normal flora of the colon and can lead to the overgrowth of Clostridium difficile. CDAD can be refractory to antimicrobial therapy, and appropriate therapeutic measures should be initiated if the diagnosis of CDAD is suspected or confirmed.

Hemorrhage:

Cefixime should not be used in patients with a history of cephalosporin-associated hemolytic anemia as the recurrence of hemolysis is much more severe. Hemolytic anemia, which is immune-mediated, has been observed in patients taking cephalosporin class antibacterials, including Cefixime. Severe cases of hemolytic anemia, including fatalities, have been reported with cephalosporins in both adults and children. If a patient develops anemia at any time during, or within 2-3 weeks subsequent to, the administration of Cefixime, the diagnosis of a cephalosporin-associated anemia should be considered, and the drug should be discontinued until the etiology is determined. Patients may benefit from periodic monitoring for signs and symptoms of hemolytic anemia, including measurement of hematological parameters or drug-induced antibody testing, where appropriate.

Cefixime 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 Cefixime is administered to a nursing woman.

Pregnancy Category B

The safety of using Cefixime to treat infections in pregnant women has not been established. However, in reproduction studies conducted on mice and rats, doses up to 400 times the human dose did not result in impaired fertility or harm to the fetus due to cefixime. It is worth noting that animal reproduction studies are not always indicative of human response. Thus, the use of this drug during pregnancy should only be considered if the potential benefits of using Cefixime outweigh the potential risks to the fetus and/or the mother.

There are no specific food warnings related to the use of cefixime. However, cefixime should be taken with meals to improve its absorption and to reduce the risk of stomach upset. Additionally, patients should avoid consuming alcohol while taking cefixime as it may increase the risk of certain side effects such as nausea, vomiting, and headaches. It is also important to follow a well-balanced and healthy diet to support the body's immune system during the course of antibiotic therapy.

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

Common:

• Diarrhea
• Nausea
• Abdominal pain
• Vaginitis
• Dyspepsia
• Flatulence
• Headache
• Dizziness

Less Common:

• Rash
• Itching
• Hives
• Fever
• Chills
• Fatigue
• Eosinophilia
• Leukopenia
• Neutropenia
• Thrombocytopenia
• Stevens-Johnson syndrome
• Toxic epidermal necrolysis
• Anaphylaxis

Rare:

• Clostridium difficile-associated diarrhea
• Pseudomembranous colitis
• Hepatitis
• Jaundice
• Nephritis
• Seizures
• Hallucinations
• Agitation
• Confusion
• Arthralgia
• Myalgia
• Hemolytic anemia
• Pancreatitis
• Vasculitis
• Angioedema

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

Antacids containing aluminum, magnesium or calcium may reduce the absorption of Cefixime. Therefore, Cefixime should be administered at least 2 hours before or after the antacid.

Probenecid may decrease the renal excretion of Cefixime, leading to an increase in serum concentrations of Cefixime.

Concomitant use of Cefixime and warfarin may increase the anticoagulant effect of warfarin. Therefore, close monitoring of prothrombin time or international normalized ratio (INR) is recommended.

Cefixime may enhance the nephrotoxicity of aminoglycosides such as gentamicin.

Cefixime may reduce the efficacy of oral contraceptives. Therefore, an alternative or additional method of contraception should be used during treatment with Cefixime.

Cefixime may increase the serum concentrations of carbamazepine, resulting in toxicity. Therefore, close monitoring of carbamazepine concentrations and signs of toxicity is recommended.

The following are the side effects involving Cefixime :

• Diarrhea
• Nausea
• Vomiting
• Abdominal pain
• Headache
• Dizziness
• Skin rash
• Itching
• Swelling
• Joint pain
• Fever
• Vaginal itching or discharge.

Pregnancy

Pregnancy Category B

The safety of using Cefixime to treat infections in pregnant women has not been established. However, in reproduction studies conducted on mice and rats, doses up to 400 times the human dose did not result in impaired fertility or harm to the fetus due to cefixime. It is worth noting that animal reproduction studies are not always indicative of human response. Thus, the use of this drug during pregnancy should only be considered if the potential benefits of using Cefixime outweigh the potential risks to the fetus and/or the mother.

Nursing Mothers:

Cefixime 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 Cefixime is administered to a nursing woman.

Pediatric Use:

A study was conducted to evaluate the dose proportionality of Cefixime suspension in 42 pediatric patients who were 6 months of age or older. The results indicated that serum concentrations at a single time point after administration (3.5 hours) increased with dose, but not in a proportional manner. Specifically, the 8 mg/kg dose did not produce twice the serum level observed with the 4 mg/kg dose. The mean serum concentrations following the 4 mg/kg dose were between 2.2 and 2.6 µg/mL, whereas the serum concentrations after the 6 and 8 mg/kg doses were between 2.5 and 4.8 µg/mL.

Geriatric Use:

All adults, regardless of age, may be prescribed the same dosage of Cefixime. A study was conducted to compare the pharmacokinetics of a 400 mg dose of Cefixime in 12 healthy men between the ages of 18 to 35 and 12 men over 64 years of age. The participants received a once-daily dose for 5 consecutive days, and blood and urine samples were collected at frequent intervals. The results, as shown in Table 11, indicated that the mean serum concentration-time profiles of cefixime were higher in the elderly group compared to the young subjects, with statistically significant differences in Cmax and AUC on the first and fifth days of dosing. However, the magnitude of the differences was not considered clinically significant. No differences in T1/2 values were observed between the two groups. Therefore, based on these findings, there is no need to adjust the dosage of Cefixime in elderly patients.

Physicians should be knowledgeable and vigilant about the treatment and identification of overdosage of Cefixime.

According to the USFDA, there is limited information on the effects of over dosage of cefixime in humans. In case of overdosage, supportive and symptomatic treatment should be administered. Cefixime is not effectively removed from the body by hemodialysis or peritoneal dialysis. However, in animal studies, a single massive dose of cefixime resulted in diarrhea and lethargy. It is important to seek medical attention immediately in case of suspected overdose.

Pharmacodynamics

Cefixime, classified as a third-generation cephalosporin like ceftriaxone and cefotaxime, is an antibiotic that exhibits remarkable stability in the presence of beta-lactamase enzymes. Consequently, cefixime may be effective against many organisms that are resistant to penicillins and some cephalosporins due to the presence of beta-lactamases. The antibacterial properties of cefixime stem from its ability to inhibit mucopeptide synthesis in the bacterial cell wall.

Pharmacokinetics

• Absorption

Cefixime is an oral medication that is approximately 40% to 50% absorbed. In adults, a single 200 mg tablet of Cefixime results in an average peak serum concentration of about 2 mcg/mL (range 1 to 4 mcg/mL), while a single 400 mg tablet results in an average concentration of approximately 3.5 mcg/mL (range 1.3 to 7.7 mcg/mL). The oral suspension produces average concentrations of 2.8 mcg/mL (range 1 to 4.5 mcg/mL) and 4.4 mcg/mL (range 1.9 to 7.7 mcg/mL) following 200 mg and 400 mg doses, respectively. If the oral suspension is substituted for the tablet, it should be noted that the area under the time versus concentration curve is greater by approximately 26.4% with the oral suspension after doses of 400 mg.

Peak serum concentrations are typically reached between 2 and 6 hours after the oral administration of a single 200 mg or 400 mg tablet or 400 mg suspension of Cefixime. For a single administration of 200 mg suspension, peak serum concentrations occur between 2 and 5 hours. It is important to consider these absorption and peak concentration characteristics when administering Cefixime to patients.

• Distribution

Not Available

• Metabolism

There is no indication of any in vivo metabolism of cefixime.

• Excretion

The excretion of cefixime occurs through both renal and biliary mechanisms. In 12 healthy men within a 24-hour period, approximately 20% and 16% of the 200 mg and 400 mg doses, respectively, were excreted in the urine, while an additional 10% or more was recovered from bile.

• https://www.mayoclinic.org/drugs-supplements/cefixime-oral-route/side-effects/drg-20073374?p=1
• https://www.webmd.com/drugs/2/drug-3778-7011/cefixime-oral/cefixime-oral/details
• https://www.drugs.com/cefixime.html
• https://www.rxlist.com/bacterial_infections_101_slideshow_pictures/article.htm
• https://go.drugbank.com/drugs/DB00671
• https://my.clevelandclinic.org/health/drugs/20534-cefixime-oral-tablets-or-capsules
• https://pdf.hres.ca/dpd_pm/00002280.PDF
• https://pdf.hres.ca/dpd_pm/00040170.PDF
• https://medlineplus.gov/druginfo/meds/a690007.html#:~:text=Cefixime is used to treat,of medications called cephalosporin antibiotics.