Cefpodoxime Proxetil

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

Cefpodoxime Proxetil had been approved to relieve symptoms and also for the treatment and maintenance of Chronic obstructive pulmonary disease, Odontogenic soft tissue infection, Otitis media, Pneumonia, community-acquired, Rhinosinusitis, Skin and soft tissue infection, Streptococcal pharyngitis, Urinary tract infection.

Cefpodoxime proxetil is a prodrug that is rapidly and extensively absorbed from the gastrointestinal tract after oral administration. Once absorbed, it is rapidly hydrolyzed to its active form, cefpodoxime. Cefpodoxime has a high degree of protein binding and a relatively long half-life, which allows for once-daily dosing. It is primarily excreted unchanged in the urine, with a small amount eliminated in the feces. The pharmacokinetics of cefpodoxime are linear and dose-proportional over the recommended dose range. However, the drug's clearance may be reduced in patients with impaired renal function.

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

Cefpodoxime Proxetil is available in the form of Cefpodoxime Proxetil is available in the form of Oral suspension, Tablets.

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

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

Cefpodoxime has a broad spectrum of activity against both Gram-positive and Gram-negative bacteria. It is not affected by beta-lactamase enzymes, which allows it to be effective against organisms that are resistant to other penicillins and cephalosporins. However, certain extended spectrum beta-lactamases can inactivate cefpodoxime. The drug's bactericidal effect comes from its ability to inhibit cell wall synthesis. Specifically, the active metabolite of cefpodoxime targets penicillin binding protein , which prevents the production of peptidoglycan, a key component of bacterial cell walls.

Cefpodoxime Proxetil had been approved to relieve symptoms and also for the treatment and maintenance of Chronic obstructive pulmonary disease, Odontogenic soft tissue infection, Otitis media, Pneumonia, community-acquired, Rhinosinusitis, Skin and soft tissue infection, Streptococcal pharyngitis, Urinary tract infection.

Cefpodoxime proxetil is a prodrug that is rapidly absorbed from the gastrointestinal tract and hydrolyzed to its active form, cefpodoxime. The maximum plasma concentration (Cmax) of cefpodoxime is achieved approximately 2 to 3 hours after oral administration (tmax).

The onset of action is relatively fast, with a noticeable decrease in bacterial count within 2 to 4 hours after administration. The duration of action of cefpodoxime is about 12 to 24 hours, depending on the severity and type of infection being treated. However, it is important to note that individual responses to the drug may vary, and the duration of action may be affected by factors such as age, renal function, and the presence of other medical conditions.

Cefpodoxime Proxetil is found to be available in the form of Oral suspension, Tablets.

Cefpodoxime Proxetil can be used in the following treatment:

• Chronic obstructive pulmonary disease
• Odontogenic soft tissue infection
• Otitis media
• Pneumonia, community-acquired
• Rhinosinusitis
• Skin and soft tissue infection
• Streptococcal pharyngitis
• Urinary tract infection

Cefpodoxime Proxetil can help to relieve symptoms and also for the treatment and maintenance of Chronic obstructive pulmonary disease, Odontogenic soft tissue infection, Otitis media, Pneumonia, community-acquired, Rhinosinusitis, Skin and soft tissue infection, Streptococcal pharyngitis, Urinary tract infection.

Cefpodoxime Proxetil is approved for use in the following clinical indications:

● Chronic obstructive pulmonary disease

● Odontogenic soft tissue infection

● Otitis media

● Pneumonia, community-acquired

● Rhinosinusitis

● Skin and soft tissue infection

● Streptococcal pharyngitis

● Urinary tract infection

• Chronic obstructive pulmonary disease, acute exacerbation: It should be avoided in patients with risk factors for Pseudomonas infection or poor outcomes (such as ≥65 years of age with major comorbidities, FEV1 <50% predicted, frequent exacerbations) . The recommended oral dose is 200 mg twice daily for 5 to 7 days .

• Odontogenic soft tissue infection, pyogenic (initial therapy for mild infection or step-down therapy after parenteral treatment) (alternative agent) (off-label use): It is used for patients unable to take penicillin . The recommended oral dose is 400 mg twice daily in combination with metronidazole; continue until clinical resolution, usually for 7 to 14 days. It should be used in addition to appropriate surgical management (such as drainage and/or extraction) .

• Otitis media, acute (alternative agent for patients with penicillin allergy that does not preclude cephalosporin use): The recommended oral dose is 200 mg twice daily. The duration of therapy is 5 to 7 days for mild to moderate infection and 10 days for severe infection .

• Pneumonia, community-acquired, outpatient empiric therapy (alternative agent): The recommended oral dose is 200 mg twice daily as part of an appropriate combination regimen. The duration of therapy is for a minimum of 5 days; patients should be clinically stable with normal vital signs before therapy is discontinued .

• Rhinosinusitis, acute bacterial (alternative agent for patients with penicillin allergy who are able to tolerate cephalosporins): In uncomplicated acute bacterial rhinosinusitis, initial observation and symptom management without antibiotic therapy is appropriate in most patients. Reserve antibiotic therapy for poor follow-up or lack of improvement over the observation period. The recommended oral dose is 200 mg twice daily with clindamycin for 5 to 7 days; some experts use it as monotherapy when the risk of drug-resistant S. pneumoniae is low (such as <65 years of age, low endemic resistance, few comorbidities, no recent hospitalization or antibiotic use).

• Skin and soft tissue infection (alternative agent): The recommended oral dose is 400 mg every 12 hours for 7 to 14 days .

• Streptococcal pharyngitis, group A (alternative agent for mild, nonanaphylactic penicillin allergy): Cephalosporin selection depends on the type of hypersensitivity reaction to penicillin. To avoid the development of resistance, narrower spectrum cephalosporins (such as cephalexin or cefadroxil) are preferred when possible . The recommended oral dose is 100 mg twice daily for 5 to 10 days.

• Urinary tract infection (alternative agent): It should only be used when preferred agents cannot be used; limited evidence suggests inferior efficacy of oral beta-lactams. For cystitis, acute uncomplicated or acute simple cystitis (infection limited to the bladder without signs/symptoms of upper tract, prostate, or systemic infection), the recommended oral dose is 100 mg twice daily for 5 to 7 days . For complicated urinary tract infection (including pyelonephritis) (off-label use), the recommended oral dose is 200 mg twice daily for 10 to 14 days ; for patients with symptomatic improvement within the first 48 to 72 hours of therapy, some experts recommend shorter courses of 7 to 10 days . Oral beta-lactam therapy should generally follow appropriate parenteral therapy.

Oral suspension : 50mg/5mL, 100mg/5mL

Tablet : 100mg , 200mg

Oral suspension, Tablets.

Dosage Adjustments in Kidney Patients:

• For patients who have creatinine clearance (CrCl) of 30 mL/minute or greater, no dosage adjustment is needed.
• For patients with a CrCl less than 30 mL/minute, the usual recommended dose should be given every 24 hours.
• For patients undergoing intermittent hemodialysis (three times a week), cefpodoxime proxetil is dialyzable (about 50%) and a dose of 100 to 200 mg should be given every 24 hours. If the scheduled dose falls on a dialysis day, the medication should be given after hemodialysis.
• For patients undergoing peritoneal dialysis, clearance of the drug is negligible and a dose of 100 to 200 mg should be given every 24 hours.
• For patients who are undergoing continuous renal replacement therapy (CRRT), drug clearance depends on effluent flow rate, filter type, and method of renal replacement. The usual recommended dose for patients with a CrCl of 30 mL/minute or greater is appropriate, but an intravenous antimicrobial agent is generally preferred.

• For patients undergoing sustained low-efficiency diafiltration (PIRRT), appropriate dosing requires consideration of adequate drug concentrations at the site of infection and initial loading doses. The usual recommended dose for patients with a CrCl of 30 mL/minute or greater is appropriate, but an intravenous antimicrobial agent is generally preferred. One of the twice-daily doses should be given after PIRRT on PIRRT treatment days, if possible. Close monitoring for drug accumulation and adverse reactions is important in all cases.

Dosage Adjustments in Pediatric Patients:

• For infants, children, and adolescents, the usual oral dose of cefpodoxime proxetil is 5 mg/kg every 12 hours, with a maximum dose of 200 mg per dose.
  

There are no specific dietary restrictions related to cefpodoxime proxetil. However, it is important to follow a prescribed dosage ass well as administration instructions provided by the healthcare provider. Additionally, it is recommended to take the medication with a full glass of water and to avoid consuming alcohol while taking cefpodoxime proxetil.

Cefpodoxime Proxetil may be contraindicated under the following conditions:

• In patients with known hypersensitivity to cephalosporin class of antibiotics.
• In patients with a history of anaphylaxis, cephalosporin-associated jaundice, or hepatic dysfunction.
• In patients with a history of colitis, since the drug may exacerbate the condition.
• In patients with a creatinine clearance of less than 20 mL/min, as the drug is primarily excreted via the kidneys and may accumulate in patients with renal impairment.

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

Antacids: A Concomitant administration of high doses of antacids such as sodium bicarbonate and aluminum hydroxide or H2 blockers can reduce peak plasma levels of cefpodoxime proxetil by 24% to 42% and the extent of absorption by about 27% to 32%. However, the rate of absorption remains unchanged. Oral anticholinergic medications like propantheline can delay peak plasma levels by 47% (increase in Tmax) but do not affect the extent of absorption (AUC).

Probenecid: Probenecid, a beta-lactam antibiotic, can inhibit renal excretion of cefpodoxime proxetil, resulting in an approximately 31% increase in AUC and a 20% increase in peak cefpodoxime plasma levels.

Nephrotoxic drugs: While nephrotoxicity has not been reported with cefpodoxime proxetil alone, close monitoring of renal function is recommended when cefpodoxime proxetil is administered concurrently with compounds known to be nephrotoxic.

There is a potential interaction between alcohol and Cefpodoxime Proxetil, which may increase the risk of certain side effects such as stomach upset, nausea, and vomiting. It is generally recommended to avoid alcohol consumption while taking this medication. Patients should discuss any concerns or questions about alcohol use with their healthcare provider.

Cefpodoxime can be found in human milk, as demonstrated in a study of 3 lactating women. Four hours after taking an oral dose of 200 mg cefpodoxime proxetil, the levels of cefpodoxime in human milk were found to be 0%, 2%, and 6% of the levels found in the bloodstream. At 6 hours post-dosing, the levels were 0%, 9%, and 16% of the levels found in the bloodstream. As there is a risk of serious reactions in nursing infants, a decision should be made regarding whether to discontinue nursing or the drug, taking into account the importance of the drug to the mother.

Pregnancy Category B

Cefpodoxime proxetil has been tested on rats and rabbits during organogenesis and was not found to be teratogenic or embryocidal at doses up to 100 mg/kg/day and 30 mg/kg/day respectively, which are 2 times and 1-2 times the human dose based on mg/m2. However, there have been no sufficient and well-controlled studies conducted on pregnant women using cefpodoxime proxetil. Since the results of animal reproduction studies are not always applicable to humans, the use of this drug during pregnancy should be limited to situations where it is clearly necessary.

There are no known food warnings related to the use of cefpodoxime proxetil. However, taking the medication with food may help to reduce stomach upset.

The adverse reactions related to Cefpodoxime Proxetil can be categorized as follows:

Common :

• Diarrhea
• Nausea
• Vomiting
• Abdominal pain
• Headache
• Vaginitis
• Rash

Less Common :

• Allergic reactions, such as hives or itching
• Anemia
• Increased liver enzymes
• Joint pain
• Dizziness
• Fatigue

Rare :

• Stevens-Johnson syndrome (a severe skin reaction)
• Toxic epidermal necrolysis (a life-threatening skin disorder)
• Pseudomembranous colitis (a severe intestinal infection)
• Hepatitis (inflammation of the liver)
• Nephritis (inflammation of the kidneys)
• Seizures
• Confusion
• Hallucinations

The clinically relevant drug interactions of Cefpodoxime Proxetil is briefly summarized here:

Probenecid: May increase the concentration of Cefpodoxime in the body, leading to a higher risk of side effects.

Antacids: Antacids containing aluminum, magnesium, or calcium can decrease the absorption of Cefpodoxime, reducing its effectiveness.

Warfarin: Cefpodoxime may enhance the anticoagulant effect of warfarin, leading to an increased risk of bleeding.

Aminoglycosides: Co-administration of Cefpodoxime with aminoglycosides can increase the risk of nephrotoxicity.

Oral Contraceptives: Cefpodoxime may reduce the efficacy of oral contraceptives, leading to unintended pregnancies.

Loop Diuretics: Cefpodoxime can increase the risk of nephrotoxicity when used concurrently with loop diuretics.

The following are the side effects involving Cefpodoxime Proxetil :

• Diarrhea
• Nausea
• Stomach pain
• Vomiting
• Headache
• Dizziness
• Insomnia
• Rash

Pregnancy

Pregnancy Category B

Cefpodoxime proxetil has been tested on rats and rabbits during organogenesis and was not found to be teratogenic or embryocidal at doses up to 100 mg/kg/day and 30 mg/kg/day respectively, which are 2 times and 1-2 times the human dose based on mg/m2. However, there have been no sufficient and well-controlled studies conducted on pregnant women using cefpodoxime proxetil. Since the results of animal reproduction studies are not always applicable to humans, the use of this drug during pregnancy should be limited to situations where it is clearly necessary.

Nursing Mothers:

Cefpodoxime can be found in human milk, as demonstrated in a study of 3 lactating women. Four hours after taking an oral dose of 200 mg cefpodoxime proxetil, the levels of cefpodoxime in human milk were found to be 0%, 2%, and 6% of the levels found in the bloodstream. At 6 hours post-dosing, the levels were 0%, 9%, and 16% of the levels found in the bloodstream. As there is a risk of serious reactions in nursing infants, a decision should be made regarding whether to discontinue nursing or the drug, taking into account the importance of the drug to the mother.

Pediatric Use:

The safety and efficacy of cefpodoxime proxetil in infants under two months of age have not been established.

Geriatric Use:

In multiple-dose clinical studies of cefpodoxime proxetil film-coated tablets involving 3338 patients, 521 (16%) were 65 years and older, and 214 (6%) were 75 years and older. No significant differences were found in terms of safety or effectiveness between the elderly and younger patients. In healthy elderly subjects with normal renal function, the average half-life of cefpodoxime in plasma was 4.2 hours, and urinary recovery was 21% after a 400 mg dose was administered every 12 hours for 15 days. Other pharmacokinetic parameters were similar to those observed in healthy younger subjects. Therefore, no dose adjustments are necessary in elderly patients with normal renal function.

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

An overdose of cefpodoxime proxetil can cause symptoms such as nausea, vomiting, stomach pain, and diarrhea. In severe cases, an overdose can lead to seizures or kidney damage.

If an overdose is suspected, immediate medical attention should be sought. Treatment may involve measures to support and stabilize the patient, such as gastric lavage (stomach pumping) or activated charcoal to absorb the drug. Dialysis may also be necessary in severe cases.

It's important to take cefpodoxime proxetil exactly as prescribed by a healthcare provider, and to never take more than the recommended dose.

Pharmacodynamics

Cefpodoxime has been proven to be an effective treatment for a broad range of bacteria, including many Gram positive and Gram negative strains. However, it is not effective against certain bacteria, such as Pseudomonas aeruginosa, Enterococcus, and Bacteroides fragilis.

Pharmacokinetics

• Absorption

Cefpodoxime proxetil is a prodrug that is taken orally and absorbed through the gastrointestinal tract. Once inside the body, it is converted to cefpodoxime, its active form. When 100 mg of cefpodoxime proxetil was given to fasting subjects, about half of the cefpodoxime dose was absorbed into the bloodstream.

• Distribution

The volume of distribution for cefpodoxime is not currently known. Studies have shown that 22 to 33% of cefpodoxime in serum and 21 to 29% in plasma bind to proteins.

• Metabolism

The metabolism of cefpodoxime is not yet understood.

• Excretion

Over a recommended dosage range of 100 to 400 mg, approximately 29 to 33% of the administered cefpodoxime dose was excreted unchanged in the urine within a 12-hour period.

• https://www.sciencedirect.com/topics/pharmacology-toxicology-and-pharmaceutical-science/cefpodoxime-proxetil
• https://www.healthlinkbc.ca/medications/cefpodoxime-proxetil-oral
• https://www.webmd.com/drugs/2/drug-8749/cefpodoxime-oral/details
• https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/050674s015,050675s018lbl.pdf
• https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/050674s015,050675s018lbl.pdf
• https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/065462s005lbl.pdf
• https://www.seattle.gov/Documents/Departments/AnimalShelter/Cefpodoxime Info Sheet.pdf
• https://go.drugbank.com/drugs/DB01416