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Cefditoren
Cefditoren
Cefditoren
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Cefditoren
Clinical data
Trade namesZostom-O, Meiact, Spectracef
AHFS/Drugs.comMonograph
MedlinePlusa605003
Pregnancy
category
  • B
Routes of
administration		By mouth
ATC code
Identifiers
  • (7R)-7-((Z)-2-(2-Aminothiazol-4-yl)-2-(methoxyimino)acetamido)-3-((Z)-2-(4-methylthiazol-5-yl)vinyl)-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid
CAS Number
PubChem CID
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
CompTox Dashboard (EPA)
Chemical and physical data
FormulaC19H18N6O5S3
Molar mass506.57 g·mol−1
3D model (JSmol)
  • O=C3N2/C(=C(/C=C\c1scnc1C)CS[C@@H]2[C@@H]3NC(=O)C(=N\OC)/c4nc(sc4)N)C(=O)O
  • InChI=1S/C19H18N6O5S3/c1-8-11(33-7-21-8)4-3-9-5-31-17-13(16(27)25(17)14(9)18(28)29)23-15(26)12(24-30-2)10-6-32-19(20)22-10/h3-4,6-7,13,17H,5H2,1-2H3,(H2,20,22)(H,23,26)(H,28,29)/b4-3-,24-12-/t13-,17-/m1/s1 checkY
  • Key:KMIPKYQIOVAHOP-YLGJWRNMSA-N checkY
 ☒NcheckY (what is this?)  (verify)

Cefditoren, also known as cefditoren pivoxil is an antibiotic used to treat infections caused by Gram-positive and Gram-negative bacteria that are resistant to other antibiotics. It is mainly used for treatment of community acquired pneumonia. It is taken by mouth and is in the cephalosporin family of antibiotics, which is part of the broader beta-lactam group of antibiotics.[1]

Structure

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Like other cephalosporins, cefditoren has a β-lactam ring at the 7 position of cephalosporin ring that is responsible for its inhibitory action on bacterial cell wall synthesis. In addition to the cephem nucleus common to all cephalosporins, cefditoren has an aminothiazole group that enhances its activity against Gram-negative organisms, a methylthiazole group that enhances its activity against Gram-positive organisms, a methoxyimino group that gives it stability against β-lactamases, and a pivoxil ester group that enhances oral bioavailability.[2]

Antimicrobial activity

[edit]

The spectrum of cefditoren includes both Gram-positive and Gram-negative bacterial species. It has strong antimicrobial activity because of its high affinity for penicillin binding protein 2X, which responsible for cephalosporin resistance when mutated. Cefditoren pivoxil high intrinsic activity against Streptococcus pneumoniae, including penicillin-resistant strains. Cefditoren holds a balanced antimicrobial spectrum that includes the three major pathogens of community-acquired lower-respiratory tract infections: Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis.[3] Aerobic Gram-positive microorganisms: Staphylococcus aureus (methicillin-susceptible strains, including β-lactamase-producing strains), Streptococcus pneumoniae, Streptococcus pyogenes Aerobic Gram-negative microorganisms: Haemophilus influenzae (including β-lactamase-producing strains), Haemophilus parainfluenzae (including β-lactamase-producing strains), Moraxella catarrhalis (including β-lactamase-producing strains.[4]

Pharmacokinetics

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Absorption

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Oral bioavailability: following oral administration, cefditoren pivoxil is absorbed from the gastrointestinal tract and hydrolyzed to cefditoren by esterases. Maximal plasma concentrations of cefditoren under fasting conditions average 1.8 ± 0.6 μg/mL following 200 mg dose and occur 1.5 to 3 hours following dosing. Cefditoren does not accumulate in plasma following twice daily administration to subjects with normal renal function. Under fasting conditions, the estimated absolute bioavailability of cefditoren pivoxil is approximately 14%.[5]

Distribution

[edit]

Binding of cefditoren to plasma proteins averages 88%, and the mean volume of distribution of cefditoren at steady state is 9.3L. Cefditoren has been shown to penetrate into bronchial mucosa, epithelial lining fluid, skin blister fluid and tonsillar tissue and clinically relevant concentrations against common pathogens are achieved in these tissues for at least 4 hours.[5]

Metabolism and Excretion

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Cefditoren is predominantly eliminated by the kidneys as unchanged drug and has a renal clearance of 4.1–5.6 L/h after multiple doses; its elimination half-life is 1.5 hours.[5]

Medical uses

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Cefditoren pivoxil is indicated to treat uncomplicated skin and skin structure infections, community-acquired pneumonia, acute bacterial exacerbation of chronic bronchitis, pharyngitis, and tonsillitis, acute maxillary sinusitis, otitis media (indications may differ in some countries).[6][5]

Spectrum of bacterial susceptibility

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Cefditoren pivoxil has a broad spectrum of activity and has been used to treat bacterial infections of the skin and respiratory tract, including bronchitis, pneumonia, and tonsillitis. The following represents minimum inhibitory concentration data for several medically significant microorganisms.

Cefditoren does not have antibacterial activity against Pseudomonas aeruginosa.[9]

Dosage and administration

[edit]

Adults and Adolescents (≥12 Years)

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  • Community-acquired pneumonia: 400 mg twice daily for 14 days
  • Acute bacterial exacerbation of chronic bronchitis: 400 mg twice daily for 10 days
  • Pharyngitis/tonsillitis, otitis media, sinusitis: 200 mg twice daily for 10 days
  • Uncomplicated skin and skin structure infections: 200 mg twice daily for 10 days[10]

Children (2 months to 12 years of age)

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  • Pneumonia, otitis media or sinusitis: 3 mg/kg/dose, 3 times a day, after meals. The dosage may be increased up to 6 mg/kg/dose as needed, but not exceed the maximum dose for adults.
  • For children with diseases other than above: 3 mg/kg/dose, 3 times a day after meals. The dosage may be adjusted according to the disease or the patients age and symptoms, but not exceed the maximum dose for adults. Safety in low birth weight infants and newborns has not been established.[11]

Pregnancy

[edit]

Pregnancy Category B

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Cefditoren pivoxil was not teratogenic up to the highest doses tested in rats and rabbits. In rats, this dose was 1000 mg/kg/day, which is approximately 24 times a human dose of 200 mg twice daily based on mg/m2/day. In rabbits, the highest dose tested was 90 mg/kg/day, which is approximately four times a human dose of 200 mg twice daily based on mg/m2/day. This dose produced severe maternal toxicity and resulted in fetal toxicity and abortions.

In a postnatal development study in rats, cefditoren pivoxil produced no adverse effects on postnatal survival, physical and behavioral development, learning abilities, and reproductive capability at sexual maturity when tested at doses of up to 750 mg/kg/day, the highest dose tested. This is approximately 18 times a human dose of 200 mg twice daily based on mg/m2/day. There are, however, no adequate and well-controlled studies in pregnant women. Because animal reproductive studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed.[10]

Geriatric use

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Of the 2675 patients in clinical studies who received cefditoren pivoxil 200 mg twice daily, 308 (12%) were >65 years of age. Of the 2159 patients in clinical studies who received cefditoren pivoxil 400 mg twice daily, 307 (14%) were >65 years of age. No clinically significant differences in effectiveness or safety were observed between older and younger patients. No dose adjustments are necessary in geriatric patients with normal renal function. This drug is substantially excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function.[10]

International approvals

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Cefditoren pivoxil is available as 200 and 400 mg tablets in the United States. It was marketed under the trade name Spectracef by Vansen Pharma Inc.[12] Cefditoren is also marketed under the name Meiact by Meiji Seika Pharma Co., Ltd.[13] In India it is marketed under the brand name Zostum-O by Zuventus Healthcare.

Proprietary Preparations and Countries

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US:Spectracef; India:Zostum-O; Japan:Meiact; Russia:Spectracef; China:Meiact; Greece:Spectracef; Indonesia:Meiact; Italy:Giasion; Mexico:Spectracef; Portugal:Meiact; Thailand:Meiact; Turkey: Cftiten, Meiact; Sefporin Spain: Spectracef, Meiact.

Contraindications

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  • In patients with known allergy to the cephalosporin class of antibiotics or any of its components.
  • Patients with carnitine deficiency or inborn errors of metabolism that may result in clinically significant carnitine deficiency, because use of cefditoren causes renal excretion of carnitine.[10]

Safety and tolerability

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  • Cefditoren pivoxil is generally well-tolerated, with most adverse events being of mild-to-moderate severity and self-limiting. Gastrointestinal adverse events (e.g., diarrhoea, nausea and abdominal pain) were the most commonly reported adverse events, although they seldom led to treatment discontinuation.
  • In a post-marketing surveillance evaluating safety in 2006 children with acute otitis media treated with cefditoren (median daily dose: 10.0 mg/kg with a median total treatment period of 7 days), the incidence of adverse reactions was 1.79%, without unexpected or serious adverse drug reactions reported. The most frequent adverse drug reaction was diarrhea (1.30%) that resolved or subsided during treatment or after discontinuation or completion of therapy in all cases.[14]
  • Data from the clinical studies carried out with cefditoren in the treatment of pharyngotonsillitis from 2007 to 2010 in Japan showed that the percentage of adverse events was very low and diarrhea was the most frequent event. In the largest study (734 children), the incidence of adverse reactions was 1.50% (11 events in 11 patients), with 3 events of diarrhea and three of hematuria in urinalysis without clinical symptoms. In a study carried out in children in Thailand comparing cefditoren (66 patients) with amoxicillin/clavulanic acid (72 patients) for 10 days in the treatment of acute bacterial rhinosinusitis, the most frequent adverse event was diarrhea, with significant (P = 0.02) differences in the percentages found for both compounds (4.5% with cefditoren vs. 18.1% for amoxicillin/clavulanic acid).[15]

Guidelines

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Japanese Guidelines

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  1. Japanese guidelines for the management of respiratory infectious diseases in children recommend cefditoren pivoxil as an initial antimicrobial therapy in children (2 months and older).[16]

A panel of 70 pulmonologists, coordinated by 9 experts in respiratory care recommendations

[edit]
  • A consensus on appropriate prescribing in lower respiratory tract infection therapy was appraised by Delphi exercise, based on a panel of 70 pulmonologists, coordinated by a scientific committee of nine experts in respiratory medical care.
  • Amongst 3rd-generation oral cephalosporins, cefditoren pivoxil has the highest intrinsic activity against Streptococcus pneumoniae, penicillin-resistant strains included.
  • Amongst 3rd-generation oral cephalosporins, the spectrum of cefditoren is particularly balanced, includes both Gram-positive and Gram-negative species.
  • The experts expressed the opinion that, due to its high intrinsic activity, cefditoren appears as an appropriate agent for either the treatment of lower respiratory tract infections and for parenteral to oral switch therapy as well.[17]

Ideal for switch therapy

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  • The characteristics of oral antibiotics to be considered for the switch therapy (parenteral to oral antibiotic) are: (i) similar antimicrobial spectrum, (ii) high bioavailability, (iii) administration time 12–24 hours, (iv) good tolerability
  • The expert panel reached a high level of consensus on cefditoren pivoxil as the most appropriate option for the switch therapy from parenteral third-generation cephalosporins (like cefotaxime or ceftriaxone) to oral therapy, because of the similar spectrum and the highest intrinsic activity.[17]

References

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Revisions and contributorsEdit on WikipediaRead on Wikipedia

Cefditoren

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Cefditoren, administered orally as its cefditoren pivoxil and formerly marketed under the brand name Spectracef in the United States (discontinued in 2012), is a broad-spectrum third-generation used to treat mild to moderate bacterial infections of the and caused by susceptible Gram-positive and Gram-negative pathogens. It is effective against bacteria such as , , and methicillin-susceptible , and is indicated for patients aged 12 years and older. Approved by the U.S. in 2001, cefditoren pivoxil is hydrolyzed by intestinal esterases to the active form during absorption, achieving of approximately 14-16% under conditions and higher when taken with food. The primary indications include acute bacterial exacerbations of chronic bronchitis, , and due to , and uncomplicated skin and skin structure infections. It is typically dosed as 200 mg or 400 mg tablets taken twice daily with meals for 10 days, depending on the indication, with the full course required to prevent bacterial resistance. Cefditoren should not be used for viral infections like the or flu, and concurrent use with multivalent cation-containing antacids or supplements should be avoided to prevent reduced absorption. Contraindicated in patients with known to cephalosporins or carnitine deficiency, it requires dose adjustments in renal impairment. Common side effects include gastrointestinal issues such as , , and . Overall, cefditoren provided a convenient oral option for community-acquired infections when available.

Chemistry

Chemical structure

Cefditoren features the characteristic cephem nucleus of cephalosporins, consisting of a β-lactam ring fused to a six-membered dihydrothiazine ring. At the 7-position, it bears a (2Z)-2-(2-amino-1,3-thiazol-4-yl)-2-(methoxyimino)acetamido side chain, which is typical of third-generation cephalosporins and enhances its activity against . At the 3-position, a (Z)-2-(4-methyl-1,3-thiazol-5-yl)ethenyl provides additional steric and electronic properties that contribute to its broad-spectrum efficacy. The orally administered form is the prodrug cefditoren pivoxil, a pivaloyloxymethyl ester of the carboxylic acid group at the 4-position, designed to improve gastrointestinal absorption by masking the polar carboxyl functionality until hydrolysis in vivo releases the active cefditoren. The molecular formula of cefditoren is C₁₉H₁₈N₆O₅S₃, with a molecular weight of 506.58 g/mol. Compared to earlier cephalosporins, the methoxyimino group in cefditoren's 7-side chain confers greater stability against hydrolysis by various β-lactamases, including some extended-spectrum enzymes produced by Gram-negative pathogens, allowing better retention of activity in resistant strains.

Physicochemical properties

Cefditoren is a solid compound that appears as a white to off-white crystalline powder. It exhibits low aqueous solubility, with a value of less than 0.1 mg/mL in water, classifying it as practically insoluble, while it is freely soluble in dilute hydrochloric acid and soluble in ethanol at 6.06 mg/mL. The compound is also soluble in organic solvents such as methanol and dimethylformamide, which facilitates formulation processes. The pKa values for cefditoren are approximately 2.27 for the group and 3.69 for the basic nitrogen in the dihydrothiazine ring, influencing its profile and contributing to its physicochemical behavior in biological environments. The (log P) is estimated at 1.7, reflecting moderate that affects membrane permeability and distribution. Regarding stability, cefditoren is inherently sensitive to degradation by enzymes due to its beta-lactam ring structure. However, the form, cefditoren pivoxil, enhances acid stability in the gastric environment, enabling effective oral before to the active form by intestinal esterases. This design is critical for formulation and therapeutic efficacy.

Pharmacology

Mechanism of action

Cefditoren, a third-generation cephalosporin antibiotic, exerts its bactericidal effects by binding to penicillin-binding proteins (PBPs) in the bacterial cytoplasmic membrane, thereby inhibiting the final stages of peptidoglycan synthesis in the cell wall. Specifically, it shows high affinity for PBP-1A in Gram-positive bacteria such as Streptococcus pneumoniae and for PBP-1A and PBP-3A/B in Gram-negative bacteria like Haemophilus influenzae, which are essential transpeptidases and carboxypeptidases involved in cross-linking peptidoglycan layers. This binding prevents the formation of peptide cross-links, leading to weakened cell wall integrity and activation of autolytic enzymes that cause bacterial cell lysis and death. The inhibition of transpeptidase and carboxypeptidase activities by cefditoren disrupts the balance between synthesis and degradation, promoting autolysis through endogenous enzymes such as autolysins. This mechanism is particularly effective against actively growing , as it targets the dynamic process of cell wall remodeling during replication. Cefditoren's enhanced activity against beta-lactamase-producing strains stems from its structural features, including the aminothiazole side chain at the C-7 position, which confers resistance to hydrolysis by many beta-lactamases, such as penicillinases and certain cephalosporinases. This stability allows the beta-lactam ring to remain intact long enough to bind PBPs effectively, broadening its utility against resistant pathogens.

Antimicrobial spectrum

Cefditoren demonstrates potent activity against several key Gram-positive respiratory pathogens. It is particularly effective against Streptococcus pneumoniae, including penicillin-intermediate resistant strains, with MIC90 values typically ranging from 0.25 to 0.5 μg/mL. Against Streptococcus pyogenes, cefditoren shows even greater potency, achieving MIC90 values of ≤0.06 μg/mL. The antibiotic also exhibits strong bactericidal effects against common Gram-negative respiratory bacteria. For , including β-lactamase-producing strains, MIC90 values are ≤0.016 μg/mL. Similarly, is highly susceptible, with MIC90 values of ≤0.016 μg/mL, regardless of β-lactamase production. Activity against other Gram-positive organisms is more limited. Cefditoren inhibits methicillin-susceptible (MSSA), but with higher MIC90 values of 1 μg/mL, and shows no activity against methicillin-resistant strains. For Enterobacteriaceae such as , susceptibility is variable due to prevalent resistance mechanisms, resulting in inconsistent MIC values across isolates. Cefditoren lacks activity against species, enterococci, and anaerobic bacteria, limiting its utility to specific aerobic pathogens. Emerging resistance, primarily through production of extended-spectrum β-lactamases in , has been noted, though cefditoren remains stable against many common β-lactamases.

Pharmacokinetics

Absorption

Cefditoren is administered orally as the cefditoren pivoxil, which undergoes by intestinal esterases to yield the active drug during gastrointestinal absorption. This process results in an estimated absolute of approximately 14% in the state. The absorption of cefditoren pivoxil is notably influenced by intake. In the state, peak plasma concentrations (Cmax) reach approximately 1.8 ± 0.6 μg/mL following a 200 mg dose, whereas administration with a high-fat increases AUC by approximately 70% and elevates Cmax to 3.1 ± 1.0 μg/mL due to delayed gastric emptying that prolongs exposure to esterases. Pharmacokinetics of cefditoren show less-than-dose-proportional increases in AUC and Cmax within the therapeutic range. The time to reach maximum concentration (Tmax) typically occurs between 1.5 and 3 hours post-administration.

Distribution

Following oral administration, cefditoren exhibits a steady-state (Vd) of 9.3 ± 1.6 L, reflecting distribution primarily into extracellular fluids, which supports its efficacy against extracellular bacterial pathogens in tissues such as the and . This relatively low Vd is consistent with the pharmacokinetic profile of other third-generation cephalosporins, facilitating adequate penetration into infection sites without significant intracellular accumulation. Cefditoren demonstrates high of approximately 88%, which is concentration-independent over the range of 0.05–10 μg/mL and occurs primarily through reversible binding to . Binding affinity decreases in conditions of , potentially increasing the free fraction available for tissue distribution and antimicrobial activity. Penetration into red blood cells is negligible, further emphasizing its extracellular localization. In skin blister fluid, cefditoren achieves substantial penetration, with the area under the curve (AUC) representing 56 ± 15% of simultaneous plasma levels following a 400 mg dose; peak concentrations of 1.1 ± 0.42 μg/mL occur 4–6 hours post-dose, supporting its use in skin and soft tissue infections. In tissue, concentrations reach 0.18 ± 0.07 μg/g (approximately 12% of serum AUC) following a 200 mg dose. For tissues, concentrations in bronchial mucosa reach 0.56–1.04 mg/kg and in epithelial lining fluid 0.30–0.39 mg/L between 1–4 hours after a 400 mg dose, yielding tissue-to-plasma ratios of approximately 0.32–0.55 at 4 hours, which exceed typical minimum inhibitory concentrations for common respiratory pathogens. Data on penetration into are not available, though as with other oral cephalosporins, access is generally limited in the absence of meningeal inflammation.

Metabolism and excretion

Cefditoren undergoes minimal hepatic metabolism following of its form, cefditoren pivoxil, to the active drug. The is rapidly converted to cefditoren by nonspecific esterases in the plasma and tissues, releasing pivalate as a . This pivalate is conjugated with carnitine to form pivaloylcarnitine, which is primarily eliminated renally (>99%), potentially leading to decreased plasma carnitine levels and associated risks with repeated dosing. Cefditoren is primarily excreted unchanged, with renal elimination accounting for the majority via glomerular filtration and active tubular secretion, while a smaller portion undergoes biliary mediated by transporters such as and Bcrp, leading to fecal elimination. Studies in healthy volunteers indicate urinary recovery of approximately 15-18% of the administered dose as unchanged cefditoren over 24 hours. The elimination of cefditoren is approximately 100 minutes (1.6-1.7 hours) in healthy adults, with total body clearance of 60-80 mL/min and renal clearance of 4-5 L/h. In renal impairment, clearance decreases proportionally; for clearance <30 mL/min, the recommended dose adjustment is to 200 mg once daily to avoid accumulation.

Clinical use

Indications

Cefditoren pivoxil is approved by the U.S. (FDA) for the treatment of mild to moderate acute bacterial exacerbations of chronic bronchitis due to Haemophilus influenzae, Haemophilus parainfluenzae, Streptococcus pneumoniae (penicillin-susceptible strains only), or Moraxella catarrhalis; caused by the same pathogens; / due to Streptococcus pyogenes; and uncomplicated skin and skin-structure infections caused by Staphylococcus aureus or S. pyogenes in adults and adolescents aged 12 years and older. In , where cefditoren pivoxil was first developed and approved, it is indicated for a broader range of infections, including acute and in both adults and children, in addition to respiratory tract infections such as and , and skin infections. Clinical trials have demonstrated high efficacy for respiratory infections, with clinical success rates ranging from 85% to 95% in treating , acute exacerbations of chronic , and / caused by susceptible pathogens. Cefditoren is also suitable as step-down therapy from intravenous third-generation cephalosporins, such as , for transitioning stable patients with respiratory or skin infections to oral treatment in outpatient settings. The Japanese Association for Infectious Diseases (JAID) and Japanese Society of Chemotherapy (JSC) guidelines for respiratory infectious diseases reference cefditoren pivoxil as an effective option for community-acquired respiratory infections, particularly in pediatric and adult populations with mild to moderate disease.

Dosage and administration

Cefditoren pivoxil is administered orally in tablet form, available as 200 mg or 400 mg tablets containing the equivalent of cefditoren. Tablets must be taken with meals to enhance and should be swallowed whole without crushing, chewing, or breaking, as this may affect the release of the drug. The standard duration of therapy is 10 days for most indications, including acute exacerbations of chronic bronchitis, /, and uncomplicated skin and skin structure infections, while typically requires 14 days of treatment. In patients with renal impairment, dose reductions are recommended to avoid accumulation: for creatinine clearance of 30–49 mL/min, the maximum dose is 200 mg twice daily; for clearance less than 30 mL/min, the dose should be limited to 200 mg once daily. Completion of the full prescribed course is essential to minimize the risk of developing bacterial resistance, even if symptoms improve earlier.

Adults and adolescents

Cefditoren pivoxil is administered to adults and adolescents aged 12 years and older at a dose of 200 mg twice daily for the treatment of and caused by susceptible strains of or uncomplicated and structure infections caused by or . For acute exacerbations of chronic bronchitis or due to relevant pathogens such as or , the recommended dose is 400 mg twice daily. Treatment durations typically range from 10 to 14 days depending on the indication, and the medication should be taken with meals to optimize absorption. The maximum recommended daily dose is 800 mg, and no dosage adjustment is required for patients with hepatic impairment. Clinical trials have demonstrated that the efficacy of cefditoren in adolescents aged 12 years and older is comparable to that observed in adults, with overall clinical success rates exceeding 85% across respiratory and studies. In particular, trials reported an 88% clinical success rate in this population, supporting its use for mild to moderate community-acquired cases.

Pediatrics

Cefditoren pivoxil is not approved by the FDA for use in patients under 12 years of age, as and efficacy have not been established in this population. However, it is approved for pediatric use in various international markets, including , where granule formulations are available for children, with clinical trials including infants from 28 days of age. Use in infants under 6 months is generally not recommended due to limited pharmacokinetic and data. In , the standard pediatric dose is 3 mg/kg (as active cefditoren) three times daily after meals for most indications; this may be increased to 6 mg/kg three times daily for bacterial pneumonia, acute otitis media, or acute rhinosinusitis suspected to involve drug-resistant bacteria. Maximum doses are weight-based but typically do not exceed adult equivalents (e.g., 200-400 mg per dose). Treatment durations range from 5-14 days depending on the indication. Clinical trials evaluating cefditoren pivoxil in children have shown no serious adverse events, with gastrointestinal effects such as being the most common but mild and self-limiting. Efficacy in treating reached approximately 90% clinical response rates, demonstrating comparable outcomes to standard therapies like amoxicillin. The oral tablet formulation may be dispersed in a small amount of or similar soft food for easier administration in young children who cannot swallow tablets whole, ensuring the full dose is consumed immediately.

Special populations

Pregnancy and breastfeeding

Cefditoren pivoxil was previously classified as FDA Pregnancy Category B, indicating that animal reproduction studies did not demonstrate fetal risk, though there are no adequate and well-controlled studies in humans. In rats, no teratogenic effects were observed at doses up to 1000 mg/kg/day, approximately 24 times the recommended maximum human dose of 400 mg/day based on body surface area. In rabbits, doses up to 90 mg/kg/day, approximately 4 times the human dose, also showed no teratogenicity, although higher doses led to maternal toxicity, fetal toxicity, and abortions. A postnatal development study in rats at doses up to 750 mg/kg/day, approximately 18 times the human dose, revealed no adverse effects on growth or reproduction. Limited human data from a case series involving 285 first-trimester exposures reported adverse outcomes at rates comparable to the general population, including 1.2% major congenital malformations (3 cases), 5.6% miscarriages, and 4.6% preterm births among live births, with no significant increase in risk. Cefditoren should be used during pregnancy only if clearly needed, with alternatives preferred in the first trimester when possible. The extent of placental transfer of cefditoren in humans is unknown, though it is not expected to cross significantly based on its pharmacokinetic profile similar to other third-generation cephalosporins. Cefditoren is excreted into human at low concentrations, with an average peak level of 11.3 mcg/L occurring about 5 hours after dosing and an average concentration of 5.65 mcg/L over 12 hours. The relative infant dose is approximately 0.025% of the maternal weight-adjusted dose (or up to 0.05% at steady state), resulting in negligible exposure unlikely to cause adverse effects in breastfed infants. No specific adverse events in infants have been reported, but as with other beta-lactam antibiotics, monitoring for potential gastrointestinal disturbances such as or oral thrush is advisable. Cefditoren is considered compatible with .

Geriatric use

Cefditoren pivoxil requires no dose adjustment in geriatric patients solely based on age; however, renal function should be monitored due to the common age-related decline in creatinine clearance, with adjustments made if impairment is present. Pharmacokinetic studies in elderly subjects (aged ≥65 years) demonstrate higher plasma exposure compared to younger adults, including a 26% increase in maximum concentration (Cmax), a 33% increase in area under the curve (AUC), a 16-26% longer elimination half-life, and 20-24% lower renal clearance, attributable to reduced glomerular filtration rate. These changes do not necessitate routine dose modifications in elderly patients with normal renal function for their age. Clinical trials for and other respiratory infections included 12-14% geriatric patients (approximately 615 individuals across studies receiving 200 mg or 400 mg twice daily), showing comparable to younger adults, with clinical success rates of approximately 85% against Haemophilus influenzae and 90% against Streptococcus pneumoniae. Geriatric patients often present with higher rates of comorbidities, which may influence overall treatment outcomes but do not alter cefditoren's specific profile. Safety profiles in geriatric patients are similar to those in younger adults, with no clinically significant differences observed in adverse event incidence or severity; common gastrointestinal effects like occurred in 11-15% of trial participants overall. Caution is advised with concurrent medications due to potential in this population. Post-marketing surveillance has identified no unique risks in geriatric patients beyond those associated with renal impairment.

Safety

Contraindications

Cefditoren is contraindicated in patients with a known to cephalosporins, other beta-lactam antibiotics, or any components of the formulation, as this can lead to severe allergic reactions including . Patients with a history of severe reactions, such as or Stevens-Johnson , to cephalosporins, penicillins, or related beta-lactams should not receive cefditoren due to the risk of . Approximately 10% of patients allergic to penicillins may exhibit with cephalosporins like cefditoren, particularly those sharing similar side chains, necessitating avoidance in such cases. The cefditoren pivoxil releases upon , which conjugates with and is excreted renally, potentially depleting carnitine stores; therefore, it is contraindicated in patients with known carnitine deficiency or primary/secondary carnitine insufficiency, including that impair carnitine . Prolonged therapy exacerbates this risk, and monitoring or supplementation may be required in at-risk patients, but initiation is prohibited if deficiency is established. For patients with severe renal impairment (creatinine clearance [CLcr] <30 mL/min), the dose should be reduced to 200 mg once daily; use with caution in those with CLcr <10 mL/min not undergoing dialysis, monitoring closely for drug accumulation and toxicity. Hypersensitivity to milk proteins (e.g., sodium caseinate in the tablet coating) also constitutes an absolute contraindication, distinct from lactose intolerance.

Adverse effects

Cefditoren, like other antibiotics, is generally well-tolerated, but adverse effects occur in a dose-dependent manner, with higher incidences observed at the 400 mg twice-daily regimen compared to 200 mg twice daily. In clinical trials involving over 4,800 patients, the overall incidence of treatment-related adverse events was approximately 12-15%, leading to discontinuation in about 2-3% of cases, primarily due to gastrointestinal issues. Common adverse effects, occurring in more than 1% of patients, include gastrointestinal disturbances and . Diarrhea affects 11% of patients at 200 mg twice daily and 15% at 400 mg twice daily, 4-6%, 2-3%, 2-3%, and vaginal moniliasis 3-6% in females. These events are typically mild to moderate and resolve upon discontinuation. Uncommon adverse effects, with incidences between 0.1% and 1%, include , dyspepsia, and . These are less frequent and often self-limiting. Rare adverse effects, occurring in less than 0.1% of patients, include reactions such as and urticaria, pseudomembranous associated with difficile overgrowth, and elevated liver enzymes (transient increases in ALT and AST). requires immediate medical intervention, while may range from mild to severe cases necessitating hospitalization. Prolonged use of cefditoren beyond 2 weeks may lead to carnitine depletion due to its pivalate moiety, resulting in plasma carnitine reductions of 39-63% after 10-14 days of , which typically reverses within 7-10 days post-treatment. In susceptible individuals, such as those with underlying carnitine deficiency, this can precipitate metabolic disturbances including and . No clinical symptoms were noted in short-term trials, but monitoring is advised for extended courses. In pediatric populations, adverse effect rates are generally lower than in adults, with occurring in 1-4% of cases across studies involving hundreds of children. As of 2025, no new severe s have been reported in post-marketing surveillance or recent analyses.

Drug interactions

Cefditoren pivoxil, a of cefditoren, exhibits pharmacokinetic interactions primarily related to its absorption and renal excretion. Agents that reduce gastric acidity, such as antacids containing aluminum or magnesium hydroxides, H2-receptor antagonists like famotidine, and inhibitors like omeprazole, can decrease the oral absorption of cefditoren. For instance, co-administration with magnesium (800 mg) and aluminum (900 mg) hydroxides reduces the maximum plasma concentration (Cmax) by 14% and the area under the curve (AUC) by 11%, while famotidine (20 mg IV) reduces Cmax by 27% and AUC by 22%. These reductions, typically ranging from 20-40% for similar acid-suppressing agents, may compromise efficacy; administration should be separated by at least 2 hours. Probenecid inhibits the renal tubular secretion of cefditoren, prolonging its and increasing systemic exposure. Co-administration results in a 49% increase in Cmax, a 122% increase in AUC, and a 53% prolongation of the compared to cefditoren alone; this combination should be avoided to prevent potential from elevated levels. Cefditoren does not significantly interact with the (CYP450) enzyme system, showing no notable effects on drugs metabolized via these pathways. It has minimal pharmacokinetic impact on , with no reported changes in its plasma levels, though pharmacodynamic monitoring for risk is advised due to general effects. Similarly, cefditoren does not alter the of ethinyl in oral contraceptives. As a pivalate-containing , cefditoren pivoxil can deplete carnitine stores through urinary excretion of pivaloylcarnitine, with short-term use (200-400 mg BID for 10-14 days) reducing plasma carnitine by 39-63%. Concomitant use with other pivalate prodrugs, such as pivampicillin or , may exacerbate this depletion, potentially leading to carnitine deficiency in prolonged therapy; monitoring is recommended in at-risk patients. As of 2025, no new drug interactions have been identified in recent studies beyond these established pharmacokinetic effects.

Society and culture

Development and approvals

Cefditoren pivoxil was developed by in during the late as an oral of the third-generation cefditoren, designed for enhanced oral through by intestinal esterases. The compound was first approved for marketing in on April 1, 1994, under the brand name Meiact, for the treatment of respiratory tract infections and and infections caused by susceptible . In the United States, the (FDA) granted approval for cefditoren pivoxil tablets (Spectracef) on August 29, 2001, initially for use in adults and adolescents aged 12 years and older to treat acute exacerbations of chronic bronchitis, , pharyngitis/tonsillitis, and uncomplicated skin and skin structure infections. This approval was based on clinical trials demonstrating against common respiratory pathogens. It was not approved for pediatric use in children under 12 years of age. The product was withdrawn from the market in 2011 by its manufacturer, BioPharma, primarily due to low sales volumes and manufacturing challenges, with no associated safety or efficacy concerns prompting the discontinuation. Internationally, cefditoren pivoxil received approvals in various Asian countries following its Japanese launch, including licensing agreements for markets like and Korea by the early 2000s. In , initial approval occurred in in 2004, with subsequent registrations in other member states prior to 2010 under agreements with partners like . As of November 2025, no significant new regulatory milestones have been reported globally, though a new drug submission is under review by as of July 2025.

Availability

Cefditoren has been discontinued in the United States since 2011, with no generic versions available or revived as of 2025. In the European Union, it is not marketed and shows negligible consumption across EU/EEA countries. As a result, access is limited to specific regions outside North America and Europe. The drug remains available in Japan under the brand name Meiact, manufactured by Meiji Seika Pharma, and in India as Zostum-O by Zuventus Healthcare or Ceftor and other generics from manufacturers like Cipla. It is also marketed in select Asian markets, such as parts of Southeast Asia, and Latin American countries including Brazil and Mexico, where demand for oral cephalosporins supports ongoing distribution. Common formulations include 100 mg and 200 mg film-coated tablets, typically taken orally with food to enhance absorption. In approved regions, cefditoren is available as a prescription-only , with no over-the-counter status identified for mild infections. Low-cost generic versions in developing countries like are priced affordably, with a typical 10-tablet strip costing around ₹400–500 (approximately $5–6 USD), making a standard 10-day course accessible at $5–10 USD. As of November 2025, there have been no new regulatory approvals globally, and its use is confined to areas where local bacterial resistance patterns align with its broad-spectrum activity against respiratory pathogens.

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