Cefditoren

Pharmacologic Category

Antibiotic, Cephalosporin (Third Generation)

Dosing: Adult

Acute bacterial exacerbation of chronic bronchitis: Oral: 400 mg twice daily for 10 days

Community-acquired pneumonia: Oral: 400 mg twice daily for 14 days

Pharyngitis, tonsillitis, uncomplicated skin and skin structure infections: Oral: 200 mg twice daily for 10 days

* See Dosage and Administration in AHFS Essentials for additional information.

Dosing: Geriatric

Refer to adult dosing.

Dosing: Renal Impairment: Adult

CrCl >50 mL/minute/1.73 m²: No dosage adjustment necessary.

CrCl 30 to 49 mL/minute/1.73 m²: Maximum dose: 200 mg twice daily

CrCl <30 mL/minute/1.73 m²: Maximum dose: 200 mg once daily

End-stage renal disease (ESRD): There are no specific dosage adjustments provided in the manufacturer’s labeling; safety and efficacy have not been established.

Dosing: Hepatic Impairment: Adult

Mild-to-moderate impairment (Child-Pugh class A or B): No dosage adjustment necessary.

Severe impairment (Child-Pugh class C): There are no dosage adjustments provided in the manufacturer’s labeling (has not been studied).

Dosing: Pediatric

Bronchitis, chronic; acute bacterial exacerbation: Children ≥12 years and Adolescents: Oral: 400 mg twice daily for 10 days.

Pharyngitis, tonsillitis:

Infants ≥8 months and Children: Limited data available: Oral: 3 mg/kg/dose 3 times daily for 5 days; dosing based on a prospective study comparing 5 days of cefditoren (n=103, age range: 0.7 to 12.4 years) to 10 days of amoxicillin (n=155); efficacy and tolerability were similar for both groups; Note: Cefditoren was administered as a granule formulation that is not available in the US (Ozaki 2008).

Children ≥12 years and Adolescents: Oral: 200 mg twice daily for 10 days.

Pneumonia, community-acquired: Children ≥12 years and Adolescents: Oral: 400 mg twice daily for 10 to 14 days. Note: Based on experience with other antibiotics, a shorter duration (10 days) of therapy may be appropriate based on patient severity and response (IDSA [Bradley 2011]).

Rhinosinusitis, acute bacterial: Limited data available: Children and Adolescents ≤15 years: Oral: 4 to 6 mg/kg/dose twice daily for 14 day; reported maximum daily dose: 400 mg/day (Poachanukoon 2008; Poachanukoon 2015); dosing based on two prospective studies. In one trial, cefditoren (4 to 6 mg/kg/dose twice daily) (n=66) was compared to high-dose amoxicillin/clavulanate (n=72) for acute bacterial rhinosinusitis in patients aged 1 to 15 years; both treatments offered similar efficacy; however, cefditoren was associated with less diarrhea (Poachanukoon 2008). Another study compared low-dose cefditoren (4 to 6 mg/kg/dose twice daily) to high-dose cefditoren (8 to 12 mg/kg/dose twice daily); efficacy and tolerability were similar between the groups (Poachanukoon 2015). Note: Cefditoren was administered as a granule formulation that is not available in the US.

Skin and skin structure infections, uncomplicated: Children ≥12 years and Adolescents: Oral: 200 mg twice daily for 10 days.

Dosing: Renal Impairment: Pediatric

Children ≥12 years and Adolescents:

CrCl ≥50 mL/minute/1.73 m²: No dosage adjustment necessary

CrCl 30-49 mL/minute/1.73 m²: Maximum dose: 200 mg twice daily

CrCl <30 mL/minute/1.73 m²: Maximum dose: 200 mg once daily

End stage renal disease: Appropriate dose has not been determined

Dosing: Hepatic Impairment: Pediatric

Children ≥12 years and Adolescents:

Mild to moderate impairment (Child-Pugh Class A or B): No dosage adjustment necessary.

Severe impairment (Child-Pugh Class C): There are no dosage adjustment guidelines provided in the manufacturer's labeling (not studied).

Calculations

Use: Labeled Indications

Treatment of acute bacterial exacerbation of chronic bronchitis or community-acquired pneumonia (due to susceptible organisms including Haemophilus influenzae, Haemophilus parainfluenzae, Streptococcus pneumoniae-penicillin susceptible only, Moraxella catarrhalis); pharyngitis or tonsillitis (Streptococcus pyogenes); and uncomplicated skin and skin-structure infections (Staphylococcus aureus - not MRSA, Streptococcus pyogenes)

* See Uses in AHFS Essentials for additional information.

Class and Related Monographs

Cephalosporins

Clinical Practice Guidelines

Pneumonia, Community-Acquired:

ATS/IDSA, "Diagnosis and Treatment of Adults With Community-Acquired Pneumonia," 2019. Note: Information contained within this monograph is pending revision based on these more recent guidelines.

Administration: Oral

Administer with meals.

Administration: Pediatric

Oral: Administer with meals.

Dietary Considerations

Cefditoren should be taken with meals. Plasma carnitine levels are decreased during therapy (39% with 200 mg dosing, 63% with 400 mg dosing); normal concentrations return within 7-10 days after treatment is discontinued.

Storage/Stability

Store at 25°C (77°F); excursions permitted between 15°C and 30°C (59°F and 86°F). Protect from light and moisture.

Medication Patient Education with HCAHPS Considerations

• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

• Patient may experience nausea or diarrhea. Have patient report immediately to prescriber bruising, bleeding, chills, sore throat, severe loss of strength and energy, unable to pass urine, passing out, seizures, vaginal pain, itching, and discharge, or signs of Clostridium difficile (C. diff)-associated diarrhea (abdominal pain or cramps, severe diarrhea or watery stools, or bloody stools) (HCAHPS).

• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for healthcare professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience and judgment in diagnosing, treating and advising patients.

Medication Safety Issues

International issues:

Contraindications

Hypersensitivity to cefditoren, any component of the formulation, other cephalosporins, or milk protein; carnitine deficiency or inborn errors of metabolism that may result in clinically significant carnitine deficiency.

Warnings/Precautions

Concerns related to adverse effects:

• Elevated INR: May be associated with increased INR, especially in nutritionally-deficient patients, prolonged treatment, hepatic or renal disease.

• Penicillin allergy: Use with caution in patients with a history of penicillin allergy, especially IgE-mediated reactions (eg, anaphylaxis, angioedema, urticaria).

• Superinfection: Prolonged use may result in fungal or bacterial superinfection, including C. difficile-associated diarrhea (CDAD) and pseudomembranous colitis; CDAD has been observed >2 months postantibiotic treatment.

Disease-related concerns:

• Carnitine deficiency: Do not use in patients with carnitine deficiency; causes renal excretion of carnitine.

• Hepatic impairment: Use with caution in patients with hepatic impairment.

• Renal impairment: Use with caution in patients with renal impairment; modify dosage in moderate-to-severe impairment.

• Seizure disorders: Use with caution in patients with a history of seizure disorder; high levels, particularly in the presence of renal impairment, may increase risk of seizures.

Dosage form specific issues:

• Sodium caseinate: Tablets contain sodium caseinate, which may cause hypersensitivity reactions in patients with milk protein hypersensitivity; this does not affect patients with lactose intolerance.

Other warnings/precautions:

• Duration of therapy: Not for long-term therapy due to the possible development of carnitine deficiency over time.

* See Cautions in AHFS Essentials for additional information.

Geriatric Considerations

Adjust dose for renal function.

Warnings: Additional Pediatric Considerations

Carnitine deficiency may result from prolonged use; cefditoren causes renal excretion of carnitine; plasma carnitine concentrations usually return to normal range within 7 to 10 days after discontinuation of therapy. Therapy with cefditoren is contraindicated in patients with carnitine deficiency or inborn errors of metabolism that may result in clinically significant carnitine deficiency.

Pregnancy Risk Factor

Pregnancy Considerations

Adverse events have not been observed in animal reproduction studies. An increase in most types of birth defects was not found following first trimester exposure to cephalosporins.

Breast-Feeding Considerations

It is not known whether cefditoren is excreted in human milk. The manufacturer recommends caution when using cefditoren during breast-feeding. If cefditoren reaches the breast milk, the limited oral absorption may minimize the effect on the nursing infant. Nondose-related effects could include modification of bowel flora.

Lexicomp Pregnancy & Lactation, In-Depth

Cefditoren

Briggs' Drugs in Pregnancy & Lactation

Cefditoren

Adverse Reactions

>10%: Gastrointestinal: Diarrhea (11% to 15%)

1% to 10%:

Endocrine & metabolic: Increased serum glucose (1% to 2%)

Gastrointestinal: Nausea (4% to 6%), abdominal pain (2%), dyspepsia (1% to 2%), vomiting (1%)

Genitourinary: Vulvovaginal candidiasis (3% to 6%), hematuria (3%), urine abnormality (increased leukocytes: 2%)

Hematologic & oncologic: Decreased hematocrit (2%)

Nervous system: Headache (2% to 3%)

<1%, postmarketing, and/or case reports: Abnormal dreams, acute renal failure, decreased serum albumin, anorexia, arthralgia, asthma, change in WBC count (decrease or increase), coagulation time increased, constipation, decreased hemoglobin, decreased neutrophils, decreased serum calcium, decreased serum sodium, diaphoresis, dizziness, drowsiness, dysgeusia, eosinophilic pneumonitis, eosinophilia, eructation, erythema multiforme, facial edema, fever, flatulence, fungal infection, gastritis, gastrointestinal disease, hyperglycemia, hypersensitivity reaction, hypochloremia, hypoglycemia (Kennedy 2019), hypophosphatemia, increased appetite, increased blood urea nitrogen, increased serum ALT, increased serum AST, increased serum cholesterol, increased serum potassium, increased thirst, insomnia, interstitial pneumonitis, leukopenia, leukorrhea, lymphocytosis, myalgia, nervousness, oral candidiasis, oral mucosa ulcer, pain, peripheral edema, pharyngitis, positive direct Coombs test, pseudomembranous colitis, proteinuria, pruritus, rhinitis, sinusitis, skin rash, Stevens-Johnson syndrome, stomatitis, thrombocythemia, thrombocytopenia, toxic epidermal necrolysis, urinary frequency, urticaria, vaginitis, weakness, weight loss, xerostomia

* See Cautions in AHFS Essentials for additional information.

Allergy and Idiosyncratic Reactions

Cephalosporin Allergy

Metabolism/Transport Effects

None known.

Drug Interactions Open Interactions

Antacids: May decrease the serum concentration of Cefditoren. Management: Concomitant use of cefditoren with antacids is not recommended. Consider alternative methods to control acid reflux (eg, diet modification) or alternative antimicrobial therapy. If antacid therapy can not be avoided, separate dosing by several hours. Risk D: Consider therapy modification

Histamine H2 Receptor Antagonists: May decrease the serum concentration of Cefditoren. Management: Concomitant use of cefditoren with H2-antagonists and antacids is not recommended. Consider alternative methods to control acid reflux (eg, diet modification) or alternative antimicrobial therapy if use of H2-antagonists can not be avoided. Risk D: Consider therapy modification

Probenecid: May increase the serum concentration of Cephalosporins. Risk C: Monitor therapy

Proton Pump Inhibitors: May decrease the serum concentration of Cefditoren. Management: If possible, avoid use of cefditoren with proton pump inhibitors (PPIs). Consider alternative methods to minimize/control acid reflux (eg, diet modification) or alternative antimicrobial therapy if use of PPIs can not be avoided. Risk D: Consider therapy modification

Vitamin K Antagonists (eg, warfarin): Cephalosporins may enhance the anticoagulant effect of Vitamin K Antagonists. Risk C: Monitor therapy

Food Interactions

Moderate- to high-fat meals increase bioavailability and maximum plasma concentration. Management: Take with meals. Maintain adequate hydration, unless instructed to restrict fluid intake.

Test Interactions

May induce a positive direct Coomb’s test. May cause a false-negative ferricyanide test. Glucose oxidase or hexokinase methods recommended for blood/plasma glucose determinations. False-positive urine glucose test when using copper reduction based assays (eg, Clinitest®).

Monitoring Parameters

Monitor renal function. Observe for signs and symptoms of anaphylaxis during first dose.

Advanced Practitioners Physical Assessment/Monitoring

Assess results of culture/sensitivity tests and patient's allergy history prior to therapy. Teach patient to report hypersensitivity, opportunistic infection, gastrointestinal upset, and diarrhea.

Nursing Physical Assessment/Monitoring

Results of culture/sensitivity tests and patient's allergy history should be assessed prior to therapy. Teach patient to report hypersensitivity, opportunistic infection, gastrointestinal upset, and diarrhea.

Dosage Forms: US

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Tablet, Oral:

Spectracef: 400 mg [contains sodium caseinate]

Generic: 200 mg, 400 mg

Anatomic Therapeutic Chemical (ATC) Classification

J01DD16

Generic Available (US)

Yes

Pricing: US

Tablets (Cefditoren Pivoxil Oral)

200 mg (per each): $14.74

400 mg (per each): $14.74

Tablets (Spectracef Oral)

400 mg (per each): $17.85

Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.

Mechanism of Action

Inhibits bacterial cell wall synthesis by binding to one or more of the penicillin-binding proteins (PBPs) which in turn inhibits the final transpeptidation step of peptidoglycan synthesis in bacterial cell walls, thus inhibiting cell wall biosynthesis. Bacteria eventually lyse due to ongoing activity of cell wall autolytic enzymes (autolysins and murein hydrolases) while cell wall assembly is arrested.

Pharmacodynamics/Kinetics

Distribution: 9.3 ± 1.6 L

Protein binding: 88% (in vitro), primarily to albumin

Metabolism: Cefditoren pivoxil is hydrolyzed by esterases to cefditoren (active) and pivalate; cefditoren is not appreciable metabolized

Bioavailability: ~14% to 16%, increased by moderate- to high-fat meal (mean AUC by 70%; maximum plasma concentration by 50%)

Half-life elimination: 1.6 ± 0.4 hours; increased with moderate (2.7 hours) and severe (4.7 hours) renal impairment

Time to peak: 1.5 to 3 hours

Excretion: Urine (as cefditoren and pivaloylcarnitine)

Pharmacodynamics/Kinetics: Additional Considerations

Renal function impairment:

Moderate impairment (CrCl 30 to 49 mL/minute/1.73 m²): Unbound C_max is 90% higher, AUC is 232% higher

Severe impairment (CrCl less than 30 mL/minute/1.73 m²): Unbound C_max is 114% higher, AUC is 324% higher

Geriatric: C_max is increased 26% and AUC 33%, half-life is 16% to 26% longer, and renal clearance is 20% to 24% lower.

Dental Use

Bactericidal antibiotic for infections due to susceptible organisms

* See Uses in AHFS Essentials for additional information.

Local Anesthetic/Vasoconstrictor Precautions

No information available to require special precautions

Effects on Dental Treatment

No significant effects or complications reported

Effects on Bleeding

No information available to require special precautions

Dental Usual Dosing

Dental infections (off-label use): Children ≥12 years and Adults: Oral: 400 mg twice daily for 10 days

Index Terms

Cefditoren Pivoxil

FDA Approval Date

August 29, 2001

References

Bradley JS, Byington CL, Shah SS, et al. The management of community-acquired pneumonia in infants and children older than 3 months of age: clinical practice guidelines by the Pediatric Infectious Diseases Society and the Infectious Diseases Society of America. Clin Infect Dis. 2011;53(7):e25-76.[PubMed 21880587]

Darkes MJ and Plosker GL, “Cefditoren Pivoxil,” Drugs, 2002, 62(2):319-36.[PubMed 11817976]

Kennedy KE, Teng C, Patek TM, Frei CR. Hypoglycemia associated with antibiotics alone and in combination with sulfonylureas and meglitinides: an epidemiologic surveillance study of the FDA Adverse Event Reporting System (FAERS) [published online December 20, 2019]. Drug Saf. 2019;10.[PubMed 31863282]

Metlay JP, Waterer GW, Long AC, et al. Diagnosis and treatment of adults with community-acquired pneumonia. An official clinical practice guideline of the American Thoracic Society and Infectious Diseases Society of America. Am J Resp Crit Care Med. 2019;200(7):e45-e67. doi:10.1164/rccm.201908-1581ST.[PubMed 31573350]

Ozaki T, Nishimura N, Suzuki M, et.al. Five-day oral cefditoren pivoxil versus 10-day oral amoxicillin for pediatric group A streptococcal pharyngotonsillitis. J Infect Chemother. 2008;14:213-218.[PubMed 18574657]

Poachanukoon O, Kitcharoensakkul M. Efficacy of cefditoren pivoxil and amoxicillin/clavulanate in the treatment of pediatric patientswith acute bacterial rhinosinusitis in Thailand: a randomized, investigator-blinded, controlled trial. Clin Ther. 2008;30(10):1870-1879.[PubMed 19014842]

Poachanukoon O, Tangsathapornpong A, Tanuchit S. A comparison of cefditoren pivoxil 8-12 mg/kg/day and cefditoren pivoxil 16-20 mg/kg/day in treatment of children with acute presumed bacterial rhinosinusitis: a prospective, randomized, investigator-blinded, parallel-group study. Clin Exp Otorhinolaryngol. 2015;8(2):129-135.[PubMed 26045911]

Spectracef (cefditoren pivoxil) [prescribing information]. Cornerstone Therapeutics: Cary, NC; 2011.

Spectracef (cefditoren) [prescribing information]. Westmount, Quebec: Vansen Pharma Inc; June 2013.

Brand Names: International

Ceftor (BD); Ceftoren (BD); Geralcef (EG); Giasion (IT); Hidetron (EG); Meiact (AE, BH, CN, ES, ET, HK, JO, JP, KR, KW, LB, QA, SA, TH, VN); Meiacton (EG); MS Fine Granules 10% (ID); Spacef (BD); Spectracef (CR, DO, ES, GR, HN, NI, PA, PT, SV); Spektracef (TR); Telo (ES)

Last Updated 3/6/20

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