Cefditoren

J01D - Other beta-lactam antibacterials ATC J01DD16 Small molecule Natural product

JFDA label: Meiact

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.

Indications

Off-label

Bacterial Infections

Class profile

gramStatus	Both
spectrumBreadth	Broad
atypicalCoverage	No
isBactericidal	1
moaCategory	Cell wall synthesis inhibitor (beta-lactam, 3rd generation cephalosporin)
pdIndex	Time-dependent
postAntibioticEffect	None
mrsaCoverage	0
resistanceMechanisms	ESBL production,AmpC beta-lactamase

Contraindications

Source: Lexicomp

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

Adverse Reactions

Very Common >10%Common 1–10%Uncommon 0.1–1% Rare 0.01–0.1%Very Rare <0.01%Not Known

Nervous system disorders (1)

Common Headache

Renal and urinary disorders (3)

Common hematuria · urine abnormality · Vulvovaginal candidiasis

Blood and lymphatic system disorders (1)

Common Decreased hematocrit

Metabolism and nutrition disorders (1)

Common Increased serum glucose

Gastrointestinal disorders (4)

Common abdominal pain · dyspepsia · Nausea · vomiting

Other (1)

Very Common Gastrointestinal: Diarrhea

Dosing

Source: Lexicomp

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

(For additional information see "Cefditoren: Pediatric drug information") Children ≥12 years and Adolescents: Refer to adult dosing.

Refer to adult dosing.

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 2: 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.

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).

Warnings & Precautions

Source: Lexicomp

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.

Pregnancy & Lactation

Pregnancy

FDA category B

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.

Lactation

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.

Monitoring

Efficacy	Culture and susceptibility testing; clinical resolution (temperature, WBC, CRP, procalcitonin)
Toxicity	Renal function (dose adjustment in renal impairment); hepatic function for hepatically cleared agents; signs of C. difficile infection (diarrhoea)
Clinical pearl	Culture results guide de-escalation to narrower-spectrum therapy. Review antibiotic appropriateness at 48–72 h (antimicrobial stewardship).
Counseling	Complete the full course. Report persistent diarrhoea, rash, or lack of improvement after 48–72 h.

Chemistry & Properties

Formula	C19H18N6O5S3
Molecular weight	506.59 g/mol
IUPAC name	(6R,7R)-7-[[(2Z)-2-(2-amino-1,3-thiazol-4-yl)-2-methoxyiminoacetyl]amino]-3-[(Z)-2-(4-methyl-1,3-thiazol-5-yl)ethenyl]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid
CAS	104145-95-1
PubChem CID	9870843
InChIKey	`KMIPKYQIOVAHOP-YLGJWRNMSA-N`
logP	1.29 (XLogP 0.7)
Polar surface area	160.1 Å²
H-bond acceptors / donors	11 / 3
Drug-likeness (QED)	0.29
Lipinski violations	2

SMILES

CO/N=C(\C(=O)N[C@@H]1C(=O)N2C(C(=O)O)=C(/C=C\c3scnc3C)CS[C@H]12)c1csc(N)n1

Biology & Pharmacokinetics

Pharmacokinetics

BBB penetrant	No

Enzyme interactions

Enzyme	Role	Detail
CYP2C8	Inhibitor	—

Transporters

BCRP (Inhibitor)BSEP (Inhibitor)MRP1 (Inhibitor)OATP1B1 (Inhibitor)OATP1B3 (Inhibitor)P-gp (Inhibitor)OATP1B1 (Substrate)OATP1B3 (Substrate)P-gp (Substrate)PEPT1 (Substrate)

Drug–drug interactions (25, DDInter)

Interacting drug	Severity	Management
Aluminum hydroxide	moderate
Calcium carbonate	moderate
Chloramphenicol	moderate
Cimetidine	moderate
Dexlansoprazole	moderate
Dicoumarol	moderate
Esomeprazole	moderate
Ethinylestradiol	moderate
Famotidine	moderate
Lansoprazole	moderate
Magaldrate	moderate
Magnesium carbonate	moderate
Magnesium hydroxide	moderate
Magnesium oxide	moderate
Mycophenolic acid	moderate
Nizatidine	moderate
Omeprazole	moderate
Pantoprazole	moderate
Pemetrexed	moderate
Rabeprazole	moderate
Ranitidine	moderate
Ranitidine (bismuth citrate)	moderate
Sodium bicarbonate	moderate
Sodium citrate	moderate
Warfarin	moderate

Registered Products (1)

Brand	Form / strength	Pack	Agent	Citizen (JOD)
Meiact	Tablet (as Pivoxil) 200 mg	20 tab	Sukhtian Group	18.940