Cefdinir and its role in otitis media, clinical study, indications, dosages, advantage, role of clavunalic acid, hepatotoxicity role all the research features are includes here to be prepared for Rajshahi Medical College, Focusing ENT specialist

1. Cefexta
An Extended Spectrum Antibiotic
Rezaur Rahman Siddiqui
Senior Product Manager
UniMed UniHealth Pharmaceutical Ltd

2. Otitis is one of the most frequent
diseases in early childhood and one of
the reasons for first prescription of
antibiotics.
Streptococcus pneumoniae (SP) is the
most frequent pathogen identified and
increasing resistance may influence
antibiotic treatment.
Key Concept in Otitis Media
Ref: Textbook of Infectious Disease 2017, P 236

3. Key Concept in Otitis Media
Ref: Drugs 2004; 64 (13): 1433-1464
S. pneumoniae 25–50% of cases,
H. influenzae (incidence 15–35%)
M. catarrhalis (3–20%).
β-lactamase producing M. catarrhalis strains
have become more prevalent during the last
30 years such that currently >90% of strains
worldwide are β-lactamase producers.

4. Recommended Therapy
Textbook of Infectious Diseases 2017, 4th ED

7. Structure of Cefdinir

8. Unique Structure offers

9. Why Cefexta ?
Ref: Principles and Practice of INFECTIOUS DISEASES, 2015, C 21
Including TEM 1 by H. Influenzae
BRO-1, BRO-2 by M. Catterhallis (Chormosomal)

10. Why Cefexta ?

11. Why Cefexta ?

12. Why Cefexta ?

13. Why Cefexta ?
in vitro potency of cefdinir against these pathogens and supports clinical
consideration of this agent as an alternative to parenteral cephems in infections
where adequate tissue and body fluid concentrations can be safely achieved.

14. Why Cefexta ?

15. Why Cefexta ?
Recommended as first-line therapy for URTIs5
American Academy of Pediatrics recommended in Otitis Media as first-
line therapy in children with penicillin allergy
In addition to acute otitis media, cefdinir is currently approved by the
for the treatment of pharyngitis or tonsillitis in children and adults, as well
as uncomplicated skin and skin structure infections. It is also approved for
use in community acquired pneumonia, acute exacerbations of chronic
bronchitis, and acute maxillarysinusitis in adolescents and adults.

16. Why Cefexta ?

17. Why Cefexta ?

18. CLINICAL EFFICACY in OTITIS MEDIA vs AM/C

19. CLINICAL EFFICACY in OTITIS MEDIA vs AM/C
Cefdinir given either once daily or twice-daily is a safe and effective treatment for pediatric
patients with acute suppurative otitis media.

20. Conclusion: For children with nonrefractory AOM, based only on clinical endpoints, 5
days of therapy with cefdinir 14 mg/kg divided or 300mg twice daily was comparable
overall with 10 days of therapy with low dose amoxicillin/clavulanate 45/6.4 mg/kg
divided twice daily.
(Pediatr Infect Dis J 2004;23: 834–838)
CLINICAL EFFICACY in OTITIS MEDIA vs AM/C

21. CLINICAL EFFICACY in OTITIS MEDIA
cefdinir resulted in an overall successful clinical response at end of treatment of 83%. This
regimen was efficacious against penicillin-susceptible S. pneumoniae

22. CLINICAL EFFICACY in OTITIS MEDIA
Conclusions. A 5-day regimen of cefdinir was effective in the eradication of the common
causative pathogens of nonrefractory AOM, including intermediate penicillin-resistant S.
pneumoniae and beta-lactamase-producing organisms.
Cefdinir should be considered a suitable second line antibiotic for AOM.

23. CLINICAL EFFICACY in OTITIS MEDIA
Journal of Clinical Therapeutics

24. CLINICAL EFFICACY in Other Indications

25. CLINICAL EFFICACY in Other Indications

26. CLINICAL EFFICACY in Other Indications

27. The total daily dose for all infections is 600 mg.
Once daily dosing for 10 days is as effective as
BID dosing.
Once daily dosing has not been studied in
pneumonia or skin infections.
Cefexta Capsules may be taken without regard
to meals.
Dosage and administration:

28. Pharmacology
Mechanism of Action
Third-generation cephalosporin; inhibits mucopeptide synthesis in bacterial cell
wall; typically bactericidal, depending on organism susceptibility, dose, and serum
or tissue concentrations
Absorption
Bioavailability: 16-21% (capsule); 25% (suspension)
Peak plasma time: 2-4 hr
Plasma protein: 60-70%
Distribution
Distributed into blister fluid, middle-ear fluid, tonsils, sinus tissue, bronchial
mucosa, epithelial lining fluid
Vd: 0.29-1.05 L/kg (6 months-12 years); 0.06-0.64 L/kg (adults)
Metabolism
Not appreciably metabolized
Elimination
Half-life: 100 min, Excretion: Urine (7-25% as unchanged drug)

29. Type of Infection Dosage Duration
AECB
300mg BID or
600mg OD
5-10 days
Pharyngitis/Tonsillitis
Acute Bacterial Otitis
Media
Acute Maxillary Sinusitis 10 days
Community Acquired
Pneumonia
300mg BID 10 days
Uncomplicated Skin and
Skin Structure Infection
Age 13 to older
Dosage and administration:

30. Type of Infection Dosage Duration
Pharyngitis/Tonsillitis
7mg/kg BID or
14mg/kg OD
5-10 daysAcute Bacterial Otitis
Media
Acute Maxillary Sinusitis 10 days
Community Acquired
Pneumonia
7mg/kg BID 10 days
Uncomplicated Skin and
Skin Structure Infection
Age 6months to 12 years
Dosage and administration:

31. Drug interaction

32. Side Effects
Diarrhea
Vaginal Moniliasis
Nausea and Vomiting
Headache
Rash etc

33. Dosing Modifications
•Renal impairment
•CrCl <30 mL/min : Not to exceed 300 mg/day
or 7 mg/kg PO
•Hepatic impairment
•No dosage adjustment necessary
Cefdininr does not undergo appreciable
metabolism in the liver and hepatic insufficiency
is not expected to alter its pharmacokinetic
profile.

34. Role of Clavulanic Acid
&
Hepatotoxicity

35. • Isolated from Streptomyces clavuligerus in 1970s
• Not effective by itself as an antibiotic
• It is a β-lactamase inhibitor or an irreversible
‘suicide’ inhibitor or called suicidal drug
• It has a high affinity for the class A β-lactamases.
Inclcudes TEM and SHV enzymes, is found frequently
in members of the
– Enterobacteriaceae,
– Haemophilus influenzae and Neisseria gonorrhoeae.
– Klebsiella pneumoniae, Proteus mirabilis, Proteus
vulgaris, Bacteroides fragilis and Moraxella catarrhalis
Clavulanic Acid
Journal of Antimicrobial Chemotherapy (2003) 52, 18–23

36. • Alteration of the penicillin binding protein
• Production of Beta-lactamase enzyme
• Reduced drug accumulation: by Efflux
• Alteration of metabolic pathway:
Mechanism of antibiotic resistance

37. NOT all bacteria are able to produce Beta Lactamase to became resistance
Clavulanic Acid
So why should I take this combination?

38. FACTS

39. Chronic liver injury induced by drugs: a
systematic review
Most common drugs associated with drug-
induced liver injury, antibiotics
• Amoxicillin-clavulanic acid,
• Trimethoprim-sulfamethoxazole,
• Azithromycin) are most likely to cause
chronic injury.
Liver Int. 2015 Nov 8.
FACTS

40. Comedications alter drug-induced liver injury
reporting frequency: Data mining in the WHO
VigiBase™
• They examined the effect of these drug-drug interactions
on liver safety reports of four drugs highly associated
with hepatotoxicity. In the WHO VigiBase™, liver event
reports were examined for
• acetaminophen,
• isoniazid,
• valproic acid, and
• amoxicillin/clavulanic acid.
Regul Toxicol Pharmacol. 2015 Aug;72
FACTS

41. FACTS

42. • associated with jaundice and can be severe
and prolonged (with jaundice lasting 4 to 24
weeks)
http://livertox.nih.gov/AmoxicillinClavulanate.htm
Amoxicillin/clavulanate is the most
common cause of drug induced acute liver
injury both in the USA and Europe

43. • The liver injury appears to be due to the clavulanate rather
than amoxicillin, as re-exposure to amoxicillin alone has
not been associated with recurrence, whereas re-exposure
to the combination is usually followed by a more rapid
onset of a more severe hepatic injury, which can include
prolonged cholestasis and development of cirrhosis.
http://livertox.nih.gov/AmoxicillinClavulanate.htm
• cause -unknown
• probably immunoallergic in origin.

44. • Other beta lactamase inhibitors (tazobactam
and subactam) have not been reported to
cause a similar hepatic injury, although it has
been reported with other penicillins when
combined with clavulanate
(ticarcillin/clavulanate)
http://livertox.nih.gov/AmoxicillinClavulanate.htm

45. • Contraindication
• History of jaundice/hepatic impairment due to
amoxicillin/clavulanic acid
https://www.medicines.org.uk/emc/medicine/19190
FACTS

46. CLAVUNALIC
ACID
DRUG induced Hepatotoxicity

47. UniHealth Offers

48. Cefexta

49. www.unimedunihealth.com

50. Partner

51. Partner (Active Ingredients & Excipients)

52. Partner (Active Ingredients & Excipients)