Date post: | 11-Jan-2017 |
Category: |
Health & Medicine |
Upload: | rezaur-siddiqui |
View: | 43 times |
Download: | 3 times |
Cefexta An Extended Spectrum Antibiotic
Rezaur Rahman SiddiquiSenior Product Manager
UniMed UniHealth Pharmaceutical Ltd
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
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.
Recommended Therapy Textbook of Infectious Diseases 2017, 4th ED
Structure of Cefdinir
Unique Structure offers
Why Cefexta ?
Ref: Principles and Practice of INFECTIOUS DISEASES, 2015, C 21
Including TEM 1 by H. InfluenzaeBRO-1, BRO-2 by M. Catterhallis (Chormosomal)
Why Cefexta ?
Why Cefexta ?
Why Cefexta ?
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.
Why Cefexta ?
Why Cefexta ?
American Academy of Pediatrics recommended in Otitis Media as first-line therapyin children with penicillinallergyIn addition to acute otitis media, cefdinir is currentlyapproved bythefor the treatment of pharyngitis or tonsillitis in children and adults, as wellas uncomplicated skin and skin structure infections. It is also approved foruse in community acquired pneumonia, acute exacerbations of chronicbronchitis, and acute maxillarysinusitis in adolescents and adults.
Why Cefexta ?
Why Cefexta ?
CLINICAL EFFICACY in OTITIS MEDIA vs AM/C
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.
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
CLINICAL EFFICACY in OTITIS MEDIA
cefdinir resulted in an overall successful clinical response at end of treatment of 83%. Thisregimen was efficacious against penicillin-susceptible S. pneumoniae
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.
CLINICAL EFFICACY in OTITIS MEDIA
Journal of Clinical Therapeutics
CLINICAL EFFICACY in Other Indications
CLINICAL EFFICACY in Other Indications
CLINICAL EFFICACY in Other Indications
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:
PharmacologyMechanism of ActionThird-generation cephalosporin; inhibits mucopeptide synthesis in bacterial cell wall; typically bactericidal, depending on organism susceptibility, dose, and serum or tissue concentrations
AbsorptionBioavailability: 16-21% (capsule); 25% (suspension)Peak plasma time: 2-4 hrPlasma protein: 60-70%
DistributionDistributed into blister fluid, middle-ear fluid, tonsils, sinus tissue, bronchial mucosa, epithelial lining fluidVd: 0.29-1.05 L/kg (6 months-12 years); 0.06-0.64 L/kg (adults)
MetabolismNot appreciably metabolized
EliminationHalf-life: 100 min, Excretion: Urine (7-25% as unchanged drug)
Type of Infection Dosage Duration
AECB
300mg BID or 600mg OD
5-10 daysPharyngitis/Tonsillitis
Acute Bacterial Otitis Media
Acute Maxillary Sinusitis 10 daysCommunity Acquired Pneumonia
300mg BID 10 daysUncomplicated Skin and Skin Structure Infection
Age 13 to older
Dosage and administration:
Type of Infection Dosage Duration
Pharyngitis/Tonsillitis
7mg/kg BID or 14mg/kg OD
5-10 daysAcute Bacterial Otitis Media
Acute Maxillary Sinusitis 10 daysCommunity Acquired Pneumonia
7mg/kg BID 10 daysUncomplicated Skin and Skin Structure Infection
Age 6months to 12 years
Dosage and administration:
Drug interaction
Side EffectsDiarrheaVaginal MoniliasisNausea and Vomiting HeadacheRash etc
Dosing Modifications
• Renal impairment• CrCl <30 mL/min : Not to exceed 300 mg/day
or 7 mg/kg PO
• Hepatic impairment• No dosage adjustment necessaryCefdininr does not undergo appreciable metabolism in the liver and hepatic insufficiency is not expected to alter its pharmacokinetic profile.
Role of Clavulanic Acid &
Hepatotoxicity
• 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
• Alteration of the penicillin binding protein
• Production of Beta-lactamase enzyme
• Reduced drug accumulation: by Efflux
• Alteration of metabolic pathway:
Mechanism of antibiotic resistance
NOT all bacteria are able to produce Beta Lactamase to became resistance
Clavulanic Acid
So why should I take this combination?
FACTS
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
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
FACTS
• 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
• 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.
• 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
• Contraindication• History of jaundice/hepatic impairment due to
amoxicillin/clavulanic acid
https://www.medicines.org.uk/emc/medicine/19190
FACTS
CLAVUNALIC ACID
DRUG induced Hepatotoxicity
UniHealth Offers
Cefexta
www.unimedunihealth.com
Partner
Partner (Active Ingredients & Excipients)
Partner (Active Ingredients & Excipients)