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Friday, February 12, 2016

Augmentin Dosing: An Update

Availability in HKGU
  • IV Amoxycillin 1000mg/ Clavulanate 200mg (Augmentin)- 5:1
  • Tablet Amoxycillin 500mg/ Clavulanate 125mg (Augmentin) – 4:1
  • Syrup Amoxycillin 200mg/ Clavulanate 28mg in 5ml (Clamovid BID Granules) – 7:1
ORAL AUGMENTIN
Adult
  • mean AUC values for amoxicillin are essentially the same following BD dosing of AUGMENTIN 875/125 mg tablet (7:1) or TDS dosing of AUGMENTIN 500/125 mg tablet (4:1), in adults.
  • No differences between are seen when comparing the amoxicillin T1/2, or Cmax after normalisation for the different doses of amoxicillin administered.
  • Similarly, no differences are seen for the clavulanate T1/2, Cmax or AUC values after appropriate dose normalisation
Dosing Guide
  • Respiratory Tract Infection
    • Mild-Moderate (625mg BD) for 10 days
    • Severe / COPD (625 mg TDS) 7-10 days 
  • Other type of infections are generally dosed at 625mg TDS (check specific indications before recommending)  


Children
  • The clinical efficacy of AUGMENTIN DUO 400 (7:1 ratio) and AUGMENTIN FORTE (4:1 ratio) have been shown to be comparable in the approved indications, despite the differences in some pharmacokinetic parameters.
Oral Suspension Dosing
AUC (μg.h/mL)
Cmax (μg/mL)
Amoxycillin
Clavulanate
Amoxycillin
Clavulanate
AUGMENTIN 7:1 (45mg/kg/day)
Given as BD
35.2
13.3
12.0
5.49
AUGMENTIN 4:1 (40mg/kg/day)
Given as TDS
18.6
5.51
7.33
2.66
  • AUGMENTIN DUO (7:1) contains aspartame, and should be used with caution in patients with phenylketonuria.
  • In children with renal impairment, dosage should be adjusted according to degree of impairment using the alternative AUGMENTIN (4:1 ratio) 125mg/31.25mg or 250mg/62.5mg formulations.
  • AUGMENTIN DUO (7:1) formulation is not recommended for use in children with renal impairment.
Dosing
Neonates and infants aged < 12 weeks (3 months):
  • Due to incompletely developed renal function affecting elimination of amoxicillin in this age group, the recommended dose of AUGMENTIN is 30 mg/kg/day divided every 12 hours, based on the amoxicillin component. 
  • Clavulanate elimination is unaltered in this age group. 
  • Experience with the 200 mg/5 mL formulation in this age group is limited and, thus, use of the 125 mg/5 mL oral suspension is recommended.

Pediatric Patients Weighing 40 kg and More:

Usual Dose

Augmentin 500/125mg (4:1) BD

Augmentin 250/125mg (2:1) TDS

Severe Infections

Augmentin 875/125mg (7:1) BD

Augmentin 500/125mg (4:1) TDS

 

significantly fewer experienced severe diarrhea or withdrawals with diarrhea versus adults treated with 500 mg every 8 hours

Other Dosing Recomendations:
 
Other Affecting Factors
  • For clavulanate AUC and Cmax, the highest mean values and smallest inter-subject variabilities were achieved by administering AUGMENTIN at the start of a meal, compared to the fasting state or 30 or 150 minutes after the start of a meal.
  • Use the 7:1 formulation (ie, bid formulation) in higher doses to minimize GI tract effects
INTRAVENOUS AUGMENTIN
Intravenous Dosing
  • Children 0-3 months:
    • Infants < 4kg  : 30mg/kg* AUGMENTIN every 12 hours
    • infants >4kg  : 30mg/kg* AUGMENTIN every 8 hours
  • Children 3 months - 12 years:
    • Usually 30mg/kg* AUGMENTIN 8 hourly.
    • In more serious infections, increase frequency to 6 hourly intervals.
  • Adults and Children 40kg and over:
    • Usually 1.2g 8 hourly.
    • In more serious infections, increase frequency to 6 hourly intervals.
*Each 30mg AUGMENTIN provides 5mg clavulanic acid with 25mg amoxicillin.
Dosage for surgical prophylaxis:
  • procedures for less than 1 hour are : 1.2g at induction of anaesthesia.
  • Longer operations : subsequent doses of 1.2g (up to 4 doses in 24 hours)
  • this regime can be continued for several days if the procedure has significantly increased the risk of infection.
References:
  1. AUGMENTIN® DUO 400 SUSPENSION PRODUCT INFORMATION
  2. AUGMENTINTMSUSPENSION 228 MG/5 ml and 457 MG/5 ml Data Sheet
  3. Augmentin , Amoxicillin sodium/potassium clavulanate (injections)Data Sheet
  4. http://www.drugs.com/pro/augmentin.html
  5. http://www.drugs.com/dosage/augmentin-oral-suspension.html
  6. http://reference.medscape.com/drug/augmentin-amoxicillin-clavulanate-342474

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