Megamox is indicated for the treatment of the following infections in adults and children (see sections 4.2, 4.4 and 5.1):

• Acute bacterial sinusitis (adequately diagnosed)
• Acute otitis media
• Acute exacerbations of chronic bronchitis (adequately diagnosed)
• Community acquired pneumonia
• Cystitis
• Pyelonephritis
• Skin and soft tissue infections in particular cellulitis, animal bites, severe dental abscess with spreading cellulitis.
• Bone and joint infections, in particular osteomyelitis.

Consideration should be given to official guidance on the appropriate use of antibacterial agents.

 

(See Section 5.2 Pharmacokinetic properties-special patient population)

Doses  are  expressed  throughout  in  terms  of  amoxicillin/clavulanic  acid  content  except when doses are stated in terms of an individual component.

The  dose  of  Megamox  that  is selected to  treat  an  individual  infection  should  take  into account:

• The  expected  pathogens  and  their  likely  susceptibility  to  antibacterial  agents  (see section 4.4)
•  The severity and the site of the infection
• The age, weight and renal function of the patient as shown below.

The use of alternative presentations of Megamox (e.g. those that provide higher doses of amoxicillin and/or different ratios of amoxicillin to clavulanic acid) should be considered as necessary (see sections 4.4 and 5.1).

For adults and children ≥ 40 kg, this formulation of Megamox provides a total daily dose of  1500  mg  amoxicillin/375  mg  clavulanic  acid,  when  administered  as  recommended below. For children < 40 kg, this formulation of Megamox provides a maximum daily dose of  2400  mg  amoxicillin/600  
mg  clavulanic  acid,  when  administered  as  recommended below.  If  it  is  considered  that  a  higher  daily  dose  of  amoxicillin  is  required,  it  is recommended  that  another  preparation  of  Megamox  is  selected  in  order  to  avoid administration of unnecessarily high daily doses 
of clavulanic acid (see sections 4.4 and 5.1)

The  duration  of  therapy  should  be  determined  by  the  response  of  the  patient.  Some infections (e.g. osteomyelitis) require longer periods of treatment. Treatment should not be  extended  beyond  14  days  without  review  (see  section  4.4  regarding  prolonged therapy).

• Adults and children ≥ 40 kg

One 500 mg/125 mg dose taken three times a day.

• Children < 40 kg

20 mg/5 mg/kg/day to 60 mg/15 mg/kg/day given in three divided doses. Children may be treated with Megamox tablets or suspensions.
Children aged 6 years and below should preferably be treated with Megamox suspension or paediatric sachets.
No  clinical  data  are  available  on  doses  of  Megamox  4:1  formulations  higher  than  40 mg/10 mg/kg per day in children under 2 years.

 

• Elderly

No dose adjustment is considered necessary.

• Renal impairment

Dose adjustments are based on the maximum recommended level of amoxicillin.
No  adjustment  in  dose  is  required  in  patients  with  creatinine  clearance  (CrCl)  greater than 30 ml/min.

_ Adults and children ≥ 40 kg

CrCl: 10-30 ml/min	500 mg/125 mg twice daily
CrCl < 10 ml /min	500 mg/125 mg once daily
Haemodialysis	500 mg/125 mg every 24 hours, plus 500 mg/125 mg during dialysis, to be repeated at the end of dialysis (as serum concentrations of both amoxicillin and clavulanic acid are decreased)

_ Children < 40 kg

CrCl: 10-30 ml/min	15 mg/3.75 mg/kg twice daily (maximum 500 mg/125 mg twice daily).
CrCl < 10 ml /min	15 mg/3.75 mg/kg as a single daily dose (maximum 500 mg/125 mg).
Haemodialysis	15 mg/3.75 mg/kg per day once daily. Prior to haemodialysis 15 mg/3.75 mg/kg. In order to restore circulating drug levels, 15 mg/3.75 mg per kg should be administered after haemodialysis.

• Hepatic impairment

Dose with caution and monitor hepatic function at regular intervals (see sections 4.3 and 4.4).

• Method of administration

Megamox is for oral use.
Administer at the start of a meal to minimise potential gastrointestinal intolerance and optimise absorption of amoxicillin/clavulanic acid.
Therapy   can   be   started   parenterally   according   the  SPC  of the IV-formulation  and continued with an oral preparation.
Shake to loosen powder, add water as directed, invert and shake.
Shake the bottle before each dose (see section 6.6).
 

- Hypersensitivity to the active substances, to any of the penicillins or to any of the excipients. - History of a severe immediate hypersensitivity reaction (e.g. anaphylaxis) to another beta-lactam agent (e.g. a cephalosporin, carbapenem or monobactam). - History of jaundice/hepatic impairment due to amoxicillin/clavulanic acid (see section 4.8).

Before initiating therapy with amoxicillin/clavulanic acid, careful enquiry should be made concerning  previous  hypersensitivity  reactions  to  penicillins,  cephalosporins  or  other beta-lactam agents (see sections 4.3 and 4.8).

Serious   and   occasionally   fatal   hypersensitivity   (anaphylactoid)   reactions   have   been reported  in  patients  on  penicillin  therapy.  These  reactions  are  more  likely  to  occur  in individuals  with  a  history  of  penicillin  hypersensitivity  and  in  atopic  individuals.  If  an allergic  reaction  occurs,  amoxicillin/clavulanic  acid  therapy  must  be  discontinued  and appropriate alternative therapy instituted.

In   the   case   that   an   infection   is   proven   to   be   due   to   an   amoxicillin-susceptible organisms(s) then consideration should be given to switching from amoxicillin/clavulanic acid to amoxicillin in accordance with official guidance.

This presentation of Megamox is not suitable for use when there is a high risk that the presumptive pathogens have reduced susceptibility or resistance to beta-lactam agents that is not mediated by beta-lactamases susceptible to inhibition by clavulanic acid. This presentation should not be used 
to treat penicillin-resistant S. pneumoniae.

Convulsions may occur in patients with impaired renal function or in those receiving high doses (see section 4.8).

Amoxicillin/clavulanic  acid  should  be  avoided  if  infectious  mononucleosis  is  suspected since  the  occurrence  of  a  morbilliform  rash  has  been  associated  with  this  condition following the use of amoxicillin.

Concomitant  use  of  allopurinol  during  treatment  with  amoxicillin  can  increase  the likelihood of allergic skin reactions.

Prolonged use may occasionally result in overgrowth of non-susceptible organisms.

The occurrence at the treatment initiation of a feverish generalised erythema associated with  pustula  may  be  a  symptom  of  acute  generalised  exanthemous  pustulosis  (AGEP) (see Section 4.8). This reaction requires  Megamox discontinuation and contra-indicates any 
subsequent administration of amoxicillin.

Amoxicillin/clavulanic  acid  should  be  used  with  caution  in  patients  with  evidence  of hepatic impairment (see section 4.2).

Hepatic events have been reported predominantly in males and elderly patients and may be associated  with prolonged treatment. These events have been very rarely reported in children.  In  all  populations,  signs  and  symptoms  usually  occur  during  or  shortly  after treatment  but  in  some  cases  may  not  become  apparent  until  several  weeks  after treatment has ceased. These  are usually reversible. Hepatic events may be severe and, in extremely  rare  circumstances,  deaths  have  been  reported.  These  have  almost  always occurred in patients with serious underlying disease or taking concomitant medications known to have the potential for hepatic effects (see section 4.8).

Antibiotic-associated  colitis  has  been  reported  with  nearly  all  antibacterial  agents  and may  range  in  severity  from  mild  to  life  threatening  (see  section  4.8).  Therefore,  it  is important  to  consider  this  diagnosis  in  patients  who  present  with  diarrhoea  during  or subsequent  to  the  administration  of  any  antibiotics.  Should  antibiotic-associated  colitis occur,  amoxicillin/clavulanic  acid  should  immediately  be  discontinued,  a  physician  be consulted  and  an  appropriate  therapy  initiated.  Anti-peristaltic  medicinal  products  are contra-indicated in this situation.

Periodic    assessment    of    organ    system    functions,    including    renal,   hepatic  and haematopoietic function is advisable during prolonged therapy.

Prolongation   of   prothrombin   time   has   been   reported   rarely   in   patients   receiving amoxicillin/clavulanic    acid.    Appropriate    monitoring    should    be    undertaken    when anticoagulants   are   prescribed    concomitantly.   Adjustments    in   the   dose    of    oral  anticoagulants  may  be  necessary  to  maintain  the  desired  level  of  anticoagulation  (see  section 4.5 and 4.8).

In patients with renal impairment, the dose should be adjusted according to the degree of impairment (see section 4.2).

In  patients  with  reduced  urine  output,  crystalluria  has  been  observed  very  rarely, predominantly  with  parenteral  therapy.  During  the  administration  of  high  doses  of amoxicillin, it is advisable to maintain adequate fluid intake and urinary output in order to reduce the possibility of amoxicillin crystalluria. In patients with bladder catheters, a regular check of patency should be maintained (see section 4.9).

During  treatment  with  amoxicillin,  enzymatic  glucose  oxidase  methods  should  be  used whenever testing for the presence of glucose in urine because false positive results may occur with non-enzymatic methods.
The presence of Clavulanic acid in Megamox may cause a non-specific binding of IgG and albumin by red cell membranes leading to a false positive Coombs test.

There have been reports of positive test results using the Bio-Rad Laboratories Platelia Aspergillus   EIA    test    in    patients   receiving   amoxicillin/clavulanic   acid   who    were subsequently   found   to   be   free   of   Aspergillus   infection.   Cross-reactions   with   non- Aspergillus   polysaccharides   and   polyfuranoses   with   Bio-Rad   Laboratories   Platelia Aspergillus  EIA  test  have  been  reported.  Therefore,  positive  test  results  in  patients receiving  amoxicillin/clavulanic  acid  should  be  interpreted  cautiously and  confirmed  by other diagnostic methods.

Megamox  125  mg/31.25  mg/5  ml  powder  for  oral  suspension  contains  2.5  mg  of aspartame (E951) per ml, a source of phenylalanine. This medicine should be used with caution in patients with phenylketonuria.
 

 

• Oral anticoagulants

Oral anticoagulants and penicillin antibiotics have been widely used in practice without reports  of   interaction.   However,   in   the   literature   there   are   cases   of   increased international normalised ratio in patients maintained on acenocoumarol or warfarin and prescribed  a  course  of  amoxicillin.  If  co-administration  is  necessary,  the  prothrombin time or international normalised ratio should be carefully monitored with the addition or withdrawal of amoxicillin. Moreover, adjustments in the dose of oral anticoagulants may be necessary (see sections 4.4 and 4.8).

• Methotrexate

Penicillins  may  reduce  the  excretion  of  methotrexate  causing  a  potential  increase  in toxicity.

• Probenecid

Concomitant  use  of probenecid  is not  recommended. Probenecid  decreases  the  renal tubular secretion of amoxicillin. Concomitant use of probenecid may result in increased and prolonged blood levels of amoxicillin but not of clavulanic acid.
 

 

• Pregnancy

Animal   studies   do   not   indicate   direct   or   indirect   harmful   effects   with  respect   to pregnancy,  embryonal/foetal  development,  parturition  or  postnatal  development  (see section  5.3). Limited  data  on  the use  of  amoxicillin/clavulanic acid  during pregnancy in humans do not indicate an increased risk of congenital malformations. In a single study in women with preterm, premature rupture of the foetal membrane it was reported that prophylactic  treatment   with   amoxicillin/clavulanic   acid   may   be   associated  with  an increased  risk  of  necrotising  enterocolitis  in  neonates.  Use  should  be  avoided  during  pregnancy, unless considered essential by the physician.

• Lactation

Both  substances  are  excreted  into  breast  milk  (nothing  is  known  of  the  effects  of clavulanic acid on the breast-fed infant). Consequently, diarrhoea and fungus infection of the  mucous  membranes  are  possible  in  the  breast-fed  infant,  so  that  breast-feeding might  have  to  be  discontinued.  Amoxicillin/clavulanic  acid  should  only  be  used  during breast-feeding after benefit/risk assessment by the physician in charge.
 

No studies on the effects on the ability to drive and use machines have been performed. However,  undesirable  effects  may  occur  (e.g.  allergic  reactions,  dizziness,  convulsions), which may influence the ability to drive and use machines (see section 4.8).
 

The most commonly reported adverse drug reactions (ADRs) are diarrhoea, nausea and vomiting.

The  ADRs  derived  from clinical  studies  and  post-marketing    surveillance   with Amoxicillin/clavulanic acid, sorted by MedDRA System Organ Class are listed below.
The  following  terminologies  have  been  used  in  order  to  classify  the  occurrence  of undesirable effects.
Very common (≥1/10)

Common (≥1/100 to <1/10)
Uncommon (≥1/1,000 to <1/100)

Rare (≥1/10,000 to <1/1,000)

Very rare (<1/10,000)
Not known (cannot be estimated from the available data)

Infections and infestations
Mucocutaneous candidosis	Common
Overgrowth of non-susceptible organisms	Not known
Blood and lymphatic system disorders
Reversible leucopenia (including neutropenia)	Rare
Reversible agranulocytosis ,Haemolytic anaemia ,Prolongation of bleeding time and prothrombin time1	Not known
Immune system disorders10
Angioneurotic oedema ,Anaphylaxis, Serum sickness-like syndrome , Hypersensitivity vasculitis	Not known
Nervous system disorders
Dizziness , Headache,	Uncommon
Reversible hyperactivity , Convulsions2	Not known
Gastrointestinal disorders
Diarrhoea , Nausea3 , Vomiting	common
Indigestion	Uncommon
Antibiotic-associated colitis4,Black hairy tongue	Not known
Hepatobiliary disorders
Rises in AST and/or ALT5	Uncommon
Hepatitis6 ,Cholestatic jaundice6	Not known
Skin and subcutaneous tissue disorders 7
Skin rash ,Pruritus ,Urticaria	Uncommon
Erythema multiforme	Rare
Stevens-Johnson syndrome, Toxic epidermal necrolysis, Bullous exfoliative-dermatitis, Acute generalised exanthemous pustulosis (AGEP)9	Not known
Renal and urinary disorders
Interstitial nephritis	Not known
Crystalluria8	Not known
1 See section 4.4 2 See section 4.4. 3 Nausea is more often associated with higher oral doses. If gastrointestinal reactions are evident, they may be reduced by taking amoxicillin/clavulanic acid at the start of a meal. 4 Including pseudomembranous colitis and haemorrhagic colitis (see section 4.4) 5 A moderate rise in AST and/or ALT has been noted in patients treated with beta-lactam class antibiotics, but the significance of these findings is unknown. 6 These events have been noted with other penicillins and cephalosporins (see section 4.4). 7 If any hypersensitivity dermatitis reaction occurs, treatment should be discontinued (see section 4.4). 8 See section 4.9 9 See section 4.4 10 Section 4.3 and 4.4

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via:

• Saudi Arabia

The National Pharmacovigilance Centre (NPC)
SFDA Call Center: 19999
E-mail: npc.drug@sfda.gov.sa
Website: https://ade.sfda.gov.sa

• Other GCC States

Please contact the relevant competent authority.

 

• Symptoms and signs of overdose

Gastrointestinal symptoms and disturbance of the fluid and electrolyte balances may be evident. Amoxicillin crystalluria, in some cases leading to renal failure, has been observed (see section 4.4).
Convulsions may occur in patients with impaired renal function or in those receiving high doses. Amoxicillin  has  been  reported  to  precipitate  in  bladder  catheters,  predominantly  after intravenous administration of large doses.  A regular check  of  patency  should  be maintained (see section 4.4).

• Treatment of intoxication

Gastrointestinal   symptoms   may   be   treated   symptomatically,   with   attention to  the water/electrolyte balance.
Amoxicillin/clavulanic acid can be removed from the circulation by haemodialysis.
 

Pharmacotherapeutic group: Combinations of penicillins, incl. beta-lactamase inhibitors;
ATC code: J01CR02.

• Mode of action

Amoxicillin is a semisynthetic penicillin (beta-lactam antibiotic) that inhibits one or more enzymes  (often  referred  to  as  penicillin-binding  proteins,  PBPs)  in  the  biosynthetic pathway  of  bacterial  peptidoglycan,  which  is  an  integral  structural  component  of  the bacterial  cell  wall.  Inhibition  of  peptidoglycan  synthesis  leads  to  weakening  of  the  cell wall, which is usually followed by cell lysis and death.

Amoxicillin  is  susceptible  to  degradation  by  beta-lactamases  produced  by  resistant bacteria  and  therefore  the  spectrum  of  activity  of  amoxicillin  alone  does  not  include organisms which produce these enzymes.Clavulanic  acid  is  a  beta-lactam  structurally  related  to  penicillins.  It  inactivates  some beta-lactamase  enzymes  thereby  preventing  inactivation  of  amoxicillin.  Clavulanic  acid alone does not exert a clinically useful antibacterial effect.

• PK/PD relationship

The time above the  minimum  inhibitory concentration (T>MIC) is considered to be the major determinant of efficacy for amoxicillin.

• Mechanisms of resistance

The two main mechanisms of resistance to amoxicillin/clavulanic acid are:
- Inactivation by those bacterial beta-lactamases that are not themselves inhibited by clavulanic acid, including class B, C and D.
- Alteration of PBPs, which reduce the affinity of the antibacterial agent for the target.

Impermeability of bacteria or efflux pump mechanisms may cause or contribute to bacterial resistance, particularly in Gram-negative bacteria.

• Breakpoints

MIC breakpoints for amoxicillin/clavulanic acid are those of the European Committee on Antimicrobial Susceptibility Testing (EUCAST)

Organism	Susceptibility Breakpoints (μg/ml)
	Susceptible	Intermediate	Resistant
Haemophilus influenzae1	≤ 1	-	> 1
Moraxella catarrhalis1	≤ 1	-	> 1
Staphylococcus aureus 2	≤ 2	-	> 2
Coagulase-negative staphylococci2	≤ 0.25		> 0.25
Enterococcus1	≤ 4	8	> 8
Streptococcus A, B, C, G5	≤ 0.25	-	> 0.25
Streptococcus pneumoniae3	≤ 0.5	1-2	> 2
Enterobacteriaceae1,4	-	-	> 8
Gram-negative Anaerobes1	≤ 4	8	> 8
Gram-positive Anaerobes1	≤ 4	8	> 8
Non-species related breakpoints1	≤ 2	4-8	> 8
1 The reported values are for Amoxicillin concentrations. For susceptibility testing purposes, the concentration of Clavulanic acid is fixed at 2 mg/l. 2 The reported values are Oxacillin concentrations. 3 Breakpoint values in the table are based on Ampicillin breakpoints. 4 The resistant breakpoint of R>8 mg/l ensures that all isolates with resistance mechanisms are reported resistant. 5 Breakpoint values in the table are based on Benzylpenicillin breakpoints.

The prevalence of resistance may vary geographically and with time for selected species, and  local  information  on   resistance  is  desirable, particularly  when  treating  severe infections.  As  necessary,  expert  advice  should  be  sought  when  the  local  prevalence  of resistance  is  such  that  the  utility  of  the  agent  in  at  least  some  types  of  infections  is questionable.

Commonly susceptible species

- Aerobic Gram-positive micro-organisms Enterococcus faecalis Gardnerella vaginalis Staphylococcus aureus ( methicillin-susceptible)£ Coagulase-negative staphylococci (methicillin-susceptible) Streptococcus agalactiae Streptococcus pneumoniae1 Streptococcus pyogenes and other beta-hemolytic streptococci Streptococcus viridans group - Aerobic Gram-negative micro-organisms Capnocytophaga spp.  Eikenella corrodens  Haemophilus influenzae2 Moraxella catarrhalis  Pasteurella multocida -  Anaerobic micro-organisms Bacteroides fragilis  Fusobacterium nucleatum Prevotella spp.

Species for which acquired resistance may be a problem

- Aerobic Gram-positive micro-organisms Enterococcus faecium $ - Aerobic Gram-negative micro-organisms Escherichia coli  Klebsiella oxytoca Klebsiella pneumoniae Proteus mirabilis Proteus vulgaris

Inherently resistant organisms

- Aerobic Gram-negative micro-organisms Acinetobacter sp. Citrobacter freundii Enterobacter sp. Legionella pneumophila Morganella morganii Providencia spp. Pseudomonas sp. Serratia sp. Stenotrophomonas maltophilia -  Other micro-organisms Chlamydophila pneumoniae Chlamydophila psittaci Coxiella burnetti Mycoplasma pneumonia

$ Natural intermediate susceptibility in the absence of acquired mechanism of resistance.  £All methicillin-resistant staphylococci are resistant to amoxicillin/clavulanic acid 1 Streptococcus pneumoniae that are resistant to penicillin should not be treated with this presentation of amoxicillin/clavulanic acid (see sections 4.2 and 4.4). 2 Strains with decreased susceptibility have been reported in some countries in the EU with a frequency higher than 10%.

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

• Absorption

Amoxicillin and clavulanic acid, are fully dissociated in aqueous solution at physiological pH. Both components are rapidly and well absorbed by the oral route of administration. Absorption of amoxicillin/clavulanic acid is optimised when taken at the start of a meal. Following  oral  
administration,  amoxicillin  and  clavulanic  acid  are  approximately  70% bioavailable. The plasma profiles of both components are similar and the time to peak plasma concentration (T_max) in each case is approximately one hour.

The pharmacokinetic results for a study, in which amoxicillin/clavulanic acid (500 mg/125 mg tablets three times daily) was administered in the fasting state to groups of healthyvolunteers are presented below.

Mean (± SD) pharmacokinetic parameters
Active substance(s) administered	Dose	C max	T max *	AUC (0-24h)	T 1/2
	(mg)	(μg/ml)	(h)	(μg.h/ml)	(h)
Amoxicillin
AMX/CA 500 mg/125 mg	500	7.19 ± 2.26	1.5 (1.0-2.5)	53.5 ± 8.87	1.15 ± 0.20
Clavulanic acid
AMX/CA   500 mg/125 mg	125	2.40   ± 0.83	1.5   (1.0-2.0)	15.72   ± 3.86	0.98   ± 0.12
AMX – amoxicillin, CA – clavulanic acid * Median (range)

Amoxicillin and clavulanic acid serum concentrations achieved with amoxicillin/clavulanic acid  are  similar  to  those  produced  by  the  oral  administration  of  equivalent  doses  of amoxicillin or clavulanic acid alone.

• Distribution

About 25% of total plasma clavulanic acid and 18% of total plasma amoxicillin is bound to protein.  The  apparent  volume  of  distribution  is  around  0.3-0.4  l/kg  for  amoxicillin  and around 0.2 l/kg for clavulanic acid.
Following  intravenous  administration,  both  amoxicillin  and  clavulanic  acid  have  been found in gall bladder, abdominal tissue, skin, fat, muscle tissues, synovial and peritoneal fluids,  bile  and  pus.  Amoxicillin  does  not  adequately  distribute  into  the  cerebrospinal fluid.
From animal studies there is no evidence for significant tissue retention of drug-derived material  for  either  component.  Amoxicillin,  like  most  penicillins,  can  be  detected  in breast milk. Trace quantities of clavulanic acid can also be detected in breast milk (see section 4.6).
Both amoxicillin and clavulanic acid have been shown to cross the placental barrier (see section 4.6).

• Biotransformation

Amoxicillin  is  partly  excreted  in  the  urine  as  the  inactive  penicilloic  acid  in  quantities equivalent   to   up   to   10   to   25%   of   the   initial   dose.   Clavulanic   acid   is   extensively metabolized in man and eliminated in urine and faeces and as carbon dioxide in expired air.

• Elimination

The  major  route  of  elimination  for  amoxicillin  is via  the  kidney,  whereas  for clavulanic acid it is by both renal and non-renal mechanisms.
Amoxicillin/clavulanic  acid  has  a  mean  elimination  half-life  of  approximately  one  hour and a mean total clearance of approximately 25 l/h in healthy subjects. Approximately 60 to 70% of the amoxicillin and approximately 40 to 65% of the clavulanic acid are excreted unchanged     in     urine    during     the     first  6h  after administration  of  single Amoxicillin/clavulanic  acid  250  mg/125  mg  or  500  mg/125  mg  tablets.  Various  studies
have found the urinary excretion to be 50-85% for amoxicillin and between 27-60% for clavulanic acid over a 24 hour period. In the case of clavulanic acid, the largest amount of drug is excreted during the first 2 hours after administration. Concomitant  use  of  probenecid  delays  amoxicillin  excretion  but  does  not  delay  renal excretion of clavulanic acid (see section 4.5).

• Age

The elimination half-life of amoxicillin is similar for children aged around 3 months to 2 years   and   older   children   and   adults.   For   very   young   children   (including   preterm newborns) in the first week of life the interval of administration should not exceed twice daily  administration  due  to  immaturity  of  the  renal  pathway  of  elimination.  Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function.

• Gender

Following oral administration of amoxicillin/clavulanic acid to healthy males and female subjects, gender has no significant impact on the pharmacokinetics of either amoxicillin or clavulanic acid.

•  Renal impairment

The total  serum  clearance  of amoxicillin/clavulanic acid decreases proportionately with decreasing  renal  function.  The  reduction  in  drug  clearance  is  more  pronounced  for amoxicillin than for clavulanic acid, as a higher proportion of amoxicillin is excreted  via the renal route. Doses in renal impairment must therefore prevent undue accumulation of amoxicillin while maintaining adequate levels of clavulanic acid (see section 4.2).

• Hepatic impairment

Hepatically   impaired   patients   should   be   dosed   with   caution   and   hepatic   function monitored at regular intervals.
 

Nonclinical data reveal no special hazard for humans based on studies of safety pharmacology, genotoxicity and toxicity to reproduction.

Repeat dose toxicity studies performed in dogs with amoxicillin/clavulanic acid demonstrate gastric irritancy and vomiting, and discoloured tongue.
Carcinogenicity studies have not been conducted with Megamox or its components.
 

-  Xanthan Gum (Keltro)
-  Succinic Acid micronized
-  Colloidal anhydrous silica
-  Aspartame
-  Hydroxy Propyl Methyl Cellulose (Methocel E5)
-  Golden Syrup Flavor
-  Orange Flavor
-  Silicon Dioxide (Syloid AL-1-FP)
 

None
 

2 years

Store below 30°C
The  dry  powder  should  be  stored  in  a  dry  place.  Reconstituted  suspensions  should  be kept in a refrigerator (but not frozen) for up to 7 days.
 

Glass bottle Amber 125 ml,28mm induction plastic CRC Caps
 

Check  cap  seal  is  intact  before  using.  Shake  bottle  to  loosen  powder.  Add  volume  of water (as indicated below) invert and shake well. Alternatively fill the bottle with water to  just below  the  mark  on  bottle  label,  invert  and  shake  well,  then  top  up  with  water exactly to the mark, invert and again shake well.

Strength	Volume of water to be added at reconstitution (ml)	Final volume of reconstituted oral suspension (ml)
250 mg/62.5 mg/5 ml	Make up to mark	60
	72	80
	90	100

Shake the bottle well before each dose