Amoxicillin/ Clavulanic Acid

These indications are based on manufacturer information for both originator and generic products. For product specific registered indications, please refer to product specific manufacturer information

Registered South African indications: 

• Infections caused by amoxicillin-resistant organisms producing β-lactamases sensitive to clavulanic acid
  - Upper respiratory tract infections, such as sinusitis, recurrent otitis media, tonsillitis 
  - Lower respiratory tract infections, such as acute exacerbations of chronic bronchitis, bronchopneumonia,community-acquired pneumonia, acute bacterial sinusitis
  - Genito-urinary tract infections, such as cystitis, urethritis, pyelonephritis
  - Skin and soft tissue infections 

Contraindications

• Hypersensitivity to the active ingredient or any of its excipients
• History of hypersensitivity to any of the penicillins
• History of severe immediate hypersensitivity (e.g. anaphylaxis) to another beta-lactam agents (e.g. a cephalosporin, carbapenem or monobactam)
• History of amoxicillin/ clavulanate-induced jaundice/ hepatic impairment

Cautions

• Pregnancy
• Breastfeeding
• Renal impairment (CrCl ≤30ml/min)
• Hepatic impairment
• Elderly
• Atopic individuals
• High risk that the presumptive pathogens have resistance to beta-lactam agents that is not mediated by beta-lactamases susceptible to inhibition by clavulanic acid
• Penicillin-resistant S. pneumoniae 
• High dose therapy
• Prolonged use
• Infectious mononucleosis
• Male patients  
• Serious underlying disease
• Patients with bladder catheters
• Coadministration with agents known to have the potential for hepatic effects
• Coadministration with allopurinol
• Sodium controlled diet
• Phenylketonuria (sus)
• Glucose-galactose malabsorption (sus)

Forms avail. in SA and covered in this monograph: inj, tab

Dosages below include:

• South African Standard Treatment Guidelines indications and dosages
• South African registered indications and dosages
• Indications and dosages registered in other jurisdictions

Infections caused by: Bacteroides fragilis, Capnocytophagia, Haemophilus influenzae, Moraxella catarrhalis, Pasteurella multocida, Staphylococcus saprophyticus, Actinomyces sp., Arcanobacter. sp.Borrelia burgdorferi, Corynebacterium diphtheriae, Campylobacter jejuni, Clostridium sp., Escherichia coli (S), Enterococcus faecalis (S), Eikenella sp., Fusobacterium necrophorum, Klebsiella oxytoca, Klebsiella pneumoniae (S), Kingella sp., Listeria monocytogenes, Leptospira sp., Propionibacterium acnes, Proteus mirabilis, Proteus vulgaris,  Peptostreptococci,  Prevotella spp., Staphylococcus aureus (MSSA), Staphylococcus epidermidis (S), Staphylococcus lugdunensis, Salmonella sp., Shigella sp., Staphylococcus coag-neg (S), Streptococcus agalactiae (B), Streptococcus pneumoniae, Streptococcus anginosus gp, Streptococcus gp C, F, G, Streptococcus pyogenes (A)

Specific doses based on individual indications

Please note that the dosages below should be used in combination with regional guidelines, taking into account local antibiotic sensitivities

South African Standard Treatment Guidelines indications and dosages

Doses below based on the combined amoxicillin/ clavulanic acid components

Uncomplicated diverticulitis

• Oral (tab): 1000mg, 12hrly; Treatment duration: 10 days, depending on clinical response
  (STG, Adult 2019)

- In those unable to tolerate oral therapy

• IV: 1200mg, 8hrly; Treatment duration: 10 days, depending on clinical response
  (STG, Adult 2019)

Abscess of the pancreas in acute pancreatitis
- Broad-spectrum cover

• IV: 1200mg, 8hrly; Treatment duration: 10 days, depending on clinical response
  (STG, Adult 2019)

Pyogenic liver abscess
- Empiric antibiotic therapy

• Oral (tab): 1000mg, 12hrly; Treatment duration: Ill defined, but may need to be for as long as 12 weeks in cases of multiple abscesses
  (STG, Adult 2019)

- In those unable to tolerate oral therapy

• IV: 1200mg, 8hrly; Treatment duration: Ill defined, but may need to be for as long as 12 weeks in cases of multiple abscesses
  (STG, Adult 2019)

Bacterial peritonitis
- Empiric antibiotic therapy for surgical causes of peritonitis

• IV: 1.2g, 8hrly

- Once able to tolerate oral medication

• Oral (tab): 1000mg, 12hrly
  (STG, Adult 2019)

Acute cholangitis
Acute cholecystitis
- If signs of infection and/or risk factors for severe disease are present, such as elderly patients (>60 years), co-morbid conditions or the immune compromised

• Oral (tab): 1000mg, 12hrly
  (STG, Adult 2019)

- In those unable to tolerate oral therapy

• IV: 1200mg, 8hrly
  (STG, Adult 2019)

Complicated leg ulcers
- If there is surrounding cellulitis

• Oral (tab): 1000mg, 12hrly; Treatment duration: 7 days
  (STG, Adult 2019)

Pelvic inflammatory disease - stage II-IV (Additional agent required)
- As an IV to oral switch option within 24-48hrs

• Oral (tab): 1000mg, 12hrly; Treatment duration: 10 days (this includes IV treatment days)
  (STG, Adult 2019)

Septic miscarriage

• IV: 1200mg, 8hrly
  (STG, Adult 2019)

- As an IV to oral switch after clinical improvement

• Oral (tab): 1000mg, 12hrly; Treatment duration: 7-10 days
  (STG, Adult 2019)

Postpartum fever
- Empiric therapy
Lung abscess

• IV: 1200mg, 8hrly
  (STG, Adult 2019; Adult 2023)

- As an IV to oral switch if patient is apyrexial for 24hrs

• Oral (tab): 1000mg, 12hrly
  (STG, Adult 2023)

Acute pyelonephritis in pregnancy
- As IV to oral switch as soon as the patient is able to take oral fluids

• Oral (tab): 1000mg, 12hrly; Treatment duration: 7 days
  (STG, Adult 2023)

Diabetic foot ulcers
- For polymicrobial infections

• Oral (tab): 1000mg, 12hrly; Treatment duration: 10 days, longer course of therapy may be necessary
  (STG, Adult 2019; PHC 2020)

- Severe

• IV: 1200mg, 8hrly; Treatment duration: 10 days
  (STG, Adult 2019)

Bronchiectasis
- In patients otherwise stable and before culture results
- As follow-on oral therapy after IV ceftriaxone in more severely ill patients that may have required hospitalisation and initiation of parenteral antibiotic therapy

• Oral (tab): 1000mg, 12hrly; Treatment duration: 10 days, or longer depending on the response
  (STG, Adult 2019)

Chronic obstructive pulmonary disease with an acute infective exacerbation of chronic bronchitis
- In those who are non-responsive to the first course of antibiotic therapy
- Or in those with a moderate to severe exacerbation and who have increased sputum purulence plus more than one of the following symptoms, i.e., increased dyspnoea or increased sputum volume
Community acquired pneumonia without features of severe pneumonia
- In patients >65 years or co-morbidity (e.g., COPD, HIV, cardiac failure, diabetes) as an IV to oral switch in haemodynamically stable patients with respiratory rate <25 breaths/min and temperature <37.8^oC
Pneumonia (cyanosis, confusion, hypotension or respiratory rate >30 breaths/min) - severe (Additional agent required)
- As an IV to oral switch in haemodynamically stable patients with respiratory rate <25 breaths/min and temperature <37.8^oC
Acute otitis media (if not responding to amoxicillin)
Secondary infection in snake bites (Additional agents required)
Pneumonia in patients with underlying medical conditions or >65 years of age
Animal bites (Additional agents required)
Human bites (Additional agents required)

• Oral (tab): 1000mg, 12hrly; Treatment duration: 5 days
  (STG, Adult 2019; PHC 2020)

Aspiration pneumonia

• IV: 1200mg, 8hrly
  (STG, Adult 2019)

- As a follow-on treatment if patient is apyrexial and stable for 24hrs

• Oral (tab): 1000mg, 12hrly; Treatment duration: Continue therapy until there are no features of sepsis
  (STG, Adult 2019)

Empyema
- As a complication of pneumonia
- Or if not a complication of pneumonia

• IV: 1200mg, 8hrly
  (STG, Adult 2019)

- As a follow on treatment if patient is apyrexial for 24 hours

• Oral (tab): 1000mg, 12hrly; Treatment duration: Continued until drainage is complete
  (STG, Adult 2019)

Epiglottitis
- As follow on therapy from IV ceftriaxone as soon as patient can swallow, and the temperature is <37.8^oC for 24 hours

• Oral (tab): 1000mg, 12hrly; Treatment duration: 10 days
  (STG, Adult 2019)

Peritonsillar abscess

• IV: 1200mg, 8hrly; Treatment duration: 10 days
  (STG, Adult 2019)

- As follow on therapy as soon as patient can swallow and the temperature is <37.8^oC for 24hrs

• Oral (tab): 1000mg, 12hrly; Treatment duration: 10 days
  (STG, Adult 2019)

Acute otitis media
- In those who have taken amoxicillin in the previous 30 days; OR have a poor response to a 10-day course of amoxicillin

• Oral (tab): 1000mg, 12hrly; Treatment duration: 5-10 days
  (PHC 2020)

---

South African registered indications and dosages

Upper respiratory tract infections, such as sinusitis, recurrent otitis media, tonsillitis caused by Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis and Streptococcus pyogenes 
Lower respiratory tract infections, such as acute exacerbations of chronic bronchitis caused by amoxicillin-resistant β-lactamase producing Escherichia coli, Haemophilus influenzae and Haemophilus para-influenzae 
Bronchopneumonia
Genito-urinary tract infections, such as cystitis, urethritis, pyelonephritiscaused by Enterobacteriaceae (mainly Escherichia coli), Staphylococcus saprophyticus and Enterococcus species
Skin and soft tissue infectionscaused by methicillin susceptible Staphylococcus aureus, Streptococcus pyogenes and Bacteroides species 

• IV: 1200mg, 6-8hrly as an injection over 2min OR infusion over 30min

---

IV therapy should be followed by oral therapy with tablets at the recommended dose after a satisfactory therapeutic response has been obtained

---

If no response has occurred within 48 hours therapy must be reviewed

---

IV therapy should not be extended >10 days without review and the total daily administration of clavulanic acid should not exceed 800mg

---

• Oral (tab): 375-625mg, 8hrly (depending of severity)
  OR
• Oral (tab): 1000mg, 12hrly

---

375mg tablets are not recommended for use in lower respiratory tract infections

---

Community-acquired pneumonia 

• Oral (SR tab): 2125mg, 12hrly; Treatment duration: 7-10 days

Acute bacterial sinusitis, typically caused by Streptococcus pneumoniae

• Oral (SR tab): 2125mg, 12hrly; Treatment duration: 7 days

Acute exacerbations of chronic bronchitis

• Oral (SR tab): 2125mg, 12hrly; Treatment duration: 10 days

---

All oral forms should be administered with a meal to minimise potential gastrointestinal intolerance

---

Indications and dosages registered in other jurisdictions

Infections caused by: Enterococcus faecalis, Gardnerella vaginalis, Staphylococcus aureus (methicillin-susceptible), Coagulase-negative staphylococci (methicillin-susceptible), Streptococcus agalactiae, Streptococcus pneumoniae, Streptococcus pyogenes and other beta-haemolytic streptococci, Streptococcus viridans group, Actinobacillus actinomycetemcomitans, Capnocytophaga spp., Eikenella corrodens, Haemophilus influenzae, Moraxella catarrhalis, Neisseria gonorrhoeae, Pasteurella multocida, Bacteroides fragilis, Fusobacterium nucleatum, Prevotella spp., Enterococcus faecium, Escherichia coli, Klebsiella oxytoca, Klebsiella pneumoniae, Proteus mirabilis, Proteus vulgaris

Acute bacterial sinusitis
Cystitis
Pyelonephritis
Cellulitis
Animal bites
Severe dental abscess with spreading cellulitis

2:1 tablet

• Oral (tab): 375mg, 8hrly

---

2:1 oral tablet preparation provides a total daily dose of 750 mg amoxicillin/375 mg clavulanic acid, when administered as recommended. If it is considered that a higher daily dose of amoxicillin is required, it is recommended that another preparation of amoxicillin/ clavulanic acid is selected in order to avoid administration of unnecessarily high daily doses of clavulanic acid

---

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

• IV: 1200mg, 8hrly; Max duration: 14 days

4:1 tablet/ suspension

• Oral (tab, sus): 625mg, 8hrly;Max duration: 14 days

7:1 tablet

• Oral (tab) 1000mg, 8-12hrly; Max duration: 14 days

---

IV: May be administered either by slow IV injection over a period of 3-4 minutes directly into a vein or via a drip tube or by infusion over 30-40 minutes

---

Acute bacterial sinusitis
Acute otitis media

4:1 tablet/ suspension

• Oral (tab, sus): 625mg, 8hrly;Max duration: 14 days

7:1 tablet

• Oral (tab) 1000mg, 8-12hrly; Max duration: 14 days

Severe infections of the ear, nose and throat (such as mastoiditis, peritonsillar infections, epiglottitis and sinusitis when accompanied by severe systemic signs and symptoms)
Intra-abdominal infections
Female genital infections

• IV: 1200mg, 8hrly; Max duration: 14 days

---

IV: May be administered either by slow IV injection over a period of 3-4 minutes directly into a vein or via a drip tube or by infusion over 30-40 minutes

---

The duration of therapy should be determined by the response of the patient. Treatment should not be extended beyond 14 days without review

---

Prophylaxis against infections associated with major surgical procedures in adults, such as those involving the gastrointestinal tract, pelvic cavity, head and neck and biliary tract surgery

- Surgical procedures <1hr in duration

• IV: 1200-2200mg at induction of anaesthesia

- Surgical procedures >1hr in duration

• IV: 1200-2200mg at induction of anaesthesia; THEN up to 3 doses of 1200mg/24hrs 

---

IV: May be administered either by slow IV injection over a period of 3-4 minutes directly into a vein or via a drip tube or by infusion over 30-40 minutes

---

Clear clinical signs of infection at operation will require a normal course of IV or oral therapy post-operatively

Paed. forms avail. in SA and covered in this monograph: inj, tab, sus

Paed. dosages below include:

• South African Standard Treatment Guidelines indications and dosages
• South African registered indications and dosages
• Indications and dosages registered in other jurisdictions

Infections caused by: Bacteroides fragilis, Capnocytophagia, Haemophilus influenzae, Moraxella catarrhalis, Pasteurella multocida, Staphylococcus saprophyticus, Actinomyces sp., Arcanobacter. sp.Borrelia burgdorferi, Corynebacterium diphtheriae, Campylobacter jejuni, Clostridium sp., Escherichia coli (S), Enterococcus faecalis (S), Eikenella sp., Fusobacterium necrophorum, Klebsiella oxytoca, Klebsiella pneumoniae (S), Kingella sp., Listeria monocytogenes, Leptospira sp., Propionibacterium acnes, Proteus mirabilis, Proteus vulgaris,  Peptostreptococci,  Prevotella spp., Staphylococcus aureus (MSSA), Staphylococcus epidermidis (S), Staphylococcus lugdunensis, Salmonella sp., Shigella sp., Staphylococcus coag-neg (S), Streptococcus agalactiae (B), Streptococcus pneumoniae, Streptococcus anginosus gp, Streptococcus gp C, F, G, Streptococcus pyogenes (A)

Specific doses based on individual indications

Please note that the dosages below should be used in combination with regional guidelines, taking into account local antibiotic sensitivities

South African Standard Treatment Guidelines indications and dosages

Urinary tract infection (UTI)
- All neonates and acutely ill infants

• IV: 25mg/kg/dose of amoxicillin component, 8hrly
  (STG, Paed. 2023)

- As an oral switch in those with evidence of good clinical response

• Oral (sus, tab): 25mg/kg/dose of amoxicillin component, 8hrly
  (STG, Paed. 2023)

- In children who are unwell but not acutely ill and who are not vomiting

Older than 3 months

• Oral (sus, tab): 25mg/kg/dose of amoxicillin component, 8hrly: Treatment duration: Uncomplicated UTI: 3 days; Complicated UTI: 7 days
  (STG, Paed. 2023)

---

Increase duration to 10-14 days in infants who have acute pyelonephritis or septicaemia

---

All neonates and acutely ill infants should preferably be treated parenterally for the first few days until temperature has normalised and they are able to tolerate feeds

---

Necrotising periodontitis

• Oral (sus, tab): 25mg/kg/dose of amoxicillin component, 8hrly; Treatment duration: 5 days
  (STG, Paed. 2017)

Suspected secondary bacterial infection in measles

• IV: 25mg/kg/dose, 8hrly; THEN
  (STG, Paed. 2017)
• Oral (sus, tab): 30mg/kg/dose, 12hrly; Treatment duration: 5-7 days
  (STG, Paed. 2017)

Animal bite wounds
- As pre-emptive antibiotic therapy only if hand is bitten or for extensive wounds or human bites

• Oral (sus, tab): 30mg/kg/dose of amoxicillin component, 8hrly
  (STG, Paed. 2017)

Confirmed preseptal cellulitis

• Oral (sus, tab): 30mg/kg/dose of amoxicillin component, 8hrly; Treatment duration: 10 days
  (STG, Paed. 2023)

Pneumonia - severe or very severe disease
Purulent effusion
Bronchiectasis
- As empiric antibiotic therapy for acute lung infections

• IV: 25mg/kg/dose of amoxicillin component, 8hrly; THEN, switch to oral as soon as there is a response
• Oral (sus, tab): 45mg/kg/dose, 12hrly; Treatment duration: 10 days in total
  (STG, Paed. 2023)

Pneumonia due to anaerobic infection
- Empiric antibiotic therapy

• IV: 25mg/kg/dose of amoxicillin component, 8hrly: Treatment duration: ≥7 days
  (STG, Paed. 2023)

Recurrent pneumonia

• IV: 25mg/kg/dose of amoxicillin component, 8hrly
  (STG, Paed. 2023)

Lung abscess
- Empiric antibiotic therapy

• IV: 25mg/kg/dose of amoxicillin component, 8hrly
  (STG, Paed. 2023)

- If there is evidence of good clinical response

• Oral (sus, tab): 45mg/kg/dose, 12hrly; Treatment duration: 14 days in total
  (STG, Paed. 2023)

Suspected bacterial infection in acute viral laryngotracheobronchitis (CROUP) (Additional agents required)
- Grade 4 obstruction

• IV: 25mg/kg/dose of amoxicillin component, 8hrly; Treatment duration: 7 days
  (STG, Paed. 2023)

Retropharyngeal abscess
- Empiric therapy

• IV: 25mg/kg/dose of amoxicillin component, 8hrly
  (STG, Paed. 2023)

- As soon as there is a response and patient can tolerate oral medication
Acute mastoiditis
- As an oral switch from IV ceftriaxone as soon as there is a response and patient can tolerate oral medication
Complicated sinusitis
- As an oral switch from IV ceftriaxone as soon as there is a response and patient can tolerate oral medication

• Oral (sus, tab): 45mg/kg/dose of amoxicillin component, 12hrly; Treatment duration: 14 days; Max: 1.5g, 12hrly of amoxicillin component
  (STG, Paed. 2023)

Early complications of tonsillitis
- Peritonsillar cellulitis
- Peritonsillar abscess

• IV: 25mg/kg/dose of amoxicillin component, 8hrly
  (STG, Paed. 2023)

- As soon as there is a response and patient can tolerate oral medication
Acute otitis media
- For poor response to amoxicillin therapy, OR in those who have received amoxicillin in the last 30 days

• Oral (sus, tab): 45mg/kg/dose of amoxicillin component, 12hrly; Treatment duration: 10 days; Max: 1.5g, 12hrly of amoxicillin component
  (STG, Paed. 2023)

Acute bacterial rhinosinusitis
- For poor response to amoxicillin therapy, OR in those who have received amoxicillin in the last 30 days

• Oral (sus, tab): 45mg/kg/dose of amoxicillin component, 12hrly; Treatment duration: 5-10 days; Max: 1.5g, 12hrly of amoxicillin component
  (STG, Paed. 2023)

---

Do not exceed 10mg/kg/day of clavulanate component

---

Change antibiotics according to culture and sensitivity results. Watch for complications. Some patients may require longer antibiotic duration

---

If pathogens are cultured in blood from sanctuary sites, e.g., bone, heart valves, etc., treat according to sensitivity for prolonged period of 21–42 days

---

Doses below based on the combined amoxicillin/ clavulanic acid components

---

South African registered indications and dosages

Upper respiratory tract infections, such as sinusitis, otitis media, recurrent tonsillitis
Lower respiratory tract infections, such as acute exacerbations of chronic bronchitis (caused by amoxicillin-resistant β-lactamase producing Escherichia coli, Haemophilus influenzae and Haemophilus parainfluenzae)
Bronchopneumonia
Genito-urinary tract infections, such as cystitis, urethritis, pyelonephritis
Skin and soft tissue infections

Oral (sus)

4:1 suspension

• <40kg: 25-50mg/kg/day, 8hrly; Max: 75mg/kg/day
• ≥40kg: See adult dosage

7:1 suspension

• Younger than 2 months: Not recommended for use
• <40kg: 28.6-51.4mg/kg/day, 12hrly; Max: 80mg/kg/day
• ≥40kg: See adult dosage

---

7:1 suspensions are not recommended for children <2 months of age, due to immature renal function, the dose would need to be adjusted according to the amoxicillin content. However, with high amoxicillin/ clavulanate ratios, this might lead to reduced doses of clavulanate and such doses have not been studied in this patient group. The 4:1 suspensions are therefore recommended

---

All oral forms should be administered with a meal to minimise potential gastrointestinal intolerance

---

Indications and dosages registered in other jurisdictions

Infections caused by: Enterococcus faecalis, Gardnerella vaginalis, Staphylococcus aureus (methicillin-susceptible), Coagulase-negative staphylococci (methicillin-susceptible), Streptococcus agalactiae, Streptococcus pneumoniae, Streptococcus pyogenes and other beta-haemolytic streptococci, Streptococcus viridans group, Actinobacillus actinomycetemcomitans, Capnocytophaga spp., Eikenella corrodens, Haemophilus influenzae, Moraxella catarrhalis, Neisseria gonorrhoeae, Pasteurella multocida, Bacteroides fragilis, Fusobacterium nucleatum, Prevotella spp., Enterococcus faecium, Escherichia coli, Klebsiella oxytoca, Klebsiella pneumoniae, Proteus mirabilis, Proteus vulgaris

Acute exacerbations of chronic bronchitis 
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

Oral (sus)

4:1 suspension

• <40kg: 25-75mg/kg/day, in 3 divided doses; Max duration: 14 days  
• ≥40kg: See adult dosage

---

Children aged <6 years should preferably be treated with the suspension

---

No clinical data are available on doses of 4:1 formulations >40mg/10 mg/kg/day in children <2 years

---

7:1 suspension

• <40kg: 28.6-51.4mg/kg/day, in 2 divided doses; Max: 80mg/kg/day

---

A maximum of 80mg/kg/day as two divided doses may be considered for some infections (such as otitis media, sinusitis and lower respiratory tract infections)

---

Oral (tab)

4:1 tablet

• <25kg: Not recommended for use
• 25-40kg: 25-75mg/kg/day, in 3 divided doses; Max duration: 14 days
• >40kg: See adult dosage

---

As the tablets cannot be divided, children weighing <25kg must not be treated with tablets

---

No clinical data are available on doses of 4:1 formulations >40 mg/10 mg/kg/day in children <2 years

---

IV

Younger than 3 months or <4kg

• IV: 30mg/kg, 12hrly; Max duration: 14 days

Older than 3 months and between <40kg

• IV: 30mg/kg, 8hrly; Max duration: 14 days

Acute bacterial sinusitis (adequately diagnosed)
Acute otitis media

Oral (sus)

4:1 suspension

• <40kg: 25-75mg/kg/day, in 3 divided doses; Max duration: 14 days
• ≥40kg: See adult dosage

---

Children aged <6 years should preferably be treated with the suspension

---

No clinical data are available on doses of 4:1 formulations >40 mg/10 mg/kg/day in children <2 years

---

7:1 suspension

• <40kg: 28.6-51.4mg/kg/day, in 2 divided doses; Max: 80mg/kg/day

---

A maximum of 80mg/kg/day as two divided doses may be considered for some infections (such as otitis media, sinusitis and lower respiratory tract infections)

---

Oral (tab)

4:1 tablet

• <25kg: Not recommended for use
• 25-40kg: 25-75mg/kg/day, in 3 divided doses; Max duration: 14 days
• >40kg: See adult dosage

7:1 tablet

• <25kg: Not recommended for use
• 25-40kg: 28.6-51.4mg/kg/day, in 2 divided doses; Max: 80mg/kg/day
• >40kg: See adult dosage

---

As the tablets cannot be divided, children weighing <25kg must not be treated with tablets

---

No clinical data are available on doses of 4:1 formulations >40 mg/10mg/kg/day in children <2 years

---

No clinical data are available for doses of 7:1 formulations of >45mg/6.4mg/kg/day in children <2 years

---

No clinical data are available for 7:1 formulations for patients <2 months of age. Dosing recommendations in this population therefore cannot be made

---

Acute bacterial sinusitis
Cystitis
Pyelonephritis
Cellulitis
Animal bites
Severe dental abscess with spreading cellulitis

Oral (tab)

2:1 tablet

• <40kg: Not recommended for use
•  ≥40kg: See adult dosage

Severe infections of the ear, nose and throat (such as mastoiditis, peritonsillar infections, epiglottitis and sinusitis when accompanied by severe systemic signs and symptoms)
Intra-abdominal infections
Female genital infections

Younger than 3 months or <4kg

• IV: 30mg/kg, 12hrly; Max duration: 14 days

Older than 3 months and between <40kg

• IV: 30mg/kg, 8hrly; Max duration: 14 days

---

May be administered either by slow IV injection over a period of 3-4 minutes directly into a vein or via a drip tube or by infusion over 30-40 minutes

---

Children <3 months should be administered amoxicillin/ clavulanic acid by infusion only

Pregnancy

• Caution
• Animal studies do not indicate direct or indirect harmful effects with respect to pregnancy, embryonal/ foetal development, parturition or postnatal development. 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

Breastfeeding

• Caution
• 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 breastfed infant, so that breastfeeding might have to be discontinued. The possibility of sensitisation should be taken into account. Amoxicillin/ clavulanic acid should only be used during breastfeeding after benefit/ risk assessment by the physician in charge

Fertility

• Amoxicillin/ clavulanate potassium at oral doses of up to 1200mg/kg/day was found to have no effect on fertility in rats dosed with a 2:1 ratio formulation of amoxicillin:clavulanate
• The effect on fertility in man is unknown

Renal Impairment

• CrCl>30ml/min: No dose adjustment recommended 
• CrCl≤30ml/min: Caution; dose adjustment recommended 
  The use of oral preparations with an amoxicillin to clavulanic acid ratio of 7:1 is not recommended
  The use of SR tabs is not recommended

CrCl (ml/min)	Adults and children ≥40kg	Children <40kg
10-30	Oral:  2:1 preparations (i.e. 375mg tab): 250mg/125mg, 12hrly   4:1 preparations: 500mg/125mg, 12hrly IV:  Initial dose: 1000mg/200mg; THEN 500mg/100mg, 12hrly	Oral:  2:1 preparations (i.e. 375mg tab): Not recommended for use 4:1 preparations: 15mg/3.75mg/kg, 12hrly; Max: 500mg/125mg/12hrs IV: 25mg/5mg/kg, 12hrly
<10	Oral:  2:1 preparations: 250mg/125mg, dly   4:1 preparations: 500mg/125mg, dly IV:  Initial dose: 1000mg/200mg; THEN 500mg/100mg, 24hrly	Oral:  2:1 preparations: Not recommended for use 4:1 preparations: 15mg/3.75mg/kg, dly; Max: 500mg/125mg/24hrs  IV:  25mg/5mg/kg, 24hrly
Haemodialysis	Oral:  2:1 preparations: Two doses of 250mg/125mg 24hrly, plus two doses of 250mg/125mg during dialysis; Repeat at the end of dialysis 4:1 preparations: 500mg/125mg, dly; plus 500mg/125mg during dialysis, to be repeated at the end of dialysis IV:  Initial dose: 1000mg/200mg; THEN 500mg/100mg, 24hrly; plus a dose of 500mg/100mg at the end of dialysis	Oral:  2:1 preparations: Not recommended for use 4:1 preparations: 15mg/3.75mg/kg, dly, prior to haemodialysis; 15mg/3.75mg/kg after haemodialysis IV:  25mg/5mg/kg, 24hrly; plus a dose of 12.5mg/2.5mg/kg at the end of dialysis

Hepatic Impairment

• Caution; no dose adjustment recommended 
  Monitor hepatic function at regular intervals

Elderly

• Caution; no dose adjustment recommended

Porphyria Information

• Not porphyrinogenic (NP)

Drugs in Sport

• Permitted - No warnings

Central Nervous System Disorders

• Dizziness
• Headache
• Seizures
• Aseptic meningitis
• Reversible hyperactivity

Cardiovascular Disorders

• Thrombophlebitis

Gastrointestinal Disorders

• Diarrhoea  
• Nausea and vomiting
• Indigestion
• Antibiotic-associated colitis
  - Pseudomembranous colitis
  - Haemorrhagic colitis
• Black hairy tongue
• Tooth discolouration

Hepatobiliary Disorders

• Increased aspartate transaminase
• Increased alanine aminotransferase
• Hepatitis
• Cholestatic jaundice

Genitourinary Disorders

• Interstitial nephritis
• Crystalluria

Skin and Subcutaneous Tissue Disorders

• Skin rash
• Pruritus
• Urticaria
• Erythema multiforme
• Stevens-Johnson syndrome
• Toxic epidermal necrolysis
• Bullous exfoliative-dermatitis
• Acute generalised exanthemous pustulosis (AGEP)
• Drug reaction with eosinophilia and systemic symptoms (DRESS)

Immune, Blood and Lymphatic System Disorders

• Mucocutaneous candidosis
• Overgrowth of non-susceptible organisms
• Angioneurotic oedema  
• Anaphylaxis
• Serum sickness-like syndrome
• Hypersensitivity vasculitis
• Reversible leucopenia  
  - Neutropenia  
• Thrombocytopenia
• Reversible agranulocytosis
• Haemolytic anaemia  
• Prolongation of bleeding time and prothrombin time

• Oral anticoagulants
• Allopurinol
• Methotrexate
• Probenecid
• Mycophenolate mofetil
• Agents known to have the potential for hepatic effects

None routine. Specific cases may require

• Renal function
• Hepatic function
• Haematologic function
• Prothrombin time
• INR

Additional observations

• Infection
• Signs of anaphylaxis (during first dose)

Suspension 400mg/57.5, - EML  (Hospital)

Injection (per 20ml) 500mg/100mg, Injection (per 20ml) 1000mg/200mg, Suspension 125mg/31.25mg, Suspension 250mg/62.5mg, Suspension 600mg/42.9, Tablet 250mg/125mg, Tablet 875mg/125mg - EML (Primary) 

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Antibiotic-associated colitis

• Antibiotic-associated colitis has been reported with nearly all antibacterial agents including amoxicillin and may range in severity from mild to life threatening. 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 contraindicated in this situation

Resistance

• This presentation of amoxicillin/ clavulanic acid may not be suitable for use when there is a high risk that the presumptive pathogens have resistance to beta-lactam agents that is not mediated by beta-lactamases susceptible to inhibition by clavulanic acid. As no specific data for T>MIC are available and the data for comparable oral presentations are borderline, this presentation (without additional amoxicillin) may not be suitable for the treatment of penicillin-resistant S. pneumoniae

Test incompatibilities

• 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 amoxicillin/ clavulanic acid 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

Administration directions (IV)

• For IV use only. Do not administer IM
• May be administered either by slow intravenous injection over a period of 3-4min directly into a vein or via a drip tube or by infusion over 30-40 minutes
• Children <3 months should be administered amoxicillin/ clavulanic acid by infusion only
• Reconstitution directions:
  - The reconstitution/ dilution is to be made under aseptic conditions. The solution is to be inspected visually for particulate matter and discoloration prior to administration. The solution should only be used if the solution is clear and free from particles
  - IV injection: Water for Injection is the normal solvent. 500/100mg: Dissolve in 10ml of solvent. This yields approximately 10.4ml of solution for single-dose use. Administer within 20 minutes of reconstitution. 1000/200mg: Water for Injection is the normal solvent. Dissolve in 20ml of solvent. This yields approximately 20.7ml of solution for single-dose use, administer within 20 minutes of reconstitution
  IV infusion: Reconstitute as described above for injection. Without delay the reconstituted solution should be added to 50ml of infusion fluid using a minibag or in-line burette. 1000/200mg: Reconstitute as described above for injection. Without delay the reconstituted solution should be added to 100ml of infusion fluid using a minibag or in-line burette

Oral administration

• All oral forms should be administered with a meal to minimise potential gastrointestinal intolerance

Amoxicillin
Amoxicillin, a semisynthetic penicillin beta-lactam antibiotic, inhibits penicillin-binding proteins (PBPs) in the biosynthetic pathway of bacterial peptidoglycan, 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
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.

Spectrum of activity: Enterococcus faecalis, Gardnerella vaginalis, Staphylococcus aureus (methicillin-susceptible), Coagulase-negative staphylococci (methicillin-susceptible), Staphylococcus saprophyticus, Staphylococcus epidermidis, Staphylococcus lugdunensis, Streptococcus agalactiae, Streptococcus pneumoniae, Streptococcus anginosus gp, Streptococcus pyogenes and other beta-haemolytic streptococci, Streptococcus viridans group, Actinomyces sp., Arcanobacter. sp. Actinobacillus actinomycetemcomitans, Capnocytophaga spp., Eikenella sp., Eikenella corrodens, Haemophilus influenzae, Moraxella catarrhalis,  Neisseria gonorrhoeae, Pasteurella multocida, Bacteroides fragilis, Fusobacterium necrophorum, Prevotella spp., Escherichia coli, Klebsiella oxytoca, Klebsiella pneumoniae, Proteus mirabilis, Proteus vulgaris, Salmonella sp., Shigella sp., Peptostreptococci, Propionibacterium acnes, Leptospira sp., Listeria monocytogenes, Kingella sp., Clostridum sp., Campylobacter jejuni Corynebacterium diphtheriae, Borrelia burgdorferi

COMBINATION PREPARATIONS

Amoxicillin/ Clavulanic acid

Tablet 250mg/125mg

• Adco Amoclav (Adcock Ingram)
• Amoclan (Cipla Medpro)
• Apex Clavutin (Camox)
• Augmaxcil 375 (Litha)
• Augmentin (GSK) originator
• Austell-Co-Amoxiclav (Austell)
• Auro Amoxiclav (Aurobindo)
• Betaclav (Ranbaxy)
• Bio-Amoksiklav (Biotech)
• Bindoclav (Actor)
• Clamentin (Xixia)
• Myclav 375 (Unichem SA)
• Ranclav (Ranbaxy)
• Sandoz Co-Amoxyclav (Sandoz)

Tablet 500mg/125mg

• Adco Amoclav  (Adcock Ingram)
• Amoclan Forte (Cipla Medpro)
• Apex-Clavutin (Camox)
• Augmaxcil 625 (Litha)
• Austell-Co-Amoxiclav (Austell)
• Auro Amoxiclav (Aurobindo)
• Betaclav (Ranbaxy)
• Bio-Amoksiklav (Biotech)
• Bindoclav (Actor)
• Curam (Sandoz)
• Myclav 625 (Unichem SA)
• Ranclav 625 (Ranbaxy)
• Sandoz Co-Amoxyclav (Sandoz)

Tablet dispersible 500mg/125mg

• Sandoz Co-Amoxyclav (Sandoz)

Tablet 875mg/125mg

• Actimentin 1000 (Trinity Pharma)
• Adco Amoclav BD (Adcock Ingram)
• Amoclan BD (Cipla Medpro)
• Auro Amoxiclav (Aurobindo)
• Augmentin BD (GSK) originator
• Augspec 1g (Trinity Pharma)
• Betaclav (Ranbaxy)
• Bio-Amoksiklav (Biotech)
• Bindoclav (Actor)
• Clamentin (Xixia)
• Co-Amoxyclav BD (Austell Laboratories)
• Curam (Sandoz)
• Ranclav (Ranbaxy)
• Sandoz Co-Amoxyclav (Sandoz)

Tablet dispersible 875mg/125mg

• Forcid Solutab (Astellas)
• Klavimaxcil (Sandoz)

Tablet 1000mg/62.5mg

• Augmentin SR (GSK) originator

Suspension (per 5ml) 125mg/31,25mg

• Adco Amoclav S (Adcock Ingram)
• Amoclan S (Cipla Medpro)
• Augmaxcil S (Litha)
• Augmentin S (GSK) originator
• Auro-Amoxiclav (Aurobindo)
• Bio-Amoksiklav S (Biotech)
• Clamentin S (Xixia)
• Clavumox S (Pharmacare)
• Ranclav S (Ranbaxy)
• Sandoz Co-Amoxyclav S (Sandoz)

Suspension (per 5ml) 250mg/62,5mg

• Adco Amoclav Forte (Adcock Ingram)
• Amoclan SF (Cipla Medpro)
• Apex-Clavutin SF (Camox)
• Augmaxcil SF (Litha)
• Augmentin SF (GSK) originator
• Auro-Amoxiclav (Aurobindo)
• Bio-Amoksiklav SF (Biotech)
• Clamentin SF (Xixia)
• Clavumox SF (Pharmacare)
• Ranclav Forte (Ranbaxy)
• Sandoz Co-Amoxyclav SF (Sandoz)

Suspension (per 5ml) 200mg/28.5mg

• Augmentin BD (GSK) originator
• Sandoz Co-Amoxiclav BD (Sandoz)

Suspension (per 5ml) 400mg/57mg

• Augmentin BD SF (GSK) originator
• Austell Co-Amoxiclav BD SF (Austell)
• Curam BD (Sandoz)
• Sandoz Co-Amoxiclav BD (Sandoz)

Suspension (per 5ml) 600mg/42.9mg

• Augmentin ES (GSK) originator
• Austell Co-Amoxiclav ES 600 (Austell)
• Camox Co-Amoxiclav ES 600 (Camox)

Injection (per vial) 500mg/100mg

• Apoclav 0.6g (Apothecon Labs)
• Augmentin IV 0.6 (GSK) originator
• Gulf Amoxy Co (Gulf)
• Sandoz Co-Amoxyclav 0.6 (Sandoz)

Injection (per vial) 1000mg/200mg

• Apoclav 1.2g (Apothecon Labs)
• Augmaxcil (Pharmacare)
• Augmentin IV 1.2 (GSK) originator
• Clamentin (Pharmacare)
• Gulf Amoxy Co (Gulf)
• Sandoz Co-Amoxyclav 1.2 (Sandoz)