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Logo AUGMAXCIL INJECTION (Injection)

SCHEDULING STATUS:
S4

PROPRIETARY NAME
(and dosage form):

AUGMAXCIL INJECTION (Injection)

COMPOSITION:
Each vial contains:

Amoxicillin Sodium equivalent to
Amoxicillin 1000 mg and Potassium Clavulanate (sterile) equivalent to Clavulanic Acid 200 mg.

PHARMACOLOGICAL CLASSIFICATION:
A 20.1.2 - Penicillins

PHARMACOLOGICAL ACTION:
AUGMAXCIL INJECTION is a combination of amoxicillin and clavulanic acid.
Amoxicillin is a semisynthetic beta-lactamase-susceptible penicillin, which has in vitro bactericidal activity against a broad spectrum of non beta-lactamase-producing Gram-positive and Gram-negative organisms. The spectrum of activity does not include those organisms that produce lactamase, namely resistant staphylococci, and all strains of Pseudomonas, Klebsiella and Enterobacter.
Clavulanic acid has been shown in vitro to be an irreversible inhibitor of beta-lactamases produced by: Staphylococcus aureus, Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, Proteus vulgaris, Haemophilus influenzae, Neisseria gonorrhoea and Bacteroides fragilis. Clavulanic acid does not inactivate the chromosomally mediated (Sykes Type 1 Cephalosporinase) beta-lactamases produced by Acinetobacter species, Citrobacter species, Enterobacter, Indole positive Proteus, Providencia species and Serratia marcescens. In vitro the formulation showed synergism against Amoxicillin-resistant organisms, with no evidence of antagonism and the activity was not reduced in the presence of serum. (In vitro activity does not necessarily imply in vivo efficacy). The clavulanic acid component has very little bactericidal activity.
Pharmacokinetics:
Absorption:
Amoxicillin is stable in the presence of acidic gastric secretions. Peak blood levels are achieved 1-2 hours after administration. There is a linear dose response in peak serum levels.
The pharmacokinetics of amoxicillin and clavulanic acid are closely allied and neither is adversely affected by the presence of food in the stomach.
Distribution:
Approximately 18% of the total plasma amoxicillin content is protein bound. Amoxicillin diffuses readily into most body tissues with the exception of the brain and spinal fluid. Inflammation generally increases the permeability of the meninges to penicllins and this may apply to amoxicillin.
Excretion:
The elimination half-life of amoxicillin is approximately 1 hour. Coadministration of probenicid has little effect on the excretion of the clavulanic acid component of the formulation. Small amounts of amoxicillin are also excreted in the faeces and bile.

INDICATIONS:
AUGMAXCIL INJECTION is indicated for the treatment of infections caused by Amoxicillin resistant organisms producing beta-lactamases sensitive to clavulanic acid:
Upper respiratory tract infections, such as tonsillitis, sinusitis and recurrent otitis media.
Lower respiratory tract infections, such as bronchitis and bronchopneumonia.
Genito-urinary tract infections, such as cystitis, urethritis and pyelonephritis.
Skin and soft tissue infections.

CONTRA-INDICATIONS:
Hypersensitivity to penicillins or to cephalosporins. Cross-sensitivity between penicillins and cephalosporins is well documented.
AUGMAXCIL INJECTION is contraindicated in patients with a previous history of amoxicillin/clavulanic -associated jaundice/hepatic dysfunction.
Safety and efficacy in children has not been established with the parenteral forms of AUGMAXCIL INJECTION.

WARNINGS:
Serious and occasionally fatal hypersensitivity (anaphylactic) reactions have been reported in patients on penicillin therapy. Before initiating therapy with AUGMAXCIL INJECTION, careful enquiry should be made concerning previous hypersensitivity reactions to penicillins, cephalosporins or other allergens. Although anaphylaxis is more frequent following parenteral therapy, it has occurred in patients on oral penicillins. These reactions are more likely to occur in individuals with a history of penicillin hypersensitivity and/or a history of sensitivity to multiple allergens. There have been reports of individuals with a history of penicillin hypersensitivity, who have experienced severe reactions when treated with cephalosporins.
If an allergic reaction occurs, AUGMAXCIL INJECTION should be discontinued and the appropriate therapy instituted. Serious anaphylactic reactions may require immediate emergency treatment with adrenaline. Oxygen, intravenous steroids and airway management may also be required.
AUGMAXCIL INJECTION should be avoided if infectious mononucleosis is suspected since the occurrence of a morbiliform rash has been associated with this condition following the use of amoxicillin.
Prolonged use may result in overgrowth of non-susceptible organisms. Pseudomembranous enterocolitis has been reported.
Prolongation of prothrombin time has been reported rarely in patients receiving AUGMAXCIL INJECTION. Appropriate monitoring should be undertaken when anticoagulants are prescribed concurrently.
Periodic assessment of organ function, including renal, hepatic and haematopoietic functions, is advisable during prolonged therapy.
Transient hepatitis and cholestatic jaundice has been reported. AUGMAXCIL INJECTION should be used with caution in patients with evidence of hepatic dysfunction. AUGMAXCIL INJECTION should not be used in patients with a glomerular filtration rate of less than 30 mL/minute.
AUGMAXCIL INJECTION should not be given intramuscularly or subcutaneously.
AUGMAXCIL INJECTION should not be mixed with aminoglycosides in the same syringe or giving set, as substantial inactivation of the aminoglycosides can result.

INTERACTIONS:
Probenecid decreases the renal tubular secretion of Amoxicillin, but does not affect clavulanic acid excretion. Concurrent use with AUGMAXCIL INJECTION may result in increased and prolonged blood levels of Amoxicillin but not of clavulanic acid. AUGMAXCIL INJECTION may reduce the efficacy of oral contraceptives and patients should be warned accordingly.
The concomitant administration of allopurinol and ampicillin substantially increases the incidence of skin rashes in patients receiving both agents as compared to patients receiving ampicillin alone. It is not known whether this potentiation of ampicillin rashes is due to allopurinol or the hyperuricaemia present in these patients. Tetracyclines and other bacteriostatic drugs may interfere with the bactericidal effects of amoxicillin.
Interaction with laboratory tests:
It is recommended that when testing for the presence of glucose in the urine during AUGMAXCIL INJECTION treatment, enzymatic glucose oxidase methods should be used. Due to the high urinary concentrations of amoxicillin, false positive readings are common with chemical methods.

PREGNANCY AND LACTATION:
Use in pregnancy:
The safety of AUGMAXCIL INJECTION has not been established.
Use in lactation:
Amoxicillin is distributed in breast milk. Although significant problems in humans have not been documented, the use of amoxicillin by nursing mothers may lead to sensitization, diarrhoea, candidiasis and skin rash in the infant.

DOSAGE AND DIRECTIONS FOR USE:
Directions for use:
To reconstitute dissolve contents in 20 mL of water for Injections USP. The reconstituted solution should be used within 20 minutes.
Compatibility and stability:
AUGMAXCIL INJECTION should not be mixed with aminoglycosides in the same syringe or giving set, as substantial inactivation of the aminoglycosides can result.
For storage at 5°C, the reconstituted solutions should be added to a pre-refrigerated bag of infusion solution. In use, the solution should be allowed to reach room temperature and then administered without delay. The reconstituted solution should be used immediately after preparation.
Administration:
AUGMAXCIL INJECTION should not be given intramuscularly or subcutaneously. The reconstituted vials can be administered intravenously by injection (2 minutes) or slow intravenous infusion (30 minutes). Infusion should be completed within the period of stability of AUGMAXCIL INJECTION after reconstitution and dilution as reflected in the table under compatibility and stability above.
The contents of the vials must be used within 20 minutes and thereafter any unused solution must be discarded.
Dosages:
For infections caused by amoxicillin sensitive organisms, the dosage is that approved for amoxicillin as the clavulanic acid component does not contribute to the therapeutic effect.
Adult (intravenous):
For severe infections of the respiratory tract, urinary tract and skin and soft tissue requiring parenteral therapy, initially one AUGMAXCIL INJECTION 1,2 g vial containing the equivalent of 1000 mg amoxicillin and 200 mg clavulanic acid, can be administered intravenously 6 to 8 hourly by intravenous injection (2 minutes) or intravenous infusion (30 minutes) until the condition settles followed by oral therapy with amoxicillin/clavulanic acid 375 tablets at the recommended dose. If no response has occurred within 48 hours therapy must be reviewed.
Intravenous treatment with AUGMAXCIL INJECTION should not be extended beyond 10 days without review and the total daily administration of clavulanic acid should not exceed 800 mg. Treatment can be continued with amoxicillin/clavulanic acid 375 tablets orally where appropriate after a satisfactory therapeutic response has been obtained.
Dosage guide:
AMOXICILLIN-SENSITIVE ORGANISMS:
Adults: Upper respiratory
tract infections
Lower respiratory
tract infections
Urinary tract
infections
Skin & soft
tissue infections
AUGMAXCIL
INJECTION
1 vial 6-8 hourly 1 vial 6-8 hourly 1 vial 6-8 hourly 1 vial 6-8 hourly

Amoxicillin-RESISTANT ORGANISMS:
Adults Upper respiratory
tract infections
(otitis media)
Lower respiratory
tract infections
(bronchitis)
Urinary tract
infections
Skin & soft
tissue infections
AUGMAXCIL
INJECTION
1 vial 6-8 hourly 1 vial 6-8 hourly 1 vial 6-8 hourly 1 vial 6-8 hourly
NOTE: Insufficient evidence exists at present to recommend an intravenous dosage in children.
Patients with renal impairment:
Each AUGMAXCIL INJECTION vial contains 1,0 mmol of potassium and 2,8 mmol of sodium.
As both the amoxicillin and clavulanic acid components of AUGMAXCIL INJECTION are excreted by the kidneys, accumulation of both may occur in patients with renal insufficiency. In these cases monitoring of the serum levels and a reduction in the number of administrations of the suggested dosage may be required.
Experience in a limited number of patients with varying degrees in renal insufficiency suggests that the following schedule of dosage based on the creatinine clearance of the patients, may be used as a guideline:
Creatinine clearance Dosage
        > 30 mL/min No dosage adjustment
        10-30 mL/min 1,2 g AUGMAXCIL INJECTION initially and then 600 mg 12 hourly
        < 10 mL/min 1,2 g AUGMAXCIL INJECTION initially and then 600 mg daily

SIDE EFFECTS AND SPECIAL PRECAUTIONS:
Side-effects:
The following side-effects have been reported but the frequencies are unknown:
The most frequently reported adverse effects are diarrhoea, nausea, vomiting, indigestion, abdominal pain, skin rashes, urticaria, and erythema multiforme, vaginitis, abnormal taste, headache, dizziness, tiredness and hot flushes.
The incidence and severity of adverse effects, particularly nausea and diarrhoea, increased with the higher recommended dose and can be minimized by administering AUGMAXCIL INJECTION at the start of a meal. In addition, as these symptoms are especially related to the potassium clavulanate component, where these gastro-intestinal symptoms occur and a higher concentration of amoxicillin is required, consideration should be given to administering the additional amoxicillin separately.
The following adverse reactions have been reported with AUGMAXCIL INJECTION:
Hypersensitivity reactions:
Skin rashes, pruritis, urticaria, serum sickness-like syndrome, erythema multiforme, rare cases of Stevens-Johnson syndrome and less frequently bullous exfoliative dermatitis and toxic epidermal necrolysis have been reported. Whenever such reactions occur, AUGMAXCIL INJECTION should be discontinued. Serious and occasional fatal hypersensitivity (anaphylactic) reactions and angioneurotic oedema can occur with oral penicillin (see WARNINGS).
Interstitial nephritis can occur rarely.
Gastro-intestinal reactions:
Nausea, vomiting, diarrhoea, gastritis, stomatitis, glossitis, black `hairy' tongue, enterocolitis, mucocutaneous candidiasis and antibiotic-associated colitis (including pseudomembranous colitis and haemorrhagic colitis). If gastro-intestinal reactions are evident, they may be reduced by taking AUGMAXCIL INJECTION at the start of a meal.
Hepatic effects:
Hepatitis and cholestatic jaundice have been reported. The events may be severe, and occur predominantly in adult or elderly patients. 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.
The hepatic events are usually reversible. However, in extremely rare circumstances, death has been reported. These have almost always been cases associated with serious underlying disease or concomitant medication.
A moderate rise in Aspartate transaminase (AST) and/or Alanine transaminase (ALT) has been noted in patients treated with AUGMAXCIL INJECTION, but the significance of these findings is unknown.
Renal effects:
Crystalluria has been reported.
Haematological effects:
Haemolytic anaemia, reversible thrombocytopenia, thrombocytopenic purpura, eosinophilia, leucopenia and agranulocytosis have been reported. These reactions are usually reversible on discontinuation of therapy and are believed to be hypersensitivity phenomena. A slight thrombocytosis was noted in less than 1% of the patients treated with AUGMAXCIL INJECTION. Prolongation of bleeding time and prothrombin time has also been reported less frequently. Appropriate monitoring should be undertaken when anticoagulants are prescribed concomitantly.
Central nervous system effects (CNS effects):
CNS effects have been seen rarely. These include reversible hyperactivity, dizziness, headache and convulsions. Convulsions may occur with impaired renal function or in those receiving high doses.
Special precautions:
Caution is needed when administering amoxicillin to patients with syphilis, as the Jarisch-Herxheimer reaction may occur in these patients.
When high doses are administered, adequate fluid intake and urinary output must be maintained.
The sodium content must be taken into account in patients on a sodium-restricted diet if the administration of high doses is necessary.
The use of lignocaine or benzyl alcohol together with amoxicillin must be used only when administering an intramuscular injection and not given intravenously.
Periodic assessment of organ system functions, including renal, hepatic and haematopoietic function, is advisable during prolonged therapy. Since AUGMAXCIL INJECTION contains amoxicillin, an aminopenicillin, it is not the treatment of choice in patients presenting with sore throat or pharyngitis because of the possibility that the underlying cause is infectious mononucleosis, in the presence of which there is a high incidence of rash if amoxicillin is used. AUGMAXCIL INJECTION should be given with caution to patients with lymphatic leukaemia since they are especially susceptible to amoxicillin induced skin rashes.
The possibility of superinfections with mycotic or bacterial pathogens should be kept in mind during therapy. If superinfections occur (usually involving Aerobacter, Pseudomonas or Candida), the agent should be discontinued and/or appropriate therapy instituted.
Impaired hepatic function:
Changes in liver function tests have been observed in some patients receiving AUGMAXCIL INJECTION. It should be used with care in patients with evidence of severe hepatic dysfunction.
Impaired renal function:
In patients with moderate or severe renal impairment, AUGMAXCIL INJECTION dosage should be adjusted.
Use in lactation:
Amoxicillin is excreted in the milk; there is no data on the excretion of clavulanic acid in human milk. Therefore, caution should be exercised when AUGMAXCIL INJECTION is administered to a nursing woman.
The use of AUGMAXCIL INJECTION may lead to the selection of resistant strains of organisms and sensitivity testing should, therefore, be carried out whenever possible, to demonstrate the appropriateness of therapy.
Intravenous administration can cause local irritation, induration and phlebitis at the injections site.

KNOWN SYMPTOMS OF OVERDOSAGE AND PARTICULARS OF ITS TREATMENT:
Overdosage with amoxicillin is usually asymptomatic. However, gastrointestinal effects such as nausea, vomiting and diarrhoea may be evident and symptoms of water and electrolyte imbalance should be treated symptomatically.
Adequate fluid intake and urinary output must be maintained to minimize the possibility of crystalluria.
Amoxicillin may be removed from the circulation by haemodialysis. The molecular weight, degree of protein binding and pharmacokinetic profile of clavulanic acid together with information from a single patient with renal insufficiency all suggest that this compound may also be removed by haemodialysis.

IDENTIFICATION:
A white to yellowish coloured powder filled into 20 mL Type I flint vial (Moulded or Tubular) and plugged with 20 mm dark grey coloured rubber plug and sealed with 20 mm violet coloured flip off aluminium seal.
The reconstituted solution is a clear, colourless to pale yellow solution, free from visible particles.

PRESENTATION:
1 x 20 mL flint, tubular, clear, colourless, Type 1 glass vial, with 20 mm flip off aluminium seals.

STORAGE CONDITIONS:
Store in a cool, dry place below 25ºC. Protect from light. Do not remove from carton until required for use. The reconstituted solution should be used immediately after preparation.
KEEP OUT OF REACH OF CHILDREN.

REGISTRATION NUMBER:
37/20.1.2/0674.

NAME AND BUSINESS ADDRESS OF THE APPLICANT:
PHARMACARE LIMITED
Building 12
Healthcare Park
Woodlands Drive
Woodmead
Sandton
2148

DATE OF PUBLICATION OF THIS PACKAGE INSERT:
24 April 2006.

1008655

New addition to this site: February 2010
Source: Pharmaceutical Industry
Product launch: October 2007

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