Augmentin Injection

AUGMENTIN IV is indicated for the treatment of infections caused by amoxicillin resistant organisms producing u03b2-lactamases sensitive to clavulanic acid:

• upper respiratory tract infections, such as sinusitis, otitis media, tonsillitis caused by Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis and Streptococcus pyogenes sensitive to AUGMENTIN IV
• lower respiratory tract infections, such as bronchitis (caused by amoxicillin-resistant u03b2-lactamase producing Escherichia coli, Haemophilus influenzae and Haemophilus para-influenzae), bronchopneumonia sensitive to AUGMENTIN IV
• urinary tract infections, such as cystitis, urethritis, pyelonephritis caused by Enterobacteriaceae (mainly Escherichia coli), Staphylococcus saprophyticus and Enterococcus species
• skin and soft tissue infections caused by methicillin susceptible Staphylococcus aureus, Streptococcus pyogenes and Bacteroides species sensitive to AUGMENTIN IV.

AUGMENTIN IV will also be effective in the treatment of infections caused by amoxicillin-sensitive organisms at the appropriate amoxicillin dosage since in this situation the clavulanic acid component does not contribute to the therapeutic effect.

Directions for use: AUGMENTIN IV 0,6 powder for injection can be reconstituted by dissolving in 10 ml Water for Injections B.P. AUGMENTIN IV 1,2 powder for injection can be reconstituted by dissolving in 20 ml Water for Injections B.P. When a diluent is added a transient pink colouration or slight opalescence will be observed whereafter, a pale yellow fluid.

For intravenous infusion, the reconstituted vial should be further diluted with the desired volume of a suitable infusion fluid (see Compatibility and stability below).

Administration: Note: AUGMENTIN IV vials are not suitable for intramuscular or subcutaneous administration. 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 AUGMENTIN IV infusions after reconstitution and dilution as reflected in the table under the section u201cCompatibility and stabilityu201d presented above. The contents of the vials must be used within 20 minutes and thereafter any unused material discarded.

Hypersensitivity to penicillins, amoxicillin and cephalosporins or any other ingredient of AUGMENTIN. Safety and efficacy in children has not been established with the parenteral forms of AUGMENTIN. AUGMENTIN is contra-indicated in patients with a previous history of AUGMENTIN-associated jaundice/hepatic dysfunction.

Serious and occasionally fatal hypersensitivity reactions including anaphylaxis have been reported in patients on therapy with a penicillin. 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. Before initiating therapy with AUGMENTIN, careful inquiry should be made concerning previous hypersensitivity reactions to penicillins, cephalosporins or other allergens. If an allergic reaction occurs, AUGMENTIN IV should be discontinued and the appropriate therapy instituted which may include epinephrine (adrenaline), corticosteroids and antihistamines.

Since AUGMENTIN 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 morbilliform rash if amoxicillin is used. AUGMENTIN should be avoided if infectious mononucleosis is suspected.

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

Abnormal prolongation of prothrombin time (increased international normalised ratio (INR)) has been reported in patients receiving amoxicillin-clavulanate and oral anticoagulants. Appropriate monitoring should be undertaken when anticoagulants are prescribed concurrently. Adjustments in the dose of oral anticoagulants may be necessary to maintain the desired level of anticoagulation.

Changes in liver function tests have been observed in some patients receiving AUGMENTIN. Transient hepatitis and cholestatic jaundice has been reported. AUGMENTIN should be used with caution in patients with evidence of hepatic dysfunction.

In patients with moderate or severe renal impairment AUGMENTIN dosage should be adjusted according to the degree of renal impairment (see DOSAGE AND DIRECTIONS FOR USE).

The presence of clavulanic acid in amoxicillin-clavulanate may cause a non-specific binding of IgG and albumin by red cell membranes leading to a false positive Coombs test.

If the parenteral administration of high doses is necessary, the sodium content must be taken into account in patients on a sodium restricted diet. In patients with reduced urine output, crystalluria has been observed 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 (refer to KNOWN SYMPTOMS OF OVERDOSAGE AND PARTICULARS OF ITS TREATMENT).

AUGMENTIN IV should not be given intramuscularly or subcutaneously. AUGMENTIN IV should not be mixed with aminoglycosides in the same syringe or giving set, as substantial inactivation of the aminoglycosides can result. AUGMENTIN IV should be used with caution in patients with a history of gastrointestinal disease, especially antibiotic associated colitis since penicillins may cause pseudomembranous colitis. Periodic assessment of organ system functions, including renal, hepatic and haematopoietic function, is advisable during prolonged therapy. AUGMENTIN should be given with caution to patients with lymphatic leukaemia since they are especially susceptible to amoxicillin induced skin rashes.

Probenecid decreases the renal tubular secretion of amoxicillin, but does not affect clavulanic acid excretion. Concomitant use with AUGMENTIN may result in increased and prolonged blood levels of amoxicillin but not of clavulanic acid.

The concomitant administration of allopurinol and ampicillin substantially increases the incidence of 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. There is no data on AUGMENTIN and allopurinol administered concomitantly.

No information is available about the concurrent use of AUGMENTIN and alcohol. However, the ingestion of alcohol whilst being treated with some other beta-lactam antibiotics has precipitated a disulfiram-like reaction in some patients. Therefore, the ingestion of alcohol should be avoided during and for several days after treatment with AUGMENTIN.

Following administration of ampicillin to pregnant woman a transient decrease in plasma concentration of total conjugate oestriol, oestriol-glucuronide, conjugated oestrone and oestradiol has been noted. This effect may also occur with AUGMENTIN leading to lower oestrogen re-absorption and reduced efficacy of combined oral contraceptives.

The use of AUGMENTIN 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 injection site. The presence of clavulanic acid in amoxicillin-clavulanate may cause a non-specific binding of IgG and albumin by red cell membranes leading to a false positive Coombs test (antiglobulin test).

Increased INR ratio in patients maintained on warfarin and prescribed a course of AUGMENTIN may occur. If co-administration is necessary, the prothrombin time or international normalised ratio should be carefully monitored with the addition or withdrawal of AUGMENTIN.

Use in pregnancy: Safety in pregnancy has not been established. In women with pre-term, premature rupture of the foetal membrane (pPROM), it was reported that prophylactic treatment with amoxicillin-clavulanate may be associated with an increased risk of necrotising enterocolitis in neonates.

Use in lactation: Amoxicillin is excreted in the milk. There is no data on the excretion of clavulanic acid in human milk. Mothers on treatment with AUGMENTIN should not breastfeed their infants.

Data from large clinical trials was used to determine the frequency of very common to rare undesirable effects. The frequencies assigned to all other undesirable effects (i.e., those occurring at <1/10 000) were mainly determined using post-marketing data and refer to a reporting rate rather than a true frequency. The following convention has been used for the classification of frequency: very common (u2265 1/10), common (u22651/100, < 1/10), uncommon (u22651/1 000, <1/100), rare (u22651/10 000, <1/1 000), very rare (<1/10 000).

Clinical trial data:

• Infections and infestations: Common: mucocutaneous candidiasis (including vaginitis, stomatitis, glossitis)
• Blood and lymphatic system disorders: Rare: reversible leucopenia (including neutropenia) and thrombocytopenia
• Nervous system disorders: Uncommon: dizziness, headache
• Vascular disorders: Rare: thrombophlebitis at the site of injection
• Gastrointestinal disorders: Common: diarrhoea; Uncommon: nausea, vomiting, indigestion, gastritis. The incidence and severity of adverse effects, particularly nausea and diarrhoea, increased with the higher recommended dose and can be minimised by administering AUGMENTIN at the start of a meal. In addition, as these symptoms are especially related to the potassium clavulanate component, where these gastrointestinal symptoms occur and a higher concentration of amoxicillin is required, consideration should be given to administering the additional amoxicillin separately.
• Hepatobiliary disorders: Uncommon: a moderate rise in AST and/or ALT has been noted in patients treated with AUGMENTIN; Very rare: hepatitis and cholestatic jaundice. Hepatic events may be severe and fatal. 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.
• Skin and subcutaneous tissue disorders: Uncommon: skin rash, pruritus, urticaria; Rare: erythema multiforme.

Side effects reported from post-marketing spontaneous reports:

• Blood and lymphatic system disorders: Reversible agranulocytosis, haemolytic anaemia, prolongation of bleeding time and prothrombin time (increased INR). Appropriate monitoring should be undertaken when anticoagulants are prescribed concomitantly.
• Immune system disorders: Angioedema, anaphylaxis, serum sickness-like syndrome, hypersensitivity vasculitis.
• Nervous system disorders: Convulsions may occur in patients with impaired renal function or in those receiving high doses.
• Gastrointestinal disorders: Antibiotic-associated colitis (including pseudomembranous colitis and haemorrhagic colitis) (refer to WARNINGS AND SPECIAL PRECAUTIONS).
• Hepatobiliary disorders: Hepatitis and cholestatic jaundice. These events have been noted with other penicillins and cephalosporins. Hepatic events may be severe and fatal occurring predominantly in males and elderly patients, and may be associated with prolonged treatment. 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.
• Skin and subcutaneous tissue disorders: Stevens-Johnson syndrome, toxic epidermal necrolysis, bullous exfoliative-dermatitis, acute generalised exanthemous pustulosis (AGEP). If any hypersensitivity dermatitis reaction occurs, treatment should be discontinued.
• Renal and urinary disorders: Interstitial nephritis, crystalluria (refer to KNOWN SYMPTOMS OF OVERDOSAGE AND PARTICULARS OF ITS TREATMENT).

Nausea, vomiting and diarrhoea may occur with overdosing. If encountered, gastrointestinal symptoms and disturbance of the fluid and electrolyte balances may be evident. They may be treated symptomatically with attention to the water/electrolyte imbalance. Amoxicillin may be removed from 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.

During the administration of high doses of AUGMENTIN, adequate fluid intake and urinary output should be maintained to minimise the possibility of amoxicillin crystalluria. Amoxycillin crystalluria, in some cases leading to renal failure, has been observed (refer to WARNINGS AND SPECIAL PRECAUTIONS). Amoxicillin has been reported to precipitate in bladder catheters after intravenous administration of large doses. A regular check of patency should be maintained.