Augpen IV 1.2g

Amoxycillin and Potassium Clavulanate Injection IP

Augpen I.V. 150 mg

Each vial contains :

Sterile mixture of,

Amoxycillin Sodium IP equivalent to Amoxycillin 125 mg

Potassium Clavulanate IP equivalent to Clavulanic Acid 25 mg

This pack contains one ampoule of Sterile Water for Injections IP 5 ml

Augpen I.V. 300 mg

Each vial contains :

Sterile mixture of,

Amoxycillin Sodium IP equivalent to Amoxycillin 250 mg

Potassium Clavulanate IP equivalent to Clavulanic Acid 50 mg

This pack contains one ampoule of Sterile Water for Injections IP 5 ml

Augpen I.V. 600 mg

Each vial contains :

Sterile mixture of,

Amoxycillin Sodium IP equivalent to Amoxycillin 500 mg

Potassium Clavulanate IP equivalent to Clavulanic Acid 100 mg

This pack contains one ampoule of Sterile Water for Injections IP 10 ml

Augpen I.V. 1.2 g

Each vial contains :

Sterile mixture of,

Amoxycillin Sodium IP equivalent to Amoxycillin 1 g

Potassium Clavulanate IP equivalent to Clavulanic Acid 200 mg

This pack contains one ampoule of Sterile Water for Injections IP 20 ml

Sterile powder for injection

4.1 Therapeutic indication

• Upper respiratory tract infections (including ENT) e.g. recurrent tonsillitis, sinusitis, otitis media
• Lower respiratory tract infections e.g. acute exacerbation of chronic bronchitis, lobar and bronchopneumonia.
• Genito-urinary tract infections e.g. cystitis, urethritis, pyelonephritis.
• Skin and soft tissue infections e.g. boils, abscesses, cellulitis, wound infections.
• Bone and joint infections e.g. osteomyelitis
• Other infections e.g. intra-abdominal sepsis

Augpen is also indicated for prophylaxis against infection which may be associated with major surgical procedures such as gastrointestinal, pelvic, head and neck, cardiac, renal, joint replacement and biliary tract

4.2 Posology and method of administration

* Each 30 mg AUGPEN contains 25 mg amoxycillin and 5 mg clavulanate.

Adult dosage for surgical prophylaxis

The usual dose is 1.2 g I.V. AUGPEN given at the induction of anaesthesia. Operations where there is a high risk of infection, e.g. colorectal surgery, may require three, and up to four, doses of 1.2 g I.V.

AUGPEN in a 24-hour period. These doses are usually given at 0, 8, 16 (and 24) hours. This regimen can be continued for several days if the procedure has a significantly increased risk of infection.

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

Renal Impairment

Adults

Children

Similar reductions in dosage should be made for children.

Hepatic Impairment

Dose with caution; monitor hepatic function at regular intervals.

PREPARATION AND ADMINISTRATION :

AUGPEN I.V. intravenous should be administered only by intravenous injections or by intermittent I.V. infusion.

150 mg vial : to reconstitute dissolve contents in 2.5 ml Sterile Water for Injections IP (final volume: 2.62 ml).

300 mg vial : to reconstitute dissolve contents in 5 ml Sterile Water for Injections IP (final volume: 5.25 ml).

600 mg vial : to reconstitute dissolve contents in 10 ml Sterile Water for Injections IP (final volume: 10.5 ml).

1.2 g vial : to reconstitute dissolve contents in 20 ml of Sterile Water for Injections IP (final volume: 20.9 ml).

A transient pink colouration may appear during reconstitution. Reconstituted solutions normally have a pale or straw colour. Intravenous Injection : Within 20 minutes of reconstituting AUGPEN I.V. intravenous the same should be injected slowly over 3 to 4 minutes. AUGPEN I.V. intravenous may be injected either directly into a vein or through an intravenous line.

Intravenous Infusion : AUGPEN I.V. intravenous may be infused in Water for Injection IP or sodium chloride intravenous injection IP (0.9% w/v). Add without delay 600 mg reconstituted solution to 50 ml infusion fluid or 1.2 g reconstituted solution to 100 ml infusion fluid (preferably using a mini-bag or in-line burette). Infuse over 30-40 minutes and complete within 4 hours of reconstitution.

4.3 Contraindications

Patients with a history of hypersensitivity to beta-lactams, e.g. penicillins and cephalosporins.

Patients with a previous history of AUGPEN-associated jaundice/hepatic dysfunction.

4.4 Special warnings and precautions for use

Before initiating therapy with AUGPEN, careful enquiry should be made concerning previous hypersensitivity reactions, cephalosporins, or other allergens. Serious and occasionally fatal hypersensitivity reactions (including anaphylactoid and severe cutaneous adverse reactions) have been reported in patients on penicillin therapy. These reactions are more likely to occur in individuals with a history of penicillin hypersensitivity. If an allergic reaction occurs, AUGPEN therapy must be discontinued and appropriate alternative therapy instituted. Serious anaphylactic reactions require immediate emergency treatment with adrenaline. Oxygen, intravenous (i.v.) steroids and airway management (including intubation) may also be required. Changes in liver function tests have been observed in some patients receiving AUGPEN. The clinical significance of these changes is uncertain but AUGPEN should be used with caution in patients with evidence of hepatic dysfunction. Cholestatic jaundice, which may be severe, but is usually reversible, has been reported rarely. Signs and symptoms may not become apparent for up to six weeks after treatment has ceased. In patients with renal impairment AUGPEN dosage should be adjusted as recommended in the Posology and Method of Administration section. AUGPEN 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 amoxycillin. Prolonged use may also occasionally result in overgrowth of non-susceptible organisms. Pseudomembranous colitis has been reported with the use of antibiotics and may range in severity from mild to life-threatening. Therefore, it is important to consider its diagnosis in patients who develop diarrhoea during or after antibiotic use. If prolonged or significant diarrhoea occurs or the patient experiences abdominal cramps, treatment should be discontinued immediately and the patient investigated further. Abnormal prolongation of prothrombin time [increased International Normalized Ratio (INR)] has been reported rarely in patients receiving AUGPEN 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. 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 very rarely, predominantly with parenteral therapy. During administration of high doses of amoxycillin it is advisable to maintain adequate fluid intake and urinary output in order to reduce the possibility of amoxycillin crystalluria. The presence of clavulanic acid in AUGPEN may cause a non-specific binding of IgG and albumin by red cell membranes leading to a false positive Coombs test.

4.5 Drugs interactions

Concomitant use of probenecid is not recommended. Probenecid decreases the renal tubular secretion of amoxycillin. Concomitant use with AUGPEN may result in increased and prolonged blood levels of amoxycillin but not of clavulanate. Concomitant use of allopurinol during treatment with amoxycillin can increase the likelihood of allergic skin reactions. There are no data on the concomitant use of AUGPEN and allopurinol. In common with other antibiotics, AUGPEN may affect the gut flora, leading to lower oestrogen reabsorption and reduced efficacy of combined oral contraceptives. The presence of clavulanic acid in AUGPEN may cause a non-specific binding of IgG and albumin by red cell membranes leading to a false positive Coombs test. In the literature there are rare cases of increased international normalised ratio in patients maintained on acenocoumarol or warfarin and prescribed a course of amoxycillin. If coadministration is necessary, the prothrombin time or international normalised ratio should be carefully monitored with the addition or withdrawal of AUGPEN. In patients receiving mycophenolate mofetil, reduction in pre-dose concentration of the active metabolite mycophenolic acid of approximately 50% has been reported following commencement of oral amoxicillin plus clavulanic acid. The change in pre-dose level may not accurately represent changes in overall MPA exposure.

4.6 Use in special populations

Pregnancy

Reproduction studies in animals (mice and rats) with orally and parenterally administered AUGPEN have shown no teratogenic effects. In a single study in women with preterm, premature rupture of the foetal membrane (pPROM), it was reported that prophylactic treatment with AUGPEN may be associated with an increased risk of necrotising enterocolitis in neonates. As with all medicines, use should be avoided in pregnancy, especially during the first trimester, unless considered essential by the physician.

Lactation

AUGPEN may be administered during the period of lactation. With the exception of the risk of sensitisation, associated with the excretion of trace quantities in breast milk, there are no detrimental effects for the infant.

4.7 Effects on ability to drive and use machines

Adverse effects on the ability to drive or operate machinery have not been observed

4.8 Undesirable effects

Infections and infestations

Common : Mucocutaneous candidiasis

Blood and lymphatic system disorders

Rare : Reversible leucopenia (including neutropenia) and thrombocytopenia

Very rare : Reversible agranulocytosis and haemolytic anaemia. Prolongation of bleeding time and prothrombin time

Immune system disorders

Very rare : Angioneurotic oedema, anaphylaxis, serum sickness-like syndrome, hypersensitivity vasculitis

Nervous system disorders

Uncommon : Dizziness, headache

Very rare : Aseptic meningitis, convulsions. Convulsions may occur in patients with impaired renal function or in those receiving high doses.

Vascular disorders

Rare : Thrombophlebitis at the site of injection

Gastrointestinal disorders

Common : Diarrhoea

Uncommon : Nausea, vomiting, indigestion

Very rare : Antibiotic-associated colitis (including pseudomembranous colitis and haemorrhagic colitis) are less likely to occur after parenteral administration.

Hepatobiliary disorders

Uncommon : 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. Very rare : Hepatitis and cholestatic jaundice. These events have been noted with other penicillins and cephalosporins. Hepatic events have been reported 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. 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.

Skin and subcutaneous tissue disorders

Uncommon : Skin rash, pruritus, urticaria

Rare : Erythema multiforme

Very rare : Stevens-Johnson syndrome, toxic epidermal necrolysis, bullous exfoliative-dermatitis, acute generalised exanthemous pustulosis (AGEP), drug reaction with eosinophilia and systemic symptoms (DRESS) If any hypersensitivity dermatitis reaction occurs, treatment should be discontinued.

Renal and urinary disorders

Very rare : Interstitial nephritis, crystalluria

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 email to : medico@zuventus.com

By reporting side effects, you can help provide more information on the safety of this medicine.

4.9 Overdose

Gastrointestinal symptoms and disturbance of the fluid and electrolyte balances may be evident. Gastrointestinal symptoms may be treated symptomatically with attention to the water electrolyte balance. Amoxycillin crystalluria, in some cases leading to renal failure, has been observed. AUGPEN can be removed from the circulation by haemodialysis. Amoxycillin has been reported to precipitate in bladder catheters after intravenous administration of large doses. A regular check of patency should be maintained.

5.1 Mechanism of action

Amoxycillin is a semisynthetic antibiotic with a broad spectrum of antibacterial activity against many grampositive and gram-negative micro-organisms. Amoxycillin is, however, susceptible to degradation by betalactamases and therefore the spectrum of activity of amoxycillin alone does not include organisms which produce these enzymes. Clavulanic acid is a beta-lactam, structurally related to the penicillins, which possesses the ability to inactivate a wide range of beta-lactamase enzymes commonly found in microorganisms resistant to penicillins and cephalosporins. In particular, it has good activity against the clinically important plasmid mediated betalactamases frequently responsible for transferred drug resistance. It is generally less effective against chromosomally-mediated type 1 beta-lactamases. The presence of clavulanic acid in amoxycillin-clavulanate formulations protects amoxycillin from degradation by beta-lactamase enzymes and effectively extends the antibacterial spectrum of amoxycillin to include many bacteria normally resistant to amoxycillin and other penicillins and cephalosporins. Thus amoxycillin-clavulanate possesses the distinctive properties of a broad spectrum antibiotic and a betalactamase inhibitor.

5.2 Pharmacodynamic properties

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.

5.3 Pharmacokinetic properties

The pharmacokinetics of the two components of AUGPEN are closely matched. Both clavulanate and amoxycillin have low levels of serum binding; about 70% remains free in the serum. Doubling the dosage of AUGPEN approximately doubles the serum levels achieved.

6.1 Animal toxicology or pharmacology

No known animal toxicology data

AUGPEN (beta-lactam antibacterial penicillin coformulated with a beta- lactamase inhibitor) is an antibiotic agent with a notably broad spectrum of activity against the commonly occurring bacterial pathogens in general practice and hospital. The beta-lactamase inhibitory action of clavulanate extends the spectrum of amoxycillin to embrace a wider range of organisms, including many resistant to other beta-lactam antibiotics.

8.1 Incompatibilities

Not applicable

8.2 Shelf-life

Refer on the pack

8.3 Packaging information

Augpen I.V. 150 mg : A vial of 150 mg with SWFI IP 5 ml.

Augpen I.V. 600 mg : A vial of 600 mg with SWFI IP 10 ml.

Augpen I.V. 300 mg : A vial of 300 mg with SWFI IP 5 ml

Augpen I.V. 1.2 g : A vial of 1.2 g with SWFI IP 20 ml.

8.4 Storage and handing instructions

Store below 25°C. Protect from moisture. Do not freeze.

Keep out of reach of children. After reconstitution, do not use in case any foreign particulate matter is observed inside the vial

Reconstituted solutions not be frozen.

For storage at 5°C, the reconstituted solution is added to pre-refrigerated infusion bags which can be stored for up to 8 hours. Thereafter, the infusion should be administered immediately after reaching room temperature. AUGPEN I.V. intravenous should not be mixed with blood products, other proteinaceous fluids such as protein hydrolysates or with Intravenous lipid emulsions. If AUGPEN I.V. intravenous is prescribed concurrently with an aminoglycoside the antibiotics should not be mixed in the same syringe, Intravenous fluid container or I.V. set because loss of aminoglycoside activity can occur under these conditions.

Talk to your doctor or pharmacist or nurse before having Augpen if you:

• have glandular fever
• are being treated for liver or kidney problems
• are not passing water regularly.

If you are not sure if any of the above apply to you, talk to your doctor, pharmacist or nurse before taking Augpen. In some cases, your doctor may investigate the type of bacteria that is causing your infection. Depending on the results, you may be given a different strength of Augpen or a different medicine.

Conditions you need to look out for

Augpen can make some existing conditions worse, or cause serious side effects. These include allergic reactions, convulsions (fits) and inflammation of the large intestine. You must look out for certain symptoms while you are taking Augpen, to reduce the risk of any problems.

Blood and urine tests

If you are having blood tests (such as red blood cell status tests or liver function tests) or urine tests (for glucose), let the doctor or nurse know that you are taking Augpen. This is because Augpen can affect the results of these types of tests.

Other medicines and Augpen

• Tell your doctor, pharmacist or nurse if you are using, have recently used or might use any other medicines.
• If you are taking allopurinol (used for gout) with Augpen, it may be more likely that you will have an allergic skin reaction.
• If you are taking probenecid (used for gout), your doctor may decide to adjust your dose of Augpen.
• If medicines to help stop blood clots (such as warfarin) are taken with Augpen then extra blood tests may be needed.
• Augpen can affect how methotrexate (a medicine used to treat cancer or rheumatic diseases) works.
• Augpen can affect how mycophenolate mofetil (a medicine used to prevent the rejection of transplanted organs) works.

18 July 2022