Informations for option: Co-Amoxiclav 500/100 Mg Powder For Solution For Injection/Infusion, show other option

Select option:

1. Co-Amoxiclav 500/100 Mg Powder For Solution For Injection/Infusion
2. Co-Amoxiclav 500/100 Mg Powder For Solution For Injection/Infusion

Document: document 0 change

• document 0
• document 1

---

SUMMARY OF PRODUCT CHARACTERISTICS

1. NAME OF THE MEDICINAL PRODUCT

Co-Amoxiclav 500/100 mg Powder for Solution for Injection/Infusion

2.    QUALITATIVE AND QUANTITATIVE COMPOSITION

Each vial contains 500 mg amoxicillin (as the sodium salt) and 100 mg clavulanic acid (as the potassium salt).

The sodium content of each vial is 1.7 mmol. The potassium content of each vial is 0.5 mmol. For the full list of excipients, see section 6.1

3    PHARMACEUTICAL FORM

Powder for solution for injection Powder for solution for infusion White or almost white crystalline powder

4    CLINICAL PARTICULARS

4.1    Therapeutic indications

Co-Amoxiclav 500/100 mg Powder for solution for injection/infusion is indicated for the treatment of the following infections in adults and children (see sections 4.2, 4.4 and 5.1):

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

•    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

•    Intra-abdominal infections

•    Female genital infections.

Prophylaxis against infections associated with major surgical procedures in adults, such as those involving the:

•    Gastrointestinal tract

•    Pelvic cavity

•    Head and neck

•    Biliary tract surgery.

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

4.2 Posology and method of administration

Posology

Doses are expressed throughout in terms of Co-Amoxiclav content except when doses are stated in terms of an individual component.

The dose of Co-Amoxiclav 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 Co-Amoxiclav (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).

This Co-Amoxiclav powder for solution for injection or infusion provides a total daily dose of 3000 mg amoxicillin and 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 an alternative intravenous formulation of Co-Amoxiclav is selected in order to avoid administration of unnecessarily high daily doses of clavulanic acid.

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).

Consideration should be given to local guidelines on appropriate dosing frequencies for Co-Amoxiclav.

Adults and children >40 kg:

For treatment of infections as indicated in section 4.1: 1000 mg/ 200 mg every 8 hours

Paediatric population Children <40 kg

Recommended doses:

•    Children aged 3 months and over: 25 mg/5 mg per kg every 8 hours

•    Children aged less than 3 months or weighing less than 4 kg: 25 mg/5 mg per kg every 12 hours.

Older people

No dose adjustment is considered necessary.

Patients with renal impairment

Dose adjustments are based on the maximum recommended level of amoxicillin.

No dose adjustment is required in patients with creatinine clearance (CrCl) greater than 30 ml/min.

Adults and children >40 kg

CrCl: 10-30 ml/min	Initial dose of 1000 mg/200 mg and then 500 mg/100 mg given twice daily
CrCl < 10 ml /min	Initial dose of 1000 mg/200 mg and then 500 mg/100 mg given every 24 hours
Haemodialysis	Initial dose of 1000 mg/200 mg and then followed by 500 mg/100 mg every 24 hours, plus a dose of 500 mg/100 mg at the end of dialysis (as serum concentrations of both amoxicillin and clavulanic acid are decreased)

Children < 40 kg

CrCl: 10 to 30 ml/min	25 mg/5 mg per kg given every 12 hours
CrCl < 10 ml /min	25 mg/5 mg per kg given every 24 hours
Haemodialysis	25 mg/5 mg per kg given every 24 hours, plus a dose of 12.5 mg/2.5 mg per kg at the end of dialysis (as serum concentrations of both amoxicillin and clavulanic acid are decreased).

Patients with hepatic impairment

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

Precautions to be taken before handling or administering the medicinal product

Co-Amoxiclav is for intravenous use.

Co-Amoxiclav may be administered either by slow intravenous injection over a period of 3 to 4 min directly into a vein or via a drip tube or by infusion over 30 to 40 min. Co-Amoxiclav is not suitable for intramuscular administration.

Children aged less than 3 months should be administered Co-Amoxiclav by infusion only.

Treatment with Co-Amoxiclav may be initiated by the use of an intravenous preparation and completed with an appropriate oral presentation as considered appropriate for the individual patient.

For instructions on reconstitution of the medicinal product before administration, see section 6.6.

4.3 Contraindications

•    Hypersensitivity to the active substances, to any of the penicillins or to any of the excipients listed in section 6.1.

•    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).

4.4 Special warnings and precautions for use

Before initiating therapy with Co-Amoxiclav , careful enquiry should be made concerning previous hypersensitivity reactions to penicillins, cephalosporins or other beta-lactam agents (see section 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, Co-Amoxiclav 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 Co-Amoxiclav to amoxicillin in accordance with official guidance.

This presentation of Co-Amoxiclav 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.

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

Co-Amoxiclav 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 Co-Amoxiclav discontinuation and contra-indicates any subsequent administration of amoxicillin.

Co-Amoxiclav should be used with caution in patients with evidence of hepatic impairment (see sections 4.2, 4.3 and 4.8).

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, Co-Amoxiclav 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 Co-amoxiclav. 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 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 nonenzymatic methods.

The presence of clavulanic acid in Co-Amoxiclav 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 Co-Amoxiclav 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 Co-Amoxiclav should be interpreted cautiously and confirmed by other diagnostic methods.

This medicinal product contains 1.70 mmol sodium per vial. To be taken into consideration by patients on a controlled sodium diet.

This medicinal product contains less than 1 mmol (0.5 mmol) potassium per vial, i.e. it is essentially potassium free.

4.5 Interaction with other medicinal products and other forms of interaction

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 coadministration 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.

Mycophenolate mofetil (MPA)

Reductions in pre-dose (trough) MPA concentrations of about 50% have been reported in renal transplant recipients in the days immediately following commencement of amoxicillin plus clavulanic acid. This effect tended to diminish with continued amoxicillin plus clavulanic acid use and to cease within a few days of their discontinuation. The change in predose level may not accurately represent changes in overall MPA exposure. Therefore, a change in the dose of mycophenolate mofetil should not normally be necessary in the absence of clinical evidence of graft dysfunction. However, close clinical monitoring should be performed during the combination and shortly after antibiotic treatment.

4.6    Fertility, pregnancy and lactation

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 Co-Amoxiclav 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 Co-Amoxiclav may be associated with an increased risk of necrotising enterocolitis in neonates. Use should be avoided during pregnancy, unless considered essential by the physician.

Breast-feeding

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. Co-Amoxiclav should only be used during breast-feeding after benefit/risk assessment by the physician in charge.

4.7    Effects on ability to drive and use machines

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).

4.8 Undesirable effects

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

Thrombocytopenia	Rare
Reversible agranulocytosis	Not known
Haemolytic anaemia	Not known
Prolongation of bleeding time and prothrombin time1	Not known
Immune system disorders10
Angioneurotic oedema	Not known
Anaphylaxis	Not known
Serum sickness-like syndrome	Not known
Hypersensitivity vasculitis	Not known
Nervous system disorders
Dizziness	Uncommon
Headache	Uncommon
Convulsions2	Not known
Aseptic meningitis	Not known
Vascular disorders
Thrombophlebitis3	Rare
Gastrointestinal disorders
Diarrhoea	Common
Nausea	Uncommon
Vomiting	Uncommon
Indigestion	Uncommon
Antibiotic-associated colitis4	Not known
Hepatobiliary disorders
Rises in AST and/or ALT5	Uncommon
Hepatitis6	Not known
Cholestatic jaundice6	Not known
Skin and subcutaneous tissue disorders7
Skin rash	Uncommon
Pruritus	Uncommon
Urticaria	Uncommon
Erythema multiforme	Rare
Stevens-Johnson syndrome	Not known
Toxic epidermal necrolysis	Not known
Bullous exfoliative-dermatitis	Not known
Acute generalised exanthemous pustulosis (AGEP) 9	Not known
Renal and urinary disorders
Interstitial nephritis	Not known
Crystalluria8	Not known

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 the Yellow Card Scheme at: www.mhra.gov.uk/yellowcard.

4.9 Overdose

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.

Co-Amoxiclav can be removed from the circulation by haemodialysis.

5 PHARMACOLOGICAL PROPERTIES

Pharmacotherapeutic group:Combinations of penicillins, incl. beta-lactamase inhibitors ATC Code: J01C R02

Mechanism 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.

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 (pg/ml)
	Susceptible	Intermediate	Resistant
Haemophilus influenzae1	< 1	-	> 1
Moraxella catarrhalis1	< 1	-	> 1
Staphylococcus aureus 2	< 2	-	> 2
Coagulase-negative staphylococci 2	< 0.25		> 0.25
Enterococcusl	< 4	8	> 8
Streptococcus A, B, C, Gs	< 0.25	-	> 0.25
Streptococcus ■ 3 pneumomae	< 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.

5.2 Pharmacokinetic properties

Absorption

The pharmacokinetic results for studies in which Co-Amoxiclav was administered to groups of healthy volunteers as either 500 mg/100 mg or 1000 mg/200 mg given as a bolus intravenous injection are presented below.

Mean (±SD) pharmacokinetic parameters Bolus intravenous injection
Dose Amoxicillin administered	Amoxicillin
	Dose	Mean peak serum conc (pg/ml)	T 1/2 (h)	AUC (h.mg/l)	Urinary recovery (%, 0 to 6 h )
AMX/CA 500 mg/100 mg	500 mg	32.2	1.07	25.5	66.5
AMX/CA 1000 mg/200 mg	1000 mg	105.4	0.9	76.3	77.4
	Clavulanic acid
AMX/CA 500 mg/100 mg	100mg	10.5	1.12	9.2	46.0
AMX/CA 1000 mg/200 mg	200mg	28.5	0.9	27.9	63.8
AMX - amoxicillin, CA - clavulanic acid

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).

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.

Co-Amoxiclav 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 6 h after administration of a single 500/100 mg or a single 1000/200 mg bolus intravenous injection. 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.

Renal impairment

The total serum clearance of Co-Amoxiclav 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.

Pharmacokinetic/Pharmacodynamic relationship

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

5.3    Preclinical safety data

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

Repeat dose toxicity studies performed in dogs with Co-amoxiclav demonstrate gastric irritancy and vomiting, and discoloured tongue.

Carcinogenicity studies have not been conducted with Co-amoxiclav or its components.

6    PHARMACEUTICAL PARTICULARS

6.1    List of excipients

None

6.2    Incompatibilities

Amoxicilline/Clavulanic acid 500/100 mg Powder for solution for injection/infusion must not be mixed with amino acid solutions, lipid emulsions, blood and glucose solutions.

Amoxicillin/Clavulanic Acid 500/100 mg Powder for solution for injection/infusion is less stable in infusions containing dextran or bicarbonate. Reconstituted solution should, therefore, not be added to such infusions but may be injected into the drip tubing over a period of three to four minutes.

Because of the inactivation of aminoglycosides by amoxicillin, in-vitro mixing should be avoided.

Cloudiness can occur in individual cases when mixed with a lidocaine solution. It is then recommended that the solution should be discarded.

6.3 Shelf life

Powder: 2 years.

Reconstituted solution for injection: 15 minutes. From a microbiological point of view, unless the method of reconstitution precludes the risk of microbial contamination, the injection and infusion solutions should be used immediately. If not used immediately, in-use storage times and conditions are the responsibility of the user.

6.4    Special precautions for storage

Do not store above 25°C. Store in the original container.

Storage conditions after reconstitution: do not store above 25°C.

6.5    Nature and contents of container

Clear type II 10 and 20 ml glass vial(s) with bromobutyl rubber stopper and flip-off aluminium cap.

Pack sizes: 1 or 10 vials.

Not all pack sizes may be marketed

6.6 Special precautions for disposal

No special requirements.

Any unused medicinal product or waste material should be disposed of in accordance with local requirements.

Reconstitution must be carried out under aseptic conditions. The solution is to be inspected visually for particulate matter prior to administration. The solution should only be used if the solution is clear and free from particles. Any unused solution should be discarded.

Co-Amoxiclav 500/100 mg Powder for solution for injection / infusion vials are not suitable for multi-dose use.

Preparation of solutions for intravenous injection

Vials of 500/100 mg are diluted with 10 ml or up to 20 ml of water for injections.

Vial of	Water for	Volume after	Concentration after
	injection	reconstitution1	reconstitution1
500/100 mg	10 ml	10.0 ml	50,0/10,0 mg/ml
500/100 mg	20 ml	20.2 ml	24,8/5,0 mg/ml

Solutions for intravenous infusion should be administered in full within 60 min of preparation. After dissolution a light yellow colour change may occur.

7.    MARKETING AUTHORISATION HOLDER

Teva UK Ltd

Brampton Road, Hampden Park Eastbourne

East Sussex, BN22 9AG England

8.    NUMBER(S) IN THE COMMUNITY REGISTER OF MEDICINAL PRODUCTS

PL 00289/0706

9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

28/10/2005

10 DATE OF REVISION OF THE TEXT

26/06/2015

1

data based on laboratory studies

Co-Amoxiclav 500/100 mg Powder for solution for injection should be administered within 15 min of reconstitution.

Preparation of solutions for intravenous infusion

Vials of 500/100 mg are diluted with 10 ml or up to 20 ml of water for injections. If the product is dissolved in water for injection as specified, this solution may be mixed with the following solvents: Water for injection, Physiological saline, Sodium lactate 167 mmol/l, Ringer’s solution, Hartmann's solution.