Consumer medicine information

Curam 125/31.25

Amoxicillin; Clavulanic acid

BRAND INFORMATION

Brand name

Curam 125/31.25 Powder for Suspension

Active ingredient

Amoxicillin; Clavulanic acid

Schedule

What is in this leaflet

This leaflet answers some common questions about Curam 125/31.25.

It does not contain all the available information. It does not take the place of talking to your doctor or pharmacist.

All medicines have risks and benefits. Your doctor has weighed the risks of your child taking this medicine against the benefits they expect it will have.

If you have any concerns about your child taking this medicine, ask your doctor or pharmacist.

Keep this leaflet with the medicine. You may need to read it again.

What Curam 125/31.25 is used for

This medicine is used to treat a wide range of infections caused by bacteria. These infections may affect:

the chest (bronchitis or pneumonia)
the bladder (cystitis)
the sinuses (sinusitis)
the ears (otitis media)
or the skin.

It works by killing the bacteria that cause these infections.

This medicine contains the active ingredients amoxicillin (as trihydrate) and clavulanic acid (as potassium clavulanate). Amoxicillin belongs to the penicillin group of antibiotics. Clavulanic acid is used to increase the effectiveness of amoxicillin against certain types of bacteria.

Ask your doctor if you have any questions about why this medicine has been prescribed for your child. Your doctor may have prescribed it for another reason.

There is no evidence that this medicine is addictive.

This medicine is available only with a doctor's prescription.

Before you give Curam 125/31.25

When you must not give it

Do not give this medicine if your child has an allergy to:

amoxicillin trihydrate or potassium clavulanate, the active ingredients, or to any of the other ingredients listed at the end of this leaflet under Product description
any other similar medicines (such as penicillins, cephalosporins, carbapenems, monobactams or any other types of antibiotics).

Some of the symptoms of an allergic reaction may include:

shortness of breath
wheezing or difficulty breathing
swelling of the face, lips, tongue or other parts of the body
rash, itching or hives on the skin.

If your child has ever had an allergic reaction when taking an antibiotic, you should tell the doctor before this medicine is given.

Do not give this medicine if your child has previously experienced liver problems after taking Curam 125/31.25 or any other medicines.

Do not give this medicine after the expiry date printed on the pack or if the packaging is torn or shows signs of tampering. If it has expired or is damaged, return it to your pharmacist for disposal.

If you are not sure whether your child should be given this medicine, talk to your doctor.

Before your child starts taking it

Tell your doctor if your child has allergies to any other medicines, foods, preservatives or dyes.

Tell your doctor if your child has or has had any of the following medical conditions:

an allergic reaction (such as a rash) to any antibiotics in the past
glandular fever (mononucleosis) or a blood disorder
liver or kidney problems. The dosage of Curam 125/31.25 may need to be changed or your child may need to be given an alternative medicine.
phenylketonuria.
Curam 125/31.25 contains aspartame.

Tell your doctor if your child's urine has to be tested for sugar. Curam 125/31.25 may affect the results of these tests.

If you have not told your doctor about any of the above, tell him/her before you give Curam 125/31.25 to your child.

Taking other medicines

Tell your doctor or pharmacist if your child is taking any other medicines, including any that you get without a prescription from your pharmacy, supermarket or health food shop.

Some medicines and Curam 125/31.25 may interfere with each other. These include:

probenecid
allopurinol
warfarin or other medicines used to prevent blood clots
mycophenolate
methotrexate, a medicine used to treat arthritis and some types of cancer
other antibiotics. These may interfere with the actions of Curam 125/31.25.

These medicines may be affected by Curam 125/31.25 or may affect how well it works. Your child may need different amounts of their medicines, or they may need to take different medicines.

Your doctor and pharmacist have more information on medicines to be careful with or avoid while taking this medicine.

How to give Curam 125/31.25 to your child

Follow all directions given to you by your doctor or pharmacist carefully. They may differ from the information contained in this leaflet.

If you do not understand the instructions, ask your doctor or pharmacist for help.

How much to give

Give Curam 125/31.25 as directed by your doctor or pharmacist.

The usual dose of Curam 125/31.25 is one dose given three times a day. The dose may vary depending on your child's weight.

Ask your doctor or pharmacist if you are unsure of the correct dose for your child. They will tell you exactly how much to give.

Follow the instructions they give you. If you give the wrong dose, Curam 125/31.25 may not work as well and your child's problem may not improve.

How to give it

The suspension will be prepared by your pharmacist who checks the seal prior to reconstitution. Shake the bottle well and accurately measure the dose with a measuring spoon. Your pharmacist will explain how many millilitres of suspension will be needed to receive the correct dose.

Do not use the reconstituted suspension if the colour is not offwhite.

Shaking the bottle and using a measuring spoon will make sure that you get the correct dose. A measuring spoon is included with the product. Make sure the whole dose is swallowed each time.

When to give Curam 125/31.25

Space the doses as evenly as possible throughout the day. If your child is taking Curam 125/31.25 three times a day, give a dose about every eight hours.

Curam 125/31.25 should be given immediately before or with the first mouthful of food. Curam 125/31.25 works best when given this way. It may also help to prevent stomach upsets. However, this medicine will still work if given without food.

How long to give Curam 125/31.25

Continue giving this medicine until the course is finished or for as long as your doctor advises. Do not stop giving this medicine just because your child feels better as the infection can return.

Do not stop giving Curam 125/31.25, or change the dose without first checking with your doctor.

If you forget to give it

Give the missed dose as soon as you remember, and continue to give it as you would normally. If it is almost time for the next dose, skip the dose you missed and give the next dose when you are meant to.

Do not give two doses within four hours of each other.

Do not give a double dose to make up for the dose that you missed. This may increase the chance of your child getting an unwanted side effect.

If you are not sure what to do, ask your doctor or pharmacist.

If you have trouble remembering to give the medicine, ask your pharmacist for some hints.

If you give too much (overdose)

Immediately telephone your doctor or the Poisons Information Centre (telephone 13 11 26) for advice, or go to Accident and Emergency at the nearest hospital, if you think that your child or anyone else may have taken too much Curam 125/31.25. Do this even if there are no signs of discomfort or poisoning. Your child may need urgent medical attention.

There are unlikely to be any serious problems following an overdose of Curam 125/31.25.

While you are giving Curam 125/31.25

Things you must do

If your child is about to be started on any new medicine, remind your doctor and pharmacist that your child is taking Curam 125/31.25.

Tell any other doctors, dentists, and pharmacists who are treating your child that he/she is taking this medicine.

If your child is about to have any blood tests, tell your doctor that your child is taking this medicine. It may interfere with the results of some tests.

Keep all of your doctor's appointments so that your child's progress can be checked. Your doctor may do some tests from time to time to make sure the medicine is working and to prevent unwanted side effects.

Tell your doctor if, for any reason, you have not given the medicine exactly as directed. Otherwise, your doctor may think that it was not working as it should and change your child's treatment unnecessarily.

If your child develops itching, swelling or a skin rash while taking Curam 125/31.25, do not give any more and tell the doctor immediately.

If your child develops severe diarrhoea either while taking Curam 125/31.25 or within several weeks after treatment, tell the doctor as soon as possible. Do not give any medication to stop the diarrhoea (e.g. Lomotil® or Imodium®).

Things you must not do

Do not give Curam 125/31.25 to treat any other complaints unless your doctor tells you to.

Do not give this medicine to anyone else, even if they have the same condition as your child.

Do not stop giving Curam 125/31.25 or lower the dosage without checking with your doctor.

Side effects

Tell your doctor or pharmacist as soon as possible if your child does not feel well while taking Curam 125/31.25.

All medicines can have side effects. Sometimes they are serious, most of the time they are not. Your child may need medical attention if he/she gets some of the side effects.

Do not be alarmed by the following lists of side effects. Your child may not experience any of them.

Ask your doctor or pharmacist to answer any questions you may have.

Tell your doctor or pharmacist if you or your child notices any of the following and they worry you:

diarrhoea (several loose bowel movements per day), indigestion, pain in the stomach, feeling sick or being sick
soreness of the mouth or tongue, abnormal taste, hairy tongue
aseptic meningitis, headache, dizziness, tiredness, hot flushes
oral thrush (white, furry sore tongue and mouth)
vaginal thrush (sore and itchy vagina, vaginal discharge)
unusually active (hyperactive).

The above list includes the more common side effects of your medicine.

Tell your doctor as soon as possible if you or your child notices any of the following:

itching
rash
yellowing of the skin or eyes
dark urine or pale stools
severe diarrhoea
unusual bleeding or bruising.

The above list includes serious side effects that may require medical attention. Serious side effects are rare.

Stop giving Curam 125/31.25 if any of the following happen, tell your doctor immediately or go to Accident and Emergency at your nearest hospital:

wheezing, swelling of the lips/mouth, difficulty in breathing or swallowing, hayfever, lumpy rash (hives) or fainting, joint discomfort or swelling, swollen lymph glands, nausea and vomiting. These could be symptoms of an allergic reaction.

The above list includes very serious side effects. Your child may need urgent medical attention or hospitalisation. These side effects are rare.

Rare events that have been reported with Curam 125/31.25 include:

inflammation of the bowel (colitis)
inflammation of the liver or kidney
blood disorders
crystals in the urine (crystalluria).

Tell your doctor or pharmacist if you notice anything else that is making your child feel unwell. Other side effects not listed above may also occur in some people.

After giving Curam 125/31.25

Storage

Keep this medicine in the original container.

If you take it out of its original container it may not keep well.

Do not store Curam 125/31.25 or any other medicine in the bathroom or near a sink. Do not leave it on a window sill or in the car.

Keep it where children cannot reach it.

Keep the bottle in the refrigerator where the temperature stays between 2 and 8°C. Heat can destroy Curam 125/31.25.

Do not use any suspension left in the bottle 7 days after collecting from the pharmacy or if the expiry date has passed.

Disposal

If your doctor tells you to stop giving this medicine or the expiry date has passed, ask your pharmacist what to do with any medicine that is left over.

Product description

What it looks like

Curam 125/31.25 powder for suspension is available as an off-white powder, and when reconstituted with water it becomes an off-white suspension.

Available in 100 mL bottles containing 75 mL suspension, with a measuring spoon included.

Ingredients

Active ingredients:

Each 5 mL of Curam 125/31.25 suspension contains 125mg of amoxicillin (as trihydrate) and 31.25 mg clavulanic acid (as potassium clavulanate).

Inactive ingredients:

lemon flavouring 15.02.0598
orange flavouring 55301 AP0551
peach apricot flavouring 26F22
citric acid
sodium citrate
aspartame
purified talc
guar gum
silicon dioxide.

This medicine does not contain sucrose, gluten, tartrazine or any other azo dyes.

Supplier

Sandoz Pty Ltd
ABN 60 075 449 553
54 Waterloo Road
Macquarie Park, NSW 2113
Tel: 1800 726 369

This leaflet was revised in February 2021.

Australian Register Number(s)
125/31.25 powder for suspension: AUST R 146979 (bottles).

Published by MIMS April 2021

BRAND INFORMATION

Brand name

Curam 125/31.25 Powder for Suspension

Active ingredient

Amoxicillin; Clavulanic acid

Schedule

1 Name of Medicine

Amoxicillin trihydrate/potassium clavulanate.

2 Qualitative and Quantitative Composition

Each 5 mL of reconstituted suspension contains 125 mg amoxicillin (as trihydrate) and 31.25 mg clavulanic acid (as potassium clavulanate).
When reconstituted as directed, Curam 125/31.25 contains aspartame 8.5 mg/5 mL.
Each 5 mL of suspension contains 0.16 mmol of potassium.
For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

Curam 125/31.25 amoxicillin 125 mg/5 mL (as trihydrate) and clavulanic acid 31.25 mg/5 mL (as potassium clavulanate) powder for suspension: off-white powder and off-white suspension.

4 Clinical Particulars

4.1 Therapeutic Indications

Curam 125/31.25 (amoxicillin and clavulanic acid) is indicated for the treatment of the following infections when caused by Curam 125/31.25 sensitive, beta-lactamase producing organisms:
Skin and skin structure infections, including cases caused by beta-lactamase producing Staph. aureus, E. coli and Klebsiella sp. (only some strains may be sensitive).
Urinary tract infections, including cases caused by beta-lactamase producing E. coli, P. mirabilis and Klebsiella sp.
Upper respiratory tract infections, such as sinusitis, including cases caused by beta-lactamase producing H. influenzae and M. catarrhalis, and otitis media, especially cases caused by beta-lactamase producing H. influenzae, M. catarrhalis and Staph. aureus.
Lower respiratory tract infections, especially cases caused by beta-lactamase producing H. influenzae and M. catarrhalis.
Appropriate culture and susceptibility studies should be performed to identify the causative organism(s) and determine its (their) susceptibility to Curam 125/31.25 (amoxicillin and clavulanic acid). However, when there is reason to believe an infection may involve any of the beta-lactamase producing organisms listed in Microbiology, therapy may be instituted prior to obtaining the results from bacteriological and susceptibility studies. Once these results are known, therapy should be adjusted if appropriate.
The treatment of mixed infections caused by amoxicillin susceptible organisms and beta-lactamase producing organisms susceptible to Curam 125/31.25 (amoxicillin and clavulanic acid) should not require the addition of another antibiotic due to the amoxicillin content of Curam 125/31.25.

4.2 Dose and Method of Administration

Dosage.

Adults.

Curam 125/31.25 (amoxicillin and clavulanic acid) should be taken immediately before or with the first mouthful of food, to minimise potential gastrointestinal intolerance and to optimise absorption.

Infants and children.

The usual dose is 20 mg/kg/day, based on the amoxicillin component, in divided doses every eight hours. For otitis media, sinusitis, lower respiratory tract infections and other more severe infections, the dose should be 40 mg/kg/day, based on the amoxicillin component in divided doses every eight hours.
The children's dosage is intended for individuals whose weight will not cause dosage to be calculated greater than that recommended for adults.
Children weighing 40 kg and more should be dosed according to the adult recommendations for other Curam preparations (for more information refer to the product information for Curam Duo 400/57).
Treatment should usually be continued for 48 to 72 hours beyond the time that the patient becomes asymptomatic or evidence of bacterial eradication has been obtained. Treatment should not exceed ten days except for lower respiratory tract infection due to H. influenzae where treatment may be extended up to 14 days.

Method of administration.

Directions for reconstituting the oral suspension.

Prepare a suspension at time of dispensing as follows. Tap bottle until all the powder flows freely. Add approximately half of the total amount of water for reconstitution (see below) and shake vigorously to suspend powder. Add remainder of the water and again shake vigorously.
Add 71 mL of water to 6.75 g of the powder for reconstitution of 75 mL ready-for-use suspension.
Each 5 mL will contain amoxicillin (as the trihydrate) 125 mg and clavulanic acid (as the potassium salt) 31.25 mg.
Reconstituted suspension must be stored under refrigeration (2°C to 8°C) and discarded after seven days.

Dosage adjustment.

Renal impairment. Both amoxicillin and clavulanic acid are excreted by the kidneys and the serum half-life of each increases in patients with renal failure. No adjustment to the initial Curam 125/31.25 (amoxicillin and clavulanic acid) dose is necessary, but the dosing interval should be extended according to the degree of renal impairment. The following schedule is proposed.

Mild impairment.

Creatinine clearance > 30 mL/minute: no change in dosage.

Moderate impairment.

Creatinine clearance 10 to 30 mL/minute: one dose every 12 hours.

Severe impairment.

Creatinine clearance < 10 mL/minute: half a dose every 12 hours.
Haemodialysis decreases serum concentrations of both amoxicillin and clavulanic acid and an additional dose should be administered at the end of dialysis.
Hepatic impairment. Data are currently insufficient for a dosage recommendation. Dose with caution and monitor hepatic function at regular intervals.

4.3 Contraindications

Curam 125/31.25 (amoxicillin and clavulanic acid) is contraindicated in patients with hypersensitivity to the active substance or to any of the excipients.
Curam 125/31.25 (amoxicillin and clavulanic acid) is contraindicated in patients with a history of allergic reaction to beta-lactams, e.g. penicillins, cephalosporins, carbapenems or monobactams.
Curam 125/31.25 (amoxicillin and clavulanic acid) is also contraindicated in patients with a previous history of cholestatic jaundice/ hepatic dysfunction associated with amoxicillin and clavulanic acid.

4.4 Special Warnings and Precautions for Use

Use with caution in the following circumstances.

Curam 125/31.25 (amoxicillin and clavulanic acid) contains aspartame, and should be used with caution in patients with phenylketonuria.
Before initiating therapy with amoxicillin/ clavulanic acid, careful enquiry should be made concerning previous hypersensitivity reactions to penicillins, cephalosporins or other allergens.
Serious and occasionally fatal hypersensitivity (including anaphylactoid and severe cutaneous adverse reactions) reactions have been reported in patients on penicillin therapy. 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. Before initiating therapy with any penicillin, careful inquiry should be made concerning previous hypersensitivity reactions to penicillins, cephalosporins or other allergens. Hypersensitivity reactions can also progress to Kounis syndrome, a serious allergic reaction that can result in myocardial infarction. Presenting symptoms of such reactions can include chest pain occurring in association with an allergic reaction to amoxicillin/clavulanic acid (see Section 4.8 Adverse Effects (Undesirable Effects)). If an allergic reaction occurs, Curam 125/31.25 (amoxicillin and clavulanic acid) should be discontinued and the appropriate therapy instituted. Serious anaphylactoid reactions require immediate emergency treatment with adrenaline. Oxygen, intravenous steroids and airway management, including intubation, should also be administered as indicated.
Drug-induced enterocolitis syndrome (DIES) has been reported mainly in children receiving amoxicillin/clavulanate (see Section 4.8 Adverse Effects (Undesirable Effects)). DIES is an allergic reaction with the leading symptom of protracted vomiting (1-4 hours after administration of amoxicillin/clavulanate) in the absence of allergic skin or respiratory symptoms. Further symptoms could comprise abdominal pain, diarrhoea, hypotension or leucocytosis with neutrophilia. There have been severe cases including progression to shock.
Antibiotic associated pseudomembranous colitis has been reported with many antibiotics including amoxicillin. A toxin produced by Clostridium difficile appears to be the primary cause. The severity of the colitis may range from mild to life threatening. It is important to consider this diagnosis in patients who develop diarrhoea or colitis in association with antibiotic use (this may occur up to several weeks after cessation of antibiotic therapy). Mild cases usually respond to drug discontinuation alone. However in moderate to severe cases appropriate therapy with a suitable oral antibiotic agent effective against Clostridium difficile should be considered. Fluids, electrolytes and protein replacement should be provided when indicated. Drugs which delay peristalsis, e.g. opiates and diphenoxylate with atropine (Lomotil) may prolong and/or worsen the condition and should not be used.
As with any potent drug, periodic assessment of organ system functions, including renal, hepatic and haemopoietic function is advisable during prolonged therapy.
Since Curam 125/31.25 (amoxicillin and clavulanic acid) 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.
Curam 125/31.25 (amoxicillin and clavulanic acid) should be given with caution to patients with lymphatic leukaemia since they are especially susceptible to amoxicillin induced skin rashes.
Amoxicillin/ clavulanic acid 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.
Prolonged use may also occasionally result in overgrowth of non-susceptible organisms.
Abnormal prolongation of prothrombin time (increased INR) has been reported rarely in patients receiving amoxicillin/ clavulanic acid 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.
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 drug should be discontinued and/or appropriate therapy instituted.
Cholestatic hepatitis, which may be severe but is usually reversible, has been reported. Signs and symptoms may not become apparent until several weeks after treatment has ceased. In most cases resolution has occurred with time. However, in extremely rare circumstances, deaths have been reported. These have almost always been cases associated with serious underlying disease or concomitant medications. Hepatic events subsequent to amoxicillin and clavulanic acid have occurred predominantly in males and elderly patients and may be associated with prolonged treatment. These events have been very rarely reported in children.

Use in hepatic impairment.

Curam 125/31.25 (amoxicillin and clavulanic acid) should be used with care in patients with evidence of hepatic dysfunction.

Use in renal impairment.

In patients with moderate or severe renal impairment, Curam 125/31.25 (amoxicillin and clavulanic acid) dosage should be adjusted (see Section 4.2 Dose and Method of Administration).
In patients with reduced urine output, crystalluria (including acute renal injury) has been observed very rarely, predominantly 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 (see Section 4.8 Adverse Effects (Undesirable Effects); Section 4.9 Overdose).

Use in the elderly.

No data available.

Paediatric use.

For more information, see Section 4.2 Dose and Method of Administration.

Effects on laboratory tests.

Oral administration of Curam 125/31.25 (amoxicillin and clavulanic acid) will result in high urine concentrations of amoxicillin. Since high urine concentrations of ampicillin may result in false positive reactions when testing for the presence of glucose in urine using Clinitest, Benedict's solution or Fehling's solution, it is recommended that glucose tests based on enzymatic glucose oxidase reactions (such as Clinistix or Testape) be used.
The presence of clavulanic acid in amoxicillin/clavulanic acid tablets 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.
Following administration of ampicillin to pregnant women a transient decrease in plasma concentration of total conjugated oestriol, oestriol-glucuronide, conjugated oestrone and oestradiol has been noted. This effect may also occur with amoxicillin and therefore Curam 125/31.25 (amoxicillin and clavulanic acid).

4.5 Interactions with Other Medicines and Other Forms of Interactions

Concomitant use of probenecid is not recommended. Probenecid decreases the renal tubular secretion of amoxicillin but does not notably affect clavulanic acid excretion. Concurrent use with Curam 125/31.25 (amoxicillin and clavulanic acid) may result in increased and prolonged blood levels of amoxicillin but not of clavulanic acid.
The concurrent administration of allopurinol and ampicillin increases substantially the incidence of rashes in patients receiving both drugs 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 are no data with Curam 125/31.25 (amoxicillin and clavulanic acid) and allopurinol administered concurrently.
No information is available about the concurrent use of Curam 125/31.25 (amoxicillin and clavulanic acid) and alcohol. However, the ingestion of alcohol while being treated with some other beta-lactam antibiotics has precipitated a disulfiram (Antabuse)-like reaction in some patients. Therefore, the ingestion of alcohol should be avoided during and for several days after treatment with Curam 125/31.25 (amoxicillin and clavulanic acid).
In common with other antibiotics, Curam 125/31.25 (amoxicillin and clavulanic acid) may affect the gut flora, leading to lower oestrogen reabsorption and reduced efficacy of oral contraceptives.
In the literature there are rare cases of increased international normalised ratio in patients maintained on acenocoumarol or warfarin and prescribed a course of amoxicillin. If co-administration is necessary, the prothrombin time or international normalised ratio should be carefully monitored with the addition or withdrawal of amoxicillin.
Penicillins may reduce the excretion of methotrexate causing a potential increase in toxicity.
In patients receiving mycophenolate mofetil, reduction in pre-dose concentration of the active metabolite mycophenolic acid (MPA) 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. However, close clinical monitoring should be performed during the combination and shortly after antibiotic treatment.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

Amoxicillin and clavulanic acid at oral doses of up to 1,200 mg/kg/day had no effect on fertility and reproductive performance in rats dosed with a 2:1 ratio formulation of amoxicillin and clavulanate.
(Category B1)
Animal studies with orally and parenterally administered amoxicillin and clavulanic acid have shown no teratogenic effects. There is limited experience of the use of amoxicillin and clavulanic acid in human pregnancy. In women with preterm, premature rupture of the foetal membrane (pPROM), prophylactic treatment with amoxicillin and clavulanic acid 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 doctor.

Use in labour and delivery.

Oral ampicillin class antibiotics are generally poorly absorbed during labour. Studies in guinea pigs have shown that intravenous administration of ampicillin decreased the uterine tone, frequency of contractions, height of contractions and duration of contractions. However, it is not known whether the use of amoxicillin and clavulanic acid in humans during labour or delivery has immediate or delayed adverse effects on the foetus, prolongs the duration of labour or increases the likelihood that forceps delivery or other obstetric intervention or resuscitation of the newborn infant will be necessary.
Both amoxicillin and clavulanic acid are excreted into breast milk. Consequently, diarrhoea and fungus infection of the mucous membranes are possible in the breastfed infant. The possibility of sensitisation should be taken into account. Therefore, caution should be exercised when Curam 125/31.25 (amoxicillin and clavulanic acid) is administered to a breastfeeding woman.

4.7 Effects on Ability to Drive and Use Machines

Adverse effects on the ability to drive or operate machinery have not been observed. However, undesirable effects may occur (e.g. allergic reactions, dizziness, convulsions), which may influence the ability to drive and use machines.

4.8 Adverse Effects (Undesirable Effects)

Amoxicillin and clavulanic acid is generally well tolerated. In clinical trials, the overall incidence of adverse effects, of suspected or unknown relationship to the drug, varied between 16 and 23.3%, depending on the dose. The majority of side effects observed were of a mild and transient nature, but therapy was discontinued because of drug related side effects in 4.2% of cases at the low dose (one amoxicillin and clavulanic acid (250/125 mg) tablet three times daily) and 7% of cases at the high dose (one amoxicillin and clavulanic acid (500/125 mg) tablet three times daily). The most frequently reported adverse effects were diarrhoea (6%), nausea (2%), vomiting (1%), 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.
The following adverse reactions which follow have been reported for ampicillin class antibiotics and may occur with Curam 125/31.25 (amoxicillin and clavulanic acid).
Very common: ≥ 1/10; common: ≥ 1/100 and < 1/10; uncommon: ≥ 1/1000 and < 1/100; rare: ≥ 1/10,000 and < 1/1000; very rare: < 1/10,000. Not known: cannot be estimated from the available data.

Infections and infestations.

Common: mucocutaneous candidiasis.
Not known: overgrowth of non-susceptible organisms.

Cardiac disorders.

Not known: Kounis syndrome (see Section 4.4 Special Warnings and Precautions for Use).

Gastrointestinal disorders.

Very common: diarrhoea.
Common: nausea, vomiting.
Uncommon: indigestion.
Rare: gastritis, stomatitis, glossitis, black 'hairy' tongue, enterocolitis, antibiotic associated colitis (including pseudomembranous colitis and haemorrhagic colitis) (see Section 4.4 Special Warnings and Precautions for Use).
Not known: drug-induced enterocolitis syndrome, pancreatitis acute.

Hypersensitivity and skin.

Common: skin rashes, pruritus, urticaria.
Rare: angioneurotic oedema, anaphylaxis, serum sickness-like syndrome, erythema multiforme, Stevens-Johnson syndrome, hypersensitivity, vasculitis, toxic epidermal necrolysis, bullous exfoliative dermatitis and acute generalised exanthematous pustulosis (AGEP) and drug reactions with eosinophilia and systemic symptoms (DRESS) have been reported rarely. Whenever such reactions occur, Curam 125/31.25 (amoxicillin and clavulanic acid) should be discontinued, unless in the opinion of the doctor no alternative treatment is available and continued use of Curam 125/31.25 (amoxicillin and clavulanic acid) is considered essential. Serious and occasional fatal hypersensitivity (anaphylactic) reactions and angioneurotic oedema can occur with oral penicillin (see Section 4.4 Special Warnings and Precautions for Use).
Not known: linear IgA disease.

Renal and urinary disorders.

Rare: interstitial nephritis.
Not known: crystalluria (including acute renal injury) (see Section 4.9 Overdose).

Hepatobiliary.

Uncommon: moderate rise in AST and/or ALT.
Rare: hepatitis, cholestatic jaundice, which may be severe but is usually reversible (see Section 4.4 Special Warnings and Precautions for Use).

Haemopoietic and lymphatic systems.

Uncommon: thrombocytosis.
Rare: anaemia, thrombocytopenia, thrombocytopenic purpura, eosinophilia, reversible leucopenia (including neutropenia or agranulocytosis); these are usually reversible on discontinuation of therapy and are believed to be hypersensitivity phenomena; prolongation of bleeding time and prothrombin time.
Not known: haemolytic anaemia.

Nervous system disorders.

Uncommon: dizziness, headache.
Very rare: reversible hyperactivity, and convulsions. Convulsions may occur with impaired renal function or in those receiving high doses.
Not known: aseptic meningitis.

Miscellaneous.

Rare: superficial tooth discolouration which can usually be removed by brushing.

Reporting suspected adverse effects.

Reporting suspected adverse reactions after registration 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 at www.tga.gov.au/reporting-problems.

4.9 Overdose

Problems of overdosage with Curam 125/31.25 (amoxicillin and clavulanic acid) are unlikely to occur. If encountered, gastrointestinal symptoms and disturbance of the fluid and electrolyte balance may be evident. They may be treated symptomatically, with attention to the water/ electrolyte balance.
Amoxicillin crystalluria, in some cases leading to renal failure, has been observed (see Section 4.4 Special Warnings and Precautions for Use).
Amoxicillin may be removed from the circulation by haemodialysis.
For information on the management of overdose, contact the Poisons Information Centre on 131126 (Australia).

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Pharmacotherapeutic group: combinations of penicillins, incl. beta-lactamase inhibitors; ATC code: J01CR02.

Mechanism of action.

Microbiology. Like other penicillins, amoxicillin has a bactericidal effect on sensitive organisms during the stage of active multiplication. However, amoxicillin is susceptible to hydrolysis by beta-lactamases and the addition of clavulanic acid in Curam 125/31.25 extends the antimicrobial spectrum of amoxicillin to include organisms normally resistant to amoxicillin due to beta-lactamase production.

In vitro studies.

In vitro studies do not always reflect the target patient population, in which the host's immune system usually plays an important role in the clinical and microbiological outcome of infection. For example, they are essentially simulations of infection in immunocompromised persons in that the total antibacterial activity observed is solely dependent on the medicine. Also methodological differences between laboratories and the difficulties of dilution and diffusion techniques can make the data unreliable.
Susceptibility tests. Dilution or diffusion techniques, either quantitative (MIC) or breakpoint, should be used following a regularly updated, recognised and standardised method (e.g. CLSI formerly NCCLS). Standardised susceptibility test procedures require the use of laboratory control microorganisms to control the technical aspects of the laboratory procedures.
Current standards for amoxicillin/ clavulanic acid powder should provide the following MIC values. See Table 1.

Recommended interpretive criteria based on usual dosage regimens and routes of administration (interpretive breakpoints) as defined by the Clinical and Laboratory Standard Institute (CLSI) guidelines are listed below.

Susceptible (S).

A report of "susceptible" indicates that the pathogen is likely to be inhibited if the antimicrobial compound in the blood reaches the concentrations usually achievable.

Intermediate (I).

A report of "intermediate" category includes isolates with antimicrobial agent MICs that approach usually attainable blood and tissue levels and for which response rates may be lower than for susceptible isolates. This category implies possible clinical applicability in body sites where the drug is physiologically concentrated or in situations where high dosage of drug can be used. This category also provides a buffer zone, which prevents small uncontrolled technical factors from causing major discrepancies in interpretation.

Resistant (R).

A report of "resistant" indicates that the pathogen is not likely to be inhibited if the antimicrobial compound in the blood reaches the concentrations usually achievable; other therapy should be selected.

Note.

The prevalence of resistance may vary geographically for selected species and local information on resistance is desirable, particularly when treating severe infections.
Streptococcus pneumoniae. Antimicrobial susceptibility and resistance by S. pneumoniae is usually defined and discussed in the context of activity by penicillin. By definition, a S. pneumoniae isolate with a minimum inhibitory concentration (MIC) ≤ 0.06 microgram/mL or less is considered to be susceptible. Nonsusceptible isolates are defined as intermediate nonsusceptible (0.12-1 microgram/mL) or resistant (≥ 2 microgram/mL). Until 2000, the MIC interpretive standards for penicillin and amoxicillin were similar for S. pneumoniae.

For S. pneumoniae from nonmeningitis sources.

Isolates should be tested using amoxicillin/ clavulanic acid and the following criteria should be used (see Table 2).

Resistance in Streptococcus pneumoniae.

Following antimicrobial resistance in clinically significant isolates of Streptococcus pneumoniae was reported by the Australian Group for Antimicrobial Resistance (AGAR). See Table 3.

Further evidence of the increase in antibiotic resistance is provided by a 1997 Australian-wide surveillance study showing that approximately 25% of the 1,020 isolated strains were non-susceptible to penicillin (16.8% were intermediately resistant and 8.6% were resistant). Rates of resistance to amoxicillin-clavulanate was found to be 3.1%.
Resistance in Haemophilus influenzae. See Table 4.

These interpretive standards are applicable only to broth microdilution test with Haemophilus influenzae using Haemophilus test medium (HTM).
Minimal inhibitory concentrations (MICs) to 16 different antibiotics were determined for collection of 970 isolates of H. influenzae within Australia. The overall rate of beta-lactamase production was 16% but there was wide variation between the states. In invasive strains beta-lactamase production was 22.3% but in respiratory tract isolates it was 35.3%. In non-invasive strains the resistance to amoxicillin-clavulanate was 2.1%.

Clinical trials.

No data available.

5.2 Pharmacokinetic Properties

Absorption.

Amoxicillin and clavulanic acid are stable in the presence of gastric acid. These two components are rapidly absorbed if administered before or with a meal, but if given after meals, the serum levels of clavulanic acid are significantly reduced. In fasting subjects mean peak serum levels after one amoxicillin and clavulanic acid (250/125 mg) tablet were 2.98 mg/L (range 1.2 to 5.1) for clavulanic acid and 3.89 mg/L (range 2.4 to 6.0) for amoxicillin. These levels occurred at 30 to 120 minutes and 60 to 240 minutes respectively after dosing. Following one amoxicillin and clavulanic acid (500/125 mg) tablet, peak serum levels in fasting subjects were 3.28 to 4.72 mg/L for clavulanic acid and 10.28 to 12.06 mg/L for amoxicillin, and were achieved 60 to 120 minutes after dosing.
Following oral administration of amoxicillin and clavulanic acid (125/31.25 mg in 5 mL) suspension at a dose of 8.3 mg/kg (amoxicillin 6.6 mg/kg and clavulanic acid 1.7 mg/kg) to children with otitis media, the means of peak concentrations were 2.76 mg/L for amoxicillin and 0.78 mg/L for clavulanic acid. In children given amoxicillin and clavulanic acid (400/57 mg in 5 mL) suspension 16.6 mg/kg (amoxicillin 13.3 mg/kg and clavulanic acid 3.3 mg/kg), the means of peak values were 4.94 mg/L for amoxicillin and 1.53 mg/L for clavulanic acid. Peak concentrations were reached at approximately 60 minutes (range 40 to 120 minutes).
The half-life of the amoxicillin is approximately 1.2 hours and that of clavulanic acid approximately 1.0 hour.
Oral administration of single doses of Curam 125/31.25 amoxicillin 125 mg/5 mL and clavulanic acid 31.25 mg/5 mL oral suspension to fasting adult volunteers yielded comparable pharmacokinetic data to reference amoxicillin 125 mg/5 mL and clavulanic acid 31.25 mg/5 mL oral suspension and these data are tabulated in Table 5.

The following mean amoxicillin and clavulanic acid pharmacokinetic parameters in children have been reported for reference amoxicillin/ clavulanic acid suspension products. See Table 6.

Distribution.

Following administration of amoxicillin and clavulanic acid, both amoxicillin and clavulanic acid have been shown to diffuse in significant concentrations into pus, pleural and peritoneal fluids. Both penetrate poorly into the cerebrospinal fluid (CSF) when the meninges are normal. Amoxicillin penetrates into the CSF better through inflamed meninges but the maximum concentrations are still much lower than the peak serum levels. There are no data at present on the CSF penetration of clavulanic acid in patients with meningeal inflammation.

Metabolism.

No data available.

Excretion.

Approximately 70% of the dose of amoxicillin is excreted as amoxicillin and approximately 30 to 40% of a dose of clavulanic acid is excreted in the urine, as clavulanic acid, during the first six hours after administration. Following the administration of radiolabelled potassium clavulanate 125 mg orally to normal volunteers, 68% of the administered radioactivity was recovered in the 24 hour urine. Of this, 34% (i.e. 23% of the administered dose) represented unchanged clavulanic acid. 2,5-dihydro-4-(2-hydroxyethyl)-5-oxo-1H-pyrrole-3-carboxylic acid (the major metabolite) and 1-amino-4-hydroxy-butan-2-one accounted for a further 23 and 12% (i.e. 16 and 8% respectively of the administered dose). Small amounts of other yet unidentified metabolites were also present. These metabolites were also present in the urine of rat and dog. The extent of urinary excretion of clavulanic acid and its metabolites is lower in rat urine than in dog and human urine.
Concurrent administration of probenecid delays amoxicillin excretion but does not delay renal excretion of clavulanic acid.
Clavulanic acid has been variously reported to be bound to human serum in the range of 9 to 30% and amoxicillin approximately 20% bound.

5.3 Preclinical Safety Data

Genotoxicity.

The genotoxic potential of amoxicillin and clavulanic acid was investigated in assays for chromosomal damage (mouse micronucleus test and a dominant lethal test) and gene conversion. All were negative.

Carcinogenicity.

Long-term studies in animals have not been performed to evaluate the carcinogenic potential of amoxicillin and clavulanic acid.

6 Pharmaceutical Particulars

6.1 List of Excipients

Lemon flavouring 15.02.0598 (PI 10094), peach-apricot flavour 26F22 (PI 10089), citric acid, sodium citrate, aspartame, purified talc, orange 55301 AP0551 (PI 12686), guar gum and silicon dioxide. Contains sulfites.

6.2 Incompatibilities

Incompatibilities were either not assessed or not identified as part of the registration of this medicine.
For information on interactions with other medicines and other forms of interactions, see Section 4.5 Interactions with Other Medicines and Other Forms of Interactions.

6.3 Shelf Life

In Australia, information on the shelf life can be found on the public summary of the Australian Register of Therapeutic Goods (ARTG). The expiry date can be found on the packaging.

6.4 Special Precautions for Storage

Store dry powder below 25°C. Under these conditions the shelf life is 3 years.
Store reconstituted suspension at 2°C to 8°C in a refrigerator. Under these conditions the shelf life is 7 days.

6.5 Nature and Contents of Container

Packaged in 100 mL amber glass bottle with screw closure.
Also contains a 5 mL measuring spoon.

6.6 Special Precautions for Disposal

In Australia, any unused medicine or waste material should be disposed of by taking to your local pharmacy.

6.7 Physicochemical Properties

Amoxicillin trihydrate.

Curam 125/31.25 is a combination product containing the semisynthetic antibiotic, amoxicillin (as the trihydrate) and the beta-lactamase inhibitor, clavulanic acid (as the potassium salt). Amoxicillin is susceptible to hydrolysis by beta-lactamases.

Chemical structure.

Chemical name: (2S, 5R, 6R)-6-[[(2R)-2-amino-2-(4-hydroxyphenyl)acetyl]amino]- 3,3-dimethyl-7-oxo-4-thia- 1-azabicyclo[3.2.0] heptane-2-carboxylic acid trihydrate
Molecular formula: C₁₆H₁₉N₃O₅S.3H₂O.
Molecular weight: 419.5.

Potassium clavulanate.

Clavulanic acid is produced by the fermentation of Streptomyces clavuligerus. It is an irreversible inhibitor of many beta-lactamase enzymes except type 1 (Richmond). It is a beta-lactam compound with only weak antibacterial activity.

Chemical structure.

Chemical name: potassium (2R, 3Z, 5R)-3-(2-hydroxyethylidene)-7-oxo-4-oxa- 1-azabicyclo[3.2.0] heptane-2-carboxylate.
Molecular formula: C₈H₈KNO₅.
Molecular weight: 237.3.

CAS number.

Amoxicillin trihydrate: 61336-70-7.
Potassium clavulanate: 61177-45-5.

7 Medicine Schedule (Poisons Standard)

S4 - Prescription Only Medicine.

Log in

Consumer medicine information

Curam 125/31.25

Amoxicillin; Clavulanic acid

Keep track of your medicines

BRAND INFORMATION