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

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Curam 125/31.25.

SUMMARY CMI

CURAM® 125/31.25

Consumer Medicine Information (CMI) summary

The full CMI on the next page has more details. If you are worried about using this medicine, speak to your doctor or pharmacist.

1. Why is my child using Curam 125/31.25?

Curam 125/31.25 contains the active ingredients amoxicillin and clavulanic acid. Curam 125/31.25 is used for the short term treatment of a wide range of infections caused by bacteria. These infections may affect the chest (e.g. bronchitis or pneumonia), bladder (e.g. cystitis), sinuses (e.g. sinusitis), the ears (e.g. otitis media) or the skin.

For more information, see Section 1. Why is my child using Curam 125/31.25? in the full CMI.

2. What should I know before giving my child Curam 125/31.25?

Do not use if you have ever had an allergic reaction to amoxicillin, clavulanic acid, other penicillin based antibiotics or similar antibiotics (such as cephalosporins) or any of the ingredients listed at the end of the CMI.

Talk to your doctor if you have any other medical conditions, take any other medicines, or are pregnant or plan to become pregnant or are breastfeeding.

For more information, see Section 2. What should I know before giving my child Curam 125/31.25? in the full CMI.

3. What if my child is taking other medicines?

Some medicines may interfere with Curam 125/31.25 and affect how it works.

A list of these medicines is in Section 3. What if my child is taking other medicines? in the full CMI.

4. How do I give Curam 125/31.25?

  • Always use this medicine exactly as the doctor or pharmacist has told you to.
  • The usual dose of this medicine is one dose taken twice a day. The dose may vary depending on your child's weight.

More instructions can be found in Section 4. How do I give Curam 125/31.25? in the full CMI.

5. What should I know while giving Curam 125/31.25?

Things you should do
  • Tell your doctor, if, for any reason, your child has not taken this medicine exactly as directed.
  • Remind any doctor, dentist or pharmacist your child visits that your child is using Curam 125/31.25.
  • If your child is about to be started on any new medicines, tell the doctor or pharmacist that your child is taking Curam 125/31.25.
Things you should not do
  • Do not use this medicine to treat any other complaints unless your child's doctor says to.
  • Do not give this medicine to anyone else, even if their symptoms seem similar to your child's.
Driving or using machines
  • Be careful before you drive or use any machines or tools until you know how Curam 125/31.25 affects you.
Looking after your medicine
  • Once made up, the suspension should be stored in a refrigerator (2°C to 8°C). Do not freeze.
  • Dispose of any unused suspension 7 days after first making up.

For more information, see Section 5. What should I know while giving Curam 125/31.25? in the full CMI.

6. Are there any side effects?

Side effects include diarrhoea, thrust, nausea, vomiting, dizziness, headache, indigestion, skin rash, and itching. Serious side effects include severe allergic reactions, skin reactions, yellowing of skin/eyes (liver problems), and severe diarrhoea.

For more information, including what to do if you have any side effects, see Section 6. Are there any side effects? in the full CMI.



FULL CMI

CURAM® 125/31.25

Active ingredient(s): amoxicillin trihydrate & potassium clavulanate

Consumer Medicine Information (CMI)

This leaflet provides important information about using Curam 125/31.25. You should also speak to your doctor or pharmacist if you would like further information or if you have any concerns or questions about using Curam 125/31.25.

Where to find information in this leaflet:

1. Why is my child using Curam 125/31.25?
2. What should I know before giving my child Curam 125/31.25?
3. What if my child is taking other medicines?
4. How do I give Curam 125/31.25?
5. What should I know while giving Curam 125/31.25?
6. Are there any side effects?
7. Product details

1. Why is my child using Curam 125/31.25?

Curam 125/31.25 contains two active ingredients. One of these is a penicillin called amoxicillin and the other is clavulanic acid. Curam 125/31.25 belongs to the penicillin group of antibiotics.

Curam 125/31.25 is used for the short term treatment of a wide range of infections caused by bacteria. These infections may affect the chest (e.g. bronchitis or pneumonia), bladder (e.g. cystitis), sinuses (e.g. sinusitis), the ears (e.g. otitis media) or the skin.

Curam 125/31.25 works by killing the bacteria that cause these infections.

Curam 125/31.25 is used for the treatment of the infections listed. However, the doctor may prescribe these medicines for another use. If you want more information, ask the doctor.

There is no evidence that Curam 125/31.25 is addictive.

2. What should I know before giving my child Curam 125/31.25?

Warnings

Do not give Curam 125/31.25 if:

  • your child is allergic to amoxicillin, clavulanic acid, other penicillin based antibiotics or similar antibiotics (such as cephalosporins) or any of the ingredients listed at the end of this leaflet. If your child has ever had an allergic reaction (such as a rash) when taking an antibiotic you should tell the doctor before any Curam 125/31.25 is given.
    Always check the ingredients to make sure you can use this medicine.
  • your child has previously experienced liver problems or jaundice when taking an antibiotic or any other medicines.
  • the expiry date (EXP) printed on the pack has passed.
  • the packaging is torn or shows signs of tampering.

This medicine is for the person named by the doctor. Do not give this medicine to anyone else.

Check with your doctor if your child:

  • has ever had an allergic reaction (such as a rash) to any antibiotics or medicines in the past
  • is allergic to foods, dyes, preservatives or any other medicines.
  • has glandular fever (mononucleosis) or a blood disorder.
  • has 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.
  • Is not urinating regularly or not able to drink very much.
  • has phenylketonuria. Curam 125/31.25 contains aspartame.
  • is required to have urine glucose (sugar) test.
    This medicine may affect the results of these tests.

Curam 125/31.25 can make some existing conditions worse, or cause serious side effects, such as severe allergic reactions, serious skin reactions, chest pain, repetitive vomiting within 1 to 4 hours of Curam 125/31.25 administration, serious liver problems or severe diarrhoea or inflammation of the large intestines (pseudomembranous colitis). You must look out for certain symptoms while giving this medicine to your child to help reduce the risk of any problems.

During treatment, your child may be at risk of developing certain side effects. It is important you understand these risks and how to monitor for them. See additional information under Section 6. Are there any side effects?

Pregnancy and breastfeeding

If your child is pregnant or intend to become pregnant, do not take this medicine without checking with your doctor.

Before taking this medicine, talk to your doctor if your child is breastfeeding or intend to breastfeed.

Your doctor will consider the risks and benefits of this treatment.

3. What if my child is taking other medicines?

Tell your doctor or pharmacist if you are giving your cild any other medicines, including any medicines, vitamins or supplements that you buy without a prescription from your pharmacy, supermarket or health food shop.

In particular, tell the doctor if your child is taking any of the following:

  • warfarin or other anticoagulants used to prevent blood clots
  • mycophenolate
  • medicines used to treat gout (e.g. probenecid or allopurinol)
  • other antibiotics
  • methotrexate (a medicine used to treat cancer or rheumatic diseases
  • contraceptive pill. As with other antibiotics, your child may need to use extra birth control methods (e.g. condoms) while taking Curam 125/31.25.

These may affect how Curam 125/31.25 works or make it more likely that your child will have side effects.

Some medicines may interfere with Curam 125/31.25 and affect how it works.

Check with your doctor or pharmacist if you are not sure about what medicines, vitamins or supplements your child is taking and if these affect Curam 125/31.25.

4. How do I give Curam 125/31.25?

Always follow the directions given to you by the doctor or pharmacist. Their directions may differ from the information contained in this leaflet.

Please read the direction label carefully. If you have any concerns about how to give this medicine, talk to the doctor or pharmacist.

How much to give

  • Give this medicine as directed by the doctor or pharmacist
  • The usual dose of this medicine is one dose taken twice 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 Curam 125/31.25

  • 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 off-white.
  • 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

  • Give this medicine at about the same time each day.
  • Giving this medicine at about the same time each day will have the best effect. It will also help you remember when to give it.
  • 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 Curam 125/31.25

Give the missed dose as soon as you remember, and continue to give it as you would normally.

If it is almost time for your next dose, skip the dose you missed and give that next dose when you are meant to.

Do not take a double dose to make up for the dose 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 your child takes too much Curam 125/31.25

If you think that your child has used too much Curam 125/31.25, your child may need urgent medical attention.

You should immediately:

  • phone the Poisons Information Centre
    (by calling 13 11 26), or
  • contact your doctor, or
  • go to the Emergency Department at your nearest hospital.

You should do this even if there are no signs of discomfort or poisoning.

5. What should I know while giving Curam 125/31.25?

Things you should do

Tell your doctor if, for any reason, your child has not taken this medicine exactly as directed. Otherwise, your doctor may think that it was not effective and change your child's treatment unnecessarily.

If your child is about to be started on any new medicines, tell the doctor or pharmacist that your child is taking Curam 125/31.25.

Call your doctor straight away if your child:

  • develops itching, swelling or a skin rash while taking Curam 125/31.25, do not give any more this medicine.
  • develops severe diarrhoea either while taking this medicine or within several weeks after treatment. Do not give any medication to stop the diarrhoea (e.g. Lomotil® or Imodium®).

Remind any doctor, dentist or pharmacist your child visits that your child is using Curam 125/31.25.

Things you should not do

  • Do not give this medicine to anyone else, even if their symptoms seem similar to your child's.
  • Do not use this medicine to treat any other complaints unless your child's doctor says to.

Driving or using machines

Be careful before your child drives or uses any machines or tools until you know how Curam 125/31.25 affects your child.

Looking after your medicine

  • Do not keep the bottle of Curam 125/31.25 longer than 7 days after it has been made up and store in the fridge between 2°C and 8°C. Do not freeze.

Follow the instructions in the carton on how to take care of your medicine properly.

Store it in a cool dry place away from moisture, heat or sunlight; for example, do not store it:

  • in the bathroom or near a sink, or
  • in the car or on window sills.

Keep out of the sight and reach of children.

Getting rid of any unwanted medicine

If you no longer need to use this medicine or it is out of date, take it to any pharmacy for safe disposal.

Do not use this medicine after the expiry date.

6. Are there any side effects?

All medicines can have side effects. If you do experience any side effects, most of them are minor and temporary. However, some side effects may need medical attention.

See the information below and, if you need to, ask your doctor or pharmacist if you have any further questions about side effects.

Less serious side effects

Less serious side effectsWhat to do
Fungal Infection related:
  • soreness of the mouth or tongue, abnormal taste, white or furry tongue (oral thrush) or itching of the vagina and/or discharge (vaginal thrush)
Gut or Gastrointestinal related:
  • diarrhoea (several loose bowel movements per day), indigestion, pain in the stomach, feeling sick or being sick
  • nausea, vomiting
General disorders:
  • dizziness
  • headache
  • tiredness
Others:
  • hot flushes
  • unusually active (hyperactive).
Speak to your doctor if your child has any of these less serious side effects and they worry you.

Serious side effects

Serious side effectsWhat to do
Gut or Gastrointestinal related:
  • severe diarrhoea
Allergy related:
  • itching, rash
  • signs of allergic reaction including wheezing, fainting, swelling of the lips/mouth, difficulty in breathing or swallowing, hayfever, lumpy rash (hives), joint discomfort or swelling, swollen lymph glands, nausea, chest pain, stomach pain, abnormal drowsiness, low blood pressure, repetitive vomiting or fever.
Liver related:
  • yellowing of the skin or eyes
  • dark urine or pale stools
Others:
  • unusual bleeding or bruising
  • collapse
  • aseptic meningitis
  • a red rash commonly seen on both sides of buttocks, upper inner thighs, armpits, neck
Call your doctor straight away, or go straight to the Emergency Department at your nearest hospital if you notice any of these serious side effects.

Tell your doctor or pharmacist if you notice anything else that may be making you feel unwell.

Other side effects not listed here may occur in some people.

Reporting side effects

After you have received medical advice for any side effects your child experiences, you can report side effects to the Therapeutic Goods Administration online at www.tga.gov.au/reporting-problems. By reporting side effects, you can help provide more information on the safety of this medicine.

Always make sure you speak to your doctor or pharmacist before you decide to stop giving any of your child's medicines.

7. Product details

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

What Curam 125/31.25 contains

Active ingredient
(main ingredient)
  • amoxicillin trihydrate
  • potassium clavulanate
Other ingredients
(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.

Curam 125/31.25 does not contain sucrose, gluten, tartrazine or any other azo dyes.

Do not take this medicine if you are allergic to any of these ingredients.

What Curam 125/31.25 looks like

Curam 125/31.25 powder for suspension – 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. (Aust R 146979).

Who distributes Curam 125/31.25

Sandoz Pty Ltd
100 Pacific Highway
North Sydney, NSW 2060
Australia

Tel 1800 726 369

This leaflet was prepared in June 2024.

® Registered Trade Mark. The trade marks mentioned in this material are the property of their respective owners.

Published by MIMS September 2024

BRAND INFORMATION

Brand name

Curam 125/31.25 Powder for Suspension

Active ingredient

Amoxicillin; Clavulanic acid

Schedule

S4

 

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, acute generalised exanthematous pustulosis (AGEP), drug reactions with eosinophilia and systemic symptoms (DRESS), and symmetrical drug-related intertriginous and flexural exanthema (SDRIFE) (baboon syndrome) 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.

Summary Table of Changes