Co-Amoxiclav (Amoxicillin and Clavulanic Acid)

What Is Amoxicillin and Clavulanic Acid?

Amoxicillin is a penicillin-type antibiotic that stops infection-causing bacteria from growing. It's used to treat pneumonia, as well as infections of the mouth, ear and urinary tract, among others. In Australia, it's commonly prescribed in general practice for a range of everyday bacterial infections when clinically appropriate.

Clavulanic acid is added to amoxicillin to help protect it from being broken down by bacteria. It belongs to a group of medicines called beta-lactamase inhibitors.

Overview

Amoxicillin works by stopping bacteria from building their cell walls. Without these protective walls, the bacteria can't survive. On its own, amoxicillin may not always work well because some bacteria are resistant to it. That's where clavulanic acid helps, by making amoxicillin more effective.

How Supplied

The combination comes in 4 forms:

• Regular tablets.
  Taken just before a meal every 8 or 12 hours.
• Chewable tablets.
  Taken just before a meal every 8 or 12 hours. Chew them thoroughly; do not swallow them whole.
• Extended-release tablets.
  Taken with a meal or snack every 12 hours. They shouldn't be chewed or crushed, so swallow the tablet whole and drink enough water afterwards (a glass is usually enough).
• Oral suspension.
  Taken just before a meal every 8 or 12 hours. Shake it well to make sure the medicine is mixed properly.

It's recommended to take the tablets or suspension at the same time each day so you're less likely to miss a dose. Don't take more or less than your doctor has prescribed.

Take amoxicillin and clavulanic acid regularly as prescribed, even if you start feeling better before the course is finished. If you stop too early or skip doses, the infection may not be fully treated and could come back. It can also make the bacteria more resistant, which may limit treatment options later.

Indications and Uses of Amoxicillin and Clavulanic Acid

It's important to understand what the amoxicillin and clavulanic acid combination is used for. Before taking it, you need to be sure the infection is caused by bacteria that can be treated with Augmentin or similar medicines. Otherwise, drug-resistant bacteria may increase, making future treatment less likely to work.

It's ideal if your doctor has culture results, but if not, local Australian epidemiology patterns may help guide the choice of treatment.

So, what does this combination treat?

Lower Respiratory Tract Infections

Lower respiratory tract infections affect the lungs and the parts of the airways below the voice box. Bronchitis and pneumonia are among the most common. They can be caused by isolates of Moraxella catarrhalis and Haemophilus influenzae.

Acute Bacterial Otitis Media

Acute bacterial otitis media can develop after allergies, a sinus infection, a cold or the flu, exposure to cigarette smoke, and other triggers. It can also be caused by isolates of Haemophilus influenzae (H. influenzae) and Moraxella catarrhalis (M. catarrhalis).

Sinusitis

Sinusitis is inflammation in the paranasal sinuses, which may be acute or chronic. It may result from severe allergies, bacteria (beta-lactamase-producing isolates of H. influenzae and M. catarrhalis), fungi and other causes.

Skin and Skin Structure Infections

Skin and skin structure infections, whether complicated or uncomplicated, are usually caused by beta-lactamase-producing isolates of bacteria such as:

• Escherichia coli;
• Staphylococcus aureus;
• Klebsiella species.

Urinary Tract Infections

Urinary tract infections, which can affect the ureters, urethra, bladder or kidneys, are usually caused by isolates of:

• Klebsiella species;
• Escherichia coli;
• Enterobacter.

Limitations of Use

Clavulanic acid and amoxicillin should not be taken if testing shows susceptibility to amoxicillin alone.

Dosage

The dosage of amoxicillin & clavulanic acid varies depending on age, weight and the type of medicine prescribed.

Some dosage recommendations for adults or paediatric patients weighing over 40 kg are:

• A 500 mg tablet every 8 to 12 hours (2-3 times a day);
• A 250 mg tablet every 8 hours (3 times a day);
• 875 mg every 12 hours (2 times a day);
• 2000 mg every 12 hours (2 times a day) for complicated conditions.

The dosage is based solely on the amount of amoxicillin needed to treat the infection.

If a paediatric patient weighs less than 40 kg, the recommended dosage will fall somewhere between 20-45 mg per kilogram 2-3 times a day.

To help avoid amoxicillin and clavulanic acid side effects such as an upset stomach, take your doses with food, and make sure you don't take more than one tablet at a time. Too much clavulanic acid may also cause stomach upset. Also, keep in mind that:

• Both 250 mg and 500 mg tablets have the same amount of clavulanic acid, so you should not take two 250 mg tablets if your prescription says to take one 500 mg tablet;
• You should not substitute regular tablets for chewable tablets.

Side Effects

Amoxicillin & clavulanic acid can cause a range of side effects. Some of the most common are:

• Abdominal discomfort;
• Diarrhoea;
• Excess gas;
• Bloating;
• Heartburn;
• Nausea and vomiting;

Side effects can broadly be divided into two groups: those that need urgent medical attention and those that usually do not.

Side effects requiring immediate medical attention

If you have any of the following amoxicillin / clavulanic acid side effects, get medical attention as soon as possible:

• Severe itching and skin rash;
• Trouble swallowing or breathing;
• Severe vaginal itching and discharge;
• Yellowing of the eyes and/or skin;
• Bloody diarrhoea;
• Darker urine than usual;
• High fever;
• Weakness, drowsiness and confusion;
• Severe swelling of the tongue and/or face;
• Other unusual allergic reactions;
• Easy bruising, etc.

If you experience severe or unusual side effects after taking amoxicillin and clavulanic acid, you can report them to the Therapeutic Goods Administration (TGA) in Australia. Your doctor can also help you describe your symptoms clearly when making a report.

There are also rare side effects, including seizures, anaphylaxis, a lack of red blood cells, colon inflammation and others. Antibiotics don't just kill harmful bacteria; they can also affect the useful bacteria in your body. This may cause a range of digestive problems. Make sure you take probiotics during or soon after finishing the antibiotic course. It's still best to ask your doctor for advice rather than choosing another medicine yourself.

Side effects not requiring immediate medical attention

Some side effects usually do not need urgent medical help. They are usually mild, but you should still tell your doctor about them to make sure they do not get worse:

• Regular diarrhoea;
• Nausea and vomiting;
• Upset stomach;
• Mild bloating;
• Mild skin rash.

If you are thinking about taking another medicine to manage any of the side effects above, check with your doctor first.

Drug Interactions

Medicines containing amoxicillin and clavulanic acid can interact with certain substances. Never take any additional medicine without first checking with your doctor about possible interactions.

Here are some drugs that interact with Augmentin and similar medicines:

• Probenecid is commonly used to treat gout. One effect of it is that it can stop amoxicillin from being cleared by the kidneys. This buildup can lead to toxic levels of amoxicillin and cause complications.
• Birth control pills.
  The combination may reduce or stop the effect of oral contraceptive pills. If you are not using another form of protection as well, this may result in an unintended pregnancy.
• If you are taking Zyloprim, Aloprim or other medicines containing allopurinol, the combination of amoxicillin and clavulanic acid is more likely to cause a skin rash.
• Oral anticoagulants.
  Combining oral anticoagulants with amoxicillin may lead to an increased International Normalised Ratio (INR). To help both medicines work as intended, ask your doctor whether the anticoagulant dose needs to be adjusted.

It can be helpful to write down all the medicines and dietary supplements you take before starting a course of amoxicillin and clavulanic acid. That way, you are less likely to forget anything, and your doctor can adjust treatment to suit your needs.

Warnings & Precautions

There are several warnings and precautions to keep in mind before using amoxicillin and clavulanic acid. Here are the main points every patient should know:

• Know your allergies.
  If you have ever had an allergy to medicines such as Trimox, Amoxil, Wymox, or others containing amoxicillin, clavulanic acid or penicillin, make sure you tell your doctor. If you are not sure of the medicine or its name, try to remember the allergic reactions you have had.
• Remember all medicines you are taking.
  As you can see, amoxicillin and clavulanic acid may interact with many substances. Some may not be obvious, so make sure you bring a list of all medicines and supplements you take, no matter how minor they seem, when seeing an Australian doctor. This helps treatment go as smoothly as possible and may reduce side effects.
• Tell your doctor about your medical conditions.
  If you have severe allergies, asthma, liver or kidney disease, glandular fever, hay fever, hives or other conditions, tell your doctor before testing.
• Think about whether you plan to become pregnant.
  If you are planning a pregnancy or are already pregnant or breastfeeding, tell your doctor beforehand. If you become pregnant during the course of amoxicillin, see your doctor as soon as possible. Remember that you should use another form of contraception besides birth control pills while taking amoxicillin.
• Plan your diet.
  Ask your doctor whether you need to make any changes to your diet. While major changes are not usually needed, diet can become more important when supplements and other medicines are involved. As for alcohol, there are no known problems related to drinking it with amoxicillin and clavulanic acid.
• See your doctor regularly.
  Don't miss your lab or follow-up appointments. You may need extra tests to check whether treatment is working well and whether any medicine or dose changes are needed.
• Change the test if you are diabetic.
  For urine glucose tests, use TesTape or Clinistix. Avoid using Clinitest, as it may give incorrect results if you take amoxicillin regularly.
• Don't give your medicine to anyone else.
  Usually, a prescription for amoxicillin and clavulanic acid is not refillable. If you give someone else a tablet, you may miss your final dose and affect your recovery. If you have finished the course but still have symptoms of infection, contact your doctor as soon as possible.

These warnings are not hard to remember and can help your treatment for a bacterial infection go as smoothly as possible.

Hypersensitivity Reactions

If you have ever had penicillin hypersensitivity, even once, you must tell your doctor. If this is overlooked, an anaphylactic reaction may be fatal. Even if penicillin is not listed among your allergies, it is still helpful to show your doctor your full allergy list if it is long.

Before starting Augmentin or similar medicines, talk to your doctor to reduce the risk of serious side effects. If you notice unusual allergic reactions, contact your doctor and stop taking the medicine until you have been advised what to do next.

Hepatic Dysfunction

Hepatitis and cholestatic jaundice are among the serious side effects that may occur in patients with liver impairment who take amoxicillin and clavulanic acid. In most cases, this hepatitis is reversible, but fatal outcomes have been reported.

These patients need regular monitoring to check whether the liver toxicity can be reversed. The groups considered most at risk are:

• Male;
• Older people;
• Patients treated with the same medicines for a long time.

Even if the medicine has been stopped, this side effect may still appear over the next couple of months.

Clostridium difficile-associated diarrhea (CDAD)

CDAD is a common side effect linked to many antibacterial medicines. When treatment disrupts the normal microbiome in your body, bacteria in the colon can react and cause inflammation and other problems. CDAD can range from a mild, treatable episode to fatal colitis.

CDAD should be considered in anyone taking antibacterial treatment who develops diarrhoea. The condition may become serious and resistant to treatment. Some patients may need a colectomy. Even if the problem appears within 2 months after the course has finished, it may still be related. This is another reason why an accurate medical history is important.

If a patient is diagnosed with CDAD, all antibacterial treatments not being used to treat it will need to be stopped. Further treatment may include protein supplementation, fluid and electrolyte management, another antibacterial medicine against Clostridium difficile (C. difficile), and surgical assessment if the condition becomes difficult to control.

Skin Rash in Patients With Mononucleosis

It is not recommended to take amoxicillin and clavulanic acid if the patient has mononucleosis. A skin rash is very likely as a side effect, and complications may follow.

Potential for Microbial Overgrowth

As with any antibacterial treatment, changing the microbiome by killing certain bacteria may allow another organism to overgrow. If this is not controlled properly, it may lead to a superinfection. If this is suspected, the current antibacterial treatment should be stopped and further testing carried out to guide new treatment.

Phenylketonurics

People with the metabolic disorder phenylketonuria should be especially careful when taking amoxicillin / clavulanic acid/potassium medicines such as Augmentin. The brand's chewable tablets and powder for suspension contain aspartame, which contains phenylalanine and may cause complications in phenylketonurics.

Regular and extended-release tablets do not contain this substance.

Development of Drug-Resistant Bacteria

Augmentin and similar medicines should only be prescribed if a bacterial infection has been confirmed. Otherwise, the treatment is unlikely to help and may encourage the growth of drug-resistant bacteria. If the patient later develops another bacterial infection, treatment may be less effective.

Use in Specific Populations

The dosage changes depending on the population group the patient belongs to, such as pregnant or breastfeeding women, paediatric patients under or over 40 kg, and geriatric patients.

Pregnancy

If the patient is not allergic to penicillin, this type of antibacterial treatment may be used, and there should be no teratogenic effects. However, it is worth noting that the topic has not been fully studied. Some reproduction studies in pregnant mice found that doses of even 1200 mg/kg/day did not affect the fetus. That dosage was several times higher than the maximum dose allowed for humans.

Animal responses are not always the same as human ones, however. So treatment should only be prescribed after a bacterial infection has been confirmed.

Labor and Delivery

There is no clear information on whether amoxicillin and/or clavulanic acid or clavulanate potassium affects the fetus or changes the length of labour.

It is known, however, that oral ampicillin-type antibiotics are not absorbed well during labour.

Nursing Mothers

Amoxicillin and clavulanic acid are excreted in breast milk and may cause digestive problems in infants. Medicines containing either substance should be prescribed to breastfeeding women with caution and only if clearly needed.

Pediatric Use

The dosage must be adjusted according to the age and/or weight of the paediatric patient:

• Infants younger than 3 months old should only have 30 mg/kg/day, 2 times a day;
• For patients aged 3 months and older, dosage differs depending on the diagnosis and weight;
• Patients weighing over 40 kg can receive adult doses according to the prescription.

Keep in mind that chewable tablets and oral suspension should not be prescribed to phenylketonurics. Regular tablets are also not recommended before a child weighs 40 kg because the ratio of components is different. Also keep in mind that amoxicillin is cleared more slowly from the body in infants.

Geriatric Use

In analyses of clinical studies of medicines containing amoxicillin and clavulanic acid (Augmentin), there were around 3,100 patients overall. Of these, 32% were aged 65 years and over, and some patients were aged 75 years and older.

No major differences in response were found when older patients were compared with younger patients. No changes in safety or effectiveness were seen unless the patient had increased sensitivity to one or more components of the drug, or had metabolic or kidney dysfunction.

These conditions should be checked before the drug is prescribed.

If a patient of any age has impaired kidney function, the response to amoxicillin can be more complicated. The substance is mostly excreted by the kidneys, so they need to be functioning reasonably well to reduce unwanted effects. Dose selection should be guided by whether kidney disease is present.

Undesirable Effects

The undesirable effects are connected to overdose or missing a dose of amoxicillin and clavulanic acid. Make sure you have a schedule and follow it closely. Some symptoms of penicillin overdose are:

• Severe stomach pain;
• Diarrhoea;
• Skin rash;
• Nausea and vomiting;
• Drowsiness or hyperactivity;

Remember that taking the medicine at the same time every day reduces the chance of overdose or a missed dose.

Overdose

If an overdose happens:

• Stop taking it immediately;
• Treat the symptoms to ease the condition;
• Drink plenty of fluids;
• Take other supportive measures to keep the person stable;
• Call the doctor.

If the dose was not over 250 mg per kg, there should be no serious symptoms or consequences, but it is still recommended to contact the doctor for further instructions. If the dose was much higher, there may be interstitial nephritis, which can lead to kidney failure if not treated quickly.

Crystalluria is another sign of penicillin overdose and may also lead to kidney failure.

It is important to maintain steady fluid intake and diuresis in the event of an overdose.

There is a possibility of reversing kidney impairment caused by an overdose of the drug by stopping treatment and removing excess amoxicillin and/or clavulanic acid by means of haemodialysis.

Missed Dose

Missing a dose is generally less dangerous than an overdose, but take it as soon as you remember unless it is nearly time for the next one. Never take a double dose to make up for it, as this may lead to an overdose.

Storage

Here are some key points for storing medicines that contain amoxicillin/clavulanic acid:

• Keep the medicine in its original container;
• Keep it out of the reach of children and pets;
• Keep the container tightly closed at all times;
• Store it in a place that is not too hot or humid (room temperature is preferred);
• If using liquid medicine, store it in the fridge but do not freeze it;
• Throw away the liquid if it has not been used within 10 days.

It is very important to keep children away from where medicines are stored. Many drops, creams and other medicines do not have child-resistant caps, so even when closed tightly, they may still be opened.

Choose a storage spot carefully - somewhere high up and out of reach of young children. According to Up and Away, about 50,000 children are taken to emergency departments because of their "experiments" with unknown containers of medicines.

It's also important to know how to dispose of unwanted medicines properly. Do it in a way that prevents any child, animal or other person from taking them after they've been thrown away. You also shouldn't flush medicines down the toilet, especially in large quantities.

There are take-back programs for unwanted medicines. You can ask your pharmacist or doctor about the best disposal option, and some local councils may also provide information. In Australia, you can also find guidance online through the Return Unwanted Medicines (RUM) Project if you're unsure how to dispose of medicines safely.

The bottom line

Overall, this combination can be used in pregnant women, children and older adults when the correct dose is given. Make sure you complete the full course of treatment, don't share the medicine with anyone else, and dispose of any leftover tablets or suspension in line with Australian guidance for medicine disposal.