Co-Amoxiclav (Amoxicillin And Clavulanic Acid)

What Is Amoxicillin and Clavulanic Acid?

Amoxicillin is a penicillin antibiotic that stops infection-causing bacteria from growing. In Canada, it is commonly prescribed for infections such as pneumonia, as well as mouth, ear, and urinary tract infections, among others.

Clavulanic acid helps amoxicillin work better by protecting it from being broken down by bacteria. It belongs to a group of medicines called beta-lactamase inhibitors.

Overview

Amoxicillin works by preventing bacteria from building the protective cell walls they need to survive. On its own, it may not work well enough if the bacteria are resistant to it. Clavulanic acid helps by boosting amoxicillin's effect.

How Supplied

The combination comes in 4 forms:

• Regular tablets.
  Taken right before a meal every 8 or 12 hours.
• Chewable tablets.
  Taken right 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. Do not chew or crush them. Swallow the tablet whole and drink enough water afterward.
• Oral suspension.
  Taken right before a meal every 8 or 12 hours. Shake it well before each dose to make sure the medication is mixed.

It's best to take the tablets or suspension at the same time each day so you don't miss a dose. Do not take more or less than your doctor prescribed.

Take amoxicillin and clavulanic acid regularly as prescribed, even if you start to feel better before you finish the prescription. If you stop too soon or skip doses, the infection may not be fully treated and could come back. The bacteria may also become resistant, which can make future treatment harder.

Indications and Uses of Amoxicillin and Clavulanic Acid

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

Ideally, the doctor will have culture results, but if not, local epidemiology patterns in Canada may help guide the choice of medication.

So, what does the combination treat?

Lower Respiratory Tract Infections

Lower respiratory tract infections affect the lungs and the parts of the airway below the voice box. Bronchitis and pneumonia are among the most common examples. They may 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 more. The condition can also be caused by isolates of Haemophilus influenzae (H. influenzae) and Moraxella catarrhalis (M. catarrhalis).

Sinusitis

Sinusitis is inflammation of the paranasal sinuses, either 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 used if testing shows the bacteria are susceptible to amoxicillin alone.

Dosage

The dose of amoxicillin & clavulanic acid varies depending on age, weight, and the form of the medication.

Some dosage recommendations for adults or pediatric patients who weigh 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 pediatric 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 side effects such as stomach upset, 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 upset your stomach. Also keep in mind that:

• Both 250 mg and 500 mg tablets contain the same amount of clavulanic acid, so you should not take two 250 mg tablets if the 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;
• Diarrhea;
• Excess gas;
• Bloating;
• Heartburn;
• Nausea and vomiting;

Side effects can be divided into two groups: those that need immediate 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 your eyes and/or skin;
• Bloody diarrhea;
• Darker urine than usual;
• High fever;
• Weakness, drowsiness, and confusion;
• Severe swelling of your tongue and/or face;
• Other unusual allergic reactions;
• Easy bruising, etc.

Keep in mind that if you develop serious or unusual side effects after taking amoxicillin and clavulanic acid, you can report them to Health Canada's MedEffect Canada program. Ask your doctor about the best way to describe your condition.

Rare side effects can also happen, including seizures, anaphylaxis, low red blood cell counts, and inflammation of the colon. Antibiotics do not only kill harmful bacteria; they can also affect the helpful bacteria in your body. This can lead to digestive problems. Ask your doctor before taking probiotics during or after your antibiotic course.

Side effects not requiring immediate medical attention

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

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

If you are thinking about taking another medication to manage these side effects, talk to your doctor first.

Drug Interactions

Medications containing amoxicillin and clavulanic acid can interact with certain substances. Do not take any additional medicine without first checking with your doctor.

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

• Probenecid is commonly used to treat gout. One effect it has is preventing amoxicillin from being cleared by the kidneys. This can cause amoxicillin to build up and lead to complications.
• Birth control pills.
  The combination may reduce or cancel out the effect of birth control pills. If you are not using another form of protection as well, an unplanned pregnancy may result.
• If you're taking Zyloprim, Aloprim, or other medications 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 Normalized Ratio (INR). To help both medications work as intended, your doctor may need to adjust the dose of the anticoagulant.

It can help to write down all the medications and dietary supplements you're taking before starting amoxicillin and clavulanic acid. That way, you are less likely to forget anything, and your doctor can adjust the dose to suit your needs.

Warnings & Precautions

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

• Know your allergies.
  If you have an allergy to medications like Trimox, Amoxil, Wymox, or others containing amoxicillin, clavulanic acid, or penicillin, tell your doctor. If you're not sure of the exact medicine or name, describe the allergic reactions you have had.
• Remember all medications you're taking.
  As you can see, amoxicillin and clavulanic acid can interact with many substances. Some may not be obvious, so bring a list of all medications and supplements you take, no matter how minor they seem, when you see your doctor. This can help the treatment go more smoothly and lower the chance of side effects.
• Tell your doctor about your medical conditions.
  If you have severe allergies, asthma, liver or kidney disease, mononucleosis, hay fever, hives, or other conditions, tell your doctor before testing.
• Think about pregnancy plans.
  If you are planning a pregnancy or are already pregnant or breastfeeding, tell your doctor in advance. If you become pregnant while taking 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, this may matter when supplements and other medications are involved. As for alcohol, there are no known problems linked to drinking alcohol with amoxicillin clavulanic acid.
• See your doctor regularly.
  Keep your lab and follow-up appointments. You may need additional tests to make sure the treatment is working and that no changes to your medication or dose are needed.
• Use the right urine glucose test if you have diabetes.
  For urine glucose testing, 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 not have enough to finish your own treatment. If you have finished the course but still have symptoms of infection, contact your doctor as soon as possible.

These precautions are straightforward and can help your treatment for a bacterial infection go as smoothly as possible.

Hypersensitivity Reactions

If you've ever had a penicillin hypersensitivity reaction, you must tell your doctor. If this is overlooked, an anaphylactic reaction can be fatal. Even if penicillin is not on your list of allergens, it is still useful to show your doctor your full allergy list.

Before taking Augmentin or similar medications, 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 medication until you get further advice.

Hepatic Dysfunction

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

These patients need regular monitoring to check whether hepatic toxicity can be reversed. The groups considered most susceptible are:

• Male patients;
• Older adults;
• Patients treated with the same medications for a long time.

Even after the medication is stopped, this side effect may appear within the next couple of months.

Clostridium difficile-associated diarrhea (CDAD)

CDAD is a common side effect of many antibacterial medications. When your microbiome is disrupted, bacteria in the colon can react and cause inflammation and other problems. CDAD can range from mild illness that is easy to treat to fatal colitis.

CDAD should be considered in anyone taking antibacterial treatment who develops diarrhea. The condition can become severe and difficult to treat. Some patients may need a colectomy. Even if the problem appears within 2 months after treatment ends, it may still be related. This is another reason why an accurate medical history matters.

If a patient is diagnosed with CDAD, any antibacterial treatment not being used to treat it will need to be stopped. Further treatment may include protein supplementation, management of fluids and electrolytes, another antibacterial medication that works against Clostridium difficile (C. difficile), and surgical assessment if the condition becomes severe.

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, and complications may follow.

Potential for Microbial Overgrowth

Like any antibacterial treatment, this combination can disrupt your microbiome by killing certain bacteria. That may allow another organism to overgrow. If this is not properly controlled, it can lead to a superinfection. If this is suspected, the current antibacterial treatment should be stopped and further testing done to guide a new treatment.

Phenylketonurics

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

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

Development of Drug-Resistant Bacteria

Augmentin and similar medications should only be prescribed when a bacterial infection is confirmed or strongly suspected. If not, the treatment is unlikely to help and may encourage the growth of drug-resistant bacteria. In the future, that could make treatment less effective if the patient develops another bacterial infection.

Use in Specific Populations

The dose may change depending on the population the patient belongs to, including pregnant or breastfeeding women, pediatric 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 teratogenic effects are not expected. However, the topic has not been studied extensively. Some reproduction studies in pregnant mice showed that doses of even 1200 mg/kg/day did not affect the fetus. This was several times higher than the maximum dose used in humans.

Animal findings are not always the same as human outcomes, however. Treatment should therefore be prescribed only after a bacterial infection has been confirmed.

Labor and Delivery

There is no clear information on whether the use of 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 well absorbed during labour.

Nursing Mothers

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

Pediatric Use

The dose must be adjusted based on the age and/or weight of the pediatric patient:

• Infants younger than 3 months old should only have 30 mg/kg/day, 2 times a day;
• For patients 3 months and older, the dosage differs depending on the diagnosis and weight;
• Patients who weigh 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 reaches 40 kg because the ratio of components is different. Also remember that amoxicillin is cleared more slowly from the body in infants.

Geriatric Use

In an analysis of clinical studies of medications containing amoxicillin and clavulanic acid (Augmentin), there were around 3,100 patients in total. Of these, 32% were 65 years of age or older, including patients aged 75 and over.

No major differences in response were found between older and younger patients. No clear differences in safety or effectiveness were found unless the patient had greater sensitivity to one or more components of the drug, metabolic dysfunction, or kidney problems.

Patients should be assessed for these conditions before being prescribed the drug.

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 the risk of unwanted effects. Dose selection should be guided by whether kidney disease is present.

Undesirable Effects

The undesirable effects are related 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 include:

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

Taking your medication at the same time every day can reduce the chance of an overdose or a missed dose.

Overdose

If an overdose happens:

• Stop taking it right away;
• Treat the symptoms to help ease the condition;
• Drink plenty of fluids;
• Take other supportive measures as needed;
• Call your doctor.

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

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 case of an overdose.

Kidney impairment caused by an overdose may improve after stopping the medication and removing excess amoxicillin and/or clavulanic acid through hemodialysis.

You can find more information from the Canadian Association for Poison Centres and Clinical Toxicology. In case of suspected poisoning, contact your local poison centre right away. If the person has collapsed, had a seizure, or is having trouble breathing, call 911 immediately.

Missed Dose

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

Storage

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

• Keep the drug in its original container;
• Keep it out of 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 medication, store it in the fridge but do not freeze it;
• Throw out the liquid if it has not been used within 10 days.

It's very important to keep medications where children can't get to them. Many drops, creams, and other medicines do not come with child-resistant caps, so even if you close them tightly, a child may still be able to open them.

Choose a storage spot carefully. Keep medications up high and out of reach of small children. According to Up and Away, about 50,000 children are taken to emergency rooms because of their "experiments" with medicine containers.

It's also important to dispose of unneeded medications properly. Do it in a way that prevents children, animals, or anyone else from taking them after they have been thrown out. You should not flush medications down the toilet either, especially in large amounts.

There are take-back programs specifically for disposing of unneeded medications. You can ask a pharmacist or your doctor about local options, and some municipalities or recycling services may also provide information. If no take-back program is available in your area, you can also check Health Canada guidance online for safe disposal of medications.

The Bottom Line

Overall, this combination can be used in pregnant women, children, and older adults when the correct dose is given. Be sure to finish the full course of treatment, do not share the medication with anyone, and dispose of any remaining tablets or suspension according to Health Canada guidance.