Amoxicillin / Clavulanic Acid (Clavulin)

1. Health Canada Product Monograph — Amoxicillin / Clavulanic Acid

• Amoxicillin and clavulanic acid is used to treat sinusitis caused by beta-lactamase-producing bacteria.
• It is used to treat middle ear infections (otitis media) caused by beta-lactamase-producing bacteria.
• It is used to treat lower respiratory tract infections caused by susceptible beta-lactamase-producing bacteria.
• It is used to treat skin and soft tissue infections caused by beta-lactamase-producing Staphylococcus aureus.
• It is used to treat urinary tract infections caused by beta-lactamase-producing E. coli.

• Use during pregnancy should generally be avoided unless considered essential by the treating physician.
• In one study of women with preterm rupture of membranes, preventive treatment with amoxicillin and clavulanic acid was linked to an increased risk of a serious bowel condition in newborns (necrotizing enterocolitis).

• Penicillin-type antibiotics, including amoxicillin, pass into human breast milk.
• It is not known whether clavulanic acid passes into breast milk.
• Caution should be used when this medicine is given to a breastfeeding mother.

• Older adults may have a higher chance of developing liver-related side effects, particularly with prolonged treatment.

• This medicine can be used in infants 12 weeks of age and older, with dosing based on body weight.
• In infants younger than 12 weeks, the dose is adjusted because of incompletely developed kidney function that affects how amoxicillin is cleared from the body; the 125 mg/5 mL suspension is recommended for this age group.
• Twice-daily dosing is preferred over three-times-daily dosing in infants and children because it causes significantly less diarrhea.

• For mild to moderate infections in adults, the usual dose is one 500 mg tablet every 12 hours.
• For more severe infections, including chronic urinary tract infections and lower respiratory infections, the dose is one 875 mg tablet every 12 hours or one 500 mg tablet every 8 hours.
• In children 12 weeks of age and older, dosing is based on body weight and the amoxicillin component, ranging from 25 mg/kg/day to 45 mg/kg/day divided into two or three doses depending on the infection and its severity.
• The usual course of treatment is 7 to 10 days, and treatment should continue for at least 48 to 72 hours after symptoms resolve; infections caused by streptococcus require at least 10 days of treatment to prevent complications like rheumatic fever.
• In adults with reduced kidney function, the dose is reduced to 500 mg/125 mg twice daily for creatinine clearance between 10 and 30 mL/min, and to 500 mg/125 mg once daily for creatinine clearance below 10 mL/min; the 875 mg tablet should only be used if creatinine clearance is above 30 mL/min.
• Patients on hemodialysis should take one 500 mg/125 mg tablet every 24 hours, plus an extra tablet during dialysis, repeated at the end of dialysis.
• If a dose is missed, it should be taken as soon as remembered unless it is almost time for the next dose, in which case the missed dose should be skipped; doses should never be doubled.

If overdose is suspected, seek emergency medical attention immediately or contact your regional Poison Control Centre without delay.

• Most people who take an overdose have no symptoms, or develop stomach pain, vomiting, and diarrhea.
• Rash, unusual excitability, or drowsiness have been observed in a small number of overdose cases.
• Crystals of amoxicillin can form in the kidneys after an overdose, which has led to kidney failure in some cases; maintaining good fluid intake and urine output can reduce this risk.
• Both amoxicillin and clavulanic acid can be removed from the body by hemodialysis if needed.
• Activated charcoal may be given to help remove unabsorbed drug, along with general supportive care.

• Diarrhea may occur and is the most commonly reported side effect.
• Nausea may occur.
• Vomiting may occur.
• Yeast infections of the mouth or vagina (candidiasis) may occur.
• Stomach cramping, gas, or indigestion may occur.
• Loss of appetite may occur.
• Headache may occur.
• Dizziness may occur.
• Vaginal irritation (vaginitis) may occur.
• Taking this medicine at the start of a meal can help reduce stomach upset.

Serious side effects require immediate discussion with the prescriber or emergency care.

• Serious, occasionally fatal allergic reactions, including anaphylaxis and severe skin reactions, can occur with this medicine.
• Severe diarrhea caused by Clostridium difficile infection can occur, sometimes weeks after finishing treatment, and can range from mild to life-threatening.
• Liver problems, including hepatitis and jaundice, have been reported, more often in men, older adults, and after prolonged treatment; these are usually reversible after stopping the medicine.
• Severe skin reactions, including Stevens-Johnson syndrome, toxic epidermal necrolysis, and drug reaction with eosinophilia and systemic symptoms (DRESS), have been reported.
• Kounis syndrome, a serious allergic reaction that can trigger a heart attack, has been reported.
• Blood disorders, including anemia, low platelet counts, and low white blood cell counts, have been reported rarely and are usually reversible after stopping the medicine.
• Interstitial nephritis, a kidney inflammation, can occur rarely.
• Convulsions may occur, particularly in patients with reduced kidney function or those receiving high doses.
• Black, hairy discolouration of the tongue, or tooth discolouration in children, has been reported very rarely and is not permanent.
• Seek urgent medical attention for facial or throat swelling, difficulty breathing, severe or bloody diarrhea, yellowing of the skin or eyes, or a widespread blistering rash.

• Use with caution in patients with a history of allergies to multiple substances, since they are more likely to have a hypersensitivity reaction.
• Use with caution in patients with reduced kidney function, since the dose needs to be adjusted.
• Use with caution in patients with liver disease or a history of liver problems related to this medicine.
• Use with caution in patients taking oral blood thinners such as warfarin, since this medicine can increase bleeding risk and requires closer monitoring.
• Use with caution in patients with reduced urine output, since crystal formation in the kidneys is more likely.
• Use with caution in patients with phenylketonuria when using the oral suspension, since it contains aspartame.
• Avoid use in patients with infectious mononucleosis, since a rash is more likely to occur.

• Contraindicated in patients with a known hypersensitivity to penicillins, cephalosporins, or any ingredient in the formulation.
• Contraindicated in patients with suspected or confirmed infectious mononucleosis.
• Contraindicated in patients with a previous history of jaundice or liver problems caused by this medicine.

• This medicine may reduce the effectiveness of combined oral contraceptives; an additional non-hormonal method of birth control is recommended during treatment.
• Probenecid is not recommended with this medicine, since it increases and prolongs amoxicillin levels in the blood.
• Combined use with warfarin or acenocoumarol can increase bleeding time and INR, requiring closer monitoring when the antibiotic is started or stopped.
• This medicine can reduce blood levels of mycophenolic acid in transplant patients taking mycophenolate mofetil.
• This medicine may reduce the clearance of methotrexate, increasing the risk of methotrexate toxicity.

• Amoxicillin and clavulanic acid can be taken with or without food, but the clavulanic acid component is absorbed better when taken with food.
• Taking this medicine at the start of a meal is recommended to improve absorption and reduce the chance of stomach upset.

• This medicine is usually taken at the start of a meal to improve absorption of the clavulanic acid component and reduce stomach upset.
• Doses should be spaced evenly through the day (every 8 or 12 hours, depending on the regimen) to maintain consistent antibiotic levels.

• Store tablets in a dry place at room temperature (15°C to 25°C).
• Store unmixed suspension powder in a dry place at room temperature (15°C to 25°C).
• Once mixed, refrigerate the oral suspension (2°C to 8°C) and discard any unused portion after 7 to 10 days, depending on the formulation.

• Take this medicine at the start of a meal to help prevent stomach upset.
• Finish the entire course of this medicine, even if you feel better, unless your healthcare professional tells you to stop.
• Tell your healthcare professional if you develop severe or watery diarrhea, even after you finish this medicine.
• This medicine can make hormonal birth control pills less effective; use a backup method of contraception during treatment.
• Seek urgent care for facial swelling, difficulty breathing, or a severe skin rash.