amoxicillin/clavulanate

Amoxicillin/clavulanate is a combination antibacterial medication used to treat various types of bacterial infections.

Amoxicillin is an antibiotic, while clavulanate does not have antibacterial activity, but instead prevents the degradation of amoxicillin by bacterial enzymes. The combination is effective against many strains of gram-positive and gram-negative bacteria. Gram-negative bacteria have an additional membrane outside the cell wall that gram-positive bacteria lack and the two types are identified by the Gram stain lab test.

Amoxicillin is a semisynthetic broad-spectrum antibiotic that belongs to the penicillin class of antibiotics. Amoxicillin kills bacteria by inhibiting the synthesis of peptidoglycan, a vital constituent that provides stability to the bacterial cell wall. Amoxicillin contains a beta-lactam ring in its chemical structure, a compound that binds to and blocks penicillin-binding proteins, enzymes that are essential for the biosynthesis of peptidoglycan.

Many bacteria, however, develop resistance to beta-lactam antibiotics by producing beta-lactamases, enzymes that cleave the beta-lactam rings in the antibiotics and destroy them. Clavulanate has the ability to inactivate many of the beta-lactamases commonly found in bacteria resistant to penicillin and cephalosporin classes of antibiotics. The addition of clavulanate prevents the degradation of amoxicillin and extends its activity.

The uses of amoxicillin/clavulanate include:

FDA-approved:

Adult and pediatric:

• Lower respiratory tract infections
• Community acquired pneumonia
• Acute otitis media
• Sinusitis
• Acute bacterial rhinosinusitis
• Skin and skin structure infections
• Urinary tract infection

Off-label:

Adult:

• Prophylaxis or treatment of bite wound (animal or human bite)
• Acute exacerbation of bronchiectasis
• Acute exacerbation of chronic obstructive pulmonary disease (COPD)
• Diabetic foot infection
• Mild to moderate intra-abdominal infection, community acquired in patients without risk factors for resistance or treatment failure
• Neutropenic fever in low-risk cancer patients (empiric therapy)
• Odontogenic infection
• Peritonsillar cellulitis or abscess
• Streptococcus (group A), chronic carriage

Organisms susceptible to amoxicillin/clavulanate include:

Gram-positive:

• Staphylococcus aureus (beta-lactamase and non-beta-lactamase–producing)
• Streptococcus pneumoniae (including isolates with penicillin minimum inhibitory concentrations (MICs) 2 mcg/mL or less)

Gram-negative:

• Enterobacter species (urinary tract infections)
• Escherichia coli (beta-lactamase and non-beta-lactamase–producing)
• Haemophilus influenzae (beta-lactamase and non-beta-lactamase–producing)
• Haemophilus parainfluenzae (including β-lactamase–producing isolates)
• Klebsiella species (all known strains are beta-lactamase–producing)
• Moraxella catarrhalis (beta-lactamase and non-beta-lactamase–producing)

• Do not use amoxicillin/clavulanate in patients with a history of allergic reaction to any penicillin, cephalosporin, or other beta-lactam antibiotics, or any of the components of the amoxicillin/clavulanate formulation.
• Do not use in patients with a history of cholestatic jaundice or liver dysfunction associated with amoxicillin/clavulanate.
• Do not use amoxicillin/clavulanate in patients with severe kidney impairment and patients receiving hemodialysis.
• Do not use extended-release tablets in patients with kidney impairment.
• The safety and efficacy of extended-release tablets are not established in children below 16 years of age.
• Do not interchange different formulations, because the ratios of amoxicillin to clavulanate are different.
• Avoid use in patients with mononucleosis, the risk of developing a rash is high.
• Serious and occasionally fatal hypersensitivity reactions including anaphylaxis may occur, especially in patients with known hypersensitivity to penicillin antibiotics or those with sensitivity to multiple allergens. In case of serious anaphylactic reactions, discontinue amoxicillin/clavulanate immediately and institute appropriate treatment.
• As with most antibacterial drugs, amoxicillin/clavulanate use can alter the gut flora and lead to Clostridium difficile overgrowth that can cause pseudomembranous colitis and C. difficile-associated diarrhea (CDAD), even up to two months after discontinuation. Monitor patients for signs of colon inflammation (colitis) and diarrhea, and treat promptly.
• Use amoxicillin/clavulanate with caution in patients with impaired liver function.
• Although penicillin antibiotics have low toxicity, patient’s kidney and liver function and blood count should be monitored periodically while on therapy.
• In the absence of a proven or strongly suspected bacterial infection or a prophylactic indication, amoxicillin/clavulanate is unlikely to be beneficial and increases the risk of development of drug-resistant bacteria. If fungal or bacterial superinfections occur, discontinue amoxicillin/clavulanate and institute appropriate treatment.
• Amoxicillin/clavulanate treatment may cause severe skin adverse reactions such as Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), drug reaction with eosinophilia and systemic symptoms (DRESS), and acute generalized exanthematous pustulosis (AGEP). Monitor closely patients who develop a rash and discontinue the drug if lesions progress.
• Some formulations of amoxicillin/clavulanate contain phenylalanine, an amino acid. Use of these formulations should be avoided in patients with phenylketonuria, a hereditary condition that causes inability to breakdown phenylalanine.

Common side effects of amoxicillin/clavulanate include:

• Diarrhea
• Nausea
• Vomiting
• Abdominal distress
• Gas (flatulence)
• Candida yeast infection (candidiasis)
• Diaper rash
• Candidal diaper rash
• Skin rash
• Hives (urticaria)
• Vaginal fungal infection (mycosis)
• Vaginal inflammation (vaginitis)
• Headache
• Excessive platelet production (thrombocytosis)

Less common side effects of amoxicillin/clavulanate include:

• Clostridium difficile colitis
• C. difficile-associated diarrhea (CDAD)
• Intestinal inflammation (enterocolitis) including drug-induced enterocolitis syndrome
• Hemorrhagic colitis
• Gastritis
• Inflammation of the pancreas (pancreatitis)
• Tongue inflammation (glossitis)
• Blackening of the tongue (melanoglossia)
• Staining of tooth
• Oral inflammation (stomatitis)
• Mucocutaneous candidiasis
• Liver toxicity
• Elevation of liver enzymes ALT and AST
• Liver inflammation due to impaired bile flow (cholestatic hepatitis)
• Cholestatic jaundice
• Liver cell inflammation (hepatocellular hepatitis)
• Inflammation in the kidney (interstitial nephritis)
• Crystals in urine (crystalluria)
• Blood in urine (hematuria)
• Agitation
• Anxiety
• Confusion
• Insomnia
• Dizziness
• Reversible hyperactivity
• Muscle twitches and jerks (myoclonus)
• Aseptic inflammation in the membrane around brain and spinal cord (meningitis)
• Blood disorders including:
  • Low red blood cell count (anemia)
  • Anemia due to rapid destruction of red blood cells (hemolytic anemia)
  • Severely low count of granulocyte immune cells (agranulocytosis)
  • Low count of leukocyte immune cells (leukopenia)
  • Low platelet count (thrombocytopenia)
  • Immune thrombocytopenia
  • High count of eosinophil inflammatory immune cells (eosinophilia)
• Severe skin reactions including:
  • Itching (pruritus)
  • Bullous dermatitis
  • Exfoliative dermatitis
  • Fixed drug eruption
  • Erythema multiforme
  • Sweet syndrome
  • Stevens-Johnson syndrome (SJS)
  • Toxic epidermal necrolysis (TEN)
  • Acute generalized exanthematous pustulosis (AGEP)
• Hypersensitivity reactions, including:
  • Swelling of tissue beneath the skin and mucous membranes (angioedema)
  • Blood vessel inflammation (hypersensitive angiitis/vasculitis)
  • Type IV hypersensitivity reaction
  • Drug reaction with eosinophilia and systemic symptoms (DRESS)
  • Serum sickness like reaction
  • Severe allergic reaction (anaphylaxis)
  • Non-immune anaphylaxis
  • Urticaria accompanied by joint inflammation (arthritis), joint pain (arthralgia), muscle pain (myalgia), or/and fever

Call your doctor immediately if you experience any of the following symptoms or serious side effects while using this drug:

• Serious heart symptoms include fast or pounding heartbeats, fluttering in your chest, shortness of breath, and sudden dizziness;
• Severe headache, confusion, slurred speech, severe weakness, vomiting, loss of coordination, feeling unsteady;
• Severe nervous system reaction with very stiff muscles, high fever, sweating, confusion, fast or uneven heartbeats, tremors, and feeling like you might pass out; or
• Serious eye symptoms include blurred vision, tunnel vision, eye pain or swelling, or seeing halos around lights.

This is not a complete list of all side effects or adverse reactions that may occur from the use of this drug. Call your doctor for medical advice about serious side effects or adverse reactions. You may also report side effects or health problems to the FDA at 1-800-FDA-1088.

Amoxicillin/Clavulanate

Oral Suspension

• 125 mg/31.25 mg/5 mL
• 200 mg/28.5 mg/5 mL
• 250 mg/62.5 mg/5 mL
• 400 mg/57 mg/5 mL
• 600 mg/42.9 mg/5 mL

Tablet

• 250 mg/125 mg
• 500 mg/125 mg
• 875 mg/125 mg

Tablet, Extended Release

• 1000 mg/62.5 mg

Tablet, Chewable

• 200 mg/28.5 mg
• 400 mg/57 mg

Adult:

Lower Respiratory Tract Infection

• Beta-lactamase−producing strains of Haemophilus influenzae and Moraxella catarrhalis
• Mild to moderate: 500/125 mg orally every 12 hours or 250/125 mg every 8 hours for 10 days
• Severe: 875/125 mg orally every 12 hours or 500/125 mg every 8 hours or 2000 mg (2 extended-release tabs) every 12 hours for 7-10 days

Chronic Obstructive Pulmonary Disease

• 500 mg orally every 8 hours

Acute Bacterial Sinusitis

Beta-lactamase−producing strains of H. influenzae and M. catarrhalis

• 2000 mg (2 extended-release tablets) orally every 12 hours for 10 days

Animal/Human Bite Wounds

• 875 mg orally every 12 hours or 500 mg every 8 hours for 3-5 days

Erysipelas

• 875 mg orally every 12 hours or 500 mg every 8 hours for 7-10 days

Pyelonephritis

Beta-lactamase−producing strains of Escherichia coli, Klebsiella spp, and Enterobacter spp

• 875 mg orally every 12 hours or 500 mg every 8 hours

Skin Abscess

Beta-lactamase−producing strains of Staphylococcus aureus, E coli, and Klebsiella spp

• 875 mg orally every 12 hours

Diabetic Foot

• Mild to moderate, localized cellulitis
• 2000 mg (2 extended-release tablets) orally every 12 hours for 7-14 days

Group A Streptococci, Chronic Carrier

• 40 mg/kg/day orally divided every 8 hours for 10 days; not to exceed 2000 mg/day

Dosing Modifications

Renal impairment

• Creatinine clearance (CrCl) below 30 mL/minute: Do not use 875/125 mg tablet or extended-release tablets
• CrCl 10-30 mL/minute: 250-500/125 mg orally every 12 hours
• CrCl below 10 mL/minute: 250-500/125 mg orally every 24 hours
• Hemodialysis: 250-500/125 mg orally every 24 hours; administer additional dose both during and at end of dialysis

Hepatic impairment

• Dose with caution; monitor hepatic function regularly

Administration

• Take with meals to avoid gastrointestinal upset
• Take suspension at start of meal to enhance absorption
• Dysphagia: May substitute 250 mg/5 mL suspension for 500/125 mg tablet; may substitute 200 mg/5 mL or 400 mg/5 mL suspension for 875/125 mg tablet

Pediatric:

General Dosing for Infections for Neonates and Infants below 3 months

• Indicated for susceptible isolates of lower respiratory tract infections, acute bacterial otitis media, sinusitis, skin and skin structure infections, and urinary tract infections
• Recommended dosing based on amoxicillin component
• Age below 3 months: 30 mg/kg/day divided every 12 hours, based on amoxicillin component; use 125 mg/ 31.25 mg per 5 mL oral suspension

Acute Bacterial Otitis Media

• Indicated for acute bacterial otitis media caused by beta-lactamase-producing isolates of H. influenzae and M. catarrhalis

Children above 3 months and weight under 40 kg

• 45 mg/kg/day divided q12hr; use 200mg/28.5mg per 5 mL or 400mg/57mg per 5 mL suspension
• 40 mg/kg/day divided q8hr; use 125mg/31.25mg per 5ml or 250mg/62.5 mg per 5 mL suspension
• Treatment duration: 10 days

Children 40 kg or more

• Dose according to adult recommendations
• Do not use amoxicillin and clavulanate potassium tablet 250 mg/125 mg until child weighs less than 40 kg, due to different amoxicillin to clavulanic acid ratios in amoxicillin-clavulanate potassium tablet 250 mg/125 mg versus amoxicillin-clavulanate potassium chewable tablet 250 mg/62.5 mg

Sinusitis, Lower Respiratory Tract Infections, and More Severe Infections

• Indicated for lower respiratory tract infections and sinusitis caused by beta-lactamase-producing isolates of H. influenzae and M. catarrhalis

Children above 3 months and weight under 40 kg

• 45 mg/kg/day orally divided every 12 hours; use 200 mg/28.5 mg per 5 mL or 400 mg/57 mg per 5 mL suspension
• 40 mg/kg/day orally divided every 8 hours; use 125 mg/31.25 mg per 5 ml or 250 mg/62.5 mg per 5 mL suspension

Children 40 kg or more

• Dose according to adult recommendations
• Do not use amoxicillin and clavulanate potassium tablet 250 mg/125 mg until child weighs less than 40 kg, due to different amoxicillin to clavulanic acid ratios in amoxicillin-clavulanate potassium tablet 250 mg/125 mg versus amoxicillin-clavulanate potassium chewable tablet 250 mg/62.5 mg

Less Severe Infections

Children above 3 months and weight under 40 kg

• 25 mg/kg/day orally divided every 12 hours; use 200 mg/28.5 mg per 5 mL or 400 mg/57 mg per 5 mL suspension
• 20 mg/kg/day orally divided every 8 hours; use 125 mg/31.25 mg per 5 ml or 250 mg/62.5 mg per 5 mL suspension

Children 40 kg or more

• Dose according to adult recommendations
• Do not use amoxicillin and clavulanate potassium tablet 250 mg/125 mg until child weighs less than 40 kg, due to different amoxicillin to clavulanic acid ratios in amoxicillin-clavulanate potassium tablet 250 mg/125 mg versus amoxicillin-clavulanate potassium chewable tablet 250 mg/62.5 mg

Dosage Modifications

Renal impairment

• GFR less than 30 mL/minute: Do not use amoxicillin-clavulanate potassium tablets 875 mg/125 mg dose
• GFR 10-30 mL/minute: Dose amoxicillin-clavulanate potassium to 500 mg/125 mg or 250 mg/125 mg every 12 hours, depending on the severity of the infection
• GFR less than 10 mL/minute: Dose amoxicillin-clavulanate potassium to 500 mg/125 mg or 250 mg/125 mg every 24 hours, depending on severity of infection
• Hemodialysis: Dose amoxicillin-clavulanate potassium to 500 mg/125 mg or 250 mg/125 mg every 24 hours, depending on severity of infection; also, requires an additional dose both during and at end of dialysis

Dosing Considerations

• Because of the different amoxicillin-to-clavulanate ratios in the 250-mg tablet (amoxicillin 250 mg, clavulanate 125 mg) and the 250-mg chewable tablet (amoxicillin 250 mg, clavulanate 62.5 mg), the 250-mg tablet should not be used if the pediatric patient weighs less than 40 kg (adverse reaction, including severe diarrhea, may occur due to excessive clavulanic acid in 250-mg tablet)
• Every 12-hour dosing associated with less diarrhea
• Phenylketonuria: Do not use 200 mg/28.5 mg per 5 mL and 400 mg/57 mg per 5 mL suspension and chewable tablets 200 mg/28.5 mg and 400 mg/57 mg since these contain aspartame
• Safety and efficacy of extended-release tablets in children below 16 years old have not been established

Overdose

• Amoxicillin/clavulanate overdose can cause symptoms that include vomiting, abdominal pain, diarrhea, rash, hyperactivity, and/or drowsiness.
• There have been a few reports of crystals in the urine, kidney inflammation, and kidney failure with amoxicillin/clavulanate overdose.
• Overdose may be treated with symptomatic and supportive care. Blood levels of the drug may be reduced with hemodialysis.

Inform your doctor of all medications you are currently taking, who can advise you on any possible drug interactions. Never begin taking, suddenly discontinue, or change the dosage of any medication without your doctor’s recommendation.

• Amoxicillin/clavulanate has no known severe interactions with other drugs.
• Serious interactions of amoxicillin/clavulanate include:
  • BCG vaccine live
  • cholera vaccine
  • demeclocycline
  • doxycycline
  • eravacycline
  • minocycline
  • mycophenolate
  • omadacycline
  • pexidartinib
  • pretomanid
  • sarecycline
  • tetracycline
  • typhoid vaccine live
• Amoxicillin/clavulanate has moderate interactions with at least 21 other drugs. 
• Mild interactions of amoxicillin/clavulanate include:
  • amiloride
  • azithromycin
  • aztreonam
  • chloramphenicol
  • clarithromycin
  • erythromycin base
  • erythromycin ethylsuccinate
  • erythromycin lactobionate
  • erythromycin stearate
  • pyridoxine (Antidote)

The drug interactions listed above are not all of the possible interactions or adverse effects. For more information on drug interactions, visit the RxList Drug Interaction Checker.

It is important to always tell your doctor, pharmacist, or health care provider about all prescription and over-the-counter medications you use, as well as the dosage for each, and keep a list of the information. Check with your doctor or healthcare provider if you have any questions about the medication.

• Animal reproductive studies do not show evidence of fetal harm, however, animal studies are not always predictive of human response. Amoxicillin/clavulanate should be used during pregnancy only if clearly needed.
• Amoxicillin/clavulanate use during pregnancy may increase the risk of necrotizing enterocolitis in neonates or bowel disorders in children when used to prevent infection in preterm pre-labor rupture of fetal membranes.
• Amoxicillin/clavulanate is present in breastmilk. Use with caution in nursing mothers.

• Take amoxicillin/clavulanate exactly as prescribed.
• Do not interchange different formulations of the drug.
• Complete the prescribed amoxicillin/clavulanate therapy. Do not miss doses or discontinue therapy if you feel better. It can decrease the effectiveness of treatment and can also lead to the development of drug-resistant bacteria.
• Inform your physician immediately if you develop hypersensitivity reactions to amoxicillin/clavulanate.
• Diarrhea is a common problem with antibiotic treatments, which should resolve with the completion of the therapy. Seek medical help if you have watery or bloody stools, with or without stomach cramps and fever. Symptoms can develop even up to two months after the last dose of antibiotic.
• Store amoxicillin/clavulanate safely out of reach of children.
• In case of overdose, seek medical help or contact Poison Control.