Amoxicillin/Clavulanate potassium

Description

Amoxicillin and clavulanate potassium for oral suspension USP is an oral antibacterial combination that includes the semisynthetic antibacterial amoxicillin and the beta-lactamase inhibitor clavulanate potassium, the potassium salt of clavulanic acid. Amoxicillin, an analog of ampicillin, is derived from the basic penicillin nucleus, 6-aminopenicillanic acid, with a molecular formula of C₁₆H₁₉N₃O₅S-3H₂O and a molecular weight of 419.46. Its chemical structure is defined as (2S,5R,6R)-6-((R)-(-)-2-amino-2-(p-hydroxyphenyl)acetamido-3,3-dimethyl-7-oxo-4-thia-1-azabicyclo3.2.0heptane-2-carboxylic acid trihydrate.

Clavulanic acid, produced by the fermentation of Streptomyces clavuligerus, is a beta-lactam structurally related to penicillins. It effectively inactivates a wide variety of beta-lactamases by blocking their active sites, particularly those that are plasmid-mediated and responsible for drug resistance to penicillins and cephalosporins. The molecular formula for clavulanate potassium is C₈H₈KNO₅, with a molecular weight of 237.25, and its chemical structure is potassium (Z)-(2R,5R)-3-(2-hydroxyethylidene)-7-oxo-4-oxa-1-azabicyclo3.2.0-heptane-2-carboxylate.

Upon reconstitution, each 5 mL of the oral suspension contains 600 mg of amoxicillin as the trihydrate and 42.9 mg of clavulanic acid, equivalent to 51.1 mg of clavulanate potassium. Additionally, each 5 mL of the suspension provides approximately 9 mg of potassium and 6 mg of sodium. Inactive ingredients include carboxymethylcellulose sodium, sucralose, sodium citrate, anhydrous citric acid, silicon dioxide, colloidal silicon dioxide, xanthan gum, and flavoring agents such as vanilla and tutti frutti, which consist of maltodextrin, glyceryl triacetate, corn starch, propylene glycol, alpha tocopherol, and other flavoring components.

Uses and Indications

Amoxicillin and clavulanate potassium for oral suspension, 600 mg/42.9 mg per 5 mL is indicated for the treatment of pediatric patients with recurrent or persistent acute otitis media caused by specific bacterial pathogens. These include Streptococcus pneumoniae (with penicillin minimum inhibitory concentrations MICs less than or equal to 2 mcg/mL), Haemophilus influenzae (including beta-lactamase–producing strains), and Moraxella catarrhalis (including beta-lactamase-producing strains). The targeted patient population includes those with risk factors such as antibacterial exposure for acute otitis media within the preceding 3 months, age 2 years or younger, and daycare attendance.

Limitations of use include the fact that Amoxicillin and clavulanate potassium for oral suspension is not indicated for the treatment of acute otitis media due to S. pneumoniae with penicillin MICs greater than or equal to 4 mcg/mL. Additionally, acute otitis media caused solely by S. pneumoniae can be effectively treated with amoxicillin alone. Therapy may be initiated prior to obtaining bacteriological study results if there is a reasonable suspicion that the infection may involve both S. pneumoniae (with penicillin MICs less than or equal to 2 mcg/mL) and the aforementioned beta-lactamase-producing organisms.

To reduce the development of drug-resistant bacteria and maintain the effectiveness of Amoxicillin and clavulanate potassium for oral suspension, it should be used exclusively to treat or prevent infections that are proven or strongly suspected to be caused by bacteria.

Dosage and Administration

Pediatric patients aged 3 months to 12 years who weigh less than or equal to 40 kg should receive a dosage of 90 mg/kg/day. This total daily dose should be divided into two administrations, given every 12 hours. The treatment course is to be continued for a duration of 10 days.

Healthcare professionals are advised to calculate the total daily dose based on the patient's weight and ensure that the medication is administered at consistent intervals to maintain effective therapeutic levels.

Contraindications

Use of amoxicillin and clavulanate potassium for oral suspension, 600 mg/42.9 mg per 5 mL is contraindicated in patients with a history of serious hypersensitivity reactions, including anaphylaxis or Stevens-Johnson syndrome, to this medication or to other beta-lactams such as penicillins or cephalosporins. Additionally, it is contraindicated in individuals with a history of cholestatic jaundice or hepatic dysfunction associated with this medication.

Warnings and Precautions

Serious hypersensitivity reactions, including fatal outcomes, have been associated with the use of amoxicillin and clavulanate potassium for oral suspension, 600 mg/42.9 mg per 5 mL. In the event of such a reaction, it is imperative to discontinue the medication immediately and initiate appropriate therapeutic measures.

Healthcare professionals should remain vigilant for severe cutaneous adverse reactions (SCAR). Close monitoring of patients is essential, and the medication should be discontinued if any rash progresses.

The occurrence of drug-induced enterocolitis syndrome (DIES) has been reported in patients using amoxicillin, a component of this formulation. Should DIES be suspected, it is crucial to discontinue amoxicillin and clavulanate potassium for oral suspension, 600 mg/42.9 mg per 5 mL and provide suitable therapy.

Patients with hepatic dysfunction may experience cholestatic jaundice. It is recommended to discontinue the medication if any signs or symptoms of hepatitis arise. Additionally, liver function tests should be monitored in patients with pre-existing hepatic impairment to ensure safety.

Clostridium difficile-associated diarrhea (CDAD) is a potential complication; therefore, healthcare providers should evaluate patients promptly if diarrhea occurs during treatment.

Particular caution is warranted for patients with mononucleosis, as those receiving amoxicillin and clavulanate potassium for oral suspension, 600 mg/42.9 mg per 5 mL may develop a skin rash. The use of this medication should be avoided in such patients to prevent adverse reactions.

Side Effects

Patients receiving amoxicillin and clavulanate potassium for oral suspension may experience a range of adverse reactions. Common adverse reactions include coughing, vomiting, contact dermatitis (such as diaper rash), fever, upper respiratory tract infections, and diarrhea.

Serious adverse reactions have been reported and require immediate attention. These include serious hypersensitivity reactions, which can be fatal; in such cases, amoxicillin and clavulanate potassium should be discontinued, and appropriate therapy should be initiated. Severe cutaneous adverse reactions (SCAR) necessitate close monitoring, with discontinuation of the medication if a rash progresses. Drug-induced enterocolitis syndrome (DIES) is another serious reaction that warrants discontinuation of the drug and appropriate therapeutic measures. Hepatic dysfunction and cholestatic jaundice have also been observed; patients should be monitored for signs and symptoms of hepatitis, and the medication should be discontinued if these occur. Additionally, Clostridium difficile-associated diarrhea (CDAD) should be evaluated if diarrhea develops. It is important to note that patients with mononucleosis who receive this medication may develop a skin rash, and its use should be avoided in these individuals.

Other important considerations include a history of serious hypersensitivity reactions, such as anaphylaxis or Stevens-Johnson syndrome, to amoxicillin and clavulanate potassium or other beta-lactams, including penicillins and cephalosporins. A history of cholestatic jaundice or hepatic dysfunction associated with this medication is also significant.

In cases of overdosage, patients have primarily experienced gastrointestinal symptoms, including stomach and abdominal pain, vomiting, and diarrhea. Some patients have reported rash, hyperactivity, or drowsiness. Rarely, interstitial nephritis resulting in oliguric renal failure has been documented following overdosage, as has crystalluria, which in some instances has led to renal failure in both adult and pediatric patients.

Drug Interactions

Coadministration of amoxicillin and clavulanate potassium for oral suspension, 600 mg/42.9 mg per 5 mL, with probenecid is not recommended due to potential adverse interactions.

When used concurrently with oral anticoagulants, amoxicillin and clavulanate potassium may lead to an increased prolongation of prothrombin time. Monitoring of prothrombin time is advised in patients receiving this combination to ensure safe anticoagulation levels.

The combination of amoxicillin and clavulanate potassium with allopurinol has been associated with an increased risk of rash. Caution is advised when these medications are prescribed together.

Additionally, amoxicillin and clavulanate potassium may reduce the efficacy of oral contraceptives. Patients should be informed of this potential interaction and advised to consider alternative or additional contraceptive measures during treatment.

Packaging & NDC

The table below lists all NDC Code configurations of Amoxicillin and Clavulanate Potassium, the U.S. brand-name prescription product. Columns show Packaging, Formulation Type, and Active Ingredient Strength.

Pediatric Use

The safety and effectiveness of Amoxicillin and clavulanate potassium for oral suspension, 600 mg/42.9 mg per 5 mL, have been established in pediatric patients aged 3 months to 12 years weighing less than or equal to 40 kg for the treatment of acute otitis media and acute bacterial sinusitis. However, the safety and effectiveness in pediatric patients younger than 3 months of age have not been established. Additionally, the use of this formulation in pediatric patients aged 3 months to 12 years who weigh more than 40 kg has not been evaluated.

Geriatric Use

Elderly patients may experience an increased risk of hepatic dysfunction when treated with amoxicillin and clavulanate potassium, particularly those with pre-existing liver conditions. The safety and effectiveness of amoxicillin and clavulanate potassium for oral suspension, 600 mg/42.9 mg per 5 mL, have not been established in adults and pediatric patients weighing more than 40 kg.

In geriatric patients, it is essential to monitor hepatic function at regular intervals, especially in those with known hepatic impairment. Caution is advised when prescribing this medication to elderly patients, as hepatic dysfunction, including elevations in serum transaminases (AST and/or ALT), serum bilirubin, and/or alkaline phosphatase, has been reported more frequently in this population.

While hepatic dysfunction associated with amoxicillin and clavulanate potassium is typically reversible, it can be severe and has been linked to fatalities in patients with serious underlying diseases or those taking concomitant medications. Therefore, careful consideration and monitoring are warranted when administering this medication to elderly patients, particularly those with evidence of hepatic dysfunction.

Pregnancy

Available data from published epidemiologic studies and pharmacovigilance case reports over several decades of use with amoxicillin and clavulanate during pregnancy have not established a drug-associated risk of major birth defects, miscarriage, or adverse maternal outcomes. However, a study involving women with preterm prelabor rupture of membranes (PPROM) indicated that prophylactic treatment with amoxicillin and clavulanate may be associated with an increased risk of necrotizing enterocolitis in neonates. Specifically, the rate of proven neonatal necrotizing enterocolitis was significantly higher in the amoxicillin and clavulanate group (1.9%) compared to the placebo group (0.5%) (p = 0.001).

Reproduction studies conducted in pregnant rodents, which received doses up to approximately 2 times the amount of amoxicillin and 15 times the amount of clavulanate in the Maximum Human Recommended Dose (MHRD) of amoxicillin and clavulanate potassium for oral suspension (600 mg/42.9 mg per 5 mL), revealed no evidence of harm to the fetus. Similarly, studies in pregnant rats and mice given amoxicillin and clavulanate at oral doses up to 1200 mg/kg/day also showed no evidence of fetal harm.

It is important to note that the background risk of major birth defects and miscarriage for the indicated populations is unknown. All pregnancies carry a background risk of birth defects, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. Given these considerations, healthcare professionals should weigh the potential benefits and risks when prescribing amoxicillin and clavulanate to pregnant patients.

Lactation

Amoxicillin is present in human milk, as indicated by data from a published clinical lactation study. Lactating mothers using amoxicillin and clavulanate potassium for oral suspension, 600 mg/42.9 mg per 5 mL should be aware of potential adverse effects in breastfed infants. Reports have noted instances of diarrhea, irritability, and rash in infants exposed to amoxicillin and clavulanate through breast milk; therefore, careful monitoring for these symptoms is recommended.

Currently, there are no data available regarding the effects of amoxicillin and clavulanate on milk production. When considering the use of amoxicillin and clavulanate potassium for oral suspension, 600 mg/42.9 mg per 5 mL, healthcare professionals should weigh the developmental and health benefits of breastfeeding against the mother's clinical need for the medication and any potential adverse effects on the breastfed child stemming from the medication or the underlying maternal condition.

Renal Impairment

There is no specific information available regarding dosage adjustments, special monitoring, or safety considerations for patients with renal impairment. Healthcare professionals should exercise caution when prescribing to patients with reduced kidney function, as the absence of detailed guidance necessitates careful clinical judgment. Regular monitoring of renal function may be advisable in this patient population.

Hepatic Impairment

Patients with hepatic impairment should be closely monitored for liver function tests. In the event that signs or symptoms of hepatitis occur, the treatment should be discontinued. It is essential to assess liver function regularly to ensure patient safety and to make any necessary adjustments to the treatment regimen.

Overdosage

Following an overdosage of amoxicillin and clavulanate potassium for oral suspension, patients have primarily exhibited gastrointestinal symptoms. These symptoms include stomach and abdominal pain, vomiting, and diarrhea. Additionally, a small number of patients have reported experiencing rash, hyperactivity, or drowsiness.

In the event of an overdosage, it is recommended to discontinue the administration of amoxicillin and clavulanate potassium. Symptomatic treatment should be initiated, and supportive measures should be implemented as necessary. If the overdosage has occurred recently and there are no contraindications, healthcare professionals may consider inducing emesis or employing other methods to remove the drug from the stomach. A prospective study involving 51 pediatric patients at a poison control center indicated that overdosages of less than 250 mg/kg of amoxicillin are not associated with significant clinical symptoms and do not necessitate gastric emptying.

There have been reports of interstitial nephritis leading to oliguric renal failure in a small number of patients following overdosage with amoxicillin. Furthermore, crystalluria, which in some cases has resulted in renal failure, has been documented in both adult and pediatric patients after amoxicillin overdosage. To mitigate the risk of crystalluria, it is essential to maintain adequate fluid intake and diuresis.

Renal impairment observed in these cases appears to be reversible upon cessation of the drug. It is important to note that patients with impaired renal function may experience higher blood levels of the drug due to decreased renal clearance of both amoxicillin and clavulanate. Both compounds can be effectively removed from the circulation through hemodialysis.

Nonclinical Toxicology

Long-term studies in animals have not been conducted to assess the carcinogenic potential of amoxicillin and clavulanate potassium. In mutagenicity testing, the 4:1 ratio formulation of amoxicillin and clavulanate was found to be non-mutagenic in both the Ames bacterial mutation assay and the yeast gene conversion assay. However, it exhibited weakly positive results in the mouse lymphoma assay, where the observed trend toward increased mutation frequencies coincided with decreased cell survival at the tested concentrations. The formulation was negative in the mouse micronucleus test and in the dominant lethal assay in mice.

Clavulanate potassium, when tested alone, also yielded negative results in the Ames bacterial mutation assay and the mouse micronucleus test.

In terms of reproductive toxicity, the 2:1 ratio formulation of amoxicillin and clavulanate potassium, administered at oral doses of up to 1,200 mg/kg/day, demonstrated no adverse effects on fertility and reproductive performance in rats. This dose, when adjusted for body surface area based on a 20 kg child, is approximately twice the recommended clinical dose of amoxicillin and clavulanate potassium for oral suspension, which is 90/6.4 mg/kg/day. For clavulanate, the dose corresponds to approximately 15 times the recommended clinical daily dose, also calculated based on body surface area.

Postmarketing Experience

Clinical assessments conducted 15 to 18 days following therapy may have been influenced by the presence of viral infections and the occurrence of new episodes of acute otitis media as time progressed post-treatment. These factors were noted in reports received through voluntary submissions and surveillance programs.

Patient Counseling

Patients should be informed to take Amoxicillin and clavulanate potassium for oral suspension, 600 mg/42.9 mg per 5 mL, every 12 hours with a meal or snack to minimize the risk of gastrointestinal upset. They should be advised to contact their doctor if they experience severe diarrhea that lasts more than 2 or 3 days.

It is important to counsel patients that Amoxicillin and clavulanate potassium for oral suspension contains a penicillin class drug, which may cause allergic reactions in some individuals. Patients should be made aware of the signs and symptoms of serious skin reactions. They should be instructed to discontinue the medication immediately and report any signs or symptoms of skin rash, mucosal lesions, or other indications of hypersensitivity.

Patients should also be informed that diarrhea is a common side effect associated with antibacterial drugs, typically resolving upon discontinuation of the medication. However, they should be cautioned that watery and bloody stools, with or without stomach cramps and fever, can occur even up to 2 months after completing the treatment. If such symptoms arise, patients should seek medical attention promptly.

Counsel patients that antibacterial drugs, including Amoxicillin and clavulanate potassium for oral suspension, are effective only against bacterial infections and do not treat viral infections, such as the common cold. When prescribed this medication for a bacterial infection, patients should be advised to adhere strictly to the prescribed regimen. Skipping doses or failing to complete the full course of therapy may reduce the effectiveness of treatment and increase the risk of bacterial resistance, making future infections harder to treat.

Patients should be instructed to keep the suspension refrigerated and to shake it well before use. When administering the suspension to a child, a dosing spoon or medicine dropper should be used, and it is essential to rinse the spoon or dropper after each use. Patients should follow their doctor’s instructions regarding the appropriate dosage and duration of treatment for their child, and any unused medicine should be discarded.

Storage and Handling

The reconstituted suspension must be stored under refrigeration. Any unused suspension should be discarded after 10 days to ensure safety and efficacy. The dry powder formulation should be stored at a temperature range of 20° to 25°C (68° to 77°F), in accordance with USP Controlled Room Temperature guidelines. It is essential to dispense the product in its original container, ensuring that it remains tightly closed when not in use. Additionally, all medications, including this product, should be kept out of the reach of children to prevent accidental ingestion.

Additional Clinical Information

No further data are available.

FDA Insert (PDF)

This document is the official FDA-approved prescribing information for Amoxicillin and Clavulanate Potassium as submitted by Devatis Inc.. It includes detailed information about indications, dosage, contraindications, warnings, and clinical pharmacology.

View full prescribing information (PDF)