CO-AX

CO-AX

amoxicillin + clavulanic acid

Manufacturer:

ADP Pharma

Distributor:

Metro Drug

Marketer:

Seville Pharma
Full Prescribing Info
Contents
Co-amoxiclav: Amoxicillin and clavulanic acid.
Description
Each 625 mg film-coated tablet contains amoxicillin trihydrate equivalent to amoxicillin 500 mg and potassium clavulanate equivalent to clavulanic acid 125 mg.
Amoxicillin is an analog of ampicillin, derived from the basic penicillin nucleus, 6-aminopenicillanic acid. It is (2S,5R,6R)-6-[[(2R)-2-amino-2-(4-hydroxyphenyl)acetyl]amino]-3,3-dimethyl-7-oxo-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid trihydrate, with a molecular formula of C16H19N3O5S·3H2O and molecular weight of 419.4.
Amoxicillin sodium is (2S,5R,6R)-6-[(R)-(-)-2-Amino-2-(p-hydroxyphenyl) acetamido]-3,3-dimethyl-7-oxo-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid monosodium salt, with a molecular formula of C16H18N3O5S·Na, and molecular weight of 387.4.
Clavulanate potassium is potassium (Z)-(2R,5R)-3-(2-hydroxyethylidene)-7-oxo-4-oxa-1-azabicyclo [3.2.0]heptane-2-carboxylate, with a molecular formula is C8H8KNO5 and molecular weight of 237.25.
Action
Co-amoxiclav is an antibacterial combination consisting of the semisynthetic antibiotic amoxicillin and the β-lactamase inhibitor clavulanate potassium (the potassium salt of clavulanic acid).
Pharmacology: Mechanism of Action: Amoxicillin is a semisynthetic antibiotic with a broad-spectrum of bactericidal activity against many gram-positive and -negative microorganisms. Amoxicillin is, however, susceptible to degradation by β-lactamases and therefore, the spectrum of activity does not include organisms, which produce these enzymes. Clavulanic acid is a β-lactam, structurally related to the penicillins, which possesses the ability to inactivate a wide range of β-lactamase enzymes commonly found in microorganisms resistant to penicillins and cephalosporins. In particular, it has good activity against the clinically important plasmid mediated β-lactamases frequently responsible for transferred drug resistance. The formulation of amoxicillin and clavulanic acid protects amoxicillin from degradation by β-lactamase enzymes and effectively extends the antibiotic spectrum of amoxicillin to include many bacteria normally resistant to amoxicillin and other β-lactam antibiotics. Thus, amoxicillin/clavulanate potassium combination possesses the distinctive properties of a broad-spectrum antibiotic and a β-lactamase inhibitor.
Pharmacodynamics: Resistance to many antibiotics is caused by bacterial enzymes which destroy the antibiotic before it can act on the pathogen. The clavulanate component in co-amoxiclav anticipates this defense mechanism by blocking the β-lactamase enzymes, thus rendering the organism sensitive to amoxicillin's rapid bactericidal effect at concentrations readily attainable in the body.
Microbiology: CO-AX has been shown to be active against most strains.
Clavulanate by itself has little antibacterial activity; however, in association with amoxicillin, it produces an antibiotic agent of broad-spectrum with wide application in hospital and general practice.
Co-amoxiclav is bactericidal to a wide range of organism, both in vitro and in clinical infections:
Gram-Positive Aerobes: Staphylococcus aureus [Staphylococci which are resistant to methicillin/oxacillin must be considered resistant to co-amoxiclav (β-lactamase and non-β-lactamase producing)], Bacillus anthracis, Listeria monocytogenes.
Gram-Negative Aerobes: Enterobacter sp (although most strains of Enterobacter sp are resistant in vitro, clinical efficacy has been demonstrated with co-amoxiclav combination in urinary tract infections caused by these organisms), Escherichia coli (β-lactamase and non-β-lactamase producing), Haemophilus influenzae (β-lactamase and non-β-lactamase producing), Klebsiella sp (all known strains are β-lactamase producing), Moraxella catarrhalis [Branhamella catarrhalis (β-lactamase and non-β-lactamase producing)], Proteus vulgaris, Shigella sp, Bordetella pertussis, Brucella sp, Neisseria gonorrhoeae, Neisseria meningitidis, Vibrio cholerae, Pasteurella multocida, Salmonella sp (some members of this species of bacteria produce β-lactamase, rendering them insensitive to amoxicillin alone).
The following in vitro data are available, but their clinical significance is unknown.
Co-amoxiclav exhibits in vitro minimal inhibitory concentrations (MICs) of ≤2 mcg/mL against most (≥90%) strains of Streptococcus pneumoniae (because amoxicillin has greater in vitro activity against S. pneumoniae than does ampicillin or penicillin, the majority of S. pneumoniae strains with intermediate susceptibility to ampicillin or penicillin are fully susceptible to amoxicillin); MICs of ≤0.06 mcg/mL against most (≥90%) strains of Neisseria gonorrhoeae; MICs of ≤4 mcg/mL against most (≥90%) strains of staphylococci and anaerobic bacteria; and MICs of ≤8 mcg/mL against most (≥90%) strains of other listed organism. However, with the exception of organisms shown to respond to amoxicillin alone, the safety and effectiveness of co-amoxiclav in treating clinical infections due to these microorganisms have not been established in adequate and well-controlled clinical trials.
Because amoxicillin has greater in vitro activity against Streptococcus pneumoniae than does ampicillin or penicillin, the majority of S. pneumoniae strains with intermediate susceptibility to ampicillin or penicillin are fully susceptible to amoxicillin.
Gram-Positive Aerobes: Enterococcus faecalis*, Staphylococcus epidermidis (β-lactamase and non-β-lactamase producing) and other coagulase-negative staphylococci (some members of these species of bacteria produce β-lactamase, rendering them insensitive to amoxicillin alone), Staphylococcus saprophyticus (β-lactamase and non-β-lactamase producing), Streptococcus pneumoniae*+ (these are non-β-lactamase -producing organisms and, therefore, are susceptible to amoxicillin alone), Streptococcus pyogenes*+ (these are non-β-lactamase-producing organisms and, therefore, are susceptible to amoxicillin alone), Viridans-group Streptococcus*+ (these are non-β-lactamase -producing organisms and, therefore, are susceptible to amoxicillin alone), Corynebacterium sp.
Gram-Negative Aerobes: Eikenella corrodens (β-lactamase and non-β-lactamase producing), Neisseria gonorrhoeae* (β-lactamase and non-β-lactamase producing), Proteus mirabilis* (β-lactamase and non-β-lactamase producing).
Anaerobic Bacteria: Bacteroides sp, including Bacteroides fragilis (β-lactamase and non-β-lactamase producing), Fusobacterium sp (β-lactamase and non-β-lactamase producing), Peptostreptococcus sp*+, Clostridium sp, Peptococcus sp.
Note: *Adequate and well-controlled clinical trials have established the effectiveness of amoxicillin alone in treating certain clinical infections due to these organisms.
+ Non-β-lactamase producing organisms and therefore, are susceptible to amoxicillin.
Pharmacokinetics: Amoxicillin and clavulanate potassium are well absorbed from the GIT after oral administration of co-amoxiclav. Dosing in the fasted or fed state has minimal effect on the pharmacokinetics of amoxicillin. While co-amoxiclav can be given without regard to meals, absorption of clavulanate potassium when taken with food is greater relative to the fasted state. In 1 study, the relative bioavailability of clavulanate was reduced when co-amoxiclav was dosed at 30 and 150 min after the start of a high fat breakfast. The safety and efficacy of co-amoxiclav have been established in clinical trials where co-amoxiclav was taken without regard to meals (see Table).

Click on icon to see table/diagram/image

Amoxicillin serum concentrations achieved with co-amoxiclav are similar to those produced by the oral administration of equivalent doses of amoxicillin alone. The t½ of amoxicillin after the oral administration of co-amoxiclav is 1.3 hrs and that of clavulanic acid is 1 hr.
Approximately 50-70% of the amoxicillin and approximately 25-40% of the clavulanic acid are excreted unchanged in urine during the first 6 hrs after administration of a single 250- or 500-mg tablet of co-amoxiclav.
Concurrent administration of probenecid delays amoxicillin excretion does not delay renal excretion of clavulanic acid.
Neither component in co-amoxiclav is highly protein bound; clavulanic acid has been found to be approximately 25% bound to human serum and amoxicillin approximately 18% bound.
Amoxicillin diffuses readily into most body tissues and fluids with the exception of the brain and spinal fluid. The results of experiments involving the administration of clavulanic acid to animals suggest that this compound, like amoxicillin, is well distributed in body tissues.
Indications/Uses
Treatment of infections caused by susceptible strains of the designated organisms in the following conditions: Lower respiratory tract infections, sinusitis and otitis media caused by β-lactamase-producing strains of Haemophilus influenzae and Moraxella catarrhalis.
Skin and skin structure infections caused by β-lactamase-producing strains of Staphylococcus aureus and Escherichia coli and Klebsiella spp.
Urinary tract infections caused by β-lactamase-producing strains of Escherichia coli, Klebsiella spp and Enterobacter spp.
While co-amoxiclav is indicated only for the previously mentioned conditions, infections caused by ampicillin-susceptible organisms are also amenable to treatment with co-amoxiclav due to its amoxicillin content; therefore, mixed infections caused by ampicillin-susceptible organisms and β-lactamase-producing organisms susceptible to co-amoxiclav should not require the addition of another antibiotic. Because amoxicillin has greater in vitro against Streptococcus pneumoniae than does ampicillin or penicillin, the majority of S. pneumoniae strains with intermediate susceptibility to ampicillin or penicillin are fully susceptible to amoxicillin and co-amoxiclav.
To reduce the development of drug resistant bacteria and maintain the effectiveness of amoxicillin and co-amoxiclav should be used only to treat or prevent infections that are proven or strongly suspected to be caused by susceptible bacteria. When culture and susceptibility information are available, they should be considered in selecting or modifying antibacterial therapy. In the absence of such data, local epidemiology and susceptibility patterns may contribute to the empiric selection of therapy.
Bacteriological studies to determine the causative organisms and their susceptibility to co-amoxiclav should be performed together with any indicated surgical procedures.
Dosage/Direction for Use
Since both 250- and 500-mg tablets of CO-AX contain the same amount of clavulanic acid (ie, 125 mg clavulanic acid as potassium salt), two 250-mg CO-AX tablets are not equivalent to one 500-mg CO-AX tablet; therefore, two 250-mg CO-AX tablets should not be substituted for one 500-mg CO-AX tablet.
Adults: Usual Dose: 250-500 mg every 8 hrs or 500-875 mg every 12 hrs.
Severe Infections and Infections of the Respiratory Tract: 500 mg every 8 hrs or 875 mg every 12 hrs.
Renal Impairment: Patients with impaired renal function do not generally require a reduction in dose unless the impairment is severe.
Patient with Glomerular Filtration Rate (<30 mL/min): 1 g; 10-30 mL/min: 500 or 250 mg every 12 hrs depending on the severity of the infection; <10 mL/min: 500 or 250 mg every 24 hrs depending on the severity of the infection.
Hemodialysis Patient: 500 or 250 mg every 24 hrs depending on severity of the infection. They should receive an additional dose both during and at the end of dialysis.
Hepatic Impairment: Hepatically impaired patients should be dosed with caution and hepatic function must be monitored at regular intervals (see Warnings).
Children: Pediatric patients weighing ≥40 kg should be dosed according to the adult recommendations.
Administration: CO-AX may be taken without regard to meals; however, absorption of clavulanate potassium is enhanced when CO-AX tablet is administered at the start of a meal. To minimize the potential for GI intolerance, CO-AX tablet should be taken at the start of a meal.
Overdosage
Symptoms: Following overdosage, patients have experienced primarily GI symptoms including stomach and abdominal pain, vomiting, and diarrhea. Disturbance of the fluid and electrolyte balances may be evident. Rash, hyperactivity or drowsiness has also been observed in a small number of patients.
Interstitial nephritis resulting in oliguric renal failure has been reported in a small number of patients after overdosage with amoxicillin.
Crystalluria, in some cases leading to renal failure, has also been reported after amoxicillin overdosage in adult and pediatric patients.
Treatment: In the case of overdosage, discontinue amoxicillin/clavulanate potassium, treat symptomatically and institute supportive measures as required. If the overdosage is very recent and there is no contraindication, an attempt at emesis or other means of removal of drug from the stomach may be performed. A prospective study of 51 pediatric patients at a poison center suggested that overdosages of <250 mg/kg of amoxicillin are not associated with significant clinical symptoms and do not require gastric emptying. Co-amoxiclav can be removed from the circulation by hemodialysis.
Adequate fluid intake and diuresis should be maintained to reduce the risk of amoxicillin crystalluria.
Renal impairment appears to be reversible with cessation of co-amoxiclav administration. High blood levels may occur more readily in patients with impaired renal function because of decreased renal clearance of both amoxicillin and clavulanate. Both amoxicillin and clavulanate are removed from the circulation by hemodialysis (see Dosage & Administration for recommended dosing for patients with impaired renal function).
Contraindications
Patients with a history of allergic reactions to any penicillin. Attention should be paid to possible cross-sensitivity with other β-lactam antibiotics eg, cephalosporins. Patients with a previous history of cholestatic jaundice/hepatic dysfunction associated with CO-AX.
Warnings
Serious and occasionally fatal hypersensitivity (anaphylactic) reactions have been reported in patients on penicillin therapy. These reactions are more likely to occur in individuals with a history of penicillin hypersensitivity and/or a history of sensitivity to multiple allergens. There have been reports of individuals with a history of penicillin hypersensitivity who have experienced severe infections when treated with cephalosporins.
Erythematous rashes have been associated with glandular fever in patients receiving amoxicillin.
Before initiating therapy with co-amoxiclav, careful inquiry should be made concerning previous hypersensitivity reactions to penicillins, cephalosporins or other allergens. If an allergic reaction occurs, co-amoxiclav should be discontinued and the appropriate therapy instituted. Serious anaphylactic reactions require immediate emergency treatment with epinephrine. Oxygen, IV steroids and airway management, including intubation, should also be administered as indicated.
Prolonged use may also occasionally result in overgrowth of non-susceptible organisms. Clostridium difficile-associated diarrhea (CDAD) has been reported with use of nearly all antibacterial agents, including co-amoxiclav and may range in severity from mild diarrhea to fatal colitis. Treatment with antibacterial agents alters the normal flora of the colon leading to overgrowth of C. difficile.
C. difficile produces toxins A and B which contribute to the development of CDAD. Hypertoxin-producing strains of C. difficile cause increased morbidity and mortality, as these infections can be refractory to antimicrobial therapy and may require colectomy. CDAD must be considered in all patients who present with diarrhea following antibiotic use. Careful medical history is necessary since CDAD has been reported to occur >2 months after the administration of antibacterial agents.
If CDAD is suspected or confirmed, ongoing antibiotic use not directed against C. difficile may need to be discontinued. Appropriate fluid and electrolyte management, protein supplementation, antibiotic treatment of C. difficile and surgical evaluation should be instituted as clinically indicated.
Co-amoxiclav should be used with caution in patients with evidence of hepatic dysfunction. Hepatic toxicity associated with the use of co-amoxiclav potassium is usually reversible. On rare occasions, deaths have been reported (<1 death reported per estimated 4 million prescriptions worldwide). These have generally been cases associated with serious underlying disease or concomitant medications (see Contraindications and Adverse Reactions).
Cholestatic jaundice, which may be severe, but is usually reversible, has been reported rarely. Signs and symptoms may not become apparent for several weeks after treatment has ceased.
Special Precautions
While co-amoxiclav possesses the characteristic low toxicity of the penicillin group of antibiotics, periodic assessment of organ system functions, including renal, hepatic and hematopoietic function, is advisable during prolonged therapy.
A high percentage of patients with mononucleosis who receive ampicillin developed an erythematous skin rash. Thus, ampicillin class antibiotics should not be administered to patients with mononucleosis.
The possibility of superinfections with mycotic or bacterial pathogens should be kept in mind during therapy. If superinfections occur (usually involving Pseudomonas or Candida), the drug should be discontinued and/or appropriate therapy instituted.
Prescribing co-amoxiclav in the absence of a proven or strongly suspected bacterial infection or a prophylactic indication is unlikely to provide benefit to the patient and increases the risk of the development of drug-resistant bacteria.
Information for Patients: Patients should be counseled that antibacterial drugs including co-amoxiclav, should only be used to treat bacterial infections. They do not treat viral infections (eg, the common cold). When co-amoxiclav is prescribed to treat a bacterial infection, patients should be told that although it is common to feel better early in the course of therapy, the medication should be taken exactly as directed. Skipping doses or not completing the full course of therapy may: (1) decrease the effectiveness of the immediate treatment, and (2) increase the likelihood that bacteria will develop resistance and will not be treatable by co-amoxiclav or other antibacterial drugs in the future.
Diarrhea is a common problem caused by antibiotics which usually ends when the antibiotic is discontinued. Sometimes after starting treatment with antibiotics, patients can develop watery and bloody stools (with or without stomach cramps and fever) even as late as ≥2 months after having taken the last dose of the antibiotic.
Carcinogenicity, Mutagenicity and Impairment of Fertility: Long-term carcinogenicity studies in animals have not been performed to evaluate carcinogenic potential.
The mutagenic potential of co-amoxiclav was investigated in vitro with an Ames test, a human lymphocyte cytogenic assay, a yeast test and a mouse lymphoma forward mutation assay and in vitro with mouse micronucleus tests and a dominant lethal test. All were negative apart from in vitro mouse lymphoma assay where weak activity was found at very high, cytotoxic concentrations.
Co-amoxiclav at oral doses of up to 1200 mg/kg/day (5.7 times the maximum human dose, 1480 mg/m2/day, based on body surface area) was found to have no effect on fertility and reproductive performance in rats, dosed with a 2:1 ratio formulation of co-amoxiclav.
Use in pregnancy: Teratogenic Effects: Reproduction studies performed in pregnant rats and mice given with co-amoxiclav administered orally and parenterally with dosages up to 1200 mg/kg/day, equivalent to 7200 and 4080 mg/m2/day, respectively (4.9 and 2.8 times the maximum human oral dose based on body surface area), revealed no evidence of harm to the fetus due to co-amoxiclav.
There are however, no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, co-amoxiclav should be used during pregnancy only if clearly needed.
Labor and Delivery: Oral ampicillin class antibiotics are generally poorly absorbed during labor. Studies in guinea pigs have shown that IV administration of ampicillin decreased the uterine tone, frequency of contractions, height of contractions and duration of contractions. However, it is not known whether the use of co-amoxiclav in humans during labor or delivery has immediate or delayed adverse effects on the fetus, prolongs the duration of labor or increases the likelihood that forceps delivery or other obstetrical intervention or resuscitation of the newborn will be necessary.
In a single study in women with preterm, premature rupture of the fetal membrane (pPROM), it was reported that prophylactic treatment with co-amoxiclav may be associated with an increase risk of necrotizing enterocolitis in neonates. As with all medicines, use should be avoided in pregnancy especially during the 1st trimester, unless considered essential by the physician.
Use in lactation: Ampicillin class antibiotics are excreted in the milk; therefore, caution should be exercised when co-amoxiclav is administered to a nursing woman.
Co-amoxiclav may be administered during the period of lactation. With the exception of the risk of sensitization, associated with the excretion of trace quantities in breast milk, there are no known detrimental effects for the breastfed infant.
Use in children: Pediatric patients weighing ≥40 kg should be dosed according to the adult recommendations (see Pediatric Patients under Dosage & Administration). Safety and effectiveness of co-amoxiclav tablets in pediatric patients weighing <40 kg have not been established. (See also Dosage & Administration.)
Use in elderly: An analysis of clinical studies of co-amoxiclav was conducted to determine whether subjects ≥65 years respond differently from younger subjects. Of the 3119 patients in this analysis, 68% were <65 years, 32% were ≥65 years and 14% were ≥75 years.
This analysis and other reported clinical experience have not identified differences in responses between the elderly and younger patients, but a greater sensitivity of some older individuals cannot be ruled out.
Co-amoxiclav is known to be substantially excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function.
Adverse Reactions
Co-amoxiclav is generally well tolerated. The majority of adverse effects observed in clinical trials were of a mild and transient nature and <3% of patients discontinued therapy because of drug-related adverse effects. The most frequently reported adverse effects were diarrhea/loose stools (9%), nausea (3%), skin rashes and urticaria (3%), vomiting (1%) and vaginitis (1%). The overall incidence of adverse effects, and in particular diarrhea, increased with the higher recommended dose. Other less frequently reported reactions include abdominal discomfort, flatulence and headache.
The following adverse reactions have been reported for ampicillin class antibiotics: Gastrointestinal: Diarrhea, nausea, vomiting, indigestion, gastritis, stomatitis, glossitis, black "hairy" tongue, mucocutaneous candidiasis, enterocolitis and hemorrhagic/pseudomembranous colitis. Onset of pseudomembranous colitis symptoms may occur during or after antibiotic treatment (see Warnings).
Hypersensitivity Reactions: Skin rashes, pruritus, urticaria, angioedema, serum sickness-like reactions (urticaria or skin rash accompanied by arthritis, arthralgia, myalgia and frequently fever), erythema multiforme (rarely Stevens-Johnson syndrome), acute generalized exanthematous pustulosis and an occasional case of exfoliative dermatitis (including toxic epidermal necrolysis) have been reported. These reactions may be controlled with antihistamines and if necessary, systemic corticosteroids. Whenever such reactions occur, the drug should be discontinued, unless the opinion of the physician dictates otherwise. Serious and occasional fatal hypersensitivity (anaphylactic) reactions can occur with oral penicillin (See Warnings).
Liver: A moderate rise in AST (SGOT) and/or ALT (SGPT) has been noted in patients treated with ampicillin class antibiotics but the significance of these findings is unknown. Hepatic dysfunction, including increases in serum transaminases (AST and/or ALT), serum bilirubin and/or alkaline phosphatase, has been infrequently reported with co-amoxiclav. It has been reported more commonly in the elderly, in males or in patients on prolonged treatment. The histologic findings on liver biopsy have consisted of predominantly cholestatic, hepatocellular or mixed cholestatic-hepatocellular changes. The onset of signs/symptoms of hepatic dysfunction may occur during or several weeks after therapy have been discontinued. The hepatic dysfunction, which may be severe, is usually reversible. On rare occasions, deaths have been reported (<1 death reported per estimated 4 million prescriptions worldwide). These have generally been cases associated with serious underlying diseases or concomitant medications.
Renal: Interstitial nephritis and hematuria have been reported rarely. Crystalluria has also been reported (see Overdosage).
Hemic and Lymphatic Systems: Anemia, including hemolytic anemia, thrombocytopenia, thrombocytopenic purpura, eosinophilia, leukopenia and agranulocytosis have been reported during therapy with penicillins. These reactions are usually reversible on discontinuation of therapy and are believed to be hypersensitivity phenomena. A slight thrombocytosis was noted in <1% of the patients treated with co-amoxiclav. There have been reports of increased prothrombin time in patients receiving co-amoxiclav and anticoagulant therapy concomitantly.
Central Nervous System: Agitation, anxiety, behavioral changes, confusion, convulsions, dizziness, insomnia, and reversible hyperactivity have been reported rarely.
Miscellaneous: Tooth discoloration (brown, yellow or gray staining) has been rarely reported. Most reports occurred in pediatric patients. Discoloration was reduced or eliminated with brushing or dental cleaning in most cases.
The following convention has been utilized for the classification of frequency: Very common (>1/10), common (>1/100, <1/10); uncommon (>1/1000, <1/100); rare (>1/10,000, <1/1000); very rare (<1/10,000). The majority of adverse effects listed as follows are not unique to co-amoxiclav and may occur when using other penicillins.
Infections and Infestations: Common: Mucocutaneous candidiasis.
Blood and Lymphatic System Disorders: Rare: Reversible leukopenia (including neutropenia) and thrombocytopenia. Very Rare: Reversible agranulocytosis and hemolytic anemia. Prolongation of bleeding time and prothrombin time (see Interactions).
Immune System Disorders: Very Rare: As with other antibiotics, severe allergic reactions, including angioneurotic edema, anaphylaxis, serum sickness-like syndrome and hypersensitivity vasculitis.
If hypersensitivity reaction is reported, the treatment must be discontinued.
Nervous System Disorders: Uncommon: Dizziness, headache. Very Rare: Convulsions may occur in patients with impaired renal function or in those receiving high doses.
Vascular Disorders: Rare: Thrombophlebitis at the site of injection.
Gastrointestinal Disorders: Common: Diarrhea. Uncommon: Nausea, vomiting, indigestion. Very Rare: Antibiotic-associated colitis (including pseudomembranous colitis and hemorrhagic colitis), less likely to occur after parenteral administration.
Hepatobiliary Disorders: Uncommon: Moderate rise in AST, the significance is unknown. Very Rare: Hepatitis and cholestatic jaundice.
Hepatic events have been reported predominately in males and elderly patients and may be associated with prolonged treatment.
Signs and symptoms usually occur during or shortly after treatment but in some cases may not become apparent until several weeks after treatment has ceased. These are usually reversible. Hepatic events may be severe and in extremely rare circumstances. Deaths have been reported.
Skin and Subcutaneous Tissue Disorders: Uncommon: Skin rash, pruritus, urticaria. Rare: Erythema multiforme. Very Rare: Stevens-Johnson syndrome, toxic epidermal necrolysis, bullous exfoliative dermatitis, acute generalized exanthemous pustulosis (AGEP).
If any hypersensitivity dermatitis reaction is reported, the treatment must be discontinued.
Renal and Urinary Disorders: Very Rare: Interstitial nephritis, crystalluria (see Overdosage).
Drug Interactions
Probenecid decreases the renal tubular secretion of amoxicillin. Concurrent use with co-amoxiclav may result in increased and prolonged blood levels of amoxicillin. Co-administration of probenecid cannot be recommended.
Penicillins reduce the excretion of methotrexate (potential increased toxicity).
Drug/Laboratory Test Interactions: Administration of co-amoxiclav will result in high urine concentrations of amoxicillin. High urine concentrations of ampicillin may result in false-positive reactions when testing for the presence of glucose in urine using Benedict's or Fehling's solution. Since this effect may also occur with amoxicillin and therefore co-amoxiclav, it is recommended that glucose tests based on enzymatic glucose-oxidase reactions to be used.
Following administration of ampicillin to pregnant women, a transient decrease in plasma concentration of total conjugated estriol, estriol-glucuronide, conjugated estrone and estradiol has been noted. This effect may also occur with amoxicillin as well as with co-amoxiclav.
The presence of clavulanic acid in Co-amoxiclav may cause a nonspecific binding of IgG and albumin by red cell membrane leading to a false-positive Coombs' test.
Storage
Store at temperature not exceeding 30°C.
Protect from light and moisture.
MIMS Class
ATC Classification
J01CR02 - amoxicillin and beta-lactamase inhibitor ; Belongs to the class of penicillin combinations, including beta-lactamase inhibitors. Used in the systemic treatment of infections.
Presentation/Packing
FC tab 625 mg x  60's.
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