Co-Amoxiclav (amoxicillin trihydrate, clavulanate potassium).
Each tablet contains Amoxicillin (as trihydrate) 500 mg, Clavulanic Acid (as clavulanate potassium) 125 mg.
Pharmacology: Pharmacodynamics: Mechanism of Action: Amoxicillin acts through inhibition of biosynthesis of the bacterial cell wall mucopeptide. It is bactericidal against susceptible organisms during the stage of active multiplication. Amoxicillin is active against Gram-positive and Gram-negative pathogens. However, it is susceptible to degradation by beta-lactamases and therefore its spectrum does not include organisms which produce these enzymes. Clavulanic acid is beta lactam structurally spectrum does not include organisms which produce these enzymes. Clavulanic acid is beta lactam structurally related to penicillins, found in micro-organisms resistant to penicillins. The formulation of amoxicillin with clavulanic acid protects amoxicillin from degradation by beta-lactamase enzymes and effectively extends the antibiotic spectrum of amoxicillin to include many bacteria normally resistant to amoxicillin and other beta-lactam antibiotics.
Pharmacokinetics: Amoxicillin and Clavulanate Potassium are both well absorbed after oral administration and are stable in the presence of gastric acid. Food does not affect the absorption and this combination product may be given without regard to meals. The oral bioavailability of amoxicillin and clavulanic acid is approximately 90% and 75% respectively. Clavulanic acid has about the same plasma elimination half-life (1 hour) as that of amoxicillin (1.3 hrs). Amoxicillin and clavulanic acid are widely distributed to most tissues and body fluids including peritoneal fluid, blister fluid, pleural fluid, middle ear fluid, intestinal mucosa, bone, gallbladder, lungs, female reproductive tissues and bile. The penetration into CSF through non-inflamed meninges and into purulent bronchial secretions is low. Amoxicillin and clavulanic acid readily cross the placenta and are distributed into breast milk in low concentrations. Amoxicillin is bound to serum proteins to an extent of 17-20% while clavulanic acid is 20-30% bound to serum proteins. Approximately 10% of the dose of amoxicillin and less than 50% of dose of clavulanic acid are metabolized. Amoxicillin and clavulanic acid are eliminated primarily unchanged through the renal route (glomerular filtration and tubular secretions). Approximately 50-78% of amoxicillin and 25-40% of clavulanic acid are excreted unchanged in urine within the first 6 hours after administration.
Co-amoxiclav is indicated for the treatment of the following infections caused by susceptible pathogens: lower respiratory tract infections, acute otitis media, sinusitis, urinary tract infections, skin and tissue infections. Co-amoxiclav is also indicated for bacterial infections likely to be caused by amoxicillin-resistant beta-lactamase producing strains and that treatment should not usually exceed 14 days. It is also considered for the following conditions: Recurrent tonsillitis; Acute exacerbations of chronic bronchitis, bronchopneumonia; Urinary tract infection especially recurrent and complicated but not prostatitis; Septic abortion, pelvic or puerperal sepsis & intra-abdominal sepsis; Cellulitis, animal bites and several dental abscess with spreading cellulitis.
To treat following condition: Lower respiratory tract infections, acute bacterial otitis media, sinusitis - caused by beta-lactamase-producing isolates of Haemophilus influenzae and Moraxella catarrhalis.
Skin and skin structure infections caused by beta-lactamase-producing isolates of Staphylococcus aureus, Escherichia coli, Klebsiella species.
Urinary tract infections caused by beta-lactamase-producing isolates of E. coli, Klebsiella species, and Enterobacter species.
Co-amoxiclav may be taken without regard to meals; however, absorption of clavulanate potassium is enhanced when Co-amoxiclav is administered at the start of a meal. To minimize the potential for gastrointestinal intolerance, Co-amoxiclav should be taken at the start of a meal. The usual adult dose is tablet of every 12 hours. For more severe infections and infections of the respiratory tract, the dose should be one 500 mg tablet of Co-amoxiclav every 8 hours.
Patients with Renal Impairment: Patients with impaired renal function do not generally require a reduction in dose unless the impairment is severe. Renal impairment patients with a glomerular filtration rate of <30 mL/min should not receive 875-mg dose. Patients with glomerular filtration rate of 10 to 30 mL/min should receive 500 mg or 250 mg every 12 hours, depending on the severity of the infection. Patients with a glomerular rate less than 10 mL/min should receive 500 mg or 250 mg every 24 hours, depending on severity of the infection. Hemodialysis patients should receive 500 mg or 250 mg every 24 hours, depending on severity of the infection. They should receive an additional dose both during and at the end of dialysis.
In case of overdosage, discontinue medication, treat symptomatically, and institute supportive measures as required.
Interstitial nephritis resulting in oliguric renal failure has been reported in patients after overdosage with amoxicillin/clavulanate potassium. Crystalluria, in some cases leading to renal failure, has also been reported after amoxicillin/clavulanate potassium overdosage in adult and pediatric patients. In case of overdosage, adequate fluid intake and diuretics should be maintained to reduce the risk of amoxicillin/clavulanate potassium crystalluria. Renal impairment appears to be reversible with cessation of drug administration. High blood levels may occur more readily in patients with impaired renal function because of decreased renal clearance of amoxicillin/clavulanate potassium. Amoxicillin/clavulanate potassium may be removed from circulation by hemodialysis.
Serious Hypersensitivity Reactions: Contraindicated in patients with a history of serious hypersensitivity reactions (e.g., anaphylaxis or Stevens-Johnson syndrome) to amoxicillin, clavulanate or to other beta-lactam antibacterial drugs (e.g., penicillins and cephalosporins).
Cholestatic Jaundice/Hepatic Dysfunction: Contraindicated in patients with a previous history of cholestatic jaundice/hepatic dysfunction.
Hypersensitivity Reactions: Serious and occasionally fatal hypersensitivity (anaphylactic) reactions have been reported in patients receiving beta-lactam antibacterials. These reactions are more likely to occur in individuals with a history of penicillin hypersensitivity and/or a history of sensitivity to multiple allergens. Before initiating therapy careful inquiry should be made regarding previous hypersensitivity reactions to penicillins, cephalosporin, or other allergens. If an allergic reaction occurs, should be discontinued and appropriate therapy instituted.
Patients with Renal impairment: Patients with impaired renal function do not generally require a reduction in dose unless the impairment is severe. Renal impairment patients with glomerular filtration rate of <30 mL/min should not receive the 875-mg dose. Patients with a glomerular filtration rate of 10 to 30 mL/min should receive 500 mg or 250 mg every 12 hours, depending on the severity of the infection. Patients with a glomerular filtration rate less than 10 mL/min should receive 500 mg or 250 mg every 24 hours, depending on severity of the infection. Hemodialysis patients receive 500 mg or 250 mg every 24 hours, depending on severity of the infection. They should receive additional dose both during and at the end of dialysis.
Hepatic Dysfunction: Hepatic dysfunction, including hepatitis, and cholestatic jaundice has been associated with hepatic toxicity is usually reversible; however, deaths have been reported. Hepatic function should be monitored at regular intervals in patients with hepatic impairment.
Clostridium difficile Associated Diarrhea (CDAD): Clostridium difficile associated diarrhea (CDAD) has been reported with use of nearly all antibacterial agents, and may range in severity from diarrhea to fatal colitis. Treatment with antibacterial agents alters the normal flora of the colon leading to overgrowth of C. difficile. C. difficile produces toxin 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 antibacterial use.
Careful medical history is necessary since CDAD has been reported to occur over 2 months after the administration of antibacterial agents.
If CDAD is suspected or confirmed, ongoing antibacterial use not directed against C. difficile may need to be discontinued. Appropriate fluid and electrolyte management, protein supplementation, antibacterial treatment of C. difficile, and surgical evaluation should be instituted as clinically indicated.
Skin Rash in Patients with Mononucleosis: A high percentage of patients with mononucleosis who receive amoxicillin develop an erythematous skin rash. Thus, should not be administered to patients with mononucleosis.
Potential for Microbial Overgrowth: The possibility of superinfections with fungal or bacterial pathogens should be considered during therapy. If superinfection occurs, amoxicillin/clavulanate potassium should be discontinued and appropriate therapy instituted.
Development of Drug-Resistant Bacteria: Prescribing in the absence of a proven or strongly suspected bacterial infection is unlikely to provide benefit to the patient, and increases the risk of the development of drug-resistant bacteria.
Dosing in Renal Impairment: Amoxicillin is primarily eliminated by the kidney and dosage adjustment is usually required in patients with severe renal impairment (GFR <30 mL/min). See Dosage & Administration.
Use in Children: Because of incompletely developed renal function in neonates and young infants, the elimination of amoxicillin may be delayed. Dosing of should be modified in pediatric patients aged <12 week (<3 months).
Use in Elderly: This drug is known to be substantially excreted by the kidney, and the risk of adverse 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.
Use in Pregnancy: Pregnancy Category B. This drug should be used during pregnancy only if clearly needed.
Labor and Delivery: Oral ampicillin-class antibiotics are poorly absorbed during labor. It is not known whether use of amoxicillin/clavulanate potassium in humans during labor or delivery has immediate or delayed adverse effects on the fetus, prolongs the duration of labor, or increases the likelihood of necessary for an obstetrical intervention.
Use in Lactation: Amoxicillin has been shown to be excreted in human milk. Amoxicillin/clavulanate potassium use by nursing mothers may lead to sensitization of infants. Caution should be exercised when amoxicillin/clavulanate potassium is administered to a nursing woman.
Hepatitis and cholestatic jaundice have been reported with the combination amoxicillin with clavulanic acid, the clavulanic acid component has been implicated erythema multiforme, Stevens-Johnson syndrome, and toxic epidermal necrolysis, exfoliative dermatitis, nausea, vomiting, diarrhea, rashes and antibiotic associated colitis have been reported occasionally noted.
Probenecid: Probenecid decreases the renal tubular secretion of amoxicillin but does not delay renal excretion of clavulanic acid. Concurrent use may result in increased and prolonged blood concentrations of amoxicillin. Co-administration of probenecid is not recommended.
Oral Anticoagulants: Abnormal prolongation of prothrombin time (increased international normalized ratio [INR]) has been reported in patients receiving amoxicillin and oral anticoagulants. Appropriate monitoring should be undertaken when anticoagulants are prescribed concurrently with amoxicillin/clavulanate potassium. Adjustment in the dose of oral anticoagulants may be necessary to maintain the desired level of anticoagulants.
Allopurinol: The concurrent administration of allopurinol and amoxicillin increases the incidence of rashes in patients receiving amoxicillin alone. It is not known whether this potentiation of amoxicillin rashes is due to allopurinol or the hyperuricemia present in these patients.
Oral contraceptives: May affect intestinal flora, leading to lower estrogen reabsorption and reduced efficacy of combined oral estrogen/progesterone contraceptives.
Effects on Laboratory Tests: High urine concentration of amoxicillin may result in false-positive reactions when testing for the presence of glucose in urine using CLINITEST, Benedict's Solution, or Fehling's Solution. Since this effect may also occur, it is recommended that glucose tests based on enzymatic glucose oxidase reactions be used. Following administration of amoxicillin to pregnant women, a transient decrease in plasma concentration of total conjugated estriol, estriol-glucuronide, conjugated estrone, and estradiol has been note.
Store in a dry place below 25°C.
J01CR02 - amoxicillin and beta-lactamase inhibitor ; Belongs to the class of penicillin combinations, including beta-lactamase inhibitors. Used in the systemic treatment of infections.