NATRAVOX Co-Amoxiclav 375mg (250mg / 125mg) Film-Coated Tablet 48's
Indications/Uses
Lower Respiratory Tract Infections: Acute exacerbations of chronic bronchitis, bronchopneumonia, urinary-tract infections often caused by Streptococcus pneumonia, Haemophilus influenzae and Moraxella catarrhalis.
Genitourinary Tract and Abdominal Infections: In particular cystitis (especially when recurrent or complicated, but not prostatitis), septic abortion, pelvic or puerperal sepsis and intra-abdominal sepsis. These infections are often caused by Enterobacteriaceae (mainly Escherichia coli), Staphylococcus saprophyticus, Enterococcus species.
Skin and Soft Tissue Infections: In particular cellulitis, animal bites and severe dental abscess with spreading cellulites caused by Staphylococcus aureus, Streptococcus pyogenes and Bacteroides species.
Dosage/Direction for Use
Tablets: Tablets are not recommended in children ≤12 years.
Since both 250 mg/125 mg and 500 mg/125 mg tablets contain the same amount of clavulanic acid, two 250 mg/125 mg tablets are not equivalent to one 500 mg/125 mg tablet. Therefore, two 250 mg/125 mg tablets should not be substituted for one 500 mg/125 mg tablet.
Adults: Usual Dose: Mild to Moderate Infections: 250 mg/125 mg tab 3 times a day or 500 mg/125 mg tab twice a day.
Severe Infections: 500 mg/125 mg tab 3 times a day.
Dental Infections: 250 mg/125 mg tab 3 times a day for 5 days or 500 mg/125 mg tab twice a day for 5 days.
Suspension: Children: Based on the amoxicillin component, Natravox suspension should be dosed as follows: Patients ≥3 months: Severe Infections, Otitis Media, Lower Respiratory Tract Infections: 125 mg/31.25 mg/5 mL and 250 mg/62.5 mg/5 mL: 40 mg/kg/day every 8 hrs.
400 mg/57 mg/5 mL: 45 mg/kg/day every 8 hrs.
Neonates and Infants <3 months: 125 mg/31.25 mg/5 mL and 250 mg/62.5 mg/5 mL: 30 mg/kg/day divided every 12 hrs (125 mg/5 mL suspension is recommended).
Less Severe Infections: 125 mg/31.25 mg/5 mL and 250 mg/62.5 mg/5 mL: 20 mg/kg/day every 8 hrs.
400 mg/57 mg/5 mL: 25 mg/kg/day every 8 hrs.
Treatment duration for otitis media is 10 days.
Administration: Swallow whole without chewing. To minimize potential GI intolerance, administer at the start of a meal. The absorption of co-amoxiclav is optimized when taken at the start of a meal.
Overdosage
During the administration of high doses of co-amoxiclav, adequate fluid intake and urinary output should be maintained to minimize the possibility of amoxicillin crystalluria.
Amoxicillin crystalluria, in some cases leading to renal failure, has been observed.
Administration
Contraindications
Special Precautions
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.
In patients with reduced urine output crystalluria has been observed very rarely, predominantly with parenteral therapy. During administration of high doses of amoxicillin it is advisable to maintain adequate fluid intake and urinary output in order to reduce the possibility of amoxicillin crystalluria. Amoxicillin has been reported to precipitate in bladder catheters after intravenous administration of large doses. A regular check of potency should be maintained.
Serious and occasionally fatal hypersensitivity (anaphylactoid) reactions have been reported in patients on penicillin therapy. These reactions are more likely to occur in individuals with a history of penicillin hypersensitivity.
Erythematous rashes have been associated with glandular fever in patients receiving amoxicillin.
Prolonged use may also occasionally result in overgrowth of non-susceptible organisms.
Renal function should be monitored in patients with moderate to severe renal impairment and co-amoxiclav dosage should be adjusted.
Treatment with co-amoxiclav may give rise to a maculopapular rash during therapy or within a few days after completion. The incidence of maculopapular rash is especially high in patients suffering from infectious mononucleosis.
The use of this antibiotic may lead to the selection of resistant strains of organisms and sensitivity testing should, therefore, be carried out whenever possible, to demonstrate the appropriateness of therapy. Monilial overgrowth eg, vaginitis and thrush have been reported.
Treatment with co-amoxiclav can cause gastrointestinal symptoms eg, diarrhea, nausea and vomiting which are dose-related and can be minimized by administering the drug at the start of a meal. In addition, as these symptoms are especially related to the potassium clavulanate component, where these gastrointestinal symptoms occur and a higher concentration of amoxicillin is required, consideration should be given to administering the additional amoxicillin separately.
Use in Pregnancy: There are, however, no adequate studies in pregnant women. Because animal reproduction studies are not always predictive of human response, Natravox should be used during pregnancy only if clearly needed.
Use in Lactation: Amoxicillin-class antibiotics are excreted in the milk; therefore, caution should be exercised when co-amoxiclav is administered to a nursing mother.
Use In Pregnancy & Lactation
Co-amoxiclav may be administered during the period of lactation. With the exception of the risk of sensitisation, associated with the excretion of trace quantities in breast milk, there are no known detrimental effects for the breast-fed infant.
Adverse Reactions
Gastrointestinal Reactions: Diarrhea, indigestion, nausea, gastritis, stomatitis, glossitis, black "hairy" tongue, vomiting and mucocutaneous candidiasis have been reported. Antibiotic-associated colitis (including pseudomembranous colitis and hemorrhage colitis) has been reported rarely with its onset occurring during or after antibiotic treatment. Nausea, although uncommon, is more often associated with higher oral dosages. If gastrointestinal adverse effects occur with oral therapy, they may be reduced by taking co-amoxiclav at the start of meals.
Superficial tooth discoloration has been reported rarely, mostly with the suspension. It can usually be removed by brushing.
Renal and Urinary Tract Disorders: Crystalluria has been reported very rarely.
Genitourinary Effects: Vaginal itching, soreness and discharge may occur.
Hepatic Effects: Moderate and asymptomatic rises in aspartate transaminase (AST) and/or alanine transaminase (ALT) and alkaline phosphatases have been reported occasionally. Hepatitis and cholestatic jaundice have been reported rarely. These hepatic reactions have been reported more commonly with co-amoxiclav than with other penicillins.
After co-amoxiclav hepatic reactions have been reported more frequently in males and elderly patients, particularly those >65 years. The risk increases with duration of treatment >14 days. These reactions have been very rarely reported in children. Signs and symptoms usually occur during or shortly after treatment but in some cases, may not occur until several weeks after treatment has ended. Hepatic reactions are usually reversible but they may be severe and very rarely, deaths have been reported.
Hypersensitivity Reactions: Urticarial and erythematous skin rashes sometimes occur. Rarely erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis, bullous exfoliative dermatitis, acute generalized exanthematous pustulosis (AGEP), serum sickness-like syndrome and hypersensitivity vasculitis have been reported. Treatment should be discontinued if one of these disorders occurs. In common with other β-lactam antibiotics, angioedema and anaphylaxis have been reported. Interstitial nephritis can occur rarely.
Hematological Effects: As with other β-lactams, transient leukopenia (including neutropenia and agranulocytosis), thrombocytopenia and hemolytic anemia have been reported rarely. Prolongation of bleeding time and prothrombin time has also been reported rarely.
Central Nervous System (CNS) Effects: CNS effects have been seen very rarely. These include reversible hyperactivity, dizziness, headache and convulsions. Convulsions may occur with impaired renal function or in those receiving high doses.
Drug Interactions
Co-amoxiclav may reduce the efficacy of oral contraceptives and patients should be warned accordingly.
Penicillins such as co-amoxiclav may decrease the removal of methotrexate from the body increasing the risk of toxicity.
Antibiotics such as co-amoxiclav may alter the effect of anticoagulants such as warfarin.
Caution For Usage
Storage
Once reconstituted, store suspension in a refrigerator at 2-8°C (but not frozen) and use within 7 days.
Action
Neither component of co-amoxiclav is highly protein bound; clavulanic acid has been found to be approximately 25% bound to human serum and amoxicillin 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.
Microbiology: Antimicrobial Actions: Co-amoxiclav is an antibacterial combination consisting of amoxicillin (as sodium) and the beta-lactamase inhibitor, clavulanic acid (as potassium clavulanate).
Amoxicillin is the 4-hydroxy analogue of ampicillin. Amoxicillin hinders the cell wall synthesis of sensitive bacteria and is bactericidal against many Gram-positive and Gram-negative bacteria. It is active against all penicillin-sensitive bacteria: Streptococci and most strains of pneumococci, gonococci and meningococci are sensitive. Bacteria that produce beta-lactamase (e.g. most of the staphylococci) are resistant. Amoxicillin is also active against strains of Haemophilus influenza that do not produce beta-lactamase. Amoxicillin is inactivated by β-lactamases and complete cross-resistance has been reported between amoxicillin and ampicillin. The spectrum of activity of amoxicillin may be extended by use with a β-lactamase inhibitor eg, clavulanic acid. As well as reversing resistance to amoxicillin in β-lactamase producing strains of species otherwise sensitive, clavulanic acid has also been reported to enhance the activity of amoxicillin against several species not generally considered sensitive. These have included: Bacteroides, Legionella and Nocardia spp, Haemophilus influenzae, Moraxella catarrhalis and Pseudomonas pseudomallei.
Clavulanic acid has a beta-lactam structure resembling that of penicillin nucleus, except that the fused thiazolidine ring of the penicillins is replaced by an oxazolidine ring. In general, clavulanic acid has only weak antibacterial activity. It is potent progressive inhibitor of plasmid-mediated and some chromosomal beta-lactamases produced by Gram-negative bacteria including Haemophilus ducreyi, H. influenzae, Neisseria gonorrhoeae, Moraxella catarrhalis (Branhamella catarrhalis), Bacteroides fragilis and some Enterobacteriaceae. It is also an inhibitor of the beta-lactamases produced by Staphylococcus aureus. Clavulanic acid can permeate bacterial cell walls and can therefore inactivate both extracellular enzymes and those that are bound to the cell. Its mode of action depends on the particular enzyme inhibited, but it generally acts as a competitive, and often irreversible, inhibitor. Clavulanic acid consequently enhances the activity of penicillin and cephalosporin antibacterials against many resistant strains of bacteria. However, it is generally less effective against chromosomally medicated type 1 beta-lactamases: therefore, many Citrobacter, Enterobacter, Morganella and Serratia spp. And Pseudomonas aeruginosa remain resistant. Some plasmid-mediated extended-spectrum beta lactamases in Klebsiella pneumoniae, some other Enterobacteriaceae, and Ps. aeruginosa are also not inhibited by beta-lactamases inhibitors.
Co-amoxiclav is bactericidal to a wide range of organisms including: Gram-Positive: Aerobes: Enterococcus faecalis, Enterococcus faecium, Streptococcus pneumoniae, Streptococcus pyogenes, Streptococcus viridans, Staphylococcus aureus, Coagulase-negative staphylococci (including Staphylococcus epidermidis), Corynebacterium species, Bacillus anthracis, Listeria monocytogenes.
Anaerobes: Clostridium species, Peptococcus species, Peptostreptococcus.
Gram-Negative: Aerobes: Haemophilus influenzae, Moraxella catarrhalis (Branhamella catarrhalis), Escherichia coli, Proteus mirabilis, Proteus vulgaris, Klebsiella species, Salmonella species, Neisseria gonorrhoeae, Neisseria meningitidis, Vibrio cholerae, Pasteurella multocida.
Anaerobes: Bacteroides species, including B. fragilis.
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- Co-Amoxiclav