Rusocilin
RUSOCILIN
Amoxicillin and Clavulanate Potassium Tablets USP 625 mg
-
FORMULATION
Each film coated tablets contains:
Amoxicillin Trihydrate Equivalent to Amoxicillin: 500mg
Clavulanate Potassium Equivalent to Clavulanic Acid: 125mg
-
PHARMACOLOGY
Amoxicillin has been reported to be more active in vitro than Ampicillin against Enterococcus feacalis, Helicobacter pylori, and Salmonella spp., but less active against Shigella spp.
The spectrum of activity of amoxicillin may be extended by the concomitant use of a beta-Iactamase inhibitor such as Clavulanic acid. As well as reversing resistance to amoxicillin in beta-Iactamase-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 and Burkholderia pseudomallei (Pseudomonas pseudomallei). However, Ps. aeruginosa, Serratia marcescens, and many other Gram-negative bacteria remain resistant. Transferable resistance has been reported in H. pylori.
Clavulanic acid is produced by cultures of Streptomyces clavuligerus. It has a beta-Iactam structure resembling that of the penicillin nucleus, except that the fused thiazolidine ring of the penicillin is replaced by an oxazolidone ring. In general, Clavulanic acid has only weak antibacterial activity. It is a potent progressive inhibitor of plasmid-mediated and some chromosomal beta-Iactamases produced by Gram-negative bacteria including Haemophilus ducreyi, H. influenzae, Neisseria gonorrhea, Moraxella cartarrhalis (Branhamellla catarrhalis), Bacteroides fragilis, and some Enterobacteriaceae.
It is also an inhibitor of the beta-Iactamases 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 amoxicillin against many resistant strains of bacteria. However, it is generally less effective against chromosomally mediated type 1 beta-Iactamases; therefore, many Citrobacter, Enterobacter, Morganella, and Serratia spp., and Pseudomonas aeruginosa remain resistant. Some plasmid-mediated extended-spectrum lactamases in Klebsiella pneumoniae, some other Enterobacteriaceae, and Ps. aeruginosa are also not inhibited by beta-Iactamase inhibitors.
-
PHARMACOKINETICS
Amoxicillin is resistant to inactivation by gastric acid. Peak plasma-amoxicillin concentrations of about 5 meg per mL have been observed 1 to 2 hours after a dose of 250mg, with detectable amounts present for up to 8 hours.
Doubling the dose can double the concentration. The presence of food in the stomach does not appear to diminish the total amount absorbed. Amoxicillin is given by injection and similar concentrations are achieved with intramuscular as with oral administration.
About 20% is bound to plasma proteins in the circulation and plasma half-lives of 1 to 1.5 hours have been reported. The half-life may be longer in neonates and the elderly; in renal failure the half-life may be 7 to 20 hours. Amoxicillin is widely distributed at varying concentrations in body tissues and fluids. It crosses the placenta; small amounts are distributed into breast milk. Little amoxicillin passes into the CSF unless the meninges are inflamed.
Amoxicillin metabolized to a limited extent to penicilloic acid which is excreted in the urine. About 60% of an oral dose of amoxicillin is excreted unchanged in the urine in 6 hours by glomerular filtration and tubular secretion. Urinary concentrations above 300 mcg per mL have been reported after a dose of 250 mg. Probenecid retards renal excretion. Amoxicillin is removed by haemodialysis. High concentrations have been reported in bile; some may be excreted in the faeces.
The pharmacokinetics of amoxicillin and clavulanic acid are broadly similar and neither appears to affect the other to any great extent.
-
INDICATIONS
Amoxicillin is used in a variety of susceptible infections. These include actinomycosis, biliary-tract infections, bronchitis, endocarditis (particularly for prophylaxis), gastro-enteritis (including salmonella enteritis, but not shigellosis), gonorrhea, Lyme disease, mouth infections, otitis media, pneumonia, spleen disorders (pneumococcal infection prophylaxis), typhoid and paratyphoid fever, and urinary-tract infections.The beta-Iactamase inhibitor clavulanic acid widens amoxicillin's antimicrobial spectrum and a combined preparation can be used when resistance to amoxicillin is prevalent for example in respiratory-tract infections due to Haemophilus influenzae or Moraxella catarrhalis (Branhamella catarrhalis), in the empirical treatment of animal bites, or in infections such as chancroid and melioidosis.
Amoxicillin is also given as part of treatment regimens to eradicate Helicobacter pylori infection in patients with peptic ulcer disease.
-
DOSAGE AND ADMINISTRATION
The usual oral dose is amoxicillin 250mg to 500mg every 8 hours. Children up to 10 years of age may be given 125 to 250 mg every 8 hours; under 20 kg body-weight, a dose of 20 to 40 mg per kg daily in divided doses every 8 hours may be employed; in infants less than 3 months of age, the maximum dose should be 30 mg per kg daily in divided doses every 12 hours.
Higher oral doses of amoxicillin, either as a single dose or in short courses are used in some conditions. For example, amoxicillin is given a single dose of 3g, with probenicid 1g, in the treatment of uncomplicated gonorrhoea in areas where gonococci remain sensitive.
A dose of 3g repeated once after 8 hours may be used for dental abscesses.
A 3g dose may be given for uncomplicated acute-urinary-tract infections, and repeated once after 10 to 12 hours.
For the prophylaxis of endocarditis in patient at risk, amoxicillin 2g or 3g is given about 1 hour before dental procedures under local or no anesthesia.
A high-dose regimen of amoxicillin 3g twice daily may be used in patients with severe or recurrent infections of the respiratory tract.
If necessary, children aged 3 to 10 years with otitis media may be given 750 mg twice daily for 2 days. For the eradication of H.pylori, amoxicillin is given in combination with either metronidazole or clarithromycin and a bismuth compound or an antisecretory drug; usual doses of amoxicillin are 0.75 or 1g twice daily or 500mg three times daily.
Doses should be reduced in severe renal impairment.
Amoxicillin with clavulanic acid.
Amoxicillin in combination with clavulanic acid (co-amoxiclav) is administered by mouth in a ratio of amoxicillin (as trihydrate) 2, 4, or 7 parts to 1 part of clavulanic acid (as the potassium salt), or intravenously in a ratio of 5 parts of amoxicillin (as the sodium salt) to 1 part of clavulanic acid (as the potassium salt).Doses of the combination calculated on amoxicillin content, are similar to those of amoxicillin alone.
Or as prescribed by the physician.
-
ADVERSE EFFECTS
The incidence of diarrhea is less with amoxicillin.
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, toxic epidermal necrolysis, and exfoliative dermatitis have also been attributed occasionally to amoxicillin with clavulanic acid.
Skin rashes are the most common side-effects and are generally either urticarial or maculopapular; the urticarial reactions are typical of penicillin hypersensitivity, while the erythematous maculopapular eruptions are characteristic of penicillin and amoxicillin and often appear more than 7 days after commencing treatment. Such rashes may be due to hypersensitivity to the beta-lactam moiety or to the amino group in side chain, or toxic reaction.
The occurrence of maculopapular rash during amoxicillin administration does not necessarily preclude the subsequent administration of penicillin.
Since it may be difficult in practice to distinguish between hypersensitive and toxic responses, skin testing for hypersensitivity may be advisable before penicillin is used in patients who have had amoxicillin rashes. Most patients with infectious mononucleosis develop a maculopapular rash when treated with amoxicillin has occasionally been reported.
Gastrointestinal adverse effects, particularly diarrhoea and nausea and vomiting, occur quite frequently, usually following administration by mouth. Pseudomembranous colitis has also been reported.
-
PRECAUTION
Cholestatic jaundice can occur either during or shortly after the use of Co-Amoxiclav. The duration of treatment should be appropriate to the indication and should not exceed 14 days.
-
DRUG INTERACTIONS
Amoxicillin together with allopurinol may increase frequency of rashes compared with those receiving antibacterial alone.
-
CAUTION
NAFDAC ACT prohibits dispensing without prescription. -
AVAILABILITY
Alu-alu foil pack x 7's -
STORAGE CONDITION
Store below 25°C, protected from humidity.
Keep out of reach of children. -
DOSAGE
As directed by physician. -
NAFDAC REG. No
A4-8763