Ranclav

Ranclav

amoxicillin + clavulanic acid

Manufacturer:

Ranbaxy

Distributor:

DKLL
Full Prescribing Info
Contents
Co-amoxiclav: Amoxicillin and clavulanic acid.
Description
Each 625 mg and 1 g film-coated tablet contains Amoxicillin USP equivalent to anhydrous amoxicillin 500 mg and 875 mg, clavulanate potassium equivalent to clavulanic acid 125 mg, respectively.
Each 5 ml suspension contains Amoxicillin USP equivalent to amoxicillin 200 mg, clavulanate potassium equivalent to clavulanic acid 28.5 mg.
Each 5 ml suspension contains Amoxicillin USP equivalent to amoxicillin 400 mg, clavulanate potassium equivalent to clavulanic acid 57 mg.
Action
Pharmacology: Pharmacodynamics: Mechanism of Action: Amoxicillin acts through inhibition of biosynthesis of the bacterial cell wall mucopeptide. It is bactericidal against many gram-positive and gram-negative organisms during the stage of active multiplication. However it is susceptible to degradation by beta-lactamases and therefore its spectrum does not include lactamase producing bacteria.
625-mg FC tab: Clavulanic acid is a beta-lactam structurally related to the penicillins, which possess the ability to inactivate a wide range of beta-lactamase commonly found in bacteria resistant to beta-lactam antibiotics.
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.
1-g FC tab and Susp: Clavulanic acid inhibits a wide range of bacterial beta-lactamases and protects amoxicillin from degradation by beta-lactamase enzymes and effectively extends the antibacterial spectrum of amoxicillin to include many beta-lactamase producing strains of bacteria.
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. However, administration at the start of a meal improves the absorption of clavulanate and minimize the potential for gastrointestinal intolerance (1-g FC tab and Susp).
The oral bioavailability of amoxicillin and clavulanate potassium is approximately 90% and 75% (FC tab), 75-90% and 75% (Susp), respectively. Clavulanic acid has about the same plasma elimination half-life (1 hr) as that of amoxicillin (1.3 hrs) (FC tab); plasma elimination half-life (0.8-1 hr) as that of amoxicillin (1 hr) (Susp).
Amoxicillin and clavulanic acid are widely distributed to most tissues and body fluids including peritoneal fluid, blister fluid, urine, pleural fluid, middle ear fluid, intestinal mucosa, bone, gallbladder, lung, female reproductive tissues and bile. Penetration into CSF through non-inflamed meninges and into purulent bronchial secretions is low. Amoxicillin and clavulanic acid readily crosses the placenta and are secreted into breastmilk in low concentrations.
Amoxicillin is bound to serum proteins to an extent of 17-20% (FC tab), 20% (Susp) while clavulanic acid is 20-30% (FC tab), 22-30% (Susp) bound to serum proteins.
FC tab: Approximately 10% of the dose of amoxicillin and less than 50% of dose of clavulanate are metabolised.
Amoxicillin and clavulanic acid combination is eliminated primarily unchanged through the renal route (glomerular filtration and tubular secretion). Approximately 50-78% (625-mg FC tab), 50-70% (1-g FC tab), 60-75% (Susp) of amoxicillin and 25-40% (FC tab), 30-40% (Susp) of clavulanic acid are excreted unchanged in urine within the first 6 hrs after administration.
Microbiology: Antibacterial Spectrum: The following pathogens have been found to be susceptible to amoxicillin & clavulanate potassium combination: 625-mg FC tab: Gram-positive bacteria: Staphylococcus aureus (beta-lactamase and non-beta-lactamase producing), Staph. epidermidis (beta-lactamase and non-beta lactamase producing) Staph. saprophyticus, Strep.pneumoniae, Enterococcus faecalis and Strep. viridans. Among anaerobes it is active against Clostridia, Peptocooccus and Peptostreptococcus.
Gram-negative bacteria: N.gonorrhoea, H.influenzae (beta-lactamase and non-beta lactamase producing), Moraxella catarrhalis (beta-lactamase and non-beta lactamase producing), E.coli, Pr. mirabilis, Klebsiella spp., Salmonella spp., Shigella spp. Among anaerobes it is active against bacteroides including B. fragilis.
Resistance: Gram-negative bacilli that produce type I chromosomally mediated beta-lactamases (e.g. Citrobacter, Enterobacter cloacae, Serratia spp., Ps. aeruginosa) are generally resistance to amoxicillin & clavulanate potassium combination since clavulanate potassium does not inhibit type 1 beta lactamase.
1-g FC tab: Gram-positive: Aerobes: Enterococcus faecalis, Strep. pneumoniae, Strep. pyogenes, Strep. viridans, Staphylococcus aureus*, coagulase negative staphylococci* (including Staph. epidermidis*), Corynebacterium spp., Bacillus anthracis, Listeria monocytogenes.
Anaerobes: Clostridium spp., Peptococcus spp., Peptostreptococcus spp.
Gram-negative: Aerobes: H. influenzae*, E. coli*, Pr. mirabilis*, Klebsiella spp.*, Moraxella catarrhalis* (Branhamella catarrhalis), Salmonella spp*., Bordetella pertussis, Brucella spp., N. gonorrhoeae*, N. meningitidis, Vibrio cholerae, Pasteurella multocida.
Anaerobes: Bacteroides spp.* (including B. fragilis).
(Remarks - *including β-lactamase producing strains resistant to Ampicillin and Amoxicillin.)
Susp: Gram-positive: Aerobes: Enterococcus faecalis*, Streptococcus pneumoniae, Streptococcus pyogenes, Streptococcus viridans, Staphylococcus aureus*, Coagulase­-negative staphylococci* (including Staphylococcus epidermidis*), Corynebacterium spp., Bacillus anthracis*, Listeria monocytogenes.
Anaerobes: Clostridium spp., Peptococcus spp., Peptostreptococcus spp.
Gram-negative: Aerobes: Haemophilus influenzae*, Moraxella catarrhalis* (Branhamella catarrhalis), Escherichia coli*, Proteus mirabilis*, Proteus vulgaris*, Klebsiella spp*., Salmonella spp.*, Shigella spp.*, Bordetella pertussis, Brucella spp., Neisseria gonorrhoeae*, Neisseria meningitidis*, Vibrio cholerae, Pasteurella multocida.
Anaerobes: Bacteroides spp.* (including B. fragilis).
* Some members of these species of bacteria produce beta-lactamase, rendering them insensitive to amoxicillin alone.
Indications/Uses
625-mg FC tab: RANCLAV is indicated for the treatment of following infections caused by susceptible pathogens: Lower respiratory tract infections (e.g.pneumonia, bronchitis); Acute otitis media.
Sinusitis.
Urinary tract infections.
Skin and soft tissue infections.
1-g FC tab: RANCLAV tablets are indicated for the treatment of following infections by susceptible pathogens: Upper respiratory tract infections (including otorhinolaryngeal) e.g. sinusitis, otitis media, tonsillitis.
Lower respiratory tract infections (e.g. lobar and bronchopneumonia, acute and chronic bronchitis).
Genito-urinary tract infections (e.g. cystitis, urethritis, pyelonephritis).
Skin and soft tissue infections (e.g. boils, abscesses, cellulitis, wound infections).
Bone and joint infections (e.g. osteomyelitis).
Dental infections (e.g. dentoalveolar abscess).
Other infections (e.g. septic abortion, puerperal sepsis, intra-abdominal sepsis).
Susp: Ranclav 228.5 & 457 Suspension is indicated for the short term treatment of bacterial infections at the following sites when amoxicillin resistant beta-lactamase producing strains are suspected as a cause. In other situations, amoxicillin alone should be considered.
Upper respiratory tract infections (including ENT) in particular sinusitis, otitis media, recurrent tonsillitis. These infections are often caused by Streptococcus pneumoniae, Haemophilus influenzae*, Moraxella catarrhalis* and Streptococcus pyogenes.
Lower respiratory tract infections in particular acute exacerbations of chronic bronchitis (especially if considered severe), lobar and bronchopneumonia. These indications are often caused by Streptococcus pneumoniae, Haemophilus influenzae* and Moraxella catarrhalis*.
Urinary tract infections in particular cystitis (especially when recurrent or complicated excluding prostatitis). These infections are often caused by Enterobacteriaceae* (mainly Escherichia coli*), Staphylococcus saprophyticus, Enterococcus species*.
Dosage/Direction for Use
Usual dosages for treatment of infection: Adults and children over 12 years: 625-mg FC tab: Mild-Moderate Infections: One RANCLAV 625 mg tablet two times a day.
For more severe infections and infections of respiratory tract, the usual oral dosage is one tablet containing 500 mg of amoxicillin and 125 mg of clavulanic acid (One Ranclav 625 tablet) every 8 hours.
1-g FC tab: Severe infections: One RANCLAV 1 G tablet two times a day.
Therapy can be started parenterally and continued with an oral preparation.
Dosage in dental infections (e.g. dentoalveolar abscess): Adults and children over 12 years: One RANCLAV 1 G tab two times a day for five days.
RANCLAV 625 mg and 1 G tab are not recommended in children of 12 years and under.
Dosage in renal impairment: Adults: The RANCLAV 1 G tab should only be used in patients with a glomerular filtration rate of >30 mL/min.
Mild impairment (Creatinine clearance >30 ml/min): No change in dosage (i.e. either one 625 tablet bid or one 1 G tablet bid).
Moderate impairment (Creatinine clearance 10-30 ml/min): One 625 mg tab bid. The 1 G tab should not be administered.
Severe impairment (Creatinine clearance <10 ml/min): Not more than one 625 mg tablet every 24 hrs.
Dosage in hepatic impairment: Dose with caution; monitor hepatic function at regular intervals.
Oral administration: Tablets should be swallowed whole without chewing. If required, tablets may be broken in half and swallowed without chewing. To minimize potential gastrointestinal intolerance, administer at the start of a meal. The absorption of Amoxicillin and Clavulanate Potassium combination is optimised when taken at the start of a meal. Treatment should not be extended beyond 14 days without review.
Susp: The usual recommended daily dosage is: Adult and Children (weight > 40 kg): oral 250-500 mg (amoxicillin) every 8 hours or 500-875 mg (amoxicillin) every 12 hours. Maximum dose is 2-3 gram/day.
Children (weight <40 kg): Oral 20-50 mg/kg/day divided every 8-12 hours or 125-250 mg (amoxicillin) every 8 hours or 200-400 mg (amoxicillin) every 12 hours.
Renal impairment: See table.

Click on icon to see table/diagram/image
Overdosage
625-mg FC tab: In the event of overdosage amoxicillin & clavulanic acid may be removed from the blood by haemodialysis.
1-g FC tab and Susp: Overdosage with Amoxicillin and Clavulanate combination is unlikely to occur.
Symptomatic and supportive measures should be instituted with particular attention to the restoraion of fluid and electrolyte imbalance. Amoxicillin and Clavulanate combination may be removed from the circulation by haemodialysis.
Contraindications
625-mg FC tab: A history of allergic reactions to beta-lactam antibiotics.
1-g FC tab and Susp: Penicillin hypersensitivity.
Attention should be paid to possible cross-sensitivity with other β-lactam antibiotics eg. cephalosporins.
A history of RANCLAV or penicillin associated jaundice/hepatic dysfunction.
Warnings
Serious and occasionally fatal hypersensitivity (anaphylactic) reactions have been reported in patients on penicillin therapy. Although anaphylaxis is more frequent following parenteral therapy, it has occurred in patients on oral penicillins. These reactions are more likely to occur in individuals with a history of penicillin hypersensitivity and/or a history of sensitivity to multiple allergens; careful inquiry should be made concerning previous hypersensitivity reactions to penicillins, cephalosporins, or other allergens. If an allergic reaction occurs, the amoxicillin and clavulanate potassium combination should be discontinued and the appropriate therapy instituted. Serious anaphylactic reactions require immediate emergency treatment with epinephrine. Oxygen, intravenous steroids and airway management, including intubation, should also be administered as indicated.
Pseudomembranous colitis has been reported with nearly all antibacterial agents, including amoxicillin and clavulanate potassium combination and has ranged in severity from mild to life threatening. Therefore, it is important to consider this diagnosis in patients who present with diarrhoea subsequent to the administration of antibacterial agents.
1-g FC tab: Prolonged bleeding time and prothrombin time have been reported in patients receiving Amoxicillin and Clavulanate Potassium combination. Hence, caution should be exercised in patients on anti-coagulation therapy.
Special Precautions
1-g FC tab & Susp: RANCLAV tablets and Ranclav 228.5 & 457 Suspension should be used with caution in patients with evidence of severe hepatic dysfunction; change in liver function tests have been observed in some patients receiving Amoxicillin and Clavulanic acid combination.
1-g FC tab: RANCLAV 1 G tablets should not be used in patients with moderate to severe renal impairment (creatinine clearance of ≤30 ml/min).
Susp: Ranclav 228.5 & 457 Suspension contains Aspartame and should not be used by phenylketonurics.
1-g FC tab and Susp: Erythematous rashes have been associated with glandular fever in patients receiving amoxicillin.
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 appropriate therapy instituted.
FC tab and Susp: Laboratory value alterations: Urine glucose test: High urinary concentrations of a penicillin may produce false-positive or falsely elevated test results with copper-reduction test [Benedict's, Clinitest, or Fehling's]. Glucose enzymatic tests [Clinistix or Testape] are not affected. Direct antiglobulin (Coombs') test: False-positive result may occur during therapy with any penicillin.
625-mg FC tab: Liver function tests: A moderate rise in SGOT, SGPT, alkaline phosphatase and serum bilirubin have been reported in a few patients with use of amoxicillin & clavulanate potassium combination.
1-g FC tab and Susp: Carcinogenicity: Long-term carcinogenicity studies in animals have not been performed with amoxicillin and clavulanate potassium combination.
Mutagenicity: Long-term studies in animals have been performed to evaluate the mutagenic potential of Amoxicillin and Clavulanate Potassium combination.
Use in Children: 1-g FC tab: Paediatrics patients over 12 years of age should be dosed according to adult recommendation. There is lack of data pertaining to use of RANCLAV 625 mg / 1 G tablets in children less than 12 years of age.
Susp: No paediatrics-specific problems have been documented when given according to the recommended dosage.
Use in the Elderly: 1-g FC tab and Susp: Penicillins have been used in geriatric patients and no geriatrics­ specific problems have been documented to date. However, elderly patients are more likely to have an age-related decrease in renal function, which may require an adjustment in dosage in patients receiving penicillins.
Use In Pregnancy & Lactation
1-g FC tab and Susp: No adverse effects were observed in pregnant rats and mice when amoxicillin and Clavulanate Potassium combination was administered at doses equivalent to 10 times the usual human dose. There is limited experience on the use of amoxicillin and clavulanate combination in human pregnancy. As with all medicines, use should be avoided in pregnancy, especially during the first trimester, unless considered essential by the physician.
Amoxicillin and Clavulanate Potassium combination can be administered to nursing mothers; no specific adverse event other than risk of sensitization for the infant has been reported.
Adverse Reactions
625-mg FC tab: Gastrointestinal effects: Diarrhoea, nausea, vomiting, discomfort, anorexia, flatulence, dyspepsia, gastritis, stomatitis, glossitis, black or hairy tongue and enterocolitis.
Pseudomembranous colitis: Antibiotic associated pseudomembranous colitis may occur during or following discontinuance of amoxicillin & clavulanate potassium combination.
Hypersensitivity Reactions: Rash and urticaria have been reported in 3% of patients receiving amoxicillin and clavulanate potassium combination. Angioedema, serum sickness like reactions and rarely exfoliative dermatitis have been reported.
Haematopoeitic side effects: Anemia, thrombocytopenia, leukopenia and agranulocytosis have been reported during therapy with penicillins.
CNS Effects: Reversible hyperactivity, agitation, anxiety, insomnia. and dizziness have been reported rarely.
1-g FC tab and Susp: Side effect with RANCLAV are uncommon and mainly of a mild and transitory nature. Reported side effects include diarrhoea, indigestion, nausea, vomiting and mucocutaneous candidiasis.
Susp: Superficial tooth discoloration has been reported rarely, mostly with the suspension. It can usually be removed by brushing.
1-g FC tab and Susp: Occasionally moderate and asymptomatic rises in AST and/or ALT and alkaline phosphatases; and rarely hepatitis and cholestatic jaundice have been reported to occur. Signs and symptoms may occur during treatment but have been more frequently reported after cessation of therapy with a delay of up to 6 weeks.
Susp: After amoxicillin and clavulanic acid combination, hepatic reactions have been reported more frequently in males and elderly patients, particularly over 65 years of age. The risk increases with duration of treatment longer than 14 days.
These reactions have been very rarely reported in children.
1-g FC tab and Susp: Urticaria and erythematous rashes have been reported occasionally.
Erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis, bullous exfoliative dermatitis, serum sickness like syndrome, hypersensitivity vasculitis, interstitial nephritis, pseudomembranous colitis, prolongation of bleeding time and prothrombin time have been reported to occur rarely.
In common with other β-lactam antibiotics, angioedema and anaphylaxis, transient leucopenia, thrombocytopenia and haemolytic anaemia have been reported rarely.
Side effects involving the CNS which include reversible hyperactivity, dizziness, headache and convulsions may occur very rarely.
Drug Interactions
625-mg FC tab: Probenecid: Oral probenecid administered shortly before or concomitantly with amoxicillin & clavulanic acid slows the rate of renal tubular secretion of amoxicillin and produces higher and prolonged serum concentrations of amoxicillin.
However, concomitant administration of probenecid with amoxicillin & clavulanate potassium combination does not affect the area under the serum concentration time curve (AUC), half-life or peak serum concentration of clavulanic acid.
Allopurinol: An increased incidence of rash has been reported in patients with hyperuricemia who are receiving allopurinol and concomitant amoxicillin or ampicillin. Therefore, some clinicians suggest that concomitant use of the drugs should be avoided, if possible.
1-g FC tab and Susp: Prolongation of bleeding time and prothrombin time may occur in some patients receiving Amoxicillin and Clavulanate combination. This combination should be used with caution in patients receiving anti-coagulant therapy. An increased incidence of rash may occur in patients with hyperuricemia who are receiving allopurinol and concomitant Amoxicillin or Ampicillin.
In common with other broad spectrum antibiotics, Amoxicillin and Clavulanate Potassium combination may reduce the efficacy of oral contraceptives. Concomitant use of probenecid is not recommended. Probenecid decreases the renal tubular secretion of Amoxicillin.
Concomitant use with RANCLAV may result in increased and prolonged blood levels of Amoxicillin but not of Clavulanic acid.
Caution For Usage
Directions for Use: Ranclav 228.5 & 457 Suspension: Boil water, allow it to cool. Slowly add cooled water up to the arrow mark. Shake vigorously. Adjust the volume up to the mark by adding more water, if necessary. The constituted suspension should be consumed within 7 days of preparation.
The constituted suspension should be stored in a refrigerator at a temperature between 2 to 8°C and used within one week of constitution. To minimize potential gastrointestinal intolerance, administer Ranclav 228.5 & 457 Suspension at the start of a meal. The absorption of amoxicillin and clavulanic acid combination is optimized when taken at the start of a meal.
Treatment should not be extended beyond 14 days without review.
Storage
Do not store above 30°C. Protect from 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
625 mg FC tab x 10 x 10's. 1 g FC tab x 10 x 2's, 25 x 4's, 3 x 4's. 228.5 mg/5 mL BID susp x 70 mL. 457 mg/5 mL BID susp x 50 mL, 70 mL.
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