Full Prescribing Info
Contents
Amoxicillin and clavulanic acid.
Description
Tablet: Each tablet contains 250 mg, 500 mg or 875 mg amoxicillin and 125 mg clavulanic acid.
The amoxicillin is present as amoxicillin trihydrate U.S.P. and the Clavulanic acid is present as Clavulanate Potassium U.S.P.
INDCLAV* presentations do not contain sucrose, tartrazine or any other azo dyes.
Syrup: Each 5 ml reconstituted suspension contains: Amoxicillin Trihydrate USP equivalent to Amoxicillin 125 mg, Clavulanate Potassium USP equivalent to Clavulanic Acid 31.25 mg.
Action
Pharmacology: Pharmacodynamics: Clavulanic acid enhances the antibacterial spectrum of amoxicillin by rendering most Beta-lactamase-producing isolates susceptible to the drug. In clinical trials amoxicillin/Clavulanic acid is clinically and bacteriologically superior to amoxicillin alone and at least as effective as numerous other comparative agents, such as orally administered cephalosporin. The antibacterial activity of amoxicillin/Clavulanic acid has been well established. Clavulanic acid alone possesses only weak anti-bacterial activity, except against Legionella spp., and certain strains of Branhamella catarrhalis, B. fragilis and Neisseria gonorrhoeae. The in-vitro synergy of clavulanic acid combined with amoxicillin has been confirmed in vivo in numerous experimental infections in animals. The combination of amoxicillin with clavulanic acid appears to suppress the development of resistance under experimental conditions.
Pharmacokinetics: Combining Clavulanic acid with amoxicillin causes no appreciable alteration of the pharmacokinetics of either drug compared with their separate administration. After oral administration, both components achieve maximum plasma concentrations in about 1 hour and these concentrations show a direct relationship to the dose administered. The absolute bioavailability of Clavulanic acid is about 60%. Absorption is unaffected by concomitant administration of food, milk etc. Clavulanic acid has a volume of distribution of about 25% of body weight and is about 22% protein bound in vitro. Both Clavulanic acid and amoxicillin possess a mean elimination half-life of about 1 hour and a mean total clearance of about 25L/h healthy subjects. The main route of elimination is via the urine.
Indications/Uses
Tablet: INDCLAV* is an antibiotic with a notably broad spectrum of activity against the commonly occurring bacterial pathogens in general practice and hospitals.
The beta-lactamase inhibitory action of Clavulanic acid extends the spectrum of amoxicillin to embrace a wide range of organisms including many resistant to other beta lactam antibiotics.
INDCLAV* oral presentation for twice daily dosing, are indicated for short-term treatment of bacterial infections of the following sites: Upper respiratory tract infections (including ENT) e.g. tonsillitis, sinusitis, otitis media; lower respiratory tract infection e.g. acute and chronic bronchitis, lobar and bronchopneumonia; genito-urinary tract infections, e.g. cystitis, urethritis, pyelonephritis; skin & soft tissue infections e.g. boils, abscesses, cellulitis, wound infections; bone & joint infections e.g. osteomyelitis; dental infections e.g. dentoalveolar abscess; other infections e.g. septic abortion, puerperal sepsis, intra-abdominal sepsis.
INDCLAV* is bactericidal to a wide range of organisms including: Gram-positive Aerobes: Enterococcus faecalis, 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, Escherichia coli, Proteus mirabilis, Proteus vulgaris, Klebsiella species, Moraxella catarrhalis, Salmonella species, Shigella species, Bordetella pertussis, Brucella species, Neisseria gonorrhoeae, Neisseria meningitidis, Vibrio cholerae, Pasteurella multicoda.
Anaerobes: Bacteroides spp. including B. fragilis; including lactamase producing strains resistant to ampicillin and amoxicillin.
Syrup: It is indicated for Urinary tract infections, Other gram-negative an-aerobic infections, Respiratory tract infections, Skin and soft tissue infections, Gonorrhea, Chancroid, etc.
Dosage/Direction for Use
Tablet: Usual dosages for the treatment of indication: Adults and children over 12 years: Mild to Moderate Infections: One INDCLAV* 625 tablet two times a day (bid). One tablet eight hourly (tid).
Severe Infections: One INDCLAV 1000 tablet two times a day (bid).
Therapy can be started parenterally and continued with an oral preparation.
Dosage in dental infections (e.g. dentoalveolar abscess): Adult and children over 12 years: One INDCLAV* 625 tablet two times a day for five days.
INDCLAV* 625 tablet and INDCLAV* 1000 tablets are not recommended in children 12 years and under.
Dosage in renal impairment: Adults: The INDCLAV* 1000 tablet 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 INDCLAV* 625 tablet bid or one INDCLAV 1000 tablet bid).
Moderate Impairment (Creatinine clearance 10 to 30 ml/min): One INDCLAV* 625 tablet bid. The INDCLAV* 1000 tablet should not be administered.
Severe impairment (Creatinine clearance <10 ml/min): Not more than one INDCLAV* 625 tablet every 24 hours.
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, swallowed without chewing. To minimize potential gastrointestinal intolerance, administer at the start to a meal. The absorption of INDCLAV* optimized when taken at the start of a meal.
Treatment should not be extended beyond 14 days without review.
Syrup: The usual recommended daily dosage: Mild to moderate infections: 25/3.6 mg/kg/day e.g. recurrent tonsillitis, lower respiratory infections and skin and soft tissue infections; Serious infections: 45/6.4 mg/kg/day (upper respiratory tract infections e.g. otitis media and sinusitis, lower respiratory tract infections and skin and soft tissue infections). (See table.)

Click on icon to see table/diagram/image

Oral Administration.
To minimize potential gastrointestinal intolerance, administer at the start of a meal. The absorption of INDCLAV* Syrup is optimized when taken at the start of a meal. Therapy can be started parenterally and continued with an oral preparation.
Overdosage
Tablet: Cases of overdosage with INDCLAV* are unlikely to occur. If encountered, gastrointestinal symptoms and disturbance of the fluid and electrolyte balances may be evident. They may be treated symptomatically with attention to the water electrolyte balance. INDCLAV* may be removed from the circulation by haemodialysis.
Contraindications
Tablet: Penicillin hypersensitivity.
Attention should be paid to possible cross-sensitivity with other beta lactam antibiotics, e.g. cephalosporins, a previous history of INDCLAV* or penicillin-associated jaundice/hepatic dysfunction.
Syrup: Amoxicillin/Clavulanic acid should be administered with food and is contraindicated in patients with a known history of beta-lactam hypersensitivity.
Special Precautions
Tablet: Changes in liver function tests have been observed in some patients receiving INDCLAV*. The clinical significance of these changes is uncertain but INDCLAV* should be used with caution in patients with evidence of hepatic dysfunction. Cholestatic jaundice, which may be severe, but is usually reversible, has been reported rarely. Signs and symptoms may not become apparent for up to six weeks after treatment has ceased.
In patients with moderate or severe renal impairment, INDCLAV* dosage should be adjusted as recommended in the Dosage & Administration section.
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 (see Contraindications). Erythematous rashes have been associated with glandular fever in patients receiving amoxicillin. INDCLAV*, should be avoided if glandular fever is suspected.
Prolonged use may also occasionally result in overgrowth of non -susceptible organisms.
Further Information: Resistance to many antibiotics is caused by bacterial enzymes, which destroy the antibiotic before it can act on the pathogen. The clavulanic acid in INDCLAV* anticipates this mechanism by blocking the beta-lactamase enzymes, thus rendering the organisms sensitive to amoxicillin's rapid bactericidal effect of concentrations readily attainable in the body. Clavulanic acid by itself has little antibacterial activity. However, in association with amoxicillin as INDCLAV*, it produces an antibiotic agent of broad spectrum with wide application in hospital and general practice. The pharmacokinetics of the two components of INDCLAV* are closely matched. Peak serum levels of both occur about 1 hour after oral administration and about 70% remains free in the serum. Doubling the dosage of INDCLAV* approximately doubles the serum levels achieved.
INDCLAV* is also available as INDCLAV* intravenous for the short-term treatment of bacterial infections and for prophylaxis against infection which may be associated with major surgical procedures. INDCLAV* intravenous is described in a separate pack insert. INDCLAV* is also available as a syrup for two times daily for administration to children under the age of 12 years for the treatment of bacterial infections. INDCLAV* syrup is described in a separate Pack Insert.
Use In Pregnancy & Lactation
Tablet: Reproduction studies in animals (mice & rats) with parenterally administered INDCLAV* have shown no teratogenic effects. There is limited experience of the use of INDCLAV* in human pregnancy. As with all medicines, use should be avoided in pregnancy especially during the first trimester. Unless considered essential by the physician, INDCLAV* may be administered during the period of lactation. With the exception of the risk sensitization associated with the excretion of trace quantities in breast milk, there are no detrimental effects for the infant.
Adverse Reactions
Syrup: About 13% of patients report adverse effects with amoxicillin/Clavulanic acid, requiring withdrawal of treatment in less than 3% of patients; the adverse effects are primarily mild gastrointestinal disturbances, including diarrhoea, nausea, vomiting and indigestion. There have been isolated reports of urticaria, anaphylaxis, behavioral changes and laboratory test abnormalities. Gastrointestinal adverse effects may be reduced by taking the drug with food.
Side Effects
Tablet: Side effects, as with amoxicillin, are uncommon and mainly of mild and transitory nature. Gastrointestinal reactions, effects include diarrhea, indigestion, nausea and vomiting. Candidiasis, antibiotic associated colitis (including pseudomembranous colitis and haemorrhagic colitis) have been reported rarely. Nausea, although uncommon, is more often associated with higher oral dosages. If gastrointestinal side effects occur with oral therapy, they may be reduced by taking INDCLAV* at the start of meal. As with other antibiotics, gastrointestinal side effects may be raised in children under 2 years. In clinical trials, however, only 4% of children under 2 years were withdrawn from treatment.
Hepatic effects: A moderate rise in AST and/or ALT has been noted in patients with semi-synthetic penicillins, but the significance of these findings is unknown.
Hepatitis and cholestatic jaundice have been reported rarely with INDCLAV*. They may be severe and continue for several months. They are reported as occurring predominantly in adult or elderly patients and slightly more frequently in males. Signs and symptoms may occur during treatment but are more frequently reported after cessation of therapy with a delay of up to six weeks. The hepatic events are usually reversible. However, in extremely rare circumstances, deaths have been reported. Hepatic events have been reported predominantly in males and elderly patients and may be associated with prolonged treatment.
Hypersensitivity reactions: Urticarial and erythematous rashes sometimes occur. Rarely, erythema multiforme, Stevens Johnson syndrome, toxic epidermal necrolysis and exfoliative dermatitis have been reported. Treatment should be discontinued if one of these types of rash appears.
In common with other beta-lactam antibiotics, angioedema, anaphylaxis, serum sickness-like syndrome and hypersensitivity vasculitis have been reported.
Interstitial nephritis can occur rarely.
Haematological effects: As with other beta-lactams, reversible leucopenia (including neutropenia or agranulocytosis), reversible thrombocytopenia and haemolytic anaemia have been reported rarely. 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.
Syrup: Gastrointestinal side-effects, such as nausea, vomiting and diarrhoea, seem to be more common with amoxicillin/Clavulanic acid than with amoxicillin alone.
Drug Interactions
Tablet: Prolongation of bleeding time and prothrombin time has been reported in some patients receiving INDCLAV*. INDCLAV* should be used with care in patients on anti-coagulation therapy. In common with other broad spectrum antibiotics, INDCLAV* may reduce the efficacy of oral contraceptives and patients should be warned accordingly.
Concomitant use of probenecid is not recommended. Probenecid decreases the renal tubular secretion of amoxicillin. Concomitant use with INDCLAV* may result in increased and prolonged blood levels of amoxicillin but not of clavulanic acid.
Concomitant use of Allopurinol during treatment with amoxicillin can increase the likelihood of allergic skin reactions. There are no data on the concomitant use of INDCLAV* and Allopurinol.
Storage
Tablet: INDCLAV* tablet should be stored in un-opened, original packs in a dry place below 30°C.
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 [white to off-white colored, elliptical (375 mg) or oblong (625 mg and 1000 mg), biconvex] 375 mg x 2 x 10's. 625 mg x 2 x 10's. 1000 mg x 10's. Syr 156.25 mg/5 mL x 100 mL.
Register or sign in to continue
Asia's one-stop resource for medical news, clinical reference and education
Sign up for free
Already a member? Sign in