375mg,

 625mg,  1g   Tablets and cephalosporins. Thus, amoxicillin/clavulanate potassium possesses the distinctive properties
156.25mg/5mL,   312.5mg/5mL,   457mg/5mL  Suspension, of a broad-spectrum antibiotic and a β-lactamase inhibitor.
62.5mg/mL  Drops Microbiology
DESCRIPTION Co-amoxiclav is bactericidal to a wide range of organisms including:
AMCLAV (Co-amoxiclav) is an oral antibacterial combination consisting of the semisynthetic
antibiotic amoxicillin and the β-lactamase inhibitor, Clavulanate potassium (the potassium salt of Gram-Positive aerobes:
Clavulanic acid). Amoxicillin is an analog of ampicillin, derived from the basic penicillin nucleus, *Bacillus anthracis
6-aminopenicillanic acid. The amoxicillin molecular formula is C16H19N3O5S•3H2 O. Chemically, Corynebacterium species
amoxicillin is (2S,5R,6R)-6-[(R)(-)-2-Amino-2-(p-hydroxyphenyl) acetamido]-3,3-dimethyl-7-oxo- *Enterococcus faecalis
4-thia-1-azabicyclo[3.2.0]heptane-2carboxylic acid trihydrate and may be represented structurally *Enterococcus faecium
as: Listeria monocytogenes
Nocardia asteroides
*Staphylococcus aureus
*Coagulase negative staphylococci (including *Staphylococcus epidermidis)
Streptococcus agalactiae
Streptococcus pneumoniae
Amoxicillin Trihydrate Streptococcus pyogenes
Streptococcus species
Clavulanic acid is produced by the fermentation of Streptomyces clavuligerus. It is a β -lactam Streptococcus viridians
structurally related to the penicillins and possesses the ability to inactivate a wide variety of β -
lactamases by blocking the active sites of these enzymes. Clavulanic acid is particularly active Gram-Negative aerobes:
against the clinicallyimportant plasmid-mediated β-lactamases frequently responsible for transferred Bordetella pertussis
drug resistance to penicillins and cephalosporins. The clavulanate potassium molecular formula Brucella species
is C8H8KNO5. Chemically, Clavulanate potassium is potassium (Z) (2R,5R)-3-(2-hydroxyethylidene)- *Escherichia coli
7-oxo-4-oxa-1-azabicyclo[3.2.0]-heptane-2-carboxylate, and may be represented structurally as: Gardnerella vaginalis
*Haemophilus influenzae
Helicobacter pylori
*Klebsiella species
Legionella species
*Moraxella catarrhalis (Branhamella catarrhalis)
*Neisseria gonorrhoeae
Clavulanate Potassium *Neisseria meningitidis
Pasteurella multocida
QUALITATIVE AND QUANTITATIVE COMPOSITION *Proteus mirabilis
AMCLAV (Co-amoxiclav) is available for oral administration as: *Proteus vulgaris
*Salmonella species
1. AMCLAV Tablets 375mg *Shigella species
Each film-coated tablet contains: Vibrio cholerae
Amoxicillin USP…250mg *Yersinia enterocolitica
(as amoxicillin trihydrate)
Clavulanic acid…125mg Gram-Positive anaerobes:
(as clavulanate potassium USP) Clostridium species
Peptococcus species
2. AMCLAV Tablets 625mg Peptostreptococcus species
Each film-coated tablet contains:
Amoxicillin USP…500mg Gram-Negative anaerobes:
(as amoxicillin trihydrate) *Bacteroides species (including Bacteroides fragilis)
Clavulanic acid…125mg *Fusobacterium species
(as clavulanate potassium USP) Others:
Borrelia burgdorferi
3. AMCLAV Tablets 1g Chlamydiae
Each film-coated tablet contains: Leptospira icterohaemorrhagiae
Amoxicillin USP…875mg *Some members of these species of bacteria produce beta-lactamase, rendering them insensitive
(as amoxicillin trihydrate) to amoxicillin
Clavulanic acid…125mg
(as clavulanate potassium USP) Pharmacokinetics
Absorption / Distribution:
4. AMCLAV Suspension 156.25mg/5mL Amoxicillin and clavulanic acid are fully dissociated in aqueous solution at physiological pH. Both
Each reconstituted 5mL contains: components are rapidly and well absorbed by the oral route of administration. Absorption of
Amoxicillin USP… 125mg amoxicillin/clavulanate potassium is optimised when taken at the start of a meal. Neither amoxicillin
(as amoxicillin trihydrate) nor clavulanic acid is highly protein bound.
Clavulanic acid…31.25mg
(as clavulanate potassium USP) Metabolism / Excretion:
Clavulanic acid is extensively metabolised to 2,5-dihydro-4-(2-hydroxyethyl)-5-oxo-1H-pyrrole-3-
5. AMCLAV-DS Suspension 312.5mg/5mL carboxylic acid and 1-amino-4-hydroxy-butane-2-one.
Each reconstituted 5mL contains: The major route of elimination for amoxicillin is via the kidneys. It is partly excreted in the urine
Amoxicillin USP… 250mg as penicilloic acid in quantities equivalent to 10-25% of the initial dose, whereas for clavulanate it
(as amoxicillin trihydrate) is by both renal andnon-renal mechanisms. Its metabolite is eliminated in urine and feces as carbon
Clavulanic acid…62.5mg dioxide in expired air. Approximately 60-70% of the amoxicillin and approximately 40-65% of the
(as clavulanate potassium USP) clavulanic acid are excreted unchanged in urine during the first 6 hours after administration of
amoxicillin/clavulanate potassium tablets.
6. AMCLAV-PLUS Suspension 457mg/5mL
Each reconstituted 5mL contains: THERAPEUTIC INDICATIONS
Amoxicillin USP… 400mg AMCLAV (Co-amoxiclav) is indicated for the short term treatment of bacterial infections such as:
(as amoxicillin trihydrate) - Upper Respiratory Tract Infections (including ENT) e.g., tonsillitis,
Clavulanic acid…57mg sinusitis, otitis media.
(as clavulanate potassium USP) - Lower Respiratory Tract Infections e.g., acute exacerbations of chronic bronchitis, lobar and
broncho-pneumonia.
7. AMCLAV Drops 62.5mg/mL - Genito-urinary Tract Infections e.g., cystitis, urethritis, pyelonephritis, female genital infections.
Each reconstituted mL contains: - Skin and Soft Tissue Infections e.g., boils, abscesses, cellulitis and wound infection.
Amoxicillin USP…50mg - Bone and Joint Infections e.g., osteomyelitis.
(as amoxicillin trihydrate) - Other Infections e.g., septic abortion, puerperal sepsis, intra-abdominal sepsis, septicaemia,
Clavulanic acid…12.5mg peritonitis, post-surgical infections.
(as clavulanate potassium USP) AMCLAV (Co-amoxiclav) is also indicated for prophylaxis against infection which may be
associated with major surgical procedures such as gastro-intestinal, pelvic, head and neck,
CLINICAL PHARMACOLOGY cardiac, renal, joint replacement and biliary tract surgery.
Mechanism of Action Mixed infections caused by amoxicillin susceptible organism in conjunction with AMCL AV
Amoxicillin is a semisynthetic antibiotic with a broad spectrum of antibacterial activity against many (Co-amoxiclav) -susceptible beta-lactamase-producing organisms may therefore be treated by
gram-positive andgram-negativemicroorganisms. Amoxicillin is, however, susceptible to degradation AMCLAV (Co-amoxiclav).
by β-lactamases, and therefore, the spectrum of activity does not include organisms which produce
these enzymes. DOSAGE AND ADMINISTRATION
Clavulanic acid is a β-lactam, structurally related to the penicillins, which possesses the ability to Dosage depends on the age, weight and renal function of the patient and severity of the infection.
inactivate a wide range of β-lactamase enzymes commonly found in microorganisms resistant to AMCLAV (Co-amoxiclav) should be taken at the start of a meal to enhance the absorption of
penicillins and cephalosporins. In particular, it has good activity against the clinically important amoxicillin and to minimize the potential for gastrointestinal intolerance. Two AMCLAV 375mg
plasmid-mediated β-lactamases frequently responsible for transferred drug resistance. It isgenerally tablets should not be substituted for one AMCLAV 625mg tablet since they are not equivalent.
less effective against chromosomally-mediated type 1 β -lactamases. Adults
The formu lation of amoxicillin and clavulanic acid in amoxicillin/clavulanate potassium Mild to moderate infections
protects amoxicillin from degradation by β-lactamase enzymes and effectively extends the antibiotic 1 AMCLAV 375mg tablet taken three times daily.
spectrum of amoxicillin to include many bacteria normally resistant to amoxicillin, other penicillins 1 AMCLAV 625mg tablet taken two or three times daily.
1 AMCLAV 1g tablet taken twice daily. Rare: Reversible Leucopenia (including neutropenia) and thrombocytopenia, Erythema multiforme.
Severe infections (Including chronic and recurrent urinary tract infections and those of the lower
respiratory tract). Very Rare: Reversible agranulocytosis and haemolytic anaemia. Prolongation of bleeding time and
1 to 2 AMCLAV 625mg tablet given three times daily. prothrombin time, Angioneurotic oedema, anaphylaxis, serum sickness-like sydndrome, hypersensitivity
1 AMCLAV 1g tablet given two or three times daily. vasculitis. Antibiotic associated colitis(including pseudomembranous colitis and hemorrhagic colitis).
Superficial tooth discoloration which can be removed usually by brushing. Hepatitis and cholestatic
Children up to 12 years jaundice usually associated with prolonged treatment predominantly in males and elderly. Steven-
The usual recommended daily dosage is 25mg/kg/day in divided doses every eight hours. Johnson syndrome, toxic epidermal necrolysis, bullous exfoliative-dermatitis, acute generalised
Under 1 year: exanthemous pustulosis (AGEP). Interstitial nephritis and crystalluria.
25mg/kg/day (for example a 7.5kg child would require 2mL AMCLAV 156.25mg syrup three times
daily) CONTRAINDICATIONS
1-6 Years (10-15kg): Co-amoxiclav is contraindicated in patients with;
5mL AMCLAV 156.25mg suspension three times a day. - a history of hypersensitivity to beta-lactams, e.g., penicillins and cephalosporins.
Over 6 years (18-40kg): - a previous history of amoxicillin-clavulanate-associated jaundice/hepatic dysfunction.
5mL AMCLAV-DS 312.5mg suspension three times a day or 5mL AMCLAV-PLUS 475mg suspension
two times a day. WARNINGS AND PRECAUTIONS
- Before initiating therapy with co-amoxiclav, careful enquiry should be made concerning previous
Children weighing 40kg and over should be dosed according to the adult recommendations. hypersensitivity reactions to penicillins, cephalosporins, or other allergens.
- If an allergic reaction occurs, co-amoxiclav therapy should be discontinued and appropriate
The lower dose is recommended for infections such as skin and soft tissue and recurrent tonsillitis. alternative therapy instituted. Serious anaphylactoid reactions require immediate emergency
The higher dose is recommended for infections such as otitis media, sinusitis, lower respiratory treatment with adrenaline. Oxygen, intravenous steroids and airway management, including
tract infections and urinary tract infections. intubation may also be required.
- Co-amoxiclav should be avoided if infectious mononucleosis is suspected since the occurrence
Infants of a morbilliform rash has been associated with this condition following the use of amoxicillin.
Every Eight hours in divided doses - Prolonged use may also occasionally result in overgrowth of non- susceptible organisms.
AMCLAV 62.5mg/mL drops - In general co-amoxiclav is well tolerated and possesses the characteristic low toxicity of the
Recommended dose
25 mg/kg/day penicillin group of antibiotics. Periodic assessment of organ system functions, including renal,
In serious infections dose may be doubled up to 50 mg/kg/day hepatic and haematopoietic function is advisable during prolonged therapy.
- Abnormal prolongation of prothrombin time (increased INR) has been reported rarely in patients
AMCLAV (Co-amoxiclav) Drops should be administered using the supplied dropper. The dropper receiving amoxicillin-clavulanate and oral anticoagulants. Appropriate monitoring should be
has markings which correspond to the required volume of the dose. The dose should be withdrawn undertaken when anticoagulants are prescribed concurrently. Adjustments in the dose of oral
to corresponding volume marked on the dropper. A similar dose should be administered once every anticoagulants ma y be necessary to maintain the desired level of anticoagulation.
eight hours. For information, the volumes of AMCLAV (Co-amoxiclav) Drops which correspond - Co-amoxiclav should be used with caution in patients with evidence of hepatic dysfunction.
to the weight markings are shown below: - In patients with renal insufficency, dosage should be adjusted according to the degree of
impairment.
Weight Volume (mL) of Weight Volume (mL) of - In patients with reduced urine output crystalluria has been observed very rarely, predominantly
(kg) AMCLAV Drops (kg) AMCLAV Drops 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
1 0.13 6 0.80 crystalluria.
1.5 0.20 6.5 0.87
Pregnancy
2 0.27 7 0.93 Co-amoxiclav should be used during pregnancy only if the potential benefit justifies the potential
2.5 0.33 7.5 1.00 risk to the fetus.
3 0.40 8 1.07 Nursing Mothers
3.5 0.47 8.5 1.14 Co-amoxiclav may be administered during the period of lactation. With the exception of the risk
of sensitization, associated with the excretion of trace quantities in breast milk, there are no
4 0.53 9 1.20 detrimental effects for the breast-fed infant.
4.5 0.60 9.5 1.27
DRUG INTERACTIONS
5 0.67 10 1.34 - Concomitant use of probenecid is not recommended. Probenecid decreases the renal tubular
5.5 0.73 secretion of amoxicillin. Concomitant use with Co-amoxiclav may result in increased and
prolonged blood levels of amoxicillin, but not of clavulanic acid.
Duration of therapy should be appropriate to the indication and should not be extended beyond - Concomitant use of allopurinol during treatment with amoxicillin can increase the likelihood of
14 days without review. allergic skin reactions.
- In common with other antibiotics, Co-amoxiclav may affect the gut flora, leadingto lower estrogen
Renal Insufficiency reabsorption and reduced efficacy of combined oral contraceptives.
Adults
Creatinine Clearance greater than 30mL/min STORAGE
No adjustment necessary Store at 25°C (Excursions permitted between 15°C to 30°C).
Creatinine Clearance 10 to 30mL/min Protect from sunlight & moisture.
1 tablet of AMCLAV 625mg taken twice daily or 1 to 2 tablets of AMCLAV 375mg, depending upon The expiration date refers to the product correctly stored at the required conditions.
severity of infection,taken twice daily.
Creatinine Clearance less than 10mL/min HOW SUPPLIED
1 tablet of AMCLAV 625mg given once daily or 1 to 2 tablets of AMCLAV 375mg , depending upon 1. AMCLAV (Co-amoxiclav) Tablets375mg are available in bottle of 6’s.
severity of infection, taken once daily. 2. AMCLAV (Co-amoxiclav) Tablets 625mg are available inbottle of 6’s.
3. AMCLAV (Co-amoxiclav) Tablets 1g are available in bottle of 6’s.
Children 4. AMCLAV (Co-amoxiclav) Suspension 156.25mg/5mL is available in bottle of 60mL.
Creatinine Clearance greater than 30mL/min 5. AMCL AV-DS (Co-amoxiclav) Suspension 312.5mg/5mL is available in bottle of 60mL.
No adjustment necessary 6. AMCLAV-PLUS (Co-amoxiclav) Suspension 457mg/5mL is available in bottle of 70mL.
Creatinine Clearance 10 to 30mL/min 7. AMCLAV (Co-amoxiclav) Drops 62.5mg/mL is available in bottle of 20mL.
15mg/3.75mg/kg taken twice daily.
Creatinine Clearance less than 10ml/min Keep out of reach of children.
15mg/3.75mg/kg taken as a single daily dose.
To be sold on prescription of a registered medical practitioner only.
Infants
Creatinine Clearance greater than 30mL/min:
No adjustment necessary.
Creatinine Clearance 10 to 30mL/min: Please read the contents carefully before use.
The recommended dose mentioned in table above, given twice daily instead of three times per
day*. This package insert is continually updated from time to time.
Creatinine Clearance less than 10mL/min:
The recommended dose mentioned in table above, given once daily instead of three times per
day*.

*In more serious cases this dose may be doubled.

Hemodialysis
Adults
1 tablet of AMCLAV 625mg or 2 tablets of AMCLAV 375mg taken every 24 hours, plus one dose
during dialysis, to be repeated at the end of dialysis (as serum concentrations of both amoxicillin
and clavulanic acid are decreased).
The AMCLAV 1g should only be used in patients with a creatinine clearance of more than 30mL/min.

Children
15mg/3.75mg/kg/day given as a single daily dose. Prior to haemodialysis one additional dose of
15mg/3.75mg/kg should be administered. In order to restore circulating drug levels, another dose
of 15mg/3.75mg/kg should be administered after hemodialysis.

Hepatic Insufficiency
Caution should be taken while dosing and monitoring of hepatic function at regular interval is very
necessary. Manufactured by:
CSH Pharmaceuticals (Pvt.) Ltd.
Direction for reconstitution: 32-KM, Ferozepur Road, Lahore.
Add a little amount of previously boiled and cooled water. Invert bottle and shake until powder is
dispersed. Then add more water upto the mark on the label.
The reconstituted suspension can be used within 7 days when stored in refrigerator.

ADVERSE REACTIONS Manufactured for:

Common: Mucocutaneous candidiasis, nausea, vomiting.

Uncommon: Dizziness, headache, Skin rash, pruritus, urticaria.