For Medical Professional Only

Tabs / Susp.
U.S.P. Specs.
(Co-amoxiclav)

DESCRIPTION 4. CALAMOX Suspension 156.25mg/5mL

CALAMOX (Co-amoxiclav) is an oral antibacterial combination consisting Each 5mL contains:
of the semisynthetic antibiotic amoxicillin and the β-lactamase inhibitor, Amoxicillin Trihydrate U.S.P. eq: to 125 mg Amoxicillin
Clavulanate potassium (the potassium salt of Clavulanic acid). Amoxicillin Clavulanate Potassium U.S.P. eq: to 31.25 mg Clavulanic acid
is an analog of ampicillin, derived from the basic penicillin nucleus, (Product Specs.: U.S.P.)
6-aminopenicillanic acid. The amoxicillin molecular formula is
C16H19N3O5S•3H2O. Chemically, amoxicillin is (2S,5R,6R)-6-[(R)(-)-2 5. CALAMOX-DS Suspension 312.5mg/5mL
-Amino-2-(p-hydroxyphenyl)acetamido]-3,3-dime- Each 5mL contains:
thyl-7-oxo-4-thia-1-azabicyclo[ 3.2.0]heptane-2carboxylic acid trihydrate. Amoxicillin Trihydrate U.S.P. eq: to 250 mg Amoxicillin
Clavulanate Potassium U.S.P. eq: to 62.5 mg Clavulanic acid
Clavulanic acid is produced by the fermentation of Streptomyces (Product Specs.: U.S.P.)
clavuligerus. It is a β-lactam structurally related to the penicillins and
possesses the ability to inactivate a wide variety of β-lactamases by CLINICAL PHARMACOLOGY
blocking the active sites of these enzymes. Clavulanic acid is particularly Mechanism of Action
active against the clinically important plasmid-mediated β-lactamases Amoxicillin is a semisynthetic antibiotic with a broad spectrum of
frequently responsible for transferred drug resistance to penicillins and antibacterial activity against many gram-positive and gram-negative
cephalosporins. The clavulanate potassium molecular formula is microorganisms. Amoxicillin is, however, susceptible to degradation by
C8H8KNO5. Chemically, Clavulanate potassium is potassium (Z) β-lactamases, and therefore, the spectrum of activity does not include
(2R,5R)-3-(2-hydroxyethylidene)-7-oxo-4-oxa-1-azabicyclo[3.2.0]-heptane organisms which produce these enzymes.
-2-carboxylate
Clavulanic acid is a β-lactam, structurally related to the penicillins, which
QUALITATIVE AND QUANTITATIVE COMPOSITION possesses the ability to inactivate a wide range of β-lactamase enzymes
CALAMOX (Co-amoxiclav) is available for oral administration as: commonly found in microorganisms resistant to penicillins and
cephalosporins. In particular, it has good activity against the clinically
1. CALAMOX Tablets 375 mg important plasmid-mediated β-lactamases frequently responsible for
Each Film-Coated Tablet Contains: transferred drug resistance. It is generally less effective against
Amoxicillin Trihydrate U.S.P. eq: to 250 mg Amoxicillin chromosomally-mediated type 1 β-lactamases.
Clavulanate Potassium U.S.P. eq: to 125 mg Clavulanic acid
(Product Specs.: U.S.P.) The formulation of amoxicillin and clavulanic acid in amoxicillin/clavulanate
potassium protects amoxicillin from degradation by β-lactamase enzymes
2. CALAMOX Tablets 625 mg and effectively extends the antibiotic spectrum of amoxicillin to include
Each Film-Coated Tablet Contains: many bacteria normally resistant to amoxicillin, other penicillins and
Amoxicillin Trihydrate U.S.P. eq: to 500 mg Amoxicillin cephalosporins. Thus, amoxicillin/clavulanate potassium possesses the
Clavulanate Potassium U.S.P. eq: to 125 mg Clavulanic acid distinctive properties of a broad-spectrum antibiotic and a β-lactamase
(Product Specs.: U.S.P.) inhibitor.

3. CALAMOX Tablets 1 G Microbiology

Each Film-Coated Tablet Contains: Co-amoxiclav is bactericidal to a wide range of organisms including:
Amoxicillin Trihydrate U.S.P. eq: to 875 mg Amoxicillin Gram-Positive aerobes:
Clavulanate Potassium U.S.P. eq: to 125 mg Clavulanic acid *Bacillus anthracis
(Product Specs.: U.S.P.) Corynebacterium species
*Enterococcus faecalis
*Enterococcus faecium - Acute bacterial sinusitis
*Staphylococcus aureus - Acute otitis media
*Coagulase negative staphylococci (including *Staphylococcus epidermidis) - Lower Respiratory Tract Infections e.g., acute exacerbations of chronic
Streptococcus agalactiae bronchitis, lobar and
Streptococcus pneumoniae - broncho-pneumonia.
Streptococcus pyogenes - Genito-urinary Tract Infections e.g., cystitis, urethritis, pyelonephritis,
Streptococcus species female genital infections.
Streptococcus viridians - Skin and Soft Tissue Infections e.g., boils, abscesses, cellulitis and
Gram-Negative aerobes: wound infection.
Bordetella pertussis - Bone and Joint Infections e.g., osteomyelitis.
Brucella species - Other Infections e.g., septic abortion, puerperal sepsis, intra-abdominal
*Escherichia coli sepsis, septicaemia, peritonitis, post-surgical infections.
Gardnerella vaginalis
*Haemophilus influenzae CALAMOX (Co-amoxiclav) is also indicated for prophylaxis against
*Klebsiella species infection which may be associated with major surgical procedures such as
Legionella species gastro-intestinal, pelvic, head and neck, cardiac, renal, joint replacement
*Moraxella catarrhalis (Branhamella catarrhalis) and biliary tract surgery.
*Neisseria gonorrhoeae
*Neisseria meningitidis DOSAGE AND ADMINISTRATION
Pasteurella multocida Dosage depends on the age, weight and renal function of the patient and
*Proteus mirabilis severity of the infection. CALAMOX (Co-amoxiclav) should be taken at the
*Proteus vulgaris start of a meal to enhance the absorption of amoxicillin and to minimize the
*Yersinia enterocolitica potential for gastrointestinal intolerance. Two CALAMOX 375mg tablets
Gram-Positive anaerobes: should not be substituted for one CALAMOX 625mg tablet since they are
Clostridium species not equivalent.
Peptostreptococcus species
Gram-Negative anaerobes: Adults
*Bacteroides species (including Bacteroides fragilis) Mild to moderate infections
*Fusobacterium species 1 CALAMOX 375mg tablet taken three times daily.
Others: 1 CALAMOX 625mg tablet taken two or three times daily.
Chlamydiae 1 CALAMOX 1g tablet taken twice daily.
Leptospira icterohaemorrhagiae Severe infections (Including chronic and recurrent urinary tract infections
*Some members of these species of bacteria produce beta-lactamase, and those of the lower respiratory tract).
rendering them insensitive to amoxicillin. 1 to 2 CALAMOX 625mg tablet given three times daily.
1 CALAMOX 1g tablet given two or three times daily.
Pharmacokinetics
Absorption / Distribution: Children up to 12 years
Amoxicillin and clavulanic acid are fully dissociated in aqueous solution at The usual oral recommended daily dosage is 25mg/kg/day in divided
physiological pH. Both components are rapidly and well absorbed by the doses every eight hours.
oral route of administration. Absorption of amoxicillin/clavulanate
potassium is optimised when taken at the start of a meal. Neither Under 1 year:
amoxicillin nor clavulanic acid is highly protein bound. 25mg/kg/day (for e.g a 7.5kg child would require 2mL CALAMOX
156.25mg syrup three times daily)
Metabolism / Excretion: 1-6 Years (10-15kg):
Clavulanic acid is extensively metabolised to 2,5-dihydro-4-(2 hydroxyeth- 5mL CALAMOX 156.25mg suspension three times a day.
yl)-5-oxo-1H-pyrrole-3-carboxylic acid and 1-amino-4-hydroxy -butane- Over 6 years (18-40kg):
2-one. The major route of elimination for amoxicillin is via the kidneys. It is 5mL CALAMOX-DS 312.5mg suspension three times a day.
partly excreted in the urine as penicilloic acid in quantities equivalent to Children weighing 40kg and over should be dosed according to the adult
10-25% of the initial dose, whereas for clavulanate it is by both renal and recommendations.
non-renal mechanisms. Its metabolite is eliminated in rine and feces as The lower dose is recommended for infections such as skin and soft tissue
carbon dioxide in expired air. Approximately 60-70% of the amoxicillin and and recurrent tonsillitis.
approximately 40-65% of the clavulanic acid are excreted unchanged in The higher dose is recommended for infections such as otitis media,
urine during the first 6 hours after administration amoxicillin / sinusitis, lower respiratory tract infections and urinary tract infections.
clavulanate potassium tablets.
Renal Insufficiency
THERAPEUTIC INDICATIONS Adults
CALAMOX (Co-amoxiclav) is indicated for the short term treatment of Creatinine Clearance greater than 30mL/min
bacterial infections such as: No adjustment necessary
Creatinine Clearance 10 to 30mL/min
1 tablet of CALAMOX 625mg taken twice daily or 1 to 2 tablets of exfoliative-dermatitis, acute generalised exanthemous pustulosis (AGEP).
CALAMOX 375mg, depending upon severity of infection, taken twice daily. Interstitial nephritis and crystalluria.
Creatinine Clearance less than 10mL/min
1 tablet of CALAMOX 625mg given once daily or 1 to 2 tablets of CONTRAINDICATIONS
CALAMOX 375mg , depending upon severity of infection, taken once daily. Co-amoxiclav is contraindicated in patients with;
- History of hypersensitivity to beta-lactams, e.g., penicillins and
Children cephalosporins.
Creatinine Clearance greater than 30mL/min - Previous history of amoxicillin-clavulanate-associated jaundice/hepatic
No adjustment necessary dysfunction.
Creatinine Clearance 10 to 30mL/min
15mg/3.75mg/kg taken twice daily. WARNINGS AND PRECAUTIONS
Creatinine Clearance less than 10ml/min - Before initiating therapy with co-amoxiclav, careful enquiry should be
15mg/3.75mg/kg taken as a single daily dose. made concerning previous hypersensitivity reactions to penicillins,
cephalosporins, or other allergens.
Infants - If an allergic reaction occurs, co-amoxiclav therapy should be
Creatinine Clearance greater than 30mL/min: discontinued and appropriate alternative therapy instituted. Serious
No adjustment necessary. anaphylactoid reactions require immediate emergency treatment with
Creatinine Clearance 10 to 30mL/min: adrenaline. Oxygen, intravenous steroids and airway management,
The recommended dose given twice daily instead of three times per day*. including intubation may also be required.
Creatinine Clearance less than 10mL/min: - Co-amoxiclav should be avoided if infectious mononucleosis is
The recommended dose given once daily instead of three times per day*. suspected since the occurrence of a morbilliform rash has been
*In more serious cases this dose may be doubled. associated with this condition following the use of amoxicillin.
- Prolonged use may also occasionally result in overgrowth of non-
Hemodialysis susceptible organisms.
Adults - In general co-amoxiclav is well tolerated and possesses the
1 tablet of CALAMOX 625mg or 2 tablets of CALAMOX 375mg taken every characteristic low toxicity of the penicillin group of antibiotics. Periodic
assessment of organ system functions, including renal, hepatic and
24 hours, plus one dose during dialysis, to be repeated at the end of
haematopoietic function is advisable during prolonged therapy.
dialysis (as serum concentrations of both amoxicillin and clavulanic acid
- Abnormal prolongation of prothrombin time (increased INR) has been
are decreased).
reported rarely in patients receiving amoxicillin-clavulanate and oral
The CALAMOX 1g should only be used in patients with a creatinine
anticoagulants. Appropriate monitoring should be undertaken when
clearance of more than 30mL/min.
anticoagulants are prescribed concurrently. Adjustments in the dose of
oral anticoagulants may be necessary to maintain the desired level of
Children anticoagulation.
15mg/3.75mg/kg/day given as a single daily dose. Prior to haemodialysis - Co-amoxiclav should be used with caution in patients with evidence of
one additional dose of 15mg/3.75mg/kg should be administered. In order hepatic dysfunction.
to restore circulating drug levels, another dose of 15mg/3.75mg/kg should - In patients with renal insufficency, dosage should be adjusted according
be administered after hemodialysis. to the degree of impairment.
- In patients with reduced urine output crystalluria has been observed very
Hepatic Insufficiency rarely, predominantly with parenteral therapy. During administration of
Caution should be taken while dosing and monitoring of hepatic function at high doses of amoxicillin it is advisable to maintain adequate fluid intake
regular interval is very necessary. and urinary output in order to reduce the possibility of amoxicillin
crystalluria.
ADVERSE REACTIONS
Very Common: Diarrhea Pregnancy
Common: Mucocutaneous candidiasis, nausea, vomiting. Co-amoxiclav should be used during pregnancy only if the potential benefit
Nausea is more often associated with higher oral dosages. If gastrointesti- justifies the potential risk to the fetus.
nal reactions are evident, they may be reduced by taking Co-amoxiclav at
the start of the meal. Lactation
Uncommon: Dizziness, headache, Skin rash, pruritus, urticaria. Calamox has been showed to be excreted in human milk. Caution should
Rare: Reversible Leucopenia (including neutropenia) and thrombocytope- be exercised when Calamox is administered to nursing mothers.
nia, Erythema multiforme.
Not Known: Reversible agranulocytosis and haemolytic anaemia. DRUG INTERACTIONS
Prolongation of bleeding time and prothrombin time, Angioneurotic - Concomitant use of probenecid is not recommended. Probenecid
oedema, anaphylaxis, serum sickness-like sydndrome, hypersensitivity decreases the renal tubular secretion of Amoxicillin. Concomitant use
vasculitis. Antibiotic associated colitis (including pseudomembranous with Co-amoxiclav may result in increased and prolonged blood levels of
colitis and hemorrhagic colitis). Superficial tooth discoloration which can amoxicillin, but not of clavulanic acid.
be removed usually by brushing. Hepatitis and cholestatic jaundice usually - Concomitant use of allopurinol during treatment with amoxicillin can
associated with prolonged treatment predominantly in males and elderly. increase the likelihood of allergic skin reactions.
Steven-Johnson syndrome, toxic epidermal necrolysis, bullous - In common with other antibiotics, Co-amoxiclav may affect the gut flora,
 leading to lower estrogen reabsorption and reduced efficacy of Direction for reconstitution (for Suspension):
combined oral contraceptives. Add a little amount of previously boiled and cooled water. Invert bottle and
- Concomitant administration of amoxicillin and coumarin anticoagulants, shake until powder is dispersed. Then add more water upto the mark on
such as warfarin, may increase the incidence of bleeding. the label.
The reconstituted suspension can be used within 7 days when stored in
PRESENTATION: refrigerator. Do not freeze.
Calamox Tablets 375mg: 1x6’s in Alu Alu Blister Pack.
Calamox Tablets 625mg: 1x6’s & 2x6’s in Alu Alu Blister Pack. INSTRUCTIONS:
Calamox Tablets 1000mg: 1x6’s & 2x6’s in Alu Alu Blister Pack. - Keep bottle tightly closed.
Calamox for oral Suspension: 156.25mg/5ml 60ml (after reconstitution) in - Protect from heat, sunlight & moisture, store below 25°C.
90ml Amber Glass Bottle. - The Expiration date refers to the product correctly stored at required
Calamox for oral Suspension: 156.25mg/5ml 90ml (after reconstitution) in condition.
120ml Amber Glass Bottle. - Patients and healthcare professionals can also report suspected
Calamox for oral Suspension: 312.5mg/5ml (DS) 60ml (after reconstitution) adverse drug reaction at [email protected].
in 90ml Amber Glass Bottle. - Keep out of the reach of children.
Calamox for oral Suspension: 312.5mg/5ml (DS) 90ml (after reconstitution) - To be sold on prescription of a registered medical practitioner only.
in 120ml Amber Glass Bottle.

SHELF LIFE:
Calamox Tablets & Suspension has shelf life of two Years

Manufactured by:
Bosch Pharmaceuticals (Pvt) Ltd.
221-223, Sector 23, Korangi Industrial Area,
Karachi - Pakistan