Amoxil Amoxicillin Trihydrate Capsules and Suspension

AMOXIL™

Amoxicillin

 

QUALITATIVE AND QUANTITATIVE COMPOSITION

AMOXIL Capsules 250 mg: Each capsule contains amoxicillin 250 mg as Amoxicillin Trihydrate.

AMOXIL Capsules 500 mg: Each capsule contains amoxicillin 500 mg as Amoxicillin Trihydrate.

AMOXIL oral suspension 125 mg/5 ml: Each 5m1 after reconstitution contains amoxicillin 125 mg as Amoxicillin Trihydrate.

 

PHARMACEUTICAL FORM

AMOXIL Capsules 250 & 500 mg: Hard gelatin capsules filled with almost white granular powder.

AMOXIL oral suspension 125 mg/5 ml: Off white free flowing granular powder.

 

CLINICAL PARTICULARS

Indications

AMOXIL should be used in accordance with local official antibiotic-prescribing guidelines and local susceptibility data.

AMOXIL is a broad spectrum antibiotic indicated for the treatment of commonly occurring bacterial infections such as:

• Upper respiratory tract infections e.g. ear, nose and throat infections, otitis media

• Lower respiratory tract infections e.g. acute exacerbations of chronic bronchitis, lobar and bronchopneumonia

• Gastrointestinal tract infections e.g. typhoid and parathyroid fever

• Genito-urinary tract infections e.g. cystitis, urethritis, pyelonephritis, bacteriuria in pregnancy, septic abortion, puerperal sepsis

• Other infections including Borreliosis (Borrelia burgdorferi) (Lyme disease)

• Skin and soft tissue infections

• Billiary tract infections

• Bone infections

• Pelvic infections

• Gonorrhoea (non-penicillinase producing strains)

• Septicaemia

• Endocarditis

• Meningitis

• Peritonitis

• Dental abscess (as an adjunct to surgical management)

• Helicobacterpylori eradication in peptic (duodenal and gastric) ulcer disease.

Infections such as septicaemia, endocarditis and meningitis due to susceptible organisms should be treated initially with high doses of a parenteral therapy and, where appropriate, in combination with another antibiotic.

Prophylaxis of endocarditis: AMOXIL may be used for the prevention of bacteraemia associated with procedures such as dental extraction, in patients at risk of developing endocarditis (see Table in Dosage and Administration).

Susceptibility to amoxicillin will vary with geography and time and local susceptibility data should be consulted where available and microbiological sampling and susceptibility testing performed where necessary (see Pharmacodynamics).

 

Dosage and Administration

Adults and children over 40 kg

Standard adult dosage: 250 mg 3 times daily, increasing to 500 mg 3 times daily for more severe infections.

High dosage therapy (maximum recommended oral dosage 6 g daily in divided doses): A dosage of 3 g twice daily is recommended in appropriate cases for the treatment of severe or recurrent purulent infection of the respiratory tract.

Short course therapy: Simple acute urinary tract infection: Two 3 g doses with 10 to 12 hours between the doses. Dental abscess: two 3 g doses with 8 hours between the doses. Gonorrhoea: single 3 g dose.

AMOXIL Eradication of H. Pylori: amoxicillin 750 mg to 1 g twice daily in combination with a proton pump inhibitor (e.g. omeprazole, lansoprazole) and another antibiotic (e.g. clarithromycin, metronidazole) for 7 days.

 

Children under 40 kg

Standard children’s dosage: 125 mg 3 times daily, increasing to 250 mg 3 times daily for more severe infections.

AMOXIL Paediatric Suspension is recommended for children under 6 months of age. Acute otitis media: 750 mg twice a day for 2 days may be used as an alternative course of treatment.

 

Patients with renal impairment

In renal impairment the excretion of the antibiotic will be delayed and, depending on the degree of impairment, it may be necessary to reduce the total daily dosage according to the following scheme:

 

Adults and Children over 40 kg

Mild impairment (creatinine clearance greater than 30 ml/min) – No change in dosage.

Moderate impairment (creatinine clearance 10 to 30 ml/min) – 500 mg twice a day maximum.

Severe impairment (creatinine clearance less than 10 ml/min) – 500 mg/day maximum.

 

Children under 40 kg

Mild impairment (creatinine clearance greater than 30 ml/min) – No change in dosage.

Moderate impairment (creatinine clearance 10 to 30 ml/min) – 15 mg/kg twice a day (maximum 500 mg/twice daily).

Severe impairment (creatinine clearance less than 10 ml/min) – 15 mg/kg once a day (maximum 500 mg).

 

Patients receiving peritoneal dialysis

Amoxicillin maximum 500 mg/day. Dosing as for patients with severe renal impairment (creatinine clearance less than 10 ml/min). Amoxicillin is not removed by peritoneal dialysis.

 

Patients receiving haemodialysis

Dosing as for patients with severe renal impairment (creatinine clearance less than 10 ml/min). Amoxicillin is removed from the circulation by haemodialysis. Therefore, 1 additional dose (500 mg for adults or 15 mg/kg for children under 40 kg) may be administered during dialysis and at the end of each dialysis.

Prophylaxis of endocarditis: see table below.

 

Prophylaxis of endocarditis

AMOXIL is given twice within 1 month, emergence of resistant streptococci is unlikely to be a problem.

Alternative antibiotics are recommended if more frequent prophylaxis is required, or if the patient has received a course of treatment with penicillin during the previous month.
Note 2.

To minimise pain on injection, AMOXIL may be given as 2 injections of 500mg dissolved in sterile 1% lignocaine solution.

Condition   Adults’ Dosage (Including Elderly) Children’s Dosage Notes
Dental procedures: Prophylaxis for patients undergoing extraction, scaling or surgery involving gingival tissues and who have not received a penicillin in the previous month (N.B. Patients with prosthetic heart valves should be referred to hospital- see below).

 

 

 

Patient not having general anaesthetic. 3 g AMOXIL orally, 1 hour before procedure. A second dose may be given 6 hours later, if considered necessary.

 

Under 10 years: half adult dose.

Under 5 years:
quarter adult dose.

The use of AMOXIL 500 mg Dispersible Tablets or 750 mg Sachets SF is recommended.

 

Note 1.

If prophylaxis with AMOXIL is given twice within 1 month, emergence of streptococci is unlikely to be a problem.

Alternative antibiotics are recommended if more frequent prophylaxis is required, or if the patient has received a course of treatment with penicillin during the previous month.

Note 2

To minimize pain on injection, AMOXIL may be given as 2 injections of 500 mg dissolved in sterile 1% lignocaine solution.

Patient having general anaesthetic: if oral antibiotics are considered to be appropriate. Initially 3 g AMOXIL orally 4 hours prior to anaesthesia, followed by 3 g orally (or 1g IV or IM if oral dose not tolerated) as soon as possible after the operation.
Patient having general anaesthetic: if oral antibiotics not appropriate 1 g AMOXIL IV or IM immediately before induction; with 500 mg orally, 6 hours later.
Dental procedures:
Patients for whom referral to hospital is recommended:
a) Patients to be given a general anaesthetic who have been given penicillin in the previous month.
b) Patients to be given a general anaesthetic who have a prosthetic heart valve.
c) Patients who have had one or more attacks of endocarditis.
Initially: 1g AMOXIL IV or IM with 120 mg gentamicin IV or IM immediately prior to anaesthesia (if given) or 15 minutes prior to dental procedure. Followed by (6 hours later): 500 mg
AMOXIL orally.
Under 10 years: the doses of AMOXIL should be half the adult dose; the dose of gentamicin should be 2 mg/kg. See Note 2. Note 3. AMOXIL and gentamicin should not be mixed in the same syringe.
Note 4. Please consult the appropriate data sheet for full prescribing information on gentamicin.
Genitourinary Surgery or Instrumentation:
Prophylaxis for patients who have no urinary tract infection and who are to have genito-urinary surgery or instrumentation under general anaesthesia.
Obstetric and Gynaecological Procedures and Gastrointestinal Procedures: Routine prophylaxis is recommended only for patients with prosthetic heart valves
Initially: 1 g AMOXIL IV or IM with 120 mg gentamicin IV or IM, immediately before induction, Followed by (6 hours later): 500 mg AMOXIL orally or IV or IM according to clinical condition Under 10 years: the doses of AMOXIL should be half the adult dose; the dose of gentamicin should be 2 mg/kg.
Under 5years: the doses of AMOXIL should be quarter the adult dose; the dose of gentamicin should be 2 mg/kg.
See Notes 2, 3 and 4 above.
Surgery or Instrumentation of the Upper Respiratory Tract Patients other than those with prosthetic heart valves. 1 g AMOXIL IV or IM immediately before induction; 500 mg AMOXIL IV or IM 6 hours later. Under 10 years: half adult dose.
Under 5 years: quarter adult dose.
See Note 2 above.
Note 5.
The second dose of AMOXIL may be administered orally as AMOXIL suspension sucrose free.
  Patients with prosthetic heart valves. Initially: 1 g AMOXIL IV or IM with 120mg gentamicin IV or IM, immediately before induction; followed by (6 hours later) 500 mg AMOXIL IV or IM. Under 10 years: the dose of AMOXIL should be half the adult dose; the gentamicin dose should be 2 mg/kg. Under 5 years: the dose of AMOXIL should be quarter the adult dose; the dose of gentamicin should be 2 mg/kg. See Notes 2, 3, 4 and 5 above.

Parenteral therapy is indicated if the oral route is considered impracticable or unsuitable, and particularly for the urgent treatment of severe infection.

 

Contraindications

Amoxicillin is a penicillin and should not be given to patients with a history of hypersensitivity to beta-lactam antibiotics (e.g. penicillins, cephalosporins).

 

Warnings and Precautions

Before initiating therapy with AMOXIL, careful enquiry should be made concerning previous hypersensitivity reactions to penicillins or cephalosporins. 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 hypersensitivity to beta lactam antibiotics (see Contraindications). If an allergic reaction occurs, amoxicillin should be discontinued and appropriate alternative therapy instituted. Serious anaphylactic reactions may require immediate emergency treatment with adrenaline. Oxygen, intravenous steroids and airway management, including intubation, may also be required.

Amoxicillin should be avoided if infectious mononucleosis is suspected since the occurrence of a morbilliform rash has been associated with this condition following the use of amoxicillin.

Prolonged use may also occasionally result in overgrowth of non-susceptible organisms.

Pseudomembranous colitis has been reported with the use of antibiotics and may range in severity from mild to life-threatening. Therefore, it is important to consider its diagnosis in patients who develop diarrhoea during or after antibiotic use. If prolonged or significant diarrhoea occurs or the patient experiences abdominal cramps, treatment should be discontinued immediately and the patient investigated further.

Dosage should be adjusted in patients with renal impairment (see Dosage and Administration).

In patients with reduced urine output, crystalluria has been observed very rarely, predominantly with parenteral therapy. During the 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 crystalluria (see Overdose).

Abnormal prolongation of prothrombin time (increased INR) has been reported rarely in patients receiving AMOXIL and oral anticoagulants. Appropriate monitoring should be undertaken when anticoagulants are prescribed concurrently. Adjustments in the dose of oral anticoagulants may be necessary to maintain the desired level of anticoagulation.

AMOXIL suspensions contain sodium benzoate which is a mild irritant to the skin, eyes and mucus membrane. It may increase the risk of jaundice in newborn babies.

AMOXIL suspensions may contain aspartame which is a source of phenylalanine and so should be used with caution in patients with phenylketonuria.

AMOXIL suspensions may contain sorbitol. If you have been told by your doctor that you have an intolerance to some sugars, contact your doctor before taking this medicinal product.

 

Interactions

Probenecid decreases the renal tubular secretion of amoxicillin. Concomitant use with AMOXIL may result in increased and prolonged blood levels of amoxicillin.

In common with other antibiotics, AMOXIL may affect the gut flora, leading to lower oestrogen reabsorption and reduced efficacy of combined oral contraceptives.

Concurrent administration of allopurinol during treatment with amoxicillin can increase the likelihood of allergic skin reactions.

It is recommended that when testing for the presence of glucose in urine during AMOXIL treatment, enzymatic glucose oxidase methods should be used. Due to the high urinary concentrations of amoxicillin, false positive readings are common with chemical methods.

In the literature there are rare cases of increased international normalised ratio in patients maintained on acenocoumarol or warfarin and prescribed a course of amoxicillin. If co-administration is necessary, the prothrombin time or international normalised ratio should be carefully monitored with the addition or withdrawal of AMOXIL.

 

Pregnancy and Lactation

Pregnancy: The safety of this medicinal product for use in human pregnancy has not been established by well controlled studies in pregnant women. Reproduction studies have been performed in mice and rats at doses of up to 10 times the human dose and these studies have revealed no evidence of impaired fertility or harm to the foetus due to amoxicillin. AMOXIL may be used in pregnancy when the potential benefits outweigh the potential risks associated with treatment.

Lactation: AMOXIL may be given during lactation. With the exception of the risk of sensitisation associated with the excretion of trace quantities of amoxicillin in breast milk, there are no known detrimental effects for the breast-fed infant.

 

Effects on Ability to Drive and Use Machines

Adverse effects on the ability to drive or operate machinery have not been observed.

Adverse Reactions

The following convention has been utilised for the classification of undesirable effects: Very common (≥1/10); common (≥1/100 to <1/10); uncommon (≥1/1000 to <1/100); rare (≥1/10,000 to <1/1,000); Very rare (≤1/10,000).

The majority of the side-effects listed below are not unique to AMOXIL and may occur when using other penicillins.

Unless otherwise stated, the frequency of adverse events (AEs) has been derived from more than 30 years of post-marketing reports.

 

Blood and lymphatic system disorders

Very rare: Reversible leucopenia (including severe neutropenia or agranulocytosis), reversible thrombocytopenia and haemolytic anaemia.

Prolongation of bleeding time and prothrombin time.

 

Immune system disorders

Very rare: As with other antibiotics, severe allergic reactions, including angioneurotic oedema, anaphylaxis (see Warnings and Precautions), serum sickness and hypersensitivity vasculitis.

If a hypersensitivity reaction is reported, the treatment must be discontinued (see also Skin and subcutaneous tissue disorders).

 

Nervous system disorders

Very rare: Hyperkinesia, dizziness and convulsions. Convulsions may occur in patients with impaired renal function or in those receiving high doses.

 

Infections and Infestations

Very rare: Mucocutaneous candidiasis.

 

Gastrointestinal disorders

#Common: Diarrhoea and nausea.

#Uncommon: Vomiting.

Very rare: Antibiotic associated colitis (including pseudomembraneous colitis and haemorrhagic colitis see Warnings and Precautions).

Black hairy tongue.

Superficial tooth discolouration has been reported in children. Good oral hygiene may help to prevent tooth discolouration as it can usually be removed by brushing (for suspension formulations only).

 

Hepatobiliary disorders

Very rare: Hepatitis and cholestatic jaundice. A moderate rise in AST and/or ALT. The significance of a rise in AST and/or ALT is unclear.

 

Skin and subcutaneous tissue disorders

#Common: Skin rash.

#Uncommon: Urticaria and pruritus.

Very rare: Skin reactions such as erythema multiforme, Stevens-Johnson Syndrome, toxic epidermal necrolysis, bullous and exfoliative dermatitis and acute generalised exanthematous pustulosis (AGEP). (See also Immune system disorders).

 

Renal and urinary tract disorders

Very rare: Interstitial nephritis, crystalluria (see Overdose).

#The incidence of these AEs was derived from clinical studies involving a total of approximately 6,000 adult and paediatric patients taking amoxicillin.

Overdose: Gastrointestinal effects such as nausea, vomiting and diarrhoea may be evident and symptoms of water/electrolyte balance should be treated symptomatically.

Amoxicillin crystalluria, in some cases leading to renal failure, has been observed (see Warnings and Precautions).

AMOXIL can be removed from the circulation by hemodialysis.

 

PHARMACOLOGICAL PROPERTIES

Pharmacodynamics: Amoxicillin is a semi-synthetic aminopenicillin of the beta-lactam group of antibiotics. It has a broad spectrum of antibacterial activity against many Gram-positive and Gram-negative micro-organisms, acting through the inhibition of biosynthesis of cell wall mucopeptide. Amoxicillin is, however, susceptible to degradation by beta-lactamases and therefore the spectrum of activity does not include organisms which produce these enzymes including resistant staphylococci, and all strains of Pseudomonas, Kiebsiella and Enterobacter. It is rapidly bactericidal and possesses the safety profile of penicillin.

The prevalence of acquired resistance is geographically and time dependent and for select species may be very high. Local information on resistance is desirable, particularly when treating severe infections.

 

In vitro susceptibility of micro-organisms to Amoxicillin

Where clinical efficacy of amoxicillin has been demonstrated in clinical trials this is indicated with an asterisk (*).

†Natural intermediate susceptibility in the absence of acquired mechanism of resistance.

 

Commonly Susceptible Species

Gram-positive aerobes:

Bacillus anthracis

Beta -hemolytic streptococci*

Enterococcus faecalis*

Listeria monocytogenes

Gram-negative aerobes:

Bordetella pertussis

 

Other:

Leptospira icterohaemorrhagiae

Treponema pallidum

 

Species for which acquired resistance may be a problem

Gram-negative aerobes:

Escherichia coli*

Shigella spp.

Haemophilus intluenzae *

Neisseria gonorrhoeae *

Helicobacter pylori*

Pasteurella spp.

Proteus mirabilis *

Vibrio cholerae

Salmonella spp.

 

Gram-positive aerobes:

Coagulase negative staphylococcus *

Streptococcus pneumoniae *

Corynebacterium spp.

Viridans group streptococcus*

Staphylococcus aureus *

 

Gram-positive anaerobes:

Clostridium spp.

 

Gram-negative anaerobes:

Fusobacterium spp.

 

Other:

Borrelia burgdorferi

 

Inherently resistant organisms

Gram-positive aerobes:

Enterococcus faecium

 

Gram-negative aerobes:

Acinetobacter spp.

Klebsiella spp.

Enterobacter spp.

Pseudomonas spp.

 

Gram-negative anaerobes:

Bacteroides spp. (many strains of Bacteroides fragilis are resistant).

 

Others:
Chlamydia spp.

Legionella spp.

Mycoplasma spp.

 

Pharmacokinetics

Amoxicillin is well absorbed. Oral administration, usually at convenient three times a day dosage, produces high serum levels independent of the time at which food is taken.

Amoxicillin gives good penetration into bronchial secretions and high urinary concentrations of unchanged antibiotic.

Amoxicillin is not highly protein bound; approximately 18% of total plasma drug content is bound to protein. Amoxicillin diffuses readily into most body tissues and fluids, with the exception of the brain and spinal fluid. Inflammation generally increases the permeability of the meninges to penicillins and this may apply to amoxicillin.

The major route of elimination for amoxicillin is via the kidney. Approximately 60 to 70% of amoxicillin is excreted unchanged in urine during the first six hours after administration of a standard dose. The elimination half-life is approximately one hour.

Amoxicillin is also partly excreted in the urine as the inactive penicilloic acid in quantities equivalent to 10 to 25% of the initial dose.

Concurrent administration of probenecid delays amoxicillin excretion. Small amounts of the drug are also excreted in faeces and bile.

 

PHARMACEUTICAL PARTICULARS

List of excipients

AMOXIL Capsules 250 & 500 mg: Colloidal Anhydrous Silica, Magnesium Stearate, Hard Empty Gelatin Capsule.

AMOXIL oral suspension 125 mg/5 ml: Silicon Dioxide, Disodium Edetate, Sodium Benzoate, Xanthan gum, Colloidal Anhydrous Silica, Quinoline Yellow Supra, Peach Dry Flavour, Strawberry Dry Flavour, Lemon Dry Flavour, Sorbitol.

 

Special Precautions for Storage

AMOXIL Capsules 250 mg and 500 mg: Store in a dry place below 25°C

AMOXIL oral suspension 125 mg/5 ml: Store in a dry place below 25°C. Keep the bottle tightly closed and use within 7 days of reconstitution.

 

Shelf-Life

The expiry date is indicated on the packaging.

 

Nature and contents of container

AMOXIL Capsules 250 mg and 500 mg: Tropical blister and Alu/Alu

AMOXIL oral suspension 125 mg/5 ml: Bottles

 

Instructions for Use and Handling

Directions for making up the suspension:

• Check cap seal is intact before use.

• Invert and shake bottle to loosen powder.

• Fill the bottle with boiled and cooled water to just below the mark on the label. Invert and shake well, then top up with boiled and cooled water to the mark on the label. Invert and shake again.

• Shake well before taking each dose.

 

KEEP OUT OF REACH OF CHILDREN

 

Not all presentations are available in every country.

 

Version number: 04 GA

Version date: 19 NOVEMBER 2014

 

AMOXIL is a trademark of the GlaxoSmithKline group of companies.

© 2014 GlaxoSmithKline

 

Manufactured under licence by

MEDREICH LIMITED

Bangalore, INDIA.

Koact Co amoxiclav Tablets

KOACT

Co-amoxiclav Tablets BP 250-125 mg, 500-125 mg and 875-125 mg

Rx Only

 

NAME OF DRUG PRODUCT

Co-amoxiclav Tablets BP 250-125 mg

Co-amoxiclav Tablets BP 500-125 mg

Co-amoxiclav Tablets BP 875-125 mg

 

(TRADE) NAME OF PRODUCT

KOACT 375

KOACT 625

KOACT 1000

 

STRENGTH

375 mg, 625 mg and 1000 mg.

 

PHARMACEUTICAL DOSAGE FORM

Tablet

 

QUALITATIVE AND QUANTITATIVE COMPOSITIONS

Co-amoxiclav Tablets BP 375 mg

Each film-coated tablet contains:

Amoxicillin Trihydrate Ph.Eur. equivalent to Amoxicillin 250 mg and Potassium

Clavulanate Ph.Eur. equivalent to Clavulanic Acid 125 mg.

 

Co-amoxiclav Tablets BP 625 mg

Each film-coated tablet contains:

Amoxicillin Trihydrate Ph.Eur. equivalent to Amoxicillin 500 mg and Potassium

Clavulanate Ph.Eur. equivalent to Clavulanic Acid 125 mg.

 

Co-amoxiclav Tablets BP 1000 mg

Each film-coated tablet contains:

Amoxicillin Trihydrate Ph.Eur. equivalent to Amoxicillin 875 mg and Potassium

Clavulanate Ph.Eur. equivalent to Clavulanic Acid 125 mg.

 

PHARMACEUTICAL FORM

Co-amoxiclav Tablets BP 375 mg: White oval shaped film coated tablets, debossed with ‘A’ on one side and ‘63’ on the other side.

Co-amoxiclav Tablets BP 625 mg: White oval shaped film coated tablets, debossed with ‘A’ on one side and ‘64’ on the other side.

Co-amoxiclav Tablets BP 1000 mg: White colored capsule shaped film coated tablets, debossed with ‘A’ on one side and with a score line in between ‘6’ and ‘5’ on the other side.

 

CLINICAL PARTICULARS

Therapeutic indications

Co-amoxiclav is an antibiotic agent with a notably broad spectrum of activity against the commonly occurring bacterial pathogens in general practice and hospital. The β-lactamase inhibitory action of clavulanate extends the spectrum of amoxicillin to embrace a wider range of organisms, including many resistant to other β-lactam antibiotics.

Co-amoxiclav oral preparations are indicated for short-term treatment of bacterial infections at the following sites when amoxicillin resistant β-lactamase-producing strains are suspected as the 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), bronchopneumonia. These infections are often caused by Streptococcus pneumoniae, Haemophilus influenzae* and Moraxella catarrhalis*.

– Genito-urinary Tract and Abdominal Infections in particular cystitis (especially when recurrent or complicated – excluding prostatitis), septic abortion, pelvic or puerperal sepsis and intra-abdominal sepsis. These infections are often caused by Enterobacteriaceae* (mainly Escherichia coli*), Staphylococcus saprophyticus, Enterococcus species.*

– Skin and Soft Tissue Infections in particular cellulitis, animal bites and severe dental abscess with spreading cellulitis. These infections are often caused by Staphylococcus aureus*, Streptococcus pyogenes and Bacteroides species*.

* Some members of these species of bacteria produce b-lactamase, rendering them insensitive to amoxicillin alone.

Mixed infections caused by amoxicillin-susceptible organisms in conjunction with Co-amoxiclav-susceptible 3-lactamase-producing organisms may be treated with Co-amoxiclav. These infections should not require the addition of another antibiotic resistant to β-lactamases.

 

Posology and method of administration

Since both the 375 mg and 625 mg tablets of Co-amoxiclav contain the same amount of Clavulanic acid (125 mg, as the potassium salt), two 375mg tablets of Co-amoxiclav are not equivalent to one 625 mg tablet of Co-amoxiclav; therefore, two 375 mg tablets of Co-amoxiclav should not be substituted for one 625 mg tablet of Co-amoxiclav.

 

Adults

The usual adult dose is one 625 mg tablet of Co-amoxiclav every 12 hours or one 375 mg tablet of Co-amoxiclav every 8 hours. For more severe infections and infections of the respiratory tract, the dose should be one 1000 mg tablet of Co-amoxiclav every 12 hours or one 625 mg tablet of Co-amoxiclav every 8 hours.

Patients with impaired renal function do not generally require a reduction in dose unless the impairment is severe. Severely impaired patients with a glomerular filtration rate of <30 mL/min should not receive the 100 mg tablet. Patients with a glomerular filtration rate of 10 to 30 mL/min should receive 625 mg or 375 mg every 12 hours, depending on the severity of the infection.

Patients with a less than 10 mL/min glomerular filtration rate should receive 625 or 375 every 24 hours, depending on severity of the infection.

Hemodialysis patients should receive 625 mg or 375 mg every 24 hours, depending on severity of the infection. They should receive an additional dose both during and at the end of dialysis.

Hepatically impaired patients should be dosed with caution and hepatic function monitored at regular intervals.

 

Pediatric Patients

Pediatric patients weighing 40 kg or more should be dosed according to the adult recommendations.

Due to the different amoxicillin to Clavulanic acid ratios in the 375 mg tablet of Co-amoxiclav (250/125) versus the 250 mg chewable tablet of Co-amoxiclav (250/62.5), the 375 mg tablet of Co-amoxiclav should not be used until the pediatric patients weighs at least 40 kg or more.

 

Administration

Co-amoxiclav may be taken without regard to meals; however, absorption of clavulanate potassium is enhanced when Co-amoxiclav is administered at the start of a meal.

To minimize the potential for gastrointestinal intolerance, Co-amoxiclav should be taken at the start of a meal.

 

Contraindications

Penicillin hypersensitivity. Attention should be paid to possible cross-sensitivity with other β-lactam antibiotics, e.g. cephalosporins.

A previous history of Co-amoxiclav or penicillin-associated jaundice/hepatic dysfunction.

 

Special Warnings and Precautions for use

Changes in liver function may occur in some patients receiving Co-amoxiclav. The clinical significance of these changes is uncertain but Co-amoxiclav should be used with caution in patients with evidence of hepatic dysfunction.

Cholestatic jaundice, which may be severe, but is usually reversible, may occur rarely. Signs and symptoms may not become apparent for several weeks after treatment has ceased.

In patients with renal impairment, dosage should be adjusted according to the degree of impairment.

In patients with reduced urine output, crystalluria may occur very rarely, predominately with parenteral therapy. During the 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 crystalluria Serious and occasionally fatal hypersensitivity (anaphylactoid) reactions may occur in patients on penicillin therapy. These reactions are more likely to occur in individuals with a history of penicillin hypersensitivity.

Erythematous rashes have been associated with glandular fever in patients receiving amoxicillin.

Prolonged use may also occasionally result in overgrowth of non-susceptible organisms.

 

Interaction with other drugs and other forms of interactions

Prolongation of bleeding time and prothrombin time may occur in some patients receiving Co-amoxiclav. Co-amoxiclav should be used with care in patients on anti-coagulation therapy.

In common with other broad-spectrum antibiotics, Co-amoxiclav may reduce the efficacy of oral contraceptives and patients should be warned accordingly.

Concomitant use of allopurinol during treatment with amoxicillin can increase the likelihood of allergic skin reactions.

 

Use in pregnancy and lactation

Treatment with Co-amoxiclav may be associated with an increased risk of necrotising enterocolitis in neonates. As with all medicines, use should be avoided in pregnancy, especially during the first trimester, unless considered essential bsç the physician. Co-amoxiclav may be administered during the period of lactation. With the exception of the risk of sensitisation, associated with the excretion of trace quantities in breast milk, there are no known detrimental effects for the breast-fed infant.

 

Effects on ability to drive and use machines

None Known.

 

Undesirable effects

Side effects are uncommon and mainly of a mild and transitory nature.

 

Gastrointestinal reactions

Diarrhoea, indigestion, nausea, vomiting, and mucocu-taneous candidiasis may occur. Antibiotic-associated colitis (including pseudomembranous. colitis and haemorrhagic colitis) may occur 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 Co-amoxiclav at the start of meals.

Superficial tooth discolouration may occur rarely, mostly with the suspension. It can usually be removed by brushing.

 

Renal and urinary tract disorders

Crystalluria occurs very rarely.

 

Genito-urinary effects

Vaginal itching, soreness and discharge may occur.

 

Hepatic effects

Moderate and asymptomatic rises in AST and/or ALT and alkaline phosphatases occurs occasionally. Hepatitis and cholestatic jaundice occurs rarely. These hepatic reactions occurs more commonly with Co-amoxiclav than with other penicillins.

After Co-amoxiclav hepatic reactions occurs more frequently in males and elderly patients, particularly those over 65 years. The risk increases with duration of treatment longer than 14 days. These reactions may occur very rarely in children.

Signs and symptoms usually occur during or shortly after treatment but in some cases may not occur until several weeks after treatment has ended. Hepatic reactions are usually reversible but they may be severe and very rarely, deaths occurs.

 

Hypersensitivity reactions

Urticarial and erythematous skin rashes sometimes occur. Rarely erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis, bullous exfoliative dermatitis, acute generalised exanthematous pustulosis (AGEP), serum sickness-like syndrome and hypersensitivity vasculitis occurs. Treatment should be discontinued if one of these disorders occurs. In common with other β-lactam antibiotics angioedema and anaphylaxis occurs. Interstitial nephritis can occur rarely.

 

Haematological effects

As with other β-lactams transient leucopenia (including neutropenia and agranulocytosis), thrombocytopenia and haemolytic anaemia occurs rarely.

Prolongation of bleeding time and prothrombin time also occurs rarely.

 

CNS effects

CNS effects occurs very rarely. These include reversible hyperactivity, dizziness, headache and convulsions. Convulsions may occur with impaired renal function or in those receiving high doses.

 

Overdosage

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. Co-amoxiclav may be removed from the circulation by haemodialysis.

Amoxicillin crystalluria, in some cases leading to renal failure, may occur.

 

PHARMACOLOGICAL PROPERTIES

Pharmacokinetic properties

The pharmacokinetics of the two components of Co-amoxiclav is closely matched. Peak serum levels of both occur about one hour after oral administration. Absorption of Co-amoxiclav is optimized at the start of a meal. Both clavulanate and amoxicillin have low levels of serum binding: about 70% remains free in the serum.

Doubling the dosage of Co-amoxiclav approximately doubles the serum levels achieved.

 

Pharmacodynamic properties

Bacterial enzymes that destroy the antibiotic before it can act on the pathogen cause resistance to many antibiotics. The clavulanate in Co-amoxiclav anticipates this defence mechanism by blocking the β-lactamase enzymes, thus rendering the organisms sensitive to amoxicillin’s rapid bactericidal effect at concentrations readily attainable in the body.

Clavulanate by itself has little antibacterial activity; however, in association with amoxicillin as Co-amoxiclav, it produces an antibiotic agent of broad spectrum with wide application in hospital and general practice.

 

Gram-positive

Aerobes: Enterococcus faecalis*, Enterococcus faecium*, Streptococcus pneumonia, Streptococcus pyogenes, Streptococcus varidans, Staphylococcus aureus*, Coagulase negative staphylococci* (including Staphylococcus epidermis*), Coryne-bacterium species, Bacillus anthracis*, Listeria monocytogenes.

Anaerobes: Clostridium species, Peptococcus species, Peptostrptococcus.

 

Gram-negative

Aerobes: Haemophilus influenza*, Moraxella catarrhalis* (Branhamella catarrhalis), Escherichia coli*, Proteus mirabilis*, Proteus vulgaris*, Klebsiella species*, Salmonella species*, Shigella species*, Bordetella pertussis, Brucella species, Neisseria gonorrhoeae*, Neisseria meningitides*, Vibrio cholerae, Pasteurella multocida.

Anaerobes: Bacteroides species* including B. fragilis.
Some members of these species of bacteria produce beta-lactamase, rendering them insensitive to amoxicillin alone.

 

PHARMACEUTICAL PARTICULARS

List of Excipients

Cellulose, Microcrystalline, Purified Water, Sodium Starch Glycolate, Silica, Colloidal anhydrous, Magnesium Stearate, Opadry white, lsopropyl alcohol and Methylene chloride.

 

Incompatibilities

None.

 

Shelf-life

24 months.

 

Special precautions for storage

Store in a dry place at or below 30°C. Protect from moisture.

Keep out of the reach of children.

 

Authorisation Numbers

KOACT 375

TFDA. Reg. No: TAN 07,138 J01C AUR

NAFDAC. Reg. No: A4-3715

Zambia. Reg. No: 127/068

 

KOACT 625

TFDA. Reg. No: TAN 07, 266 J01C AUR

NAFDAC Reg. No: A4-4185

Zambia Reg. No: 127/069

 

KOACT 1000

TFDA. Reg. No: TZ 15 H 0245

Zambia Reg. No: 127/070

 

Nature and contents of container

KOACT 375, KOACT 625 and KOACT 1000: Blister of 5 tablets.

HDPE Container Pack:

KOACT 375 and KOACT 625: 100 and 500 tablets.

KOACT 1000: 60 Tablets.

 

MARKETING AUTHORIZATION HOLDER

Aurobindo Pharma Ltd.,

Plot No.: 2, Maitrivihar,

Ameerpet, Hyderabad-500 038,

Telangana State, India.

 

DATE OF PREPARATION OF THIS LEAFLET

April 2016.

Rotexmedica Oxytocin Injection BP

OXYTOCINE INJECTION BP

 

Presentation

OXYTOCIN INJECTION BP is available in ampoules containing 3 IU (5.00 µg/ml Oxytocin BP with an activity of 600 units per mg) and 10 IU/ml of 600 units per mg), 5 IU/ml (8.33µg/ml) and 10 IU/ml (16.66 µg/m/). Other ingredients: Sodium chloride, acetic acid, sodium acetate, Water for injections.

 

Uses

Principal action

The active principle of OXYTOCIN INJECTION BP is a synthetic nonapeptide identical with Oxytocin, a hormone released by the posterior lobe of the pituitary. It exerts a stimulatory effect on the smooth musculature of the uterus, particularly towards the end of pregnancy, during labour, after delivery, and in the puerperium, i.e. at times when the number of specific oxytocin receptors in the myometrium is increased.

When given by low-dose intravenous infusion, OXYTOCIN INJECTION BP elicits rhythmic uterine contractions that are indistinguishable in frequency, force, and duration from those observed during spontaneous labour. At higher infusion dosages, or when given by single injection, the drug is capable of causing sustained uterine contractions.

Being synthetic, OXYTOCIN INJECTION BP does not contain vasopressin, but even in its pure form oxytocin possesses some weak intrinsic vasopressin-like antidiuretic activity. Another pharmacoIogical effect observed with high doses of oxytocin, particularly when administered by rapid intravenous bolus injection, consists in a transient direct relaxing effect on vascular smooth muscle, resulting in brief hypotension, flushing, and reflex tachycardia.

 

Indications

OXYTOCIN INJECTION BP may be used for: Induction of labour for medical reasons; stimulation of labour in hypotonic uterine inertia; during caesarian section following the delivery of the child; prevention and treatment of postpartum uterine atony and haemorrhage. OXYTOCIN INJECTION BP may also be indicated in early stages of pregnancy as an adjunctive therapy for the management of incomplete, inevitable or missed abortion.

 

Dosage and administration

Induction or enhancement of labour

OXYTOCIN INJECTION BP should be administered as an intravenous drip infusion or, preferably, by means of a variable-speed infusion pump. For drip infusion it is recommended that 10 IU of OXYTOCIN INJECTION BP be added to 1/ of a physiologic electrolyte solution. For patients in whom infusion of sodium chloride must be avoided, 5% dextrose solution may be used as the diluent (see ‘Precautions’). To ensure even mixing, the bottle or bag must be turned upside down several times before use. The initial infusion rate should be set at 1- 4 mU/min (2-8 drops/min) It may be gradually increased at intervals not shorter than 20 min, until a contraction pattern similar to that of normal labour is established. In pregnancy near term this can often be achieved with an infusion of less than 10 mU/min (20 drops/min), and the recommended maximum rate is 20 mU/min (40 drops/min). In the unusual event that higher rates are required, as may occur in the management of foetal death in utero or for induction of labour at an earlier stage of pregnancy, when the uterus is less sensitive to oxytocin, it is advisable to use a more concentrated OXYTOCIN INJECTION BP solution, e.g. 10 IU in 500 ml.

When using a motor-driven infusion pump which delivers smaller volumes than those given by drip infusion, the concentration suitable for infusion within the recommended dosage range must be calculated according to the specifications of the pump.

The frequency, strength, and duration of contractions as well as the foetal heart rate must be carefully monitored throughout the infusion. Once an adequate level of uterine activity is attained, the infusion rate can often be reduced. In the event of uterine hyperactivity and/or foetal distress,the infusion must be discontinued
immediately.

If, in women who are at term or near term, regular contractions are not established after the infusion of a total amount of 5 IU, it is recommended that the attempt to induce labour be ceased; it may be repeated on the following day, starting again from a rate of 1-4 mU/min.

 

Caesarean section

5 IU by slow intravenous injection immediately after delivery.

 

Prevention of postpartum Uterine haemorrhage

The usual dose is 5 IU slowly i.v. after delivery of the placenta. In women given OXYTOCIN INJECTION BP for induction or enhancement of labour, the infusion should be continued at an increased rate during the third stage of labour and for the next few hours thereafter.

 

Treatment of postpartum uterine haemorrhage

5- 10 IU i.m. or 5 IU slowly i.v., followed in severe cases by intravenous infusion of a solution containing 5-20 IU of oxytocin in 500 ml of a non-hydrating diluent, run at the rate necessary to control uterine atony.

 

Incomplete, inevitable, or missed abortion

5 IU i.m. or slowly i.v., if necessary followed by intravenous infusion at a rate of 20-40 mU/min or higher.

 

Contraindications, warnings, etc.

Contraindications

Hypersensitivitv to the drug, Hypertonic uterine contractions, mechanical obstruction to delivery, foetal distress. Any condition in which for foetal or maternal reasons spontaneous labour is inadvisable and/or vaginal delivery is contraindicated: e.g. significant cephalopelvic disproportion, foetal malpresentation; placenta praevia and vasa praeyia, placental abruption, cord presentation or prolapse, overdistension or impaired resistance of the uterus to rupture as in multiple pregnancy, polyhydramnios, grand multiparity and in the presence of a uterine scar resulting from major surgery including classical caesarean section.

OXYTOCIN LNJECTION BP should not be used for prolonged periods in patients with oxytocinresistant uterine inertia, severe pre-eclamptic toxaemia or severe cardiovascular disorders.

 

Precautions

The induction of labour by means of oxytocin should be attempted only when strictly indicated for medical reasons. Administration should only be under hospital conditions and qualified medical supervision. When given for induction and enhancement of labour, OXYTOCIN INJECTION BP must only be administered as an intravenous infusion and never by intravenous bolus injection. Careful monitoring of foetal heart rate and uterine motility (frequency, strength, and duration of contractions) is essential, so that the dosage may be adjusted to individual response.

When OXYTOCIN INJECTION BP, is given for induction or enhancement of labour particular caution is required in the presence of borderline cephalopelvic disproportion, secondary uterine inertia, mild to moderate degrees of pregnancy-induced hypertension or cardiac disease and in patients above 35 years of age or with a history of lower-uterine-segment caesarean sections.

In the case of foetal death in utero, and/or in the presence of meconium-stained amniotic fluid, tumultuous labour must be avoided, as it may cause amniotic fluid embolism.

Because oxytocin possesses slight antidiuretic activity, its prolonged intravenous administration at high doses in conjunction with large volumes of fluid, as may be be the case in the treatment of inevitable or missed abortion, or in the management of postpartum haemorrhage, may cause water intoxication associated with hyponatraemia.

To avoid this rare complication, the following precautions must be observed whenever high doses of oxytocin are administered over a long time: an electrolyte-containing diluent must be used (not dextrose); the volume of infused fluid should be kept low (by infusing oxytocin at a higher concentration than recommended for the induction or enhancement of labour at term); fluid intake by mouth must be restricted; a fluid balance chart should be kept, and serum electrolytes should be measured when electrolyte imbalance is suspected.

When OXYTOCIN INJECTION BP, is used for prevention or treatment of uterine haemorrhage, rapid intravenous injection should be avoided, as it, may cause an acute short-lasting drop in blood pressure. Prostaglandins may potentiate the uterotonic effect of oxytocin and vice versa; therefore, concomitant administration requires very careful monitoring.

Some inhalation anaesthetics, e.g. cyclopropane or halothane, may enhance the hypotensive effect of oxytocin and reduce its oxytocic action. Their concurrent use with oxytocin has also been reported to cause cardiac rhythm disturbances.

When given during or after caudal block anaesthesia, oxytocin may potentiate the pressor effect of sympathomimetic vasoconstrictor agents.

 

Overdosage

The fatal dose of OXYTOCIN INJECTION BP has not been established. OXYTOCIN INJECTION BP is subject to inactivation by proteolytic enzymes of the alimentary tract. Hence it is not absorbed from the intestine and is not likely to have toxic effects when ingested. The symptoms and consequences of overdosage are those mentioned under ‘Side-effects’. Ln addition, as a result of uterine overstimulation, placental abruption and/or amniotic fluid embolism have been reported.

 

Treatment

When signs or symptoms of overdosage occur during continuous i.v. administration of OXYTOCIN INJECTION BP, the infusion must be discontinued at once and oxygen should be given to the mother. In cases of water intoxication it is essential to restrict fluid intake, promote diuresis, correct electrolyte imbalance, and control convulsions that may eventually occur, by judicious use of diazepam. In the case of coma, a free airway shoud be maintained with routine measures normally employed in the nursing of the unconscious patient.

 

Side effects

As there is a wide variation in uterine sensitivity, uterine spasm may be caused in some instances by what are normally considered to be low doses.

When OXYTOCIN INJECTION BP is used by i.v. infusion for the induction or enhancement of labour, its administration at too high doses results in uterine overstimulation which may cause foetal distress, asphyxia, and death, or may lead to hypertonicity, tetanic contractions, soft tissue damage or rupture of the uterus.

Water intoxication associated with maternal and neonatal hyponatraemia has been reported in cases where high doses of oxytocin together with large amounts of electrolyte-free fluid have been administered over a prolonged period of time (see ‘Precautions’). Symptoms of water intoxication include:

1. Headache, anorexia, nausea, vomiting and abdominal pain.

2. Lethargy, drowsiness, unconsciousness and grandmal type seizures.

3. Low blood electrolyte concentration.

Rapid intravenous bolus injection of oxytocin at doses amounting to several IU may result in acute short-lasting hypotension accompanied with flushing and reflex tachycardia.

Oxytocin may occasionally cause nausea, vomiting, or cardiac arrhythmias. In a few cases, skin rashes and anaphylactoid reactions associated with dyspnoea, hypotension, or shock have been reported.

 

Pharmaceutical precautions

Store between +2 oC and +8 oC. Do not freeze. Any portion of the contents remaining should be discarded. OXYTOCN INJECTION BP should not be infused via the same apparatus as blood or plasma, because the peptide linkages are rapidly inactivated by oxytocin-inactivating enzymes.

OXYTOCIN INJECTION BP is incompatible with solutions containing sodium metabisulphite as a stabiliser.

OXYTOCIN INJECTION BP is compatible with the following infusion fluids, but due attention should be paid to the advisability of using electrolyte fluids in individual patients: Dextrose 5%, Sodium/potassium chloride (103 mmol Na+ and 51 mmol K+), Laevulose 20%, Macrodex 6%, Sodium bicarbonate 1.39%, Sodium chloride 0.9%, Sodium lactate 1.72%, Rheomacrodex 10%, Ringer’s solution.

 

Date of Issue: December 2000.

 

ROTEXMEDICA GmbH

BUNSENSTRASSE 4

22946 TRITTAU/GERMANY