Amoxicillin for Injection 500mg Taj Pharma

  1. NAME OF THE MEDICINAL PRODUCT

Amoxicillin for Injection 500mg Taj Pharma

  1. QUALITATIVE AND QUANTITATIVE COMPOSITION

Each vial contains:
Amoxicillin sodium
Equivalent to Amoxicillin              500mg
Water for Injection                          10ml

For the full list of excipients, see section 6.1.

  1. PHARMACEUTICAL FORM

Powder for solution for injection

Vials containing a white to off-white sterile powder.

  1. CLINICAL PARTICULARS

4.1 Therapeutic indications

Amoxicillin is indicated for the treatment of the following infections in adults and children (see sections 4.2, 4.4 and 5.1):

  • Severe infections of the ear, nose and throat (such as mastoiditis, peritonsillar infections, epiglottitis, and sinusitis when accompanied by severe systemic signs and symptoms)
  • Acute exacerbations of chronic bronchitis
  • Community acquired pneumonia
  • Acute cystitis
  • Acute pyelonephritis
  • Severe dental abscess with spreading cellulitis
  • Prosthetic joint infections
  • Lyme disease
  • Bacterial meningitis
  • Bacteremia that occurs in association with, or is suspected to be associated with, any of the infections listed above

Amoxicillin is also indicated for the treatment and prophylaxis of endocarditis.

Consideration should be given to official guidance on the appropriate use of antibacterial agents.

4.2 Posology and method of administration

Posology

The dose of Amoxicillin that is selected to treat an individual infection should take into account:

  • The expected pathogens and their likely susceptibility to antibacterial agents (see section 4.4)
  • The severity and the site of the infection
  • The age, weight and renal function of the patient; as shown below

The duration of therapy should be determined by the type of infection and the response of the patient, and should generally be as short as possible. Some infections require longer periods of treatment (see section 4.4 regarding prolonged therapy).

Adults and children ≥ 40 kg

Indication* Dose*
Severe infections of the ear, nose and throat (such as mastoiditis peritonsillar infections, epiglottis and sinusitis when accompanied by severe systemic signs and symptoms 750 mg to 2 g every 8 hours, or 2 g every 12 hours, maximum of 12 g/day
Acute exacerbations of chronic bronchitis
Community acquired pneumonia
Acute cystitis
Acute pyelonephritis
Severe dental abscess with spreading cellulitis
Prosthetic joint infections 750 mg to 2 g every 8 hours, or 2 g every 12 hours, maximum of 12 g/day
Prophylaxis of endocarditis 2 g single dose 30 to 60 minutes before procedure.
Treatment of endocarditis 1 g to 2 g every 4 to 6 hours, maximum of 12 g/day
Bacterial meningitis 1 g to 2g every 4 to 6 hours, maximum of 12 g/day
Lyme disease (see section 4.4) Late stage (systemic involvement): 2 g every 8 hours
Bacteraemia that occurs in association with, or is suspected to be associated with, any of the infections listed in section 4.1 1 g to 2 g every 4, 6 or 8 hours, maximum of 12 g/day
*Consideration should be given to the official treatment guidelines for each indication.

Intramuscular

Maximum daily dosage: 4 g/day.

Maximum single dose: 1 g.

Children < 40 kg

Infants and toddlers >3 months and children < 40 kg

Indication*

Dose*
Severe infections of the ear, nose and throat (such as mastoiditis peritonsillar infections, epiglottis and sinusitis when accompanied by severe systemic signs and symptoms 20 to 200 mg/kg/day given in 2 to 4 equally divided doses of up to 25 mg/kg or infusions of up to 50 mg/kg
Community acquired pneumonia
Acute cystitis
Acute pyelonephritis
Severe dental abscess with spreading cellulitis
Prophylaxis of endocarditis 50 mg/kg single dose 30 to 60 minutes before procedure
Treatment of endocarditis 200 mg/kg/day in 3 to 4 equally divided does of up to 25 mg/kg or infusions of up to 50 mg/kg
Bacterial meningitis 100 to 200 mg/kg/day in 3 to 4 equally divided doses of up to 25 mg/kg or infusions of up to 50 mg/kg
Lyme disease (see section 4.4) Early stage: 25 to 50 mg/kg/day in three divided doses for 10 days (range 10 to 21 days)

Late stage (systemic involvement): 50 mg/kg/day in three divided doses

Bacteraemia that occurs in association with, or is suspected to be associated with, any of the infections listed in section 4.1 50 to 150 mg/kg/day given in 3 equally divided doses of up to 25 mg/kg or infusions of up to 50 mg/kg
*Consideration should be given to the official treatment guidelines for each indication.
Neonates ≥ 4kg and infants up to 3 months

Indication*

Dose*
Most infections Usual daily dose of 20 to 150 mg/kg/day given in 3 equally divided doses of up to 25 mg/kg or infusions of up to 50 mg/kg
Treatment of endocarditis 150 mg/kg/day given in 3 equally divided doses of up to 25 mg/kg or infusions of up to 50 mg/kg
Bacterial meningitis 150 mg/kg/day given in three divided doses
Lyme disease (see section 4.4) Early stage: 25 to 50 mg/kg/day in three divided doses for 10 days (range 10 to 21 days)

Late stage (systemic involvement): 50 mg/kg/day in three divided doses

Bacteraemia that occurs in association with, or is suspected to be associated with, any of the infections listed in section 4.1 Usual daily dose of 50 to 150 mg/kg/day given in 3 equally divided doses of up to 25 mg/kg or infusions of up to 50 mg/kg
*Consideration should be given to the official treatment guidelines for each indication.

 

Premature Neonates < 4kg

Indication*

Dose*
Most infections Usual daily dose of 20 to 100 mg/kg/day given in 2 equally divided doses of up to 25 mg/kg or infusions of up to 50 mg/kg
Treatment of endocarditis 100 mg/kg/day given in two divided doses
Bacterial meningitis 100 mg/kg/day given in two divided doses
Lyme disease (see section 4.4) Early stage: 25 to 50 mg/kg/day in two divided doses for 10 days (range 10 to 21 days)

Late stage (systemic involvement): 50 mg/kg/day in two divided doses

Bacteraemia that occurs in association with, or is suspected to be associated with, any of the infections listed in section 4.1 Usual daily dose of 50 to 100 mg/kg/day given in 2 equally divided doses of up to 25 mg/kg or infusions of up to 50 mg/kg
*Consideration should be given to the official treatment guidelines for each indication.

Intramuscular:

Maximum daily dosage: 120 mg/kg/day as 2 to 6 equally divided doses.

Elderly

No adjustment needed; as for adults.

Renal impairment

Adults and children ≥ 40 kg Children < 40 kg
GFR (ml/min) Intravenous Intramuscular Intravenous Intramuscular
greater than 30 No adjustment No adjustment No adjustment No adjustment
10 to 30 1g stat, then 500 mg to 1 g twice day 500 mg every 12 hours 25 mg/kg twice daily 15 mg/kg every 12 hours
less than 10 1 g stat, then 500 mg/day 500 mg/day given as a single dose 25 mg/kg/day given as a single dose 15 mg/kg/day given as a single dose

In patients receiving haemodialysis and peritoneal dialysis

Amoxicillin may be removed from the circulation by haemodialysis.

Haemodialysis Peritoneal dialysis
Intravenous Intramuscular Intravenous Intramuscular
Adults and children ≥ 40 kg 1 g at the end of dialysis, then 500 mg every 24 hours 500 mg during dialysis, 500 mg at the end, then 500 mg every 24 hours 1 g stat, then 500 mg/day 500 mg/day given as a single dose
Children < 40 kg 25 mg/kg stat and 12.5 mg/kg at the end of the dialysis, then 25 mg/kg/day 15 mg/kg during and at the end of dialysis, then 15 mg/kg every 24 hours 25 mg/kg/day given as a single dose 15 mg/kg/day given as a single dose

Method of administration

The standard recommended route of administration is by intravenous injection or intravenous infusion. Intramuscular administration should only be considered when the intravenous route is not possible or less appropriate for the patient.

Intravenous

Amoxicillin may be administered either by slow intravenous injection over a period of 3 to 4 minutes directly into a vein or via a drip tube or by infusion over 20 to 30 minutes.

Intramuscular

The maximum single dose is 1 g in adults and children ≥ 40 kg.

Do not inject more than 60 mg/kg at one time in children < 40 kg.

4.3 Contraindications

Hypersensitivity to the active substance, to any of the penicillins or to any of the excipients listed in section 6.1.

History of a severe immediate hypersensitivity reaction (e.g. anaphylaxis) to another beta-lactam agent (e.g. a cephalosporin, carbapenem or monobactam).

4.4 Special warnings and precautions for use

Hypersensitivity reactions

Before initiating therapy with amoxicillin, careful enquiry should be made concerning previous hypersensitivity reactions to penicillins, cephalosporins or other beta-lactam agents (see sections 4.3 and 4.8).

Serious and occasionally fatal hypersensitivity reactions (including anaphylactoid and severe cutaneous adverse reactions) have been reported in patients on penicillin therapy. These reactions are more likely to occur in individuals with a history of penicillin hypersensitivity and in atopic individuals. If an allergic reaction occurs, amoxicillin therapy must be discontinued and appropriate alternative therapy instituted.

Non-susceptible microorganisms

Amoxicillin is not suitable for the treatment of some types of infection unless the pathogen is already documented and known to be susceptible or there is a very high likelihood that the pathogen would be suitable for treatment with amoxicillin (see section 5.1). This particularly applies when considering the treatment of patients with urinary tract infections and severe infections of the ear, nose and throat.

Convulsions

Convulsions may occur in patients with impaired renal function or in those receiving high doses or in patients with predisposing factors (e.g. history of seizures, treated epilepsy or meningeal disorders (see section 4.8).

Renal impairment

In patients with renal impairment, the dose should be adjusted according to the degree of impairment (see section 4.2).

Skin reactions

The occurrence at the treatment initiation of a feverish generalised erythema associated with pustula may be a symptom of acute generalised exanthemous pustulosis (AGEP, see section 4.8). This reaction requires amoxicillin discontinuation and contra-indicates any subsequent administration.

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.

Jarisch-Herxheimer reaction

The Jarisch-Herxheimer reaction has been seen following amoxicillin treatment of Lyme disease (see section 4.8). It results directly from the bactericidal activity of amoxicillin on the causative bacteria of Lyme disease, the spirochaete Borrelia burgdorferi. Patients should be reassured that this is a common and usually self-limiting consequence of antibiotic treatment of Lyme disease.

Overgrowth of non-susceptible microorganisms

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

Antibiotic-associated colitis has been reported with nearly all antibacterial agents and may range in severity from mild to life threatening (see section 4.8). Therefore, it is important to consider this diagnosis in patients who present with diarrhoea during, or subsequent to, the administration of any antibiotics. Should antibiotic-associated colitis occur, amoxicillin should immediately be discontinued, a physician consulted and an appropriate therapy initiated. Anti-peristaltic medicinal products are contra-indicated in this situation.

Prolonged therapy

Periodic assessment of organ system functions; including renal, hepatic and haematopoietic function is advisable during prolonged therapy. Elevated liver enzymes and changes in blood counts have been reported (see section 4.8).

Anticoagulants

Prolongation of prothrombin time has been reported rarely in patients receiving amoxicillin. Appropriate monitoring should be undertaken when anticoagulants are prescribed concomitantly. Adjustments in the dose of oral anticoagulants may be necessary to maintain the desired level of anticoagulation (see section 4.5 and 4.8).

Crystalluria

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. In patients with bladder catheters, a regular check of patency should be maintained (see section 4.8 and 4.9).

Interference with diagnostic tests

Elevated serum and urinary levels of amoxicillin are likely to affect certain laboratory tests. Due to the high urinary concentrations of amoxicillin, false positive readings are common with chemical methods.

It is recommended that when testing for the presence of glucose in urine during amoxicillin treatment, enzymatic glucose oxidase methods should be used.

The presence of amoxicillin may distort assay results for oestriol in pregnant women.

Important information about excipients

This medicinal product contains 63 mg (2.74 mmol) of sodium per vial. To be taken into consideration by patients on a controlled sodium diet.

Lidocaine may be used only when administering amoxicillin by the intramuscular route.

4.5 Interaction with other medicinal products and other forms of interaction

Probenecid

Concomitant use of probenecid is not recommended. Probenecid decreases the renal tubular secretion of amoxicillin. Concomitant use of probenecid may result in increased and prolonged blood levels of amoxicillin.

Allopurinol

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

Tetracyclines

Tetracyclines and other bacteriostatic drugs may interfere with the bactericidal effects of amoxicillin.

Oral anticoagulants

Oral anticoagulants and penicillin antibiotics have been widely used in practice without reports of interaction. However, in the literature there are 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 amoxicillin. Moreover, adjustments in the dose of oral anticoagulants may be necessary (see sections 4.4 and 4.8).

Methotrexate

Penicillins may reduce the excretion of methotrexate causing a potential increase in toxicity.

4.6 Fertility, pregnancy and lactation

Pregnancy

Animal studies do not indicate direct or indirect harmful effects with respect to reproductive toxicity. Limited data on the use of amoxicillin during pregnancy in humans do not indicate an increased risk of congenital malformations. Amoxicillin may be used in pregnancy when the potential benefits outweigh the potential risks associated with treatment.

Breastfeeding

Amoxicillin is excreted into breast milk in small quantities with the possible risk of sensitisation. Consequently, diarrhoea and fungus infection of the mucous membranes are possible in the breast-fed infant, so that breast-feeding might have to be discontinued. Amoxicillin should only be used during breast-feeding after benefit/risk assessment by the physician in charge.

Fertility

There are no data on the effects of amoxicillin on fertility in humans. Reproductive studies in animals have shown no effects on fertility.

4.7 Effects on ability to drive and use machines

No studies on the effects on the ability to drive and use machines have been performed. However, undesirable effects may occur (e.g. allergic reactions, dizziness, convulsions), which may influence the ability to drive and use machines (see section 4.8).

4.8 Undesirable effects

The most commonly reported adverse drug reactions (ADRs) are diarrhoea, nausea and skin rash.

The ADRs derived from clinical studies and post-marketing surveillance with amoxicillin, presented by MedDRA System Organ Class are listed below.

The following terminologies have been used in order to classify the occurrence of undesirable effects.

Very common (≥1/10)

Common (≥1/100 to <1/10)

Uncommon (≥1/1,000 to <1/100)

Rare (≥1/10,000 to <1/1,000)

Very rare (<1/10,000)

Not known (cannot be estimated from the available data)

Infections and infestations
Very rare Mucocutaneous candidiasis
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 (see section 4.4).

Immune system disorders
Very rare Severe allergic reactions, including angioneurotic oedema, anaphylaxis, serum sickness and hypersensitivity vasculitis (see section 4.4).
Not known Jarisch-Herxheimer reaction (see section 4.4).
Nervous system disorders
Very rare Hyperkinesia, dizziness and convulsions (see section 4.4).
Gastrointestinal disorders
Clinical Trial Data
*Common Diarrhoea and nausea
*Uncommon Vomiting
Post-marketing Data
Very rare Antibiotic associated colitis (including pseudomembraneous colitis and haemorrhagic colitis see section 4.4).
Hepatobiliary disorders
Very rare Hepatitis and cholestatic jaundice. A moderate rise in AST and/or ALT.
Skin and subcutaneous tissue disorders
Clinical Trial Data
*Common Skin rash
*Uncommon Urticaria and pruritus
Post-marketing Data
Very rare Skin reactions such as erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis, bullous and exfoliative dermatitis, acute generalised exanthematous pustulosis (AGEP) (see section 4.4), and drug reaction with eosinophilia and systemic symptoms (DRESS).
Renal and urinary tract disorders
Very rare: Interstitial nephritis

Crystalluria (see sections 4.4 and 4.9 Overdose)

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

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product.

4.9 Overdose

Symptoms and signs of overdose

Gastrointestinal symptoms (such as nausea, vomiting and diarrhoea) and disturbance of the fluid and electrolyte balances may be evident. Amoxicillin crystalluria, in some cases leading to renal failure, has been observed. Convulsions may occur in patients with impaired renal function or in those receiving high doses (see sections 4.4 and 4.8).

Amoxicillin has been reported to precipitate in bladder catheters, predominantly after intravenous administration of large doses. A regular check of patency should be maintained (see section 4.4)

Treatment of intoxication

Gastrointestinal symptoms may be treated symptomatically, with attention to the water/electrolyte balance.

Amoxicillin can be removed from the circulation by haemodialysis.

  1. PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic properties

Pharmacotherapeutic group: penicillins with extended spectrum.

Mechanism of action

Amoxicillin is a semisynthetic penicillin (beta-lactam antibiotic) that inhibits one or more enzymes (often referred to as penicillin-binding proteins, PBPs) in the biosynthetic pathway of bacterial peptidoglycan, which is an integral structural component of the bacterial cell wall. Inhibition of peptidoglycan synthesis leads to weakening of the cell wall, which is usually followed by cell lysis and death.

Amoxicillin is susceptible to degradation by beta-lactamases produced by resistant bacteria and therefore the spectrum of activity of amoxicillin alone does not include organisms which produce these enzymes.

Pharmacokinetic/pharmacodynamic relationship

The time above the minimum inhibitory concentration (T>MIC) is considered to be the major determinant of efficacy for amoxicillin.

Mechanisms of resistance

The main mechanisms of resistance to amoxicillin are:

  • Inactivation by bacterial beta-lactamases.
  • Alteration of PBPs, which reduce the affinity of the antibacterial agent for the target.

Impermeability of bacteria or efflux pump mechanisms may cause or contribute to bacterial resistance, particularly in Gram-negative bacteria.

Breakpoints

MIC breakpoints for amoxicillin are those of the European Committee on Antimicrobial Susceptibility Testing (EUCAST) version 5.0.

Organism MIC breakpoint (mg/L)
Susceptible ≤ Resistant >
Enterobacteriaceae 81 8
Staphylococcus spp. Note2 Note 2
Enterococcus spp.3 4 8
Streptococcus groups A, B, C and G Note 4 Note 4
Streptococcus pneumoniae Note 5 Note 5
Viridans group steprococci 0.5 2
Haemophilus influenzae 26 26
Moraxella catarrhalis Note 7 Note 7
Neisseria meningitidis 0.125 1
Gram positive anaerobes except Clostridium difficile8 4 8
Gram negative anaerobes8 0.5 2
Helicobacter pylori 0.1259 0.1259
Pasteurella multocida 1 1
Non- species related breakpoints10 2 8
1Wild type Enterobacteriaceae are categorised as susceptible to aminopenicillins. Some countries prefer to categorise wild type isolates of E. coli and P. mirabilis as intermediate. When this is the case, use the MIC breakpoint S ≤ 0.5 mg/L

2Most staphylococci are penicillinase producers, which are resistant to amoxicillin. Methicillin resistant isolates are, with few exceptions, resistant to all beta-lactam agents.

3Susceptibility to amoxicillin can be inferred from ampicillin

4The susceptibility of streptococcus groups A, B, C and G to penicillins is inferred from the benzylpenicillin susceptibility.

5Breakpoints relate only to non-meningitis isolates. For isolates categorised as intermediate to ampicillin avoid oral treatment with amoxicillin. Susceptibility inferred from the MIC of ampicillin.

6Breakpoints are based on intravenous administration. Beta-lactamase positive isolates should be reported resistant.

7Beta lactamase producers should be reported resistant

8Susceptibility to amoxicillin can be inferred from benzylpenicillin.

9The breakpoints are based on epidemiological cut-off values (ECOFFs), which distinguish wild-type isolates from those with reduced susceptibility.

10The non-species related breakpoints are based on doses of at least 0.5 g x 3or 4 doses daily (1.5 to 2 g/day).

The prevalence of resistance may vary geographically and with time for selected species, and local information on resistance is desirable, particularly when treating severe infections. As necessary, expert advice should be sought when the local prevalence of resistance is such that the utility of the agent in at least some types of infections is questionable.

In vitro susceptibility of micro-organisms to Amoxicillin
Commonly Susceptible Species
Gram-positive aerobes:

Enterococcus faecalis

Beta-hemolytic streptococci (Groups A, B, C and G)

Listeria monocytogenes

Species for which acquired resistance may be a problem
Gram-negative aerobes:

Escherichia coli

Haemophilus influenzae

Helicobacter pylori

Proteus mirabilis

Salmonella typhi

Salmonella paratyphi

Pasteurella multocida

Gram-positive aerobes:

Coagulase negative staphylococcus

Staphylococcus aureus£

Streptococcus pneumoniae

Viridans group streptococcus

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.

Enterobacter spp.

Klebsiella spp.

Pseudomonas spp.

Gram-negative anaerobes:

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

Others:

Chlamydia spp.

Mycoplasma spp.

Legionella spp.

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

£ Almost all S.aureus are resistant to Amoxicillincillin due to production of penicillinase. In addition, all methicillin-resistant strains are resistant to amoxicillin.

5.2 Pharmacokinetic properties

The pharmacokinetic results for studies in which amoxicillin was administered to groups of healthy volunteers given as a bolus intravenous injection are presented below.

Mean pharmacokinetic parameters

Bolus intravenous injection

Dose administered
Peak serum conc (μg/ml) T 1/2 (h) AUC (µg.h/ml) Urinary recovery (%, 0 to 6 h )
500 mg 32.2 1.07 25.5 66.5
1000 mg 105.4 0.9 76.3 77.4

Distribution

About 18% of total plasma amoxicillin is bound to protein and the apparent volume of distribution is around 0.3 to 0.4 l/kg.

Following intravenous administration, amoxicillin has been found in gall bladder, abdominal tissue, skin, fat, muscle tissues, synovial and peritoneal fluids, bile and pus. Amoxicillin does not adequately distribute into the cerebrospinal fluid.

From animal studies there is no evidence for significant tissue retention of drug-derived material. Amoxicillin, like most penicillins, can be detected in breast milk (see section 4.6).

Biotransformation

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

Elimination

The major route of elimination for amoxicillin is via the kidney

Amoxicillin has a mean elimination half-life of approximately one hour and a mean total clearance of approximately 25 l/hour in healthy subjects. Approximately 60 to 70% of the amoxicillin is excreted unchanged in urine during the first 6 hours after administration of a single 250 mg or 500 dose of amoxicillin. Various studies have found the urinary excretion to be 50 to 85% for amoxicillin over a 24 hour period.

Concomitant use of probenecid delays amoxicillin excretion (see section 4.5).

Gender

Following oral administration of amoxicillin to healthy males and female subjects, gender has no significant impact on the pharmacokinetics of amoxicillin.

Age

The elimination half-life of amoxicillin is similar for children aged around 3 months to 2 years and older children and adults. For very young children (including preterm newborns) in the first week of life the interval of administration should not exceed twice daily administration due to immaturity of the renal pathway of elimination. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function.

Renal impairment

The total serum clearance of amoxicillin decreases proportionately with decreasing renal function (see section 4.2).

Hepatic impairment

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

5.3 Preclinical safety data

Non-clinical data reveal no special hazard for humans based on studies of safety pharmacology, repeated dose toxicity, genotoxicity and toxicity to reproduction and development.

Carcinogenicity studies have not been conducted with amoxicillin.

  1. PHARMACEUTICAL PARTICULARS

6.1 List of excipients

None

6.2 Incompatibilities

This medicinal product must not be mixed with other medicinal products except those mentioned in section 6.6.

Amoxicillin should not be mixed with blood products, other proteinaceous fluids such as protein hydrolysates or with intravenous lipid emulsions. If prescribed concomitantly with an aminoglycoside, the antibiotics should not be mixed in the syringe, intravenous fluid container or giving set because of loss of activity of the aminoglycoside under these conditions.

Amoxicillin solutions should not be mixed with infusions containing dextran or bicarbonate.

6.3 Shelf life

2 years

6.4 Special precautions for storage

Do not store above 25 °C.

For storage conditions after reconstitution of the medicinal product, see section 6.3.

6.5 Nature and contents of container

Amoxicillin 500ng powder for solution for injection  is packaged in a clear vial.

Packs of: 1, 10 or 30 vials.

Not all pack sizes may be marketed.

6.6 Special precautions for disposal and other handling

Intravenous administration

Vial Diluent (ml)
500mg 10

Water for injections is the normal diluent.

A transient pink colouration may or may not develop during reconstitution. Reconstituted solutions are normally colourless or a pale straw colour. All solutions should be shaken vigorously before injection.

If amoxicillin 500mg is to be administered by direct injection, it should be administered within 20 minutes of reconstitution.

7. Manufactured In India By:
TAJ PHARMACEUTICALS LTD.
Mumbai, India
Unit No. 214.Old Bake House,
Maharashtra chambers of  Commerce Lane,
Fort, Mumbai – 400001
at:Gujarat, INDIA.
Customer Service and Product Inquiries:
1-800-TRY-FIRST (1-800-222-434 & 1-800-222-825)
Monday through Saturday 9:00 a.m. to 7:00 p.m. EST
E-mail: tajgroup@tajpharma.com

Amoxicillin for Injection 500mg
(Amoxicillin)

Package leaflet: Information for the user

 

Read all of this leaflet carefully before you are given this medicine because it contains important information for you.

  • Keep this leaflet. You may need to read it again.
  • If you have any further questions, ask your doctor, pharmacist or nurse.
  • If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side effects not listed in this leaflet. See section 4.

What is in this leaflet:

  1. What Amoxicillin is and what it is used for
  2. What you need to know before you are given Amoxicillin
  3. How Amoxicillin is given
  4. Possible side effects
  5. How to store Amoxicillin
  6. Contents of the pack and other information

 

  1. WHAT AMOXICILLIN IS AND WHAT IT IS USED FOR

The name of your medicine is Amoxicillin Sodium Powder for Solution for Injection. The vials contain a medicine called sodium amoxicillin.

This belongs to a group of medicines called ‘penicillin’.

What Amoxicillin is used for

Amoxicillin is used to treat infections caused by bacteria in different parts of the body.

Amoxicillin Powder for Solution for Injection is usually used for urgent treatment of severe infection or if patients cannot take Amoxicillin by mouth.

  1. WHAT YOU NEED TO KNOW BEFORE YOU ARE GIVEN AMOXICILLIN

You should not be given Amoxicillin

  • if you are allergic to amoxicillin or penicillin. There are no other ingredients in this medicine (see section 6).
  • if you have had an allergic reaction to any antibiotic. This can include a skin rash or swelling of the face or throat.
  • if you have previously been told that your infection cannot be treated with amoxicillin or ampicillin.

You should not be given Amoxicillin if any of the above applies to you. If you are not sure speak to your doctor, nurse or pharmacist.

Warnings and precautions

Talk to you doctor , pharmacist or nurse before you are given Amoxicillin if you:

  • have glandular fever (fever, sore throat, swollen glands and extreme tiredness)
  • have kidney problems
  • are not urinating regularly.
  • have a problem with your heart
  • have undiagnosed sore throat (pharyngitis) or a type of cancer known as lymphatic lymphoma, which affects white blood cells
  • have HIV

If you are not sure if any of the above apply to you, talk to your doctor, pharmacist or nurse before taking Amoxicillin.

Blood and urine tests

If you are having:

  • Urine tests (glucose) or blood tests for liver function
  • Oestriol tests (used during pregnancy to check the baby is developing normally)

Tell your doctor, pharmacist or nurse that you are taking Amoxicillin. This is because Amoxicillin can affect the results of these tests.

Children

Care should be taken in newborns and young infants as there is the chance of higher levels of amoxicillin in the blood.

Other medicines and Amoxicillin

Tell your doctor, pharmacist or nurse if you are taking, have recently taken or might take any other medicines, including medicines obtained without a prescription.

  • If you are taking allopurinol (used for gout) with Amoxicillin, it may be more likely that you will have an allergic skin reaction.
  • If you are taking probenecid (used for gout), your doctor may decide to adjust your dose of Amoxicillin.
  • If you are taking medicines to help stop blood clots (such as warfarin), you may need extra blood tests.
  • If you are taking other antibiotics (such as tetracycline) Amoxicillin may be less effective.
  • If you are taking methotrexate (used for the treatment of cancer and severe psoriasis) Amoxicillin may cause an increase in side effects.

Pregnancy and breast-feeding

If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your doctor for advice before you are given this medicine.

Driving and using machines

Amoxicillin can have side effects and the symptoms (such as allergic reactions, dizziness and convulsions) may make you unfit to drive. Do not drive or operate machinery unless you are feeling well.

  1. HOW AMOXICILLIN IS GIVEN

You will never give yourself this medicine. A qualified person, like a doctor or a nurse, will give you this medicine.

  • Your medicine will be given to you by injection into a muscle (intramuscularly) or into a vein (intravenously) or as an infusion into a vein.
  • Your doctor will decide how much you need each day and how often the injections should be given.
  • Make sure you drink plenty of fluids while having Amoxicillin.

To treat infections the usual doses are as follows:

Children up to 40 kg

  • Most infections: 20 mg to 200 mg for every kilogram of body weight in divided doses throughout the day.
  • Lyme disease (an infection spread by parasites called ticks): isolated erythema migrans (early stage – red or pink circular rash)

25 mg to 50 mg for every kilogram of body weight in divided doses throughout the day; systemic manifestations (late stage – for more

serious symptoms or when the disease spreads around your body) 100 mg for every kilogram of body weight in divided doses throughout the day.

  • Intravenous maximum single dose: 50 mg for every kilogram of body weight.
  • Intramuscular maximum daily dose: 120 mg for every kilogram of body weight as 2 to 6 equally divided doses.

Adults, elderly patients and children weighing 40 kg or more

  • Usual daily dosage: 750 mg to 6 g administered in divided doses.
  • Intravenous maximum daily dose: 12 g per day.
  • Intravenous maximum single dose: 2 g by infusion or 1 g by bolus
  • Intramuscular maximum daily dose: 4 g per day
  • Intramuscular maximum single dose: 1 g.
  • Lyme disease (an infection spread by parasites called ticks): isolated erythema migrans (early stage – red or pink circular rash)

4 g per day; systemic manifestations (late stage – for more serious symptoms or when the disease spreads around your body) 6 g per day.

Patients with kidney problems

If you have kidney problems the dose might be lower than the usual dose. Amoxicillin is removed by dialysis (artificial filtration and purification of the blood). Therefore, patients receiving dialysis may require another dose of Amoxicillin at the end of their dialysis session.

If you are given more Amoxicillin than you should

This medicine is given to you by a doctor or a nurse. It is unlikely that you will be given too much, but if you think you have been given too much Amoxicillin, tell your doctor or nurse immediately. Signs might be an upset stomach (feeling sick, being sick or diarrhoea) or crystals in the urine, which may be seen as cloudy urine or problems urinating.

The doctor will assess your condition and decide how to treat an overdose.

If you think you have missed a dose of Amoxicillin

If you think that a dose of Amoxicillin has been missed, speak to your doctor or nurse.

How long will you need to take Amoxicillin for?

You will not normally be given Amoxicillin for more than 2 weeks without the doctor reviewing your treatment.

Thrush (a yeast infection of moist areas of the body which can cause soreness, itching and white discharge) may develop if Amoxicillin is used for a long time. If this occurs, tell your doctor, pharmacist or nurse.

If you are given Amoxicillin for a long time, your doctor may perform additional tests to check your kidneys, liver and blood are working normally.

If you have any further questions about how this product is given, ask your doctor, pharmacist or nurse.

  1. POSSIBLE SIDE EFFECTS

Like all medicines, this medicine can cause side effects, although not everybody gets them.

Stop taking Amoxicillin and see a doctor or nurse straight away if you notice any of the following serious side effects – you may need urgent medical treatment:

The following are very rare (may affect up to 1 in 10,000 people)

  • allergic reactions, the signs may include: skin itching or rash, swelling of the face, lips, tongue, body or breathing difficulties. These can be serious and occasionally deaths have occurred
  • rash or pinpoint flat red round spots under the skin surface or bruising of the skin. This is due to inflammation of blood vessel walls due to an allergic reaction. It can be associated with joint pain (arthritis) and kidney problems
  • a delayed allergic reaction can occur usually 7 to 12 days after having amoxicillin, some signs include: rashes, high temperature (fever), joint pain, and enlargement of the lymph nodes especially under the arms
  • a skin reaction known as ‘erythema multiforme’ where you may develop: itchy reddish purple patches on the skin, especially on the palms of the hands or soles of the feet, ‘hive-like’ raised swollen areas on the skin, tender areas on the surfaces of the mouth, eyes and genitals. You may have a fever and be very tired
  • other severe skin reactions can include: changes in skin colour, bumps under the skin, blistering, pustules, peeling, redness, pain, itching, scaling. These may be associated with fever, headaches and body aches
  • flu-like symptoms with a rash, fever, swollen glands, and abnormal blood test results (including increased white blood cells (eosinophilia) and liver enzymes) (Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS))
  • fever, chills, a sore throat or other signs of an infection, or if you bruise easily. These may be signs of a problem with your blood cells
  • the Jarisch-Herxheimer reaction which occurs during treatment with Amoxicillin for Lyme disease and causes fever, chills, headache, muscle pain and skin rash.
  • inflammation of the large bowel (colon) with diarrhoea (sometimes containing blood), pain and fever
  • serious liver side effects may occur which are often reversible. They are mainly associated with people having treatment over a long period, males and the elderly. You must tell your doctor or nurse urgently if you get:
    • severe diarrhoea with bleeding
    • blisters, redness or bruising of the skin
    • darker urine or paler stools
    • yellowing of the skin or the whites of the eyes (jaundice). See also

anaemia below which might result in jaundice.

These can happen when having the medicine or for up to several weeks after.

If any of the above occurs talk to your doctor or nurse straight away.

Sometimes you may get less severe skin reactions such as:

  • a mildly itchy rash (round, pink-red patches), ‘hive-like’ swollen areas on forearms, legs, palms, hands or feet. This is uncommon (may affect up to 1 in 100 people).

If you have any of these talk to your doctor or nurse as Amoxicillin will need to be stopped.

The other possible side effects are:

Common (may affect up to 1 in 10 people)

  • skin rash
  • feeling sick (nausea)

Uncommon (may affect up to 1 in 100 people)

  • being sick (vomiting)

Very rare (may affect up to 1 in 10,000 people)

  • thrush (a yeast infection of the vagina, mouth or skin folds), you can get treatment for thrush from your doctor, pharmacist or nurse
  • kidney problems
  • fits (convulsions), seen in patients on high doses or with kidney problems
  • dizziness
  • hyperactivity
  • crystals in the urine, which may be seen as cloudy urine, or difficulty or discomfort in passing urine. Make sure you drink plenty of fluids to reduce the chance of these symptoms
  • an excessive breakdown of red blood cells causing a form of anaemia. Signs include: tiredness, headaches, shortness of breath, dizziness, looking pale and yellowing of the skin and the whites of the eyes
  • low number of white blood cells
  • low number of cells involved with blood clotting
  • the blood may take longer to clot than it normally would. You may notice this if you have a nosebleed or cut yourself.

Not known (frequency cannot be estimated from the available data)

  • Changes in your salt and electrolyte levels (shown in blood tests, e.g. low potassium)
  • Hallucinations (hearing or seeing things that are not there)
  • Signs of central nervous system toxicity (e.g. ringing in the ears or being sensitive to sound, difficulty in speaking, numbness of the tongue or around the mouth, fits, feeling sleepy, shakiness, blurred vision), generally associated with large intravenous doses of amoxicillin or kidney problems.
  • Encephalopathy (disease of the brain, e.g. confusion, fever, headache, hallucinations, paralysis, light sensitivity, disturbances in sight and movement, stiff neck), has been reported when administered into the arachnoid membrane of the brain or spinal cord and can be fatal.
  • Coma may develop with high doses of amoxicillin.
  • Difficulty breathing or shortness of breath; generally associated with

large intravenous doses of amoxicillin or kidney problems.

Sore mouth and tongue.

Reporting of side effects

If you get any side effects, talk to your doctor, pharmacist or nurse. This also includes any possible side effects not listed in this leaflet.

  1. HOW TO STORE AMOXICILLIN

Keep this medicine out of the sight and reach of children.

  • Do not use this medicine after the expiry date which is stated on the label. The expiry date refers to the last day of that month.
  • Store below 25°C, in the original container.
  • Reconstituted solutions should be used immediately after preparation. Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. These measures will help protect the environment.
  1. CONTENTS OF THE PACK AND OTHER INFORMATION

What Amoxicillin contains

Each vial contains:
Amoxicillin sodium
Equivalent to Amoxicillin              500mg
Water for Injection                          10ml

There are no other ingredients. However, please see section 2 for further important information about sodium in Amoxicillin.

What Amoxicillin looks like and the contents of the pack

Amoxicillin 500ng powder for solution for injection  is packaged in a clear vial.

Packs of: 1, 10 or 30 vials.

Not all pack sizes may be marketed.

  1. Manufactured in India by:
    TAJ PHARMACEUTICALS LTD.
    Mumbai, India
    Unit No. 214.Old Bake House,
    Maharashtra chambers of  Commerce Lane,
    Fort, Mumbai – 400001
    at:Gujarat, INDIA.
    Customer Service and Product Inquiries:
    1-800-TRY-FIRST (1-800-222-434 & 1-800-222-825)
    Monday through Saturday 9:00 a.m. to 7:00 p.m. EST
    E-mail: tajgroup@tajpharma.com