Treatment of Infection: E-MOX is a broad spectrum antibiotic indicated for the treatment of commonly occurring bacterial infections such as:
Upper respiratory tract infections
Otitis media
Acute and chronic bronchitis
Chronic bronchial sepsis
Lobar and bronchopneumonia
Cystitis, urethritis, pyelonephritis
Bacteriuria in pregnancy
Gynaecological infections including puerperal sepsis and septic abortion
Gonorrhoea
Peritonitis
Intra-abdominal sepsis
Septicaemia
Bacterial endocarditis
Typhoid and paratyphoid fever
Skin and soft tissue infections
Dental abscess (as an adjunct to surgical management)
Helicobacter pylori eradication in peptic (duodenal and gastric) ulcer disease.
In children with urinary tract infection the need for investigation should be considered.
Prophylaxis of endocarditis: Amoxicillin may be used for the prevention of bacteraemia, associated with procedures such as dental extraction, in patients at risk of developing bacterial endocarditis.
Consideration should be given to official local guidance (e.g. national requirements) on the appropriate use of antibacterial agents. ”Susceptibility of the causative organism to the treatment should be tested (if possible), although the therapy may be initiated before the results are available.

Treatment of Infection:
Adult dosage (including elderly patients):
Standard adult dosage: 250 mg three times daily, increasing to 500 mg three 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 10-12 hours between the doses. Dental abscess: two 3 g doses with 8 hours between the doses. Gonorrhoea: single 3 g dose.

Dosage in impaired renal function:
The dose should be reduced in patients with severe renal function impairment. In patients with a creatinine clearance of less than 30 ml/min an increase in the dosage interval and a reduction in the total daily dose is recommended (see section 4.4 and 5.2):
Glomerular filtration rate>30ml/min No adjustment necessary.
Glomerular filtration rate 10-30ml/min: Amoxicillin. max.500mg b.d
Glomerular filtration rate<10ml/min: Amoxicillin. Max. 500mg/day
Helicobacter eradication in peptic (duodenal and gastric) ulcer disease:
E-MOX is recommended at a dose of twice daily in association with a proton pump inhibitor and antimicrobial agents as detailed below:
Omeprazole 40 mg daily, Amoxicillin 1G BID, Clarithromycin 500mg
BID x 7days
Or
Omeprazole 40mg daily, Amoxicillin750mg-1G BID, Metronidazole 400mg
TID x 7 days
Children weighing < 40 kg
The daily dosage for children is 40 - 90 mg/kg/day in two to three divided doses* (not exceeding 3 g/day) depending on the indication, severity of the disease and the susceptibility of the pathogen (see special dosage recommendations below and sections 4.4, 5.1 and 5.2).
* PK/PD data indicate that dosing three times daily is associated with enhanced efficacy, thus twice daily dosing is only recommended when the dose is in the upper range.
Children weighing more than 40 kg should be given the usual adult dosage.
Renal impairment in children under 40 kg:

E-MOX Paediatric Suspension is recommended for children under six months of age.
Special dosage recommendation
Tonsillitis: 50 mg/kg/day in two divided doses.
Acute otitis media: In areas with high prevalence of pneumococci with reduced susceptibility to penicillins, dosage regimens should be guided by national/local recommendations. In severe or recurrent acute otitis media, especially where compliance may be a problem, 750 mg twice a day for two days may be used as an alternative course of treatment in children aged 3 to 10 years.
Early Lyme disease (isolated erythema migrans): 50 mg/kg/day in three divided doses, over 14-21days.

Prophylaxis of endocarditis: see the table.
Administration: Oral:
Treatment should be continued for 2 to 3 days following the disappearance of symptoms. It is recommended that at least 10 days treatment be given for any infection caused by beta-haemolytic streptococci in order to achieve eradication of the organism.
Prophylaxis of endocarditis:

Prolonged use of anti-infective agent may result in superinfection by organisms resistant to that anti-infective.
In patients with renal impairment, the rate of excretion of amoxicillin will be reduced depending on the degree of impairment and it may be necessary to reduce the total daily unit amoxicillin dosage accordingly.
Serious and occasionally fatal hypersensitivity (anaphylactoid) reactions have been reported in patients on penicillin therapy. Although anaphylaxis is more frequent following parenteral therapy, it has occurred in patients on oral penicillins. These reactions are more likely to occur in persons with a history of penicillin hypersensitivity and/ or a history of sensitivity to multiple allergens. There have been reports of individuals with a history of severe reactions when treated with cephalosporin. Before initiating therapy with any penicillin, careful inquiry should be made concerning previous hypersensitivity reactions to penicillins, cephalosporins, or other allergens.
Erythematous (mornilliform) rashes have been associated with glandular fever in patients receiving amoxicillin.
If allergic reaction occurs, amoxicillin should be discontinued and appropriate therapy should be instituted and discontinuance of amoxicillin therapy considered.
Serious anaphylactoid reactions require immediate emergency treatment with epinephrine. Oxygen, intravenous steroids, and airway management, including intubation, should be administered as indicated.
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
Precaution should be taken in premature children and during the neonatal period: renal, hepatic and haematological functions should be monitored.
This medicinal product contains sucrose. Patients with rare hereditary problems of fructose intolerance, glucose-galactose malabsorption or sucrose-isomaltase insufficiency should not take this medicine.

When administered concurrently, the following drugs may interact with amoxicillin:
Oral Contraceptives: In common with other broad spectrum antibiotics, amoxicillin may reduce the efficacy of oral contraceptives and patients should be warned accordingly.
Bacteriostatic antibiotics: Chloramphenicol, erythromycins, sulfonamides or tetracyclines may interfere with the bactericidal effects of penicillins. This has been demonstrated in vitro; however, the clinical significance of this interaction is not well documented.

Probenecid: Probenecid may decrease renal tubular secretion of amoxicillin resulting in increased blood levels and/or amoxicillin toxicity.
Drug/Laboratory Test Interactions:
After treatment with amoxicillin, a false-positive reaction for glucose in the urine may occur with copper sulphate tests (Benedict's solution, fehling's solution, or Clinitest tablets) but not with enzyme based tests..
Allopurinol: Concurrent administration of allopurinol during treatment with amoxicillin can increase the likelihood of allergic skin reactions.
Methotrexate: Excretion of methotrexate is reduced by penicillins; increased risk of toxicity.
Oral typhoid vaccine: The oral typhoid vaccine is inactivated by antibacterials
Sulfinpyrazone: Excretion of penicillins is reduced by sulfinpyrazone.
Anticoagulants: Prolongation of prothrombin time has been reported rarely in patients receiving amoxicillin. Appropriate monitoring should be undertaken when anticoagulants are prescribed concurrently.
Muscle relaxants: Piperacillin (and possibly other penicillins) enhance the effects of non-depolarising muscle relaxants and suxamethonium.
Antibacterials: Absorption of phenoxymethylpenicillin (and possibly other penicillins) reduced by neomycin.
Guar Gum: Reduced absorption of penicillins.
Digoxin: An increase in the absorption of digoxin is possible on concurrent administration with amoxicillin.

Animal studies with amoxicillin have shown no teratogenic effects. Amoxicillin has been in extensive clinical use and its suitability in human pregnancy has been well documented in clinical studies. The product should only be used during pregnancy where potential benefits outweigh the potential risks associated with treatment.
Amoxicillin may be administered during the period of 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.

None.

The following convention has been utilised for the classification of undesirable effects:-
Very common (>1/10), common (>1/100, <1/10), uncommon (>1/1000,<1/100), rare (>1/10,000, <1/1000), very rare (<1/10,000)
The majority of side effects listed below are not unique to amoxicillin and may occur when using other pencillins.
Unless otherwise stated, the frequency of adverse events has been derived from more than 30 years of post-marketing reports.

Infections and Infestations:
Very rare: Mucocutaneous candidiasis
Blood and lymphatic system disorders:
Very rare: As with other beta-lactam antibiotics, reversible leucopenia (including severe neutropenia and agranulocytosis), reversible thrombocytopenia and haemolytic anaemia have been reported.
Prolongation of bleeding time and prothrombin time have also been reported (see section 4.5 Interaction with other medicinal products and other forms of interaction).
Immune System disorders:
Hypersensitivity reactions: As with other antibiotics, severe allergic reactions including angioneurotic oedema, and anaphylaxis (see section 4.4 Special Warnings and Precautions for Use) serum sickness and hypersensitivity vasculitis have been reported rarely.
If hypersensitivity reaction occurs, the treatment should 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.
Gastrointestinal disorders:
Clinical Trial Data:
*Common: Diarrhoea and nausea
*Uncommon: Vomiting
Post-marketing data:
Very rare: Antibiotic associated colitis including pseudomembranous colitis and haemorrhagic colitis have been reported
Black hairy tongue.
Superficial tooth discolouration has been reported in children. This may respond to brushing.
Hepato-biliary disorders:
Very rare: Hepatitis and cholestatic jaundice. A moderate rise in AST and/or ALT, but the significance of this is unclear.
Skin and subcutaneous tissue disorders:
Clinical Trial Data:
*Common: Skin rash,
*Uncommon: Pruritus and urticaria.
Post Marketing Data:
Very rare: Skin reactions such as erythema multiforme and 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
Very rare: Crystalluria (See section 4.9 Overdose) can occur.

*The incidence of these AEs was derived from clinical studies involving a total of approximately 6,000 adult and paediatric patients taking amoxicillin.
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of benefit/risk balance of the medicinal product. Health care professionals are asked to report any suspected adverse reactions.
Reporting of suspected adverse reactions
National pharmacovigilance & Drug safety centre (NPC):
NPC Contact Information:
Fax: +966-11-205-7662.
Call NPC at +966-11-2038222, Exts: 2317-2356-2353-2354-2334-2340.
Toll free phone: 8002490000.
E-mail: npc.drug@sfda.gov.sa.
Website: www.sfda.gov.sa/npc.

Other GCC States:
Please contact the relevant competent authority.

Gastrointestinal effects such as nausea, vomiting and diarrhoea may be evident and should be treated symptomatically with attention to the water/electrolyte balance. Amoxicillin crystalluria, in some cases leading to renal failure has been observed (see section 4.4 Special warnings and precautions for use).
Amoxicillin may be removed from the circulation by haemodialysis.

Amoxicillin is a broad spectrum antibiotic which is bactericidal for both gram positive and gram negative bacteria.
Amoxicillin is well absorbed by the oral route. Oral administration, usually at convenient t.d.s. dosage, produces high serum levels independent of the time at which the food is taken. Amoxicillin gives good penetration into bronchial secretions and high urinary concentrations of unchanged antibiotic. It is rapidly bactericidal and possesses the safety profile of a penicillin.
In portal systemic encephalopathy (PSE) or (pre)coma hepaticum, the effect has been attributed to suppression of proteolytic bacteria by an increase of acidophilic bacteria (e.g. lactobacillus), trapping of ammonia in the ionic form by acidification of the colonic contents, catharsis due to the low pH in the colon as well as an osmotic effect, and alteration of the bacterial nitrogen metabolism by stimulating the bacteria to utilize ammonia for bacterial protein synthesis.

Amoxicillin is rapidly absorbed from the gastro-intestinal tract; it is not converted to ampicillin. It is widely distributed and is reported to product peak antibiotic plasma concentrations that are up to twice as high as those from the same dose of ampicillin.

Peak plasma-amoxicillin concentrations of about 5 mcg/ml have been observed 2 hours after a dose of 250mg, with detectable amounts present for up to 8 hours. Doubling the dose can produce double the concentration. The presence of food in the stomach does not appear to diminish absorption significantly.
Up to 20% is bound to plasma proteins in the circulation and plasma half-lives of about one hour have been reported. Amoxicillin diffuses across the placenta: little appears to be excreted in breast milk. It penetrates well into purulent and mucoid sputum and low concentrations have been found in ocular fluid. About 60% of an oral dose is excreted in the urine in six hours.
In preterm infants with gestational age 26-33 weeks, the total body clearance after intravenous dosing of amoxicillin, day 3 of life, ranged between 0.75 – 2 ml/min, very similar to the inuline clearance (GFR) in this population. Following oral administration, the absorption pattern and the bioavailability of amoxicillin in small children may be different to that of adults. Consequently, due to the decreased CL, the exposure is expected to be elevated in this group of patients, although this increase in exposure may in part be diminished by decreased bioavailability when given orally.

None.

Capsules: Maize Starch, Microcrystalline Cellulose, Talc Purified, Magnesium Stearate, Colloidal Silicon Dioxide.

None known.

Store at a temperature not exceeding 30° C.

E-MOX 500 mg Capsules: A carton box contain 1 or 2 Blisters each of 8 capsules and pamphlet.

None.