Treatment of Infection: Hymox 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: Hymox 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:

Hymox 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:

Hymox 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 table on next page.

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:

Before initiating therapy with amoxicillin, careful enquiry should be made concerning previous hypersensitivity reactions to penicillins, 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 4.3).

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

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

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 Section 4.9 Overdose).

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 (see section 4.2).

Abnormal prolongation of prothrombin time (increased INR) has been reported rarely in patients receiving amoxicillin and oral anticoagulants. 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 sections 4.5 and 4.8)

Precaution should be taken in premature children and during the neonatal period: renal, hepatic and haematological functions should be monitored

Severe Cutaneous Adverse Reactions

Amoxicillin may cause severe cutaneous adverse reactions (SCAR), such as Stevens- Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), drug reaction with eosinophilia and systemic symptoms (DRESS), and acute generalized exanthematous pustulosis (AGEP). If patients develop a skin rash they should be monitored closely and amoxicillin discontinued if lesions progress.

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

In common with other antibiotics, amoxicillin 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.

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 amoxicillin (see sections 4.4 and 4.8).

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

Animal studies with Hymox have shown no teratogenic effects. The product has been in extensive clinical use since 1972 and its suitability in human pregnancy has been well documented in clinical studies. When antibiotic therapy is required during pregnancy, Hymox may be considered appropriate when the potential benefits outweigh the potential risks associated with treatment.

Use in lactation:

Amoxicillin 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.

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

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 penicillins.

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

Prolongation of bleeding time and prothrombin time (see section 4.4 – Special Warnings and Precautions for Use.

Immune system disorders

Very rare:           As with other antibiotics, severe allergic reactions, including angioneurotic oedema, anaphylaxis (see Section 4.4 - Special Warnings and Precautions for Use), 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.

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).

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.

Hepato-biliary 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

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 and acute generalised exanthematous pustulosis (AGEP), and drug reaction with eosinophilia and systemic symptoms (DRESS).

(See also Immune system disorders).

Renal and urinary tract disorders Very rare:                             Interstitial nephritis.

Very rare:             Crystalluria (see Section 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.

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 special precautions for use).

Amoxicillin may be removed from the circulation by haemodialysis.

Hymox is a broad spectrum antibiotic.

It is rapidly bactericidal and possesses the safety profile of a penicillin.

The wide range of organisms sensitive to the bactericidal action of Hymox include: 

Aerobes:

Anaerobes:

Clostridium species

Hymox is well absorbed by the oral and parenteral routes. Oral administration, usually at convenient t.d.s. dosage, produces high serum levels independent of the time at which food is taken. Hymox gives good penetration into bronchial secretions and high urinary concentrations of unchanged antibiotic.

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.

Not applicable.

Hymox 250mg and 500mg Caps:

Magnesium Stearate Gelatin Capsule No. 2 Gelatin Capsule No. 0el

Hymox 875mg film coated tablets:

Avicel PH 102, Crospovidone NF, Sodium Starch Glycolate, Colloidal Silicon Dioxide, Magnesium Stearate and Opadry Pink YS-1-14725

Not Applicable

Store in a dry place below 25

Hymox 250mg and 500mg Capsules:

20/pack (250mg and 500mg)Transparent PVC/PVDC and aluminium foil lid

Hymox 875mg film coated tablets:

14/pack (875mg) Transparent PVC/PVDC and aluminium foil lid

Not applicable.