QUALITATIVE AND QUANTITATIVE COMPOSITION

Each film coated tablet contains:

Active ingredients :

Amoxicillin  trihydrate equivalent to 875mg Amoxicillin

Clavulanate potassium equivalent to 125mg Clavulanic acid

Inactive ingredients:  

Magnesium stearate, silica anhydrous, colloidal, sodium starch glycollate, cellulose microcrystalline, Talc, Titanium dioxide, Hypromellose, Diethyl phthate, Dimeticone.

PHARMACOLOGY

Amoxicillin is a semi-synthetic antibiotic, which shows antibacterial activity against a broad spectrum of Gram- positive and Gram- negative microorganisms. Amoxicillin is sensitive to inactivation by beta-lactamases, therefore the antimicrobial spectrum of Amoxicillin alone does not include microorganisms which produce these enzymes.

Clavulanic acid is a beta-lactam antibiotic, structually related to the penicillins, which inactivates a broad spectrum of beta-lactamase enzymes, commonly found in microorganisms resistant to penicillins and cephalosporins. More specific, clavulanic acid is active against the clinically significant plasmid-mediated beta-lactamases, which are often responsible for transmission of pharmaceutical resistance. It is less potent against the type I beta-lactamases, which are cromosomal-mediated.

The presence of clavulanic acid in Fugentin  prevents amoxicillin from inactivation by beta-lactamase enzymes and extends the antimicrobial spectrum of amoxicillin, to include a lot of bacteria normally resistant to amoxicillin and other penicillins and cephalosporins. Therefore Fugentin  has the characteristics of a broad spectrum antibiotic and a beta-lactamase inhibitor.

Fugentin  shows bactericidal activity against a broad spectrum of microorganisms which include:

Gram-positive aerobia

Bacillus anthracis, Corynebacterium species                          

Enterococcus faecalis*, Enterococcus faecium*                     

Listeria monocytogenes, Nocardia asteroides                         

Staphylococcus aureus, Coagulase-negative Staphylococci

(including Staphylococcus epidermidis)

Streptococcus agalactiae, Streptococcus pneumoniae

Streptococcus pyogenes*, Streptococcus species*

Streptococcus viridans*, Anaerobia, Clostridium species, Peptococcus species*, Peptostreptococcus species*

Gram- negative aerobia

Bordetella pertussis*, Brucella species*, Escherichia coli, Gardnerella vaginalis, Haemophilus influenze

Klebsiella species,  Moraxella catarrhalis (Branhamella catarrhalis), Neisseria gonorrhoeae

Neisseria meningitidis*,  Pasteurella multocida

Proteus mirabilis, Proteus vulgaris, Salmonella species, Shigella species, Vibrio cholerae, Yersinia enterocolitica

Anaerobia

Bacteroides species (including Bacteroides fragilis)

Fusobacterium species

Leptospira icterophaemorrhagiae

Other

Borrelia burgdorferi*

* Strains not producing beta-lactamases, which are therefore susceptible to amoxicillin.

PHARMACOKINETICS

The pharmacokinetics of both amoxicillin and clavulanate in FUGENTIN  are closely allied and neither is adversely affected by the presence of food in stomach. After oral administration of FUGENTIN,  it is well absorbed from the gastrointestinal tract with a peak serum level occurring about 1 hour. Absorption of FUGENTIN   is optimized at the start of meal. Both amoxicillin and clavulanic acid have low level of serum bindings. Neither component in FUGENTIN is highly protein bound, approximately 50 to 70 % of amoxicillin and approximately 25 to 45 % of the clavulanic acid are excreted unchanged in urine during the first 6 hours.

Doubling of the dosage of FUGENTIN   approximately doubles the serum levels.

THERAPEUTIC INDICATIONS

Fugentin is indicated for short period treatment of bacterial infections, caused by beta-lactamase producing organisms, which are susceptible to this drug. The duration of treatment depends on the therapeutic indication and it must not exceed 14 days.

• Upper Respiratory Tract Infections (including ear, nose and throat infections), i.e. recurrent tonsillitis, sinusitis, otitis media (especially in recurrence or in severe cases).
• Lower Respiratory Tract Infections i.e. acute exacerbations of chronic bronchitis, lobar pneumonia and bronchopneumonia.

• Genitourinary Tract Infections i.e. cystitis, urethritis (not prostatitis), pyelonephritis, infections of the female genital organs (excluding infections caused by chlamydia).

• Skin and Soft Tissue Infections.

• Bone and Joint Infections i.e. osteomyelitis.

• Other Infections i.e. septic abortion, puerperal sepsis, intra-abdominal sepsis.

DOSAGE AND ADMINISTRATION

Adults and children over 12 years old

Mild, moderate and severe infections: 875/125 mg every 12 hours.

Elderly

No special dosage recommendations are required. Same dosage as per adults is recommended, except for cases of moderate or severe urogenital infections or renal impairment.

Renal Impairment

Glomerular Filtration Rate > 30ml/min (mild to moderate renal impairment):

No dosage adjustment is required.

Glomerular Filtration Rate 10 – 30ml/min (severe renal impairment): 500/125 mg, depending on the severity, administered twice per day.

Glomerular Filtration Rate < 10ml/min (final stage renal impairment): 500/125 mg, depending on the severity, administered every 24 hrs.

Haemodialysis: 500/125 mg every 24 hrs, plus an additional dose during the haemodialysis which must be repeated at the end of the haemodialysis as well (due to the decrease of the amoxicillin and clavulanic acid concentrations in the blood serum).

Hepatic Impairment

Administer with caution and monitor hepatic function at regular intervals. Up to date there are no sufficient data to define a dose regimen.

Administration

Fugentin should be administered at the start of a meal, to decrease the potential for gastrointestinal intolerance. Absorption is enhanced when Fugentin is taken at the start of a meal. Treatment period should not exceed 14 days without review. The treatment may start parenterally and be continued orally. For the treatment of moderate infections in the community, the possibility of administering amoxicillin alone should be considered, especially to patients over 65 years of age.

ADVERSE REACTIONS

Large scale clinical studies gave evidence used for the determination of the frequency of undesirable effects which varies from Very Common to Rare. The frequencies determined for all of the remaining undesirable effects (i.e. those occurring < 1/10.000) were mainly estimated based on data revealed during the drug post-marketing period and mainly refer to reported that to real incidence.

Frequencies are classified as follows:

Very common > 1/10

Common > 1/100 and < 1/10

Uncommon > 1/1.000 and < 1/100

Rare > 1/10.000 and < 1/1.000

Very rare < 1/10.000

Infections

Common:  Dermal mycosis and mycosis of the mucous membranes.

Blood and lymphatic system disorders

Rare : Reversible leucopenia (including neutropenia) and thrombocytopenia.

Very rare: Reversible agranulocytosis and haemolytic anaemia. Clotting and prothrombin time prolongation.  Thrombocytopenic purpura and eosinophilia have also been reported.

Immune system disorders

Very rare : Angioneurotic oedema, anaphylaxis, hypersensitivity vasculitis, serum sickness-like reactions.

Nervous system disorders

Uncommon:   Dizziness, headache.

Very rare:   Reversible hyperactivity and convulsions. Convulsions may occur with  impaired renal function or in those receiving high doses.

Gastrointestinal disorders

Very common : Diarrhoea.

Common :  Nausea, vomiting.

Nausea is more often associated with higher oral dosages.

If gastrointestinal rections are intense, they may be reduced by taking Fugentin  at the start of meals.

Uncommon:   Indigestion.

Very rare:   Colitis related to antibiotics (including pseudomembranous colitis and haemorrhagic colitis). Superficial coloration of the teeth has very rarely                                          occurred in children. A good level of oral hygiene may help prevent teeth                                         coloration, which however may usually be removed by brushing.

Other reactions:  may include unformed faeces, gastritis, abdominal pain, stomatitis,   glossitis, black “hairy” tongue. Intestinal candidiasis related to antibiotics  has rarely been reported.

Hepato-biliary disorders

Uncommon :  In patients treated with antibiotics of the ampicillin group, a moderate  rise in AST and/or ALT has been observed, but the significance of those                                          findings is unknown.

Very rare:  Hepatitis and cholestatic jaundice. These have also been reported with  other penicillins and cephalosporins.

Histologic findings include cholostasis and/or hepatic cellular damage.

Amoxicillin + clavulanic acid related hepatic effects occur mainly in male or elderly patients. The risk rises if the duration of the treatment exceeds 14 days. Signs and symptoms occur usually during treatment or shortly after cessation of therapy, but in some cases they may as well appear with a delay of up to several weeks after the end of the treatment. These hepatic events are usually reversible.

Hepatic disorders may be severe. In extremely rare circumstances, deaths have been reported in patients with severe underlying disease, who were also taking other drugs known for their potential hepatic activity.

Skin and subcutaneous tissue disorders

Uncommon:  Rash, pruritus and urticaria.

Rare:  Erythema multiforme.

Very rare:  Stevens-Johnson syndrome, toxic epidermal necrolysis, exfoliative dermatitis and acute generalized exanthematous pustulosis.

Treatment should be discontinued if any type of skin hypersensitivity reaction appears.

Maculopapular rash and Schonlein-Henoch type purpura with renal participation, have also been reported.

Serious and occasionally fatal hypersensitivity (anaphylactic) reactions have occurred in patients treated with penicillin.

Renal and urinary disorders

Very rare:   Interstitial nephritis, crystalluria.   

Inform doctors with side effects when using medicine

CONTRAINDICATIONS

Fugentin is contra-indicated to patients with a history of hypersensitivity to beta-lactam antibiotics (such as penicillins and cephalosporins).

Fugentin is also contra-indicated to patients with a previous history of Fugentin associated jaundice/hepatic dysfunction.

PRECAUTIONS

Prior to the treatment initiation with Fugentin detailed medical record should be kept regarding any previous cases of hypersensitivity reactions towards penicillin, cephalosporin or other allergens. Serious and occasionally fatal hypersensitivity (anaphylactic) reactions have been reported in patients under penicillin treatment. These reactions are most likely to occur to individuals with a history of hypersensitivity to penicillin. If an allergic reaction occurs, therapy with the drug should be discontinued and an alternative treatment should be applied.

Fugentin must be avoided in cases of suspected infectious mononucleosis as there have been reports of erythematous rashes in patients suffering from this condition, treated with amoxicillin.

Prolonged use may in some cases result to excessive development of resistant microorganisms.

Generally Fugentin is well tolerated having the low toxicity rates of penicillins. During prolonged therapy, periodic monitoring of the systemic functions -including renal, hepatic and hemopoietic function- is recommended.

USE IN PREGNANCY AND LACTATION

Reproduction studies in animals (mice and rats) with orally and parenterally administered amoxicillin + clavulanic acid in doses 10 times the recommended human dose, have shown no teratogenic effects. There is limited experience of the use of amoxicillin + clavulanic acid in human pregnancy. In a clinical study on women with premature rupture of the amniotic membranes, the possibility that prophylactic treatment with the drug may be associated with increased risk of necrotizing enterocolitis in infants, was mentioned. As with all medicines, use should be avoided in pregnancy, especially during the first trimester, unless considered essential by the physician. Antibiotics of the ampicillin group are excreted in breast milk. A hypersensitivity reaction to the infant may be possible. Fugentin should be administered with caution to lactating women.

DRUG INTERACTIONS

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

Concomitant use of allopurinol during treatment with ampicillin increases the incidence of skin rashes in patients receiving both drugs, compared to patients receiving only ampicillin, especially hyperuricaemic patients. It is unknown whether this increase is caused by allopurinol or by the presence of hypeuricaemia in these patients. There are no data on the concomitant use of Fugentin and allopurinol.

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

False positive direct Coombs tests have occurred.

With tetracyclines the bactericidal action of amoxicillin may be impaired.

A false positive reaction for urine glucose may occur with sulphate copper test.

OVERDOSE

Gastrointestinal symptoms and disturbance of the fluid and electrolyte balances may be evident.

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

Product may be removed from the circulation by hemodialysis.

STORAGE

Store at temperatures not exceeding 30^oC.

Protect from sunlight and moisture.

SPECIFICATION: BP2009

USE TERM: 2 years since the manufacturing date

HOW  SUPPLIED: Box of 3 blisters x 4 tablets.

WARNING

Read carefully the leaflet before use.

For further information, please contact your doctor

This drug is dispensed on prescription only.

Keep out of reach of children.

Manufactured by:  

ELPEN PHARMACEUTICALS CO. INC.

95, Marathonos Ave., 190 09 Pikermi, Attica, Greece