SUPRAX® | Antibiotic

200 mg and 400 mg, hard gelatin capsule

100 mg / 5 ml granules for suspension

Company name: The Egyptian Co. for Pharmaceutical & chemical industries SAE (EPCI), for Hikma Pharma -Egypt under license of Astellas-Japan.

سوبراكس شراب معلق 

Neme of the medical supplier

Suprax capsule .

granules for suspension.

Qualitative and quantitative composition

Suprax 200 mg :

Each herd gelatin capsule contans:

Active ingredient:

Cefixime trihydrate 223.8 mg (eq. To 200 mg cefixime)

Suprax .400 mg:

Each hard gelatin capsule contains:

Active ingredient:

Cefixime trihydrate 447.8 mg (eq. To 400 mg cefixime)

Inactive ingredients :

Carboxymethylcellulose Calcium ,  Magnesium stearate , colloidal slicon dioxide.

Suprax 100 mg / 5 ml granules for oral suspension

 Each 5 ml contains :

Active ingredient:

Cefixime trihydrate 111.9 mg (eq. To 100 mg cefixime)

Inactive ingredients:

Xanthan Gum , Sodium benzoate, Strawberry powder flavor , sucrose.

Pharmaceutical form

Hard gelatin capsule.

granules for oral suspension

Therapeutic indication

Suprax is an orally active cephalosporin antibiotic which has marked in vitro bactericidal activity against a wide variety of Gram-positive and Gram- negative organisms.

It is indicated for the treatment of the following acute infections when caused by susceptible micro-organisms:

Upper Respiratory Tract Infections (URTI): e g. otitis madia and other URTI where the causative organism is known or suspected to be resistant to other commonly used antibiotics, or where treatment failure carry significant risk .

Lower Respiratory Tract Infections: e g. bronchitis .

Urinary Tract Infections : e.g. cystitis, cystourethritis , uncomplicated pyelonephritis.

Clinical efficacy has been demonstrated in infections caused by commonly occuring pathogens including : Strepto-coccus pneumoniae, Streptococcus pyogenes, Escherichia coli, Proteus mirabilis, Kliebsiella species. Haemophilus influenzaa (bete-lactamase posntive and negative ), Branhamella catarrhalis  (bete-lactamase posntive and negative) and Enterobacter species . suprax is highly stable in the presence of beta -lactamese enzymes.

Suprax resistant organismis

Most strains of enterococci (Sterptococcus faecalis, group D Streptococci) and Staphylococci (including positive and negative strains and methicillin resistant strains) are resistant to Suprax. In addition , most strains of Pseu­domonas, Bacteriodes fragalis. Listeria monocytogenes and Clostridia are resistant to Suprax

Posology and method of administration

Absorption of Suprax is not significantly modified by the presence of food . The usual course of treatment is 7 days. This may be continued for up to 14 days if required.

Adults and Children over 10 Years : The recommended adult dosage is 200-400 rng daily accordinq to tile severity of infection , given either as a single dose or in two divided  doses.

The Elderly : Elderly patients May be given the same recommended dose for adults. Renal function should be assessed and dosage should be adjusted in severe renal impairment .

Children ( use pediatric oral suspension ) : The recommended dosage for children is 8 mg/kg/day administered as a single dose or in two divided doses . As a general guide for prescribing in children following daily doses in terms of volume pediatric Oral Suspension are suggested:

 6 months up to 1 year 3.75 ml daily Children 1 4 years 5 ml daily Chidren 5 10 years 10 ml daily

Children weighting more than 50 kg or older than 10 years should be treated with the recommended adult dose (200· 400 mg daily depending on the severity of infection).

The safety and efficacy of cefixime has not been established in children less than 6 months.

Dosage in Renal Impairment :

Suprax may be administered in the presence of impaired renal function.

Normal dose and schedule may be given in patients with creatinine clearances of 20 ml/min or greater.

In patients whose creatinine clearance is less than 20 ml/min, it is recommended that a dose of 200 mg once daily should not be exceeded .

The dose and regimen for patients who are maintained on chronic ambulatory peritoneal dialysis or haemodialysis should follow the same recommendation as that for patients with creatinine clearances less than 20 ml/min.

Contraindication

Patients with known hypersensitivity to Cefixime, to other cephalosporin’s or to any of the excipients .

Previous immediate and/or sever hypersensitivity reaction to a penicillin or to any other beta-Iactam medicinal products.

Special warning and precaution for use

Severe cutaneous adverse reactions

Severe cutaneous adverse reactions such as. toxic epidermal necrolysis , Stevens-Johnson syndrome and drug rash with eosinophilia and systemic symptoms (DRESS) have been reported In some patients on cefixime . When severe cutaneous adverse reactions occur, Cefixime should be discontinued and appropriate therapy and/or measures should be taken.

Suprax should be given with caution to patients who have shown hypersensitive to other drugs .

Hypersensitivity to penicillins

As with other  cephalosporin , Cefixime should be given with caution to  patients with a history of Hypersensitivity to penicillins , , as there is some evidence of partial cross-allergericity between the penicillin and cephalosporin.

Special caution is required to determine any other type of previous hypersensnivity reactions to penicillin or to other beta-Lactam medicinal products because partial cross-allergericity to these medicines may be hypersensitive to Suprax as well (cross- allergy).

Patients have had sever reactions (including anaphylaxis) to both classes of drugs. If an allergic effect occurs With Suprax, the drug should be discontinued and the patient treated with appropriate agents if necessary

Renal failure acute

As with other cephalosporins , Cefixime may cause acute renal failure including tubulointerstital nephritis as all under-lying pathological condition ., When acute renal failure  occurs. Cefixime should be discontinued and appropriate therepy and/or measures should be taken.

Renal impairment

Suprax .should be administered with caution in patients with elderly impaired renal function.

Pediatric use

Safety of Cefixime in premature or newborn infant has not been established.

Antibiotic associated pseudomembranous colitis

Treatment with broad spectrum antibiotics alters the normal flora of the colon and may permit overgrowth of clostridia .

Studies indicate that a toxin produced by Clostridium difficlle is a primary cause of antibiotic-associated diarrhoea . Pseudomembranous colitis is associated with the use of broad-spectrum antibiotics (including macrolid , semi-synthetic penicillin , lincosamides , cephalosporins ) : it is therefore important to consider its diagnosis in patents who develop diarrhoea in association with the use of antibiotics. Svmptoms of pseudomembranous colitis  may Occur during or after antibiotic treatment .

Management of pseudomembranous colitis should include sigmoidoscopy , appropriate bacteriologic studis , fluids , electrolytes and protein supplement. f the colitis doos not improve after the drug has been discontinued , or if the symptoms are severe. Oral vancomycin is the drug of choice for antibiotic associated pseudomembranous colitis Produced by C difficile . other causes of colitis should be excluded .

Interaction with other medication products and other forms of interaction

Anticoagulants

In common with other cephalosporin’s, increases in prothrombin time have been  noticed in a few patients. Care should therefore be taken in patients receiving anticoagulation therapy.

Cefixime should be administered with caution to patents ‘receiving coumarine type anticoagulant , e.g  : warfarin. Since Cefixime may” enhance effects of the anticoagulants , prolonged prothrombin time with or without bleeding may occur.

Other forms of lnteraction

A false positive reaction for glucose in the urine may occur with bendict’s or Fehling’s solutions or with copper -sulphate test tablets, but not with tests based on enzymatic glucose oxidise reactions.

A false positive direct Coombs test has been reported during treatment with cephalosporins antibiotics , therefore it should be recognised that a positive Coombs test may be due to the drug.

Pregnancy and lactation

Reproduction studies have been performed in Mice and rats at doses up to 400 times the human dose and have revealed no evidence of impaired fertility or harm to the foetus due ti Cefixime .

In the rabbit, at doses up to 4 times the human dose, there was no evidence of a teratogenic effect , there was high incidence of abortion and maternal death which is an expected consequence of the known sensitivity of rabbits to antibiotic-induced changes ill too population of the microflora of the intestine.

There are no adequate and well-controlled studies in pregnant woman. Suprax should therefore not be used in pregnancy or in nursing mothers unless considered essential by the physician.

Effect on ability to drive and use machines

 None.

Undesirable effects

Suprax is generally well tolerated .

The  majorty of adverse reactions observed in clinical trials were mild and self-lim­iting in nature.

The following adverse reaction:

Blood and lymphatic system disorders :

Eosinophilia .

Agranulocytosis

Leucopenia .

Haemolytic anaemia .

Gastrontestinal :

Abdominal pain

Diarrhoa

Nausea

Vomiting .

Hepatobilary disorder :

Infections and infestations:

Pseudomembranous colitis.

Investigations:

Aspartata aminotransferase increased .

Alanine amonitransferase increased.

Blood bilirubin increased.

Blood urea increased.

Blood creatinine increased.

Nervous system disorders :

Respiratory , thoracic and mediastiral disorders :

Renal and urinary disorder :

Renal failure aute including tubulointerstitial nephritis as an underlying pathological condition.

Immune system disorders , administrative site conditions , skin and subcutaneous tissue disorders :

Anaphylactic reactions .

Serum sickness-like reaction .

Drug rash with eaosinophilia and systemic symptoms ( DRESS ).

DRUG FEVER.

ERYTHEMA MULTIFORMA.

STEVENS JOHNSON SYNDROME.

Vaginitis .

Gental pruritis.

The above mentioned adverse reactions have been observed during clinical studies and / or during marketed use .

Diarrhoea has been more commonly associated with higher doses. Some cases of moderate to severe diarrhoea have been reported ; this has occasionally warranted cessation .

Suprax should be discontinued  if marked diarrhoea occurs

Overdose

There is no experience with overdoses with Suprax.

Adverse reactions seen at dose levels up to 2 gram .

Suprex in normal subjects did not differ from the profile seen  in patients treated at the recommended doses.

 No specific antidote exists.

Cefixime is not removed from the circulation in significant quantities by dialysis , general supportive measures are recommended.

Pharmacological property Pharmacodynamical properties:

Clinical efficacy has been demonstrated in infections caused by commonly occuring pathogens including : Strepto-coccus pneumoniae, Streptococcus pyogenes, Escherichia coli, Proteus mirabilis, Kliebsiella species. Haemophilus influenzaa (bete-lactamase posntive and negative ), Branhamella catarrhalis  (bete-lactamase posntive and negative) and Enterobacter species . suprax is highly stable in the presence of beta -lactamese enzymes.

Most strains of enterococci (Sterptococcus faecalis, group D Streptococci) and Staphylococci (including positive and negative strains and methicillin resistant strains) are resistant to Suprax. In addition , most strains of Pseu­domonas, Bacteriodes fragalis. Listeria monocytogenes and Clostridia are resistant to Suprax

Pharmacokinetics properties:

The absolute oral bloovailability of cefixime is in the range of 22- 54 % .

Absorption is not significantly modified by tbe presence of food.Cefixime may therefore be given without regard to meals.

From in vitro studies. serum or urine concentrations of 1 mcg/ml or greater were considered to be adequate for most common pathogens against which Cefixime is active.

Typically, tile peak serum levels following the recommenced adult or paediatric doses are between 1.5 and 3 mcg/ml.

Little or no accumulation of cifixime occurs fcllowing rnultple dosing.

The pharmacokinetics of cetixime in healthy olderly (age> 64 years) and young volunteers (11-35) compared the administration of 400 mg doses once dailY for 5 days. Mean C max.. and AUC values were slightly greater in the elder1y. Elderly patients may be given the same dose as the general populat ion.

Cefixime is predominantly eliminated as unchanged drug in the urine. Glomerular filtration is considered the predomi­nant mechanism. Metabolites of cefixime have not been isolated from human serum or urine .

Serum protein binding is well characterised for human and animal sera; Cefixime is almost exduslively bound to the albumin fraction, the mean free fraction being approximately 30%’.

Protein binding of Cefixime is only concentration dependent In human serum at very high concentrations which are not seen following clinical dosing.

Transfer of carbon 14 -Iabelled cefixime from lactating rats to their nursing offspring through breast milk was quantitatively small (approximately 1.5% of the mothers’ body content of Cefixime in the pup ) .

No data are available on secretion of cefixime in human breast milk .

Placental transfer of Cefixime was small in pregnant rats dosed with labelled Cefixime .

Storage

Store at temperature not exceed 30 C. in dry place.

Keep away from reach OF CHILDREN.

Package

Suprax 200 mgH_G. capsule:

Carton box containing one PVC/AL blisters, of 8 hard gelatin capsules wIth leaflet.

Suprax 400 mg H.G capsule:

Carton box containing one PVC /AL bilster  of 5 hard gelatine capsules with leaflet.

Suprax 100mg/5ml granules for suspension

Carton box containing AMber g ass bottle of granules to make 30m;, suspension after reconstitution and inserted leaflet.

Carton box containing Amber g ass bone of granules to make 60 ml suspension after reconstitution and inset leaflet.