1. Name Of The Medicinal Product
Suprax Powder for Paediatric Oral Suspension
2. Qualitative And Quantitative Composition
Each 5mL of reconstituted suspension contains 100 mg cefixime (anhydrous).
3. Pharmaceutical Form
For oral administration.
Bottles of powder for the preparation of suspension. When reconstituted, each 5 ml volume contains 100 mg of cefixime. The suspension contains 2.5 g of sucrose in 5 ml.
4. Clinical Particulars
4.1 Therapeutic Indications
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 media; and other URTI where the causative organism is known or suspected to be resistant to other commonly used antibiotics, or where treatment failure may carry significant risk.
Lower Respiratory Tract Infection: 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 Streptococcus pneumoniae, Streptococcus pyogenes, Escherichia coli, Proteus mirabilis, Kliebsiella species, Haemophilus influenzae (beta-lactamase positive and negative), Branhamella catarrhalis (beta-lactamase positive and negative) and Enterobacter species. Suprax is highly stable in the presence of beta-lactamase enzymes.
Most strains of enterococci (Streptococcus faecalis, group D Streptococci) and Staphylococci (including coagulase 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.
4.2 Posology And Method Of Administration
Route of Administration: Oral
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 mg daily according to the severity of infection, given either as a single dose or in two divided doses.
The Elderly: Elderly patients may be given the same dose as recommended for adults. Renal function should be assessed and dosage should be adjusted in severe renal impairment (See “Dosage in Renal Impairment”).
Children (Use Paediatric 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 the following daily doses in terms of volume of Paediatric Oral Suspension are suggested:
6 months up to 1 year: 3.75 ml daily
Children 1-4 years: 5 ml daily
Children 5-10 years: 10 ml daily
(A spoon is supplied to aid correct dosing - see “Nature and Contents of Container”).
Children weighing 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 of less than 20 ml/min.
4.3 Contraindications
Patients with known hypersensitivity to cephalosporin antibiotics.
4.4 Special Warnings And Precautions For Use
Suprax should be given with caution to patients who have shown hypersensitivity to other drugs. Cephalosporins should be given with caution to penicillin-sensitive patients, as there is some evidence of partial cross-allergenicity between the penicillins and cephalosporins.
Patients have had severe 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.
Suprax should be administered with caution in patients with markedly impaired renal function (See “Dosage in Renal Impairment”).
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 difficile is a primary cause of antibiotic-associated diarrhoea. Pseudomembranous colitis is associated with the use of broad-spectrum antibiotics (including macrolides, semi-synthetic penicillins, lincosamides and cephalosporins); it is therefore important to consider its diagnosis in patients who develop diarrhoea in association with the use of antibiotics. Symptoms of pseudomembranous colitis may occur during or after antibiotic treatment.
Management of pseudomembranous colitis should include sigmoidoscopy, appropriate bacteriologic studies, fluids, electrolytes and protein supplementation. If the colitis does 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.
4.5 Interaction With Other Medicinal Products And Other Forms Of Interaction
A false positive reaction for glucose in the urine may occur with Benedict's or Fehling's solutions or with copper sulphate test tablets, but not with tests based on enzymatic glucose oxidase reactions.
A false positive direct Coombs test has been reported during treatment with cephalosporin antibiotics, therefore it should be recognised that a positive Coombs test may be due to the drug.
In common with other cephalosporins, increases in prothrombin times have been noted in a few patients. Care should therefore be taken in patients receiving anticoagulation therapy.
4.6 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 to cefixime. In the rabbit, at doses up to 4 times the human dose, there was no evidence of a teratogenic effect; there was a high incidence of abortion and maternal death which is an expected consequence of the known sensitivity of rabbits to antibiotic-induced changes in the population of the microflora of the intestine. There are no adequate and well-controlled studies in pregnant women. Suprax should therefore not be used in pregnancy or in nursing mothers unless considered essential by the physician.
4.7 Effects On Ability To Drive And Use Machines
None.
4.8 Undesirable Effects
Suprax is generally well tolerated. The majority of adverse reactions observed in clinical trials were mild and self-limiting in nature.
Gastrointestinal Disturbances: The most frequent side effects seen with Suprax are diarrhoea and stool changes; diarrhoea has been more commonly associated with higher doses. Some cases of moderate to severe diarrhoea have been reported; this has occasionally warranted cessation of therapy. Suprax should be discontinued if marked diarrhoea occurs. Other gastrointestinal side effects seen less frequently are nausea, abdominal pain, dyspepsia, vomiting and flatulence. Pseudomembranous colitis has been reported (see above).
Central Nervous System: Headache and dizziness.
Hypersensitivity Reactions: Allergies in the form of rash, pruritus, drug fever and arthralgia have been observed, including rare cases of urticaria or angioedema. These reactions usually subsided upon discontinuation of therapy. Rarely, erythema multiforme, Stevens-Johnson syndrome and toxic epidermal necrolysis have been reported.
Haematological and Clinical Chemistry: Thrombocytosis, thrombocytopenia, leucopenia, hypereosinophilia, neutropenia and agranulocytosis have been reported. These reactions were infrequent and reversible. Mild transient changes in liver and renal function tests have been observed.
Hepatic Disorders: Transient rises in liver transaminases, alkaline phosphatase and jaundice can also occur.
Miscellaneous: Other possible reactions include genital pruritus and vaginitis.
4.9 Overdose
There is no experience with overdoses with Suprax.
Adverse reactions seen at dose levels up to 2 g Suprax in normal subjects did not differ from the profile seen in patients treated at the recommended doses. Gastric lavage may be indicated in overdosage. No specific antidote exists. Cefixime is not removed from the circulation in significant quantities by dialysis.
5. Pharmacological Properties
5.1 Pharmacodynamic Properties
Cefixime is an oral third generation cephalosporin which has marked in vitro bactericidal activity against a wide variety of Gram-positive and Gram-negative organisms.
Clinical efficacy has been demonstrated in infections caused by commonly occurring pathogens including Streptococcus pneumoniae, Streptococcus pyogenes, Escherichia coli, Proteus mirabilis, Klebsiella species, Haemophilus influenzae (beta-lactamase positive and negative), Branhamella catarrhalis (beta-lactamase positive and negative) and Enterobacter species. It is highly stable in the presence of beta-lactamase enzymes.
Most strains of enterococci (Streptococcus faecalis, group D Streptococci) and Staphylococci (including coagulase positive and negative strains and methicillin-resistant strains) are resistant to cefixime. In addition, most strains of Pseudomonas, Bacteroides fragilis, Listeria monocytogenes and Clostridia are resistant to cefixime.
5.2 Pharmacokinetic Properties
The absolute oral bioavailability of cefixime is in the range of 22-54%. Absorption is not significantly modified by the 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, the peak serum levels following the recommended adult or paediatric doses are between 1.5 and 3 mcg/ml. Little or no accumulation of cefixime occurs following multiple dosing.
The pharmacokinetics of cefixime in healthy elderly (age> 64 years) and young volunteers (11-35) compared the administration of 400 mg doses once daily for 5 days. Mean Cmax and AUC values were slightly greater in the elderly. Elderly patients may be given the same dose as the general population.
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 exclusively 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 14C-labelled 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. Placetal transfer of cefixime was small in pregnant rats dosed with labelled cefixime.
5.3 Preclinical Safety Data
There are no pre-clinical data of relevance to the prescriber which are additional to that already included in other sections of the Summary of Product Characteristics.
6. Pharmaceutical Particulars
6.1 List Of Excipients
Sucrose, xantham gum, sodium benzoate and strawberry flavour.
6.2 Incompatibilities
None.
6.3 Shelf Life
2 years unopened.
2 weeks after reconstitution.
6.4 Special Precautions For Storage
Do not store unreconstituted product above 25°C.
Bottled product: To reconstitute, add 33 ml of water (50 ml bottle) or 66 ml of water (100 ml bottle) in two portions shaking after each addition. After reconstitution, the suspension may be stored at room temperature (below 25ยบ C) for 14 days without significant loss of potency. Do not freeze. Keep bottles tightly closed and shake well before use. Discard any unused portion after 14 days. Dilution of the suspension is not recommended.
6.5 Nature And Contents Of Container
Type III amber glass screw necked bottle with child resistant push/turn closure with white polyethylene cap with polyethylene film seal on expanded low density polyethylene. Bottles are supplied with a single ended transparent polypropylene (plastic) spoon capable of measuring 3.75 and 5.0ml of the suspension. Pack sizes of 50 and 100 ml.
6.6 Special Precautions For Disposal And Other Handling
None stated.
7. Marketing Authorisation Holder
Aventis Pharma Limited
50 Kings Hill Avenue
Kings Hill
West Malling
Kent
ME19 4AH
UK
or trading as
Sanofi-aventis
One Onslow Street
Guildford
Surrey
GU1 4YS
UK
8. Marketing Authorisation Number(S)
PL 04425/0622
9. Date Of First Authorisation/Renewal Of The Authorisation
14 October 1998
10. Date Of Revision Of The Text
17th July 2010
11 LEGAL CLASSIFICATION
POM
No comments:
Post a Comment