Cefutil^® is an oral prodrug of the bactericidal cephalosporin antibiotic cefuroxime, which is resistant to most (beta)-lactamases and is active against a wide range of Gram-positive and Gram-negative organisms.  It is indicated for the treatment of infections caused by susceptible bacteria. Susceptibility to Cefutil^® will vary with geography and time and local susceptibility data should be consulted where available (See Pharmacological properties, Pharmacodynamics).

Indications include:

·      Upper respiratory tract infections for example, ear, nose and throat infections, such as otitis media, sinusitis, tonsillitis and pharyngitis in adults and children over 12 years old.

·      Lower respiratory tract infections for example, pneumonia acute exacerbations of chronic obstructive pulmonary disease in adults and children over 12 years old.

·      Genito-urinary tract infections (for example: pyelonephritis, cystitis and urethritis) in adults and children over 12 years old.

·      Skin and soft tissue infections (for example: furunculosis, pyoderma and impetigo) in adults and children over 12 years old.

·      Treatment of early Lyme disease and subsequent prevention of late Lyme disease in adults and children over 12 years old.

The usual course of therapy is seven days. (Range 5 to 10 days).

·                Cefutil^® should be taken after food for optimum absorption.

Adults

 Sequential therapy

Pneumonia

1.5 g cefuroxime Sodium three times a day or twice a day (intravenous (i.v.) or intramuscular (i.m)) for 48 to 72 hours, followed by Cefutil^® (cefuroxime axetil) oral therapy 500 mg twice a day for 7 to 10 days.

Acute exacerbations of chronic bronchitis

750 mg cefuroxime Sodium three times a day or twice a day (iv or im) for 48 to 72 hours, followed by Cefutil^® (cefuroxime axetil) oral therapy 500mg twice a day for 5 to 10 days.

Duration of both parenteral and oral therapy is determined by the severity of the infection and the clinical status of the patient.

·                Children

Cefutil^® tablets should not be crushed and are therefore unsuitable for treatment of patients, such as younger children, who cannot swallow tablets. In children Cefuroxime oral suspension may be used.

There is no experience of using cefuroxime in children under the age of 3 months.

·                Renal impairment

Cefuroxime is primarily excreted by the kidneys. In patients with markedly impaired renal function it is recommended that the dosage of cefuroxime be reduced to compensate for its slower excretion (see the table below).

Special care is indicated in patients who have experienced an allergic reaction to penicillins or other beta-lactams.

As with other antibiotics, use of Cefutil^® may result in the overgrowth of Candida. Prolonged use may also result in the overgrowth of other non-susceptible organisms (e.g. enterococci and Clostridium difficile), which may require interruption of treatment.

Pseudomembranous colitis has been reported with the use of antibiotics and may range in severity from mild to life-threatening. Therefore, it is important to consider its diagnosis in patients who develop diarrhoea during or after antibiotic use. If prolonged or significant diarrhoea occurs or the patient experiences abdominal cramps, treatment should be discontinued immediately and the patient investigated further.

The Jarisch-Herxheimer reaction has been seen following cefuroxime treatment of Lyme disease.  It results directly from the bactericidal activity of cefuroxime on the causative organism of Lyme disease, the spirochaete Borrelia burgdorferi.  Patients should be reassured that this is a common and usually self-limiting consequence of antibiotic treatment of Lyme disease.

With a sequential therapy regime the timing of change to oral therapy is determined by severity of the infection, clinical status of the patient and susceptibility of the pathogens involved. If there is no clinical improvement within 72 hours, then the parenteral course of treatment must be continued.

Please refer to the relevant prescribing information for cefuroxime sodium before initiating sequential therapy.

Drugs which reduce gastric acidity may result in a lower bioavailability of cefuroxime compared with that of the fasting state and tend to cancel the effect of enhanced post-prandial absorption.

In common with other antibiotics, cefuroxime may affect the gut flora, leading to lower oestrogen reabsorption and reduced efficacy of combined oral contraceptives.

As a false negative result may occur in the ferricyanide test, it is recommended that either the glucose oxidase or hexokinase methods are used to determine blood/plasma glucose levels in patients receiving cefuroxime.  This antibiotic does not interfere in the alkaline picrate assay for creatinine.

There is no experimental evidence of embryopathic or teratogenic effects attributable to cefuroxime but, as with all drugs, it should be administered with caution during the early months of pregnancy. 

Cefuroxime is excreted in human milk, and consequently caution should be exercised when cefuroxime is administered to a nursing mother.

As this medicine may cause dizziness, patients should be warned to be cautious when driving or operating machinery.

Adverse drug reactions to cefuroxime  are generally mild and transient in nature.

The frequency categories assigned to the adverse reactions below are estimates, as for most reactions suitable data (for example from placebo-controlled studies) for calculating incidence were not available.  In addition, the incidence of adverse reactions associated with cefuroxime  may vary according to the indication.

Data from large clinical studies were used to determine the frequency of very common to rare undesirable effects.  The frequencies assigned to all other undesirable effects (i.e. those occurring at <1/1000) were mainly determined using post-marketing data and refer to a reporting rate rather than true frequency.  Placebo-controlled trial data were not available.  Where incidences have been calculated from clinical trial data, these were based on drug-related (investigator assessed) data.

The following convention has been used for the classification of frequency:

 Very common ≥1/10

Common ≥1/100 to <1/10

Uncommon ≥1/1000 to <1/100

Rare ≥1/10,000 to <1/1000

Very rare <1/10,000

Infections and infestations

Common: Overgrowth of Candida.

Blood and lymphatic system disorders                       

Common:  Eosinophilia.

Uncommon: Positive Coombs’ test, thrombocytopenia, leucopenia (sometimes profound).

Very rare: Haemolytic anaemia.

Cephalosporins as a class tend to be absorbed onto the surface of red cells membranes and react with antibodies directed against the drug to produce a positive Coombs’ test (which can interfere with cross-matching of blood) and very rarely haemolytic anaemia.

Immune system disorders

Hypersensitivity reactions including:

Uncommon: Skin rashes.

Rare:  Urticaria, pruritus.

Very rare: Drug fever, serum sickness, anaphylaxis.

Nervous system disorders

Common: Headache, dizziness.

Gastrointestinal disorders

Common: Gastrointestinal disturbances including diarrhoea, nausea, abdominal pain.

Uncommon: Vomiting.

Rare: Pseudomembranous colitis (See Warnings and Precautions).

Hepatobiliary disorders

Common: Transient increases of hepatic enzyme levels, [ALT (SGPT), AST (SGOT), LDH].

Very rare: Jaundice (predominantly cholestatic), hepatitis.

Skin and subcutaneous tissue disorders

Very rare:  Erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis (exanthematic necrolysis).

See also Immune system disorders.

To report any side effect(s):

•Saudi Arabia:

The National Pharmacovigilance Center (NPC):

SFDA Call Center: 19999

E-mail: npc.drug@sfda.gov.sa

Website: https://ade.sfda.gov.sa

•United Arab of Emirates:

Pharmacovigilance and Medical Device Section

P.O. Box: 1853, Tel: 80033784

Email: pv@ede.gov.ae

Drug Department, Ministry of Health & Prevention

Dubai-UAE.

• Sultanate of Oman

Department of Pharmacovigilance & Drug Information

Drug Safety Center

Ministry of health, Sultanate of Oman

Phone No: 22357687 / 22357690

Fax: 22358489

Email: pharma-vigil@moh.gov.om

Website: www.moh.gov.om

•Other GCC States:

Please contact the relevant competent authority.

Signs and symptoms

Overdosage of cephalosporins can cause cerebral irritation leading to convulsions.

Treatment

Serum levels of cefuroxime can be reduced by haemodialysis and peritoneal dialysis.

The prevalence of acquired resistance is geographically and time dependent and for select species may be very high.  Local information on resistance is desirable, particularly when treating severe infections.

Absorption

After oral administration cefuroxime is slowly absorbed from the gastrointestinal tract and rapidly hydrolysed in the intestinal mucosa and blood to release cefuroxime into the circulation.

Optimum absorption occurs when it is administered shortly after a meal.

Following administration of cefuroxime  tablets peak serum levels (2.1 mg/l for a 125 mg dose, 4.S-S1 mg/l for a 250 mg dose, 7.0 mg/l for a 500 mg dose and 13.6 mg/l for a 1 g dose) occur approximately 2 to 3 hours after dosing when taken withfood.

Distribution

Protein binding has been variously stated as 33-50% depending on the methodology used.

Metabolism

Cefuroxime is not metabolised.

Elimination

The serum half life is between 1 and 1.5 hours.

Cefuroxime is excreted by glomerular filtration and tubular secretion. Concurrent administration of probenecid increases the area under the mean serum concentrations time curve by 50%.

Renal impairment:

Cefuroxime pharmacokinetics have been investigated in patients with various degrees of renal impairment.  Cefuroxime elimination half-life increases with decrease in renal function which serves as the basis for dosage adjustment recommendations in this group of patients (See Dosage and Administration).  In patients undergoing haemodialysis, at least 60% of the total amount of cefuroxime present in the body at the start of dialysis will be removed during a 4-hour dialysis period.   Therefore, an additional single dose of cefuroxime should be administered following the completion of haemodialysis.

Animal toxicity studies indicated that cefuroxime axetil is of low toxicity with no significant findings.

Microcrystalline cellulose, croscarmellose sodium, sodium starch glycolate, sodium lauryl sulfate, Silica Colloidal Anhydrous, magnesium stearate, opadry OY-L white, FD&C Blue #1, PEG.

Not applicable

Store below 30^oC.

Cefutil^® 250 mg: blue, oval, film coated, deep convex, non-scored tablets, engraved with PhI on one face, presented in Alu/Alu blisters, intended for oral use.

Pack size: 10 film coated tablets.

Cefutil^® 500 mg: blue, oval, film coated, deep convex, non-scored tablets, engraved with PhI on one face, presented in HDPE bottles, intended for oral use.

Pack size: 10 film coated tablets.

14 film coated tablets.

No special requirements.