Cefugen 250 mg and 500 mg Film-coated tablets

CEFUGEN is indicated for the treatment of patients with infections caused by susceptible organisms in the following diseases:

• Pharyngitis and Tonsillitis caused by Streptococcus pyogenes. (Penicillin is the usual medicine of choice in the treatment and prevention of Streptococcal infections, including the prophylaxis of rheumatic fever. CEFUGEN is generally effective in the eradication of streptococci from the oral pharynx. CEFUGEN is not indicated for the prophylaxis of subsequent rheumatic fever because data to support such use is not available).
• Otitis Media caused by Streptococcus pneumoniae, Haemophilus influenzae (ampicillin-susceptible and ampicillin-resistant strains), Moraxella (Branhamella) catarrhalis, and Streptococcus pyogenes.
• Sinusitis caused by Streptococcus pneumoniae and Haemophilus influenzae.
• Acute and chronic bronchitis caused by Streptococcus pneumoniae, Haemophilus influenzae (ampicillin-susceptible strains), and Haemophilus parainfluenzae (ampicillin-susceptible strains).
• Acute uncomplicated cystitis caused by Escherichia coli and Klebsiella pneumoniae.
• Lyme Disease caused by the spirochaete Borrelia burgdorferi. CEFUGEN is indicated for the treatment of early Lyme disease and subsequent prevention of late Lyme disease in adults and children over 12 years old.

Posology

Adults

• Pharyngitis and tonsillitis: 250 mg twice daily for seven days (range 5 - 10 days)
• Otitis media: 500 mg twice daily for seven days (range 5 - 10 days)
• Sinusitis: 250 mg twice daily for seven days (range 5 - 10 days).
• Acute and chronic bronchitis: 250 mg twice daily for seven days (range 5 - 10 days)
• Acute uncomplicated cystitis: 250 mg twice daily for seven days (range 5 - 10 days).
• Lyme disease: 500 mg twice daily for 14 days. (range 10 - 21 days).

Children 12 years and older

Lyme disease in children over the age of 12 years: the usual dose is 500 mg twice daily for 14 days. (range 10 - 21 days).

Special Populations

Elderly: No special precaution is necessary in the elderly patients with normal renal function at dosages up to the normal maximum of 1 g per day. Elderly patients are more likely to have decreased renal function; therefore, the dose should be adjusted in accordance with the renal function in the elderly (see Table 1: Recommended doses for renal impairment below).

Renal impairment: Cefuroxime is primarily excreted by the kidneys. It is recommended that the dosage for patients with markedly impaired renal function (i.e. CrCl <30 ml/minute) should be reduced to compensate for the slower excretion (see Table 1: Recommended doses for renal impairment below).

Table 1: Recommended doses for renal impairment

Hepatic impairment: Since cefuroxime is primarily eliminated by the kidney, the presence of hepatic dysfunction is expected to have no effect on the pharmacokinetics of cefuroxime.

Paediatric population: In older infants (aged >3 months) and in children, the pharmacokinetics of cefuroxime are similar to that observed in adults. There is no clinical trial data available on the use of cefuroxime axetil in children under the age of 3 months. Only children older than 12 years may use CEFUGEN.

Method of Administration

For oral administration only. CEFUGEN should be taken half an hour after food for optimum absorption. Because of the bitter taste of cefuroxime axetil, CEFUGEN tablets should not be crushed and are therefore unsuitable for treatment of patients who cannot swallow tablets.

• Hypersensitivity to cephalosporin antibiotics, the active substance, or to any of the excipients listed in section 6.1.
• History of severe hypersensitivity (e.g. anaphylactic reaction) to any other type of beta-lactam antibacterial medicine (penicillins, monobactams and carbapenems).

Prescribers must adhere to the principles of antibiotic stewardship. Special care is indicated in patients who have experienced an allergic reaction to penicillins or other beta-lactam antibiotics. There is a risk of cross-sensitivity. In the case of severe hypersensitivity reactions, treatment with CEFUGEN must be discontinued immediately and adequate emergency measures must be initiated. CEFUGEN should be used with caution in patients with:

• a history of gastro-intestinal disease, especially ulcerative colitis, regional enteritis or pseudomembranous colitis.
• renal function impairment a reduced dose may be required.
• porphyria, as safety has not been established.

Hypersensitivity reactions Serious and occasionally fatal hypersensitivity reactions have been reported. There have been reports of hypersensitivity reactions which progressed to Kounis syndrome (acute allergic coronary arteriospasm that can result in myocardial infarction, see section 4.8).

Before beginning treatment with CEFUGEN, it should be established whether the patient has a history of severe hypersensitivity reactions to cefuroxime, to other cephalosporins or to any other type of beta-lactam medicine. Caution should be used if CEFUGEN is given to patients with a history of non-severe hypersensitivity to other beta-lactam medicine.

Jarisch-Herxheimer reaction The Jarisch-Herxheimer reaction has been seen following cefuroxime treatment of Lyme disease. It results directly from the bactericidal activity of cefuroxime axetil on the causative bacteria 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 (see section 4.8).

Overgrowth of non-susceptible microorganisms Use of CEFUGEN may result in the overgrowth of Candida. Prolonged use may also result in the overgrowth of other non-susceptible microorganisms (e.g. Enterococci and Clostridium difficile), which may require discontinuation of treatment (see section 4.8).

Pseudomembranous colitis Antibacterial medicine u2013 associated pseudomembranous colitis have been reported with cefuroxime as in CEFUGEN and may range in severity from mild to life threatening. This diagnosis should be considered in patients who develop abdominal or stomach cramps, abdominal tenderness, severe and watery diarrhoea (which may be bloody) and fever during or subsequent to the administration of CEFUGEN. If the diagnosis of pseudomembranous colitis is suspected, discontinue therapy with CEFUGEN and the administration of specific treatment for Clostridium difficile should be considered. Medicinal products that inhibit peristalsis should not be given (see section 4.8).

Interference with serological testing Slight interference with copper reduction methods (Benedict's, Fehling's, Clinitest) may be observed. However, this should not lead to false-positive results. Cefuroxime does not interfere with enzyme-based tests for glucosuria. Cefuroxime may cause false-negative reactions in the ferricyanide test.

Hence it is recommended that either the glucose oxidase or hexokinase methods are used to determine blood/plasma glucose levels in patients receiving cefuroxime axetil as in CEFUGEN. Cefuroxime can cause a falsely high reading in the alkaline picrate assay for creatinine, although the degree of elevation is unlikely to be of clinical importance. It is possible that cefuroxime may also interfere with this determination. The development of a positive Coombu2019s Test associated with the use of cefuroxime may interfere with cross matching of blood (see section 4.8).

Important information about excipients This medicine contains less than 1 mmol of sodium (23 mg) per tablet.

Medicines which reduce gastric acidity: Concurrent use with CEFUGEN may result in a lower bioavailability of cefuroxime compared with that of the fasting state and tend to cancel the effect of enhanced absorption after food.

Probenecid: CEFUGEN is excreted by glomerular filtration and tubular secretion. Concomitant use of probenecid is not recommended as probenecid significantly increases the peak concentration area under the serum concentration time curve and elimination half-life of cefuroxime.

Concomitant use of cefuroxime and furosemide should be avoided when possible, due to enhanced nephrotoxicity. The combined use of cephalosporins and aminoglycosides should be undertaken with caution, due to nephrotoxicity.

Oral contraceptives: CEFUGEN may affect the gut flora, leading to lower oestrogen reabsorption and reduced efficacy of combined oral contraceptives.

Oral anticoagulants: Concomitant use with oral anticoagulants may give rise to increased international normalised ratio (INR).

Women of childbearing potential / Contraception in males and females: Concurrent use of CEFUGEN and oral contraceptives decreases the efficacy of the oral contraceptive. Patients should be strongly advised to use an alternative or additional method of contraception while taking CEFUGEN (see section 4.5).

Pregnancy: Safety in pregnancy has not been established (see section 4.3). There are limited data from the use of CEFUGEN in pregnant women. Studies in animals have shown no harmful effects on pregnancy, embryonal or foetal development, parturition or postnatal development.

Breastfeeding: Safety in lactation has not been established (see section 4.3). CEFUGEN is excreted in human milk in small quantities. Adverse effects at therapeutic doses are not expected, although the possibility of sensitisation should be taken into account and the risk of diarrhoea and fungus infection of the mucous membranes cannot be excluded. Breastfeeding might have to be discontinued due to these effects.

Fertility: There is no data available on the effects of CEFUGEN on fertility in humans. Reproductive studies in animals have shown no effects on fertility.

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

The most common adverse reactions are Candida overgrowth, eosinophilia, headache, dizziness, gastrointestinal disturbances and transient rise in liver enzymes.

The following undesirable effects have been observed and reported during treatment with cefuroxime:

Tabulated list of adverse reactions

Description of selected adverse reactions

Cephalosporins as a class tend to be absorbed onto the surface of red cells membranes and react with antibodies directed against the medicine to produce a positive Coombsu2019 test (which can interfere with cross-matching of blood) and very rarely haemolytic anaemia. Transient rises in serum liver enzymes have been observed which are usually reversible.

Paediatric population The safety profile for CEFUGEN in children is consistent with the profile in adults.

Reporting of suspected adverse reactions Reporting suspected adverse reactions after authorisation of the medicine is important. It allows continued monitoring of the benefit/risk balance of the medicine. Health care providers are asked to report any suspected adverse reactions to SAHPRA via the Med Safety APP (Medsafety X SAHPRA) and eReporting platform (who-umc.org) found on SAHPRA website.

See section 4.8.

Symptoms of overdose: Seizures have been reported. Overdose can lead to neurological sequelae including encephalopathy, convulsions and coma. Symptoms of overdose can occur if the dose is not reduced appropriately in patients with renal impairment (see sections 4.2 and 4.4).

Treatment of overdose: Treatment is symptomatic and supportive. Serum levels of cefuroxime can be reduced by haemodialysis and peritoneal dialysis.