Zamur is indicated in the following infections caused by cefuroxime-sensitive microorganisms: Upper respiratory tract: tonsillitis, pharyngitis, otitis media, sinusitis. Lower respiratory tract: acute bronchitis and acute exacerbations of chronic bronchitis, pneumonia. 
Urinary tract: pyelonephritis, cystitis, urethritis. 
Skin and soft tissue: furunculosis, pyoderma, impetigo.  
Gonorrhoea: acute uncomplicated urethritis and cervicitis. 
Lyme’s disease: stage I, erythema chronicum migrans with possible transient joint symptoms or transitory and limited neurological reactions. Official recommendations on the appropriate use of antibiotics should be followed, particularly recommendations for use regarding the prevention of increased resistance to antibiotics.

The usual duration of treatment is 7 (5-10) days, depending on the severity and course of the infection. 
 
To ensure optimal absorption, Zamur should be taken with meals. Due to their bitter taste, the film-coated tablets should not be chewed or crushed and are therefore unsuitable for children below 5 years of age. Usual dosage 
Adults and children over 12 years 
Standard dosage: 250 mg twice daily (every 12 hours). 
Mild to moderate lower respiratory tract infections: 250 mg twice daily (every 12 hours). 
Severe lower respiratory tract infections: 500 mg twice daily (every 12 hours). 
Uncomplicated gonorrhoea: one single dose of 1 g. 
Lyme’s disease: 500 mg twice daily (every 12 hours) for 20 days. 
Alternative dosage 
- Mild to moderate community-acquired pneumonia: 1.5 g cefuroxime sodium IV or IM twice daily for 48 – 72 hours, followed by 500 mg Zamur orally twice daily for 7 – 10 days. - Acute exacerbations of chronic bronchitis: 750 mg cefuroxime sodium IV or IM twice daily for 48 – 72 hours, followed by 500 mg Zamur orally twice daily for 5 – 10 days. The time for switching from parenteral to oral treatment is dependent on the severity of infection, the patient’s clinical condition and microbial sensitivity. If no clinical improvement has occurred within 72 hours, parenteral treatment must be continued. Children aged 5 to 12 years: 
Standard dosage: 
For most infections, the dosage for children aged 5-12 years weighing at least 15 kg is  125 mg (2 x ½ film-coated tablet) twice daily (every 12 hours), up to a maximum daily dose of 250 mg. Otitis media or serious infection in children from 5 years of age weighing at least 20 kg: 250 mg twice daily (every 12 hours). Maximum daily dose: 500 mg. Children under 5 years: 
It is not possible to treat children under 5 years with the pharmaceutical formulations available for Zamur. 

 
Dosage in impaired renal function 
Cefuroxime is mainly excreted via the kidneys. 
In patients with significant renal impairment (creatinine clearance below 30 mL/min), it is recommended that the cefuroxime dosage be reduced on account of the slower elimination (see table below).  

Creatinine clearance : T½ (hours) : Recommended dosage 
≥30 mL/min/1.73 m2 : 1.4-2.4 : No dose adjustment required (usual dose of 125 mg to 500 mg twice daily) 
10– 29 mL/min/1.73 m2 :  4.6 : Standard single dose, every 24 hours 
<10 mL/min/1.73 m2 : 16.8 : Standard single dose, every 48 hours 
On haemodialysis : 2-4 :  After every dialysis session, an additional standard single dose should be administered. 
 
 

In general, caution is advised when administering beta-lactam antibiotics to patients who are susceptible to allergic reactions. As with other antibiotics, administration may result in increased growth of Candida. With prolonged administration, increased growth of non-sensitive microbes (e.g. enterococci, Clostridium difficile) may also occur, which may necessitate discontinuation of treatment. Close patient observation is therefore essential. If a superinfection occurs during treatment, appropriate measures must be taken. 
The onset of diarrhoea during or after treatment with Zamur, especially if it is severe, persistent and/or bloody, may be a symptom of infection with Clostridium difficile. Its most severe form is pseudomembranous colitis. If any such complication is suspected, treatment with Zamur must be discontinued immediately and the patient should be thoroughly examined to initiate, if necessary, 

 
specific antibiotic therapy (e.g. metronidazole, vancomycin). The use of antiperistaltic agents is contraindicated in this clinical situation. 
In cases of impaired renal function, the Zamur dosage must be adjusted to the degree of renal insufficiency (see “Dosage in impaired renal function”). Caution is advised when combining high-dose cephalosporins with potent diuretics and/or aminoglycosides, as this might adversely affect renal function (see “Interactions”). During treatment, renal function should be constantly monitored in patients on combination therapy, in patients with pre-existing renal damage and generally in elderly patients. In case of (epilepsy-like) seizures (see “Overdose”), the usual appropriate emergency measures are indicated (e.g. maintaining airway patency and administration of anticonvulsants). In association with cefuroxime treatment for Lyme’s disease, occurrence of a Jarisch- Herxheimer reaction was observed in approximately 17% of patients. This reaction is a direct consequence of the bactericidal action of cefuroxime on Borrelia burgdorferi, the spirochete which causes Lyme’s disease. The patient should be assured that this is a usual and normally transient consequence of antibiotic treatment for Lyme’s disease. Patients must be informed that taking this medicinal product can cause dizziness and may thereby impair the ability to drive and use machines (see sections “Effects on ability to drive and use machines” and “Undesirable effects”). 
 

Cephalosporin antibiotics should only be given with extreme caution in combination with aminoglycosides and potent diuretics such as furosemide, as these combinations can have an adverse effect on renal function. 
Taking medicines that reduce gastric acid levels may decrease the bioavailability of Zamur and offset the normally increased rate of absorption after a meal. Probenecid leads to a reduction in the renal clearance of Zamur, thereby increasing concentrations of Zamur and prolonging its residence time within the body. As with other antibiotics, cefuroxime can adversely affect the intestinal flora, which can lead to reductions in oestrogen absorption and efficacy of combined oral contraceptives. 
Bacteriostatic agents can interfere with the bactericidal action of cephalosporins. 
Antagonism with cefoxitin, imipenem and chloramphenicol has been demonstrated in rare cases. The clinical relevance of these in vitro results is not known. 

 
For blood/plasma glucose determination, enzymatic methods (glucose oxidase or hexokinase method) should be used, as interference has been observed in reduction tests. To determine creatinine, the alkaline picrate assay (Jaffé reaction) should be used. 

Pregnancy 
Experimental studies revealed no indications of embryopathic or teratogenic effects. No controlled studies are available on pregnant women. Zamur should not be used during pregnancy unless clearly necessary.

Lactation 
Small quantities of cefuroxime are excreted in human milk. Use during lactation is therefore not recommended. 
 

This medicinal product can cause dizziness. Patients should therefore be warned that dizziness occurring while driving or using machines can affect their own safety and that of others. 
 

The frequency categories stated below are estimates, as no appropriate data (e.g. from placebo-controlled studies) were available for calculating the incidence of most reactions. In addition, the incidence of adverse reactions associated with cefuroxime axetil may vary according to the indication. Data from large clinical studies were used to determine the frequency of very common to rare undesirable effects. Frequencies for all other undesirable effects (i.e. with an incidence of < 1/10,000) mainly come from post-marketing reports and therefore refer to the reporting rate rather than actual frequency of occurrence. No data were available from placebo-controlled studies. In cases where incidence values were calculated from clinical study data, drug-related data (according to investigator assessment) were used. The following convention has been used for the classification of frequency: 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 and infestations Common: increased growth of Candida with long-term use. 
Blood and lymphatic system disorders Common: eosinophilia. 

 
Uncommon: positive Coombs’ test, thrombocytopenia, leukopenia (occasionally very pronounced), neutropenia. Very rare: haemolytic anaemia. 
Cephalosporins as a substance class tend to attach to the surface of red cell membranes and react with antibodies directed against the medicinal product, thus producing a positive Coombs’ test and, very rarely, haemolytic anaemia. Serological cross-matching may be affected. Immune system disorders 
Hypersensitivity reactions including: Uncommon: rash including maculopapular or morbilliform exanthema. Rare: urticaria, pruritus (itching). Very rare: drug fever, serum sickness, anaphylaxis. 
Nervous system disorders Common: headache, dizziness. Gastrointestinal disorders 
Common: gastrointestinal disorders including diarrhoea, nausea, abdominal pain. Uncommon: vomiting. 
Rare: pseudomembranous colitis (see “Special warnings and precautions for use”). Very rare: heartburn. 
When treating Lyme’s disease, there may be increased incidence of diarrhoea (around 10% in controlled studies), due to the prolonged duration of treatment (20 days). Hepatobiliary disorders 
Common: transient elevations of liver enzyme values: (ALT [SGPT], AST [SGOT], LDH). Uncommon: transient increase in alkaline phosphatase. The bilirubin concentration may also rise temporarily. Very rare: jaundice (predominantly cholestatic jaundice), hepatitis. Skin and subcutaneous tissue disorders 
Very rare: erythema exsudativum multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis (exanthema necrolysis). 
See also Immune system disorders. 
 
To report any side effect(s): Saudi Arabia: 

 
The National Pharmacovigilance and Drug Safety Centre (NPC)  Fax: +966-11-205-7662  Call NPC at +966-11-2038222, Exts: 2317-2356-2353-2354-2334-2340.  Toll free phone: 8002490000  E-mail: npc.drug@sfda.gov.sa  Website: www.sfda.gov.sa/npc 

Cases of overdose with cephalosporins can cause cerebral disorders, which may manifest as seizures. Anticonvulsant treatment may be indicated. Excessively high cefuroxime levels can be reduced by haemodialysis or peritoneal dialysis.

ATC code: J01DC02 
Mechanism of action 
Cefuroxime axetil (1-acetoxyethylester of cefuroxime) is a semi-synthetic second- generation cephalosporin, which is effective when given orally. Cefuroxime may only be administered parenterally. Cefuroxime axetil, a prodrug, is converted in the body to the active metabolite cefuroxime, which exerts a bactericidal action by inhibiting cell wall synthesis. Zamur is stable against most β-lactamases and is active in vitro against the following microorganisms. The prevalence of acquired resistance varies depending on the geographic region, as well as over time, and may be very high in certain species. Information on resistance in each specific region is useful, especially for the treatment of severe infections. 
In vitro sensitivity of pathogens to cefuroxime 
* Clinical efficacy of cefuroxime has been proven in clinical studies. + All methicillin-resistant Staphylococcus spp. are resistant to cefuroxime. Sensitive microorganisms 
 
Normally sensitive microorganisms:   Gram-positive aerobes:   Streptococcus pyogenes* (and other β-haemolytic streptococci)   

 
Staphylococcus aureus *(methicillin-sensitive isolates) + coagulase-negative staphylococci (methicillin-sensitive isolates) 
  
Gram-negative aerobes:   Haemophilus influenzae (incl. ampicillin-resistant strains)*   Haemophilus parainfluenzae*   Moraxella catarrhalis*   Spirochetes: Borrelia burgdorferi* Species in which acquired resistance may pose a problem Gram-positive aerobes: Streptococcus pneumoniae* Gram-negative aerobes: Citrobacter spp. excl. C. freundii Enterobacter spp. excl. E. aerogenes and E. cloacae Escherichia coli* Klebsiella spp. incl. K. pneumoniae* Neisseria gonorrhoea* (penicillinase-and non-penicillinase-producing strains) Proteus mirabilis Proteus spp. excl. P. penneri and P. vulgaris Providencia spp. Gram-positive anaerobes:    Clostridium spp. with C. difficile   Peptostreptococcus spp.   
Propionibacterium spp.   
Gram-negative anaerobes: Bacteroides spp. excl. B. fragilis   Fusobacterium spp.   Naturally resistant species: Gram-positive aerobes: Enterococcus spp. incl. E. faecalis and E. faecium Listeria monocytogenes Gram-negative aerobes: Acinetobacter spp. Burkholderia cepacia 

 
Campylobacter spp. Citrobacter freundii Enterobacter aerogenes Enterobacter cloacae Morganella morganii Proteus penneri Proteus vulgaris Pseudomonas spp. incl. P. aeruginosa Serratia spp. Stenotrophomonas maltophilia Gram-positive anaerobes: Clostridium difficile Gram-negative anaerobes: Bacteroides fragilis Other microorganisms:   Chlamydia species   Mycoplasma species   Legionella species   It is recommended that a sensitivity test be carried out in infections caused by moderately sensitive microorganisms, so that possible resistance can be excluded. Sensitivity to cefuroxime can be determined via standardised procedures, as recommended for example by the Clinical and Laboratory Standards Institute (CLSI), using disc or dilution tests. The following parameters are recommended by the CLSI as sensitivity criteria: 
 Disc test (30 µg) diameter (mm) Dilution test MIC (mg/L) Sensitive ≥23 ≤4 Intermediate 15-22 8-16 Resistant ≤14 ≥32 
 
Laboratory results in the dilution test or the standardised disc diffusion test should be interpreted according to the following criteria: Moderately sensitive microorganisms are sensitive at high dosage or when the infection is restricted to tissues and fluids in which high antibiotic levels are achieved. In vitro, synergistic or additive effects have been observed for cefuroxime with a number of bactericidal antibiotics, especially aminoglycosides. 

 
Antagonism with cefoxitin, imipenem and chloramphenicol has been demonstrated in rare cases. The clinical significance of these in vitro results is not known. As with other penicillins and cephalosporins, cross-resistance can occur within the same class of antibiotic.

Absorption 
Following oral administration, cefuroxime axetil is absorbed from the gastrointestinal tract and rapidly hydrolysed in the intestinal mucosa. It enters the blood circulation as cefuroxime. Absorption is optimal when taken after meals. The absolute bioavailability of the film-coated tablets is 40-60% when taken with meals and 3040% when taken on an empty stomach. Peak blood levels are achieved after 2-3 hours, amounting to 2-3 mg/L after 125 mg, 4-6 mg/L after 250 mg, 5-8 mg/L after 500 mg and 9- 14 mg/L after 1 g when the film-coated tablets are taken with food. Distribution 
The apparent volume of distribution after an oral dose is 17.4 L. Protein binding is 33-50%, depending on the assay method used. In pregnant women, small amounts of cefuroxime cross the placental barrier. Small amounts of cefuroxime are excreted in human milk. Metabolism 
Following oral administration, cefuroxime axetil is rapidly hydrolysed by non-specific esterases in the intestines and blood. The axetil fraction is converted to acetaldehyde and acetic acid, while cefuroxime is excreted unchanged. Elimination 
The serum half-life is 1-1.5 h. Cefuroxime is not metabolised and is excreted by glomerular filtration and tubular secretion. Within 12 hours, approximately 50% of the active substance is found in the urine. 
 
Kinetics of special patient groups Probenecid 
Concomitant administration of probenecid increases the area under the plasma level/time curve by 50%. Renal impairment 
The pharmacokinetics of cefuroxime have been studied in patients with various degrees of impaired renal function. The elimination half-life of cefuroxime increases with diminishing renal 

 
function; based on this, the recommendations for dose adjustment in this patient group are made (see Posology/Administration). In patients receiving haemodialysis, at least 60% of the total baseline amount of cefuroxime present in the body is removed during a 4-hour dialysis session. For this reason, an additional single dose of cefuroxime should be administered upon completion of the haemodialysis session. 

General toxicology 
In animal studies, cefuroxime axetil has been shown to have only very low toxicity. There were no indications of target organ toxicity in repeated-dose studies with rats and dogs at dosages exceeding those in therapeutic use. Mutagenicity/carcinogenicity 
Only negative findings were obtained for cefuroxime axetil in a standard series of in vitro tests and an in vivo micronucleus test in mice. As expected, the substance induced chromosomal aberrations in human lymphocytes under in vitro conditions. However, this property can also be observed with other beta- lactam antibiotics and there is no evidence to suggest that this indicates a carcinogenic potential. As cefuroxime axetil is used for short-term treatment only, no carcinogenicity studies have been conducted. Reproductive toxicology 
Cefuroxime axetil showed no adverse effects on the fertility or peri/postnatal development of rats, or on the embryofoetal development of mice or rats, at dosages significantly exceeding those in therapeutic use. 
 

Table core: croscarmellose sodium, crospovidone, sodium laurilsulfate, castor oil, hydrogenated, methylcellulose, silica, precipitated. Film-coating: hypromellose, cellulose, microcrystalline, macrogol 8 stearate, talcum, titanium dioxide. 
 

Effect on diagnostic methods 
During Zamur treatment, the direct Coombs’ test can become temporarily positive. This can 

 
affect serological cross-matching. Enzymatic methods (glucose oxidase or hexokinase method) should be used for blood/plasma glucose determination, as interference has been observed in reduction tests. To determine creatinine, the alkaline picrate assay (Jaffé test) should be used. 

Do not store above 30 ºC. 

PVC/PVDC foil blisters or aluminium-foil / aluminium-foil blisters. 

Zamur 250 mg, film-coated tablets (with a score line): 14 and 10x14 Zamur 500 mg, film-coated tablets (with a score line): 14 and 10x14 Not all presentations may be marketed.