Cefotaxime 0.5 G Powder For Solution For Injection

SUMMARY OF PRODUCT CHARACTERISTICS

1 NAME OF THE MEDICINAL PRODUCT

Cefotaxime 0.5 g Powder for solution for injection.

2 QUALITATIVE AND QUANTITATIVE COMPOSITION

Each 0.5 g vial contains 0.524 g cefotaxime sodium, equivalent to 0.5 g cefotaxime.

Excipient(s):

Each gram of Cefotaxime contains 48 mg (2.09 mmol) of sodium.

3 PHARMACEUTICAL FORM

Cefotaxime 0.5 g:

Powder for solution for injection.

Appearance: White to slightly yellow powder.

4 CLINICAL PARTICULARS

4.1 Therapeutic indications

Cefotaxime is indicated in the treatment of the following severe infections when known or thought very likely to be due to bacteria that are susceptible to Cefotaxime (see section 5.1):

• Bacterial pneumonia,

• Complicated urinary tract infection including pyelonephritis,

• Bacterial meningitis,

• Intraabdominal infections (such as peritonitis),

• Severe skin and soft tissue infections,

• Genital infections caused by gonococci,

• Preoperative prophylaxis in colorectal surgery

Consideration should be given to official local guidance on the appropriate use of antibiotics when using Cefotaxime.

4.2 Posology and method of administration

Cefotaxime may be administered by intravenous bolus injection, by intravenous infusion, or by intramuscular injection, after reconstitution of the solution according to the directions given below. Dosage, route and frequency of administration should be based on the severity of the infection, susceptibility of the causative organism and the patient's condition. Therapy may be started before the results of sensitivity tests are known.

Cefotaxime and aminoglycosides should not be mixed in the same syringe or perfusion fluid.

Dose recommendations:

Adults and adolescents (12 to 16-18 years)

The usual dose is 1 g cefotaxime every 12 hours. However, dosage may be varied according to the severity of the infection, sensitivity of causative organisms and condition of the patient.

In severe cases, the daily dose can be increased up to 12 g. Daily doses up to 6 g can be divided into at least two individual administrations at 12 hour intervals. Higher daily doses must be divided into at least 3 to 4 individual administrations at 8 or 6-hour intervals respectively.

The following table may serve as a guide to dosages:

Type of infection

Single

dose

cefota

xime

Dose

interval

Daily

dose

cefot

axim

Typical infections, in which a sensitive bacterium is proven or suspected

¹ g

12 h

2 g

Infections, in which various bacteria with high to medium sensitivity are demonstrated or

2 g

12 h

4 g

suspected
Severe infections	2-3 g	8 h	6-9 g
		6 h	8-12
			^g

Infants, toddlers (28 days to 23 months) and children (2 to 11 years)

The usual dose is 50 to 150 mg cefotaxime according to the severity of the infection per kilogram of body weight per day in 2 to 4 divided doses (every 12 - 6 hours).

In very severe infections up to 200 mg/kg/day divided into 2-4 doses may be required. For children >50 kg the adult dosage should be used, without exceeding the maximum daily dosage of 12 g.

Neonates (0-27 days)

The recommended dosage is 50 mg cefotaxime per kilogram of body weight per day in 2 to 4 divided doses (every 12-6 hours). In case of life-threatening situations it may be necessary to increase the daily dose. For severe infections 150-200 mg/kg/day , in divided doses have been given. The following table may serve as a guide to dosages:

Age

Daily dose of cefotaxime

0-7 days

8 days - 1 month

50 mg/kg every 12 hours i.v. 50 mg/kg every 8 hours i.v.

Elderly:

No dosage adjustment is required, provided that the renal and hepatic functions are normal.

Other recommendations:

Gonorrhoea:

For gonorrhoea, a single injection Cefotaxime 0.5 g - 1 g is administered (intramuscularly or intravenously). For complicated infections consideration should be given to available official guidelines. Syphilis should be excluded before initiating the treatment.

Intra-abdominal infections:

Cefotaxime should be used in combination with an antibiotic that is active against anaerobes in the treatment of intra-abdominal infections (please refer to section 5.1).

Bacterial meningitis:

Adults and adolescents over 12 years:

In adults daily doses of 6 to 12 g divided into equal doses every 6 to 8 hours are recommended.

Infants and children (from 1 month up to 12 years of age):

150 to 200 mg/kg divided into equal doses every 6 to 8 hours.

Neonates:

In neonates 0-7 days old 50 mg/kg cefotaxime may be administered every 12 hours and in infants 8 -28 days old every 8 hours.

Duration of therapy:

The duration of therapy with Cefotaxime depends on the clinical condition of the patient and varies according to the cause of the disease. Administration of Cefotaxime should be continued until symptoms have subsided or evidence of bacterial eradication has been obtained.

Treatment over at least 10 days is necessary in infections caused by Streptococcus pyogenes (parenteral therapy may be switched to an adequate oral therapy before the end of the 10 day period).

Impaired renal function:

In adult patients with a creatinine clearance of < 5 ml/min, the initial dose is equal to the recommended usual dose but the maintenance dose should be reduced by half without change in the frequency of dosing.

Dialysis or peritoneal dialysis:

In patients on haemodialysis and peritoneal dialysis an i.v. injection of 0.5-2 g, administered at the end of each dialysis session and repeated every 24 hours, is sufficient to treat most infections effectively.

Method of administration:

Cefotaxime is administered by intravenous injection, intravenous infusion or intramuscular injection (see section 4.4). The product is made into solution according to the instructions in the section 6.6.

In order to avoid any risk of infection, the reconstitution of the infusion should be done in close aseptic conditions. Do not postpone the infusion after the reconstitution of the solution.

Intravenous infusion:

For short intravenous infusion: Following reconstitution the solution should be administered as a 20 minute intravenous infusion.

For long lasting intravenous infusion: Following reconstitution, the solution should be administered as a 50-60 minutes intravenous infusion.

Intravenous administration (injection or infusion):

For intermittent I.V. injections, the solution must be injected over a period of 3 to 5 minutes.

Intramuscular injection:

The solution should be administered by deep intramuscular injection.

The following table shows the volume of dissolution for each vial size.

	Mode of administration
Via l siz e	Short intraveno us infusion	Long- lasting intraveno us infusion	Intraveno us injection	Intramuscu lar injection
0.5 g	-	-	2 ml	2ml
¹ g	40-50 ml	-	4 ml	4 ml
2 g	40-50 ml	100 ml	10 ml	-

For instructions on reconstitution of the product before administration, see section 6.6.

4.3 Contraindications

Hypersensitivity to cefotaxime or other cephalosporins.

History of an acute and/or severe hypersensitivity to penicillin or any other type of beta-lactam antibiotic.

4.4 Special warnings and precautions for use

• Anaphylactic reactions

As with all beta-lactam antibacterial agents, serious and occasionally fatal hypersensitivity reactions have been reported in patients receiving cefotaxime (see sections 4.3 and 4.8).

If a hypersensitivity reaction occurs, treatment must be stopped. The use of cefotaxime is strictly contra-indicated in subjects with a previous history of immediate-type hypersensitivity to cephalosporins. Since cross allergy exists between cephalosporins and other beta-lactam antibiotics, cefotaxime should be given with caution to patients who have had any type of hypersensitivity reaction to penicillin or any other beta-lactam antibiotic (see 4.3).

• Cefotaxime should be used with caution in patients with allergic diathesis and asthma.

• Patients with renal insufficiency:

The dosage should be modified according to the creatinine clearance calculated. Caution should be exercised if cefotaxime is administered together with aminoglycosides or other nephrotoxic drugs (see section 4.5). Renal function must be monitored in these patients, the elderly, and those with pre-existing renal impairment.

• Neurotoxicity:

High doses of beta-lactam antibiotics, including cefotaxime, particularly in patients with renal insufficiency, may result in encephalopathy (e.g. impairment of consciousness, abnormal movements and convulsions) (see section 4.8). Patients should be advised to contact their doctor immediately prior to continuing treatment if such reactions occur.

• As with other antibiotics, the use of cefotaxime, especially if prolonged, may result in overgrowth of non-susceptible organisms. Repeated evaluation of the patient's condition is essential. If superinfection occurs during therapy, appropriate measures should be taken.

• Serious bullous reactions:

Cases of serious bullous skin reactions like Stevens-Johnson syndrome or toxic epidermal necrolysis have been reported with cefotaxime ( see section 4.8). Patients should be advised to contact their doctor immediately prior to continuing treatment if skin and/or mucosal reactions occur.

• Clostridium difficile associated disease (e.g. pseudomembranous colitis): Diarrhea, particularly if severe and/or persistent, occurring during treatment or in the initial weeks following treatment, may be symptomatic of Clostridium difficile associated disease (CDAD). CDAD may range in severity from mild to life threatening, the most severe form of which is pseudo-membranous colitis. The diagnosis of this rare but possibly fatal condition can be confirmed by

endoscopy and/or histology.

It is important to consider this diagnosis in patients who present with diarrhoea during or subsequent to the administration of cefotaxime.

If a diagnosis of pseudomembranous colitis is suspected, cefotaxime should be stopped immediately and appropriate specific antibiotic therapy should be started without delay.

Clostridium difficile associated disease can be favoured by faecal stasis. Medicinal products that inhibit peristalsis should not be given.

• Haematological reactions

Leukopenia, neutropenia and, more rarely, agranulocytosis may develop during treatment with cefotaxime, particularly if given over long periods. For treatment courses lasting longer than 7-10 days, the blood white cell count should be monitored and treatment stopped in the event of neutropenia.

Some cases of eosinophilia and thrombocytopenia, rapidly reversible on stopping treatment, have been reported. Cases of haemolytic anemia have also been reported. (see section 4.8).

• Do not mix aminoglycosides and cefotaxime in the same syringe or liquids for perfusion.

• Precautions for administration:

During post-marketing surveillance, potentially life-threatening arrhythmia has been reported in a very few patients who received rapid intravenous administration of cefotaxime through a central venous catheter. The recommended time for injection or infusion should be followed (see section 4.2). In case of severe infections, intramuscular injection is not recommended. It is recommended that no more than 4 ml is injected unilaterally. If the daily dose exceeds 2 g cefotaxime, or if cefotaxime is injected more frequently than twice per day, the i.v. route is recommended.

• Effects on Laboratory Tests:

As with other cephalosporins a positive Coombs' test has been found in some patients treated with cefotaxime. This phenomenon can interfere with the crossmatching of blood.

Urinary glucose testing with non-specific reducing agents may yield falsepositive results. This phenomenon is not seen when a glucose-oxydase specific method is used.

• Cefotaxime constituted with lidocaine should never be used:

- by the intravenous route

- in infants under 30 months

- in subjects with a previous history of hypersensitivity to this product

- in patients who have unpaced heart block

- in patients with severe heart failure

• The product information of the chosen lidocaine-containing medicinal product must be regarded.

Sodium

The sodium content is 2.09 mmol/g; caution in patients with cardiac insufficiency/patients requiring sodium retention.

The sodium content of cefotaxime sodium (48.2 mg/g) should be taken into account.

4.5 Interaction with other medicinal products and other forms of interaction

Probenecid:

Probenecid interferes with the renal tubular transfer of cephalosporins, thereby delaying their excretion and increasing their plasma concentrations.

Oral contraceptives:

The efficacy of oral contraceptives may be decreased by concomitant use of cefotaxime. Therefore during therapy with Cefotaxime additional contraceptive methods should be used.

Aminoglycocides, diuretics:

As with other cephalosporins, cefotaxime may potentiate the nephrotoxic effects of nephrotoxic drugs such as aminoglycosides or potent diuretics (e.g. furosemide). Renal function must be monitored (see section 4.4).

Bacteriostatic antibiotics:

Cefotaxime should not be combined with bacteriostatic antibiotics (e.g. tetracyclines, erythromycin and chloramphenicol) because an antagonistic effect is possible.

Other forms of interactions:

As with other cephalosporins, a positive Coombs' test has been seen in some patients treated with cefotaxime. This phenomenon can interfere with the cross-matching of blood.

A false-positive reaction to glucose may occur with reducing substances (Benedict's or Fehling's solution, or with Clinitest tablets) but not with the use of specific enzyme-based tests (glucose oxidase methods).

4.6 Fertility, Pregnancy and lactation

Pregnancy:

The safety of cefotaxime has not been established in human pregnancy.

Animal studies do not indicate direct or indirect harmful effects with respect to reproductive toxicity. There are, however, no adequate and well controlled studies in pregnant women.

Cefotaxime crosses the placental barrier. Therefore, cefotaxime should not be used during pregnancy unless the anticipated benefit outweighs any potential risks.

Lactation:

Cefotaxime passes into human breast milk.

Effects on the physiological intestinal flora of the breast-fed infant leading to diarrhoea, colonisation by yeast-like fungi, and sensitisation of the infant cannot be excluded.

Therefore, a decision must be made whether to discontinue breast-feeding or to discontinue therapy taking into account the benefit of breast-feeding for the child and the benefit of therapy for the woman.

4.7 Effects on ability to drive and use machines

The effect of cefotaxime on the ability to drive and use machines has not been investigated.

In individual cases, with high doses of cefotaxime, particularly in patients with renal insufficiency, impairment of consciousness, abnormal movements and dizziness have been reported. Under these circumstances, the described activities should be stopped.

4.8 Undesirable effects

System organ class	Very Common (>1/10)	Common (>1/100 to <1/10 )	Uncommon (>1/1,000 to <1/100)	Rare (>1/10,000 to <1/1,000)	Very rare (< 1/10,000)	Not known (cannot be estimated from available data)*
Infections and infestations						Superinfection (see section 4.4)
Blood and the lymphatic system disorders			Leukopenia Eosinophilia Thrombo cytopenia			Neutropenia Agranulocytosi s (see section 4.4) Haemolytic anaemia
Immune system disorders			Jarisch- Herxheimer reaction			Anaphylactic reactions Angioedema Bronchospasm Anaphylactic shock

System organ class	Very Common (>1/10)	Common (>1/100 to <1/10 )	Uncommon (>1/1,000 to <1/100)	Rare (>1/10,000 to <1/1,000)	Very rare (< 1/10,000)	Not known (cannot be estimated from available data)*
Nervous system disorders			Convulsions (see section 4.4)			Headache Dizziness Encephalopathy (e.g. impairment of consciousness, abnormal movements) (see section 4.4)
Cardiac disorders						Arrhythmia following rapid bolus infusion through central venous catheter
Gastro intestinal disorders			Diarrhea			Nausea Vomiting Abdominal pain Pseudomembra nous colitis (see section 4.4)
Hepato-bilary disorders			Increase in liver enzymes (ALAT, ASAT, LDH, gamma-GT and/or alkaline phosphatase) and/or bilirubin			Hepatitis* (sometimes with jaundice)
Skin and subcutaneous tissue disorders			Rash Pruritus Urticaria			Erythema multiforme Stevens- Johnson syndrome Toxic epidermal necrolysis (see section 4.4)

System organ class

Very

Common

(>1/10)

Common (>1/100 to <1/10 )

Uncommon (>1/1,000 to <1/100)

Rare

(>1/10,000

<1/1,000)

Very

rare

1/10,000)

Not known (cannot be estimated from available data)*

Renal and

Urinary

disorders

Decrease in renal function/ increase of creatinine (particularly when coprescribed with aminoglycosides)

Interstititial

nephritis

General disorders and administration site

conditions

For IM formulations

Pain at the injection site

Fever

Inflammatory reactions at the injection site, including phlebitis/ thrombophlebitis

For IM

formulatio

ns (since

the solvent

contains

lidocaine):

Systemic

reactions

lidocaine

* postmarketing experience Hepatobiliary disorders

Increase in liver enzymes (ALAT, ASAT, LDH, gamma-GT and/or alkaline phosphatase) and/or bilirubin have been observed. These laboratory abnormalities may rarely exceed twice the upper limit of the normal range and elicit a pattern of liver injury, usually cholestatic and most often asymptomatic.

4.9 Overdose

Symptoms of overdose may largely correspond to the profile of side effects.

There is a risk of reversible encephalopathy in cases of administration of high doses of P-lactam antibiotics including cefotaxime.

In case of overdose, cefotaxime must be discontinued, and supportive treatment initiated, which includes measures to accelerate elimination, and symptomatic treatment of adverse reactions (e.g. convulsions).

No specific antidote exists. Serum levels of cefotaxime can be reduced by haemodialysis or peritoneal dialysis.

5 PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic properties

Pharmacotherapeutic group: Other Beta-Lactam Antibacterials ATC Code: J01D D01

Cefotaxime is a parenteral betalactam-antibiotic of the group of cephalosporins.

Mechanism of action

The bactericidal activity of cefotaxime results from the inhibition of bacterial cell wall synthesis (during the period of growth) caused by an inhibition of penicillin-binding proteins (PBPs) like transpeptidases.

Pharmacokinetics and pharmacodynamics relationship

The extent of the bactericidal activity depends on the period of time when the serum level exceeds the minimal inhibitory concentration (MIC) of the pathogen.

Mechanism of resistance

A resistance to cefotaxime may be caused by following mechanisms:

- inactivation by beta-lactamases. Cefotaxime can be hydrolysed by certain beta-lactamases, especially by extended-spectrum beta-lactamases (ESBLs) which can be found in strains of Escherichia coli or Klebsiella pneumoniae, or by chromosomal encoded inducible or constitutive beta-lactamases of the AmpC type which can be detected in Enterobacter cloacae. Therefore infections caused by pathogens with inducible, chromosomal encoded AmpC- beta-lactamases should not be treated with cefotaxime even in case of proven in-vitro-susceptibility because of the risk of the selection of mutants with constitutive, derepressed AmpC- beta-lactamases-expression.

- reduced affinity of PBPs against cefotaxime. The acquired resistance of Pneumococci and other Streptococci is caused by modifications of already existing PBPs as a consequence of a mutation process.

In contrast to this concerning the methicillin-(oxacillin-) resistant Staphylococcus, the creation of an additional PBP with reduced affinity against cefotaxime is responsible for resistance.

- inadequate penetration of cefotaxime through the outer cell membrane of gram-negative bacteria so that the inhibition of the PBPs is insufficient.

- the presence of transport mechanism (efflux pumps) being able to actively transport cefotaxime out of the cell.

A complete cross resistance of cefotaxime occurs with ceftriaxone and partially with other penicillins and cephalosporins.

Breakpoints:

The following minimal inhibitory concentrations were defined for sensitive and resistant germs: EUCAST (European Committee on Antimicrobial Susceptibility Testing) break points (2009-05-25):

Pathogen	Susceptible	Resistant
Enterobacteriaceae	1 mg/l	> 2 mg/l
Staphylococcus spp.	--*	--*
Streptococcus (group A, B, C, g)	--**	--**
Other Streptococci	0.5 mg/l	0.5 mg/l
Streptococcus pneumoniae	0.5 mg/l	> 2 mg/l
Haemophilus influenzae	0.12 mg/l	>
Moraxella catarrhalis	1 mg/l	> 2 mg/l
Neisseria gonorrhoeae	0.12 mg/l	>
Neisseria meningitides	0.12 mg/l	>
Not species-specific	1 mg/l	> 2 mg/l

*For Staphylococcus the test results of oxacillin is used. Oxacillin-resistent Staphylococcus is assessed as resistant against cefotaxime.

** The susceptibility of streptococcus groups A, B, C and g can be inferred from their susceptibility to benzylpenicillin.

*** generally based on serum pharmacokinetics

Susceptibility

The prevalence of acquired resistance may vary geographically and with time for selected species and local information on resistance is desirable, particularly when treating severe infections. If the efficacy of cefotaxime is questionable due to the local prevalence of resistance, expert opinion should be sought regarding the choice of therapy. In particular in the case of severe infections or failure of therapy a microbiological diagnosis including a verification of the germ and its susceptibility should be aspired.

Commonly susceptible species Gram-positive aerobes

Staphylococcus aureus (methicillin-susceptible)

Streptococcus agalactiae

Streptococcus pneumoniae (incl. penicillin-resistant) Streptococcus pyogenes Gram-negative aerobes

Escherichia coli%

Haemophilus influenzae Klebsiella oxytoca%

Klebsiella pneumoniae^#%

Moraxella catarrhalis Morganella morganii Neisseria gonorrhoeae Neisseria meningitidis Proteus mirabilis%

Species for which acquired resistance may be a problem

Gram-positive aerobes

Staphylococcus aureus Staphylococcus epidermidis⁺

Staphylococcus haemolyticus Staphylococcus hominis⁺

Gram-negative aerobes Citrobacter freundii Enterobacter aerogenes Enterobacter cloacae Proteus vulgaris Serratia marcescens Anaerobes Bacteroides fragilis

Inherently resistant species Gram-positive aerobes

Enterococcus spp.

Listeria monocytogenes

Staphylococcus aureus (methicillin-resistant)

Gram-negative aerobes

Acinetobacter baumannii Pseudomonas aeruginosa Stenotrophomonas maltophilia Anaerobes Clostridium difficile Others

Chlamydia spp.

Chlamydophila spp.

Legionella pneumophila Mycoplasma spp.

Treponema pallidum

Literature data, reference books and therapy guidelines support susceptibility. + In at least one region the resistance rate is > 50%.

# In Intensive Care Units the resistance rate is 10%.

% Extended Spectrum Beta-Lactamase (ESBL) producing strains are always resistant.

In the community area the resistance rate is <10%.

5.2 Pharmacokinetic properties

Absorption:

Cefotaxime is for parenteral application. Mean peak concentrations 5 minutes after intravenous administration are about 81-102 mg/l following a 1 g dose of cefotaxime and about 167-214 mg/l 8 minutes after a 2 g dose. Intramuscular injection produces mean peak plasma concentrations of 20 mg/l within 30 minutes following a 1 g dose.

Distribution:

Cefotaxime has good penetration into different compartments. Therapeutic drug levels exceeding the minimum inhibitory levels for common pathogens can rapidly be achieved. Cerebrospinal fluid concentrations are low when the meninges are not inflamed but cefotaxime usually passes the blood-brain barrier in levels above the MIC of the sensitive pathogens when the meninges are inflamed (3-30 pg/ml). Cefotaxime concentrations (0.2-5.4 pg/ml), inhibitory for most gram-negative bacteria, are attained in purulent sputum, bronchial secretions and pleural fluid after doses of 1 or 2 g. Concentrations likely to be effective against most sensitive organisms are similarly attained in female reproductive organs, otitis media effusions, prostatic tissue, interstitial fluid, peritoneal fluid and gall bladder wall, after therapeutic doses. High concentrations of Cefotaxime and O-desacetyl-cefotaxime are achieved in bile. Cefotaxime passes the placenta and attains high concentrations in foetal fluid and tissues (up to 6 mg/kg). Small amounts of cefotaxime diffuse into the breast milk.

Protein binding for cefotaxime is approximately 25-40%.

The apparent distribution volume for cefotaxime is 21-37 l after 1 g intravenous infusion over 30 minutes.

Biotransformation:

Cefotaxime is partly metabolised in humans. Approximately 15-25% of a parenteral dose are metabolised to the O-desacetyl-cefotaxime metabolite, which also has antibiotic properties.

Elimination:

The main route of excretion of cefotaxime and O-desacetyl-cefotaxime is through the kidneys. Only a small amount (2%) of cefotaxime is excreted in the bile. In the urine collected within 6 hours 40-60% of the administered dose of cefotaxime is recovered as unchanged cefotaxime and 20% is found as O-desacetylcefotaxime. After administration of radioactive labelled cefotaxime more than 80% can be recovered in the urine; 50-60% of this fraction is unchanged cefotaxime and the rest contains metabolites.

The total clearance of cefotaxime is 240-390 ml/min and the renal clearance is 130-150 ml/min.

The serum half-lives of cefotaxime and O-desacetyl-cefotaxime are normally about 50-80 and 90 minutes, respectively. In elderly, the serum half-life of cefotaxime is 120-150 min.

In patients with severely impaired renal function (creatinine clearance 3-10 ml/min) the serum half- life of cefotaxime can be increased to 2.5-3.6 hours.

There is no accumulation following administration of 1000 mg intravenously or 500 mg intramuscularly for 10 or 14 days.

In neonates the pharmacokinetics are influenced by gestation and chronological age, the half-life being prolonged in premature and low birth weight neonates of the same age.

5.3 Preclinical safety data

Preclinical data reveal no special hazard for humans based on conventional studies of safety pharmacology, repeated dose toxicity, genotoxicity, and toxicity to reproduction.

Cefotaxime passes through the placenta. After intravenous administration of 1 g cefotaxime during the birth values of 14 pg/ml were measured in the umbilical cord serum in the first 90 minutes after administration, which dropped to approximately 2.5 pg/ml by the end of the second hour after application. In the amniotic fluid, the highest concentration of 6.9 pg/ml was measured after 3-4 hours. This value exceeds the MIC for most gram-negative bacteria

6 PHARMACEUTICAL PARTICULARS

6.1 List of excipients

None.

6.2 Incompatibilities

This medicinal product must not be mixed with other medicinal products except those mentioned in section 6.6.Cefotaxime should not be dissolved in solutions having a pH-value of more than 7.5 e.g. sodium bicarbonate.

6.3 Shelf life

0.5 g powder for solution for injection: 2 years Reconstituted solution: Should be used immediately.

6.4 Special precautions for storage

This medicinal product does not require any special temperature storage conditions.

Keep the vial in the outer carton in order to protect from light For storage of reconstituted solution, please refer to section 6.3.

6.5 Nature and contents of container

0.5 g: colourless glass vials (type I flint vial, 10 ml) with rubber stopper with a green flip off aluminium seal.

0.5 g: 10 vials

Not all pack sizes may be marketed.

6.6 Special precautions for disposal

Compatibility:

Cefotaxime is compatible with:

Sodium chloride 0.9%; Glucose 10%, Ringer-lactate; lidocaine solution 1.0%.

- Aseptic techniques should be used to reconstitute the solution.

- The reconstituted solution should be administered immediately.

- Any unused solution should be discarded.

Intravenous infusion:

For short term intravenous infusion 1 g or 2 g Cefotaxime should be dissolved in 40-50 ml water for injections or in another compatible solution.

For long lasting intravenous infusion 2 g Cefotaxime should be dissolved in 100 ml of a suitable solution, like 0.9 % sodium chloride or isotonic glucose solution.

To produce an infusion using vials with an infusion connector or sterile transfer device, remove the safety cap and directly connect the infusion bag. The needle in the closure will automatically pierce the vial stopper. Pressing the infusion bag will transfer solvent into the vial.

Reconstitute by shaking the vial and finally, transfer the reconstituted solution back to the infusion bag ready for use.

Intravenous injection:

Cefotaxime 0.5 g / 1 g / 2 g is dissolved in 2 ml / 4 ml / 10 ml water for injections or Cefotaxime 1 g is dissolved in 4 ml water for injections.

Intramuscular injection:

Cefotaxime 0.5 g / 1 g / 2 g is dissolved in 2 ml / 4 ml / 10 ml water for injections or Cefotaxime 1.0 g is dissolved in 4 ml water for injections.

In order to prevent pain caused by the injection, Cefotaxime 0.5 g may be dissolved in 2 ml 1% lidocaine hydrochloride or Cefotaxime 1 g may be dissolved in 4 ml 1% lidocaine hydrochloride (see also section 4.2)

Following reconstitution the solution should be clear and pale yellow to brownish yellow. Do not use if any particulate matter is visible. For single use only.

7 MARKETING AUTHORISATION HOLDER

Generics [UK] Limited t/a Mylan

Station Close

Potters Bar

Hertfordshire

EN6 1TL

United Kingdom

8 MARKETING AUTHORISATION NUMBER(S)

PL 04569/1596

9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

19/07/2012

10 DATE OF REVISION OF THE TEXT

12/03/2015