Kemicetine Succinate Injection

SUMMARY OF PRODUCT CHARACTERISTICS

1 NAME OF THE MEDICINAL PRODUCT

2 QUALITATIVE AND QUANTITATIVE COMPOSITION

3 PHARMACEUTICAL FORM

4 CLINICAL PARTICULARS

MARKETING AUTHORISATION HOLDER

8 MARKETING AUTHORISATION NUMBER(S)

9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

10 DATE OF REVISION OF THE TEXT

4.1 Therapeutic indications

4.2 Posology and method of administration

4.3 Contraindications

4.4 Special warnings and precautions for use

4.5 Interaction with other medicinal products and other forms of interaction

4.6 Fertility, Pregnancy and lactation

4.7 Effects on ability to drive and use machines

4.8 Undesirable effects

4.9 Overdose

5.1 Pharmacodynamic properties

5.2 Pharmacokinetic properties

5.3 Preclinical safety data

6.1 List of excipients

6.2 Incompatibilities

6.3 Shelf life

6.4 Special precautions for storage

6.5 Nature and contents of container

6.6 Special precautions for disposal

Kemicetine Succinate Injection

Each vial contains 1.377 g of chloramphenicol sodium succinate (equivalent to 1.0g of laevorotatory chloramphenicol)

Freeze dried powder for solution for injection

Kemicetine succinate is indicated for typhoid, meningitis caused by H. influenzae and other serious infections caused by bacteria susceptible to chloramphenicol.

It is also indicated wherever chloramphenicol is deemed the antibiotic of choice and oral administration is not possible, or where higher than usual blood concentrations are required.

Posology

The dose administered and the concentration used is dependent on the severity of the infection. The recommended standard dosage is as follows:

Adults : The equivalent of 1 g of chloramphenicol every 6-8 hours.

Elderly : The usual adult dosage should be given subject to normal hepatic and renal function.

Children : The equivalent of 50 mg/kg chloramphenicol according to body weight, daily in divided doses every 6 hours (this dose should not be exceeded). The patient should be carefully observed for signs of toxicity.

Neonates and Premature Infants : 25 mg/kg in divided doses.

Only 10% or lower concentrations to be used. The 10% solution can be prepared by extracting 5ml of the 20% solution and adding 5ml of diluent (Water for Injections, Sodium Chloride Injection or Dextrose Injection 5%) under aseptic conditions.

The 10 % solution should be given by intravenous injection over a period of about a minute, or in a larger volume of fluid, by slow intravenous infusion. The concurrent administration of intravenous Kemicetine succinate with topical treatment has been found to be very effective in the treatment of osteomyelitic foci, abscesses, empyema and skin and urinary infections.

In exceptional cases, such as patients with septicaemia or meningitis, dosage schedule up to 100 mg/kg/day may be prescribed. However, these high doses should be decreased as soon as clinically indicated. To prevent relapses treatment should be continued after the temperature has returned to normal for 4 days in rickettsial diseases and for 8 - 10 days in typhoid fever.

Method of administration

To be given by intravenous or intramuscular injection.

In order to ensure rapid attainment of high blood levels, Kemicetine succinate is best administered by intravenous injection. Where this is not possible, however, intramuscular administration may be used, although it should be borne in mind that absorption may be slow and unpredictable.

The injection should be reconstituted with Water for Injections, Sodium Chloride Injection, or Dextrose Injection 5 %. The following dilution table may be useful for the administration of a proportion of the contents of a vial:

Concentration	Solution strength	Volume of diluent to be added	Total volume after dilution
40%	400 mg/ml	1.7 ml	2.5 ml
25%	250 mg/ml	3.2 ml	4.0 ml
20%	200 mg/ml	4.2 ml	5.0 ml

Kemicetine succinate is contraindicated in patients with a previous history of sensitivity and/or toxic reaction to chloramphenicol

Kemicetine is to be administered only under the direction of a medical practitioner. It should be reserved for serious infections caused by organisms susceptible to its antimicrobial effects when less toxic antibiotics are ineffective or contraindicated. However, chloramphenicol may be chosen to initiate antibiotic therapy based on the clinical impression. In vitro sensitivity tests should be performed concurrently so that the drug may be discontinued as soon as possible if a less toxic antibiotic is indicated by the results of such tests. The decision to continue use of chloramphenicol, rather than another antibiotic when both are suggested by in vitro studies to be effective against a specific pathogen, should be based upon severity of the infection, susceptibility of the pathogen to the various antimicrobial drugs, and the efficacy of the various drugs in the infection.

Kemicetine should not be used for trivial infections due to the possibility of severe blood dyscrasias, which may prove fatal.

Chloramphenicol may cause severe bone marrow depression which may lead to agranulocytosis, thrombocytopenic purpura or aplastic anaemia. These effects of the haemopoietic system are usually associated with a high dose, prolonged administration, or repeated courses, but they may occur at relatively low doses.

Chloramphenicol should not be used in the treatment of any infection for which a less toxic antibiotic is available. It is also advisable to perform blood tests in the case of prolonged or repeated administration. Evidence of any detrimental effect on blood elements is an indication to discontinue therapy immediately.

The dosage of chloramphenicol should be reduced in patients with impairment of hepatic or renal function.

Because of its toxic nature it is important to monitor serum levels of this antibiotic particularly in new-born and premature infants, in the elderly, in patients with renal or hepatic disease and in those receiving other drugs with which chloramphenicol may interact.

Chloramphenicol has been shown to interact with, and enhance the effects of coumarin anticoagulants, some hypoglycaemic agents (e.g. tolbutamide) and

phenytoin. When given concurrently, a dose reduction of these agents may be necessary.

Plasma concentrations of chloramphenicol may be reduced with concomitant usage of phenobarbital and rifampicin

The use of chloramphenicol is contraindicated in pregnancy and whilst breastfeeding

None stated.

Tabulated summary of adverse reactions

The adverse reactions are grouped according to their system organ classes and the frequencies ranked according to the following convention: 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 the available data).

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 the available data)
Infections and infestations						Fungal superinfection
Blood and lymphatic system disorders					Aplastic anaemia	Agranulocytosis Bone marrow failure Pancytopenia Thrombocytopenic purpura
Psychiatric disorders						Depression
Nervous system disorders						Peripheral neuritis Headache

Bone marrow depression and blood disorders

Chloramphenicol may cause severe bone marrow depression which may lead to serious and potentially fatal blood dyscrasias, such as agranulocytosis, thrombocytopenic purpura or aplastic anaemia (see section 4.4).

Paediatric population

Grey syndrome is a serious adverse effect that has been reported in neonates and infants following the intravenous administration of chloramphenicol (see section 4.4).

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorization of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions to:

United Kingdom Yellow card system www.mhra.gov.uk/yellowcard

Levels exceeding 25 mcg/ml are frequently considered toxic.

Chloramphenicol toxicity can be evidenced by serious haemopoietic effects such as aplastic anaemia, thrombocytopenia, leucopenia, as well as increasing serum iron levels, nausea, vomiting and diarrhoea.

In the case of serious overdosage, charcoal haemoperfusion may be effective in removing chloramphenicol from plasma.

Exchange transfusion is of questionable value following massive overdosage, especially in neonates and infants.

After administration chloramphenicol is rapidly released from chloramphenicol sodium succinate. Chloramphenicol is active against many gram-positive and gram negative organisms, Spirillae and Rickettsia. It acts by interfering with bacterial protein synthesis. Chloramphenicol is widely distributed in body tissues and fluids and enters the cerebrospinal fluid.

Chloramphenicol sodium succinate, free chloramphenicol and metabolites are excreted in the urine.

Absorption

After intravenous administration steady state peak concentrations were reached on average 18.0 minutes after cessation of the infusion.

Distribution

Chloramphenicol is widely distributed in body tissues and fluids and enters the cerebrospinal fluid.

Biotransformation

After administration chloramphenicol is rapidly released from chloramphenicol sodium succinate. Chloramphenicol sodium succinate, free chloramphenicol and metabolites are excreted in the urine.

Elimination

After intravenous administration of chloramphenicol succinate every 6 hours, the elimination half-lives were 4.03 hours for chloramphenicol and 2.65 hours for chloramphenicol succinate.

Paediatric population

In infants and children aged 3 days to 16 years the apparent half-life was extremely variable ranging from 1.7 to 12.0 hours

None stated.

None

None stated.

48 months.

Keep container in the outer carton.

Type III colourless glass vials with grey chlorobutyl rubber bung and aluminium seal.

Pack size: 1, 20 or 25 vials

To be reconstituted with Water for Injections, Sodium Chloride Injection or Dextrose Injection 5%.

Any unused medicinal product or waste material should be disposed of in accordance with local requirements

Pfizer Limited

IPC 5-1-71, Walton oaks

Dorking Road

Tadworth

Surrey

KT20 7NS

PL 00057/1001

02/03/2009

Eye disorders

Optic neuritis Transient blindness Blurred vision

Cardiac disorders

Neonatal Grey syndrome

Gastrointestinal

disorders

Vomiting Diarrhoea Nausea Dry mouth

Skin and subcutaneous tissue disorders

31/07/2014