Clindamycin 150mg/Ml Solution For Injection
SUMMARY OF PRODUCT CHARACTERISTICS
1 NAME OF THE MEDICINAL PRODUCT
Clindamycin 150mg/ml, solution for injection
2 QUALITATIVE AND QUANTITATIVE COMPOSITION
Each ml of solution contains clindamycin phosphate equivalent to 150 mg clindamycin.
For a full list of excipients, see section 6.1.
3 PHARMACEUTICAL FORM
Solution for Injection.
Clear, colourless, sterile solution.
4 CLINICAL PARTICULARS
4.1 Therapeutic indications
Antibacterial. Serious infections caused by susceptible Gram-positive organisms, staphylococci (both penicillinase- and non-penicillinase-producing), streptococci (except Streptococcus faecalis) and pneumococci. It is also indicated in serious infections caused by susceptible anaerobic pathogens such as Bacteroides spp, Fusobacterium spp, Propionibacterium spp, Peptostreptococcus spp. and microaerophilic streptococci.
Clindamycin does not penetrate the blood/brain barrier in therapeutically effective quantities.
Consideration should be given to official guidance on the appropriate use of antibacterial agents including national and local guidelines
4.2 Posology and method of administration
Routes of administration:
Intramuscular injection Intravenous infusion Adults:
Serious infections: 600 mg - 1.2 g/day in two, three or four equal doses.
More severe infections: 1.2 - 2.7 g/day in two, three or four equal doses.
Single i.m. injections of greater than 600 mg are not recommended nor is administration of more than 1.2 g in a single one hour infusion.
For more serious infections, these doses may have to be increased. In life-threatening situations, doses as high as 4.8 g daily have been given intravenously to adults.
Alternatively, the drug may be administered in the form of a single rapid infusion of the first dose followed by continuous IV. infusion.
Renal and/or hepatic insufficiency
The dosage may require reduction in patients with renal and/or hepatic insufficiency due to prolongation of the serum half life.
Children (over 1 month of age):
Serious infections: 15 - 25 mg/kg bodyweight/day in three or four equal doses.
More severe infections: 25 - 40 mg/kg bodyweight/day in three or four equal doses.
In severe infections it is recommended that children be given no less than 300 mg/day regardless of body weight.
Elderly patients:
The half-life, volume of distribution and clearance, and extent of absorption after administration of clindamycin phosphate are not altered by increased age. Analysis of data from clinical studies has not revealed any age-related increase in toxicity. Dosage requirements in elderly patients should not be influenced, therefore, by age alone. See section 4.4. for other factors which should be taken into consideration.
Treatment for infections caused by beta-haemolytic streptococci should be continued for at least 10 days to guard against subsequent rheumatic fever or glomerulonephritis.
Method of administration
Parenteral (intramuscular or intravenous administration). Clindamycin injection must be diluted prior to intravenous administration and should be infused over at least 10 -60 minutes. The minimum time over which infusion should take place depends upon the amount of injection being administered. See following table.
The concentration of clindamycin in diluent for infusion should not exceed 18 mg per mL and infusion rates should not exceed 30mg per minute. The usual infusion rates are as follows:
|
Dose |
Diluent |
Time |
|
300 mg |
50 mL |
10 min |
|
600 mg |
50 mL |
20 min |
|
900 mg |
50-100 mL |
30 min |
|
1200 mg |
100 mL |
40 min |
4.3 Contraindications
Clindamycin Injection is contra-indicated in patients previously found to be sensitive to clindamycin, lincomycin or to any component of the formulation.
4.4 Special warnings and precautions for use
Warnings
Clindamycin Injection should only be used in the treatment of serious infections. In considering the use of the product, the practitioner should bear in mind the type of infection and the potential hazard of the diarrhoea which may develop, since cases of colitis have been reported during, or even two or three weeks following, the administration of clindamycin.
Studies indicate a toxin(s) produced by clostridia (especially Clostridium difficile) is the principal direct cause of antibiotic-associated colitis. These studies also indicate that this toxigenic clostridium is usually sensitive in vitro to vancomycin. When 125 mg to 500 mg of vancomycin are administered orally four times a day for 7 - 10 days, there is a rapid observed disappearance of the toxin from faecal samples and a coincident clinical recovery from the diarrhoea. (Where the patient is receiving cholestyramine in addition to vancomycin, consideration should be given to separating the times of administration). Colitis is a disease which has a clinical spectrum from mild, watery diarrhoea to severe, persistent diarrhoea, leucocytosis, fever, severe abdominal cramps, which may be associated with the passage of blood and mucus. If allowed to progress, it may produce peritonitis, shock and toxic megacolon. This may be fatal. The appearance of marked diarrhoea should be regarded as an indication that the product should be discontinued immediately. The disease is likely to follow a more severe course in older patients or patients who are debilitated. Diagnosis is usually made by the recognition of the clinical symptoms, but can be substantiated by endoscopic demonstration of pseudomembranous colitis. The presence of the disease may be further confirmed by culture of the stool for C. difficile on selective media and assay of the stool specimen for the toxin(s) of C. difficile.
Precautions
Caution should be used when prescribing Clindamycin Injection to individuals with a history of gastro-intestinal disease, especially colitis.
Periodic liver and kidney function tests should be carried out during prolonged therapy. Such monitoring is also recommended in infants. Safety and appropriate dosage in infants less than one month old have not been established.
The dosage of Clindamycin Injection may require reduction in patients with renal or hepatic impairment due to prolongation of the serum half-life.
Prolonged administration of Clindamycin Injection, as with any anti-infective, may result in super-infection due to organisms resistant to clindamycin.
Care should be observed in the use of Clindamycin Injection in atopic individuals.
This medicinal product contains less than 1 mmol sodium (23mg) per ampoule i.e. essentially “sodium free”.
4.5 Interaction with other medicinal products and other forms of interaction
Clindamycin has been shown to have neuromuscular blocking properties that may enhance the action of other neuromuscular blocking agents. It should be used with caution therefore, in patients receiving such agents.
Antagonism has been demonstrated between clindamycin and erythromycin in vitro. Because of possible clinical significance, the two drugs should not be administered concurrently.
Vitamin K antagonists
Increased coagulation tests (PT/INR) and/or bleeding, have been reported in patients treated with clindamycin in combination with a vitamin K antagonist (e.g. warfarin, acenocoumarol and fluindione). Coagulation tests, therefore, should be frequently monitored in patients treated with vitamin K antagonists.
4.6 Pregnancy and lactation
Pregnancy
Safety for use in pregnancy has not been established.
Lactation
Clindamycin is excreted in human milk. Caution should be exercised when Clindamycin Injection is administered to a nursing mother. It is unlikely that a nursing infant can absorb a significant amount of clindamycin from its gastrointestinal tract.
4.7 Effects on ability to drive and use machines
None known
4.8 Undesirable effects
Adverse events are ranked under the following frequency headings: Common (>1/100, <1/10)
Uncommon (>1/1,000, <1/100)
Rare (>1/10,000, <1/1,000)
Very rare (<1/10,000)
|
Blood and the lymphatic system disorders | |
|
Uncommon |
Transient neutropenia (leucopenia), eosinophilia, agranulocytosis and thrombocytopenia, although no direct aetiologic relationship to concurrent clindamycin therapy could be made. |
|
Immune system c |
isorders |
|
Very rare |
Anaphylactoid reactions |
|
Cardiac disorders | |
|
Rare |
Cardiopulmonary arrest has been reported following too rapid intravenous administration (see section 4.2. for recommended rates of infusion) |
|
Vascular disorders | |
|
Rare |
Hypotension following too rapid intravenous administration (see section 4.2. for recommended rates of infusion) |
|
Gastrointestinal c |
isorders |
|
Common |
Nausea, vomiting, abdominal pain and diarrhoea (see section 4.4). In most cases, these are mild in nature and disappear during or after completion of treatment. |
|
Hepato-biliary disorders | |
|
Very rare |
Jaundice |
|
Skin and subcutaneous tissue disorders | |
|
Rare |
Pruritus, urticaria, maculopapular rash and exfoliative and vesiculobullous dermatitis. Generalised mild to moderate morbilliform-like skin rashes |
|
Very rare |
Erythema multiforme and Stevens-Johnson syndrome |
|
General disorders and administration site conditions | |
|
Uncommon |
Local irritation, pain, abscess formation at the place of injection after intramuscular administration. Thrombophlebitis after intravenous administration. These reactions can be minimised by deep i.m. injection and avoiding the use of an indwelling catheter. |
|
Reproductive system and breast disorders | |
|
Rare |
Vaginitis |
|
Investigations | |
|
Common |
Abnormalities in liver function tests |
Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorisation 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 via the Yellow Card Scheme at: www.mhra.gov.uk/yellowcard.
4.9 Overdose
In cases of overdosage no specific treatment is indicated.
The serum biological half-life of clindamycin is 2-3 hours. Clindamycin cannot readily be removed from the blood by dialysis or peritoneal dialysis.
If an allergic adverse reaction occurs, therapy should be with the usual emergency treatments, including corticosteroids, adrenaline and antihistamines.
5 PHARMACOLOGICAL PROPERTIES
5.1 Pharmacodynamic properties
Pharmacotherapeutic group: Lincosamides, ATC code: J01FF01 Mode of action
Clindamycin is a lincosamide antibiotic with a primarily bacteriostatic action against Gram-positive aerobes and a wide range of anaerobic bacteria. Lincosamides such as clindamycin bind to the 50S subunit of the bacterial ribosome similarly to macrolides such as erythromycin and inhibit the early stages of protein synthesis. The action of clindamycin is predominantly bacteriostatic although high concentrations may be slowly bactericidal against sensitive strains.
Mechanisms of resistance
Resistance to Clindamycin usually occurs via macrolide-lincosamide-streptogramin-B type of resistance which may be constitutive or inducible. This is mediated by a variety of acquired genes that encode methylases targeted at the peptidyl transferase centre of 23S ribosomal RNA. Methylation impedes binding of antibacterials to the ribosome and gives rise to no cross-resistance to macrolides (all macrolides when constitutive), lincosamides (clindamycin and lincomycin) and type B streptogramins, but not to type A streptogramins.
Breakpoints
The British Society for Antimicrobial Chemotherapy recommends the following breakpoints for staphylococci and a-haemolytic streptococci: susceptible < 0.5 mg/L; resistant > 1.0 mg/L.
Susceptibility:
The following table lists organisms according to their inherent susceptibility to clindamycin. 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.
Susceptible species
Gram positive aerobes:
Staphylococcus aureus *
Staphylococcus epidermis Streptococcus pneumoniae Streptococcus pyrogens Streptococcus viridans
Gram positive anaerobes:
Bifidobacterium spp.
Eubacterium spp.
Propionbacterium spp.
Clostridium perfringens Peptococcus spp.
Peptostreptococcus spp.
Gram negative anaerobes:
Bacteroides fragilis group Bacteroides melaninogenicus Fusobacterium spp.
Veillonella spp.
Resistant species:
Gram positive aerobes and anaerobes: Enterococci
Clostridia spp.
Gram negative anaerobes:
Fusobacterium varium
* Up to 50% of methicillin-susceptible S. aureus have been reported to be resistant to Clindamycin in some areas. More than 90% of methicillin-resistant S. aureus (MRSA) are resistant to Clindamycin. Clindamycin should not be used while awaiting susceptibility test results if there is any suspicion of resistance to methicillin.
Consideration should be given to official guidance regarding the appropriate use of antibacterial agents.
5.2 Pharmacokinetic properties
General characteristics of active substance
Following parenteral administration, the biologically inactive clindamycin phosphate is hydrolysed to clindamycin. When the equivalent of 300 mg of clindamycin is injected intramuscularly, a mean peak plasma concentration of 6 microgram/ml is achieved within three hours; 600 mg gives a peak concentration of 9 microgram/ml.
In children, peak concentration may be reached within one hour. When the same doses are infused intravenously, peak concentrations of 7 and 10 micrograms per ml respectively are achieved by the end of infusion.
Clindamycin is widely distributed in body fluids and tissues including bone, but it does not reach the cerebrospinal fluid in significant concentrations. It diffuses across the placenta into the foetal circulation and appears in breast milk. High concentrations occur in bile. It accumulates in leucocytes and macrophages. Over 90% of clindamycin in the circulation is bound to plasma proteins. The half-life is 2 to 3 hours, although this may be prolonged in pre-term neonates and patients with severe renal impairment.
Clindamycin undergoes metabolism, to the active N-demethyl and sulphoxide metabolites and also some inactive metabolites. About 10% of the drug is excreted in the urine as active drug or metabolites and about 4% in the faeces; the remainder is excreted as inactive metabolites. Excretion is slow and takes place over several days. It is not effectively removed from the blood by dialysis.
Characteristics in patients
No special characteristics. See section 4.4 "Special warnings and precautions for use" for further information.
5.3 Preclinical safety data
Not applicable
6 PHARMACEUTICAL PARTICULARS
6.1 List of excipients
Edetate Disodium
Sodium hydroxide
Water for injections
6.2 Incompatibilities
Solutions of clindamycin salts have a low pH and incompatibilities may reasonably be expected with alkaline preparations or drugs unstable at low pH. Incompatibility has been reported with: ampicillin sodium, aminophylline, barbiturates, calcium gluconate, ceftriaxone sodium, ciprofloxacin, diphenylhydantoin, idarubicin hydrochloride, magnesium sulphate, phenytoin sodium and ranitidine hydrochloride.
6.3 Shelf life
18 months
6.4 Special precautions for storage
Do not store above 25°C. Do not refrigerate or freeze.
6.5 Nature and contents of container
Type 1 uncoloured glass ampoule containing 2 ml or 4ml sterile solution.
Each carton contains 1, 5, 10, 20 or 50 ampoules.
6.6 Special precautions for disposal
Clindamycin Injection has been shown to be physically and chemically compatible for at least 24 hours in 5% dextrose and sodium chloride injection solutions. From a microbiological point of view, the product should be used immediately. If not used immediately, in-use storage times and conditions are the responsibility of the user and would normally be no longer than 24 hours at 2-8°C unless dilution has taken place in controlled and validated aseptic conditions.
The product should not be admixed with other drug products which are chemically or physically unstable at low pH (see section 6.2).
The compatibility and duration of stability of drug admixtures will vary depending upon concentration and other conditions.
7 MARKETING AUTHORISATION HOLDER
Villerton Invest S.A.
40 Avenue Monterey L-2163 Luxembourg
8 MARKETING AUTHORISATION NUMBER(S)
PL 24780/0002
9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION
06/02/2008
10 DATE OF REVISION OF THE TEXT
21/07/2014