Skip to Content

CLINDAMYCIN 150MG/ML SOLUTION FOR INJECTION OR INFUSION

Active substance(s): CLINDAMYCIN PHOSPHATE / CLINDAMYCIN PHOSPHATE / CLINDAMYCIN PHOSPHATE

View full screen / Print PDF » Download PDF ⇩

PDF Transcript

SUMMARY OF PRODUCT CHARACTERISTICS

1

NAME OF THE MEDICINAL PRODUCT
Clindamycin 150mg/ml Solution for Injection or Infusion

2

QUALITATIVE AND QUANTITATIVE COMPOSITION
Each 1ml of solution contains clindamycin phosphate equivalent to 150mg
clindamycin.
Each 2ml ampoule contains 300mg clindamycin
Each 4ml ampoule contains 600mg clindamycin

Excipients:
Sodium 6.57mg per ml (prior to dilution)
For a full list of excipients, see section 6.1.

3

PHARMACEUTICAL FORM
Solution for Injection or Infusion
Clear, colourless, solution.

4

CLINICAL PARTICULARS

4.1

Therapeutic indications
Clindamycin is indicated for the treatment of severe infections (see section 4.4 and
5.1). Consideration should be given to official guidance on the appropriate use of
antibacterial agents.
Clindamycin does not penetrate the blood/brain barrier in therapeutically effective
quantities.

4.2

Posology and method of administration
Parenteral (IM or IV administration). Clindamycin 150mg/ml Solution for
Injection and Infusion must be diluted prior to I.V. administration and should
be infused over at least 10-60 minutes.

Adults: Serious infections: 600mg-1.2g/day in two, three or four equal doses.
More severe infections: 1.2-2.7g/day in two, three or four equal doses.
Single I.M. injections of greater than 600mg are not recommended nor is
administration of more than 1.2g in a single one-hour infusion.
For more serious infections, these doses may have to be increased. In lifethreatening situations, doses as high as 4.8g 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.
Children (over 1 month of age): Serious infections: 15-25mg/kg/day in three
or four equal doses.
More severe infections: 25-40mg/kg/day in three or four equal doses. In
severe infections it is recommended that children be given no less than
300mg/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.
Dosage in renal/hepatic impairment: clindamycin dosage modification is not
necessary in patients with renal or hepatic insufficiency
Treatment for infections caused by beta-haemolytic streptococci should be
continued for at least 10 days to guard against subsequent rheumatic fever or
glomerulonephritis.
The concentration of clindamycin in diluent for infusion should not exceed
18mg per ml and INFUSION RATES SHOULD NOT EXCEED 30MG PER
MINUTE. The usual infusion rates are as follows:

4.3

Dose

Diluent

Time

300mg

50ml

10 min

600mg

50ml

20 min

900mg

50-100ml

30 min

1200mg

100ml

40 min

Contraindications
Clindamycin 150mg/ml Solution for Injection and Infusion is contra-indicated
in patients previously found to be sensitive to clindamycin, lincomycin or to
any of the excipients.

4.4

Special warnings and precautions for use
Warnings
Clindamycin 150mg/ml Solution for Injection and Infusion 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
125mg to 500mg 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.
Clostridium difficile associated diarrhoea (CDAD) has been reported with use of
nearly all antibacterial agents, including clindamycin, and may range in severity from
mild diarrhoea to fatal colitis. Treatment with antibacterial agents alters the normal
flora of the colon leading to overgrowth of C difficile.
C. difficile produces toxins A and B which contribute to the development of CDAD.
Hypertoxin producing strains of C. difficile cause increased morbidity and mortality,
as these infections can be refractory to antimicrobial therapy and may require
colectomy. CDAD must be considered in all patients who present with diarrhoea
following antibiotic use. Careful medical history is necessary since CDAD has been
reported to occur over two months after the administration of antibacterial agents.
Precautions
Caution should be used when prescribing Clindamycin 150mg/ml Solution for
Injection and Infusion to individuals with a history of gastro-intestinal disease,
especially colitis.
Periodic liver and kidney function and haematology tests should be carried out during
prolonged therapy. Such monitoring is also recommended in neonates and infants.
Safety and appropriate dosage in infants less than one month old have not been
established.

Prolonged administration of Clindamycin 150mg/ml Solution for Injection and
Infusion, as with any anti-infective, may result in super-infection due to organisms
resistant to clindamycin. The use of Clindamycin 150mg/ml Solution for Injection
and Infusion may result in the overgrowth of non-susceptible organisms particularly
yeasts.
Care should be observed in the use of Clindamycin 150mg/ml Solution for Injection
and Infusion in atopic individuals, particularly those with asthma.
Since Clindamycin 150mg/ml Solution for Injection and Infusion does not diffuse
adequately into cerebrospinal fluid, the drug should not be used in the treatment of
meningitis.
Antibiotics can reduce the efficacy of the combined oral contraceptive pill.
Additional contraceptive precautions should be taken during treatment and for up to
seven days after stopping treatment.
This medicinal product contains 0.286mMol (or 6.57mg) sodium per ml of solution
(prior to dilution). To be taken into consideration by patients on a controlled sodium
diet.

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
Safety for use in pregnancy has not been established. Animal studies do not
indicate reproductive toxicity (see section 5.3).
Lactation
Clindamycin is excreted in human milk. Caution should be exercised when
Clindamycin 150mg/ml Solution for Injection and Infusion is administered to
a nursing mother. It is unlikely that a nursing infant can absorb a significant
amount of clindamycin from its gastro-intestinal tract.

4.7

Effects on ability to drive and use machines
None known.

4.8

Undesirable effects
Gastro-intestinal tract disorders: Oesophageal ulcers have been reported as serious
adverse events during postmarketing surveillance, and oesophagitis with oral
preparations, nausea, vomiting, abdominal pain and diarrhoea (See Section 4.4
Special Warnings and Precautions for use: Warnings).
Blood and lymphatic system disorders: Transient neutropenia (leucopenia),
eosinophilia, agranulocytosis and thrombocytopenia have been reported. No direct
aetiologic relationship to concurrent clindamycin therapy could be made in any of the
foregoing.
Immune system disorders: a few cases of anaphylactoid reactions have been reported.
Skin and subcutaneous tissue disorders: Maculopapular rash and urticaria have been
observed during drug therapy. Generalised mild to moderate morbilliform-like skin
rashes are the most frequently reported reactions. Rare instances of erythema
multiforme some resembling Stevens-Johnson syndrome, have been associated with
clindamycin. Pruritus, vaginitis and rare instances of exfoliative and vesiculobullous
dermatitis have been reported. Serious cutaneous adverse reaction (SCAR) and rare
cases of toxic epidermal necrolysis have been reported during postmarketing
surveillance.
Hepatobiliary disorders: Jaundice and abnormalities in liver function tests have been
observed during clindamycin therapy.
Cardiac disorders: Rare instances of cardiopulmonary arrest and hypotension have
been reported following too rapid intravenous administration. (See Section 4.2
Posology and method of administration)
Nervous system disorders: Frequent cases of dysgeusia have been observed upon
systemic administration of clindamycin using injectables (IM or IV), capsules or oral
granulate solutions, which include a few (non-frequent) serious adverse events.
General disorders and administration site conditions: Local irritation, pain, abscess
formation have been observed in conjunction with IM injection. These reactions can
be minimised by deep IM injection and avoiding the use of an indwelling catheter.
Thrombophlebitis has been reported with IV injection.
Reporting of side effects
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 2.4 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: J01 FF01
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.
Mechanism of resistance
Resistance to clindamycin usually occurs via macrolide-lincosamide-streptogramin B
(MLSB) type of resistance, which may be constitutive or inducible. Clindamycin
demonstrates cross-resistance with lincomycin. When tested by in vitro methods,
some staphylococcal strains originally resistant to erythromycin rapidly developed
resistance to clindamycin. The mechanisms for resistance are the same as for
erythromycin, namely methylation of the ribosome binding site, chromosomal
mutation of the ribosomal protein and in a few staphylococcal isolates emzymatic
inactivation by a plasmid-mediated adenyltransferase.
Breakpoints
The minimum inhibitory concentrations (MIC) breakpoints are as follows:
Eucast
Staphylococci: sensitive ≤ 0.5 resistant > 0.5
Streptococci ABCG and pneumoniae: sensitive ≤ 0.5 resistant > 0.5
Gram positive anaerobes: sensitive ≤ 4 resistant > 4
Gram negative anaerobes: sensitive ≤ 4 resistant > 4
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. As necessary, expert advice should be sought when local

prevalence of resistance is such that the utility of the agent in at least some types of
infections is questionable.
Species
Susceptible
Gram-positive aerobes
Staphylococcus aureus *
Staphylococcus epidermidis
Streptococcus pneumoniae
Streptococcus pyogenes
Streptococcus viridans

Anaerobes
Bacteriodes fragilis group
Bacteroides melaninogenicus
Bifidobacterium spp.
Clostridium perfringens
Eubacterium spp
Fusobacterium spp.
Peptococcus spp.
Peptostreptococcus spp.
Propionibacterium spp.
Veillonella spp.

Resistant
Clostridia spp.
Enterococci
Enterobacteriaceae
* 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 and it should not be used while awaiting susceptibility
test results if there is any suspicion of MRSA.

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 300mg of

clindamycin is injected intramuscularly, a mean peak plasma concentration of
6 microgram/ml is achieved within three hours; 600mg 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 preterm 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 special
precautions for use" for further information.

5.3

Preclinical safety data
Preclinical data reveal no special hazard for humans based on studies of repeat
dose toxicity, reproductive toxicity or genotoxicity. Carcinogenicity studies
have not been conducted. In dogs, repeated high oral doses produced
ulceration of the mucosa of the stomach and gall bladder.

6

PHARMACEUTICAL PARTICULARS

6.1

List of excipients
Disodium edetate
Sodium hydroxide (for pH adjustment)
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. This medicinal product must not be
mixed with other medicinal products except those mentioned in sections 6.6.

6.3

Shelf life
Unopened: 2 years
After dilution: 24 hours
Chemical and physical in-use stability has been demonstrated for 24 hours at
25ºC. From a microbiological point of view, the product should be used
immediately. If not used immediately, in-use storage times and conditions
prior to use are the responsibility of the user and would normally be no longer
than 24 hours at 2 to 8ºC, unless reconstitution/dilution (etc) has taken place in
controlled and validated aseptic conditions.

6.4

Special precautions for storage
Do not store above 25°C. Keep ampoules in the outer carton. Do not refrigerate or
freeze.
Please refer to Sections 6.3 and 6.6 for storage after dilution.

6.5

Nature and contents of container
Type 1 flint glass ampoule containing 2ml or 4ml sterile, aqueous solution,
packed in cardboard carton, together with a leaflet. 1 or 5 ampoules in each
pack.
Not all pack sizes may be marketed.

6.6

Special precautions for disposal
Any unused product or waste material should be disposed of in accordance
with local requirements.
Solution for injection is for single use only. Any unused product should be
discarded.
Infusion: Clindamycin 150mg/ml Solution for Injection and Infusion has been
shown to be physically and chemically compatible for at least 24 hours in
dextrose 5% water and sodium chloride injection solutions containing the
following antibiotics in usually administered concentrations: Amikacin
sulphate, aztreonam, cefotaxime sodium, , ceftazidime sodium, gentamicin
sulphate, , piperacillin and tobramycin. The compatibility and duration of
stability of drug admixtures will vary depending upon concentration and other
conditions. The compatibility and duration of stability of drug admixtures will
vary depending upon concentration and other conditions. The
reconstitution/dilution should be made under aseptic conditions. The solution
should be inspected visually for particulate matter and discoloration prior to
administration. The solution should only be used if the solution is clear and
free from particles.

7

MARKETING AUTHORISATION HOLDER
Focus Pharmaceuticals Ltd
Capital House,
85 King William Street,
London EC4N 7BL,
United Kingdom.

8

MARKETING AUTHORISATION NUMBER(S)
PL 20046/0072

9

DATE OF FIRST AUTHORISATION/RENEWAL OF THE
AUTHORISATION
11/01/2010

10

DATE OF REVISION OF THE TEXT

30/06/2015

Expand Transcript

Source: Medicines and Healthcare Products Regulatory Agency

Disclaimer: Every effort has been made to ensure that the information provided here is accurate, up-to-date and complete, but no guarantee is made to that effect. Drug information contained herein may be time sensitive. This information has been compiled for use by healthcare practitioners and consumers in the United States. The absence of a warning for a given drug or combination thereof in no way should be construed to indicate that the drug or combination is safe, effective or appropriate for any given patient. If you have questions about the substances you are taking, check with your doctor, nurse or pharmacist.

Hide