1. Name Of The Medicinal Product
Dalacin C Phosphate Sterile Solution
2. Qualitative And Quantitative Composition
Each ml of solution contains clindamycin phosphate equivalent to 150 mg clindamycin.
For 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 GramStreptococcus 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.
4.2 Posology And Method Of Administration
Parenteral (IM or IV administration). Dalacin C Phosphate must be diluted prior to IV administration and should be infused over at least 10
Adults: Serious infections: 600 mg
More severe infections: l.2
Single IM injections of greater than 600 mg are not recommended nor is administration of more than 1.2 g in a single one
For more serious infections, these doses may have to be increased. In life
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
More severe infections: 25
Elderly patients: The half
Dosage in Renal/Hepatic Impairment: clindamycin dosage modification is not necessary in patients with renal or hepatic insufficiency.
Treatment for infections caused by beta
The concentration of clindamycin in diluent for infusion should not exceed 18 mg per mL and INFUSION RATES SHOULD NOT EXCEED 30 MG PER MINUTE. The usual infusion rates are as follows:
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4.3 Contraindications
Dalacin C Phosphate is contra
4.4 Special Warnings And Precautions For Use
Warnings
This product contains benzyl alcohol. Benzyl alcohol has been reported to be associated with a fatal "Gasping syndrome" in premature infants.
Dalacin C Phosphate 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 antibioticin 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 colestyramine 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 diarrhea (CDAD) has been reported with use of nearly all antibacterial agents, including clindamycin, and may range in severity from mild diarrhea to fatal colitis. Treatment with antibacterial agents alters the normal flora of the colon leading to overgrowth of C difficile. [134-147]
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 diarrhea following antibiotic use. Careful medical history is necessary since CDAD has been reported to occur over two months after the administration of antibacterial agents. [134-147]
Precautions
Caution should be used when prescribing Dalacin C Phosphate 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 neonates and infants. Safety and appropriate dosage in infants less than one month old have not been established.
Prolonged administration of Dalacin C Phosphate, as with any anti
Care should be observed in the use of Dalacin C Phosphate in atopic individuals.
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.
4.6 Pregnancy And Lactation
Safety for use in pregnancy has not been established.
Clindamycin is excreted in human milk. Caution should be exercised when Dalacin C Phosphate 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
The effect of clindamycin on the ability to drive or operate machinery has not been systematically evaluated.
4.8 Undesirable Effects
Gastro: 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 Special 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 minimized by deep IM injection and avoiding the use of an indwelling catheter.
Thrombophlebitis has been reported with IV injection.
4.9 Overdose
In cases of overdosage no specific treatment is indicated.
The serum biological half
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
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.
Most Gram-negative aerobic bacteria, including the Enterobacteriaceae, are resistant to clindamycin. Clindamycin demonstrates crossin 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 ribosomal binding site, chromosomal mutation of the ribosomal protein and in a few staphylococcal isolates enzymatic inactivation by a plasmid-mediated adenyltransferase.
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 fetal 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 special precautions for use" for further information.
6. Pharmaceutical Particulars
6.1 List Of Excipients
Benzyl alcohol
Disodium edetate
Sterilised 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
24 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 flint glass ampoule containing 2 ml or 4 ml sterile, aqueous solution, packed in cardboard carton, together with a leaflet.
6.6 Special Precautions For Disposal And Other Handling
Dalacin C Phosphate 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, cefamandole nafate, cephazolin sodium, cefotaxime sodium, cefoxitin sodium, ceftazidime sodium, ceftizoxime sodium, gentamicin sulphate, netilmicin sulphate, piperacillin and tobramycin.
The compatibility and duration of stability of drug admixtures will vary depending upon concentration and other conditions.
7. Marketing Authorisation Holder
Pharmacia Limited
Ramsgate Road
Sandwich, Kent
CT13 9NJ
UK
8. Marketing Authorisation Number(S)
PL 00032/0042R
9. Date Of First Authorisation/Renewal Of The Authorisation
27th December 1997 / 22nd May 2002/7th August 2009
10. Date Of Revision Of The Text
May 2010
Legal category
POM
DA4_0
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