INDICATIONS     CONTRA-INDICATIONS     DOSAGE     SIDE-EFFECTS     PREGNANCY     OVERDOSE     IDENTIFICATION     PATIENT INFORMATION
DALACIN C™ 600 mg(Injection)

SCHEDULING STATUS:
S4

PROPRIETARY NAME
(and dosage form):

DALACIN C™ 600 mg(Injection)

COMPOSITION:
Each mL DALACIN C contains clindamycin phosphate equivalent to 150 mg clindamycin base. Benzyl alcohol (preservative) 0,9% m/v.

PHARMACOLOGICAL CLASSIFICATION:
A 20.1.1 Broad and medium spectrum antibiotics

PHARMACOLOGICAL ACTION:
Microbiology:
Although clindamycin phosphate is inactive in-vitro, rapid in vivo hydrolysis converts this compound to the antibacterially active clindamycin.
The DALACIN spectrum of in vitro activity includes the following gram-positive aerobic organisms: Staphylococcus aureus, and Staphylococcus epidermidis (both penicillinase and non- penicillinase producing strains), Streptococci (except S. faecalis), Pneumococci organisms as follows: anaerobic gram-negative bacilli such as Bacteroides species and Fusobacterium species; anaerobic gram-positive, non-sporeforming bacilli such as Propionibacterium, Eubacterium and Actinomyces species; and anaerobic and micro-aerophilic gram-positive cocci, such as Peptococcus species, Peptostreptococcus species, and Micro-aerophilic streptococci; and Clostridium species.
Clindamycin demonstrates cross-resistance with lincomycin.
When tested by in vitro methods, some staphylococcal strains originally resistant to erythromycin rapidly developed resistance to DALACIN.
DALACIN Susceptibility Discs* may be used for determination of the in vitro susceptibility of aerobic bacteria to DALACIN. DALACINSusceptibility Powder** may be used for determination of the in vitro susceptibility of anaerobic and aerobic bacteria to DALACIN.
* DALACIN (clindamycin) Susceptibility Discs 2 mcg. See package insert for use.
** DALACIN (clindamycin) Susceptibility Powder 20 mg. See package insert for use.
Human Pharmacology:
Biologically inactive clindamycin phosphate is rapidly converted to active clindamycin.
By the end of short-term intravenous infusion, peak serum levels of active clindamycin are reached. Biologically inactive clindamycin phosphate disappears rapidly from the serum; the average disappearance half-life is 6 minutes; however, the serum disappearance half-life of active clindamycin is about 3 hours in adults and 2 hours in children. After intramuscular injection of clindamycin phosphate, peak levels of active clindamycin are reached within 3 hours in adults and 1 hour in children. Serum level curves may be constructed from IV peak serum levels as given in Table 1, by application of disappearance half-lives listed above after IM injection. Serum levels of clindamycin can be maintained above the in vitro minimum inhibitory concentrations for most indicated organisms by administration of clindamycin phosphate every 8-12 hours in adults and every 6-8 hours in children, or by continuous intravenous infusion. An equilibrium state is reached by the third dose.
The disappearance half-life of clindamycin is increased in patients with markedly reduced renal or hepatic function; dosage schedules need not be modified in the presence of mild or moderate renal or hepatic disease.
Serum assays for active clindamycin require an inhibitor to prevent in vitro hydrolysis of clindamycin phosphate.

Table 1. Average peak serum concentration after dosing with clindamycin phosphate
Dosage Regimen Healthy Adult Males (Post equilibrium)	Clindamycin mcg/mL	Clindamycin Phosphate mcg/mL
300 mg IV in 10 min. q8h	7	15
600 mg IV in 20 min. q8h	10	23
900 mg IV in 30 min. q12h	11	29
1200 mg IV in 45 min. q12h	14	49
300 mg IM q8h	6	3
600 mg IM q12h	9	3
Children (first dose)*
5-7 mg/kg IV in 1 hr	10
3-5 mg/kg IM	4
5-7 mg/kg IM	8

*Data in this group from patients treated for infection.

INDICATIONS:
DALACIN C is indicated in the treatment of serious infections caused by susceptible strains of the following micro-organisms:
Streptococci:

•	Upper respiratory tract infections (injectable benzathine penicillin is considered to be the drug of choice in treatment and prevention of streptococcal pharyngitis and in long-term prophylaxis of rheumatic fever. DALACIN C is effective in the eradication of streptococci from the nasopharynx, however, data establishing the efficacy of DALACIN C in the subsequent prevention of rheumatic fever are not available at present).
•	Lower respiratory tract infections
•	Skin and soft tissue infections
•	Septicaemia

Staphylococci:

•	Upper and lower respiratory tract infections
•	Skin and soft tissue infections
•	Septicaemia

Pneumococci:

•	Upper and lower respiratory tract infections

Anaerobic bacteria:

•	Lower respiratory tract infections such as empyema, anaerobic pneumonitis and lung abscess.
•	Skin and soft tissue infections
•	Septicaemia
•	Intra-abdominal infectionssuch as peritonitis and intra-abdominal abscess caused by sensitive anaerobic organisms (Typically resulting from anaerobic organisms resident in the normal gastro-intestinal tract).
•	Infections of the female pelvis and genital tract, such as endometritis , non-gonococcal tubo-ovarian abscess, pelvic cellulitis, and postsurgical vaginal cuff infection.

DALACIN is indicated as adjunctive therapy in dental infections due to susceptible organisms.
Bacteriological studies to determine the causative organisms should be performed and their susceptibility to DALACIN tested.
Clindamycin phosphate, when used concurrently with an aminoglycoside antibiotic, such as gentamycin or tobramycin, has been shown to be effective in preventing peritonitis after bowel perforation and bacterial contamination secondary to trauma.

CONTRA-INDICATIONS:
This drug is contra-indicated in individuals with a history of hypersensitivity to preparations containing clindamycin or lincomycin.
Since Clindamycin does not diffuse adequately into the cerebrospinal fluid, the medicine should not be used in the treatment of meningitis.

WARNINGS:
Use in pregnancy: Safety for use in pregnancy has not been established.
Use in newborns and infants: When DALACIN C is administered to infants; appropriate monitoring of organ system functions is desirable. Safety and appropriate dosages in infants less than one month old have not been established.
Antagonism has been demonstrated between DALACIN and erythromycin in vitro. Because of possible clinical significance, these two drugs should not be administered concurrently.
SERIOUS ANAPHYLACTOID REACTIONS REQUIRE IMMEDIATE EMERGENCY TREATMENT WITH EPINEPHRINE; OXYGEN AND INTRAVENOUS CORTICOSTEROIDS SHOULD ALSO BE ADMINISTERED AS INDICATED.
Cases of severe and persistent diarrhoea have been reported during or after therapy with DALACIN C. This diarrhoea has been associated with blood and mucous in the stools and has resulted in acute colitis. When endoscopy has been performed, some of these cases have shown pseudomembrane formation.
If significant diarrhoea occurs during therapy, this drug should be discontinued. Significant diarrhoea occurring up to several weeks post-therapy should be managed as if antibiotic-associated.
If colitis is suspected, endoscopy is recommended. Mild cases showing minimal mucosal changes may respond to simple drug discontinuance. Moderate to severe cases, including those showing ulceration or pseudomembranous formation, should be managed with fluid, electrolyte, and protein supplementation as indicated.
Anticholinergics and antiperistaltic agents may worsen the condition.
Other causes of colitis should be considered.

DOSAGE AND DIRECTIONS FOR USE:
• Adults:
Parenteral (IM or IV administration)
Mild infections or infections due to highly susceptible pathogens: 600 mg/day in 2 equal doses.
Moderately severe infections: 600-1200 mg/day in 2, 3 or 4 equal doses.
Severe infections: 1200-2700 mg/day in 2, 3 or 4 equal doses.
Note:
For more serious infections, these doses may have to be increased. In life-threatening situations, doses of as much as 4,8 grams daily have been given intravenously to adults. See “Dilution and Infusion Rates”section below. Alternatively, drug may be administered in the form of a single rapid infusion of the first dose followed by continuous IV infusion as follows:

To maintain serum clindamycin levels	Rapid infusion rate	Maintenance infusion rate
Above 4 mcg/mL	10 mg/min. for 30 min.	0,75 mg/min.
Above 5 mcg/mL	15 mg/min. for 30 min.	1,00 mg/min.
Above 6 mcg/mL	20 mg/min. for 30 min.	1,25 mg/min.

• Children (over 1 month of age):
Parenteral (IM or IV Administration):
Mild infections or infections due to highly susceptible pathogens:
10-15 mg/kg/day in 3 or 4 equal doses.
Moderately severe infections:
15-25 mg/kg/day in 3 or 4 equal doses.
Severe infections:
25-40 mg/kg/day in 3 or 4 equal doses.
As an alternative to dosing on a body weight basis, children may be dosed on the basis of square metre body surface:
350 mg/m²/day for mild to moderately severe infections and
450 mg/m²/day for moderately severe or severe infections.
Note:
In severe infections it is recommended that children be given no less than 300 mg/day regardless of body weight.
Dilution and Infusion Rates
Single IM injections of greater than 600 mg are not recommended. Clindamycin phosphate must be diluted prior to IV administration to a dilution of 300 mg in 50 mL of diluent (6 mg/mL) or more.

DOSE	DILUENT	TIME
300 mg	50 mL	10 min.
600 mg	50 mL	20 min.
900 mg	100 mL	30 min.
1200 mg	100 mL	40 min.

Administration of more than 1200 mg in a single 1-hour infusion is not recommended.

DIRECTIONS FOR USE OF THE AMPOULE:
No ampoule file is needed to open the ampoules. The neck of the ampoule is prescored at the point of constriction. A coloured dot on the ampoule helps to orientate the ampoule. Take the ampoule and face the coloured dot. The ampoule opens easily by placing the thumb on the coloured dot and gently pressing downwards as shown.
{illustrated}

Dilution and Compatibility:
Physical and biological compatibility studies monitored for 24 hours at room temperature have demonstrated no inactivation or incompatibility with the use of DALACIN C in IV solutions containing NaCl, glucose, calcium or potassium in concentrations usually used clinically. No incompatibility has been demonstrated with the antibiotics cephalothin, kanamycin, gentamicin, penicillin or carbenicillin. DALACIN C should not be used with solutions containing vitamin B complex because of physical incompatibility.

SIDE-EFFECTS AND SPECIAL PRECAUTIONS:
Precautions
DALACIN C should be prescribed with caution in atopic individuals. During prolonged therapy periodic liver and kidney function tests and blood counts should be performed. The use of DALACIN C may result in overgrowth of non-susceptible organisms –particularly yeasts. Should superinfection occur, appropriate measures should be taken as indicated by the clinical situation. DALACIN C should not be injected undiluted as an intravenous bolus, but should be infused over at least 20-60 minutes as directed in “Dosage and Directions for Use”section.
Patients with renal disease and/or hepatic diseases accompanied by metabolic abberation should be dosed with caution.
Side-effects
The following reactions have been reported in clinical studies with DALACIN C.

Local reactions:	Pain, induration and sterile abscess have been reported after intramuscular injection and thrombophlebitis after intravenous infusion. Reactions can be minimized or avoided by giving deep intramuscular injections and avoiding prolonged use of indwelling intravenous cathethers.
Gastro-intestinal:	The symptoms include abdominal pain, nausea, vomiting, diarrhoea; relationship to parenteral clindamycin therapy is unknown.
Hypersensitivity	Maculopapular rash and urticaria have been observed during the drug
reactions:	therapy. If a hypersensitivity reaction occurs, the treatment should be discontinued.
Liver	Abnormalities in liver function tests (elevations of serum transaminases) have been observed during DALACIN C therapy.
Haematopoietic:	Transient neutropenia (leucopenia) and eosinophilia have been reported; relationship to therapy is unknown.

KNOWN SYMPTOMS OF OVERDOSAGE AND PARTICULARS OF ITS TREATMENT:
Treatment should be symptomatic and supportive.
Haemodialysis and peritoneal dialysis are not effective in removing clindamycin from serum.

IDENTIFICATION:
Colourless solution for injection

PRESENTATION:
DALACIN C 600 mg injection is available in 4 mL ampoules.

STORAGE INSTRUCTIONS:
Store at room temperature (15°C - 30°C)
Keep out of reach of children.

REGISTRATION NUMBER:
F/20.1.1/169

NAME AND BUSINESS ADDRESS OF THE APPLICANT:
Pharmacia South Africa (Pty) Limited
Alphen West G
George Street
Midrand
1685

DATE OF PUBLICATION OF THIS PACKAGE INSERT:
13 February 1992

^{TM =} Trademark

New addition to this site: February 2005
Source: Pharmaceutical Industry
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