The clindamycin phosphate injectable formulation contains benzyl alcohol (9.45 mg/ml) as preservative. Intravenous administration of the preservative benzyl alcohol has been associated with serious adverse events, and death in paediatric patients including neonates characterized by central nervous system depression, metabolic acidosis, gasping respirations, cardio-vascular failure and haematological anomalies (“gasping syndrome”). Although normal therapeutic doses of this product ordinarily deliver amounts of benzyl alcohol that are substantially lower than those reported in association with the “gasping syndrome”, the minimum amount of benzyl alcohol at which toxicity may occur is not known. Use only if it is necessary and if there are no alternatives possible. If given in high volumes, should be used with caution and preferably for short term treatment in subjects with liver or kidney impairment because of the risk of accumulation and toxicity (metabolic acidosis).
Premature and low-birth weight infants may be more likely to develop toxicity.
Benzyl Alcohol containing products should not be used in pre-term or full-term neonates unless strictly necessary.
Severe hypersensitivity reactions, including severe skin reactions such as drug reaction with eosinophilia and systemic symptoms (DRESS), Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and acute generalized exanthematous pustulosis (AGEP) have been reported in patients receiving clindamycin therapy. If a hypersensitivity or severe skin reaction occurs, clindamycin should be discontinued and appropriate therapy should be initiated (see sections 4.3 and 4.8).
Dalacin C Phosphate should only be used in the treatment of serious infections. In considering the use of Dalacin C Phosphate, 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 Dalacin C Phosphate.
Studies indicate a toxin(s) produced by clostridia (especially Clostridium difficile) is the principal direct cause of antibiotic-associated colitis. 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 product peritonitis, shock and toxic megacolon. This may be fatal.
The disease is likely to follow a more severe course in older patients or patients who are debilitated. Diagnosis is usually made by 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 Clostridia difficile on selective media and assay of the stool specimen for the toxin(s) of C. Difficile.
Treatment with antibacterial agents alters the normal flora of the colon leading to overgrowth of Clostridium difficile. This has been reported with use of nearly all antibacterial agents, including clindamycin. Clostridium difficile produces toxins A and B which contribute to the development of Clostridium difficile associated diarrhoea (CDAD) and is a primary cause of 'antibiotic-associated colitis'.
It is important to consider the diagnosis of CDAD in patients who present with diarrhoea subsequent to the administration of antibacterial agents. This may progress to colitis, including pseudomembranous colitis (see section 4.8), which may range from mild to fatal colitis. If antibiotic-associated diarrhoea or antibiotic-associated colitis is suspected or confirmed, ongoing treatment with antibacterial agents, including clindamycin, should be discontinued and adequate therapeutic measures should be initiated immediately. Drugs inhibiting peristalsis are contraindicated in this situation.
Caution should be used when prescribing Dalacin C Phosphate to individuals with a history of gastro-intestinal disease, especially colitis.
Since clindamycin does not diffuse adequately into cerebrospinal fluid, the drug should not be used in the treatment of meningitis.
If therapy is prolonged, liver and kidney function and haematology tests should be performed, and in infants under the age of one year. Safety and appropriate dosage in infants less than one month old have not been established.
The use of clindamycin phosphate may result in overgrowth of non-susceptible organisms, particularly yeasts.
Prolonged administration of Dalacin C Phosphate, as with any anti-infective, may result in super-infection due to organisms resistant to Dalacin C Phosphate.
The drug should be used with caution in patients with the atopic syndrome, particularly with asthma.
Antibiotics can reduce the efficacy of the oral contraceptive pill. Additional contraceptive precautions should be taken during treatment.
Clindamycin phosphate should not be injected intravenously undiluted as a bolus, but should be infused over at least 10-60 minutes as directed in section 4.2.