CLINDAMYCIN Solution for Injection or Infusion Ref.[6726] Active ingredients: Clindamycin

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.

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.

Pregnancy

Safety for use in pregnancy has not been established. Animal studies do not indicate reproductive toxicity (see section 5.3).

Breast-feeding

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.

Fertility

No data available.

None known.

The frequency of undesirable effects listed below is defined using the following convention: Very common (≥1/10), Common (≥1/100 to <1/10), Uncommon (≥1/1,000 to <1/100), Rare (≥1/10,000 to <1/1,000), Very rare (<1/10,000), Not known (cannot be estimated from the available data).

Blood and lymphatic system disorders

Not Known: Transient neutropenia (leucopenia), eosinophilia, agranulocytosis and thrombocytopenia

Cardiac disorders

Not Known: Cardiopulmonary arrest and hypotension have been reported following too rapid intravenous administration (see section 4.2)

Hepatobiliary disorders

Not Known: Jaundice and abnormalities in liver function

Immune system disorders

Not Known: Anaphylactoid reactions

Nervous system disorders

Not known: Dysgeusia have been observed upon systemic administration of clindamycin using injectables (IM or IV), capsules or oral granulate solutions

Gastrointestinal disorders

Not Known: Oesophageal ulcers, oesophagitis with oral preparations, nausea, vomiting, abdominal pain and diarrhoea (see section 4.4)

General disorders and administration site conditions

Not Known: 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

Skin and subcutaneous tissue disorders

Not Known: Generalised mild to moderate morbilliform-like skin rashes, Erythema multiforme resembling Stevens-Johnson syndrome, exfoliative and vesiculobullous dermatitis, toxic epidermal necrolysis, Maculopapular rash, urticaria, Pruritus, Serious cutaneous adverse reaction (SCAR)

Infections and infestations

Not Known: Vaginitis

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.

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.