Clindamycin Equity 150 mg Capsule

Clindamycin Equity is indicated in serious infections caused by organisms susceptible to its action. In vitro susceptibility studies should be performed. Infections due to sensitive organisms which responds to an effective dose of this oral preparation include infections of the:

• Upper respiratory tract including pharyngitis, tonsillitis, sinusitis, otitis media.
• Lower respiratory including bronchitis, and pneumonia.
• Skin and soft tissue including abscesses, cellulitis, infected wounds, and dental infections (peri-apical abscesses and gingivitis).
• Bones and joints including acute and chronic osteomyelitis.
• Bacteraemia has responded to the usually recommended dosages.

Posology

Adults:

• Mild to moderately severe infection: 150 mg approximately every six hours.
• Severe infections: Up to 450 mg every six hours.

Special populations

Elderly patients

The half-life, volume of distribution, clearance and extent of absorption after administration of clindamycin 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, therefore, should not be influenced by age alone.

Paediatric population

• Mild infections: 8-12 mg/kg/day divided into 3 or 4 equal doses.
• Moderately severe infections: 13-16 mg/kg/day divided into 3 or 4 equal doses.
• Severe infections: 17-25 mg/kg/day divided into 3 or 4 equal doses.

Clindamycin Equity capsules should only be used for children who are able to swallow capsules. Do not give Clindamycin Equity capsules to children weighing less than 10 kg. The use of whole capsules may not be suitable to provide the exact mg/kg doses required for the treatment of children.

Note: With u00df-haemolytic streptococcal infections, treatment should continue for at least ten days to diminish the likelihood of subsequent severe complications such as rheumatic fever or glomerulonephritis.

Method of administration

For oral use. Capsules should be taken with a full glass of water to avoid the possibility of oesophageal irritation.

• Patients previously found to be hypersensitive to clindamycin, lincomycin or doxorubicin or to any of the excipients listed in section 6.1.
• Do not use in patients with diarrhoeal states or gastrointestinal disease, particularly those with a history of colitis.
• Safety for use in pregnancy has not been established.
• Clindamycin has been reported to appear in breast milk. Do not use in lactation.

Prescribers should adhere to the principles of antibiotic stewardship.

Warnings: 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 generalised exanthematous pustulosis (AGEP) have been reported in patients receiving clindamycin therapy. If a hypersensitivity or severe skin reaction occurs, Clindamycin Equity should be discontinued and appropriate therapy should be initiated (see sections 4.3 and 4.8).

Clindamycin Equity should only be used in the treatment of serious infections. In considering the use of the product, the medical 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 following the administration of clindamycin. Clindamycin Equity-associated colitis may end fatally. Toxins produced by Clostridium difficile are regarded as the principal cause of antibiotic-associated colitis. Colitis has a clinical spectrum from mild, watery diarrhoea to severe, persistent diarrhoea, leucocytosis, fever and severe abdominal cramps which may be associated with the passage of blood and mucus which, if allowed to progress, may produce peritonitis, shock and toxic megacolon. Diagnosis is made on basis of the clinical symptoms and can be substantiated by endoscopic demonstration of pseudomembranous colitis. The presence of the disease may be further confirmed by culture of the stool for Clostridium difficile on selective media and assay of the stool specimen for the toxin(s) of the C. difficile. Antibiotic-associated colitis has occurred during the administration or even two to three weeks following administration of Clindamycin Equity. The disease is likely to take a more severe course in older patients or in patients who are debilitated.

For treatment of antibiotic-associated colitis see section below.

Treatment of antibiotic-associated colitis

If persistent diarrhoea occurs during therapy, Clindamycin Equity should be discontinued. Significant diarrhoea occurring up to several weeks post-therapy should be managed as if antibiotic-associated.

• Mild colitis: May respond to discontinuation of Clindamycin Equity alone.
• Moderate colitis: Discontinue Clindamycin Equity and treat with fluid, electrolyte and protein replacement.
• Severe colitis: In cases not responding to the above, discontinue Clindamycin Equity and treat with appropriate fluid, electrolyte and protein supplementation and with one of the following:

• vancomycin 125 to 500 mg orally, every 6 hours for 5 to 10 days
• metronidazole 250 to 500 mg orally, every 8 hours
• cholestyramine 4 grams orally, four times a day

Relapses must be treated with a second course of the above medicines.

Cholestyramine and colestipol resins bind to C. difficile toxin in vitro. When administered concurrently with vancomycin, it is advisable to administer the medicines several hours apart since the resins have been shown to bind to oral vancomycin.

Anti-peristaltic anti-diarrhoeals are not recommended since they may delay the removal of toxins from the colon, thereby prolonging and/or worsening the condition.

Cross-resistance has been demonstrated between lincomycin hydrochloride and Clindamycin Equity. Since Clindamycin Equity does not diffuse adequately into cerebrospinal fluid, it should not be used in the treatment of meningitis.

Clindamycin Equity should be prescribed with caution in atopic individuals or in patients with a history of gastrointestinal disease, particularly colitis. The use of antibiotics may result in overgrowth of non-susceptible organisms, particularly yeasts. Should superinfections occur, appropriate measures should be taken as indicated by the clinical situation.

Lactose intolerance

Clindamycin Equity contains lactose monohydrate. Patients with rare hereditary problems of galactose intolerance, total lactase deficiency or glucose-galactose malabsorption should not take Clindamycin Equity.

Clindamycin has been shown to have neuromuscular blocking properties that may enhance the action of other neuromuscular blocking medicines. Therefore, it should be used with caution in patients receiving such medicines.

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.

Co-administration of clindamycin with inhibitors of CYP3A4 and CYP3A5

Clindamycin is metabolised predominantly by CYP3A4, and to a lesser extent by CYP3A5, to the major metabolite clindamycin sulfoxide and minor metabolite N-desmethylclindamycin. Therefore, inhibitors of CYP3A4 and CYP3A5 may reduce clindamycin clearance and inducers of these isoenzymes may increase clindamycin clearance. In the presence of strong CYP3A4 inducers such as rifampicin, monitor for loss of effectiveness.

In vitro studies indicate that clindamycin does not inhibit CYP1A2, CYP2C9, CYP2C19, CYP2E1 or CYP2D6 and only moderately inhibits CYP3A4. Therefore, clinically important interactions between clindamycin and co-administered medicines metabolised by these CYP enzymes are unlikely.

Antagonism with erythromycin has been demonstrated in vitro, therefore it is not recommended that the two medicines be given at the same time.

Pregnancy

Clindamycin as contained in Clindamycin Equity crosses the placenta in humans. After multiple doses, amniotic fluid concentrations were approximately 30 % of maternal blood concentrations. Safety for use in pregnancy has not been established.

Breastfeeding

Clindamycin Equity has been reported to appear in human breast milk in ranges from < 0,5 to 3,8 u03bcg/mL. Because of the potential for serious adverse reactions in nursing infants, Clindamycin Equity should not be taken by nursing mothers (see section 4.3).

Fertility

Fertility studies in rats treated orally with clindamycin revealed no effects on fertility or mating ability. There is no clinical data on human fertility.

The effect of Clindamycin Equity on the ability to drive or operate machinery has not been systemically evaluated.

Tabulated summary of adverse reactions

System Organ Class Frequency Side effect

Blood and lymphatic system disorders Frequent Eosinophilia

Nervous system disorders Less frequent Dysgeusia

Gastrointestinal disorders Frequent Diarrhoea, abdominal pain

Less frequent Vomiting, nausea

Skin and subcutaneous tissue disorders Frequent Maculopapular rash

Less frequent Urticaria, erythema multiforme, pruritus

Investigations Frequent Abnormalities in liver function test (elevation of alkaline phosphatases and serum transaminases)

Post-marketing experience

Adverse reactions identified from post-marketing experience include the following:

System Organ Class Side effect

Infections and infestations Pseudomembranous colitis, clostridium difficile colitis, vaginal infection

Blood and lymphatic system disorders Agranulocytosis, neutropenia, leukopenia, thrombocytopenia

Immune system disorders Anaphylactic shock, anaphylactoid reaction, anaphylactic reaction, hypersensitivity

Gastrointestinal disorders Oesophageal ulcer, oesophagitis

Hepato-biliary disorders Jaundice

Skin and subcutaneous tissue disorders Toxic epidermal necrolysis (TEN), Stevens-Johnson syndrome (SJS), drug reaction with eosinophilia and systemic symptoms (DRESS), acute generalised exanthematous pustulosis (AGEP), angioedema, exfoliative dermatitis, bullous dermatitis, morbilliform rash

Paediatric population

Adverse reactions in children are not expected to be different than in adults.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicine is important. It allows continued monitoring of the benefit/risk balance of the medicine. Healthcare providers are asked to report any suspected adverse reactions to SAHPRA via the u201c6.04 Adverse Drug Reactions Reporting Formu201d, found online under SAHPRAu2019s publications: https://www.sahpra.org.za/Publications/Index/8

The incidence of gastro-intestinal side effects is greater with higher doses. Haemodialysis and peritoneal dialysis are not effective means of removing clindamycin from the blood. Treatment is symptomatic and supportive.