DALACIN C Capsule Ref.[50846] Active ingredients: Clindamycin

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 should be discontinued and appropriate therapy should be initiated (see section 4.3 and section 4.8). The usual agents (adrenaline, corticosteroids, antihistamines, colloid infusion) should be available for emergency treatment of serious reactions.

As has been reported with other antibiotics, clindamycin therapy has been associated with severe colitis, which may end fatally. It should not be used in patients with non-bacterial infections. Studies indicate a toxin(s) produced by Clostridia is one primary cause of antibiotic associated colitis. Cholestyramine and colestipol resins have been shown to bind the toxin in vitro. The colitis is usually characterised by mild watery diarrhoea to severe, persistent diarrhoea leukocytosis, fever, severe abdominal cramps which may be associated with the passage of blood and mucous and if allowed to progress may produce peritonitis, shock and toxic megacolon. Endoscopic examination may reveal pseudomembranous colitis.

Mild cases usually respond to drug discontinuation alone. However, in moderate to severe cases, appropriate therapy with a suitable oral antibacterial agent effective against Clostridioides difficile should be considered. Fluids, electrolytes and protein replacement should be provided when indicated.

Drugs which delay peristalsis, e.g. opiates and diphenoxylate hydrochloride with atropine sulfate (LOMOTIL), may prolong and/or worsen the condition and should not be used. Antibiotic-associated colitis and diarrhoea (due to C. difficile) occur more frequently and may be more severe in debilitated and/or elderly patients (>60 years). When clindamycin is indicated in these patients, they should be carefully monitored for change in bowel frequency.

C. 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.

Stool culture for C. difficile and stool assay for C. difficile toxin may be helpful diagnostically.

When significant diarrhoea occurs, the drug should be discontinued or, if necessary, continued only with close observation of the patient. Large bowel endoscopy has been recommended.

Antiperistaltic agents such as opiates and diphenoxylate with atropine (Lomotil) may prolong and/or worsen the condition. Vancomycin has been found to be effective in the treatment of antibiotic associated pseudomembranous colitis produced by C. difficile. The usual adult dose is 500 mg to 2 g of vancomycin orally per day in three to four divided doses administered for seven to ten days. Cholestyramine or colestipol resins bind vancomycin in vitro.

If both a resin and vancomycin are to be administered concurrently, it may be advisable to separate the time of administration of each drug.

Diarrhoea, colitis, and pseudomembranous colitis have been observed to begin up to several weeks following cessation of therapy with clindamycin.

Review of experience to date suggests that a sub-group of older patients with associated severe illness may tolerate diarrhoea less well. When clindamycin is indicated in these patients, they should be carefully monitored for change in bowel frequency.

DALACIN C should be prescribed with caution in individuals with a history of gastrointestinal disease, particularly colitis.

Mild cases of colitis may respond to drug discontinuance alone. Moderate to severe cases should be managed with fluid, electrolyte and protein supplementation as indicated.

Systemic corticoids and corticoid retention enemas may help relieve the colitis. Other causes of colitis should also be considered.

A careful inquiry should be made concerning previous sensitivities to medicines and other allergens.

Paediatric use

When DALACIN C is administered to newborns and infants, appropriate monitoring of organ system functions is desirable. For formulation reasons, DALACIN C capsules are not recommended in newborns, infants and children.

Use in meningitis

Since clindamycin does not diffuse adequately into the cerebrospinal fluid the medicine should not be used in the treatment of meningitis. Clindamycin should not be used in patients with non-bacterial infections.

DALACIN C should be prescribed with caution in atopic individuals.

During prolonged therapy, periodic liver function tests and blood counts should be performed.

Clindamycin is potentially nephrotoxic. Acute kidney injury including acute renal failure has been reported. Therefore, monitoring of renal function should be considered during therapy of patients with pre-existing renal dysfunction or taking concomitant nephrotoxic drugs and monitoring of renal function should be performed if therapy is prolonged.

Certain infections may require incision and drainage or other indicated surgical procedures in addition to antibiotic therapy. The use of DALACIN C occasionally results in overgrowth of non-susceptible organisms, particularly yeasts. Should superinfection occur, appropriate measures should be taken as indicated by the clinical situation.

Clindamycin dosage modification is not necessary in patients with renal disease. In patients with moderate to severe liver disease, prolongation of the half-life of clindamycin has been found, but a pharmacokinetic study has shown that, when given every eight hours, accumulation of clindamycin should rarely occur. Therefore, dosage reduction in liver disease is not considered necessary.

Patients with very severe renal disease and/or very severe hepatic disease accompanied by severe metabolic aberrations should be dosed with caution, and serum clindamycin levels monitored during high-dose therapy

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

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 drugs metabolised by these CYP enzymes are unlikely.

Pregnancy

Category A

Clindamycin crosses the placenta in humans. After multiple doses, amniotic fluid concentrations were approximately 30% of maternal concentrations. Clindamycin should be used in pregnancy only if clearly needed.

Breast-feeding

Clindamycin has been reported to appear in human breast milk in ranges from <0.5 to 3.8 micrograms/mL. Clindamycin has the potential to cause adverse effects on the breastfed infant’s gastrointestinal flora such as diarrhoea or blood in the stool, or rash. Therefore, clindamycin is not recommended for nursing mothers.

If oral or intravenous clindamycin is required by a nursing mother, it is not a reason to discontinue breastfeeding, but an alternate drug may be preferred. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for clindamycin and any potential adverse effects on the breastfed child from clindamycin or from the underlying maternal condition.

The effect of clindamycin on the ability to drive or operate machinery has not been systematically evaluated.

The adverse effects listed in the table below are presented by system organ class. Within each frequency category, the adverse effects are presented in the order of frequency and then by decreasing medical seriousness.

CIOMS III categories: Very Common ≥1/10 (≥10%); Common ≥1/100 to <1/10 (≥1% and <10%); Uncommon ≥1/1000 to <1/100 (≥0.1% and <1%); Rare ≥1/10,000 to <1/1000 (≥0.01% and <0.1%); Very Rare <1/10,000 (< 0.01%)
^‡ Adverse reactions apply only to oral formulation.

h2.Post-Marketing Experience

The following additional adverse reactions have been reported during post-marketing experience.

Infections and infestations

Frequency not known: C. difficile colitis.

Immune system disorders

Frequency not known: Anaphylactic shock, anaphylactic reaction, hypersensitivity.

Skin and subcutaneous tissue disorders

Frequency not known: Angioedema.

Renal and urinary disorders

Frequency not known: Acute kidney injury.

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 professionals are asked to report any suspected adverse reactions https://nzphvc.otago.ac.nz/reporting/

None stated.