Document: spc-doc_PL 13931-0061 change

• spc-doc_PL 13931-0061
• spc-doc_PL 30306-0676

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SUMMARY OF PRODUCT CHARACTERISTICS

1    NAME OF THE MEDICINAL PRODUCT

Clindamycin 150 mg Hard Capsule

2    QUALITATIVE AND QUANTITATIVE COMPOSITION

Each capsule contains clindamycin hydrochloride equivalent to 150 mg clindamycin.

Also contains lactose.

For a full list of excipients, see section 6.1.

3    PHARMACEUTICAL FORM

Capsule, hard.

A capsule with a lavender body and maroon cap imprinted with CL 150 in white.

4.    CLINICAL PARTICULARS

4.1.    Therapeutic indications

Clindamycin is indicated for the treatment of severe infections caused by susceptible gram-positive aerobic organisms or by susceptible anaerobic organisms.

Consideration should be given to official guidance regarding the appropriate use of antibacterial agents

Posology and method of administration

To be taken orally. Clindamycin Capsules should always be taken with a glass of water and in an upright position.

Absorption of Clindamycin Capsules is not appreciably modified by the presence of food.

Adults (including the elderly):

Moderately severe infection: 150 - 300 mg every six hours Severe infections: 300 - 450 mg every six hours.

Paediatric population:

3 - 6 mg/kg every six hours depending on the severity of the infection.

Dosage in Renal/Hepatic Impairment:

Clindamycin dosage modification is not necessary in patients with renal or hepatic insufficiency.

Note: In cases of beta-haemolytic streptococcal infections, treatment with Clindamycin Capsules should continue for at least 10 days to diminish the likelihood of subsequent rheumatic fever or glomerulonephritis.

4.3 Contraindications

Clindamycin is contraindicated in patients previously found to be hypersensitive to this antibiotic. Although cross-sensitisation to lincomycin has not been demonstrated, it is recommended that clindamycin is not used in patients who have demonstrated lincomycin sensitivity.

4.4 Special warnings and precautions for use

Clindamycin Capsules should only be used in the treatment of serious infections. In considering the use of this product the practitioner should bear in mind the type of infection and the potential hazard of the diarrhoea that may develop, since cases of colitis have been reported. The appearance of marked diarrhoea should be regarded as an indication that the drug should be discontinued immediately, since it may progress to pseudomembranous colitis.

Studies indicate a toxin(s) produced by clostridia (especially Clostridium difficile) is the principal cause of antibiotic-associated colitis. These studies also indicate that this toxigenic clostridium is usually sensitive in vitro to vancomycin. When 125 - 500 mg of vancomycin are administered orally four times a day, there is a rapid observed disappearance of the toxin from faecal samples and a coincident recovery from the diarrhoea.

Care should be observed in the use of Clindamycin Capsules in atopic individuals e.g. asthma and allergy.

Periodic liver function tests and blood counts 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 an anti-infective may result in super-infection due to organisms resistant to the anti-infective.

This medicinal product contains lactose. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.

4.5 Interaction with other medicinal products and other forms of interaction

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.

Antagonism has been demonstrated between clindamycin and erythromycin in vitro. Because of possible clinical significance, these two drugs should not be administered concurrently.

4.6 Fertility, pregnancy and lactation

Safety for use in pregnancy has not yet been established. This drug should only be used in pregnancy or lactation if considered essential by the physician. It crosses the placenta and is excreted in breast milk. There is no evidence of teratogenic effect in animals nor to date in man

4.7 Effects on ability to drive and use machines

None stated.

4.8 Undesirable effects

Anaphylaxis and anaphylactoid reactions have been reported.

Gastro-intestinal tract: Oesophageal ulcers have been reported as serious adverse events; oesophagitis with oral preparations, nausea, vomiting, abdominal pain and diarrhoea (see Section 4.4 Special Warnings and Special Precautions for Use, Warnings).

Haemopoietic: Transient neutropenia (leucopenia), eosinophilia, agranulocytosis and thrombocytopenia have been reported.

Skin and mucous membranes: Maculopapular rash and urticaria have been observed during drug therapy and have been reported in up to 10% of recipients. Generalised mild to moderate morbilliform-like skin rashes are the most frequently reported reactions. Vesicobullous eruptions may also occur. Rare instances of erythema multiforme and of Stevens-Johnson syndrome have been reported.

Vaginitis has been reported.

Hepatic: Jaundice and abnormalities in liver function tests have been observed during clindamycin therapy.

Renal: renal dysfunction, or worsening of renal insufficiency, has been reported.

Musculoskeletal: polyarthritis has been reported. Nervous system: taste disorder.

4.9 Overdose

Symptoms from overdosing are nausea, vomiting and diarrhoea.

In cases of overdosage that may have led to adverse reactions, therapy should be discontinued and the usual emergency treatment, including corticosteroids, adrenaline and antihistamines, instituted.

The serum biological half-life of clindamycin is 2.4 hours. Clindamycin cannot readily be removed from the blood by dialysis or peritoneal dialysis.

5. PHARMACOLOGICAL PROPERTIES

5.1. Pharmacodynamic properties

Clindamycin is a lincosamide antibiotic with a primarily bacteriostatic action. Clindamycin binds to the 50S subunit of the bacterial ribosome and inhibit the early stages of protein synthesis.

Breakpoints:

The following MICs have been proposed to separate susceptible from intermediately susceptible and resistant organisms.

Susceptible: < 1.6 pg/ml Intermediate: > 1.6 - < 4.8 pg/ml Resistant:    > 4.8 pg/ml

The BSAC-recommended breakpoints for staphylococci are S: < 0.5 pg/ml;

R: > 1.0 pg/ml

Susceptibility:

The following table lists organisms according to their inherent susceptibility to clindamycin. The prevalence of acquired resistance may vary geographically and with time for selected species and local information on resistance is desirable, particularly when treating severe infections.

* Up to 50% of methicillin-susceptible S. aureus have been reported to be resistant to clindamycin in some areas. More than 90% of methicillin-resistant S.aureus (MRSA) are resistant to clindamycin and clindamycin should not be used while awaiting susceptibility test results if there is any suspicion of MRSA.

Resistance:

Resistance to clindamycin usually occurs via macrolide-lincosamide-streptograminB (MLSB) type of resistance, which may be constitutive or inducible. This is mediated by a variety of acquired genes that encode methylases targeted at the peptidyl transferase center of 23S ribosomal RNA. Methylation impedes binding of antibacterials to the ribosome and gives rise to cross-resistance to macrolides (all macrolides when constitutive), lincosamides (clindamycin and lincomycin) and type B streptogramins, but not to type A streptogramins.

5.2 Pharmacokinetic properties

Serum level studies with a 150mg oral dose of clindamycin in 24 normal adult volunteers showed that clindamycin was rapidly absorbed after oral administration. An average peak serum level of 2.5 mcg/mL was reached in 45 minutes: serum levels averaged 1.51 mcg/mL at 3 hours and 0.70 mcg/mL at 6 hours. Absorption of an oral dose is virtually complete (90%) and the concomitant administration of food does not appreciably modify the serum concentrations; serum levels have been uniform and predictable from person to person and dose to dose. Serum levels studies following multiple dose of clindamycin for up to 14 days show no evidence of accumulation or altered metabolism of drug. Serum half-life of clindamycin is increased slightly in patients with markedly reduced renal function. Haemodialysis and peritoneal dialysis are not effective in removing clindamycin from the serum. Concentrations of clindamycin in the serum increased linearly with increased dose. Serum levels exceed the MIC (minimum inhibitory concentrations) for most indicated organisms for at least six hours following administration of the usually recommended doses.

Clindamycin is widely distributed in body fluids and tissues (including bones). The average biological half-life is 2.4 hours. Approximately 10% of the bioactivity is excreted in the urine and 3.6% in the faeces; the remainder is excreted as bioinactive metabolites. Doses of up to 2 grams of clindamycin per day for 14 days have been well tolerated by healthy volunteers, except that the incidence of gastrointestinal side effects is greater with the higher doses. No significant levels of clindamycin are attained in the cerebrospinal fluid, even in the presence of inflamed meninges.

Pharmacokinetic studies in elderly volunteers (61-79 years) and younger adults (18-39 years) indicate that age alone does not alter clindamycin pharmakinetics (clearance, elimination half-life, volume of distribution, and area under the serum concentrations time curve) after IV administration of clindamycin phosphate. After oral administration of clindamycin, elimination half-life is increased to approximately 4.0 hours (range 3.4-5.1 h) in the elderly compared to 3.2 hours (range 2.1-4.2 h) in younger adults. The extent of absorption however, is not different between age groups and no dosage alteration is necessary for the elderly with normal hepatic function and normal (age-adjusted) renal function.

5.3 Preclinical safety data

There is no evidence of teratogenic effect in animals nor to date in man.

Carcinogenesis:

Long term studies in animals have not been performed with clindamycin to evaluate carcinogenic potential.

Mutagenesis:

Genotoxicity tests performed included a rat micronucleus test and an Ames Salmonella reversion test. Both tests were negative.

Impairment of Fertility:

Fertility studies in rats treated orally with up to 300 mg/kg/day (approximately

1.1 times the highest recommended adult human dose based on mg/m2) revealed no effects on fertility or mating ability.

6 PHARMACEUTICAL PARTICULARS

6.1    List of excipients

Capsule Contents

Lactose Monohydrate Maize Starch Magnesium Stearate Purified Talc

Capsule Body

Gelatin

Erythrosin (E127)

Indigo carmine FD&C Blue (E132)

Capsule Cap

Gelatin

Erythrosin (E127)

Indigo carmine FD&C Blue (E132)

Titanium dioxide (E171)

Printing ink contains: Shellac, propylene Glycol (E1520), titanium dioxide (E171) and ethanol.

6.2    Incompatibilities

Not applicable

6.3    Shelf life

3 years

6.4    Special precautions for storage

No special precautions for storage.

6.5    Nature and contents of container

Blister packs composed of PVC / PE / PVdC aluminium foil; pack sizes: 4, 8, 16, 20, 24, 30, 32, 40 and 100. Polypropylene containers with polyethylene tamper evident lids; pack size: 100. Not all pack sizes may be marketed.

Special precautions for disposal

No special requirements.

7    MARKETING AUTHORISATION HOLDER

Chanelle Medical,

Loughrea, Co. Galway,

Ireland

8    MARKETING AUTHORISATION NUMBER(S)

PL 13931/0061

9    DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

10/02/2013

10    DATE OF REVISION OF THE TEXT

12/05/2013