1. Name Of The Medicinal Product
Clindamycin 150mg Capsules
2. Qualitative And Quantitative Composition
Each capsule contains clindamycin hydrochloride equivalent to 150 mg clindamycin.
For a full list of excipients, see section 6.1.
3. Pharmaceutical Form
Capsules, hard.
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.
4.2 Posology And Method Of Administration
Adults: The usual dose is 150 - 450 mg every six hours, depending on the severity of the infection.
Elderly patients: Dosage requirements in elderly patients should not be influenced by age alone.
Children: The usual dose is 3 - 6 mg/kg every six hours depending on the severity of the infection (not to exceed the adult dose).
Children under one year of age and/or under 10 kg may require a lower dose.
Neonates (0-28 days), especially if premature, require special attention to dose reductions and/or extended dose intervals due to the prolonged elimination half-life.
Clindamycin capsules are not suitable for children who are unable to swallow them whole. The capsules do not provide exact mg/kg doses therefore it may be necessary to use the parenteral formulation in some cases.
Renal impairment
In severe renal impairment, peak plasma levels of clindamycin may be up to three times normal and the elimination half-life is prolonged. Dose reduction and/or an increased dose interval should be considered.
Hepatic impairment
In moderate and severe degrees of hepatic impairment, peak plasma levels of clindamycin are higher than normal and the elimination half-life is prolonged. Dose reduction and/or an increased dose interval should be considered.
Duration of treatment
The duration of treatment depends on the clinical response of the patient. Up to ten days therapy may be necessary to eradicate S. pyogenes from the upper respiratory tract.
However, due to the risk of severe disruption of the faecal flora and its consequences (see sections 4.4 and 4.8), treatment should be kept to the minimum. If prolonged therapy is considered to be unavoidable, the patient should be carefully monitored for adverse effects (see section 4.4).
Method of administration
Oral.
The absorption of clindamycin is not appreciably modified when taken with food.
The capsules should always be taken with a glass of water.
4.3 Contraindications
Clindamycin is contra-indicated in patients with a history of hypersensitivity to clindamycin or lincomycin, or to any of the inactive ingredients in the capsules.
Clindamycin should not be used in patients with existing diarrhoea.
4.4 Special Warnings And Precautions For Use
Clindamycin should only be used in the treatment of serious infections and when the possible benefit of using clindamycin is considered to outweigh the risk of antibiotic-associated diarrhoea or colitis, which may progress to pseudomembraneous colitis, peritonitis, shock, toxic megacolon and death. Pseudomembranous colitis can develop during, or two or three weeks following the administration of clindamycin. These intestinal complications are more likely to be severe and to become life-threatening 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 pseudomembraneous colitis. Stool culture for C.Difficile and/or assay for C.Difficile toxin may be helpful to diagnosis.
Caution should also be used when prescribing clindamycin for individuals with a history of gastro-intestinal disease, especially colitis.
If diarrhoea or colitis occurs during therapy, clindamycin should be discontinued immediately and appropriate diagnostic and therapeutic measures should be instituted. It should be noted that the onset of these intestinal complications of clindamycin treatment may be delayed until several weeks following the cessation of therapy. The most commonly implicated cause is an overgrowth of toxin-producing Clostridium difficile as a result of disruption of the bowel flora by clindamycin.
In addition to the risk of selecting for C. difficile in the intestinal tract, prolonged administration of clindamycin, as with any anti-infective, may result in other super-infections due to organisms resistant to clindamycin, mainly yeasts.
Periodic laboratory tests for renal and hepatic function should be carried out if treatment exceeds 10 days. Close monitoring is also recommended in patients with renal or hepatic insufficiency, and in neonates and infants.
The dosage may require reduction and/or an extended interval between doses in patients with renal or hepatic impairment and in neonates and infants (see section 4.2).
Care should be observed in the use of Clindamycin in atopic individuals.
Clindamycin can be an effective alternative for patients with an allergy to penicillin, because an allergic cross-reaction is not known or expected; however isolated cases of anaphylaxis have been observed after clindamycin treatment for patients with an existing penicillin allergy.
Clindamycin should not be given to patients with acute viral infection of the respiratory tract.
Since clindamycin does not penetrate the blood/brain barrier in adequate quantities, it should not be used in the treatment of meningitis.
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.
Clindamycin may adversely affect the reliability of contraceptives.
Avoid in porphyria.
4.5 Interaction With Other Medicinal Products And Other Forms Of Interaction
Muscle relaxants:
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.
Antibacterial agents:
Antagonism has been demonstrated between clindamycin and erythromycin in vitro. Because there is a possibility of a clinically significant interaction, clindamycin should not be given in combination with macrolides or streptogramin antibacterial agents.
Neostigmine and pyridostigmine
Clindamycin antagonises the effects of the above anticholinesterases.
Oestrogens:
Clindamycin possibly reduces the contraceptive effect of oestrogen. Though the risk is small, additional contraceptive precautions are recommended during concomitant use and for 7 days after discontinuing clindamycin.
Vaccines:
Oral typhoid vaccine is inactivated by concomitant administration of antibacterials. Thus, clindamycin should be avoided for 3 days before and after oral typhoid vaccination.
4.6 Pregnancy And Lactation
Clindamycin crosses the placenta. There are inadequate data regarding the safety of Clindamycin in pregnancy. Therefore, Clindamycin should only be administered to pregnant women if the potential benefit is considered to outweigh the possible risk to the fetus.
Clindamycin is excreted in human milk. If possible, mothers should stop breast-feeding during therapy. Diarrhoea, fungus infection of the mucous membranes or other serious adverse events could occur in the breast-fed infant, so that nursing might have to be discontinued The possibility of sensitivity should be borne in mind.
4.7 Effects On Ability To Drive And Use Machines
Clindamycin is not known to interfere with the ability to drive or operate machinery.
4.8 Undesirable Effects
Immune system disorders: Anaphylaxis and anaphylactoid reactions have been reported.
Gastro-intestinal disorders: 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 precautions for use). Diarrhoea occurs in up to 20% of patients; it may commence during treatment or may be delayed until some time after therapy has been completed. This may progress to colitis, including pseudomembraneous colitis, which may have life-threatening complications. Fatalities have been reported.
Blood and the lymphatic system disorders: Transient neutropenia (leucopenia), eosinophilla, agranulocytosis and thrombocytopenia have been reported. No direct aetiologic relationship to concurrent clindamycin therapy could be made in any of the foregoing.
Skin and subcutaneous tissue disorders: Maculopapular rash and urticaria have been observed during drug therapy. Generalised mild to moderate morbilliform-like skin rashes are the most frequently reported reactions. Rare instances of erythema multiforme, some resembling Stevens-Johnson syndrome have been associated with clindamycin. Pruritus, vaginitis and rare instances of exfoliative and vesiculobullous dermatitis have been reported. Serious cutaneous adverse reaction (SCAR) and rare cases of toxic epidermal necrolysis have been reported during post-marketing surveillance
Hepatobiliary disorders: 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 Disorders: Frequent cases of Dysgeusia have been observed upon systemic administration of clindamycin using injectables (IM or IV), capsules, or oral granulate solutions, which include a few (non-frequent) serious adverse events.
4.9 Overdose
In cases of overdosage no specific treatment is indicated.
Features: Antibiotics cause very little effect when taken in acute overdosage. There may be nausea and vomiting. Skin rashes may occur if the patient is already allergic to the antibiotic.
Management:The serum biological half-life of clindamycin is 2.4 hours. Clindamycin cannot readily be removed from the blood by dialysis or peritoneal dialysis.
Gastric decontamination is not necessary. Give oral fluids for severe vomiting and diarrhoea if required. Other measures should be taken as indicated by the patient's clinical condition. If an allergic reaction occurs therapy should be with the usual emergency treatments, including corticosteroids, adrenaline and antihistamines.
5. Pharmacological Properties
5.1 Pharmacodynamic Properties
General properties:
Clindamycin is a lincosamide antibiotic with a primarily bacteriostatic action. Clindamycin binds to the 50S subunit of the bacterial ribosome and inhibits the early stages of protein synthesis.
Breakpoints:
The following MICs have been proposed to separate susceptible from intermediately susceptible and resistant organisms.
Susceptible:
Intermediate:>1.6 -
Resistant:> 4.8 μg/ml
The BSAC-recommended breakpoints for staphylococci are S:
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.
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* 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
About 90% of a dose of clindamycin hydrochloride is absorbed from the gastro-intestinal tract; concentrations of 2 to 3 micrograms per ml occur within one hour after a 150 mg dose of clindamycin, with average concentrations of about 0.7 micrograms per ml after 6 hours. After doses of 300 and 600 mg peak plasma concentrations of 4 and 8 micrograms per ml, respectively, have been reported. Absorption is not significantly diminished by food in the stomach, but the rate of absorption may be reduced.
Clindamycin is widely distributed in body fluids and tissues including bone, but it does not reach the cerebrospinal fluid in significant concentrations. It diffuses across the placenta into the fetal circulation and appears in breast milk. High concentrations occur in bile. It accumulates in leucocytes and macrophages. Over 90% of clindamycin in the circulation is bound to plasma proteins. The half-life is 2 to 3 hours, although this may be prolonged in pre-term neonates and patients with severe renal impairment.
Clindamycin undergoes metabolism, presumably in the liver, to the active N-demethyl and sulphoxide metabolites and also some inactive metabolites. About 10% of the drug is excreted in the urine as active drug or metabolites and about 4% in the faeces; the remainder is excreted as inactive metabolites. Excretion is slow and takes place over several days. It is not effectively removed from the blood by dialysis.
5.3 Preclinical Safety Data
There is no evidence of teratogenic effect in animals nor to date in man.
6. Pharmaceutical Particulars
6.1 List Of Excipients
Lactose Monohydrate, Maize Starch, Magnesium Stearate, Purified Talc.
The capsule shells contain:
Gelatin, Azorubine E122, Indigo carmine E132.
Printing inks:
Titanium dioxide (E171), IMS 74 OP, Shellac, Purified water, N-Butyl alcohol, Soya lecithin.
6.2 Incompatibilities
None known.
6.3 Shelf Life
3 years.
6.4 Special Precautions For Storage
Do not store above 25°C. Store in the original package.
6.5 Nature And Contents Of Container
Packs of 24 and 100 capsules.
24's: Blister packs composed of white PVC / PE / PVdC 250.25.90 micron and plain 20 µm hard tempered aluminium foil, one side coated with Heatseal Laquer, reverse side primed for printing. Each blister contains 8 capsules.
100's: Polypropylene container with low density polyethylene tamper evident lids.
6.6 Special Precautions For Disposal And Other Handling
None stated.
7. Marketing Authorisation Holder
Sandoz Ltd
Woolmer Way
Bordon
Hants
GU35 9QE
United Kingdom
8. Marketing Authorisation Number(S)
PL 4416/0429
9. Date Of First Authorisation/Renewal Of The Authorisation
19 November 2002
10. Date Of Revision Of The Text
12/2009
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