Dalacin

Dalacin C 150 mg Capsules

Clindamycin 150 mg Capsules

Each capsule contains clindamycin hydrochloride equivalent to 150 mg clindamycin.

For the full list of excipients, see section 6.1

Capsule

Hard capsule (white/white) with markings of 'CLIN 150 and Pfizer' on cap and body.

Antibacterial. Serious infections caused by susceptible gram-positive organisms, staphylococci (both penicillinase- and non-penicillinase-producing), streptococci (except Streptococcus faecalis) and pneumococci. It is also indicated in serious infections caused by susceptible anaerobic pathogens.

Clindamycin does not penetrate the blood/brain barrier in therapeutically effective quantities.

Posology

Adults

Moderately severe infection, 150 - 300 mg every six hours; severe infection, 300 - 450 mg every six hours.

Elderly patients

The half-life, volume of distribution and clearance, and extent of absorption after administration of clindamycin hydrochloride 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

Clindamycin capsules should only be used for children who are able to swallow capsules.

Clindamycin should be dosed based on total body weight regardless of obesity.

Doses of 12-25 mg/kg/day six hourly depending on the severity of the infection.

The use of whole capsules may not be suitable to provide the exact mg/kg doses required for the treatment of children.

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 infection, treatment with this medicine should continue for at least 10 days to diminish the likelihood of subsequent rheumatic fever or glomerulonephritis.

Method of administration

Oral. Capsules should always be taken whole with a full glass of water and no less than 30 minutes before lying down to avoid the possibility of oesophageal irritation. Absorption of this medicine is not appreciably modified by the presence of food.

This medicine is contra-indicated in patients previously found to be sensitive to clindamycin, lincomycin or to any of the excipients listed in section 6.1.

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 should be discontinued, and appropriate therapy should be initiated (see sections 4.3 and 4.8).

This medicine 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 Clostridioides difficile) is the principal direct cause of antibiotic-associated colitis. These studies also indicate that this toxigenic clostridioides is usually sensitive in vitro to vancomycin. When 125 mg to 500 mg 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 Clostridioides difficile on selective media and assay of the stool specimen for the toxin(s) of C. difficile.

Clostridioides 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.

Due to the risk of oesophagitis and oesophageal ulcer, it is important to ensure compliance with administration guidance (see Sections 4.2 and 4.8)

Precautions

Caution should be used when prescribing this medicine to individuals with a history of gastro-intestinal disease, especially colitis.

Periodic liver and kidney function tests should be carried out during prolonged therapy. Such monitoring is also recommended in neonates and infants.

Acute kidney injury, including acute renal failure, has been reported infrequently. In patients suffering from pre-existing renal dysfunction or taking concomitant nephrotoxic drugs, monitoring of renal function should be considered (see section 4.8).

Prolonged administration of this medicine, as with any anti-infective, may result in super-infection due to organisms resistant to clindamycin.

Care should be observed in the use of this medicine in atopic individuals.

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.

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 metabolized 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 metabolized by these CYP enzymes are unlikely.

Pregnancy

There was evidence of maternal toxicity and embryo-foetal toxicity in animal studies (see section 5.3).

Clindamycin crosses the placenta in humans. After multiple doses, amniotic fluid concentrations were approximately 30% of maternal blood concentrations.

In clinical trials with pregnant women, the systemic administration of clindamycin during the second and third trimesters has not been associated with an increased frequency of congenital abnormalities. There are no adequate and well-controlled studies in pregnant women during the first trimester of pregnancy. Clindamycin should be used in pregnancy only if clearly needed.

Breast-feeding

Orally and parenterally administered clindamycin has been reported to appear in human breast milk in ranges from <0.5 to 3.8 µg/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. 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.

Fertility

Fertility studies in rats treated orally with clindamycin revealed no effects on fertility or mating ability.

Clindamycin has no or negligible influence on the ability to drive and use machines.

The table below lists the adverse reactions identified through clinical trial experience and post-marketing surveillance by system organ class and frequency. Adverse reactions identified from post-marketing experience are included in italics. The frequency grouping 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); and Not known (cannot be estimated from the available data). Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness.

* ADR identified post-marketing.

‡ ADRs apply only to oral formulations.

# See section 4.4.

≠ Possible occurrence of oesophagitis and oesophageal ulcer, particularly if taken in a lying position and/or with a small amount of water.

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 or search for MHRA Yellow Card in the Google Play or Apple App Store.

In cases of overdosage no specific treatment is indicated.

The serum biological half-life of clindamycin is 2.4 hours. Haemodialysis and peritoneal dialysis are not effective in removing clindamycin from the serum.

If an allergic adverse reaction occurs, therapy should be with the usual emergency treatments, including corticosteroids, adrenaline and antihistamines.

Pharmacotherapeutic group: Lincosamide antibiotics, ATC Code J01FF01.

Mode of action

Clindamycin is a lincosamide antibiotic with a primarily bacteriostatic action against gram-positive aerobes and a wide range of anaerobic bacteria. Lincosamides such as clindamycin bind to the 50S subunit of the bacterial ribosome similarly to macrolides such as erythromycin and inhibit protein synthesis. The action of clindamycin is predominantly bacteriostatic although high concentrations may be slowly bactericidal against sensitive strains. Although clindamycin phosphate is inactive in vitro, rapid in vivo hydrolysis converts this compound to the antibacterially active clindamycin.

Resistance

Resistance to clindamycin usually occurs via macrolide-lincosamide-streptogramin B (MLSB) type of resistance, which may be constitutive or inducible.

Breakpoints

The minimum inhibitory concentrations (MIC) breakpoints are as follows:

EUCAST

Staphylococci: sensitive ≤ 0.25 resistant > 0.5

Streptococci ABCG and pneumoniae: sensitive ≤ 0.5 resistant > 0.5

Gram positive anaerobes: sensitive ≤ 4 resistant > 4

Gram negative anaerobes: ≤ 4 resistant > 4

PK/PD relationship

Efficacy is related to the ratio of the area of the concentration-time curve of unbound antibiotic to the MIC for the pathogen (fAUC/MIC).

Susceptibility

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. As necessary, expert advice should be sought when local prevalence of resistance is such that the utility of the agent in at least some types of infections is questionable.

Species

Susceptible

Gram-positive aerobes

Staphylococcus aureus*

Staphylococcus epidermidis

Streptococcus pneumonia

Streptococcus pyogenes

Viridans streptococci

Anaerobes

Bacteriodes fragilis group

Prevotella formerly known as Bacteroides melaninogenicus

Bifidobacterium spp.

Clostridioides perfringens

Eubacterium spp.

Fusobacterium spp.

Peptococcus spp.

Peptostreptococcus spp.

Propionibacterium spp.

Veillonella spp.

Resistant

Clostridia spp.

Enterococci

Enterobacteriaceae

*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 it should not be used while awaiting susceptibility test results if there is any suspicion of MRSA.

General characteristics of active substance

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 csf in significant concentrations. It diffuses across the placenta into the foetal circulation and has been reported to appear 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. In vitro studies in human liver and intestinal microsomes indicated that clindamycin is predominantly oxidized by CYP3A4, with minor contribution from CYP3A5, to form clindamycin sulfoxide and a minor metabolite, N-desmethylclindamycin. 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 a dose 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.

Characteristics in patients

No special characteristics. See section 4.4 for further information.

Obese paediatric patients aged 2 to less than 18 years and obese adults aged 18 to 20 years

An analysis of pharmacokinetic data in obese paediatric patients aged 2 to less than 18 years and obese adults aged 18 to 20 years demonstrated that clindamycin clearance and volume of distribution normalized by total body weight are comparable regardless of obesity.

None stated.

Lactose monohydrate

Maize starch

Talc

Magnesium stearate

Capsule shell:

Gelatin

Titanium dioxide (E 171)

Printing ink:

Shellac

Soya lecithin

Dimeticone (Antifoam DC 1510)

Black Iron Oxide (E 172)

Not applicable.

Bottle: 60 months

Blister: 60 months

Do not store above 25°C.

This medicine is available in blister packs (aluminium foil/PVC) of 24 and 100 capsules and bottle packs (high density polyethylene or amber glass) of 24, 100 or 500 capsules.

Not all pack sizes may be marketed.

No special requirements.

Any unused medicinal product or waste material should be disposed of in accordance with local requirements.

Pfizer Limited

Ramsgate Road

Sandwich, Kent

CT13 9NJ

UK

PL 00057/0957

Date of first authorisation: 20 February 1989

Date of latest renewal: 22 May 2001

02/2024

Ref: DA 21_1