DALACIN T clindamycin 1% (10 mg/mL) (as phosphate) lotion. The chemical name for clindamycin phosphate is methyl 7-chloro-6,7,8-trideoxy-6-(1-methyl- trans-4-propyl-L-2-pyrrolidinecarboxamido)-1-thio-L-threo--D-galacto-octopyranoside-2-0- dihydrogen phosphate. It has a molecular weight of 504.96, and the molecular formula is C18H34C1N208PS. CAS Number: 24729-96-2 The structural formula is represented below:
CH3
N H HC Cl
CH3CH2CH2
C NH CH
O
H O HO H
OH H
H
SCH3
x H2O
H O
O P OH
. OH
Clindamycin phosphate is a water soluble ester of the semi-synthetic antibiotic produced by a 7(S)-chloro-substitution of the 7(R)-hydroxyl group of the parent antibiotic lincomycin. It is a white to off-white, odourless, hygroscopic, crystalline powder, found to be soluble in water, slightly soluble in dehydrated alcohol, sparingly soluble in dehydrated alcohol, sparingly soluble in acetone, and practically insoluble in chloroform and ether.
Clindamycin phosphate is a prodrug which is converted to its biologically active form, clindamycin, by phosphate hydrolysis. Cross resistance has been demonstrated between clindamycin and lincomycin. Antagonism has been demonstrated between clindamycin and erythromycin.
Following multiple topical applications of clindamycin phosphate lotion at a concentration equivalent to 10 mg clindamycin per mL in an isopropyl alcohol and water solution, very low levels of clindamycin are present in serum (Cmax 2.7 ng/mL) and about 0.23% of the dose is recovered in urine as clindamycin. Clindamycin in the serum is extensively metabolised. Approximately 10% of an oral dose is excreted as biologically active clindamycin in urine. Inactive metabolites are also excreted in urine. Clindamycin activity has been demonstrated in comedones from acne patients. The mean concentration of antibiotic activity in extracted comedones after application of clindamycin phosphate topical solution for 4 weeks was 597 g eq/g of comedonal material (range 0- 1490). Clindamycin in vitro inhibits all Propionibacterium acnes cultures tested (MICs 0.4 mcg/mL). Free fatty acids on the skin surface have been decreased from approximately 14% to 2% following application of a 1% clindamycin solution containing alcohol.
Five randomised, controlled clinical trials have been performed to evaluate the efficacy and safety of clindamycin phosphate topical lotion in patients with moderate to severe acne vulgaris (defined in the studies as 12 to 70 inflammatory pustules and no more than 6 cystic lesions on the face). All studies were either double-blind or investigator blind studies. Four studies compared the lotion with placebo and two of these studies also included clindamycin phosphate solution (an alcohol based formulation) as a comparator. Efficacy was based upon the reduction in numbers of acne lesions (including papules, pustules and open and closed comedones). A total of 362 patients were enrolled in these comparative studies, and 276 patients were evaluable for efficacy. Patients were evaluated at 3, 6, 9 and 12 weeks. A statistically significant change (p<0.05) in mean acne lesion scores from baseline favouring DALACIN T lotion (n = 47) over placebo (n = 48) was seen in one study. There was a trend for DALACIN T (n = 56) to produce a superior response to placebo (n = 55) in three other studies in the observation period. The adverse events recorded during treatment with the lotion in these studies were minor and unrelated to therapy.
DALACIN T topical lotion is indicated in the treatment of acne vulgaris, particularly forms in which comedones, papules and pustules predominate.
DALACIN T topical lotion is contraindicated in individuals with a history of hypersensitivity to preparations containing clindamycin or lincomycin. DALACIN T topical lotion is also contraindicated in individuals with a history of inflammatory bowel disease or a history of antibiotic-associated colitis.
Oral and parenteral clindamycin have been associated with severe diarrhoea and pseudomembraneous colitis which may result in patient death. Use of the clindamycin phosphate topical lotion (DALACIN T) results in absorption of the antibiotic from the skin surface. Diarrhoea, bloody diarrhoea and pseudomembraneous colitis have been reported with the use of topical and systemic clindamycin. It is important to consider the diagnosis of antibiotic-associated colitis in patients who develop diarrhoea or colitis associated with antibiotic use. Antibiotic-associated colitis (whether pseudomembraneous or not) appears to result from a toxin produced by Clostridium difficile in the alimentary tract. The severity of the colitis may range from mild watery diarrhoea to severe, persistent, life-threatening bloody diarrhoea. The diagnosis is usually made by recognition of the clinical symptoms. The symptoms may occur during therapy or up to several weeks after cessation of therapy. Additional confirmatory signs of antibiotic-associated colitis include pseudomembrane formation seen with colonoscopy, C. difficile culture from the stool, or assay of the stool for C. difficile toxin. Mild cases usually respond to drug discontinuation alone. However, in moderate to severe cases appropriate therapy with a suitable oral antibacterial agent effective against C. difficile should be considered. Fluids, electrolytes and protein replacement should be provided when indicated. Drugs which delay peristalsis, e.g. opiates and diphenoxylate with atropine (LOMOTIL(r)), may prolong and/or worsen the condition and should not be used. DALACIN T should be prescribed with caution in atopic individuals. For external use only. Avoid contact with sensitive surfaces such as the eyes, lips and mucous membranes. DALACIN T is not generally effective in severe (nodulocystic) acne. Use of topical clindamycin (DALACIN T) has been associated with the development of strains of Propioniibacterium acnes resistant to clindamycin in some patients. If there is evidence of the development of clinical resistence during treatment, consideration should be given to discontinuation of treatment with topical antibiotics.
Fertility was not impaired in rats given 300 mg/kg/day in the diet.
Category A
Reproductive studies have been performed in rats and mice using oral and parenteral doses of clindamycin phosphate up to 300 mg/kg/day and have revealed no evidence of harm to the fetus due to clindamycin. There are however, no adequate and well-controlled studies in pregnant women.
It is not known if clindamycin is excreted in human milk following the use of topically administered clindamycin phosphate. However, after oral or parenteral administration, clindamycin has been detected in human milk. Therefore, use of DALACIN T in lactating mothers is not recommended.
Long-term studies in animals to evaluate the carcinogenic potential of clindamycin phosphate have not been performed.
Clindamycin phosphate was negative in assays evaluating the potential to cause gene mutations and chromosomal damage
Clinical studies for Dalacin T did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects.
The effect of clindamycin on the ability to drive or operate machinery has not been systematically evaluated.
Clindamycin has been shown to have neuromuscular blocking properties that may enhance the actions of other neuromuscular blocking agents. Therefore it should be used with caution in patients receiving such agents. Antagonism has been demonstrated in between clindamycin and erythromycin in vitro. Because of possible clinical significance, these two drugs should not be administered concurrently.
The most common adverse reactions are abdominal pain, skin irritation, gastrointestinal disturbances, contact dermatitis, stinging of the eye, gram negative folliculitis, and skin oiliness.
Clinical Trial data
Table 1. Adverse events reported with DALACIN T topical lotion, solution and placebo in 5 USA comparative clinical studies. Included are all adverse events with an incidence of 1% or greater in any treatment group.1
| Number of Patients that experienced an adverse event | ||||||
| Lotion | Solution | Placebo | ||||
| Body system | (N=121) | (N=52) | (N=103) | |||
| n | % | n | % | n | % | |
| Total number of patients with adverse events | 29 | 24.0 | 16 | 30.8 | 31 | 30.1 |
| Body as a whole | ||||||
| Cold/flu | 6 | 5.0 | - | - | 3 | 2.9 |
| Urogenital system | ||||||
| Urinary tract infection | 3 | 2.5 | - | - | 1 | 1.0 |
| Digestive system | ||||||
| Diarrhoea | 5 | 4.1 | 5 | 9.6 | 5 | 4.9 |
| Vomiting | 1 | 0.8 | 1 | 1.9 | 1 | 1.0 |
| Dental procedure | 1 | 0.8 | 1 | 1.9 | - | - |
| Abdominal cramps, pain | - | - | 3 | 5.8 | 1 | 1.0 |
| Nausea | - | - | 1 | 1.9 | 2 | 1.9 |
| Reproductive disorders, female | ||||||
| Vaginitis | - | - | 1 | 1.9 | - | - |
| Respiratory | ||||||
| Sore throat/tonsillitis/ Laryngitis | 3 | 2.5 | - | - | 5 | 4.9 |
| Upper respiratory tract infection/cough/tracheitis | 1 | 0.8 | - | - | 3 | 2.9 |
| Sinusitis/congestion | - | - | 2 | 3.8 | - | - |
| Psychiatric Disorders | ||||||
| Anxiety | - | - | - | - | 2 | 1.9 |
| Musculo-skeletal system disorders | ||||||
| Fracture | 1 | 0.8 | 2 | 3.8 | - | - |
| Skin and appendages | ||||||
| Skin problems | 3 | 2.5 | 1 | 1.9 | 1 | 1.0 |
1. Note that a causal relationship to the study treatment has not been determined.
Post-marketing data
Table 2. The following adverse events have been reported since marketing of Dalacin T lotion in spontaneous post-marketing surveillance:1
| Body as a whole Rare Very rare | facial swelling, allergic reaction urticaria, hives, facial erythema, fungal infection, oedema, welts |
| Cardiovascular system Very rare | rapid heartbeat, chest tightness |
| Digestive system Common Rare Very rare | diarrhoea nausea, abdominal cramping acute colitis, abdominal pain, bloating, constipation, coloured tongue, dyspepsia, elevated liver enzymes, flatulence, gastrointestinal distress, gastrointestinal reflux, heartburn, pseudomembraneous colitis, rectal bleeding, sore throat, vomiting |
| Metabolic and nutritional system Very rare | weight loss |
| Haematologic system Very rare | leukopenia |
| Nervous system Very rare | headache, dizziness, facial numbness |
| Reproductive Very rare | fertility disorders |
| Respiratory system Very rare | epistaxis, voice loss |
| Skin and appendages Common Uncommon Rare Very rare Frequency not known | skin irritation burning sensation, rash, erythema itching, oily skin, contact dermatitis, eruption numbers blisters, dry skin, folliculitis, hair loss, papular pruritic skin rash, pruritis, skin inflammation, scaling, skin discolouration urticaria |
| Special senses Very rare | eye irritation, metallic taste |
| Urinary tract system Very rare | bladder infection |
| Infections and Infestations | Gram negative folliculitis. |
1. Note that no causal relationship to the treatment has been determined.
NB: Very Common ( 10%), Common (>=1% and <10%), Uncommon (>=0.1% and <1%), Rare (>=0.01% and
<0.1%) and Very Rare (<0.01%).
Apply a thin film of DALACIN T topical lotion twice daily to the affected area. DALACIN T topical lotion should be shaken immediately before using. The efficacy of DALACIN T lotion has not been demonstrated beyond 12 week's duration. Please refer to the Clinical Trials section.
Topically applied DALACIN T can be absorbed in sufficient amounts to produce systemic effects. In the event of overdosage, general symptomatic and supportive measures are indicated as required. Contact the Poisons Information Centre on 13 11 26 for advice on the management of an overdose.
DALACIN T topical lotion: White to off-white emulsion containing clindamycin phosphate equivalent to clindamycin 10 mg/mL, in an aqueous base containing glycerol, sodium lauroyl sarcosinate, stearic acid, glyceryl monostearate, mono- and di- glycerides, water - purified, potassium hydroxide, cetostearyl alcohol, isostearyl alcohol and methyl hydroxybenzoate. DALACIN T topical lotion is available in 60 mL bottles.
Store below 25deg C.
Pfizer Australia Pty Ltd 38-42 Wharf Road West Ryde NSW 2114 Australia
Schedule 4 (Prescription Only Medicine).
22 February 1999
04 October 2013 (r) Registered Trademark