No information provided.
Vaginally applied clindamycin phosphate vaginal cream 2% could be absorbed in sufficient amounts to produce systemic effects.
For management of a suspected drug overdose, contact your regional Poison Control Centre.
SymptomsTopically applied clindamycin phosphate from Antirobe® can be absorbed in sufficient amounts to produce systemic gastrointestinal side effects including abdominal pain, nausea, vomiting and diarhhea (see WARNINGS). In the case of excessive application or accidental ingestion of Antirobe®, the use of the pledgets should be discontinued for several days before resuming therapy (see WARNINGS).
Antirobe® contains a significant quantity of isopropyl alcohol (44%). Systemic absorption of isopropyl alcohol should be considered a possibility in the event of accidental ingestion.
TreatmentNo specific antidote is available. In the case of excessive application or accidental ingestion of Antirobe® the application site should be washed off with lukewarm water and the use of the pledgets should be discontinued for several days before resuming therapy (see WARNINGS).
Not applicable.
Blood and Lymphatic System Disorders: Transient neutropenia (leucopenia), eosinophilia, agranulocytosis and thrombocytopenia have been reported. No direct aetiologic relationship to concurrent clindamycin therapy could be made in any of the foregoing.
Immune System Disorders: A few cases of anaphylactoid reactions have been reported.
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 postmarketing surveillance.
Hepatobiliary disorders: Jaundice and abnormalities in liver function tests have been observed during clindamycin therapy.
)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.
General Disorders and Administration Site Conditions: Local irritation, pain, abscess formation have been observed in conjunction with IM injection. These reactions can be minimized by deep IM injection and avoiding the use of an indwelling catheter.
Thrombophlebitis has been reported with IV injection.
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.
Gastro-intestinal tract disorders: Oesophageal ulcers have been reported as serious adverse events during postmarketing surveillance, and oesophagitis with oral preparations, nausea, vomiting, abdominal pain and diarrhoea (See Section 4.4 Special Warnings and Precautions for use: Warnings).
Blood and lymphatic system disorders: Transient neutropenia (leucopenia), eosinophilia, agranulocytosis and thrombocytopenia have 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.
General disorders and administration site conditions: Local irritation, pain, abscess formation have been observed in conjunction with IM injection. These reactions can be minimised by deep IM injection and avoiding the use of an indwelling catheter.
Thrombophlebitis has been reported with IV injection.
Reporting of side effects
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.
In 18 clinical studies of various formulations of Antirobe using placebo vehicle and/or active comparator drugs as controls, patients experienced a number of treatment emergent adverse dermatologic events.
Number of Patients Reporting Events
| Treatment Emergent | Solution | Gel | Lotion |
| Adverse Event | n=553(%) | n=148(%) | n=160(%) |
| Burning | 62 (11) | 15 (10) | 17 (11) |
| Itching | 36 ( 7) | 15 (10) | 17 (11) |
| Burning/Itching | 60 (11) | # ( – ) | # ( – ) |
| Dryness | 105 (19) | 34 (23) | 29 (18) |
| Erythema | 86 (16) | 10 ( 7) | 22 (14) |
| Oiliness/Oily Skin | 8 ( 1) | 26 (18) | 12* (10) |
| Peeling | 61 (11) | # ( – ) | 11 ( 7) |
| # not recorded * of 126 subjects |
Orally and parenterally administered clindamycin has been associated with severe colitis which may end fatally.
Cases of diarrhea, bloody diarrhea and colitis (including pseudomembranous colitis) have been reported as adverse reactions in patients treated with oral and parenteral formulations of clindamycin and rarely with topical clindamycin (see WARNINGS).
Abdominal pain, gastrointestinal disturbances, gram-negative folliculitis, eye pain and contact dermatitis have also been reported in association with the use of topical formulations of clindamycin.
The table below lists the adverse reactions identified through clinical trial experience and post-marketing surveillance by system organ class and frequency. 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 (frequency cannot be estimated from the available data). Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness.
Adverse reactions possibly or probably related to Antirobe Topical lotion based on clinical trial experience and post-marketing surveillance:
| Very Common (>1/10) | Common (>1/100 to <1/10) | Frequency Not Known | |
| Infections and Infestations | Gram-negative folliculitis | ||
| Eye Disorders | Stinging of the eye | ||
| Gastrointestinal Disorders | Abdominal pain Gastrointestinal disturbances | ||
| Skin and Subcutaneous Tissue Disorders | Skin irritation Urticaria, Dry Skin | Skin Oiliness | Contact Dermatitis |
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
The table below lists the adverse reactions identified through clinical trial experience and post-marketing surveillance by system organ class and frequency. 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 (frequency cannot be estimated from the available data). Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness.
Adverse reactions possibly or probably related to Clindamycin Phosphate Topical lotion based on clinical trial experience and post-marketing surveillance:
| Very Common (>1/10) | Common (>1/100 to <1/10) | Frequency Not Known | |
| Infections and Infestations | Gram-negative folliculitis | ||
| Eye Disorders | Stinging of the eye | ||
| Gastrointestinal Disorders | Abdominal pain Gastrointestinal disturbances | ||
| Skin and Subcutaneous Tissue Disorders | Skin irritation Urticaria, Dry Skin | Skin Oiliness | Contact Dermatitis |
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
Clinical Trials ExperienceBecause clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice.
A total of 439 subjects with mild to moderate acne vulgaris were treated once daily for 12 weeks with Antirobe Foam.
The incidence of adverse reactions occurring in ≥1% of the subjects in clinical trials comparing Antirobe Foam and its vehicle is presented in Table 1.
Table 1: Adverse Reactions Occurring in ≥1% of Subjects
| Adverse Reactions | Number (%) of Subjects | |
| Antirobe Foam N = 439 | Vehicle Foam N = 154 | |
| Headache | 12 (3%) | 1 (1%) |
| Application site burning | 27 (6%) | 14 (9%) |
| Application site pruritus | 5 (1%) | 5 (3%) |
| Application site dryness | 4 (1%) | 5 (3%) |
| Application site reaction, not otherwise specified | 3 (1%) | 4 (3%) |
In a contact sensitization study, none of the 203 subjects developed evidence of allergic contact sensitization to Antirobe Foam.
Postmarketing ExperienceThe following adverse reactions have been identified during post approval use of Antirobe Foam: application site pain, application site erythema, diarrhea, urticaria, abdominal pain, hypersensitivity, rash, abdominal discomfort, nausea, seborrhea, application site rash, dizziness, pain of skin, colitis (including pseudomembranous colitis), and hemorrhagic diarrhea. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
Abdominal pain and gastrointestinal disturbances, as well as gram-negative folliculitis, have also been reported in association with the use of topical formulations of clindamycin. Orally and parenterally administered clindamycin have been associated with severe colitis, which may end fatally.
Clinical Study ExperienceBecause clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
The data described below reflect exposure to Antirobe (clindamycin phosphate) in 368 patients. Antirobe (clindamycin phosphate) was studied in three clinical studies: placebo-controlled (n=85), active-controlled (n=263), and single-arm (n=20). The population was female, aged 18 to 78, who were diagnosed with bacterial vaginosis. Patient demographics in the trials were 51% Caucasian, 36% Black, 10% Hispanic, and 3% Asian, other or unknown. All patients received 100 mg clindamycin phosphate cream intravaginally in a single dose.
Of the 368 women treated with a single dose of Antirobe (clindamycin phosphate) , 1.6% of the patients discontinued therapy due to adverse reactions. Adverse reactions occurred in 126 of 368 patients (34%) treated with Antirobe (clindamycin phosphate) and in 32 of 85 patients (38%) treated with placebo.
Adverse reactions occurring in ≥ 1% of patients receiving Antirobe (clindamycin phosphate) in the three clinical studies are shown in Table 1.
Table 1: Adverse Reactions Occurring in ≥ 1% of Antirobe (clindamycin phosphate) -Treated Patients and at a Higher Rate than Placebo-Treated Patients
| Adverse Event | Antirobe (clindamycin phosphate) N=368 n (%) | Placebo N=85 n (%) |
| Vaginosis fungal NOS* | 52 (14) | 7 (8) |
| Headache NOS | 10 (3) | 2 (2) |
| Back pain | 6 (2) | 1 (1) |
| Constipation | 4 (1) | 0 (0) |
| Urinary tract infection NOS | 4 (1) | 0 (0) |
| N = number of patients in intent-to-treat population n (%) = number and percentage of patients with reported adverse reaction NOS = not otherwise specified * The use of clindamycin may result in the overgrowth of non-susceptible fungal organisms in the vagina and may require antifungal treatment |
Other reactions reported by < 1% of those women treated with Antirobe (clindamycin phosphate) include:
Dermatologic: Pruritic rash
Gastrointestinal: Diarrhea, vomiting
General: Fatigue
Immune System: Hypersensitivity
Nervous System: Dizziness
Reproductive System: Dysfunctional uterine bleeding, dysmennorrhea, intermenstrual bleeding, pelvic pain, vaginal burning, vaginal irritation, vulvar erythema, vulvitis, vulvovaginal discomfort, vulvovaginal dryness, vulvovaginitis
Other Clindamycin FormulationsAntirobe (clindamycin phosphate) affords minimal peak serum levels and systemic exposure (AUCs) of clindamycin compared to an oral or intravenous dose of clindamycin. Data from well-controlled trials directly comparing clindamycin administered orally to clindamycin administered vaginally are not available.
The following additional adverse reactions and altered laboratory tests have been reported with the oral or parenteral use of clindamycin:
Gastrointestinal: Abdominal pain, esophagitis, nausea, Clostridium difficile-associated diarrhea
Hematopoietic: Transient neutropenia (leukopenia), eosinophilia, agranulocytosis, and thrombocytopenia have been reported. No direct etiologic relationship to concurrent clindamycin therapy could be made in any of these reports.
Hypersensitivity Reactions: Maculopapular rash, vesiculobullous rash, and urticaria have been observed during drug therapy. Generalized mild to moderate morbilliform-like skin rashes are the most frequently reported of all adverse reactions. Cases of erythema multiforme, some resembling Stevens-Johnson syndrome, have been associated with clindamycin. A few cases of anaphylactoid reactions have been reported.
Liver: Jaundice and abnormalities in liver function tests have been observed during clindamycin therapy.
Musculoskeletal: Cases of polyarthritis have been reported.
Renal: Although no direct relationship of clindamycin to renal damage has been established, renal dysfunction as evidenced by azotemia, oliguria, and/or proteinuria has been observed in rare instances.
Postmarketing ExperienceThe following adverse reactions have been identified during postapproval use of Antirobe (clindamycin phosphate). Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
Dermatologic: Rash
Gastrointestinal: Hematochezia
Reproductive System: Vaginal erythema, vulvovaginal pruritis, vaginal discharge, vaginal swelling, vaginal bleeding, vaginal pain
Clinical Trial Adverse Drug ReactionsThe safety was assessed in 150 acne vulgaris patients from a placebo-controlled study in which Antirobe® or placebo (vehicle) pledgets were applied twice daily over a period of 11 weeks. The number of patients with worsening scores of erythema, peeling and burning is presented in Table 1.
Table 1: Patients with worsening signs or symptoms of acne in a Antirobe® Clinical Trial
| Local Tolerance* | ||||||
| Signs and Symptoms | Treatment | Number of Patients with Worsening Score | ||||
| Week 2 n/N (%) | Week 5 n/N (%) | Week 8 n/N (%) | Week 11 n/N(%) | |||
| General disorders and administrative site conditions | Erythema | Antirobe® | 1/73 (1.4) | 2/72 (2.8) | 0 | 0 |
| Vehicle | 1/72 (1.4) | 2/70 (2.9) | 0 | 0 | ||
| Peeling | Antirobe® | 2/73 (2.7) | 2/72 (2.8) | 1/73 (1.4) | 0 | |
| Vehicle | 1/72 (1.4) | 3/70 (4.3) | 0 | 0 | ||
| Burning | Antirobe® | 4/73 (5.5) | 1/72 (1.4) | 2/73 (2.7) | 1/73 (1.4) | |
| Vehicle | 4/72 (5.6) | 4/70 (5.7) | 0 | 0 | ||
| * Change from Baseline of Signs and Symptoms| |
Number of patients reporting common (≥1%) treatment emergent adverse reactions are provided in Table 2.
Table 2: Most common drug related adverse reactions reported by ≥1% of patients in a Antirobe® Clinical Trial
| Adverse Drug Reaction | Antirobe® % N=75 | Vehicle % N=75 | |
| Nervous system disorders | Paresthesia | - | 1.3 |
| Headache | 1.3 | - | |
| Gastrointestinal disorders | Diarrhea | 1.3 | 1.3 |
| Nausea | 1.3 | - |
The following additional common adverse drug reactions (≥ 1%) have been reported in clinical trials involving other clindamycin phosphate formulations:
Skin and subcutaneous disorders: pruritus, rash, stinging, dryness, oiliness, small red bumps (including gram negative folliculitis pustules).
Immune system disorders: urticaria, whealing, swollen lips.
Gastrointestinal disorders: abdominal cramping.
Post-Market Adverse Drug ReactionsImmune system disorders: allergic reaction.
Gastrointestinal disorders: bloody diarrhea, colitis (including pseudomembranous colitis) (See WARNINGS, Gastrointestinal, CDAD).
Embryo fetal development studies using oral doses in rats and subcutaneous doses in rats and rabbits, revealed no evidence of developmental toxicity except at doses that produced maternal toxicity. In reproductive studies in rats there was no evidence of impaired fertility.
Clindamycin was not genotoxic when evaluated in the in vivo rat micronucleus test and the Ames test.
Long-term studies in animals to evaluate carcinogenic potential have not been performed with clindamycin.
Pharmacotherapeutic group: Lincocosamide antibiotics, ATC Code D10AF01.
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.
Clostridium 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.
Most Gram-negative aerobic bacteria, including the Enterobacteriaceae, are resistant to clindamycin. Clindamycin demonstrates cross-resistance with lincomycin. When tested by in vitro methods, some staphylococcal strains originally resistant to erythromycin rapidly developed resistance to clindamycin. The mechanisms for resistance are the same as for erythromycin, namely methylation of the ribosomal binding site, chromosomal mutation of the ribosomal protein and in a few staphylococcal isolates enzymatic inactivation by a plasmid-mediated adenyltransferase.
Pharmacotherapeutic group: Lincosamides
ATC Code: J01 FF01
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 the early stages of protein synthesis. The action of clindamycin is predominantly bacteriostatic although high concentrations may be slowly bactericidal against sensitive strains.
Mechanism of resistance
Resistance to clindamycin usually occurs via macrolide-lincosamide-streptogramin B (MLSB) type of resistance, which may be constitutive or inducible. Clindamycin demonstrates cross-resistance with lincomycin. When tested by in vitro methods, some staphylococcal strains originally resistant to erythromycin rapidly developed resistance to clindamycin. The mechanisms for resistance are the same as for erythromycin, namely methylation of the ribosome binding site, chromosomal mutation of the ribosomal protein and in a few staphylococcal isolates emzymatic inactivation by a plasmid-mediated adenyltransferase.
Breakpoints
The minimum inhibitory concentrations (MIC) breakpoints are as follows:
Eucast
Staphylococci: sensitive ≤ 0.5 resistant > 0.5
Streptococci ABCG and pneumoniae: sensitive ≤ 0.5 resistant > 0.5
Gram positive anaerobes: sensitive ≤ 4 resistant > 4
Gram negative anaerobes: sensitive ≤ 4 resistant > 4
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 pneumoniae Streptococcus pyogenes Streptococcus viridans Anaerobes Bacteriodes fragilis group Bacteroides melaninogenicus Bifidobacterium spp. Clostridium 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.
Pharmacotherapeutic group: Anti-infectives for treatment of acne, ATC Code: DA10AF01.
Microbiology
Clindamycin is a lincosamide antibiotic that inhibits bacterial protein synthesis. It binds to the 50S ribosomal subunit and affects both ribosome assembly and the translation process. Although Antirobe is inactive in vitro, rapid in vivo hydrolysis converts this compound to the antibacterially active clindamycin.
Clindamycin has been shown to have in vitro activity against isolates of the following organisms:
Anaerobic gram positive nonsporeforming bacilli, including:
- Propionibacterium acnes.
EUCAST has established susceptibility interpretive criteria for gram-negative and gram-positive anaerobes (with the exception of C. difficile): susceptible, ≤4 mg/L; resistant, >4 mg/L.
In a U.S. surveillance study, clindamycin MICs were ≤4 mg/L for 97% of P. acnes isolates tested.
In some bacterial species, cross resistance has been demonstrated in vitro among lincosamides, macrolides, and streptogramins B.
Clinical efficacy and safety
P. acnes produces an extracellular lipase that hydrolyses sebum triglycerides to glycerol, used by the organism as a growth substrate, and free fatty acids, which have pro-inflammatory and comedogenic properties. A double-blind study had been conducted to examine the effect of topical 1% clindamycin hydrochloride hydrate in a hydroalcoholic vehicle as compared to the effect of the vehicle alone. Fourteen patients applied clindamycin or vehicle alone twice daily for eight weeks. Free fatty acid surface lipid percentages, quantitative bacterial counts, and clinical response were assessed every two weeks. A significant reduction (88%) in the percentage of free fatty acids in the surface lipids was seen in the clindamycin-treated group and not in the vehicle-treated group. Free fatty acids on the skin surface have been decreased from approximately 14% to 2% following application of clindamycin solution in a hydroalcoholic base to 9 patients (average age 22.3 years) with acne vulgaris. There was no significant change in the surface microflora. Despite the short duration of treatment, objective clinical improvement was seen in three of nine treated patients, while none was observed in the placebo-treated patients.
Pharmacotherapeutic group: Anti-infectives for treatment of acne, ATC Code: DA10AF01.
Microbiology
Clindamycin is a lincosamide antibiotic that inhibits bacterial protein synthesis. It binds to the 50S ribosomal subunit and affects both ribosome assembly and the translation process. Although clindamycin phosphate is inactive in vitro, rapid in vivo hydrolysis converts this compound to the antibacterially active clindamycin.
Clindamycin has been shown to have in vitro activity against isolates of the following organisms:
Anaerobic gram positive nonsporeforming bacilli, including:
- Propionibacterium acnes.
EUCAST has established susceptibility interpretive criteria for gram-negative and gram-positive anaerobes (with the exception of C. difficile): susceptible, ≤4 mg/L; resistant, >4 mg/L.
In a U.S. surveillance study, clindamycin MICs were ≤4 mg/L for 97% of P. acnes isolates tested.
In some bacterial species, cross resistance has been demonstrated in vitro among lincosamides, macrolides, and streptogramins B.
Clinical efficacy and safety
P. acnes produces an extracellular lipase that hydrolyses sebum triglycerides to glycerol, used by the organism as a growth substrate, and free fatty acids, which have pro-inflammatory and comedogenic properties. A double-blind study had been conducted to examine the effect of topical 1% clindamycin hydrochloride hydrate in a hydroalcoholic vehicle as compared to the effect of the vehicle alone. Fourteen patients applied clindamycin or vehicle alone twice daily for eight weeks. Free fatty acid surface lipid percentages, quantitative bacterial counts, and clinical response were assessed every two weeks. A significant reduction (88%) in the percentage of free fatty acids in the surface lipids was seen in the clindamycin-treated group and not in the vehicle-treated group. Free fatty acids on the skin surface have been decreased from approximately 14% to 2% following application of clindamycin solution in a hydroalcoholic base to 9 patients (average age 22.3 years) with acne vulgaris. There was no significant change in the surface microflora. Despite the short duration of treatment, objective clinical improvement was seen in three of nine treated patients, while none was observed in the placebo-treated patients.
Pharmacodynamics of Antirobe Foam is unknown.
General characteristics of active substance
Following parenteral administration, the biologically inactive clindamycin phosphate is hydrolysed to clindamycin. When the equivalent of 300 mg of clindamycin is injected intramuscularly, a mean peak plasma concentration of 6 microgram/ml is achieved within three hours; 600 mg gives a peak concentration of 9 microgram/ml. In children, peak concentration may be reached within one hour. When the same doses are infused intravenously, peak concentrations of 7 and 10 micrograms per ml respectively are achieved by the end of infusion.
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 foetal 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, 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.
Characteristics in patients
"Special warnings and special precautions for use" for further information.General characteristics of active substance
Following parenteral administration, the biologically inactive clindamycin phosphate is hydrolysed to clindamycin. When the equivalent of 300mg of clindamycin is injected intramuscularly, a mean peak plasma concentration of 6 microgram/ml is achieved within three hours; 600mg gives a peak concentration of 9 microgram/ml. In children, peak concentration may be reached within one hour. When the same doses are infused intravenously, peak concentrations of 7 and 10 micrograms per ml respectively are achieved by the end of infusion.
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 foetal 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, 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.
Characteristics in patients
No special characteristics."Special warnings and special precautions for use" for further information.
Following multiple topical applications of Antirobe 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 the serum (0-3 ng/mL) and less than 0.2% of the dose is recovered in urine as clindamycin.
Clindamycin concentrations has been demonstrated in comedones from acne patients. The mean (±SD) concentration of clindamycin in extracted comedones after application of clindamycin topical solution for 4 weeks was 0.60±0.11 mcg.
Older people
Clinical studies for topical clindamycin did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects.
Following multiple topical applications of clindamycin phosphate 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 the serum (0-3 ng/mL) and less than 0.2% of the dose is recovered in urine as clindamycin.
Clindamycin concentrations has been demonstrated in comedones from acne patients. The mean (±SD) concentration of clindamycin in extracted comedones after application of clindamycin topical solution for 4 weeks was 0.60±0.11 mcg.
Older people
Clinical studies for topical clindamycin did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects.
In an open label, parallel group study in 24 subjects with acne vulgaris, 12 subjects (3 male and 9 female) applied 4 grams of Antirobe Foam once-daily for five days, and 12 subjects (7 male and 5 female) applied 4 grams of a clindamycin gel, 1%, once daily for five days. On Day 5, the mean Cmax and AUC(0-12) were 23% and 9% lower, respectively, for Antirobe Foam than for the clindamycin gel, 1%.
Following multiple applications of Antirobe Foam, less than 0.024% of the total dose was excreted unchanged in the urine over 12 hours on Day 5.
Following a single intravaginal application of Antirobe (clindamycin phosphate) cream to 20 healthy women, the mean (range) AUC0-inf and Cmax estimates were 175 (38.6 to 541) ng/mL·hr and 6.6 (0.8 to 39) ng/mL, respectively. The mean Cmax of clindamycin for Antirobe (clindamycin phosphate) was approximately 0.3%, 0.1%, and 7.6% of that observed after the administration of a 150 mg Cleocin oral capsule (2.5 mcg/mL), a 600 mg Cleocin intravenous injection (10.9 mcg/mL), and a single dose of 100 mg of Cleocin Vaginal Cream (86.5 ng/mL), respectively. The peak serum concentration of clindamycin was attained approximately 20 hours post dosing for Antirobe (clindamycin phosphate).
The effect of clindamycin on the ability to drive or operate machinery has not been systematically evaluated.
No special requirements.
