Cleocin Hydrochloride

Cleocin Hydrochloride Topical Solution, Cleocin Hydrochloride Topical Gel and Cleocin Hydrochloride Topical Lotion are indicated in the treatment of acne vulgaris. In view of the potential for diarrhea, bloody diarrhea and pseudomembranous colitis, the physician should consider whether other agents are more appropriate (see CONTRAINDICATIONS, WARNINGS and ADVERSE REACTIONS).

Cleocin Hydrochloride^® (clindamycin phosphate pledget) is indicated in the treatment of moderate acne vulgaris.

Apply a thin film of Cleocin Hydrochloride Topical Solution, Cleocin Hydrochloride Topical Lotion, Cleocin Hydrochloride Topical Gel, or use a Cleocin Hydrochloride Topical Solution pledget for the application of Cleocin Hydrochloride twice daily to affected area. More than one pledget may be used. Each pledget should be used only once and then be discarded.

Lotion: Shake well immediately before using.

Pledget: Remove pledget from foil just before use. Do not use if the seal is broken. Discard after single use.

Keep all liquid dosage forms in containers tightly closed.

Cleocin Hydrochloride^® (clindamycin phosphate pledget) should be applied to areas affected by acne twice daily, in the morning and at night. The area to be treated should be washed first with a mild soap or cleanser, rinsed well and patted dry. A thin film of medication should be applied avoiding the eyes and mouth. Each pledget should be removed from the foil immediately before use, used only once and then discarded.

Hands should be washed after application. Cleocin Hydrochloride^® is not for oral, ophthalmic, or intravaginal use. Six to eight weeks of treatment may be required before a therapeutic effect is observed. Treatment should be discontinued if there has been no improvement or if the condition becomes worse.

Due to increased risk of antimicrobial resistance, the benefit of continuing treatment beyond 12 weeks should be evaluated.

Elderly

There are no specific recommendations for use in the elderly.

Renal Impairment

No dosage adjustment is necessary. As percutaneous absorption is low following topical application, renal impairment is not expected to result in systemic exposure of clinical significance.

Hepatic Impairment

No dosage adjustment is necessary. As percutaneous absorption is low following topical application, hepatic impairment is not expected to result in systemic exposure of clinical significance.

Cleocin Hydrochloride Topical Solution, Cleocin Hydrochloride Topical Gel and Cleocin Hydrochloride Topical Lotion are contraindicated in individuals with a history of hypersensitivity to preparations containing clindamycin or lincomycin, a history of regional enteritis or ulcerative colitis, or a history of antibiotic-associated colitis.

Cleocin Hydrochloride^® (clindamycin phosphate pledget) is contraindicated in individuals with a history of hypersensitivity to preparations containing clindamycin or lincomycin, or any other component of the preparation. Cleocin Hydrochloride^® is also contraindicated in patients with or with a history of regional enteritis or ulcerative colitis, or a history of antibioticassociated colitis (including pseudomembranous colitis).

WARNINGS

Orally and parenterally administered clindamycin has been associated with severe colitis which may result in patient death. Use of the topical formulation of clindamycin results in absorption of the antibiotic from the skin surface. Diarrhea, bloody diarrhea, and colitis (including pseudomembranous colitis) have been reported with the use of topical and systemic clindamycin.

Studies indicate a toxin(s) produced by clostridia is one primary cause of antibiotic-associated colitis. The colitis is usually characterized by severe persistent diarrhea and severe abdominal cramps and may be associated with the passage of blood and mucus. Endoscopic examination may reveal pseudomembranous colitis. Stool culture for Clostridium difficile and stool assay for C. difficile toxin may be helpful diagnostically.

When significant diarrhea occurs, the drug should be discontinued. Large bowel endoscopy should be considered to establish a definitive diagnosis in cases of severe diarrhea.

Antiperistaltic agents such as opiates and diphenoxylate with atropine may prolong and/or worsen the condition. Vancomycin has been found to be effective in the treatment of antibiotic-associated pseudomembranous colitis produced by Clostridium difficile. The usual adult dosage is 500 milligrams to 2 grams of vancomycin orally per day in three to four divided doses administered for 7 to 10 days. Cholestyramine or colestipol resins bind vancomycin in vitro. If both a resin and vancomycin are to be administered concurrently, it may be advisable to separate the time of administration of each drug.

Diarrhea, colitis, and pseudomembranous colitis have been observed to begin up to several weeks following cessation of oral and parenteral therapy with clindamycin.

PRECAUTIONS

General

Cleocin Hydrochloride Topical Solution contains an alcohol base which will cause burning and irritation of the eye. In the event of accidental contact with sensitive surfaces (eye, abraded skin, mucous membranes), bathe with copious amounts of cool tap water. The solution has an unpleasant taste and caution should be exercised when applying medication around the mouth.

Cleocin Hydrochloride should be prescribed with caution in atopic individuals.

Pregnancy

Teratogenic Effects

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 studies in pregnant women during the first trimester of pregnancy. Clindamycin should be used during the first trimester of pregnancy only if clearly needed.

Nursing Mothers

It is not known whether clindamycin is excreted in human milk following use of Cleocin Hydrochloride. However, orally and parenterally administered clindamycin has been reported to appear in breast milk. Clindamycin has the potential to cause adverse effects on the breastfed infant's gastrointestinal flora. 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. Monitor the infant for possible adverse effects on the gastrointestinal flora, such as diarrhea, candidiasis (thrush, diaper rash) or rarely, blood in the stool indicating possible antibiotic-associated colitis.

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.

Pediatric Use

Safety and effectiveness in pediatric patients under the age of 12 have not been established.

Geriatric Use

Clinical studies for Cleocin Hydrochloride did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients.

WARNINGS

Skin

FOR EXTERNAL USE ONLY. NOT FOR OPHTHALMIC USE. Cleocin Hydrochloride^® (clindamycin phosphate pledget) is known to be a mild irritant in humans and animals. Avoid contact with eyes, mouth, lips, other mucous membranes, or areas of broken skin. In the event of sensitization or severe local irritation from Cleocin Hydrochloride ^®, usage should be discontinued immediately, the solution carefully washed off, and appropriate therapy initiated.

The solution contains isopropyl alcohol. In the event of accidental contact with sensitive surfaces (eyes, abraded skin, mucous membranes), wash with large amounts of cool tap water.

Gastrointestinal

Clostridium Difficile-Associated Disease (CDAD)

Use of topical formulation of clindamycin results in absorption of clindamycin from the skin surface. Clostridium difficile-associated disease (CDAD), including pseudomembranous colitis has been reported with the use of topical, oral and parenteral administration of clindamycin (see ADVERSE REACTIONS). CDAD may range in severity from mild diarrhea to fatal colitis. It is important to consider this diagnosis in patients who present with diarrhea, or symptoms of colitis, pseudomembranous colitis, toxic mega colon, or perforation of colon subsequent to the administration of any antibacterial agent. CDAD has been reported to occur 2 months after the administration of antibacterial agents.

Treatment with antibacterial agents may alter the normal flora of the colon and may permit overgrowth of Clostridium difficile. Clostridium difficile produces toxins A and B, which contribute to the development of CDAD. CDAD may cause significant morbidity and mortality.

If the diagnosis of CDAD is suspected or confirmed, appropriate therapeutic measures should be initiated. Mild cases of CDAD usually respond to discontinuation of antibacterial agents not directed against Clostridium difficile. In moderate to severe cases, consideration should be given to management with fluids and electrolytes, protein supplementation, and treatment with an antibacterial agent clinically effective against Clostridium difficile. Surgical evaluation should be instituted as clinically indicated, as surgical intervention may be required in certain severe cases.

PRECAUTIONS

General

The use of preparations containing antibiotics such as clindamycin may be associated with overgrowth of antibiotic resistant microorganisms including those initially sensitive to the drug. The treatment of acne with topical antibiotics is associated with the development of antimicrobial resistance in Propionibacterium acnes as well as other bacteria (e.g. Staphylococcus aureus, Streptococcus pyogenes). The use of clindamycin may result in developing inducible resistance in these organisms. If this occurs, therapy should be discontinued and alternative acne therapy should be initiated. Resistance to clindamycin is often associated with resistance to erythromycin. It is therefore advisable to avoid concurrent use of the two agents either by topical or oral treatment.

Concomitant topical acne therapy should be used with caution since a possible cumulative irritancy effect may occur, especially with the use of peeling, desquamating or abrasive agents. If irritancy or dermatitis occurs, clindamycin should be discontinued.

Flammability

Due to the flammable nature of Cleocin Hydrochloride^®, patients should avoid smoking or being near an open flame during application and immediately after use.

Use In Pregnancy

The safety of Cleocin Hydrochloride^® during pregnancy has not been established. No adequate and well-controlled reproduction studies have been conducted with clindamycin in pregnant women. Systemic absorption of clindamycin following topical administration of clindamycin phosphate is less than 5%. Clindamycin readily crosses placental barrier. Animal reproduction studies have not been conducted with Cleocin Hydrochloride^® (clindamycin phosphate pledget) and it is not known whether Cleocin Hydrochloride^® can cause fetal harm when administered to pregnant women or can affect reproduction capacity. Cleocin Hydrochloride^® should not be administered to a pregnant woman unless the potential benefits to the mother clearly outweigh the possible risks to the fetus.

Reproduction studies have been performed in rats and mice using subcutaneous and oral doses of clindamycin ranging from 100 to 600 mg/kg/day and have revealed no evidence of impaired fertility or harm to the fetus due to clindamycin (see Toxicology). Conclusions from such animal studies may not always be predictive of the effects on human reproduction.

Use In Nursing Mothers

The safety of Cleocin Hydrochloride^® in nursing women has not been established. No adequate and well-controlled data in nursing women treated with clindamycin 1% (clindamycin as clindamycin phosphate) solution are available. It is not known if topically applied clindamycin is excreted in human milk following the topical use of Cleocin Hydrochloride^®. Orally and parenterally administered clindamycin is excreted in breast milk. Because of the potential for serious adverse reactions in nursing infants, a decision should be made whether to discontinue nursing or to discontinue the Cleocin Hydrochloride^® therapy to the mother. If used during lactation, clindamycin should not be applied to the breast area to avoid accidental ingestion by the infant.

Pediatric Use

Safety and effectiveness in the pediatric population under the age of 13 have not been established.

In 18 clinical studies of various formulations of Cleocin Hydrochloride 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

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.

Clinical Trial Adverse Drug Reactions

The safety was assessed in 150 acne vulgaris patients from a placebo-controlled study in which Cleocin Hydrochloride^® 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 Cleocin Hydrochloride^® Clinical Trial

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 Cleocin Hydrochloride^® Clinical Trial

Additional Adverse Drug Reactions Reported In Other Clindamycin Phosphate Clinical Trials

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 Reactions

Immune system disorders: allergic reaction.

Gastrointestinal disorders: bloody diarrhea, colitis (including pseudomembranous colitis) (See WARNINGS, Gastrointestinal, CDAD).

Topically applied Cleocin Hydrochloride can be absorbed in sufficient amounts to produce systemic effects (see WARNINGS).

For management of a suspected drug overdose, contact your regional Poison Control Centre.

Symptoms

Topically applied clindamycin phosphate from Cleocin Hydrochloride^® 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 Cleocin Hydrochloride^®, the use of the pledgets should be discontinued for several days before resuming therapy (see WARNINGS).

Cleocin Hydrochloride^® contains a significant quantity of isopropyl alcohol (44%). Systemic absorption of isopropyl alcohol should be considered a possibility in the event of accidental ingestion.

Treatment

No specific antidote is available. In the case of excessive application or accidental ingestion of Cleocin Hydrochloride^® 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).