Acne ABC Gel

Overview of Acne ABC Gel

Dosage Strength of Acne ABC Gel

Adapalene / Benzoyl Peroxide / Clindamycin 0.1/2.5/1% 30 mL Pump

General Information

Adapalene

Adapalene is a topical retinoid-like drug for the treatment of mild to moderate acne vulgaris. Unlike tretinoin, adapalene is a naphtholic acid derivative and causes less skin irritation. Adapalene is more effective than tretinoin gel (0.025%) in the treatment of acne vulgaris.1 Adapalene is commercially available as a cream, lotion, or gel and is reported to be cosmetically appealing to most patients, according to clinical trial data. The drug was approved by the FDA June 3, 1996.

Benzoyl Peroxide

Benzoyl peroxide is a topical acne product. Benzoyl peroxide exhibits antibacterial activity. It also has drying actions, sebostatic effects, and causes mild skin desquamation. Benzoyl peroxide improves both inflammatory and non-inflammatory acne lesions. Benzoyl peroxide is effective as monotherapy in mild cases of acne and is used as an adjuvant in moderate to severe cases of acne. A study 2 in the United Kingdom showed that an OTC 5% benzoyl peroxide topical formulation (Panoxyl Aquagel) was as effective as topical benzoyl peroxide/erythromycin combination and the oral tetracyclines minocycline and oxytetracycline for treatment of mild to moderate acne. Topical benzoyl peroxide and benzoyl peroxide/erythromycin combinations were not associated with propionibacterial antibiotic resistance which occurs with the tetracyclines. Benzoyl peroxide has also been used in the off-label treatment of decubitus ulcers. Benzoyl peroxide is available as prescription and non-prescription products and is available in combination with erythromycin, hydrocortisone, and sulfur (see separate monographs for each of the combination products). The FDA has revised labeling requirements for all non-prescription (over-the-counter) topical acne products, including benzoyl peroxide, to ensure consistency with the standardized 'Drug Facts' formatting. Benzoyl peroxide is a generally recognized as safe and effective (GRASE) active ingredient in over-the-counter topical acne drug products.

Clindamycin Phosphate

Clindamycin is an antibiotic structurally similar to lincomycin, from which it is derived. Clindamycin traditionally has been considered an effective anti-anaerobic antibiotic, but it recently has been shown to be effective in combination with pyrimethamine in treating toxoplasmic encephalitis in patients with AIDS 3. Clindamycin was approved by the FDA in 1970 and is marketed as the hydrochloride salt for oral administration and as the phosphate salt for parenteral, topical or vaginal administration. The FDA approved a single-dose vaginal cream (Clindesse™) for bacterial vaginosis in November 2004. The FDA approved Evoclin™, an aerosol topical foam containing 1% clindamycin, for the treatment of acne vulgaris in December 2004.

Mechanism of Action

Adapalene

Adapalene binds to specific retinoic acid nuclear receptors but does not bind to the cytosolic receptor protein. Adapalene reportedly penetrates deeply into the hair follicle. As a result of its actions, adapalene modulates cell differentiation and keratinization. Adapalene also possesses potent antiinflammatory and comedolytic properties.

Benzoyl Peroxide

Benzoyl peroxide exhibits antimicrobial effects against Propionibacterium acnes, which is the predominant organism in sebaceous follicles and comedones. The antibacterial effects of benzoyl peroxide are due to the release of free-radical oxygen species, which are capable of oxidizing bacterial proteins. Resolution of acne usually occurs within 4—6 weeks of initiation of treatment. Resolution coincides with a reduction in levels of P. acnes, lipids, and free fatty acids in the skin follicle. Benzoyl peroxide also demonstrates keratolytic activity, which produces drying and desquamative actions that contribute to its efficacy in comedone treatment. In the treatment of decubitus ulcers, benzoyl peroxide stimulates epithelial cell proliferation and the production of granulation tissue.

Clindamycin Phosphate

Clindamycin binds to the 23S RNA of the 50S ribosomal subunit of the bacteria, which inhibits protein synthesis. As with lincomycin, antibacterial activity results from inhibition of protein synthesis. Clindamycin is bacteriostatic. The mechanism of action of clindamycin in treating acne vulgaris is unknown.45

The susceptibility interpretive criteria for clindamycin are delineated by pathogen. The MICs are defined for beta-hemolytic streptococci, S. viridans group, and S. pneumoniae as susceptible at 0.25 mcg/mL or less, intermediate at 0.5 mcg/mL, and resistant at 1 mcg/mL or more. The MICs are defined for Staphylococcus sp. as susceptible at 0.5 mcg/mL or less, intermediate at 1 to 2 mcg/mL, and resistant at 4 mcg/mL or more. The MICs are defined for anaerobes as susceptible at 2 mcg/mL or less, intermediate at 4 mcg/mL, and resistant at 8 mcg/mL or more.67

Resistance to clindamycin is most often caused by modification of specific bases of the 23S ribosomal RNA. Cross-resistance between clindamycin and lincomycin is complete. Due to overlapping binding sites, cross-resistance is sometimes observed among lincosamides, macrolides, and streptogramin B. Clindamycin inducible resistance has been identified in macrolide-resistant organisms; therefore, macrolide-resistant and clindamycin-susceptible strains should be screened for inducible clindamycin resistance using the D-zone test.458[46693]7

Clindamycin is a well-known cause of pseudomembranous colitis, possibly due to overgrowth of Clostridia difficile, and 10% to 20% of strains of Clostridia perfringens can be resistant to clindamycin.4 Increased resistance has also been seen in some strains of B. fragilis.9 One study reported marked antibiotic resistance after treatment of bacterial vaginosis with clindamycin; resistance persisted for up to 90 days after treatment.10

Pharmacokinetics

Adapalene

Adapalene is applied topically to the skin.  The distribution and metabolism of absorbed adapalene is unknown.  Excretion appears to be primarily by the biliary route.   

Route-Specific Pharmacokinetics 

Topical Route 

Following application, absorption through human skin is low. Trace amounts (< 0.25 ng/mL) of the parent compound have been found in the plasma of acne patients after chronic topical application in controlled clinical trials.

Benzoyl Peroxide

Benzoyl peroxide is applied topically. In the skin, benzoyl peroxide is metabolized to benzoic acid. Approximately 5% of the benzoic acid is systemically absorbed and excreted in the urine.

After topical application to the skin, benzoyl peroxide is absorbed through the epidermis. Approximately 5% of the benzoic acid is systemically absorbed.

Clindamycin Phosphate

Clindamycin is administered by the oral, parenteral, topical, and vaginal routes. Oral or parenteral doses are widely distributed into most body tissues, with high concentrations in bone, bile, and urine. Cerebrospinal fluid (CSF) concentrations are poor, and clindamycin is not indicated for the treatment of meningitis. It is, however, useful in treating toxoplasma encephalitis.11 It is highly protein bound (80% to 95%), primarily to alpha1-acid glycoprotein.12 Clindamycin is metabolized to 2 bioactive metabolites, clindamycin sulfoxide and N-desmethylclindamycin, and various inactive metabolites. After oral dosage, only about 10% is excreted in the urine as active drug and metabolites, and about 3.6% in the feces. The remainder is excreted as inactive metabolites. The plasma half-life in adults with normal renal function is 2 to 3 hours.13

Affected cytochrome P450 isoenzymes and drug transporters: CYP3A4, CYP3A5

Clindamycin is metabolized primarily by CYP3A4, and to a lesser extent by CYP3A5. Drugs that are inhibitors or inducers of these enzymes may interact with clindamycin. In vitro studies have shown that clindamycin does not inhibit CYP1A2, CYP2C9, CYP2C19, CYP2E1, or CYP2D6, and only moderately inhibits CYP3A4.13

Topical Route Some systemic absorption does occur after topical administration, depending on the surface area covered. Clindamycin phosphate appears to be less well absorbed through the skin than is the hydrochloride. Topical preparations are marketed as clindamycin phosphate.5

Contraindications/Precautions

Adapalene

According to the manufacturer, adapalene should only be used during pregnancy if the potential benefit justifies the potential risk to the fetus. There are no adequate and well controlled studies in pregnant women. Further, during clinical trials women of childbearing potential initiated treatment only after negative pregnancy tests were obtained. However, 2 women receiving the topical lotion and 6 women receiving the topical gel became pregnant during adapalene clinical trials. Pregnancy outcomes for these 8 women were: 3 healthy full term deliveries, 2 premature deliveries, 2 elective pregnancy terminations, and 1 lost to follow-up. In animal studies, teratogenic changes were observed in rats and rabbits receiving oral doses of more than 25 mg adapalene/kg/day representing 123- and 246-times the maximum recommended human dose. These teratogenic changes included cleft palate, microphthalmia, exophthalmos, encephalocele, skeletal abnormalities, umbilical hernia, and kidney abnormalities.1415 

According to the manufacturer, it is not known whether adapalene distributes into breast milk. Because adapalene is poorly absorbed through human intact skin, the amount of drug excreted into the breast milk is expected to be low 16, and therefore risk to the nursing infant is also expected to be low.17 Do not apply near the nipple area, and be careful to avoid direct contact between the infant and the treated area. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. If a breast-feeding infant experiences an adverse effect related to a maternally administered drug, healthcare providers are encouraged to report the adverse effect to the FDA. 

Topical adapalene is for external use only. Avoid contact with the eyes, lips, angles of the nose and other mucous membranes. Apply only to affected areas; accidental exposure to unaffected skin may cause irritation. Do not apply to skin that is cut or is affected with seborrheic dermatitis, eczema, a skin abrasion, or sunburn. As with other retinoids, avoid the use of waxing as a depilatory method. Avoid the use of other potentially irritating topical products. If sun exposure cannot be avoided during topical adapalene therapy, sunscreen products and physical sun blocks (protective clothing, hats) are recommended for protection of treated areas.18 Sunlight (UV) exposure may potentiate the effects of adapalene. Patients who may have considerable sun exposure due to their occupation and those patients with inherent sensitivity to sunlight should exercise particular caution when using topical adapalene. Weather extremes, such as wind or cold, also may be irritating to patients receiving adapalene. 

No information is available on the relationship of age to the effects of adapalene in pediatric patients. Safety and efficacy in children less than 12 years of age have not been established. 

Clinical studies of adapalene were mainly conducted in patients aged 12 to 30 years, and did not include a sufficient number of geriatric patients (>= 65 years) to determine any differences in response as compared to younger patients. Other reported clinical experience has not identified differences in responses between elderly and younger patients.

Benzoyl Peroxide

Benzoyl peroxide is contraindicated in individuals having known sensitivity to benzoyl peroxide or any other listed ingredients.19

Use of benzoyl peroxide products in patients with skin disease such as dermatitis, seborrhea, and eczema or with skin abrasion or inflammation, denuded skin, including sunburn or windburn, may increase the risk of skin irritation. The benzoyl peroxide product should be discontinued until skin sensitivity resolves. Patients should limit their sunlight (UV) exposure and use sunscreen while using benzoyl peroxide products to decrease the risk for skin irritation.

Avoid accidental exposure of benzoyl peroxide products to the eyes, lips, mucus membranes and inflamed or raw skin due to severe irritation. If unintended mucus membrane or ocular exposure occurs, thoroughly rinse affected areas with water.

The safety and efficacy of benzoyl peroxide products have not been established in children.

Benzoyl peroxide products are considered FDA pregnancy risk category C agents. It is not known if benzoyl peroxide causes fetal harm or can affect reproductive capacity. However, topical application is generally considered safe during pregnancy.

It is not known if benzoyl peroxide is excreted in breast milk. However, very little benzoic acid is absorbed systemically with topical use of benzoyl peroxide; therefore, minimal risk to the infant would be expected.20 Only water-miscible cream products should be applied to the breast because ointments may expose the infant to high levels of mineral paraffins.21 Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. If a breast-feeding infant experiences an adverse effect related to a maternally administered drug, healthcare providers are encouraged to report the adverse effect to the FDA.

Clindamycin Phosphate

Clindamycin is contraindicated in patients with known clindamycin hypersensitivity. Because some cross-sensitivity may occur, lincomycin hypersensitivity is also a contraindication for clindamycin use. Use the drug with caution in patients with asthma or a significant history of allergy (atopy). Some oral capsule preparations contain tartrazine dye and can precipitate bronchial asthma or other allergic reactions in patients with tartrazine dye hypersensitivity.13 Serious rash events, including toxic epidermal necrolysis (TEN), Stevens-Johnson syndrome (SJS), and drug reaction with eosinophilia and systemic symptoms (DRESS), some with fatal outcomes, have been reported with systemic clindamycin therapy. Clindamycin should be permanently discontinued if severe skin or hypersensitivity reactions occur.413

Clindamycin can cause the overgrowth of nonsusceptible bacteria resulting in superinfection, particularly yeast and fungal infection. Should superinfection occur, take appropriate measures.13

Clindamycin has been associated with severe colitis, more so than some other antimicrobials. Topical (topical solution, gel, and lotion) and vaginal (cream, ovules) preparations of clindamycin are contraindicated in patients with a history of regional enteritis or ulcerative colitis, or a history of pseudomembranous colitis; other product preparations warn against use in patients with pseudomembranous colitis.51322 Almost all antibacterial agents have been associated with pseudomembranous colitis (antibiotic-associated colitis), which may range in severity from mild to life-threatening. In the colon, overgrowth of Clostridia may occur when normal flora is altered subsequent to antibacterial administration. The toxin produced by Clostridium difficile is a primary cause of pseudomembranous colitis. C. difficile carriage rates average 37% for neonatal patients, 30% for infants 1 to 6 months of age, and 14% for infants 6 to 12 months of age; however, nursing significantly reduces carriage rates.23 By 3 years of age, carriage rates are similar to those of non-hospitalized adults (3% or less). Consider pseudomembranous colitis as a potential diagnosis in patients presenting with diarrhea after antibacterial administration. Systemic antibiotics should be prescribed with caution to patients with inflammatory bowel disease such as ulcerative colitis or other GI disease. If diarrhea develops during therapy, discontinue the drug. After a diagnosis of pseudomembranous colitis, institute therapeutic measures. Practitioners should be aware that antibiotic-associated colitis can occur over 2 months or more after discontinuation of systemic antibiotic therapy; a careful medical history should be taken.13

Clindamycin topical solution contains an alcohol base that will cause burning and irritation of the eye; therefore, avoid ocular exposure. In the event of accidental contact with sensitive surfaces (eye, abraded skin, mucous membranes), bathe with water.5

Clindamycin may be used to treat certain sexually transmitted diseases (STD). All patients with a diagnosed or suspected STD should be tested for other STDs, which may include HIV, syphilis, chlamydia, and gonorrhea, at the time of diagnosis. Initiate appropriate therapy and perform follow-up testing as recommended based upon sexually transmitted disease diagnosis.24

Reported clinical experience indicates that antibiotic-associated colitis and diarrhea (due to Clostridium difficile) seen in association with most systemic antibiotics, such as clindamycin, occur more frequently in the geriatric adult (60 years or older) and may be more severe. These patients should be carefully monitored for the development of diarrhea.413 The federal Omnibus Budget Reconciliation Act (OBRA) regulates medication use in residents (e.g., geriatric adults) of long-term care facilities (LTCFs). According to OBRA, use of antibiotics should be limited to confirmed or suspected bacterial infections. Antibiotics are non-selective and may result in the eradication of beneficial microorganisms while promoting the emergence of undesired ones, causing secondary infections such as oral thrush, colitis, or vaginitis. Any antibiotic may cause diarrhea, nausea, vomiting, anorexia, and hypersensitivity reactions.25

Pregnancy

Adapalene

According to the manufacturer, adapalene should only be used during pregnancy if the potential benefit justifies the potential risk to the fetus. There are no adequate and well controlled studies in pregnant women. Further, during clinical trials women of childbearing potential initiated treatment only after negative pregnancy tests were obtained. However, 2 women receiving the topical lotion and 6 women receiving the topical gel became pregnant during adapalene clinical trials. Pregnancy outcomes for these 8 women were: 3 healthy full term deliveries, 2 premature deliveries, 2 elective pregnancy terminations, and 1 lost to follow-up. In animal studies, teratogenic changes were observed in rats and rabbits receiving oral doses of more than 25 mg adapalene/kg/day representing 123- and 246-times the maximum recommended human dose. These teratogenic changes included cleft palate, microphthalmia, exophthalmos, encephalocele, skeletal abnormalities, umbilical hernia, and kidney abnormalities.1415

Benzoyl Peroxide

Benzoyl peroxide products are considered FDA pregnancy risk category C agents. It is not known if benzoyl peroxide causes fetal harm or can affect reproductive capacity. However, topical application is generally considered safe during pregnancy.

Clindamycin Phosphate

In clinical trials with pregnant women, no congenital abnormalities have been associated with systemic administration of clindamycin during the second or third trimester.13 However, in a large population-based cohort study (n = 139,938 live births) assessing antibiotic exposure during the first trimester of pregnancy (n = 15,469 exposures) and the risk of major birth defects, clindamycin was associated with an increased risk of major congenital malformations (adjusted odds ratio (aOR) 1.34; 95% CI: 1.02 to 1.77; 60 exposed cases). Clindamycin exposure increased the risk of musculoskeletal system malformations (aOR 1.67; 95% CI: 1.12 to 2.48; 29 exposed cases) and ventricular/atrial septal defect (aOR 1.81; 95% CI: 1.04 to 3.16; 13 exposed cases).26 Use clindamycin during the first trimester of pregnancy only if clearly needed and the benefits outweigh the risks.13 Placental concentrations are roughly 50% of maternal serum concentrations.2728 Parenteral clindamycin also contains benzyl alcohol, which can cross the placenta; benzyl alcohol has been associated with a fatal 'gasping syndrome' in neonates.451313 Clindamycin vaginal cream has been studied during pregnancy to reduce preterm birth and treat asymptomatic bacterial vaginosis. In 1 trial (n = 409), women who were treated with 2% clindamycin vaginal cream prior to 20 weeks gestation demonstrated a reduction in preterm birth compared to placebo (p less than 0.03).29 In 3 other trials, intravaginal clindamycin cream was administered at 16 to 32 weeks gestation, and an increase in adverse events, such as low birthweight, pre-term delivery, premature rupture of the membranes, and neonatal infections, was observed in newborns.303132 There are no adequate, well-controlled studies of topical clindamycin in pregnant women.533

Breast-feeding

Adapalene

According to the manufacturer, it is not known whether adapalene distributes into breast milk. Because adapalene is poorly absorbed through human intact skin, the amount of drug excreted into the breast milk is expected to be low 16, and therefore risk to the nursing infant is also expected to be low.17 Do not apply near the nipple area, and be careful to avoid direct contact between the infant and the treated area. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. If a breast-feeding infant experiences an adverse effect related to a maternally administered drug, healthcare providers are encouraged to report the adverse effect to the FDA.

Benzoyl Peroxide

It is not known if benzoyl peroxide is excreted in breast milk. However, very little benzoic acid is absorbed systemically with topical use of benzoyl peroxide; therefore, minimal risk to the infant would be expected.20 Only water-miscible cream products should be applied to the breast because ointments may expose the infant to high levels of mineral paraffins.21 Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. If a breast-feeding infant experiences an adverse effect related to a maternally administered drug, healthcare providers are encouraged to report the adverse effect to the FDA.

Clindamycin Phosphate

Clindamycin is excreted into human breast milk after administration by the oral or parenteral routes in concentrations of less than 0.5 to 3.8 mcg/mL. Because of the potential for serious gastrointestinal adverse reactions in the breast-fed infant, an alternative drug to clindamycin may be preferred during breast-feeding. Consider the developmental and health benefits of breast-feeding along with the mother's clinical need for clindamycin and any potential adverse effects on the breast-fed infant from clindamycin or the underlying maternal condition. If clindamycin is used during breast-feeding, 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.413 Diarrhea and bloody stools were reported in a 5-day-old infant whose mother was receiving intravenous clindamycin and gentamicin for suspected endometriosis.34 Previous American Academy of Pediatrics recommendations considered clindamycin as usually compatible with breast-feeding.35 It is unknown if clindamycin is excreted into human breast milk after the use of vaginally or topically administered clindamycin.51333 If clindamycin is topically applied to the chest, care should be taken to avoid accidental ingestion by the infant.33

 

Adverse Reactions/Side Effects

Adapalene

Local cutaneous adverse reactions may occur with adapalene therapy. Erythema, skin scaling, dryness of skin (xerosis), burning, and pruritus occur in 10—40% of patients using adapalene gel. Pruritus or burning immediately after application occurs in 20% of patients using adapalene gel. The frequency and severity (mild, moderate, or severe) of local cutaneous irritations were reported for patients using adapalene cream in clinical trials. Mild and moderate xerosis were reported in 42% and 9% of patients, respectively. Erythema was reported as mild in 38% of patients and moderate in 10% of patients. Mild scaling was reported in 35% of patients; moderate scaling was reported in 6% of patients. Persistent pruritus was reported as mild in 21% of patients and moderate in 4% of patients. Persistent burning and/or stinging was reported as mild in 24% of patients and moderate in 4% of patients. Erythema, scaling, dryness, persistent pruritus, and persistent burning/stinging were all reported as severe in < 1% of patients. Photosensitivity (sunburn) occurred in 2% of patients using adapalene cream and <= 1% of patients using the gel. Skin irritation and discomfort were reported rarely (<= 1%) among patients using the gel or cream. Acne vulgaris flares occur in patients receiving adapalene gel (<= 1%) and cream (< 1%). Additional adverse events reported in < 1% of patients using adapalene cream include dermatitis and contact dermatitis, blepharedema (eyelid edema), conjunctivitis, skin discoloration, rash (unspecified), and atopic dermatitis (as eczema).3637 Among patients receiving adapalene lotion in clinical trials, 7.7% reported dry skin, 1.5% reported skin irritation, 0.9% reported skin burning and discomfort, and 0.6% reported sunburn. For patients whose irritation scores were higher while on therapy compared to baseline, mild, moderate, and severe erythema occurred in 21.8%, 8%, and 0.2% of patients, respectively. Mild scaling occurred in 25.3% of patients; moderate and severe scaling were reported in 6.5% and 0.1% of patients, respectively. Dry skin was reported as mild in 36.1% of patients, moderate in 7.3% of patients, and severe in 0.3% of patients. Stinging and/or burning of the skin was reported as mild, moderate, and severe in 22.1%, 7%, and 0.9% of patients, respectively. In an open-label post-marketing study of 13 adolescent subjects, 8 out of 13 reported incidents of pruritus.14 The local cutaneous adverse reactions seen with use of adapalene are most common during the first 2—4 weeks of treatment, decrease in frequency and severity over time, and are reversible with discontinuation of therapy.363714 Depending upon the severity of cutaneous adverse reactions, patients should be instructed to use moisturizer,14 reduce the frequency of application of adapalene, or discontinue use.363714

Benzoyl Peroxide

The most common adverse reactions to benzoyl peroxide products are xerosis (drying of skin). Xerosis may include marked peeling, erythema, and skin irritation. Peeling of the skin usually occurs after a few days. Patients with skin irritation may experience mild stinging, feelings of warmth, or erythema upon application of benzoyl peroxide products. Occasionally, some patients may develop contact dermatitis including a rash (unspecified), pruritus, blistering, crusting or swelling of the skin.19 In patients who develop severe symptoms, discontinue benzoyl peroxide and consider using emollients, cool compresses, or topical corticosteroids (if indicated), to reduce symptoms and increase healing.

Topical over-the-counter (OTC) acne products, including benzoyl peroxide, have been associated with rare but serious and potentially life-threatening hypersensitivity reactions. These reactions may occur within minutes to a day or longer after use of the product. Instruct patients to stop using topical acne products if they experience signs of anaphylactoid reactions such as throat tightness; difficulty breathing; feeling faint; or swelling of the eyes, face, lips, or tongue. The product should also be discontinued in patients who develop urticaria or pruritus. Based on the information reported to the FDA, it is uncertain whether the reactions are caused by the active ingredients benzoyl peroxide or salicylic acid, the inactive ingredients, or a combination of both. When initiating therapy with an OTC topical acne product, advise patients to apply a small amount to one or two small affected areas for 3 days and monitor for signs of a hypersensitivity reaction. If no discomfort occurs, the instructions on the Drug Facts label may be followed.38

Clindamycin Phosphate

Gastrointestinal (GI) adverse events are more commonly associated with systemic clindamycin therapy; however, GI disturbances have also been reported in association with the use of topical and vaginal preparations. Diarrhea has been reported in up to 20% of patients receiving systemic therapy and is more common with the oral formulation; it has also been reported in less than 1% of patients using vaginal products and has occurred with the use of topical products. Other adverse events reported in less than 1% of patients using vaginal products and also with other formulations include abdominal pain/cramps, halitosis, nausea, vomiting, dyspepsia, flatulence, and gastrointestinal disorder. Constipation has been reported in 2% or less of patients using the vaginal product. Administration of oral formulations with food can reduce minor gastric distress. Esophagitis may occur with the oral formulations of clindamycin.45331381322394041 Esophagitis may be associated with odynophagia, dysphagia, and retrosternal pain. Most symptoms resolve within a few days to weeks after discontinuing the drug. Pseudomembranous colitis (Clostridium difficile-associated diarrhea, CDAD) has been reported with the use of clindamycin. Early reporting showed a rate of 0.01% to 10%; however, CDAD has become more frequent and severe. CDAD may occur during therapy or after therapy has been discontinued and may result in minor diarrhea or fatal colitis. CDAD is more commonly associated with systemic therapy; however, the topical and vaginal products do have some systemic absorption, and CDAD may occur.45331381322394041 A metallic taste (dysgeusia) has been reported with the administration of the intravenous and oral clindamycin products and taste perversion has been reported in less than 1% of patients receiving the vaginal cream.41313 Hematochezia was noted in postmarketing reports with the vaginal cream.[44987]

Transient neutropenia (leukopenia) and eosinophilia have been reported during clindamycin therapy. Reports of agranulocytosis and thrombocytopenia have been made. No direct relationship to concurrent clindamycin therapy has been made.453313813223940

Rashes including rash (unspecified), maculopapular rash, vesicular rash, or bullous rash as well as urticaria have been observed during systemic clindamycin therapy and may be associated with hypersensitivity. Severe skin reactions, such as toxic epidermal necrolysis and Stevens-Johnson syndrome, have been reported and some cases have been fatal. Clindamycin should be permanently discontinued if severe skin or hypersensitivity reactions occur. Acute generalized exanthematous pustulosis (AGEP), angioedema, drug reaction with eosinophilia and systemic symptoms (DRESS), erythema multiforme, and exfoliative dermatitis have also been reported with systemic clindamycin.13 Pruritus/itching has also been noted with topical (1% to 11%), vaginal (less than 1% to 1.1%), and systemic therapy. Topical application has been associated with burning (6% to 11%), xerosis (dry skin) (1% to 23%), erythema (7% to 16%), oiliness/oily skin (1% to 18%), peeling (7% to 11%), seborrhea, application site rash, folliculitis, and application site pain. Xerosis may be attributed to the solvent used in the topical preparation. Alcohol in some topical formulations may cause ocular irritation or ocular pain or irritate the mucous membranes or abraded skin resulting in contact dermatitis.5331322

Intramuscular injection of clindamycin can cause an injection site reaction consisting of pain, induration, and sterile abscess. Thrombo-phlebitis has been reported after intravenous infusion.4

Although no direct relationship has been established, renal dysfunction evidenced by azotemia, oliguria, and/or proteinuria has been observed in rare instances with clindamycin therapy. Dysuria was reported in less than 1% of patients using vaginal clindamycin.453313813223940

Anaphylactoid reactions and anaphylactic shock have been reported with clindamycin. Clindamycin should be permanently discontinued if anaphylactic or serious hypersensitivity reactions occur. Treat patients with an allergy to tartrazine dye cautiously since some oral capsule preparations contain the dye.13

In women treated with vaginal clindamycin preparations, vaginal irritation (3.4%), vulvovaginitis (6% or less), vaginal pain (1.9%), vulvovaginal disorder (3.2% to 6.7%), trichomonal vaginitis (0.2%), vaginal erythema, vulvovaginal pruritus, vaginal discharge, vaginal swelling, and vaginal bleeding occurred. Other adverse events noted in less than 1% of patients include menstrual disorder, vaginal discharge, vaginal infection, dysfunctional uterine bleeding, dysmenorrhea, intermenstrual bleeding, pelvic pain, vaginal burning, vaginal irritation, vulvar erythema, vulvitis, vulvovaginal discomfort, vulvovaginal dryness, vaginal pain, metrorrhagia, endometriosis, and menstrual disorder. Abnormal labor was noted in 1.1% of pregnant patients. Vaginitis has also been reported with vaginal products (3.6% or less) and with systemic use of clindamycin.4138132240

Jaundice and abnormal/elevated hepatic enzymes have been observed during clindamycin therapy.45331381322 3940

Headache (7% or less) and dizziness (less than 1%) were noted with the use of the topical clindamycin foam as well as the vaginal products. Vertigo (less than 1%) was also reported with the vaginal products.33132240

Back pain (5%) has been reported with the use of vaginal clindamycin.440 Cases of polyarthritis have been reported with systemic therapy.138

Use of clindamycin may lead to potential infection with overgrowth of nonsusceptible organisms or superinfection. Systemic or local fungal infections, including candidiasis, may occur. Vaginal candidiasis has been reported to occur in 1.5% to 14% of patients, and systemic candidiasis has been reported in 1.7% or less of patients receiving vaginal clindamycin. Urinary tract infection was reported in 2% or less of patients using vaginal clindamycin, with pyelonephritis reported in less than 1% of patients. Upper respiratory tract infection and unspecified bacterial infection were also reported in less than 1% of patients using the vaginal product.453313813223940

General adverse events reported in less than 1% of patients with the use of clindamycin vaginal products include inflammatory swelling, hyperthyroidism, epistaxis, fever, generalized pain, localized edema, and fatigue.422240

Storage

Store this medication in its original container at 68°F to 77°F (20°C to 25°C) and away from heat, moisture and light. Keep all medicine out of the reach of children. Throw away any unused medicine after the beyond-use date. Do not flush unused medications or pour down a sink or drain.

  • 1. Shalita A, Weiss JS, Chalker DK, et al. A comparison of the efficacy and safety of adapalene gel 0.1% and tretinoin gel 0.025% in the treatment of acne vulgaris. J Am Acad Derm 1996;34:482-5.
  • 2. Ozolins M, Eady EA, Avery AJ, et al. Comparison of five antimicrobial regimens for treatment of mild to moderate inflammatory facial acne vulgaris in the community: randomised controlled trial. Lancet 2004;364:2188-95.
  • 3. Luft BJ, Hafner R, Korzun AH, et al. Toxoplasmic encephalitis in patients with the acquired immunodeficiency syndrome. N Engl J Med 1993;329:995-1000.
  • 4. a. b. c. d. e. f. g. h. i. j. k. l. m. n. o. p. q. Cleocin (clindamycin injection) package insert. New York, NY: Pharmacia and Upjohn Company; 2020 Feb.
  • 5. a. b. c. d. e. f. g. h. i. j. k. l. m. n. o. Cleocin T (topical clindamycin phosphate) package insert. New York, NY: Pharmacia and Upjohn Company; 2019 Dec.
  • 6. US Food and Drug Administration (FDA). FDA-recognized antimicrobial susceptibility test interpretive criteria. Retrieved March 3, 2020. Available on the World Wide Web at https://www.fda.gov/Drugs/DevelopmentApprovalProcess/DevelopmentResources/ucm410971.htm.
  • 7. a. b. Clinical and Laboratory Standards Institute (CLSI). Performance standards for antimicrobial susceptibility testing, 30th Edition. Retrieved March 3, 2020. Available on the World Wide Web at http://em100.edaptivedocs.net/GetDoc.aspx?doc=CLSI%20M100%20ED30:2020&scope=user.
  • 8. a. b. c. d. e. f. g. h. i. Cleocin (clindamycin granules for soln) package insert. New York, NY: Pharmacia and Upjohn Co; 2020 Feb.
  • 9. Snydman DR, Jacobus NV, McDermott LA, et al. National survey on the susceptibility of Bacteroides fragilis group: report and analysis of trends in the United States from 1997 to 2004. Antimicrob Agents Chemother 2007;51:1649-1655.
  • 10. Beigi RH, Austin MN, Meyn LA, et al. Antimicrobial resistance associated with the treatment of bacterial vaginosis. Am J Obstet Gynecol 2004;191:1124-9.
  • 11. Panel on Opportunistic Infections in HIV-Infected Adults and Adolescents. Guidelines for the prevention and treatment of opportunistic infections in adults and adolescents with HIV: recommendations from the Centers for Disease Control and Prevention, the National Institutes of Health, and the HIV Medicine Association of the Infectious Diseases Society of America. Accessed Feb 11, 2020. Available at http://aidsinfo.nih.gov/guidelines.
  • 12. Flaherty JF, Gatti G, White J, et al. Protein binding of clindamycin in sera of patients with AIDS. Antimicrob Agents Chemother 1996;40:1134-1138.
  • 13. a. b. c. d. e. f. g. h. i. j. k. l. m. n. o. p. q. r. s. t. u. v. w. x. y. z. . . . . . . . . . Cleocin (clindamycin capsules) package insert. New York, NY: Pharmacia and Upjohn Co; 2020 Feb.
  • 14. a. b. c. d. e. f. Differin lotion (adapalene) package insert. Fort Worth, TX: Galderma Laboratories, L.P.; 2013 Dec.
  • 15. a. b. Differin (adapalene 0.3% gel) package insert. Fort Worth, TX: Galderma Laboratories, L.P.; 2012 Feb.
  • 16. a. b. Adapalene cream 0.1% package insert. Melville, NY: E. Fougera and Co.; 2008 Aug.
  • 17. a. b. Adapalene. In: Drugs in Pregnancy and Lactation. A Reference Guide to Fetal and Neonatal Risk. Briggs GG, Freeman RK, Yaffe SJ, (eds.) 9th ed., Philadelphia PA: Lippincott Williams and Wilkins; 2011:26.
  • 18. Moore DE. Drug-induced cutaneous photosensitivity: incidence, mechanism, prevention and management. Drug Saf 2002;25:345-72.
  • 19. a. b. BP Wash (benzoyl peroxide) package insert. Dallas, TX: Cintex Services, LLC; 2011 Dec.
  • 20. a. b. Leachman SA, Reed BR. The use of dermatologic drugs in pregnancy and lactation. Dermatol Clin. 2006;24:167-97.
  • 21. a. b. Noti A, Grob K, Biedermann M et al. Exposure of babies to C(15)-C(45) mineral paraffins from human milk and breast salves. Regul Toxicol Pharmacol. 2003;38:317-25.
  • 22. a. b. c. d. e. f. g. h. i. j. k. Cleocin (clindamycin vaginal ovules) package insert. New York, NY: Pharmacia and Upjohn Co; 2020 Mar.
  • 23. American Academy of Pediatrics (AAP) Committee on Infectious Diseases. Clostridium difficile infection in infants and children. Pediatrics 2013;131:196-200.
  • 24. Centers for Disease Control and Prevention (CDC). Sexually Transmitted Diseases Treatment Guidelines 2015. MMWR. 2015;64(3):1-137
  • 25. Health Care Financing Administration. Interpretive Guidelines for Long-term Care Facilities. Title 42 CFR 483.25(l) F329: Unnecessary Drugs. Revised 2015.
  • 26. Muanda FT, Sheehy O, Berard A. Use of antibiotics during pregnancy and the risk of major congenital malformations: A population based cohort study. Br J Clin Pharmacol 2017; July 19 [Epub ahead of print].
  • 27. Philipson A, Sabath LD, Charles D. Transplacental passage of erythromycin and clindamycin. New Engl J Med 1973;288:1219-21.
  • 28. Weinstein AJ, Gibbs RS, Gallagher M. Placental transfer of clindamycin and gentamicin in term pregnancy. Am J Obstet Gynecol 1976;124:688-91.
  • 29. Lamont RF, Duncan SLB, Mandal D. Intravaginal clindamycin to reduce preterm birth in women with abnormal genital tract flora. Obstet Gynecol 2003;101:516-522.
  • 30. McGregor JA, French JI, Jones W, et al. Bacterial vaginosis is associated with prematurity and vaginal fluid mucinase and sialidase: results of a controlled trial of topical clindamycin cream. Am J Obstet Gynecol 1994;170:1048-59.
  • 31. Joesoef MR, Hillier SL, Wiknjosastro G, et al. Intravaginal clindamycin treatment for bacterial vaginosis: effects on preterm delivery and low birth weight. Am J Obstet Gynecol 1995;173:1527-31.
  • 32. Vermeulen GM, Bruinse HW. Prophylactic administration of clindamycin 2% vaginal cream to reduce the incidence of spontaneous preterm birth in women with an increased recurrence risk: a randomised placebo-controlled double-blind trial. Br J Obstet Gynaecol 1999;106:652-7.
  • 33. a. b. c. d. e. f. g. h. i. j. k. Evoclin (clindamycin phosphate foam) package insert. Morgantown, WV: Mylan Pharmaceuticals, Inc.; 2018 Apr.
  • 34. Mann CF. Clindamycin and breast-feeding. Pediatrics 1980;66:1030-1.
  • 35. American Academy of Pediatrics (AAP) Committee on Drugs. Transfer of drugs and other chemicals into human milk. Pediatrics 2001;108(3):776-789.
  • 36. a. b. c. Adapalene gel package insert. Hawthorne, NY: Taro Pharmaceuticals U.S.A., Inc.; 2010 Jul.
  • 37. a. b. c. Adapalene cream package insert. Melville, NY: Fougera Pharmaceuticals, Inc.; 2013 Dec.
  • 38. Food and Drug Administration MedWatch. Over-The-Counter Topical Acne Products: Drug Safety Communication - Rare But Serious Hypersensitivity Reactions. Retrieved June 25, 2014. Available on the World Wide Web http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHum
  • 39. a. b. c. d. e. f. ClindaReach (clindamycin topical pledgets) package insert. Wilmington, MA: DUSA Pharmaceutical, Inc.; 2010 Feb.
  • 40. a. b. c. d. e. f. g. h. i. j. Clindesse (clindamycin vaginal cream 2%) package insert. St. Louis, MO: Ther-Rx Corporation; 2011 May.
  • 41. a. b. Sivapalasingam S, Steigbigel NH. Macrolides, clindamycin, and ketolides. In: Mandell GL, Bennett JE, Dolin R, eds. Principles and Practice of Infectious Diseases, 7th ed. New York: Churchill Livingstone; 2009:427-48.
  • 42. Cleocin (clindamycin vaginal cream) package insert. New York, NY: Pharmacia and Upjohn Co; 2020 Mar.

Related Medications