Clindesse is indicated for the treatment of bacterial vaginosis (formerly referred to as Haemophilus vaginitis, Gardnerella vaginitis, nonspecific vaginitis, Corynebacterium vaginitis, or anaerobic vaginosis) in non-pregnant women.

The recommended dose is the complete contents of a single pre-filled applicator containing 5 g of Clindesse cream administered once intravaginally at any time of the day.

{ "type": "p", "children": [], "text": "The recommended dose is the complete contents of a single pre-filled applicator containing 5 g of Clindesse cream administered once intravaginally at any time of the day." }

Not for ophthalmic, dermal, or oral use.

{ "type": "p", "children": [], "text": "Not for ophthalmic, dermal, or oral use." }

Clindesse is an intravaginal cream containing clindamycin phosphate 2%. Each pre-filled, single-dose applicator delivers approximately 5 g of cream containing approximately 100 mg of clindamycin.

{ "type": "p", "children": [], "text": "Clindesse is an intravaginal cream containing clindamycin phosphate 2%. Each pre-filled, single-dose applicator delivers approximately 5 g of cream containing approximately 100 mg of clindamycin." }

Clindesse is contraindicated in individuals with a history of hypersensitivity to clindamycin or other lincosamides. Reported reactions to other formulations of clindamycin include rashes, urticaria, erythema multiforme, and anaphylactoid reactions [see Adverse Reactions (6.2)].

Clindesse is contraindicated in patients with regional enteritis, ulcerative colitis, or a history of Clostridioides difficile-associated diarrhea.

Clostridioides difficile-associated diarrhea (CDAD) has been reported with use of nearly all antibacterial agents, including clindamycin, and may range in severity from mild diarrhea to fatal colitis. Treatment with antibacterial agents alters the normal flora of the colon leading to overgrowth of C. difficile.

C. difficile produces toxins A and B which contribute to the development of CDAD. Hypertoxin producing strains of C. difficile cause increased morbidity and mortality, as these infections can be refractory to antimicrobial therapy and may require colectomy. CDAD must be considered in all patients who present with diarrhea following antibiotic use. Careful medical history is necessary since CDAD has been reported to occur over two months after the administration of antibacterial agents.

If CDAD is suspected or confirmed, ongoing antibiotic use not directed against C. difficile may need to be discontinued. Appropriate fluid and electrolyte management, protein supplementation, antibiotic treatment of C. difficile, and surgical evaluation should be instituted as clinically indicated [see Adverse Reactions (6.2)].

This cream contains mineral oil that may weaken latex or rubber products such as condoms or vaginal contraceptive diaphragms. Therefore, the use of such barrier contraceptives is not recommended concurrently or for 5 days following treatment with Clindesse. During this time period, condoms may not be reliable for preventing pregnancy or for protecting against transmission of HIV and other sexually transmitted diseases [see Use in Specific Populations (8.3)].

Because 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 Clindesse in 368 patients. Clindesse 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 Clindesse, 1.6% of the patients discontinued therapy due to adverse reactions. Adverse reactions occurred in 126 of 368 patients (34%) treated with Clindesse and in 32 of 85 patients (38%) treated with placebo.

Adverse reactions occurring in ≥2% of patients receiving Clindesse in the placebo-controlled clinical trial are shown in Table 1.

Table 1. Adverse Reactions Occurring in ≥2% of Clindesse-Treated Patients and at a Higher Rate than Placebo-Treated Patients

<div class="scrollingtable"><table width="100%"> <col width="33%"/> <col width="33%"/> <col width="33%"/> <tbody class="Headless"> <tr class="First"> <td class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First"> <span class="Bold">Adverse Reactions</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First"> <span class="Bold">Clindesse<br/>N=85<br/>n (%)</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First"> <span class="Bold">Placebo<br/>N=85<br/>n (%)</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Vaginosis fungal NOS*</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">12 (14)</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">7 (8)</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Headache NOS</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">6 (7)</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">2 (2)</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Back Pain</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">4 (5)</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">1 (1)</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Constipation</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">2 (2)</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">0 (0)</p> </td> </tr> <tr class="Last"> <td class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">Urinary tract infection NOS</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">2 (2)</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">0 (0)</p> </td> </tr> </tbody> </table></div>

N = number of patients in intent-to-treat population

n (%) = number and percentage of patients with reported adverse reaction

NOS = not otherwise specified

Clindesse affords minimal peak serum levels and systemic exposure (AUCs) of clindamycin compared to an oral or intravenous dose of clindamycin [see Clinical Pharmacology (12.3)]. 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, Clostridioides difficile-associated diarrhea [see Warnings and Precautions (5.1)].

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.

Immune System: Drug reaction with eosinophilia and systemic symptoms (DRESS) cases have been reported.

The following adverse reactions have been identified during postapproval use of Clindesse. 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

Orally or intravenously administered clindamycin has neuromuscular blocking properties that may enhance the action of other neuromuscular blocking agents. Therefore, it should be used with caution in patients receiving such agents.

Risk Summary

Clindesse has not been studied in pregnant women. The systemic exposure (based on AUC and Cmax) of Clindesse administered intravaginally is substantially lower than clindamycin administered intravenously [see Clinical Pharmacology (12.3)]; therefore, maternal use is not likely to result in significant fetal exposure to the drug. Available data from published observational studies and randomized controlled trials over decades of use with other clindamycin products during pregnancy have not identified an increased risk of major birth defects, miscarriage, or other adverse maternal and fetal outcomes.

In animal reproduction studies, no adverse developmental outcomes were observed in pregnant rats and mice administered oral doses of clindamycin at up to 600 mg/kg/day (58 and 29 times, respectively, the recommended human dose based on a body surface area comparison) (see Data).

The background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.

Data

Animal Data

Reproduction studies have been performed in rats and mice using oral doses of clindamycin up to 600 mg/kg/day (58 and 29 times, respectively, the recommended human dose based on body surface area comparisons) and have revealed no evidence of harm to the fetus due to clindamycin.

Risk Summary

The systemic exposure (based on AUC and Cmax) of Clindesse is substantially lower than intravenous administration of clindamycin [see Clinical Pharmacology (12.3)]; therefore, adverse effects on the breastfed infant are not expected from transfer of clindamycin into breastmilk. There are no data on the effect of clindamycin on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for Clindesse and any potential adverse effects on the breastfed infant from Clindesse or from the underlying maternal condition.

Contraception

Clindesse contains mineral oil that may weaken latex or rubber products such as condoms or vaginal contraceptive diaphragms. Therefore, the use of such barrier contraceptives is not recommended concurrently or for 5 days following treatment with Clindesse. During this time period, condoms may not be reliable for preventing pregnancy or for protecting against transmission of HIV and other sexually transmitted diseases [see Warnings and Precautions (5.2)].

The safety and efficacy of Clindesse in the treatment of bacterial vaginosis in post-menarchal females have been established on the extrapolation of clinical trial data from adult women. The safety and efficacy of Clindesse in pre-menarchal females have not been established.

Clinical studies with Clindesse did not include sufficient numbers of subjects 65 years of age or older to determine whether they respond differently than younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients.

Vaginally applied clindamycin phosphate vaginal cream 2% could be absorbed in sufficient amounts to produce systemic effects [see Warnings and Precautions (5.1) and Adverse Reactions (6.2)].

{ "type": "p", "children": [], "text": "Vaginally applied clindamycin phosphate vaginal cream 2% could be absorbed in sufficient amounts to produce systemic effects [see Warnings and Precautions (5.1) and Adverse Reactions (6.2)]." }

Clindamycin phosphate, a lincosamide, is a water soluble ester of the semi-synthetic antibiotic produced by a 7(S)-chloro-substitution of the 7(R)-hydroxyl group of the parent antibiotic lincomycin. The chemical name for clindamycin phosphate is methyl 7-chloro- 6,7,8-trideoxy-6-(1-methyl- trans- 4-propyl-L-2-pyrrolidinecarboxamido)-1-thio-L-threo-(alpha)-D-galacto-octopyranoside 2-(dihydrogen phosphate). It has a molecular weight of 504.96, and the molecular formula is C18H34CIN2O8PS. The structural formula is represented below:

{ "type": "p", "children": [], "text": "Clindamycin phosphate, a lincosamide, is a water soluble ester of the semi-synthetic antibiotic produced by a 7(S)-chloro-substitution of the 7(R)-hydroxyl group of the parent antibiotic lincomycin. The chemical name for clindamycin phosphate is methyl 7-chloro- 6,7,8-trideoxy-6-(1-methyl- trans- 4-propyl-L-2-pyrrolidinecarboxamido)-1-thio-L-threo-(alpha)-D-galacto-octopyranoside 2-(dihydrogen phosphate). It has a molecular weight of 504.96, and the molecular formula is C18H34CIN2O8PS. The structural formula is represented below:" }

Clindesse is a semi-solid, white cream, which contains clindamycin phosphate, USP, at a concentration equivalent to 20 mg clindamycin base per gram. The cream also contains edetate disodium, glycerol monoisostearate, lecithin, methylparaben, microcrystalline wax, mineral oil, polyglyceryl-3-oleate, propylparaben, purified water, silicon dioxide and sorbitol solution.

{ "type": "p", "children": [], "text": "Clindesse is a semi-solid, white cream, which contains clindamycin phosphate, USP, at a concentration equivalent to 20 mg clindamycin base per gram. The cream also contains edetate disodium, glycerol monoisostearate, lecithin, methylparaben, microcrystalline wax, mineral oil, polyglyceryl-3-oleate, propylparaben, purified water, silicon dioxide and sorbitol solution." }

Clindesse does not comply with the pH test of the USP monograph for clindamycin phosphate vaginal cream.

{ "type": "p", "children": [], "text": "Clindesse does not comply with the pH test of the USP monograph for clindamycin phosphate vaginal cream." }

Clindamycin is an antibacterial drug [see Clinical Pharmacology, Microbiology (12.4)].

Following a single intravaginal application of Clindesse 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 Clindesse 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 Clindesse.

Mechanism of Action

Clindamycin inhibits bacterial protein synthesis at the level of the bacterial ribosome. The antibiotic binds preferentially to the 50S ribosomal subunit and affects the process of peptide chain initiation. Although clindamycin phosphate is inactive in vitro, in vivo hydrolysis converts this compound to the antibacterially active clindamycin.

Activity In Vitro

Clindamycin is an antibacterial agent active in vitro against most strains of the following organisms that have been reported to be associated with bacterial vaginosis:

Bacteroides spp.

Gardnerella vaginalis

Mobiluncus spp.

Mycoplasma hominis

Peptostreptococcus spp.

Standard methodology for the susceptibility testing of the potential bacterial vaginosis pathogens has not been defined. Culture and sensitivity testing of bacteria are not routinely performed to establish the diagnosis of bacterial vaginosis [see Clinical Studies (14)].

Long-term studies in animals have not been performed with clindamycin to evaluate carcinogenic potential. Genotoxicity tests performed included a rat micronucleus test and an Ames test. Both tests were negative. Fertility studies in rats treated orally with up to 300 mg/kg/day (29 times the recommended human dose based on body surface area comparisons) revealed no effects on fertility or mating ability.

Two clinical studies were conducted to evaluate the efficacy of Clindesse for the treatment of bacterial vaginosis. A clinical diagnosis of bacterial vaginosis was defined by the presence of a homogeneous vaginal discharge that (a) has a pH of greater than 4.5, (b) emits a “fishy” amine odor when mixed with a 10% KOH solution, and (c) contains clue cells on microscopic examination. Gram’s stain results consistent with a diagnosis of bacterial vaginosis include (a) markedly reduced or absent Lactobacillus morphology, (b) predominance of Gardnerella morphotype, and (c) absent or few white blood cells.

{ "type": "p", "children": [], "text": "Two clinical studies were conducted to evaluate the efficacy of Clindesse for the treatment of bacterial vaginosis. A clinical diagnosis of bacterial vaginosis was defined by the presence of a homogeneous vaginal discharge that (a) has a pH of greater than 4.5, (b) emits a “fishy” amine odor when mixed with a 10% KOH solution, and (c) contains clue cells on microscopic examination. Gram’s stain results consistent with a diagnosis of bacterial vaginosis include (a) markedly reduced or absent Lactobacillus morphology, (b) predominance of Gardnerella morphotype, and (c) absent or few white blood cells." }

In a randomized, double-blind, placebo-controlled, clinical study involving 144 non-pregnant female patients aged 18 to 64 with a baseline Nugent score ≥4, Clindesse demonstrated statistically significantly higher cure rates over placebo as measured by therapeutic cure, clinical cure, and Nugent score cure (Table 2) assessed at 21-30 days after administration of the drug. Therapeutic cure was a composite endpoint which required both clinical cure and Nugent score cure. Clinical cure required normal vaginal discharge, vaginal pH < 4.7, < 20% clue cells on wet mount preparation, and negative “whiff” test (detection of amine odor on addition of 10% KOH solution to sample of the vaginal discharge). A Nugent score of 0-3 was considered a Nugent score cure. The Nugent scoring is based on microscopic examination of the Gram’s stained vaginal smears for quantification of specific bacterial morphotypes. Cure rates were consistently higher for Clindesse compared to placebo for the following demographic subsets: age, race, height, weight, sexual behavior, and recalcitrant infection status.

{ "type": "p", "children": [], "text": "In a randomized, double-blind, placebo-controlled, clinical study involving 144 non-pregnant female patients aged 18 to 64 with a baseline Nugent score ≥4, Clindesse demonstrated statistically significantly higher cure rates over placebo as measured by therapeutic cure, clinical cure, and Nugent score cure (Table 2) assessed at 21-30 days after administration of the drug. Therapeutic cure was a composite endpoint which required both clinical cure and Nugent score cure. Clinical cure required normal vaginal discharge, vaginal pH < 4.7, < 20% clue cells on wet mount preparation, and negative “whiff” test (detection of amine odor on addition of 10% KOH solution to sample of the vaginal discharge). A Nugent score of 0-3 was considered a Nugent score cure. The Nugent scoring is based on microscopic examination of the Gram’s stained vaginal smears for quantification of specific bacterial morphotypes. Cure rates were consistently higher for Clindesse compared to placebo for the following demographic subsets: age, race, height, weight, sexual behavior, and recalcitrant infection status." }

Table 2. Efficacy of Clindesse for Treatment of Bacterial Vaginosis in a Randomized, Double-Blind, Placebo-Controlled, Parallel Group Study

{ "type": "p", "children": [], "text": "\nTable 2. Efficacy of Clindesse for Treatment of Bacterial Vaginosis in a Randomized, Double-Blind, Placebo-Controlled, Parallel Group Study\n" }

<div class="scrollingtable"><table width="100%"> <col width="29%"/> <col width="21%"/> <col width="21%"/> <col width="29%"/> <tbody class="Headless"> <tr class="First"> <td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First"> <span class="Bold">Outcome</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First"> <span class="Bold">Clindesse<br/>N=78<br/>% Cure</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First"> <span class="Bold">Placebo<br/>N=66<br/>% Cure</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First"> <span class="Bold">Treatment<br/>Difference<span class="Sup">†</span> (%)</span> </p> <p> <span class="Bold">[97.5% Confidence Interval]</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Therapeutic Cure</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">29.5</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">3.0</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">26.5 [14.0, 39.0]</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Clinical Cure</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">41.0</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">19.7</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">21.3 [4.7, 38.0]</p> </td> </tr> <tr class="Last"> <td class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">Nugent Score Cure</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">44.9</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">6.1</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">38.8 [24.6, 53.1]</p> </td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table width=\"100%\">\n<col width=\"29%\"/>\n<col width=\"21%\"/>\n<col width=\"21%\"/>\n<col width=\"29%\"/>\n<tbody class=\"Headless\">\n<tr class=\"First\">\n<td align=\"center\" class=\"Botrule Lrule Rrule Toprule\" valign=\"top\">\n<p class=\"First\">\n<span class=\"Bold\">Outcome</span>\n</p>\n</td><td align=\"center\" class=\"Botrule Lrule Rrule Toprule\" valign=\"top\">\n<p class=\"First\">\n<span class=\"Bold\">Clindesse<br/>N=78<br/>% Cure</span>\n</p>\n</td><td align=\"center\" class=\"Botrule Lrule Rrule Toprule\" valign=\"top\">\n<p class=\"First\">\n<span class=\"Bold\">Placebo<br/>N=66<br/>% Cure</span>\n</p>\n</td><td align=\"center\" class=\"Botrule Lrule Rrule Toprule\" valign=\"top\">\n<p class=\"First\">\n<span class=\"Bold\">Treatment<br/>Difference<span class=\"Sup\">†</span> (%)</span>\n</p>\n<p>\n<span class=\"Bold\">[97.5% Confidence Interval]</span>\n</p>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule\" valign=\"top\">\n<p class=\"First\">Therapeutic Cure</p>\n</td><td align=\"center\" class=\"Botrule Lrule Rrule Toprule\" valign=\"top\">\n<p class=\"First\">29.5</p>\n</td><td align=\"center\" class=\"Botrule Lrule Rrule Toprule\" valign=\"top\">\n<p class=\"First\">3.0</p>\n</td><td align=\"center\" class=\"Botrule Lrule Rrule Toprule\" valign=\"top\">\n<p class=\"First\">26.5 [14.0, 39.0]</p>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule\" valign=\"top\">\n<p class=\"First\">Clinical Cure</p>\n</td><td align=\"center\" class=\"Botrule Lrule Rrule Toprule\" valign=\"top\">\n<p class=\"First\">41.0</p>\n</td><td align=\"center\" class=\"Botrule Lrule Rrule Toprule\" valign=\"top\">\n<p class=\"First\">19.7</p>\n</td><td align=\"center\" class=\"Botrule Lrule Rrule Toprule\" valign=\"top\">\n<p class=\"First\">21.3 [4.7, 38.0]</p>\n</td>\n</tr>\n<tr class=\"Last\">\n<td class=\"Botrule Lrule Rrule Toprule\" valign=\"top\">\n<p class=\"First\">Nugent Score Cure</p>\n</td><td align=\"center\" class=\"Botrule Lrule Rrule Toprule\" valign=\"top\">\n<p class=\"First\">44.9</p>\n</td><td align=\"center\" class=\"Botrule Lrule Rrule Toprule\" valign=\"top\">\n<p class=\"First\">6.1</p>\n</td><td align=\"center\" class=\"Botrule Lrule Rrule Toprule\" valign=\"top\">\n<p class=\"First\">38.8 [24.6, 53.1]</p>\n</td>\n</tr>\n</tbody>\n</table></div>" }

N = number of patients in treatment group (modified intent-to-treat population defined as all subjects randomized who received at least one dose of study medication, and who had a baseline Nugent score of at least 4)

{ "type": "p", "children": [], "text": "N = number of patients in treatment group (modified intent-to-treat population defined as all subjects randomized who received at least one dose of study medication, and who had a baseline Nugent score of at least 4)" }

†Treatment difference = Clindesse minus placebo cure rates

{ "type": "p", "children": [], "text": "\n†Treatment difference = Clindesse minus placebo cure rates" }

In a second controlled clinical study involving 432 patients aged 18 to 78 with a baseline Nugent score of ≥4, 221 women self-administered a single dose of Clindesse, and 211 women self-administered a single daily dose of a formulation of clindamycin vaginal cream for 7 days. A single dose of Clindesse was shown to be similar to 7 daily doses of the clindamycin vaginal cream for treatment of bacterial vaginosis as measured by therapeutic cure, clinical cure or Nugent score cure assessed at 21-30 days after administration of the drug in the modified intent-to-treat population (Table 3) and for the per protocol population (Table 4). The study endpoints were identical to those described above for the placebo-controlled study. Statistical analyses did not reveal any significant differences when controlling for the following demographic variables: age, race, height, weight, sexual behavior, and recalcitrant infection status.

{ "type": "p", "children": [], "text": "In a second controlled clinical study involving 432 patients aged 18 to 78 with a baseline Nugent score of ≥4, 221 women self-administered a single dose of Clindesse, and 211 women self-administered a single daily dose of a formulation of clindamycin vaginal cream for 7 days. A single dose of Clindesse was shown to be similar to 7 daily doses of the clindamycin vaginal cream for treatment of bacterial vaginosis as measured by therapeutic cure, clinical cure or Nugent score cure assessed at 21-30 days after administration of the drug in the modified intent-to-treat population (Table 3) and for the per protocol population (Table 4). The study endpoints were identical to those described above for the placebo-controlled study. Statistical analyses did not reveal any significant differences when controlling for the following demographic variables: age, race, height, weight, sexual behavior, and recalcitrant infection status." }

The cure rates reported in the clinical studies with Clindesse were based on resolution of 4 out of 4 Amsel criteria and a Nugent score of < 4, while the criteria for cure in previous clinical studies with the clindamycin vaginal cream were based solely on resolution of 2 out of 4 Amsel criteria, resulting in higher reported rates of cure for bacterial vaginosis.

{ "type": "p", "children": [], "text": "The cure rates reported in the clinical studies with Clindesse were based on resolution of 4 out of 4 Amsel criteria and a Nugent score of < 4, while the criteria for cure in previous clinical studies with the clindamycin vaginal cream were based solely on resolution of 2 out of 4 Amsel criteria, resulting in higher reported rates of cure for bacterial vaginosis." }

Table 3. Efficacy of Clindesse in Treatment of Bacterial Vaginosis in a Randomized, Investigator-Blind, Active-Controlled Comparative Study – Modified-Intent-to-Treat

{ "type": "p", "children": [], "text": "\nTable 3. Efficacy of Clindesse in Treatment of Bacterial Vaginosis in a Randomized, Investigator-Blind, Active-Controlled Comparative Study – Modified-Intent-to-Treat\n" }

<div class="scrollingtable"><table width="100%"> <col width="25%"/> <col width="25%"/> <col width="25%"/> <col width="25%"/> <tbody class="Headless"> <tr class="First"> <td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First"> <span class="Bold">Outcome</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First"> <span class="Bold">Clindesse<br/>Single Dose<br/>N=221<br/>% Cure</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First"> <span class="Bold">Clindamycin<br/>Vaginal Cream<br/>(7 doses) N=211<br/>% Cure</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First"> <span class="Bold">Treatment <br/>Difference<span class="Sup">†</span> (%)<br/>[95% Confidence Interval]</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Therapeutic Cure</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">33.0</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">37.0</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">-3.9 [-12.9, 5.1]</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Clinical Cure</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">53.4</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">54.0</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">-0.6 [-10.0, 8.8]</p> </td> </tr> <tr class="Last"> <td class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">Nugent Score Cure</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">45.7</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">49.3</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">-3.6 [-13.1, 5.8]</p> </td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table width=\"100%\">\n<col width=\"25%\"/>\n<col width=\"25%\"/>\n<col width=\"25%\"/>\n<col width=\"25%\"/>\n<tbody class=\"Headless\">\n<tr class=\"First\">\n<td align=\"center\" class=\"Botrule Lrule Rrule Toprule\" valign=\"top\">\n<p class=\"First\">\n<span class=\"Bold\">Outcome</span>\n</p>\n</td><td align=\"center\" class=\"Botrule Lrule Rrule Toprule\" valign=\"top\">\n<p class=\"First\">\n<span class=\"Bold\">Clindesse<br/>Single Dose<br/>N=221<br/>% Cure</span>\n</p>\n</td><td align=\"center\" class=\"Botrule Lrule Rrule Toprule\" valign=\"top\">\n<p class=\"First\">\n<span class=\"Bold\">Clindamycin<br/>Vaginal Cream<br/>(7 doses) N=211<br/>% Cure</span>\n</p>\n</td><td align=\"center\" class=\"Botrule Lrule Rrule Toprule\" valign=\"top\">\n<p class=\"First\">\n<span class=\"Bold\">Treatment <br/>Difference<span class=\"Sup\">†</span> (%)<br/>[95% Confidence Interval]</span>\n</p>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule\" valign=\"top\">\n<p class=\"First\">Therapeutic Cure</p>\n</td><td align=\"center\" class=\"Botrule Lrule Rrule Toprule\" valign=\"top\">\n<p class=\"First\">33.0</p>\n</td><td align=\"center\" class=\"Botrule Lrule Rrule Toprule\" valign=\"top\">\n<p class=\"First\">37.0</p>\n</td><td align=\"center\" class=\"Botrule Lrule Rrule Toprule\" valign=\"top\">\n<p class=\"First\">-3.9 [-12.9, 5.1]</p>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule\" valign=\"top\">\n<p class=\"First\">Clinical Cure</p>\n</td><td align=\"center\" class=\"Botrule Lrule Rrule Toprule\" valign=\"top\">\n<p class=\"First\">53.4</p>\n</td><td align=\"center\" class=\"Botrule Lrule Rrule Toprule\" valign=\"top\">\n<p class=\"First\">54.0</p>\n</td><td align=\"center\" class=\"Botrule Lrule Rrule Toprule\" valign=\"top\">\n<p class=\"First\">-0.6 [-10.0, 8.8]</p>\n</td>\n</tr>\n<tr class=\"Last\">\n<td class=\"Botrule Lrule Rrule Toprule\" valign=\"top\">\n<p class=\"First\">Nugent Score Cure</p>\n</td><td align=\"center\" class=\"Botrule Lrule Rrule Toprule\" valign=\"top\">\n<p class=\"First\">45.7</p>\n</td><td align=\"center\" class=\"Botrule Lrule Rrule Toprule\" valign=\"top\">\n<p class=\"First\">49.3</p>\n</td><td align=\"center\" class=\"Botrule Lrule Rrule Toprule\" valign=\"top\">\n<p class=\"First\">-3.6 [-13.1, 5.8]</p>\n</td>\n</tr>\n</tbody>\n</table></div>" }

†Treatment difference = Clindesse minus clindamycin vaginal cream cure rates

{ "type": "p", "children": [], "text": "\n†Treatment difference = Clindesse minus clindamycin vaginal cream cure rates" }

N = number of patients in treatment group (modified intent-to-treat population defined as all subjects randomized who received at least one dose of study medication, and who had a baseline Nugent score of at least 4)

{ "type": "p", "children": [], "text": "N = number of patients in treatment group (modified intent-to-treat population defined as all subjects randomized who received at least one dose of study medication, and who had a baseline Nugent score of at least 4)" }

Table 4. Efficacy of Clindesse in Treatment of Bacterial Vaginosis in a Randomized, Investigator-Blind, Active-Controlled Comparative Study – Per Protocol

{ "type": "p", "children": [], "text": "\nTable 4. Efficacy of Clindesse in Treatment of Bacterial Vaginosis in a Randomized, Investigator-Blind, Active-Controlled Comparative Study – Per Protocol\n" }

<div class="scrollingtable"><table width="100%"> <col width="25%"/> <col width="25%"/> <col width="25%"/> <col width="25%"/> <tbody class="Headless"> <tr class="First"> <td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First"> <span class="Bold">Outcome</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First"> <span class="Bold">Clindesse<br/>Single Dose<br/>N=126<br/>% Cure</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First"> <span class="Bold">Clindamycin<br/>Vaginal Cream<br/>(7 doses) N=125<br/>% Cure</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First"> <span class="Bold">Treatment <br/>Difference<span class="Sup">†</span> (%)<br/>[95% Confidence Interval]</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Therapeutic Cure</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">42.1</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">45.6</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">-3.5 [-15.8, 8.7]</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Clinical Cure</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">64.3</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">63.2</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">1.1 [-10.8, 13.0]</p> </td> </tr> <tr class="Last"> <td class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">Nugent Score Cure</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">56.5<span class="Sup">‡</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">57.7<span class="Sup">‡</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">-1.3 [-13.6, 11.1]</p> </td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table width=\"100%\">\n<col width=\"25%\"/>\n<col width=\"25%\"/>\n<col width=\"25%\"/>\n<col width=\"25%\"/>\n<tbody class=\"Headless\">\n<tr class=\"First\">\n<td align=\"center\" class=\"Botrule Lrule Rrule Toprule\" valign=\"top\">\n<p class=\"First\">\n<span class=\"Bold\">Outcome</span>\n</p>\n</td><td align=\"center\" class=\"Botrule Lrule Rrule Toprule\" valign=\"top\">\n<p class=\"First\">\n<span class=\"Bold\">Clindesse<br/>Single Dose<br/>N=126<br/>% Cure</span>\n</p>\n</td><td align=\"center\" class=\"Botrule Lrule Rrule Toprule\" valign=\"top\">\n<p class=\"First\">\n<span class=\"Bold\">Clindamycin<br/>Vaginal Cream<br/>(7 doses) N=125<br/>% Cure</span>\n</p>\n</td><td align=\"center\" class=\"Botrule Lrule Rrule Toprule\" valign=\"top\">\n<p class=\"First\">\n<span class=\"Bold\">Treatment <br/>Difference<span class=\"Sup\">†</span> (%)<br/>[95% Confidence Interval]</span>\n</p>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule\" valign=\"top\">\n<p class=\"First\">Therapeutic Cure</p>\n</td><td align=\"center\" class=\"Botrule Lrule Rrule Toprule\" valign=\"top\">\n<p class=\"First\">42.1</p>\n</td><td align=\"center\" class=\"Botrule Lrule Rrule Toprule\" valign=\"top\">\n<p class=\"First\">45.6</p>\n</td><td align=\"center\" class=\"Botrule Lrule Rrule Toprule\" valign=\"top\">\n<p class=\"First\">-3.5 [-15.8, 8.7]</p>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule\" valign=\"top\">\n<p class=\"First\">Clinical Cure</p>\n</td><td align=\"center\" class=\"Botrule Lrule Rrule Toprule\" valign=\"top\">\n<p class=\"First\">64.3</p>\n</td><td align=\"center\" class=\"Botrule Lrule Rrule Toprule\" valign=\"top\">\n<p class=\"First\">63.2</p>\n</td><td align=\"center\" class=\"Botrule Lrule Rrule Toprule\" valign=\"top\">\n<p class=\"First\">1.1 [-10.8, 13.0]</p>\n</td>\n</tr>\n<tr class=\"Last\">\n<td class=\"Botrule Lrule Rrule Toprule\" valign=\"top\">\n<p class=\"First\">Nugent Score Cure</p>\n</td><td align=\"center\" class=\"Botrule Lrule Rrule Toprule\" valign=\"top\">\n<p class=\"First\">56.5<span class=\"Sup\">‡</span>\n</p>\n</td><td align=\"center\" class=\"Botrule Lrule Rrule Toprule\" valign=\"top\">\n<p class=\"First\">57.7<span class=\"Sup\">‡</span>\n</p>\n</td><td align=\"center\" class=\"Botrule Lrule Rrule Toprule\" valign=\"top\">\n<p class=\"First\">-1.3 [-13.6, 11.1]</p>\n</td>\n</tr>\n</tbody>\n</table></div>" }

†Treatment difference = Clindesse minus clindamycin vaginal cream cure rates

{ "type": "p", "children": [], "text": "\n†Treatment difference = Clindesse minus clindamycin vaginal cream cure rates" }

N = number of patients in treatment group (per protocol population defined as all subjects included in the modified intent-to-treat population who completed the study without significant protocol violation)

{ "type": "p", "children": [], "text": "N = number of patients in treatment group (per protocol population defined as all subjects included in the modified intent-to-treat population who completed the study without significant protocol violation)" }

‡Four subjects (2 from each treatment group) did not have complete Nugent scores and were not included in the Nugent Score cure analysis

{ "type": "p", "children": [], "text": "\n‡Four subjects (2 from each treatment group) did not have complete Nugent scores and were not included in the Nugent Score cure analysis" }

Clindesse (clindamycin phosphate) Vaginal Cream, 2%, is available in cartons containing one single-dose, pre-filled disposable applicator (NDC 45802-042-01). Each applicator delivers approximately 5 g of vaginal cream containing approximately 100 mg of clindamycin.

{ "type": "p", "children": [], "text": "Clindesse (clindamycin phosphate) Vaginal Cream, 2%, is available in cartons containing one single-dose, pre-filled disposable applicator (NDC 45802-042-01). Each applicator delivers approximately 5 g of vaginal cream containing approximately 100 mg of clindamycin." }

Store at 20°-25°C (68°-77°F). [See USP Controlled Room Temperature.]

{ "type": "p", "children": [], "text": "Store at 20°-25°C (68°-77°F). [See USP Controlled Room Temperature.]" }

Avoid heat above 30°C (86°F).

{ "type": "p", "children": [], "text": "Avoid heat above 30°C (86°F)." }

Vaginal Intercourse and Use with Vaginal Products

{ "type": "p", "children": [], "text": "\nVaginal Intercourse and Use with Vaginal Products\n" }

Instruct the patient not to engage in vaginal intercourse, or use other vaginal products (such as tampons or douches) during treatment with this product.

{ "type": "p", "children": [], "text": "Instruct the patient not to engage in vaginal intercourse, or use other vaginal products (such as tampons or douches) during treatment with this product." }

Use with Condoms and Vaginal Contraceptive Diaphragms

{ "type": "p", "children": [], "text": "\nUse with Condoms and Vaginal Contraceptive Diaphragms\n" }

Advise the patient that Clindesse contains mineral oil that may weaken latex or rubber products such as condoms or vaginal contraceptive diaphragms. Therefore, do not use barrier contraceptives concurrently or for 5 days following treatment with Clindesse. During this time period, condoms may not be reliable for preventing pregnancy or for protecting against transmission of HIV and other sexually transmitted diseases [see Warnings and Precautions (5.2) and Use in Specific Populations (8.3)].

{ "type": "p", "children": [], "text": "Advise the patient that Clindesse contains mineral oil that may weaken latex or rubber products such as condoms or vaginal contraceptive diaphragms. Therefore, do not use barrier contraceptives concurrently or for 5 days following treatment with Clindesse. During this time period, condoms may not be reliable for preventing pregnancy or for protecting against transmission of HIV and other sexually transmitted diseases [see Warnings and Precautions (5.2) and Use in Specific Populations (8.3)]." }

Fungal Vaginal Infections

{ "type": "p", "children": [], "text": "\nFungal Vaginal Infections\n" }

Inform the patient that vaginal fungal infections can occur following use of Clindesse and may require treatment with an antifungal drug [see Adverse Reactions (6.1)].

{ "type": "p", "children": [], "text": "Inform the patient that vaginal fungal infections can occur following use of Clindesse and may require treatment with an antifungal drug [see Adverse Reactions (6.1)]." }

Accidental Exposure to the Eye

{ "type": "p", "children": [], "text": "\nAccidental Exposure to the Eye\n" }

Inform the patient that Clindesse contains ingredients which cause burning and irritation of the eye. In the event of accidental contact with the eye, rinse the eye with copious amounts of cool tap water and consult a physician.

{ "type": "p", "children": [], "text": "Inform the patient that Clindesse contains ingredients which cause burning and irritation of the eye. In the event of accidental contact with the eye, rinse the eye with copious amounts of cool tap water and consult a physician." }

Manufactured by Padagis® Yeruham, Israel

{ "type": "p", "children": [], "text": "Manufactured by Padagis® \nYeruham, Israel" }

Patents at www.padagis.com/patents

{ "type": "p", "children": [], "text": "Patents at www.padagis.com/patents" }

Cleocin is a registered trademark of Pharmacia & Upjohn Company.

{ "type": "p", "children": [], "text": "Cleocin is a registered trademark of Pharmacia & Upjohn Company." }

2S000 RC SUB PH7

{ "type": "p", "children": [], "text": "2S000 RC SUB PH7" }

<div class="scrollingtable"><table width="100%"> <col width="100%"/> <tbody class="Headless"> <tr class="First"> <td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First"> <span class="Bold">PATIENT INFORMATION</span> </p> <p> <span class="Bold">Clindesse (clin-DESS)</span> </p> <p> <span class="Bold">(clindamycin phosphate)</span> </p> <p> <span class="Bold">Vaginal Cream, 2%</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First"> <span class="Bold">Important Information: </span>Clindesse is for intravaginal use only. Do not use in the eyes, mouth, or on your skin.</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First"> <span class="Bold">What is Clindesse?</span> </p> <p>•  Clindesse vaginal cream is a prescription medicine used to treat bacterial vaginal infections in women who are not pregnant.</p> <p>•  It is not known if Clindesse is safe and effective in females who have not yet reached puberty.</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First"> <span class="Bold">Do not use Clindesse if you:</span> </p> <p>•  are allergic to clindamycin or other lincosamide antibiotic medicines or are allergic to any of the ingredients in Clindesse. See the end of this leaflet for a complete list of ingredients in Clindesse.</p> <p>•  have had bowel problems such as:</p> <p>    ◦  inflammation of your intestines (enteritis)</p> <p>    ◦  inflammation of your colon (colitis)</p> <p>    ◦  diarrhea due to a <span class="Italics">Clostridioides difficile</span>-associated diarrhea (CDAD)</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First"> <span class="Bold">Before using Clindesse, tell your healthcare provider about all of your medical conditions, including if you:</span> </p> <p>•  are pregnant or plan to become pregnant. It is not known if Clindesse will harm your unborn baby. Tell your healthcare provider if you become pregnant during treatment with Clindesse.</p> <p>•  are breastfeeding or plan to breastfeed. The amount of Clindesse which passes into your breast milk is low and is not expected to harm your baby. Talk with your healthcare provider about the best way to feed your baby while using Clindesse.</p> <p> <span class="Bold">Tell your healthcare provider about all the medicines you take</span>, including prescription and over-the-counter medicines, vitamins, and herbal supplements.</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First"> <span class="Bold">How should I use Clindesse?</span> </p> <p>•  Use Clindesse exactly as your healthcare provider tells you to use it.</p> <p>•  Use 1 filled applicator of Clindesse in the vagina at any time of the day.</p> <p>•  Do not use any medicine from the tube or applicator more than 1 time. Clindesse is for 1 time (single-use) only.</p> <p>•  Do not use Clindesse in the eyes, mouth, or on your skin. If you accidently get Clindesse in your eyes rinse your eyes with cool tap water right away and call your healthcare provider.</p> <p>•  See the <span class="Bold">Instructions for Use</span> at the end of this Patient Information leaflet for more information about how to fill the applicator and use Clindesse.</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First"> <span class="Bold">What should I avoid while using Clindesse?</span> </p> <p> <span class="Bold">After you insert Clindesse:</span> </p> <p>•  <span class="Bold">Do not</span> have vaginal sex or use vaginal products (such as tampons or douches) during your treatment.</p> <p>•  <span class="Bold">Do not</span> use barrier contraceptive products during your treatment or for 5 days after your treatment.</p> <p>    ◦  Barrier contraceptives include condoms or contraceptive diaphragms used for birth control or to protect yourself against Human Immunodeficiency Virus (HIV) or other sexually transmitted diseases (STDs).</p> <p>    ◦  Clindesse contains mineral oil that may weaken latex or rubber products in condoms or vaginal contraceptive diaphragms.</p> <p>    ◦  Condoms or vaginal contraceptive diaphragms may not work as well for preventing pregnancy, or for protecting against HIV and other STDs.</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First"> <span class="Bold">What are the possible side effects of Clindesse?</span> </p> <p> <span class="Bold">Clindesse may cause serious side effects, including diarrhea. </span>One type of diarrhea is caused by an infection in your intestines called <span class="Italics">Clostridioides difficile</span>-associated diarrhea (CDAD), which may range in severity from mild diarrhea to colitis that can lead to death. If you have diarrhea after you use Clindesse, call your healthcare provider.</p> <p> <span class="Bold">The most common side effects of Clindesse include:</span> </p> <p>•  fungal infection in your vagina that may require treatment with an antifungal medicine.</p> <p>•  headache</p> <p>•  back pain</p> <p>•  constipation</p> <p>•  urinary tract infection</p> <p>Tell your healthcare provider if you have any side effect that bothers you or that does not go away.</p> <p>These are not all of the possible side effects of Clindesse. For more information, ask your healthcare provider or pharmacist.</p> <p>Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First"> <span class="Bold">How should I store Clindesse?</span> </p> <p>•  Store Clindesse between 68°F to 77°F (20°C to 25°C).</p> <p> <span class="Bold">Keep Clindesse and all medicines out of the reach of children.</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First"> <span class="Bold">General information about the safe and effective use of Clindesse.</span> </p> <p>Medicines are sometimes prescribed for purposes other than those listed in a patient information leaflet. Do not use Clindesse for a condition for which it was not prescribed. Do not give Clindesse to other people, even if they have the same symptoms you have. It may harm them.</p> <p>You can ask your pharmacist or healthcare provider for information about Clindesse that is written for health professionals.</p> </td> </tr> <tr class="Last"> <td class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First"> <span class="Bold">What are the ingredients in Clindesse?</span> </p> <p> <span class="Bold">Active ingredient: </span>clindamycin phosphate</p> <p> <span class="Bold">Inactive ingredients: </span>edetate disodium, glycerol monoisostearate, lecithin, methylparaben, microcrystalline wax, mineral oil, polyglyceryl-3-oleate, propylparaben, purified water, silicon dioxide and sorbitol solution.</p> <p></p> <p>For more information, go to www.clindesse.com or call 1-866-634-9120</p> </td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table width=\"100%\">\n<col width=\"100%\"/>\n<tbody class=\"Headless\">\n<tr class=\"First\">\n<td align=\"center\" class=\"Botrule Lrule Rrule Toprule\" valign=\"top\">\n<p class=\"First\">\n<span class=\"Bold\">PATIENT INFORMATION</span>\n</p>\n<p>\n<span class=\"Bold\">Clindesse (clin-DESS)</span>\n</p>\n<p>\n<span class=\"Bold\">(clindamycin phosphate)</span>\n</p>\n<p>\n<span class=\"Bold\">Vaginal Cream, 2%</span>\n</p>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule\" valign=\"top\">\n<p class=\"First\">\n<span class=\"Bold\">Important Information: </span>Clindesse is for intravaginal use only. Do not use in the eyes, mouth, or on your skin.</p>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule\" valign=\"top\">\n<p class=\"First\">\n<span class=\"Bold\">What is Clindesse?</span>\n</p>\n<p>•  Clindesse vaginal cream is a prescription medicine used to treat bacterial vaginal infections in women who are not pregnant.</p>\n<p>•  It is not known if Clindesse is safe and effective in females who have not yet reached puberty.</p>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule\" valign=\"top\">\n<p class=\"First\">\n<span class=\"Bold\">Do not use Clindesse if you:</span>\n</p>\n<p>•  are allergic to clindamycin or other lincosamide antibiotic medicines or are allergic to any of the ingredients in Clindesse. See the end of this leaflet for a complete list of ingredients in Clindesse.</p>\n<p>•  have had bowel problems such as:</p>\n<p>    ◦  inflammation of your intestines (enteritis)</p>\n<p>    ◦  inflammation of your colon (colitis)</p>\n<p>    ◦  diarrhea due to a <span class=\"Italics\">Clostridioides difficile</span>-associated diarrhea (CDAD)</p>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule\" valign=\"top\">\n<p class=\"First\">\n<span class=\"Bold\">Before using Clindesse, tell your healthcare provider about all of your medical conditions, including if you:</span>\n</p>\n<p>•  are pregnant or plan to become pregnant. It is not known if Clindesse will harm your unborn baby. Tell your healthcare provider if you become pregnant during treatment with Clindesse.</p>\n<p>•  are breastfeeding or plan to breastfeed. The amount of Clindesse which passes into your breast milk is low and is not expected to harm your baby. Talk with your healthcare provider about the best way to feed your baby while using Clindesse.</p>\n<p>\n<span class=\"Bold\">Tell your healthcare provider about all the medicines you take</span>, including prescription and over-the-counter medicines, vitamins, and herbal supplements.</p>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule\" valign=\"top\">\n<p class=\"First\">\n<span class=\"Bold\">How should I use Clindesse?</span>\n</p>\n<p>•  Use Clindesse exactly as your healthcare provider tells you to use it.</p>\n<p>•  Use 1 filled applicator of Clindesse in the vagina at any time of the day.</p>\n<p>•  Do not use any medicine from the tube or applicator more than 1 time. Clindesse is for 1 time (single-use) only.</p>\n<p>•  Do not use Clindesse in the eyes, mouth, or on your skin. If you accidently get Clindesse in your eyes rinse your eyes with cool tap water right away and call your healthcare provider.</p>\n<p>•  See the <span class=\"Bold\">Instructions for Use</span> at the end of this Patient Information leaflet for more information about how to fill the applicator and use Clindesse.</p>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule\" valign=\"top\">\n<p class=\"First\">\n<span class=\"Bold\">What should I avoid while using Clindesse?</span>\n</p>\n<p>\n<span class=\"Bold\">After you insert Clindesse:</span>\n</p>\n<p>•  <span class=\"Bold\">Do not</span> have vaginal sex or use vaginal products (such as tampons or douches) during your treatment.</p>\n<p>•  <span class=\"Bold\">Do not</span> use barrier contraceptive products during your treatment or for 5 days after your treatment.</p>\n<p>    ◦  Barrier contraceptives include condoms or contraceptive diaphragms used for birth control or to protect yourself against Human Immunodeficiency Virus (HIV) or other sexually transmitted diseases (STDs).</p>\n<p>    ◦  Clindesse contains mineral oil that may weaken latex or rubber products in condoms or vaginal contraceptive diaphragms.</p>\n<p>    ◦  Condoms or vaginal contraceptive diaphragms may not work as well for preventing pregnancy, or for protecting against HIV and other STDs.</p>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule\" valign=\"top\">\n<p class=\"First\">\n<span class=\"Bold\">What are the possible side effects of Clindesse?</span>\n</p>\n<p>\n<span class=\"Bold\">Clindesse may cause serious side effects, including diarrhea. </span>One type of diarrhea is caused by an infection in your intestines called <span class=\"Italics\">Clostridioides difficile</span>-associated diarrhea (CDAD), which may range in severity from mild diarrhea to colitis that can lead to death. If you have diarrhea after you use Clindesse, call your healthcare provider.</p>\n<p>\n<span class=\"Bold\">The most common side effects of Clindesse include:</span>\n</p>\n<p>•  fungal infection in your vagina that may require treatment with an antifungal medicine.</p>\n<p>•  headache</p>\n<p>•  back pain</p>\n<p>•  constipation</p>\n<p>•  urinary tract infection</p>\n<p>Tell your healthcare provider if you have any side effect that bothers you or that does not go away.</p>\n<p>These are not all of the possible side effects of Clindesse. For more information, ask your healthcare provider or pharmacist.</p>\n<p>Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.</p>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule\" valign=\"top\">\n<p class=\"First\">\n<span class=\"Bold\">How should I store Clindesse?</span>\n</p>\n<p>•  Store Clindesse between 68°F to 77°F (20°C to 25°C).</p>\n<p>\n<span class=\"Bold\">Keep Clindesse and all medicines out of the reach of children.</span>\n</p>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule\" valign=\"top\">\n<p class=\"First\">\n<span class=\"Bold\">General information about the safe and effective use of Clindesse.</span>\n</p>\n<p>Medicines are sometimes prescribed for purposes other than those listed in a patient information leaflet. Do not use Clindesse for a condition for which it was not prescribed. Do not give Clindesse to other people, even if they have the same symptoms you have. It may harm them.</p>\n<p>You can ask your pharmacist or healthcare provider for information about Clindesse that is written for health professionals.</p>\n</td>\n</tr>\n<tr class=\"Last\">\n<td class=\"Botrule Lrule Rrule Toprule\" valign=\"top\">\n<p class=\"First\">\n<span class=\"Bold\">What are the ingredients in Clindesse?</span>\n</p>\n<p>\n<span class=\"Bold\">Active ingredient: </span>clindamycin phosphate</p>\n<p>\n<span class=\"Bold\">Inactive ingredients: </span>edetate disodium, glycerol monoisostearate, lecithin, methylparaben, microcrystalline wax, mineral oil, polyglyceryl-3-oleate, propylparaben, purified water, silicon dioxide and sorbitol solution.</p>\n<p></p>\n<p>For more information, go to www.clindesse.com or call 1-866-634-9120</p>\n</td>\n</tr>\n</tbody>\n</table></div>" }

This Patient Information has been approved by the U.S. Food and Drug Administration

{ "type": "p", "children": [], "text": "This Patient Information has been approved by the U.S. Food and Drug Administration" }

01/2025

{ "type": "p", "children": [], "text": "01/2025" }

Clindesse (clin-DESS)

{ "type": "p", "children": [], "text": "\nClindesse (clin-DESS)\n" }

(clindamycin phosphate)

{ "type": "p", "children": [], "text": "\n(clindamycin phosphate)\n" }

Vaginal Cream, 2%

{ "type": "p", "children": [], "text": "\nVaginal Cream, 2%\n" }

For vaginal use only.

{ "type": "p", "children": [], "text": "\nFor vaginal use only.\n" }

Do not put Clindesse in your eyes, mouth, or on your skin.

{ "type": "p", "children": [], "text": "\nDo not put Clindesse in your eyes, mouth, or on your skin.\n" }

It is important that you read and follow these directions on how to use Clindesse vaginal cream properly.

{ "type": "p", "children": [], "text": "It is important that you read and follow these directions on how to use Clindesse vaginal cream properly." }

Clindesse comes in a single-dose, pre-filled, disposable applicator that gives you a certain amount of clindamycin cream to be inserted into your vagina.

{ "type": "p", "children": [], "text": "Clindesse comes in a single-dose, pre-filled, disposable applicator that gives you a certain amount of clindamycin cream to be inserted into your vagina." }

Step 1. Prepare the applicator.

{ "type": "p", "children": [], "text": "\nStep 1. Prepare the applicator.\n" }

Peel back the protective foil and remove the pre-filled applicator. Do not remove the tip.

{ "type": "p", "children": [], "text": "Peel back the protective foil and remove the pre-filled applicator. Do not remove the tip. " }

The applicator is made to be used with the tip in place.

{ "type": "p", "children": [], "text": "The applicator is made to be used with the tip in place. " }

Do not use the applicator if the tip has been removed (see Figure 1).

{ "type": "p", "children": [], "text": "Do not use the applicator if the tip has been removed (see Figure 1)." }

Activate the plunger before you use it. To activate the plunger, pull the ring back to fully extend the plunger while you firmly hold the applicator (see Figure 2).

{ "type": "p", "children": [], "text": "Activate the plunger before you use it. To activate the plunger, pull the ring back to fully extend the plunger while you firmly hold the applicator (see Figure 2)." }

Step 2. Insert the applicator.

{ "type": "p", "children": [], "text": "\nStep 2. Insert the applicator.\n" }

Gently insert the applicator into your vagina as far as it will comfortably go (see Figure 3).

{ "type": "p", "children": [], "text": "Gently insert the applicator into your vagina as far as it will comfortably go (see Figure 3)." }

Step 3. Apply the cream.

{ "type": "p", "children": [], "text": "\nStep 3. Apply the cream.\n" }

Push the plunger in until all of the cream goes into your vagina (see Figures 4 and 5).

{ "type": "p", "children": [], "text": "Push the plunger in until all of the cream goes into your vagina (see Figures 4 and 5)." }

Step 4. Remove the empty applicator from your vagina and throw it away in the trash.

{ "type": "p", "children": [], "text": "\nStep 4. Remove the empty applicator from your vagina and throw it away in the trash.\n" }

This Instructions for Use has been approved by the U.S. Food and Drug Administration

{ "type": "p", "children": [], "text": "This Instructions for Use has been approved by the U.S. Food and Drug Administration" }

01/2025

{ "type": "p", "children": [], "text": "01/2025" }

Clindesse®

{ "type": "p", "children": [], "text": "Clindesse®" }

(clindamycin phosphate) Vaginal Cream, 2%

{ "type": "p", "children": [], "text": "(clindamycin phosphate) Vaginal Cream, 2%" }

NDC 45802-042-01

{ "type": "p", "children": [], "text": "NDC 45802-042-01" }

Rx Only

{ "type": "p", "children": [], "text": "Rx Only" }

This applicator delivers approximately 5 g of vaginal cream containing approximately 100 mg of clindamycin.

{ "type": "p", "children": [], "text": "This applicator delivers approximately 5 g of vaginal cream containing approximately 100 mg of clindamycin." }

One complete course of therapy in a convenient, prefilled, and disposable applicator.

{ "type": "p", "children": [], "text": "One complete course of therapy in a convenient, prefilled, and disposable applicator." }

NET WT 5.8 g

{ "type": "p", "children": [], "text": "NET WT 5.8 g" }

The following image is a placeholder representing the product identifier that is either affixed or imprinted on the drug package label during the packaging operation.

{ "type": "p", "children": [], "text": "The following image is a placeholder representing the product identifier that is either affixed or imprinted on the drug package label during the packaging operation." }

CABTREO is indicated for the topical treatment of acne vulgaris in adult and pediatric patients 12 years of age and older.

{ "type": "p", "children": [], "text": "CABTREO is indicated for the topical treatment of acne vulgaris in adult and pediatric patients 12 years of age and older." }

Cleanse the affected area gently. After the skin is dry, apply a thin layer of CABTREO to the affected area once daily.

{ "type": "p", "children": [], "text": "Cleanse the affected area gently. After the skin is dry, apply a thin layer of CABTREO to the affected area once daily." }

Wash hands thoroughly after application of CABTREO.

{ "type": "p", "children": [], "text": "Wash hands thoroughly after application of CABTREO." }

Avoid the eyes, mouth, paranasal creases, mucous membranes, and areas of broken, eczematous, or sunburned skin [ see Warnings and Precautions ( 5.3)].

{ "type": "p", "children": [], "text": "Avoid the eyes, mouth, paranasal creases, mucous membranes, and areas of broken, eczematous, or sunburned skin [\n \n see Warnings and Precautions (\n \n 5.3)].\n \n \n" }

CABTREO is for topical use only. Not for oral, ophthalmic, or intravaginal use.

{ "type": "p", "children": [], "text": "CABTREO is for topical use only. Not for oral, ophthalmic, or intravaginal use." }

Topical gel: 1.2% clindamycin phosphate, 0.15% adapalene, and 3.1% benzoyl peroxide as a white to off-white, opaque gel.

{ "type": "p", "children": [], "text": "Topical gel: 1.2% clindamycin phosphate, 0.15% adapalene, and 3.1% benzoyl peroxide as a white to off-white, opaque gel." }

CABTREO is supplied in 20-gram and 50-gram pumps.

{ "type": "p", "children": [], "text": "CABTREO is supplied in 20-gram and 50-gram pumps." }

CABTREO is contraindicated in patients with:

{ "type": "p", "children": [], "text": "CABTREO is contraindicated in patients with:" }

{ "type": "ul", "children": [ "Known hypersensitivity to clindamycin, adapalene, benzoyl peroxide, any other components of CABTREO, or lincomycin [\n \n see Warnings and Precautions(\n \n 5.1)].\n \n \n", "A history of regional enteritis, ulcerative colitis, or antibiotic-associated colitis [\n \n see Warnings and Precautions (\n \n 5.2)].\n \n \n" ], "text": "" }

Hypersensitivity reactions, including anaphylaxis, angioedema, and urticaria, have been reported with use of clindamycin phosphate, benzoyl peroxide, and adapalene [see Adverse Reactions ( 6.2)]. If a serious hypersensitivity reaction occurs, discontinue CABTREO immediately and initiate appropriate therapy.

Diarrhea, bloody diarrhea, and colitis have been reported with the use of topical and systemic clindamycin. Severe colitis has occurred with an onset of up to several weeks following cessation of therapy. Antiperistaltic agents such as opiates and diphenoxylate with atropine may prolong and/or worsen severe colitis. Severe colitis may result in death. Discontinue CABTREO if diarrhea occurs.

CABTREO may increase sensitivity to ultraviolet light. Avoid or minimize sun exposure (including use of tanning beds, and sun lamps) following CABTREO application. Instruct patients to use sunscreen products and wear protective apparel (e.g., hat) when exposure to sun cannot be avoided.

Stinging/burning/pain, erythema, dryness, irritation, exfoliation, and dermatitis have been reported with use of CABTREO. These application site adverse reactions occurred at a greater frequency in CABTREO-treated subjects than in vehicle-treated subjects. These adverse reactions are most likely to occur during the first four weeks of treatment [ see Adverse Reactions ( 6.1)] .

Irritant and allergic contact dermatitis have been reported with use of CABTREO.

Weather extremes, such as wind or cold, may be irritating to patients under treatment with CABTREO.

Depending upon the severity of these adverse reactions, instruct patients to use a moisturizer, reduce the frequency of the application of CABTREO, or discontinue use. Avoid applying CABTREO to areas of broken, eczematous, or sunburned skin. Avoid use of “waxing” as a depilatory method on skin treated with CABTREO.

Avoid concomitant use of other potentially irritating topical products such as peeling, desquamating, or abrasive agents and products with high concentrations of alcohol, astringents, spices, or limes.

Use of CABTREO with concomitant topical acne therapy has not been evaluated.

Because 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.

In two multicenter, randomized, double-blind, vehicle-controlled clinical trials (Trial 1 and Trial 2), 363 adult and pediatric subjects 10 years of age and older with facial acne vulgaris were treated with CABTREO or vehicle topically once daily for 12 weeks [see Clinical Studies ( 14)] . Adverse reactions reported by >1% of subjects treated with CABTREO and more frequently than subjects treated with vehicle are summarized in Table 1. These adverse reactions were mild (59%), moderate (36.4%), and severe (4.5%). Overall, 2.5% (6/242) of subjects discontinued CABTREO because of local skin reactions.

<div class="scrollingtable"><table width="100%"> <caption> <span>Table 1: Adverse Reactions Reported by &gt;1% of Subjects with Facial Acne Vulgaris Treated with CABTREO (and More Frequently than Vehicle) in Trials 1 and 2</span> </caption> <col width="37%"/> <col width="33%"/> <col width="30%"/> <thead> <tr class="First"> <th align="center" class="Botrule Lrule Rrule Toprule" colspan="3" valign="bottom"><span class="Bold">Adverse Reactions</span> <br/> <span class="Bold">N (%)</span></th> </tr> <tr class="Last"> <th align="left" class="Botrule Lrule Rrule" valign="bottom"></th><th align="center" class="Botrule Lrule Rrule" valign="bottom"><span class="Bold">CABTREO</span> <br/> <span class="Bold">N=242</span></th><th align="center" class="Botrule Lrule Rrule" valign="bottom"><span class="Bold">Vehicle</span> <br/> <span class="Bold">N=121</span></th> </tr> </thead> <tfoot> <tr> <td align="left" colspan="3"> <dl class="Footnote"> <dt> <a href="#footnote-reference-1" name="footnote-1">*</a> </dt> <dd>Application site pain also includes application site stinging and burning</dd> <dt> <a href="#footnote-reference-2" name="footnote-2">†</a> </dt> <dd>Application site erythema also includes erythema</dd> <dt> <a href="#footnote-reference-3" name="footnote-3">‡</a> </dt> <dd>Application site dryness also includes xerosis</dd> </dl> </td> </tr> </tfoot> <tbody> <tr class="First"> <td class="Botrule Lrule Rrule Toprule" valign="bottom"> <p class="First">Application site pain <a class="Sup" href="#footnote-1" name="footnote-reference-1">*</a> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="bottom"> <p class="First">33 (13.6)</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="bottom"> <p class="First">1 (0.8)</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="bottom"> <p class="First">Application site erythema <a class="Sup" href="#footnote-2" name="footnote-reference-2">†</a> </p> </td><td align="center" class="Botrule Lrule Rrule" valign="bottom"> <p class="First">11 (4.5)</p> </td><td align="center" class="Botrule Lrule Rrule" valign="bottom"> <p class="First">0</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="bottom"> <p class="First">Application site dryness <a class="Sup" href="#footnote-3" name="footnote-reference-3">‡</a> </p> </td><td align="center" class="Botrule Lrule Rrule" valign="bottom"> <p class="First">10 (4.1)</p> </td><td align="center" class="Botrule Lrule Rrule" valign="bottom"> <p class="First">1 (0.8)</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="bottom"> <p class="First">Application site irritation</p> </td><td align="center" class="Botrule Lrule Rrule" valign="bottom"> <p class="First">5 (2.1)</p> </td><td align="center" class="Botrule Lrule Rrule" valign="bottom"> <p class="First">0</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="bottom"> <p class="First">Application site exfoliation</p> </td><td align="center" class="Botrule Lrule Rrule" valign="bottom"> <p class="First">4 (1.7)</p> </td><td align="center" class="Botrule Lrule Rrule" valign="bottom"> <p class="First">0</p> </td> </tr> <tr class="Last"> <td class="Botrule Lrule Rrule" valign="bottom"> <p class="First">Application site dermatitis</p> </td><td align="center" class="Botrule Lrule Rrule" valign="bottom"> <p class="First">3 (1.2)</p> </td><td align="center" class="Botrule Lrule Rrule" valign="bottom"> <p class="First">0</p> </td> </tr> </tbody> </table></div>

Local tolerability evaluations were conducted at each study visit by assessment of erythema, scaling, itching, burning, and stinging. Table 2 presents the signs and symptoms of local facial tolerability during the 12 Week treatment period in subjects treated with CABTREO.

<div class="scrollingtable"><table width="100%"> <caption> <span>Table 2: Facial Cutaneous Tolerability Assessment During 12-Week Treatment Period in Subjects with Acne Vulgaris Treated with CABTREO in Trials 1 and 2</span> </caption> <col width="14%"/> <col width="14%"/> <col width="14%"/> <col width="14%"/> <col width="14%"/> <col width="14%"/> <col width="13%"/> <tfoot> <tr> <td align="left" colspan="7"> <dl class="Footnote"> <dt> <a href="#footnote-reference-4" name="footnote-4">*</a> </dt> <dd>The denominators for calculating the percentages were the number of subjects with at least one post-baseline cutaneous tolerability assessment.</dd> <dt> <a href="#footnote-reference-5" name="footnote-5">†</a> </dt> <dd>The denominators for calculating the percentages were the number of subjects with Week 12 assessment.</dd> </dl> </td> </tr> </tfoot> <tbody class="Headless"> <tr class="First"> <td class="Botrule Lrule Rrule Toprule" rowspan="2" valign="bottom"></td><td align="center" class="Botrule Lrule Rrule Toprule" colspan="3" valign="middle"> <p class="First">Maximum During Treatment <a class="Sup" href="#footnote-4" name="footnote-reference-4">*</a> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" colspan="3" valign="top"> <p class="First">Week 12 (End of Treatment) <a class="Sup" href="#footnote-5" name="footnote-reference-5">†</a> </p> </td> </tr> <tr> <td align="center" class="Botrule Lrule Rrule" valign="middle"> <p class="First">Mild <br/> (%) </p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">Mod <br/> (%) </p> </td><td align="center" class="Botrule Lrule Rrule" valign="middle"> <p class="First">Severe <br/> (%) </p> </td><td align="center" class="Botrule Lrule Rrule" valign="middle"> <p class="First">Mild <br/> (%) </p> </td><td align="center" class="Botrule Lrule Rrule" valign="middle"> <p class="First">Mod <br/> (%) </p> </td><td align="center" class="Botrule Lrule Rrule" valign="middle"> <p class="First">Severe <br/> (%) </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" colspan="7" valign="bottom"> <p class="First">CABTREO (N = 242)</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="bottom"> <p class="First">Erythema</p> </td><td align="center" class="Botrule Lrule Rrule" valign="middle"> <p class="First">34.2</p> </td><td align="center" class="Botrule Lrule Rrule" valign="middle"> <p class="First">19.7</p> </td><td align="center" class="Botrule Lrule Rrule" valign="middle"> <p class="First">2.1</p> </td><td align="center" class="Botrule Lrule Rrule" valign="middle"> <p class="First">22.4</p> </td><td align="center" class="Botrule Lrule Rrule" valign="middle"> <p class="First">6.5</p> </td><td align="center" class="Botrule Lrule Rrule" valign="middle"> <p class="First">0.5</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="bottom"> <p class="First">Burning</p> </td><td align="center" class="Botrule Lrule Rrule" valign="middle"> <p class="First">29.6</p> </td><td align="center" class="Botrule Lrule Rrule" valign="middle"> <p class="First">10.7</p> </td><td align="center" class="Botrule Lrule Rrule" valign="middle"> <p class="First">3.0</p> </td><td align="center" class="Botrule Lrule Rrule" valign="middle"> <p class="First">4.2</p> </td><td align="center" class="Botrule Lrule Rrule" valign="middle"> <p class="First">1.4</p> </td><td align="center" class="Botrule Lrule Rrule" valign="middle"> <p class="First">0.9</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="bottom"> <p class="First">Scaling</p> </td><td align="center" class="Botrule Lrule Rrule" valign="middle"> <p class="First">26.7</p> </td><td align="center" class="Botrule Lrule Rrule" valign="middle"> <p class="First">3.4</p> </td><td align="center" class="Botrule Lrule Rrule" valign="middle"> <p class="First">0</p> </td><td align="center" class="Botrule Lrule Rrule" valign="middle"> <p class="First">7.0</p> </td><td align="center" class="Botrule Lrule Rrule" valign="middle"> <p class="First">0.9</p> </td><td align="center" class="Botrule Lrule Rrule" valign="middle"> <p class="First">0</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="bottom"> <p class="First">Itching</p> </td><td align="center" class="Botrule Lrule Rrule" valign="middle"> <p class="First">24.3</p> </td><td align="center" class="Botrule Lrule Rrule" valign="middle"> <p class="First">3.4</p> </td><td align="center" class="Botrule Lrule Rrule" valign="middle"> <p class="First">0.4</p> </td><td align="center" class="Botrule Lrule Rrule" valign="middle"> <p class="First">6.0</p> </td><td align="center" class="Botrule Lrule Rrule" valign="middle"> <p class="First">0.9</p> </td><td align="center" class="Botrule Lrule Rrule" valign="middle"> <p class="First">0</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="bottom"> <p class="First">Stinging</p> </td><td align="center" class="Botrule Lrule Rrule" valign="middle"> <p class="First">20.5</p> </td><td align="center" class="Botrule Lrule Rrule" valign="middle"> <p class="First">5.1</p> </td><td align="center" class="Botrule Lrule Rrule" valign="middle"> <p class="First">2.6</p> </td><td align="center" class="Botrule Lrule Rrule" valign="middle"> <p class="First">2.3</p> </td><td align="center" class="Botrule Lrule Rrule" valign="middle"> <p class="First">0.9</p> </td><td align="center" class="Botrule Lrule Rrule" valign="middle"> <p class="First">0.5</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" colspan="7" valign="bottom"> <p class="First">Vehicle (N = 121)</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="bottom"> <p class="First">Erythema</p> </td><td align="center" class="Botrule Lrule Rrule" valign="middle"> <p class="First">22.5</p> </td><td align="center" class="Botrule Lrule Rrule" valign="middle"> <p class="First">21.7</p> </td><td align="center" class="Botrule Lrule Rrule" valign="middle"> <p class="First">1.7</p> </td><td align="center" class="Botrule Lrule Rrule" valign="middle"> <p class="First">25.5</p> </td><td align="center" class="Botrule Lrule Rrule" valign="middle"> <p class="First">5.5</p> </td><td align="center" class="Botrule Lrule Rrule" valign="middle"> <p class="First">0</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="bottom"> <p class="First">Burning</p> </td><td align="center" class="Botrule Lrule Rrule" valign="middle"> <p class="First">2.5</p> </td><td align="center" class="Botrule Lrule Rrule" valign="middle"> <p class="First">0.8</p> </td><td align="center" class="Botrule Lrule Rrule" valign="middle"> <p class="First">0.8</p> </td><td align="center" class="Botrule Lrule Rrule" valign="middle"> <p class="First">0.9</p> </td><td align="center" class="Botrule Lrule Rrule" valign="middle"> <p class="First">0</p> </td><td align="center" class="Botrule Lrule Rrule" valign="middle"> <p class="First">0</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="bottom"> <p class="First">Scaling</p> </td><td align="center" class="Botrule Lrule Rrule" valign="middle"> <p class="First">12.5</p> </td><td align="center" class="Botrule Lrule Rrule" valign="middle"> <p class="First">0</p> </td><td align="center" class="Botrule Lrule Rrule" valign="middle"> <p class="First">0</p> </td><td align="center" class="Botrule Lrule Rrule" valign="middle"> <p class="First">4.5</p> </td><td align="center" class="Botrule Lrule Rrule" valign="middle"> <p class="First">0</p> </td><td align="center" class="Botrule Lrule Rrule" valign="middle"> <p class="First">0</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="bottom"> <p class="First">Itching</p> </td><td align="center" class="Botrule Lrule Rrule" valign="middle"> <p class="First">11.6</p> </td><td align="center" class="Botrule Lrule Rrule" valign="middle"> <p class="First">0.8</p> </td><td align="center" class="Botrule Lrule Rrule" valign="middle"> <p class="First">0</p> </td><td align="center" class="Botrule Lrule Rrule" valign="middle"> <p class="First">1.8</p> </td><td align="center" class="Botrule Lrule Rrule" valign="middle"> <p class="First">0</p> </td><td align="center" class="Botrule Lrule Rrule" valign="middle"> <p class="First">0</p> </td> </tr> <tr class="Last"> <td class="Botrule Lrule Rrule" valign="bottom"> <p class="First">Stinging</p> </td><td align="center" class="Botrule Lrule Rrule" valign="middle"> <p class="First">3.3</p> </td><td align="center" class="Botrule Lrule Rrule" valign="middle"> <p class="First">0.8</p> </td><td align="center" class="Botrule Lrule Rrule" valign="middle"> <p class="First">0</p> </td><td align="center" class="Botrule Lrule Rrule" valign="middle"> <p class="First">1.8</p> </td><td align="center" class="Botrule Lrule Rrule" valign="middle"> <p class="First">0</p> </td><td align="center" class="Botrule Lrule Rrule" valign="middle"> <p class="First">0</p> </td> </tr> </tbody> </table></div>

Local tolerability scores for erythema, scaling, itching, burning, and stinging increased during the first two weeks of treatment and decreased thereafter.

The following adverse reactions have been identified during post-approval use of products containing clindamycin phosphate, adapalene, and benzoyl peroxide as the active ingredients. Because post-marketing adverse 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.

Immune system disorders:anaphylaxis and allergic reactions including eyelid edema, throat tightness, swelling of the face, and eczema. [see Contraindications ( 4)] .

Local Adverse Reactions:sunburn, blister, pruritis, hyperpigmentation and hypopigmentation.

Gastrointestinal Disorders:abdominal pain and gastrointestinal disturbances.

Bacterial infections:gram negative folliculitis

Neuromuscular Blocking Agents

{ "type": "p", "children": [], "text": "\nNeuromuscular Blocking Agents\n" }

Clindamycin has been shown to have neuromuscular blocking properties that may enhance the action of other neuromuscular blocking agents. Use CABTREO with caution in patients receiving such agents.

{ "type": "p", "children": [], "text": "Clindamycin has been shown to have neuromuscular blocking properties that may enhance the action of other neuromuscular blocking agents. Use CABTREO with caution in patients receiving such agents." }

Risk Summary

Available data with CABTREO use in pregnant women are insufficient to evaluate a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. Animal reproduction studies have not been conducted with CABTREO.

Clindamycin

In published clinical trials and observational studies with pregnant women, oral or IV administration of clindamycin has not been associated with an increased frequency of major birth defects, miscarriage, or other adverse maternal or fetal outcomes. In animal reproduction studies, clindamycin phosphate did not cause malformations or embryofetal development toxicity in pregnant rats and mice when administered during the period of organogenesis at systemic doses up to 192 times the maximum recommended human dose (MRHD) of 2.5 g CABTREO, based on a body surface area (mg/m 2) comparison.

Adapalene

Available data from clinical trials with adapalene topical gel use in pregnant women are insufficient to establish a drug-associated risk of major birth defects, miscarriage or other adverse maternal or fetal outcomes. In animal reproduction studies, oral administration of adapalene to pregnant rats and rabbits during organogenesis at doses 64 and 128 times, respectively, the MRHD resulted in fetal skeletal and visceral malformations ( see Data).

Benzoyl peroxide

The systemic exposure of topical benzoyl peroxide is unknown. Based on published literature, benzoyl peroxide is rapidly metabolized to benzoic acid (an endogenous substance), which is eliminated in the urine. Hence, maternal use is not expected to result in fetal exposure of the drug.

The background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, and other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively.

Data

Animal Data

Animal reproductive/developmental toxicity studies have not been conducted with CABTREO. Clindamycin phosphate administration during the period of organogenesis in pregnant rats and mice at oral doses up to 600 mg/kg/day (192 and 96 times the MRHD, respectively, based on a mg/m 2comparison) or subcutaneous doses up to 200 mg/kg/day (64 and 32 times the MRHD, respectively, based on a mg/m 2comparison) did not cause fetal malformations or fetotoxicity.

No malformations were observed in rats treated with oral adapalene doses of 0.15 to 5.0 mg/kg/day (up to 13 times the MRHD based on a mg/m 2comparison). However, malformations were observed in rats and rabbits when treated with oral doses of ≥ 25 mg/kg/day adapalene (64 and 128 times the MRHD, respectively, based on a mg/m 2comparison). Findings included cleft palate, microphthalmia, encephalocele, and skeletal abnormalities in rats and umbilical hernia, exophthalmos, and kidney and skeletal abnormalities in rabbits.

Dermal adapalene embryofetal development studies in rats and rabbits at doses up to 6.0 mg/kg/day adapalene (up to 15 and 30 times the MRHD, respectively, based on a mg/m 2comparison) exhibited no fetotoxicity and only minimal increases in skeletal variations (supernumerary ribs in both species and delayed ossification in rabbits).

Risk Summary

The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for CABTREO and any potential adverse effects on the breastfed child from CABTREO or from the underlying maternal condition.

Clindamycin

There are no data on the presence of clindamycin in human milk, the effects on the breastfed child, or the effects on milk production following topical administration. However, clindamycin has been reported to be present in human milk in small amounts following oral and parenteral administration.

Adapalene

There are no data on the presence of topical adapalene gel or its metabolite in human milk, the effects on the breastfed infant, or the effects on milk production. In animal studies, adapalene is present in rat milk with oral administration of the drug. When a drug is present in animal milk, it is likely that the drug will be present in human milk. It is possible that topical administration of large amounts of adapalene could result in sufficient systemic absorption to produce detectable quantities in human milk ( see Clinical Considerations).

Benzoyl peroxide

There are no data on the presence of topical benzoyl peroxide in human milk, its effects on the breastfed infant, or its effects on milk production. The systemic exposure of benzoyl peroxide is unknown. Based on the published literature, benzoyl peroxide is rapidly metabolized to benzoic acid (an endogenous substance), which is eliminated in the urine. Any amount of benzoyl peroxide excreted into human milk by a nursing mother would be expected to be rapidly metabolized by tissue and stomach esterases.

Clinical Considerations

To minimize potential exposure to the breastfed infant via breastmilk, use CABTREO on the smallest area of skin and for the shortest duration possible while breastfeeding. To avoid direct infant exposure, advise patients who are breastfeeding not to apply CABTREO directly to the nipple and areola. If applied to the patient’s chest, care should be taken to avoid infant exposure via direct contact with the infant skin.

The safety and effectiveness of CABTREO for the topical treatment of acne vulgaris have been established in pediatric patients 12 years of age and older. Use of CABTREO for this indication is supported by data from two randomized, double-blind, vehicle-controlled trials [ see Clinical Studies ( 14)].

The safety and effectiveness of CABTREO have not been established in pediatric patients younger than 12 years of age.

Clinical studies of CABTREO did not include any subjects 65 years of age and older to determine whether they respond differently from younger adult subjects.

CABTREO (clindamycin phosphate, adapalene, and benzoyl peroxide) topical gel is a white to off-white, opaque gel. Each gram of CABTREO contains 12 mg (1.2%) clindamycin phosphate, equivalent to 10 mg (1%) clindamycin and 1.5 mg (0.15%) adapalene, and 31 mg (3.1%) benzoyl peroxide. Clindamycin phosphate is a water-soluble ester of the semisynthetic antibiotic produced by a 7(S)-chloro-substitution of the 7(R)-hydroxyl group of the parent antibiotic lincomycin. Adapalene, a synthetic retinoid, is a naphthoic acid derivative with retinoid-like properties. Benzoyl peroxide is an oxidizing agent.

{ "type": "p", "children": [], "text": "CABTREO (clindamycin phosphate, adapalene, and benzoyl peroxide) topical gel is a white to off-white, opaque gel. Each gram of CABTREO contains 12 mg (1.2%) clindamycin phosphate, equivalent to 10 mg (1%) clindamycin and 1.5 mg (0.15%) adapalene, and 31 mg (3.1%) benzoyl peroxide. Clindamycin phosphate is a water-soluble ester of the semisynthetic antibiotic produced by a 7(S)-chloro-substitution of the 7(R)-hydroxyl group of the parent antibiotic lincomycin. Adapalene, a synthetic retinoid, is a naphthoic acid derivative with retinoid-like properties. Benzoyl peroxide is an oxidizing agent." }

The chemical name for clindamycin phosphate is Methyl-7-chloro-6,7,8-trideoxy-6-(1-methyl-trans-4-propyl-L-2-pyrrolidinecarboxamido)-1-thio-L-threo-α-D-galacto-octopyranoside 2-(dihydrogen phosphate). The structural formula for clindamycin phosphate is represented below:

{ "type": "p", "children": [], "text": "The chemical name for clindamycin phosphate is Methyl-7-chloro-6,7,8-trideoxy-6-(1-methyl-trans-4-propyl-L-2-pyrrolidinecarboxamido)-1-thio-L-threo-α-D-galacto-octopyranoside 2-(dihydrogen phosphate). The structural formula for clindamycin phosphate is represented below:" }

Clindamycin phosphate:

{ "type": "p", "children": [], "text": "Clindamycin phosphate:" }

Molecular Formula: C 18H 34ClN 2O 8PS Molecular Weight: 504.97

{ "type": "p", "children": [], "text": "Molecular Formula: C\n \n 18H\n \n 34ClN\n \n 2O\n \n 8PS \n Molecular Weight: 504.97\n\n " }

The chemical name for adapalene is 6-[3-(1-Adamantyl)-4-methoxyphenyl]-2-naphthoic acid. The structural formula for adapalene is represented below:

{ "type": "p", "children": [], "text": "The chemical name for adapalene is 6-[3-(1-Adamantyl)-4-methoxyphenyl]-2-naphthoic acid. The structural formula for adapalene is represented below:" }

Adapalene:

{ "type": "p", "children": [], "text": "Adapalene:" }

Molecular Formula: C 28H 28O 3

{ "type": "p", "children": [], "text": "Molecular Formula: C\n \n 28H\n \n 28O\n \n 3\n" }

Molecular Weight: 412.52

{ "type": "p", "children": [], "text": "Molecular Weight: 412.52" }

The chemical name for benzoyl peroxide is dibenzoyl peroxide. The structural formula for benzoyl peroxide is represented below:

{ "type": "p", "children": [], "text": "The chemical name for benzoyl peroxide is dibenzoyl peroxide. The structural formula for benzoyl peroxide is represented below:" }

Benzoyl peroxide:

{ "type": "p", "children": [], "text": "Benzoyl peroxide:" }

Molecular Formula: C 14H 10O 4 Molecular Weight: 242.23

{ "type": "p", "children": [], "text": "Molecular Formula: C\n \n 14H\n \n 10O\n \n 4\n Molecular Weight: 242.23\n\n " }

CABTREO contains the following inactive ingredients: carbomer homopolymer type C (carbomer 980), potassium hydroxide, propylene glycol, and purified water.

{ "type": "p", "children": [], "text": "CABTREO contains the following inactive ingredients: carbomer homopolymer type C (carbomer 980), potassium hydroxide, propylene glycol, and purified water." }

Clindamycin:Clindamycin is a lincosamide antibacterial [see Microbiology ( 12.4)] .

Adapalene:Adapalene binds to specific retinoic acid nuclear receptors but does not bind to cytosolic receptor protein. Biochemical and pharmacological profile studies have demonstrated that adapalene is a modulator of cellular differentiation, keratinization and inflammatory processes. However, the significance of these findings with regard to the mechanism of action of adapalene for the treatment of acne is unknown.

Benzoyl Peroxide:Benzoyl peroxide is an oxidizing agent with bactericidal and keratolytic effects but the precise mechanism of action is unknown.

Pharmacodynamics of CABTREO are unknown.

Systemic exposure following topical application of CABTREO was evaluated in 28 subjects in an open-label, randomized, pharmacokinetic study. Subjects aged 12 years and older with moderate to severe acne vulgaris applied 2.2 ± 0.4 (mean ± SD) grams of CABTREO to the entire face (excluding eyes and lips), neck, upper chest, upper back and shoulders once daily for 28 days.

Clindamycin phosphate concentrations were measurable in the majority of samples following single and repeated topical administration of CABTREO (LOQ = 0.05 ng/mL). The mean C maxand mean AUC [0-t]values for clindamycin phosphate were 2.44 ng/mL (range: 0.15 to 6.14 ng/mL) and 30.7 ng•h/mL (range: 1.04 to 87.4 ng•h/mL) on Days 28-29, respectively. Clindamycin (C maxand AUC [0-t]) accumulated up to approximately 3-fold between Days 1-2 and Days 28-29 following once daily application of CABTREO.

Adapalene concentrations were measurable in the majority of samples following single and repeated topical administration of CABTREO (LOQ = 0.10 ng/mL). The mean C maxand mean AUC (0-t)values for adapalene were 0.10 ng/mL (range: 0 to 0.27 ng/mL) and 2.40 ng•h/mL (range: 0.56 to 3.87 ng•h/mL) on Days 28-29, respectively. Adapalene (AUC [0-t]) accumulated up to approximately 3-fold between Days 1-2 and Days 28-29 for CABTREO.

Benzoyl peroxide is absorbed by the skin where it is converted to benzoic acid and eliminated in the urine.

Drug Interaction Studies

In Vitro Studies

Erythromycin products:Concurrent use with erythromycin topical or oral products may reduce the efficacy of CABTREO. This finding is based upon the mechanistic understanding of these drugs and published in vitro antagonism between erythromycin and clindamycin. This finding was not confirmed by a dedicated clinical study. While the clinical significance of this finding is unknown, it still warrants consideration given the potential impact on the efficacy of CABTREO.

Clindamycin binds to the 50S ribosomal subunits of susceptible bacteria and prevents elongation of peptide chains by interfering with peptidyl transfer, thereby suppressing bacterial protein synthesis.

Clindamycin and benzoyl peroxide individually have been shown to have in vitro activity against Cutibacterium acnes (C. acnes), an organism which has been associated with acne vulgaris. In an in vitro study, the minimum inhibitory concentration (MIC) for benzoyl peroxide against C. acnesis 128 mg/L. The clinical significance of this activity against C. acnesis not known.

C. acnesresistance to clindamycin has been documented. Resistance to clindamycin is often associated with resistance to erythromycin.

No carcinogenicity, genotoxicity, or fertility studies were conducted with CABTREO.

Carcinogenicity studies have been conducted with a gel formulation containing 1% clindamycin phosphate and 5% benzoyl peroxide. In a 2-year dermal carcinogenicity study in mice, treatment with the gel formulation at doses up to 15,000 mg/kg/day (up to 24 times the MRHD for clindamycin phosphate and up to 47 times the MRHD for benzoyl peroxide based on a mg/m 2comparison) did not cause any increase in tumors. However, in a 2-year dermal carcinogenicity study in rats using a different gel formulation containing 1% clindamycin phosphate and 5% benzoyl peroxide increased the incidence of keratoacanthoma at the treated skin site of male rats treated with 2,000 mg/kg/day (6.4 times the MRHD for clindamycin phosphate and 12.4 times the MRHD for benzoyl peroxide based on a mg/m 2comparison). In an oral (gavage) carcinogenicity study in rats, treatment with the gel formulation at doses up to 3,000 mg/kg/day (up to 10 times the MRHD for clindamycin phosphate and up to 19 times the MRHD for benzoyl peroxide based on a mg/m 2comparison) for up to 97 weeks did not cause any increase in tumors.

Carcinogenicity studies with adapalene were conducted in mice at topical doses of 0.4, 1.3, and 4.0 mg/kg/day of adapalene, and in rats at oral doses of 0.15, 0.5, and 1.5 mg/kg/day of adapalene. The highest dose levels are 5.1 (mice) and 3.8 (rats) times the MRHD based on a mg/m 2comparison. In the rat study, an increased incidence of benign and malignant pheochromocytomas reported in the adrenal medulla of male rats was observed.

Benzoyl peroxide is a tumor promoter in several animal species. The significance of this finding in humans is unknown.

Clindamycin phosphate was not genotoxic in the human lymphocyte chromosome aberration assay.

Bacterial mutagenicity assays (Ames test) with benzoyl peroxide provided mixed results; mutagenic potential was observed in a few but not in a majority of investigations. It has been shown to produce single-strand DNA breaks in human bronchial epithelial and mouse epidermal cells, caused DNA-protein cross-links in the human cells, and also induced a dose-dependent increase in sister chromatid exchanges in Chinese hamster ovary cells.

Adapalene did not exhibit mutagenic or genotoxic effects in vitro (Ames test, Chinese hamster ovary cell assay, or mouse lymphoma TK assay) or in vivo (mouse micronucleus test).

Fertility studies in rats treated orally with up to 300 mg/kg/day of clindamycin phosphate (approximately 96 times the MRHD based on a mg/m 2comparison) revealed no effects on fertility or mating ability.

In rat oral studies, 20 mg/kg/day adapalene (51 times the MRHD based on a mg/m 2comparison) did not affect the reproductive performance and fertility of F 0males and females, or the growth, development and reproductive function of F 1offspring.

The efficacy of CABTREO was evaluated in two multicenter, randomized, double-blind clinical trials (Trial 1 and Trial 2, NCT04214639 and 2 NCT04214652, respectively) in 363 adult and pediatric subjects 10 years of age and older with facial acne vulgaris. While subjects aged 10 to less than 12 years were included in these trials, CABTREO is not approved for use in patients less than 12 years of age.

{ "type": "p", "children": [], "text": "The efficacy of CABTREO was evaluated in two multicenter, randomized, double-blind clinical trials (Trial 1 and Trial 2, NCT04214639 and 2 NCT04214652, respectively) in 363 adult and pediatric subjects 10 years of age and older with facial acne vulgaris. While subjects aged 10 to less than 12 years were included in these trials, CABTREO is not approved for use in patients less than 12 years of age." }

Subjects were randomized 2:1 to receive CABTREO or vehicle applied once daily for 12 weeks. The trial population included 74% White, 15% Black or African American, 7% Asian, 4% Other, and <1% Native Hawaiian or Other Pacific Islander; for ethnicity, 78% identified as non-Hispanic/Latino and 22% identified as Hispanic/Latino. Fifty-eight percent were female and 42% were male. The median age of the trial population was 18 years (range: 10 to 48 years). Enrolled subjects had a score of moderate (3) or severe (4) on the Evaluator’s Global Severity Score (EGSS), 30 to 100 inflammatory lesions (papules, pustules, and nodules), 35 to 150 non-inflammatory lesions (open and closed comedones) and two or fewer facial nodules. At baseline, most subjects (91%) had EGSS scores that equated to moderate acne. The co-primary efficacy endpoints of success on the EGSS, absolute change in noninflammatory lesion count, and absolute change in inflammatory lesion count were assessed at Week 12. Success on the EGSS was defined as at least a 2-grade improvement from baseline and an EGSS score of clear (0) or almost clear (1).

{ "type": "p", "children": [], "text": "Subjects were randomized 2:1 to receive CABTREO or vehicle applied once daily for 12 weeks. The trial population included 74% White, 15% Black or African American, 7% Asian, 4% Other, and <1% Native Hawaiian or Other Pacific Islander; for ethnicity, 78% identified as non-Hispanic/Latino and 22% identified as Hispanic/Latino. Fifty-eight percent were female and 42% were male. The median age of the trial population was 18 years (range: 10 to 48 years). Enrolled subjects had a score of moderate (3) or severe (4) on the Evaluator’s Global Severity Score (EGSS), 30 to 100 inflammatory lesions (papules, pustules, and nodules), 35 to 150 non-inflammatory lesions (open and closed comedones) and two or fewer facial nodules. At baseline, most subjects (91%) had EGSS scores that equated to moderate acne. The co-primary efficacy endpoints of success on the EGSS, absolute change in noninflammatory lesion count, and absolute change in inflammatory lesion count were assessed at Week 12. Success on the EGSS was defined as at least a 2-grade improvement from baseline and an EGSS score of clear (0) or almost clear (1)." }

Table 3 lists the efficacy results for Trials 1 and 2.

{ "type": "p", "children": [], "text": "Table 3 lists the efficacy results for Trials 1 and 2." }

Table 3: Efficacy Results at Week 12

{ "type": "p", "children": [], "text": "Table 3: Efficacy Results at Week 12" }

<div class="scrollingtable"><table width="98.38%"> <caption> <span>Table 3: Efficacy Results at Week 12 in Subjects with Facial Acne Vulgaris in Trials 1 and 2</span> </caption> <col width="32%"/> <col width="26%"/> <col width="23%"/> <col width="19%"/> <tbody class="Headless"> <tr class="First"> <td class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First"> <span class="Bold">Trial 1</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First"> <span class="Bold">CABTREO</span> <br/> <span class="Bold">N=122</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First"> <span class="Bold">Vehicle</span> <br/> <span class="Bold">N=61</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First"> <span class="Bold">Treatment Difference (95% Confidence Interval)</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First"> <span class="Bold">EGSS</span> </p> </td><td class="Botrule Lrule Rrule" valign="top"></td><td class="Botrule Lrule Rrule" valign="top"></td><td class="Botrule Lrule Rrule" valign="top"></td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Clear or Almost Clear and 2-Grade Reduction from Baseline</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">49.6%</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">24.9%</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">24.7 (10.7, 38.7)</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First"> <span class="Bold">Non-Inflammatory Facial Lesions</span> </p> </td><td class="Botrule Lrule Rrule" valign="top"></td><td class="Botrule Lrule Rrule" valign="top"></td><td class="Botrule Lrule Rrule" valign="top"></td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Mean Absolute Reduction</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">35.4</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">23.5</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">11.9 (7.1, 16.6)</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Mean Percent Reduction</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">72.7%</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">47.6%</p> </td><td class="Botrule Lrule Rrule" valign="top"></td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First"> <span class="Bold">Inflammatory Facial Lesions</span> </p> </td><td class="Botrule Lrule Rrule" valign="top"></td><td class="Botrule Lrule Rrule" valign="top"></td><td class="Botrule Lrule Rrule" valign="top"></td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Mean Absolute Reduction</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">27.7</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">21.7</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">5.9 (3.1, 8.7)</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Mean Percent Reduction</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">75.7%</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">59.6%</p> </td><td class="Botrule Lrule Rrule" valign="top"></td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First"> <span class="Bold">Trial 2</span> </p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First"> <span class="Bold">CABTREO</span> <br/> <span class="Bold">N=120</span> </p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First"> <span class="Bold">Vehicle</span> <br/> <span class="Bold">N=60</span> </p> </td><td class="Botrule Lrule Rrule" valign="top"></td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First"> <span class="Bold">EGSS</span> </p> </td><td class="Botrule Lrule Rrule" valign="top"></td><td class="Botrule Lrule Rrule" valign="top"></td><td class="Botrule Lrule Rrule" valign="top"></td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Clear or Almost Clear and</p> <p>2-Grade Reduction from Baseline</p> </td><td align="center" class="Botrule Lrule Rrule" valign="bottom"> <p class="First">50.5%</p> </td><td align="center" class="Botrule Lrule Rrule" valign="bottom"> <p class="First">20.5%</p> </td><td align="center" class="Botrule Lrule Rrule" valign="bottom"> <p class="First">30.0 (16.4, 43.6)</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First"> <span class="Bold">Non-Inflammatory Facial Lesions</span> </p> </td><td class="Botrule Lrule Rrule" valign="top"></td><td class="Botrule Lrule Rrule" valign="top"></td><td class="Botrule Lrule Rrule" valign="top"></td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Mean Absolute Reduction</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">35.2</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">22.0</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">13.3 (8.8, 17.7)</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Mean Percent Reduction</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">73.3%</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">49.0%</p> </td><td class="Botrule Lrule Rrule" valign="top"></td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First"> <span class="Bold">Inflammatory Facial Lesions</span> </p> </td><td class="Botrule Lrule Rrule" valign="top"></td><td class="Botrule Lrule Rrule" valign="top"></td><td class="Botrule Lrule Rrule" valign="top"></td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Mean Absolute Reduction</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">30.1</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">20.8</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">9.3 (6.2, 12.4)</p> </td> </tr> <tr class="Last"> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Mean Percent Reduction</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">80.1%</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">56.2%</p> </td><td class="Botrule Lrule Rrule" valign="top"></td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table width=\"98.38%\">\n<caption>\n<span>Table 3: Efficacy Results at Week 12 in Subjects with Facial Acne Vulgaris in Trials 1 and 2</span>\n</caption>\n<col width=\"32%\"/>\n<col width=\"26%\"/>\n<col width=\"23%\"/>\n<col width=\"19%\"/>\n<tbody class=\"Headless\">\n<tr class=\"First\">\n<td class=\"Botrule Lrule Rrule Toprule\" valign=\"top\">\n<p class=\"First\">\n<span class=\"Bold\">Trial 1</span>\n</p>\n</td><td align=\"center\" class=\"Botrule Lrule Rrule Toprule\" valign=\"top\">\n<p class=\"First\">\n<span class=\"Bold\">CABTREO</span>\n<br/>\n<span class=\"Bold\">N=122</span>\n</p>\n</td><td align=\"center\" class=\"Botrule Lrule Rrule Toprule\" valign=\"top\">\n<p class=\"First\">\n<span class=\"Bold\">Vehicle</span>\n<br/>\n<span class=\"Bold\">N=61</span>\n</p>\n</td><td align=\"center\" class=\"Botrule Lrule Rrule Toprule\" valign=\"top\">\n<p class=\"First\">\n<span class=\"Bold\">Treatment Difference (95% Confidence Interval)</span>\n</p>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule\" valign=\"top\">\n<p class=\"First\">\n<span class=\"Bold\">EGSS</span>\n</p>\n</td><td class=\"Botrule Lrule Rrule\" valign=\"top\"></td><td class=\"Botrule Lrule Rrule\" valign=\"top\"></td><td class=\"Botrule Lrule Rrule\" valign=\"top\"></td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule\" valign=\"top\">\n<p class=\"First\">Clear or Almost Clear and 2-Grade Reduction from Baseline</p>\n</td><td align=\"center\" class=\"Botrule Lrule Rrule\" valign=\"top\">\n<p class=\"First\">49.6%</p>\n</td><td align=\"center\" class=\"Botrule Lrule Rrule\" valign=\"top\">\n<p class=\"First\">24.9%</p>\n</td><td align=\"center\" class=\"Botrule Lrule Rrule\" valign=\"top\">\n<p class=\"First\">24.7 (10.7, 38.7)</p>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule\" valign=\"top\">\n<p class=\"First\">\n<span class=\"Bold\">Non-Inflammatory Facial Lesions</span>\n</p>\n</td><td class=\"Botrule Lrule Rrule\" valign=\"top\"></td><td class=\"Botrule Lrule Rrule\" valign=\"top\"></td><td class=\"Botrule Lrule Rrule\" valign=\"top\"></td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule\" valign=\"top\">\n<p class=\"First\">Mean Absolute Reduction</p>\n</td><td align=\"center\" class=\"Botrule Lrule Rrule\" valign=\"top\">\n<p class=\"First\">35.4</p>\n</td><td align=\"center\" class=\"Botrule Lrule Rrule\" valign=\"top\">\n<p class=\"First\">23.5</p>\n</td><td align=\"center\" class=\"Botrule Lrule Rrule\" valign=\"top\">\n<p class=\"First\">11.9 (7.1, 16.6)</p>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule\" valign=\"top\">\n<p class=\"First\">Mean Percent Reduction</p>\n</td><td align=\"center\" class=\"Botrule Lrule Rrule\" valign=\"top\">\n<p class=\"First\">72.7%</p>\n</td><td align=\"center\" class=\"Botrule Lrule Rrule\" valign=\"top\">\n<p class=\"First\">47.6%</p>\n</td><td class=\"Botrule Lrule Rrule\" valign=\"top\"></td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule\" valign=\"top\">\n<p class=\"First\">\n<span class=\"Bold\">Inflammatory Facial Lesions</span>\n</p>\n</td><td class=\"Botrule Lrule Rrule\" valign=\"top\"></td><td class=\"Botrule Lrule Rrule\" valign=\"top\"></td><td class=\"Botrule Lrule Rrule\" valign=\"top\"></td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule\" valign=\"top\">\n<p class=\"First\">Mean Absolute Reduction</p>\n</td><td align=\"center\" class=\"Botrule Lrule Rrule\" valign=\"top\">\n<p class=\"First\">27.7</p>\n</td><td align=\"center\" class=\"Botrule Lrule Rrule\" valign=\"top\">\n<p class=\"First\">21.7</p>\n</td><td align=\"center\" class=\"Botrule Lrule Rrule\" valign=\"top\">\n<p class=\"First\">5.9 (3.1, 8.7)</p>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule\" valign=\"top\">\n<p class=\"First\">Mean Percent Reduction</p>\n</td><td align=\"center\" class=\"Botrule Lrule Rrule\" valign=\"top\">\n<p class=\"First\">75.7%</p>\n</td><td align=\"center\" class=\"Botrule Lrule Rrule\" valign=\"top\">\n<p class=\"First\">59.6%</p>\n</td><td class=\"Botrule Lrule Rrule\" valign=\"top\"></td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule\" valign=\"top\">\n<p class=\"First\">\n<span class=\"Bold\">Trial 2</span>\n</p>\n</td><td align=\"center\" class=\"Botrule Lrule Rrule\" valign=\"top\">\n<p class=\"First\">\n<span class=\"Bold\">CABTREO</span>\n<br/>\n<span class=\"Bold\">N=120</span>\n</p>\n</td><td align=\"center\" class=\"Botrule Lrule Rrule\" valign=\"top\">\n<p class=\"First\">\n<span class=\"Bold\">Vehicle</span>\n<br/>\n<span class=\"Bold\">N=60</span>\n</p>\n</td><td class=\"Botrule Lrule Rrule\" valign=\"top\"></td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule\" valign=\"top\">\n<p class=\"First\">\n<span class=\"Bold\">EGSS</span>\n</p>\n</td><td class=\"Botrule Lrule Rrule\" valign=\"top\"></td><td class=\"Botrule Lrule Rrule\" valign=\"top\"></td><td class=\"Botrule Lrule Rrule\" valign=\"top\"></td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule\" valign=\"top\">\n<p class=\"First\">Clear or Almost Clear and</p>\n<p>2-Grade Reduction from Baseline</p>\n</td><td align=\"center\" class=\"Botrule Lrule Rrule\" valign=\"bottom\">\n<p class=\"First\">50.5%</p>\n</td><td align=\"center\" class=\"Botrule Lrule Rrule\" valign=\"bottom\">\n<p class=\"First\">20.5%</p>\n</td><td align=\"center\" class=\"Botrule Lrule Rrule\" valign=\"bottom\">\n<p class=\"First\">30.0 (16.4, 43.6)</p>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule\" valign=\"top\">\n<p class=\"First\">\n<span class=\"Bold\">Non-Inflammatory Facial Lesions</span>\n</p>\n</td><td class=\"Botrule Lrule Rrule\" valign=\"top\"></td><td class=\"Botrule Lrule Rrule\" valign=\"top\"></td><td class=\"Botrule Lrule Rrule\" valign=\"top\"></td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule\" valign=\"top\">\n<p class=\"First\">Mean Absolute Reduction</p>\n</td><td align=\"center\" class=\"Botrule Lrule Rrule\" valign=\"top\">\n<p class=\"First\">35.2</p>\n</td><td align=\"center\" class=\"Botrule Lrule Rrule\" valign=\"top\">\n<p class=\"First\">22.0</p>\n</td><td align=\"center\" class=\"Botrule Lrule Rrule\" valign=\"top\">\n<p class=\"First\">13.3 (8.8, 17.7)</p>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule\" valign=\"top\">\n<p class=\"First\">Mean Percent Reduction</p>\n</td><td align=\"center\" class=\"Botrule Lrule Rrule\" valign=\"top\">\n<p class=\"First\">73.3%</p>\n</td><td align=\"center\" class=\"Botrule Lrule Rrule\" valign=\"top\">\n<p class=\"First\">49.0%</p>\n</td><td class=\"Botrule Lrule Rrule\" valign=\"top\"></td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule\" valign=\"top\">\n<p class=\"First\">\n<span class=\"Bold\">Inflammatory Facial Lesions</span>\n</p>\n</td><td class=\"Botrule Lrule Rrule\" valign=\"top\"></td><td class=\"Botrule Lrule Rrule\" valign=\"top\"></td><td class=\"Botrule Lrule Rrule\" valign=\"top\"></td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule\" valign=\"top\">\n<p class=\"First\">Mean Absolute Reduction</p>\n</td><td align=\"center\" class=\"Botrule Lrule Rrule\" valign=\"top\">\n<p class=\"First\">30.1</p>\n</td><td align=\"center\" class=\"Botrule Lrule Rrule\" valign=\"top\">\n<p class=\"First\">20.8</p>\n</td><td align=\"center\" class=\"Botrule Lrule Rrule\" valign=\"top\">\n<p class=\"First\">9.3 (6.2, 12.4)</p>\n</td>\n</tr>\n<tr class=\"Last\">\n<td class=\"Botrule Lrule Rrule\" valign=\"top\">\n<p class=\"First\">Mean Percent Reduction</p>\n</td><td align=\"center\" class=\"Botrule Lrule Rrule\" valign=\"top\">\n<p class=\"First\">80.1%</p>\n</td><td align=\"center\" class=\"Botrule Lrule Rrule\" valign=\"top\">\n<p class=\"First\">56.2%</p>\n</td><td class=\"Botrule Lrule Rrule\" valign=\"top\"></td>\n</tr>\n</tbody>\n</table></div>" }

How Supplied

{ "type": "p", "children": [], "text": "\nHow Supplied\n" }

CABTREO (clindamycin phosphate, adapalene, and benzoyl peroxide) topical gel is a white to off-white, opaque topical gel. CABTREO contains 1.2% clindamycin phosphate, 0.15% adapalene, and 3.1% benzoyl peroxide and is supplied as follows:

{ "type": "p", "children": [], "text": "CABTREO (clindamycin phosphate, adapalene, and benzoyl peroxide) topical gel is a white to off-white, opaque topical gel. CABTREO contains 1.2% clindamycin phosphate, 0.15% adapalene, and 3.1% benzoyl peroxide and is supplied as follows:" }

{ "type": "ul", "children": [ "20 g pump (NDC 0187-0006-10)", "50 g pump (NDC 0187-0006-25)" ], "text": "" }

Storage and Handling

{ "type": "p", "children": [], "text": "\nStorage and Handling\n" }

{ "type": "ul", "children": [ "\nPrior to Dispensing:Store CABTREO in a refrigerator between 2° to 8°C (36° to 46°F) until dispensed to the patient. Dispense CABTREO with a 10-week expiration date.\n \n ", "\nAfter Dispensing:Store CABTREO at room temperature at or below 25°C (77°F).\n \n ", "Do not freeze.", "Keep away from heat.", "Store pump upright." ], "text": "" }

Advise the patient to read the FDA-approved patient labeling (Patient Information).

{ "type": "p", "children": [], "text": "Advise the patient to read the FDA-approved patient labeling (Patient Information)." }

Administration Instructions

{ "type": "p", "children": [], "text": "\nAdministration Instructions\n" }

Advise patients to apply CABTREO as a thin layer to affected areas, avoiding the eyes, lips, paranasal creases, mucous membranes, and areas of broken, eczematous, or sunburned skin [see Dosage and Administration ( 2)] .

{ "type": "p", "children": [], "text": "Advise patients to apply CABTREO as a thin layer to affected areas, avoiding the eyes, lips, paranasal creases, mucous membranes, and areas of broken, eczematous, or sunburned skin\n \n [see Dosage and Administration (\n \n 2)]\n \n .\n\n " }

Instruct patients to wash hands after application. [see Dosage and Administration ( 2)] .

{ "type": "p", "children": [], "text": "Instruct patients to wash hands after application.\n \n [see Dosage and Administration (\n \n 2)]\n \n .\n\n " }

Advise patients that CABTREO may bleach hair and colored fabric.

{ "type": "p", "children": [], "text": "Advise patients that CABTREO may bleach hair and colored fabric." }

Hypersensitivity

{ "type": "p", "children": [], "text": "\nHypersensitivity\n" }

Inform patients that hypersensitivity reactions may occur. Advise patients to discontinue use of CABTREO and contact their healthcare provider immediately if symptoms of an allergic reaction, such as severe swelling or shortness of breath, occur [see Warnings and Precautions ( 5.1), Contraindications ( 4)] .

{ "type": "p", "children": [], "text": "Inform patients that hypersensitivity reactions may occur. Advise patients to discontinue use of CABTREO and contact their healthcare provider immediately if symptoms of an allergic reaction, such as severe swelling or shortness of breath, occur\n \n [see Warnings and Precautions (\n \n 5.1), Contraindications (\n \n 4)]\n \n .\n\n " }

Colitis

{ "type": "p", "children": [], "text": "\nColitis\n" }

Advise patients to discontinue use of CABTREO and contact their healthcare provider if diarrhea occurs [ see Warnings and Precautions ( 5.2)] .

{ "type": "p", "children": [], "text": "Advise patients to discontinue use of CABTREO and contact their healthcare provider if diarrhea occurs [\n \n see Warnings and Precautions (\n \n 5.2)]\n \n .\n\n " }

Photosensitivity

{ "type": "p", "children": [], "text": "\nPhotosensitivity\n" }

Advise patients to minimize or avoid exposure to sunlight or sunlamps, including tanning beds. Instruct patients to use sunscreen and wear protective clothing (e.g., hat) over treated areas when exposure to sun cannot be avoided [see Warnings and Precautions ( 5.3)] .

{ "type": "p", "children": [], "text": "Advise patients to minimize or avoid exposure to sunlight or sunlamps, including tanning beds. Instruct patients to use sunscreen and wear protective clothing (e.g., hat) over treated areas when exposure to sun cannot be avoided\n \n [see Warnings and Precautions (\n \n 5.3)]\n \n .\n\n " }

Skin Irritation and Allergic Contact Dermatitis

{ "type": "p", "children": [], "text": "\nSkin Irritation and Allergic Contact Dermatitis\n" }

Inform patients that CABTREO may cause irritation, such as erythema, scaling, dryness, itching, stinging or burning. Depending on the severity of the reactions, advise patients to use a moisturizer, reduce the frequency of application, or discontinue use of CABTREO [see Warnings and Precautions ( 5.4)] .

{ "type": "p", "children": [], "text": "Inform patients that CABTREO may cause irritation, such as erythema, scaling, dryness, itching, stinging or burning. Depending on the severity of the reactions, advise patients to use a moisturizer, reduce the frequency of application, or discontinue use of CABTREO\n \n [see Warnings and Precautions (\n \n 5.4)]\n \n .\n\n " }

Lactation

{ "type": "p", "children": [], "text": "\nLactation\n" }

Advise patients to use CABTREO on the smallest area of skin and for the shortest duration possible while breastfeeding. To avoid direct infant exposure, instruct patients who are breastfeeding not to apply CABTREO directly to the nipple and areola. Instruct patients to avoid inadvertent contact of treated areas with infant skin [ see Use in Specific Populations ( 8.2)].

{ "type": "p", "children": [], "text": "Advise patients to use CABTREO on the smallest area of skin and for the shortest duration possible while breastfeeding. To avoid direct infant exposure, instruct patients who are breastfeeding not to apply CABTREO directly to the nipple and areola. Instruct patients to avoid inadvertent contact of treated areas with infant skin [\n \n see Use in Specific Populations (\n \n 8.2)].\n \n \n" }

Distributed by: Bausch Health US, LLC Bridgewater, NJ 08807 USA

{ "type": "p", "children": [], "text": "\nDistributed by:\n Bausch Health US, LLC \n Bridgewater, NJ 08807 USA\n\n " }

Manufactured by: Bausch Health Companies Inc. Laval, Quebec H7L 4A8, Canada

{ "type": "p", "children": [], "text": "\nManufactured by:\n Bausch Health Companies Inc. \n Laval, Quebec H7L 4A8, Canada\n\n " }

Patented. See https://patents.ortho-dermatologics.com for US patent information.

{ "type": "p", "children": [], "text": "Patented. See https://patents.ortho-dermatologics.com for US patent information." }

CABTREO is a trademark of Bausch Health Companies Inc. or its affiliates.

{ "type": "p", "children": [], "text": "CABTREO is a trademark of Bausch Health Companies Inc. or its affiliates." }

© 2025 Bausch Health Companies Inc. or its affiliates 90001201

{ "type": "p", "children": [], "text": "© 2025 Bausch Health Companies Inc. or its affiliates \n 90001201\n " }

<div class="scrollingtable"><table class="Noautorules" width="100%"> <col width="100%"/> <tbody class="Headless"> <tr> <td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First"> <span class="Bold">PATIENT INFORMATION</span> <br/> <span class="Bold">CABTREO <span class="Sup">®</span>(kab-TREE-oh) </span> <br/> <span class="Bold">(clindamycin phosphate, adapalene and benzoyl peroxide)</span> <br/> <span class="Bold">topical gel</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First"> <span class="Bold">Important information:</span>CABTREO is for use on skin only <span class="Bold">(topical use)</span>. Do not use CABTREO in your mouth, eyes, or vagina. </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First"> <span class="Bold">What is CABTREO?</span> </p> <p>CABTREO is a prescription medicine used on the skin (topical) to treat acne vulgaris in adults and children 12 years of age and older.</p> <p>It is not known if CABTREO is safe and effective in children under 12 years of age.</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First"> <span class="Bold">Do not use CABTREO if you have:</span> </p> <ul> <li>had an allergic reaction to clindamycin, adapalene, benzoyl peroxide, lincomycin, or any of the ingredients in CABTREO. See the end of this Patient Information leaflet for a complete list of ingredients in CABTREO.</li> <li>Crohn's disease or ulcerative colitis.</li> <li>had inflammation of the colon (colitis), or severe diarrhea with past antibiotic use.</li> </ul> <p>Talk with your healthcare provider if you are not sure if you have any of the conditions listed above.</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First"> <span class="Bold">Before using CABTREO, tell your healthcare provider about all of your medical conditions, including if you:</span> </p> <ul> <li>plan to have surgery. CABTREO may affect how certain medicines work that may be given during surgery.</li> <li>are pregnant or plan to become pregnant. It is not known if CABTREO will harm your unborn baby.</li> <li>are breastfeeding or plan to breastfeed. It is not known if CABTREO passes into your breast milk. Clindamycin when taken by mouth or by injection has been reported to appear in breast milk. Talk to your healthcare provider about the best way to feed your baby during treatment with CABTREO.</li> <li> <span class="Bold">If you use CABTREO while breastfeeding:</span> </li> <li>use CABTREO on the smallest area of skin and for the shortest time needed.</li> <li> <span class="Bold">do not</span>apply CABTREO directly to the nipple and areola to avoid getting CABTREO into your baby’s mouth. </li> <li>avoid direct skin contact with your baby if CABTREO is applied to your chest.</li> </ul> <p> <span class="Bold">Tell your healthcare provider about all the medicines you take,</span>including prescription and over-the-counter medicines, vitamins, and herbal supplements. </p> <ul> <li> <span class="Bold">Especially tell your healthcare provider</span>if you take medicine by mouth that contains erythromycin or use products on your skin that contain erythromycin. CABTREO should not be used with products that contain erythromycin. <p class="First">Especially tell your healthcare provider about any skin products you use. Other skin and topical acne products may increase the irritation of your skin when used with CABTREO.</p> </li> </ul> <p>Know the medicines you take. Keep a list of them to show to your healthcare provider and pharmacist when you get a new medicine.</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First"> <span class="Bold">How should I use CABTREO?</span> </p> <ul> <li>Use CABTREO exactly as your healthcare provider tells you to use it. See the detailed <span class="Bold">“Instructions for Use”</span>for directions about how to apply CABTREO. </li> <li>Apply a thin layer of CABTREO to cover the treatment area 1 time each day.</li> <li>Avoid applying CABTREO to the eyes, lips, creases around your nose, your mouth, and areas of your skin with cuts, abrasions, or sunburned skin.</li> <li>Before you apply CABTREO, wash your face gently with a mild or soapless cleanser, rinse with warm water, and pat your skin dry.</li> <li>Wash your hands right away after applying CABTREO.</li> </ul> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <ol> <li> <span class="Bold">What should I avoid during treatment with CABTREO?</span> </li> <li>Avoid or limit your time in sunlight, including use of tanning beds or sunlamps during treatment with CABTREO. CABTREO can make you more sensitive to the sun, and the light from sunlamps and tanning beds. You could get severe sunburn. Use sunscreen and wear wide-brimmed hat and clothes that cover the treated area of your skin if you have to be in sunlight.</li> <li>Cold weather and wind may irritate skin treated with CABTREO.</li> <li>Avoid applying CABTREO to areas with skin problems, including cuts, abrasions, sunburn, or eczema.</li> <li>Avoid skin products that may dry or irritate your skin such as medicated or harsh soaps, astringents, cosmetics that make your skin dry, and products containing high levels of alcohol, spices, or limes.</li> <li>Avoid the use of “waxing” as a hair removal method on skin treated with CABTREO.</li> <li>Avoid getting CABTREO in your hair or on colored fabric. CABTREO may bleach hair or colored fabric.</li> </ol> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First"> <span class="Bold">What are the possible side effects of CABTREO?</span> </p> <p> <span class="Bold">CABTREO may cause serious side effects, including:</span> </p> <ul> <li> <span class="Bold">Allergic reactions.</span>Stop using CABTREO, and get help right away if you have any of the following symptoms during treatment with CABTREO: <ul> <li>hives, rash, or severe itching</li> <li>swelling of your face, eyes, lips, tongue, or throat</li> <li>trouble breathing or throat tightness</li> <li>feeling faint, dizzy, or lightheaded</li> </ul> </li> <li> <span class="Bold">Inflammation of the colon (colitis).</span>Stop using CABTREO and call your healthcare provider right away if you have severe stomach (abdominal) cramps, watery diarrhea, or bloody diarrhea during treatment, and within several weeks after treatment with CABTREO. </li> <li> <span class="Bold">Sensitivity to sunlight.</span>See <span class="Bold">“What should I avoid while using CABTREO?”</span> </li> <li> <span class="Bold">Skin irritation.</span>Skin irritation is common with CABTREO and is most likely to happen during the first 4 weeks of treatment, and usually lessen with continued use of CABTREO. Skin reactions at the treatment area include redness, scaling, dryness, stinging, burning, itching, and swelling. Tell your healthcare provider if you get any skin reactions. </li> </ul> <p>Tell your healthcare provider if you have any side effect that bothers you or that does not go away.</p> <p>These are not all of the possible side effects of CABTREO.</p> <p>Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First"> <span class="Bold">How should I store CABTREO?</span> </p> <ul> <li>Store CABTREO at room temperature at or below 77°F (25°C).</li> <li>Do not freeze CABTREO.</li> <li>Keep CABTREO away from heat.</li> <li>Store CABTREO pump upright.</li> <li>Throw away (discard) CABTREO that has passed the expiration date.</li> </ul> <p> <span class="Bold">Keep CABTREO and all medicines out of the reach of children.</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First"> <span class="Bold">General information about the safe and effective use of CABTREO.</span> </p> <p>Medicines are sometimes prescribed for purposes other than those listed in a Patient Information leaflet. Do not use CABTREO for a condition for which it was not prescribed. Do not give CABTREO to other people, even if they have the same symptoms that you have. It may harm them. You can ask your pharmacist or healthcare provider for information about CABTREO that is written for health professionals.</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First"> <span class="Bold">What are the ingredients in CABTREO?</span> </p> <p> <span class="Bold">Active ingredient:</span>clindamycin phosphate, adapalene, and benzoyl peroxide. </p> <p> <span class="Bold">Inactive ingredients:</span>carbomer homopolymer type C (carbomer 980), potassium hydroxide, propylene glycol, and purified water. </p> <p> <span class="Bold">Distributed by:</span>Bausch Health US, LLC, Bridgewater, NJ 08807 USA </p> <p> <span class="Bold">Manufactured by:</span>Bausch Health Companies Inc., Laval, Quebec H7L 4A8, Canada </p> <p>Patented. See https://patents.ortho-dermatologics.com for US patent information.</p> <p>CABTREO is a trademark of Bausch Health Companies Inc. or its affiliates.</p> <p>© 2025 Bausch Health Companies Inc. or its affiliates</p> <p>For more information about CABTREO, call 1-800-321-4576.</p> </td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table class=\"Noautorules\" width=\"100%\">\n<col width=\"100%\"/>\n<tbody class=\"Headless\">\n<tr>\n<td align=\"center\" class=\"Botrule Lrule Rrule Toprule\" valign=\"top\">\n<p class=\"First\">\n<span class=\"Bold\">PATIENT INFORMATION</span>\n<br/>\n<span class=\"Bold\">CABTREO\n \n <span class=\"Sup\">®</span>(kab-TREE-oh)\n \n </span>\n<br/>\n<span class=\"Bold\">(clindamycin phosphate, adapalene and benzoyl peroxide)</span>\n<br/>\n<span class=\"Bold\">topical gel</span>\n</p>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule\" valign=\"top\">\n<p class=\"First\">\n<span class=\"Bold\">Important information:</span>CABTREO is for use on skin only\n \n <span class=\"Bold\">(topical use)</span>. Do not use CABTREO in your mouth, eyes, or vagina.\n \n </p>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule\" valign=\"top\">\n<p class=\"First\">\n<span class=\"Bold\">What is CABTREO?</span>\n</p>\n<p>CABTREO is a prescription medicine used on the skin (topical) to treat acne vulgaris in adults and children 12 years of age and older.</p>\n<p>It is not known if CABTREO is safe and effective in children under 12 years of age.</p>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule\" valign=\"top\">\n<p class=\"First\">\n<span class=\"Bold\">Do not use CABTREO if you have:</span>\n</p>\n<ul>\n<li>had an allergic reaction to clindamycin, adapalene, benzoyl peroxide, lincomycin, or any of the ingredients in CABTREO. See the end of this Patient Information leaflet for a complete list of ingredients in CABTREO.</li>\n<li>Crohn's disease or ulcerative colitis.</li>\n<li>had inflammation of the colon (colitis), or severe diarrhea with past antibiotic use.</li>\n</ul>\n<p>Talk with your healthcare provider if you are not sure if you have any of the conditions listed above.</p>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule\" valign=\"top\">\n<p class=\"First\">\n<span class=\"Bold\">Before using CABTREO, tell your healthcare provider about all of your medical conditions, including if you:</span>\n</p>\n<ul>\n<li>plan to have surgery. CABTREO may affect how certain medicines work that may be given during surgery.</li>\n<li>are pregnant or plan to become pregnant. It is not known if CABTREO will harm your unborn baby.</li>\n<li>are breastfeeding or plan to breastfeed. It is not known if CABTREO passes into your breast milk. Clindamycin when taken by mouth or by injection has been reported to appear in breast milk. Talk to your healthcare provider about the best way to feed your baby during treatment with CABTREO.</li>\n<li>\n<span class=\"Bold\">If you use CABTREO while breastfeeding:</span>\n</li>\n<li>use CABTREO on the smallest area of skin and for the shortest time needed.</li>\n<li>\n<span class=\"Bold\">do not</span>apply CABTREO directly to the nipple and areola to avoid getting CABTREO into your baby’s mouth.\n \n </li>\n<li>avoid direct skin contact with your baby if CABTREO is applied to your chest.</li>\n</ul>\n<p>\n<span class=\"Bold\">Tell your healthcare provider about all the medicines you take,</span>including prescription and over-the-counter medicines, vitamins, and herbal supplements.\n \n </p>\n<ul>\n<li>\n<span class=\"Bold\">Especially tell your healthcare provider</span>if you take medicine by mouth that contains erythromycin or use products on your skin that contain erythromycin. CABTREO should not be used with products that contain erythromycin.\n \n <p class=\"First\">Especially tell your healthcare provider about any skin products you use. Other skin and topical acne products may increase the irritation of your skin when used with CABTREO.</p>\n</li>\n</ul>\n<p>Know the medicines you take. Keep a list of them to show to your healthcare provider and pharmacist when you get a new medicine.</p>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule\" valign=\"top\">\n<p class=\"First\">\n<span class=\"Bold\">How should I use CABTREO?</span>\n</p>\n<ul>\n<li>Use CABTREO exactly as your healthcare provider tells you to use it. See the detailed\n \n <span class=\"Bold\">“Instructions for Use”</span>for directions about how to apply CABTREO.\n \n </li>\n<li>Apply a thin layer of CABTREO to cover the treatment area 1 time each day.</li>\n<li>Avoid applying CABTREO to the eyes, lips, creases around your nose, your mouth, and areas of your skin with cuts, abrasions, or sunburned skin.</li>\n<li>Before you apply CABTREO, wash your face gently with a mild or soapless cleanser, rinse with warm water, and pat your skin dry.</li>\n<li>Wash your hands right away after applying CABTREO.</li>\n</ul>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule\" valign=\"top\">\n<ol>\n<li>\n<span class=\"Bold\">What should I avoid during treatment with CABTREO?</span>\n</li>\n<li>Avoid or limit your time in sunlight, including use of tanning beds or sunlamps during treatment with CABTREO. CABTREO can make you more sensitive to the sun, and the light from sunlamps and tanning beds. You could get severe sunburn. Use sunscreen and wear wide-brimmed hat and clothes that cover the treated area of your skin if you have to be in sunlight.</li>\n<li>Cold weather and wind may irritate skin treated with CABTREO.</li>\n<li>Avoid applying CABTREO to areas with skin problems, including cuts, abrasions, sunburn, or eczema.</li>\n<li>Avoid skin products that may dry or irritate your skin such as medicated or harsh soaps, astringents, cosmetics that make your skin dry, and products containing high levels of alcohol, spices, or limes.</li>\n<li>Avoid the use of “waxing” as a hair removal method on skin treated with CABTREO.</li>\n<li>Avoid getting CABTREO in your hair or on colored fabric. CABTREO may bleach hair or colored fabric.</li>\n</ol>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule\" valign=\"top\">\n<p class=\"First\">\n<span class=\"Bold\">What are the possible side effects of CABTREO?</span>\n</p>\n<p>\n<span class=\"Bold\">CABTREO may cause serious side effects, including:</span>\n</p>\n<ul>\n<li>\n<span class=\"Bold\">Allergic reactions.</span>Stop using CABTREO, and get help right away if you have any of the following symptoms during treatment with CABTREO:\n \n <ul>\n<li>hives, rash, or severe itching</li>\n<li>swelling of your face, eyes, lips, tongue, or throat</li>\n<li>trouble breathing or throat tightness</li>\n<li>feeling faint, dizzy, or lightheaded</li>\n</ul>\n</li>\n<li>\n<span class=\"Bold\">Inflammation of the colon (colitis).</span>Stop using CABTREO and call your healthcare provider right away if you have severe stomach (abdominal) cramps, watery diarrhea, or bloody diarrhea during treatment, and within several weeks after treatment with CABTREO.\n \n </li>\n<li>\n<span class=\"Bold\">Sensitivity to sunlight.</span>See\n \n <span class=\"Bold\">“What should I avoid while using CABTREO?”</span>\n</li>\n<li>\n<span class=\"Bold\">Skin irritation.</span>Skin irritation is common with CABTREO and is most likely to happen during the first 4 weeks of treatment, and usually lessen with continued use of CABTREO. Skin reactions at the treatment area include redness, scaling, dryness, stinging, burning, itching, and swelling. Tell your healthcare provider if you get any skin reactions.\n \n </li>\n</ul>\n<p>Tell your healthcare provider if you have any side effect that bothers you or that does not go away.</p>\n<p>These are not all of the possible side effects of CABTREO.</p>\n<p>Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.</p>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule\" valign=\"top\">\n<p class=\"First\">\n<span class=\"Bold\">How should I store CABTREO?</span>\n</p>\n<ul>\n<li>Store CABTREO at room temperature at or below 77°F (25°C).</li>\n<li>Do not freeze CABTREO.</li>\n<li>Keep CABTREO away from heat.</li>\n<li>Store CABTREO pump upright.</li>\n<li>Throw away (discard) CABTREO that has passed the expiration date.</li>\n</ul>\n<p>\n<span class=\"Bold\">Keep CABTREO and all medicines out of the reach of children.</span>\n</p>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule\" valign=\"top\">\n<p class=\"First\">\n<span class=\"Bold\">General information about the safe and effective use of CABTREO.</span>\n</p>\n<p>Medicines are sometimes prescribed for purposes other than those listed in a Patient Information leaflet. Do not use CABTREO for a condition for which it was not prescribed. Do not give CABTREO to other people, even if they have the same symptoms that you have. It may harm them. You can ask your pharmacist or healthcare provider for information about CABTREO that is written for health professionals.</p>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule Toprule\" valign=\"top\">\n<p class=\"First\">\n<span class=\"Bold\">What are the ingredients in CABTREO?</span>\n</p>\n<p>\n<span class=\"Bold\">Active ingredient:</span>clindamycin phosphate, adapalene, and benzoyl peroxide.\n \n </p>\n<p>\n<span class=\"Bold\">Inactive ingredients:</span>carbomer homopolymer type C (carbomer 980), potassium hydroxide, propylene glycol, and purified water.\n \n </p>\n<p>\n<span class=\"Bold\">Distributed by:</span>Bausch Health US, LLC, Bridgewater, NJ 08807 USA\n \n </p>\n<p>\n<span class=\"Bold\">Manufactured by:</span>Bausch Health Companies Inc., Laval, Quebec H7L 4A8, Canada\n \n </p>\n<p>Patented. See https://patents.ortho-dermatologics.com for US patent information.</p>\n<p>CABTREO is a trademark of Bausch Health Companies Inc. or its affiliates.</p>\n<p>© 2025 Bausch Health Companies Inc. or its affiliates</p>\n<p>For more information about CABTREO, call 1-800-321-4576.</p>\n</td>\n</tr>\n</tbody>\n</table></div>" }

{ "type": "ul", "children": [ "This Patient Information has been approved by the U.S. Food and Drug Administration.", "Revised: 03/2025", "90001201" ], "text": "" }

CABTREO ®(kab-TREE-oh) (clindamycin phosphate, adapalene and benzoyl peroxide)

{ "type": "p", "children": [], "text": "\nCABTREO\n \n ®(kab-TREE-oh)\n \n \n\n(clindamycin phosphate, adapalene and benzoyl peroxide)\n" }

topical gel

{ "type": "p", "children": [], "text": "\ntopical gel\n" }

This Instructions for Use contains information on how to apply CABTREO.

{ "type": "p", "children": [], "text": "\nThis Instructions for Use contains information on how to apply CABTREO.\n" }

Important information: CABTREO is for use on skin only (topical use). CABTREO is not for use in your mouth, eyes, or vagina.

{ "type": "p", "children": [], "text": "\nImportant information: CABTREO is for use on skin only (topical use). CABTREO is not for use in your mouth, eyes, or vagina.\n" }

Read this Instructions for Use before you start using CABTREO and each time you get a refill. There may be new information. This information does not take the place of talking with your healthcare provider about your medical condition or treatment.

{ "type": "p", "children": [], "text": "Read this Instructions for Use before you start using CABTREO and each time you get a refill. There may be new information. This information does not take the place of talking with your healthcare provider about your medical condition or treatment." }

{ "type": "ul", "children": [ "Apply CABTREO to your face 1 time each day as prescribed.", "Before you apply CABTREO, wash your face gently with a cleanser, rinse with warm water, and pat your skin dry." ], "text": "" }

Step 1

{ "type": "p", "children": [], "text": "\nStep 1\n" }

To apply CABTREO to your face, use the pump to dispense one pea-sized amount of CABTREO onto your fingertip. See Figure 1.

{ "type": "p", "children": [], "text": "To apply CABTREO to your face, use the pump to dispense one pea-sized amount of CABTREO onto your fingertip.\n \n See Figure 1.\n" }

{ "type": "", "children": [], "text": "" }

Figure 1

{ "type": "p", "children": [], "text": "\nFigure 1\n" }

Step 2

{ "type": "p", "children": [], "text": "\nStep 2\n" }

Dot the one pea-sized amount of CABTREO onto six areas of your face (chin, left cheek, right cheek, nose, left forehead, right forehead). See Figure 2.

{ "type": "p", "children": [], "text": "Dot the one pea-sized amount of CABTREO onto six areas of your face (chin, left cheek, right cheek, nose, left forehead, right forehead).\n \n See Figure 2.\n" }

Figure 2

{ "type": "p", "children": [], "text": "\nFigure 2\n" }

Step 3

{ "type": "p", "children": [], "text": "\nStep 3\n" }

Spread the gel over your face and gently rub it in. It is important to spread the gel over your entire face.If your healthcare provider tells you to put CABTREO on other areas of your skin with acne, be sure to ask how much you should use.

{ "type": "p", "children": [], "text": "Spread the gel over your face and gently rub it in.\n \n It is important to spread the gel over your entire face.If your healthcare provider tells you to put CABTREO on other areas of your skin with acne, be sure to ask how much you should use.\n\n " }

Step 4

{ "type": "p", "children": [], "text": "\nStep 4\n" }

Wash your hands after applying CABTREO.

{ "type": "p", "children": [], "text": "Wash your hands after applying CABTREO." }

How should I store CABTREO?

{ "type": "p", "children": [], "text": "\nHow should I store CABTREO?\n" }

{ "type": "ul", "children": [ "Store CABTREO at room temperature at or below 77°F (25°C).", "Do not freeze CABTREO.", "Keep CABTREO away from heat.", "Store CABTREO pump upright.", "Throw away (discard) CABTREO that has passed the expiration date." ], "text": "" }

Keep CABTREO and all medicines out of the reach of children.

{ "type": "p", "children": [], "text": "\nKeep CABTREO and all medicines out of the reach of children.\n" }

Distributed by:Bausch Health US, LLC, Bridgewater, NJ 08807 USA

{ "type": "p", "children": [], "text": "\nDistributed by:Bausch Health US, LLC, Bridgewater, NJ 08807 USA\n\n " }

Manufactured by:Bausch Health Companies Inc., Laval, Quebec H7L 4A8, Canada

{ "type": "p", "children": [], "text": "\nManufactured by:Bausch Health Companies Inc., Laval, Quebec H7L 4A8, Canada\n\n " }

Patented. See https://patents.ortho-dermatologics.com for US patent information.

{ "type": "p", "children": [], "text": "Patented. See https://patents.ortho-dermatologics.com for US patent information." }

CABTREO is a trademark of Bausch Health Companies Inc. or its affiliates.

{ "type": "p", "children": [], "text": "CABTREO is a trademark of Bausch Health Companies Inc. or its affiliates." }

© 2025 Bausch Health Companies Inc. or its affiliates

{ "type": "p", "children": [], "text": "© 2025 Bausch Health Companies Inc. or its affiliates" }

<div class="scrollingtable"><table class="Noautorules" width="100%"> <col width="100%"/> <tbody class="Headless"> <tr> <td valign="top"> <p class="First">This Instructions for Use has been approved by the U.S. Food and Drug Administration. Revised: 03/2025</p> </td> </tr> <tr> <td valign="top"></td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table class=\"Noautorules\" width=\"100%\">\n<col width=\"100%\"/>\n<tbody class=\"Headless\">\n<tr>\n<td valign=\"top\">\n<p class=\"First\">This Instructions for Use has been approved by the U.S. Food and Drug Administration. Revised: 03/2025</p>\n</td>\n</tr>\n<tr>\n<td valign=\"top\"></td>\n</tr>\n</tbody>\n</table></div>" }

90001201

{ "type": "p", "children": [], "text": "90001201" }

NDC0187-0006-25

{ "type": "p", "children": [], "text": "\nNDC0187-0006-25\n\n " }

Rx only

{ "type": "p", "children": [], "text": "\nRx only\n" }

CABTREO® (clindamycin phosphate, adapalene and benzoyl peroxide) Topical Gel 1.2%/0.15%/3.1%

{ "type": "p", "children": [], "text": "\nCABTREO®\n\n(clindamycin phosphate, adapalene \n and benzoyl peroxide) Topical Gel \n 1.2%/0.15%/3.1%\n\n " }

Not for Oral, Ophthalmic, or Intravaginal Use

{ "type": "p", "children": [], "text": "Not for Oral, Ophthalmic, \n or Intravaginal Use\n " }

KEEP OUT OF REACH OF CHILDREN

{ "type": "p", "children": [], "text": "\nKEEP OUT OF\n\nREACH OF\n\nCHILDREN\n" }

Net Wt. 50 g

{ "type": "p", "children": [], "text": "\nNet Wt. 50 g\n" }

ORTHO Dermatologics

{ "type": "p", "children": [], "text": "\nORTHO Dermatologics\n" }

90000701

{ "type": "p", "children": [], "text": "\n90000701\n" }

Clindamycin Phosphate in Sodium Chloride Injection is indicated for the treatment of serious infections caused by susceptible anaerobic bacteria in adults and pediatric patients for whom appropriate dosing with this formulation can be achieved [see Indications and Usage (1.3 - 1.7)].

Clindamycin Phosphate in Sodium Chloride Injection is indicated for the treatment of serious infections due to susceptible isolates of streptococci, pneumococci, and staphylococci in adults and pediatric patients for whom appropriate dosing with this formulation can be achieved. Its use should be reserved for penicillin-allergic patients or other patients for whom, in the judgment of the physician, a penicillin is inappropriate. Because of the risk of antibacterial-associated pseudomembranous colitis, [see Boxed Warning], before selecting clindamycin the physician should consider the nature of the infection and the suitability of less toxic alternatives (e.g., erythromycin).

Bacteriologic studies should be performed to determine the causative organisms and their susceptibility to clindamycin.

Indicated surgical procedures should be performed in conjunction with antibacterial therapy.

Clindamycin Phosphate in Sodium Chloride Injection is indicated for the treatment of serious lower respiratory tract infections including pneumonia, empyema, and lung abscess caused by susceptible isolates of anaerobes, Streptococcus pneumoniae, other streptococci (except E. faecalis), and Staphylococcus aureus in adults and pediatric patients for whom appropriate dosing with this formulation can be achieved.

Clindamycin Phosphate in Sodium Chloride Injection is indicated for the treatment of serious skin and skin structure infections caused by susceptible isolates of Streptococcus pyogenes, Staphylococcus aureus, and anaerobes in adults and pediatric patients for whom appropriate dosing with this formulation can be achieved.

Clindamycin Phosphate in Sodium Chloride Injection is indicated for the treatment of serious gynecological infections including endometritis, nongonococcal tubo-ovarian abscess, pelvic cellulitis, and postsurgical vaginal cuff infection caused by susceptible anaerobes in adults and pediatric patients for whom appropriate dosing with this formulation can be achieved.

Clindamycin Phosphate in Sodium Chloride Injection is indicated for the treatment of serious intra-abdominal infections including peritonitis and intra-abdominal abscess caused by susceptible anaerobic organisms in adults and pediatric patients for whom appropriate dosing with this formulation can be achieved.

Clindamycin Phosphate in Sodium Chloride Injection is indicated for the treatment of serious septicemia caused by susceptible isolates of Staphylococcus aureus, streptococci (except Enterococcus faecalis), and susceptible anaerobes in adults and pediatric patients for whom appropriate dosing with this formulation can be achieved.

Clindamycin Phosphate in Sodium Chloride Injection is indicated for the treatment of serious bone and joint infections including acute hematogenous osteomyelitis caused by susceptible isolates of Staphylococcus aureus and as adjunctive therapy in the surgical treatment of chronic bone and joint infections due to susceptible organisms in adults and pediatric patients for whom appropriate dosing with this formulation can be achieved.

Since clindamycin does not diffuse adequately into the cerebrospinal fluid, Clindamycin Phosphate in Sodium Chloride Injection should not be used in the treatment of meningitis [see Clinical Pharmacology (12.3)].

To reduce the development of drug-resistant bacteria and maintain the effectiveness of Clindamycin Phosphate in Sodium Chloride Injection and other antibacterial drugs, Clindamycin Phosphate in Sodium Chloride Injection should be used only to treat or prevent infections that are proven or strongly suspected to be caused by susceptible bacteria. When culture and susceptibility information are available, they should be considered in selecting or modifying antibacterial therapy. In the absence of such data, local epidemiology and susceptibility patterns may contribute to the empiric selection of therapy.

If a dose of Clindamycin Phosphate in Sodium Chloride Injection is required that does not equal 300 mg 600 mg or 900 mg, this product is not recommended for use and an alternative formulation of clindamycin should be considered.

Administer Clindamycin Phosphate in Sodium Chloride Injection by intravenous infusion over at least 10 minutes. Infusion rates should NOT exceed 30 mg per minute. The usual infusion rates are described in Table 1.

<div class="scrollingtable"><table width="100%"> <caption> <span>Table 1: Usual Infusion Rates for the Administration of Clindamycin Phosphate in Sodium Chloride Injection</span> </caption> <col width="45%"/> <col width="45%"/> <tbody class="Headless"> <tr class="First Toprule"> <td align="center" class="Botrule Toprule" valign="top"> <p class="First"> <span class="Bold">Dose</span> </p> </td><td align="center" class="Botrule Toprule" valign="top"> <p class="First"> <span class="Bold">Time</span> </p> </td> </tr> <tr> <td align="center" class="Toprule" valign="top"> <p class="First">300 mg</p> </td><td align="center" class="Toprule" valign="top"> <p class="First">10 min</p> </td> </tr> <tr> <td align="center" valign="top"> <p class="First">600 mg</p> </td><td align="center" valign="top"> <p class="First">20 min</p> </td> </tr> <tr class="Botrule Last"> <td align="center" class="Botrule" valign="top"> <p class="First">900 mg</p> </td><td align="center" class="Botrule" valign="top"> <p class="First">30 min</p> </td> </tr> </tbody> </table></div>

Discontinue Clindamycin Phosphate in Sodium Chloride Injection if diarrhea occurs during therapy [see Boxed Warning].

The recommended dosing regimen for Clindamycin Phosphate in Sodium Chloride Injection is 600-1200 mg/day in 2, 3, or 4 equal doses by intravenous infusion for serious infections due to aerobic gram-positive cocci and the more susceptible anaerobes (NOT generally including Bacteroides fragilis, Peptococcus species and Clostridium species other than Clostridium perfringens).

For more severe infections, particularly those due to proven or suspected Bacteroides fragilis, Peptococcus species, or Clostridium species other than Clostridium perfringens, the recommended dosing regimen is 1200-2700 mg/day in 2, 3, or 4 equal doses by intravenous infusion.

In life-threatening situations, these doses may be increased. Doses of as much as 4800 mg daily have been given intravenously to adults.

Alternatively, drug may be administered in the form of a single rapid infusion of the first dose followed by continuous intravenous infusion as follows:

<div class="scrollingtable"><table cellpadding="0pt" width="100%"> <caption> <span>Table 2: Infusion Rates for the Administration of Clindamycin Injection by Single Rapid Infusion followed by Continuous Intravenous Infusion for the Maintenance of Serum Clindamycin Levels</span> </caption> <col width="33%"/> <col width="32%"/> <col width="34%"/> <tbody class="Headless"> <tr class="First"> <td align="center" class="Botrule Toprule" valign="middle"> <p class="First"> <span class="Bold">To maintain serum<br/>clindamycin levels</span> </p> </td><td align="center" class="Botrule Toprule" valign="middle"> <p class="First"> <span class="Bold">Rapid infusion rate</span> </p> </td><td align="center" class="Botrule Toprule" valign="middle"> <p class="First"> <span class="Bold">Maintenance infusion rate</span> </p> </td> </tr> <tr> <td align="center" class="Toprule" valign="top"> <p class="First">Above 4 mcg/mL</p> </td><td align="center" class="Toprule" valign="top"> <p class="First">10 mg/min for 30 min</p> </td><td align="center" class="Toprule" valign="top"> <p class="First">0.75 mg/min</p> </td> </tr> <tr> <td align="center" valign="top"> <p class="First">Above 5 mcg/mL</p> </td><td align="center" valign="top"> <p class="First">15 mg/min for 30 min</p> </td><td align="center" valign="top"> <p class="First">1.00 mg/min</p> </td> </tr> <tr class="Last"> <td align="center" class="Botrule" valign="top"> <p class="First">Above 6 mcg/mL</p> </td><td align="center" class="Botrule" valign="top"> <p class="First">20 mg/min for 30 min</p> </td><td align="center" class="Botrule" valign="top"> <p class="First">1.25 mg/min</p> </td> </tr> </tbody> </table></div>

If a dose of Clindamycin Phosphate in Sodium Chloride Injection is required that does not equal 300 mg, 600 mg or 900 mg, this product is not recommended for use and an alternative formulation of clindamycin should be considered. The recommended pediatric dosing regimen of Clindamycin Phosphate in Sodium Chloride Injection is as follows:

Pediatric patients (1 month of age to 16 years old):

The recommended dosage is 20 to 40 mg/kg/day in 3 or 4 equal doses.

The higher doses would be used for more severe infections. As an alternative to dosing on a body weight basis, pediatric patients may be dosed on the basis of square meters body surface: 350 mg/m2/day for serious infections and 450 mg/m2/day for more severe infections.

Parenteral therapy may be changed to oral formulations of clindamycin when the condition warrants and at the discretion of the physician.

In cases of β-hemolytic streptococcal infections, treatment should be continued for at least 10 days.

Pediatric Patients (less than 1 month):

The recommended dosage is 15 to 20 mg/kg/day in 3 to 4 equal doses. See Table 3 regarding the dosing regimen for pediatric patients with post-menstrual age (PMA) less than or equal to 32 weeks or greater than 32 weeks to less than or equal to 40 weeks.

<div class="scrollingtable"><table class="Noautorules" width="100%"> <caption> <span>Table 3: Dosing Regimens for Pediatric Patients with PMA less than or equal to 32 weeks, or greater than 32 weeks to less than or equal to 40 weeks</span> </caption> <col width="39%"/> <col width="29%"/> <col width="32%"/> <tbody class="Headless"> <tr> <td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First"> <span class="Bold">PMA (weeks)</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First"> <span class="Bold">Dose (mg/kg)</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First"> <span class="Bold">Dosing Interval (hours)</span> </p> </td> </tr> <tr> <td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First"> <span class="Bold">Less than or equal to 32<br/> </span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">5</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">8</p> </td> </tr> <tr> <td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First"> <span class="Bold">Greater than or equal to 32 weeks to less than or equal to 40<br/> </span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">7</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">8</p> </td> </tr> </tbody> </table></div>

PMA: Post-Menstrual Age

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.

Premixed Clindamycin Phosphate in Sodium Chloride Injection is for intravenous infusion using sterile equipment. Check for minute leaks prior to use by squeezing bag firmly. If leaks are found, discard solution as sterility may be impaired. Do NOT add supplementary medication. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration whenever solution and container permit. Do NOT use unless solution is clear and seal is intact.

Do NOT use plastic containers in series connections. Such use could result in air embolism due to residual air being drawn from the primary container before administration of the fluid from the secondary container is complete.

Clindamycin Phosphate in Sodium Chloride Injection should not be injected intravenously undiluted as a bolus, but should be infused over at least 10 minutes.

Preparation for Administration:

Injection: Clindamycin Phosphate in Sodium Chloride Injection is a clear, colorless and sterile solution available in three strengths:

{ "type": "p", "children": [], "text": "Injection: Clindamycin Phosphate in Sodium Chloride Injection is a clear, colorless and sterile solution available in three strengths:" }

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Clindamycin Phosphate in Sodium Chloride Injection is contraindicated in individuals with a history of hypersensitivity to preparations containing clindamycin or lincomycin.

{ "type": "p", "children": [], "text": "Clindamycin Phosphate in Sodium Chloride Injection is contraindicated in individuals with a history of hypersensitivity to preparations containing clindamycin or lincomycin." }

Clostridioides difficile-associated diarrhea (CDAD) has been reported with use of nearly all antibacterial agents, including Clindamycin Phosphate in Sodium Chloride Injection, and may range in severity from mild diarrhea to fatal colitis. Treatment with antibacterial agents alters the normal flora of the colon leading to overgrowth of C. difficile.

C. difficile produces toxins A and B which contribute to the development of CDAD. Hypertoxin producing isolates of C. difficile cause increased morbidity and mortality, as these infections can be refractory to antimicrobial therapy and may require colectomy. CDAD must be considered in all patients who present with diarrhea following antibacterial use. Careful medical history is necessary since CDAD has been reported to occur over two months after the administration of antibacterial agents.

If CDAD is suspected or confirmed, ongoing antibacterial use not directed against C. difficile may need to be discontinued. Appropriate fluid and electrolyte management, protein supplementation, antibacterial treatment of C. difficile, and surgical evaluation should be instituted as clinically indicated [see Boxed Warning].

Anaphylactic shock and anaphylactic reactions have been reported [see Adverse Reactions (6)]. Severe hypersensitivity reactions, including severe skin reactions such as toxic epidermal necrolysis (TEN), drug reaction with eosinophilia and systemic symptoms (DRESS), and Stevens-Johnson syndrome (SJS), some with fatal outcome, have been reported [see Adverse Reactions (6)].

In case of such an anaphylactic or severe hypersensitivity reaction, discontinue treatment permanently and institute appropriate therapy.

A careful inquiry should be made concerning previous sensitivities to drugs and other allergens.

Clindamycin is potentially nephrotoxic and cases with acute kidney injury have been reported. Consider monitoring of renal function particularly in patients with pre-existing renal dysfunction or those taking concomitant nephrotoxic drugs. In case of acute kidney injury, discontinue Clindamycin Phosphate in Sodium Chloride Injection when no other etiology is identified [see Adverse Reactions (6)].

Elderly patients with associated severe illness may have a greater risk of developing adverse reactions from diarrhea. When clindamycin is indicated in these patients, they should be carefully monitored for change in bowel frequency [see Use in Specific Populations (8.5)].

Clindamycin Phosphate in Sodium Chloride Injection products should be avoided in individuals with a history of gastrointestinal disease, particularly colitis.

Clindamycin Phosphate in Sodium Chloride Injection should be avoided in atopic individuals.

During prolonged therapy periodic liver and kidney function tests and blood counts should be performed.

Clindamycin dosage modification is not necessary in patients with renal disease. In patients with moderate to severe liver disease, prolongation of clindamycin half-life has been found. However, it was postulated from studies that when given every eight hours, accumulation should rarely occur. Therefore, dosage modification in patients with liver disease may not be necessary. However, periodic liver enzyme determinations should be made when treating patients with severe liver disease.

The use of Clindamycin Phosphate in Sodium Chloride Injection may result in overgrowth of nonsusceptible organisms-particularly yeasts. If such infections occur, appropriate measures should be taken as indicated by the clinical situation.

Prescribing Clindamycin Phosphate in Sodium Chloride Injection in the absence of a proven or strongly suspected bacterial infection or a prophylactic indication is unlikely to provide benefit to the patient and increases the risk of the development of drug-resistant bacteria.

The following serious adverse reactions to clindamycin are described below and elsewhere in the labeling:

{ "type": "p", "children": [], "text": "The following serious adverse reactions to clindamycin are described below and elsewhere in the labeling:" }

{ "type": "", "children": [], "text": "" }

The following adverse reactions associated with the use of clindamycin were identified in clinical trials or postmarketing reports. Because these reactions were reported voluntarily from a population of uncertain size, it is not always possible to estimate their frequency reliably, or to establish a causal relationship to drug exposure.

{ "type": "p", "children": [], "text": "The following adverse reactions associated with the use of clindamycin were identified in clinical trials or postmarketing reports. Because these reactions were reported voluntarily from a population of uncertain size, it is not always possible to estimate their frequency reliably, or to establish a causal relationship to drug exposure." }

Infections and Infestations

{ "type": "p", "children": [], "text": "\nInfections and Infestations\n" }

Clostridioides difficile colitis

{ "type": "p", "children": [], "text": "\nClostridioides difficile colitis" }

Gastrointestinal

{ "type": "p", "children": [], "text": "\nGastrointestinal\n" }

Antibacterial-associated colitis [see Warnings and Precautions (5.1)], pseudomembranous colitis, abdominal pain, nausea, and vomiting. The onset of pseudomembranous colitis symptoms may occur during or after antibacterial treatment [see Warnings and Precautions (5.1)]. An unpleasant or metallic taste has been reported after intravenous administration of the higher doses of clindamycin phosphate.

{ "type": "p", "children": [], "text": "Antibacterial-associated colitis [see Warnings and Precautions (5.1)], pseudomembranous colitis, abdominal pain, nausea, and vomiting. The onset of pseudomembranous colitis symptoms may occur during or after antibacterial treatment [see Warnings and Precautions (5.1)]. An unpleasant or metallic taste has been reported after intravenous administration of the higher doses of clindamycin phosphate." }

Hypersensitivity Reactions

{ "type": "p", "children": [], "text": "\nHypersensitivity Reactions\n" }

Maculopapular 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.

{ "type": "p", "children": [], "text": "Maculopapular 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." }

Severe skin reactions such as Toxic Epidermal Necrolysis, some with fatal outcome, have been reported [see Warnings and Precautions (5.2)]. Cases of Acute Generalized Exanthematous Pustulosis (AGEP), erythema multiforme, some resembling Stevens-Johnson syndrome, have been associated with clindamycin. Anaphylactic shock, anaphylactic reaction and hypersensitivity have also been reported [see Warnings and Precautions (5.2)].

{ "type": "p", "children": [], "text": "Severe skin reactions such as Toxic Epidermal Necrolysis, some with fatal outcome, have been reported [see Warnings and Precautions (5.2)]. Cases of Acute Generalized Exanthematous Pustulosis (AGEP), erythema multiforme, some resembling Stevens-Johnson syndrome, have been associated with clindamycin. Anaphylactic shock, anaphylactic reaction and hypersensitivity have also been reported [see Warnings and Precautions (5.2)].\n" }

Skin and Mucous Membranes

{ "type": "p", "children": [], "text": "\nSkin and Mucous Membranes\n" }

Pruritus, vaginitis, angioedema and rare instances of exfoliative dermatitis have been reported [see Warnings and Precautions (5.2)].

{ "type": "p", "children": [], "text": "Pruritus, vaginitis, angioedema and rare instances of exfoliative dermatitis have been reported [see Warnings and Precautions (5.2)].\n" }

Liver

{ "type": "p", "children": [], "text": "\nLiver\n" }

Jaundice and abnormalities in liver function tests have been observed during clindamycin therapy.

{ "type": "p", "children": [], "text": "Jaundice and abnormalities in liver function tests have been observed during clindamycin therapy." }

Renal

{ "type": "p", "children": [], "text": "\nRenal\n" }

Acute kidney injury [see Warnings and Precautions (5.3)].

{ "type": "p", "children": [], "text": "Acute kidney injury [see Warnings and Precautions (5.3)].\n" }

Hematopoietic

{ "type": "p", "children": [], "text": "\nHematopoietic\n" }

Transient neutropenia (leukopenia) and eosinophilia have been reported. Reports of agranulocytosis and thrombocytopenia have been made.

{ "type": "p", "children": [], "text": "Transient neutropenia (leukopenia) and eosinophilia have been reported. Reports of agranulocytosis and thrombocytopenia have been made." }

Immune System

{ "type": "p", "children": [], "text": "\nImmune System\n" }

Drug reaction with eosinophilia and systemic symptoms (DRESS) cases have been reported.

{ "type": "p", "children": [], "text": "Drug reaction with eosinophilia and systemic symptoms (DRESS) cases have been reported." }

Local Reactions

{ "type": "p", "children": [], "text": "\nLocal Reactions\n" }

Thrombophlebitis has been reported after intravenous infusion. Avoid prolonged use of indwelling intravenous catheters.

{ "type": "p", "children": [], "text": "Thrombophlebitis has been reported after intravenous infusion. Avoid prolonged use of indwelling intravenous catheters." }

Musculoskeletal

{ "type": "p", "children": [], "text": "\nMusculoskeletal\n" }

Polyarthritis cases have been reported.

{ "type": "p", "children": [], "text": "Polyarthritis cases have been reported." }

Cardiovascular

{ "type": "p", "children": [], "text": "\nCardiovascular\n" }

Cardiopulmonary arrest and hypotension have been reported following too rapid intravenous administration [see Dosage and Administration (2)].

{ "type": "p", "children": [], "text": "Cardiopulmonary arrest and hypotension have been reported following too rapid intravenous administration [see Dosage and Administration (2)]." }

Clindamycin has been shown to have neuromuscular blocking properties that may enhance the action of other neuromuscular blocking agents. Therefore, it should be avoided in patients receiving such agents.

Inhibitors of CYP3A4 and/or CYP3A5 may increase plasma concentrations of clindamycin [see Clinical Pharmacology (12.3)]. Monitor for adverse reactions when strong CYP3A4 and/or CYP3A5 inhibitors are coadministered with clindamycin.

Inducers of CYP3A4 and/or CYP3A5 may reduce plasma concentrations of clindamycin. In the presence of strong CYP3A4 and/or CYP3A5 inducers such as rifampicin, monitor for loss of effectiveness.

In limited published 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 major birth defects.

The limited published data on use of clindamycin in pregnant women with exposure during the first trimester are insufficient to inform a drug-associated risk of pregnancy-related adverse outcomes [see Data]. In animal reproduction studies, no evidence of any adverse developmental outcomes was observed when oral or subcutaneous doses of clindamycin were administered to pregnant rats and mice during organogenesis at doses half to twice the highest clinically relevant dose based on body surface area comparison [see Data]. The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively.

Human Data

In limited published trials in pregnant women administered clindamycin during the first trimester of pregnancy, there was no difference in the rate of major birth defects reported among in utero exposed infants compared to unexposed infants. From these observational data, it is not possible to draw any conclusions on the rate of specific major birth defects associated with clindamycin. These data cannot definitely establish or exclude any clindamycin-associated risk during pregnancy.

Animal Data

Reproduction studies performed during organogenesis (gestational days 6-15) in pregnant rats and mice that were administered oral doses of clindamycin up to 600 mg/kg/day (twice or equivalent to the highest recommended adult human dose based on a body surface area comparison, respectively) or subcutaneous doses of clindamycin up to 250 mg/kg/day (equivalent to or half the highest recommended adult human dose based on a body surface area comparison, respectively) revealed no evidence of teratogenicity.

Clindamycin has been reported to appear in breast milk in the range of less than 0.5 to 3.8 mcg/mL at dosages of 150 mg orally to 600 mg intravenously. Clindamycin has the potential to cause adverse effects on the breastfed infant’s gastrointestinal flora.

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 breast-fed child from clindamycin or from the underlying maternal condition.

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 blood in the stool indicating possible antibacterial-associated colitis.

Clindamycin Phosphate in Sodium Chloride Injection is indicated for the treatment of serious infections caused by susceptible anaerobic bacteria, infections due to susceptible isolates of streptococci, pneumococci and staphylococci, lower respiratory tract Infections, skin and skin structure infections, gynecological infections, intra-abdominal infections, septicemia and bone and joint infections in pediatric patients for whom appropriate dosing with this formulation can be achieved [see Indications and Usage (1.1-1.8)] and Dosage and Administration (2.3)].

When Clindamycin Phosphate in Sodium Chloride Injection is administered to the pediatric population (less than 1 month to 16 years old) appropriate dosing and monitoring of organ system functions is desirable. Because of the limitations of the available strengths and administration requirements (i.e., administration of fractional doses is not recommended) of Clindamycin Phosphate in Sodium Chloride Injection, and to avoid unintentional overdose, this product is not recommended for use if a dose of Clindamycin Phosphate in Sodium Chloride Injection is required that does not equal 300 mg 600 mg or 900 mg is required and an alternative formulation of clindamycin should be considered [see Dosage and Administration (2.3)].

The potential for the toxic effect in the pediatric population from chemicals that may leach from the single dose premixed Clindamycin Phosphate in Sodium Chloride Injection preparation in plastic has not been evaluated.

Clinical studies of clindamycin did not include sufficient numbers of patients age 65 and over to determine whether they respond differently from younger patients. However, other reported clinical experience indicates that antibacterial-associated colitis and diarrhea (due to Clostridioides difficile) seen in association with most antibacterial drugs occur more frequently in the elderly (>60 years) and may be more severe. These patients should be carefully monitored for the development of diarrhea.

Pharmacokinetic studies with clindamycin have shown no clinically important differences between young and elderly subjects with normal hepatic function and normal (age-adjusted) renal function after oral or intravenous administration [see Clinical Pharmacology (12.3)].

Significant mortality was observed in mice at an intravenous dose of 855 mg/kg (~3 times the human dose based on body surface area) and in rats at an oral or subcutaneous dose of approximately 2618 mg/kg (~18 times the human dose based on body surface area). In the mice, convulsions and depression were observed and in rats depression was observed prior to death.

{ "type": "p", "children": [], "text": "Significant mortality was observed in mice at an intravenous dose of 855 mg/kg (~3 times the human dose based on body surface area) and in rats at an oral or subcutaneous dose of approximately 2618 mg/kg (~18 times the human dose based on body surface area). In the mice, convulsions and depression were observed and in rats depression was observed prior to death." }

Hemodialysis and peritoneal dialysis are not effective in removing clindamycin from the serum.

{ "type": "p", "children": [], "text": "Hemodialysis and peritoneal dialysis are not effective in removing clindamycin from the serum." }

Clindamycin Phosphate in Sodium Chloride Injection contains clindamycin phosphate, a water-soluble ester of clindamycin. Clindamycin is a semisynthetic antibacterial produced by a 7(S)-chloro-substitution of the 7(R)-hydroxyl group of the parent antibacterial lincomycin.

{ "type": "p", "children": [], "text": "Clindamycin Phosphate in Sodium Chloride Injection contains clindamycin phosphate, a water-soluble ester of clindamycin. Clindamycin is a semisynthetic antibacterial produced by a 7(S)-chloro-substitution of the 7(R)-hydroxyl group of the parent antibacterial lincomycin." }

The chemical name of clindamycin phosphate is L-threo-α-D-galacto-Octopyranoside, methyl-7-chloro-6,7,8-trideoxy-6-[[(1-methyl-4-propyl-2-pyrrolidinyl)carbonyl]amino]01-thio-, 2-(dihydrogen phosphate), (2S-trans)-.

{ "type": "p", "children": [], "text": "The chemical name of clindamycin phosphate is L-threo-α-D-galacto-Octopyranoside, methyl-7-chloro-6,7,8-trideoxy-6-[[(1-methyl-4-propyl-2-pyrrolidinyl)carbonyl]amino]01-thio-, 2-(dihydrogen phosphate), (2S-trans)-." }

The molecular formula is C18H34CIN2O8PS and the molecular weight is 504.96.

{ "type": "p", "children": [], "text": "The molecular formula is C18H34CIN2O8PS and the molecular weight is 504.96." }

The structural formula is represented below:

{ "type": "p", "children": [], "text": "The structural formula is represented below:" }

Clindamycin Phosphate in Sodium Chloride Injection is a clear, colorless and sterile solution for intravenous infusion available in three strengths, 300 mg/50 mL, 600 mg/50 mL, and 900 mg/50 mL, containing 300 mg, 600 mg or 900 mg clindamycin, respectively (as clindamycin phosphate, USP). Each 50 mL of all the strengths of Clindamycin Phosphate in Sodium Chloride Injection also contains, 450 mg of sodium chloride USP, 2 mg of edetate disodium dihydrate USP, and water for Injection USP. The pH is adjusted with sodium hydroxide and /or hydrochloric acid. Clindamycin Phosphate in Sodium Chloride Injection is filled in GALAXY plastic container fabricated from a specially designed multilayer plastic. Solutions in contact with the plastic container can leach out certain of its chemical components in very small amounts within the expiration period. The suitability of the plastic has been confirmed in tests in animals according to the USP biological tests for plastic containers, as well as by tissue culture toxicity studies.

{ "type": "p", "children": [], "text": "Clindamycin Phosphate in Sodium Chloride Injection is a clear, colorless and sterile solution for intravenous infusion available in three strengths, 300 mg/50 mL, 600 mg/50 mL, and 900 mg/50 mL, containing 300 mg, 600 mg or 900 mg clindamycin, respectively (as clindamycin phosphate, USP). Each 50 mL of all the strengths of Clindamycin Phosphate in Sodium Chloride Injection also contains, 450 mg of sodium chloride USP, 2 mg of edetate disodium dihydrate USP, and water for Injection USP. The pH is adjusted with sodium hydroxide and /or hydrochloric acid. Clindamycin Phosphate in Sodium Chloride Injection is filled in GALAXY plastic container fabricated from a specially designed multilayer plastic. Solutions in contact with the plastic container can leach out certain of its chemical components in very small amounts within the expiration period. The suitability of the plastic has been confirmed in tests in animals according to the USP biological tests for plastic containers, as well as by tissue culture toxicity studies." }

Clindamycin is an antibacterial drug [see Microbiology (12.4)].

Clindamycin phosphate is a water-soluble ester prodrug of clindamycin. Biologically inactive clindamycin phosphate is converted to active clindamycin. By the end of short-term intravenous infusion, peak serum concentrations of active clindamycin are reached.

After intramuscular injection of clindamycin phosphate, peak concentrations of active clindamycin are reached within 3 hours in adults and 1 hour in pediatric patients. Serum concentration-time curves may be constructed from intravenous peak serum concentrations by application of elimination half-lives described in the elimination section below.

Serum concentrations of clindamycin can be maintained above the in vitro minimum inhibitory concentrations for most indicated organisms by administration of clindamycin phosphate every 8 to 12 hours in adults and every 6 to 8 hours in pediatric patients, or by continuous intravenous infusion. An equilibrium state is reached by the third dose.

No significant concentrations of clindamycin are attained in the cerebrospinal fluid even in the presence of inflamed meninges.

Clindamycin is metabolized predominantly by CYP3A4, and to a lesser extent by CYP3A5, to the major metabolite clindamycin sulfoxide and minor metabolite N-desmethylclindamycin. Biologically inactive clindamycin phosphate disappears from the serum with 6 minutes of the average elimination half-life; however, the average serum elimination half-life of active clindamycin is about 3 hours in adults and 2.5 hours in pediatric patients.

Patients with Renal/Hepatic Impairment

The elimination half-life of clindamycin is increased slightly in patients with markedly reduced renal or hepatic function. Hemodialysis and peritoneal dialysis are not effective in removing clindamycin from the serum. Dosage schedules do not need to be modified in patients with renal or hepatic disease.

Geriatric Patients

Pharmacokinetic studies in elderly volunteers (61-79 years) and younger adults (18-39 years) indicate that age alone does not alter clindamycin pharmacokinetics (clearance, elimination half-life, volume of distribution, and area under the serum concentration-time curve) after intravenous administration of clindamycin phosphate. After oral administration of clindamycin hydrochloride, the average elimination half-life is increased to approximately 4.0 hours (range 3.4-5.1 h) in the elderly, compared to 3.2 hours (range 2.1-4.2 h) in younger adults. The extent of absorption, however, is not different between age groups and no dosage alteration is necessary for the elderly with normal hepatic function and normal (age-adjusted) renal function1.

Pharmacokinetics in Pediatric Patients with PMA ≤ 32 weeks, or > 32 to ≤ 40 weeks

Systemic clearance (CL) in premature infants increases with increases in bodyweight (kg) and post-menstrual age (PMA). The dosing regimens for pediatric patients ≤ 32 weeks PMA (5 mg/kg) and 32 to ≤ 40 weeks PMA (7 mg/kg), both administered IV every 8 hours, achieve exposures comparable to therapeutic exposures in adults (weighing 70 kg) administered clindamycin 600 mg every 8 hours (Table 4).

<div class="scrollingtable"><table class="Noautorules" width="100%"> <caption> <span>Table 4: Predicted Drug Exposure (Mean ± SD) of Clindamycin in Adults and in Pediatric Patients with PMA ≤ 32 weeks, or &gt; 32 to ≤ 40 weeks</span> </caption> <col width="26%"/> <col width="24%"/> <col width="24%"/> <col width="25%"/> <tbody class="Headless"> <tr> <td class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First"> <span class="Bold">Age</span> </p> </td><td class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First"> <span class="Bold">Adult (70 kg)</span> </p> </td><td class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First"> <span class="Bold">PMA ≤ 32 weeks</span> </p> </td><td class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First"> <span class="Bold">PMA &gt; 32 - ≤ 40 weeks</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First"> <span class="Bold">Dose (every 8 hours)</span> </p> </td><td class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">600 mg</p> </td><td class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">5 mg/kg</p> </td><td class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">7 mg/kg</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First"> <span class="Bold">AUC<span class="Sub">ss,0-8</span><span class="Sub">hour</span> <br/>(mcg.h/mL)</span> </p> </td><td class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">50.5 (30.9)</p> </td><td class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">52.5 (17.0)</p> </td><td class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">55.9 (23.6)</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First"> <span class="Bold">C<span class="Sub">max,ss</span> (mcg/mL)</span> </p> </td><td class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">12.0 (3.5)</p> </td><td class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">9.0 (2.2)</p> </td><td class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">10.5 (2.8)</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First"> <span class="Bold">C<span class="Sub">min,ss </span>(mcg/mL)</span> </p> </td><td class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">3.1 (3.3)</p> </td><td class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">4.6 (2.0)</p> </td><td class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">4.4 (2.8)</p> </td> </tr> </tbody> </table></div>

PMA: post-menstrual age; AUCss,0-8 hour: area under the concentration-time curve during a dosing interval at steady state; Cmax,ss: maximum drug concentration at steady state; Cmin,ss: minimum or trough drug concentration at steady state

Obese Pediatric Patients Aged 2 to Less than 18 Years and Obese Adults Aged 18 to 20 Years

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

Drug Interaction Studies

In vitro studies indicate that clindamycin does not inhibit CYP1A2, CYP2C9, CYP2C19, CYP2E1 or CYP2D6 and only moderately inhibits CYP3A4.

Clindamycin inhibits bacterial protein synthesis by binding to the 23S RNA of the 50S subunit of the ribosome. Clindamycin is bacteriostatic.

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. Because the binding sites for these antibacterial drugs overlap, cross-resistance is sometimes observed among lincosamides, macrolides and streptogramin B. Macrolide-inducible resistance to clindamycin occurs in some isolates of macrolide-resistant bacteria. Macrolide-resistant isolates of staphylococci and beta-hemolytic streptococci should be screened for induction of clindamycin resistance using the D-zone test.

Clindamycin has been shown to be active against most isolates of the following microorganisms, both in vitro and in clinical infections [see Indications and Usage (1)].

The following in vitro data are available, but their clinical significance is unknown. At least 90 percent of the following bacteria exhibit an in vitro minimum inhibitory concentration (MIC) less than or equal to the susceptible breakpoint for clindamycin against isolates of similar genus or organism group. However, the efficacy of clindamycin in treating clinical infections caused by these bacteria has not been established in adequate and well-controlled clinical trials.

For specific information regarding susceptibility test interpretive criteria, and associated test methods and quality control standards recognized by FDA for this drug, please see https://www.fda.gov/STIC.

Long term studies in animals have not been performed with clindamycin to evaluate carcinogenic potential. Genotoxicity tests performed included a rat micronucleus test and an Ames Salmonella reversion test. Both tests were negative.

Fertility studies in rats treated orally with up to 300 mg/kg/day (approximately 1.1 times the highest recommended adult human dose based on mg/m2) revealed no effects on fertility or mating ability.

{ "type": "", "children": [], "text": "" }

Clindamycin Phosphate in Sodium Chloride Injection is a clear, colorless and sterile solution for intravenous infusion. Each 50 mL of Clindamycin in Phosphate in Sodium Chloride Injection, 300 mg/50 mL, 600mg/50mL, and 900 mg/50 mL, contains 300 mg, 600 mg, or 900 mg clindamycin, respectively (as clindamycin phosphate, USP) in 0.9% sodium chloride solution. Clindamycin in Phosphate in Sodium Chloride Injection in single-dose GALAXY containers is available as follows:

{ "type": "p", "children": [], "text": "Clindamycin Phosphate in Sodium Chloride Injection is a clear, colorless and sterile solution for intravenous infusion. Each 50 mL of Clindamycin in Phosphate in Sodium Chloride Injection, 300 mg/50 mL, 600mg/50mL, and 900 mg/50 mL, contains 300 mg, 600 mg, or 900 mg clindamycin, respectively (as clindamycin phosphate, USP) in 0.9% sodium chloride solution. Clindamycin in Phosphate in Sodium Chloride Injection in single-dose GALAXY containers is available as follows:" }

<div class="scrollingtable"><table class="Noautorules" width="100%"> <col width="21%"/> <col width="45%"/> <col width="33%"/> <tbody class="Headless"> <tr> <td valign="top"> <p class="First">2G3455</p> </td><td valign="top"> <p class="First">Twenty-four (24)-300 mg/50 mL containers</p> </td><td valign="top"> <p class="First">NDC 0338-9545-24</p> </td> </tr> <tr> <td valign="top"> <p class="First">2G3456</p> </td><td valign="top"> <p class="First">Twenty-four (24)-600 mg/50 mL containers</p> </td><td valign="top"> <p class="First">NDC 0338-9549-24</p> </td> </tr> <tr> <td valign="top"> <p class="First">2G3457</p> </td><td valign="top"> <p class="First">Twenty-four (24)-900 mg/50 mL containers</p> </td><td valign="top"> <p class="First">NDC 0338-9553-24</p> </td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table class=\"Noautorules\" width=\"100%\">\n<col width=\"21%\"/>\n<col width=\"45%\"/>\n<col width=\"33%\"/>\n<tbody class=\"Headless\">\n<tr>\n<td valign=\"top\">\n<p class=\"First\">2G3455</p>\n</td><td valign=\"top\">\n<p class=\"First\">Twenty-four (24)-300 mg/50 mL containers</p>\n</td><td valign=\"top\">\n<p class=\"First\">NDC 0338-9545-24</p>\n</td>\n</tr>\n<tr>\n<td valign=\"top\">\n<p class=\"First\">2G3456</p>\n</td><td valign=\"top\">\n<p class=\"First\">Twenty-four (24)-600 mg/50 mL containers</p>\n</td><td valign=\"top\">\n<p class=\"First\">NDC 0338-9549-24</p>\n</td>\n</tr>\n<tr>\n<td valign=\"top\">\n<p class=\"First\">2G3457</p>\n</td><td valign=\"top\">\n<p class=\"First\">Twenty-four (24)-900 mg/50 mL containers</p>\n</td><td valign=\"top\">\n<p class=\"First\">NDC 0338-9553-24</p>\n</td>\n</tr>\n</tbody>\n</table></div>" }

Exposure of pharmaceutical products, including clindamycin phosphate in sodium chloride, to heat should be minimized. It is recommended that GALAXY plastic containers be stored at 20°C to 25°C (68°F to 77°F) excursions permitted to 15°C to 30°C (59°F to 86°F) [see USP Controlled Room Temperature]. Avoid temperatures above 30°C.

{ "type": "p", "children": [], "text": "Exposure of pharmaceutical products, including clindamycin phosphate in sodium chloride, to heat should be minimized. It is recommended that GALAXY plastic containers be stored at 20°C to 25°C (68°F to 77°F) excursions permitted to 15°C to 30°C (59°F to 86°F) [see USP Controlled Room Temperature]. Avoid temperatures above 30°C." }

C. difficile-Associated Diarrhea (CDAD)

{ "type": "p", "children": [], "text": "\nC. difficile-Associated Diarrhea (CDAD)\n" }

Advise patients that diarrhea is a common problem caused by antibacterial drugs including Clindamycin Phosphate in Sodium Chloride Injection, that usually ends when the antibacterial is discontinued. Sometimes after starting treatment with antibacterial drugs, including Clindamycin Phosphate in Sodium Chloride Injection, patients can develop watery and bloody stools (with or without stomach cramps and fever) even as late as two or more months after having taken the last dose of the antibacterial drugs. If this occurs, contact physician as soon as possible [see Warnings and Precautions (5.1)].

{ "type": "p", "children": [], "text": "Advise patients that diarrhea is a common problem caused by antibacterial drugs including Clindamycin Phosphate in Sodium Chloride Injection, that usually ends when the antibacterial is discontinued. Sometimes after starting treatment with antibacterial drugs, including Clindamycin Phosphate in Sodium Chloride Injection, patients can develop watery and bloody stools (with or without stomach cramps and fever) even as late as two or more months after having taken the last dose of the antibacterial drugs. If this occurs, contact physician as soon as possible [see Warnings and Precautions (5.1)].\n" }

Antibacterial Resistance

{ "type": "p", "children": [], "text": "\nAntibacterial Resistance\n" }

Patients should be counseled that antibacterial drugs including Clindamycin Phosphate in Sodium Chloride Injection should only be used to treat bacterial infections. They do not treat viral infections (e.g., the common cold). When Clindamycin Phosphate in Sodium Chloride Injection is prescribed to treat a bacterial infection, patients should be told that although it is common to feel better early in the course of therapy, the medication should be taken exactly as directed. Skipping doses or not completing the full course of therapy may (1) decrease the effectiveness of the immediate treatment and (2) increase the likelihood that bacteria will develop resistance and will not be treatable by Clindamycin Phosphate in Sodium Chloride Injection or other antibacterial drugs in the future.

{ "type": "p", "children": [], "text": "Patients should be counseled that antibacterial drugs including Clindamycin Phosphate in Sodium Chloride Injection should only be used to treat bacterial infections. They do not treat viral infections (e.g., the common cold). When Clindamycin Phosphate in Sodium Chloride Injection is prescribed to treat a bacterial infection, patients should be told that although it is common to feel better early in the course of therapy, the medication should be taken exactly as directed. Skipping doses or not completing the full course of therapy may (1) decrease the effectiveness of the immediate treatment and (2) increase the likelihood that bacteria will develop resistance and will not be treatable by Clindamycin Phosphate in Sodium Chloride Injection or other antibacterial drugs in the future." }

Lactation

{ "type": "p", "children": [], "text": "\nLactation\n" }

Advise a woman to monitor the breastfed infant for diarrhea and bloody stools [see Use in Specific Populations (8.2)].

{ "type": "p", "children": [], "text": "Advise a woman to monitor the breastfed infant for diarrhea and bloody stools [see Use in Specific Populations (8.2)]." }

Baxter Healthcare Corporation Deerfield, IL 60015 USA

{ "type": "p", "children": [], "text": "\nBaxter Healthcare Corporation\nDeerfield, IL 60015 USA" }

Made in USA.

{ "type": "p", "children": [], "text": "Made in USA." }

Baxter and Galaxy are registered trademarks of Baxter International Inc.

{ "type": "p", "children": [], "text": "Baxter and Galaxy are registered trademarks of Baxter International Inc." }

07-19-09-273

{ "type": "p", "children": [], "text": "07-19-09-273" }

{ "type": "", "children": [], "text": "" }

NDC 0338-9545-50Clindamycin Phosphate in 0.9% Sodium Chloride Injection300 mg per 50 mL (6 mg / mL)

{ "type": "p", "children": [], "text": "\nNDC 0338-9545-50Clindamycin Phosphate in 0.9% Sodium Chloride Injection300 mg per 50 mL (6 mg / mL)\n" }

50 mL Single-Dose GALAXY ContainerCode 2G3455

{ "type": "p", "children": [], "text": "\n50 mL Single-Dose GALAXY ContainerCode 2G3455\n" }

Discard unused portionSterile Nonpyrogenic

{ "type": "p", "children": [], "text": "\nDiscard unused portionSterile Nonpyrogenic\n" }

For Intravenous Infusion Only

{ "type": "p", "children": [], "text": "\nFor Intravenous Infusion Only\n" }

Cautions: Do not add supplementary medication. Must not be used in series connections. Check for minute leaks and solution clarity.

{ "type": "p", "children": [], "text": "Cautions: Do not add supplementary medication. Must not be used in series connections. Check for minute leaks and solution clarity." }

Each 50 mL contains: Clindamycin phosphate, USP equivalent to 300 mg clindamycin, 450 mg sodium chloride, USP, 2 mg edetate disodium dihydrate, USP, and Water for Injection, USP. pH may have been adjusted with sodium hydroxide and/or hydrochloric acid.

{ "type": "p", "children": [], "text": "Each 50 mL contains: Clindamycin phosphate, USP equivalent to 300 mg clindamycin, 450 mg sodium chloride, USP, 2 mg edetate disodium dihydrate, USP, and Water for Injection, USP. pH may have been adjusted with sodium hydroxide and/or hydrochloric acid." }

Dosage: See prescribing information.

{ "type": "p", "children": [], "text": "Dosage: See prescribing information." }

Rx only Store at 20°C to 25°C (68°F to 77°F)[see USP Controlled Room Temperature]. Avoid temperatures above 30°C.

{ "type": "p", "children": [], "text": "\nRx only\nStore at 20°C to 25°C (68°F to 77°F)[see USP Controlled Room Temperature]. Avoid temperatures above 30°C." }

BAXTER Logo

{ "type": "p", "children": [], "text": "\nBAXTER Logo\n" }

Baxter and Galaxy are registered trademarks of Baxter International Inc. Baxter Healthcare Corporation, Deerfield, IL 60015 USAMade in USA

{ "type": "p", "children": [], "text": "Baxter and Galaxy are registered trademarks of Baxter International Inc.\nBaxter Healthcare Corporation, Deerfield, IL 60015 USAMade in USA" }

07-34-00-2141

{ "type": "p", "children": [], "text": "07-34-00-2141" }

Bar Code Position Only303389545507

{ "type": "p", "children": [], "text": "Bar Code Position Only303389545507" }

{ "type": "", "children": [], "text": "" }

GALAXY Container

{ "type": "p", "children": [], "text": "\nGALAXY Container" }

BAXTER Logo

{ "type": "p", "children": [], "text": "\nBAXTER Logo\n" }

Baxter and Galaxy are registered trademarks of Baxter International Inc. Baxter Healthcare Corporation, Deerfield, IL 60015 USAMade in USA

{ "type": "p", "children": [], "text": "Baxter and Galaxy are registered trademarks of Baxter International Inc.\nBaxter Healthcare Corporation, Deerfield, IL 60015 USAMade in USA" }

07-04-00-1232

{ "type": "p", "children": [], "text": "07-04-00-1232" }

Clindamycin Phosphate in 0.9% Sodium Chloride Injection300 mg per 50 mL (6 mg / mL)Contains 12 - 50 mL Single-Dose Containers Store at 20°C to 25°C (68°F to 77°F) [see USP Controlled Room Temperature]. Avoid temperatures above 30°C.

{ "type": "p", "children": [], "text": "\nClindamycin Phosphate in 0.9% Sodium Chloride Injection300 mg per 50 mL (6 mg / mL)Contains 12 - 50 mL Single-Dose Containers\nStore at 20°C to 25°C (68°F to 77°F) [see USP Controlled Room Temperature]. Avoid temperatures above 30°C.\n" }

Rx only NDC 0338-9545-24Code 2G3455

{ "type": "p", "children": [], "text": "\nRx only\n\nNDC 0338-9545-24Code 2G3455\n" }

FOR BAR CODE POSITION ONLY (01) 20303389545242

{ "type": "p", "children": [], "text": "\nFOR BAR CODE POSITION ONLY\n(01) 20303389545242" }

For Intravenous Infusion Only Sterile Nonpyrogenic

{ "type": "p", "children": [], "text": "\nFor Intravenous Infusion Only \nSterile Nonpyrogenic" }

Each 50 mL contains: Clindamycin phosphate, USP equivalent to 300 mg clindamycin, 450 mg sodium chloride, USP, 2 mg edetate disodium dihydrate, USP, and Water for Injection, USP. pH may have been adjusted with sodium hydroxide and/or hydrochloric acid.Dosage: See prescribing information.Cautions: Do not add supplementary medication. Must not be used in series connections.Check for minute leaks and solution clarity.

{ "type": "p", "children": [], "text": "Each 50 mL contains: Clindamycin phosphate, USP equivalent to 300 mg clindamycin, 450 mg sodium chloride, USP, 2 mg edetate disodium dihydrate, USP, and Water for Injection, USP. pH may have been adjusted with sodium hydroxide and/or hydrochloric acid.Dosage: See prescribing information.Cautions: Do not add supplementary medication. Must not be used in series connections.Check for minute leaks and solution clarity." }

{ "type": "", "children": [], "text": "" }

NDC0338-9549-50 Clindamycin Phosphate in 0.9% Sodium Chloride Injection

{ "type": "p", "children": [], "text": "\nNDC0338-9549-50\nClindamycin Phosphate in 0.9% Sodium Chloride Injection\n" }

600 mg per 50 mL (12 mg / mL)

{ "type": "p", "children": [], "text": "\n600 mg per 50 mL (12 mg / mL)\n" }

50 mL Single-Dose GALAXY ContainerCode 2G3456

{ "type": "p", "children": [], "text": "\n50 mL Single-Dose GALAXY ContainerCode 2G3456\n" }

Discard unused portionFor Intravenous Use Only

{ "type": "p", "children": [], "text": "\nDiscard unused portionFor Intravenous Use Only\n" }

Sterile Nonpyrogenic

{ "type": "p", "children": [], "text": "\nSterile Nonpyrogenic\n" }

Cautions: Do not add supplementary medication. Must not be used inseries connections. Check for minute leaks and solution clarity.

{ "type": "p", "children": [], "text": "Cautions: Do not add supplementary medication. Must not be used inseries connections. Check for minute leaks and solution clarity." }

Each 50 mL contains: Clindamycin phosphate, USP equivalent to 600 mg clindamycin, 450 mg sodium chloride, USP, 2 mg edetate disodium dihydrate, USP, and Water for Injection, USP. pH may have been adjusted with sodium hydroxide and/or hydrochloric acid.

{ "type": "p", "children": [], "text": "Each 50 mL contains: Clindamycin phosphate, USP equivalent to 600 mg clindamycin, 450 mg sodium chloride, USP, 2 mg edetate disodium dihydrate, USP, and Water for Injection, USP. pH may have been adjusted with sodium hydroxide and/or hydrochloric acid." }

Dosage: See prescribing information.

{ "type": "p", "children": [], "text": "Dosage: See prescribing information." }

Rx only Store at 20° to 25°C (68° to 77°F) [see USP Controlled Room Temperature].Avoid temperatures above 30°C.

{ "type": "p", "children": [], "text": "\nRx only\nStore at 20° to 25°C (68° to 77°F) [see USP Controlled Room Temperature].Avoid temperatures above 30°C." }

BAXTER Logo

{ "type": "p", "children": [], "text": "\nBAXTER Logo\n" }

Baxter and Galaxy are registered trademarks of Baxter International Inc. Baxter Healthcare Corporation, Deerfield, IL 60015 USAMade in USA

{ "type": "p", "children": [], "text": "Baxter and Galaxy are registered trademarks of Baxter International Inc.\nBaxter Healthcare Corporation, Deerfield, IL 60015 USAMade in USA" }

07-34-00-2158

{ "type": "p", "children": [], "text": "07-34-00-2158" }

BAR CODE POSTION ONLY303389549505

{ "type": "p", "children": [], "text": "BAR CODE POSTION ONLY303389549505" }

{ "type": "", "children": [], "text": "" }

GALAXY Container

{ "type": "p", "children": [], "text": "\nGALAXY Container" }

BAXTER Logo

{ "type": "p", "children": [], "text": "\nBAXTER Logo\n" }

Baxter and Galaxy are registered trademarks of Baxter International Inc. Baxter Healthcare Corporation, Deerfield, IL 60015 USAMade in USA

{ "type": "p", "children": [], "text": "Baxter and Galaxy are registered trademarks of Baxter International Inc.\nBaxter Healthcare Corporation, Deerfield, IL 60015 USAMade in USA" }

07-04-00-1233

{ "type": "p", "children": [], "text": "07-04-00-1233" }

Clindamycin Phosphate in 0.9% Sodium Chloride Injection600 mg per 50 mL (12 mg / mL)Contains 12 - 50 mL Single-Dose Containers Store at 20°C to 25°C (68°F to 77°F)[see USP Controlled Room Temperature]. Avoid temperatures above 30°C.

{ "type": "p", "children": [], "text": "\nClindamycin Phosphate in 0.9% Sodium Chloride Injection600 mg per 50 mL (12 mg / mL)Contains 12 - 50 mL Single-Dose Containers\nStore at 20°C to 25°C (68°F to 77°F)[see USP Controlled Room Temperature]. Avoid temperatures above 30°C.\n" }

Rx onlyNDC 0338-9549-24Code 2G3456

{ "type": "p", "children": [], "text": "\nRx onlyNDC 0338-9549-24Code 2G3456\n" }

FOR BAR CODE POSITION ONLY (01) 20303389549240

{ "type": "p", "children": [], "text": "FOR BAR CODE POSITION ONLY (01) 20303389549240" }

For Intravenous Infusion Only Sterile Nonpyrogenic

{ "type": "p", "children": [], "text": "\nFor Intravenous Infusion Only \nSterile Nonpyrogenic" }

Each 50 mL contains: Clindamycin phosphate, USP equivalent to 600 mg clindamycin, 450 mg sodium chloride, USP, 2 mg edetate disodium dihydrate, USP, and Water for Injection, USP. pH may have been adjusted with sodium hydroxide and/or hydrochloric acid.Dosage: See prescribing information.Cautions: Do not add supplementary medication. Must not be used in series connections. Check for minute leaks and solution clarity.

{ "type": "p", "children": [], "text": "Each 50 mL contains: Clindamycin phosphate, USP equivalent to 600 mg clindamycin, 450 mg sodium chloride, USP, 2 mg edetate disodium dihydrate, USP, and Water for Injection, USP. pH may have been adjusted with sodium hydroxide and/or hydrochloric acid.Dosage: See prescribing information.Cautions: Do not add supplementary medication. Must not be used in series connections. Check for minute leaks and solution clarity." }

{ "type": "", "children": [], "text": "" }

NDC 0338-9553-50Clindamycin Phosphate in 0.9% Sodium Chloride Injection

{ "type": "p", "children": [], "text": "\nNDC 0338-9553-50Clindamycin Phosphate in 0.9% Sodium Chloride Injection\n" }

900 mg per 50 mL (18 mg / mL)

{ "type": "p", "children": [], "text": "\n900 mg per 50 mL (18 mg / mL)\n" }

50 mL Single-Dose GALAXY ContainerCode 2G3457Discard unused portionSterile NonpyrogenicFor Intravenous Infusion Only

{ "type": "p", "children": [], "text": "\n50 mL Single-Dose GALAXY ContainerCode 2G3457Discard unused portionSterile NonpyrogenicFor Intravenous Infusion Only\n" }

Cautions: Do not add supplementary medication. Must not be used in series connections. Check for minute leaks and solution clarity.

{ "type": "p", "children": [], "text": "Cautions: Do not add supplementary medication. Must not be used in series connections. Check for minute leaks and solution clarity." }

Each 50 mL contains: Clindamycin phosphate, USP equivalent to 900 mg clindamycin, 450 mg sodium chloride, USP, 2 mg edetate disodium dihydrate, USP, and Water for Injection, USP. pH may have been adjusted with sodium hydroxide and/or hydrochloric acid.Dosage: See prescribing information.

{ "type": "p", "children": [], "text": "Each 50 mL contains: Clindamycin phosphate, USP equivalent to 900 mg clindamycin, 450 mg sodium chloride, USP, 2 mg edetate disodium dihydrate, USP, and Water for Injection, USP. pH may have been adjusted with sodium hydroxide and/or hydrochloric acid.Dosage: See prescribing information." }

Rx only Store at 20° to 25°C (68° to 77°F) [see USP Controlled Room Temperature].Avoid temperatures above 30°C.

{ "type": "p", "children": [], "text": "\nRx only\nStore at 20° to 25°C (68° to 77°F) [see USP Controlled Room Temperature].Avoid temperatures above 30°C." }

BAXTER Logo

{ "type": "p", "children": [], "text": "\nBAXTER Logo\n" }

Baxter and Galaxy are registered trademarks of Baxter International Inc. Baxter Healthcare Corporation, Deerfield, IL 60015 USAMade in USA

{ "type": "p", "children": [], "text": "Baxter and Galaxy are registered trademarks of Baxter International Inc.\nBaxter Healthcare Corporation, Deerfield, IL 60015 USAMade in USA" }

07-34-00-2159

{ "type": "p", "children": [], "text": "07-34-00-2159" }

BAR CODE POSITION ONLY303389553502

{ "type": "p", "children": [], "text": "BAR CODE POSITION ONLY303389553502" }

{ "type": "", "children": [], "text": "" }

GALAXY Container

{ "type": "p", "children": [], "text": "\nGALAXY Container " }

BAXTER Logo

{ "type": "p", "children": [], "text": "\nBAXTER Logo\n" }

Baxter and Galaxy are registered trademarks of Baxter International Inc. Baxter Healthcare Corporation, Deerfield, IL 60015 USAMade in USA

{ "type": "p", "children": [], "text": "Baxter and Galaxy are registered trademarks of Baxter International Inc.\nBaxter Healthcare Corporation, Deerfield, IL 60015 USAMade in USA" }

07-04-00-1234

{ "type": "p", "children": [], "text": "07-04-00-1234" }

Clindamycin Phosphate in 0.9% Sodium Chloride Injection900 mg per 50 mL (18 mg / mL)Contains 12 - 50 mL Single-Dose Containers Store at 20°C to 25°C (68°F to 77°F)[see USP Controlled Room Temperature]. Avoid temperatures above 30°C.

{ "type": "p", "children": [], "text": "\nClindamycin Phosphate in 0.9% Sodium Chloride Injection900 mg per 50 mL (18 mg / mL)Contains 12 - 50 mL Single-Dose Containers\nStore at 20°C to 25°C (68°F to 77°F)[see USP Controlled Room Temperature]. Avoid temperatures above 30°C.\n" }

Rx onlyNDC 0338-9553-24Code 2G3457

{ "type": "p", "children": [], "text": "\nRx onlyNDC 0338-9553-24Code 2G3457\n" }

FOR BAR CODE POSITION ONLY (01) 20303389553247

{ "type": "p", "children": [], "text": "FOR BAR CODE POSITION ONLY (01) 20303389553247" }

For Intravenous Infusion Only Sterile Nonpyrogenic

{ "type": "p", "children": [], "text": "\nFor Intravenous Infusion Only \nSterile Nonpyrogenic" }

Each 50 mL contains: Clindamycin phosphate, USP equivalent to 900 mg clindamycin, 450 mg sodium chloride, USP, 2 mg edetate disodium dihydrate, USP, and Water for Injection, USP. pH may have been adjusted with sodium hydroxide and/or hydrochloric acid.Dosage: See prescribing information.Caution: Do not add supplementary medication. Must not be used in series connections. Check for minute leaks and solution clarity.

{ "type": "p", "children": [], "text": "Each 50 mL contains: Clindamycin phosphate, USP equivalent to 900 mg clindamycin, 450 mg sodium chloride, USP, 2 mg edetate disodium dihydrate, USP, and Water for Injection, USP. pH may have been adjusted with sodium hydroxide and/or hydrochloric acid.Dosage: See prescribing information.Caution: Do not add supplementary medication. Must not be used in series connections. Check for minute leaks and solution clarity." }