FDA

Xaciato

Approved 7 Dec 2021VaginalGel

Indications

XACIATO is a lincosamide antibacterial indicated for the treatment of bacterial vaginosis in female patients 12 years of age and older. ( 1.1 )

1.1Bacterial Vaginosis

XACIATO ® is indicated for the treatment of bacterial vaginosis in females 12 years and older [see Use in Specific Populations ( 8.1 ) and Clinical Studies ( 14 )] .

Contraindications

History of hypersensitivity to clindamycin or lincomycin. ( 4.1 )

4.1Hypersensitivity

XACIATO is contraindicated in individuals with a history of hypersensitivity to clindamycin or lincomycin. [see Adverse Reactions ( 6.2 )] .

Warnings and precautions

Clostridioides difficile -Associated Diarrhea: Discontinue and evaluate if diarrhea occurs. ( 5.1 ) Use with Polyurethane Condoms: Polyurethane condoms are not recommended during treatment with XACIATO or for 7 days following treatment. During this time period, polyurethane condoms may not be reliable for preventing pregnancy or for protecting against transmission of HIV and other sexually transmitted diseases. Latex or polyisoprene condoms should be used ( 5.2 )

5.1 Clostridioides difficile -Associated Diarrhea (CDAD) 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 which can lead 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 antibacterial use. Careful medical history is necessary since CDAD has been reported to occur over two months after the administration of antibacterial agents. Patients with inflammatory bowel disease, including ulcerative colitis and Crohn’s disease, have a higher risk of developing CDAD.

At a glance

Brand name: Xaciato
Active substance: clindamycin phosphate
Route: Vaginal
Dosage form: Gel
Applicant: Organon LLC
Status: Prescription
FDA approval: 7 Dec 2021
Application: NDA215650-001

Indications

XACIATO is a lincosamide antibacterial indicated for the treatment of bacterial vaginosis in female patients 12 years of age and older. ( 1.1 )

1.1Bacterial Vaginosis

XACIATO ® is indicated for the treatment of bacterial vaginosis in females 12 years and older [see Use in Specific Populations ( 8.1 ) and Clinical Studies ( 14 )] .

Warnings and precautions

Pregnancy and breastfeeding

8.1Pregnancy Risk Summary

Other clindamycin vaginal products have been used to treat pregnant women during the second and third trimester. XACIATO has not been studied in pregnant women. However, based on the low systemic absorption of XACIATO following the intravaginal route of administration in nonpregnant women, maternal use is not likely to result in significant fetal exposure to the drug [see Clinical Pharmacology ( 12.3 )] . Available data from published observational studies, based on first trimester exposure to oral and IV clindamycin, did not identify consistent increases in the rate of major birth defects.

Available data from published observational studies and randomized controlled trials, based on second and third trimester exposure to oral and IV clindamycin, did not identify an increased risk of miscarriage or other adverse maternal or fetal outcomes. Most of the reported exposures to clindamycin occurred during the second and third trimesters of the pregnancy. In animal reproduction studies, no adverse developmental outcomes were observed when XACIATO was vaginally administered to pregnant rats and rabbits during organogenesis at doses approximately equivalent to the recommended human dose.

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 9 to 58 times the recommended human 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% to 4% and 15% to 20%, respectively. Data Animal Data Reproduction studies performed during organogenesis in pregnant rats (gestational days 6-17) and rabbits (gestational days 7-19) administered vaginal XACIATO at 0.1 g and 1 g/day (2 mg and 20 mg clindamycin phosphate/day) showed no evidence of developmental toxicity.

These doses are approximately equivalent to the applied recommended clinical dose based on g/cm 2 vaginal surface area and body surface area (BSA) comparisons. 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 (58 and 29 times, respectively, the recommended human dose based on a body surface area comparison) or subcutaneous doses of clindamycin up to 250 mg/kg/day (24- and 12-times, respectively, the MRHD based on BSA comparisons) revealed no evidence of teratogenicity.

Vaginal administration of XACIATO to pregnant/lactating female rats during a pre- and post-natal development (gestation day 6 through gestation day 21) study at 2 mg clindamycin phosphate/day had no adverse effects on dams or their offspring.

Adverse reactions

The following clinically significant adverse reactions are described elsewhere in the labeling: Clostridioides difficile -Associated Diarrhea (CDAD) [see Warnings and Precautions ( 5.1 )] Use with Polyurethane Condoms [see Warnings and Precautions ( 5.2 )] Vaginal Candida Infections [see Warnings and Precautions ( 5.3 )] The most common adverse reactions reported in >2% of patients and at a higher rate in the XACIATO group than in the placebo group were vulvovaginal candidiasis and vulvovaginal discomfort.

( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Organon LLC, at 1-844-674-3200 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

6.1Clinical Trials Experience

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. In the placebo-controlled trial (Trial 1), 202 patients with bacterial vaginosis were treated with a single dose of XACIATO, and 103 patients were treated with a single dose of placebo gel.

The median age of the patients in the trial was 35 years (range 15-59 years). The population was 56% Black or African American and 41% White. Persons of Hispanic or Latino ethnicity made up 25% of the population. A history of prior bacterial vaginosis was noted in 89% of the population. Most Common Adverse Reactions Adverse reactions were reported by 76/202 (38%) of patients who received XACIATO and 28/103 (27%) of patients who received placebo in Trial 1.

Table 1 displays the most common adverse reactions (occurring in >2% of patients and at a higher rate in the XACIATO group than in the placebo group) in Trial 1. Table 1: Adverse Reactions Occurring in >2% of Patients Receiving XACIATO in Trial 1 Adverse Reaction XACIATO N=202 n (%) Placebo N=103 n (%) Vulvovaginal candidiasis 35 (17) 4 (4) Vulvovaginal discomfort Vulvovaginal discomfort includes the terms vulvovaginal pruritus, vulvovaginal burning sensation, vulvovaginal erythema, vulvovaginal dryness, and vulvovaginal discomfort. 13 (6) 5 (5)

6.2Other Clindamycin Formulations

XACIATO affords low peak serum levels and systemic exposure 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: Acute kidney injury. Immune: Drug reaction with eosinophilia with systemic symptoms (DRESS) cases have been reported.

Xaciato

Indications

1.1Bacterial Vaginosis

Contraindications

4.1Hypersensitivity

Warnings and precautions

At a glance

Two medicines in one question?

Xaciato

Indications

1.1Bacterial Vaginosis

Contraindications

4.1Hypersensitivity

Warnings and precautions

At a glance

Two medicines in one question?

5.2Use with Polyurethane Condoms

5.3Vaginal Candida Infections

Interactions

7.1Neuromuscular Blocking Agents

Pregnancy and breastfeeding

8.1Pregnancy Risk Summary

Adverse reactions

6.1Clinical Trials Experience

6.2Other Clindamycin Formulations

Composition

Official product information