XOLEGEL- ketoconazole gel 
Aqua Pharmaceuticals

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HIGHLIGHTS OF PRESCRIBING INFORMATION

These highlights do not include all the information needed to use XOLEGEL Gel safely and effectively. See full prescribing information for XOLEGEL Gel.

XOLEGEL® (ketoconazole) gel for topical use
For Topical Use Only
Initial U.S. Approval: 1981

INDICATIONS AND USAGE

  • XOLEGEL is an azole antifungal indicated for topical treatment of seborrheic dermatitis in immunocompetent adults and children 12 years of age and older. (1, 12.1)
  • Safety and efficacy of XOLEGEL for treatment of fungal infections have not been established. (1)

DOSAGE AND ADMINISTRATION

  • XOLEGEL is for topical use only, and not for oral, ophthalmic, or intravaginal use. (2)
  • XOLEGEL should be applied once daily to the affected area for 2 weeks. (2)

DOSAGE FORMS AND STRENGTHS

  • Gel containing 2% ketoconazole. (3)

CONTRAINDICATIONS

  • None.

WARNINGS AND PRECAUTIONS

XOLEGEL is flammable. Avoid using near fire, flame, or smoking during and immediately following application of XOLEGEL. (5.1)


ADVERSE REACTIONS

  • The most common treatment-related adverse reaction was application site burning (4%). (6.1)

To report SUSPECTED ADVERSE REACTIONS, contact Almirall at 1-866-665-2782 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.


See 17 for PATIENT COUNSELING INFORMATION and FDA-approved patient labeling.

Revised: 12/2019

FULL PRESCRIBING INFORMATION: CONTENTS*

1 INDICATIONS AND USAGE

2 DOSAGE AND ADMINISTRATION

3 DOSAGE FORMS AND STRENGTHS

4 CONTRAINDICATIONS

5 WARNINGS AND PRECAUTIONS

5.1 Flammable Contents

5.2 Systemic Effects

5.3 Local Effects

6 ADVERSE REACTIONS

6.1 Clinical Trials Experience

7 DRUG INTERACTIONS

8 USE IN SPECIFIC POPULATIONS

8.1 Pregnancy

8.2 Lactation

8.4 Pediatric Use

8.5 Geriatric Use

11 DESCRIPTION

12 CLINICAL PHARMACOLOGY

12.1 Mechanism of Action

12.2 Pharmacodynamics

12.3 Pharmacokinetics

13 NONCLINICAL TOXICOLOGY

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

14 CLINICAL STUDIES

16 HOW SUPPLIED/STORAGE AND HANDLING

16.1 How Supplied

16.2 Storage and Handling

17 PATIENT COUNSELING INFORMATION

*
Sections or subsections omitted from the full prescribing information are not listed.

FULL PRESCRIBING INFORMATION

1 INDICATIONS AND USAGE

XOLEGEL is indicated for the topical treatment of seborrheic dermatitis in immunocompetent adults and children 12 years of age and older.

Safety and efficacy of XOLEGEL for treatment of fungal infections have not been established.

2 DOSAGE AND ADMINISTRATION

XOLEGEL is for topical use only, and not for oral, ophthalmic, or intravaginal use.

XOLEGEL should be applied once daily to the affected area for 2 weeks.

3 DOSAGE FORMS AND STRENGTHS

XOLEGEL is a translucent to clear amber colored gel containing 2% ketoconazole.

4 CONTRAINDICATIONS

None.

5 WARNINGS AND PRECAUTIONS

5.1 Flammable Contents

XOLEGEL is flammable. Avoid being near fire, flame, or smoking during and immediately following application of XOLEGEL.

5.2 Systemic Effects

Hepatitis and, at high doses, lowered testosterone and ACTH induced corticosteroid serum levels have been seen with orally administered ketoconazole; these effects have not been seen with topically administered ketoconazole.

5.3 Local Effects

XOLEGEL can cause local irritation at the application site. If irritation occurs or if the disease worsens, use of the medication should be discontinued and the health care provider should be contacted [see ADVERSE REACTIONS (6.1)].

6 ADVERSE REACTIONS

6.1 Clinical 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 clinical practice.

In the 3 safety and efficacy trials, 65 of 933 subjects (7%) experienced at least one treatment-related adverse event. The most common treatment-related adverse reaction was application site burning (4%). Treatment-related application site reactions that were reported in < 1% of subjects were: dermatitis, discharge, dryness, erythema, irritation, pain, pruritus, and pustules. Other treatment-related adverse reactions that were reported in < 1% of subjects were: eye irritation, eye swelling, keratoconjunctivitis sicca, impetigo, pyogenic granuloma, dizziness, headache, paresthesia, acne, nail discoloration, facial swelling.

7 DRUG INTERACTIONS

Formal drug interaction studies with XOLEGEL have not been performed. Coadministration of oral ketoconazole with CYP3A4 metabolized HMG-CoA reductase inhibitors such as simvastatin, lovastatin and atorvastatin, may increase the risk of skeletal muscle toxicity, including rhabdomyolysis. These effects have not been observed with topically administered ketoconazole.

8 USE IN SPECIFIC POPULATIONS

8.1 Pregnancy

Risk Summary
There are no available data on XOLEGEL use in pregnant women to evaluate for a drug associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes.

In animal reproduction studies with pregnant rats, structural abnormalities (syndactylia and oligodactylia) were observed following oral doses of ketoconazole during organogenesis (see Data). The available data do not allow calculation of relevant comparisons between the systemic exposure of ketoconazole observed in animal studies to the systemic exposure observed in humans after topical use of XOLEGEL.

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.

Data
Animal Data
Oral administration of ketoconazole at 80 mg/kg/day to pregnant rats during organogenesis was associated with structural abnormalities (syndactylia and oligodactylia) . However, these effects may be related to maternal toxicity, which was also seen at this and higher dose levels.

In oral peri- and postnatal development studies in rats, maternal toxicity, prolonged gestation, embryolethality and fetotoxicity were observed at ketoconazole doses of 40 mg/kg/day and higher.

8.2 Lactation

Risk Summary
There are no data available on the presence of ketoconazole in human milk, its effects on the breastfed infant, or its effects on milk production. After topical application, ketoconazole concentrations in plasma are low and therefore concentrations in human breast milk are likely to be low [see Clinical Pharmacology (12.3)].

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

Clinical Considerations
Advise breastfeeding women not to apply XOLEGEL directly to the nipple and areola to avoid direct infant exposure.

8.4 Pediatric Use

Safety and effectiveness in pediatric subjects below the age of 12 have not been established.

8.5 Geriatric Use

Of the 933 subjects in the three safety and efficacy trials, 193 (20.7%) were 65 and older, while 61 (6.5%) were 75 and older. No overall differences in safety or effectiveness were observed between these subjects and younger subjects but greater sensitivity of some older individuals cannot be ruled out.

11 DESCRIPTION

XOLEGEL contains the antifungal agent ketoconazole USP at 2% in a topical anhydrous gel vehicle for topical administration.

Chemically, ketoconazole is (±)-cis-1-Acetyl-4-[p-[[2-(2,4-dichlorophenyl)-2-(1H-imidazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy]phenyl]piperazine, with the molecular formula C26H28Cl2N4O4 and a molecular weight of 531.43.


Figure 1

Chemical Structure


Each gram contains: 20 mg ketoconazole USP, dehydrated alcohol (34%), ascorbic acid, butylated hydroxytoluene, citric acid monohydrate, glycerin, hydroxypropyl cellulose, polyethylene glycol 400, PPG-15 stearyl ether, propylene glycol, FD&C yellow No. 6, and FD&C yellow No. 10.

XOLEGEL is a smooth, translucent to clear, amber gel.

12 CLINICAL PHARMACOLOGY

12.1 Mechanism of Action

The mechanism of action of ketoconazole in the treatment of seborrheic dermatitis is unknown.

12.2 Pharmacodynamics

Pharmacodynamic markers for seborrheic dermatitis have not been identified.

12.3 Pharmacokinetics

In a pharmacokinetic absorption trial, eighteen subjects, both males and females, with severe seborrheic dermatitis (range 1-14% of body surface area) applied XOLEGEL once daily for 2 weeks. The median total amount of gel applied was 4.6 g (range 1.65–46.3 g). Daily doses ranged from 0.05 to 3.47 g. Mean (± standard deviation [SD]) peak plasma levels were 1.35 (± 3.18) ng/mL on Day 7 (range from <0.1 ng/mL, to 13.9 ng/mL), and 0.80 (± 1.22) ng/mL on Day 14 (range from <0.1 ng/mL to 5.4 ng/mL). Median Tmax was 8 hours on Day 7 and 7 hours on Day 14. Mean (± SD) AUC0-24 values were 20.8 (± 44.7) ng∙h/mL and 15.6 (± 26.4) ng∙h/mL on Day 7 and 14, respectively.

The plasma levels from an oral dose of 200 mg ketoconazole taken with a meal are approximately 250 times higher than the resulting plasma levels of ketoconazole following topical application of XOLEGEL.

13 NONCLINICAL TOXICOLOGY

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

A 2-year dermal carcinogenicity study conducted in mice with topical administration of ketoconazole gel at doses up to 80 mg ketoconazole/kg/day exhibited no evidence of carcinogenic activity. A long-term feeding study in mice and in rats showed no evidence of carcinogenic activity.

Ketoconazole produced no evidence of mutagenicity in the dominant lethal mutation test in male and female mice at single oral doses up to 80 mg/kg. When tested in the Ames assay, ketoconazole was not mutagenic to Salmonella typhimurium in the presence or absence of metabolic activation. Ketoconazole, in combination with another drug, gave equivocal results in the mouse micronucleus test.

At oral doses of 75 mg/kg/day, ketoconazole impaired the reproductive performance in female (decreased pregnancy and implantation rates) and male (increased abnormal sperm and decreased sperm motility) rats.

14 CLINICAL STUDIES

Study 1 was a multicenter, double-blind, randomized, vehicle-controlled trial which enrolled 459 subjects 12 years of age and older with moderate to severe seborrheic dermatitis. A total of 229 subjects were treated with XOLEGEL, and 230 subjects were treated with vehicle. All subjects were treated once daily for 14 days, and efficacy was assessed at Day 28 (i.e., 2 weeks after end of treatment). Effective Treatment was defined as:

The proportion of subjects effectively treated is shown in Table 1.

Table 1: Trial Results
XOLEGEL
N=229
Vehicle
N=230
Number and proportion of subjects effectively treated58 (25.3%)32 (13.9%)

Two additional double-blind, randomized, vehicle-controlled, parallel, and multicenter trials that included a total of 316 subjects treated with XOLEGEL provided supportive evidence of the efficacy of XOLEGEL for treatment of seborrheic dermatitis. Subjects applied either XOLEGEL or vehicle study treatment to the affected area(s) once daily for 14 days and were followed through Day 28. Efficacy was assessed by the proportion of subjects who were completely clear at Day 28.

The contribution to efficacy of individual components of the vehicle has not been established.

16 HOW SUPPLIED/STORAGE AND HANDLING

16.1 How Supplied

XOLEGEL® (ketoconazole) Gel, 2% is supplied in 45-gram (NDC 16110-080-45) white-coated aluminum tubes with white caps, and is dispensed with FDA-Approved Patient Labeling.

16.2 Storage and Handling

Store at 25°C (77°F); excursions permitted to 15° - 30°C (59° - 86°F).

Contents are flammable.

Keep out of reach of children.

17 PATIENT COUNSELING INFORMATION

[See FDA-Approved Patient Labeling (Patient Information)]


PATIENT INFORMATION

XOLEGEL® (Xol-a-gel)

(ketoconazole) Gel, 2%


Read the Patient Information that comes with XOLEGEL carefully before you start using it and each time you get a refill. There may be new information. This leaflet does not take the place of talking with your health care provider. If you have any questions about XOLEGEL, ask your health care provider.

What is XOLEGEL?

XOLEGEL is a prescription medicine used on the skin to treat a skin condition called seborrheic dermatitis.

Patients with seborrheic dermatitis can have areas of dry, flaky skin on the scalp, face, ears, chest, or upper back. XOLEGEL is only to be used in adults and in children older than 12 years of age who have a normal (healthy) immune system. XOLEGEL has not been studied in children below the age of 12.

It is not known whether XOLEGEL can be used to treat fungal infections.

XOLEGEL is a translucent to clear, amber colored gel.

What should I tell my health care provider before using XOLEGEL?

How should I use XOLEGEL?

What should I avoid while using XOLEGEL?

What are the possible side effects of XOLEGEL?

These are not all of the side effects of XOLEGEL. For more information, ask your health care provider or pharmacist.

How should I store XOLEGEL?

General information about XOLEGEL

Medicines are sometimes prescribed for conditions that are not mentioned in Patient Information leaflets. Do not use XOLEGEL for a condition for which it was not prescribed. Do not give XOLEGEL to other people, even if they have the same symptoms that you have. It may harm them.

This Patient Information leaflet summarizes the most important information about XOLEGEL. If you would like more information, talk with your health care provider. You can also ask your pharmacist or health care provider for information about XOLEGEL that is written for health professionals.

What are the ingredients in XOLEGEL?

Active ingredient: ketoconazole, USP

Inactive ingredients: dehydrated alcohol, ascorbic acid, butylated hydroxytoluene, citric acid monohydrate, glycerin, hydroxypropyl cellulose, polyethylene glycol 400, PPG-15 stearyl ether, propylene glycol, FD&C yellow No. 6, and FD&C Yellow No. 10.


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

The Patient Information leaflet was last revised: May 2012.


Manufactured for Almirall, LLC
Exton, PA 19341


Revised 12/2019
XOLEGEL is a registered trademark of Almirall, LLC.


© 2019 Almirall.

almirall


PRINCIPAL DISPLAY PANEL - 45 g Carton

NDC 16110-080-45

Xolegel®
(ketoconazole) Gel, 2%

AQUA
PHARMACEUTICALS

45 grams
Rx only. For topical use only.

PRINCIPAL DISPLAY PANEL - 45 g Carton


PRINCIPAL DISPLAY PANEL - 45 g Carton

NDC 16110-080-45

Xolegel®
(ketoconazole) Gel, 2%

AQUA
PHARMACEUTICALS

45 grams
Rx only. For topical use only.

PRINCIPAL DISPLAY PANEL - 45 g Tube


XOLEGEL 
ketoconazole gel
Product Information
Product TypeHUMAN PRESCRIPTION DRUGItem Code (Source)NDC:16110-080
Route of AdministrationTOPICAL
Active Ingredient/Active Moiety
Ingredient NameBasis of StrengthStrength
KETOCONAZOLE (UNII: R9400W927I) (KETOCONAZOLE - UNII:R9400W927I) KETOCONAZOLE20 mg  in 1 g
Inactive Ingredients
Ingredient NameStrength
ALCOHOL (UNII: 3K9958V90M)  
ASCORBIC ACID (UNII: PQ6CK8PD0R)  
BUTYLATED HYDROXYTOLUENE (UNII: 1P9D0Z171K)  
CITRIC ACID MONOHYDRATE (UNII: 2968PHW8QP)  
GLYCERIN (UNII: PDC6A3C0OX)  
HYDROXYPROPYL CELLULOSE (1600000 WAMW) (UNII: RFW2ET671P)  
POLYETHYLENE GLYCOL 400 (UNII: B697894SGQ)  
PPG-15 STEARYL ETHER (UNII: 1II18XLS1L)  
PROPYLENE GLYCOL (UNII: 6DC9Q167V3)  
FD&C YELLOW NO. 6 (UNII: H77VEI93A8)  
D&C YELLOW NO. 10 (UNII: 35SW5USQ3G)  
Packaging
#Item CodePackage DescriptionMarketing Start DateMarketing End Date
1NDC:16110-080-451 in 1 CARTON07/28/2006
145 g in 1 TUBE; Type 0: Not a Combination Product
Marketing Information
Marketing CategoryApplication Number or Monograph CitationMarketing Start DateMarketing End Date
NDANDA02194607/28/2006
Labeler - Aqua Pharmaceuticals (605425912)
Establishment
NameAddressID/FEIBusiness Operations
DPT Laboratories, Ltd.832224526ANALYSIS(16110-080) , LABEL(16110-080) , MANUFACTURE(16110-080)

Revised: 1/2020
Document Id: c7651cd3-8eb8-47c8-84ab-13177c9a46b7
Set id: 855e42bb-b57f-4772-bffa-d766ddcc46ce
Version: 6
Effective Time: 20200122
 
Aqua Pharmaceuticals