XOLEGEL- ketoconazole gel
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
DOSAGE AND ADMINISTRATION
DOSAGE FORMS AND STRENGTHS
WARNINGS AND PRECAUTIONS
XOLEGEL is flammable. Avoid using near fire, flame, or smoking during and immediately following application of XOLEGEL. (5.1)
See 17 for PATIENT COUNSELING INFORMATION and FDA-approved patient labeling.
FULL PRESCRIBING INFORMATION: CONTENTS*
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.
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.
XOLEGEL is a translucent to clear amber colored gel containing 2% ketoconazole.
XOLEGEL is flammable. Avoid being near fire, flame, or smoking during and immediately following application of XOLEGEL.
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.
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)].
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.
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.
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.
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.
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.
Advise breastfeeding women not to apply XOLEGEL directly to the nipple and areola to avoid direct infant exposure.
Safety and effectiveness in pediatric subjects below the age of 12 have not been established.
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.
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.
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.
The mechanism of action of ketoconazole in the treatment of seborrheic dermatitis is unknown.
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.
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.
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.
|Number and proportion of subjects effectively treated||58 (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.
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.
[See FDA-Approved Patient Labeling (Patient Information)]
(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
XOLEGEL is a registered trademark of Almirall, LLC.
© 2019 Almirall.
PRINCIPAL DISPLAY PANEL - 45 g Carton
(ketoconazole) Gel, 2%
Rx only. For topical use only.
|Labeler - Aqua Pharmaceuticals (605425912)|
|DPT Laboratories, Ltd.||832224526||ANALYSIS(16110-080) , LABEL(16110-080) , MANUFACTURE(16110-080)|