Ketoconazole (gel)
- Safety and efficacy of XOLEGEL for treatment of fungal infections have not been established.

# Dosing Information
- 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 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.
- 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.
- Reproductive toxicity studies have not been performed with XOLEGEL. Ketoconazole was tested for its effects on offspring in the rat at oral doses of 10, 20, 40, 80, and 160 mg/kg. Ketoconazole was teratogenic (syndactylia and oligodactylia) at 80 mg/kg/day and embryotoxic at 160 mg/kg/day (76 and 152 times the human dose, respectively). However, these effects may be related to maternal toxicity, which was also seen at these dose levels.
- Oral doses of 10, 20, 40, 80, and 160 mg/kg were studied in pre- and postnatal development studies in rats. Doses of 40 mg/kg (38 times the human dose) and above were associated with maternal toxicity, an increase in the length of gestation, and an increase in the number of stillborn fetuses. These doses of ketoconazole were also toxic to the offspring, resulting in a decrease in fetal/pup weights and viability.
- If used during lactation and XOLEGEL is applied to the chest, care should be taken to avoid accidental ingestion by the infant.
- There has been no experience of overdose with XOLEGEL. No incidents of accidental ingestion have been reported. A health care provider or poison control center should be contacted in the event of accidental ingestion.
- 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.
- The carcinogenic potential of ketoconazole gel has been evaluated in a 2-year dermal carcinogenicity study in CD-1 mice. Ketoconazole gel applied topically at doses up to 80 mg ketoconazole/kg/day (76 times the human dose) exhibited no evidence of dermal or systemic tumorigenic effects attributable to ketoconazole or the gel vehicle. A long-term feeding study in Swiss Albino mice and in Wistar rats showed no evidence of oncogenic activity. Ketoconazole gel at a dosage up to 5 mg/kg/dose is not photocarcinogenic when topically applied to hairless mice five days per week for a period of 40 weeks. 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 found to be non-mutagenic to Salmonella typhimurium in the presence and absence of metabolic activation. Ketoconazole, in combination with another drug, gave equivocal results in the mouse micronucleus test. At oral doses of 75 to 80 mg/kg/day (71 to 76 times the human dose) ketoconazole impaired the reproductive performance in female (decreased pregnancy and implantation rates) and male (increased abnormal sperm and decreased sperm motility) rats.
- an Investigator's Global Assessment score of  1 (completely clear or almost clear) and
erythema and scaling scores of 0 (none) if the baseline score was 2, or 1 (mild) if the baseline score was 3.
- The proportion of subjects effectively treated is shown in Table 1.
- 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.
- Contents are flammable.
- Keep out of reach of children.
NDC 16110-080-45
Xolegel 
(ketoconazole) Gel, 2%
AQUA 
PHARMACEUTICALS
45 grams
Rx only. For topical use only.
- XOLEGEL may be irritating to mucus membranes. Contact with the eyes, nostrils, and mouth should be avoided.
- As with any topical medication, patients should wash their hands after application.
- This medication should not be used for any disorder other than that for which it has been prescribed.
- Patients should report any signs of adverse reactions to their health care provider.