Sorilux

Dosage Forms And Strengths

0.005%, white foam

How Supplied

SORILUX (calcipotriene) Foam, 0.005%, is supplied as follows:

60 g aluminum can NDC 0145-2130-06

Storage and Handling

• Store at 25°C (77°F); excursions permitted to 15-30°C (59-86°F).
• FLAMMABLE. AVOID FIRE. FLAME. OR SMOKING DURING AND IMMEDIATELY FOLLOWING APPLICATION. Contents under pressure. Do not puncture or incinerate. Do not expose to heat or store at temperatures above 120°F (49°C).
• Avoid contact with eyes.
• Keep out of reach of children.

Manufactured for: Stiefel Laboratories, Inc. Research Triangle Park, NC 27709. Manufactured by: DPT Laboratories, Ltd. 307 E. Josephine Street San Antonio, TX 78215. Revised: 2010

SORILUX (calcipotriene foam) Foam is indicated for the topical treatment of plaque psoriasis in patients aged 18 years and older.

For topical use only. SORILUX (calcipotriene foam) Foam is not for oral, ophthalmic, or intravaginal use.

Apply a thin layer of SORILUX (calcipotriene foam) Foam twice daily to the affected areas and rub in gently and completely.

SORILUX (calcipotriene foam) Foam should not be used by patients with known hypercalcemia.

WARNINGS

Included as part of the PRECAUTIONS section.

PRECAUTIONS

FlammabiUty

The propellant in SORILUX (calcipotriene foam) is flammable. Instruct the patient to avoid fire, flame, and/or smoking during and immediately following application.

Effects on Calcium Metabolism

Transient, rapidly reversible elevation of serum calcium has occurred with use of calcipotriene. If elevation in serum calcium outside the normal range should occur, discontinue treatment until normal calcium levels are restored.

Ultraviolet Light Exposure

Instruct the patient to avoid excessive exposure of the treated areas to either natural or artificial sunlight, including tanning booths and sun lamps. Physicians may wish to limit or avoid use of phototherapy in patients who use SORILUX (calcipotriene foam) Foam.

Unevaluated Uses

SORILUX (calcipotriene foam) Foam has not been evaluated in patients with erythrodermic, exfoliative, or pustular psoriasis.

Patient Counseling Information

The patient should be instructed as follows:

• Do not place SORILUX (calcipotriene foam) Foam in the refrigerator or freezer.
• Avoid excessive exposure of the treated areas to either natural or artificial sunlight, including tanning beds and sun lamps.
• If SORILUX (calcipotriene foam) Foam gets in or near their eyes, to rinse thoroughly with water.
• Talk to their doctor if their skin does not improve after treatment with SORILUX (calcipotriene foam) Foam for 8 weeks.
• Wash their hands after applying SORILUX (calcipotriene foam) Foam unless their hands are the affected site
• Avoid fire, flame, or smoking during and immediately following application since SORILUX (calcipotriene foam) Foam is flammable.

Nonclinical Toxicology

Carcinogenesis, Mutagenesis, Impairment of Fertility

Calcipotriene topically administered to mice for up to 24 months at dose levels of 3, 10, or 30 mcg/kg/day (corresponding to 9, 30, or 90 mcg/m²/day) showed no significant changes in tumor incidence when compared to controls. In a study in which albino hairless mice were exposed to both UVR and topically applied calcipotriene, a reduction in the time required for UVR to induce the formation of skin tumors was observed (statistically significant in males only), suggesting that calcipotriene may enhance the effect of UVR to induce skin tumors.

The genotoxic potential of calcipotriene was evaluated in an Ames assay, a mouse lymphoma TK locus assay, a human lymphocyte chromosome aberration assay, and a mouse micronucleus assay. All assay results were negative.

Studies in rats at doses up to 54 mcg/kg/day (318 mcg /m²/day) of calcipotriene indicated no impairment of fertility or general reproductive performance.

Use In Specific Populations

Pregnancy

Teratogenic Effects, Pregnancy Category C

There are no adequate and well-controlled studies in pregnant women. Therefore, SORILUX (calcipotriene foam) Foam should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Studies of teratogenicity were done by the oral route where bioavailability is expected to be approximately 40-60% of the administered dose. Increased rabbit maternal and fetal toxicity was noted at 12 mcg/kg/day (132 mcg/m²/day). Rabbits administered 36 mcg/kg/day (396 mcg/m²/day) resulted in fetuses with a significant increase in the incidences of incomplete ossification of pubic bones and forelimb phalanges. In a rat study, doses of 54 mcg/kg/day (318 mcg/m²/day) resulted in a significantly higher incidence of skeletal abnormalities consisting primarily of enlarged fontanelles and extra ribs. The enlarged fontanelles are most likely due to calcipotriene's effect upon calcium metabolism. The maternal and fetal no-effect exposures in the rat (43.2 mcg/m²/day) and rabbit (17.6 mcg/m²/day) studies are approximately equal to the expected human systemic exposure level (18.5 mcg/m²/day) from dermal application.

Nursing Mothers

It is not known whether calcipotriene is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when SORILUX (calcipotriene foam) Foam is administered to a nursing woman.

Pediatric Use

Safety and effectiveness of SORILUX (calcipotriene foam) Foam in pediatric patients less than 18 years of age have not been established.

Geriatric Use

Clinical studies of SORILUX (calcipotriene foam) Foam did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients.

SIDE EFFECTS

Clinical Trials Experience

Because clinical studies are conducted under widely varying conditions, adverse reaction rates observed in clinical studies of a drug cannot be directly compared to rates in the clinical studies of another drug and may not reflect the rates observed in clinical practice.

SORILUX (calcipotriene foam) Foam was studied in three-vehicle controlled trials. Seven hundred and thirty one subjects with plaque psoriasis, including 473 exposed to SORILUX (calcipotriene foam) Foam were treated twice daily for 8 weeks.

Adverse events reported in greater than 1% of subjects and in a higher rate in subjects treated with SORILUX (calcipotriene foam) Foam compared to vehicle were limited to erythema.

DRUG INTERACTIONS

No drug interaction studies were conducted with SORILUX (calcipotriene foam) Foam.

Teratogenic Effects, Pregnancy Category C

There are no adequate and well-controlled studies in pregnant women. Therefore, SORILUX (calcipotriene foam) Foam should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Studies of teratogenicity were done by the oral route where bioavailability is expected to be approximately 40-60% of the administered dose. Increased rabbit maternal and fetal toxicity was noted at 12 mcg/kg/day (132 mcg/m²/day). Rabbits administered 36 mcg/kg/day (396 mcg/m²/day) resulted in fetuses with a significant increase in the incidences of incomplete ossification of pubic bones and forelimb phalanges. In a rat study, doses of 54 mcg/kg/day (318 mcg/m²/day) resulted in a significantly higher incidence of skeletal abnormalities consisting primarily of enlarged fontanelles and extra ribs. The enlarged fontanelles are most likely due to calcipotriene's effect upon calcium metabolism. The maternal and fetal no-effect exposures in the rat (43.2 mcg/m²/day) and rabbit (17.6 mcg/m²/day) studies are approximately equal to the expected human systemic exposure level (18.5 mcg/m²/day) from dermal application.

Clinical Trials Experience

Because clinical studies are conducted under widely varying conditions, adverse reaction rates observed in clinical studies of a drug cannot be directly compared to rates in the clinical studies of another drug and may not reflect the rates observed in clinical practice.

SORILUX (calcipotriene foam) Foam was studied in three-vehicle controlled trials. Seven hundred and thirty one subjects with plaque psoriasis, including 473 exposed to SORILUX (calcipotriene foam) Foam were treated twice daily for 8 weeks.

Adverse events reported in greater than 1% of subjects and in a higher rate in subjects treated with SORILUX (calcipotriene foam) Foam compared to vehicle were limited to erythema.

Topically applied calcipotriene can be absorbed in sufficient amounts to produce systemic effects. Elevated serum calcium has been observed with use of topical calcipotriene.

The pharmacodynamics of SORILUX (calcipotriene foam) Foam are unknown.

The systemic absorption of calcipotriene in psoriatic subjects was evaluated at steady state following application of SORILUX Foam or calcipotriene ointment. In the SORILUX Foam treatment group, 15 out of 16 subjects showed calcipotriene plasma concentrations below the limit of quantitation (10 pg/mL), while in the calcipotriene ointment treated group, 5 out of 16 subjects had measurable calcipotriene plasma concentrations at various time points. All measurable plasma calcipotriene concentrations were below 25 pg/mL.

The systemic disposition of calcipotriene is expected to be similar to that of the naturally occurring vitamin D. Absorbed calcipotriene is known to be converted to inactive metabolites within 24 hours of application and the metabolism occurs via a similar pathway to the natural hormone.