Clinical Information
Gen. Code and Des.
47346 tacrolimus TOPICAL OINT. (G) 0.03 %
GCN and Des.
12289 tacrolimus TOPICAL OINT. (G) 0.03 %
Strength
0.03%
Dose Form
OINTMENT (GRAM)
Product Category
RX Pharmaceuticals
Fine Line Class
850085008510 All Rx Products
DEA Class
NC
OMP Family
AHFS Class
84920000 SKIN AND MUCOUS MEMBRANE AGENTS, MISC.
Active Ingredients
4446 tacrolimus 109581933
PROTOPIC- tacrolimus ointment
Astellas Pharma US Inc.
Rx Only
Prescribing Information
See boxed WARNING concerning long-term safety of topical calcineurin inhibitors
DESCRIPTION
PROTOPIC (tacrolimus) Ointment contains tacrolimus, a macrolide immunosuppressant produced by Streptomyces tsukubaensis. It is for topical dermatologic use only. Chemically, tacrolimus is designated as [3S -[3R *[E (1S *,3S *,4S *)],4S *,5R *,8S *,9E ,12R *,14R *,15S *,16R *,18S *,19S *,26aR *]]-5,6,8,11,12,13,14,15,16,17,18,19,24,25,26,26a-hexadecahydro-5,19-dihydroxy-3-[2-(4-hydroxy-3-methoxycyclohexyl)-1-methylethenyl]-14,16-dimethoxy-4,10, 12,18-tetramethyl-8-(2-propenyl)-15,19-epoxy-3H-pyrido[2,1-c ][1,4] oxaazacyclotricosine-1,7,20,21(4H,23H)-tetrone,monohydrate.
Tacrolimus has an empirical formula of C44 H69 NO12 �H2 O and a formula weight of 822.03. Each gram of PROTOPIC Ointment contains (w/w) either 0.03% or 0.1% of tacrolimus in a base of mineral oil, paraffin, propylene carbonate, white petrolatum and white wax.
CLINICAL PHARMACOLOGY
Mechanism of Action
The mechanism of action of tacrolimus in atopic dermatitis is not known. While the following have been observed, the clinical significance of these observations in atopic dermatitis is not known. It has been demonstrated that tacrolimus inhibits T-lymphocyte activation by first binding to an intracellular protein, FKBP-12. A complex of tacrolimus-FKBP-12, calcium, calmodulin, and calcineurin is then formed and the phosphatase activity of calcineurin is inhibited. This effect has been shown to prevent the dephosphorylation and translocation of nuclear factor of activated T-cells (NF-AT), a nuclear component thought to initiate gene transcription for the formation of lymphokines (such as interleukin-2, gamma interferon). Tacrolimus also inhibits the transcription for genes which encode IL-3, IL-4, IL-5, GM-CSF, and TNF-?, all of which are involved in the early stages of T-cell activation. Additionally, tacrolimus has been shown to inhibit the release of pre-formed mediators from skin mast cells and basophils, and to down regulate the expression of Fc?RI on Langerhans cells.
INDICATIONS AND USAGE
PROTOPIC Ointment, both 0.03% and 0.1% for adults, and only 0.03% for children aged 2 to 15 years, is indicated as second-line therapy for the short-term and non-continuous chronic treatment of moderate to severe atopic dermatitis in non-immunocompromised adults and children who have failed to respond adequately to other topical prescription treatments for atopic dermatitis, or when those treatments are not advisable.
PROTOPIC Ointment is not indicated for children younger than 2 years of age (see boxed WARNING, WARNINGS and PRECAUTIONS: Pediatric Use).
CONTRAINDICATIONS
PROTOPIC (tacrolimus) Ointment is contraindicated in patients with a history of hypersensitivity to tacrolimus or any other component of the ointment.
WARNINGS
WARNING
Long-term Safety of Topical Calcineurin Inhibitors Has Not Been Established
Although a causal relationship has not been established, rare cases of malignancy (e.g., skin and lymphoma) have been reported in patients treated with topical calcineurin inhibitors, including PROTOPIC Ointment.
Therefore:
Continuous long-term use of topical calcineurin inhibitors, including PROTOPIC Ointment, in any age group should be avoided, and application limited to areas of involvement with atopic dermatitis.
PROTOPIC Ointment is not indicated for use in children less than 2 years of age. Only 0.03% PROTOPIC Ointment is indicated for use in children 2-15 years of age.
Prolonged systemic use of calcineurin inhibitors for sustained immunosuppression in animal studies and transplant patients following systemic administration has been associated with an increased risk of infections, lymphomas, and skin malignancies. These risks are associated with the intensity and duration of immunosuppression.
Based on the information above and the mechanism of action, there is a concern about potential risk with the use of topical calcineurin inhibitors, including PROTOPIC Ointment. While a causal relationship has not been established, rare cases of skin malignancy and lymphoma have been reported in patients treated with topical calcineurin inhibitors, including PROTOPIC Ointment. Therefore:
PROTOPIC Ointment should not be used in immunocompromised adults and children.
If signs and symptoms of atopic dermatitis do not improve within 6 weeks, patients should be re-examined by their healthcare provider and their diagnosis be confirmed (see PRECAUTIONS: General).
The safety of PROTOPIC Ointment has not been established beyond one year of non-continuous us.
OVERDOSAGE
PROTOPIC Ointment is not for oral use. Oral ingestion of PROTOPIC Ointment may lead to adverse effects associated with systemic administration of tacrolimus. If oral ingestion occurs, medical advice should be sought.
DOSAGE AND ADMINISTRATION
Adult
PROTOPIC Ointment 0.03% and 0.1%
Apply a thin layer of PROTOPIC (tacrolimus) Ointment to the affected skin twice daily. The minimum amount should be rubbed in gently and completely to control signs and symptoms of atopic dermatitis. Stop using when signs and symptoms of atopic dermatitis resolve.
If signs and symptoms (e.g. itch, rash, and redness) do not improve within 6 weeks, patients should be re-examined by their healthcare provider to confirm the diagnosis of atopic dermatitis.
Continuous long-term use of topical calcineurin inhibitors, including PROTOPIC Ointment should be avoided, and application should be limited to areas of involvement with atopic dermatitis.
The safety of PROTOPIC Ointment under occlusion, which may promote systemic exposure, has not been evaluated. PROTOPIC Ointment should not be used with occlusive dressings.