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Uses

Atopic Dermatitis

Second-line therapy for short-term and noncontinuous chronic treatment of moderate to severe atopic dermatitis (eczema) in immunocompetent adults and children 2–15 years of age who are unable to tolerate or have not responded to first-line therapies or for whom first-line therapies are inadvisable. (See Carcinogenicity under Cautions.)

Not indicated for use in children <2 years of age.

Dosage and Administration

Administration

Topical Administration

Apply topically to the skin as a 0.03 or 0.l% ointment.

For external use only; do not use in the eyes or ingest.

Apply in thin layers; rub gently and completely into affected areas of skin.

Use minimum amount required to control symptoms; limit application to areas affected with atopic dermatitis. (See Carcinogenicity under Cautions.)

Use with caution on the face or neck, large areas of the body (i.e., >50% of the total body surface area), or areas of broken skin. (See Absorption under Pharmacokinetics.)

Do not use occlusive dressings or wrappings.

Dosage

Pediatric Patients

Atopic Dermatitis

Topical

Children 2–15 years of age: Apply 0.03% ointment to affected areas twice daily, approximately 12 hours apart.

Adolescents ≥16 years of age: Apply 0.03 or 0.l% ointment to affected areas twice daily, approximately 12 hours apart.

Discontinue treatment following resolution of signs and symptoms (e.g., pruritus, rash, erythema). If manifestations persist beyond 6 weeks, reexamine patient and confirm diagnosis.

Adults

Atopic Dermatitis

Topical

Apply 0.03 or 0.l% ointment to affected areas twice daily, approximately 12 hours apart.

Discontinue treatment following resolution of signs and symptoms (e.g., pruritus, rash, erythema). If manifestations persist beyond 6 weeks, reexamine patient and confirm diagnosis.

Prescribing Limits

Pediatric Patients

Atopic Dermatitis

Topical

For short-term and intermittent use only; avoid continuous long-term use. Safety of noncontinuous use for >1 year not established. (See Carcinogenicity under Cautions.)

Adults

Atopic Dermatitis

Topical

For short-term and intermittent use only; avoid continuous long-term use. Safety of noncontinuous use for >1 year not established. (See Carcinogenicity under Cautions.)

Special Populations

Dosage in Hepatic Impairment

No dosage adjustment appears necessary; effect of hepatic impairment on the pharmacokinetics of topical tacrolimus has not been evaluated.

Dosage in Renal Impairment

No dosage adjustment appears necessary. Effect of renal impairment on the pharmacokinetics of topical tacrolimus has not been evaluated; following IV administration of tacrolimus, elimination in patients with renal dysfunction is similar to that in healthy individuals.

Cautions

Contraindications

• Known hypersensitivity to tacrolimus or any ingredient in the formulation.

Warnings/Precautions

Warnings

Carcinogenicity

Possible increased risk of malignancies. (See Boxed Warning.)

Malignancies (including lymphoma and skin cancers) reported rarely in children and adults receiving topical tacrolimus. Concerns also based on case reports of malignancies (including lymphoma and skin cancers) in patients (including transplant patients) receiving prolonged systemic therapy with calcineurin inhibitors (e.g., cyclosporine, tacrolimus); animal studies indicating dose-related increases in the risk of lymphoma and other malignancies (particularly of the skin) with tacrolimus and other calcineurin inhibitors, possibly due to immunosuppression; and known pharmacologic effects of these immunosuppressants.

Systemic administration of tacrolimus in kidney and liver transplant patients is associated with development of lymphoma and skin cancers. Risk appears to be related to dose and duration of exposure.

Tacrolimus may be absorbed into systemic circulation following topical application, but concentrations generally are very low. The lowest blood tacrolimus concentration associated with systemic effects (e.g., immunosuppression) has not been determined. (See Absorption under Pharmacokinetics.)

Risk associated with systemic therapy is related to intensity and duration of immunosuppression. The potential for systemic immunosuppression with topical tacrolimus and the drug’s role in the development of malignancies in humans have not been established. Long-term studies in humans are needed to determine whether topical tacrolimus is associated with an increased risk of malignancies. Until such data are available, FDA recommends limiting use to the labeled indication, reserving the drug for use as a second-line agent for short-term and intermittent treatment. (See Atopic Dermatitis under Uses, see Immunocompromised Patients under Cautions, and see Dosage and Administration.) Carefully evaluate potential risks and benefits of therapy.

Avoid use for malignant or premalignant skin conditions (e.g., cutaneous T-cell lymphoma [CTCL]), which may appear clinically similar to dermatitis.

General Precautions

Lymphadenopathy

Lymphadenopathy reported; usually related to infections and resolves following appropriate anti-infective therapy. Also reported in association with malignancy. Investigate etiology if lymphadenopathy develops. Discontinue tacrolimus in the absence of a clear etiology or in the presence of acute infectious mononucleosis. Monitor patients with lymphadenopathy to ensure that it resolves.

Netherton’s Syndrome

Not recommended for use in patients with Netherton’s syndrome because of the potential for increased systemic absorption of tacrolimus.

Generalized Erythroderma

Safety in patients with generalized erythroderma has not been established.

Dermatologic Reactions

Possible burning sensation (burning, stinging, soreness) or pruritus at the treatment site within the first few days of initiating therapy. Reactions usually improve as the lesions of atopic dermatitis resolve.

Infectious Complications

Clinical infections (e.g., bacterial, viral) at treatment sites should be cleared before initiating tacrolimus therapy. Safety and efficacy not established for treatment of clinically infected atopic dermatitis.

Possible increased risk of varicella-zoster infections (chickenpox or shingles), herpes simplex virus infection, or eczema herpeticum.

Systemic administration of tacrolimus in kidney and liver transplant patients associated with increased susceptibility to infection.

Phototoxicity

Although phototoxicity not reported in humans, it may be prudent to minimize or avoid natural or artificial sunlight exposure during tacrolimus therapy (including periods when no drug is on skin). Potential effects on skin response to ultraviolet (UV) damage are not known.

Animal photocarcinogenicity studies indicate shortened time to skin tumor formation following chronic topical tacrolimus dosing with concurrent UV radiation exposure.

Immunocompromised Patients

Safety and efficacy not established and not recommended for use in immunocompromised adults or children.

Renal Effects

Acute renal failure reported rarely in patients receiving topical tacrolimus. Increased risk of systemic absorption in patients with epidermal barrier defects, especially following topical application to large body surface areas.

Use with caution in patients predisposed to renal impairment.

Specific Populations

Pregnancy

Category C.

Lactation

Not known whether distributed into milk following topical administration. Discontinue nursing or the drug.

Blacks

0.03% ointment is ineffective; use the 0.1% ointment.

Pediatric Use

Safety and efficacy not established and not recommended for use in children <2 years of age.

Use only the 0.03% ointment when topical tacrolimus is indicated in immunocompetent children 2–15 years of age. (See Atopic Dermatitis under Uses).

Long-term effects on the developing immune system in infants and children are not known.

Not recommended for use in immunocompromised children.

Geriatric Use

No substantial differences in safety relative to younger adults.

Renal Impairment

Use with caution in patients predisposed to renal impairment. (See Renal Effects.)

Common Adverse Effects

Burning sensation, pruritus, flu-like symptoms, skin erythema, headache.