Version July 2025
Although a causal relationship has not been established, rare cases of malignancy (ie, skin cancer and lymphoma) have been reported in patients treated with topical calcineurin inhibitors, including tacrolimus ointment. Avoid continuous long-term use of topical calcineurin inhibitors, including tacrolimus ointment, in any age group, and limit application to areas of involvement with atopic dermatitis.
Tacrolimus ointment is not indicated for use in children younger than 2 years of age. Only tacrolimus 0.03% ointment is indicated for use in children 2 to 15 years of age.
Allergic contact dermatitis (alternative agent) (off-label use): Topical: Apply a thin layer of 0.1% ointment to the affected area(s) twice daily (Ref).
Atopic dermatitis (moderate to severe): Topical:
Treatment: Apply thin layer of 0.03% or 0.1% ointment to affected area twice daily; rub in gently and completely. Discontinue use when symptoms have cleared. If no improvement within 6 weeks, patients should be re-examined to confirm diagnosis.
Maintenance therapy (off-label use): Apply one application (thin layer of 0.03% or 0.1% ointment) to areas usually affected twice daily twice a week (Ref).
Oral lichen planus (off-label use): Topical: Apply thin layer of 0.1% ointment to affected area(s) up to 4 times daily; the treatment period in clinical trials ranged from 4 to 6 weeks (Ref).
Psoriasis (intertriginous and facial) (off-label use): Topical: Apply thin layer of 0.1% ointment to affected area twice daily; the treatment period in clinical trials was 6 to 8 weeks (Ref).
Pyoderma gangrenosum (refractory) (off-label use): Topical: Apply thin layer of 0.1% ointment to affected area once daily. May taper to 0.03% ointment once daily after improvement is evident following several weeks of initial therapy (Ref).
Vitiligo (primarily the head and neck region ) (off-label use): Topical: Apply thin layer of 0.1% ointment to affected area twice daily; reassess every 3 to 6 months for adequate response (Ref).
There are no dosage adjustments provided in the manufacturer's labeling.
There are no dosage adjustments provided in the manufacturer's labeling.
Refer to adult dosing.
(For additional information see "Tacrolimus (topical): Pediatric drug information")
Atopic dermatitis, moderate to severe: Note: Discontinue use when symptoms have cleared. If no improvement occurs within 6 weeks, patients should be reexamined to confirm diagnosis. Topical:
Ointment 0.03%: Children ≥2 years and Adolescents: Apply a thin layer to affected area twice daily; rub in gently and completely
Ointment 0.1%: Adolescents ≥16 years: Apply a thin layer of 0.1% ointment to affected area twice daily; rub in gently and completely
There are no dosage adjustments provided in the manufacturer's labeling.
There are no dosage adjustments provided in the manufacturer's labeling.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Adverse reactions reported in children, adolescents, and adults, unless otherwise noted.
>10%:
Dermatologic: Burning sensation of skin (43% to 58%), erythema of skin (adults: 25% to 28%), pruritus (41% to 46%), skin infection (adults: 12%)
Hypersensitivity: Hypersensitivity reaction (adults: 12%)
Nervous system: Headache (adults: 19% to 20%)
Respiratory: Flu-like symptoms (23% to 31%), increased cough (children and adolescents: 18%)
Miscellaneous: Fever (children and adolescents: 21%)
1% to 10%
Cardiovascular: Hypertension (adults: 1%), peripheral edema (adults: 3% to 4%)
Dermatologic: Acne vulgaris (adults: 4% to 7%), alopecia (adults: 1%), contact dermatitis (3% to 4%), eczema (herpeticum: 1% to 2%), folliculitis (2% to 6%), fungal dermatitis (adults: 1% to 2%), pustular rash (adults: 3% to 4%), skin rash (adults: 2% to 5%), sunburn (adults: 2%), urticaria (adults: 6%), vesiculobullous dermatitis (children and adolescents: 4%), xeroderma (children and adolescents: 1%)
Gastrointestinal: Abdominal pain (children and adolescents: 3%), diarrhea (4% to 5%), dyspepsia (adults: 4%), gastroenteritis (adults: 2%), nausea (children and adolescents: 1%), vomiting (adults: 1%)
Genitourinary: Dysmenorrhea (adults: 4%), urinary tract infection (adults: 1%)
Hematologic & oncologic: Lymphadenopathy (children and adolescents: 3%)
Infection: Herpes zoster (≤5%), infection (adults: 2%), varicella zoster infection (≤5%)
Nervous system: Asthenia (adults: 2% to 3%), depression (adults: 2%), hyperesthesia (adults: 3% to 7%), insomnia (adults: 4%), pain (1% to 2%), paresthesia (adults: 3%), tingling of skin (2% to 8%)
Neuromuscular & skeletal: Arthralgia (adults: 3%), back pain (adults: 2%), myalgia (adults: 2% to 3%)
Ocular: Conjunctivitis (adults: 2%)
Respiratory: Asthma (adults: 6%), bronchitis (adults: 2%), pharyngitis (adults: 4%), pneumonia (adults: 1%), rhinitis (children and adolescents: 6%), sinusitis (adults: 2% to 4%)
Miscellaneous: Cyst (adults: 1% to 3%)
<1%:
Cardiovascular: Chest pain, edema, heart valve disease, syncope, tachycardia, vasodilation
Dermatologic: Cutaneous candidiasis, dermal ulcer, diaphoresis, ecchymoses, furunculosis, leukoderma, nail disease, seborrhea, skin carcinoma, skin discoloration, skin hypertrophy, skin photosensitivity
Endocrine & metabolic: Dehydration, hypercholesterolemia, hypothyroidism
Gastrointestinal: Anorexia, colitis, constipation, dysgeusia, gastritis, hernia of abdominal cavity, oral candidiasis, oral mucosa ulcer, rectal disease, stomatitis, xerostomia
Genitourinary: Cystitis, vaginitis, vulvovaginal candidiasis
Hematologic & oncologic: Anemia, benign neoplasm (breast), neoplasm (benign)
Hepatic: Hyperbilirubinemia
Hypersensitivity: Nonimmune anaphylaxis
Infection: Abscess, candidiasis
Nervous system: Anxiety, changes in thinking, chills, dizziness, hypertonia, malaise, migraine, vertigo
Neuromuscular & skeletal: Arthritis, arthropathy, bone disease, bursitis, muscle cramps, neck pain, osteoarthritis, tendinopathy
Ophthalmic: Blepharitis, cataract, conjunctival edema, dry eye syndrome, eye pain, visual disturbance
Respiratory: Dry nose, dyspnea, epistaxis, laryngitis
Postmarketing:
Dermatologic: Basal cell carcinoma of skin, impetigo (bullous), malignant melanoma, rosacea
Hematologic & oncologic: Malignant lymphoma, squamous cell carcinoma
Infection: Septicemia
Local: Application-site edema
Nervous system: Seizure
Neuromuscular & skeletal: Osteomyelitis
Renal: Kidney impairment (including acute kidney injury)
Hypersensitivity to tacrolimus or any component of the formulation
Concerns related to adverse events:
• Infection: Do not apply to areas of active bacterial or viral infection; infections at the treatment site should be cleared prior to therapy. Patients with atopic dermatitis are predisposed to skin infections, and tacrolimus therapy has been associated with risk of developing eczema herpeticum, varicella zoster, and herpes simplex.
• Lymphadenopathy: May be associated with development of lymphadenopathy; possible infectious causes should be investigated. Discontinue use in patients with unknown cause of lymphadenopathy or acute infectious mononucleosis.
• Malignancy: Avoid use on malignant or premalignant skin conditions (eg, cutaneous T-cell lymphoma). Limit sun and ultraviolet light exposure; use appropriate sun protection.
• Renal failure: Acute renal failure has been observed (rarely) with topical use.
Disease related concerns:
• Immunosuppression: Should not be used in immunocompromised patients. Safety and efficacy have not been evaluated.
• Skin diseases with altered absorption: Not recommended for use in patients with skin disease which may increase systemic absorption (eg, Netherton's syndrome).
Special populations:
• Pediatric: [US Boxed Warning] Use in children <2 years of age is not recommended, only the 0.03% ointment should be used in children ages 2 to 15 years.
Other warnings/precautions:
• Appropriate use: Topical calcineurin agents are considered second-line therapies in the treatment of atopic dermatitis/eczema, and should be limited to use in patients who have failed treatment with other therapies. Safety not established in patients with generalized erythroderma. If atopic dermatitis is not improved in <6 weeks, re-evaluate to confirm diagnosis. Safety of intermittent use for >1 year has not been established, particularly since the effect on immune system development is unknown.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Ointment, External:
Protopic: 0.03% (30 g [DSC], 60 g [DSC], 100 g [DSC]); 0.1% (30 g [DSC], 60 g [DSC], 100 g [DSC])
Generic: 0.03% (30 g, 60 g, 100 g); 0.1% (30 g, 60 g, 100 g)
Yes
Ointment (Tacrolimus External)
0.03% (per gram): $2.80 - $9.65
0.1% (per gram): $4.00 - $11.01
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Ointment, External:
Protopic: 0.03% (30 g, 60 g, 100 g); 0.1% (30 g, 60 g, 100 g)
Topical: Wash hands before and after application. Use the smallest amount of ointment needed to control symptoms. Use with occlusive dressings is not recommended; however, occlusion may be considered on photo-exposed areas in the treatment of nonfacial vitiligo (Ref). Do not bathe, shower, or swim right after application. Limit sun exposure during the treatment period. Limit application to involved areas.
Oral lichen planus (off-label use): Apply a thin layer of tacrolimus using finger or cotton tip or a latex glove. Lesion should be dried before applying medication. Do not eat or drink for at least 30 minutes after application (Ref).
For external use only; avoid exposure to eyes or mouth. Wash hands before and after application. Use the smallest amount of ointment needed to control the signs and symptoms of atopic dermatitis. Do not cover with occlusive dressings. Do not bathe, shower, or swim right after application. Moisturizers can be applied after application. Limit sun exposure during the treatment period. Burning at the application site is most common in first few days; improves as atopic dermatitis improves.
Hazardous agent (NIOSH 2024 [table 2]).
Use appropriate precautions for receiving, handling, storage, preparation, dispensing, transporting, administration, and disposal. Follow NIOSH and USP 800 recommendations and institution-specific policies/procedures for appropriate containment strategy (NIOSH 2023; NIOSH 2024; USP-NF 2020).
Note: Facilities may perform risk assessment of some hazardous drugs to determine if appropriate for alternative handling and containment strategies (USP-NF 2020). Refer to institution-specific handling policies/procedures.
An FDA-approved patient medication guide, which is available with the product information and at http://www.fda.gov/downloads/Drugs/DrugSafety/ucm088996.pdf, must be dispensed with this medication.
Atopic dermatitis (moderate to severe): Treatment of moderate to severe atopic dermatitis in immunocompetent patients not responsive to conventional therapy or when conventional therapy is not appropriate.
Allergic contact dermatitis; Atopic dermatitis (maintenance therapy); Oral lichen planus; Psoriasis (intertriginous and facial); Pyoderma gangrenosum (refractory); Vitiligo
Tacrolimus may be confused with everolimus, pimecrolimus, sirolimus, tamsulosin, temsirolimus
Substrate of CYP3A4 (Minor); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential;
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the drug interactions program by clicking on the “Launch drug interactions program” link above.
Alcohol (Ethyl): May increase dermatologic adverse effects of Tacrolimus (Topical). Risk C: Monitor
Corticosteroids (Systemic): May increase immunosuppressive effects of Tacrolimus (Topical). Risk X: Avoid
CYP3A4 Inhibitors (Moderate): May increase serum concentration of Tacrolimus (Topical). Risk C: Monitor
CYP3A4 Inhibitors (Strong): May increase serum concentration of Tacrolimus (Topical). Risk C: Monitor
Immunosuppressants (Cytotoxic Chemotherapy): May increase immunosuppressive effects of Tacrolimus (Topical). Risk X: Avoid
Immunosuppressants (Miscellaneous Oncologic Agents): May increase immunosuppressive effects of Tacrolimus (Topical). Risk X: Avoid
Immunosuppressants (Therapeutic Immunosuppressant Agents): May increase immunosuppressive effects of Tacrolimus (Topical). Risk X: Avoid
Methotrexate: May increase immunosuppressive effects of Tacrolimus (Topical). Risk X: Avoid
Topical tacrolimus may be used for the treatment of atopic dermatitis and psoriasis in patients planning a pregnancy (AAD-NPF [Elmets 2021]; Vestergaard 2019).
Tacrolimus crosses the human placenta following systemic use.
When preferred treatments are insufficient, topical tacrolimus may be used for the treatment of atopic dermatitis and psoriasis in pregnant patients (AAD-NPF [Elmets 2021]; Vestergaard 2019).
Also refer to the Tacrolimus (Systemic) monograph for additional information
Tacrolimus is present in breast milk following systemic administration.
Due to the potential for adverse reactions in the breastfed infant, the manufacturer recommends a decision be made to discontinue breastfeeding or to discontinue the drug, considering the importance of treatment to the mother. Apply tacrolimus immediately after breastfeeding; avoid use on nipples and clean nipples prior to the next feeding (AAD-NPF [Elmets 2021]; Vestergaard 2019).
Refer to the Tacrolimus (Systemic) monograph for additional information.
Suppresses cellular immunity (inhibits T-lymphocyte activation), by binding to an intracellular protein, FKBP-12 and complexes with calcineurin dependent proteins to inhibit calcineurin phosphatase activity
Absorption: Minimally absorbed; serum concentrations range from undetectable to 20 ng/mL (~2 ng/mL in majority of adult patients studied)
Bioavailability: ~0.5%
