PROTOPIC®(tacrolimus)

Ointment 0.03%
Ointment 0.1%

FOR DERMATOLOGIC USE ONLY
NOT FOR OPHTHALMIC USE

Rx Only

Prescribing Information

See boxed WARNINGS concerning long-term safety of topical calcineurin inhibitors

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. It has the following structural formula:

Tacrolimus has an empirical formula of C₄₄H₆₉NO₁₂●H₂O 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.

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-α, 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 FcεRI on Langerhans cells.

Three randomized, double-blind, vehicle-controlled, multi-center, phase 3 studies were conducted to evaluate PROTOPIC Ointment for the treatment of patients with moderate to severe atopic dermatitis. One (Pediatric) study included 351 patients 2-15 years of age, and the other two (Adult) studies included a total of 632 patients 15-79 years of age. Fifty-five percent (55%) of the patients were women and 27% were black. At baseline, 58% of the patients had severe disease and the mean body surface area (BSA) affected was 46%. Over 80% of patients had atopic dermatitis affecting the face and/or neck region. In these studies, patients applied either PROTOPIC Ointment 0.03%, PROTOPIC Ointment 0.1%, or vehicle ointment twice daily to 10% - 100% of their BSA for up to 12 weeks.

In the pediatric study, a significantly greater (p < 0.001) percentage of patients achieved at least 90% improvement based on the physician’s global evaluation of clinical response (the pre-defined primary efficacy endpoint) in the PROTOPIC Ointment 0.03% treatment group compared to the vehicle treatment group, but there was insufficient evidence that PROTOPIC Ointment 0.1% provided more efficacy than PROTOPIC Ointment 0.03%.

In both adult studies, a significantly greater (p < 0.001) percentage of patients achieved at least 90% improvement based on the physician’s global evaluation of clinical response in the PROTOPIC Ointment 0.03% and PROTOPIC Ointment 0.1% treatment groups compared to the vehicle treatment group. There was evidence that PROTOPIC Ointment 0.1% may provide more efficacy than PROTOPIC Ointment 0.03%. The difference in efficacy between PROTOPIC Ointment 0.1% and 0.03% was particularly evident in adult patients with severe disease at baseline, adults with extensive BSA involvement, and black adults. Response rates for each treatment group are shown below by age groups. Because the two adult studies were identically designed, the results from these studies were pooled in this table.

A statistically significant difference in the percentage of adult patients with ≥ 90% improvement was achieved by week 1 for those treated with PROTOPIC Ointment 0.1%, and by week 3 for those treated with PROTOPIC Ointment 0.03%. A statistically significant difference in the percentage of pediatric patients with ≥ 90% improvement was achieved by week 2 for those treated with PROTOPIC Ointment 0.03%.

In adult patients who had achieved ≥ 90% improvement at the end of treatment, 35% of those treated with PROTOPIC Ointment 0.03% and 41% of those treated with PROTOPIC Ointment 0.1%, regressed from this state of improvement at 2 weeks after end-of-treatment. In pediatric patients who had achieved ≥ 90% improvement, 54% of those treated with PROTOPIC Ointment 0.03% regressed from this state of improvement at 2 weeks after end-of-treatment. Because patients were not followed for longer than 2 weeks after end-of-treatment, it is not known how many additional patients regressed at periods longer than 2 weeks after cessation of therapy.

In both PROTOPIC Ointment treatment groups in adults and in the PROTOPIC Ointment 0.03% treatment group in pediatric patients, a significantly greater improvement compared to vehicle (p < 0.001) was observed in the secondary efficacy endpoints of percent body surface area involved, patient evaluation of pruritus, erythema, edema, excoriation, oozing, scaling, and lichenification. The following two graphs depict the time course of improvement in the percent body surface area affected in adult and in pediatric patients as a result of treatment.

The following two graphs depict the time course of improvement in erythema in adult and in pediatric patients as a result of treatment.

 

The time course of improvement in the remaining secondary efficacy variables was similar to that of erythema, with improvement in lichenification slightly slower.

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 ).

PROTOPIC (tacrolimus) Ointment is contraindicated in patients with a history of hypersensitivity to tacrolimus or any other component of the ointment.

The use of PROTOPIC Ointment should be avoided on pre-malignant and malignant skin conditions. Some malignant skin conditions, such as cutaneous T-cell lymphoma (CTCL), may mimic atopic dermatitis.

The use of PROTOPIC Ointment in patients with Netherton’s Syndrome or other skin diseases where there is the potential for increased systemic absorption of tacrolimus is not recommended. The safety of PROTOPIC Ointment has not been established in patients with generalized erythroderma.

The use of PROTOPIC Ointment may cause local symptoms such as skin burning (burning sensation, stinging, soreness) or pruritus. Localized symptoms are most common during the first few days of PROTOPIC Ointment application and typically improve as the lesions of atopic dermatitis resolve. With PROTOPIC Ointment 0.1%, 90% of the skin burning events had a duration between 2 minutes and 3 hours (median 15 minutes). 90% of the pruritus events had a duration between 3 minutes and 10 hours (median 20 minutes). (see ADVERSE REACTIONS).

Before commencing treatment with PROTOPIC Ointment, cutaneous bacterial or viral infections at treatment sites should be resolved. Studies have not evaluated the safety and efficacy of PROTOPIC Ointment in the treatment of clinically infected atopic dermatitis.

While patients with atopic dermatitis are predisposed to superficial skin infections including eczema herpeticum (Kaposi’s varicelliform eruption), treatment with PROTOPIC Ointment may be independently associated with an increased risk of varicella zoster virus infection (chicken pox or shingles), herpes simplex virus infection, or eczema herpeticum.

In clinical studies, 112/13494 (0.8%) cases of lymphadenopathy were reported and were usually related to infections (particularly of the skin) and noted to resolve upon appropriate antibiotic therapy. Of these 112 cases, the majority had either a clear etiology or were known to resolve. Transplant patients receiving immunosuppressive regimens (e.g., systemic tacrolimus) are at increased risk for developing lymphoma; therefore, patients who receive PROTOPIC Ointment and who develop lymphadenopathy should have the etiology of their lymphadenopathy investigated. In the absence of a clear etiology for the lymphadenopathy, or in the presence of acute infectious mononucleosis, PROTOPIC Ointment should be discontinued. Patients who develop lymphadenopathy should be monitored to ensure that the lymphadenopathy resolves.

During the course of treatment, patients should minimize or avoid natural or artificial sunlight exposure, even while PROTOPIC is not on the skin. It is not known whether PROTOPIC Ointment interferes with skin response to ultraviolet damage.

The safety and efficacy of PROTOPIC Ointment in immunocompromised patients have not been studied.

Rare post-marketing cases of acute renal failure have been reported in patients treated with PROTOPIC Ointment. Systemic absorption is more likely to occur in patients with epidermal barrier defects especially when PROTOPIC is applied to large body surface areas. Caution should also be exercised in patients predisposed to renal impairment.

(See MEDICATION GUIDE)

Patients using PROTOPIC Ointment should receive and understand the information in the Medication Guide. Please refer to the Medication Guide for providing instruction and information to the patient.

What is the most important information patients should know about PROTOPIC Ointment?

The safety of using PROTOPIC Ointment for a long period of time is not known. A very small number of people who have used PROTOPIC Ointment have had cancer (for example, skin or lymphoma). However, a link with PROTOPIC Ointment has not been shown. Because of this concern, instruct patients:

• Do not use PROTOPIC Ointment continuously for a long time.
• Use PROTOPIC Ointment only on areas of skin that have eczema.
• Do not use PROTOPIC Ointment on a child under 2 years old.
  

PROTOPIC Ointment comes in two strengths:

• Only PROTOPIC Ointment 0.03% is for use on children aged 2 to 15 years.
• Either PROTOPIC Ointment 0.03% or 0.1% can be used by adults and children 16 years and older.
  

Advise patients to talk to their prescriber for more information.

How should PROTOPIC Ointment be used?

Advise patients to:

• Use PROTOPIC Ointment exactly as prescribed.
• Use PROTOPIC Ointment only on areas of skin that have eczema.
• Use PROTOPIC Ointment for short periods, and if needed, treatment may be repeated with breaks in between.
• Stop PROTOPIC Ointment when the signs and symptoms of eczema, such as itching, rash, and redness go away, or as directed.
• Follow their doctor’s advice if symptoms of eczema return after treatment with PROTOPIC Ointment.
• Call their doctor if:
  • Their symptoms get worse with PROTOPIC Ointment.
  • They get an infection on their skin.
  • Their symptoms do not improve after 6 weeks of treatment. Sometimes other skin diseases can look like eczema.
    

To apply PROTOPIC Ointment:

Advise patients:

• Wash their hands before applying PROTOPIC.

• Apply a thin layer of PROTOPIC Ointment twice daily to the areas of skin affected by eczema.

• Use the smallest amount of PROTOPIC Ointment needed to control the signs and symptoms of eczema.

• If they are a caregiver applying PROTOPIC Ointment to a patient, or if they are a patient who is not treating their hands, wash their hands with soap and water after applying PROTOPIC. This should remove any ointment left on the hands.

• Do not bathe, shower, or swim right after applying PROTOPIC. This could wash off the ointment.
• Moisturizers can be used with PROTOPIC Ointment. Make sure they check with their doctor first about the products that are right for them. Because the skin of patients with eczema can be very dry, it is important to keep up good skin care practices. If they use moisturizers, apply them after PROTOPIC Ointment.
  

What should patients avoid while using PROTOPIC Ointment?

Advise patients:

• Do not use ultraviolet light therapy, sun lamps, or tanning beds during treatment with PROTOPIC Ointment.
• Limit sun exposure during treatment with PROTOPIC Ointment even when the medicine is not on their skin. If patients need to be outdoors after applying PROTOPIC Ointment, wear loose fitting clothing that protects the treated area from the sun. Doctors should advise what other types of protection from the sun patients should use.
• Do not cover the skin being treated with bandages, dressings or wraps. Patients can wear normal clothing.
• Avoid getting PROTOPIC Ointment in the eyes or mouth. Do not swallow PROTOPIC Ointment. Patients should call their doctor if they swallow PROTOPIC Ointment.

Formal topical drug interaction studies with PROTOPIC Ointment have not been conducted. Based on its extent of absorption, interactions of PROTOPIC Ointment with systemically administered drugs are unlikely to occur but cannot be ruled out (see CLINICAL PHARMACOLOGY). The concomitant administration of known CYP3A4 inhibitors in patients with widespread and/or erythrodermic disease should be done with caution. Some examples of such drugs are erythromycin, itraconazole, ketoconazole, fluconazole, calcium channel blockers and cimetidine.

No evidence of genotoxicity was seen in bacterial (Salmonella and E. coli) or mammalian (Chinese hamster lung-derived cells) in vitro assays of mutagenicity, the in vitro CHO/HGPRT assay of mutagenicity, or in vivo clastogenicity assays performed in mice. Tacrolimus did not cause unscheduled DNA synthesis in rodent hepatocytes.

Oral (feed) carcinogenicity studies have been carried out with systemically administered tacrolimus in male and female rats and mice. In the 80-week mouse study and in the 104-week rat study no relationship of tumor incidence to tacrolimus dosage was found at daily doses up to 3 mg/kg [9X the Maximum Recommended Human Dose (MRHD) based on AUC comparisons] and 5 mg/kg (3X the MRHD based on AUC comparisons), respectively.

A 104-week dermal carcinogenicity study was performed in mice with tacrolimus ointment (0.03% - 3%), equivalent to tacrolimus doses of 1.1-118 mg/kg/day or 3.3-354 mg/m²/day. In the study, the incidence of skin tumors was minimal and the topical application of tacrolimus was not associated with skin tumor formation under ambient room lighting. However, a statistically significant elevation in the incidence of pleomorphic lymphoma in high dose male (25/50) and female animals (27/50) and in the incidence of undifferentiated lymphoma in high dose female animals (13/50) was noted in the mouse dermal carcinogenicity study. Lymphomas were noted in the mouse dermal carcinogenicity study at a daily dose of 3.5 mg/kg (0.1% tacrolimus ointment) (26X MRHD based on AUC comparisons). No drug-related tumors were noted in the mouse dermal carcinogenicity study at a daily dose of 1.1 mg/kg (0.03% tacrolimus ointment) (10X MRHD based on AUC comparisons).

In a 52-week photocarcinogenicity study, the median time to onset of skin tumor formation was decreased in hairless mice following chronic topical dosing with concurrent exposure to UV radiation (40 weeks of treatment followed by 12 weeks of observation) with tacrolimus ointment at ≥0.1% tacrolimus.

Reproductive toxicology studies were not performed with topical tacrolimus. In studies of oral tacrolimus no impairment of fertility was seen in male and female rats. Tacrolimus, given orally at 1.0 mg/kg (0.12X MRHD based on body surface area [BSA]) to male and female rats, prior to and during mating, as well as to dams during gestation and lactation, was associated with embryolethality and with adverse effects on female reproduction. Effects on female reproductive function (parturition) and embryolethal effects were indicated by a higher rate of pre-implantation loss and increased numbers of undelivered and nonviable pups. When given at 3.2 mg/kg (0.43X MRHD based on BSA), tacrolimus was associated with maternal and paternal toxicity as well as reproductive toxicity including marked adverse effects on estrus cycles, parturition, pup viability, and pup malformations.

PROTOPIC Ointment is not indicated for children less than 2 years of age.

Only the lower concentration, 0.03%, of PROTOPIC Ointment is recommended for use as a second-line therapy for short-term and non-continuous chronic treatment of moderate to severe atopic dermatitis in non-immunocompromised children 2 to 15 years of age who have failed to respond adequately to other topical prescription treatments for atopic dermatitis, or when those treatments are not advisable.

The long-term safety and effects of PROTOPIC Ointment on the developing immune system are unknown (see boxed WARNING, WARNINGS and INDICATIONS AND USAGE).

Four studies were conducted involving a total of about 4,400 patients 2-15 years of age: one 12-week randomized vehicle-controlled study and three open-label safety studies of one to three years duration. About 2,500 of these patients were 2 to 6 years of age.

The most common adverse events from these studies associated with PROTOPIC Ointment application in pediatric patients were skin burning and pruritus (see ADVERSE REACTIONS). In addition to skin burning and pruritus, the less common events (< 5%) of varicella zoster (mostly chicken pox), and vesiculobullous rash were more frequent in patients treated with PROTOPIC Ointment 0.03% compared to vehicle. In the open-label safety studies, the incidence of adverse events, including infections, did not increase with increased duration of study drug exposure or amount of ointment used. In about 4,400 pediatric patients treated with PROTOPIC Ointment, 24 (0.5%) were reported with eczema herpeticum. Since the safety and efficacy of PROTOPIC Ointment have not been established in pediatric patients below 2 years of age, its use in this age group is not recommended.

In an open-label study, immune response to a 23-valent pneumococcal polysaccharide vaccine was assessed in 23 children 2 to 12 years old with moderate to severe atopic dermatitis treated with tacrolimus ointment 0.03%. Protective antibody titers developed in all patients. Similarly, in a seven-month, double-blind trial, the vaccination response to meningococcal serogroup C was equivalent in children 2 to 11 years old with moderate to severe atopic dermatitis treated with tacrolimus ointment 0.03% (n=121), a hydrocortisone ointment regimen (n=111), or normal children (n=44).

Four hundred and four (404) patients ≥ 65 years old received PROTOPIC Ointment in phase 3 studies. The adverse event profile for these patients was consistent with that for other adult patients.

No phototoxicity and no photoallergenicity were detected in clinical studies with 12 and 216 normal volunteers, respectively. One out of 198 normal volunteers showed evidence of sensitization in a contact sensitization study.

In three 12 week randomized vehicle-controlled studies and four safety studies, 655 and 9,163 patients respectively, were treated with PROTOPIC Ointment. The duration of follow-up for adult and pediatric patients in the safety studies is tabulated below.

The following table depicts the adjusted incidence of adverse events pooled across the 3 identically designed 12-week controlled studies for patients in vehicle, PROTOPIC Ointment 0.03%, and PROTOPIC Ointment 0.1% treatment groups. The table also depicts the unadjusted incidence of adverse events in four safety studies, regardless of relationship to study drug.

Other adverse events which occurred at an incidence between 0.2% and less than 1% in clinical studies in the above table include: abnormal vision, abscess, anaphylactoid reaction, anemia, anorexia, anxiety, arthritis, arthrosis, bilirubinemia, blepharitis, bone disorder, breast neoplasm benign, bursitis, cataract NOS, chest pain, chills, colitis, conjunctival edema, constipation, cramps, cutaneous moniliasis, cystitis, dehydration, dizziness, dry eyes, dry mouth/nose, dyspnea, ear disorder, ecchymosis, edema, epistaxis, eye pain, furunculosis, gastritis, gastrointestinal disorder, hernia, hypercholesterolemia, hypertonia, hypothyroidism, joint disorder, laryngitis, leukoderma, lung disorder, malaise, migraine, moniliasis, mouth ulceration, nail disorder, neck pain, neoplasm benign, oral moniliasis, otitis externa, photosensitivity reaction, rectal disorder, seborrhea, skin carcinoma, skin discoloration, skin hypertrophy, skin ulcer, stomatitis, tendon disorder, thinking abnormal, tooth caries, sweating, syncope, tachycardia, taste perversion, unintended pregnancy, vaginal moniliasis, vaginitis, valvular heart disease, vasodilatation, and vertigo.

The following adverse reactions have been identified during postapproval use of PROTOPIC Ointment. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

CNS

Seizures

Neoplasms

Lymphomas, basal cell carcinoma, squamous cell carcinoma, malignant melanoma

Infections

Bullous impetigo, osteomyelitis, septicemia

Renal

Acute renal failure in patients with or without Netherton’s syndrome, renal impairment

Skin

Rosacea

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.

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.

PROTOPIC Ointment 0.03%

• Apply a thin layer of PROTOPIC (tacrolimus) Ointment, 0.03% 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.

PROTOPIC® (tacrolimus) Ointment 0.03%

NDC 0469-5201-30 Product Code 520130

30 gram laminate tube

NDC 0469-5201-60 Product Code 520160

60 gram laminate tube

NDC 0469-5201-11 Product Code 520111

100 gram laminate tube

PROTOPIC® (tacrolimus) Ointment 0.1%

NDC 0469-5202-30 Product Code 520230

30 gram laminate tube

NDC 0469-5202-60 Product Code 520260

60 gram laminate tube

NDC 0469-5202-11 Product Code 520211

100 gram laminate tube

Store at room temperature 25°C (77°F); excursions permitted to 15°-30°C (59°-86°F).

Marketed by:

Astellas Pharma US, Inc.

Deerfield, IL 60015-2548

Manufactured by:

Astellas Pharma Manufacturing, Inc.

Grand Island, NY 14072

Revised: January 2006

PROTOPIC^®  [pro-TOP-ik]

(tacrolimus)

Ointment 0.03%

Ointment 0.1%

Read the Medication Guide every time you or a family member gets PROTOPIC Ointment. There may be new information. This Medication Guide does not take the place of talking to your doctor about your medical condition or treatment. If you have questions about PROTOPIC Ointment, ask your doctor or pharmacist.

What is the most important information I should know about PROTOPIC Ointment?

The safety of using PROTOPIC Ointment for a long period of time is not known. A very small number of people who have used PROTOPIC Ointment have had cancer (for example, skin or lymphoma). However, a link with PROTOPIC Ointment has not been shown. Because of this concern:

• Do not use PROTOPIC Ointment continuously for a long time.
• Use PROTOPIC Ointment only on areas of your skin that have eczema.
• Do not use PROTOPIC Ointment on a child under 2 years old.
  

PROTOPIC Ointment comes in two strengths:

• Only PROTOPIC Ointment 0.03% is for use on children aged 2 to 15 years.
• Either PROTOPIC Ointment 0.03% or 0.1% can be used by adults and children 16 years and older.
  

Talk to your doctor for more information.

What is PROTOPIC Ointment?

PROTOPIC Ointment is a prescription medicine used on the skin (topical) to treat eczema (atopic dermatitis). PROTOPIC Ointment is in a class of medicines called topical calcineurin inhibitors. It is for adults and children 2 years of age and older who do not have a weakened immune system. PROTOPIC Ointment is used on the skin for short periods, and if needed, treatment may be repeated with breaks in between.

PROTOPIC Ointment is for use after other prescription medicines have not worked for you, or if your doctor recommends that other prescription medicines should not be used.

Who should not use PROTOPIC Ointment?

PROTOPIC Ointment should not be used:

• on children younger than 2 years of age.

• if you are allergic to PROTOPIC Ointment or anything in it. See the end of this Medication Guide for a complete ul of ingredients.
  

What should I tell my doctor before starting PROTOPIC Ointment?

Before you start using PROTOPIC, you and your doctor should talk about all of your medical conditions, including if you:

• have a skin disease called Netherton’s syndrome (a rare inherited condition).
• have any infection on your skin including chicken pox or herpes.
• have been told you have a weakened immune system.
• are pregnant, breastfeeding, or planning to become pregnant.
  

Tell your doctor about all the medicines you take and skin products you use including prescription and nonprescription medicines, vitamins, and herbal supplements.

Know the medicines you take. Keep a ul of them with you to show your doctor and pharmacist each time you get a new medicine.

How should I use PROTOPIC Ointment?

• Use PROTOPIC Ointment exactly as prescribed.
• Use PROTOPIC Ointment only on areas of your skin that have eczema.
• Use PROTOPIC Ointment for short periods, and if needed, treatment may be repeated with breaks in between.
• Stop PROTOPIC Ointment when the signs and symptoms of eczema, such as itching, rash, and redness go away, or as directed by your doctor.
• Follow your doctor’s advice if symptoms of eczema return after treatment with PROTOPIC Ointment.
• Call your doctor if :
  • your symptoms get worse with PROTOPIC Ointment.
  • you get an infection on your skin.
  • your symptoms do not improve after 6 weeks of treatment. Sometimes other skin diseases can look like eczema.
    

To apply PROTOPIC Ointment:

• Wash your hands before applying PROTOPIC.

• Apply a thin layer of PROTOPIC Ointment twice daily to the areas of skin affected by eczema.

• Use the smallest amount of PROTOPIC Ointment needed to control the signs and symptoms of eczema.

• If you are a caregiver applying PROTOPIC Ointment to a patient, or if you are a patient who is not treating your hands, wash your hands with soap and water after applying PROTOPIC. This should remove any ointment left on the hands.

• Do not bathe, shower, or swim right after applying PROTOPIC. This could wash off the ointment.
• You can use moisturizers with PROTOPIC Ointment. Make sure you check with your doctor first about the products that are right for you. Because the skin of patients with eczema can be very dry, it is important to keep up good skin care practices. If you use moisturizers, apply them after PROTOPIC Ointment.
  

What should I avoid while using PROTOPIC Ointment?

• Do not use ultraviolet light therapy, sun lamps, or tanning beds during treatment with PROTOPIC Ointment.
• Limit sun exposure during treatment with PROTOPIC Ointment even when the medicine is not on your skin. If you need to be outdoors after applying PROTOPIC Ointment, wear loose fitting clothing that protects the treated area from the sun. Ask your doctor what other types of protection from the sun you should use.
• Do not cover the skin being treated with bandages, dressings or wraps. You can wear normal clothing.
• Avoid getting PROTOPIC Ointment in the eyes or mouth. Do not swallow PROTOPIC Ointment. If you do, call your doctor.
  

What are the possible side effects of PROTOPIC Ointment?

Please read the first section of this Medication Guide.

The most common side effects of PROTOPIC Ointment at the skin application site are stinging, burning, or itching of the skin treated with PROTOPIC. These side effects are usually mild to moderate, are most common during the first few days of treatment, and usually go away as your skin heals.

Other side effects include acne, swollen or infected hair follicles, headache, increased sensitivity of the skin to hot or cold temperatures, or flu-like symptoms such as the common cold and stuffy nose, skin tingling, upset stomach, muscle pain, swollen glands (enlarged lymph nodes), or skin infections including cold sores, chicken pox or shingles.

Talk to your doctor if you have a skin infection or if side effects (for example, swollen glands) continue or bother you.

While you are using PROTOPIC, drinking alcohol may cause the skin or face to become flushed or red and feel hot.

These are not all the side effects with PROTOPIC Ointment. Ask your doctor or pharmacist for more information.

How should I store PROTOPIC Ointment?

• Store PROTOPIC Ointment at room temperature (59° to 86°F). Do not leave PROTOPIC Ointment in your car in cold or hot weather. Make sure the cap on the tube is tightly closed.

• Keep PROTOPIC Ointment and all medicines out of the reach of children.

General advice about PROTOPIC Ointment

Medicines are sometimes prescribed for purposes other than those uled in a Medication Guide. Do not use PROTOPIC Ointment for a condition for which it was not prescribed. Do not give PROTOPIC Ointment to other people, even if they have the same symptoms you have. It may not be right for them.

This Medication Guide summarizes the most important information about PROTOPIC Ointment. If you would like more information, talk with your doctor.

Your doctor or pharmacist can give you information about PROTOPIC Ointment that is written for health care professionals. For more information, you can also visit the PROTOPIC website at www.protopic.com or call 1-800-727-7003.

What are the ingredients in PROTOPIC Ointment?

Active Ingredient: tacrolimus, either 0.03% or 0.1%

Inactive Ingredients: mineral oil, paraffin, propylene carbonate, white petrolatum and white wax.

Marketed by:

Astellas Pharma US, Inc.

Deerfield, IL 60015-2548

Manufactured by:

Astellas Pharma Manufacturing, Inc.

Grand Island, NY 14072

This Medication Guide has been approved by the U.S. Food and Drug Administration