Protopic

Tacrolimus ointment may cause side effects. Tell your doctor if any of these symptoms are severe or do not go away:

• skin burning, stinging, redness or soreness
• tingling skin
• increased sensitivity of the skin to hot or cold temperatures
• itching
• acne
• swollen or infected hair follicles
• headache
• muscle or back pain
• flu-like symptoms
• stuffy or runny nose
• nausea

Some side effects can be serious. If you experience any of the following symptoms, call your doctor immediately:

• swollen glands
• rash
• crusting, oozing, blistering or other signs of skin infection
• cold sores
• chicken pox or other blisters
• swelling of the hands, arms, feet, ankles, or lower legs

Tacrolimus ointment may cause other side effects. Call your doctor if you have any unusual problems while taking this medication.

If you experience a serious side effect, you or your doctor may send a report to the Food and Drug Administration's (FDA) MedWatch Adverse Event Reporting program online (http://www.fda.gov/Safety/MedWatch) or by phone (1-800-332-1088).

Topical tacrolimus comes as an ointment to apply to the skin. It's typically used twice a day.

Follow these steps when using the ointment:

• Wash your hands with soap and water.
• Be sure that the affected area is dry before application.
• Apply a thin layer of the ointment to the affected area.
• Gently rub the ointment into your skin.
• Wash your hands with soap and water after application.

You can cover the treated area with clothing, but don't wrap it in bandages or dressings.

Don't shower, bathe, or swim immediately after applying the ointment.

Try to apply the medicine around the same time each day.

Follow your doctor's instructions carefully when using this medicine. Don't apply more or less tacrolimus than is recommended.

Tacrolimus Overdose

An overdose of tacrolimus ointment is not expected to be dangerous.

However, if you suspect an overdose or if you accidently ingest the medicine, contact a poison control center or emergency room immediately.

You can get in touch with a poison control center at 800-222-1222.

Missed Dose of Tacrolimus

If you miss a dose of topical tacrolimus, take it as soon as you remember.

However, skip the missed dose if it's almost time for your next scheduled dose.

Don't apply extra medicine to make up for a missed dose.

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 use.

(See CLINICAL PHARMACOLOGY, BOXED WARNING, INDICATIONS AND USAGE, and DOSAGE AND ADMINISTRATION).

Protopic is a prescription medicine used as second-line therapy for the short-term and non-continuous chronic treatment of moderate to severe eczema (itchy inflammation of the skin) for adults and children aged 2 years and older who do not have a weakened immune system. Protopic is used on the skin for short periods, and if needed, treatment may be repeated with breaks in between.

Protopic 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.

This medication may be prescribed for other uses. Ask your doctor or pharmacist for more information.

Tell your doctor about all the medicines you take, including prescription and non-prescription medicines, vitamins, and herbal supplements. Drug interaction studies with Protopic have not been done but based on its limited absorption into the body it is unlikely to interact with medications taken by mouth. However, drug interactions cannot be ruled out and interactions may occur with the following medications:

• medications that block a protein in the body (CYP3A4) such as some macrolide antibiotics (clarithromycin, telithromycin), some HIV protease inhibitors (indinavir, nelfinavir, ritonavir, saquinavir), some HCV protease inhibitors (boceprevir, telaprevir), some azole antifungals (ketoconazole, itraconazole, posaconazole, voriconazole), conivaptan (Vaprisol), delavirdine (Rescriptor), and nefazodone

This is not a complete list of Protopic drug interactions. Ask your doctor or pharmacist for more information. 

Tell your doctor if you are pregnant or plan to become pregnant. 

The FDA categorizes medications based on safety for use during pregnancy. Five categories - A, B, C, D, and X, are used to classify the possible risks to an unborn baby when a medication is taken during pregnancy.

Protopic falls into category C. No well-controlled studies have been done in pregnant woman with topical Protopic. Protopic should be given to a pregnant woman only if clearly needed. 

Tell your doctor if you are breastfeeding or plan to breastfeed.

The active ingredient of Protopic has been detected in human breast milk. Systemic absorption of tacrolimus following topical applications of Protopic is minimal. Because of the possibility for adverse reactions in nursing infants from Protopic, a choice should be made whether to stop nursing or to stop use of this medication. The importance of the drug to the mother should be considered. 

You should not use tacrolimus topical if you are allergic to it.

Before using tacrolimus topical, tell your doctor if you have skin cancer or a skin infection (including herpes or chickenpox), any genetic skin disorder (such as Netherton's syndrome), a weak immune system, kidney disease, or swelling, redness, or irritation of large areas of your skin.

Tacrolimus can lower the blood cells that help your body fight infections. This can make it easier for you to get sick from a virus such as chicken pox or herpes (cold sores or shingles). Tell your doctor if you have been exposed to any illness.

Avoid sunlight, sun lamps, tanning beds, and phototherapy treatments with UVA or UVB light. If you must be outdoors, wear loose clothing over the skin areas treated with tacrolimus topical. Do not use sunscreen on treated skin unless your doctor has told you to.

Talk to your doctor if your skin condition does not improve after using tacrolimus topical for 6 weeks.

Do not use this medication on a child younger than 2 years old.

Some people have developed skin cancer or lymphoma after using tacrolimus or pimecrolimus (Elidel). However, it is not known if either of these medicines causes skin cancer or lymphoma. Talk to your doctor about your individual risk.

You should not use tacrolimus topical if you are allergic to it.

To make sure you can safely use tacrolimus topical, tell your doctor if you have any of these other conditions:

• skin cancer or a skin infection (including herpes or chickenpox);

• any genetic skin disorder (such as Netherton's syndrome);

• a weak immune system (caused by disease or by using certain medicines);

• kidney disease; or

• swelling, redness, or irritation of large areas of your skin.

Tacrolimus can lower the blood cells that help your body fight infections. This can make it easier for you to get sick from a virus such as chicken pox or herpes (cold sores or shingles). Tell your doctor if you have been exposed to any illness.

Some people have developed skin cancer or lymphoma after using tacrolimus or pimecrolimus (Elidel). However, it is not known if either of these medicines causes skin cancer or lymphoma. Talk to your doctor about your individual risk.

FDA pregnancy category C. It is not known whether tacrolimus topical will harm an unborn baby. Tell your doctor if you are pregnant or plan to become pregnant while using this medication.

Tacrolimus topical can pass into breast milk and may harm a nursing baby. Do not use this medication without telling your doctor if you are breast-feeding a baby.

Do not use tacrolimus topical on a child younger than 2 years old.

Use exactly as prescribed by your doctor. Do not use in larger or smaller amounts or for longer than recommended. Follow the directions on your prescription label.

If you are using this medicine on a child younger than 16 years old, use only the 0.03% ointment. The 0.1% ointment is for adults and children who are at least 16 years old, but is too strong to use on younger children.

Wash your hands before and after using tacrolimus, unless you are using the medication to treat a hand condition.

Apply the medicine in a thin layer, only to skin areas affected by eczema. Do not cover the treated skin with a bandage.

Do not bathe, shower, or swim right after applying tacrolimus topical. Water may wash off the medicine.

You may need to use a moisturizing cream or lotion to keep your skin from getting too dry. Ask your doctor about which moisturizer to use.

Tacrolimus is not for long-term use. Stop using the medicine once your symptoms have cleared up, unless your doctor has told you otherwise.

Call your doctor if your symptoms do not improve after 6 weeks of treatment, or if they get worse while using tacrolimus.

Store at room temperature. Do not freeze. Keep ointment tube tightly closed when not in use.

Apply the missed dose as soon as you remember. Skip the missed dose if it is almost time for your next scheduled dose. Do not use extra medicine to make up the missed dose.

Avoid using other medications on the areas you treat with tacrolimus topical unless your doctor tells you to.

Avoid exposure to sunlight or tanning beds, and phototherapy treatments with UVA or UVB light. If you must be outdoors, wear loose clothing over the skin areas treated with tacrolimus topical. Do not use sunscreen on treated skin unless your doctor has told you to.

Drinking alcohol while you are using tacrolimus topical may cause your skin or face to feel hot and become flushed or red.

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.

Figure 1 - Adult Patients Body Surface Area Over Time

Figure 2 - Pediatric Patients Body Surface Area Over Time

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

Figure 3 - Adult Patients Mean Erythema Over Time

Figure 4 - Pediatric Patients Mean Erythema Over Time

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

Protopic (tacrolimus)is a topical macrolide immunosuppressant. It works by decreasing cell activity in the body's immune system which helps to slow down the growth of atopic dermatitis (eczema) on your skin.

Protopic is used to treat severe atopic dermatitis (eczema).

Protopic may also be used for purposes not listed in this medication guide.

Get emergency medical help if you have any of these signs of an allergic reaction to Protopic: hives; difficult breathing; swelling of your face, lips, tongue, or throat. Stop using Protopic and call your doctor at once if you have a serious side effect such as:

• severe stinging, burning, itching, or soreness where the medicine is applied;

• swollen glands;

• redness or crusting around your hair follicles; or

• signs of a skin infection (redness, swelling, itching, oozing).

Less serious Protopic side effects may include:

• mild burning, stinging, or itching;

• skin redness;

• acne;

• cold or flu symptoms such as stuffy nose, sneezing, sore throat;

• headache; or

• feeling more sensitive to hot or cold temperatures.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.