Before commencing treatment with Tacrolimus Ointment, cutaneous bacterial or viral infections at treatment sites should be resolved. Studies have not evaluated the safety and efficacy of Tacrolimus 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 Tacrolimus 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 Tacrolimus 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, Tacrolimus 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 Tacrolimus Ointment is not on the skin. It is not known whether Tacrolimus Ointment interferes with skin response to ultraviolet damage.
The safety and efficacy of Tacrolimus Ointment in immunocompromised patients have not been studied.
Rare post-marketing cases of acute renal failure have been reported in patients treated with Tacrolimus Ointment. Systemic absorption is more likely to occur in patients with epidermal barrier defects especially when Tacrolimus Ointment is applied to large body surface areas. Caution should also be exercised in patients predisposed to renal impairment.
(See Medication Guide)
Patients using Tacrolimus 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 Tacrolimus Ointment?
The safety of using Tacrolimus Ointment for a long period of time is not known. A very small number of people who have used Tacrolimus Ointment have had cancer (for example, skin or lymphoma). However, a link with Tacrolimus Ointment has not been shown. Because of this concern, instruct patients:
- Do not use Tacrolimus Ointment continuously for a long time.
- Use Tacrolimus Ointment only on areas of skin that have eczema.
- Do not use Tacrolimus Ointment on a child under 2 years old.
Tacrolimus Ointment comes in two strengths:
- Only Tacrolimus Ointment 0.03% is for use on children aged 2 to 15 years.
- Either Tacrolimus 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 Tacrolimus Ointment be used?
Advise patients to:
- Use Tacrolimus Ointment exactly as prescribed.
- Use Tacrolimus Ointment only on areas of skin that have eczema.
- Use Tacrolimus Ointment for short periods, and if needed, treatment may be repeated with breaks in between.
- Stop Tacrolimus 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 Tacrolimus Ointment.
- Call their doctor if:
- Their symptoms get worse with Tacrolimus 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 Tacrolimus Ointment:
- Wash their hands before applying Tacrolimus Ointment.
- Apply a thin layer of Tacrolimus Ointment twice daily to the areas of skin affected by eczema.
- Use the smallest amount of Tacrolimus Ointment needed to control the signs and symptoms of eczema.
- If they are a caregiver applying Tacrolimus 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 Tacrolimus Ointment. This should remove any ointment left on the hands.
- Do not bathe, shower, or swim right after applying Tacrolimus Ointment. This could wash off the ointment.
- Moisturizers can be used with Tacrolimus 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 Tacrolimus Ointment.
What should patients avoid while using Tacrolimus Ointment?
- Do not use ultraviolet light therapy, sun lamps, or tanning beds during treatment with Tacrolimus Ointment.
- Limit sun exposure during treatment with Tacrolimus Ointment even when the medicine is not on their skin. If patients need to be outdoors after applying Tacrolimus 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 Tacrolimus Ointment in the eyes or mouth. Do not swallow Tacrolimus Ointment. Patients should call their doctor if they swallow Tacrolimus Ointment.
Formal topical drug interaction studies with Tacrolimus Ointment have not been conducted. Based on its extent of absorption, interactions of Tacrolimus 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.
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