Exposure of the skin to sunlight should be minimized and the use of ultraviolet (UV) light from a solarium, therapy with UVB or UVA in combination with psoralens (PUVA) should be avoided during use of Protopic (see Toxicology under Actions). Physicians should advise patients on appropriate sun protection methods eg, minimization of the time in the sun, use of a sunscreen product and covering of the skin with appropriate clothing.
Emollients should not be applied to the same area within 2 hrs of applying Protopic. Concomitant use of other topical preparations has not been assessed. There is no experience with concomitant use of systemic steroids or immunosuppressive agents.
Protopic has not been evaluated for its efficacy and safety in the treatment of clinically infected atopic dermatitis. Before commencing treatment with Protopic ointment, clinical infections at treatment sites should be cleared. Patients with atopic dermatitis are predisposed to superficial skin infections. Treatment with Protopic may be associated with an increased risk of herpes simplex virus infection [including herpes, cold sores and eczema herpeticum (Kaposi's varicelliform eruption)]. In the presence of these infections, the balance of risks and benefits associated with Protopic use should be evaluated.
Beyond 2 years of treatment, the potential for local immunosuppression (possibly resulting in infections or cutaneous malignancies) is unknown.
Lymphadenopathy was uncommonly (0.8%) reported in clinical trials. The majority of these cases related to infections (skin, respiratory tract, tooth) and resolved with appropriate antibiotic therapy. Transplant patients receiving immunosuppressive regimens (eg, systemic tacrolimus) are at an increased risk for developing lymphoma; therefore patients who receive Protopic and who develop lymphadenopathy should be monitored to ensure that the lymphadenopathy resolves. In case of persistent lymphadenopathy, the etiology of the lymphadenopathy should be investigated. In the absence of a clear etiology for the lymphadenopathy or in the presence of acute infectious mononucleosis, discontinuation of Protopic should be considered.
Care should be taken to avoid contact with eyes and mucous membranes. If accidentally applied to these areas, the ointment should be thoroughly wiped off and/or rinsed off with water.
The use of Protopic under occlusion has not been studied in patients. Occlusive dressings are not recommended.
As with any topical medicinal product, patients should wash their hands after application if the hands are not intended for treatment.
Tacrolimus is extensively metabolized in the liver and although blood concentrations are low following topical therapy, the ointment should be used with caution in patients with hepatic failure (see Pharmacokinetics under Actions).
The use of Protopic in patients with genetic epidermal barrier defects eg, Netherton's syndrome is not recommended due to the potential for permanently increased systemic absorption of tacrolimus. The safety of Protopic has not been established in patients with generalized erythroderma.
Effects on the Ability to Drive or Operate Machinery: No studies on the effects to drive or use machines have been performed. Protopic is administered topically and is unlikely to have an effect on the ability to drive or use machines.
Use in pregnancy & lactation: There are no adequate and well-controlled studies of topically administered tacrolimus in pregnant women. The experience with Protopic when used by pregnant women is too limited to permit assessment of the safety of its use during pregnancy. Protopic should be used during pregnancy only if the potential benefit to the mother justifies the potential risk to the fetus.
Although systemic absorption of tacrolimus following topical applications of Protopic is minimal relative to systemic administration, it is known that tacrolimus is excreted in human milk. Because of the potential for serious adverse reactions in nursing infants from tacrolimus, a decision should be made to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.
Use in children: The effect of treatment with Protopic on the developing immune system of children, especially the young, has not yet been established and this should be taken to account when prescribing to this age group (see Indications).
Controlled studies of Protopic in children were conducted involving patients 2-15 years. Documented use in patients <2 years old is limited.