Special Warning : אזהרת שימוש

4.4   Special warnings and precautions for use

Exposure of the skin to sunlight should be minimised 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 ointment (see section 5.3). Physicians should advise patients on appropriate sun protection methods, such as minimisation of the time in the sun, use of a sunscreen product and covering of the skin with appropriate clothing. Protopic ointment should not be applied to lesions that are considered to be potentially malignant or pre-malignant. The development of any new change different from previous eczema within a treated area should be reviewed by the physician.

The use of tacrolimus ointment is not recommended in patients with a skin barrier defect, such as Netherton’s syndrome, lamellar ichthyosis, generalized erythroderma, pyoderma gangrenosum or cutaneous Graft Versus Host Disease. These skin conditions may increase systemic absorption of tacrolimus. Post-marketing cases of increased tacrolimus blood level have been reported in these conditions. Protopic should not be used in patients with congenital or acquired immunodeficiencies or in patients on therapy that cause immunosuppression.

Care should be exercised if applying Protopic to patients with extensive skin involvement over an extended period of time, especially in children (see section 4.2). Patients, particularly paediatric patients should be continuously evaluated during treatment with Protopic with respect to the response to treatment and the continuing need for treatment. After 12 months this evaluation should include suspension of Protopic treatment in paediatric patients (see section 4.2). The effect of treatment with Protopic ointment on the developing immune system of children aged below 2 years has not been established (see section 4.1).

Protopic contains the active substance tacrolimus, a calcineurin inhibitor. In transplant patients, prolonged systemic exposure to intense immunosuppression following systemic administration of calcineurin inhibitors has been associated with an increased risk of developing lymphomas and skin malignancies. Patients with atopic dermatitis treated with Protopic have not been found to have significant systemic tacrolimus levels and the role of local immunosuppression is unknown.
Based on the results of long-term studies and experience, a link between Protopic ointment treatment and development of malignancies has not been confirmed, but definitive conclusions cannot be drawn.
It is recommended to use tacrolimus ointment at the lowest strength and the lowest frequency for the shortest duration necessary as determined by the physician’s evaluation of the clinical condition (see section 4.2).

Lymphadenopathy was uncommonly (0.8%) reported in clinical trials. The majority of these cases were related to infections (skin, respiratory tract, tooth) and resolved with appropriate antibiotic therapy. Lymphadenopathy present at initiation of therapy should be investigated and kept under review. In case of persistent lymphadenopathy, the aetiology of the lymphadenopathy should be investigated. In the absence of a clear aetiology for the lymphadenopathy or in the presence of acute infectious mononucleosis, discontinuation of Protopic should be considered. Patients who develop lymphadenopathy during treatment should be monitored to ensure that the lymphadenopathy resolves.
Patients with atopic dermatitis are predisposed to superficial skin infections. Protopic ointment 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. Treatment with Protopic is associated with an increased risk of folliculitis and herpes viral infections (herpes simplex dermatitis [eczema herpeticum], herpes simplex [cold sores], Kaposi’s varicelliform eruption) (see section 4.8).
In the presence of these infections, the balance of risks and benefits associated with Protopic use should be evaluated.

Emollients should not be applied to the same area within 2 hours of applying Protopic ointment. Concomitant use of other topical preparations has not been assessed. There is no experience with concomitant use of systemic steroids or immunosuppressive agents.

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 ointment 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 metabolised 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 section 5.2).

Excipients warnings
Protopic ointment contains butylhydroxytoluene (E321) as an excipient, which may cause local skin reactions (e.g. contact dermatitis), or irritation to the eyes and mucous membranes.

Effects on Driving

4.7    Effects on ability to drive and use machines
Protopic ointment has no or negligible influence on the ability to drive and use machines.