Protopic Prescribing Information

Prescribing Information for UK:

Abbreviated Prescribing Information for Protopic® (tacrolimus) 0.1% ointment and 0.03% ointment

Please refer to the full Summary of Product Characteristics (SmPC) (www.medicines.org.uk/emc) before prescribing.

Indications: Protopic® 0.1% ointment and 0.03% ointment are indicated in adults and adolescents (16 years of age and above). Protopic® 0.03% ointment is also indicated in children from the age of 2 years. Flare treatment: Adults and adolescents (16 years of age and above): Treatment of moderate to severe atopic dermatitis (AD) in adults who are not adequately responsive to, or are intolerant of, conventional therapies such as topical corticosteroids. Protopic® 0.03% ointment only: Children (2 years of age and above): Treatment of moderate to severe AD in children who failed to respond adequately to conventional therapies such as topical corticosteroids. Maintenance treatment: Treatment of moderate to severe AD for the prevention of flares and the prolongation of flare-free intervals in patients experiencing a high frequency of disease exacerbations (i.e. occurring 4 or more times per year) who have had an initial response to a maximum of 6 weeks’ treatment of twice daily tacrolimus ointment (lesions cleared, almost cleared or mildly affected).

Active ingredients: 1 g of Protopic® 0.1% ointment contains 1.0 mg of tacrolimus as tacrolimus monohydrate (0.1%). 1 g of Protopic® 0.03% ointment contains 0.3 mg of tacrolimus as tacrolimus monohydrate (0.03%).

Dosage and administration: Protopic® treatment should be initiated by physicians with experience in the diagnosis and treatment of AD. Posology: Flare treatment: Protopic® can be used for short-term and intermittent long-term treatment. Treatment should not be continuous on a long-term basis. Begin treatment at the first appearance of signs/symptoms. Treat each affected region of the skin with Protopic® until lesions are cleared, almost cleared or mildly affected. Thereafter, patients are considered suitable for maintenance treatment (see below). At the first signs of recurrence (flares) of the disease symptoms, re-initiate treatment. Adults and adolescents (16 years of age and above): Apply Protopic® 0.1% twice a day and continue until clearance of the lesion. If symptoms recur, restart twice daily treatment with Protopic® 0.1%. An attempt should be made to reduce the frequency of application or to use the lower strength Protopic® 0.03% ointment if the clinical condition allows. Generally, improvement is seen within 1 week of starting treatment. If no signs of improvement seen after 2 weeks of treatment, consider further treatment options. Elderly: Available clinical experience has not shown the necessity for dosage adjustment. Paediatric population (2-16 years): Protopic® 0.03% ointment only should be used. Start treatment twice a day for up to 3 weeks. Afterwards, reduce frequency of application to once a day until lesion clearance. Protopic® ointment should not be used in children aged below 2 years. Maintenance treatment: Suitable for patients who are responding to up to 6 weeks’ treatment using tacrolimus ointment twice daily (lesions cleared, almost cleared or mildly affected). Adults and adolescents (16 years of age and above): Apply Protopic® 0.1% ointment once a day twice weekly (e.g. Monday and Thursday) to areas commonly affected by AD to prevent progression to flares. Between applications there should be 2–3 days without Protopic treatment. After 12 months’ treatment, a review of the patient’s condition should be conducted by the physician and a decision taken whether to continue maintenance treatment in the absence of safety data for maintenance treatment beyond 12 months. If signs of a flare reoccur, re-initiate twice daily treatment (see flare treatment section above). Elderly: Specific studies have not been conducted in older people (see flare treatment section above). Paediatric population: Protopic® 0.03% ointment only (2-16 years): Apply once a day twice weekly (e.g. Monday and Thursday) to areas commonly affected by AD to prevent progression to flares. Between applications there should be 2–3 days without Protopic treatment. Review of the child’s condition after 12 months’ treatment should include suspension of treatment to assess the need to continue this regimen and to evaluate the course of the disease. Protopic® ointment should not be used in children aged below 2 years until further data are available. Method of administration: Apply as a thin layer to affected or commonly affected areas of the skin. Protopic® ointment may be used on any part of the body, including face, neck and flexure areas, except on mucous membranes. Do not apply under occlusion because this method of administration has not been studied in patients. Overdose: Overdosage following topical administration is unlikely. If ingested, general supportive measures may be appropriate. These may include monitoring of vital signs and observation of clinical status. Due to the nature of the ointment vehicle, induction of vomiting or gastric lavage is not recommended.

Contraindications: Hypersensitivity to the active substance, macrolides in general, or to any of the excipients.

Precautions and warnings: Minimise exposure of the skin to sunlight and avoid the use of ultraviolet (UV) light from a solarium, therapy with UVB or UVA in combination with psoralens (PUVA). Advise patients on appropriate sun protection methods, such as minimisation of time in the sun, use of a sunscreen product and covering of the skin with appropriate clothing. Do not apply 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. The ointment is not recommended in patients with a skin barrier defect (e.g. Netherton’s syndrome), lamellar ichthyosis, generalised erythroderma or cutaneous Graft Versus Host Disease. These skin conditions may increase systemic absorption of tacrolimus. Exercise care if applying Protopic® to patients with extensive skin involvement over an extended period of time, especially in children.

Continually evaluate patients, particularly paediatric patients, during treatment, 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. The potential for local immunosuppression (possibly resulting in infections or cutaneous malignancies) in the long-term (i.e. over a period of years) is unknown. 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. In patients using tacrolimus ointment, cases of malignancies, including cutaneous (i.e. cutaneous T Cell lymphomas) and other types of lymphoma, and skin cancers have been reported. Do not use in patients with congenital or acquired immunodeficiencies or in patients on therapy that cause immunosuppression. Patients with AD treated with Protopic have not been found to have significant systemic tacrolimus levels. Lymphadenopathy was uncommonly (0.8%) reported in clinical trials. The majority of these cases were related to infections (skin, respiratory tract, tooth), resolving with appropriate antibiotic therapy. Transplant patients receiving immunosuppressive regimens (e.g. systemic tacrolimus) are at increased risk for developing lymphoma; therefore monitor patients who receive Protopic® and who develop lymphadenopathy to ensure that the lymphadenopathy resolves. Investigate lymphadenopathy present at initiation of therapy and keep 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, consider discontinuation of Protopic® . The effect of treatment with Protopic on the developing immune system of children aged below 2 years has not been established. Protopic® ointment has not been evaluated for its efficacy and safety in the treatment of clinically infected AD. Clinical infections at treatment sites should be cleared before commencing treatment. Patients with AD are predisposed to superficial skin infections. Treatment with Protopic may be associated with an increased risk of folliculitis and herpes viral infections (herpes simplex dermatitis [eczema herpeticum], herpes simplex [cold sores], Kaposi’s varicelliform eruption). 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. Take care to avoid contact with eyes and mucous membranes. If accidentally applied to these areas, thoroughly wipe off the ointment and/or rinse off with water. Use of Protopic® under occlusion has not been studied. Occlusive dressings not recommended. Patients should wash their hands after application if the hands are not intended for treatment. Use with caution in patients with hepatic failure. Protopic contains butylhydroxytoluene (E321) as an excipient, which may cause local skin reactions (e.g. contact dermatitis), or irritation to the eyes and mucous membranes.

Drug interactions: Formal topical drug interaction studies with tacrolimus ointment have not been studied. Tacrolimus is not metabolised in human skin, indicating that there is no potential for percutaneous interactions that could affect the metabolism of tacrolimus. Concomitant systemic administration of known CYP3A4 inhibitors (e.g. erythromycin, itraconazole, ketoconazole and diltiazem) in patients with widespread and/or erythrodermic disease should be done with caution. Paediatric population: An interaction study with protein-conjugated vaccine against Neisseria menigitidis serogroup C has been investigated in children aged 2-11 years. No effect on immediate response to vaccination, the generation of immune memory, or humoral and cell-mediated immunity has been observed.

Fertility, pregnancy and lactation: Pregnancy: Protopic® ointment should not be used during pregnancy unless clearly necessary. Breast-feeding: Breast-feeding during treatment with Protopic® ointment is not recommended. Fertility: No data available.

Side effects: Very common (≥1/10): Application site burning and pruritus, usually mild to moderate and resolving within one week. Common (≥1/100 to <1/10): Local skin infection regardless of specific aetiology (including but not limited to: eczema herpeticum, folliculitis, herpes simplex, herpes virus infection, Kaposi’s varicelliform eruption), alcohol intolerance (facial flushing or skin irritation after consumption of an alcoholic beverage), paraesthesias and dysaesthesias (hyperaesthesia, burning sensation), pruritus, application site: warmth, erythema, pain, irritation, paraesthesia, rash. Uncommon (≥1/1000 to <1/100): Acne. Frequency not known: Ophthalmic herpes infection, rosacea, lentigo, application site oedema, drug level increased.

See SmPC for a full list of side effects.
Legal category: POM.
Marketing authorisation number and holder:
Protopic® 0.03% ointment, 30 g: EU/1/02/201/001
Protopic® 0.03% ointment, 60 g: EU/1/02/201/002
Protopic® 0.1% ointment, 30 g: EU/1/02/201/003
Protopic® 0.1% ointment, 60 g: EU/1/02/201/004
LEO Pharma A/S, Ballerup, Denmark.
Basic NHS price:
Protopic 0.03% ointment: £23.33/30 g, £42.55/60 g
Protopic 0.1% ointment: £25.92/30 g, £47.28/60 g;
Last revised: July 2018

Further information can be found in the Summary of Product Characteristics or from:
LEO Pharma, Horizon, Honey Lane, Hurley, Berkshire SL6 6RJ, Reino Unido.
e-mail: medical-info.uk@leo-pharma.com

Reporting of Suspected Adverse Reactions

Adverse events should be reported. Reporting forms and information can be found at:
www.mhra.gov.uk/yellowcard
or search for MHRA Yellow Card in the Google Play or Apple App Store.