Tacroz/Tacroz Forte

Tacroz: Each g contains: Tacrolimus 300 mcg, Ointment base q.s.
Tacroz Forte: Each gram of ointment contains: Tacrolimus USP 1 mg (0.1% w/w).

Pharmacology: Pharmacodynamics: The exact mechanism of action of tacrolimus in atopic dermatitis is not known. It has been demonstrated that tacrolimus inhibits T-lymphocyte activation by first binding to an intracellular protein, FKBP-12. A complex of tacrolimus-FKBP-12, calcium, calmodulin, and calcineurin is then formed and the phosphatase activity of calcineurin is inhibited. This effect has been shown to prevent the dephosphorylation and translocation of nuclear factor of activated T-cells (NF-AT), a nuclear component thought to initiate gene transcription for the formation of lymphokines (such as interleukin-2, gamma interferon). Tacrolimus also inhibits the transcription for genes which encode IL-3, IL-4, IL-5, GM-CSF, and TNF-(alpha), all of which are involved in the early stages of T-cell activation. Additionally, tacrolimus has been shown to inhibit the release of pre-formed mediators from skin mast cells and basophils, and to down regulate the expression of Fc[erg]RI on Langerhans cells.
Pharmacokinetics: Systemic absorption with topical Tacrolimus is minimal. After single or multiple doses of 0.1% Tacrolimus Ointment, peak tacrolimus blood concentrations ranged from undetectable to 20 ng/mL. The results from a pharmacokinetic study of 0.1% Tacrolimus Ointment in 20 pediatric atopic dermatitis patients (ages 6-13 years), show peak tacrolimus blood concentrations below 1.6 ng/mL in all patients.
The absolute bioavailability of topical tacrolimus is unknown. Using intravenous historical data for comparison, the bioavailability of tacrolimus from Tacrolimus Ointment in atopic dermatitis patients is less than 0.5%. In adults with an average of 53% BSA treated, exposure (i.e., AUC) of tacrolimus is approximately 30-fold less than that seen with oral immunosuppressive doses in kidney and liver transplant patients. The lowest tacrolimus blood level at which systemic effects can be observed is not known. There was no evidence based on blood concentrations that tacrolimus accumulates systemically upon intermittent topical application for periods of up to 1 year.

Tacrolimus Ointment is used for moderate to severe atopic eczema unresponsive to conventional therapy.

For treatment of atopic eczema, where conventional therapies are ineffective of unsuitable, Tacrolimus ointment may be applied 2x daily.
Method of application: Apply a thin layer of Tacrolimus Ointment to the affected skin areas twice daily and rub in gently and completely. Treatment should be continued for one week after clearing of signs and symptoms of atopic dermatitis.
The safety of Tacrolimus Ointment under occlusion which may promote systemic exposure, has not been evaluated. Tacrolimus Ointment 300 mcg (0.03%) and 1 mg (0.1%) should not be used with occlusive dressings.

Tacrolimus Ointment is not for oral use. Oral ingestion of Tacrolimus Ointment may lead to adverse effects associated with systemic administration of tacrolimus. If oral ingestion occurs, medical advice should be sought.

Tacrolimus is contraindicated in patients with a history of hypersensitivity to tacrolimus or any other components of the preparation.

Tacroz/Tacroz Forte Ointment is for external application only.
Tacroz/Tacroz Forte Ointment is not for ophthalmic, oral or intravaginal use.
Tacroz Forte: Tacroz Forte Ointment not for children.

Tacroz: Skin infections should be treated before starting therapy with topical Tacrolimus. It should not be used in immunocompromised patients or those with conditions that might increase systemic absorption of Tacrolimus. It must also not be applied to pre malignant skin conditions; some malignant skin conditions may mimic eczema.
Not use in children under 2 years of age.
Not use continuously for more than 6 weeks, with an application free period of up to 2 weeks.
Use in Children: Three, long term, phase two studies showed Tacrolimus (Tacroz) ointment 0.03% may be used in pediatric patients 2 years of age and older.
Use in Elderly: The adverse event profile in elderly subjects was same as that in other adult patients. No dosage adjustments are recommended for topical Tacrolimus (Tacroz) in elderly.
Tacroz Forte: Studies have not evaluated the safety and efficacy of Tacrolimus (Tacroz Forte) Ointment in the treatment of clinically infected atopic dermatitis. Before commencing treatment with Tacrolimus (Tacroz Forte) Ointment, clinical infections at treatment sites should be cleared.
While patients with atopic dermatitis are predisposed to superficial skin infections including eczema herpeticum (Kaposi's varicelliform eruption), treatment with Tacrolimus (Tacroz Forte) Ointment may be associated with an increased risk of varicella zoster virus infection (chicken pox or shingles), herpes simplex virus infection, or eczema herpeticum. In the presence of these infections, the balance of risks and benefits associated with Tacrollmus (Tacroz Forte) Ointment use should be evaluated.
Transplant patients receiving immunosuppressive regimens (e.g., systemic tacrolimus) are at increased risk for developing lymphoma; therefore, patients who receive Tacrolimus (Tacroz Forte) Ojntment 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, discontinuation of Tacrolimus (Tacroz Forte) Ointment should be considered. Patients who develop lymphadenopathy should be monitored to ensure that the lymphadenopathy resolves.
Patients should minimize or avoid exposure to natural or artificial sunlight (tanning beds or UVA/B treatment) while using Tacrolimus (Tacroz Forte) Ointment.
Localized symptoms (burning sensation, stinging, soreness) or pruritus are most common during the first few days of Tacrolimus (Tacroz Forte) Ointment application and typically improve as the lesions of atopic dermatitis heal.
The use of Tacrolimus (Tacroz Forte) Ointment in patients with Netherton's Syndrome is not recommended due to the potential for increased systemic absorption of tacrolimus. The safety of Tacrolimus (Tacroz Forte) Ointment has not been established in patients with generalized erythroderma.

Tacroz: Use in Pregnancy: Pregnancy Category C: There are no adequate and well-controlled studies of topically administered Tacrolimus in pregnant women. Tacrolimus is transferred across the placenta. Tacrolimus (Tacroz) ointment should be used during pregnancy only if the potential benefit to the mother justifies a potential risk to the fetus.
Use in Lactation: Tacrolimus is excreted in human milk. Because of the potential for serious adverse reactions in nursing infants, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.

Tacroz: Topical Tacrolimus has been associated with local irritation and skin disorders including an increased incidence of herpes simplex and zoster infections; headache and "flu like" symptoms.
Facial flushing and skin irritations have been reported after consumption of alcohol. Exposure of the skin to sunlight should be minimized and the use of artificial source of ultraviolet light avoided.
Tacroz Forte: Skin: Skin burning, pruritus, skin erythema, Skin tingling, folliculitis, acne, herpes simplex, (herpes, cold sores, eczema herpeticum, Kaposi's varicelliform eruption).
Nervous System: Hyperaesthesia (increased skin sensitivity, especially to hot and cold).
Body as a whole: Alcohol intolerance (facial flushing or skin irritation after consumption of an alcoholic beverage).

Tacroz: Facial flushing or skin irritaion may occur if alcohol is consumed by patients using topical Tacrolimus.
Tacroz Forte: Formal topical drug interaction studies with Tacrolimus (Tacroz Forte) Ointment have not been conducted. Based on its minimal extent of absorption, interactions of Tacrolimus (Tacroz Forte) Ointment with systemically administered drugs are unlikely to occur but cannot be ruled out. 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.

Do not freeze.
Tacroz: Store below 25°C.
Tacroz Forte: Store at temperatures not exceeding 30°C.

Information for Patients: Patients should use Tacrolimus Ointment as directed by the physician. Tacrolimus Ointment is for external use only. As with any topical medication, patients or caregivers should wash hands after application if hands are not an area for treatment.
Patients should minimize or avoid exposure to natural or artificial sunlight (tanning beds or UVA/B treatment) while using Tacrolimus Ointment.
Patients should not use this medication for any disorder other than that for which it was prescribed.
Patients should report any signs of adverse reactions to their physician.
Before applying Tacrolimus (Tacroz Forte) Ointment after a bath or shower, be sure your skin is completely dry.

Other Dermatologicals

D11AH01 - tacrolimus ; Belongs to the class of agents for atopic dermatitis, excluding corticosteroids. Used in the treatment of atopic dermatitis.

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