Tacrolimus ointment

The mechanism of action of tacrolimus in the treatment of atopic dermatitis is still unclear. Although the mechanism of action of tacrolimus is somewhat understood, the clinical relevance of these findings to atopic dermatitis is unclear. Tacrolimus has been shown to inhibit T lymphocyte activation by first binding to the intracellular protein FKBP-12 to form a complex composed of tacrolimus-FKBP-12, calcium, calmodulin, and calcineurin, thereby inhibiting the phosphatase activity of calcineurin and preventing the dephosphorylation and translocation of nuclear factor of activated T cells (NF-AT), a nuclear component that initiates gene transcription to form lymphokines (e.g., IL-2, interferon-γ). Tacrolimus also inhibits the transcription of genes encoding IL-3, IL-4, IL-5, GM-CSF, and TNF-?, all of which are involved in the early stages of T cell activation. In addition, tacrolimus can inhibit the release of synthesized mediators in skin mast cells and basophils and downregulate the expression of FCεRI on the surface of Langerhans cells.

The main ingredient of this product is tacrolimus. Each gram of this product contains 0.03% or 0.1% (w/w) tacrolimus. The ointment base is mineral oil, paraffin, propylene carbonate, white vaseline and white wax.

This product is a white to light yellow ointment.

This product is suitable for patients with moderate to severe atopic dermatitis who are not suitable for traditional treatments due to potential risks, or who have responded inadequately to traditional treatments, or who cannot tolerate traditional treatments, as a short-term or intermittent long-term treatment. Both 0.03% and 0.1% concentrations of this product can be used in adults, but only 0.03% concentration of this product can be used in children aged 2 years and above.

Adults: 0.03% and 0.1% Tacrolimus Ointment: Apply a thin layer of this product to the affected skin, rub it in gently, and cover it completely, twice a day, until one week after the symptoms and signs of atopic dermatitis disappear. Occlusive therapy may promote systemic absorption, and its safety has not been evaluated. This product should not be used externally with occlusive dressings. Children: 0.03% Tacrolimus Ointment: Apply a thin layer of this product to the affected skin, rub it in gently, and cover it completely, twice a day, until one week after the symptoms and signs of atopic dermatitis disappear. Occlusive therapy may promote systemic absorption, and its safety has not been evaluated. This product should not be used externally with occlusive dressings.

In clinical studies with 12 and 216 healthy volunteers, respectively, the drug was not found to be phototoxic and photosensitizing. In a contact sensitization study conducted on 198 healthy volunteers, one case showed signs of contact sensitization. In three randomized vehicle-controlled studies and two long-term safety studies, 655 and 571 patients were treated with this product, respectively. The following table lists the adjusted adverse event rates in the vehicle group, 0.03% and 0.1% concentration of this product in three identically designed 12-week studies, as well as the unadjusted adverse event rates in two one-year safety studies, regardless of whether these adverse events are related to the study drug. A total of 4 cases of varicella occurred in the 12-week study in children; 1 case of herpes zoster on the labialis occurred in the 12-week study in adults; 7 cases of varicella and 1 case of herpes zoster occurred in the open-label study in children; 2 cases of herpes zoster occurred in the open-label study in adults. Other adverse events with an incidence of greater than or equal to 1% in various clinical trials included alopecia, ALT or AST increased, anaphylactic reaction, angina pectoris, angioedema, anorexia, anxiety, arrhythmia, arthralgia, arthritis, bilirubinemia, breast pain, cellulitis, cerebrovascular accident, cheilitis, chills, constipation, creatinine increased, dehydration, depression, dizziness, dyspnea, ear pain, skin ecchymosis, edema, epistaxis, exacerbation of untreated areas, eye discomfort, eye pain, furunculosis, gastritis, hernia, hyperglycemia, hypertension, hypoglycemia, hypoxia, laryngitis, leukocytosis, leukopenia, abnormal liver function tests, pulmonary disorder, malaise, migraine, neck pain, neuritis, palpitations, paresthesia, peripheral vascular abnormality, photosensitivity reaction, complications of treatment procedures, skin depigmentation, sweating, taste disturbances, dental disorders, unintended pregnancy, vaginal candidiasis, vasodilation, and vertigo.

This product is contraindicated in patients with a history of hypersensitivity to tacrolimus or any other component of the formulation.

Precautions for children: 0.03% concentration of this product can be used for children aged 2 years and above. Two Phase III pediatric clinical studies have been conducted with a total of 606 patients aged 2-15 years: one is a 12-week randomized vehicle-controlled study, and the other is a one-year open long-term safety study, in which 330 patients are aged between 2 and 6 years. The most common adverse reactions of children using this product are burning sensation and itching of the skin (see adverse reactions). In addition, compared with the vehicle, patients treated with 0.03% concentration of this product have a higher frequency of less common adverse events (less than 5%) such as herpes zoster (mainly chickenpox) and vesicular herpes. In the one-year long-term safety study, a total of 255 children were treated with this product, and the incidence of adverse events (including infection) did not increase with the extension of medication time or the increase of medication dosage. Among the 491 children treated with this product, 3 cases (accounting for 0.6%) developed herpetic eczema. Since the safety and efficacy of this product in children under 2 years old have not been established, it is not recommended for use in this age group. Pregnancy and lactation precautions: Teratogenic effect: Pregnancy medication classification C There are currently no adequate and appropriately controlled studies on the topical application of this product in pregnant women. The experience of using this product in pregnant women is also very limited and is not sufficient to evaluate its safety during pregnancy. Reproductive toxicity studies of systemic tacrolimus have been conducted on rats and rabbits, and adverse reactions occurred in the fetus when the mother was given an oral toxic dose of the drug. Oral doses of 0.32 and 1.0 mg/kg of tacrolimus (equivalent to 0.04 and 0.12 times the maximum recommended dose for humans, respectively, were given to rabbits during the stage of embryonic organ formation, which produced toxic reactions in the mother rabbits and increased the abortion rate. Only in the higher dose group was an increase in the proportion of fetal malformations and developmental abnormalities seen. Oral administration of tacrolimus to rats during the period of embryonic organogenesis at a dose of 3.2 mg/kg produced toxic reactions in the mothers and resulted in increased late resorption, decreased number of live fetuses, and decreased pup weight and developmental capacity. Oral administration of tacrolimus to pregnant rats at doses of 1.0 and 3.2 mg/kg (0.04 and 0.12 times the maximum recommended human dose, based on body surface area) after the period of embryonic organogenesis and during lactation resulted in decreased pup weight. No reduction in reproductive capacity was observed in male or female animals. No adequately controlled studies have been conducted on the systemic administration of tacrolimus to pregnant women. Tacrolimus crosses the placenta, and systemic administration of tacrolimus during pregnancy has resulted in neonatal hyperkalemia and renal dysfunction. This drug should be used during pregnancy only if the benefit of treatment to the mother outweighs the potential risk to the fetus. Although systemic absorption of tacrolimus after topical application is minimal compared to systemic administration, tacrolimus is known to be excreted into breast milk. Because of the potential for serious adverse reactions in breastfeeding infants, the decision to stop breastfeeding or medication should be made based on the importance of the drug treatment to the mother. Elderly precautions: In Phase III clinical trials, 25 patients aged 65 and over were treated with this product. The adverse events in these patients were consistent with those in other adult patients.

The drug interaction of this product for topical application has not been studied. Due to the extremely small amount of absorption, this product is unlikely to interact with systemically administered drugs, but it cannot be completely ruled out. Patients with more extensive dermatitis and/or erythroderma should be cautious when taking known CYP3A4 inhibitors. Examples of these drugs include erythromycin, itraconazole, ketoconazole, fluconazole, calcium channel blockers and cimetidine.

Store at room temperature 25℃; the permissible temperature range is 15-30℃.

30 months