tacrolimus topical

Action and Spectrum

Actions and Spectrum: 

• tacrolimus ointment is a topical medication used to treat atopic dermatitis (eczema). The active ingredient in tacrolimus ointment is tacrolimus, which is a macrolide immunosuppressant that works by inhibiting T-cell activation and proliferation. T-cells are immune cells that play a vital role in developing atopic dermatitis and other inflammatory skin disorders 
• It binds to an intracellular protein called FK-binding protein-12 (FKBP-12), and the resulting complex inhibits the activity of calcineurin, a key enzyme involved in T-cell activation. By inhibiting T-cell activation, tacrolimus reduces the production and release of pro-inflammatory cytokines, chemokines, and other mediators contributing to developing atopic dermatitis. 
• tacrolimus ointment has a narrow spectrum of activity and is primarily used to treat atopic dermatitis. It is impractical for other skin disorders, such as psoriasis or acne.  
• Additionally, tacrolimus ointment should not be used to treat skin infections or wounds, as it can increase the risk of bacterial, viral, or fungal infections. tacrolimus ointment should also be used cautiously in patients with compromised immune systems or those taking immunosuppressive medications, as it can further increase the risk of infections. 

Drug Interaction

Adverse Reaction

Frequency defined 

>10% 

Pruritus (41-46%) 

Skin erythema (12-28%) 

Burning sensations (43-58%) 

Flu-like symptoms (23-31%) 

Headache (5-20%) 

Post-marketing reports 

Osteomyelitis 

Basal cell carcinoma 

Lymphomas 

Malignant melanoma 

Squamous cell carcinoma 

Application site edema 

Rosacea 

Renal impairment 

Acute renal failure in patients with or without Netherton’s syndrome 

Bullous impetigo 

Septicaemia 

Black Box Warning

Black box warning: 

• Few instances of cancer have been recorded (although causal relationship has not identified) 
• Limit application to atopic dermatitis areas and avoid long-term usage. 
• Use in children under the age of two is not advised. 
• Children between 2 and 15 should only use 0.03% of the ointment. 

Contraindication / Caution

Contraindications/caution: 

Contraindications: 

• Hypersensitivity: tacrolimus ointment should not be used in individuals who have a known hypersensitivity or allergy to tacrolimus or any of its components. 
• Viral infections: The use of tacrolimus ointment should be avoided in patients with active viral infections, such as herpes simplex, varicella-zoster, or vaccinia 
• Malignancies: tacrolimus ointment should not be used in patients with a history of malignancies, as it may increase the risk of developing skin cancer 
• Immunocompromised patients: tacrolimus ointment should be used with caution in immunocompromised patients, as they may be at an increased risk of developing infections 
• Pregnancy and breast-feeding: The safety of tacrolimus ointment has not been established in pregnant or breast-feeding women. Therefore, it should be used cautiously and only if the benefits outweigh the risks 
• Children: tacrolimus ointment should not be used in children younger than two years, as its safety and efficacy in this age group have not been established. 

Caution: 

• Infections: tacrolimus ointment may increase the risk of developing infections. Patients using tacrolimus ointment should be advised to avoid contact with people who have infections and to report any signs of infection, such as fever, redness, or swelling, to their healthcare provider. 
• Sun exposure: Patients using tacrolimus ointment should be advised to avoid prolonged exposure to sunlight, tanning booths, and sunlamps, as tacrolimus ointment may increase the risk of skin cancer 
• Immunosuppression: tacrolimus ointment suppresses the immune system, possibly increasing the risk of infections and malignancies. tacrolimus ointment patients should be closely monitored for signs of infections and malignancies 
• Topical corticosteroids: tacrolimus ointment should not be combined with topical corticosteroids, as it may increase the risk of side effects, such as skin thinning and easy bruising 
• Systemic absorption: tacrolimus ointment may be absorbed into the bloodstream, mainly if applied to a large area or broken skin. tacrolimus ointment patients should be monitored for systemic side effects, such as headache, nausea, and vomiting 
• Renal impairment: tacrolimus ointment is primarily eliminated by the kidneys. Patients with renal impairment may be at an increased risk of systemic side effects, and their tacrolimus levels should be monitored closely. 

Pregnancy / Lactation

Pregnancy consideration: C 

Lactation: Excretion of the drug in human breast milk is unknown 

Pregnancy category: 

Category A: well-controlled and Satisfactory studies show no risk to the fetus in the first or later trimester.   

Category B: there was no evidence of risk to the fetus in animal studies, and there were not enough studies on pregnant women. 

Category C: there was evidence of risk of adverse effects in animal reproduction studies, and no adequate evidence in human studies must take care of potential risks in pregnant women.    

Category D: adequate data with sufficient evidence of human fetal risk from various platforms, but despite the potential risk, and used only in emergency cases for potential benefits.    

Category X: Drugs listed in this category outweigh the risks over benefits. Hence these categories of drugs need to be avoided by pregnant women.    

Category N: There is no data available for the drug under this category 

Pharmacology

Pharmacology: 

• tacrolimus ointment is a medication used to treat eczema and other skin conditions. Its pharmacology is based on its ability to inhibit the activity of calcineurin, an enzyme involved in the activation of T-cells, a type of immune cell that plays a role in the inflammation seen in eczema and other skin disorders 
• By inhibiting calcineurin, tacrolimus ointment reduces the activation and proliferation of T-cells, which in turn reduces the production and release of inflammatory cytokines, thus reducing skin inflammation. 

Pharmacodynamics: 

• The pharmacodynamics of tacrolimus ointment is based on its mechanism of action, which is the inhibition of calcineurin, a protein phosphatase that activates T-cells, leading to the production and release of inflammatory cytokines, which contribute to the inflammation seen in eczema and other skin disorders 
• tacrolimus binds to the immunophilin protein FKBP-12, which then inhibits the activity of calcineurin, preventing the activation of T-cells and the subsequent release of inflammatory cytokines. This reduces inflammation in the skin and relieves the symptoms of eczema and other skin conditions 
• tacrolimus ointment has a selective mechanism of action, as it targets only activated T-cells, leaving other immune cells unaffected. This selectivity reduces the risk of systemic side effects, as the normal immune response to infections is not compromised 

Pharmacokinetics: 

Absorption 

tacrolimus ointment is applied topically to the skin, and absorption occurs through the skin. The extent of absorption is limited, and systemic exposure to the drug is minimal. Absorption can be increased if the drug is applied to areas with damaged skin, large areas of skin, or occluded skin (such as with a dressing or bandage) 

Distribution 

tacrolimus is distributed throughout the body via the bloodstream. However, due to its high molecular weight and hydrophobic nature, it is mainly confined to the skin and other tissues with high lipid content. The distribution is limited, and the drug does not readily cross the blood-brain barrier 

Metabolism 

The liver extensively metabolizes tacrolimus, primarily via the cytochrome P450 (CYP) 3A4 enzyme system. The major metabolite is 13-O-demethyl tacrolimus, which has negligible activity. Metabolism of tacrolimus can be affected by other drugs that inhibit or induce the CYP3A4 enzyme system 

Elimination and Excretion 

tacrolimus and its metabolites are primarily excreted in the feces, with a small amount excreted in the urine. The elimination half-life of tacrolimus is approximately 12 hours. The drug is primarily eliminated via biliary excretion, and renal impairment does not significantly affect its elimination 

Adminstartion

Administration: 

tacrolimus is available as an ointment applied topically to the affected skin. Here are some general guidelines for the administration of tacrolimus: 

• Wash and dry your hands before and after using the medication. 
• Clean the affected area with mild soap and water and pat it dry before applying the medication. 
• Apply a thin layer of the ointment to the affected area and gently rub it in until it disappears. 
• Do not cover the treated area with a bandage or wrap unless directed by your healthcare provider. 
• Please do not use more medicine or apply it more often than your healthcare provider prescribes. 
• Do not apply the medication to any area of the skin that is infected, open, or oozing. 
• Avoid contact with the eyes, nose, mouth, and other mucous membranes. If contact occurs, rinse thoroughly with water. 
• Do not use the medication on children under two without consulting a healthcare provider. 
• Store the medication at room temperature, away from heat and light 

Patient Information Leaflet

Patient information leaflet 

Generic Name: tacrolimus topical 

Pronounced: [ ta-KROE-li-mus ] 

Why do we use tacrolimus topical? 

tacrolimus topical is used to treat atopic dermatitis, also known as eczema, because it is an effective immunosuppressant that can help reduce the inflammation and itching associated with the condition.

Atopic dermatitis is a chronic inflammatory skin condition that is caused by an overactive immune response, resulting in a weakened skin barrier and increased permeability of the skin