High standard Pharmaceutical API USP Tacrolimus Monohydrate CAS 109581-93-3

Tacrolimus Monohydrate More Info

Tacrolimus is an immunosuppressive drug primarily used to prevent organ transplant rejection and treat moderate to severe atopic dermatitis. Discovered in 1987 from the soil bacterium Streptomyces tsukubaensis, it is classified as a macrolide lactone and is included on the World Health Organization's List of Essential Medicines. Tacrolimus is marketed under various brand names, including Prograf and Protopic

Mechanism of Action

Tacrolimus functions as a calcineurin inhibitor. It binds to the immunophilin FKBP12, forming a complex that inhibits calcineurin activity. This inhibition prevents the dephosphorylation of nuclear factor of activated T-cells (NF-AT), thereby blocking the transcription of interleukin-2 (IL-2) and other cytokines critical for T-cell activation and proliferation. This mechanism effectively suppresses the immune response, reducing the risk of organ rejection in transplant patients and controlling inflammation in skin conditions like eczema

Medical uses

1. Organ transplantation
It has similar immunosuppressive properties to ciclosporin, but is much more potent. Immunosuppression with tacrolimus was associated with a significantly lower rate of acute rejection compared with ciclosporin-based immunosuppression (30.7% vs 46.4%) in one study. Clinical outcome is better with tacrolimus than with ciclosporin during the first year of liver transplantation. Long-term outcome has not been improved to the same extent. Tacrolimus is normally prescribed as part of a post-transplant cocktail including steroids, mycophenolate, and IL-2 receptor inhibitors such as basiliximab. Dosages are titrated to target blood levels at specific times after medication administration.

2. Skin
As an ointment, tacrolimus is used in the treatment of dermatitis (eczema), in particular atopic dermatitis, if topical corticosteroids and moisturisers fail in helping.[17][18] It suppresses inflammation in a similar way to steroids, and is equally as effective as a mid-potency steroid. An important advantage of tacrolimus is that, unlike steroids, it does not cause skin thinning (atrophy), or other steroid related side effects.
It is applied on the active lesions until they heal off, but may also be used continuously in low doses (twice a week), and applied to the thinner skin over the face and eyelids. Clinical trials of up to one year have been conducted. Recently it has also been used to treat segmental vitiligo in children, especially in areas on the face.

3. Eyes
Tacrolimus solution, as drops, is sometimes prescribed by veterinarians for keratoconjunctivitis, and other dry eye maladies, in the eyes of domestic cats, dogs, and horses. It has been studied for use in human eyes.

Routes of Administration

Tacrolimus can be administered through various routes:
1. Oral Capsules: Commonly used for systemic immunosuppression post-transplant.
2. Topical Ointment: Applied directly to affected skin areas for conditions like eczema.
3. Intravenous Injection: Used in hospital settings for immediate immunosuppression needs

Safety and Side Effects

While tacrolimus is effective, it carries potential side effects:
Common Side Effects:
1. Skin irritation (burning, redness)
2. Increased sensitivity to temperature
3. Headaches
4. Nausea
5. Muscle pain
Serious Risks:
1. Increased risk of infections and malignancies, including skin cancer and lymphoma (particularly with long-term use).
2. Allergic reactions such as rash or swelling.
The FDA has issued a black box warning regarding these risks, emphasizing careful monitoring during treatment

Dosage Considerations

Absorption varies by route; for instance, oral bioavailability ranges from 17% to 31% depending on patient factors like organ type and genetic polymorphisms affecting drug metabolism

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