Fujimycin

Fujimycin - General Information

Fujimycin (also FK-506 or Fujimycin) is an immunosuppressive drug whose main use is after organ transplant to reduce the activity of the patient's immune system and so the risk of organ rejection. It is also used in a topical preparation in the treatment of severe atopic dermatitis, severe refractory uveitis after bone marrow transplants, and the skin condition vitiligo. It was discovered in 1984 from the fermentation broth of a Japanese soil sample that contained the bacteria Streptomyces tsukubaensis. Fujimycin is chemically known as a macrolide. It reduces peptidyl-prolyl isomerase activity by binding to the immunophilin FKBP-12 (FK506 binding protein) creating a new complex. This FKBP12-FK506 complex interacts with and inhibits calcineurin thus inhibiting both T-lymphocyte signal transduction and IL-2 transcription.

 

Pharmacology of Fujimycin

Fujimycin is a macrolide antibiotic. It acts by reducing peptidyl-prolyl isomerase activity by binding to the immunophilin FKBP-12 (FK506 binding protein) creating a new complex. This inhibits both T-lymphocyte signal transduction and IL-2 transcription. Although this activity is similar to cyclosporine studies have shown that the incidence of acute rejection is reduced by tacrolimus use over cyclosporine. Fujimycin has also been shown to be effective in the topical treatment of eczema, particularly atopic eczema. It suppresses inflammation in a similar way to steroids, but is not as powerful. An important dermatological advantage of tacrolimus is that it can be used directly on the face; topical steroids cannot be used on the face, as they thin the skin dramatically there. On other parts of the body, topical steroid are generally a better treatment.

 

Fujimycin for patients

Read this important information before you start using PROTOPIC [pro-TOP-ik] Ointment and each time you refill your prescription. There may be new information. This summary is not meant to take the place of your doctorís advice.

What Is PROTOPIC?
PROTOPIC Ointment is a prescription medicine that is used to treat eczema (atopic dermatitis). It is for adults and children age 2 years and older. You can use PROTOPIC for short or intermittent long periods of treatment. Intermittent means starting and stopping repeatedly, as directed by your doctor. You can use it on all affected areas of your skin, including your face and neck.

Who should not use PROTOPIC? Do not use PROTOPIC if you are

ï breastfeeding

ï allergic to PROTOPIC Ointment or any of its ingredients. The active ingredient is tacrolimus. Ask your doctor or pharmacist about the inactive ingredients.

Before you start using PROTOPIC, tell your doctor if you are:

ï using any other prescription medicines, non-prescription (over-the-counter) medicines, or supplements

ï receiving any form of light therapy (phototherapy, UVA or UVB) on your skin

ï using any other type of skin product ï pregnant or planning to become pregnant

How Do I Use PROTOPIC?
Use PROTOPIC only to treat eczema that has been diagnosed by a doctor.

ï Wash your hands before using PROTOPIC.

ï Apply a thin layer of PROTOPIC to all skin areas that your doctor has diagnosed as eczema. Try to cover the affected areas completely. Most people find that a pea-sized amount squeezed from the tube covers an area about the size of a two-inch circle (approximately the size of a silver dollar).

ï Apply the ointment twice a day, about 12 hours apart.

ï Before applying PROTOPIC Ointment after a bath or shower, be sure your skin is completely dry.

ï Do not cover the skin being treated with bandages, dressings or wraps. Unless otherwise instructed by your doctor, do not apply another type of skin product on top of PROTOPIC Ointment. However, you can wear normal clothing.

ï Do not bathe, shower or swim right after applying PROTOPIC. This could wash off the ointment.

ï If you are a caregiver applying PROTOPIC Ointment to a patient, or if you are a patient who is not treating your hands, wash your hands with soap and water after applying PROTOPIC. This should remove any ointment left on the hands.

ï Use PROTOPIC only on your skin. Do not swallow PROTOPIC.

Because 2 strengths of PROTOPIC are available for adult patients, your doctor will decide what strength of PROTOPIC Ointment is best for you.

Many people notice that their skin starts to improve after the first few weeks of treatment. Even though your skin looks and feels better, it is important to keep using PROTOPIC as instructed by your doctor.

If you do not notice an improvement in your eczema or if your eczema gets worse within the first few weeks of treatment, tell your doctor.

What Should I Avoid While Using PROTOPIC?

ï Avoid sunlight and sun lamps, tanning beds, and treatment with UVA or UVB light. If you need to be outdoors after applying PROTOPIC, wear loose fitting clothing that protects the treated area from the sun. In addition, ask your doctor what other type of protection from the sun you should use.

ï Check with your doctor or pharmacist before you

ï start taking any new medicines while using PROTOPIC.

ï Start using any other ointment, lotions, or creams on your skin.

What Are The Possible Side Effects of PROTOPIC?

The most common side effects of PROTOPIC are stinging, soreness, a burning feeling, or itching of the skin treated with PROTOPIC. These side effects are usually mild to moderate, are most common during the first few days of treatment, and typically lessen if your skin heals.

Less common side effects include acne, swollen or infected hair follicles, headache, increased sensitivity of the skin to hot or cold temperatures, or flu-like symptoms [common cold and congestion (stuffy nose)]. Some people may get skin tingling, upset stomach, herpes zoster (chicken pox or shingles), or muscle pain. While you are using PROTOPIC, drinking alcohol may cause the skin or face to become flushed or red and feel hot. Call your doctor if side effects continue or become a problem.

How Should I Store PROTOPIC?

Store PROTOPIC at room temperature (59° to 86°F). For instance, never leave PROTOPIC in your car in cold or hot weather. Make sure the cap on the tube is tightly closed. Keep PROTOPIC out of the reach of children.

General Advice about Prescription Medicines

Do not use PROTOPIC for a condition for which it was not prescribed. If you have any concerns about PROTOPIC, ask your doctor. Your doctor or pharmacist can give you information about PROTOPIC that was written for health care professionals. For more information, you can also visit the Fujisawa Internet site at www.fujisawa.com or call the PROTOPIC Help Line at 1-800-727-7003.

 

Fujimycin Interactions

Formal topical drug interaction studies with PROTOPIC Ointment have not been conducted. Based on its minimal extent of absorption, interactions of PROTOPIC 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.

 

Fujimycin Contraindications

PROTOPIC Ointment is contraindicated in patients with a history of hypersensitivity to tacrolimus or any other component of the preparation.

 

Additional information about Fujimycin

Fujimycin Indication: For use after allogenic organ transplant to reduce the activity of the patient's immune system and so the risk of organ rejection. It was first approved by the FDA in 1994 for use in liver transplantation, this has been extended to include kidney, heart, small bowel, pancreas, lung, trachea, skin, cornea, and limb transplants. It has also been used in a topical preparation in the treatment of severe atopic dermatitis.
Mechanism Of Action: The mechanism of action of tacrolimus in atopic dermatitis is not known. While the following have been observed, the clinical significance of these observations 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 prevents 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. Fujimycin also inhibits the transcription for genes which encode IL-3, IL-4, IL-5, GM-CSF, and TNF-, 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 downregulate the expression of FceRI on Langerhans cells.
Drug Interactions: Not Available
Food Interactions: Not Available
Generic Name: Tacrolimus
Synonyms: FK5; Tacarolimus; FK-506; K506
Drug Category: Immunosuppressive Agents
Drug Type: Small Molecule; Approved; Investigational

Other Brand Names containing Tacrolimus: Prograf; Protopic; Fujimycin;
Absorption: 20% bioavailability; less after eating food rich in fat
Toxicity (Overdose): Side effects can be severe and include blurred vision, liver and kidney problems (it is nephrotoxic), seizures, tremors, hypertension, hypomagnesemia, diabetes mellitus, hyperkalemia, itching, insomnia, confusion. LD₅₀=134-194 mg/kg (rat).
Protein Binding: 75-99%
Biotransformation: Hepatic, extensive, primarily by CYP3A4. The major metabolite identified in incubations with human liver microsomes is 13-demethyl tacrolimus. In in vitro studies, a 31-demethyl metabolite has been reported to have the same activity as tacrolimus.
Half Life: 11.3 hours (range from 3.5 to 40.6 hours)
Dosage Forms of Fujimycin: Solution Intravenous
Ointment Topical
Capsule Oral
Chemical IUPAC Name: [3S-[3R*[E(1S*,3S*,4S*)],4S*,5R*,8S*,9E,12R*,14R*,15S*,16R*,18S*,19S*,26aR*]]-5,6,8,11,12,13,14,15,16,17,18,19,24,25,26,26a-hexadecahydro-5, 19-dihydroxy-3- [2-(4-hydroxy-3-methoxycyclohexyl) -1-methylethenyl]-14, 16-dimethoxy-4,10,12,18-tetramethyl-8-(2-propenyl)-15, 19-epoxy-3H-pyrido[2,1-c][1,4] oxaazacyclotricosine-1,7,20, 21(4H,23H)-tetrone, monohydrate
Chemical Formula: C44H69NO12
Tacrolimus on Wikipedia: https://en.wikipedia.org/wiki/Tacrolimus
Organisms Affected: Humans and other mammals