| bioavailability = 20%, less after eating food rich in fat
|fdaLIADAdult======Condition1=====
| protein_bound = 92%
| metabolism = Hepatic
* Dosing Information
| elimination_half-life = 57–63 hours
| licence_EU = Rapamune
:* Dosage
| licence_US = Sirolimus
| pregnancy_AU = C
=====Condition2=====
| pregnancy_US = C
| legal_US = Rx-only
* Dosing Information
| routes_of_administration = Oral
| excretion = Mostly faecal
:* Dosage
}}
=====Condition3=====
* Dosing Information
:* Dosage
=====Condition4=====
* Dosing Information
:* Dosage
<!--Off-Label Use and Dosage (Adult)-->
<!--Guideline-Supported Use (Adult)-->
|offLabelAdultGuideSupport======Condition1=====
* Developed by:
* Class of Recommendation:
* Strength of Evidence:
* Dosing Information
:* Dosage
=====Condition2=====
There is limited information regarding <i>Off-Label Guideline-Supported Use</i> of {{PAGENAME}} in adult patients.
<!--Non–Guideline-Supported Use (Adult)-->
|offLabelAdultNoGuideSupport======Condition1=====
* Dosing Information
:* Dosage
=====Condition2=====
There is limited information regarding <i>Off-Label Non–Guideline-Supported Use</i> of {{PAGENAME}} in adult patients.
<!--Pediatric Indications and Dosage-->
<!--FDA-Labeled Indications and Dosage (Pediatric)-->
|fdaLIADPed======Condition1=====
* Dosing Information
:* Dosage
=====Condition2=====
There is limited information regarding <i>FDA-Labeled Use</i> of {{PAGENAME}} in pediatric patients.
<!--Off-Label Use and Dosage (Pediatric)-->
<!--Guideline-Supported Use (Pediatric)-->
|offLabelPedGuideSupport======Condition1=====
* Developed by:
* Class of Recommendation:
* Strength of Evidence:
* Dosing Information
:* Dosage
=====Condition2=====
There is limited information regarding <i>Off-Label Guideline-Supported Use</i> of {{PAGENAME}} in pediatric patients.
<!--Non–Guideline-Supported Use (Pediatric)-->
|offLabelPedNoGuideSupport======Condition1=====
* Dosing Information
:* Dosage
=====Condition2=====
There is limited information regarding <i>Off-Label Non–Guideline-Supported Use</i> of {{PAGENAME}} in pediatric patients.
<!--Contraindications-->
|contraindications=* Condition1
<!--Warnings-->
|warnings=* Description
====Precautions====
* Description
<!--Adverse Reactions-->
<!--Clinical Trials Experience-->
|clinicalTrials=There is limited information regarding <i>Clinical Trial Experience</i> of {{PAGENAME}} in the drug label.
=====Body as a Whole=====
=====Cardiovascular=====
=====Digestive=====
=====Endocrine=====
=====Hematologic and Lymphatic=====
=====Metabolic and Nutritional=====
=====Musculoskeletal=====
=====Neurologic=====
=====Respiratory=====
=====Skin and Hypersensitivy Reactions=====
=====Special Senses=====
=====Urogenital=====
=====Miscellaneous=====
<!--Postmarketing Experience-->
|postmarketing=There is limited information regarding <i>Postmarketing Experience</i> of {{PAGENAME}} in the drug label.
=====Body as a Whole=====
=====Cardiovascular=====
=====Digestive=====
=====Endocrine=====
=====Hematologic and Lymphatic=====
=====Metabolic and Nutritional=====
=====Musculoskeletal=====
=====Neurologic=====
=====Respiratory=====
=====Skin and Hypersensitivy Reactions=====
=====Special Senses=====
=====Urogenital=====
=====Miscellaneous=====
<!--Drug Interactions-->
|drugInteractions=* Drug
:* Description
<!--Use in Specific Populations-->
|useInPregnancyFDA=* '''Pregnancy Category'''
|useInPregnancyAUS=* '''Australian Drug Evaluation Committee (ADEC) Pregnancy Category'''
There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of {{PAGENAME}} in women who are pregnant.
|useInLaborDelivery=There is no FDA guidance on use of {{PAGENAME}} during labor and delivery.
|useInNursing=There is no FDA guidance on the use of {{PAGENAME}} with respect to nursing mothers.
|useInPed=There is no FDA guidance on the use of {{PAGENAME}} with respect to pediatric patients.
|useInGeri=There is no FDA guidance on the use of {{PAGENAME}} with respect to geriatric patients.
|useInGender=There is no FDA guidance on the use of {{PAGENAME}} with respect to specific gender populations.
|useInRace=There is no FDA guidance on the use of {{PAGENAME}} with respect to specific racial populations.
|useInRenalImpair=There is no FDA guidance on the use of {{PAGENAME}} in patients with renal impairment.
|useInHepaticImpair=There is no FDA guidance on the use of {{PAGENAME}} in patients with hepatic impairment.
|useInReproPotential=There is no FDA guidance on the use of {{PAGENAME}} in women of reproductive potentials and males.
|useInImmunocomp=There is no FDA guidance one the use of {{PAGENAME}} in patients who are immunocompromised.
<!--Administration and Monitoring-->
|administration=* Oral
* Intravenous
|monitoring=There is limited information regarding <i>Monitoring</i> of {{PAGENAME}} in the drug label.
* Description
<!--IV Compatibility-->
|IVCompat=There is limited information regarding <i>IV Compatibility</i> of {{PAGENAME}} in the drug label.
<!--Overdosage-->
|overdose====Acute Overdose===
====Signs and Symptoms====
* Description
====Management====
* Description
===Chronic Overdose===
There is limited information regarding <i>Chronic Overdose</i> of {{PAGENAME}} in the drug label.
<!--Pharmacology-->
{{CMG}}
<!--Drug box 2-->
|drugBox=<!--Mechanism of Action-->
|mechAction=*
<!--Structure-->
|structure=*
: [[File:{{PAGENAME}}01.png|thumb|none|600px|This image is provided by the National Library of Medicine.]]
'''Sirolimus''' ([[International Nonproprietary Name|INN]]) is a relatively new immunosuppressant drug used to prevent [[Transplant rejection|rejection]] in [[Organ transplant|organ transplantation]], and is especially useful in [[kidney]] transplants. It is also known as '''rapamycin'''. Sirolimus is a [[macrolide]] (''"-mycin"'') first discovered as a product of the bacterium ''Streptomyces hygroscopicus'' in a soil sample from an island called Rapa Nui, better known as Easter Island.<ref name=RapamycinOrigin>{{cite journal | author=Pritchard DI | title=Sourcing a chemical succession for cyclosporin from parasites and human pathogens | journal=Drug Discovery Today | year=2005 | volume=10 | issue = 10 | pages= 688–691 | id = PMID 15896681}}</ref> It is marketed under the trade name '''Rapamune''' by [[Wyeth]].
<!--Pharmacodynamics-->
|PD=There is limited information regarding <i>Pharmacodynamics</i> of {{PAGENAME}} in the drug label.
Interestingly, sirolimus was originally developed as an antifungal agent. However, this was abandoned when it was discovered that it had potent [[immunosuppression|immunosuppressive]] and antiproliferative properties.
<!--Pharmacokinetics-->
|PK=There is limited information regarding <i>Pharmacokinetics</i> of {{PAGENAME}} in the drug label.
==Mechanism of action==
<!--Nonclinical Toxicology-->
Despite its similar name, it is not a calcineurin inhibitor like [[tacrolimus]] or [[cyclosporin]]. However, it has a similar suppressive effect on the immune system. Sirolimus inhibits the response to [[interleukin-2]] (IL-2) and thereby blocks activation of [[T cell|T-]] and [[B cell|B-cell]]s. In contrast, tacrolimus and cyclosporine inhibit the production of IL-2.
|nonClinToxic=There is limited information regarding <i>Nonclinical Toxicology</i> of {{PAGENAME}} in the drug label.
The mode of action of sirolimus is to bind the [[cytosol]]ic protein ''[[FKBP|FK-binding protein 12]]'' (FKBP12) in a manner similar to tacrolimus. However, unlike the tacrolimus-FKBP12 complex which inhibits [[calcineurin]] (PP2B), the sirolimus-FKBP12 complex inhibits the ''[[mammalian target of rapamycin]]'' (mTOR) pathway through directly binding the mTOR Complex1 (mTORC1). mTOR is also called FRAP (FKBP-rapamycin associated protein) or RAFT (rapamycin and FKBP target). FRAP and RAFT are actually more accurate names since they reflect the fact that rapamycin must bind FKBP12 first, and only the FKBP12-rapamycin complex can bind FRAP/RAFT/mTOR.
<!--Clinical Studies-->
|clinicalStudies=There is limited information regarding <i>Clinical Studies</i> of {{PAGENAME}} in the drug label.
==Use in transplant==
<!--How Supplied-->
The chief advantage sirolimus has over calcineurin inhibitors is that it is not toxic to kidneys. Transplant patients maintained on calcineurin inhibitors long-term tend to develop impaired kidney function or even chronic renal failure, and this can be prevented by use of sirolimus instead. It is particularly advantageous in patients with kidney transplants for [[hemolytic-uremic syndrome]] as this disease is likely to recur in the transplanted kidney if a calcineurin-inhibitor is used.
|howSupplied=*
|packLabel=<!--Patient Counseling Information-->
|fdaPatientInfo=There is limited information regarding <i>Patient Counseling Information</i> of {{PAGENAME}} in the drug label.
Sirolimus can also be used alone or in conjunction with calcineurin inhibitors and/or [[mycophenolate mofetil]], to provide steroid-free immunosuppression regimes. As impaired wound healing is a possible side effect of sirolimus, some transplant centres prefer not to use it immediately after the transplant operation, and start to give it after a period of weeks or months. Its optimal role in immunosuppression has not yet been determined and is the subject of a number of ongoing clinical trials.
<!--Precautions with Alcohol-->
|alcohol=* Alcohol-{{PAGENAME}} interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.
==Anti-proliferative effects==
<!--Brand Names-->
The anti-proliferative effect of sirolimus has also been used in conjunction with coronary stents to prevent restenosis in coronary arteries following balloon angioplasty. The sirolimus is formulated in a polymer coating that affords controlled release through the healing period following coronary intervention. Several large clinical studies have demonstrated lower restenosis rates in patients treated with sirolimus eluting stents when compared to bare metal stents, resulting in fewer repeat procedures. A sirolimus eluting coronary stent is marketed by Cordis, a division of [[Johnson & Johnson]], under the tradename '''Cypher'''. It has been proposed, however, that such stents may increase the risk of vascular thrombosis.<ref name="Shuchman">{{cite journal | author = Shuchman M | title = Trading restenosis for thrombosis? New questions about drug-eluting stents | journal = [[New England Journal of Medicine|N Engl J Med]] | volume = 355 | issue = 19 | pages = 1949–52 | year = 2006 | id = PMID 17093244}}</ref>
|brandNames=* ®<ref>{{Cite web | title = | url = }}</ref>
===Cancer===
<!--Look-Alike Drug Names-->
The anti-proliferative effects of sirolimus may have a role in treating cancer. Recently, it was shown that sirolimus inhibited the progression of dermal [[Kaposi's sarcoma]] in patients with renal transplants. Other mTOR inhibitors such as [[temsirolimus]] (CCI-779) or [[everolimus]] (RAD001) are being tested for use in cancers such as [[glioblastoma multiforme]] and [[mantle cell lymphoma]].
|lookAlike=* A® — B®<ref name="www.ismp.org">{{Cite web | last = | first = | title = http://www.ismp.org | url = http://www.ismp.org | publisher = | date = }}</ref>
[[Combination therapy]] of [[doxorubicin]] and sirolimus has been shown to drive [[AKT]]-positive lymphomas into [[remission]] in mice. Akt signalling promotes cell survival in Akt-positive lymphomas and acts to prevent the [[cytotoxic]] effects of [[chemotherapy]] drugs like [[doxorubicin]] or [[cyclophosphamide]]. Sirolimus blocks Akt signalling and the cells lose their resistance to the chemotherapy. [[Bcl-2]]-positive lymphomas were completely resistant to the therapy; nor are [[eIF4E]] expressing lymphomas sensitive to sirolimus.<ref>{{cite journal | author = Sun S, Rosenberg L, Wang X, Zhou Z, Yue P, Fu H, Khuri F | title = Activation of Akt and eIF4E survival pathways by rapamycin-mediated mammalian target of rapamycin inhibition | journal = Cancer Res | volume = 65 | issue = 16 | pages = 7052–8 | year = 2005 | id = PMID 16103051}} [http://cancerres.aacrjournals.org/cgi/content/full/65/16/7052 Free full text]</ref> Rapamycin showed no effect on its own.<ref name="Chan">{{cite journal | author = Chan S | title = Targeting the mammalian target of rapamycin (mTOR): a new approach to treating cancer | journal = Br J Cancer | volume = 91 | issue = 8 | pages = 1420–4 | year = 2004 | id = PMID 15365568}}</ref><ref name="ScienceDaily">{{cite news | author = Cold Spring Harbor Laboratory | title = Combination Therapy Drives Cancer Into Remission | date = March 18, 2004 | publisher = ScienceDaily | url = http://www.sciencedaily.com/releases/2004/03/040318073757.htm | accessdate = 2007-01-10}}</ref><ref name="CSHL">{{cite press release | title = Combination Therapy for Cancer Shows Promise | date = March 17, 2004 | publisher = Cold Spring Harbor Laboratory | url = http://www.cshl.edu/public/releases/combotherapy.html | accessdate = 2007-01-10}}</ref><ref name="SignalingGateway">{{cite web | last = Novak | first = Kristine | title = Disruption of Akt signaling with the drug rapamycin reverses tumor chemoresistance in a mouse model of lymphoma | publisher = The Signaling Gateway | url = http://www.signaling-gateway.org/update/updates/200405/nrc1349.html | accessdate = 2007-01-10}}</ref>
<!--Drug Shortage Status-->
|drugShortage=
}}
{{PillImage
|fileName=No image.jpg
}}
{{LabelImage
|fileName={{PAGENAME}}11.png
}}
{{LabelImage
|fileName={{PAGENAME}}11.png
}}
<!--Pill Image-->
As with all immunosuppressive medications, rapamycin decreases the body's inherent anti-cancer activity and allows some cancers which would have been naturally destroyed to proliferate. Patients on immunosuppressive medications have a 10- to 100-fold increased risk of cancer compared to the general population. Furthermore, people who currently have or have already been treated for cancer have a higher rate of tumor progression and recurrence than patients with an intact immune system.
==References==
<div class="references-small"><references/></div>
<!--Label Display Image-->
==External links==
* [http://www.rapamune.com/ Rapamune official website]
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Black Box Warning
ConditionName:
See full prescribing information for complete Boxed Warning.
ConditionName:
Content
Overview
Sirolimus is a {{{drugClass}}} that is FDA approved for the {{{indicationType}}} of {{{indication}}}. There is a Black Box Warning for this drug as shown here. Common adverse reactions include .
Adult Indications and Dosage
FDA-Labeled Indications and Dosage (Adult)
Condition1
Dosing Information
Dosage
Condition2
Dosing Information
Dosage
Condition3
Dosing Information
Dosage
Condition4
Dosing Information
Dosage
Off-Label Use and Dosage (Adult)
Guideline-Supported Use
Condition1
Developed by:
Class of Recommendation:
Strength of Evidence:
Dosing Information
Dosage
Condition2
There is limited information regarding Off-Label Guideline-Supported Use of Sirolimus in adult patients.
Non–Guideline-Supported Use
Condition1
Dosing Information
Dosage
Condition2
There is limited information regarding Off-Label Non–Guideline-Supported Use of Sirolimus in adult patients.
Pediatric Indications and Dosage
FDA-Labeled Indications and Dosage (Pediatric)
Condition1
Dosing Information
Dosage
Condition2
There is limited information regarding FDA-Labeled Use of Sirolimus in pediatric patients.
Off-Label Use and Dosage (Pediatric)
Guideline-Supported Use
Condition1
Developed by:
Class of Recommendation:
Strength of Evidence:
Dosing Information
Dosage
Condition2
There is limited information regarding Off-Label Guideline-Supported Use of Sirolimus in pediatric patients.
Non–Guideline-Supported Use
Condition1
Dosing Information
Dosage
Condition2
There is limited information regarding Off-Label Non–Guideline-Supported Use of Sirolimus in pediatric patients.
Contraindications
Condition1
Warnings
ConditionName:
See full prescribing information for complete Boxed Warning.
ConditionName:
Content
Description
Precautions
Description
Adverse Reactions
Clinical Trials Experience
There is limited information regarding Clinical Trial Experience of Sirolimus in the drug label.
Body as a Whole
Cardiovascular
Digestive
Endocrine
Hematologic and Lymphatic
Metabolic and Nutritional
Musculoskeletal
Neurologic
Respiratory
Skin and Hypersensitivy Reactions
Special Senses
Urogenital
Miscellaneous
Postmarketing Experience
There is limited information regarding Postmarketing Experience of Sirolimus in the drug label.
