Hello jtkm-ga,
I expected this to be a quick and easy search project. I discovered
that I had to dig deep to find the appropriate vocabulary to be able
to complete this research. I ended up spending much more time than is
warranted for a question at this price because I was fascinated by the
subject.
I was surprised to find that the reasons for the interaction of
grapefruit and grapefruit juice (and other citrus plants as well )
with Prograf (generic name Tacrolimus) is not fully established and is
the subject of continuing research. I?ve included a selection of
articles that discuss the current state of research. I?ve also
included extensive information about Prograf/Tacrolimus so you can
continue exploring this subject on your own. This drug is used as an
immunosuppressant in kidney and liver transplants.
I wish you well for your further explorations.
~ czh ~
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GRAPEFRUIT DRUG INTERACTIONS ? PROGRAF / TACROLIMUS
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http://www.wholehealthmd.com/refshelf/drugs_interact/1,1748,580,00.html
Tacrolimus (FK506) - Interactions
flavonoids
Do not take a bioflavonoid preparation containing naringin (a
flavonoid present in grapefruit) with tacrolimus. A potentially
serious adverse reaction may result.
***** Tacrolimus is the generic name of Prograf. The grapefruit
component that interacts with Prograf is narigin, a flavonoid.
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https://secure.pharmacytimes.com/lessons/200303-02.asp
Drug Interactions with Grapefruit Juice: An Evidence-Based Overview
Mechanism of Action
Originally, naringin was thought to be the main component responsible
for grapefruit-drug interactions. However, studies have shown naringin
to be a weak inhibitor of CYP3A4.8,9 It was also demonstrated that the
administration of isolated naringin to humans, in quantities
comparable to those found in grapefruit juice, did not cause the same
degree of inhibition as grapefruit juice.
Certain Immunosuppressants
Cyclosporine is an immunosuppressant used widely in solid organ and
bone marrow transplantation as well as in the treatment of psoriasis.
Oral cyclosporine formulations (ie, oil/water and microemulsion) have
been well documented to interact with grapefruit juice through
inhibition of CYP3A4 and P-gp. However, intravenous cyclosporine
formulations do not interact. In one study, the mean absolute oral
bioavailability of cyclosporine increased by 62% with grapefruit juice
administration, but there was no significant effect with intravenous
cyclosporine.28 The magnitude of pharmacokinetic changes associated
with the grapefruitcyclosporine interaction is variable and
unpredictable within individuals and should not be used as a strategy
to reduce cyclosporine dosages and save on drug costs.
Tacrolimus is an immunosuppressant metabolized by CYP3A4. Because the
bioavailability of tacrolimus is doubled by ketoconazole, a potent
CYP3A4 inhibitor, an interaction with grapefruit juice may also occur.
Until more data are available, concurrent administration of tacrolimus
and grapefruit juice should be avoided.29
***** This is a long article that provides a good overview of current
research about grapefruit and drug interactions.
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http://www.transplantjournal.com/pt/re/transplantation/abstract.00007890-200304150-00029.htm;jsessionid=CqZNwKFdM20hUCKG1RbX5oaGS77BBrm2RP10r8FYYTki0tggusq1!802112076!-949856031!9001!-1
Pomelo-induced increase in the blood level of tacrolimus in a renal
transplant patient.
Transplantation. 75(7):1057, April 15, 2003.
Abstract:
Background.
Tacrolimus, an immunosuppressive agent, is widely used in patients
after transplantation to prevent allograft rejection. Because
tacrolimus has a narrow therapeutic range, it is essential to
carefully control the blood level. It has been demonstrated that
tacrolimus is metabolized mainly by cytochrome P-450 (CYP) 3A4, and
that tacrolimus is a substrate of P-glycoprotein.
Methods.
This article reports a case of considerable increase in the blood
level of tacrolimus after the intake of pomelo in a renal transplant
recipient.
Results. Pomelo may increase the blood concentration of tacrolimus by
inhibiting CYP 3A4, P-glycoprotein, or both.
Conclusions. Patients taking drugs such as tacrolimus or cyclosporine,
which have their kinetics affected by grapefruit juice, should avoid
pomelo and other grapefruit-related citrus fruits.
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http://www.intelihealth.com/IH/ihtIH/WSIHW000/8513/31402/348974.html?d=dmtContent
Grapefruit (Citrus paradisi)
***** Extensive discussion from Harvard Medical School?s Consumer
Health Information resources regarding grapefruit, including its
interaction with various drugs.
http://home.caregroup.org/clinical/altmed/interactions/Nutrients/Grapefruit_Juic.htm
Grapefruit Juice
Summary
Grapefruit Juice -- overview of interactions:
-- food potentially affecting drug pharmacokinetics, toxicity and
performance: Cytochrome P450 Inhibition
-- food affecting drug performance: Corticosteroids, including Prednisone
-- food affecting drug performance and toxicity: Cyclosporine
-- food affecting drug performance: Lovastatin
-- food affecting drug performance: Pravastatin
-- food affecting drug toxicity: Terfenadine (Seldane®)
-- food affecting drug performance and toxicity: Verapamil
***** This site provides detailed descriptions of the above list of
grapefruit juice drug interactions.
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http://www.ualberta.ca/~csps/JPPS4(3)/S.Wanwimolruk/grapefruit.htm
Inhibition of human CYP3A4 activity by grapefruit flavonoids,
furanocoumarins and related compounds
In summary, the present study has demonstrated that besides the
flavonoids, other compounds found in grapefruit including
furanocoumarins can produce strong inhibition of CYP3A4. The
grapefruit juice-drug interactions could involve CYP3A4 inhibition by
more than one component present in grapefruit juice. Bergapten was
found to be a very potent inhibitor of CYP3A4. Therefore, it may be an
important furanocoumarin responsible for the grapefruit juice drug
interactions. Concentrations of bergapten (up to 30 mM) detected in
grapefruit and commercial grapefruit juice products (44) appear
sufficient to cause significant inhibition of CYP3A4 in this study.
However, it should be noted that inhibition of CYP3A4 activity in
vitro does not necessarily imply drug interaction in vivo . Further
studies will be needed to determine if this furanocoumarin bergapten
can influence the CYP enzyme in vivo .
***** This is a long scientific article that reports on a research
project on the flavonoids in grapefruit.
-------------------------------------------------
http://www.wlap.org/wl-repository/umich/cacr/grand-rounds/20031202-annarbor-01-watkins/realaudio/thumb.htm
University of Michigan Medical School
"Grapefruit juice and the intestinal barrier in man: not pulp fiction"
Lecture Index
***** This is a audio and slide presentation that gives you an
excellent overview of the topic of grapefruit and drug interactions.
==================================================
PROGRAF / TACROLIMUS ? RX AND CONSUMER INFORMATION
==================================================
http://www.netdoctor.co.uk/medicines/100002164.html
Prograf
How does it work?
This medicine contains the active ingredient tacrolimus, which is a
type of medicine called an immunosuppressant. Immunosuppressants are
used to dampen down the activity of cells in the immune system.
Tacrolimus acts on the white blood cells. It works by blocking the
action of a substance called calcineurin that is found in white blood
cells called T-lymphocytes. This action prevents the T-lymphocytes
from producing substances called lymphokines.
What is it used for?
-- Managing rejection of a kidney or liver transplant when other
immunosuppressants have failed
-- Preventing the body rejecting a transplanted kidney or liver
Warning!
-- Unless your doctor or pharmacist tells you otherwise, you should
avoid drinking grapefruit juice while taking this medicine, as it may
affect the level of this medicine in your blood.
-- This medicine can cause the amount of potassium in your
bloodstream to increase. For this reason you should avoid consuming
large amounts of foods that have a high potassium content, for example
dried fruit, bananas, tomatoes and 'low sodium' salt, while you are
taking the medicine. You should also avoid potassium supplements.
Other medicines containing the same active ingredients ? Tacrolimus
-------------------------------------------------
http://www.netdoctor.co.uk/medicines/100004716.html
Tacrolimus
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http://www.rxlist.com/cgi/generic2/tacrolimuspo.htm
Prograf®
tacrolimus capsules
tacrolimus injection (for intravenous infusion only)
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http://www.rxlist.com/cgi/generic2/tacrolimuspo_pi.htm
PATIENT INFORMATION
What Is PROGRAF?
PROGRAF is a medicine that slows down the body's immune system. For
this reason, it works as an anti-rejection medicine. PROGRAF helps
patients who have had a liver or kidney transplant protect their new
organ and prevent it from being rejected by the body.
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http://www.fujisawa.com/medinfo/pi/pi_page_pg.htm
Prograf Prescribing Information
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http://www.rxcarecanada.com/Prograf.asp
Grapefruit juice affects P450 IIIA-mediated metabolism and should be avoided.
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SEARCH STRATEGY
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prograf
tacrolimus
prograf grapefruit
Tacrolimus grapefruit
Tacrolimus grapefruit naringin
Grapefruit juice affects P450 IIIA |
