There were haemorragic strokes in people too in one of the trials. And
then, we do not know, you are right. But I have heard Peter's story
over and over and over.

And Plavix and a statin together?

Here. Just for you Jim.

Grapefruit  statins, P450 (other drugs, foods, illness and conditions)
Further on the impaired metabolism of drugs, including statins
(excepting pravastatin).

Nurses Study
http://firstword.pslgroup.com/sn.do?pu=1&idö74F5FE75F118C185256F1D00135BCC&mains
rc=/LoadMedicalNews.do?contentid80998

DGNews
Grapefruit Juice and Medication Can Be a Deadly Mix
ROCHESTER, NY -- January 18, 2005 -

-----snip-------

Amy Karch, R.N., M.S., of the School of Nursing at the
University of Rochester Medical Center reported on a man from a
northern climate who moved to Florida for the winter -- one of tens of
thousands  of "snowbirds" who head south each winter -- and began
drinking two to  three glasses of grapefruit juice each day. Two months
later the man
died, the victim of a deadly interaction between grapefruit juice and
his
cholesterol-lowering medication.

The patient profiled in Karch's article had high
cholesterol and other risk factors for cardiac disease. The doctor put
the
patient on atorvastatin (Lipitor), and the patient began dieting and
exercising. Two months after the patient went to Florida for the
winter, he
suddenly had muscle pain, fatigue and fever, and went to the emergency
room. The patient ended up going into kidney failure and ultimately
died.

---------snip---------.

Karch, an expert on drug interactions, explains that
grapefruit juice is one of the foods most likely to cause problems with
drugs,
because it is metabolized by the same enzyme in the liver that  breaks
down many drugs. The cytochrome P-450 3A4 enzyme breaks down grapefruit

juice into useful components for body, just like it breaks down dozens
of medications. Karch says when the system is overloaded, the
grapefruit
juice can "swamp" the system, keeping the liver busy and blocking it
from
breaking down drugs and other substances.

Drugs that use the same pathway and interact with
grapefruit juice target some of the most common health problems doctors
see  today. The list consists of more than 50 medications, including
some drugs used  to treat high cholesterol, depression, high blood
pressure, cancer,
pain, impotence, and allergies.

-------snip---------

A heart patient might not get the lowered blood pressure that a
medication should deliver, or the heart's rhythms might become
irregular if
an anti-arrhythmia drug can't do its job.

The most severe effects are likely with some cholesterol-lowering
medications, Karch says. While the liver devotes its resources to
grapefruit
juice, the medication can build up to dangerous levels, causing a
breakdown
of the body's muscles and even kidney failure. This is what happened to
the
patient discussed in the article.

Drugs that Interact with Grapefruit Juice:

(from the December 2004 issue of the American Journal of Nursing)

Antibiotics: clarithromycin, erythromycin,
troleandomycin

Anxiolytics: alprazolam, buspirone, midazolam,
triazolam

Antiarrhythmics: amiodarone, quinidine

Anticoagulant: warfarin

Antiepileptic: carbamazepine

Antifungal: itraconazole

Anthelmintic: albendazole

Antihistamine: fexofenadine

Antineoplastics: cyclophosphamide, etoposide,
ifosfamide, tamoxifen,
vinblastine, vincristine

Antitussive: dextromethorphan

Antivirals: amprenavir, indinavir, nelfinavir,
ritonavir, saquinavir

Benign prostatic hyperplasia treatment: finasteride

â-blockers: carvedilol

Calcium channel blockers: diltiazem, felodipine,
nicardipine, nifedipine,
nimodipine, nisoldipine, verapamil

Erectile dysfunction drugs: sildenafil, tadalafil

Hormone replacement: cortisol, estradiol,
methylprednisolone, progesterone,
testosterone

Immunosuppressants: cyclosporine, sirolimus,
tacrolimus

HMG-CoA reductase inhibitors: atorvastatin,
fluvastatin, lovastatin,
simvastatin

Opioids: alfentanil, fentanyl, sufentanil

Selective serotonin reuptake inhibitors: fluvoxamine,
sertraline

Xanthine: theophylline

SOURCE: University of Rochester Medical Center

http://www.cmaj.ca/cgi/content/full/167/3/279?maxtoshow=&HITS&hits&RESULTFORMA
T=&fulltext=grapefruit+juice+drug+interactions&andorexactfulltext=and&searchid0
6787840721_5561&stored_search=&FIRSTINDEX=0&sortspec=relevance&resourcetype=1&jo
urnalcode=cmaj

~~~~~~~~~~
"The interaction: As little as 250 mL of grapefruit juice can change
the metabolism of some drugs.3 This drug-food interaction occurs
because of a common pathway involving a specific isoform of cytochrome
P450 - CYP3A4 - present in both the liver and the intestinal wall.
Studies suggest that grapefruit juice exerts its effect primarily at
the level of the intestine.4
Ater ingestion, a substrate contained in the grapefruit binds to the
intestinal isoenzyme, impairing first-pass metabolism directly and
causing a sustained decrease in CYP3A4 protein expression.5 Within 4
hours of ingestion, a reduction in the effective CYP3A4 concentration
occurs, with effects lasting up to 24 hours.6 The net result is
inhibition of drug metabolism in the intestine and increased oral
bioavailability. Because of the prolonged response, separating the
intake of the drug and the juice does not prevent interference.

Individuals express CYP3A4 in different proportions, those with the
highest intestinal concentration being most susceptible to grapefruit
juice-drug interactions.5 An effect is seen with the whole fruit as
well as its juice, so caution should be exercised with both.7 The
precise chemical compound in grapefruit that causes the interaction has
not been identified. There is no similar reaction with orange juice,
although there is some suspicion that "sour oranges" such as the
Seville variety, may have some effect.8 A recent study, however, that
tested the known interference of grapefruit juice with cyclosporine
showed no similar effect with Seville oranges.9

There is some interest in the potential therapeutic benefit of adding
grapefruit juice to a drug regimen to increase oral bioavailability.3
The limitation is the individual variation in patient response.
However, if the chemical that causes grapefruit's CYP3A4 inhibition is
elucidated, there may be an opportunity to modulate that pathway in a
controlled fashion.

What to do: Much of the data obtained on grapefruit juice-drug
interactions involved measuring serum drug concentrations in small
numbers of healthy volunteers. Because of the limited data and only
occasional case reports,10 it is difficult to quantify the clinical
significance for individual patients. One may assume that the
interaction occurs primarily with oral medicines, and only with those
that share the CYP3A4 metabolism pathway, with the consequence being
increased oral bioavailability, higher serum drug concentrations and
associated adverse effects.

~~~~~~~~~~~~~~~~~~~~~~~~~

With every correction you make of any error *I* make, you prove my
point: once I was accepted to law school; once I was a crack writer. No
more. But it is coming back Steve. That I use the technique without
thinking shows me my writing chops are coming back. Of course, they
will never be what they were. But still, enough to mop the floor with
you.

Zee