Re: What is the typical dosage in mg/kg/day for high-dose Urso?

[Guest guest]

30 mg/kg

Mine won’t

increase Noah’s either. She said she thinks it will cause a flare of his

UC. I am not so convinced.

[Guest guest]

Why did they reduce his dosage? Was there something that prompted

the doctor to make that decision? The typical high dosage range is

25-30 but if the doctor is reducing it there most likely is a reason.

in Seattle

UC 1991, PSC 2001

>

> Today they decreased my husband's dosage from 19 mg/kg/d to 14

mg/kg/d.

>

> I think this is too low. What is the typical high dosage range?

>

> Thanks,

>

> Nichole Rowland (wife of PSC & UC 8/04)

>

[Guest guest]

Sounds too low to me. I take 2100 mg/day (for 180 lbs) or ~27 mg/kg. " High

dosage Urso " is supposed to be 15-25 mg. However:

Lindor suggests 25-30

(http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve & db=PubMed & list_u

ids=11374699 & dopt=Abstract), which is what I'm used to seeing.

See http://www.psc-literature.org/hdurso.htm for the clinical research on

it.

Arme

54 - UC 1977, PSC 2000

Alive and (mostly) well in Minnesota

-----Original Message-----

From: [mailto: ] On

Behalf Of nichole_rowland

Today they decreased my husband's dosage from 19 mg/kg/d to 14 mg/kg/d.

I think this is too low. What is the typical high dosage range?

Thanks,

Nichole Rowland (wife of PSC & UC 8/04)

[Guest guest]

My UC symptoms actually got better after going on Urso. I've been on 1800mg/day since I began taking it. (I am 158lbs). I was actually thinking of asking my doc to raise it since it doesn't seme to affect my UC. 30, UC 1/01, PSC 5/05 wrote: 30 mg/kg Mine won’t increase Noah’s

either. She said she thinks it will cause a flare of his UC. I am not so convinced.

Yahoo! Messenger with Voice. PC-to-Phone calls for ridiculously low rates.

[Guest guest]

Thank you all so much! I have printed the abstract and the other e-

mails and plan to approach his doctor as soon as possible. I mean now

is taking half the amount they recommend for PSC, that is not

right.

Nichole Rowland (wife of PSC & UC 8/04)

[Guest guest]

Dear Nichole,

I just wanted to say that being on this lower dose a short while is

not necessarily a bad thing. Some people need to get used the the

urso, it seems a very few have problems with it.

My son started out at what his Dr. called a high dose, 1,000mg and

then after I joined this group he went to 1,500 mg and then after the

papers recommending the 25-30 mg he went to 2,000mg.

I think this gradual increase up was maybe a good thing to help my

son's body adjust to it.

Do our seasoned members have any thoughts on this?

Is it better to work up to the high dose? Or did most people have no

problem starting at this level?

This information could really help the new people who join us.

Lee

> Thank you all so much! I have printed the abstract and the other e-

> mails and plan to approach his doctor as soon as possible. I mean now

> is taking half the amount they recommend for PSC, that is not

> right.

>

> Nichole Rowland (wife of PSC & UC 8/04)

>

>

>

>

[Guest guest]

Hi I have just started on 250MG 2 twice daily so that makes 1000mg and

I was told this is quite a low doze and it may need to be increased

later on. Though I must admit I took urso when I was pregant so its

not my first time taking it, hope this helps

[Guest guest]

Dea Lee;

The idea of starting on a lower dose of ursodeoxycholic acid (UDCA)

and then slowly working up, was developed in primary biliary

cirrhosis PBC (see " First-line-medical treatment " section in this

article):

____________________

Falk Symposium 142: GASTROENTEROLOGY WEEK FREIBURG 2004 (Part I)

AUTOIMMUNE LIVER DISEASE, Freiburg (Germany), October 12 - 13, 2004,

pp. 77-78 (2004)

Treatment of primary biliary cirrhosis and overlap syndromes:

current standards.

Poupon R

Service d'Hépatologie, Hôpital Saint-Antoine, Faculté P. et M.

Curie, F-75571 Paris Cedex 12, France

Background

The low prevalence and the long and variable course of primary

biliary cirrhosis (PBC)explain at least in part the great difficulty

in conducting controlled trials of sufficient size, duration and

power to detect a beneficial effect on survival or histological

progression. Meta-analysis of short-term trials only told us that

when PBC is accompanied by ascites and high levels of serum

bilirubin, it is only treatable by liver transplantation. Critical

review of past clinical trials revealed that most of them did not

correctly select an homogenous group of patients in order to

accurately define the power of the study and thus to determine if

the tested drug could halt the progression of PBC. From all available

data, we can say that drugs such as d-penicillamine and methotrexate

lack efficacy in most of the patients with PBC; ciclosporine and

azathioprine have some efficacy (improvement of survival from one to

two years). Colchicine has been evaluated in too few patients to

draw any firm conclusions about its efficacy.

Ursodeoxycholic acid (UDCA) is currently the only drug approved for

the treatment of PBC. Several randomized trials, combined analyses

and long-term observational studies have unequivocally shown that

this agent not only improves biochemical liver indices, but also

delays histological progression and prolongs survival.

Corticosteroids have for a long time been banned in the treatment of

PBC because of a lack of significant beneficial effect on liver

biochemistry in contrast to those noted in patients with autoimmune

hepatitis, and because of frequent adverse effects, particularly on

bone. Four short-term trials to date have been performed to assess

the role of corticosteroids as adjuvant therapy to UDCA. Three of

these clearly demonstrated that the combination therapy is superior

to UDCA alone in early-stage PBC.

First-line-medical treatment

To date, UDCA should be considered as the first-line treatment for

PBC. Daily doses ranging from 13 to 20 mg/kg/day as maintenance

therapy afford the optimal enrichment in biliary UDCA as well as the

most significant changes in liver biochemical tests. However,

because of the variable response to UDCA in terms of changes in the

enterohepatic circulation of endogenous bile acids as well as

induction of CYP3A, the time-honored " start low, go slow " approach

should be strictly adopted by monitoring the clinical and

biochemical response to slowly escalating UDCA doses. This approach

is crucial in patients having pruritus. To avoid prolonged time lag

in effective UDCA therapy, rifampin (300 to 600 mg/day) a potent

inducer of PXR, is recommended.

Second line-medical treatment

Progression of liver disease towards extensive fibrosis, cirrhosis

or to end-stage disease indicates resistance to or failure of UDCA

therapy. Predictors of failure have been defined under UDCA therapy

(Gastroenterology 2002, 122: 652). Based on the monitoring of these

indices, adjuvant therapies should be given as soon as possible in

order to avoid irreversible loss of bile ducts and progression

towards end-stage disease. Based on a prospective study designed to

assess causes and adjuvant therapeutic options in patients

presenting with predictors of long-term UDCA failure, the following

proposals are put forward.

UDCA plus prednisone plus azathioprine (or mycophenolate) should be

used because of the data showing that corticosteroids potentiate

UDCA therapy and vice versa. In addition rifampin should be given

because most patients present with pruritus. Azathioprine and now

mycophenolate allow corticosteroid sparing. Mycophenolate replaced

azathioprine after 2000 in our practice because azathioprine is a

risk factor for the development of nodular regenerative hyperplasia.

Indices of UDCA failure were associated with the following variant

forms of PBC:PBC/autoimmune hepatitis overlap syndrome, PBC with

some features of auto immune hepatitis but without definite

criteria, subacute vanishing bile duct syndrome or premature

ductopenic variant of PBC, nodular regenerative hyperplasia-

associated PBC, and PBC complicated by severe fatigue and lethargy

associated with poor compliance.

All the patients with features of autoimmune hepatitis respond to

the combination therapy and none of them were transplanted. Patients

with the variant forms characterized by subacute bile duct

destruction did not respond and needed transplantation. Non

compliant patients with lethargy also needed transplantation.

Patients with PBC and nodular regenerative hyperplasia responded

transiently but incompletely.

Conclusion

Patients with PBC not responding to UDCA therapy constitute an

heterogeneous group of patients with different variant forms of the

disease necessitating different therapeutic options. In our

experience combination therapy with UDCA plus corticosteroids and

mycophenolate suppressed the need for liver transplantation in

patients having the true overlap syndrome or in those having only

some features of autoimmune hepatitis. This medical option lacks

efficacy in the other variants of PBC and liver transplantation

remains in these settings the treatment of choice. Our experience,

which needs to be confirmed by other centers, further stresses the

great difficulty in carrying out large randomized trials in PBC.

____________________

I would imagine that this should also work in PSC. I find it

interesting that rifampin is considered a first-line therapy to

avoid pruritus in PBC!

Best regards,

Dave

(father of (20); PSC 07/03; UC 08/03)

[Guest guest]

Thanks Dave,In out case it wasn't a plan from the beginning, it just happened that way as we got more information through this group and the conference.I'm just wondering if [ when we gather our collective experiences ] people had an easier time increasing it gradually or if there are those that started with the 25 -30mg with no problems. If most had no problems with the higher dose from the beginning, then why wait?If however there are a number of people who couldn't tolerate the high dose, then maybe a gradual build up would be better?Lee Dea Lee; The idea of starting on a lower dose of ursodeoxycholic acid (UDCA) and then slowly working up, was developed in primary biliary cirrhosis PBC (see "First-line-medical treatment" section in this article): ____________________ Falk Symposium 142: GASTROENTEROLOGY WEEK FREIBURG 2004 (Part I) AUTOIMMUNE LIVER DISEASE, Freiburg (Germany), October 12 - 13, 2004, pp. 77-78 (2004) Treatment of primary biliary cirrhosis and overlap syndromes: current standards. Poupon R Service d'Hépatologie, Hôpital Saint-Antoine, Faculté P. et M. Curie, F-75571 Paris Cedex 12, France Background The low prevalence and the long and variable course of primary biliary cirrhosis (PBC)explain at least in part the great difficulty in conducting controlled trials of sufficient size, duration and power to detect a beneficial effect on survival or histological progression. Meta-analysis of short-term trials only told us that when PBC is accompanied by ascites and high levels of serum bilirubin, it is only treatable by liver transplantation. Critical review of past clinical trials revealed that most of them did not correctly select an homogenous group of patients in order to accurately define the power of the study and thus to determine if the tested drug could halt the progression of PBC. From all available data, we can say that drugs such as d-penicillamine and methotrexate lack efficacy in most of the patients with PBC; ciclosporine and azathioprine have some efficacy (improvement of survival from one to two years). Colchicine has been evaluated in too few patients to draw any firm conclusions about its efficacy. Ursodeoxycholic acid (UDCA) is currently the only drug approved for the treatment of PBC. Several randomized trials, combined analyses and long-term observational studies have unequivocally shown that this agent not only improves biochemical liver indices, but also delays histological progression and prolongs survival. Corticosteroids have for a long time been banned in the treatment of PBC because of a lack of significant beneficial effect on liver biochemistry in contrast to those noted in patients with autoimmune hepatitis, and because of frequent adverse effects, particularly on bone. Four short-term trials to date have been performed to assess the role of corticosteroids as adjuvant therapy to UDCA. Three of these clearly demonstrated that the combination therapy is superior to UDCA alone in early-stage PBC. First-line-medical treatment To date, UDCA should be considered as the first-line treatment for PBC. Daily doses ranging from 13 to 20 mg/kg/day as maintenance therapy afford the optimal enrichment in biliary UDCA as well as the most significant changes in liver biochemical tests. However, because of the variable response to UDCA in terms of changes in the enterohepatic circulation of endogenous bile acids as well as induction of CYP3A, the time-honored "start low, go slow" approach should be strictly adopted by monitoring the clinical and biochemical response to slowly escalating UDCA doses. This approach is crucial in patients having pruritus. To avoid prolonged time lag in effective UDCA therapy, rifampin (300 to 600 mg/day) a potent inducer of PXR, is recommended. Second line-medical treatment Progression of liver disease towards extensive fibrosis, cirrhosis or to end-stage disease indicates resistance to or failure of UDCA therapy. Predictors of failure have been defined under UDCA therapy (Gastroenterology 2002, 122: 652). Based on the monitoring of these indices, adjuvant therapies should be given as soon as possible in order to avoid irreversible loss of bile ducts and progression towards end-stage disease. Based on a prospective study designed to assess causes and adjuvant therapeutic options in patients presenting with predictors of long-term UDCA failure, the following proposals are put forward. UDCA plus prednisone plus azathioprine (or mycophenolate) should be used because of the data showing that corticosteroids potentiate UDCA therapy and vice versa. In addition rifampin should be given because most patients present with pruritus. Azathioprine and now mycophenolate allow corticosteroid sparing. Mycophenolate replaced azathioprine after 2000 in our practice because azathioprine is a risk factor for the development of nodular regenerative hyperplasia. Indices of UDCA failure were associated with the following variant forms of PBC:PBC/autoimmune hepatitis overlap syndrome, PBC with some features of auto immune hepatitis but without definite criteria, subacute vanishing bile duct syndrome or premature ductopenic variant of PBC, nodular regenerative hyperplasia- associated PBC, and PBC complicated by severe fatigue and lethargy associated with poor compliance. All the patients with features of autoimmune hepatitis respond to the combination therapy and none of them were transplanted. Patients with the variant forms characterized by subacute bile duct destruction did not respond and needed transplantation. Non compliant patients with lethargy also needed transplantation. Patients with PBC and nodular regenerative hyperplasia responded transiently but incompletely. Conclusion Patients with PBC not responding to UDCA therapy constitute an heterogeneous group of patients with different variant forms of the disease necessitating different therapeutic options. In our experience combination therapy with UDCA plus corticosteroids and mycophenolate suppressed the need for liver transplantation in patients having the true overlap syndrome or in those having only some features of autoimmune hepatitis. This medical option lacks efficacy in the other variants of PBC and liver transplantation remains in these settings the treatment of choice. Our experience, which needs to be confirmed by other centers, further stresses the great difficulty in carrying out large randomized trials in PBC. ____________________ I would imagine that this should also work in PSC. I find it interesting that rifampin is considered a first-line therapy to avoid pruritus in PBC! Best regards, Dave (father of (20); PSC 07/03; UC 08/03)

[Guest guest]

I would be OK with that but why take him to a lower dose than he was

already taking?

>

> > Thank you all so much! I have printed the abstract and the other

e-

> > mails and plan to approach his doctor as soon as possible. I mean

now

> > is taking half the amount they recommend for PSC, that is

not

> > right.

> >

> > Nichole Rowland (wife of PSC & UC 8/04)

> >

> >

> >

> >

>

[Guest guest]

,

Sorry, I missed that he was going down in dosage.

Hmmm. I guess this something that I would want to discuss with him.

The papers that support the 25-30mg dose are on file.

When we saw my son's Dr and requested the higher dose, we brought

copies of these papers.

Lee

> I would be OK with that but why take him to a lower dose than he was

> already taking?

>

>

> >

> > Dear Nichole,

> > I just wanted to say that being on this lower dose a short while

> is

> > not necessarily a bad thing. Some people need to get used the the

> > urso, it seems a very few have problems with it.

> > My son started out at what his Dr. called a high dose, 1,000mg and

> > then after I joined this group he went to 1,500 mg and then after

> the

> > papers recommending the 25-30 mg he went to 2,000mg.

> >

[Guest guest]

Did you ask the doctor why he was reducing his dosage?

in Seattle

> >

> > > Thank you all so much! I have printed the abstract and the

other

> e-

> > > mails and plan to approach his doctor as soon as possible. I

mean

> now

> > > is taking half the amount they recommend for PSC, that

is

> not

> > > right.

> > >

> > > Nichole Rowland (wife of PSC & UC 8/04)

> > >

> > >

> > >

> > >

> >

>

[Guest guest]

No apparently the doctor thought he was only taking 1000 mg/day but

wanted to increase it to 1500 mg/day. However, was taking

2000 mg/day. This was the only time I did not go to the doctor with

and it wasn't until he went to the pharmacy to get the

prescription filled that he realized the doctor had decreased the

dosage. The pharmacy called the doctor's office and we called but we

could only talk to the assistant, who assured us that the 1500 mg/day

was the dosage that he was suppose to take.

> >

> > Today they decreased my husband's dosage from 19 mg/kg/d to 14

> mg/kg/d.

> >

> > I think this is too low. What is the typical high dosage range?

> >

> > Thanks,

> >

> > Nichole Rowland (wife of PSC & UC 8/04)

> >

>

[Guest guest]

Since our calls have not worked. I think we need to make another

appointment to see the doctor to discuss this. The Hep said he didn't

need to see for 6 months but I don't think we should wait 6

months on a lower dose. I printed copies of those papers and we will

take them with us if we can get another appointment soon.

> > >

> > > Dear Nichole,

> > > I just wanted to say that being on this lower dose a short while

> > is

> > > not necessarily a bad thing. Some people need to get used the

the

> > > urso, it seems a very few have problems with it.

> > > My son started out at what his Dr. called a high dose, 1,000mg

and

> > > then after I joined this group he went to 1,500 mg and then

after

> > the

> > > papers recommending the 25-30 mg he went to 2,000mg.

> > >

>

[Guest guest]

Dear ,I would call your Dr. back, tell the assistant or who ever answers that while this is indeed the dose the Dr. prescribed , you know it was a mistake because the Dr. said that he wanted to increase his dose and instead it has actually decreased. Just say that you want to speak with the Dr. and tell them you want a call back. You should not have to make another appointment to correct this mistake! You should not have to wait to correct this mistake.Keep calling until you speak to him.This should be an easy mistake to fix if you speak with him.You could also have your pharmacist call to question the decrease.Lee Since our calls have not worked.  I think we need to make another appointment to see the doctor to discuss this. The Hep said he didn't need to see for 6 months but I don't think we should wait 6 months on a lower dose.  I printed copies of those papers and we will take them with us if we can get another appointment soon. > > > > > > Dear Nichole, > > > I just wanted to say that being on this lower dose a short while > > is > > > not necessarily a bad thing. Some people need to get used the the > > > urso, it seems a very few have problems with it. > > > My son started out at what his Dr. called a high dose, 1,000mg and > > > then after I joined this group he went to 1,500 mg and then after > > the > > > papers recommending the 25-30 mg he went to 2,000mg. > > > >

[Guest guest]

Lee -

Your advice is excellent. Another option is to write out the details,

including that there was misunderstanding of dosage. Define what dose

he was actually on at the date of the appointment and that the new

prescription dose was incorrect. You could also attach information

regarding URSO dosage recommendations. Take or mail this information

directly to his doctor and specify if you want to pick up the new

prescription, or have it mailed to you, or give telephone number of

pharmacy you want it called into.

Good luck.

Joanne

(, Ca)

>

> Dear ,

> I would call your Dr. back, tell the assistant or who ever answers

> that while this is indeed the dose the Dr. prescribed , you know it

> was a mistake because the Dr. said that he wanted to increase his

> dose and instead it has actually decreased. Just say that you want to

> speak with the Dr. and tell them you want a call back.