PRESCRIBED MEDICATIONS
Thomas Shaw-Stiffel, MD,
Medical Director,
Living Donor Liver
Transplantation
Univ of
March
2003
Question
6
In light of the recent info about
Tylenol and its effects, is it still the best pain reliever for those of
us with PBC and arthritis? Has the maximum dose changed in light of this
info? It seems to me that our livers are already compromised and Tylenol,
which is not recommended for alcoholics or those drinking alcohol, would
affect us adversely.
Answer
6
I still recommend mild-moderate
doses of Tylenol (no more than 4 grams total a day, that's about 8 extra-strength
since each tablet is 500 mg) since it's safe unless
the patient is drinking a lot of alcohol or has advanced liver cirrhosis
(awaiting liver transplant). Far safer than the ASA or NSAIDs which can affect
platelet (the tiny blood cells that stop bleeding) or kidney function and
could cause stomach ulcers or even contribute to causing bleeding from varices
(large vessels due to cirrhosis in the esophagus and
stomach).
Howard J. Worman, M.
D.
Associate Professor of Medicine and Anatomy and
July
2003
Question 2
Why is CellCept being used in non-transplant, non-renal
patients? What are the Benefits? Side Effects? Do
you know of studies done?
Answer 2
Mycophenolate mofetil (CellCept) is an immunosuppressive agents used to prevent
allograft (transplanted organ) rejection. As PBC is likely an autoimmune
disease, some investigators have hypothesized that mycophenolate mofetil
may be useful as a treatment. Nobody knows yet if it will work in PBC.
Mycophenolate mofetil is not approved for the treatment of PBC and a patient
should not take this medication unless it is part of an IBR-approved clinical
trial. I am aware of at least one trial of mycophenolate mofetil in patients
with PBC.
Howard J. Worman, M.
D.
Associate Professor of Medicine and Anatomy and
July
2003
Question 5
Have there been any studies done on post-TX medications like Prograf and
Rapamune causing Joint and Muscle Pain? Or leading to osteoporosis?
Answer 5
I am not aware of any studies that have specifically looked at tacrolimus
(Prograf) or sirolimus (Rapamune) causing joint and muscle pain. However,
in clinical trials of these drugs, patients have reported these symptoms.
Osteoporosis is known to occur at an increased frequency after organ
transplantation and is probably aggravated by anti-rejection medications.
A few studies in laboratory animals suggest that bone loss may be faster
with cyclosporine A, somewhat less with tacrolimus and even less with sirolimus.
I am not aware of similar studies in human subjects but it is possible that
they have been done. If you are interested in published studies, you may
want to know about the National Library of Medicine resource Pub Med. You
can search the medical literature using Pub Med on the Internet. The URL
is:
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed
David Bernstein,
M.D.
Chief, Division of
Gastroenterology
July 2000
Question 1:
a. How safe are Darvocet, Celebrex and Vioxx for arthritis pain in a person
with PBC?
Answer 1a
All of these medications are safe when used in regularly prescribed
doses.
Patients with esophageal varices should use Vioxx or Celebrex with caution.
Darvocet contains 650 mg of acetaminophen so no more than 3 pills a day should
be
taken by people with PBC.
David Bernstein,
M.D.
Chief, Division of
Gastroenterology
July 2000
Question 22:
Is it recommended for patients
with PBC to have the Pneumonia vaccination? What about hepatitis A and B
vaccines?
Answer
22
I generally recommend that my PBC
patients take the pneumonia vaccine. I also encourage both hepatitis A and
B vaccination if there is no previous evidence of exposure to these viruses.
David Bernstein,
M.D.
Chief, Division of
Gastroenterology
July 2000
Question 24:
What GI problems can result from
taking Fosamax for extended periods of time? Also, can a teaspoon of Cod
Liver Oil deliver the vitamin D needed for the body and the absorption of
calcium when taking Fosamax?
Answer
24
In general, Fosamax is a safe
medication. It has, however, been associated with the development of esophageal
ulcers and bleeding from these ulcers. The risk of these complications is
greater in people with abnormalities of the esophagus such as strictures
or varices. It is important to take Fosamax with plain water, not coffee,
tea, juice or mineral water and not to lie down for at least 30 minutes after
taking Fosamax.
Fosamax may also cause abdominal
pain, worsen gastroesophageal reflux disease, lead to increased flatulence
and lead to the development of nausea and vomiting.
Fosamax use may lead to the development
low levels of calcium in the body. It is important to ensure adequate calcium
and vitamin D intake while on Fosamax. There are many sources for supplementing
vitamin D intake. One teaspoon a day of cod liver oil contains 340% of the
recommended daily allowance of vitamin D. Although it makes sense that cod
liver oil use can deliver the vitamin D needed while on Fosamax therapy,
there are no published scientific studies performed to date to substantiate
its use.
Dr. Marshall
Kaplan
Chief, Division of Gastroenterology
December 1999
17.) Is methotrexate indicated
for all PBC patients, or only those who don't respond to ursodiol?
Answer
I now use methotrexate in patients
who have failed to respond to ursodiol alone or ursodiol plus colchicine.
As you are probably aware, this is a controversial area in PBC. I have been
using methotrexate in PBC since 1986 and find that it is very effective in
many patients, particularly those who fail to respond to ursodiol and colchicine.
What I have found is that patients respond quite differently to medical
treatment. I don't know whether this means that PBC is more than one disease,
what we call a syndrome, or whether it is the same disease but with different
responses to treatment.
Dr. Marshall
Kaplan
Chief, Division of Gastroenterology
September,
1999
Dr. Kaplan gives us his thoughts
on the following article
Methotrexate and transplantation
WESTPORT, Aug 30 (Reuters Health)
- In patients with primary biliary cirrhosis, the risk of death or
transplantation is increased nearly threefold with long-term use of low-dose
methotrexate, according to the results of a 6-year, placebo-controlled study.
Dr. Mark T. Hendrickse and colleagues
at
Patients treated with methotrexate
had significantly lower "...serum alkaline phosphatase,
gamma-glutamyltransferase, [IgM], IgG, and (after 24 months) aspartate
aminotransferase and alanine aminotransferase levels..." than controls. On
the other hand, clinical factors, such as Knodell inflammatory scores and
pruritus scores, were not significantly different between the two groups.
Moreover, patients randomized to
low-dose methotrexate actually had an increased risk of death or liver
transplantation, with a relative risk of 2.9, though this association did
reach statistical significance.
The findings, published in the
August issue of Gastroenterology, indicate that use of methotrexate in patients
with primary biliary cirrhosis should be limited to the clinical trials setting,
Dr. Hendrickse and colleagues conclude. They point out that higher doses
of the drug may have enhanced efficacy in this population, but this was not
tested in the current study.
Elsewhere in the journal, Drs.
Paul Angulo and E. Rolland Dickson of the Mayo Clinic and Foundation in
Rochester, Minnesota, point out the apparent dichotomy between the effects
of low-dose methotrexate on biologic outcomes and clinically relevant outcomes
in the British study. They suggest that the biologic markers studied may
not be accurate predictors of disease status, a conclusion that is supported
by other studies, as well.
The editorialists note that several
promising drugs are currently in development for the treatment of primary
biliary cirrhosis, but that ursodeoxycholic acid should remain the initial
treatment for this disease until further data are available.
Date: 9/10/99 8:46:01 AM Central
Daylight Time
As you can see, this is a controversial
area. The British investigators used approximately one half of the dose that
I and others have found to be the minimally effective dose. A colleague and
I have published a paper in the same issue of Gastroenterology that indicates
that methotrexate improves blood tests and liver biopsy findings in patients
who respond incompletely or not at all to ursodiol. I am in the tenth year
of a double-blind trial comparing methotrexate plus ursodiol to colchine
plus ursodiol, but, because of the nature of the study, do not have any survival
results yet. All that I can say is that methotrexate appears to be effective
in my patients, but that I only use it in patients who have not responded
fully to ursodioal or colchicine.
Dr. Andrew
Mason
Medical Director of Liver
Transplantation Ochsner Clinic
Assistant Professor of Medicine,
Tulane University Medical Center
Assistant Professor of Microbiology,
Immunology, and Parasitology, Louisiana State University Medical Center
New Orleans,
La
August 2000
Question
15
Are long term antibiotics bad for
PBC?
Answer
15
As long as they are required and
not causing undue problems, long term are OK for patients with PBC. In fact,
long term non-absorbed antibiotics are used to treat hepatic encephalopathy,
if patients become confused from severe liver disease.
Dr. Melissa
Palmer Answers Our Questions
Specialty:
Gastroenterology and Hepatology
Medical advisory board of the ALF
New York Chapter
ALF National Chapter Nutrition
Education Subcommittee
January
2000
9.) Is there any current data or
can you share information on the long term effects of immunosuppressive
medications - such as Neoral, Prograf and Cyclosporin? There were indications
that Prograf had more toxicity incidents, is this still the case? We all
have concerns regarding the neuro and renal toxicities, malignancies, diabetes,
etc.; and having some information on these medications would help in deciding
which may be a better option.
Answer
Cyclosporine (Neoral) may cause
kidney failure, but this is readily reversible upon lowering the dosage.
Due to changes in sugar and fat metabolism caused by cyclosporine, the patient
may be at increased risk of hypertension and heart disease. Neoral may also
affect the central nervous system -seizures, numbness, confusion, and
hallucination have been experienced by some people while on therapy &
nbsp; Increased hair growth, especially in brunettes, is common. An enlargement
of the gums may occur often necessitating surgical correction. There also
appears to be an increased risk of cancer.
Tacrolimus (FK 506
oe Prograf) has similar side effects to those of
Neoral. Tacrolimus has been associated with greater kidney and neurological
damage according to some, but not all studies. People may experience insomnia,
headache, and decreased alertness. Diabetes may occur, requiring an adjustment
in dosage. Hypertension and high cholesterol levels can occur but less frequently
than with Neoral. Less weight gain after transplantation has been noted in
patients. Some studies, although not all, have shown that a higher percentage
of people may live longer after transplantation if placed on tacrolimus.
Dr. Howard
Worman
Division of Digestive and Liver
Diseases
Departments of Medicine and of Anatomy and Cell Biology
College of Physicians & Surgeons
Columbia University
New York, NY 10032
April 2000
19. If immunosuppression can help
prevent recurrence of PBC, isn't it plausible that immunosuppression could
help deter the disease if it were provided in the early stage?
Answer
I'm not entirely sure of what you
mean by "prevent the recurrence of PBC." I'll assume that you mean after
liver transplantation. If so, this is not the same situation from an
"immunological point of view" as the natural disease. Proteins on the cells
of the transplanted liver that play important roles in recognition by the
immune system are different. To put this another way, the new liver may not
be susceptible to PBC. In addition, the cellular targets recognized by the
immune system in transplant rejection are probably very different from whatever
targets are recognized in PBC (nobody know what they are in PBC). Therefore,
immunosuppression that keeps allograft rejection in check may not significantly
deter the immune response against the liver in PBC.
Most trials of immunosuppressive
agents to treat PBC have been disappointing. Corticosteroids, azathioprine,
cyclosporin A, chlorambucil and methotrexate have all been tested and no
trial has shown conclusive positive results. Trials of other immunosuppressive
agents are currently in progress.
I should also comment the phrase
"early stage" in reference to PBC. PBC is never really diagnosed until the
person has some liver disease. It’s really not possible at this time
to know who might develop PBC before there is already liver involvement.
Dr. Howard
Worman
Division of Digestive and Liver
Diseases
Departments of Medicine and of Anatomy and Cell Biology
College of Physicians & Surgeons
Columbia University
New York, NY 10032
April 2000
Question
25
This may be a radical thought,
or maybe one already considered and dismissed for good reason: Since many
of us have autoimmune diseases other than just PBC, I was wondering if the
drugs used to suppress the immune system after transplant (which probably
decreases the chance of PBC recurring) could be used as therapy years before
transplant in order to control the symptoms of many of our autoimmune diseases.
Answer
Many medical investigators are
considering your thought and it is neither "radical" nor has it been "dismissed
for good reason." Some of the same drugs used to prevent transplant rejection
such as tacrolimus, cyclosporin A and mycophenolate mofetil are being
investigated in the treatment of various autoimmune disorders. More studies
are necessary at this time.
Dr. Howard
Worman
Division of Digestive and Liver
Diseases
Departments of Medicine and of Anatomy and Cell Biology
College of Physicians & Surgeons
Columbia University
New York, NY 10032
April 2000
Question
27
Does Methetrexate, Urso or chocline
(sp) cause weight gain? Why? Any methods to control it?
Answer
I am not aware of methotrexate,
ursodiol or cholchicine causing significant weight gain.
Dr. Hugo
E. Vargas
Medical Director,
Transplantation
University of
Pittsburgh Medical Center
Pittsburgh,
PA
June 2000
15.) Is "benign essential tremor"
(shakiness of hands & voice) connected in any way to PBC. Medication
for this condition is Topiramate (topamax). I understand the medication is
metabolized mainly by the kidney and usually the person is on it indefinitely.
Could this medication cause problems in the liver?
Answer
Topamax can be poorly metabolized
in liver disease. However, this is not an area in which I am an expert and
your treating clinician should be consulted about this issue. Benign essential
tremor can coexist with PBC but I am not aware of any links between the
disorders.
Dr. Nathan
Bass
Professor of Medicine, Medical
Director, Liver
Transplantation
Program,
University of
California
San
Francisco
2000-2001
10.) Why is it that so many with
PBC have terrible bone aches and pains? Is it just PBC or all liver diseases?
What do you recommend we take for the pain?
Answer
Many types of liver disease may
be complicated by bone thinning, but this problem is clearly worst in PBC.
The loss of mineral (calcium) from bone in PBC is the main cause of bone
pain, and is most incapacitating when this leads to fractures or collapse
of vertebra from the weakening of bone structure. Rarely, an inflammation
of the fibrous cover of the bone may also occur (periostitis). The factors
causing bone loss in PBC include postmenopausal hormone changes in women,
poor absorption of calcium and vitamin D from the digestive tract, and factors
that accumulate in the blood stream in cholestasis that inhibit the cells
that form the bone, while there is increased activity of the cells that remodel
or remove bone tissue. Other genetic factors that determine the way an individual
responds to vitamin D may also play a role. The bone pain in PBC can be
tremendously disabling, and fortunately, can be prevented by well-timed liver
transplantation. Further bone loss should be prevented by appropriate treatment
with calcium, vitamin D, hormone replacement and bone-building medications
such as alendronate.
The pain should be treated with
painkillers as strong as needed, but not non-steroidal anti-inflammatory
drugs (e.g., Ibuprofen), as these can cause gastrointestinal bleeding in
patients with portal hypertension. Some of the newer so called COX-2 selective
drugs like Celebrex or Vioxx may be effective and safer, but are untested
in this situation and are considered contraindicated in patients with liver
disease. They occasionally have caused serious internal bleeding. Opiate
painkillers will help, but are habit forming and sedating and worsen
encephalopathy. This is a difficult problem to treat satisfactorily once
it has progressed to an advanced stage.
The Mount Sinai
Medical Center
New York, New York 10029
October 1999
2.) I tend to get nasal and chest
congestion that is allergy related. It doesn't happen often, but when it
does I take Allegra and Entex, as well as using a Vanceril inhaler. Are these
meds safe for PBCers? If not, what is acceptable?
Answer
Allegra (an antihistamine), Entex
(a decongestant) and Vanceril are relatively safe drugs for patients with
PBC. Drugs similar to Allegra can cause irregularities in the heart rhythms
of patients with liver disease. This is because of the way the drug is
metabolized or broken down. The medications that you are referring to are
unlikely to be a problem in patients with liver disease, however, any medication
has the potential to cause toxicity to the liver. You should therefore always
discuss medication use with your doctor.
The Mount Sinai
Medical Center
New York, New York 10029
February 2000
8.) Are there guidelines for
prescribing thyroid medication for PBC patients with low thyroid that are
any different from such patients without PBC?
Answer
Thyroid disease is often associated
with PBC, and is treated the same as it would be for a non- PBC patient.
Though the two diseases are associated with each other, they are treated
independently.
The Mount Sinai
Medical Center
New York, New York 10029
February 2000
15) Since I've been taking prevalite
I have been experiencing muscle aches and pains in my back, hips and knees.
Could this be a side effect of the drug? I take two packets a day in the
morning for the itching. If this is a side effect of the drug, would you
advise your patient to stop taking it? Is there something you would prescribe?
Answer
Prevalite (cholestyramine) should
not cause the symptoms you describe. However, any drug is capable of causing
any side effect in a given individual. Under your doctor's supervision, you
might want to discontinue the therapy for a week or so and see if the symptoms
resolve. If they do, I would recommend testing the medication again in a
few weeks to see if the symptoms are truly due to the Prevalite.
Alfred L. Baker, M.D.
Division
of Gastroenterology & Hepatology
Northwestern
Memorial Hospital
Chicago, IL
8/20/2002
Question 22
a. What opinion do you hold regarding hormone replacement therapy (premarin)
and its role in PBC?
b. If a person has taken hormone replacement for 20 + years do researchers
have any idea the affect it has on the PBC?
Answer 22
Several recent studies consider the benefits of hormonal replacement therapy
on cardiovascular disease and the risk of complications such as breast cancer.
I encourage my patients to consult their gynecologists to make a decision
about whether they should take hormonal replacement therapy to suppress
menopausal symptoms or for other reasons. However, hormonal replacement therapy
ordinarily does not injure the liver, even over many years of treatment.
It is reasonable to consider hormonal replacement by patch rather than by
mouth to minimize the liver's exposure to
medication.
Alfred L. Baker, M.D.
Division
of Gastroenterology & Hepatology
Northwestern
Memorial Hospital
Chicago, IL
2000-2001
3.) Do you think those with PBC
need immunizations for Hepatitis B & C? How about flu shots?
Answer
I recommend immunizations against
Hepatitis A and B for my PBC patients who are not immune to these diseases.
Infection with Hepatitis A or B might have more serious consequences in a
patient with underlying liver disease such as PBC. Both vaccines are quite
safe. Influenza vaccination also seems appropriate, particularly for older
patients with PBC, for those with more severe liver disease, and for those
with additional medical disorders such as heart disease or lung disease.
Alfred L. Baker, M.D.
Division
of Gastroenterology & Hepatology
Northwestern
Memorial Hospital
Chicago, IL
2000-2001
Question 8. What is the best method
of HRT for PBCers? ESTROGEN by mouth, is it safe to use with PBC?
Answer
8
Estrogen supplementation is generally
safe for patients with primary biliary cirrhosis. On occasion, a patient
taking estrogen supplements by mouth may have mild worsening of some liver
chemistry tests, so I generally recommend repeat liver chemistry tests a
few weeks after beginning such medications.
If the change is slight, it is
probably reasonable to continue oral estrogen therapy. Estrogens given by
patch are almost always well tolerated and represent another alternative
for taking this supplement.
Nathan M. Bass, MD, PhD
Professor of Medicine
Medical Director, Liver Transplantation Program
University of California, San Francisco
11/4/2002
1c. What medications can be used
safely with PBC to control depression if needed?
Answer 1c
Almost all commonly prescribed antidepressants are safe to use in PBC. The
class of drugs known as selective serotonin reuptake inhibitors (SSRI's)
are commonly prescribed with good results. Prozac belongs to this class of
agents, but has a very long half-life so side effects can hang around longer
after the drug is stopped. For this reason, other types of SSRI drugs are
preferred. Antidepressants are often used to alleviate itching too - doxepin
is a good example, although its effects against itching are broader than
just that of a mild antidepressant action.
Nathan M. Bass, MD, PhD
Professor of Medicine
Medical Director, Liver Transplantation Program
University of California, San Francisco
11/4/2002x
Question 5
a. Does elevated lipoprotien X in PBC cause LDL to be elevated?
b. Are they related?
c. Should elevated cholesterol due to elevated LDL in someone with PBC be
treated with medication?
d. If so, which medication would be safest?
Answer 5
This is a complex topic. Lipoprotein X contributes more to the HDL lipoprotein
fraction of cholesterol in blood, and the HDL is commonly elevated in PBC.
LDL may also be elevated, but not in all patients. The elevated cholesterol
in PBC is not clearly associated with an increased risk of coronary artery
disease, so the need for treatment is often difficult to define. If the is
clear elevation in LDL, however, and the patient has other risk factors for
heart disease including high blood pressure, a strong family history of heart
disease, diabetes, of a recent smoking history, then a statin drug may reduce
their risk of a heart attack. Liver enzymes may rise with statins several
appear safe, although fluvastatin has been the safest in my
experience.
Henry C. Bodenheimer, Jr., MD
Chief, Division of Digestive Diseases
Beth Israel Medical Center
First Ave at 16th Street
New York, NY 10003
8/2/2003
Question 1
What is your opinion of PBCers taking cholesterol lowering drugs, particularly
statins? Which, if any, is the safest to take? What about Milk Thistle?
Answer 1
Statins are particularly effective agents to lower cholesterol. The need
for cholesterol lowering agents in PBC is complicated by the fact that the
cardiac risk related to cholesterol elevation as a consequence of PBC is
not the same as risk from cholesterol elevation in the absence of liver disease.
However, some patients with PBC may have independent risk factors for coronary
artery disease such as a strong family disease of arteriosclerotic heart
disease, diabetes or smoking. Obviously, improvement in diet, avoiding smoking
and engaging exercise are the first steps to take. After this weight reduction
is often beneficial and medication is used last. A safe although less effective
alternative is the use of Welchol, however, if all these steps are ineffective,
and risk factors are present I have used statins in patients with PBC. These
drugs can be used safely, and since they also have an immune suppressive
effect studies are ongoing to look at a potential beneficial effect of statins
on the liver disease of patients with PBC. The major concern of statins is
they have been associated with elevation of biochemical liver tests.
I recommend that my patients with liver disease who use statins have liver
function tests monitored particularly during the first year of treatment.
Minor elevations of aminotransferase values (ALT, AST) is not a reason for
drug discontinuation but progressive rise is. The development of serious
liver injury with statins is quite unusual. Thus, in those patients who are
at high risk for development of arteriosclerotic heart disease and who have
cholesterol unresponsive to lifestyle modification I would use statins monitoring
liver tests periodically.
I am not aware of a significant difference in liver injury among the statins
and would treat each of the medications similarly. There is some difference
in the immune modulatory activity and some difference in the effectiveness
of cholesterol lowering.
Milk Thistle appears to be a safe adjunctive medication although it is of
limited value.
Henry C. Bodenheimer, Jr., MD
Chief, Division of Digestive Diseases
Beth Israel Medical Center
First Ave at 16th Street
New York, NY 10003
8/2/2003
Question 2
Am I correct in assuming that those with PBC should not take smallpox vaccine?
What are your thoughts about a PBCer living with others who have had the
vaccine?
Answer 2
The smallpox vaccine is not recommended for the general population. Those
with significant illnesses including PBC should not be the first volunteers
for this vaccine. However, if the unfortunate event occurs where smallpox
becomes a significant risk for those living in the United States, reassessment
of the wisdom of taking the smallpox vaccine would be made on a case by case
basis, depending upon the immune function and general health of the patient.
As regards spread of smallpox from a close contact, the smallpox vaccine
is a live vaccine and individuals who are immune compromised may be at increased
risk particularly when blistering lesions are present. The current methodology
calls for a cover for the vaccine area, which makes the risk small.
Thomas Shaw-Stiffel, MD,
MMM Medical Director,
Living Donor Liver Transplantation
Univ of Pittsburgh Medical Center
Presbyterian Hospital
Center for Liver Diseases
Pittsburgh,
PA
9/22/03
Question 3 Can thyroid medication
increase the metabolism and therefore speed up the progression of PBC. What
are your thoughts about that concept?
Answer 3 Interesting idea but I'm
not aware of any literature on this topic. If anything, most patients with
pbc have low thyroid function and need the meds, not reported to cause problems
as long as given in correct doses and thyroid tests watched carefully by
the patient's doctor.
Howard J. Worman, M. D.
Associate Professor of Medicine and Anatomy and Cell Biology
College of Physicians and Surgeons
Columbia University
New York, NY
9-29-03
Question 6
When taking Vitamin A shots can there be side effects and if so what are they?
Answer 6