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Forum Name: Rheumatology Topics

Question: Medrol and methotrexate long term?


 dbacs - Tue Jan 31, 2006 10:14 am

I have been trying to get off of medrol and on to methotrexate only. I cannot get below 4mg of medrol or my ears and chronic hives flare up. I have been doing this for almost a year now and i cannot get off of medrol.

I have started methotrexate last month and it seems to help a little bit.

So as it seems i don't think I'll ever be able to get off the medrol.

Is 4 mg and methotrexate, 10mg, safe for long term use?

I am disabled when i am not on the medrol. I want to get on with my life. Can i TELL my doctor to keep me on the medrol?

I am 31 and 135 pounds in excellent health otherwise.
 R. Zein, Pharm D - Tue Jan 31, 2006 12:21 pm

User avatar Dear dbacs

Medrol belongs to group of medicines known as Glucocorticoids , which are are naturally occurring hormones that prevent or suppress inflammation and immune responses when administered at pharmacological doses

The severity of the adverse effects associated with prolonged administration of pharmacological dosages of corticosteroids increases with duration and frequency of therapy. Short-term administration of large doses typically does not cause adverse effects, but long-term administration can lead to adrenocortical atrophy and generalized protein depletion.

In your case, the dose you are taking is considered low. high doses per see are when we talk about dosing of i mg/kg, which is not the case in yours.

However, i may stress on the importance of patient education regarding possible symptoms which have been associated with chronic use and usually with high doses:

Glucocorticoids are responsible for protein metabolism, and prolonged therapy can result in various musculoskeletal manifestations, including: myopathy (myalgia, muscle wasting, muscle weakness), impaired wound healing, bone matrix atrophy (osteoporosis), and bone fractures. These effects are more likely to occur in older or debilitated patients.

Glucocorticoids interact with calcium metabolism at many sites, including: decreasing the synthesis by osteoblasts of the principle proteins of bone matrix, malabsorption of calcium in both the nephron and the gut, and reduction of sex hormone concentrations. Although all of these actions probably contribute to glucocorticoid-induced osteoporosis, the actions on osteoblasts is most important. Glucocorticoids do not modify vitamin D metabolism. Postmenopausal women, in particular, should be monitored for signs of osteoporosis during corticosteroid therapy.

Again , these symptoms occur mainly in elderly, not in young patients.

In addition, Corticosteroid therapy can mask the symptoms of infection and should be avoided during an acute viral or bacterial infection. Immunosuppression is most likely to occur in patients receiving high-dose (e.g., equivalent to 1 mg/kg or more of prednisone daily).

Also, various adverse dermatologic effects reported during corticosteroid therapy include skin atrophy, acne vulgaris, diaphoresis, impaired wound healing, facial erythema, striae, petechiae, hirsutism, ecchymosis, and easy bruising. Hypersensitivity reactions may manifest as allergic dermatitis, urticaria, and/or angioedema.

And very importantly, pharmacologic doses of corticosteroids administered for prolonged periods can result in physiological dependence due to hypothalamic-pituitary-adrenal (HPA) suppression. This inhibition decreases ACTH-mediated synthesis of endogenous corticosteroids and androgens by the adrenal cortex. The severity of glucocorticoid-induced secondary adrenocortical insufficiency varies among individuals and is dependent on the dose, frequency, time of administration, and duration of therapy. Administering the drug on alternate days may help to alleviate this adverse effect. Patients with HPA suppression will require increased doses of corticosteroids during periods of physiologic stress.

I am mentioning this to you, in case you decide to quit it one day, make sure to do it gradual, this is because HPA suppression can last for up to 12 months following cessation of therapy.

Other possible side effects can include hypercholesterolemia, atherosclerosis, fat embolism, hyperglycemia, increase in blood pressure due to fluid retention. Corticosteroids may also decrease serum concentrations of vitamin C (ascorbic acid) and vitamin A which may rarely produce symptoms of vitamin A deficiency or vitamin C deficiency

While on long term use of medrol, you should monitor the followings, blood glucose, PFTs, and serum potassium

Now to move to the next drug, which is Methotrexate , this drug also has immunosuppressive properties and can thus, exhibit anti-inflammatory activity, like medrol. together they can produce an additive effect. and the combination seems beneficial.

The most frequently reported acute adverse reactions associated with methotrexate include stomatitis, esophagitis, oral ulceration, nausea/vomiting, and abdominal distress. hepatotoxicity has been documented ,but in very high doses.

As for methotrexate , important monitoring parameters include CBC with differential, LFTs: in patients receiving prolonged oral therapy, serum creatinine/BUN and serum uric acid

I should mention to you, that if you are using methotrexate for anti-inflammatory purpose, the dose is usually 20 mg/day. not 10 mg daily.

Finally, as for any possible interaction between the two drugs, there has been no documented interaction between the two drugs, however, since i said before, that both drugs cause immunosuppression, be careful, that these drugs can mask the symptoms of infection, and remember to monitor for any possibilities of drug-induced side effects.

Thank you very much, and i hope you always feel great
 dbacs - Wed Feb 01, 2006 12:08 am

Wow thank you that was a huge amount of information.

Ok well i actually got a lot of positive things in that info, even though there are a lot of bad side effects that you listed.

For instance the low dose i am receiving seems positive because even though i am at 4-8mg some days i can go without taking it, but usually not for more than two days.

Also i didn't know that Methotrexate can be taken up to 20 mg. This seems like it means that i can increase my methotrexate dosage and decrease my medrol dosage.

I have taken some steps to ensure some protection while on these meds. I have been consuming a protein shake 2-3 times a day. The protein shake has a good profile of amino acids and a high dose of protein. This seems like it will prevent protein wasting and muscle catabolism. In fact i think because i'm on the medrol my protein shake gets metabolised better than when i'm not on medrol.

I have also read that L-Glutamine is beneficial to those taking Methotrexate. Do you have any info on this topic? I have found information regarding this on Medline. L-Glutamine is in my protein shake.

Lastly i am thinking about adding Milk Thistle and Sam-E to my supplement regimen to offset any harmful side effects to my liver. I have also quite drinking alcohol, for 3 years now. Do you have any info on Milk Thistle and Sam-E in regards to liver protection?

Thanks again for all you help. Very much appreciated.
 R. Zein, Pharm D - Wed Feb 01, 2006 11:04 am

User avatar DEAR dbacs

i will discuss your questions shortly, i have been mistaken about the dose of methotrexate in my first response. i meant to say 20 mg/week and not 20 mg/dayfor anti-inflammatory indications.


i apologize for that, and please, do not increase your medication dose without asking your doctor.

thank you very much
 R. Zein, Pharm D - Thu Feb 02, 2006 8:58 am

User avatar Dear Dbacs

L-glutamine is a protein amino acid found in proteins of all life forms. It is classified as a semi-essential or conditionally essential amino acid. This means that under normal circumstances the body can synthesize sufficient L-glutamine to meet physiological demands. However, there are conditions where the body cannot do so.

Recently, L-glutamine has come to be regarded as one of the most important of the amino acids when the body is subjected to such metabolic stress situations as trauma (including surgical trauma), cancer, sepsis and burns. Under such conditions, L-glutamine becomes an essential amino acid, and it is therefore very important to ensure adequate intakes of the amino acid in order to meet the increased physiological demands created by these situations.

And when it comes to taking this protein while on methotrexate, there is one report that methotrexate may decrease the possible effectiveness of supplemental L-glutamine for chemotherapy-induced mucositis. In another report, nine patients with breast cancer were reported to have decreased symptoms of methotrexate-related toxicity when given supplemental L-glutamine at a dose of 0.5 gram/kilogram/day.

Doses of L-glutamine up to 21 grams daily appear to be well tolerated. Reported adverse reactions are mainly gastrointestinal and not common. They include constipation and bloating. There is one older report of two hypomanic patients whose manic symptoms were exacerbated following the use of 2 to 4 grams daily of L-glutamine. The symptoms resolved when the L-glutamine was stopped. These patients were not rechallenged, nor are there any other reports of this nature.

I have attached below a couple of references regarding this topic , in case you are interested.


Wilmore DW, Schloerb PR, Ziegler TR. Glutamine in the support of patients following bone marrow transplantation. Curr Opin Clin Nutr Metab Care. 1999;2:323-327.

Huang EY, Leung SW, Wang CJ, et al. Oral glutamine to alleviate radiation-induced oral mucositis: a pilot randomized trial. Int J Rad Oncol Biol Phys. 2000;46:535-539.

Now to address the issue of using milk thistle and the other herb you have mentioned, milk thistle is known " to be the liver herb".... it has the following advantages:

• Protects the liver from damage due to alcohol and chemicals
• Assists regeneration of liver tissue
• Detoxifies the blood
• Useful in the treatment of cirrhosis, hepatitis and fatty liver

Milk Thistle yields three main active compounds known collectively as Silymarin, which work in a number of ways to restore liver health. Firstly, Silymarin inhibits the factors responsible for causing liver damage. As well, it increases the liver's content of a substance called glutathione which is responsible for detoxifying many chemicals, drugs and hormones. Silymarin also stimulates the growth of new liver cells so that damaged areas of the liver may be regenerated

It is essential that the Milk Thistle extract you choose is standardised to provide a minimum amount of Silymarin in each dose. Without this you have no way of knowing how much of the herb's active constituents are present in the supplement.

Milk thistle is widely available, at health food stores, and even some drug stores and grocery stores. The standardized extract that has been widely tested and has also been approved in Germany for liver disease and functional liver impairment contains 70 to 80 percent silymarin. Dosage recommendations are usually on each bottle, and should be discussed with an individuals medical practioner, but a general guide offered by some for an adult humans use is 420 mg. of silymarin taken in 3 divided doses daily. If there is no liver damage, and you simply want to protect your liver from damage, it is often recommended that an adult human use around 280 mg. of silymarin daily.

Thank you very much, and my best wishes to you...
 Dr. P. M. Aries - Sat Feb 04, 2006 7:20 am

User avatar I have followed the dicussion and would like to make some more notes.

First of all what kind of diagosis do you have ? Rheumatoide Arthritis ?
The combination of medrol and MTX is the standard therapy in the whole world. Even 4mg medrol are beneficial, because some publications have seen some protective effects by the small dosage for the boneersosions, but also some have not seen this effect. Anyway, if your body tells you that below 4mg medrol is impossible there are two possiblities: Stay with 4mg or increase MTX up to 0,3mg per kg body wight a week (we are using a maximum of 25mg pwer week in europe). But, I tell my patients that 4mg merdol is absolutely perfect if disease activity is absent, therefore I would not increase MTX.
 dbacs - Sat Feb 27, 2010 4:49 pm

Hi,

This is very ironic but i was searching the net about methotrexate and protein matabolism and found one of my old topics. I was searching this because lately i've been losing weight or muscle, and have had "fibromyalgia-like" symptoms (according to my doc).

This past week i've tried eating more and adding dhea plus weight lifting and it seems to be helping somewhat. I've tried all these things before but seperately with no success.

Can anyone tell me if methotrexate, dhea and xolair is safe? I'm taking 7.5mg methotrexate, 2 shots of xolair once a month, and 50mg dhea in the morning and afternoon. I really feel much better with this "coctail" but i want to still add more muscle/weight.

I'm 5'2", 130lbs, and having 2000-3000 calories daily, with about 60 grams of protein. I want to double this by adding a shake but don't know if i should.

To update, since its been 4 years since i last posted, i lost my hearing in both ears (autoimmune). Got a cochlear implant in left ear which restored 80% hearing. Got left knee replacement and have controlled my hives pretty well. Since starting to weight lift and adding dhea hives have been gone, i have more energy and no "fibro-like" symptoms.

I want to keep doing what i'm doing, is it safe?

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