Re: ASK THE EXPERTS - Does folic acid reduce the toxicity of MTX?

[Guest guest]

Fortunately our supply of wild folics is not endangered as the run free and wild

across the great expanse of the Russian tundra, so there's enough acid

available for all who need it. I've never actually seen a " wild " folic but I'm

told they are very small and hard to catch. It must be mind boggling to collect

that much acid.

Stan,

Seattle, Rain.

[ ] ASK THE EXPERTS - Does folic acid reduce the toxicity of

MTX?

Does Folic Acid Reduce the Toxicity of Methotrexate?

From Medscape Pharmacists

Ask the Experts about Pharmacotherapy

Posted 02/19/2009

Joanna Pangilinan, PharmD, BCOP

Question

Should folic acid or folinic acid be given to patients receiving

long-term, low-dose methotrexate for rheumatoid arthritis?

Response from Joanna Pangilinan, PharmD, BCOP

Pharmacist, Comprehensive Cancer Center, University of Michigan Health

System, Ann Arbor, Michigan

Methotrexate (MTX) inhibits dihydrofolate reductase, resulting in a

decreased supply of folates. In high doses, MTX inhibits purine and

pyrimidine synthesis, rendering it useful for many malignancies. In

low doses (< 20 mg/week), MTX is commonly used as a disease-modifying

antirheumatic drug and is indicated for treatment of rheumatoid

arthritis (RA).[1] MTX's mechanism of action for this indication is

unclear. Efficacy of low-dose MTX may ultimately be the result of

anti-inflammatory,[1] immunosuppressant, or immunotoxic effects.[2]

Adverse effects of low-dose MTX in patients with RA are related to

folate antagonism and/or folate deficiency. Folate supplementation, in

the form of folic acid or folinic acid, is often coadministered with

MTX to minimize adverse effects (eg, stomatitis, gastrointestinal

intolerance, bone marrow toxicity, and abnormal liver function

tests).[1]

Studies have examined the effectiveness of folate supplementation in

decreasing adverse effects associated with low-dose MTX. A Cochrane

Review evaluated 7 randomized, double-blind, placebo-controlled trials

that assessed whether folinic acid or folic acid decreased side

effects of MTX in patients with RA. Both folinic acid and folic acid

were found to decrease gastrointestinal and mucosal side effects. The

use of folinic acid, however, may not be cost-effective unless

pharmacoeconomics studies find it to be more clinically effective than

the less expensive folic acid.[3]

A recent study by van Ede and colleagues[4] evaluated the effect of

folate supplementation on MTX-induced adverse effects in patients with

RA. Folic acid was dosed at 1 mg daily and folinic acid was dosed at

2.5 mg weekly; doses were doubled if the MTX dose reached 15 mg

weekly. Folate supplementation decreased the incidence of elevated

liver enzymes compared with placebo. However, folate supplementation

was not shown to decrease gastrointestinal or mucosal side effects.

Hoekstra and colleagues[5] found that patients on folate

supplementation remained on therapy longer, resulting in " MTX

survival " and more durable control of RA symptoms.

While some studies suggest MTX efficacy is not compromised by folate

supplementation,[3,4] results of a post hoc analysis[6] advised

caution[7] and suggested folic acid supplementation may decrease MTX

efficacy. Folic acid supplementation[4] and dietary fortification with

folic acid[8] may increase MTX dosage requirements.

Total weekly folic acid doses in the range of 5-27.5 mg have

demonstrated efficacy in decreasing MTX adverse effects. Weekly vs

daily schedules have not been compared.[1] Whittle and [1]

recommend the " pragmatic " use of folic acid 5 mg once weekly taken the

morning after MTX dosing, with a possible dose increase to 10 mg if

adverse reactions continue. Others suggest that prophylactic folate

supplementation should be reserved for those who have an increased

demand for folate, such as during infection or antibiotic

treatment.[9] If folic acid is initiated, evidence suggests that it

should continue long-term in order to prevent MTX discontinuation due

to adverse effects.[10]

A consensus for folic acid or folinic acid dosing or administration

does not exist, and the decision to initiate supplementation is

physician-dependent. Folate supplementation may reduce low-dose MTX

adverse effects and prevent earlier discontinuation of therapy,

potentially allowing for a more durable response to MTX. Clinicians

should consider that folic acid supplementation may have the

additional benefit of cardiovascular protection[11] due to its ability

to prevent MTX-induced hyperhomocysteinemia.[2,11]

http://www.medscape.com/viewarticle/588229

Not an MD

[Guest guest]

Stan,

I actually snapped a photo of this elusive creature when I was in

Lithuania two years ago, but I have misplaced the memory card which

holds the valuable image. I believe it is with Sue's stick. I better

check the toilet paper cabinet.

Not an MD

On Mon, Feb 23, 2009 at 10:30 PM, <stanpfister@...> wrote:

>

>

> Fortunately our supply of wild folics is not endangered as the run free and

> wild across the great expanse of the Russian tundra, so there's enough acid

> available for all who need it. I've never actually seen a " wild " folic but

> I'm told they are very small and hard to catch. It must be mind boggling to

> collect that much acid.

>

> Stan,

>

> Seattle, Rain.

[Guest guest]

ROTFL, !

I don't believe Stan when he says he's not able to work, do you? He

could always get a job writing for a comedian or a comedy show. LOL.

Sue

On Feb 24, 2009, at 7:22 PM, wrote:

> Stan,

>

> I actually snapped a photo of this elusive creature when I was in

> Lithuania two years ago, but I have misplaced the memory card which

> holds the valuable image. I believe it is with Sue's stick. I better

> check the toilet paper cabinet.

[Guest guest]

That's pretty good , see how one thing leads to another? Lol, soon I'll have

you believing methotrexate was derived from the mold in abandoned meth labs

across in north America. It's true, Cliff Claybourne told me all about it.

Stan,

Seattle, Rainy.

Re: [ ] ASK THE EXPERTS - Does folic acid reduce the

 toxicity of MTX?

Stan,

I actually snapped a photo of this elusive creature when I was in

Lithuania two years ago, but I have misplaced the memory card which

holds the valuable image. I believe it is with Sue's stick. I better

check the toilet paper cabinet.

Not an MD

On Mon, Feb 23, 2009 at 10:30 PM, < stanpfister@... > wrote:

>

>

> Fortunately our supply of wild folics is not endangered as the run free and

> wild across the great expanse of the Russian tundra, so there's enough acid

> available for all who need it. I've never actually seen a " wild " folic but

> I'm told they are very small and hard to catch. It must be mind boggling to

> collect that much acid.

>

> Stan,

>

> Seattle, Rain.

[Guest guest]

.....Much in the same way that the elusive Nauga has been hunted into

extinction. They were found in swamplands, which accounts for the

water repellent qualities that they developed.

I am still saddened when I see an old olive green barcalounger at a

thrift store....all those precious Naugas who gave their lives, just

to be made into a tacky, tacky Naugahyde recliner. Gotta go...getting

a little misty here...eyeliner's starting to run...looking like Alice

.....

Jane in Dallas

>

>

>

>

> Fortunately our supply of wild folics is not endangered as the run

free and wild across the great expanse of the Russian tundra, so

there's enough acid available for all who need it. I've never

actually seen a " wild " folic but I'm told they are very small and

hard to catch. It must be mind boggling to collect that much acid.

>

>

>

> Stan,

>

> Seattle, Rain.

>

>

> [ ] ASK THE EXPERTS - Does folic acid reduce the

toxicity of MTX?

>

>

>

>

>

>

> Does Folic Acid Reduce the Toxicity of Methotrexate?

>

> From Medscape Pharmacists

> Ask the Experts about Pharmacotherapy

> Posted 02/19/2009

> Joanna Pangilinan, PharmD, BCOP

>

> Question

> Should folic acid or folinic acid be given to patients receiving

> long-term, low-dose methotrexate for rheumatoid arthritis?

>

> Response from Joanna Pangilinan, PharmD, BCOP

> Pharmacist, Comprehensive Cancer Center, University of Michigan

Health

> System, Ann Arbor, Michigan

>

> Methotrexate (MTX) inhibits dihydrofolate reductase, resulting in a

> decreased supply of folates. In high doses, MTX inhibits purine and

> pyrimidine synthesis, rendering it useful for many malignancies. In

> low doses (< 20 mg/week), MTX is commonly used as a disease-

modifying

> antirheumatic drug and is indicated for treatment of rheumatoid

> arthritis (RA).[1] MTX's mechanism of action for this indication is

> unclear. Efficacy of low-dose MTX may ultimately be the result of

> anti-inflammatory,[1] immunosuppressant, or immunotoxic effects.[2]

>

> Adverse effects of low-dose MTX in patients with RA are related to

> folate antagonism and/or folate deficiency. Folate supplementation,

in

> the form of folic acid or folinic acid, is often coadministered

with

> MTX to minimize adverse effects (eg, stomatitis, gastrointestinal

> intolerance, bone marrow toxicity, and abnormal liver function

> tests).[1]

>

> Studies have examined the effectiveness of folate supplementation

in

> decreasing adverse effects associated with low-dose MTX. A Cochrane

> Review evaluated 7 randomized, double-blind, placebo-controlled

trials

> that assessed whether folinic acid or folic acid decreased side

> effects of MTX in patients with RA. Both folinic acid and folic

acid

> were found to decrease gastrointestinal and mucosal side effects.

The

> use of folinic acid, however, may not be cost-effective unless

> pharmacoeconomics studies find it to be more clinically effective

than

> the less expensive folic acid.[3]

>

> A recent study by van Ede and colleagues[4] evaluated the effect of

> folate supplementation on MTX-induced adverse effects in patients

with

> RA. Folic acid was dosed at 1 mg daily and folinic acid was dosed

at

> 2.5 mg weekly; doses were doubled if the MTX dose reached 15 mg

> weekly. Folate supplementation decreased the incidence of elevated

> liver enzymes compared with placebo. However, folate

supplementation

> was not shown to decrease gastrointestinal or mucosal side effects.

> Hoekstra and colleagues[5] found that patients on folate

> supplementation remained on therapy longer, resulting in " MTX

> survival " and more durable control of RA symptoms.

>

> While some studies suggest MTX efficacy is not compromised by

folate

> supplementation,[3,4] results of a post hoc analysis[6] advised

> caution[7] and suggested folic acid supplementation may decrease

MTX

> efficacy. Folic acid supplementation[4] and dietary fortification

with

> folic acid[8] may increase MTX dosage requirements.

>

> Total weekly folic acid doses in the range of 5-27.5 mg have

> demonstrated efficacy in decreasing MTX adverse effects. Weekly vs

> daily schedules have not been compared.[1] Whittle and [1]

> recommend the " pragmatic " use of folic acid 5 mg once weekly taken

the

> morning after MTX dosing, with a possible dose increase to 10 mg if

> adverse reactions continue. Others suggest that prophylactic folate

> supplementation should be reserved for those who have an increased

> demand for folate, such as during infection or antibiotic

> treatment.[9] If folic acid is initiated, evidence suggests that it

> should continue long-term in order to prevent MTX discontinuation

due

> to adverse effects.[10]

>

> A consensus for folic acid or folinic acid dosing or administration

> does not exist, and the decision to initiate supplementation is

> physician-dependent. Folate supplementation may reduce low-dose MTX

> adverse effects and prevent earlier discontinuation of therapy,

> potentially allowing for a more durable response to MTX. Clinicians

> should consider that folic acid supplementation may have the

> additional benefit of cardiovascular protection[11] due to its

ability

> to prevent MTX-induced hyperhomocysteinemia.[2,11]

>

> http://www.medscape.com/viewarticle/588229

>

>

> Not an MD

>

>

>

>

[Guest guest]

Yes, Sue, I think Stan could be writing for the J man catalog.

Not an MD

On Tue, Feb 24, 2009 at 6:38 PM, marysue <marysue@...> wrote:

> ROTFL, !

>

> I don't believe Stan when he says he's not able to work, do you? He

> could always get a job writing for a comedian or a comedy show. LOL.

>

> Sue

[Guest guest]

LOL, Jane.

Not an MD

On Wed, Feb 25, 2009 at 11:59 AM, JANE <janeatregis@...> wrote:

> ....Much in the same way that the elusive Nauga has been hunted into

> extinction. They were found in swamplands, which accounts for the

> water repellent qualities that they developed.

> I am still saddened when I see an old olive green barcalounger at a

> thrift store....all those precious Naugas who gave their lives, just

> to be made into a tacky, tacky Naugahyde recliner. Gotta go...getting

> a little misty here...eyeliner's starting to run...looking like Alice

> .....

> Jane in Dallas