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METHOTREXATE!
A #tweetorial for #medtwitter, #dermtwitter, & #medstudenttwitter!
I'm no pharmacologist, so this is written from a #dermatologist's POV!
Let's start with a question that still haunts med students today:
What is the mechanism of action of methotrexate (MTX)?
METHOTREXATE!
A #tweetorial for #medtwitter, #dermtwitter, & #medstudenttwitter!
I'm no pharmacologist, so this is written from a #dermatologist's POV!
Let's start with a question that still haunts med students today:
What is the mechanism of action of methotrexate (MTX)?
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MTX inhibits dihydrofolate reductase in the folate pathway, which is needed for DNA/RNA ➡️ inability for cells to rapidly divide!
Given similarities in mechanism with other drugs in this pathway, caution should be used when adding MTX on top of them, especially TMP-SMX!
MTX inhibits dihydrofolate reductase in the folate pathway, which is needed for DNA/RNA ➡️ inability for cells to rapidly divide!
Given similarities in mechanism with other drugs in this pathway, caution should be used when adding MTX on top of them, especially TMP-SMX!
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Since MTX is an antifolate, remember that Folinic Acid (Leucovorin) is used as a "rescue" when side effects go crazy. But at the doses we use in #dermatology, I've never needed it. Plus, we give folate with MTX to prevent these effects!
Which of 👇 doses is typical in derm?
Since MTX is an antifolate, remember that Folinic Acid (Leucovorin) is used as a "rescue" when side effects go crazy. But at the doses we use in #dermatology, I've never needed it. Plus, we give folate with MTX to prevent these effects!
Which of 👇 doses is typical in derm?
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The correct answer is 10 mg weekly! In dermatology (& other non-oncology fields), usual dosing maxes out at 25 mg WEEKLY.
Pills are 2.5 mg, so usually pts take 2-10 pills per week. Every other day of the week the pt takes folate 1 mg.
10,000 mg is closer to Onc dosing!
The correct answer is 10 mg weekly! In dermatology (& other non-oncology fields), usual dosing maxes out at 25 mg WEEKLY.
Pills are 2.5 mg, so usually pts take 2-10 pills per week. Every other day of the week the pt takes folate 1 mg.
10,000 mg is closer to Onc dosing!
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So a lot of the side effects patients read about are super rare at our doses. For that reason, counseling can really help a patient understand that we aren't giving them oncology doses, and they're less likely to see the scary stuff happen.
Reminder to dose adjust for a ⬇️GFR
So a lot of the side effects patients read about are super rare at our doses. For that reason, counseling can really help a patient understand that we aren't giving them oncology doses, and they're less likely to see the scary stuff happen.
Reminder to dose adjust for a ⬇️GFR
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There a ton of side effects listed for MTX, which is what usually scares patients. I think it's important for us to put it in context.
Remember that the side effects are often because of the mechanism! Decreased cell turnover can affect mucosa (GI/mouth) and cell lines!
There a ton of side effects listed for MTX, which is what usually scares patients. I think it's important for us to put it in context.
Remember that the side effects are often because of the mechanism! Decreased cell turnover can affect mucosa (GI/mouth) and cell lines!
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I usually tell my patients the following:
- The most frequent AE I see is fatigue soon after taking the dose.
- Nausea/vomiting
- dizziness/drowsiness
- Low but real ⬆️risk of infection
There's more but check out 👇 resources:
massgeneral.org/children/infla…
my.clevelandclinic.org/ccf/media/file…
I usually tell my patients the following:
- The most frequent AE I see is fatigue soon after taking the dose.
- Nausea/vomiting
- dizziness/drowsiness
- Low but real ⬆️risk of infection
There's more but check out 👇 resources:
massgeneral.org/children/infla…
my.clevelandclinic.org/ccf/media/file…
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What I DO tell patients is to call me with AEs since there are things we can do!
Injected MTX SQ can ⬇️ AEs.
Also, an easy move is to increase the folate dose to 3 or 5 mg! A @cochrane review found that this helps GI AEs!
cochranelibrary.com/cdsr/doi/10.10…
What I DO tell patients is to call me with AEs since there are things we can do!
Injected MTX SQ can ⬇️ AEs.
Also, an easy move is to increase the folate dose to 3 or 5 mg! A @cochrane review found that this helps GI AEs!
cochranelibrary.com/cdsr/doi/10.10…
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MID #TWEETORIAL RECAP!
- MTX inhibits dihydrofolate reductase to inhibit new DNA/RNA synthesis.
- Inhibits rapid cell turnover, which helps address immune cells, but also causes many of the side effects.
- Side effects can be mitigated with folate and injectable MTX!
MID #TWEETORIAL RECAP!
- MTX inhibits dihydrofolate reductase to inhibit new DNA/RNA synthesis.
- Inhibits rapid cell turnover, which helps address immune cells, but also causes many of the side effects.
- Side effects can be mitigated with folate and injectable MTX!
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Ok, let's move on!
What about lab monitoring? Given the effects on blood counts, liver, and the need to monitor renal fx for dosing purposes, I check a CBC and CMP regularly.
What say you? How soon after initiating methotrexate do you have patients return to check labs?
Ok, let's move on!
What about lab monitoring? Given the effects on blood counts, liver, and the need to monitor renal fx for dosing purposes, I check a CBC and CMP regularly.
What say you? How soon after initiating methotrexate do you have patients return to check labs?
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We used to bring folks back in 1 week to make sure they didn't have fulminant liver tox after a 5 mg test dose. However, that's fallen out of favor, and now we usually just start at our usual dose and bring patients back in 1 month. Then I space it out with a stable regimen.
We used to bring folks back in 1 week to make sure they didn't have fulminant liver tox after a 5 mg test dose. However, that's fallen out of favor, and now we usually just start at our usual dose and bring patients back in 1 month. Then I space it out with a stable regimen.
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MTX can rarely induce an acute hepatitis, but more commonly, we worry about fibrosis that can happen in an indolent way. We actually used to do liver biopsies regularly, but now based on ACR guidelines (albeit expert opinion), we stick with labs only.
onlinelibrary.wiley.com/doi/full/10.10…
MTX can rarely induce an acute hepatitis, but more commonly, we worry about fibrosis that can happen in an indolent way. We actually used to do liver biopsies regularly, but now based on ACR guidelines (albeit expert opinion), we stick with labs only.
onlinelibrary.wiley.com/doi/full/10.10…
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And remember how we memorized that in addition to LFTs, we also were to check PFTs with MTX?
Well, we usually don't worry about lung disease with MTX at low doses. This paper was a nice meta-analysis showing the lack of signal with lung disease:
bmj.com/content/350/bm…
And remember how we memorized that in addition to LFTs, we also were to check PFTs with MTX?
Well, we usually don't worry about lung disease with MTX at low doses. This paper was a nice meta-analysis showing the lack of signal with lung disease:
bmj.com/content/350/bm…
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And what about before starting MTX?
I counsel about limiting EtOH (2-3/week), and I will sometimes check hep serologies, a Quant Gold +/- HIV.
While risk of hep or TB reactivation is low, I'm usually preparing for future immunosuppressive options in case MTX doesn't work!
And what about before starting MTX?
I counsel about limiting EtOH (2-3/week), and I will sometimes check hep serologies, a Quant Gold +/- HIV.
While risk of hep or TB reactivation is low, I'm usually preparing for future immunosuppressive options in case MTX doesn't work!
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So what do we use it for?
- Pemphigoid
- Eczematous Rash
- "Hypersensitivity Rash NOS"
- Psoriasis*
- Psoriatic arthritis (but only distal small joints & I'm involving rheum often)
Many jump to biologics for psoriasis, but MTX is so much cheaper, so I still think about it!
So what do we use it for?
- Pemphigoid
- Eczematous Rash
- "Hypersensitivity Rash NOS"
- Psoriasis*
- Psoriatic arthritis (but only distal small joints & I'm involving rheum often)
Many jump to biologics for psoriasis, but MTX is so much cheaper, so I still think about it!
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One quick factoid that I find fascinating. You know how patients can develop anti-infliximab neutralizing Abs? Well, when MTX is added, sometimes it can prevent those Abs from forming! In fact, it can even work if it's added AFTER those Abs are formed!
jaad.org/article/S0190-…
One quick factoid that I find fascinating. You know how patients can develop anti-infliximab neutralizing Abs? Well, when MTX is added, sometimes it can prevent those Abs from forming! In fact, it can even work if it's added AFTER those Abs are formed!
jaad.org/article/S0190-…
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FINAL RECAP
-MTX is a nice, cheap drug with multiple non-oncologic indications.
- At low doses and with proper monitoring, it's safe and well tolerated!
- Lab monitoring is essential to avoid issues and to prepare for future therapeutic options.
FINAL RECAP
-MTX is a nice, cheap drug with multiple non-oncologic indications.
- At low doses and with proper monitoring, it's safe and well tolerated!
- Lab monitoring is essential to avoid issues and to prepare for future therapeutic options.
18/18
This was a long #thread! Sorry about that! Hope you learned something, and as always, many other folks probably use MTX differently. This is just how I was taught and how I practice now, so please feel free to leave a comment below with your thoughts!
Thanks for joining!
This was a long #thread! Sorry about that! Hope you learned something, and as always, many other folks probably use MTX differently. This is just how I was taught and how I practice now, so please feel free to leave a comment below with your thoughts!
Thanks for joining!
