Tapering off Pramipexole

[Northernchap]

In October 2024 my wife was put on Pramipexole 3 x 88mcg per night. A week later this was increased to 4 x 88mcg. This seemed to make the symptoms worse so the GP wanted to move to the modified release tablets - augmentation! Another GP countermanded this, saying it was meant for Parkinsons only. I am now trying to taper off the tablets by reducing her intake to 3 x 88mcg for one week, then 1 x 180mcg for one week, then 1 x 88mcg for week 3 before stopping altogether. Does this seem appropriate and safe?

[Joolsg]

No.

Here's the withdrawal schedule from RLS-UK website.

rls-uk.org/useful-resources

These drugs are dangerous & hell to get off.

Your Wife will need to go back to her GP and show them the Iron Therapy page and the Withdrawal schedule - scroll down to Useful Resources.

Withdrawal is hellish and brutal for most people. Experts say it's worse than heroin withdrawal.

As your wife has only been on these drugs for 6 months- she may have avoided permanent damage and her withdrawal may not be as brutal as normally.

Ensure serum ferritin is above 200ųg ideally, as this can help a little.

Switch to normal release Pramipexole first.

Then reduce by half a 0.088 pill every 2 weeks.

Ask GP for low dose opioids to take at each reduction and take for 4 or 5 nights.

Read the RLS-UK website. Learn all you can because GPs and neurologists aren't taught anything.

Dopamine agonists like Pramipexole are no longer prescribed by experts because of the extremely high rates of drug-induced worsening and Impulse Control Disorder.

Your wife should start replacement meds around 4 weeks before the last dose of Pramipexole.

The usual replacement meds are gabapentin or pregabalin, taken at night only. See RLS-UK website for medications table. Doses and timings are set out.

If her serum ferritin is below 200ųg- she will need to start iron therapy via pills or an infusion.

And ensure she's not on medication that triggers/worsens RLS like anti depressants, etc - all listed under medications to avoid.

When she drops the last dose- the withdrawals are frightening. She will need you or a friend to stay up with her for the first 4 nights as she'll get no sleep or rest and the RLS will be violent and severe. Falls from exhaustion are common.

A deep massage gun and compression socks will help.

Good luck.

[Northernchap in reply to Joolsg]

Wow, this is more complicated than I thought, so many thanks again for the detail. She had no other meds prior to last year and the Pregabalin and Gabapentin had no effect - in fact was worse. Rotigotine knocked her out. Pramipexole modified release was not started fortunately.

I am very grateful for your advice and will post back when there is more news.

[Joolsg in reply to Northernchap]

So she was on Rotigitone? How long for? That is another dangerous dopamine agonist.You say pregabalin and gabapentin had no effect.

What dose and how was it prescribed?

Most UK doctors know ZERO about RLS or the meds to treat it. They usually prescribe the wrong dose and tell patients to take it 3 times a day. That doesn't work for RLS.

Did they give her gabapentin and pregabalin before Rotigitone/Pramipexole?

[Northernchap in reply to Northernchap]

Rotigotine was a 2mg patch applied before bedtime. After the first application I found my wife in the middle of the night prostrate in the hallway. Took some time to rouse her and she was extremely confused and found it difficult to walk even with me supporting her. I took the patch off and decided not to continue with it. Gabapentin was 300mg 3 times a day but had to be discontinued because of side effects; the same with Pregabalin 150mg. One side effect for both was excessive bleeding. Yes, gabapentin and pregabalin tried before Rotigotine, and Pramipexole the last. Jerking legs keep her awake at night, so sleeplessness and daytime sleepiness make a previously active person a shadow of her former self. Also takes away her independence as she is not safe to drive.

[Joolsg in reply to Northernchap]

Sadly, you have been let down by total lack of medical training/education/knowledge.As stated- first thing the GP should have done was safely replace trigger medications and arranged blood tests to raise serum ferritin above 200ųg.

Gabapentin should NOT be prescribed 3 times daily. That is for nerve pain. For RLS it should be prescribed at NIGHT only. Medical ignorance again.

However- as the side effects were serious (excessive bleeding) your wife will need to see a knowledgeable doctor who will prescribe an iron infusion and Buprenorphine.

Where are you?

There aren't many knowledgeable neurologists. And the waiting list is long so we recommend paying to see someone privately.

To enable Buprenorphine to be prescribed, it's better to use a neurologist nearby who can issue a private prescription if your GP refuses to prescribe Buprenorphine.

And file a Yellow Card report about augmentation so doctors STOP prescribing these dopamine agonists.

Here's the link.

bnf.nice.org.uk/medicines-g...

[Northernchap in reply to Joolsg]

Many thanks again. Yes, the original GP who prescribed Pramipexole and Promthazine listed RLS as one of her areas of interest. Heaven help us! I have made an appointment for us to see Neurologist Dr Christopher Murphy privately as he gained honourable mentions here recently. He is based in Salford (NHS) and Alexandra Hospital Cheadle (privately). Still had a waiting list - seeing him on March 5th. We are between Manchester and Liverpool, and between Warrington and Wigan.

[SueJohnson in reply to Northernchap]

He is excellent.You are lucky to get an appointment so soon, even privately. He may also prescribe an iron infusion.

[SueJohnson in reply to Northernchap]

What a shame about gabapentin and pregabalin. That is a very rare side effect.

[Joolsg]

Can you confirm that your wife has never taken any other medications for RLS before October 2024?And what other meds is she taking- as many meds can trigger or worsen RLS.

And ensure the GP arranges morning, fasting, full iron panel blood tests asap and post results.

GP should have arranged this BEFORE prescribing any meds for RLS.

Raising brain iron via pills/infusions can resolve the majority of RLS cases and medication would not then be needed.

[Northernchap in reply to Joolsg]

Thank you so much for those helpful points. My wife is on the usual meds for high BP and cholesterol: Bempedoic Acid, Ezetimibe, Indapamide, Isosorbide Mononitrate. She was on Promethazine (Phenergan) for sleep but to no avail and dropped. Will arrange to see our GP re iron, which has not been mentioned. Thanks again.

[Joolsg in reply to Northernchap]

Phenergan worsens RLS.The diuretic (indapamide) is also known to worsen RLS - BUT clearly she needs it so discuss with GP.

All sedating anti histamines trigger RLS.

Melatonin worsens RLS.

Safe sleeping aids are zolpidem or a benzodiazepine.

If she gets the right meds to control her RLS- she will get 7 or 8 hour's sleep and her blood pressure will improve.

Quite a few people report that they have been able to reduce their blood pressure meds once their RLS is properly controlled.

[SueJohnson]

Welcome to the forum. You will find lots of help, support and understanding here.

I agree with everything Joolsg said.

Let me give my usual answer which will repeat a lot of what she has said but which will have some additional details.

At 4 times the .088 tablets (.88) she is taking the maximum dose of pramipexole.

Have you started the tapering and is she suffering as a result. If so go back up to a dose where she is not suffering more than when she started.

Ropinirole, pramipexole (Mirapex) and the Neupro (rotigotine) patch are no longer the first-line treatment for RLS, gabapentin or pregabalin are. They used to be the first-line treatment which is why so many doctors prescribed them but they are not uptodate on the current treatment recommendations.

To come off pramipexole, reduce by half of a .088 tablet every 2 weeks or so. She will have increased symptoms. She may need to reduce more slowly or with a smaller amount. Wait until the increased symptoms from each reduction has settled before going to the next one. She will suffer and may need a low dose opioid temporarily to help out with the symptoms especially as She nears the end. Some have used kratom or cannabis temporarily to help. But in the long run, She will be glad you came off it.

The gabapentin and pregabalin probably had no effect because she didn't take enough.

On the gabapentin or pregabalin, the beginning dose is usually 300 mg gabapentin (75 mg pregabalin). Start it 3 weeks before she is off pramipexole although it won't be fully effective until she is off it for several weeks. After that increase it by 100 mg (25 mg pregabalin) every couple of days until she finds the dose that works for her.

Take it 1-2 hours before bedtime as the peak plasma level is 2 hours. If she needs more than 600 mg take the extra 4 hours before bedtime as it is not as well absorbed above 600 mg. If she needs more than 1200 mg, take the extra 6 hours before bedtime. (She doesn't need to divide the doses on pregabalin)

Most of the side effects will disappear after a few weeks and the few that don't will usually lessen. Those that remain are usually worth it for the elimination of the RLS symptoms. According to the Mayo Clinic Updated Algorithm on RLS: "Most RLS patients require 1200 to 1800 mg of gabapentin (200 to 300 mg of pregabalin)."

If she takes magnesium even in a multivitamin, take it at least 3 hours before or after taking gabapentin (it is OK with pregabalin) as it will interfere with the absorption of gabapentin and if she takes calcium or antacids don't take it within 2 hours for the same reason (not sure about pregabalin).

Has she had her ferritin checked? If so what was it? Improving ones ferritin to 100 or more helps 60% of people with RLS and in some cases completely eliminates their symptoms. If not ask her doctor for a full iron panel. Stop taking any iron supplements 48 hours before the test, don't eat a heavy meat meal the night before and fast after midnight. Have her test in the morning before 9 am if possible.

When she gets the results, ask for her ferritin and transferrin saturation (TSAT) numbers. If her ferritin is less than 100 or her transferrin saturation is less than 20 ask for an iron infusion to quickly bring it up as this will help her withdrawal. If she can't get an infusion, let us know and we can advise you further.

Check out the Mayo Clinic Updated Algorithm on RLS which will tell you everything you want to know including about its treatment and refer her doctor to it if needed as many doctors do not know much about RLS or are not uptodate on it as hers obviously isn't or s/he would never have prescribed a dopamine agonist at Https://mayoclinicproceedings.org/a...

Meanwhile some things that can make RLS symptoms worse for some people are alcohol, nicotine, caffeine, sugar, carbs, foods high in sodium(salt), foods that cause inflammation, ice cream, eating late at night, estrogen including HRT, dehydration, MSG, collagen supplements, electrolyte imbalance, melatonin, eating late at night, stress and vigorous exercise. It is a good idea to keep a food diary to see if any food makes her RLS worse.

Some things that help some people include caffeine, moderate exercise, weighted blankets, compression socks, elastic bandages, masturbation, magnesium glycinate, fennel, low oxalate diet, selenium, 5 minute shower alternating 20 seconds cold water with 10 seconds hot water finishing with hot water for another couple of minutes, hot baths, distractions, CBD, applying a topical magnesium lotion or spray, doing a magnesium salts soak, vitamins B1, B3, B6, B12, D3, K2, if deficient, and potassium and copper if deficient, massage including using a massage gun, vibration devices like therapulse, using a standing desk, listening to music, meditation and yoga.

Many medicines and OTC supplements can make RLS worse. If she is taking any and you list them here, I can tell you if any make RLS symptoms worse and if so may be able to give you a safe substitute. I have a list of more than 300 medicines and OTC supplements that make RLS worse and have safe alternatives for most of them.

Indapamide is a non potassium sparing diuretic which means it depletes potassium which makes RLS worse which means she should take extra potassium or better yet switch to a potassium sparing one.

Bempedoic Acid, Ezetimibe should be safe for RLS.

[Northernchap in reply to SueJohnson]

Thank you so much for your detailed answer. Extremely helpful. Incidentally my wife's ferritin reading two years ago was 21 ug/L, described as (normal) as it was in the range 10 -292! I shall ask for a new test and repost when it is done.

[SueJohnson in reply to Northernchap]

That's real low. She should ask for an iron infusion to quickly bring it up. If her doctor won't prescribe one she can get it privately but it will cost around £800. If interested and you tell me what city you live in I may be able to tell you where she can get it.

Meanwhile she should take two tablets of 325 mg of ferrous sulfate or 75 mg to 100 mg of iron bisglycinate with 100 mg of vitamin C or some orange juice since that helps its absorption. Also take Lactobacillus plantarum 299v as it also helps its absorption. Ferrous sulfate is fine for most people, but if she has problems with constipation, iron bisglycinate is better.

Take it every other day preferably at night at least 1 hour before a meal or coffee or tea and at least 2 hours after a meal or coffee or tea since iron is absorbed better on an empty stomach and the tannins in coffee and tea limit absorption.

If she takes magnesium, calcium or zinc even in a multivitamin, take them at least 2 hours apart since they interfere with the absorption of iron. Also antacids interfere with its absorption so should be taken at least 4 hours before the iron or at least 2 hours after. She shouldn't take her iron tablets before or after exercise since inflammation peaks after a workout. She shouldn't take turmeric as it can interfere with the absorption of iron or at least take it in the morning if she take her iron at night. If she takes thyroid medicine she shouldn't take it within 4 hours. It takes several months for the iron tablets or iron infusion to slowly raise ones ferritin. She should ask for a new blood test after 8 weeks if she has an iron infusion or after 3 months if she is taking iron tablets.

[Northernchap in reply to SueJohnson]

Knowing where to get the infusion privately would be helpful in case our GP demurs at prescribing it or there is a long waiting list. We live halfway between Manchester and Liverpool, and halfway between Warrington and Wigan.

[SueJohnson in reply to Northernchap]

There is the Iron Clinic in Manchester - this says London but they have one in Manchester and I believe you contact them through this theironclinic.com/contact/

[Northernchap in reply to SueJohnson]

Yes, it is a monthly pop-up clinic. I'll hold that information until we have the blood test results. Thanks.

[Joolsg in reply to Northernchap]

She needs an emergency iron infusion.New NICE guidance requires GPs to ensure serum ferritin is above 50ug for 'normal' people. So yet more medical ignorance/negligence.

[Munroist in reply to Northernchap]

Hi, as others have said 21 is very low for ferritin, possibly partly due to bleeding from the pregabalin and gabapentin. Hopefully Dr Murphy will be able to arrange an infusion but if not then other people have been successful in at the RVI in Newcastle. I was refused because I’m not in the North region for healthcare, but you should be okay. I’d suggest reading the RLS-uk pages under “understanding RLS” menu to get a good view on medications. Here’s a link:

rls-uk.org/medications-avoid

Hopefully once off pramipexole and with higher ferritin levels the RLS may be tolerable but if not there is advice there on potential medications which given your situation are probably limited to low dose opioids e.g. buprenorphine.

[Northernchap in reply to Munroist]

Thanks for those tips. We live in the northwest and there is a monthly "pop-up" clinic for iron infusions in Manchester. As the "normal" range for ferritin levels was given as 10 - 291 (not as I quoted in another post) and my wife's level was 21 she was deemed to be in the normal range with no action needed! The other RLS links have proved excellent.

[Fishhag]

I am adding my recent experience of getting off dopamine agonists. I have gone against most all recommendations about going cold turkey , but that is what I have done. I was diagnosed with with RLS 12 or so years ago and was put on some form of DA (dopamine agonists) and as the augmentation got worse and worse the dosage was increased until I was on 3 times the recommended dose of Pramipexole. I was in living hell. My doctors tried many things, tested for sleep apnea, checked my iron, and tried pregamblin, gabapentin, carbadop/levadopa, but never decreased the DA. Then I found this form and I got educated! Thanks to everyone in this community. I told my sleep specialist I wanted to get off the DA and he was hesitant at first. He prescribed smaller dosages of pramipexole and gave me methadone to use as a replacement to the DA and to help with withdrawal symptoms. (gabanoids had too many side effects for me to tolerate)The first night I took .25 of pramipexole (a 1/3 decrease) and 5 mg of the methadone. It was a miracle. It was the first night in years that I was able to relax in the evening, watch TV, do a little crochet, and not feel like I was wanted to come out of my skin. The second night I figured I would just tough out the DA withdrawal with taking only the methadone. Still worked like a miracle. I have not looked back! I have been playing around with minimum dose of methadone and 5 mg seems to be adequate. It has been 5 days since going “cold turkey “and I had 7 hours of sleep, the first in years. There is only one other person on this form that I have found that also went off DAs cold turkey. No medical person would recommend this, but I am just throwing my experience out there. Good luck on your journey.

[violetta254]

I also went off of pramipexole rather quickly, in just a few weeks but with the addition of 10 mg of oxycodone. I was only on .25mg of prami. It was still pretty bad but over quickly. I don't really recommend it, just didn't know better at the time. The opioid makes all the difference and made it possible. I am now on a maintenance dose of 10 mg. of methadone, and I much prefer it to oxycodone (I wish I could get away with 5 but I really can't). I don't feel so stoned in the middle of the night with methadone although I do get sleepy in the day. The slow withdrawal is probably a better option to make sure you avoid DAWS.