Ivabradine = Heart Pain + Sleep Adrenaline

[sb4]

Hey,

I've been taking Ivabradine at various doses for 3 weeks.

Depending on the dosage I go a few days feeling better then I start to get short stabby pains in my heart and left arm and leg veins. At night as I drift off Im sprung to wake by an adrenaline shot to the heart, this goes on for an hour or two.

I thought Ivabradine was short acting so why do I only get these symptoms after a couple days dosing? Anyone else experience this?

 

[ryan31337]

I'm starting Ivabradine in a few weeks - i'll let you know!

 

[Cheesus]

I suggest you talk to your doctor about this. You should not delay in seeking advice for suspected heart problems.

 

[pattismith]

@sb4, here what is found in wiki, maybe you shouldn't take this drug without being monitored for cardiac side effects, like sick sinus syndrome, ventricular extrasystole, AV block.

While I am currently hyperthyroid with tachycardia and have some ventricular extrasystole, I seem to tolerate well a low dose Ivabradine (up to now).


Contraindications[edit]

Ivabradine is contraindicated in sick sinus syndrome. It should also not be used concomitantly with potent inhibitors of CYP3A4, including azole antifungals (such as ketoconazole), macrolide antibiotics, nefazodone and the antiretroviral drugs nelfinavir and ritonavir.[7]
Use of ivabradine with verapamil or diltiazem is contraindicated.[8]

Adverse effects[edit]

Overall, 14.5% of patients taking ivabradine experience luminous phenomena (by patients described as sensations of enhanced brightness in a fully maintained visual field). This is probably due to blockage of Ih ion channels in the retina, which are very similar to cardiac If. These symptoms are mild, transient, and fully reversible. In clinical studies, about 1% of all patients had to discontinue the drug because of these sensations, which occurred on average 40 days after the drug was started.[4]
In a large clinical trial, bradycardia (unusually slow heart rate) occurred in 2% and 5% of patients taking ivabradine at doses of 7.5 and 10 mg respectively (compared to 4.3% in those taking atenolol).[4] 2.6–4.8% reported headaches.[4]
Other common adverse drug reactions (1–10% of patients) include first-degree AV block, ventricular extrasystoles, dizziness and/or blurred vision.[9]

 

[sb4]

@pattismith Thanks for looking it up. I don't intend to try it agiain any time soon but I may tolerate it better now that I am not as bad as I was. Hopefully it works out for you, I have heard it is a game changer for many.

 

[ryan31337]

Oops, realised I never replied.

Ivabradine has been a fantastic help for me. I only need a small dose, 2.5mg. I've seen a good general improvement and it really stops the jittery, tired but wired feeling, unless I am on my feet for extended periods. I notice it start to wear off late afternoon, so take a second 2.5mg dose then. That seems to give me a good 24hr coverage and also prevents the adrenaline kicks I'd often get at 6am-7am, waking me from sleep.

Ironically I got the short stabby pains in my chest before taking Ivabradine, but no longer, unless I miss a dose. I went cold turkey on the Ivabradine for 3 days before a CPET, I was a complete mess and it really showed how much it was helping.

 

[Marylib]

All I know is that it helps keep my heart rate down when I stand and that the POTS doc always want to check my QT interval.
So far so good. I never had pain with ivabradine.
Verapamil works better for me now, actually. I take it before bed, whereas I was taking the ivabradine during the day and I still do sometimes if I know I may have to stand still without moving.
I think one of the problems with verapamil is low blood pressure. So far, my blood pressure is okay. I retain more fluids on verapamil, so I get my kidney function checked. So far so good. This makes sense in that POTS is tachycardia related to low blood volume in response to orthostatic stress.
I see the POTS doc soon and since he is a nephrologist, it should be an interesting conversation since he didn't prescribe the verapamil.

 

[pattismith]

@sb4

It seems that I can't tolerate Ivabradine any longer.

I felt great under this drug as long as I was hyperthyroid with clear tachycardia.

Then when my hyperthyroidism resolved, I started to feel something close to what you've experienced, with pain in my chest waking me in the middle of the night.
It was scary, so I checked my ECG, but could'nt find anything wrong.
Of course I stopped Ivabradine, and the chest pain went away.

I still feel my heart beat, so I know my heart is not back to normal: A bit too quick and too heavily pumping, but no more arrythmia, and rarely above 80/mn at rest.

My small fiber neuropathy is not completely resolved, so I guess my autonomic nervous system is not cured yet and may be responsible for my heart uncomfort.

 

[pattismith]

@sb4
It's strange: I got the same chest pain and slow heart bit as a side effect of another drug. It woke me up in the middle of the night after I took azithromycin.

No QT prolongation thought, and no arrhythmia.

After some researches, I hypothetise it could be induced hypomagnesemia or hypokalemia or both.

 

[sb4]

@pattismith Thats interesting that an antibiotic could cause it.

You think Ivabridine can cause hypomagnesemia/kalemia?

 

[pattismith]

@pattismith Thats interesting that an antibiotic could cause it.

You think Ivabridine can cause hypomagnesemia/kalemia?

I don't think so, but their toxicity is increased if blood Mg/K are low so tonight, after several hours in pain,I drank a few glasses of mineral water then I slept 1 or two hours and when I woke up the chest pain was gone.

Chest pain and bradycardia are known side effects of azithromycin, so I suppose I'm not so special, but it' s strange that I already took it many times and never had chest pain before with it...(Only muscle weakness when I had low T3 )

I suppose our ion channels dysfunctions makes us particularly sensitive to side effects from drugs that modify ionic balances/fluxes...

...So maybe what worked for azithro will work for Ivabradine chest pain?

 

[pattismith]

@sb4

I realised that both Ivabradine and Macrolide antibiotics (azithro and co) are hERG potassium channel inhibitors.

Increased QT toxicity may be related to this block, but I'm not sure if the chest pain may involved these channels.

(I had the pain but not the long QT). This needs more investigations...

 

[sb4]

@pattismith So a hERG potassium channel inhibitor would act like lower levels of potassium?

There could be a link here with my aversion to salt. Perhaps my potassium is already on the lower side and ivabradine made it worse?

 

[pattismith]

@pattismith So a hERG potassium channel inhibitor would act like lower levels of potassium?

not really, but the drugs that inhibit hERG have shown bigger toxicity when blood magnesium and/or potassium are low.

Here an example showing other conditions can worsen the hERG inhibition (the drug here is Fentanyl, an opioid painkiller)

Our results showed that fentanyl blocked hERG1a/1b channels with a 3-fold greater potency than hERG1a channels.
Thus, in addition to a greater susceptibility due to the presence of hERG1b in the human heart, hERG channel block by fentanyl can be exacerbated by certain conditions such as hypoxia, hypokalemia, or alkalosis, which may increase the risk of fentanyl-induced ventricular arrhythmias and sudden death.

Fentanyl-induced block of hERG channels is exacerbated by hypoxia, hypokalemia, alkalosis, and the presence of hERG1b | Molecular Pharmacology (aspetjournals.org)

 

[pattismith]

hERG channel block by fentanyl can be exacerbated by certain conditions such as hypoxia, hypokalemia, or alkalosis, which may increase the risk of fentanyl-induced ventricular arrhythmias and sudden death.

@sb4
I think Alkalosis is a key for me, and hypoxia as well.

I have blood bicarbonate at 28-30.5 mEq/l during all this year, which is borderline high (depends on the reference ranges), and I have borderline low respiratory rate (12/mn);
This fits with a chronic compensated metabolic alkalosis.

how much are your blood bicarbonates?

 

[sb4]

@sb4
I think Alkalosis is a key for me, and hypoxia as well.

I have blood bicarbonate at 28-30.5 mEq/l during all this year, which is borderline high (depends on the reference ranges), and I have borderline low respiratory rate (12/mn);
This fits with a chronic compensated metabolic alkalosis.

how much are your blood bicarbonates?

Would this be regular bloods test? Not had one of them in years.

Would urine pH be an indicator? My urine is on the acid side, cant remember exact numbers but can find them if you want.

 

[pattismith]

Would this be regular bloods test? Not had one of them in years.

Would urine pH be an indicator? My urine is on the acid side, cant remember exact numbers but can find them if you want.

I don't think your urine pH will help. Blood Bicarbonates is a regular blood test, you may have it.

 

[sb4]

I don't think your urine pH will help. Blood Bicarbonates is a regular blood test, you may have it.

Indeed I do. It appears I told a filthy lie when I said I hadn't had regular bloods done in years. In fact I have Bicarb results from last year and the year before:
28
23
Reference range = 20-30mmol/L.
So I am pretty much middle of the range.

 

[pattismith]

Indeed I do. It appears I told a filthy lie when I said I hadn't had regular bloods done in years. In fact I have Bicarb results from last year and the year before:
28
23
Reference range = 20-30mmol/L.
So I am pretty much middle of the range.

If you look at the upper limit value you will find 30 or 28 or even 26!
You should control it again. Do you know your respiratory rate? Can you ask someone to check it while you are sleeping?

 

[sb4]

If you look at the upper limit value you will find 30 or 28 or even 26!
You should control it again. Do you know your respiratory rate? Can you ask someone to check it while you are sleeping?

Control it again? You mean test again?

I just counted how many times I breathed in and out and it was around 8 per minute. Although this is probably not accurate as as soon as you notice your breathe it becomes somewhat manual.

So the reference range is 20-30 mmol/L yet it could cause problems above 26 mmol/L?

Cant get anyone to check breathing at night.