Oral Inhalation Flecainide Acetate for Acute Conversion of Recent-Onset, Symptomatic AF to Sinus Rhythm

[www.ahajournals.org]
I don’t recommend home experimenting by inhaling flecainide. It could possibly be fatal. I was in the icu for flecainide overdose in 2019 and almost died. Flecainide is a black label drug. I’m sharing for new studies one may want to know about. Perhaps one day instead of an ER ecv, they may try this technique.

Open-Label, Multicenter Study of Flecainide Acetate Oral Inhalation Solution for Acute Conversion of Recent-Onset, Symptomatic Atrial Fibrillation to Sinus Rhythm
Harry J.G.M. Crijns, MD, PhD, Arif Elvan, MD, PhD, Nadea Al-Windy, MD, Ype S. Tuininga, MD, PhD, Erik Badings, MD, PhD, Ismail Aksoy, MD, Isabelle C. Van Gelder, MD, PhD, Prashanti Madhavapeddi, PhD, A. John Camm, MD, Peter R. Kowey, MD, Jeremy N. Ruskin, MD and Luiz Belardinelli, MD
and the INSTANT Investigators
Originally published24 Feb 2022[doi.org]: Arrhythmia and Electrophysiology. 2022;0:CIRCEP.121.010204
Abstract
Background:
Oral and intravenous flecainide is recommended for cardioversion of atrial fibrillation. In this open-label, dose-escalation study, the feasibility of delivering flecainide via oral inhalation (flecainide acetate inhalation solution) for acute conversion was evaluated. We hypothesized that flecainide delivered by oral inhalation would quickly reach plasma concentrations sufficient to restore sinus rhythm in patients with recent-onset atrial fibrillation.

Methods:
Patients (n=101) with symptomatic atrial fibrillation (for ≤48 hours) self administered flecainide acetate inhalation solution using a nebulizer (30 mg [n=10], 60 mg [n=22], 90 mg [n=21], 120 mg [n=19], and 120 mg in a formulation containing saccharin [n=29]). Electrocardiograms and flecainide plasma concentrations were obtained, cardiac rhythm using 4-hour Holter was monitored, and adverse events were recorded.

Results:
Conversion rates increased with dose and with the maximum plasma concentrations of flecainide. At the highest dose, 48% of patients converted to sinus rhythm within 90 minutes from the start of inhalation. Among patients who achieved a maximum plasma concentration >200 ng/mL, the conversion rate within 90 minutes was 50%; for those who achieved a maximum plasma concentration <200 ng/mL, it was 24%. Conversion was rapid (median time to conversion of 8.1 minutes from the end of inhalation), and conversion led to symptom resolution in 86% of the responders. Adverse events were typically mild and transient and included: cough, throat pain, throat irritation; at the highest dose with the formulation containing saccharin, these adverse events were reported by 41%, 14%, and 3% of patients, respectively. Cardiac adverse events consistent with those observed with oral and intravenous flecainide were uncommon and included postconversion pauses (n=2), bradycardia (n=1), and atrial flutter with 1:1 atrioventricular conduction (n=1); none required treatment, and all resolved without sequelae.

Conclusions:
Administration of flecainide via oral inhalation was shown to be safe and to yield plasma concentrations of flecainide sufficient to restore sinus rhythm in patients with recent-onset atrial fibrillation.

REGISTRATION:
URL: [www.clinicaltrials.gov]; Unique identifier: NCT03539302.

[www.clinicaltrials.gov]

[www.clinicaltrials.gov]

Experimental: Repeat dose inhaled flecainide acetate
One 120 mg dose of flecainide acetate inhalation solution will be administered via two oral inhalations of 3.5 minutes. There will be a 1 minute break between the two inhalations. A single nebulizer will be used.



Edited 1 time(s). Last edit at 03/14/2022 01:57PM by susan.d.

It is interesting, based on this site, "Based on PVC suppression, it appears that plasma levels of 200-1000ng/ml may be needed to obtain the maximum therapeutic effect. Plasma levels above 700-1000ng/ml are associated with increased likelihood of adverse experiences." {this is with oral flec}

With the nebulizer, they were getting 48% efficacy at the very bottom end of the range (200-1000 ng/mL). Of course how far into the range the subjects got is not stated. A question would be what is the association between inhalation dose and plasma level.

For the time being, I'll stick with chewing the med to have it get into the system quickly.



Edited 1 time(s). Last edit at 03/15/2022 08:32AM by GeorgeN.

George-for safety chew and please do not experiment inhaling— chew or swallow 200mg in a 24 hour period if you weigh less than 154 pounds or chew 300mg in a 24 hour period if you weigh more than 154 pounds.

Flecainide isn't available in an inhalable form, so I don't think we need to worry about people doing that. It's an interesting idea and I could see why it would work better than a pill. The whole idea of a PIP is to get the full therapeutic dose into your system all at once and ASAP. A pill takes at least 20 minutes to begin entering your system and then it enters in a slow ramp up, whereas an inhaled medication hits the bloodstream almost immediately in full force.

I also find it interesting that someone is pursuing the idea of improving the PIP concept. Many EPs are still skeptical of PIP solutions and tend to put their patients on daily meds instead even when those meds might not be useful or needed for weeks at a time.

Quote
Carey
Flecainide isn't available in an inhalable form, so I don't think we need to worry about people doing that..

True but as an example people are already experimenting with food grade hydrogen peroxide iodine saline concoctions added to their nebulizer cup because a nebulizer rx is not available. The article gave the flecainide recipe ingredients which concerns me someone could soak a flecainide tablet with saline and try it out. Those flecainide tablets really dissolve quickly and I used to find myself with a nasty tasting dissolving tablet stuck to my tongue if I didn’t drink it down fast enough.

I echo Carey's thoughts about improving the PIP concept.

My concern is about what happens with serum levels vs intake quantity. I'm sure this is variable with oral intake. Because nebulizing is a more direct route, certainly doses would likely need to be lower so as not to have too high a serum level. In the study, they tried smaller doses, but the 120 mg seemed to be the only one that had significant efficacy.

As to experimentation with a nebulizer, I've done so with MgCl2 per Dr. Sarah MyHill in the UK (though she uses mag sulphate). My recollection is it can take quite a while to nebulize a material quantity of fluid. Hence getting the concentration right would be very important. It is not something I'd play with.

I did a search on "absorption kinetics sublingual vs tablets flecainide" and came up with nothing on flec, but certainly sublingual is much faster than oral tablets in data for other substances. I did find this paper on flec tablets vs an oral solution. The solution being much faster. I commonly do a DIY sublingual by chewing the tablets and letting the saliva/flec mixture sit under my tongue.

And a different route for intake - rectal.

The absorption kinetics of different pharmaceutical formulations of orally and rectally administered flecainide have been assessed in a cross-over study in 7 healthy volunteers. The subjects received single doses of flecainide after a washout period of at least one week. A tablet, an oral solution, a rectal solution and a 10 min i.v. infusion during 10 min each containing 100 mg flecainide were administered to the subjects in a randomized order. The mean absolute bioavailability was 98%, 78% and 81% for the rectal and oral solutions and the tablet. The lag time after administration of the oral solution was 0.33 h and it was 0.86 h after the tablet and 0.18 h after the rectal solution. The mean time to the peak serum concentration (tmax) after the rectal solution (0.67 h) was shorter than after either the tablet (4 h) or oral solution (1 h). The maximum serum concentration (Cmax) was 0.29 mg.l-1 after the rectal solution, 0.14 mg.l-1 after the tablet and 0.17 mg.l-1 after the oral solution. All the volunteers showed significantly higher serum flecainide concentrations during the first 20 min of the absorption phase after rectal administration of 100 mg flecainide as a solution compared to its oral administration. Source:

So rectal reached a peak at 0.67 h (40 minutes) {corrected GN}.





Edited 2 time(s). Last edit at 03/16/2022 08:19AM by GeorgeN.

I had been wondering about this lately. On my last successful conversion, I just chewed and let the Flec dissolve in the mouth and under the tongue, then washed down with a tiny bit of water. It did leave a bad aftertaste, and my tongue tingled for awhile, but for a successful conversion it was the small inconvenience.

The thing is food in the stomach can effect absorption, if we are using a high bolus dose (PIP conversion dose) of a drug that has a narrow therapeutic index, then it's critical to get an effective dose, but not a toxic one. Having various amounts or types of food in the Stomach could make absorption uneven from one conversion dose to the next.

This is an important topic. Having said that I would not advise anyone to use the rectal delivery method as referenced above. What if you get too much? It may be hard enough to explain to EMT's of ER staff the concept of converting a AFIB episode using a bolus dose of Flecainide in the urgency of a heated moment, just using normal the delivery method. Compounding the issue by using the rectal delivery method would make it harder to explain to medical staff what happened.

I say this from personnel experience, having overdosed in the ER room, and the nurses Doctor didn't grasp the PIP concept.



Edited 1 time(s). Last edit at 03/16/2022 06:06AM by The Anti-Fib.

Anti-afib: you too overdose flecainide too? Did you end up in the icu?

Flecainide is a very dangerous drug to experiment with.



Edited 1 time(s). Last edit at 03/16/2022 09:11PM by Carey.

No not in the ICU

Here is my account, taken from this old thread 8 years ago. It is not exaggerated account, it happened this way.
[www.afibbers.org]

What was bad, was that upon referral from my EP, I went to ER room, took the 300 Flec (1st time that high of dose), and then had an EKG done. My Doctor faxed them orders for STAT treatment, but they somehow got misplaced. It was a busy day at this ER room.

Now the EKG was normal AFIB, and I was feeling fine at that point. 45 minutes later I am begging the ER staff for a Heart monitor, as I feel as though I am about to pass out. The nurses (2 of them) shrug me off, and one of them laughs at me and said my EKG was fine, nothing to worry about, saying that the ER Doctor looked at my EKG diagnosing it as controlled afib, and thus not an emergency. I tried to explain to them what I did with the bolus dose (300mg PIP), but they didn't grasp what I was talking about. They called over the security gaurd to escort me away from the side of the ER room closest to the staff. That is when I collapsed to my knees trying to walk away. They still think I am faking it. Finally they call me back to a waiting room in the back, but that is worse, because I am now all alone and my condition is deteriorating. I am laying there trying to call out, but I can't talk loud enough to be heard. I kick over a trash can, trying to get someones attention. An older nurse comes by and scolds me, saying that Flecainide can not cause the symptoms that I am complaining about. I desperately I am now trying to call out to my EP Doctor, but I can't get a cell-signal. I go for about 30 minutes of thinking I might pass out and die, and try not to lose consciousness. I wish that I had anybody, even an enemy to help me out. After awhile I start improve, and I manage to leave the ER and stumble a bit out to the parking lot, to call my Doctor. So I come back into the ER room now, and they scold me saying they tried calling me, and that I must be fine to be able to go out for a walk in the parking lot. It's been about 90 minutes now, and I was feeling a bit better, being able to move around a little.

Long story short, 3 hours later I got cardioverted, after going from AFIB, to Flutter. I never did get the staff to really understand what the PIP strategy with the Flecainide was. The Head nurse openly complained of having to deal with my Doctor over the phone, who was by now trying to sternly deal with the situation. I could get no treatment or help when I needed it, not another EKG, not an Pulse Oxymeter, not anything. I had to borrow some ladies watch just to check my pulse rate.

Anyway I survived this, and am now looking back trying to figure out just what the Flecainide did to me.
I did discontinue everyday use of the drug, but still use it at 200mg for PIP conversion.



Edited 1 time(s). Last edit at 03/19/2022 02:15AM by The Anti-Fib.