For people taking Orkambi

imported_Momto2

New member
aboveallislove, according to my doc, its my immune system causing most of the issues. Usually I take a chemo drug to suppress my immune system, since it has fun attacking my lungs and causing bronchospasm. (I cant take the chemo and Orkambi) The past couple of years, I've had a heck of a time taking a lot of inhaled meds, including iso and mild hypertonic saline. My lungs have just HAD ENOUGH (picture a toddler crossing their arms over their chest, stamping their foot, and shaking their head). I was really really hoping that a pill, instead of a nebulizer, would bypass some of the issue. But it was not to be. On the good side, I rarely get sick :) And the super-hydrating effect that the Orkambi seems to have on my lungs and sinuses I can replicate w/o drugs via vagal nerve hyperstimulation. But it only lasts about 10 minutes, thank heaven. Its enough to really help though. THat's how I've lasted so long without out being able to do regular nebulizers.
 

DjFunkyFife

New member
And the super-hydrating effect that the Orkambi seems to have on my lungs and sinuses

Hi! Would you mind elaborating on that? How exactly does it help you hydration-wise?

My biggest gripe about my situation right now is chronic dehydration. I've discovered (through my own research, no thanks to doctors) that I'm dehydrated a lot. A LOT! As well as have electrolyte imbalance (which, not surprisingly, salt is the main one i lose) And the work it takes for me to stay hydrated/ correctly electrolyted, especially during the summer, is insane, and does not even fully work. I've gotten to where in the summer I hardly drink anything other than water and Gatorade. More often than not, that Gatorade has extra salt added to it. Yet, if I slip up, and the balance of Gatorade/water and other stuff (coffee, tea, a soda rarely, twice a week maybe) is off for even one day, I feel effects for days. It's miserable. It can affect my airway clearance too. If I have a headache (which for me are only caused by dehydration/electrolytes and sinus pressure) then I won't do my vest, because it will intensify the pain.

My digestion issues are manageable. My FEV1 hovers in the mid-upper 70's, which I'm OK with. I should be starting Orkambi next month, and if it does absolutely nothing for my lungs, or my digestion, I'll be just fine with that. I really want to see some improvement in my hydration and electrolytes, and tolerance of warm/hot weather.
 

imported_Momto2

New member
Dj this is not body hydration, its lung mucus hydration. If I drink about 12 ounces of super-cool or very very hot liquid in small sips through a straw and get it to the back of my throat and do this for a period of about 5-10 minutes, it causes a huge rush of liquid into my lungs and sinuses. Literally, my nose runs like a faucet and I can feel the same happening in my lungs. It helps if my body is either very hot or very cold (probably more temperature contrast?) The effect is short-lived though, only lasts for about 10 minutes, but during that time, I can cough a huge amount of crap up and out. I looked it up, apparently I am overstimulating the vagus nerve. Its sort of like gustatory rhinitis, but at least for me, it also causes my lungs to get very very wet. Then the mucous is super easy to cough up. The only other thing that I have ever found that duplicates this was taking the Orkambi the first two times. Unfortunately, the tightness that the orkambi caused, completely mitigated the "wet" respsonse. Either that, or my body acclimated, I dont know.
 
J

jamest

Guest
Just started. Was hoping for the immediate effects 661 had - where my lungs opened up and every cough was a productive one.

Instead, my lungs have seized shut, and every cough is dry and unproductive. My mucus is much more watery though.

Hopefully my lungs adjust and the inflammation dies down. Also not digging this fatigue.

I don't remember any side effects for the 661, hopefully that gets to market soon, because as of right now, Orkambi seems like a bust. :/
 

saintoffeon

New member
every cough is dry and unproductive. My mucus is much more watery though.

What mucus is more watery? You said you can't cough it out...are you generalizing and there are some fluke coughs that bring stuff up? Or are they trapped down there and you can feel it sloshing, or feel less dry, etc.?

Just talked to the pharmacy a couple hours ago and it's shipping today to arrive tomorrow and I'll start fresh Saturday morning and report back...
 
J

jamest

Guest
What mucus is more watery? You said you can't cough it out...are you generalizing and there are some fluke coughs that bring stuff up? Or are they trapped down there and you can feel it sloshing, or feel less dry, etc.?
The mucus I cough up. It is a lot like after using pulmozyme, except all the time. In a counter intuitive way, I find it more difficult to get this kind of mucus up. I am also on IV abx, so my lungs probably aren't making a lot anyway.

The studies suggest that after 6 days, most side effects are gone. Here's hoping for tomorrow.
 

kemcloney3

New member
This is my experience with Orkambi
7/30/15 FEV1 in clinic 37%
7/31/15 Started Orkambi
8/2/15 Symtoms started
8/15/15 Hospitalized, FEV1 in hospital 23%, taken off Orkambi
8/31/15, Discharged from hospital, FEV1 33%, restarted Orkambi
9/3/15 Symptoms started
9/17/15 Follow up hospital visit, FEV1 24%, Stopped Orkambi for good
9/19/15 75% of symptoms already gone. Still have major congestion but can cough it out

I have to go back into the hospital on Monday for 2 weeks.
 

Gammaw

Super Moderator
I suspect I'm prone to oversimplification, but am I off the mark for suggesting that the lower your lung function, the more likely Orkambi will not be helpful and potentially hurtful? It has been said in this thread that the side effects after starting are more severe in lower functions, bit in what percentage does it ultimately help - decrease exacerbations, maintain or improve function, etc. Does someone else see a different or more specific pattern here? Or aware of any research that points to a different explanation?
 

Aboveallislove

Super Moderator
A few thoughts: Vertex is doing a study on Orcambi for those <40% so that will be helpful to understand. It does seem that those with lower lung function have a rougher "start up" than those with higher. But it also seems there are some who just can't tolerate the drug even for those above the 40% lung (as the small % of those who were in the Phase 3 who dropped out). I wonder how many of those have immune response issues, as ImportedMom or if there is any other predictor that showed who dropped out because of the issues. It seems that those who have a "start up" issue would know within 3 weeks because things then improve, whereas for those who don't then it is an issue with the drug. I guess there are always those who react negatively to the meds unfortunately. I wonder if 661 will be different for those???
 

saintoffeon

New member
Started Saturday morning. 31, male, six feet, 150 lbs. No other major health problems to have any notable influence outside of bronchiectasis. Had a single partial spontaneous lung collapse in 2007 and an embolism almost two years later.

First dose took about two hours to get to some nasal drainage, then chest tightness (I normally don't even deal with that too much but wow there's no better word for it). Kind of like light pneumonia congestion feeling minus accompanying B.S. from infection.

Three separate times I got so fatigued it was like someone took my batteries out even in the middle of the day. I didn't even feel tired and didn't feel rested it even comfortable afterwards, just took me out of commission.

Coughed up some watery things. Very light, so presumably easy access unless it's that devoid of bugs right now.

Decreased appetite but less like you don't feel like eating and more like it's hard to find the will. No problems once starting. Number two in the bathroom is refreshingly regular but not sure if it's too early to credit the pill.

Squished breathing made end of day sleep a bit of an effort but once asleep not super disruptive.

Second day, sometimes not as much tightness, other times much worse. There were pockets where I had to stop and squat or walk slower just to regain myself and my heart was working a little overtime. Nasal drainage isn't constant but seems consistent after each dose. An early visit than nothing till next time.

Some sinus pressure headaches and warm feeling but for me personally no fevers or chills yet.

I don't have a means of measuring fev every day but I almost wouldn't bother until the chest clog feeling goes away. Very minor popping pains in chest and stomach. Not many thankfully. It really does feel like someone's sitting on you.

I have tried except for the resting to be as active as possible and I think it's helping. I know it's a luxury not everyone has but I'm currently unable to do even basic stuff normal sick me could do with relative ease just a couple of days ago.

That said I could feel myself hit the walls and used sheer will to try to push past. I don't have all my normal drugs yet, just pulmozyme and my vest, so concentrating on clearing things out.

Coughed up thicker darker and more colorful stuff day two, almost like it's going in order. No massive crazy gangly things yet but better out than in!

Also limb pain from inflammation and oxidative stress dying down already a bit. Noticeably. Not sure if great coincidence but it's a purer feeling than I can remember experiencing making me feel like the chest is the real focus.

Mornings were breakfast then half avocado then pills then avocado. Evenings were Babybel individual small cheese rounds half and half followed by mixed nuts (including macadamia).

Just when I think the fog is lifting I'm reminded how early it is by some extra angry bronchospasm, but it still seems like I've got one of the smoother rides reported so far. Fingers crossed.

And please do stay as active as possible. Even if you're sitting and flailing your arms because it's all you can do. I truly believe it'll help dig out of this initial week or so cycle of crap while the levels in the blood get to the the appropriate spots.
 

saintoffeon

New member
My bad. Thought I typed it. Last year it was 35 because of limited access to medications and services. Last month after being on pulmozyme and exercising for a few months it was at 43.
 

Gammaw

Super Moderator
That's a wonderfully detailed report Saintoffeon. And it's evident you have a great attitude - looking for the connections, cause and effect, and seeing the benefits while still noting the difficulties. I look forward to hearing more......
 

saintoffeon

New member
Day 3 was pretty uneventful. I slept in a little bit; having gotten up, started to get ready, and then absolutely conked out for a couple hours. It's the only time I haven't taken a dose within a couple minutes of my target time (9:19, because it's a good spot for my life/schedule and because I started on 9/19 and new that'd make me remember it).

Didn't cough much up, though had a bit of soda at Panera that made me cough and brought a few things out that, by the look of them, weren't terribly old but good to be rid of =)

Fortunately I own my own business so I have the luxury of getting to not have anyone yell at me for missing the first part of work. As a friend of mine said today, "These are the real clinical trials. Now. Like an episode of Extreme Weight Loss, it's been tested for a long time in tightly controlled situations. Now we see how people fare on their own, with no checks, facing the stresses of their ordinary lives with not nearly as much oversight."

VERY tight chest, not stabbing painful but more like, "someone beat me up and these are the internal bruises in recovery" painful. Sore. If this was a normal day for me and I felt this way I'd assume I was infected. It's 1/3 to 1/2 of the way towards going into the hospital for pneumonia kind of congested.

It's a weird bit of perspective. Even though I breathe poorly as a baseline, a few days ago before taking this seems like an easy go compared to right now. I traded out feeling decent (relatively) in the moment to feel beat up right now, on the off chance my long term prospects would ensure feeling okay or good (or even better) forever.

Time goes by much slower, though. That's the other bit of perspective. Because I'm hyper-aware of what's going on, these three days have felt like a week and a half. I keep having to tell myself that the drug isn't even up to level yet, and that I can't make judgements because it's "blip on the radar" early in the process.

Still, when you tell your brain to kick forward and lean forward to combat how slow and plodding you are, and your body needs to hear that "kick" instruction just to be able to produce a regular walk...it's taxing. Especially when you're making noises and drawing stares because you're breathing through a straw. The only difference is your mouth is open and you're making contorted faces just to sneak enough air in.

Still keeping a good outlook, though. I think I'll get farther by not giving in, which of course is easier said than done. Thanks for being so supportive! =)
 

saintoffeon

New member
One other thing. I just got my vest after twenty years of trying last month. And it's a blessing with or without Orkambi. I feel better after taking it, like right after, and also over time.

My pulmonologist said that with CF, bronchodilators and even antibiotics were only helpful to a point (in his opinion)...but the focus for him was mucociliary clearance. Another pulmo I had, his PA said if you could take an antibiotic or Pulmozyme to a deserted island, she'd pick Pulmozyme every time because it's harder for the infection to even be there to fight if you destroy the place it's trying to build a house on.

I can't imagine what this would be like without one. If you don't have one, I will pray for you to get one whether or not you're on Orkambi, but it's a monster-huge component I think in the overall team effort of therapies towards making this an effective process.
 

saintoffeon

New member
Okay, this is the last time, I promise. This just occured to me tonight...from now on if I have same-day updates I'll just edit the original post, but this is in the interest of full disclosure:

Twice now, since Saturday morning, I have taken my minimum dose of tramadol, a pain reliever. I was prescribed it last month as an alternative to actual full-on narcotics (the smallest possible dose gets me high and obliterates all feelings, not just pain, for me =)...plus they don't wanna give me anything where side effects include respiratory depression, for obvious reasons.

It did a nice job of taking the edge off of inflammatory pains, but I actually was weaning myself off before the Orkambi came because it was coming. I wanted the raw experience plus at the time I wasn't sure what possible interactions there would be.

It should be noted that while some people feel no effects from tramadol (the woman who did my lung function test recently laughed at me and said it was literally a "girlie pill" that people take for period cramps, similar to naproxen)...it is now effective for me, and has a documented SSRI component. Like Orkambi, you don't know how it'll work for you until you're on it, so tread lightly because there's a lot of good things it can mess with if you screw around with the schedule.

Now, with all of that lead-in out of the way, I will say this. Occasionally that beat-up pain I was talking about was getting disruptive to my normal productive function, so I bit the bullet and took the pills.

It was a bit like a preview of what I hope/think/believe Orkambi will be like when the fog has totally lifted. I am using it sporadically and strategically right now; if I feel well enough to move around, and that's what it takes to get me moving around and feeling free enough to do so, and I've decided that moving around is helpful, then it's a good part of the cause.

As long as I can continue to take and use it responsibly, spaced out an low dose and as needed (not advocating any of this as medical advice...be smart and talk it out =) it can give me brief windows, brief opportunities, to up my game to maximize the effect of my progress.

I am trying to get to the point where "I have CF" is something that's technically true if/when people ask, and no longer indicative of or reflective of my day to day experience.

I look mostly well enough that people don't know anyway, but if they caught the off moments where I'm hurling things, or choking-coughing like I'm dying, or squatting to catch my breath every few minutes to grocery shop...they'd change their mind.

I want it to only be something you can know if I tell you. I want "I have CF" to be trivia. I want it to surprise people.

So is it cheating, cutting corners? Maybe. But I have the chance...it's less about sneaking a peek at a better future and more about giving me enough steam to help me help myself work out all these disgusting cooties trapped inside.

Someone else mentioned hydrocodone earlier...relieving pain but also smoothing out bronchospasms. Haven't taken tramadol often enough to create a difference if it can have the same effect, but no effect noticed yet in reduction if it is indeed possible.

Ugh, the spasms on this stuff are maybe the worst part about it. Drowning in air is for the birds!
 

aslong

New member
I have been on Orkambi 3 days (6 doses- I started at night). I also just got out of the hospital after 1 week of antibiotics and I am continuing IVs at home for 5 more days (Meropenum adn oral Cipro). I also have some liver problems: fatty liver and I get gallstones in my duct that backs bile up into my liver. I have to be very careful what I put in my body or it gets inflamed. I had a slight fever the 2nd day and headache so I broke down and took 1 aleve (I usually take 2) this is the only thing that helps me. Then last night The liver was painful. Right now it is just sensitive to touch so I am trying to let it rest (eat light) hopefully it will be okay- I see the doctor tomorrow for a follow up.

I want to share my FEV 1 becuase before I started this I only heard about low FEV 1 and high FEV 1 and I was not sure how my body was going to react. My FEV 1 is 56% (right at admission-59% a week before) that is how I have been for the past year or so. As some might remember I got the swine flu a few years ago and went from 110% to 80% well, the decline continued. Probably because I did not have insurance the year after the flu until last year! I have not been in the hospital or on IVs for 5 years. I haven't cultured Pseudo for about 5 years either. I did have MRSA that was found last year when I finally went to the CF DR (in Fresno- there is an Adult Doc in Fresno now!) He is great. I also culture Achromobacter Xylosoxidans and staph A.

I have had some tightness not too bad but, I am coughing up all kinds of stuff. I was more the first day and then it started again last night. I can hear stuff moving around... I usually sound clear. I am SUPER tired! like a train hit me. It is hard to say if it is Orkambi or the IV drugs. I also have this weird heart vibrating thing- almost like I have my vest on. Again not sure if it is the IV or Orkambi. I can take a deep breathe but I get very winded walking but, I was like that before I started the meds... I have absolutely NO APPETITE and am nauseous. I also have had a low grade fever that last couple days.

I have thrown up on the first day and last night... last night there was lots of mucus- no color (white). Sinus' are good too. I guess the real test will be next week when I am off the IVs.

I went back to work yesterday- I am a college counselor and I teach a class. I got through the morning (barely) and had to leave and then slept all day. Today, I just stayed home
I know this is not much but, I wanted to give an update. I know how much it helped me when others shared!
 

saintoffeon

New member
Day four was kind of impressive. Nothing ancient or hairy or gross came out, but I easily did a month's worth of productive coughing in the past few days, bolstered by my seemingly unending stream of sputum spitting I was engaged in. Big session in the morning, big session in the afternoon (also very weak..once I got home I crashed and slept for three hours... I was COOKED) and decent session tonight.

It sounds weird to say but I am kind of excited because it's just a few days in and I see more change...it's not pleasant-feeling in the moment, but in my mind I'm fast-forwarding to, say, seven days, and wondering about what other bigger scarier gross things might leave me. Let's clear the table! =)

Also, this is the first day I was involved in any non-walking exercise. After my nuclear-level weakness and sleeping through dinnertime, I had enough energy to do some light cardio. Timing-wise I needed to do my vest to be able to take my drug on time, so I cut out early (also, they moved to doing a lot of on your back stuff, and I have trouble breathing and not coughing like that)...but what I got done was more than I thought I could do and hopefully helpful to the cause. Probably a solid 12 minutes of legitimately moving around and working things out.

I have been seeing a lot of bitter/jaded comments about the drug on social media. It's absolutely okay to react that way; in many ways it seems less and less like even the compromised version of what we thought it would be. Just remember not to dwell on that and live in that place for so long it becomes unhealthy.

We've all spent our whole lives fighting things and being bent over, so we're tough enough to live through a false positive with our character intact. We also don't need any extra stress that might cause other health problems.

Aside from trials, though, the most anyone's been on it should only be about two and a half months, and the trial results, while modest, took place over 24 weeks. I really believe patience will be rewarded. I think it's doing its job for everyone, in terms of mechanism of action, I just think there's SO much going on with each individual case that there's no way to tell how it'll play out.

Sometimes when I'm in the hospital they give me MucoMist and I say I don't want to because it dries me out, and they say, "No way, the book says that's impossible," and then they ask me to cough up something to be cultured. I can't, it's all dry in there now. It may be similar to that, where with the fifty thousand meds we have to take, the playing field is changing so much that ever-so-slightly-thinning-mucus has more of an uphill battle to produce any obvious effects.

For what it's worth, I am not backing this medicine or defending it, and I will be the first to support anyone upset by it. I'm literally throwing ideas out, and nothing I'm saying is intended to be professed as opinion. Just openly discussing theories =)

I could be taking this forever and not get any better and my views will remain the same. For as expensive as it is, you'd hope there was a better chance that it would override every other thing wrong with you to be clearly doing its job in an overt fashion, with a much more increased likelihood of overall success, but we also can't get caught up in that, this time, that may not be the case.

That's why I am trying to focus so much on what I can do with what energy I have. I think it not just benefits from the help, but may need it. It's like when you see those diet pills, and people say, "Oh, I just took it and in twenty weeks I lost 140 lbs." So you look up the drug and there's a note that says "Take one a day, and then diet and exercise." Hmm...maybe you can take anything and diet and exercise and it'll help. Maybe that's the first time they dieted and exercised, and that has more to do with it than anything. Credit doesn't go where it's due, but hey, whatever works if the end result actually happens.

Cheers to you guys for staying strong. I hope we all come out as well as possible through this.

EDIT: Almost forgot. I don't know if it's an aberration, so I was waiting a few days to see if it was the case, but I'm a lot more regular, consistently, in these past few days. None of that classic paint-stripping CF grease that can sometimes accompany our bowel movements. Also very easy to pass with little strain, and up until day it wasn't too soft or watery at all. Having just had a bout of fecal impaction prior to starting, since I stay hydrated enough, I'll take that over the alternative any day. I have always been more successful without pancreatic enzymes though (a secondary reason, aside from trying to prove eligibility to get into clinical trials for this medicine​, that we went through with a blood test/genotyping to confirm the baby diagnosis, based primarily on "failure to thrive" and sweat chloride off the charts)...so I'm not sure how that will play out for the tons of other people who need them to live.
 

Gammaw

Super Moderator
To me, it's simply fascinating to see such immediate results. . . . Can someone provide me with a little more information to help me understand the mechanism at work here? What is changing that causes the almostimmediate production of so much mucous, the difficulty with breathing, the production of new and old sputum or mucous plugs. . . . . ? Sounds like a question for LittleLab!? Anyone?
 

Aboveallislove

Super Moderator
Hey Gammaw,
I stalk investor boards and just a few days ago one of the posters (who I'm pretty sure is a former college science professor) explained Orcambi/Kalydeco in the context of the new drug they are testing it with from Parion. I didn't follow it all but it is well explained.
And does seem to explain why it would be almost immediate response to get the old coming out (along with the "normal" new):

[h=2]‘Synergy’ btw Orkambi (or Kalydeco) and VX-371[/h]VX-371 is the new name for the Parion’s ENaC inhibitor, P-1037, which Vertex in-licensed. Below I would like to argue that both VX-371 and Orkambi would strengthen the defense against infection and inflammation by hydrating lung airway mucus.

The chronic infection and inflammation of lung airway in cystic fibrosis (CF) patients is the primary reason for the progressive decline of lung function resulting in daily symptoms such as cough and sputum production. The primary cause for the infection is the very viscous mucus on the airway surface.

In CF lungs chloride ions don't flow out actively [=pumped with ATP] into the mucus water volume. Positive ions such as sodium ions cannot diffuse out into the interface water because they follow anions [=chloride ions]. On top of that, the active Na+ ion pumping by hyperactive ENaC removes Na ions out of the mucus volume. Both sodium and chloride ions are kept away from the mucus. The net result is that the mucus will be short in both ions and water [water always follows the ions]. Immune cells in the mucus will be very unhappy and cannot remove bacteria in it. This weakened immune defense against bacteria such as P. a. is central to developing airway inflammation and lowered lung function.

The total ion concentration in the mucus on the airway lining determines the water volume. If the ions flow out into the airway mucus, the airway will be hydrated and the lung will be happy. But if the ions are excessively moved into the tissue from the mucus, the airway will be dehydrated and the lung will be unhappy.

Orkambi or Kalydeco partially restores chloride pumping into the airways water volume, and VX-371 would block sodium pumping out of the mucus. So, plenty of both ions will be there and water volume will increase.

To me, it's simply fascinating to see such immediate results. . . . Can someone provide me with a little more information to help me understand the mechanism at work here? What is changing that causes the almostimmediate production of so much mucous, the difficulty with breathing, the production of new and old sputum or mucous plugs. . . . . ? Sounds like a question for LittleLab!? Anyone?
 
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