I have noticed two small differences in the last year. The first is that my mucus load is slightly down. Hardly noticeable, but over this longer term I think that it has made a difference. For example, if my average mucus load off of antibiotics is about a 4 out of 5, I’d say now it’s averaging at a 3 out of 5. So that’s an improvement! There’s been no change in my daily fevers however. It’s possible that the mucus is slightly thinner than it was before, but again, it’s pretty hard to tell.
The second change I’ve noticed is just an overall gain in stability. In the last year I’ve had one or two small bouts of pleurisy, but no other lung collapses, no large episodes of hemoptysis (just streaking, or a teaspoon here and there), and no serious infections or pneumonias (other than the usual). After my big hospitalization in May 2018, I believe I went 6 months without needing another hospitalization, which was a big deal and maybe even like a 5+ year record or something. Since then I’ve been hospitalized every 3-4 months, which is my average. So I think in the initial phase on Symdeko I got a nice bump in stability, and then after that my hospitalization schedule went back to normal. But the lack of medical emergencies in the last year has been wonderful! I think the drug has had something to do with that. Lung function loss has been unchanged however (about 2-4% loss per year, plus I lost 5-10% with the last pleurodesis surgery).
Overall there have been milder side effects compared to Orkambi, which I couldn’t tolerate. When I first started Symdeko, on the second day I had an unusual sensation in my sinuses: basically my frontal and maxillary sinuses felt swollen and full of pressure. A green plug came down the back of my throat from my nose (that happens sometimes). Then the sensation went away the next day. Sinuses rinses clear. The third day I woke up with a spasmy, tickly cough. After that it went away. By the end of the first week I felt like my mucus load was significantly reduced from what it would have been at that stage in my infection cycle. Things proceeded fairly normally after that, as I mentioned above. Sinuses overall unchanged long term.
The first thing I noticed in terms of longer-term side effects was that my blood sugars were becoming more sensitive to carbohydrates. I have a tendency towards getting reactive hypoglycemia (meaning that if I eat too many carbs my body over-produces insulin and 2 hours later I get a hypoglycemic crash) and Symdeko definitely made this worse. It was as if my endocrine pancreas was feeling a little better so it wanted to “help out” by producing more insulin. But it still functioned poorly, so the end result was more frequent episodes of reactive hypoglycemia, now triggered by even smaller amounts of carbs. Before Symdeko, I could get away with eating up to 20g of carbs without getting a reaction. But now if I eat 15g I can get a reaction (that’s about half of a big apple). And if I get a reaction in the morning (at breakfast), it sets me up for a full day of rollercoasters, one hypo reaction after the other. That had never happened before. In the past I could have one hypo reaction in the morning and be done with it. But now I can get multiple in a day (up to three)! It became a serious issue and a reason for increased anxiety, because I never knew when I was about to have a crash. It made me wary to leave the house for more than a few hours at a time, in case I had to eat suddenly. I got so sick of checking my sugars so often, and I always carried tons of dried apricots around with me in case I crashed. And worst of all, I was getting resistant to cortisol and adrenaline, so I could hardly tell when I was low anymore. I finally convinced my endocrinologist to let me try a continuous glucose monitor, so see what the heck was going on. I used it for a couple weeks to see what numbers I was getting, so that was helpful. But eventually I didn’t find the machine that helpful for preventing crashes so I stopped using it. It was bothersome on my skin and didn’t work very consistently (the Dexcom G5). What it did tell me though, is that I rarely, if ever, go above 200 mg/dL, but even then my pancreas over-reacts and over-produces insulin. It’s as if the pancreas has become hyper-sensitive.
I’ve figured it out now, and it all comes down to what I eat for breakfast. For years I’ve known that my first meal of the day has to be big(ish) and low carb. But I can’t tell you how hard it’s been to stick with that rule! Symdeko requires you take it with breakfast (dosing is ~12 hours apart with 8+g of fat). I don’t really like eating right when I wake up, but I’ve had to start doing that now. Anyway, I finally figured out what I have to eat, and that means I only have three breakfast choices: 10 cashews; 3 pieces of bacon; or a high-fat, low-carb protein shake. The protein shake is the best choice, but sometimes if I’m on the go or run out of ingredients, I just go for the cashews. Then about 2 hours later I eat my second meal of the day, which can be more lenient with carbs (ideally followed by exercise). If I stick with this rule strictly, I avoid any hypo crash and my BS remains stable throughout the day. Plus the shake provides enough protein that I stay full and have enough energy until midday.
Here’s what I put in my shake:
- 10 ounces of either unsweetened hemp milk (Tempt brand) or unsweetened chocolate almond milk
- 1 scoop of protein powder equaling about 10g protein. I’ve been trying out a few brands, and these three seem the most decent: Orgain – plant protein (chocolate flavor), Primal Kitchen collagen powder – grassfed beef protein (chocolate flavor), and Aloha – plant protein (chocolate flavor). These have the fewest ingredients, the most fiber, are low-carb, and have no sugar (sweetened with stevia or monk fruit extract mostly). And these taste the least gross of the ones I’ve tried.
- 2 tsp of liquid medium chain triglycerides (equaling about 10g of fat), coconut based. This is a game changer. This is liquid at room temp and in the fridge and mixes really well in these shakes, even when they’re cold. I wish I had known about this years ago!
- I just put all this in a glass peanut butter (actually sunflower seed butter) jar and shake it up. Quick and easy. No blender required.
The other big side effect I’ve had on Symdeko was how it messed with my testosterone level. I take testosterone injections because I am a transgendered (transmasculine) person. Symdeko (actually, ivacaftor) is a CYP3A4 inhibitor. CYP3A4 is a liver enzyme involved in metabolizing xenobiotics (i.e. chemicals that you ingest/absorb, in the form of food, drugs, cosmetics, pollution, etc.) in phase 1 liver metabolism. It is also responsible for metabolizing (breaking down and recycling) sex hormones, especially testosterone and estrogen, both endogenous and exogenous. When CYP3A4 is inhibited, that means that the enzyme pathway gets partially blocked, so all the xenobiotics and hormones that normally get processed through that pathway are less metabolized, resulting in a higher level of them circulating in the body. I have observed in some of my clients and friends on Vertex drugs (involving ivacaftor), especially people with ovaries, that they tend to get symptoms related to hormone imbalances. That might be weird menstruation, moodiness, acne, PCOS, etc. This could be the result of higher than normal testosterone and/or estrogen levels. Sometimes the body can self-adjust and eventually get back to “normal” after a few months. But maybe not for others. Personally, I started to get more acne and was more moody and less tolerant of other people than usual. So after about 3 months on Symdeko I checked my testosterone level (because I was suspicious) and it was through the roof! Over the next few months I had to experiment with adjusting my dose. Now I’m at about a third of the dose that I was on pre-Symdeko! So the drug had a really big effect on how I was metabolizing my sex hormones. I believe this is something to keep in mind for everyone taking a Vertex drug (all of them include ivacaftor), not just people taking exogenous hormones. More studies need to be done on its long term side effects, especially the effect on sex hormones. At least more case studies – I need one written on my experience!
Lastly, I did have a bout of very severe depression this winter for about 3 months, but I think that was mostly situational. Though I can’t rule out Symdeko having an effect on that. It was the worst depression I’ve ever had in my life. I am a depressive sort of person, but this was pretty unusual. But this could simply be called in clinical terms an “adverse event”, meaning that it happened during the drug trial but is not known if there is a direct connection (as opposed to an “adverse reaction”, which is a direct result of the drug/intervention).
Overall, I like Symdeko and I plan to stay on it. The effect has been mildly beneficial and I’ve figured out how to control the side effects. Oh, and I forgot to mention how outrageously expensive it is. Over $350,000 per year I believe? Unacceptable. I will resist the temptation to go on a rant about the pharmaceutical-industrial complex. Others have done so more eloquently than I could right now. Luckily I have Medicare and Medicaid and don’t pay anything out of pocket for it. Anyway, I am looking forward to Vertex’s third generation drug (the three-drug combo) coming out in 2020. I’ve heard good things about it. Although it’s super hard to tell what’s hype and what’s reality, which is the case for all Vertex drugs. Plus every single person responds differently