My Experience With Theophylline

Here’s some interesting facts about my experience with theophylline. This, I think, is an interesting story, as it shows how far asthma wisdom has improved just during my lifetime. This is where I enter into our asthma history.

During the 1920s, researchers learned that theophylline opened airways to make breathing easier. Theophylline is a white crystalline powder first isolated from a tea leaves in 1888. Theo is Latin for tea, and phylline is Greek for plant. During the 1920s was recognized as a bronchodilator and was first prescribed for asthma. During the 1940s an IV version of the medicine was used in hospitals. During the 1950s it was used to treat asthma. However, it wasn't until the late1970s (I was born in 1970) that it was commonly prescribed for the treatment of asthma (back then, asthma was only treated as an acute disease, and you didn't take medicines to prevent symptoms). During the 1970s, slow release theophylline was introduced to the market, beginning with the brand Theo-Dur. So, if you felt fine, you quit taking your medicine. My point here is that I was born at the precipice of good asthma medicine. However, I was also born about 19 years before asthma was treated as a chronic disease, where asthma preventative medicines were taken every day to prevent asthma symptoms. (5, 6)

In 1976, I was introduced to theophylline. I would have been six. It was probably a solution called Sustair. Mom kept it in the bathroom medicine cabinet, and spoon-fed it to me once or twice a day when I complained of shortness of breath. I would go without taking it for long periods of time. Around 1980 I was prescribed a white pill called Theo-Dur. I figured I would probably never get off it. My memory around this time is a little hazy. I asked my mom if the medicine I was taking was theophylline, and she had no memory. There was another medicine, one that tasted terrible, that I took when my asthma was bad. It was also a solution. Considering corticosteroids taste nasty, I'm guessing this other medicine was a steroid. If you have knowledge of medicines a kid might be prescribed for asthma during this era of our history, please let me know. I asked my mom about it, but she doesn't remember. My doctor at this time has since passed away, so I obviously can't ask him. I do know I was started on theophylline at an early date, so I think I'm safe to assume the medicine I took every day back then was theophylline.

I actually wrote a story a while back about forgetting to take it with me on vacation. Keep in mind I was not introduced to the rescue inhaler until I was 10 in 1980. Physicians had to constantly monitor patients on theophylline to monitor theophylline levels. (4) I don't remember getting poked a lot, so, if this was done, it wasn't too often, maybe once a year -- maybe never.

Update: I remember that after each of my doctor visits mom would sit in the doctor's office and talk to him. My mom was a note taker, and thankfully she kept these notes. I recently found them in an old picture book mom kept. According to these, the medicine I was prescribed in 1976 was 1 teaspoon of tedrol, which is a combination of ephedrine and theophylline. The notes also says I can take brondecon. From a quick search through Google Books I can see that this was an elixir of theophylline. Of course, the note says I should take them to August 28. Why he chose this date for me to quit is unknown. However, I would imagine that this would carry me through allergy season. Again, it should be noted here that back then you only treated acute symptoms, and once you felt better you quit taking medicine. So, this may help explain the note to quit taking them at the end of August.

Update. The medicine I was prescribed in July 2, 1980, was 2 of 150 mgm theovent at 8 a.m. & 8 p.m. till run out & as for a prescription for the 250 mg of which he'll take 1 at 8 am & 8 p.m. until further notice. So I was taking the pills by 1980. On July 26, 1980 I was prescribed 2 theovent capsules at 8 a.m, 2 p.m. and 8 p.m. every day. This change makes sense as it would help keep my theophylline level stable throughout the day. I should have stayed on this dose, and you will see why in my note for 1985 below. As an aside here, there was also a note: "Have a theophylline blood level done at hospital 10 a.m. June 26. Call about the results June 30th or July 1st."

In 1980, I had episodes of severe nausea and headache. I remember these episodes were always blamed on the flu. However, a part of me now wonders if it was due to an unintentional overdose of theophylline. A therapeutic dose is above zero. The safe zone is less than 10. In order to gain a therapeutic benefit, the dose had to be high enough that the benefits often came with side effects such as tremors and stomach problems. Sometimes I wonder about this. The headaches and nausea were so severe that, even at the age of ten, I cried. .A normal theophylline level is zero (it’s not needed). A high theophylline level has been linked with some severe side effects, such as nausea, headache, seizures, and even death.

Initially, a level of 15-20 was considered therapeutic and safe. However, later on, 5-15 (or a level of 10), was considered therapeutic and safe for most asthmatics. (6) I do not know what theophylline level my doctors were searching for.

This was also the year I was introduced to Albuterol. My albuterol history will be told at a later date. I'm sure you'll find that interesting considering I became a prototypical rescue inhaler abuser.

By 1984,  I knew caffeine was a mild bronchodilator. I don’t remember how I learned about it, but I was told from someone that caffeine opened airways. I tried it a few times with negligible results. I figured, and probably rightly so, that my was too severe and required stronger bronchodilators than just coffee.  Years later, I’d learn that theophylline is a member of the xanthine family of medicine, the same family theophylline belongs too.

For the record, coffee was first recommended as a treatment for asthma by Henry Hyde Salter in 1959. But there was no mention of it in later medical textbooks that covered asthma, such as Henry Osler's 1901 edition of "The Principles and Practice of Medicine." (3, 5)

In 1985, my theophylline dose was tweaked. I was admitted to “the Asthma Hospital” in Denver, and doctors there monitored my blood theophylline level for a 24 hour period. I had a port put into a vein in my right hand that allowed nurses to draw my blood every couple of hours. By doing this they observed that my theophylline level dipped around 2 p.m.. So, rather than me taking my dose in the a.m. and p.m., they had me take it at scheduled times, such as 6 a.m., 2 p.m. and 10p.m. This kind of sucked because I had to get up early and stay up late. I also had to remember to take it in the afternoon. But it worked. When I repeated the test a month later, my theophylline levels remained stable throughout the day, resulting in better asthma control. The doctors at this hospital also had me take Azmacort 4 puffs 4 times every day to control my asthma. The combination of these medicines worked great. The problem was being compliant with this regimen, as it was a lot of pill taking and puff inhaling. This was a problem not just for me, but for many other asthmatics at the time. The good news for asthmatics was that, during the 1980s, many other asthma medicines were approved by the FDA that reduced inflammation and kept airways open. This included a safer rescue inhaler called albuterol (Ventolin, Proventil) and inhaled corticosteroids like beclomethasone (Vanceril) and later triamcinolone (Azmacort).

In 1987, it was learned that some antibiotics caused theophylline levels to spike. I was vaguely aware of this, but like the risk of dying due to rescue inhaler abuse or simply due to having asthma, I heeded the warnings little attention. The antibiotic known to discovered to raise theophylline levels was Ciprofloxacin products. A warning was placed on the Theo-Dur package insert, so this is probably how I was alerted to this. I do not think it was my doctor. Why would a doctor warn you of the risks of taking a medicine he would never prescribe for me anyway? The labeling change was not added until 1990. Just a thought here: Maybe I was prescribed one of these medicines, and this explains my nausea-severe headache story above. Probably not, but you never know.

By 1988, I knew what happened when I forgot to take my theophylline.  In my defence, I was a college student at the time and was really busy learning. I simply forgot to take it for a couple days. My asthma became increasingly worse during the day, and my inhaler failed to remedy the situation. My chest became tight, and felt like someone was inside it with a feather tickling my airways.  I started coughing, and it was a painful cough productive of white secretions. It was a familiar feeling. I felt it before, many times. Over time, I learned it was because my theophylline level was too low. The remedy was to take theophylline. I trudged to my dorm room. By the time I got home my asthma attack was in severe mode. I took my theophylline dose, and sat all frogged up on the edge of a chair. I watched the clock. I knew I would start feeling better in about 20 minutes. It was a long, grueling 20 minutes. It’s a neat, euphoric feeling when one moment you can’t even take in half a breath, and then all of a sudden each breath gets deeper and deeper. You also don’t want to experience this. As a side note here, my room mate Frank came into the dorm room during this time and saw me in my panic stricken state. I was embarrassed. He was concerned. I said, “I will be fine. Just give me a half hour.” Of course, I said this in short, choppy sentences. What happened? A normal theophylline level is zero. My airways are chronically inflamed. Theophylline helps reduce this inflammation to make airways less twitchy and keep them open. The exact mechanisms are complicated and not well understood. However, once you start taking it, your body becomes dependent on it. When I missed a more than one doses, my theophylline level fell and this inflammation got worse. It irritated nerve cells in the area to cause that itching feeling. It irritated goblet cells to increase mucus production causing that painful cough.

In 1991, I started taking Salmeterol (Serevent). This is basically a long-acting albuterol. You were only supposed to take two puffs twice daily. I don’t know if it worked or not. I don’t know if I was even compliant with it (and probably wasn’t). What I do remember is one night my asthma was really bad, and I kept waking up and leaning to my right to grab my albuterol inhaler. I took many, many, many puffs on my inhaler that night. When I woke up, I realized that I didn’t puff on my serevent that night: I was puffing on my Serevent. This was when I realized that the fears about this great medicine are unwarranted. I realized Serevent does not kill asthmatics. If people die of asthma and a serevent inhaler was found clutched in their grasps, it was because they over relied on this medicine rather than seeking help. Of course, in the world we live in, the medicine usually gets the blame when bad things happen. Anyway, as you read on you will see why I put this in this post. My doctors tried to get me to take this medicine over the next ten years, although, especially considering I was using (and abusing) albuterol, Serevent made me too jittery. I hated this side effect, so I refused to take it.

By 1993, I was placed on the highest theophylline dose ever. The asthma hospital helped me obtain good control of my asthma. However, by 1993 it was uncontrolled once again. My doctor at that time (Dr. Oliver) increased my dose to 600 mg twice per day. It worked great to control my asthma. The problem with this is the there are side effects of theophylline, and they are similar to when you drink too much coffee. It increases mental acuity. It keeps you awake. It relaxes your esophageal sphincter and causes reflux of stomach acid, or what is now referred to as GERD. I became nauseated. My stomach was bloated. I felt horrible. I saw a surgeon. He performed a procedure called an EGD, or esophagogastroduodenoscopy. You could also call it an upper gastrointestinal endoscopy test. It confirmed I had an ulcer. There’s no way of knowing for certain the cause of an ulcer, but considering the high dose of theophylline I was on, it seemed the likely culprit. Of course, it could also have been a side effect from a steroid burst, or stress, or a bacteria.

In 1997, my new doctor (Dr. B.) was concerned about my high dose of theophylline. He was an Internist. He also said that he had never heard of such a high theophylline dose as mine. However, he checked my theophylline level and it was less than 10. He said he didn’t want to try to wean me off of theophylline due to the risks, and also due to my fear as to what would happen to me if I quit taking it (see above). Regardless, my Internist was surprised such a high dose didn’t kill me.

In 1997, Dr. B intentionally took me off my theophylline. Ironically, the day after I met Dr. B. I had a severe asthma attack. In a feeble attempt to self-help myself, I took extra theophylline. This was stupid. I was admitted to the hospital. A blood draw confirmed for the doctor my theophylline level was high. So, he cut me off my theophylline. This was equally stupid. Never take someone who is chronically addicted to theophylline off it. My asthma got worse. Seven days later I was still on high doses of corticosteroids and my asthma was still terrible. It was the weekend. My regular doctor got the day off. So, a  new doctor came to see me (Dr. M). She prescribed a dose of aminophylline. It’s basically theophylline given by IV. Within hours I was breathing easy. That doctor may have saved my life. Prior to being admitted I was still prescribed 4 puffs of Azmacort 4 times a day. However, a new medicine called Flovent had been introduced to the market. It contained fluticasone, an inhaled corticosteroid that only needed to be taken twice per day. This was my new prescription. It made compliance easier. It was also thought to be a better steroid. I don’t know that it was really better, however, other than it made compliance easier. He also prescribed Serevent. I tried to be compliant with these two inhalers. But, once again, the Serevent made me too jittery, so I quit taking it.

In 2001, I started taking Advair. It was (is) a combination of long acting bronchodilator called salmeterol. I was aware of it for a few years. However, I feared the fact that Serevent was in it. I figured it would just make me too jittery. However, I had a friend named Shauna who also had severe asthma, and her asthma (she said) greatly improved once she started taking Advair. So, I decided to try it. It worked great. My asthma greatly improved. In fact, once day, I went to Detroit to visit my brother Tony. I was with my girlfriend (and current wife). I panicked. My wife and I scrambled to find a pharmacy to get theophylline. Thankfully, I was using Rite Aid, and there was one near my brother’s home. I had my theophylline filled. A few months later, we visited her friends Carrie and Chris at their apartment. I once again forgot to bring my theophylline. However, I did not get it refilled. I had no trouble with my asthma that night. This was when I realized that Advair was doing a great job of reducing airway inflammation and keeping my airways open. I wondered, “Will I be able to finally get off theophylline?”

2003, the decline of theophylline as a top-line asthma medicine. During my annual checkup with Dr. B. he said, “Ten years earlier nearly every one of my asthmatic and COPD patients were on theophylline. Today, hardly any are.” There was a brief discussion about this, and we both decided to continue my current regimen. I had been on it so long, and it worked, so why change it. However, this got me to thinking. It was about this time I started discussing a slow wean with Dr. B. I tried several times, but there was that constant fear in the back of my mind. I failed to wean myself off it.

In 2007, I was finally weaned of theophylline. I honestly did not think it would ever happen. However, back in 1988 I was introduced to email and thought it was a stupid idea that would never fly. That same year my journalism teacher said, “I don’t ever envision a world without newspapers.  As it turned out, email was a huge success, newspapers are slowly becoming extinct, and theophylline is no longer a top-line asthma medicine. I had been on Advair for six years. I once again discussed with Dr. B. about a theophylline wean. He said to go really slow. So, this is what I did. It took me a whole year. I reduced it by half a pill a month. For many years afterwards, I kept the bottle of theophylline in my medicine cabinet. It was there as a reminder of how I was once addicted, and thought I would never get off theophylline. It’s a sign of how far asthma medicine has come in my lifetime.

It was also this same year I had a gastrointestinal bleed. I became nauseated and lightheaded one Monday afternoon. I was admitted to the hospital. My hemoglobin was 8 (normal is 13.5-17.5) I had another upper GI scope. It turned out I had another ulcer. I was taking a lot of Aspirins for headaches. I was off theophylline, so I couldn’t blame it. I was on Advair, but I can’t imagine an ulcer would be a side effect of such a low dose inhaled. Still, my doctor put me on Prilosec and said I will never be able to stop taking it. Actually, I am going to blame my theophylline and steroid history for messing up the lining of my stomach. I am because I can.

In 2010, I became addicted to coffee. Is this any surprise. Here I was chronically addicted to another member of the xanthine family. My body must have missed it. So, when I started to drink coffee for the first time in my life, I quickly became addicted. I did not know until recently that caffeine was metabolized into theophylline (actually, I probably did know this and just forgot). Still, it’s should be no surprise that I merely exchanged one member of the xanthine family for another, only a much lower dose. Hence, I still have GERD and the occasional trouble with my stomach. Interestingly, Prilosec has now been linked with dementia, so I suppose I have that to look forward to too, if I so happen to have the genes that lend to that sort of thing.

Here’s an interesting note. As a side here, I want to explain why it is I can now take Advair with no problems, when Serevent once caused me to feel jittery. Studies have shown that when you inhale a respiratory medicine with a propellant, it is distributed better in the airways, possibly resulting in better asthma control. So, it’s possible that just the change in the way Advair is delivered results in fewer side effects. Advair is a dry powdered inhaler. This is the only reason I can think of why I tolerate Advair so well, and that medicines like Serevent inhaler cause the jitters. Another interesting thought is Symbicort, Dulera, and Breo also cause the jitters. I cannot explain why Breo does this, other than it is one strong dose once a day. Serevent, Symbicort, and Dulera are all inhalers, at least when I used them.

Anyway, it’s interesting. Asthma is a heterogenous disease, meaning we are all different. This would explain why my asthma history, and what works for me, is different than what works for other asthmatics. Again, I think this little bit of history is a testament to how far asthma wisdom has advanced in my lifetime. As you follow my story, I will give many other examples.

Here are notes my mom took during a visit with my doctor on July 9, 1980. You can see that I was prescribed Theovent, Mom was instructed to have me take one capsule at 8 a.m. and 8 p.m, until further notice.
You can see here that I was also introduced to Vanceril, my first steroid inhaler.
Poly-v-flor is a multivitamin. Salt water was to relieve nasal congestion.
Allergy shots were also to be continued.

Further reading and references:

1. Breathinstephen.com: The Days of Aminophyline
2. ehealth: The quest to learn what that asthma solution was in the 1970s
3. ATS Journals: Asthma: 100 Years of Treatment and Onward
4. Mozayani, Ashraf, Lionel Raymon, editors, "Handbook of Drug Interactions," 2nd edition, pages 770-771
5. Picher, Maryse, Richard C. Boucher, editors, "Purinergic Regulation of Respiratory Diseases," 2011, Springer
6. Navarra, Tova, "The Encyclopedia of Asthma and Respiratory Disorders," 2003, pages 188-9