Aminophylline levels

Apart from when I am getting it IV (and even then it takes days of it) I never seem to get up to theaputic levels. Once I move on oral by levels slowly drop so the drs increase my dose which brings it back up little (not to theraputic levels but better than being in my boots) after a few weeks it drops again so we increase the dose again. I am pretty maxed out with tablets and any more I start to get sick. Is it possible that I build up resistance to phyllocontin?


34 Replies

  • The puzzle of aminophylline

    Bex, I have exactly the same problem with theophylline (I'm on Uniphyllin), and I wish I knew the answer!

    My levels tend to be quite erratic rather than drifting slowly down, so I can be therapeutic one day, then be admitted a few days later and found to be sub-therapeutic - we're never quite sure if I exacerbate because I go sub-therapeutic or if the effect of having a severe attack makes me go sub-therapeutic by reducing absorption etc. It's very frustrating because in some respects aminophylline is my wonder drug in that if I get it quickly enough IV it usually terminates the attack, so if I could keep my levels therapeutic I'm sure I'd be lots better! It also means that I'm always having to fight off accusations from doctors that don't know me, that I haven't actually been taking the stuff, when I go in and have a level of 2 - very annoying!

    When I used to see Prof Ayres at Heartlands he used to say that it was quite common for brittle asthmatics in particular to have this problem - just another way in which we are weird and strange! He didn't have any answers for it either unfortuately except just to keep pushing the dose up until it was therapeutic.

    In my case, at least part of the problem is absorption - without going into too many details, I've got Irritable Bowel Syndrome and my transit time is sometimes rather rapid! I try and cautiously use things like isphagula husk (a natural fibre) and as a last resort, loperamide to try to slow things down a bit. The modified release tablets are designed to stay in your gut for 12 hours and gradually release the drug, so if it passes through too rapidly your levels will drop towards the end of the 12 hour period. In the past I've taken the modified release tablet every 8 hours to try and get round this problem.

    The other issue is metabolism of the drug, and the fact that the enzyme system that metabolises it is extremely sensitive to any interaction with numerous different substances. Anything that stimulates the enzyme system will potentially make it metabolise the drug faster and make the levels lower. I'm sure you're well aware of which drugs that you need to avoid whilst on aminophylline/ theophylline. Some foods can also induce the enzymes - there's good evidence for the effects of broccoli, brussel sprouts and char-grilled meat, and some people have also implicated cabbage, spinach, leeks, onions, garlic, grapefruit juice, parsley, fried meat, smoked fiah and meat, ham and sausages. In most people these are not thought to produce clinically significant reactions, but as we all know brittle asthma does not necessarily conform to the rules! Alcohol and cigarettes can also have quite a big effect but I'm sure you're not a closet boozer/smoker!

    It seems to me that the crucial thing is to know exactly how the levels fluctuate over the course of the day - if you are reaching a therapeutic level soon after taking the tablet but then dropping sub-therapeutic later in the day, then taking the 12 hour preparation every 6-8 hours, or taking the non-sustained release preparation every 3-4 hours, ought to make a difference. There's also a preparation that you may have already tried called Phyllocontin FORTE, which is designed for smokers and other people who just clear the drug too rapidly for whatever reason.

    If, however, you are never reaching a therapeutic level, then that would suggest that you need a bigger dose, or perhaps a more easily absorbable form such as syrup, if you suspect that absorption is a problem.

    The fact that you say that bigger doses do make you feel sick makes me wonder if the former is the case - that you are reaching therapeutic levels (or even toxic levels) at some point just after you've taken it, but then it's not lasting long enough (if you were just never reaching therapeutic levels, you should not get sick, no matter how much you were on - the sickness tends to depend on the level not the dose). When they check my levels they normally check them just before a dose is due, which wouldn't detect that. I've thought of asking if I can have my levels monitored serially every two hours for a day, to try and distinguish between the two possibilities (and also to prove to them that I am actually taking the damn stuff and still have low levels!) - sounds like that might help you as well if you could persuade your docs to do it. Either way, I'd have thought that it's worth trying a different preparation (they do differ quite a lot) or a non-modified release, or syrup, if you haven't already. They used to make suppositories, which would provide an alternative (if unpleasant!) route of administration if absorption is a problem, but I'm not sure if you can get them in this country any more!

    I find that the dose I need fluctuates quite a lot depending on my weight, too - and with the inevitable pred-induced weight gain, I have to watch it quite closely from that point of view, too. Steroids also tend to make your body become more insulin-resistant, which promotes high levels of insulin secretion, which again can affect the enzyme levels and make your theophylline levels low!

    Sorry this is such a long answer - it's a complex subject and one that is close to my heart! Hope this makes sense too, if I've not been clear then let me know and I will try to explain myself better. Everyone on here seems to have such a high level of knowledge about their condition that I forget that not everyone has a medical degree!

    If you find an answer please let me know! I'm convinced that at least two of my recent admissions have been partly due to low theophylline levels, and I'm desperate to find a solution - even considered asking for subcut aminophylline to go home with (it's a no-no - apparently it's too irritant to give subcut!)

    I'm really glad you posted this as I was thinking of posting something very similar.... anyone else got any ideas?

    Well take care everyone

    Emily H

  • Sorry... really long answer!

    Didn't realise til I submitted quite how long that was! Sorry!

  • I take the Phyllocontin FORTE preparation simply as my half-life means I just cant keep Amino unless NORMAL release (not available orally now) in my system long enough!

    My system just gets rid of it too quick!

    I've been through the being watched taking it etc etc in hossie just to prove it all!

    But I think every bodys systems work differently but I know my system just hates anything slow-release!

    Anyone can build a resistance to a drug but I just find slow release preps just cause grief to me whatever ever drug they are!

  • Emily, yes that makes sense. I am using the forte version atm and have tried various forms from uniphyllin to phyllocontin continuios it does seem that I have this wierd drift down slowly. I was told my liver must be in tip top condition cos it just wacks through the absorbtion. I have been doing some remembering and all those admissions i can remember the levels for happen when it gets below 6 (moore normally somewhere around 4 but there was one where it was 6), lungs have been feeling like they are on the brink for the past week, I put to down to over-doing it but my level yesteray (6 hours post dose) was 6.3 it was 7.8 just over 2 weeks ago they increased the dose then.

    Not sure about the being sick thing, i tend to just chuck them right back up, I am like that with sando K it just comes straight back up not so much feeling sick as tummy saying oh no you don't and throwing it out.

    We have tried testing after 4 hours to see if that made any difference but the levels seem to be roughly the same as the 6 hour ones. I think I just get used to to dose.

    Until I spent ages on it IV at RBH i had never had a level above 7 I had no problem with a level of 13 when they finally stopped the IV. It then gradually started to drop down so they upped the dosage, levels went up a bit then dropped again so they up the dose now I am back at 6.3 and you can see the loop I am in! Before long I will be back at the 2.2 I was when I arrived at RBH assuming I survive that long.

    Short doses of IV amino make little difference it needs a good long course over at least a week to have any impact on my levels maybe that is why IV sal has always worked much better than IV amino, I simply don't get the short term boost it should provide.

    When my levels were above 10 apart from the morning dips I was really quite well maybe that is the key to keeping me well. Sub cut for the morning dips and a decent theo level for the rest of the day, now i just need to work out how to keep the theo level up :)


  • Bex I know this may seem mad but my cons once did a test just before when I should have had a dose (while in hossie) to check IF I had any amino in my system (after meds being supervisied) just before a dose was due!

    And have a guess the result ""NOT A TRACE""!

    Now the only way to keep the any trace is too take it closer together or split it over the day!

    But obviously with them being slow-release it can get complicated explaining it to new DR's to ya!

    But still GP has my instructions from the cons etc etc!

  • Bex i also have problems with absorbing aminoph, was told it is better to have some rather than none. Also told choc and coffee push thru system.

  • Therapeutic - Who Knows!

    Bex and Everybody else.

    I won't even try to be scientific or accurate, and I'm not medically trained like our Dr EmilyH, but this is what I know to be true for me. Please add your ideas, thoughts, experiences too, as it seems a number of us need this drug but have terrible trouble with it.

    Firstly, Amino is the one thing that has pulled me out of a hugely deep neverending asthma exascerbation hole. It succeeds where Pred doesn't.

    1.Amino seems to be affected by weight. Very small increases/decreases can affect levels/doses needed. Fact.

    2. I get a much higher level orally then with IV, but get heightened sickness with IV. Yes, Bex, I am odd!

    Current oral Level: 15.7. Highest tolerated IV Level: 11.3

    3. The Forte MR tablets are definitely stronger and give me a higher level than the corresponding dose of normal MR tablets. Fact, I think!

    4. Caffeine containing products worsen side effects. Period. I can't hack caffeine anyway. Choccie and coffee give me asthma! Cola just stains your teeth.

    5. It is vitally important FOR ME to take doses exactly 12 hours apart to lessen side effects from which I suffer unusually badly. And to take them with food. But I know that you can adjust + or - 4 hours on the 12 hourly tablets.

    6. Because my dose is keeping therapeutic level high as this is the only drug that works for me, I cannot reduce daily dose to lessen side effects, as level drops too much. But I become very toxic very quickly (15+ for me is toxic, although most say 20) So in order to stay on current dose I drop a dose every few days to maintain overall level without reducing overall dose (Double Dutch-sorry)

    7. Therapeutic Level seems to be a Logarithmic scale. Last Year, I was on 450mg bd and had a level of 4. I am now on 350mg Forte bd and have a level of 15.7. Explain that! OK I am at least 10kgs lighter!

    8. Watch which Anti Bs you are given if on Theo/Amino. Many interract and you will be in sickness hell if you take them together. I was so ill one time last summer I got blue lighted because of this.

    9. We all absorb this drug differently, some not at all. (D'oh). I have a friend on twice my dose with half my level. Again. Explain that!

    10. Personally, I have less problems with Pred, except I've wasted away on it. Amino seems to do the same, ie is possibly a cause of my extreme weightloss. This is under investigation so any ideas please let me know! I hate Amino, but my lungs love it. How do I win!

    Finally, I wish, no, I so wish I could ditch the Amino and just continue to neb my self silly to get by!

    I wish I could have one day where I didn't feel so nauseous and migrainey because of the Amino, but on the other hand I can breathe because of it, and if I stop it, my dream of returning to work will be only be dreamt of from a hospital bed.

    What do I do?

    Sus xx

  • Helloooo!

    Sus - I don't often have amo levels checked - will ask next week in opd about it.

    Anyway, Cafeine makes me feel sick too, I go downhill if I miss (or chuck up ) a dose , try to stick to 12 hrs intervals where poss give or take an hour.

    Also, If on anti Bs such as Clarithromycin 500s I leave at least an hour or 2 before attempting to take or I will chuck.

    I take Uniphylline 300mg BD.


  • Amino is the one thing that has pulled me out of a hugely deep neverending asthma exascerbation hole. It succeeds where Pred doesn't.""

    Sus, I totally agree with everything you wrote, particularly the above sentence - you could be talking about me! Weird, how this really quite old-fashioned and troublesome drug works so well (or could work so well) for so many of us!

    I've been toxic on 200mg bd and subtherapeutic on 800mg bd - work that one out!

    Also I don't understand why IV gets me better (and it really does!) even when my levels are good on oral on admission!

    This drug is a mystrey!

    Yours puzzledly

    Emily H

    PS - I really hope no-one thinks that I'm trying to come across like some sort of expert - pharmacology (especially of theophylline!) is really too complicated for me and most of what I've put in this thread is based on my own experience of it rather than anything I learnt at med school! I would hate to think that I sounded like I was trying to paint myself as a know-it-all doctor - after all we are all experts on our own condition - please let me know if I'm sounding too up myself!

  • Amino is the one thing that has pulled me out of a hugely deep neverending asthma exascerbation hole. It succeeds where Pred doesn't.""

    Sus, I totally agree with everything you wrote, particularly the above sentence - you could be talking about me! Weird, how this really quite old-fashioned and troublesome drug works so well (or could work so well) for so many of us!

    I've been toxic on 200mg bd and subtherapeutic on 800mg bd - work that one out!

    Also I don't understand why IV gets me better (and it really does!) even when my levels are good on oral on admission!

    This drug is a mystrey!

    Yours puzzledly

    Emily H

    PS - I really hope no-one thinks that I'm trying to come across like some sort of expert - pharmacology (especially of theophylline!) is really too complicated for me and most of what I've put in this thread is based on my own experience of it rather than anything I learnt at med school! I would hate to think that I sounded like I was trying to paint myself as a know-it-all doctor - after all we are all experts on our own condition - please let me know if I'm sounding too up myself!

  • Hi Emily H,

    Your info is very useful.

    It is interesting to know how varied it can be.

    I have it IV sometimes and it is a wonder drug! It does take a little longer than IV ventolin to kick in with me but when it works I only need it for a couple of days or so unlike IV ventolin which I can find difficult sometimes to reduce to a suitable level to go back onto s/c.

    ( I sometimes get greedy and need IV Amo, Ventolin & Mag! LOL)



  • Emily H no your input much appreciated I have always wonderd when I have good levels on oral why IV always makes such a difference and gets things better even if I do need days of it which sends local costa into a spin. I can tolerate buckets of the stuff was od once and had a level of 25 that did make me throw up ! Do I win the highest level prize please!


  • Den, you can only have the prize if you tell me how you do it...


  • Wierd, isn't it Den? Logically you'd think that if it's getting into you by any route enough to give good levels, it should work equally well, but I KNOW that IV works well for me even if I've got good levels when I go in! Maybe it's partly psychosomatic - I certainly have a lot of faith in IV aminophylline - if so I just wish that I could utilise the power of my psyche to keep me at home instead of having to go in!

    I'm lucky in that my levels go up very quickly on IV - within hours usually even on the 'normal' regimen of 0.5mg per kg per hour (notice how I skillfully avoided broadcasting my weight on the world wide web there!) - suggesting I suppose that it is more an absorption problem that I have with oral, rather than the rapid metabolism problem that some of the others seem to have.

    Last but one admission my admission level was 14.4 (unusually for me) on admission - went up to 17.7 with a few hours of IV and was 20 ish by the next morning, by which time I was feeling rather sick!

    Bex, when you go in and have IV do they give you a loading dose? Normally of course they would not use a loading dose with someone already on oral, but if you're starting off with low levels it might make sense! I know one time a few years ago when I was quite well, I managed to get off oral theophylline briefly (was so nice!) and when I went in and had the loading dose it was like magic!

    I've often wished that you could get a home theophylline level tester like the little glucometers, so could check my levels myself and adjust the dose accordingly. Although, as Sus points out, the relationship between the dose and the level is scarily non-linear, so it might not be all that easy!

    Yours frustratedly

    Emily H

  • Emily, bacause I take 1600mg of phyllocontin I don't get a loading dose, these days they wack up IV amino and IV Sal and worry about checking levels later. I have never ever got a level of above 13 even on 2grams over 24 hours, I weigh 13 and half stone (which is coming down slowly as the pred reduces I will be 10 and half stone and a size 12 again someday!) RBH don't tend to talk about weight they just started at 1gram and worked their way up until I got to theraputic levels.

    The idea of a home test and you adjust your dose accordingly is a fabulous idea.


  • There is ONE big diference betwen oral and IV!

    Oral are SLOW-release while IV is NORMAL-release!

  • I was just thinking about what IV Amino dose I always get when I have it!

    All I can remember is its in a 500ml bag and 500mg of Aminophylline in each bag, then the mls an hour is done on my weight!

    3.5 to 4 bags in 24hrs normally!

    They used to put 250mg in a bag till CONSULTANT said no thats not enough!

    Never have a IV loading dose as am on MAX of oral!

  • Think that's the same dose I get, Wheezer-works out as a gram per litre.

    What's this holding dose as I have never managed to stay on oral Amino this long, so if and when I next get it IVd I haven't got a clue what it means.

    Will just let the nice Docs work it out for me instead.

    I agree with Bex that Den def gets the gold medal for highest level. But can I have wooden spoon for being most intolerant or indeed biggest Amino wimp.

    Who was it who was mentioning sickness-another thread I think. I take Metaclopramide 3 times a day when bad.....

    Worth trying it-think it's available OTC Maxalon?????

  • Does anyone know what the levels are actually ideally meant to be between to be therapeutic I've just read my discharge letter again and it looks like my level was either 5.7 or 57 (writing is REALLY bad) and they've upped my nuelin to 250mg 3 times a day and given me maxalon with a bottle of cyclizine (yuck major snooze) for if that doesn't work.

    I've got a bit confused reading this today due to tiredness sorry - and i vaguely remember the hospital saying the blood should be taken 4 hours after the last tablet to me this time when i was in to check levels and that you should get your potassium and levels rechecked but have no idea how regularly (and when i asked gp she just said she wasn't sure(!) and we'd sort chest and foot out first worry about that next time!) Any ideas?

  • Sus

    Its *Loading dose* basicaly for those not on oral!

    It gives a high dose over whatever time quickly to get levl up!

    If its a gram per litre then I do 2gram in 24hrs !!

  • Numbers, numbers, numbers....

    Sus, the loading dose is a big IV dose (usually 250mg or 5mg per kg in about 100ml) that's given over 20 mins for folks who are not on regular oral theophylline, to get them up to a therapeutic level quickly. If you're already on oral, they won't give the loading dose for fear of making you toxic, so they start on the maintenance dose, which is usually 500mg in 500ml (or 1g in 1L) run at 0.5mg per kg per hour in most hospitals. I was interested though to hear that the Brompton gives a total 24 hour starting dose of 1g rather than by weight per hour - comes to the same thing for me as my calculation works out at 1080mg in 24 hours! (damn... gave away my weight! just don't do the maths, folks!) I'm lucky cos for me this gets me therapeutic very quickly, within hours, even if I came in low... now just have to sort out staying high on oral so I don't have to go in so much in the first place!

    Interesting to hear how others respond to it... I know asthmatics who come in regularly at the hospital I used to work in who require vastly differing doses to the standard protocol, and seem to spend a lot of my time persuading my colleagues that a 'one size fits all' approach doesn't really work for asthma (or indeed for any illness!) I know one teenager who can't tolerate more than 10mg per hour!

    Another thing to bear in mind though - Prof Ayres at Heartlands used to say to me that having a severe attack can MAKE your levels low... either by reducing absorption, or increasing metabolism or both. I know I usually vomit during a bad attack - even before people start poisoning me with amino - so I guess that's not going to help. In other words, if your level is found to be low in an acute attack, it's difficult to tell if you've had the attack because it's low, or whether it's low because you've had the attack. Although I guess that doesn't apply to people like Bex who are sitting at home watching it gradually drift down over a course of a few weeks.

    Well, I find this topic fascinating, if frustrating; interesting from a scientific and a personal point of view, and comforting to hear that I'm not the only one who struggles with low levels for no apparent reason. I'm aware that others may not be so enthralled though, so sorry if I'm boring anyone!

    Think I might ask if I can try taking immediate release syrup every 4-6 hours, rather than the 12 hour modified release... it'd be a hassle, but worth it if it worked.

    I'll let you know...

    Emily H

  • Wheezer, sorry, our posts crossed!

    Yours made more sense than mine... think I have a tendency to over-complicate things!

    Em H

  • I just want to know how to post a new subject on this forum.


  • EmilyH - The syrup you mentioned has been DISCONTNUED!

    It used to be called Nuelin liquid (its the normal release preparation I took for yrs then they withdrew it!)

    There are now NO oral normal release preparations at all!

  • Damn it! My BNF is too old! (They've stopped giving us free ones when a new one comes out)

    Suppose it would be technically possible to make an immediate release version by throughly crushing the modified release to destroy the little granules... NOT that I'm suggesting anyone tries that on their own, it could be a one way street to toxicity land!

  • I never get much benefit from IV amino in an acute attack, in that with Amino only I would end up ventilated, now the 2 costa's I go to most often know to wack up the amino and sal (seperate lines obviously) together and hope. So far IV sal has kept me off the vent. Usually they ween me off the IV Sal very slowly (sudden stop = sudden splatt) IV amino they normally drop by half and half again before coming off. I know there is someone at RBH who has 3 grams of IV amino over 24 hours, I have seen her and I would say her size and build is not that far off mine. As I have been told many times since being refered there they do things no-one else does.

    In Ealing they used to ask my weight and work things out from there but my levels stayed in my boots so they just kept putting the dose up till they reach their limit of 1.5 grams over 24 hours, even then I don't recall getting above a level of 7. I did once have a loading dose after they got my levels back quickly and they were only 2.2 but at the time I was only taking 450 of phyllocontin twice a day.


  • EmilyH- U can register for FREE online to access BNF online current and uptodate lol

  • I'm blushing now!

    Thanks Wheezer... seems like that's the sort of thing I should know! I'm embarrassed now!

    Just so used to being at work and there being up-to-date BNFs lying around all over the place! Or even better, the portable, interactive BNF I like to call a pharmacist!

  • Oh you have one those interactive ones too lol

    When I am in mines called Marion lol

    (I've known her so long now we good mates lol)

  • EmilyH

    I actually don't remember RBH working out what I needed for IV Amino dose from my weight?? But I was pretty out of it.

    They whacked up a gram in a litre, but my drip rate has to be set slow else I react badly. Hence I didn't used to get the whole bag, it was dripped in the low 40s, (mls per hr) or less if I wasn't doing great. Takes a few days to get going but then, wow!

    Am I right or wrong they work it out @ some set amount of Amino per kilo of body weight? Is that the same for the tablets too?

    I'd love to know. So OK I am roughly 45 kilos, with my boots on!

    They did try and increase it after initial 1g dose, and put it up to 1.3g, but I was very quickly out of it toxic, throwing up, room spinning, head blowing up, the worst ever.

    All this talk of toxicity. I was rather too poorly last night. Draped over a loo with baby neb, trying to get breath but throwing up in the process. The typical scenario. Think I was reacting to rather alot of stress this week regarding work.

    Needless to say, even though Amino is being screamed for by lungs this morning, pounding head has put a stop to it and I've had to drop the dose.

  • Sus

    Normally most hospitals run it at 0.5mg per kg per hour!

  • Sus, yeah, as Wheezer says the 'standard' regimen that most textbooks quote, and that I was taught, is 0.5mg per kg per hour, (which of course equates to 0.5ml per kg per hour with 1g in 1 litre) with the proviso that if someones going to be on it for more than a day or so it should be adjusted according to levels. So on that regimen they'd start you on 22.5 ml an hour. I get 45ml an hour cos I weigh 90kg (I'm equivalent to 2 of you! Ugh!)

    Most people (though perhaps not most people on this board) seem to get reasonable levels during the first 24-48 hours on that dose, and that's often enough, most ""normal"" asthmatics don't usually require it for much longer than that. I know that I get good levels on that regimen, although if I'm on it for more than a day or two I tend to gradually drift up into toxicity.

    From what Bex and the others were saying though, the Brompton seems to do it differently - correct me if I'm wrong, but it seems that they start with 1g over 24 hours, which would be equivalent to about 41.6 ml an hour, and then presumably titrate up or down depending on levels. Kind of makes sense I suppose as weight is only one of the many things that influences theophylline level (as we have discovered!) and I suppose they want to err on the side of giving a good dose to control things as quickly as possible.

    Suppose that's why the Brompton has the reputation it does though - because they are not afraid to push the limits and try things - after all if you don't try it you'll never know what dose you *can* tolerate.

    That pounding headache really is like nothing else on earth, though, is it? I remember being convinced that I was about to have a brain haemorrhage!

  • PS - It's usually different for the tablets, as there are so many more factors that influence levels, such as absorption and the slow release mechanism. I think most physcians just start on some smallish dose, say 200mg bd, then titrate up over a few weeks according to levels. I suppose they probably take weight into account a bit when choosing the starting dose, and they certainly take account of smoking and other drugs, but it's not a set calculation like the IV.

    Pretty sure that's the case, anyway! Someone correct me if I'm wrong!

  • Posting to bring this topic to the top

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