Complementary medicines

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Welcome to the Australian Prescriber Podcast. My name is Dr Ashlea Broomfield, and I'm here with Dr Geraldine Moses who's a clinical pharmacist working in medicines information. Thank you so much for joining us today, Geraldine.

It's my pleasure, Ashlea.

When we talk about complementary medicines, are complementary medicines complementary?

Well, it depends on how you spell the word, doesn't it? Actually, complementary with an I or an E. We know they're not free, so we'll have to not spell it with an I. They can be complementary with an E, in that the idea is that these medicines can go with conventional medicines. But obviously, the issue that then pops up is whether complementary medicines will interact with conventional medicines. We know from surveys done by fabulous organisations like NPS MedicineWise that up to two-thirds of any population is using a complementary medicine at any one time, and 50% of those people will be using their complementary medicines with conventional medicines.

There can sometimes be a negative response by clinicians when patients are talking about use of complimentary medicines because we are aware of the safety risks and the concerns and the efficacy. How can we as clinicians have a more of a positive influence in terms of helping patients make decisions about quality?

Well, I think you just have to sit back and think, well, this is no time to judge. I think you've got to assess these medicines like any other medicine. So just call on your pharmacology skills and remember how to assess any drug interaction. Again, if you know the basic pharmacokinetics of your conventional medicines, you'll be able to look up the pharmacokinetics of a lot of the complimentary medicines and certainly their key pharmacokinetic characteristics. Then again, you can calculate a lot of this in your head without having to look up any fancy drug interaction calculators. In so doing, you're not getting anything particularly accurate, but at least you're getting an idea of whether this new product that a patient might want to take could potentially create problems for the patient.

It's an interesting discussion that you've brought up in terms of being able to kind of do this on the spot because I really find that when people come in and we talk about what other medicines that they're taking that are complementary that they often aren't aware of the specific type of brand or don't know the amount of medication that's in it or are unaware of the other ingredients. So it often requires getting them back in with a bag of their medicines and having a look at all of them. Then you're kind of working through all the different ingredients. So what's a kind of easier way that clinicians can find some information that can assist them in doing this and finding out what the potential pharmacodynamics and kinetics are of the specific ingredients or medicines?

Well, I think the first thing is also to remember that patients don't know their conventional medicines either. The thing is we've already got a record of a lot of them on our medical history for the patient. The other thing is to prepare the patient for this conversation. So if you were to tell them beforehand to bring in complementary medicines, they don't have to come a second time round. So tell everyone that if you're interested in discussing potential drug interactions with their complementary medicines, that they should spend that time between when they made the appointment and when they come in next to prepare a list or to bring them with them. But the second thing is that the patient needs to be educated that these things can interact. So having this discussion will change the whole ballgame really because they'll start to be made more aware of this potential for adverse reactions and drug interactions, which a lot of them don't ever think about because they only ever hear the good stuff. You know, this product is good for your immune system. This product will give you more energy. Most of the manufacturers don't present risk with their complimentary medicines.

In your editorial of Australian Prescriber, you mentioned it's not just the main ingredient that we need to look at, but also the components of the medicines in relation to that ingredient that are really important. Can you outline what you mean by that?

Absolutely. This discussion can be divided up into being considerate of the dynamic and the kinetic issues with the so-called nonactive ingredients of complementary medicines. So if we were to discuss some of the dynamic issues, ingredients that you can see that are listed but aren't the active one, the famous ingredient of the product for example, they might say, "This is a remedy with echinacea." We all might just go, "Okay, that'll be for treating infections." But there also might be in there things like liquorice. It's frequently used in herbal remedies because it's a flavouring agent. Liquorice has the dynamic adverse effects of being aldosterone-like. So it causes sodium and fluid retention. You then need to think that this medicine might actually do things like increase the patient's blood pressure. Liquorice also has an antiplatelet effect, so it can increase the risk of bleeding. It potentially has an estrogenic effect, can stimulate estrogen receptors. So may be a no-no in someone with hormone-related malignancies or other estrogen-related medical conditions, like say, fibrocystic disease of the breast or fibroids in the uterus. And that's just a flavouring agent. Some of the other ingredients you might see in there might be bitter orange extract, which sounds yummy and delicious, but actually, bitter orange contains a substance called synephrine, which is an adrenergic agent. It's actually related to ephedrine.

And as you may know, ephedrine also comes from a herb. It comes from ma-huang, a Chinese herb. So synephrine is very similar and therefore binds to adrenergic receptors, alpha₁ and alpha₂, beta₁ and beta₂, has a stimulant effect. You'll see bitter orange extract in a lot of remedies for weight loss and bodybuilding in particular. Even in the protein powders that people who are into bodybuilding take. Again, you look at that and think, "Oh yeah, boring," and not think it would be a stimulant if you just looked at its name. A really important ingredient would be pyridoxine, vitamin B6. It's often present in vitamins and minerals and any bloomin’ thing, really. I'm not so concerned about small doses. What's at risk is a dangerous cumulative dose of the vitamin B₆. There's good evidence out there in the literature that doses of 200 mg or more of B₆ a day can cause peripheral neuropathy.

Finally, another thing that pops into a lot of remedies is caffeine. It is often under the guise of the herb that's delivering it. So it might be green tea, mate, which is a South American herb containing a high concentration of caffeine is often there, and also a thing called guarana, the active ingredient is sometimes referred to as guaranine, but that's actually caffeine just that it's a synonym. So you can sometimes get products that have all three, actually four. They'll have coffee extract, green tea, guarana, and mate, caffeine, caffeine, caffeine, and caffeine, and yet it might be labelled as a medicine that's good for your liver, something like that.

Or a Red Bull.

Yeah, that's right. Then kinetically, we look for things like, say resveratrol. You may know resveratrol, a flavonoid that's in red wine that potentially contributes the beneficial cardiovascular effect that people now make resveratrol as a tablet that you can take as a complementary medicine. It's got a lot of drug interactions both with CYP enzymes and drug transporters. So too does a thing called bromelain. It's an extract from pineapple. It's a very, very potent inhibitor of CYP2C9. Quercetin, it's a bioflavonoid that's sometimes presented as citrus bioflavonoids in complementary medicines. But if you see that in the list of ingredients in the product, these compounds are very big, and they're the sort of thing that block CYP3A4 and also the drug transporter P-glycoprotein.

All of the new oral anticoagulants are substrates of P-gp. They have to be transported by P-gp. They get passed into the lining of the gut passively, but some of them are then kicked back out again by this efflux protein, P-glycoprotein, in the gut lining. So if P-gp is blocked, which it can be by some of these herbal remedies, more of the drug will get in. So there have been documented drug interactions between the new oral anticoagulants and herbal remedies via this mechanism. So that's just some of the ingredients. They're not the active ingredients that can cause both dynamic and kinetic interactions.

And it sounds like these interactions can be quite complex in relation to if there's multiple active ingredients that can cause potential interactions.

Oh yes, absolutely. That can drive a lot of us a bit mad because it becomes so complicated. So I would encourage people to not get too carried away with calculating the drug interactions. Most of these remedies that people buy as complementary medicines do contain multiple ingredients with multiple potential interactions. So if you're finding, once you've already seen two or three that have potential interactions with the person's conventional medicines about which you might be worried, then it's out. Don't progress it any further because they can't take the remedy and just skip one of the ingredients. They have to take them all. So it's one out, all out.

A lot of my patients will go to the pharmacy, and they've been given a statin, for example, particularly, and they'll be then offered a complementary medicine on top of that, and a common one for statins would be coenzyme Q10. I often wonder what the responsibility is of the pharmacies involved in terms of interactions and making sure these medicines are safe.

Very good point. I think, like any medicine, the pharmacists have a responsibility completely for what they're recommending. I suppose in the first instance, we need to be educating our consumers so that when they do present at a pharmacy, and they're offered these companion products, that they should have the confidence to ask the pharmacist to substantiate that recommendation with evidence and say, "Well, I'll buy it if you can explain to me how it's going to work and to what degree and why it's so good for me to spend my money on this." Firstly, looking for the evidence and then secondly confirming any potential risk, and then thirdly, if they do encounter a problem that they need to make a complaint because oftentimes when people experience adverse reactions or problematic drug interactions, they tend to blame themselves and say, "Oh well, I was an idiot for having bought that product. I should never have done that. I won't tell anyone." But it's exactly the time when they should be telling everyone, isn't it? They should be telling their doctor that this adverse thing happened. Going back to the pharmacy and saying, "I had a problem with that, and you sold it to me, and I think you need to let everybody know."

It's not really with the intent of getting people into trouble or reporting them to AHPRA, but in the first instance, it's that feedback, isn't it, that this is the outcome of your recommendation to me because for a lot of people, it's just becomes this big black hole of nothingness that you never really know whether the person was benefited or harmed. The TGA is the perfect location for submitting a quick, simple adverse reaction report. At least then it's documented and recorded in a central location.

Whenever I have discussions like this, I often go, "Oh, it's just all too much." It's just easier if they don't take them. But that's not really a realistic approach.

And I would strongly encourage health professionals to use their drug information resources. Every state has a state medicines information service, and these guys are highly trained in working out drug interactions. So you don't have to do it all by yourself. You've got clinicians who can help you, and any advanced trained pharmacist can help you as well.

That's unfortunately all the time we've got for this episode. Thanks for joining us today, Geraldine.

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The views of the hosts and guests on the podcast are their own and may not represent Australian Prescriber or NPS MedicineWise. I'm Ashlea Broomfield and thank you for joining us on the Australian Prescriber Podcast.