General information for these Q&As was checked by members of the BUS standing advisory committee in April 2015.    Revised March 2023.   BUS may make changes to this information as necessary.

Immunosuppressants and medicines interactions, including herbal medicines and food supplements: some questions and answers

You want to get the best from the medicines prescribed for your birdshot uveitis. However, you need to be aware that interactions with your medicines can occur.  Prescribed medicines can interact with each other, and herbal medicines, food supplements and purchased medicines can also interact with prescribed medicines.

The apparently simple question:

‘Can I take this medicine if I’m taking immunosuppressant(s)?’

can often be very hard to answer because many medicine interactions questions do not have a straight YES or NO answer. This is a complex area of medicine, and one where your healthcare professionals need to interpret information on a potential medicines interaction and tailor their advice to you, particularly if you are taking medicines for more than one condition.

So, how do you set about checking if a medicine may interact with your birdshot treatment? You may already have tried to do this online and found conflicting or confusing results.

These Q&As are here to help you learn more about medicines interactions.

To use these Q&As, please click on the links below to find the answers to the questions.  You will find that there are links within several of the answers to take you to more information.

Posters

Follow the link to quick summaries of common interactions and side effects for: 

• Azathioprine
• Ciclosporin
• Mycophenolate Mofetil
• Tacrolimus

Note: the interactions listed on the posters are only the main interactions reported for each immunosuppressant. Other interactions exist. Read the pack information leaflet supplied with your medicines.

Q1: Why do I need to know about medicines interactions?

Q2: Who should I ask about medicines interactions?

Q3: Why is it so hard to find out whether two medicines interact or not?

Q4: How do medicines interact?

Q5: Where do I start finding out about what might interact with my immunosuppressant medicines?

Q6: What are the problems of using lists of medicines interactions?

Q7: Why do I get different answers when I use different websites to check for an interaction?

Q8: What are the special problems with herbal medicines and food supplements interactions with other medicines?

Q9: What should I look out for when searching online sites for medicines interactions?

Q10: What should I be aware of when I read a medicines interaction report?

Q11: I’ve read a report about a laboratory study of medicines interactions with a medicine I take. Do I need to be concerned?

Q12: I’ve read a newspaper report about the effects of food supplements on prescribed medicines being ‘dangerous’. What should I do?”

Q13: What causes the interaction of some immunosuppressants with grapefruit and certain other citrus fruits?

Reference websites disclaimer:

Reference websites:

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Q1: Why do I need to know about medicines interactions?

Because you are the person responsible for your health, in partnership with your doctors. You need to know how to maintain your health and how to get the best from your birdshot treatment.

You must learn to ‘think interactions’ every time you propose to take any new medicine, including herbal medicines and food supplements.

A medicines interaction can mean either that your treatment becomes less effective, putting your sight at risk, or your treatment may have too great an effect, potentially damaging your health.

The ways that the human body handles all types of medicines is a complex subject (see question 4) and getting accurate medicines interactions information is not easy (see question 3, question 6, question 7, question 8, question 9, and question 10).

We each arrive at our birdshot diagnosis with different experiences and beliefs about prescribed medicines and about purchased medicines, including complementary, herbal or alternative medicines and supplements. Although complementary medicines are widely regarded as being ‘natural’, this is not the same as being ‘safe’, particularly in combination with prescribed medicines.

What is known and published about medicines interactions represents only the tip of a very large iceberg. There is a vast number of all types of medicines and supplements on the market, and thus an enormous number of possible combinations of those medicines. Just because no interaction has been reported between a purchased medicine, herbal medicine or food supplement and your prescribed medicine, this does not mean that there may be no interaction (see question 8).

The fewer medicinal products of any sort that you take, the easier it will be for you to avoid medicines interaction problems.

Ask yourself the following questions:

• How essential is it for me to take this purchased medicine, herbal medicine or food supplement?
• How difficult is it proving/has it been to get my birdshot under control with the medicines I have been prescribed?
• Do I want to run the risk of affecting my birdshot control or my health by taking this purchased medicine, herbal medicine or food supplement?

Always raise the possibility of a medicines interaction with your medical professionals when any medicines are added to or removed from your treatment, and also seek their advice before you start or stop medicines, including purchased medicines of all kinds (see question 2 and question 8).

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Q2: Who should I ask about medicines interactions?

Ask healthcare professionals who deal regularly with medicines interactions queries:

• pharmacists
• doctors, especially medical consultants (specialists)
• specialist nurses.

Pharmacists specialise in medicines and in dealing with medicines-related queries. In the UK, there is a national network of pharmacy medicines information centres based in hospital pharmacy departments. The hospital you attend for your eye care should be able to tell you how to contact their nearest medicines information centre. Ask at the hospital pharmacy. Community pharmacists can also help you with medicines-related questions, including medicines interactions.

UK general medical practitioners (GPs) have online access to a national database of medicines interactions information for professional use.

Be prepared for healthcare professionals having to get back to you with an answer to your question. They may need to consult specialist sources of information and ask other experts to assess (evaluate) the answer first. This information will then have to be applied by your doctors to your individual circumstances, particularly if you are taking medicines for other conditions as well as for your birdshot (see question 4).

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Q3: Why is it so hard to find out whether two medicines interact or not?

Because medicines interaction is not a simple subject. It is not done by mixing two medicines in a test tube and seeing what happens. The answer to: ‘Can I take both of these medicines?’ is not always ‘Yes, you can’ or ‘No, you can’t.’ Sometimes, the answer may be: ‘We don’t know, because that particular combination of medicines has not been studied’. Often, the answer is: ‘It depends’. What it depends on includes:

• the age and weight of the person
• their liver and kidney function
• the medical condition being treated
• the doses of each medicine
• variations in the way people react to particular medicines (genetic differences)
• knowledge of how each drug is absorbed, transported, broken down (metabolised) and eliminated from the body (see question 4).

There are some combinations of medicines which are known to cause problems when they are given together. However, there are many other medicines combinations which have a known potential to cause interactions. Often, these potential interactions can be worked around (managed) by your doctor or other healthcare professionals so that both medicines may be taken. This can be done by:

• reducing or increasing the dose of one or both medicines
• choosing another member of a group (class) of similar medicines, as some medicines in a particular class may be less likely than others to cause an interaction
• choosing a different medicine altogether.

The best medicines interactions information sources will include details of the importance (significance) of an interaction, including:

• reasons why a particular combination of medicines may or may not be taken
• suggestions on how to work around (manage) a reported interaction.

Assessing (evaluating) and applying this information in practice is a job for your healthcare professionals (see question 2).

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Q4: How do medicines interact?

To answer this, you need to understand what happens to medicines in the body.

Absorption

One medicine may alter either the rate or the amount of absorption of another medicine. For example, if medicines containing calcium, aluminium or magnesium, marketed either as antacids or as food supplements, are taken at the same time of day as a dose of mycophenolate, they can reduce the amount of the mycophenolate dose which is absorbed. To avoid (manage) this potential interaction, take the antacid/food supplement at least one hour before or two hours after taking the mycophenolate.

Distribution

Some medicines combine with (bind to) proteins in the blood fluid (plasma) to travel round the body. One medicine may displace another from these plasma proteins. The displaced medicine may then produce unwanted excess actions. Tacrolimus is an example of a medicine which is extensively bound to plasma proteins.

Breakdown (metabolism)

When you take immunosuppressants, your liver function will be checked by regular blood tests. One reason for this is because many medicines are broken down (metabolised) in the liver. This is done by substances called enzymes. However, some medicines can increase (induce) or decrease (inhibit) the activity of these enzymes, which can make medicine breakdown patterns complicated.

An important group of enzymes is called cytochrome P450 (CYP450). These enzymes are found in the liver and elsewhere in the body (see also question 13). They are involved in the breakdown of several medicines. The enzyme CYP450-3A4 (also called cytochrome P3A4 or CYP3A4) breaks down medicines including ciclosporin, tacrolimus and sirolimus. All three of these medicines inhibit the action of CYP3A4 as well as being broken down by it. All three also have what is called a ‘narrow therapeutic range’, which means that there is very little room between an effective dose and one which may either be ineffective or cause harm. In particular, many medicines are known to interact with ciclosporin. So, if you are taking ciclosporin, tacrolimus or sirolimus, it is particularly important to know that starting or stopping other medications, including herbal medicines or food supplements, could increase or decrease the body’s levels of these immunosuppressants.

Elimination (excretion)

When you take immunosuppressants, your kidney function will be checked by regular blood and urine tests. One reason for this is because many medicines are eliminated (excreted) through the kidneys. Some medicines pass through the kidneys by an ‘active transport’ process. Competition can occur between medicines which use the same active transport. When this happens, the presence of one medicine can delay the elimination of the other. For example, the elimination of methotrexate can be delayed in the kidneys by the presence of aspirin or other non-steroidal anti-inflammatory drugs (NSAIDs). This can lead to an unwanted build-up of methotrexate in the body. If someone taking methotrexate needs prescribed treatment with an NSAID, this interaction may be worked around (managed) by the prescriber’s careful choice of NSAID and giving it in a lower dose than usual (see question 3).

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Q5: Where do I start finding out about what might interact with my immunosuppressant medicines?

Start with the patient information leaflets (PILs; pack inserts, medication guides) supplied with your medicines.

UK PILs have a section headed ‘Taking other medicines’, which lists medicines which the manufacturer has recorded as interacting with their product.

However, these lists of potentially-interacting medicines in PILs have limitations.

First, see question 6 for the general disadvantages of lists of interactions.

Second, if there is more than one manufacturer or marketer of a particular medicine, the PILs’ lists of medicines interactions can vary between manufacturers. These differences in content occur because some manufacturers may decide to include ‘theoretical interactions’ (see question 7) in their PILs as well as including interactions about which more is known in actual (clinical) practice. However, the different manufacturers’ PILs for a particular medicine will usually list the medicines which are most likely to interact with it.

Finally, a PIL list of interactions does not give any information on how the interaction is thought or known to happen, or how it might be got around (managed) by your prescriber (see question 3).

Use your PILs information as a first line. Read your PILs and keep them handy in your purse or wallet. PILs are useful to refer to when you see your doctors, so that they can avoid prescribing medicines which could interact with your immunosuppressant treatment. If you are thinking of buying medicines without a prescription, including herbal medicines or food supplements, first read your PILs to check for possible interactions.

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Q6: What are the problems of using lists of medicines interactions?

Just listing medicine names as ‘interactions’ does not give you any information on the importance of an interaction, how it is thought to happen, how it might be worked around (managed) or how it might be prevented.

Think of any list of medicines names stated as being ‘interactions’ as just the first step in finding out about an interaction, not the answer to your interaction question. You need more information.

Though it is important not to cause yourself harm by taking a second medicine which may interact with one you are already taking, it is equally important that you are not denied the benefits of taking a second medicine on the basis of it simply being named in an interactions list. See question 3, question 4, question 5 and question 7 for more details.

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Q7: Why do I get different answers when I use different websites to check for an interaction?

Here are two reasons why.

First, some medicines interactions are classed as being ‘theoretical’ rather than ‘actual’ Theoretical interactions are predictions of possible interactions based on scientific knowledge of how medicines work in the body (see question 4).

Many websites and patient information leaflets (PILs; pack inserts, medication guides) include theoretical medicines interactions (see question 5 and question 9) but it may not be clear that they are theoretical. This can cause confusion about whether or not a medicines interaction actually exists.

If an interaction is noted to be ‘theoretical,’ you need more information. Finding out more about a ‘theoretical’ interaction could mean that you may be able to take a particular medicine, rather than be denied it unnecessarily (see question 3).

Secondly, websites can vary in content because of the way interactions information is gathered and published.

• Medicines interactions are reported worldwide in scientific journals in many languages. These reports are then collected by teams of healthcare professionals who assemble texts and databases of medicines interactions information. They use their specialist knowledge to evaluate this information – they decide whether or not it should be included in their text or database. This leads to variations in the content of interactions reference sources.

• New interactions reports are constantly appearing in medical journals. It takes time for these reports to be included in texts and databases. Some sources of information are updated more often than others. Try to find out the date of any information you find. Note that books can soon become out of date.

For your health and safety, the decision on the importance and relevance of any medicines interaction information is one which must always be made by your healthcare professionals (see question 2).

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Q8: What are the special problems with herbal medicines and food supplements interactions with other medicines?

The answer is: variability.

Here are some of the variables:

• Herbal products are often known by several different names. For example, goji berries are also called lycium. Some databases will include more alternative names than others.

• Variations in the sources of herbal ingredients and in the ways herbal medicines are prepared in different countries lead to variations in the activity (potency) of products. A herbal product made by different manufacturers may differ in potency even though it may be labelled as containing the same amounts of active ingredients in each dose.

• The way strengths of herbal medicines and food supplements are stated on labels can vary. This can make it difficult to check, for example, the amounts of some vitamins, which may be stated in units or in milligrams.

• The worldwide market for herbal medicines and food supplements is largely  unregulated.  The regulations which do exist differ between countries. This can make it hard to be certain what a product contains.

• In the UK, many products prescribed and prepared by
  medical herbalists and traditional Chinese or Ayurvedic practitioners are not subject to any regulation.

• Purchasing herbal medicines or food supplements online without knowing the origin of the product adds to variability.

• Worldwide, what may be marketed as a herbal medicine in one country may be marketed elsewhere as a food supplement or a ‘botanical’.

• Some herbal medicines have been found to contain non-herbal ingredients such as corticosteroids (steroids).

• Reports of interactions between prescribed medicines and herbal medicines or food supplements may not state the strength, formula, maker and country of origin of the herbal medicine or supplement.

• ’No interaction found’ in one interactions site may not be the only answer to your question. Search in several sites.

Scientifically reliable reports of interactions between prescribed medicines and herbal medicines or food supplements can be hard to find. Much of the reported information tends to be:

• theoretical work (see question 7)
• single case reports (see question 10)
• laboratory studies (see question 11).

Although single case reports can be useful, they need to contain enough detail for their importance to be professionally assessed. With the variability of herbal medicines and food supplements, a single case report of an interaction can be misinterpreted and generalised, leading to misinformation being passed on about its importance or otherwise.

However, interactions between herbal medicines or food supplements and other medicines can be serious. This is a particular problem for people taking medicines with a narrow therapeutic range such as ciclosporin, tacrolimus and sirolimus (see question 4) or medicines which are broken down (metabolised) by the isoenzyme CYP3A4 (see question 4 and question 13) because some herbal medicines are also metabolised by CYP3A4.

Always be aware that the absence of interactions information does not mean that an interaction may not occur (see question 1).

Be wary of products which claim to ‘support’ or ‘strengthen’ the immune system. Your birdshot is caused by unwanted activity within your immune system. If you are taking immunosuppressants, it is unwise to take complementary medicines which are described as having an effect on your immune system unless you have checked with a healthcare professional that it is safe for you to do so. (See question 2).

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Q9: What should I look out for when searching online sites for medicines interactions?

Here are some tips:

Who hosts the site?

• National databases or those operated by national institutions give good quality information.
• Use sites operated by medical or scientific staff. You want the best information.

How often is the site content updated?

• The dates on any quoted medical or scientific papers are a clue.

What does the site include?

• A site may deal only with interactions between conventional medicines. For interactions between prescribed medicines and alternative or complementary medicines, herbal products or food supplements, you will need to search elsewhere.

How does the site work?

• Spend time finding out what a particular site can offer.

• Is the site intended for the general public, or is it aimed at healthcare professionals?

• If the site has both kinds of information, check all of it, so you can get the fullest explanations of any interactions. Some professional websites may refer to groups (classes) of medicines which can make it hard to find interactions information on a specific medicine. Be aware that not all members of a class of medicines may interact in the same way with another medicine – do not jump to conclusions.

• Is there enough information to show if an interaction has been seen in clinical practice, or is it a theoretical interaction? (See question 7).

Is the interactions information on a blog, chatroom or other informal site?

• A great deal of misinformation can be rapidly transmitted online. Information you find on these sites should always be checked elsewhere.

Is the information accurate?

• Always look for professionally-evaluated information, not statements and opinions unsupported by evidence or reasons. Check the information by using another site.

Which medicine names should I use?

• Use drug names (approved or generic names) in your search as well as trade (brand or proprietary) names. For example, search under mycophenolate mofetil and also under CellCept.

Which country hosts the database?

• There are great differences in countries’ medicine brand names and the very large numbers of branded medicines containing more than one ingredient. This can complicate an online search. Try to use medicines interaction information which has been collected in the country where you live. You can then check it with databases in other countries.

• Medicine names and spellings can vary between countries, eg, ciclosporin, cyclosporin and cyclosporine. Check the spelling if you do not get a search result.

How much information do I put in at a time?

• Although it takes longer, it is best to search for medicine interactions using pairs of medicines, to narrow down which combination of medicines might interact. This is particularly important if you are taking more than one immunosuppressant. Check each one separately for potential interactions. If you are checking a product which has several ingredients, check each ingredient against each immunosuppressant.

Some reference websites are listed at the end of these Q&As.

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Q10: What should I be aware of when I read a medicines interaction report?

 Points to consider when reading a report:

• Is it supported by published scientific research? The original source of medicines interactions information is particularly important when you read online or newspaper reports. (See question 11 and see question12).

• Is it a summary (abstract) or a full report? Abstracts may not give enough detail. Conference reports may be preliminary findings from work which is still in progress.

• Is it a laboratory (in vitro) study or work done on patients (in vivo)? (See question 11).

• Is it about a new interaction, or is it new information on medicines already known to interact?

• Is it a theoretical speculation on an interaction, or actual observations on patients? (See question 7).

• How many patients are included?

• If the report is about several patients, did the interaction affect all of them, or only some?

• Are there details of the patients’ ages, the names of the companies manufacturing the medicines, the brand names and doses of the medicines, the length of time the medicines were taken, and the medical conditions being treated?

• Is it clear whether the interaction was classed as serious or not?

• Do the authors explain the possible cause (mechanism) of the interaction (see question 4) or is further work needed to find out why it happened?

• Is the combination of medicines to be avoided altogether, or do the authors explain how the interaction could be worked around (managed) by a healthcare professional? (See question 3).

• Do the authors say if other medicines could be used instead of the one which caused the interaction?

• What conclusions are made?

• Who paid for the study and were any of the authors linked in any way with the companies producing the medicines mentioned in the report? Sponsored studies can produce reliable work, but it is important to be aware of any potential ‘conflict of interest’ in sponsored studies.

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Q11: I’ve read a report about a laboratory study of medicines interactions with a medicine I take. Do I need to be concerned?

This depends on what the report described, and its conclusions. Check whether it is about laboratory or experimental work only, or if it also involves experience with patients (see question 7 and question 8).

Predictions and clues about medicines interactions frequently come from laboratory (in vitro) work (see question 10). However, laboratory studies, though interesting, are often ‘work in progress’. Their results usually cannot be directly applied (extrapolated) to the use of medicines in humans, and it is very unwise to try to do so.

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Q12: I’ve read a newspaper report about the effects of food supplements on prescribed medicines being ‘dangerous’. What should I do?

You need to look behind the headlines of newspaper reports – and this includes online newspapers – to see what is actually being said.

Newspapers often combine opinion with facts, which can create unnecessary scare stories.  In good newspaper reports, the origin of the information should appear in the text. Use this to look up what the original scientific report said (see question 10). This is always better than relying on newspaper information which may be sensationalised to catch the reader’s eye.

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Q13: What causes the interaction of some immunosuppressants with grapefruit and certain other citrus fruits?

This interaction is related to the enzyme CYP3A4 (see question 4). CYP3A4 is found in the lining of the intestines (gut wall) as well as in the liver. Grapefruit, grapefruit juice, other grapefruit-containing products, limes, pomelos and Seville oranges (bitter or marmalade oranges) all contain compounds called furanocoumarins. These and other compounds in those fruits can reduce the levels of CYP3A4 in the gut wall. Sweet oranges do not have this effect.

Many medicines, including ciclosporin, tacrolimus and sirolimus are broken down (metabolised) by CYP3A4. Some of this breakdown is carried out by the CYP3A4 in the gut wall, meaning that part of each dose is normally destroyed there before the rest of the dose is absorbed and enters the bloodstream. When the gut wall levels of CYP3A4 are reduced by any of the citrus products which contain furanocoumarins, more of each dose of ciclosporin, tacrolimus or sirolimus is absorbed. This leads to an unwanted increase in immunosuppressant levels in the body.

The amount of CYP3A4 in the gut wall varies between individuals, as does the time for the CYP3A4 to recover after it has been reduced by consuming furanocoumarins-containing citrus products. The amount of the CYP3A4 reduction also varies according to the amount and type of furanocoumarins-containing citrus products consumed.

Because of all these variables, the safest course of action is not to consume any furanocoumarins-containing citrus products at all if you take ciclosporin, tacrolimus or sirolimus.

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Reference Websites Disclaimer:

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Reference websites (revised March 2023)

Read question 9 before using websites, particularly noting the differences in spelling of medicine names in different countries.

Medicines interactions (revised March 2023)

Drugs.com   www.drugs.com

• Site makes extensive use of US brand names and multi-ingredient preparations.
• For the fullest information on any interaction, click on the ‘Pro edition’ tab as well as on the ‘Interactions checker’ section.

Medscape  http://reference.medscape.com/drug-interactionchecker

• Contains information on a large number of prescription and over-the counter medications, herbal preparations and supplements.
• Interactions answers are brief and may contain technical language.

WebMD   http://www.webmd.com/drugs/index-drugs.aspx

• From the ‘drugs and supplements’ tab, go to ‘Drugs Interaction Checker’.
• Contains information on a large number of medications, herbal preparations and supplements.

RxList www.rxlist.com

• Owned and operated by WebMD (see above).
• Click on ‘Interaction Checker’.
• A ‘Vitamins and Supplements’ tab leads to a ‘Vitamins, Herbs and Dietary Supplements’ section which also includes interactions information.

Medline Plus http://www.nlm.nih.gov/medlineplus/druginformation.html

• Search ‘drugs, herbs and supplements’.

Medicines information – general (revised March 2023)

Electronic Medicines Compendium (eMC) www.medicines.org.uk/emc

• Detailed information on prescription medicines licensed for use in the UK.
• Information for each medicine is provided as:

~ a PIL (patient information leaflet or pack insert) which includes basic information on medicines interactions
~ an SmPC (summary of product characteristics; product data sheet) which is in a standard format, is more detailed than the PIL and is designed for healthcare professionals.

• PILs and SmPCs contain medicines interactions information.
• Not every company marketing prescription medicines in the UK is included.

Drugs@FDA www.accessdata.fda.gov/scripts/cder/drugsatfda

• Detailed information on prescription medicines licensed for use in the US.

National Center for Complementary and Integrative Health  

https://nccih.nih.gov/health

• Scroll down to ‘Health Topics A-Z’.
• ‘Herbs at a glance’ section contains factsheets about specific herbs and botanicals.
•  ‘Safe use of complementary health products and practices’ section links to other information, including ‘How safe is this product or practice?’

National Institutes of Health, Office of Dietary Supplements 

www.ods.od.nih.gov/factsheets/list-all/

• Factsheets on dietary supplements and herbal medicines.

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