Watch Out For Furanocoumarins!

This class of organic compounds can affect many different medications, in some cases stopping them from working, and in some cases causing you to overdose.

It’s naturally occurring, and found in certain fruit.

Agent of chaos

The fact that furanocoumarins can have very different (often opposite) effects on different drugs, makes it a lot harder to predict in its behavior than, for example, alcohol.

In particular, we’ve talked before about the very high furanocoumarin content of grapefruit (including: grapefruit juice), which has come up sometimes in our This or That section.

For example:

❝Another thing to bear in mind is that grapefruit contains furanocoumarin, which can inhibit cytochrome P-450 3A4 isoenzyme and P-glycoptrotein transporters in the intestine and liver—slowing down their drug metabolism capabilities, thus effectively increasing the bioavailability of many drugs manifold.

This may sound superficially like a good thing (improving bioavailability of things we want), but in practice it means that in the case of many drugs, if you take them with (or near in time to) grapefruit or grapefruit juice, then congratulations, you just took an overdose.

This happens with a lot of meds for blood pressure, cholesterol (including statins), calcium channel-blockers, anti-depressants, benzo-family drugs, beta-blockers, and more. Oh, and Viagra, too. Which latter might sound funny, but remember, Viagra’s mechanism of action is blood pressure modulation, and that is not something you want to mess around with unduly.

So, do check with your pharmacist to know if you’re on any meds that would be affected by grapefruit or grapefruit juice!

PS: the same substance is quite available in pummelos and sour oranges (but not meaningfully in sweet oranges); you can see a chart here showing the relative furanocoumarin contents of many citrus fruits, or lack thereof as the case may be, as it is for lemons and most limes).❞

Other drugs, however, will be decreased in their effects.

For example, for antihistamines like fexofenadine, grapefruit juice inhibits transport proteins that help absorb the drug, reducing its effectiveness

Here’s a cheatsheet

Caveat: this is a non-exhaustive list!

Medicines whose effects can INCREASE	Medicines whose effects can DECREASE
Cholesterol-lowering statins: simvastatin, lovastatin, atorvastatin (higher risk of muscle pain or damage)	Antihistamines: e.g: fexofenadine (less effective)
Blood pressure-lowering drugs: felodipine, nifedipine, nicardipine, nisoldipine, amlodipine, verapamil	Blood pressure meds: e.g: aliskiren (levels drop sharply, making it less effective)
Anti-anxiety and sleep medicines: midazolam, triazolam, alprazolam, diazepam, clonazepam	Beta-blockers: celiprolol, talinolol, acebutolol (weaker heart-rate control)
Erectile-dysfunction drugs: sildenafil, tadalafil, vardenafil	Chemotherapy: e.g: etoposide (reduced absorption, which lowers effectiveness)
Heart-rhythm drugs: amiodarone, dronedarone, quinidine, disopyramide, propafenone (increased risk of irregular heartbeat or toxicity)	Thyroid medicine: levothyroxine (delayed absorption, usually not a huge problem)
Immune-suppressing drugs: cyclosporine, tacrolimus, sirolimus
Mental-health medicines: buspirone, quetiapine, sertraline (increased side effects)
Pain medicines: oxycodone, methadone (overdose risk)

Source: Expanded List Of Medications That Interact With Grapefruit ← as you can see, we had to clip the “increase” list for brevity; we kept it short by a) grouping them the way we did b) prioritizing the medications that are most common and whose interactions have the strongest adverse effect

Important note on timing

Of the many ways these interactions can occur, the two most common are:

• Blocking the enzyme (CYP3A4) in the gut that normally helps break down many drugs—this causes increases in drug levels.
• Blocking the transporter protein (OATP1A2) that helps the body absorb other medicines—this causes decreases in drug levels.

The enzyme-blocking effect can last up to 3 days, so skipping grapefruit for only a few hours won’t help! You need to avoid it entirely.

See: Drug-grapefruit juice interactions: two mechanisms are clear but individual responses vary

For medicines affected by OATP inhibition (like fexofenadine), leaving a 4-hour gap usually* avoids the problem.

See: Fruit juice inhibition of uptake transport: a new type of food–drug interaction

*Not a guarantee, because individuals’ physiology can and sometimes will vary.

Want to learn more?

That’s all we have room to say about furanocoumarins for now, but let’s quickly mention a very common (and very affective!) herbal supplement that has almost as many medication interactions as grapefruit does (albeit, for completely different reasons, many of which mechanisms of action are not yet fully understood):

St. John’s wort can weaken the effects of many medicines, including crucially important medicines such as:

• Antidepressants
• Birth control pills
• Cyclosporine, which prevents the body from rejecting transplanted organs
• Some heart medications, including digoxin and ivabradine
• Some HIV drugs, including indinavir and nevirapine
• Some cancer medications, including irinotecan and imatinib
• Warfarin, an anticoagulant (blood thinner)
• Certain statins, including simvastatin

Click here for a more comprehensive list of interactions, contraindications, and potential side effects

And for our main article on St. John’s Wort, check out:

Flower Power: St. John’s Wort’s Drug-Level Effectiveness (The Herbal Supplement That Rivals Prozac)

Take care!