The number of common prescription drugs that can interact with grapefruit—with potentially serious or even fatal results—is climbing sharply, according to a new comprehensive review published in Canadian Medical Association Journal.

Researchers from Western University report that grapefruit juice can interact with more than 85 oral medications, including certain cholesterol-lowering statins, cancer medications, antibiotics, anti-depressants, pain medications, heart drugs and other widely used pills.

"What I've noticed over the last four years is really quite a disturbing trend, and that is the increase in the number of drugs that can produce not only adverse reactions but extraordinarily serious adverse drug reactions," lead researcher David Bailey, a clinical pharmacologist at the Lawson Health Research Institute, told CBC News.

Potentially Fatal Interactions

Between 2008 and 2012, the number of drugs with the potential to cause the most dangerous interactions, including acute kidney or respiratory failure, GI bleeding, has jumped from 17 to 44, says Bailey, “Half of these drugs actually can cause sudden death,” if taken within hours of drinking grapefruit juice (or eating the fruit.)

Although the tart citrus can interact with more than 85 drugs, some interactions are unlikely to cause serious harm. Here’s a closer look at the research and what you need to know to protect your health. A number of other foods, including deli meat, milk and even candy, can also react adversely with certain drugs.

Why Are Grapefruit-Drug Interactions So Dangerous?

Twenty years ago, the same team of researchers discovered that grapefruit disrupts the body’s metabolism of certain drugs. The tart citrus contains compounds called furanocoumarins that interfere with enzymes that break down the drugs in the gut.

That means more of the drug stays in your body, which could cause it to build up to toxic or even lethal levels. The same compounds are also found in other citrus fruits, including Seville oranges (the kind used in marmalade), limes and pomelos, the study reports, but not in regular oranges.

These adverse reactions can occur many hours after someone consumes grapefruit or its juice—and as little as one glass of grapefruit juice can be enough to trigger dangerous interactions, the researchers report.

Which Drugs Interact with Grapefruit?

All of the drugs cited in the review are taken orally and share certain characteristics. They have limited “bioavailability,” meaning that, normally, only small amounts of the drug circulate in the bloodstream. And they all interact in the gut with an enzyme called CYP3A4.

Although this information is included in medication packet inserts, many people, including doctors, aren’t aware of this hazard, the review reported. Drugs with the potential to interact with grapefruit include the following:

• statins (Zocor, Lipitor)
• calcium channel blockers (Procardia, Nimotop, Sular)

And certain medications for the following conditions:

• anxiety (BuSpar)
• heart arrhythmias (Cordarone)
• depression (Zoloft)
• seizures (Tegretol, Carbatrol)
• malaria (quinine)
• insomnia (Halcion)

What Kinds of Interactions Can Occur?

One of the most dangerous medications—if combined with whole grapefruit, concentrate, or fresh juice—is the heart drug Multaq (dronedarone). This interaction can trigger a rare type of ventricular tachycardia, an extremely rapid heart arrhythmia, the researchers report.

Mixing the citrus fruit with the prescription painkiller oxycodone can lead to severe breathing problems, while combining grapefruit and the statin medication Zocor (simvastatin) may spark a potentially life-threatening complication called rhabdomyolysis, in which breakdown of muscle fibers can result in kidney damage of failure.

Which Other Foods Interact With Medication?

Among the other common foods that affect absorption or effects of medication are:

Black licorice. Many forms of black licorice (used to flavor foods and candy) contain a sweet substance called glycyrrhizin, which can increase the toxicity of certain drugs or worsen side effects.

Drugs it can interact with: University of Maryland warns that if you’re taking Lanoxin (a treatment for heart failure and irregular heartbeats), licorice can dangerously raise the risk of toxic side effects. It can also lower the effectiveness of ACE inhibitors and diuretics used to regulate blood pressure, may increase adverse effects from insulin, and boosts the potency of corticosteroids. There have also been reports of women on birth control pills developing high blood pressure and low potassium levels after eating licorice.

Leafy green vegetables. Kale, spinach, Brussels sprouts, and cabbage can make medication that combats blood clots less effective. That’s because these foods are high in vitamin K, a crucial nutrient for clot formation, while the goal of anticoagulant therapy is to slow down production of vitamin K to reduce clot risk. In effect, these foods counteract the drug’s desired effect.

Drugs these foods can interact with: Warfarin (Coumadin). If you take this drug, it’s not necessary to avoid leafy greens—instead doctors advise eating a consistent amount week to week, so your dose of warfarin can be calibrated accordingly.

Milk. Milk and calcium supplements can interfere with absorption of certain infection-fighting drugs, if taken together. The best solution is to wait a few hours after taking these drugs before drinking milk, popping a calcium supplement, or taking antacids (which can also contain calcium).

Drugs it can interact with: Tetracycline and fluoroquinolones (a class of antibiotics that includes Cipro, Levaquin and Avelox).

Alcohol. Mixing alcohol with certain medications—including both prescription and over-the-counter drugs—can have a wide range of harmful effects, from nausea and vomiting to drowsiness (increasing risk for car accidents), internal bleeding, liver damage, sudden changes in blood pressure, impaired breathing, and loss of coordination, warns National Institute on Alcohol Abuse and Alcoholism (NIAAA).

Drugs it can interact with:Painkillers, OTC cold, cough, flu and allergy remedies statins, drugs for angina (Isodil), anxiety and epilepsy (Ativan, Klonopin, Xanax,), arthritis (Celebrex, Voltaren), depression (Celexa, Effexor, Lexapro), diabetes (Glucophage, Orinase), enlarged prostate, high blood pressure, infections and other conditions. NIAAA offers a detailed list of drugs that don’t mix with alcohol.

Aged, cured or pickled foods. Aged cheeses like cheddar or Swiss, cured meats, and sauerkraut contain tyramine, an amino acid that sparks one of the most feared drug-food interactions when combined with certain antidepressants. The mixture can cause facial flushing, sweating, sudden rise in blood pressure, irregular heartbeats and brain hemorrhage. Tyramine is also found in certain types of wine, such as Chianti, sherry and Riesling.

Drugs it can interact with: Monoamine oxidase inhibitors (MAOI) for depression, and the antibiotics Zyvox and isoniazid.

Chocolate. The caffeine in chocolate (and other caffeinated foods) can trigger severe jitters or tremors when combined with certain meds, and packs a double whammy by irritating the stomach lining, amplifying the side effects of drugs likely to cause nausea. Chocolate also contains some tryamine, the culprit in a food-drug interaction that killed a University of Wisconsin Hospital and Clinics patient.

Drugs it can interact with: MAO inhibitors for depression, some antibiotics, narcotic painkillers like Vicodin and Percoset, asthma medications, and stimulants, such as Ritalin.

Avoiding food-drug interactions

The best ways to protect yourself is to check medication package inserts for interaction warnings and ask your doctor and pharmacist if they advise any dietary restrictions. Drugs.com offers an online interaction checker for both interactions with other drugs and with food.