Does pineapple interact with warfarin? (3+ precautions)

In this article, we will discuss the interaction between warfarin and pineapple, along with some research studies to support our discussion. We will also discuss the foods which should be avoided while consuming warfarin. Additionally, we will discuss the ways to use warfarin safely and effectively. 

Does pineapple interact with warfarin? 

Yes, pineapple can interact with warfarin. Research studies have suggested that pineapple can increase the effect of warfarin. Warfarin is an anticoagulant which is used as a prophylaxis and in the treatment of venous thrombosis, deep venous thrombosis, pulmonary embolism, atrial fibrillation and myocardial infarction. (1,2)

Pineapple contains bromelain, which can interact with the metabolism of warfarin and potentiate its action. It is important to monitor the diet while on warfarin to avoid bleeding complications. Other fruits, vegetables, dairy products, meat, etc can also interact with warfarin. Hence it is essential to check for the possible interaction between warfarin and food. Make sure to discuss your diet with your physician to avoid any potential complications.

How does pineapple affect warfarin’s action?  

Pineapple contains bromelain, which is a mixture of cysteine proteases. Bromelain is a strong inhibitor of the CYP2C9 enzyme. Warfarin is primarily metabolised by the enzyme CYP2C9. Metabolism is important in order to remove the drug from the body; if metabolism is improper, the drug stays in the body for a longer duration. (1)

When the CYP2C9 enzyme is inhibited by the bromelain present in pineapple, it increases the plasma levels of warfarin in the body and enhances its effect. The inhibitory effect of CYP2C9 by pineapple juice is said to be dose-dependent. (1)

Bromelain is obtained from pineapple fruit and its stem. Bromelain supplements are also available as OTC medication to reduce pain, ecchymosis, swelling after surgery, etc. The primary mechanism of bromelain is the inhibition of the CYP2C9 enzyme, and along with that, it has its own anticoagulant and antiplatelet effect. A combination of pineapple and warfarin can increase the risk of bleeding and other complications. (1) 

What does the research suggest? 

A study by Navneet Attri et al. reported a case of a 50-year-old female admitted to the emergency department with hematuria, skin bruising, hemoperitoneum and left leg swelling suspicious of hematoma. She had a past history of St. Jude’s mechanical mitral valve placement and was on warfarin therapy. (1)

Upon investigation, her blood work showed the results of INR 14.7, partial thromboplastin time 167s and haemoglobin 10.8 g/dl. She didn’t consume any new medications or supplements. However, her diet included a smoothie of pineapple, papaya, almond milk, half a banana and an apple. (1)

Since pineapple contains bromelain, it inhibits the enzyme CYP2C9, which is essential for warfarin metabolism. This interaction between pineapple and warfarin led to an increase in INR and bleeding complications in the patient.  (1)

A study stated that pineapple fruit juice has a high amount of bromelain compared to other fruits, which has an enhanced effect on CYP2C9 inhibition. (3)

What are the foods that can interact with warfarin? 

There are many dietary intakes which can interact with warfarin. A diet rich in vitamin K, such as green leafy vegetables, dairy products, eggs, and cereals, contains vitamin K, and excess intake of diets containing vitamin K can interfere with the action of warfarin. (4)

A higher baseline concentration of vitamin K has been associated with a slow rise in INR, and consuming more than 250mcg per day of vitamin K has been shown to cause decreased sensitivity to warfarin and warfarin resistance. (4,5)

Many case studies have reported warfarin resistance and decreased efficacy of warfarin when the plasma concentration of vitamin K was higher, which led to complications such as MI, stroke and bleeding. (5,6) It is recommended to avoid eating leafy vegetables, milk, dairy products, meats, eggs, etc in a small quantity. 

Warfarin can interact with fruits such as pineapple, papaya, cranberry, grapefruit, pomegranate, kiwi, and avocado. These fruits inhibit the enzymes CYP2C9 and CYP3A4, which are essential for warfarin metabolism and potentiate its action. (1)

How to use warfarin safely and effectively? 

There are certain measures you need to follow in order to avoid complications during the use of warfarin. 

• Always consume the medication as prescribed by your physician. 
• Do not stop taking the medication without consulting your physician. 
• Always take the dose in the evening or as prescribed by your physician every day without changing the timing of the dose.
• Warfarin is associated with the risk of bleeding; if you notice any abnormal bruising, hematuria, bleeding gums, leg swelling, or any other bleeding signs, seek medical help immediately. 

• Avoid taking any multivitamin OTC medication and herbal supplements without consulting your physician, as the vitamin K content in the tablet can increase the risk of bleeding. 
• Avoid taking NSAIDs, as they can increase the risk of bleeding. The safer medications to treat symptoms of cold and headache include acetaminophen, guaifenesin, etc.

• Make sure you consume only a small amount of dark leafy vegetables (spinach, kale, broccoli), dairy products, meat and fruits. 
• Avoid eating animal liver as it contains high levels of vitamin K and can interact with warfarin. 
• If you are on a weight loss or weight gain diet, make sure you talk with your dietician and physician about the possible interaction between the food and warfarin. 
• Be aware of the potential side effects and complications related to warfarin. 
• Attend regular check-ups to monitor your INR levels and to track your treatment response.

According to my knowledge and experience as a pharmacist, Warfarin has the potential to interact with a wide variety of foods, and pineapple is one of them. Consuming a smoothie or raw fruit in an excess amount when you are on warfarin therapy can put you at risk of bleeding. Have a discussion with your dietician or physician about the possible interaction between the food and warfarin.

References