Drug Interactions between Coumadin and galantamine

Nutrition and diet can affect your treatment with warfarin. Therefore, it is important to keep your vitamin supplement and food intake steady throughout treatment. For example, increasing vitamin K levels in the body can promote clotting and reduce the effectiveness of warfarin. While there is no need to avoid products that contain vitamin K, you should maintain a consistent level of consumption of these products. Foods rich in vitamin K include beef liver, broccoli, Brussels sprouts, cabbage, collard greens, endive, kale, lettuce, mustard greens, parsley, soy beans, spinach, Swiss chard, turnip greens, watercress, and other green leafy vegetables. Moderate to high levels of vitamin K are also found in other foods such as asparagus, avocados, dill pickles, green peas, green tea, canola oil, margarine, mayonnaise, olive oil, and soybean oil. However, even foods that do not contain much vitamin K may occasionally affect the action of warfarin. There have been reports of patients who experienced bleeding complications and increased INR or bleeding times after consuming large quantities of cranberry juice, mangos, grapefruit, grapefruit juice, grapefruit seed extract, or pomegranate juice. Again, you do not need to avoid these foods completely, but it may be preferable to limit their consumption, or at least maintain the same level of use while you are receiving warfarin. Talk to a healthcare provider if you are uncertain about what foods or medications you take that may interact with warfarin. It is important to tell your doctor about all medications you use, including vitamins and herbs. Do not stop using any medications without first talking to your doctor.

When warfarin is given with enteral (tube) feedings, you may interrupt the feeding for one hour before and one hour after the warfarin dose to minimize potential for interaction. Feeding formulas containing soy protein should be avoided.

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Consumer information for this interaction is not currently available.

ADJUST DOSING INTERVAL: The administration of galantamine with food and adequate fluid intake may reduce the impact of nausea, vomiting, diarrhea, anorexia, and weight loss that are commonly associated with acetylcholinesterase inhibitors (AChEIs). According to product labeling, the administration of food with various galantamine formulations (e.g., liquid, immediate-release tablets, modified/extended-release capsules) has no significant effect on the systemic absorption (AUC) of galantamine. While the presence of food has been shown to delay the rate of absorption (Tmax) and reduce peak concentration (Cmax), these changes are unlikely to be clinically significant. For example, when galantamine modified release was given after food, Tmax increased by approximately 30 minutes. Similarly, in 24 healthy elderly subjects, the presence of food with galantamine immediate release tablets (12 mg twice a day) delayed the Tmax by 1.5 hours and decreased the Cmax by about 25% without affecting the AUC.

MONITOR: Grapefruit and grapefruit juice may increase the plasma concentrations of galantamine, which is partially metabolized by the CYP450 3A4 isoenzyme. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruit. Inhibition of hepatic CYP450 3A4 may also contribute. The interaction has not been studied with grapefruit juice, but has been reported with both moderate and potent CYP450 3A4 inhibitors. When study subjects (n=16) received the potent CYP450 3A4 inhibitor ketoconazole (200 mg twice daily for 4 days) with galantamine (4 mg twice daily for 8 days), the systemic exposure (AUC) of galantamine increased by 30%. However, when study subjects (n=16) received the moderate CYP450 3A4 inhibitor erythromycin (500 mg 4 times daily for 4 days) with galantamine (4 mg twice daily for 6 days), the AUC of galantamine only increased by 10%. In general, the effects of grapefruit products are concentration-, dose-, and preparation-dependent, and can vary widely among brands. Certain preparations of grapefruit (e.g., high dose, double strength) have sometimes demonstrated potent inhibition of CYP450 3A4, while other preparations (e.g., low dose, single strength) have typically demonstrated moderate inhibition. While the clinical significance of this interaction is unknown, increased exposure to galantamine may lead to AChEI related adverse effects such as vagotonic effects on the heart rate (e.g., bradycardia and heart block), neurologic side effects (e.g., seizure activity), respiratory distress, bladder outflow obstruction, dizziness or syncope, nausea, vomiting and/or diarrhea.

MANAGEMENT: According to product labeling, galantamine should be administered with food and adequate fluid intake to reduce the impact of cholinergic-related gastrointestinal adverse effects (e.g., nausea, vomiting, diarrhea, anorexia, and weight loss). Caution and closer monitoring for AChEI related adverse effects may advisable if galantamine is used in combination with grapefruit and/or grapefruit juice. Modified and/or extended-release formulations must also be swallowed whole and not crushed, chewed, or divided.

Using warfarin together with ethanol can cause you to bleed more easily. If you take warfarin you should avoid large amounts of alcohol, but moderate consumption (one to two drinks per day) are not likely to affect the response to warfarin if you have normal liver function. You may need a dose adjustment in addition to testing of your prothrombin time or International Normalized Ratio (INR). Call your doctor promptly if you have any unusual bleeding or bruising, vomiting, blood in your urine or stools, headache, dizziness, or weakness. It is important to tell your doctor about all other medications you use, including vitamins and herbs. Do not stop using any medications without first talking to your doctor.

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Rarely, vitamin supplements containing vitamin K may reduce the effectiveness of warfarin. This may be more likely to occur in individuals who have low levels of vitamin K in their blood. Before using any vitamin supplement, you should check the label to make sure it does not contain vitamin K. If it does, let your doctor know before you start using it. You may need more frequent monitoring of your INR after starting the supplement or whenever it is discontinued, and appropriate adjustments made in your dosage if necessary. It is important to tell your doctor about all other medications you use, including other nutritional supplements and herbs. Do not stop using any medications without first talking to your doctor.

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