Drug Interactions between Decadron with Xylocaine and Miradon

Consumer information for this interaction is not currently available.

MONITOR: Grapefruit and grapefruit juice may increase the plasma concentrations of lidocaine, which is primarily metabolized by the CYP450 3A4 and 1A2 isoenzymes to active metabolites (monoethylglycinexylidide (MEGX) and glycinexylidide). 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 oral and/or intravenous lidocaine and potent CYP450 3A4 inhibitor, itraconazole, as well as moderate CYP450 3A4 inhibitor, erythromycin. A pharmacokinetic study of 9 healthy volunteers showed that the administration of lidocaine oral (1 mg/kg single dose) with itraconazole (200 mg daily) increased lidocaine systemic exposure (AUC) and peak plasma concentration (Cmax) by 75% and 55%, respectively. However, no changes were observed in the pharmacokinetics of the active metabolite MEGX. In the same study, when the moderate CYP450 3A4 inhibitor erythromycin (500 mg three times a day) was administered, lidocaine AUC and Cmax increased by 60% and 40%, respectively. By contrast, when intravenous lidocaine (1.5 mg/kg infusion over 60 minutes) was administered on the fourth day of treatment with itraconazole (200 mg once a day) no changes in lidocaine AUC or Cmax were observed. However, when lidocaine (1.5 mg/kg infusion over 60 minutes) was coadministered with erythromycin (500 mg three times a day) in the same study, the AUC and Cmax of the active metabolite MEGX significantly increased by 45-60% and 40%, respectively. The observed differences between oral and intravenous lidocaine when coadministered with CYP450 3A4 inhibitors may be attributed to inhibition of CYP450 3A4 in both the gastrointestinal tract and liver affecting oral lidocaine to a greater extent than intravenous lidocaine. 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 lidocaine may lead to serious and/or life-threatening reactions including respiratory depression, convulsions, bradycardia, hypotension, arrhythmias, and cardiovascular collapse.

MONITOR: Certain foods and behaviors that induce CYP450 1A2 may reduce the plasma concentrations of lidocaine. The proposed mechanism is induction of hepatic CYP450 1A2, one of the isoenzymes responsible for the metabolic clearance of lidocaine. Cigarette smoking is known to be a CYP450 1A2 inducer. In one pharmacokinetic study of 4 smokers and 5 non-smokers who received 2 doses of lidocaine (100 mg IV followed by 100 mg orally after a 2-day washout period), the smokers' systemic exposure (AUC) of oral lidocaine was 68% lower than non-smokers. The AUC of IV lidocaine was only 9% lower in smokers compared with non-smokers. Other CYP450 1A2 inducers include cruciferous vegetables (e.g., broccoli, brussels sprouts) and char-grilled meat. Therefore, eating large or variable amounts of these foods could also reduce lidocaine exposure. The clinical impact of smoking and/or the ingestion of foods that induce CYP450 1A2 on lidocaine have not been studied, however, a loss of efficacy may occur.

MANAGEMENT: Caution is recommended if lidocaine is to be used in combination with grapefruit and grapefruit juice. Monitoring for lidocaine toxicity and plasma lidocaine levels may also be advised, and the lidocaine dosage adjusted as necessary. Patients who smoke and/or consume cruciferous vegetables may be monitored for reduced lidocaine efficacy.

Nutrition and diet can affect your treatment with anisindione. 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 anisindione. 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 anisindione. 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 anisindione. Talk to a healthcare provider if you are uncertain about what foods or medications you take that may interact with anisindione. 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 anisindione is given with enteral (tube) feedings, you may interrupt the feeding for one hour before and one hour after the anisindione dose to minimize potential for interaction. Feeding formulas containing soy protein should be avoided.

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Using anisindione together with ethanol can cause you to bleed more easily. If you take anisindione you should avoid large amounts of alcohol, but moderate consumption (one to two drinks per day) are not likely to affect the response to anisindione 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 anisindione. 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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