Drug Interaction Report

GENERALLY AVOID: Ginkgo may potentiate the risk of bleeding associated with anticoagulants, platelet inhibitors, nonsteroidal anti-inflammatory drugs (NSAIDs), and thrombolytic agents. Ginkgolide B, a component of ginkgo, inhibits platelet-activating factor by displacing it from its receptor-binding site, resulting in reduced platelet aggregation. There have been isolated reports of bleeding complications (e.g., spontaneous intracranial bleeding; spontaneous hyphema; peri- and postoperative bleeding) and prolonged bleeding times associated with the ingestion of ginkgo, some of which resolved following discontinuation of ginkgo use. Possible interactions with warfarin and aspirin have also been described in the medical literature. A patient stabilized on warfarin for five years developed intracerebral hemorrhage two months after starting ginkgo, and another who had been taking aspirin 325 mg/day for three years developed spontaneous bleeding of the iris into the anterior chamber of the eye one week after he began using ginkgo. In contrast, an investigative study found no significant effect of ginkgo pretreatment for 7 days on clotting status or the pharmacokinetics or pharmacodynamics of a single 25 mg dose of warfarin in 12 healthy volunteers. Another study consisting of 24 patients stabilized on warfarin for at least several months also found no significant effect of ginkgo on INR or warfarin dosage compared to placebo, and no major bleedings were observed in the study. However, it is important to recognize that pharmacologic effects of herbal products may be highly variable due to inconsistencies in formulation and potency of commercial preparations.

MANAGEMENT: Patients should consult a healthcare provider before taking any herbal or alternative medicine. In general, consumption of ginkgo should be avoided during use of coagulation-modifying agents and at least two weeks prior to surgery. In patients who have used this herb extensively prior to receiving anticoagulation, antiplatelet, NSAID or thrombolytic therapy, the potential for an interaction should be considered. Close clinical and laboratory observation for hematologic complications is recommended. Patients should be advised to promptly report any signs of bleeding to their physician, including pain, swelling, headache, dizziness, weakness, prolonged bleeding from cuts, increased menstrual flow, vaginal bleeding, nosebleeds, bleeding of gums from brushing, unusual bleeding or bruising, red or brown urine, or red or black stools.

MONITOR: Many psychotherapeutic and CNS-active agents (e.g., anxiolytics, sedatives, hypnotics, antidepressants, antipsychotics, opioids, alcohol, muscle relaxants) exhibit hypotensive effects, especially during initiation of therapy and dose escalation. Coadministration with antihypertensives and other hypotensive agents, in particular vasodilators and alpha-blockers, may result in additive effects on blood pressure and orthostasis.

MANAGEMENT: Caution and close monitoring for development of hypotension is advised during coadministration of these agents. Some authorities recommend avoiding alcohol in patients receiving vasodilating antihypertensive drugs. Patients should be advised to avoid rising abruptly from a sitting or recumbent position and to notify their physician if they experience dizziness, lightheadedness, syncope, orthostasis, or tachycardia. Patients should also avoid driving or operating hazardous machinery until they know how the medications affect them.

MONITOR: Calcium-containing products may decrease the effectiveness of calcium channel blockers by saturating calcium channels with calcium. Calcium chloride has been used to manage acute severe verapamil toxicity.

MANAGEMENT: Management consists of monitoring the effectiveness of calcium channel blocker therapy during coadministration with calcium products.

The consumption of grapefruit juice may slightly increase plasma concentrations of amlodipine. The mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruits. Data have been conflicting and the clinical significance is unknown. Monitoring for calcium channel blocker adverse effects (e.g., headache, hypotension, syncope, tachycardia, edema) is recommended.