Drug Interactions between aspirin / calcium carbonate and Quin-G

MONITOR: One study has suggested that the antiplatelet effects of quinidine and aspirin may be additive. The risk of bleeding could be increased.

MANAGEMENT: Patients' bleeding times should be monitored and they 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. Patients should also be counseled to avoid any other over-the-counter salicylate products.

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MONITOR: Coadministration with drugs that can increase urinary pH such as antacids, carbonic anhydrase inhibitors, or urinary alkalinizers may decrease the urinary excretion of quinidine. The proposed mechanism is increased renal tubular reabsorption due to reduced ionization of quinidine in alkaline urine. In four healthy subjects given quinidine 200 mg every 6 hours, renal clearance of quinidine was reduced by an average of 50% during coadministration with sodium bicarbonate and acetazolamide 500 mg twice a day. Average urinary quinidine level was 115 mg/L at urinary pH below 6, but fell to 13 mg/L at urinary pH above 7.5. Likewise, average quinidine urinary excretion rate fell from 103 to 31 mcg/minute with increasing pH. In another six healthy subjects studied under the same conditions, increased serum quinidine levels were observed in five subjects during urine alkalinization, and prolongations of the QT interval were reported in three of the five. Since only about 20% of a quinidine dose is typically eliminated unchanged by the kidney, the clinical significance of this interaction is unknown. A case report describes a woman who developed toxicity in association with a threefold increase in serum quinidine levels after taking eight Mylanta antacid tablets (each containing 200 mg aluminum hydroxide gel, 200 mg magnesium hydroxide, and 20 mg simethicone) everyday for a week. However, the patient also drank over a liter of orange and grapefruit juice daily, the latter of which can inhibit quinidine metabolism and may have contributed to the toxic drug levels. In pharmacokinetic studies, single doses of aluminum hydroxide alone had no significant effect on quinidine pharmacokinetics or urinary pH, although the possibility of a significant interaction in occasional patients cannot be ruled out.

MANAGEMENT: Caution is advised if quinidine is used with agents that can increase urinary pH. Quinidine levels may need to be monitored more closely following addition or discontinuation of these agents, and the quinidine dosage adjusted as necessary. Patients should be advised to seek medical attention if they experience symptoms that could indicate quinidine toxicity such as tinnitus, hearing loss, visual disturbances, diarrhea, headache, dizziness, palpitations, syncope, or irregular heartbeats.

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MONITOR: Chronic administration of antacids may reduce serum salicylate concentrations in patients receiving large doses of aspirin or other salicylates. The mechanism involves reduction in salicylate renal tubular reabsorption due to urinary alkalinization by antacids, resulting in increased renal salicylate clearance. In three children treated with large doses of aspirin for rheumatic fever, serum salicylate levels declined 30% to 70% during coadministration with a magnesium and aluminum hydroxide antacid. Other studies have found similar, albeit less dramatic results. Antacids reportedly have no effect on the oral bioavailability of aspirin in healthy adults. However, administration of antacids containing either aluminum and magnesium hydroxide or calcium carbonate two hours before aspirin dosing led to reduced absorption of aspirin in uremic patients.

MANAGEMENT: Patients treated chronically with antacids (or oral medications that contain antacids such as didanosine buffered tablets or pediatric oral solution) and large doses of salicylates (i.e. 3 g/day or more) should be monitored for potentially diminished or inadequate analgesic and anti-inflammatory effects, and the salicylate dosage adjusted if necessary.

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