Drug Interactions between Cardioquin and potassium acetate / potassium bicarbonate / potassium citrate

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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