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Drug Interactions between Maalox and Quinidex Extentabs

This report displays the potential drug interactions for the following 2 drugs:

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Moderate

quiNIDine aluminum hydroxide

Applies to: Quinidex Extentabs (quinidine) and Maalox (aluminum hydroxide / magnesium hydroxide / simethicone)

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.

References

  1. Gerhardt RE, Knouss RF, Thyrum PT, et al. "Quinidine excretion in aciduria and alkaluria." Ann Intern Med 71 (1969): 927-33
  2. Ace LN, Jaffe JM, Kunka RL "Effect of food and an antacid on quinidine bioavailability." Biopharm Drug Dispos 4 (1983): 183-90
  3. Zinn MB "Quinidine intoxication from alkali ingestion." Tex Med 66 (1970): 64-6
  4. Romankiewicz JA, Reidenberg M, Drayer D, Franklin JE "The noninterference of aluminum hydroxide gel with quinidine sulfate absorption: An approach to control quinidine-induced diarrhea." Am Heart J 96 (1978): 518-20
  5. Mauro VF, Mauro LS, Fraker TD Jr, Temesy-Armos PN, Somani P "Effect of aluminum hydroxide gel on quinidine gluconate absorption." DICP 24 (1990): 252-4
View all 5 references

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Moderate

quiNIDine magnesium hydroxide

Applies to: Quinidex Extentabs (quinidine) and Maalox (aluminum hydroxide / magnesium hydroxide / simethicone)

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.

References

  1. Gerhardt RE, Knouss RF, Thyrum PT, et al. "Quinidine excretion in aciduria and alkaluria." Ann Intern Med 71 (1969): 927-33
  2. Ace LN, Jaffe JM, Kunka RL "Effect of food and an antacid on quinidine bioavailability." Biopharm Drug Dispos 4 (1983): 183-90
  3. Zinn MB "Quinidine intoxication from alkali ingestion." Tex Med 66 (1970): 64-6
  4. Romankiewicz JA, Reidenberg M, Drayer D, Franklin JE "The noninterference of aluminum hydroxide gel with quinidine sulfate absorption: An approach to control quinidine-induced diarrhea." Am Heart J 96 (1978): 518-20
  5. Mauro VF, Mauro LS, Fraker TD Jr, Temesy-Armos PN, Somani P "Effect of aluminum hydroxide gel on quinidine gluconate absorption." DICP 24 (1990): 252-4
View all 5 references

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Drug and food interactions

Major

aluminum hydroxide food

Applies to: Maalox (aluminum hydroxide / magnesium hydroxide / simethicone)

GENERALLY AVOID: The concomitant administration of aluminum-containing products (e.g., antacids and phosphate binders) and citrates may significantly increase serum aluminum concentrations, resulting in toxicity. Citrates or citric acid are contained in numerous soft drinks, citrus fruits, juices, and effervescent and dispersible drug formulations. Citrates enhance the gastrointestinal absorption of aluminum by an unknown mechanism, which may involve the formation of a soluble aluminum-citrate complex. Various studies have reported that citrate increases aluminum absorption by 4.6- to 50-fold in healthy subjects. Patients with renal insufficiency are particularly at risk of developing hyperaluminemia and encephalopathy. Fatalities have been reported. Patients with renal failure or on hemodialysis may also be at risk from soft drinks and effervescent and dispersible drug formulations that contain citrates or citric acid. It is unknown what effect citrus fruits or juices would have on aluminum absorption in healthy patients.

MANAGEMENT: The concomitant use of aluminum- and citrate-containing products and foods should be avoided by renally impaired patients. Hemodialysis patients should especially be cautioned about effervescent and dispersible over-the-counter remedies and soft drinks. Some experts also recommend that healthy patients should separate doses of aluminum-containing antacids and citrates by 2 to 3 hours.

ADJUST DOSING INTERVAL: The administration of aluminum-containing antacids with enteral nutrition may result in precipitation, formation of bezoars, and obstruction of feeding tubes. The proposed mechanism is the formation of an insoluble complex between the aluminum and the protein in the enteral feeding. Several cases of esophageal plugs and nasogastric tube obstructions have been reported in patients receiving high-protein liquids and an aluminum hydroxide-magnesium hydroxide antacid or an aluminum hydroxide antacid.

MANAGEMENT: Some experts recommend that antacids should not be mixed with or given after high protein formulations, that the antacid dose should be separated from the feeding by as much as possible, and that the tube should be thoroughly flushed before administration.

References

  1. Cerner Multum, Inc. "UK Summary of Product Characteristics." O 0
  2. Wohlt PD, Zheng L, Gunderson S, Balzar SA, Johnson BD, Fish JT "Recommendations for the use of medications with continuous enteral nutrition." Am J Health Syst Pharm 66 (2009): 1438-67

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Moderate

quiNIDine food

Applies to: Quinidex Extentabs (quinidine)

GENERALLY AVOID: In a small, randomized, crossover study, the administration of quinidine with grapefruit juice (compared to water) to healthy volunteers significantly prolonged the time to reach peak plasma quinidine concentrations and decreased the plasma concentrations of its major metabolite, 3-hydroxyquinidine. These changes were associated pharmacodynamically with both a delay and a reduction in the maximal effect on QTc interval. The proposed mechanism is delay of gastric emptying as well as inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall induced by certain compounds present in grapefruits.

MANAGEMENT: Given the drug's narrow therapeutic index, patients receiving quinidine therapy should avoid the consumption of grapefruits and grapefruit juice to prevent any undue fluctuations in plasma drug levels.

References

  1. Ace LN, Jaffe JM, Kunka RL "Effect of food and an antacid on quinidine bioavailability." Biopharm Drug Dispos 4 (1983): 183-90
  2. Min DI, Ku YM, Geraets DR, Lee HC "Effect of grapefruit juice on the pharmacokinetics and pharmacodynamics of quinidine in healthy volunteers." J Clin Pharmacol 36 (1996): 469-76
  3. Ha HR, Chen J, Leuenberger PM, Freiburghaus AU, Follah F "In vitro inhibition of midazolam and quinidine metabolism by flavonoids." Eur J Clin Pharmacol 48 (1995): 367-71
  4. Bailey DG, Dresser GR, Kreeft JH, Munoz C, Freeman DJ, Bend JR "Grapefruit-felodipine interaction: Effect of unprocessed fruit and probable active ingredients." Clin Pharmacol Ther 68 (2000): 468-77
View all 4 references

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Therapeutic duplication warnings

No warnings were found for your selected drugs.

Therapeutic duplication warnings are only returned when drugs within the same group exceed the recommended therapeutic duplication maximum.


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Drug Interaction Classification

These classifications are only a guideline. The relevance of a particular drug interaction to a specific individual is difficult to determine. Always consult your healthcare provider before starting or stopping any medication.
Major Highly clinically significant. Avoid combinations; the risk of the interaction outweighs the benefit.
Moderate Moderately clinically significant. Usually avoid combinations; use it only under special circumstances.
Minor Minimally clinically significant. Minimize risk; assess risk and consider an alternative drug, take steps to circumvent the interaction risk and/or institute a monitoring plan.
Unknown No interaction information available.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.