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Drug Interactions between Niravam and Ron-Acid Plus

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

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Interactions between your drugs

Minor

ALPRAZolam magaldrate

Applies to: Niravam (alprazolam) and Ron-Acid Plus (magaldrate / simethicone)

A number of studies have reported that antacids can delay the gastrointestinal absorption and reduce the peak plasma concentration (Cmax) of some benzodiazepines, including clorazepate, chlordiazepoxide and diazepam, although the overall extent of absorption is generally not affected. The exact mechanism of interaction is unknown, but may involve delayed gastric emptying or cation binding of the benzodiazepine. As a result, benzodiazepine onset of action may be delayed and clinical effects diminished. However, one study reported a significant increase in diazepam absorption during coadministration with aluminum hydroxide, and there was a marginal increase in the onset of sedative effect. Aluminum hydroxide also increased triazolam Cmax and systemic exposure (AUC) in 11 dialysis patients such that their drug levels reached into the range observed for the matched controls. In contrast, another study by the same group of investigators found no significant effect of aluminum hydroxide on temazepam absorption or Cmax in 11 patients with end-stage renal disease. A multi-dose study also failed to find an effect of antacids on the steady-state levels of N-desmethyldiazepam, the active metabolite of clorazepate, although an acidic environment is thought to be necessary for the rapid conversion. Based on available data, the clinical significance of this interaction appears to be minor. As a precaution, patients may consider separating the administration times of benzodiazepines and antacids or other oral medications that contain antacids (e.g., didanosine buffered tablets or pediatric oral solution) by 2 to 3 hours.

References

  1. Chun AH, Carrigan PJ, Hoffman DJ, Kershner RP, Stuart JD "Effect of antacids on absorption of clorazepate." Clin Pharmacol Ther 22 (1977): 329-35
  2. Nair SG, Gamble JA, Dundee JW, Howard PJ "The influence of three antacids on the absorption and clinical action of oral diazepam." Br J Anaesth 48 (1976): 1175-80
  3. Greenblatt DJ, Shader RI, Harmatz JS, Franke K, Koch-Weser J "Absorption rate, blood concentrations, and early response to oral chlordiazepoxide." Am J Psychiatry 134 (1977): 559-62
  4. Greenblatt DJ, Allen MD, MacLaughlin DS, Harmatz JS, Shader RI "Diazepam absorption: effect of antacids and food." Clin Pharmacol Ther 24 (1978): 600-9
  5. Shader RI, Georgotas A, Greenblatt DJ, Harmatz JS, Allen MD "Impaired absorption of desmethyldiazepam from clorazepate by magnesium aluminum hydroxide." Clin Pharmacol Ther 24 (1978): 308-15
  6. Kroboth PD, Smith RB, Rault R, Silver MR, Sorkin MI, Puschett JB, Juhl RP "Effects of end-stage renal disease and aluminum hydroxide on temazepam kinetics." Clin Pharmacol Ther 37 (1985): 453-9
  7. Kroboth PD, Smith RB, Silver MR, Rault R, Sorkin MI, Puschett JB, Juhl RP "Effects of end stage renal disease and aluminium hydroxide on triazolam pharmacokinetics." Br J Clin Pharmacol 19 (1985): 839-42
  8. Shader RI, Ciraulo DA, Greenblatt DJ, Harmatz JS "Steady-state plasma desmethyldiazepam during long-term clorazepate use: effects of antacids." Clin Pharmacol Ther 31 (1982): 180-3
  9. Greenblatt DJ, Shader RI, Harmatz JS, Franke K, Koch-Weser J "Influence of magnesium and aluminum hydroxide mixture on chlordiazepoxide absorption." Clin Pharmacol Ther 19 (1976): 234-9
View all 9 references

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Drug and food interactions

Moderate

ALPRAZolam food

Applies to: Niravam (alprazolam)

GENERALLY AVOID: The pharmacologic activity of oral midazolam, triazolam, and alprazolam may be increased if taken after drinking grapefruit juice. The proposed mechanism is CYP450 3A4 enzyme inhibition. In addition, acute alcohol ingestion may potentiate CNS depression and other CNS effects of many benzodiazepines. Tolerance may develop with chronic ethanol use. The mechanism may be decreased clearance of the benzodiazepines because of CYP450 hepatic enzyme inhibition. Also, it has been suggested that the cognitive deficits induced by benzodiazepines may be increased in patients who chronically consume large amounts of alcohol.

MANAGEMENT: The manufacturer recommends that grapefruit juice should not be taken with oral midazolam. Patients taking triazolam or alprazolam should be monitored for excessive sedation. Alternatively, the patient could consume orange juice which does not interact with these drugs. Patients should be advised to avoid alcohol during benzodiazepine therapy.

References

  1. "Product Information. Xanax (alprazolam)." Pharmacia and Upjohn PROD (2002):
  2. "Product Information. Valium (diazepam)." Roche Laboratories PROD (2002):
  3. "Product Information. Halcion (triazolam)." Pharmacia and Upjohn PROD (2001):
  4. "Grapefruit juice interactions with drugs." Med Lett Drugs Ther 37 (1995): 73-4
  5. Kupferschmidt HHT, Ha HR, Ziegler WH, Meier PJ, Krahenbuhl S "Interaction between grapefruit juice and midazolam in humans." Clin Pharmacol Ther 58 (1995): 20-8
  6. Hukkinen SK, Varhe A, Olkkola KT, Neuvonen PJ "Plasma concentrations of triazolam are increased by concomitant ingestion of grapefruit juice." Clin Pharmacol Ther 58 (1995): 127-31
  7. 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 7 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

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