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Drug Interactions between Diltia XT and galantamine

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

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Interactions between your drugs

Moderate

dilTIAZem galantamine

Applies to: Diltia XT (diltiazem) and galantamine

MONITOR: Since acetylcholinesterase inhibitors can cause bradycardia and heart block due to vagotonic effects on the sinoatrial and atrioventricular nodes, additive effects may occur with other agents that also possess bradycardic effects such as beta-blockers, calcium channel blockers, digitalis, some protease inhibitors (atazanavir, lopinavir-ritonavir, saquinavir), amiodarone, dronedarone, moricizine, lacosamide, and mefloquine. A group of French investigators conducted a retrospective analysis of spontaneous reports in the French Pharmacovigilance Database concerning adverse drug reactions (ADRs) associated with use of the acetylcholinesterase inhibitors donepezil, galantamine, and rivastigmine. Two hundred and five cases of potential drug-drug interaction with bradycardic drugs (beta-blockers, calcium channel blockers, amiodarone, digoxin) were identified, 73 of which were associated with serious ADRs including five deaths due to syncope, bradycardia, arrhythmia, or cardiac arrest. However, no details on the individual cases such as patient characteristics or concomitant risk factors were provided, making the contribution of a potential drug interaction difficult to evaluate. The remainder of the cases were of no apparent clinical consequences. In contrast, a phase III trial of donepezil consisting of 1035 patients reported no significant increase in risk ratios for bradycardia during concomitant use of beta-blockers, nondihydropyridine calcium channel blockers, or digoxin.

MANAGEMENT: Caution is advised if acetylcholinesterase inhibitors are used concomitantly with bradycardic drugs. Patients with underlying structural heart disease, preexisting conduction system abnormalities, ischemic heart disease, or cardiomyopathies may be at increased risk for developing cardiac conduction disturbances and atrioventricular block. Patients should be advised to notify their physician if they experience dizziness, lightheadedness, fainting, or irregular heartbeat.

References

  1. "Product Information. Cognex (tacrine)." Parke-Davis PROD (2001):
  2. "Product Information. Aricept (donepezil)." Pfizer U.S. Pharmaceuticals PROD (2001):
  3. "Product Information. Exelon (rivastigmine)." Novartis Pharmaceuticals PROD (2001):
  4. "Product Information. Razadyne (galantamine)." Johnson and Johnson Medical Inc (2005):
  5. Tavassoli N, Sommet A, Lapeyre-Mestre M, Bagheri H, Montrastruc JL "Drug interactions with cholinesterase inhibitors : an analysis of the French pharmacovigilance database and a comparison of two national drug formularies (vidal, british national formulary)." Drug Saf 30 (2007): 1063-71
  6. Tiseo PJ, Perdomo CA, Friedhoff LT "Concurrent administration of donepezil HCI and digoxin: assessment of pharmacokinetic changes." Br J Clin Pharmacol 46(Suppl 1) (1998): 40-4
View all 6 references

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Drug and food interactions

Moderate

dilTIAZem food

Applies to: Diltia XT (diltiazem)

MONITOR: Like many CNS-active agents, alcohol can exhibit hypotensive effects. Coadministration with antihypertensive agents including diltiazem may result in additive effects on blood pressure and orthostasis.

MONITOR: Grapefruit juice may increase the plasma concentrations of orally administered diltiazem in some patients. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruit. In a study of ten healthy male volunteers, administration of a single 120 mg oral dose of immediate-release diltiazem in combination with 250 mL of grapefruit juice increased the diltiazem peak plasma concentration (Cmax) and systemic exposure (AUC) by an average of 22% and 20%, respectively, compared to administration with water. The time to reach Cmax (Tmax) and the terminal half-life were not affected, and no statistically significant differences in blood pressure and heart rate were observed during administration with grapefruit juice relative to water. In a different study, repeated administration of 200 mL of grapefruit juice at 0, 2, 4, 8 and 12 hours had no significant effect on the Cmax or AUC of a single 120 mg oral dose of diltiazem, but increased its half-life from 4.1 to 5.1 hours. The ratios for the N-demethyl and deacetyl metabolites to diltiazem were also not affected by grapefruit juice. However, because pharmacokinetic interactions involving grapefruit juice are often subject to a high degree of interpatient variability, the extent to which a given patient may be affected is difficult to predict.

MANAGEMENT: Patients should be advised that alcohol may potentiate the hypotensive effects of diltiazem, especially during the initiation of therapy and following a dosage increase. Caution should be exercised when rising from a sitting or recumbent position, and patients should notify their physician if they experience dizziness, lightheadedness, syncope, orthostasis, or tachycardia. Patients who regularly consume grapefruit or grapefruit juice should be monitored for increased adverse effects of diltiazem such as such as headache, irregular heartbeat, edema, unexplained weight gain, and chest pain. Grapefruit and grapefruit juice should be avoided if an interaction is suspected.

References

  1. Bailey DG, Arnold JMO, Spence JD "Grapefruit juice and drugs - how significant is the interaction." Clin Pharmacokinet 26 (1994): 91-8
  2. Sigusch H, Henschel L, Kraul H, Merkel U, Hoffmann A "Lack of effect of grapefruit juice on diltiazem bioavailability in normal subjects." Pharmazie 49 (1994): 675-9
  3. Bailey DG, Malcolm J, Arnold O, Spence JD "Grapefruit juice-drug interactions." Br J Clin Pharmacol 46 (1998): 101-10
  4. Christensen H, Asberg A, Holmboe AB, Berg KJ "Coadministration of grapefruit juice increases systemic exposure of diltiazem in healthy volunteers." Eur J Clin Pharmacol 58 (2002): 515-520
  5. Cerner Multum, Inc. "UK Summary of Product Characteristics." O 0
View all 5 references

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Moderate

dilTIAZem food

Applies to: Diltia XT (diltiazem)

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.

References

  1. Henry M, Kay MM, Viccellio P "Cardiogenic shock associated with calcium-channel and beta blockers: reversal with intravenous calcium chloride." Am J Emerg Med 3 (1985): 334-6
  2. Moller IW "Cardiac arrest following intravenous verapamil combined with halothane anaesthesia." Br J Anaesth 59 (1987): 522-6
  3. Oszko MA, Klutman NE "Use of calcium salts during cardiopulmonary resuscitation for reversing verapamil-associated hypotension." Clin Pharm 6 (1987): 448-9
  4. Schoen MD, Parker RB, Hoon TJ, et al. "Evaluation of the pharmacokinetics and electrocardiographic effects of intravenous verapamil with intravenous calcium chloride pretreatment in normal subjects." Am J Cardiol 67 (1991): 300-4
  5. O'Quinn SV, Wohns DH, Clarke S, Koch G, Patterson JH, Adams KF "Influence of calcium on the hemodynamic and anti-ischemic effects of nifedipine observed during treadmill exercise testing." Pharmacotherapy 10 (1990): 247
  6. Woie L, Storstein L "Successful treatment of suicidal verapamil poisoning with calcium gluconate." Eur Heart J 2 (1981): 239-42
  7. Morris DL, Goldschlager N "Calcium infusion for reversal of adverse effects of intravenous verapamil." JAMA 249 (1983): 3212-3
  8. Guadagnino V, Greengart A, Hollander G, Solar M, Shani J, Lichstein E "Treatment of severe left ventricular dysfunction with calcium chloride in patients receiving verapamil." J Clin Pharmacol 27 (1987): 407-9
  9. Luscher TF, Noll G, Sturmer T, Huser B, Wenk M "Calcium gluconate in severe verapamil intoxication." N Engl J Med 330 (1994): 718-20
  10. Bar-Or D, Gasiel Y "Calcium and calciferol antagonise effect of verapamil in atrial fibrillation." Br Med J (Clin Res Ed) 282 (1981): 1585-6
  11. Lipman J, Jardine I, Roos C, Dreosti L "Intravenous calcium chloride as an antidote to verapamil-induced hypotension." Intensive Care Med 8 (1982): 55-7
  12. McMillan R "Management of acute severe verapamil intoxication." J Emerg Med 6 (1988): 193-6
  13. Perkins CM "Serious verapamil poisoning: treatment with intravenous calcium gluconate." Br Med J 2 (1978): 1127
  14. Moroni F, Mannaioni PF, Dolara A, Ciaccheri M "Calcium gluconate and hypertonic sodium chloride in a case of massive verapamil poisoning." Clin Toxicol 17 (1980): 395-400
View all 14 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.

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