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Drug Interactions between colestipol and deferasirox

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

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Interactions between your drugs

Moderate

colestipol deferasirox

Applies to: colestipol and deferasirox

GENERALLY AVOID: Coadministration with cholestyramine may decrease the bioavailability and efficacy of deferasirox. The mechanism involves binding of cholestyramine to deferasirox and its glucuronide metabolites, which are secreted into the bile. This interferes with the enterohepatic recycling of deferasirox by preventing intestinal deconjugation of the glucuronide metabolites and subsequent reabsorption. In healthy volunteers, administration of cholestyramine (12 grams twice daily) 4 and 10 hours after a single dose of deferasirox resulted in a 45% decrease in deferasirox systemic exposure (AUC). The interaction has not been studied with other bile acid sequestrants.

MANAGEMENT: The concomitant use of deferasirox with cholestyramine should generally be avoided. Otherwise, consideration should be given to increasing the initial dosage of deferasirox by 50% with subsequent adjustments made according to serum ferritin levels and clinical response. It is not known whether other bile acid sequestrants interact similarly with deferasirox.

References

  1. (2005) "Product Information. Exjade (deferasirox)." Novartis Pharmaceuticals

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Drug and food interactions

Moderate

deferasirox food

Applies to: deferasirox

ADJUST DOSING INTERVAL: According to product labeling, the bioavailability of deferasirox was variably increased when taken with a meal.

MANAGEMENT: To ensure consistent plasma drug levels, deferasirox should be taken on an empty stomach 30 minutes before eating preferably at the same time everyday.

References

  1. (2005) "Product Information. Exjade (deferasirox)." Novartis Pharmaceuticals

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Moderate

colestipol food

Applies to: colestipol

ADJUST DOSING INTERVAL: Bile acid sequestrants and the phosphate binder, sevelamer, can decrease the absorption of fat-soluble vitamins A, D, E, and K. By binding bile acids, these agents may interfere with normal fat digestion and absorption, thereby preventing the absorption of fat-soluble vitamins. When 8 grams of cholestyramine was administered simultaneously with a normal meal containing 250,000 units of vitamin A acetate in four healthy young adult subjects, plasma vitamin A levels were significantly reduced during a 9-hour postprandial period compared to the values obtained with the control meal. Coadministration with 4 grams of cholestyramine had no significant effect. In a crossover study involving healthy subjects, coadministration of sevelamer with calcitriol resulted in a significant reduction in bioavailability for calcitriol (calcitriol with sevelamer vs calcitriol alone: AUC 137 pg*h/mL vs 318 pg*h/mL and Cmax 40.1 pg/mL vs 49.7 pg/mL, respectively). Chronic use of bile acid sequestrants has been rarely associated with an increased bleeding tendency due to hypoprothrombinemia resulting from vitamin K deficiency. Isolated cases of Vitamin A (including one case of night blindness) and D deficiencies have also been reported with chronic cholestyramine therapy.

MANAGEMENT: When bile acid sequestrants are given for prolonged periods, some manufacturers recommend that concomitant supplementation with water-miscible or parenteral forms of fat-soluble vitamins be considered. If oral vitamin supplements are used with cholestyramine or colestipol, advise patients to take them at least 1 hour before or 4 to 6 hours after the bile acid sequestrant to minimize the potential impact on their absorption. No recommendations are available for sevelamer, but it may be advisable to follow the same precautions.

References

  1. Gross L, Brotman M (1970) "Hypoprothrombinemia and hemorrhage associated with cholestyramine therapy." Ann Intern Med, 72, p. 95-6
  2. Shojania AM, Grewar D (1986) "Hypoprothrombinemic hemorrhage due to cholestyramine therapy." Can Med Assoc J, 134, p. 609-10
  3. Longstreth GF, Newcomer AD (1975) "Drug-induced malabsorption." Mayo Clin Proc, 50, p. 284-93
  4. Acuna R, Gonzalez Ceron M (1977) "Hypoprothrombinemia and bleeding associated to treatment with cholestyramine (author's transl)." Rev Med Chil, 105, p. 27-8
  5. (2001) "Product Information. Rocaltrol (calcitriol)." Roche Laboratories
  6. (2001) "Product Information. Welchol (colesevelam)." Daiichi Sankyo, Inc.
  7. (2005) "Product Information. Fosamax Plus D (alendronate-cholecalciferol)." Merck & Co., Inc
  8. Cerner Multum, Inc. "UK Summary of Product Characteristics."
  9. Cerner Multum, Inc. "Australian Product Information."
  10. Peirce D, Hossack S, Poole L, et al. (2011) "The effect of sevelamer carbonate and lanthanum carbonate on the pharmacokinetics of oral calcitriol." Nephrol Dial Transplant, 26, p. 1615-21
  11. Vroonhof K, van Rijn HJM, van Hattum J (2003) "Vitamin K deficiency and bleeding after long-term use of cholestyramine." Neth J Med, 61, p. 19-21
View all 11 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.