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Interactions between Cholecalciferol and Cholestyramine

1 drug interaction and 24 additional warnings found for the following 2 drugs:

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Drug interactions

Moderate drug interactions

Moderate:

cholestyramine cholecalciferol

Applies to: cholestyramine and cholecalciferol
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 to 2 hours 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 (14)
  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. (2005) "Product Information. Fosamax Plus D (alendronate-cholecalciferol)." Merck & Co., Inc
  7. Cerner Multum, Inc. "UK Summary of Product Characteristics."
  8. Cerner Multum, Inc. "Australian Product Information."
  9. 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
  10. 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
  11. (2024) "Product Information. Rayaldee (calcifediol)." OPKO Pharmaceuticals LLC, SUPPL-13
  12. "Product Information. HIDROFEROL SEMANAL (calcifediol)." FAES FARMA, S.A.
  13. (2023) "Product Information. Domnisol (calcifediol)." Flynn Pharma Ltd
  14. (2025) "Product Information. Vistella (calcifediol)." Aspen Pharmacare Australia Pty Ltd, 2

Food/lifestyle interactions

Moderate food/lifestyle interactions

Moderate:

cholecalciferol Food/Lifestyle

Applies to: cholecalciferol
Monitor

Additive effects and possible toxicity (e.g., hypercalcemia, hypercalciuria, and/or hyperphosphatemia) may occur when patients using vitamin D and/or vitamin D analogs ingest a diet high in vitamin D, calcium, and/or phosphorus. The biologically active forms of vitamin D stimulate intestinal absorption of calcium and phosphorus. This may be helpful in patients with hypocalcemia and/or hypophosphatemia. However, sudden increases in calcium or phosphorus consumption due to dietary changes could precipitate hypercalcemia and/or hyperphosphatemia. Patients with certain disease states, such as impaired renal function, may be more susceptible to toxic side effects like ectopic calcification. On the other hand, if dietary calcium is inadequate for the body's needs, the active form of vitamin D will stimulate osteoclasts to pull calcium from the bones. This may be detrimental in a patient with reduced bone density.

Monitor

Grapefruit or grapefruit juice may alter the plasma concentrations of vitamin D analogs due to CYP450 3A4 inhibition. For analogs partially metabolized by CYP450 3A4, such as calcitriol, inhibitors can increase plasma concentrations, thereby elevating the risk of adverse effects like hypercalcemia and hyperphosphatemia. For prodrug analogs, such as calcifediol and doxercalciferol, CYP450 3A4 inhibition may affect activation and metabolic pathways, leading to variable net effects depending on the specific agent and individual patient factors. The effects of CYP450 3A4 inhibition on native vitamin D (cholecalciferol and ergocalciferol) are not noted. Clinical manifestations of such interactions may include alterations in serum calcium, phosphate, and parathyroid hormone (PTH) levels. In general, the effect of grapefruit juice is concentration-, dose- and preparation-dependent, and can vary widely among brands. Certain preparations of grapefruit juice (e.g., high dose, double strength) have sometimes demonstrated potent inhibition of CYP450 3A4, while other preparations (e.g., low dose, single strength) have typically demonstrated moderate inhibition. Pharmacokinetic interactions involving grapefruit juice are also subject to a high degree of interpatient variability, thus the extent to which a given patient may be affected is difficult to predict.

Management

Given the narrow therapeutic index of vitamin D and vitamin D analogs, the amounts of calcium, phosphorus, and vitamin D present in the patient's diet, as well as grapefruit consumption may need to be taken into consideration. Specific dietary guidance should be discussed with the patient and regular lab work should be monitored as indicated. Calcium, phosphorus, and vitamin D levels should be kept within the desired ranges, which may differ depending on the patient's condition. Patients should also be counseled on the signs and symptoms of hypervitaminosis D, hypercalcemia, and/or hyperphosphatemia.

References (10)
  1. (2023) "Product Information. Drisdol (ergocalciferol)." Validus Pharmaceuticals LLC
  2. (2024) "Product Information. Fultium-D3 (colecalciferol)." Internis Pharmaceuticals Ltd
  3. (2024) "Product Information. Ostelin Specialist Range Vitamin D (colecalciferol)." Sanofi-Aventis Healthcare Pty Ltd T/A Sanofi Consumer Healthcare
  4. (2021) "Product Information. Rocaltrol (calcitriol)." Atnahs Pharma UK Ltd
  5. (2019) "Product Information. Calcitriol (calcitriol)." Strides Pharma Inc.
  6. (2024) "Product Information. Calcitriol (GenRx) (calcitriol)." Apotex Pty Ltd
  7. (2022) "Product Information. Ergocalciferol (ergocalciferol)." RPH Pharmaceuticals AB
  8. (2020) "Product Information. Sandoz D (cholecalciferol)." Sandoz Canada Incorporated
  9. Fischer V, Haffner-Luntzer M, Prystaz K, et al. (2024) Calcium and vitamin-D deficiency marginally impairs fracture healing but aggravates posttraumatic bone loss in osteoporotic mice. https://www.nature.com/articles/s41598-017-07511-2
  10. National Institutes of Health Office of Dietary Supplements (2024) Vitamin D https://ods.od.nih.gov/factsheets/VitaminD-HealthProfessional/#h37
Moderate:

cholestyramine multivitamins with minerals

Applies to: cholestyramine
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 to 2 hours 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 (14)
  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. (2005) "Product Information. Fosamax Plus D (alendronate-cholecalciferol)." Merck & Co., Inc
  7. Cerner Multum, Inc. "UK Summary of Product Characteristics."
  8. Cerner Multum, Inc. "Australian Product Information."
  9. 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
  10. 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
  11. (2024) "Product Information. Rayaldee (calcifediol)." OPKO Pharmaceuticals LLC, SUPPL-13
  12. "Product Information. HIDROFEROL SEMANAL (calcifediol)." FAES FARMA, S.A.
  13. (2023) "Product Information. Domnisol (calcifediol)." Flynn Pharma Ltd
  14. (2025) "Product Information. Vistella (calcifediol)." Aspen Pharmacare Australia Pty Ltd, 2

Disease interactions

22 potential interactions Applies to: 20 conditions, including Vitamin D Deficiency, Constipation, Arrhythmia, Anemia, and Hemorrhoids.

Anemia

Moderate:

cholestyramine

Cholestyramine has a moderate potential interaction with Anemia.

Bile acid sequestrants may interfere with the absorption of folic acid and fat soluble vitamins such as A, D, and K. Chronic use of bile acid sequestrants may cause increased bleeding tendency due to hypoprothrombinemia associated with vitamin K deficiency. Anemia may also occur due to reduced serum or red blood cell folate. Supplementation with oral vitamins and/or folate should be considered during prolonged therapy with bile acid sequestrants, particularly in patients with preexisting vitamin and/or folate deficiencies, anemia, or a bleeding diathesis.

Arrhythmia

Moderate:

cholecalciferol

Cholecalciferol has a moderate potential interaction with Arrhythmia.

Vitamin D analogs function to increase serum calcium concentrations and can exacerbate arrhythmias, particularly in patients receiving cardiac glycosides. Therapy with vitamin D analogs should be administered cautiously in patients with or predisposed to cardiac arrhythmias. Clinical monitoring of serum electrolyte concentrations and cardiac function is recommended.

Biliary Obstruction

Major:

cholestyramine

Cholestyramine has a major potential interaction with Biliary Obstruction.

The use of bile acid sequestrants is contraindicated in patients with complete biliary obstruction where bile is not secreted into the intestine. These agents adsorb and combine with bile acids in the intestine to form an insoluble complex that is excreted in the feces, resulting in partial removal of bile acids from the enterohepatic circulation. Bile acid sequestrants are ineffective if bile does not reach the intestine.

Moderate:

cholecalciferol

Cholecalciferol has a moderate potential interaction with Biliary Obstruction.

Vitamin D analogs are fat soluble and oral formulations require bile for adequate intestinal absorption. Hepatic and/or biliary dysfunction decrease the absorption of vitamin D analogs. Metabolites of vitamin D analogs are primarily excreted in bile and feces. Ergocalciferol, cholecalciferol, and dihydrotachysterol undergo hepatic hydroxylation during metabolic activation. Hepatic impairment can alter the metabolic and therapeutic activity of certain vitamin D analogs. Alternative vitamin D analogs such as calcitriol (active form) may be considered in patients with compromised hepatic function.

Coagulation Defects and Disorders

Moderate:

cholestyramine

Cholestyramine has a moderate potential interaction with Coagulation Defects and Disorders.

Bile acid sequestrants may interfere with the absorption of folic acid and fat soluble vitamins such as A, D, and K. Chronic use of bile acid sequestrants may cause increased bleeding tendency due to hypoprothrombinemia associated with vitamin K deficiency. Anemia may also occur due to reduced serum or red blood cell folate. Supplementation with oral vitamins and/or folate should be considered during prolonged therapy with bile acid sequestrants, particularly in patients with preexisting vitamin and/or folate deficiencies, anemia, or a bleeding diathesis.

Constipation

Moderate:

cholestyramine

Cholestyramine has a moderate potential interaction with Constipation.

The use of bile acid sequestrants may produce or worsen preexisting constipation. Constipation associated with these agents may aggravate hemorrhoids. Therapy with bile acid sequestrants should be administered cautiously in patients with preexisting constipation, hemorrhoids, or symptomatic coronary artery disease. The dosage should be increased very gradually according to manufacturer guidelines to minimize the risk of fecal impaction, and patients should be encouraged to increase fluid and fiber intake. Occasional use of a stool softener may also be indicated. If constipation worsens or develops during therapy, or the desired therapeutic response is not achieved at the maximum recommended daily dosage, combination therapy or an alternative agent should be considered.

Dehydration

Moderate:

cholestyramine

Cholestyramine has a moderate potential interaction with Dehydration.

Bile acid sequestrants are chloride forms of anion exchange resins and may produce hyperchloremic acidosis with chronic use. Therapy with bile acid sequestrants should be administered cautiously in patients who may be particularly susceptible, including children or smaller patients and patients with renal impairment or volume depletion.

Folic Acid/Cyanocobalamin Deficiency

Moderate:

cholestyramine

Cholestyramine has a moderate potential interaction with Folic Acid/Cyanocobalamin Deficiency.

Bile acid sequestrants may interfere with the absorption of folic acid and fat soluble vitamins such as A, D, and K. Chronic use of bile acid sequestrants may cause increased bleeding tendency due to hypoprothrombinemia associated with vitamin K deficiency. Anemia may also occur due to reduced serum or red blood cell folate. Supplementation with oral vitamins and/or folate should be considered during prolonged therapy with bile acid sequestrants, particularly in patients with preexisting vitamin and/or folate deficiencies, anemia, or a bleeding diathesis.

Hemorrhoids

Moderate:

cholestyramine

Cholestyramine has a moderate potential interaction with Hemorrhoids.

The use of bile acid sequestrants may produce or worsen preexisting constipation. Constipation associated with these agents may aggravate hemorrhoids. Therapy with bile acid sequestrants should be administered cautiously in patients with preexisting constipation, hemorrhoids, or symptomatic coronary artery disease. The dosage should be increased very gradually according to manufacturer guidelines to minimize the risk of fecal impaction, and patients should be encouraged to increase fluid and fiber intake. Occasional use of a stool softener may also be indicated. If constipation worsens or develops during therapy, or the desired therapeutic response is not achieved at the maximum recommended daily dosage, combination therapy or an alternative agent should be considered.

Hypercalcemia

Major:

cholecalciferol

Cholecalciferol has a major potential interaction with Hypercalcemia.

Vitamin D analogs such as calciferol and ergocalciferol should not be given to patients with hypercalcemia, malabsorption syndrome, or evidence of vitamin D toxicity.

Ischemic Heart Disease

Moderate:

cholestyramine

Cholestyramine has a moderate potential interaction with Ischemic Heart Disease.

The use of bile acid sequestrants may produce or worsen preexisting constipation. Constipation associated with these agents may aggravate hemorrhoids. Therapy with bile acid sequestrants should be administered cautiously in patients with preexisting constipation, hemorrhoids, or symptomatic coronary artery disease. The dosage should be increased very gradually according to manufacturer guidelines to minimize the risk of fecal impaction, and patients should be encouraged to increase fluid and fiber intake. Occasional use of a stool softener may also be indicated. If constipation worsens or develops during therapy, or the desired therapeutic response is not achieved at the maximum recommended daily dosage, combination therapy or an alternative agent should be considered.

Liver Disease

Moderate:

cholecalciferol

Cholecalciferol has a moderate potential interaction with Liver Disease.

Vitamin D analogs are fat soluble and oral formulations require bile for adequate intestinal absorption. Hepatic and/or biliary dysfunction decrease the absorption of vitamin D analogs. Metabolites of vitamin D analogs are primarily excreted in bile and feces. Ergocalciferol, cholecalciferol, and dihydrotachysterol undergo hepatic hydroxylation during metabolic activation. Hepatic impairment can alter the metabolic and therapeutic activity of certain vitamin D analogs. Alternative vitamin D analogs such as calcitriol (active form) may be considered in patients with compromised hepatic function.

Malabsorption Syndrome

Major:

cholecalciferol

Cholecalciferol has a major potential interaction with Malabsorption Syndrome.

Vitamin D analogs such as calciferol and ergocalciferol should not be given to patients with hypercalcemia, malabsorption syndrome, or evidence of vitamin D toxicity.

Phenylketonuria

Moderate:

cholestyramine

Cholestyramine has a moderate potential interaction with Phenylketonuria.

Questran Light and LoCholest Light (brands of cholestyramine) contain 16.8 mg and 22.4 mg of phenylalanine, respectively, per each dose. Flavored Colestid (brand of colestipol) contains 18.2 mg of phenylalanine per each 7.5-gram dose. WELCHOL (brand name of colesevelam) for Oral Suspension contains 13.5 mg phenylalanine per 1.875 gram dose and 27 mg phenylalanine per 3.75 gram dose. The phenylalanine content should be considered when these products are used in patients who must restrict their intake of phenylalanine (i.e. phenylketonurics). Regular Colestid, Questran and LoCholest do not contain phenylalanine.

Phosphate Imbalance

Moderate:

cholecalciferol

Cholecalciferol has a moderate potential interaction with Phosphate Imbalance.

Vitamin D analogs administered in the presence of hyperphosphatemia can result in precipitation of calcium-phosphate deposits within the vascular or renal systems or other soft tissue calcifications. A solubility product (Serum Calcium X Phosphate) should not exceed 70. Serum electrolyte concentrations should be corrected prior to vitamin D analog therapy and monitored during therapy.

Renal Dysfunction

Moderate:

cholecalciferol

Cholecalciferol has a moderate potential interaction with Renal Dysfunction.

Ergocalciferol and cholecalciferol undergo renal biotransformation during metabolic activation. Renal impairment can alter metabolic and therapeutic activity of certain vitamin D analogs. Alternative vitamin D analogs such as dihydrotachysterol (hepatic activation) and calcitriol (active form) may be considered in patients with compromised renal function.

Moderate:

cholestyramine

Cholestyramine has a moderate potential interaction with Renal Dysfunction.

Bile acid sequestrants are chloride forms of anion exchange resins and may produce hyperchloremic acidosis with chronic use. Therapy with bile acid sequestrants should be administered cautiously in patients who may be particularly susceptible, including children or smaller patients and patients with renal impairment or volume depletion.

Thrombocytopathy

Moderate:

cholestyramine

Cholestyramine has a moderate potential interaction with Thrombocytopathy.

Bile acid sequestrants may interfere with the absorption of folic acid and fat soluble vitamins such as A, D, and K. Chronic use of bile acid sequestrants may cause increased bleeding tendency due to hypoprothrombinemia associated with vitamin K deficiency. Anemia may also occur due to reduced serum or red blood cell folate. Supplementation with oral vitamins and/or folate should be considered during prolonged therapy with bile acid sequestrants, particularly in patients with preexisting vitamin and/or folate deficiencies, anemia, or a bleeding diathesis.

Thrombocytopenia

Moderate:

cholestyramine

Cholestyramine has a moderate potential interaction with Thrombocytopenia.

Bile acid sequestrants may interfere with the absorption of folic acid and fat soluble vitamins such as A, D, and K. Chronic use of bile acid sequestrants may cause increased bleeding tendency due to hypoprothrombinemia associated with vitamin K deficiency. Anemia may also occur due to reduced serum or red blood cell folate. Supplementation with oral vitamins and/or folate should be considered during prolonged therapy with bile acid sequestrants, particularly in patients with preexisting vitamin and/or folate deficiencies, anemia, or a bleeding diathesis.

Vitamin A Deficiency

Moderate:

cholestyramine

Cholestyramine has a moderate potential interaction with Vitamin A Deficiency.

Bile acid sequestrants may interfere with the absorption of folic acid and fat soluble vitamins such as A, D, and K. Chronic use of bile acid sequestrants may cause increased bleeding tendency due to hypoprothrombinemia associated with vitamin K deficiency. Anemia may also occur due to reduced serum or red blood cell folate. Supplementation with oral vitamins and/or folate should be considered during prolonged therapy with bile acid sequestrants, particularly in patients with preexisting vitamin and/or folate deficiencies, anemia, or a bleeding diathesis.

Vitamin D Deficiency

Moderate:

cholestyramine

Cholestyramine has a moderate potential interaction with Vitamin D Deficiency.

Bile acid sequestrants may interfere with the absorption of folic acid and fat soluble vitamins such as A, D, and K. Chronic use of bile acid sequestrants may cause increased bleeding tendency due to hypoprothrombinemia associated with vitamin K deficiency. Anemia may also occur due to reduced serum or red blood cell folate. Supplementation with oral vitamins and/or folate should be considered during prolonged therapy with bile acid sequestrants, particularly in patients with preexisting vitamin and/or folate deficiencies, anemia, or a bleeding diathesis.

Vitamin K Deficiency

Moderate:

cholestyramine

Cholestyramine has a moderate potential interaction with Vitamin K Deficiency.

Bile acid sequestrants may interfere with the absorption of folic acid and fat soluble vitamins such as A, D, and K. Chronic use of bile acid sequestrants may cause increased bleeding tendency due to hypoprothrombinemia associated with vitamin K deficiency. Anemia may also occur due to reduced serum or red blood cell folate. Supplementation with oral vitamins and/or folate should be considered during prolonged therapy with bile acid sequestrants, particularly in patients with preexisting vitamin and/or folate deficiencies, anemia, or a bleeding diathesis.

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More resources

cholecalciferol

A total of 116 drugs are known to interact with cholecalciferol.

cholestyramine

A total of 140 drugs are known to interact with cholestyramine.

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.

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