Child's Omega-3 Dha Multivitam (vit A palm/vit C/vitamin D3/vit E acetate/omega-3/ala/dha)

To avoid toxicity, dietary intake of vitamin A should be estimated and considered when determining the dosage of the vitamin. Vitamin A activity is expressed in terms of the equivalent amount of retinol (i.e., as retinol equivalents (RE) or retinol activity equivalents (RAE)) and is expressed also in USP units or International Units (IU, units). USP units and International Units are equivalent. One USP vitamin A unit is the specific biologic activity of 0.3 mcg of all-trans-retinol; one retinol equivalent (RE) is the specific biologic activity of 1 mcg of all-trans-retinol; one retinol activity equivalent (RAE) is equal to 1 mcg of all-trans-retinol, 12 mcg of all trans-beta-carotene, or 24 mcg of other provitamin A carotenoids. The use of RAE is preferred when calculating and reporting the amount of total vitamin A in mixed foods or assessing the amount of dietary and supplemental vitamin A consumed.

Dietary intake of ergocalciferol and cholecalciferol varies among individual patients, and dietary intake should always be considered when calculating the appropriate dosage of vitamin D analogs. During therapy with vitamin D analogs, dosage depends on the nature and severity of the patient's hypocalcemia and must be individualized to maintain serum calcium concentrations of 9-10 mg/dL. In the management of hypoparathyroidism, pseudohypoparathyroidism, and familial hypophosphatemia, the range between therapeutic and toxic effects is narrow; however, hypercalcemia may occur at any time when therapeutic doses of vitamin D analogs are used, and careful monitoring is imperative. In the management of secondary hyperparathyroidism, dosage of vitamin D analogs should be individualized according to serum or plasma intact parathyroid hormone (iPTH) concentrations and serum calcium and phosphorus concentrations.

During therapy with vitamin D analogs, patients should receive adequate amounts of calcium through management of diet or administration of calcium supplements; however, overdosage of calcium may lead to hypercalcemia. Dosage of vitamin D analogs should be decreased when symptoms improve and before biochemical normality or complete bone healing has occurred because requirements for vitamin D analogs often decrease after bone healing occurs. In patients who become bedridden (especially children), dosage reduction may occasionally be needed to avoid hypercalcemia.

Ascorbic acid is usually administered orally. When oral administration is not feasible or when malabsorption is suspected, the drug may be administered IM, IV, or subcutaneously. When given parenterally, utilization of the vitamin reportedly is best after IM administration and that is the preferred parenteral route.

Vitamin A usually is administered orally. Oral vitamin A capsules containing high strengths (e.g., 50,000 units) no longer are commercially available in the US; however, high-strength oral capsules and solutions may be available from various organizations (e.g., United Nations Children's Fund (UNICEF), the International Dispensary Association (IDA)) for treatment of deficiencies in developing countries. When oral administration is not feasible or when malabsorption is present, the drug may be given IM.

Vitamin D analogs are usually administered orally; however, calcitriol, doxercalciferol, and paricalcitol may be given by IV injection. Ergocalciferol may be given by IM injection; however, a suitable formulation of the drug for IM injection no longer is commercially available in the US.

No dosing information is available for this tab.

No dosing information is available for this tab.

Concurrent administration of more than 200 mg of ascorbic acid per 30 mg of elemental iron increases absorption of iron from the GI tract; however, most individuals are able to absorb orally ingested iron adequately without concurrent administration of ascorbic acid.

Increased urinary excretion of ascorbic acid and decreased excretion of aspirin occur when the drugs are administered concurrently.

Salicylates inhibit uptake of ascorbic acid by leukocytes and platelets. As a result, leukocyte and plasma concentrations of ascorbic acid are decreased to concentrations slightly higher than those associated with tissue depletion of the vitamin; however, there is no evidence to date that salicylate therapy precipitates ascorbic acid deficiency. Although concomitant administration of ascorbic acid supplements in patients receiving salicylates increases plasma ascorbic acid concentrations, leukocyte ascorbic acid concentrations are not increased and tissue stores of the vitamin may not be increased. Therefore, routine administration of ascorbic acid supplements to patients receiving salicylates is not warranted; however, patients receiving high dosages of salicylates who exhibit any signs or symptoms of ascorbic acid deficiency should be evaluated for such a deficiency.

Ascorbic acid has reportedly decreased the anticoagulant effect of warfarin; however, other investigators have failed to show this effect. Concurrent administration of ascorbic acid and fluphenazine reportedly resulted in decreased fluphenazine plasma concentration. Acidification of the urine following administration of ascorbic acid may result in altered excretion of other drugs.

Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient.

Vitamin A/Selected Retinoids

SEVERITY LEVEL: 1-Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient.

MECHANISM OF ACTION: The retinoids are structurally related to vitamin A. (1-6)

CLINICAL EFFECTS: Concurrent use of retinoids with vitamin A supplements may result in signs of vitamin A toxicity.(1-6) Symptoms of vitamin A toxicity include nausea, vomiting, loss of appetite, weakness, dry or itchy skin or lips, irritability, and hair loss.

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: The manufacturer of acitretin states that concomitant use of vitamin A supplements should be avoided.(1) The manufacturer of bexarotene states that patients should be advised to limit vitamin A supplements. In clinical studies, patients were advised to limit their vitamin A intake to less than or equal to 15,000 International Units/day.(2) The manufacturer of isotretinoin states that patients should be advised against taking vitamin A supplements.(3) The manufacturer of palovarotene states that concomitant use of vitamin A must be avoided.(4) The manufacturer of tretinoin states that tretinoin must not be administered in combination with vitamin A.(5) The UK manufacturer of alitretinoin states that tretinoin must not be administered in combination with vitamin A.(6)

DISCUSSION: The retinoids are structurally related to vitamin A. The concurrent use of retinoids with vitamin A may result in signs and symptoms of vitamin A toxicity.(1-6)

Severe Interaction: Action is required to reduce the risk of severe adverse interaction.

Ascorbic Acid (VITAMIN C)/Bortezomib

SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction.

MECHANISM OF ACTION: Vitamin C can form a complex with the boronic acid moiety of the bortezomib molecule, preventing its absorption into cells.(1-4) This may protect normal tissue in the body, which may have higher levels of Vitamin C.(5)

CLINICAL EFFECTS: Concurrent administration of Vitamin C may result in decreased bortezomib activity.(1-4)

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: Instruct patients receiving bortezomib therapy not to begin taking vitamin C supplements without consulting their oncologist first. Patients who are instructed to take vitamin C should follow their oncologist's instructions on how to separate dosages and should be carefully monitored for bortezomib efficacy.

DISCUSSION: An in vitro study with human plasma and multiple myeloma cells found that high levels of vitamin C (following 1 gram/day of ascorbic acid for 4 days) decreased bortezomib effectiveness by 26%. An in vivo study in mice found that vitamin C administration with bortezomib completely blocked the response of bortezomib.(6) An in vitro study in rat Schwann cells and myeloma cells(4) and an in vivo study in mice(7) found that delayed administration of vitamin C had no effect on bortezomib effects. In an in vivo study in multiple myeloma patients, concurrent ascorbic acid, arsenic trioxide, bortezomib, and high-dose melphalan in which ascorbic acid was administered close to bortezomib, the combination was safe and well tolerated, but produced no changes in response rates.(8) In another in vivo study in multiple myeloma patients, a regimen of ascorbic acid, bortezomib, and melphalan in which bortezomib was administered in the morning and ascorbic acid in the evening was found to be safe and efficacious, with 74% of patients responding to therapy.(9)

Serum Phosphate Level-Altering Drugs/Erdafitinib

SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction.

MECHANISM OF ACTION: Medications that alter serum phosphate may interfere with interpretation of phosphate levels that are needed to determine initial erdafitinib dose.(1)

CLINICAL EFFECTS: Serum phosphate levels that are elevated by concomitant medications may result in an inappropriately low dose and decreased effectiveness of erdafitinib. Serum phosphate levels that are decreased by concomitant medications may result in an inappropriately high dose and increased toxicity from erdafitinib.

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: The manufacturer of erdafitinib states that agents that alter serum phosphate levels should be avoided before the initial dose increase period for erdafitinib based on serum phosphate levels (days 14 to 21).(1)

DISCUSSION: Concomitant administration of serum phosphate level-altering agents during the initial dose increase period of erdafitinib based on serum phosphate levels (days 14 to 21) may interfere with serum phospate levels and lead to incorrect dosing of erdafitinib.(1) Agents that may alter serum phosphate levels linked to this monograph include: aluminum carbonate, aluminum hydroxide, calcium acetate, calcium carbonate, calcium citrate, cod liver oil, ferric citrate, lanthanum, magnesium carbonate, magnesium hydroxide, potassium phosphate, sevelamer, sodium phosphate, sucroferric oxyhydroxide, tenapanor, and vitamin D.(1)

Vitamin E (ALPHA TOCOPHEROL) >=800 Unit/Slt Anticoag (VIT K)

SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction.

MECHANISM OF ACTION: Vitamin E may decrease vitamin K-dependent clotting factors, resulting in additive effects with vitamin K antagonists.(1)

CLINICAL EFFECTS: Dose of vitamin E of 800 units/day or more may increase the pharmacologic effects of vitamin K antagonists.(1-7)

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: Patients receiving vitamin E supplements of 800 units/day or more may require lower dosages of vitamin K antagonists. In patients maintained on warfarin who initiate vitamin E supplements in dosages of 800 units/day or more, measured INR one to two weeks after initiation of vitamin E and also every two to four weeks during the first two months.(2)

DISCUSSION: Vitamin E doses up to 400 units/day is believed not to affect the prothrombin time in patients concomitantly receiving warfarin.(2) Vitamin E doses of 800 International Units/day and more have been reported to increase the hypoprothrombinemic effect of warfarin. However, in a double blind clinical trial, with only 13 subjects completing the study, patients who had received chronic warfarin therapy with the addition of vitamin E dose as high as 1,200 IU/day for 1 month saw negligible change in the INR or prothrombin time.(3) Selumetinib capsules contain a significant amount of vitamin E. Each 10 mg capsule contains 32 mg (48 units) and each 25 mg capsule contains (54 units) of vitamin E. The daily dose of selumetinib may contain up to 256 mg (384 units) of vitamin E. Vitamin E supplementation is not recommended if it will result in a daily vitamin E intake exceeding recommended or safe amounts.(4) Agenerase brand of amprenavir capsules and oral solution contain a significant amount of vitamin E. Each 150 mg capsule contains 109 International Units vitamin E, with a total of 1,744 International Units of vitamin E in the recommended daily adult dose. Each mL of oral solution contains 46 International Units of vitamin E.(5) One or more of the drug pairs linked to this monograph have been included in a list of interactions that could be considered for classification as "non-interruptive" in EHR systems. This DDI subset was vetted by an expert panel commissioned by the U.S. Office of the National Coordinator (ONC) for Health Information Technology.

Moderate Interaction: Assess the risk to the patient and take action as needed.

Ascorbic Acid (VITAMIN C)/Deferoxamine

SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed.

MECHANISM OF ACTION: It is believed that ascorbic acid increases the iron available for chelation from an labile intracellular iron pool. Ascorbic acid may then facilitate iron-induced oxidative tissue damage.(1)

CLINICAL EFFECTS: Dietary ascorbic acid may increase the absorption of dietary iron. Supplemental ascorbic acid therapy given during chelation therapy may improve iron output;(1-9) however, excessive dosages may result in cardiac toxicity from iron-induced oxidative tissue damage.(1,2,11-13)

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: Ascorbic acid intake is often restricted in patients with iron overload; however, it has been used in conjunction with deferoxamine to increase iron excretion.(2) Supplemental ascorbic acid therapy should only be initiated after one month of deferoxamine therapy. Ascorbic acid therapy should only be given in patients receiving deferoxamine regularly and the dose should be given after the infusion has started. The dosage of ascorbic acid should be limited to 50 mg daily in children under 10 years of age; 100 mg daily in older children; and 200 mg daily, in divided doses, in adults.(2) Cardiac function should be monitored in patients receiving concurrent therapy. Discontinue ascorbic acid therapy in patients who develop cardiac dysfunction.(2)

DISCUSSION: Supplemental ascorbic acid therapy given during chelation therapy has been shown to improve iron output,(1-9) possibly by increasing iron available for chelation from an labile intracellular iron pool.(1) However, dosages in excess of 500 mg daily have been associated with cardiac dysfunction.(1,2,11-13)

Fat Soluble Vitamins/Colesevelam

SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed.

MECHANISM OF ACTION: Colesevelam may decrease the absorption of fat-soluble vitamins A, D, E, and K.(1)

CLINICAL EFFECTS: Colesevelam may reduce absorption of fat soluble vitamins, leading to a deficiency state.

PREDISPOSING FACTORS: A pre-existing deficiency of fat soluble vitamins (A,D,E and K) or chronic malabsorption syndrome.

PATIENT MANAGEMENT: The inhibition of fat soluble vitamin absorption by colesevelam should be borne in mind during implementation of a vitamin supplementation strategy. Oral multivitamin supplements should be taken at least four hours before the dose of colesevelam.(1)

DISCUSSION: Colesevelam may decrease the absorption of fat-soluble vitamins A, D, E, and K.(1)

Fat Soluble Vitamins/Orlistat

SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed.

MECHANISM OF ACTION: The acetate ester forms of vitamin A and vitamin E must undergo hydrolysis for absorption from the gastrointestinal tract.(1) The enzyme responsible for this hydrolysis is inhibited by orlistat.(2)

CLINICAL EFFECTS: Orlistat may reduce absorption of fat soluble vitamins, leading to a deficiency state.

PREDISPOSING FACTORS: A pre-existing deficiency of fat soluble vitamins (A,D,E and K) or chronic malabsorption syndrome.

PATIENT MANAGEMENT: The inhibition of fat soluble vitamin absorption by orlistat should be borne in mind during implementation of a vitamin supplementation strategy. Patients should be strongly encouraged to take a multivitamin supplement which contains fat soluble vitamins, particularly Vitamin D as it appears most susceptible to this interaction.(4,5) Multivitamin supplements should be taken at least two hours before or after the dose of orlistat, or at bedtime.(4) Patients with chronic malabsorption syndromes should not receive orlistat.(4)

DISCUSSION: Adult patients taking orlistat without supplementation showed a greater reduction in vitamin A,D,E and beta-carotene levels compared to placebo during two or more consecutive visits in studies of 1-2 years duration; these patients had normal baseline values prior to orlistat therapy. Low vitamin values in orlistat patients were as follows: low Vitamin D 12%, low beta-carotene 6.1%, low Vitamin E 5.8%, low Vitamin A 2.2%.(4) A pharmacokinetic interaction study showed a 30% reduction in beta-carotene supplement absorption and a 60% decreased in vitamin E acetate absorption with concomitant orlistat.(4) In a study, orlistat produced the vitamin net concentration by approximately 43%.(1) In a study, no statistically significant decrease in vitamin A absorption was observed with concurrent orlistat.(2) In a study, mean vitamin D levels were significantly reduced compared with baseline after one month of orlistat therapy despite multivitamin supplementation.(5)

There is no enhanced messaging for this drug.

• Hypervitaminosis D

• Hypercalcemia
• Hyperphosphatemia
• Kidney stone

• Kidney disease with reduction in glomerular filtration rate (GFr)
• Sarcoidosis

There is no enhanced messaging for this drug.

Rare or Very Rare

• Anaphylaxis
• Hemorrhage
• Increased alanine transaminase
• Increased aspartate transaminase

Less Frequent

• Dysgeusia
• Dyspepsia
• Eructation
• Skin rash

Rare or Very Rare

• Abnormal hepatic function tests
• Constipation
• Pruritus of skin
• Urticaria
• Vomiting

No enhanced messaging available.

No enhanced messaging available.

Vitamin A is teratogenic in animals; malformations of the CNS, eye, palate, and urogenital tract have been described in several species. Adequate and well-controlled studies in humans are not available. A limited number of reports of human fetal malformations (e.g., cranial neural crest defects) following maternal ingestion of large dosages of vitamin A (10,000 units or more daily) during or both before and during pregnancy suggest potential teratogenicity, at least at high dosages. The use of vitamin A in excess of the US RDA generally is contraindicated in women who are or may become pregnant. (See Dietary and Replacement Requirements in Dosage and Administration: Dosage.)If vitamin A is used during pregnancy or if the patient becomes pregnant while receiving the drug, the patient should be apprised of the potential fetal hazard. It also has been suggested that women of reproductive age should limit their intake of dietary sources (e.g., liver) containing high concentrations of vitamin A; beta-carotene, a precursor of vitamin A, has not been shown to be teratogenic and may be considered as a source of vitamin A supplementation in such women. Dosages exceeding the RDA may be necessary in women of childbearing age with vitamin A deficiency. There is some evidence suggesting that dosages up to 10,000 units daily or up to 25,000 units weekly may be used safely in women of childbearing age (13-49 years of age), and such dosages are recommended in those with active xerophthalmia. Even higher dosages may be necessary if active corneal lesions are present. (See Vitamin A Deficiency under Dosage and Administration: Dosage.)

A characteristic physiognomy, possibly with aortic valvular stenosis, retinopathy, and mental and/or physical retardation, has occurred following prolonged hypercalcemia in infants and in neonates of mothers with hypercalcemia during pregnancy. Hypercalcemia during pregnancy may also lead to suppression of PTH concentrations in the neonate resulting in hypocalcemia, tetany, and seizures. Safe use of calcifediol, calcitriol, dihydrotachysterol (no longer commercially available in the US), paricalcitol, or ergocalciferol during pregnancy has not been established; however, the risks to the mother and fetus from untreated hypoparathyroidism or hypophosphatemia may be greater than those resulting from administration of vitamin D analogs.

Vitamin A is distributed into milk. Unless the maternal diet is inadequate, infants can usually obtain sufficient vitamin A from nursing, at least for the first 6 months of life. The effect of large maternal dosages of vitamin A on nursing infants is not known.

For information on the currently recommended RDAs of vitamin A for pregnant and lactating women, see Dietary and Replacement Requirements, under Dosage and Administration: Dosage.

Safe use of calcifediol, calcitriol, dihydrotachysterol, doxercalciferol, paricalcitol, or ergocalciferol during lactation has not been established; however, the risks to the mother and fetus from untreated hypoparathyroidism or hypophosphatemia may be greater than those resulting from administration of vitamin D analogs. Large doses of vitamin D analogs should not be administered to nursing women.

No enhanced messaging available.