Vitamin D is a fat-soluble vitamin and has two primary forms: cholecalciferol (vitamin D3) and ergocalciferol (vitamin D2). The chemical structure differences between the two forms of vitamin D do not affect the metabolism or clinical responses once activated within the body. Although animal experiments have indicated a difference in toxicity between vitamin D3 and vitamin D2, human studies have been inconclusive. Vitamin D is available in dietary supplements as ergocalciferol or cholecalciferol and is also found in fortified milk and cereal products; liver, fish liver oils, fatty fish, and egg yolks from hens have also been supplemented with vitamin D. Vitamin D must undergo hydroxylation in the liver and kidney to its active form. Vitamin D is responsible for appropriate calcium and phosphate balance and is required for normal bone growth and mineralization. Vitamin D status is determined by monitoring 25-hydroxyvitamin D [25(OH)D] serum concentrations, which represent all sources of vitamin D (e.g., sunlight and dietary or from supplements). Although labeled for use in several disease states, the primary use is for vitamin D supplementation and the prevention and treatment of vitamin D deficiency and rickets.
General Administration Information
For storage information, see the specific product information within the How Supplied section.
Route-Specific Administration
Oral Administration
-While vitamin D may be taken without regard to food, it is better absorbed when taken with foods containing fat.
Oral Liquid Formulations
-Some formulations of vitamin D oral solution/drops contain propylene glycol. When selecting oral liquid preparations for neonates, infants, and young children, ensure the correct formulation of vitamin D is chosen to avoid propylene glycol toxicity.
-Administer using a calibrated measuring device to ensure dosage accuracy. Due to the risk of inadvertently administering an incorrect dose to infants, the FDA recommends using a product with a dropper that will measure no more than 10 mcg (400 International Units) per dose.
-Administer directly into the mouth or mix with breast milk, formula, fruit juice, cereal, or other foods. If mixed, make sure the patient drinks or eats the entire portion to ensure they receive the total amount of the medication.
-Storage: After opening, store away from direct light.
In general, the use of supplemental vitamin D according to recommended dietary intakes is not associated with serious adverse reactions. Vitamin D may cause side effects in overdose, but such symptoms associated with hypervitaminosis D (and resultant hypercalcemia) are rarely reported. An excess of vitamin D causes abnormally high levels of calcium in the blood and is almost always caused by vitamin D analogs (e.g., calcitriol, doxercalciferol, paricalcitol), rather than vitamin D found in dietary supplements (e.g., cholecalciferol, ergocalciferol). However, patients taking higher doses of vitamin D supplements should report any of the following potential signs of high vitamin D/calcium concentrations: nausea/vomiting, constipation, loss of appetite, increased thirst (polydipsia), increased urinary frequency, mental/mood changes or irritability, headache, unusual fatigue or tiredness. These symptoms may require clinical evaluation. Anorexia, weight loss, polyuria, and arrhythmias may also be observed. In addition, hypercalcemia due to bone resorption leading to hypercalciuria may be observed in prolonged hypervitaminosis D. In early stages of vitamin D toxicity, hypercalcemia is mild and renal function remains normal. As vitamin D toxicity continues, continued bone resorption and increased calcium levels lead to suppression of parathyroid production. Calcification of the vasculature and other tissues has been associated with prolonged vitamin D toxicity. Data do not support that vitamin D toxicity is associated with kidney stones. Death due to vitamin D intoxication is likely due to renal and cardiovascular failure. Long-term doses of vitamin D of 250 to 1,000 mcg/day (10,000 to 40,000 International Units/day) and long-term serum 25(OH)D concentrations of 500 to 600 nmol/L (200 to 400 ng/mL) are associated with vitamin D toxicity. Symptoms of vitamin D toxicity can become apparent within 4 weeks of continual excessive ingestion. Due to the long half-life of vitamin D, symptoms of toxicity may be prolonged. Excessive sun exposure does not result in vitamin D toxicity.
Risk of growth inhibition in infants due to vitamin D supplements is based on a 1938 report of 35 infants up to 45 weeks of age where high-dose vitamin D supplementation (45 to 112.5 mcg/day [1,800 to 4,500 International Units/day] for 6 months) was associated with growth inhibition in comparison with lower dose vitamin D supplements (less than 8.5 mcg/day [340 International Units/day] for 6 months). In a subsequent but smaller study (n = 11) performed in 1966, no association between vitamin D supplements and growth inhibition was found. However, due to a possible association, no RDI for vitamin D has been set for infants. A large observational study from Finland in 2011 reported no association between growth inhibition later in life (as evaluated at 14 and 31 years of age) and the administration of vitamin D supplements (50 mcg/day [2,000 International Units/day]) during infancy.
Vitamin D is contraindicated in patients with hypercalcemia, hypervitaminosis D, and vitamin D hypersensitivity or hypersensitivity to any of the excipients in the formulation. Certain vitamin D formulations contain FD&C yellow dye No. 5 (tartrazine); these formulations should not be used in patients with tartrazine dye hypersensitivity. Hypersensitivity to vitamin D is one etiologic factor in infants with idiopathic hypercalcemia; in these patients, vitamin D intake must be seriously restricted. Some formulations of the oral solution contain propylene glycol. The clinician should be aware of the toxic potential for young children (e.g., neonates and premature neonates, infants, and children younger than 4 years) and ensure the correct formulation of vitamin D is chosen. Excessive propylene glycol can cause lactic acidosis, hyperosmolality, tachypnea, tachycardia, diaphoresis, and central nervous system toxicity (e.g., seizures, intraventricular hemorrhage).
Patients with renal disease, especially renal failure, may be at increased risk for vitamin D-induced hypercalcemia even with usual dosages. Close clinical monitoring is needed to ensure adequate supplementation and, in pediatric patients, proper growth. In patients with stage 3 or higher kidney disease, use of a vitamin D analog appears preferred, following recommendations of the National Kidney Foundation.
Vitamin D is contraindicated in patients with malabsorption syndrome. Patients with fat malabsorption due to cystic fibrosis, Crohn's disease, some forms of hepatic disease, gallbladder disease or biliary tract disease may require higher doses of vitamin D due to decreases in intestinal absorption. Some patients taking concurrent medications (e.g., certain anticonvulsants) may require higher doses as well. The prescription of active vitamin D analogs may be preferred in such cases.
Adverse effects have not been reported with the normal daily intake of Vitamin D within the recommended dietary daily intakes for a pregnant female. Animal reproduction studies have shown fetal abnormalities in several species associated with hypervitaminosis D; therefore, the use of vitamin D in excess of the recommended dietary allowance during normal pregnancy should be avoided unless, in the judgment of the physician, potential benefits outweigh the hazards involved. The RDA of vitamin D during pregnancy is 15 mcg/day (600 International Units/day) with a Tolerable Upper Intake Limit of 100 mcg/day (4,000 International Units/day).
The 25-hydroxyvitamin D metabolite of vitamin D is distributed into human breast milk at concentrations relative to the maternal serum concentration. Typical breast milk concentrations (without maternal supplementation) are not sufficient to prevent vitamin D deficiency in infants that are exclusively breast-fed and do not receive other vitamin D supplementation. Prolonged, exclusive breast-feeding of infants without recommended vitamin D supplementation is a significant cause of rickets in infants, especially in dark-skinned infants breast-fed by mothers who are not vitamin D replete. Use of vitamin D within the recommended daily dietary intake for lactating women is generally recognized as safe. The recommended maternal daily allowance of vitamin D during breast-feeding is 600 International Units/day with a Tolerable Upper Intake Limit of 4000 International Units/day. While high-dose vitamin D supplementation to nursing mothers has been shown to increase the concentration of vitamin D in breast milk and favorably increase 25(OH)D levels in infants, the results have not been validated and supplementation to infants is still recommended. Generally, the serum calcium concentrations of the infant should be monitored when a nursing mother is prescribed vitamin D in high doses, since hypercalcemia has been reported with high dose maternal use.
General dosing information
-For dosing conversion, 1 mcg vitamin D = 40 International Units.
For nutritional supplementation:
NOTE: Persons with increased risk for deficiency of vitamin D (e.g., chronic fat malabsorption disorders, persons with chronic kidney disease, persons living with HIV, or persons taking certain enzyme-inducing medications, etc.) may require higher supplemental doses than those recommended for healthy persons to maintain normal vitamin D status. In such persons, 25(OH)D concentrations can be used to guide adequate dietary supplementation.
-for nutritional supplementation in healthy persons based on recommended reference dietary intakes:
Oral dosage:
Adults older than 70 years: 20 mcg/day (800 International Units/day) PO is the RDA.
Adult 18 to 70 years: 15 mcg/day (600 International Units/day) PO is the RDA.
Adolescents: 15 mcg/day (600 International Units/day) PO is the RDA. 10 mcg/day (400 International Units/day) PO is recommended if the adolescent is not obtaining at least 10 mcg (400 International Units) through dietary sources. All dietary sources of vitamin D (e.g., fortified milk, eggs, other food) may be included in determining the daily intake.
Children: 15 mcg/day (600 International Units/day) PO is the RDA. 10 mcg/day (400 International Units/day) PO is recommended if the child is consuming less than 1 L/day of vitamin D-fortified milk.
Infants: 10 mcg/day (400 International Units/day) PO is the recommended Adequate Intake based on dietary intake of breast milk, formula, or other food sources. No RDA has been established. Infants that are exclusively breast-fed without vitamin D supplements are at increased risk for deficiency. Because most exclusively formula-fed infants ingest nearly 1 L/day of formula after the first month of life, they will achieve a vitamin D intake of 10 mcg/day (400 International Units/day). Infants who receive a mixture of human milk and formula should get a vitamin D supplement of 10 mcg/day (400 International Units/day) to ensure the AI value. As infants are weaned from human milk and/or formula, intake of vitamin D-fortified milk should be encouraged to provide at least 10 mcg/day (400 International Units/day) of vitamin D. Vitamin D supplementation should continue until the infant consumes at least 1 L/day (1 quart/day) of vitamin D-fortified milk (Whole milk (cow's milk) is not recommended until after 12 months of age).
Neonates: 10 mcg/day (400 International Units/day) PO is the recommended Adequate Intake based on dietary intake of breast milk, formula, or other food sources. No RDA has been established. Infants that are exclusively breast-fed without vitamin D supplements are at increased risk for deficiency. Because most exclusively formula-fed infants ingest nearly 1 L/day of formula after the first month of life, they will achieve a vitamin D intake of 10 mcg/day (400 International Units/day). Infants who receive a mixture of human milk and formula should get a vitamin D supplement of 10 mcg/day (400 International Units/day) to ensure the AI value. As infants are weaned from human milk and/or formula, intake of vitamin D-fortified milk should be encouraged to provide at least 10 mcg/day (400 International Units/day) of vitamin D. Vitamin D supplementation should continue until the infant consumes at least 1 L/day (1 quart/day) of vitamin D-fortified milk (Whole milk (cow's milk) is not recommended until after 12 months of age).
Premature Neonates weighing 1.5 kg or more: 10 mcg/day (400 International Units/day) PO.
Premature Neonates weighing less than 1.5 kg: 5 to 10 mcg/day (200 to 400 International Units/day) PO. If the infant is receiving less than 10 mcg/day (400 International Units/day), increase the dosage to 10 mcg/day (400 International Units/day) when a weight of more than 1.5 kg is reached and full enteral nutrition is tolerated.
-for nutritional supplementation in persons with cystic fibrosis:
NOTE: Cholecalciferol is recommended over ergocalciferol in persons with cystic fibrosis.
Oral dosage:
Adults: 20 to 50 mcg (800 to 2,000 International Units) PO once daily. Adjust dosage to maintain serum 25-hydroxyvitamin D concentrations of 30 ng/mL or more. Max: 250 mcg/day (10,000 International Units/day).
Children and Adolescents 11 to 17 years: 20 to 50 mcg (800 to 2,000 International Units) PO once daily. Adjust dosage to maintain serum 25-hydroxyvitamin D concentrations of 30 ng/mL or more. Max: 250 mcg/day (10,000 International Units/day).
Children 1 to 10 years: 20 to 25 mcg (800 to 1,000 International Units) PO once daily. Adjust dosage to maintain serum 25-hydroxyvitamin D concentrations of 30 ng/mL or more. Max: 100 mcg/day (4,000 International Units/day).
Infants: 10 to 12.5 mcg (400 to 500 International Units) PO once daily. Adjust dosage to maintain serum 25-hydroxyvitamin D concentrations of 30 ng/mL or more. Max: 50 mcg/day (2,000 International Units/day).
Neonates: 10 to 12.5 mcg (400 to 500 International Units) PO once daily. Adjust dosage to maintain serum 25-hydroxyvitamin D concentrations of 30 ng/mL or more. Max: 50 mcg/day (2,000 International Units/day).
-for nutritional supplementation in persons with thalassemia:
Oral dosage:
Adults: 50 mcg (2,000 International Units) PO once daily.
Children and Adolescents: 50 mcg (2,000 International Units) PO once daily.
-for nutritional supplementation after bariatric surgery:
Oral dosage:
Adults: 75 mcg (3,000 International Units) PO once daily until serum vitamin D concentration is more than 30 ng/mL.
For the treatment of vitamin D deficiency:
NOTE: In adults, the Institute of Medicine (IOM) defines vitamin D deficiency as 25(OH)D concentrations of 30 nmol/L or less (12 ng/mL or less) and vitamin D insufficiency as 25(OH)D concentrations of 30 to 50 nmol/L (12 to less than 20 ng/mL). Generally all persons are sufficient at levels of 50 nmol/L or more (20 ng/mL or more). In pediatric patients, the American Academy of Pediatrics (AAP) and the IOM define vitamin D deficiency as 25(OH)D concentrations of 37.5 nmol/L or less (15 ng/mL or less) and vitamin D insufficiency as 25(OH)D concentrations of 50 nmol/L or less (20 ng/mL or less). In contrast, the Endocrine Society guidelines for adults and pediatric patients define vitamin D insufficiency as 25(OH)D concentrations less than 75 nmol/L (less than 30 ng/mL) and vitamin D deficiency as 25(OH)D concentrations less than 50 nmol/L (less than 20 ng/mL).
-for the treatment of vitamin D deficiency in the general population:
Oral dosage:
Adults: 7,000 to 10,000 mcg (280,000 to 400,000 International Units) PO loading dose divided in daily or weekly doses over 6 to 10 weeks to achieve a serum vitamin D concentration more than 30 ng/mL, then 20 to 100 mcg (800 to 4,000 International Units) PO once daily or given intermittently at higher equivalent dose starting 1 month after loading. Example loading dose regimens include: 100 mcg (4,000 International Units) PO once daily for 10 weeks; 150 mcg (6,000 International Units) PO once daily for 8 weeks; 1,000 mcg (40,000 International Units) once weekly for 7 weeks; or 1,250 mcg (50,000 International Units) PO once weekly for 6 to 8 weeks. Individualize dose based on serum vitamin D concentrations.
Children and Adolescents: 50 to 125 mcg (2,000 to 5,000 International Units) PO once daily or 350 to 1,250 mcg (14,000 to 50,000 International Units) PO once weekly for at least 6 weeks to achieve a serum vitamin D concentration more than 30 ng/mL, then 15 to 25 mcg (600 to 1,000 International Units) PO once daily. Maintenance doses of 1,250 mcg (50,000 International Units) PO once monthly have also been used. Individualize dose based on serum vitamin D concentrations.
Infants: 25 to 125 mcg (1,000 to 5,000 International Units) PO once daily or 1,250 mcg (50,000 International Units) PO once weekly for at least 6 weeks to achieve a serum vitamin D concentration more than 30 ng/mL, then 10 to 25 mcg (400 to 1,000 International Units) PO once daily. Individualize dose based on serum vitamin D concentrations.
Neonates: 25 to 50 mcg (1,000 to 2,000 International Units) PO once daily or 1,250 mcg (50,000 International Units) PO once weekly for at least 6 weeks to achieve a serum vitamin D concentration more than 30 ng/mL, then 10 to 25 mcg (400 to 1,000 International Units) PO once daily. Individualize dose based on serum vitamin D concentrations.
-for the treatment of vitamin D deficiency in persons with cystic fibrosis:
NOTE: Cholecalciferol is recommended over ergocalciferol in persons with cystic fibrosis.
Oral dosage:
Adults: 40 to 150 mcg (1,600 to 6,000 International Units) PO once daily, initially. May increase the dose to a maximum of 250 mcg (10,000 International Units) PO once daily to maintain a serum vitamin D concentration of at least 30 ng/mL (75 mmol/L).
Children and Adolescents 11 to 17 years: 40 to 150 mcg (1,600 to 6,000 International Units) PO once daily, initially. May increase the dose to a maximum of 250 mcg (10,000 International Units) PO once daily to maintain a serum vitamin D concentration of at least 30 ng/mL (75 mmol/L).
Children 1 to 10 years: 40 to 75 mcg (1,600 to 3,000 International Units) PO once daily, initially. May increase the dose to a maximum of 100 mcg (4,000 International Units) PO once daily to maintain a serum vitamin D concentration of at least 30 ng/mL (75 mmol/L).
Infants: 20 to 25 mcg (800 to 1,000 International Units) PO once daily, initially. May increase the dose to a maximum of 50 mcg (2,000 International Units) PO once daily to maintain a serum vitamin D concentration of at least 30 ng/mL (75 mmol/L).
Neonates: 20 to 25 mcg (800 to 1,000 International Units) PO once daily, initially. May increase the dose to a maximum of 50 mcg (2,000 International Units) PO once daily to maintain a serum vitamin D concentration of at least 30 ng/mL (75 mmol/L).
-for the treatment of vitamin D deficiency in persons with obesity or malabsorption syndromes (i.e., inflammatory bowel disease) and persons receiving concomitant medications affecting vitamin D metabolism (i.e., anticonvulsants, HIV medications):
Oral dosage:
Adults: 75 to 250 mcg (3,000 to 10,000 International Units) PO once daily or 1,250 mcg (50,000 International Units) PO 1 to 3 times weekly to achieve a serum vitamin D concentration more than 30 ng/mL, then 75 to 150 mcg (3,000 to 6,000 International Units) PO once daily.
Children and Adolescents: 150 to 250 mcg (6,000 to 10,000 International Units) PO once daily (2 to 3 times the usual recommended dose) to achieve a serum vitamin D concentration more than 30 ng/mL, then 30 to 75 mcg (1,200 to 3,000 International Units) PO once daily.
Infants: 150 to 250 mcg (6,000 to 10,000 International Units) PO once daily (2 to 3 times the usual recommended dose) to achieve a serum vitamin D concentration more than 30 ng/mL, then 20 to 75 mcg (800 to 3,000 International Units) PO once daily.
Neonates: 100 to 150 mcg (4,000 to 6,000 International Units) PO once daily (2 to 3 times the usual recommended dose) to achieve a serum vitamin D concentration more than 30 ng/mL, then 20 to 75 mcg (800 to 3,000 International Units) PO once daily.
For the treatment of nutritional rickets:
Oral dosage:
Children and Adolescents: 50 to 500 mcg (2,000 to 20,000 International Units) PO daily for 4 to 8 weeks, with the duration of treatment determined by evidence of radiologic healing. Thereafter, supplement with the RDA to prevent further deficiency. Alternatively, at least 125 mcg (5,000 International Units) PO once daily has also been recommended for initial treatment; weekly regimens (e.g., high doses, such as 1,250 mcg [50,000 International Units] PO once weekly) or a single higher-dose course over 1 to 5 days may be considered if compliance is an issue that prevents adequate repletion. Large single dose regimens (5,000 to 15,000 mcg [200,000 to 600,000 International Units] PO divided into 2 to 4 doses administered over 1 day) have been used when compliance is a concern, but are sometimes controversial due to a purported risk for hypercalcemia. It is important to ensure adequate dietary intake of calcium and phosphorus. Active treatment may continue for 2 to 3 months to replete deficient stores, followed by maintenance dosing with the RDA. Individualize dose based upon 25(OH)D concentrations.
Infants: 25 to 125 mcg (1,000 to 5,000 International Units) PO once daily has been recommended. Radiologic evidence of healing is usually observed in 2 to 4 weeks, and the active treatment duration is usually 2 to 3 months, after which the supplementation may be reduced to maintenance dosing in accordance with RDAs to prevent further deficiency. Supplementation with calcium is necessary due to the risk of hypocalcemia during bone remineralization. It is important to ensure adequate dietary intake of calcium and phosphorus. Weekly regimens (e.g., high doses, such as 1,250 mcg [50,000 International Units] PO once weekly) have been considered in older infants if compliance is an issue that prevents adequate repletion. Individualize dose based upon 25(OH)D concentrations.
Neonates: 25 mcg (1,000 International Units) PO once daily has been recommended. Radiologic evidence of healing is usually observed in 2 to 4 weeks, and the active treatment duration is usually 2 to 3 months, after which the supplementation may be reduced to maintenance dosing in accordance with RDAs to prevent further deficiency. Supplementation with calcium is necessary due to the risk of hypocalcemia during bone remineralization. It is important to ensure adequate dietary intake of calcium and phosphorus. Individualize dose based upon 25(OH)D concentrations.
For the treatment of vitamin D-dependent rickets type 2 (hereditary vitamin D resistant rickets):
Oral dosage:
Children and Adolescents: Treatment for HVDRR is not standardized. Despite significant improvements in vitamin D concentrations following high-dose ergocalciferol (or use of a vitamin D analog like calcitriol) alone, patients may remain hypocalcemic and hypophosphatemic. High doses of ergocalciferol (vitamin D2) have been used in these patients. The following regimens have been used with variable results: 100 to 1,000 mcg/day (4,000 to 40,000 International Units/day) PO or 5 to 7 mcg/kg/day (200 to 280 International Units/kg/day) PO. However, doses as high as 5,000 mcg/day (200,000 International Units/day) PO have not been effective in improving the disease in other patients. Patients should receive a 3 to 6 month trial of high dose vitamin D along with high-dose calcium therapy. Patients without alopecia appear more likely to respond. The FDA-approved dose is 300 to 12,500 mcg (12,000 to 500,000 International Units) PO daily. Calcium intake should be adequate. Blood calcium and phosphorus determinations are recommended every 2 weeks or more frequently if clinically indicated. X-rays of the bones are recommended every month until condition is corrected and stabilized. Individualize dose based upon 25(OH)D concentrations.
For osteoporosis prophylaxis and treatment in conjunction with calcium supplementation:
Oral dosage:
Adults 50 years and older: 20 to 25 mcg (800 to 1,000 international units) PO daily is recommended by the National Osteoporosis Foundation. Supplementation regimen should include calcium for greatest benefit.
-for osteoporosis prevention in patients receiving corticosteroids:
Oral dosage:
Adults: 20 mcg (800 International Units) PO daily; different doses may be recommended dependent on concomitant pharmacological treatment or prevention. The American College of Rheumatology recommends supplementation of vitamin D and calcium in all patients receiving corticosteroid therapy, especially if treatment duration will exceed 3 months.
Children and Adolescents: 20 mcg (800 International Units) PO daily. The American College of Rheumatology recommends supplementation of vitamin D and calcium in all patients receiving corticosteroid therapy, especially if treatment duration will exceed 3 months.
For the prevention of premenstrual syndrome (PMS)*:
Oral dosage:
Adult females: A total dose of 17.5 mcg (700 International Units) PO daily from a combination of dietary and non-dietary sources. In a population-based study of 3,025 females, the daily vitamin D and calcium intake was followed to determine if vitamin D or calcium had an impact on the risk of developing PMS. Women with the highest intake of vitamin D from both dietary sources and supplements (median 17.7 mcg [706 International Units daily]) had a reduced risk of developing PMS compared with those women with the lowest intake of vitamin D of 2.8 mcg (112 International Units) daily (RR of 0.59, 95% CI 0.4 to 0.86, p = 0.01 for the trend).
For the treatment of hypoparathyroidism with calcium supplementation:
Oral Dosage:
Adults: 1,250 to 5,000 mcg (50,000 to 200,000 International Units) PO once daily along with calcium supplements.
Children and Adolescents: 1,250 to 5,000 mcg (50,000 to 200,000 International Units) PO once daily along with calcium supplements.
For the prevention and treatment of vitamin D deficiency and secondary hyperparathyroidism and resultant bone disease (renal osteodystrophy*) in patients with CKD:
Oral dosage:
Adults: 1,250 mcg (50,000 International Units) PO once weekly or monthly until target serum total hydroxyvitamin D concentrations are achieved. Cholecalciferol is more effective at raising serum total 25-hydroxyvitamin D concentrations in non-dialysis-dependent CKD patients (CKD G3a-5) compared with ergocalciferol and may be preferable in these patients.
For the treatment of familial hypocholesterolemia (e.g., abetalipoproteinemia, hypobetalipoproteinemia, and chylomicron retention disease, CRD):
Oral dosage:
Children and Adolescents 6 to 17 years: 20 to 30 mcg (800 to 1,200 International Units) PO once daily has been recommended. Alternative regimen is 15,000 mcg (600,000 International Units) PO once every 2 months. If vitamin D supplementation is started early, it prevents development of osteopenia in these patients.
Infants and Children 1 to 5 years: 20 to 30 mcg (800 to 1,200 International Units) PO once daily has been recommended. Alternative regimen is 2,500 mcg (100,000 International Units) PO once every 2 months. If vitamin D supplementation is started early, it prevents development of osteopenia in these patients.
Therapeutic Drug Monitoring:
Serum 25(OH)D concentrations are recommended for monitoring vitamin D status because it is reflective of both sources of vitamin D, sunlight and dietary. It is not, however, reflective of vitamin D body stores. Circulating 1,25(OH)2D is not a good indicator of vitamin D status due to its shorter half-life and its tight regulation by parathyroid hormone, calcium, and phosphorus. Levels of 1,25(OH)2D do not usually decrease until severe vitamin D deficiency.
The Institute of Medicine recommends the following regarding the interpretation of 25(OH)D concentrations and vitamin D status for normal healthy persons:
-less than 30 nmol/L (less than 12 ng/mL): Vitamin D deficiency; in pediatric patients, a level of 37.5 nmol/L or less (15 ng/mL or less) is considered deficiency.
-30 to 50 nmol/L (12 to 20 ng/mL): Vitamin D insufficiency; concentrations may be inadequate in some persons for bone and overall health. In pediatric patients, a level of 40 to 50 nmol/L (16 to 20 ng/mL) is considered insufficiency.
-50 nmol/L or more (20 ng/mL or more): Generally considered adequate for bone and overall health.
-75 nmol/L or more (30 ng/mL or more): No consistent evidence of increased benefit.
-more than 125 nmol/L (more than 50 ng/mL): Evidence supports a risk of adverse effects, especially at those concentrations more than 150 nmol/L (more than 60 ng/mL). Vitamin D toxicity has been associated with 25(OH)D concentrations of 500 to 600 nmol/L (200 to 240 ng/mL).
Maximum Dosage Limits:
NOTE: The Tolerable Upper Intake Level (UL) is defined as the highest daily intake of a nutrient that is likely to pose no risk in otherwise healthy individuals. The ULs are not intended to apply to individuals with specific disease states. Maximum doses for other uses are indication specific.
-Adults
Maintenance Tolerable Upper Intake Level (UL) is 100 mcg/day (4,000 International Units/day) PO.
-Geriatric
Maintenance Tolerable Upper Intake Level (UL) is 100 mcg/day (4,000 International Units/day) PO.
-Adolescents
Maintenance Tolerable Upper Intake Level (UL) is 100 mcg/day (4,000 International Units/day) PO.
-Children
Children 9 to 12 years: Maintenance Tolerable Upper Intake Level (UL) is 100 mcg/day (4,000 International Units/day) PO.
Children 4 to 8 years: Maintenance Tolerable Upper Intake Level (UL) is 75 mcg/day (3,000 International Units/day) PO.
Children 1 to 3 years: Maintenance Tolerable Upper Intake Level (UL) is 62.5 mcg/day (2,500 International Units/day) PO.
-Infants
Infants 7 to 12 months: Maintenance Tolerable Upper Intake Level (UL) is 37.5 mcg/day (1,500 International Units/day) PO.
Infants 1 to 6 months: Maintenance Tolerable Upper Intake Level (UL) is 25 mcg/day (1,000 International Units/day) PO.
-Neonates
Maintenance Tolerable Upper Intake Level (UL) is 25 mcg/day (1,000 International Units/day) PO.
Patients with Hepatic Impairment Dosing
Specific guidelines for dosage adjustments in hepatic impairment are not available; higher doses may be needed to compensate for reductions in intestinal absorption.
Patients with Renal Impairment Dosing
Specific guidelines for dosage adjustments in renal impairment are not available. However, vitamin D is activated in the kidney; close monitoring is required to ensure the appropriate dose.
*non-FDA-approved indication
Abacavir; Dolutegravir; Lamivudine: (Moderate) Administer dolutegravir 2 hours before or 6 hours after taking supplements containing calcium if given under fasting conditions. When taken with food, dolutegravir and supplements containing calcium can be taken at the same time. Simultaneous administration under fasted conditions may result in reduced bioavailability of dolutegravir.
Alendronate: (Moderate) Separate administration of alendronate and calcium-containing supplements by at least 30 minutes. Calcium will interfere with the absorption of alendronate.
Alendronate; Cholecalciferol: (Moderate) Separate administration of alendronate and calcium-containing supplements by at least 30 minutes. Calcium will interfere with the absorption of alendronate.
Aliskiren; Hydrochlorothiazide, HCTZ: (Moderate) Dose adjustment of vitamin D or vitamin D analogs may be necessary during coadministration with thiazide diuretics. Additionally, serum calcium concentrations should be monitored frequently. Monitor more frequently in patients with a history of hypercalcemia. Hypercalcemia may be exacerbated by coadministration of vitamin D or vitamin D analogs and thiazide diuretics. Thiazide diuretics are known to induce hypercalcemia by reducing the excretion of calcium in the urine. (Moderate) Monitor serum calcium concentration during concomitant calcium and thiazide diuretic use due to the risk for hypercalcemia. Thiazide diuretics may decrease urinary calcium excretion and cause intermittent and slight increases in serum calcium.
Aluminum Hydroxide; Magnesium Hydroxide: (Major) Avoid vitamin D coadministration with magnesium hydroxide in persons on chronic hemodialysis due to the risk for hypermagnesemia.
Aluminum Hydroxide; Magnesium Hydroxide; Simethicone: (Major) Avoid vitamin D coadministration with magnesium hydroxide in persons on chronic hemodialysis due to the risk for hypermagnesemia.
Amiloride; Hydrochlorothiazide, HCTZ: (Moderate) Dose adjustment of vitamin D or vitamin D analogs may be necessary during coadministration with thiazide diuretics. Additionally, serum calcium concentrations should be monitored frequently. Monitor more frequently in patients with a history of hypercalcemia. Hypercalcemia may be exacerbated by coadministration of vitamin D or vitamin D analogs and thiazide diuretics. Thiazide diuretics are known to induce hypercalcemia by reducing the excretion of calcium in the urine. (Moderate) Monitor serum calcium concentration during concomitant calcium and thiazide diuretic use due to the risk for hypercalcemia. Thiazide diuretics may decrease urinary calcium excretion and cause intermittent and slight increases in serum calcium.
Amlodipine: (Minor) Monitor blood pressure during concurrent use of calcium and calcium-channel blockers. Concomitant use may reduce the response to calcium-channel blockers.
Amlodipine; Atorvastatin: (Minor) Monitor blood pressure during concurrent use of calcium and calcium-channel blockers. Concomitant use may reduce the response to calcium-channel blockers.
Amlodipine; Benazepril: (Minor) Monitor blood pressure during concurrent use of calcium and calcium-channel blockers. Concomitant use may reduce the response to calcium-channel blockers.
Amlodipine; Celecoxib: (Minor) Monitor blood pressure during concurrent use of calcium and calcium-channel blockers. Concomitant use may reduce the response to calcium-channel blockers.
Amlodipine; Olmesartan: (Minor) Monitor blood pressure during concurrent use of calcium and calcium-channel blockers. Concomitant use may reduce the response to calcium-channel blockers.
Amlodipine; Valsartan: (Minor) Monitor blood pressure during concurrent use of calcium and calcium-channel blockers. Concomitant use may reduce the response to calcium-channel blockers.
Amlodipine; Valsartan; Hydrochlorothiazide, HCTZ: (Moderate) Dose adjustment of vitamin D or vitamin D analogs may be necessary during coadministration with thiazide diuretics. Additionally, serum calcium concentrations should be monitored frequently. Monitor more frequently in patients with a history of hypercalcemia. Hypercalcemia may be exacerbated by coadministration of vitamin D or vitamin D analogs and thiazide diuretics. Thiazide diuretics are known to induce hypercalcemia by reducing the excretion of calcium in the urine. (Moderate) Monitor serum calcium concentration during concomitant calcium and thiazide diuretic use due to the risk for hypercalcemia. Thiazide diuretics may decrease urinary calcium excretion and cause intermittent and slight increases in serum calcium. (Minor) Monitor blood pressure during concurrent use of calcium and calcium-channel blockers. Concomitant use may reduce the response to calcium-channel blockers.
Atenolol: (Minor) Calcium antacids (e.g., calcium carbonate) and supplements (e.g., other oral calcium salts) have been reported to reduce the mean peak concentrations by 51% and the AUC of atenolol by 32%. In another study, antacids reduced the AUC of atenolol by 33%. Separate doses of atenolol and calcium-containing antacids or supplements by at least 2 hours to minimize this potential interaction,. However, most clinicians consider the interaction of atenolol with antacids to be of minor clinical significance, since clinical efficacy (heart rate and blood pressure parameters) appear to be unchanged under usual intermittent clinical use.
Atenolol; Chlorthalidone: (Moderate) Dose adjustment of vitamin D or vitamin D analogs may be necessary during coadministration with thiazide diuretics. Additionally, serum calcium concentrations should be monitored frequently. Monitor more frequently in patients with a history of hypercalcemia. Hypercalcemia may be exacerbated by coadministration of vitamin D or vitamin D analogs and thiazide diuretics. Thiazide diuretics are known to induce hypercalcemia by reducing the excretion of calcium in the urine. (Moderate) Monitor serum calcium concentration during concomitant calcium and thiazide diuretic use due to the risk for hypercalcemia. Thiazide diuretics may decrease urinary calcium excretion and cause intermittent and slight increases in serum calcium. (Minor) Calcium antacids (e.g., calcium carbonate) and supplements (e.g., other oral calcium salts) have been reported to reduce the mean peak concentrations by 51% and the AUC of atenolol by 32%. In another study, antacids reduced the AUC of atenolol by 33%. Separate doses of atenolol and calcium-containing antacids or supplements by at least 2 hours to minimize this potential interaction,. However, most clinicians consider the interaction of atenolol with antacids to be of minor clinical significance, since clinical efficacy (heart rate and blood pressure parameters) appear to be unchanged under usual intermittent clinical use.
Atracurium: (Moderate) Concomitant use of neuromuscular blockers and calcium may result in resistance to neuromuscular blockade. Calcium antagonizes the potentiating effect of magnesium on neuromuscular blockade. Also, calcium triggers acetylcholine release, and therefore, may both reduce the sensitivity to neuromuscular blockers and decrease the duration of neuromuscular blockade.
Azilsartan; Chlorthalidone: (Moderate) Dose adjustment of vitamin D or vitamin D analogs may be necessary during coadministration with thiazide diuretics. Additionally, serum calcium concentrations should be monitored frequently. Monitor more frequently in patients with a history of hypercalcemia. Hypercalcemia may be exacerbated by coadministration of vitamin D or vitamin D analogs and thiazide diuretics. Thiazide diuretics are known to induce hypercalcemia by reducing the excretion of calcium in the urine. (Moderate) Monitor serum calcium concentration during concomitant calcium and thiazide diuretic use due to the risk for hypercalcemia. Thiazide diuretics may decrease urinary calcium excretion and cause intermittent and slight increases in serum calcium.
Baloxavir Marboxil: (Major) Do not administer baloxavir with products that contain calcium. Polyvalent cations, such as calcium, can chelate with baloxavir, reducing its absorption.
Benazepril; Hydrochlorothiazide, HCTZ: (Moderate) Dose adjustment of vitamin D or vitamin D analogs may be necessary during coadministration with thiazide diuretics. Additionally, serum calcium concentrations should be monitored frequently. Monitor more frequently in patients with a history of hypercalcemia. Hypercalcemia may be exacerbated by coadministration of vitamin D or vitamin D analogs and thiazide diuretics. Thiazide diuretics are known to induce hypercalcemia by reducing the excretion of calcium in the urine. (Moderate) Monitor serum calcium concentration during concomitant calcium and thiazide diuretic use due to the risk for hypercalcemia. Thiazide diuretics may decrease urinary calcium excretion and cause intermittent and slight increases in serum calcium.
Bictegravir; Emtricitabine; Tenofovir Alafenamide: (Moderate) Administer bictegravir with food at the same time as oral calcium supplements. Routine administration of bictegravir under fasting conditions simultaneously with, or 2 hours after, calcium supplements is not recommended. Calcium is a polyvalent cation that can bind bictegravir in the GI tract. Taking these drugs simultaneously without food results in reduced bioavailability of bictegravir. In drug interaction studies, simultaneous administration of bictegravir with another calcium supplement under fasted conditions decreased the mean AUC of bictegravir by approximately 33%.
Bismuth Subcitrate Potassium; Metronidazole; Tetracycline: (Moderate) Divalent or trivalent cations readily chelate with tetracycline antibiotics, forming insoluble compounds. The oral absorption of these antibiotics will be significantly reduced by other orally administered compounds that contain calcium salts, particularly if the time of administration is within 60 minutes of each other. Calcium salts and tetracyclines should not be administered within 1 to 2 hours of each other, although doxycycline chelates less with calcium than other tetracyclines.
Bismuth Subsalicylate; Metronidazole; Tetracycline: (Moderate) Divalent or trivalent cations readily chelate with tetracycline antibiotics, forming insoluble compounds. The oral absorption of these antibiotics will be significantly reduced by other orally administered compounds that contain calcium salts, particularly if the time of administration is within 60 minutes of each other. Calcium salts and tetracyclines should not be administered within 1 to 2 hours of each other, although doxycycline chelates less with calcium than other tetracyclines.
Bisoprolol; Hydrochlorothiazide, HCTZ: (Moderate) Dose adjustment of vitamin D or vitamin D analogs may be necessary during coadministration with thiazide diuretics. Additionally, serum calcium concentrations should be monitored frequently. Monitor more frequently in patients with a history of hypercalcemia. Hypercalcemia may be exacerbated by coadministration of vitamin D or vitamin D analogs and thiazide diuretics. Thiazide diuretics are known to induce hypercalcemia by reducing the excretion of calcium in the urine. (Moderate) Monitor serum calcium concentration during concomitant calcium and thiazide diuretic use due to the risk for hypercalcemia. Thiazide diuretics may decrease urinary calcium excretion and cause intermittent and slight increases in serum calcium.
Cabotegravir: (Moderate) Administer oral calcium at least two hours before or four hours after taking oral cabotegravir. Calcium is a polyvalent cation that can bind cabotegravir in the GI tract. Taking these drugs simultaneously may result in reduced oral bioavailability of cabotegravir.
Cabotegravir; Rilpivirine: (Moderate) Administer oral calcium at least two hours before or four hours after taking oral cabotegravir. Calcium is a polyvalent cation that can bind cabotegravir in the GI tract. Taking these drugs simultaneously may result in reduced oral bioavailability of cabotegravir.
Calcifediol: (Moderate) Monitor serum calcium concentrations during concomitant use of high doses of calcium and vitamin D analogs; a dosage adjustment of the vitamin D analog may be needed. Hypercalcemia may be exacerbated by concomitant administration.
Calcipotriene: (Minor) There is evidence that calcipotriene can be absorbed in amounts that are sufficient to produce systemic effects, including elevated serum calcium; hypercalcemia has been observed in normal prescription use. Use calcipotriene cautiously with other agents that can produce hypercalcemia (e.g., calcium salts or supplements including calcium carbonate).
Calcipotriene; Betamethasone: (Minor) There is evidence that calcipotriene can be absorbed in amounts that are sufficient to produce systemic effects, including elevated serum calcium; hypercalcemia has been observed in normal prescription use. Use calcipotriene cautiously with other agents that can produce hypercalcemia (e.g., calcium salts or supplements including calcium carbonate).
Calcitonin: (Moderate) Calcitonin is given to hypercalcemic patients to reduce serum calcium concentrations. For the treatment of hypercalcemia, calcium supplements should be avoided. Calcium salts, including calcium carbonate, can elevate serum calcium concentrations and antagonize the effects of the calcitonin for this condition. For the treatment of osteoporosis adequate intake of calcium salts are necessary in conjunction with calcitonin. An increase in serum calcium concentrations helps to reduce bone resorption and loss of bone mass, and offsets the effect of calcitonin in lowering serum calcium levels.
Calcitriol: (Moderate) Monitor serum calcium concentrations during concomitant use of high doses of calcium and vitamin D analogs; a dosage adjustment of the vitamin D analog may be needed. Hypercalcemia may be exacerbated by concomitant administration.
Calcium Phosphate, Supersaturated: (Moderate) The concomitant use of oral sodium phosphate monobasic monohydrate; sodium phosphate dibasic anhydrous preparations in conjunction with antacids containing calcium (e.g., calcium carbonate, calcium salts) may bind the phosphate in the stomach and reduce its absorption. If the patient requires multiple mineral supplements or concurrent use of antacids, it is prudent to separate the administration of sodium phosphate salts from calcium containing products by at least one hour.
Calcium-channel blockers: (Minor) Monitor blood pressure during concurrent use of calcium and calcium-channel blockers. Concomitant use may reduce the response to calcium-channel blockers.
Candesartan; Hydrochlorothiazide, HCTZ: (Moderate) Dose adjustment of vitamin D or vitamin D analogs may be necessary during coadministration with thiazide diuretics. Additionally, serum calcium concentrations should be monitored frequently. Monitor more frequently in patients with a history of hypercalcemia. Hypercalcemia may be exacerbated by coadministration of vitamin D or vitamin D analogs and thiazide diuretics. Thiazide diuretics are known to induce hypercalcemia by reducing the excretion of calcium in the urine. (Moderate) Monitor serum calcium concentration during concomitant calcium and thiazide diuretic use due to the risk for hypercalcemia. Thiazide diuretics may decrease urinary calcium excretion and cause intermittent and slight increases in serum calcium.
Captopril; Hydrochlorothiazide, HCTZ: (Moderate) Dose adjustment of vitamin D or vitamin D analogs may be necessary during coadministration with thiazide diuretics. Additionally, serum calcium concentrations should be monitored frequently. Monitor more frequently in patients with a history of hypercalcemia. Hypercalcemia may be exacerbated by coadministration of vitamin D or vitamin D analogs and thiazide diuretics. Thiazide diuretics are known to induce hypercalcemia by reducing the excretion of calcium in the urine. (Moderate) Monitor serum calcium concentration during concomitant calcium and thiazide diuretic use due to the risk for hypercalcemia. Thiazide diuretics may decrease urinary calcium excretion and cause intermittent and slight increases in serum calcium.
Cardiac glycosides: (Moderate) Monitor for signs and symptoms of digoxin toxicity during concomitant calcium use. Hypercalcemia may predispose persons to digoxin toxicity. If IV calcium is administered rapidly in a person receiving digoxin, serious arrhythmias may occur. Monitor ECG and calcium concentrations closely during IV calcium and digoxin administration.
Castor Oil: (Moderate) Absorption of fat-soluble vitamins may be decreased with coadministration of castor oil.
Chlorothiazide: (Moderate) Dose adjustment of vitamin D or vitamin D analogs may be necessary during coadministration with thiazide diuretics. Additionally, serum calcium concentrations should be monitored frequently. Monitor more frequently in patients with a history of hypercalcemia. Hypercalcemia may be exacerbated by coadministration of vitamin D or vitamin D analogs and thiazide diuretics. Thiazide diuretics are known to induce hypercalcemia by reducing the excretion of calcium in the urine. (Moderate) Monitor serum calcium concentration during concomitant calcium and thiazide diuretic use due to the risk for hypercalcemia. Thiazide diuretics may decrease urinary calcium excretion and cause intermittent and slight increases in serum calcium.
Chlorthalidone: (Moderate) Dose adjustment of vitamin D or vitamin D analogs may be necessary during coadministration with thiazide diuretics. Additionally, serum calcium concentrations should be monitored frequently. Monitor more frequently in patients with a history of hypercalcemia. Hypercalcemia may be exacerbated by coadministration of vitamin D or vitamin D analogs and thiazide diuretics. Thiazide diuretics are known to induce hypercalcemia by reducing the excretion of calcium in the urine. (Moderate) Monitor serum calcium concentration during concomitant calcium and thiazide diuretic use due to the risk for hypercalcemia. Thiazide diuretics may decrease urinary calcium excretion and cause intermittent and slight increases in serum calcium.
Cholestyramine: (Moderate) Cholestyramine can decrease the intestinal absorption of fat and fat-soluble vitamins. If used concurrently, administration of the two agents should be staggered for the longest time interval possible.
Ciprofloxacin: (Moderate) Administer oral ciprofloxacin at least 2 hours before or 6 hours after oral products that contain calcium. Ciprofloxacin absorption may be reduced as quinolone antibiotics can chelate with divalent or trivalent cations. Examples of compounds that may interfere with quinolone bioavailability include antacids and multivitamins that contain calcium.
Cisatracurium: (Moderate) Concomitant use of neuromuscular blockers and calcium may result in resistance to neuromuscular blockade. Calcium antagonizes the potentiating effect of magnesium on neuromuscular blockade. Also, calcium triggers acetylcholine release, and therefore, may both reduce the sensitivity to neuromuscular blockers and decrease the duration of neuromuscular blockade.
Clevidipine: (Minor) Monitor blood pressure during concurrent use of calcium and calcium-channel blockers. Concomitant use may reduce the response to calcium-channel blockers.
Cod Liver Oil: (Minor) Doses in excess of 1,500 to 2,000 mcg per day of Vitamin A may lead to bone loss and will counteract the effects of supplementation with calcium salts.
Colesevelam: (Moderate) It is not known if colesevelam can reduce the absorption of oral vitamin supplements including fat soluble vitamins A, D, E, and K. To minimize potential interactions, administer vitamins at least 4 hours before colesevelam.
Colestipol: (Moderate) Separate administration of fat-soluble vitamins by 1 hour before or 4 hours after a colestipol dose to limit effects on oral absorption. Because it sequesters bile acids, colestipol may interfere with normal fat absorption and thus may reduce absorption of fat-soluble vitamins.
Conjugated Estrogens: (Minor) Estrogens can increase calcium absorption. Use caution in patients predisposed to hypercalcemia or nephrolithiasis.
Conjugated Estrogens; Bazedoxifene: (Minor) Estrogens can increase calcium absorption. Use caution in patients predisposed to hypercalcemia or nephrolithiasis.
Conjugated Estrogens; Medroxyprogesterone: (Minor) Estrogens can increase calcium absorption. Use caution in patients predisposed to hypercalcemia or nephrolithiasis.
Delafloxacin: (Major) Administer oral delafloxacin at least 2 hours before or 6 hours after oral products that contain calcium. Delafloxacin absorption may be reduced as quinolone antibiotics can chelate with divalent or trivalent cations. Examples of compounds that may interfere with fluoroquinolone bioavailability include antacids and multivitamins that contain calcium.
Demeclocycline: (Moderate) Divalent or trivalent cations readily chelate with tetracycline antibiotics, forming insoluble compounds. The oral absorption of these antibiotics will be significantly reduced by other orally administered compounds that contain calcium salts, particularly if the time of administration is within 60 minutes of each other. Calcium salts and tetracyclines should not be administered within 1 to 2 hours of each other, although doxycycline chelates less with calcium than other tetracyclines.
Desogestrel; Ethinyl Estradiol: (Minor) Estrogens can increase calcium absorption. Use caution in patients predisposed to hypercalcemia or nephrolithiasis.
Dienogest; Estradiol valerate: (Minor) Estrogens can increase calcium absorption. Use caution in patients predisposed to hypercalcemia or nephrolithiasis.
Digoxin: (Moderate) Monitor for signs and symptoms of digoxin toxicity during concomitant calcium use. Hypercalcemia may predispose persons to digoxin toxicity. If IV calcium is administered rapidly in a person receiving digoxin, serious arrhythmias may occur. Monitor ECG and calcium concentrations closely during IV calcium and digoxin administration.
Diltiazem: (Minor) Monitor blood pressure during concurrent use of calcium and calcium-channel blockers. Concomitant use may reduce the response to calcium-channel blockers.
Dolutegravir: (Moderate) Administer dolutegravir 2 hours before or 6 hours after taking supplements containing calcium if given under fasting conditions. When taken with food, dolutegravir and supplements containing calcium can be taken at the same time. Simultaneous administration under fasted conditions may result in reduced bioavailability of dolutegravir.
Dolutegravir; Lamivudine: (Moderate) Administer dolutegravir 2 hours before or 6 hours after taking supplements containing calcium if given under fasting conditions. When taken with food, dolutegravir and supplements containing calcium can be taken at the same time. Simultaneous administration under fasted conditions may result in reduced bioavailability of dolutegravir.
Dolutegravir; Rilpivirine: (Moderate) Administer dolutegravir 2 hours before or 6 hours after taking supplements containing calcium if given under fasting conditions. When taken with food, dolutegravir and supplements containing calcium can be taken at the same time. Simultaneous administration under fasted conditions may result in reduced bioavailability of dolutegravir.
Doxercalciferol: (Moderate) Monitor serum calcium concentrations during concomitant use of high doses of calcium and vitamin D analogs; a dosage adjustment of the vitamin D analog may be needed. Hypercalcemia may be exacerbated by concomitant administration.
Doxycycline: (Moderate) Divalent or trivalent cations readily chelate with tetracycline antibiotics, forming insoluble compounds. The oral absorption of these antibiotics will be significantly reduced by other orally administered compounds that contain calcium salts, particularly if the time of administration is within 60 minutes of each other. Calcium salts and tetracyclines should not be administered within 1 to 2 hours of each other, although doxycycline chelates less with calcium than other tetracyclines.
Drospirenone; Estetrol: (Minor) Estrogens can increase calcium absorption. Use caution in patients predisposed to hypercalcemia or nephrolithiasis.
Drospirenone; Estradiol: (Minor) Estrogens can increase calcium absorption. Use caution in patients predisposed to hypercalcemia or nephrolithiasis.
Drospirenone; Ethinyl Estradiol: (Minor) Estrogens can increase calcium absorption. Use caution in patients predisposed to hypercalcemia or nephrolithiasis.
Drospirenone; Ethinyl Estradiol; Levomefolate: (Minor) Estrogens can increase calcium absorption. Use caution in patients predisposed to hypercalcemia or nephrolithiasis.
Edetate Calcium Disodium, Calcium EDTA: (Major) Because edetate disodium chelates and lowers serum calcium, oral or parenteral calcium salts should not be administered concomitantly.
Elagolix; Estradiol; Norethindrone acetate: (Minor) Estrogens can increase calcium absorption. Use caution in patients predisposed to hypercalcemia or nephrolithiasis.
Eltrombopag: (Major) Eltrombopag chelates polyvalent cations (e.g., calcium, aluminum, and magnesium) in food, mineral supplements, and antacids. In a clinical study, systemic exposure to eltrombopag was decreased by 70% when it was administered with a polyvalent cation-containing antacid. Administer eltrombopag at least 2 hours before or 4 hours after any oral products containing polyvalent cations, such as aluminum salts, (like aluminum hydroxide), calcium salts, (including calcium carbonate), and magnesium salts.
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Alafenamide: (Moderate) Separate administration of elvitegravir and calcium by at least 2 hours. Due to the formation of ionic complexes in the gastrointestinal tract, simultaneous administration results in lower elvitegravir plasma concentrations.
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Disoproxil Fumarate: (Moderate) Separate administration of elvitegravir and calcium by at least 2 hours. Due to the formation of ionic complexes in the gastrointestinal tract, simultaneous administration results in lower elvitegravir plasma concentrations.
Enalapril; Hydrochlorothiazide, HCTZ: (Moderate) Dose adjustment of vitamin D or vitamin D analogs may be necessary during coadministration with thiazide diuretics. Additionally, serum calcium concentrations should be monitored frequently. Monitor more frequently in patients with a history of hypercalcemia. Hypercalcemia may be exacerbated by coadministration of vitamin D or vitamin D analogs and thiazide diuretics. Thiazide diuretics are known to induce hypercalcemia by reducing the excretion of calcium in the urine. (Moderate) Monitor serum calcium concentration during concomitant calcium and thiazide diuretic use due to the risk for hypercalcemia. Thiazide diuretics may decrease urinary calcium excretion and cause intermittent and slight increases in serum calcium.
Eprosartan; Hydrochlorothiazide, HCTZ: (Moderate) Dose adjustment of vitamin D or vitamin D analogs may be necessary during coadministration with thiazide diuretics. Additionally, serum calcium concentrations should be monitored frequently. Monitor more frequently in patients with a history of hypercalcemia. Hypercalcemia may be exacerbated by coadministration of vitamin D or vitamin D analogs and thiazide diuretics. Thiazide diuretics are known to induce hypercalcemia by reducing the excretion of calcium in the urine. (Moderate) Monitor serum calcium concentration during concomitant calcium and thiazide diuretic use due to the risk for hypercalcemia. Thiazide diuretics may decrease urinary calcium excretion and cause intermittent and slight increases in serum calcium.
Esterified Estrogens: (Minor) Estrogens can increase calcium absorption. Use caution in patients predisposed to hypercalcemia or nephrolithiasis.
Esterified Estrogens; Methyltestosterone: (Minor) Estrogens can increase calcium absorption. Use caution in patients predisposed to hypercalcemia or nephrolithiasis.
Estradiol: (Minor) Estrogens can increase calcium absorption. Use caution in patients predisposed to hypercalcemia or nephrolithiasis.
Estradiol; Levonorgestrel: (Minor) Estrogens can increase calcium absorption. Use caution in patients predisposed to hypercalcemia or nephrolithiasis.
Estradiol; Norethindrone: (Minor) Estrogens can increase calcium absorption. Use caution in patients predisposed to hypercalcemia or nephrolithiasis.
Estradiol; Norgestimate: (Minor) Estrogens can increase calcium absorption. Use caution in patients predisposed to hypercalcemia or nephrolithiasis.
Estradiol; Progesterone: (Minor) Estrogens can increase calcium absorption. Use caution in patients predisposed to hypercalcemia or nephrolithiasis.
Estramustine: (Major) Administration of estramustine with calcium impairs the oral absorption of estramustine significantly, due to formation of a calcium-phosphate complex. Calcium-containing drugs must not be taken simultaneously with estramustine. Patients should be instructed to take estramustine with water at least 1 hour before or 2 hours after calcium supplements.
Estrogens: (Minor) Estrogens can increase calcium absorption. Use caution in patients predisposed to hypercalcemia or nephrolithiasis.
Estropipate: (Minor) Estrogens can increase calcium absorption. Use caution in patients predisposed to hypercalcemia or nephrolithiasis.
Ethinyl Estradiol; Norelgestromin: (Minor) Estrogens can increase calcium absorption. Use caution in patients predisposed to hypercalcemia or nephrolithiasis.
Ethinyl Estradiol; Norethindrone Acetate: (Minor) Estrogens can increase calcium absorption. Use caution in patients predisposed to hypercalcemia or nephrolithiasis.
Ethinyl Estradiol; Norgestrel: (Minor) Estrogens can increase calcium absorption. Use caution in patients predisposed to hypercalcemia or nephrolithiasis.
Ethotoin: (Major) Oral absorption of phenytoin can be reduced by calcium salts. Calcium salts can form complexes that are nonabsorbable. Separating the administration of phenytoin and calcium salts by at least 2 hours to help avoid this interaction. A similar interaction may occur with ethotoin. (Moderate) Phenytoin and fosphenytoin can decrease the activity of vitamin D (e.g., cholecalciferol) by increasing its metabolism. In rare cases, this has caused anticonvulsant-induced rickets and osteomalacia. Vitamin D supplementation or dosage adjustments may be required in patients who are receiving chronic treatment with anticonvulsants. (Moderate) Phenytoin and fosphenytoin can decrease the activity of vitamin D (e.g., cholecalciferol, ergocalciferol) by increasing its metabolism. In rare cases, this has caused anticonvulsant-induced rickets and osteomalacia. Vitamin D supplementation or dosage adjustments may be required in patients who are receiving chronic treatment with anticonvulsants.
Ethynodiol Diacetate; Ethinyl Estradiol: (Minor) Estrogens can increase calcium absorption. Use caution in patients predisposed to hypercalcemia or nephrolithiasis.
Etidronate: (Moderate) Separate administration of oral etidronate and calcium-containing supplements by at least 2 hours. Calcium will interfere with the absorption of oral etidronate.
Etonogestrel; Ethinyl Estradiol: (Minor) Estrogens can increase calcium absorption. Use caution in patients predisposed to hypercalcemia or nephrolithiasis.
Felodipine: (Minor) Monitor blood pressure during concurrent use of calcium and calcium-channel blockers. Concomitant use may reduce the response to calcium-channel blockers.
Fosinopril; Hydrochlorothiazide, HCTZ: (Moderate) Dose adjustment of vitamin D or vitamin D analogs may be necessary during coadministration with thiazide diuretics. Additionally, serum calcium concentrations should be monitored frequently. Monitor more frequently in patients with a history of hypercalcemia. Hypercalcemia may be exacerbated by coadministration of vitamin D or vitamin D analogs and thiazide diuretics. Thiazide diuretics are known to induce hypercalcemia by reducing the excretion of calcium in the urine. (Moderate) Monitor serum calcium concentration during concomitant calcium and thiazide diuretic use due to the risk for hypercalcemia. Thiazide diuretics may decrease urinary calcium excretion and cause intermittent and slight increases in serum calcium.
Fosphenytoin: (Moderate) Phenytoin and fosphenytoin can decrease the activity of vitamin D (e.g., cholecalciferol) by increasing its metabolism. In rare cases, this has caused anticonvulsant-induced rickets and osteomalacia. Vitamin D supplementation or dosage adjustments may be required in patients who are receiving chronic treatment with anticonvulsants. (Moderate) Phenytoin and fosphenytoin can decrease the activity of vitamin D (e.g., cholecalciferol, ergocalciferol) by increasing its metabolism. In rare cases, this has caused anticonvulsant-induced rickets and osteomalacia. Vitamin D supplementation or dosage adjustments may be required in patients who are receiving chronic treatment with anticonvulsants.
Hydantoins: (Moderate) Phenytoin and fosphenytoin can decrease the activity of vitamin D (e.g., cholecalciferol) by increasing its metabolism. In rare cases, this has caused anticonvulsant-induced rickets and osteomalacia. Vitamin D supplementation or dosage adjustments may be required in patients who are receiving chronic treatment with anticonvulsants. (Moderate) Phenytoin and fosphenytoin can decrease the activity of vitamin D (e.g., cholecalciferol, ergocalciferol) by increasing its metabolism. In rare cases, this has caused anticonvulsant-induced rickets and osteomalacia. Vitamin D supplementation or dosage adjustments may be required in patients who are receiving chronic treatment with anticonvulsants.
Hydrochlorothiazide, HCTZ: (Moderate) Dose adjustment of vitamin D or vitamin D analogs may be necessary during coadministration with thiazide diuretics. Additionally, serum calcium concentrations should be monitored frequently. Monitor more frequently in patients with a history of hypercalcemia. Hypercalcemia may be exacerbated by coadministration of vitamin D or vitamin D analogs and thiazide diuretics. Thiazide diuretics are known to induce hypercalcemia by reducing the excretion of calcium in the urine. (Moderate) Monitor serum calcium concentration during concomitant calcium and thiazide diuretic use due to the risk for hypercalcemia. Thiazide diuretics may decrease urinary calcium excretion and cause intermittent and slight increases in serum calcium.
Hydrochlorothiazide, HCTZ; Moexipril: (Moderate) Dose adjustment of vitamin D or vitamin D analogs may be necessary during coadministration with thiazide diuretics. Additionally, serum calcium concentrations should be monitored frequently. Monitor more frequently in patients with a history of hypercalcemia. Hypercalcemia may be exacerbated by coadministration of vitamin D or vitamin D analogs and thiazide diuretics. Thiazide diuretics are known to induce hypercalcemia by reducing the excretion of calcium in the urine. (Moderate) Monitor serum calcium concentration during concomitant calcium and thiazide diuretic use due to the risk for hypercalcemia. Thiazide diuretics may decrease urinary calcium excretion and cause intermittent and slight increases in serum calcium.
Ibandronate: (Moderate) Separate administration of oral ibandronate and calcium-containing supplements by at least 1 hour. Calcium will interfere with the absorption of oral ibandronate.
Ibritumomab Tiuxetan: (Major) High intake of phosphates concomitantly with vitamin D or vitamin D analogs may lead to hyperphosphatemia. Dose adjustment of vitamin D or vitamin D analogs may be necessary during coadministration with phosphorus salts. Additionally, serum calcium concentrations should be monitored frequently. Monitor more frequently in patients with a history of hypercalcemia. (Moderate) The oral absorption of phosphorus is reduced by ingestion of pharmacologic doses of calcium carbonate or other phosphate-lowering calcium salts (e.g., calcium acetate). There is, however, no significant interference with phosphorus absorption by oral dietary calcium at intakes within the typical adult range. If the patient requires multiple calcium supplements or a calcium-containing antacid, it may be wise to separate the administration of phosphorus salts from calcium-containing products. In some instances the administration of calcium salts or calcium carbonate is used therapeutically (e.g., uremia) to decrease serum phosphorus levels, so the administration of phosphorus supplements would dynamically counteract the intended use of calcium in these settings, assuming hypophosphatemia is not present. Appropriate calcium-phosphorus ratios in vivo are important for proper calcium homeostasis in tissues and bone; if the serum ionized calcium concentration is elevated, the concomitant use of calcium salts and phosphorus salts may increase the risk of calcium deposition in soft tissue.
Irbesartan; Hydrochlorothiazide, HCTZ: (Moderate) Dose adjustment of vitamin D or vitamin D analogs may be necessary during coadministration with thiazide diuretics. Additionally, serum calcium concentrations should be monitored frequently. Monitor more frequently in patients with a history of hypercalcemia. Hypercalcemia may be exacerbated by coadministration of vitamin D or vitamin D analogs and thiazide diuretics. Thiazide diuretics are known to induce hypercalcemia by reducing the excretion of calcium in the urine. (Moderate) Monitor serum calcium concentration during concomitant calcium and thiazide diuretic use due to the risk for hypercalcemia. Thiazide diuretics may decrease urinary calcium excretion and cause intermittent and slight increases in serum calcium.
Isoniazid, INH; Pyrazinamide, PZA; Rifampin: (Moderate) Rifampin is a potent inducer of the cytochrome P450 hepatic enzyme system and can decrease the plasma concentrations and possibly the efficacy of cholecalciferol, Vitamin D3. In some cases, reduced concentrations of circulating vitamin D and 1,25-dihydoxy vitamin D have been accompanied by decreased serum calcium and phosphate, and elevated parathyroid hormone. Dosage adjustments of cholecalciferol, Vitamin D3 may be required. (Moderate) Rifampin is a potent inducer of the cytochrome P450 hepatic enzyme system and can decrease the plasma concentrations and possibly the efficacy of ergocalciferol, Vitamin D2. In some cases, reduced concentrations of circulating vitamin D and 1,25-dihydoxy vitamin D have been accompanied by decreased serum calcium and phosphate, and elevated parathyroid hormone. Dosage adjustments of ergocalciferol, Vitamin D2 may be required.
Isoniazid, INH; Rifampin: (Moderate) Rifampin is a potent inducer of the cytochrome P450 hepatic enzyme system and can decrease the plasma concentrations and possibly the efficacy of cholecalciferol, Vitamin D3. In some cases, reduced concentrations of circulating vitamin D and 1,25-dihydoxy vitamin D have been accompanied by decreased serum calcium and phosphate, and elevated parathyroid hormone. Dosage adjustments of cholecalciferol, Vitamin D3 may be required. (Moderate) Rifampin is a potent inducer of the cytochrome P450 hepatic enzyme system and can decrease the plasma concentrations and possibly the efficacy of ergocalciferol, Vitamin D2. In some cases, reduced concentrations of circulating vitamin D and 1,25-dihydoxy vitamin D have been accompanied by decreased serum calcium and phosphate, and elevated parathyroid hormone. Dosage adjustments of ergocalciferol, Vitamin D2 may be required.
Isradipine: (Minor) Monitor blood pressure during concurrent use of calcium and calcium-channel blockers. Concomitant use may reduce the response to calcium-channel blockers.
Levamlodipine: (Minor) Monitor blood pressure during concurrent use of calcium and calcium-channel blockers. Concomitant use may reduce the response to calcium-channel blockers.
Levofloxacin: (Moderate) Administer oral products that contain calcium at least 2 hours before or 2 hours after orally administered levofloxacin. Levofloxacin absorption may be reduced as quinolone antibiotics can chelate with divalent or trivalent cations. Chelation of divalent cations with levofloxacin is less than with other quinolones. Examples of compounds that may interfere with quinolone bioavailability include antacids and multivitamins that contain calcium.
Levonorgestrel; Ethinyl Estradiol: (Minor) Estrogens can increase calcium absorption. Use caution in patients predisposed to hypercalcemia or nephrolithiasis.
Levonorgestrel; Ethinyl Estradiol; Ferrous Bisglycinate: (Minor) Estrogens can increase calcium absorption. Use caution in patients predisposed to hypercalcemia or nephrolithiasis.
Levonorgestrel; Ethinyl Estradiol; Ferrous Fumarate: (Minor) Estrogens can increase calcium absorption. Use caution in patients predisposed to hypercalcemia or nephrolithiasis.
Levothyroxine: (Moderate) Thyroid hormones should be administered at least 4 hours before or after the ingestion of oral calcium supplements. Calcium salts have been reported to chelate oral thyroid hormones within the GI tract when administered simultaneously, leading to decreased thyroid hormone absorption. Some case reports have described clinical hypothyroidism resulting from coadministration of thyroid hormones with oral calcium supplements.
Levothyroxine; Liothyronine (Porcine): (Moderate) Thyroid hormones should be administered at least 4 hours before or after the ingestion of oral calcium supplements. Calcium salts have been reported to chelate oral thyroid hormones within the GI tract when administered simultaneously, leading to decreased thyroid hormone absorption. Some case reports have described clinical hypothyroidism resulting from coadministration of thyroid hormones with oral calcium supplements.
Levothyroxine; Liothyronine (Synthetic): (Moderate) Thyroid hormones should be administered at least 4 hours before or after the ingestion of oral calcium supplements. Calcium salts have been reported to chelate oral thyroid hormones within the GI tract when administered simultaneously, leading to decreased thyroid hormone absorption. Some case reports have described clinical hypothyroidism resulting from coadministration of thyroid hormones with oral calcium supplements.
Liothyronine: (Moderate) Thyroid hormones should be administered at least 4 hours before or after the ingestion of oral calcium supplements. Calcium salts have been reported to chelate oral thyroid hormones within the GI tract when administered simultaneously, leading to decreased thyroid hormone absorption. Some case reports have described clinical hypothyroidism resulting from coadministration of thyroid hormones with oral calcium supplements.
Lisinopril; Hydrochlorothiazide, HCTZ: (Moderate) Dose adjustment of vitamin D or vitamin D analogs may be necessary during coadministration with thiazide diuretics. Additionally, serum calcium concentrations should be monitored frequently. Monitor more frequently in patients with a history of hypercalcemia. Hypercalcemia may be exacerbated by coadministration of vitamin D or vitamin D analogs and thiazide diuretics. Thiazide diuretics are known to induce hypercalcemia by reducing the excretion of calcium in the urine. (Moderate) Monitor serum calcium concentration during concomitant calcium and thiazide diuretic use due to the risk for hypercalcemia. Thiazide diuretics may decrease urinary calcium excretion and cause intermittent and slight increases in serum calcium.
Lithium: (Moderate) Monitor serum calcium concentrations closely if concomitant use of calcium and lithium is necessary. Concomitant use may increase the risk of hypercalcemia.
Losartan; Hydrochlorothiazide, HCTZ: (Moderate) Dose adjustment of vitamin D or vitamin D analogs may be necessary during coadministration with thiazide diuretics. Additionally, serum calcium concentrations should be monitored frequently. Monitor more frequently in patients with a history of hypercalcemia. Hypercalcemia may be exacerbated by coadministration of vitamin D or vitamin D analogs and thiazide diuretics. Thiazide diuretics are known to induce hypercalcemia by reducing the excretion of calcium in the urine. (Moderate) Monitor serum calcium concentration during concomitant calcium and thiazide diuretic use due to the risk for hypercalcemia. Thiazide diuretics may decrease urinary calcium excretion and cause intermittent and slight increases in serum calcium.
Magnesium Citrate: (Major) Avoid vitamin D coadministration with magnesium citrate in persons on chronic hemodialysis due to the risk for hypermagnesemia.
Magnesium Hydroxide: (Major) Avoid vitamin D coadministration with magnesium hydroxide in persons on chronic hemodialysis due to the risk for hypermagnesemia.
Magnesium Salts: (Major) Avoid vitamin D coadministration with magnesium-containing products, such as antacids, in persons on chronic hemodialysis due to the risk for hypermagnesemia.
Magnesium: (Major) Avoid vitamin D coadministration with magnesium-containing products, such as antacids, in persons on chronic hemodialysis due to the risk for hypermagnesemia.
Metolazone: (Moderate) Dose adjustment of vitamin D or vitamin D analogs may be necessary during coadministration with thiazide diuretics. Additionally, serum calcium concentrations should be monitored frequently. Monitor more frequently in patients with a history of hypercalcemia. Hypercalcemia may be exacerbated by coadministration of vitamin D or vitamin D analogs and thiazide diuretics. Thiazide diuretics are known to induce hypercalcemia by reducing the excretion of calcium in the urine. (Moderate) Monitor serum calcium concentration during concomitant calcium and thiazide diuretic use due to the risk for hypercalcemia. Thiazide diuretics may decrease urinary calcium excretion and cause intermittent and slight increases in serum calcium.
Metoprolol; Hydrochlorothiazide, HCTZ: (Moderate) Dose adjustment of vitamin D or vitamin D analogs may be necessary during coadministration with thiazide diuretics. Additionally, serum calcium concentrations should be monitored frequently. Monitor more frequently in patients with a history of hypercalcemia. Hypercalcemia may be exacerbated by coadministration of vitamin D or vitamin D analogs and thiazide diuretics. Thiazide diuretics are known to induce hypercalcemia by reducing the excretion of calcium in the urine. (Moderate) Monitor serum calcium concentration during concomitant calcium and thiazide diuretic use due to the risk for hypercalcemia. Thiazide diuretics may decrease urinary calcium excretion and cause intermittent and slight increases in serum calcium.
Mineral Oil: (Moderate) Absorption of fat-soluble vitamins is reported to be decreased with prolonged oral administration of mineral oil. However, despite warnings in various texts, there is little direct evidence that the interaction is of practical/clinical importance with limited use as directed. It may be prudent for those taking dietary supplements of Vitamin A, D, E, or K to separate administration by 1 hour before or 4 hours after a mineral oil oral dosage to help limit absorption interactions. Theoretically, the effect on fat-soluble vitamin absorption may more likely occur with prolonged or chronic administration of mineral oil.
Minocycline: (Moderate) Divalent or trivalent cations readily chelate with tetracycline antibiotics, forming insoluble compounds. The oral absorption of these antibiotics will be significantly reduced by other orally administered compounds that contain calcium salts, particularly if the time of administration is within 60 minutes of each other. Calcium salts and tetracyclines should not be administered within 1 to 2 hours of each other, although doxycycline chelates less with calcium than other tetracyclines.
Moxifloxacin: (Major) Administer oral moxifloxacin at least 4 hours before or 8 hours after oral products that contain calcium. Moxifloxacin absorption may be reduced as quinolone antibiotics can chelate with divalent or trivalent cations. Examples of compounds that may interfere with quinolone bioavailability include antacids and multivitamins that contain calcium.
Neuromuscular blockers: (Moderate) Concomitant use of neuromuscular blockers and calcium may result in resistance to neuromuscular blockade. Calcium antagonizes the potentiating effect of magnesium on neuromuscular blockade. Also, calcium triggers acetylcholine release, and therefore, may both reduce the sensitivity to neuromuscular blockers and decrease the duration of neuromuscular blockade.
Nicardipine: (Minor) Monitor blood pressure during concurrent use of calcium and calcium-channel blockers. Concomitant use may reduce the response to calcium-channel blockers.
NIFEdipine: (Minor) Monitor blood pressure during concurrent use of calcium and calcium-channel blockers. Concomitant use may reduce the response to calcium-channel blockers.
Nimodipine: (Minor) Monitor blood pressure during concurrent use of calcium and calcium-channel blockers. Concomitant use may reduce the response to calcium-channel blockers.
Nisoldipine: (Minor) Monitor blood pressure during concurrent use of calcium and calcium-channel blockers. Concomitant use may reduce the response to calcium-channel blockers.
Norethindrone Acetate; Ethinyl Estradiol; Ferrous fumarate: (Minor) Estrogens can increase calcium absorption. Use caution in patients predisposed to hypercalcemia or nephrolithiasis.
Norethindrone; Ethinyl Estradiol: (Minor) Estrogens can increase calcium absorption. Use caution in patients predisposed to hypercalcemia or nephrolithiasis.
Norethindrone; Ethinyl Estradiol; Ferrous fumarate: (Minor) Estrogens can increase calcium absorption. Use caution in patients predisposed to hypercalcemia or nephrolithiasis.
Norgestimate; Ethinyl Estradiol: (Minor) Estrogens can increase calcium absorption. Use caution in patients predisposed to hypercalcemia or nephrolithiasis.
Ofloxacin: (Moderate) Administer oral products that contain calcium at least 2 hours before or 2 hours after ofloxacin. Ofloxacin absorption may be reduced as quinolone antibiotics can chelate with divalent or trivalent cations. Examples of compounds that may interfere with quinolone bioavailability include antacids and multivitamins that contain calcium.
Olmesartan; Amlodipine; Hydrochlorothiazide, HCTZ: (Moderate) Dose adjustment of vitamin D or vitamin D analogs may be necessary during coadministration with thiazide diuretics. Additionally, serum calcium concentrations should be monitored frequently. Monitor more frequently in patients with a history of hypercalcemia. Hypercalcemia may be exacerbated by coadministration of vitamin D or vitamin D analogs and thiazide diuretics. Thiazide diuretics are known to induce hypercalcemia by reducing the excretion of calcium in the urine. (Moderate) Monitor serum calcium concentration during concomitant calcium and thiazide diuretic use due to the risk for hypercalcemia. Thiazide diuretics may decrease urinary calcium excretion and cause intermittent and slight increases in serum calcium. (Minor) Monitor blood pressure during concurrent use of calcium and calcium-channel blockers. Concomitant use may reduce the response to calcium-channel blockers.
Olmesartan; Hydrochlorothiazide, HCTZ: (Moderate) Dose adjustment of vitamin D or vitamin D analogs may be necessary during coadministration with thiazide diuretics. Additionally, serum calcium concentrations should be monitored frequently. Monitor more frequently in patients with a history of hypercalcemia. Hypercalcemia may be exacerbated by coadministration of vitamin D or vitamin D analogs and thiazide diuretics. Thiazide diuretics are known to induce hypercalcemia by reducing the excretion of calcium in the urine. (Moderate) Monitor serum calcium concentration during concomitant calcium and thiazide diuretic use due to the risk for hypercalcemia. Thiazide diuretics may decrease urinary calcium excretion and cause intermittent and slight increases in serum calcium.
Omadacycline: (Moderate) Divalent or trivalent cations readily chelate with tetracycline antibiotics, forming insoluble compounds. The oral absorption of these antibiotics will be significantly reduced by other orally administered compounds that contain calcium salts, particularly if the time of administration is within 60 minutes of each other. Calcium salts and tetracyclines should not be administered within 1 to 2 hours of each other, although doxycycline chelates less with calcium than other tetracyclines.
Orlistat: (Moderate) Administer vitamin E at least 2 hours before or after the administration of orlistat to limit effects on oral absorption. Orlistat has been shown to inhibit the absorption of a vitamin E acetate supplement by 60%. (Moderate) Orlistat reduced the absorption of fat-soluble vitamins during clinical trials. The bioavailability of orally administered vitamin D may also be decreased. In patients receiving orally-administered vitamin D with orlistat, close monitoring is recommended. In addition, the manufacturer recommends that fat-soluble vitamins be administered at least 2 hours before or after the administration of orlistat to limit effects on oral absorption.
Pancuronium: (Moderate) Concomitant use of neuromuscular blockers and calcium may result in resistance to neuromuscular blockade. Calcium antagonizes the potentiating effect of magnesium on neuromuscular blockade. Also, calcium triggers acetylcholine release, and therefore, may both reduce the sensitivity to neuromuscular blockers and decrease the duration of neuromuscular blockade.
Parathyroid Hormone: (Moderate) Monitor serum calcium concentrations closely if concomitant use of calcium and parathyroid hormone is necessary. Concomitant use may increase the risk of hypercalcemia.
Paricalcitol: (Moderate) Monitor serum calcium concentrations during concomitant use of high doses of calcium and vitamin D analogs; a dosage adjustment of the vitamin D analog may be needed. Hypercalcemia may be exacerbated by concomitant administration.
Perindopril; Amlodipine: (Minor) Monitor blood pressure during concurrent use of calcium and calcium-channel blockers. Concomitant use may reduce the response to calcium-channel blockers.
Phenytoin: (Moderate) Phenytoin and fosphenytoin can decrease the activity of vitamin D (e.g., cholecalciferol) by increasing its metabolism. In rare cases, this has caused anticonvulsant-induced rickets and osteomalacia. Vitamin D supplementation or dosage adjustments may be required in patients who are receiving chronic treatment with anticonvulsants. (Moderate) Phenytoin and fosphenytoin can decrease the activity of vitamin D (e.g., cholecalciferol, ergocalciferol) by increasing its metabolism. In rare cases, this has caused anticonvulsant-induced rickets and osteomalacia. Vitamin D supplementation or dosage adjustments may be required in patients who are receiving chronic treatment with anticonvulsants.
Phosphorated Carbohydrate Solution: (Major) High intake of phosphates concomitantly with vitamin D or vitamin D analogs may lead to hyperphosphatemia. Dose adjustment of vitamin D or vitamin D analogs may be necessary during coadministration with phosphorus salts. Additionally, serum calcium concentrations should be monitored frequently. Monitor more frequently in patients with a history of hypercalcemia. (Moderate) The oral absorption of phosphorus is reduced by ingestion of pharmacologic doses of calcium carbonate or other phosphate-lowering calcium salts (e.g., calcium acetate). There is, however, no significant interference with phosphorus absorption by oral dietary calcium at intakes within the typical adult range. If the patient requires multiple calcium supplements or a calcium-containing antacid, it may be wise to separate the administration of phosphorus salts from calcium-containing products. In some instances the administration of calcium salts or calcium carbonate is used therapeutically (e.g., uremia) to decrease serum phosphorus levels, so the administration of phosphorus supplements would dynamically counteract the intended use of calcium in these settings, assuming hypophosphatemia is not present. Appropriate calcium-phosphorus ratios in vivo are important for proper calcium homeostasis in tissues and bone; if the serum ionized calcium concentration is elevated, the concomitant use of calcium salts and phosphorus salts may increase the risk of calcium deposition in soft tissue.
Phosphorus: (Major) High intake of phosphates concomitantly with vitamin D or vitamin D analogs may lead to hyperphosphatemia. Dose adjustment of vitamin D or vitamin D analogs may be necessary during coadministration with phosphorus salts. Additionally, serum calcium concentrations should be monitored frequently. Monitor more frequently in patients with a history of hypercalcemia. (Moderate) The oral absorption of phosphorus is reduced by ingestion of pharmacologic doses of calcium carbonate or other phosphate-lowering calcium salts (e.g., calcium acetate). There is, however, no significant interference with phosphorus absorption by oral dietary calcium at intakes within the typical adult range. If the patient requires multiple calcium supplements or a calcium-containing antacid, it may be wise to separate the administration of phosphorus salts from calcium-containing products. In some instances the administration of calcium salts or calcium carbonate is used therapeutically (e.g., uremia) to decrease serum phosphorus levels, so the administration of phosphorus supplements would dynamically counteract the intended use of calcium in these settings, assuming hypophosphatemia is not present. Appropriate calcium-phosphorus ratios in vivo are important for proper calcium homeostasis in tissues and bone; if the serum ionized calcium concentration is elevated, the concomitant use of calcium salts and phosphorus salts may increase the risk of calcium deposition in soft tissue.
Potassium Phosphate: (Major) High intake of phosphates concomitantly with vitamin D or vitamin D analogs may lead to hyperphosphatemia. Dose adjustment of vitamin D or vitamin D analogs may be necessary during coadministration with phosphorus salts. Additionally, serum calcium concentrations should be monitored frequently. Monitor more frequently in patients with a history of hypercalcemia. (Moderate) The oral absorption of phosphorus is reduced by ingestion of pharmacologic doses of calcium carbonate or other phosphate-lowering calcium salts (e.g., calcium acetate). There is, however, no significant interference with phosphorus absorption by oral dietary calcium at intakes within the typical adult range. If the patient requires multiple calcium supplements or a calcium-containing antacid, it may be wise to separate the administration of phosphorus salts from calcium-containing products. In some instances the administration of calcium salts or calcium carbonate is used therapeutically (e.g., uremia) to decrease serum phosphorus levels, so the administration of phosphorus supplements would dynamically counteract the intended use of calcium in these settings, assuming hypophosphatemia is not present. Appropriate calcium-phosphorus ratios in vivo are important for proper calcium homeostasis in tissues and bone; if the serum ionized calcium concentration is elevated, the concomitant use of calcium salts and phosphorus salts may increase the risk of calcium deposition in soft tissue.
Potassium Phosphate; Sodium Phosphate: (Major) High intake of phosphates concomitantly with vitamin D or vitamin D analogs may lead to hyperphosphatemia. Dose adjustment of vitamin D or vitamin D analogs may be necessary during coadministration with phosphorus salts. Additionally, serum calcium concentrations should be monitored frequently. Monitor more frequently in patients with a history of hypercalcemia. (Moderate) The oral absorption of phosphorus is reduced by ingestion of pharmacologic doses of calcium carbonate or other phosphate-lowering calcium salts (e.g., calcium acetate). There is, however, no significant interference with phosphorus absorption by oral dietary calcium at intakes within the typical adult range. If the patient requires multiple calcium supplements or a calcium-containing antacid, it may be wise to separate the administration of phosphorus salts from calcium-containing products. In some instances the administration of calcium salts or calcium carbonate is used therapeutically (e.g., uremia) to decrease serum phosphorus levels, so the administration of phosphorus supplements would dynamically counteract the intended use of calcium in these settings, assuming hypophosphatemia is not present. Appropriate calcium-phosphorus ratios in vivo are important for proper calcium homeostasis in tissues and bone; if the serum ionized calcium concentration is elevated, the concomitant use of calcium salts and phosphorus salts may increase the risk of calcium deposition in soft tissue.
Quinapril; Hydrochlorothiazide, HCTZ: (Moderate) Dose adjustment of vitamin D or vitamin D analogs may be necessary during coadministration with thiazide diuretics. Additionally, serum calcium concentrations should be monitored frequently. Monitor more frequently in patients with a history of hypercalcemia. Hypercalcemia may be exacerbated by coadministration of vitamin D or vitamin D analogs and thiazide diuretics. Thiazide diuretics are known to induce hypercalcemia by reducing the excretion of calcium in the urine. (Moderate) Monitor serum calcium concentration during concomitant calcium and thiazide diuretic use due to the risk for hypercalcemia. Thiazide diuretics may decrease urinary calcium excretion and cause intermittent and slight increases in serum calcium.
Relugolix; Estradiol; Norethindrone acetate: (Minor) Estrogens can increase calcium absorption. Use caution in patients predisposed to hypercalcemia or nephrolithiasis.
Rifampin: (Moderate) Rifampin is a potent inducer of the cytochrome P450 hepatic enzyme system and can decrease the plasma concentrations and possibly the efficacy of cholecalciferol, Vitamin D3. In some cases, reduced concentrations of circulating vitamin D and 1,25-dihydoxy vitamin D have been accompanied by decreased serum calcium and phosphate, and elevated parathyroid hormone. Dosage adjustments of cholecalciferol, Vitamin D3 may be required. (Moderate) Rifampin is a potent inducer of the cytochrome P450 hepatic enzyme system and can decrease the plasma concentrations and possibly the efficacy of ergocalciferol, Vitamin D2. In some cases, reduced concentrations of circulating vitamin D and 1,25-dihydoxy vitamin D have been accompanied by decreased serum calcium and phosphate, and elevated parathyroid hormone. Dosage adjustments of ergocalciferol, Vitamin D2 may be required.
Risedronate: (Moderate) Separate administration of oral risedronate and calcium-containing supplements by at least 2 hours. Calcium will interfere with the absorption of oral risedronate.
Rocuronium: (Moderate) Concomitant use of neuromuscular blockers and calcium may result in resistance to neuromuscular blockade. Calcium antagonizes the potentiating effect of magnesium on neuromuscular blockade. Also, calcium triggers acetylcholine release, and therefore, may both reduce the sensitivity to neuromuscular blockers and decrease the duration of neuromuscular blockade.
Sarecycline: (Moderate) Divalent or trivalent cations readily chelate with tetracycline antibiotics, forming insoluble compounds. The oral absorption of these antibiotics will be significantly reduced by other orally administered compounds that contain calcium salts, particularly if the time of administration is within 60 minutes of each other. Calcium salts and tetracyclines should not be administered within 1 to 2 hours of each other, although doxycycline chelates less with calcium than other tetracyclines.
Segesterone Acetate; Ethinyl Estradiol: (Minor) Estrogens can increase calcium absorption. Use caution in patients predisposed to hypercalcemia or nephrolithiasis.
Selumetinib: (Moderate) Coadministration of selumetinib with supplemental vitamin E is not recommended if the total daily dose of vitamin E (amount in selumetinib plus the supplement) exceeds the recommended or safe daily limit; high dose vitamin E may increase the bleeding risk by antagonizing vitamin K dependent clotting factors and inhibiting platelet aggregation. Selumetinib contains 32 mg of vitamin E in the 10 mg capsules and 36 mg of vitamin E in the 25 mg capsules.
Sodium Fluoride: (Moderate) Absorption of sodium fluoride may be reduced by concomitant use of antacids that contain magnesium, aluminum, or calcium. An interval of at least 2 hours is advisable between administration of sodium fluoride and antacids.
Sodium Phosphate Monobasic Monohydrate; Sodium Phosphate Dibasic Anhydrous: (Moderate) The concomitant use of oral sodium phosphate monobasic monohydrate; sodium phosphate dibasic anhydrous preparations in conjunction with antacids containing calcium (e.g., calcium carbonate, calcium salts) may bind the phosphate in the stomach and reduce its absorption. If the patient requires multiple mineral supplements or concurrent use of antacids, it is prudent to separate the administration of sodium phosphate salts from calcium containing products by at least one hour.
Sodium Sulfate; Magnesium Sulfate; Potassium Chloride: (Major) Avoid vitamin D coadministration with magnesium-containing products, such as antacids, in persons on chronic hemodialysis due to the risk for hypermagnesemia.
Spironolactone; Hydrochlorothiazide, HCTZ: (Moderate) Dose adjustment of vitamin D or vitamin D analogs may be necessary during coadministration with thiazide diuretics. Additionally, serum calcium concentrations should be monitored frequently. Monitor more frequently in patients with a history of hypercalcemia. Hypercalcemia may be exacerbated by coadministration of vitamin D or vitamin D analogs and thiazide diuretics. Thiazide diuretics are known to induce hypercalcemia by reducing the excretion of calcium in the urine. (Moderate) Monitor serum calcium concentration during concomitant calcium and thiazide diuretic use due to the risk for hypercalcemia. Thiazide diuretics may decrease urinary calcium excretion and cause intermittent and slight increases in serum calcium.
Succinylcholine: (Moderate) Concomitant use of neuromuscular blockers and calcium may result in resistance to neuromuscular blockade. Calcium antagonizes the potentiating effect of magnesium on neuromuscular blockade. Also, calcium triggers acetylcholine release, and therefore, may both reduce the sensitivity to neuromuscular blockers and decrease the duration of neuromuscular blockade.
Sulfacetamide; Sulfur: (Major) Because edetate disodium chelates and lowers serum calcium, oral or parenteral calcium salts should not be administered concomitantly.
Telmisartan; Amlodipine: (Minor) Monitor blood pressure during concurrent use of calcium and calcium-channel blockers. Concomitant use may reduce the response to calcium-channel blockers.
Telmisartan; Hydrochlorothiazide, HCTZ: (Moderate) Dose adjustment of vitamin D or vitamin D analogs may be necessary during coadministration with thiazide diuretics. Additionally, serum calcium concentrations should be monitored frequently. Monitor more frequently in patients with a history of hypercalcemia. Hypercalcemia may be exacerbated by coadministration of vitamin D or vitamin D analogs and thiazide diuretics. Thiazide diuretics are known to induce hypercalcemia by reducing the excretion of calcium in the urine. (Moderate) Monitor serum calcium concentration during concomitant calcium and thiazide diuretic use due to the risk for hypercalcemia. Thiazide diuretics may decrease urinary calcium excretion and cause intermittent and slight increases in serum calcium.
Teriparatide: (Moderate) Monitor serum calcium concentrations closely if concomitant use of calcium and teriparatide is necessary. Concomitant use may increase the risk of hypercalcemia.
Tetracycline: (Moderate) Divalent or trivalent cations readily chelate with tetracycline antibiotics, forming insoluble compounds. The oral absorption of these antibiotics will be significantly reduced by other orally administered compounds that contain calcium salts, particularly if the time of administration is within 60 minutes of each other. Calcium salts and tetracyclines should not be administered within 1 to 2 hours of each other, although doxycycline chelates less with calcium than other tetracyclines.
Tetracyclines: (Moderate) Divalent or trivalent cations readily chelate with tetracycline antibiotics, forming insoluble compounds. The oral absorption of these antibiotics will be significantly reduced by other orally administered compounds that contain calcium salts, particularly if the time of administration is within 60 minutes of each other. Calcium salts and tetracyclines should not be administered within 1 to 2 hours of each other, although doxycycline chelates less with calcium than other tetracyclines.
Thiazide diuretics: (Moderate) Dose adjustment of vitamin D or vitamin D analogs may be necessary during coadministration with thiazide diuretics. Additionally, serum calcium concentrations should be monitored frequently. Monitor more frequently in patients with a history of hypercalcemia. Hypercalcemia may be exacerbated by coadministration of vitamin D or vitamin D analogs and thiazide diuretics. Thiazide diuretics are known to induce hypercalcemia by reducing the excretion of calcium in the urine. (Moderate) Monitor serum calcium concentration during concomitant calcium and thiazide diuretic use due to the risk for hypercalcemia. Thiazide diuretics may decrease urinary calcium excretion and cause intermittent and slight increases in serum calcium.
Thyroid hormones: (Moderate) Thyroid hormones should be administered at least 4 hours before or after the ingestion of oral calcium supplements. Calcium salts have been reported to chelate oral thyroid hormones within the GI tract when administered simultaneously, leading to decreased thyroid hormone absorption. Some case reports have described clinical hypothyroidism resulting from coadministration of thyroid hormones with oral calcium supplements.
Tipranavir: (Major) Tipranavir should be used with caution in patients who may be at risk of increased bleeding, such as in patients taking high doses of vitamin E. In vitro, tipranavir was observed to inhibit human platelet aggregation at concentrations consistent with human exposure at regular doses. In rats, coadministration with vitamin E increased the bleeding effects of tipranavir.
Trandolapril; Verapamil: (Minor) Monitor blood pressure during concurrent use of calcium and calcium-channel blockers. Concomitant use may reduce the response to calcium-channel blockers.
Triamterene; Hydrochlorothiazide, HCTZ: (Moderate) Dose adjustment of vitamin D or vitamin D analogs may be necessary during coadministration with thiazide diuretics. Additionally, serum calcium concentrations should be monitored frequently. Monitor more frequently in patients with a history of hypercalcemia. Hypercalcemia may be exacerbated by coadministration of vitamin D or vitamin D analogs and thiazide diuretics. Thiazide diuretics are known to induce hypercalcemia by reducing the excretion of calcium in the urine. (Moderate) Monitor serum calcium concentration during concomitant calcium and thiazide diuretic use due to the risk for hypercalcemia. Thiazide diuretics may decrease urinary calcium excretion and cause intermittent and slight increases in serum calcium.
Trientine: (Major) In general, oral mineral supplements should not be given since they may block the oral absorption of trientine. However, iron deficiency may develop, especially in children and menstruating or pregnant women, or as a result of the low copper diet recommended for Wilson's disease. If necessary, iron may be given in short courses, but since iron and trientine each inhibit oral absorption of the other, 2 hours should elapse between administration of trientine and iron doses.
Valsartan; Hydrochlorothiazide, HCTZ: (Moderate) Dose adjustment of vitamin D or vitamin D analogs may be necessary during coadministration with thiazide diuretics. Additionally, serum calcium concentrations should be monitored frequently. Monitor more frequently in patients with a history of hypercalcemia. Hypercalcemia may be exacerbated by coadministration of vitamin D or vitamin D analogs and thiazide diuretics. Thiazide diuretics are known to induce hypercalcemia by reducing the excretion of calcium in the urine. (Moderate) Monitor serum calcium concentration during concomitant calcium and thiazide diuretic use due to the risk for hypercalcemia. Thiazide diuretics may decrease urinary calcium excretion and cause intermittent and slight increases in serum calcium.
Vecuronium: (Moderate) Concomitant use of neuromuscular blockers and calcium may result in resistance to neuromuscular blockade. Calcium antagonizes the potentiating effect of magnesium on neuromuscular blockade. Also, calcium triggers acetylcholine release, and therefore, may both reduce the sensitivity to neuromuscular blockers and decrease the duration of neuromuscular blockade.
Verapamil: (Minor) Monitor blood pressure during concurrent use of calcium and calcium-channel blockers. Concomitant use may reduce the response to calcium-channel blockers.
Vitamin A: (Minor) Doses in excess of 1,500 to 2,000 mcg per day of Vitamin A may lead to bone loss and will counteract the effects of supplementation with calcium salts.
Vitamin D analogs: (Moderate) Monitor serum calcium concentrations during concomitant use of high doses of calcium and vitamin D analogs; a dosage adjustment of the vitamin D analog may be needed. Hypercalcemia may be exacerbated by concomitant administration.
Warfarin: (Moderate) Vitamin E should be used cautiously in patients receiving warfarin. While the mechanism is unclear, it is believed that concomitant administration of large doses of vitamin E (e.g., more than 400 units per day) with warfarin potentiates hypoprothrombinemia due to the vitamin K antagonistic activity of vitamin E.
Both forms of vitamin D are metabolized to the active form, calcitriol (1,25-dihydroxyvitamin D); all vitamin D activity is due to this metabolite. Calcitriol promotes renal reabsorption of calcium, increases intestinal absorption of calcium and phosphorus, and increases calcium mobilization from bone to plasma. Calcitriol promotes intestinal absorption of calcium through binding to a specific receptor in the mucosal cytoplasm of the intestine. Subsequently, calcium is absorbed through formation of a calcium-binding protein. The synthesis of calcitriol is enhanced by elevated parathyroid hormone levels and low plasma phosphorus levels. Hypocalcemia causes release of parathyroid hormone, which stimulates the production of calcitriol.
The vitamin D receptor (VDR) is present in numerous tissues throughout the body; the exact action of calcitriol within these tissues is not completely understood. There is evidence that calcitriol plays a role in the immune system. Calcitriol has been shown to inhibit cancer growth and stimulate cell differentiation.
Vitamin D is administered orally. Maximal clinical effects of a given dosage are usually observed in 4 weeks. Dietary vitamin D is absorbed from the GI tract in the presence of bile salts and is initially bound to chylomicrons, then is slowly transferred to vitamin D binding protein (DBP) in the serum. The uptake by chylomicrons results in vitamin D update by adipose tissue and muscle; remaining vitamin D in circulation is then metabolized by the liver. The uptake by the liver and other tissues accounts results in a plasma half-life of 4 to 6 hours for supplemental vitamin D. However, studies have shown that the whole-body half-life is about 2 months due to the stores in these tissues.
Ergocalciferol and cholecalciferol are considered prohormones and are converted in the liver by a group of activating cytochrome P450 (CYP) enzymes, CYP2R1, CYO27A1, and CYP27B1, to 25-hydroxyvitamin D (25(OH)D, calcidiol), the predominant form of vitamin D in the blood. This metabolite has a half-life of about 15 days. Serum 25(OH)D concentrations increase in a non-linear fashion in response to increased vitamin D intake based on baseline concentrations and duration of supplementation. Increasing serum 25(OH)D levels to more than 50 nmol/L requires a greater amount of vitamin D than increasing baseline levels that are less than 50 nmol/L. The impact on serum 25(OH)D concentrations is less when doses are at least 25 mcg/day (1,000 International Units/day) compared to doses less than 25 mcg/day (1,000 International Units/day). For example, for vitamin D doses of at least 25 mcg/day (1,000 International Units/day), the increase in serum 25(OH)D concentrations is about 1 nmol/L for each 1 mcg (40 International Units) of vitamin D. Conversely, for vitamin D doses of 15 mcg (600 International Units) or less, the increase in 25(OH)D concentrations is about 2.3 nmol/L for each 1 mcg (40 International Units) of vitamin D. In the kidneys, 25-hydroxyvitamin D is further converted to its active, hormonal form, 1,25-dihydroxyvitamin D (1,25(OH)2D, calcitriol), which has a half-life of about 15 hours and accounts for only a small portion of the total body amount of vitamin D. Synthesis to this active form by renal CYP27B1 is tightly regulated by parathyroid hormone and serum phosphate levels. All metabolites of vitamin D are excreted through the bile into the feces; very little is excreted in the urine.
-Route-Specific Pharmacokinetics
Oral Route
Vitamin D is well absorbed orally in most individuals without conditions associated with fat malabsorption. There is a time lag of 10 to 24 hours between the oral administration of vitamin D and the initiation of its action in the body due to the necessity of synthesis of the active metabolites in the liver and kidneys.
-Special Populations
Hepatic Impairment
Vitamin D absorption can be decreased in patients with any hepatic disease associated with fat malabsorption.
Pediatrics
Of relevance to breastfed children, the 25-hydroxyvitamin D metabolite is distributed into maternal breast milk; however, the concentration in breast milk is dependent upon the maternal serum concentration. Typical breast milk concentrations of vitamin D without maternal vitamin D supplementation are less than 0.625 to 1.95 mcg/L (25 to 78 International Units/L); these levels of vitamin D will not be sufficient to prevent vitamin D deficiency in infants who are exclusively breastfed. Administration of high-dose vitamin D supplementation to nursing mothers has been shown to increase the concentration of vitamin D in breast milk and favorably increase 25(OH)D levels in infants; however, the results have not been validated and supplementation to infants is still recommended.
Obesity
Persons with body mass index (BMI) of 30 or more have lower 25(OH)D levels as compared to those with a lower BMI. In addition, people who are obese may require higher doses of vitamin D to achieve 25(OH)D levels comparable to non-obese people. The increased amounts of subcutaneous fat in these persons sequester more vitamin D and alter its release into the circulation. Also, obese patients who have undergone gastric bypass surgery will become vitamin D deficient over time without sufficient supplementation, since part of the small intestine where vitamin D is absorbed is bypassed and vitamin D mobilization from fat stores will not compensate over time.
Other
Biliary or GI Disease
Vitamin D absorption can be decreased in patients with any biliary or GI disease that results in fat malabsorption.