Folicet

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Folicet

Classes

Calcium Supplements in Combination with Other Agents
Folic Acid and Derivative Supplements
Vitamin B9 (Folic acid) Supplements

Administration
Oral Administration

If the patient is unable to swallow the tablets, a dilute solution for oral or parenteral use may be prepared by diluting 1 mL of the 5 mg/mL folic acid injection with 49 mL of sterile water for injection to give a folic acid concentration of 0.1 mg/mL.

Injectable Administration

The parenteral route is only indicated when oral therapy is not feasible.
Folic acid, vitamin B9 is administered subcutaneously, intravenously, or by deep intramuscular injection.
Do not use preparations containing benzyl alcohol in neonates.
Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit. The color of the solution may range from yellow to orange-yellow.

Intravenous Administration

Direct IV injection:
Inject IV at a rate of 5 mg over at least 1 minute.
 
Continuous IV infusion:
Folic acid, vitamin B9 may be added to hyperalimentation solution.

Intramuscular Administration

Inject deeply into a large muscle mass. Aspirate prior to injection to avoid injection into a blood vessel.

Subcutaneous Administration

Inject subcutaneously taking care not to inject intradermally.

Adverse Reactions
Severe

anaphylactoid reactions / Rapid / Incidence not known
bronchospasm / Rapid / Incidence not known

Moderate

erythema / Early / Incidence not known
confusion / Early / Incidence not known
depression / Delayed / Incidence not known
excitability / Early / Incidence not known

Mild

rash / Early / Incidence not known
pruritus / Rapid / Incidence not known
malaise / Early / Incidence not known
dysgeusia / Early / Incidence not known
anorexia / Delayed / Incidence not known
nausea / Early / Incidence not known
flatulence / Early / Incidence not known
irritability / Delayed / Incidence not known

Common Brand Names

Folacin, Folicet, Q-TABS

Dea Class

OTC, Rx

Description

Oral/parenteral, water-soluble B-vitamin; found in foods including leafy green vegetables and fortified grains; regulates homocysteine. Used for megaloblastic and macrocytic anemias, use may mask vitamin B-12 deficiency. Not clinically useful in offsetting the action of folate reductase inhibitors. Also used to treat tropical sprue, alcoholism. Adequate intake by women of conceptual age substantially decreases risk of congenital neural tube defects. Further data to refine effect on CHD and other chronic disease.

Dosage And Indications
For the treatment of folate deficiency megaloblastic anemia due to malnutrition, pregnancy, infancy or childhood, alcohol use disorders, and nontropical or tropical sprue. For the treatment of folate deficiency megaloblastic anemia due to malnutrition, pregnancy, infancy or childhood, and nontropical sprue. Oral dosage Adults

1 mg PO once daily, initially; resistant cases may require higher doses. Reduce dose to 0.4 mg PO once daily when clinical symptoms have subsided and laboratory parameters have normalized.

Pregnant or Lactating Persons

1 mg PO once daily, initially; resistant cases may require higher doses. Reduce dose to 0.8 mg PO once daily when clinical symptoms have subsided and laboratory parameters have normalized.

Children and Adolescents 4 to 17 years

1 mg PO once daily, initially; resistant cases may require higher doses. Reduce dose to 0.4 mg PO once daily when clinical symptoms have subsided and laboratory parameters have normalized.

Children 1 to 3 years

1 mg PO once daily, initially; resistant cases may require higher doses. Reduce dose to 0.1 to 0.3 mg PO once daily when clinical symptoms have subsided and laboratory parameters have normalized.

Infants

1 mg PO once daily, initially; resistant cases may require higher doses. Reduce dose to 0.1 mg PO once daily when clinical symptoms have subsided and laboratory parameters have normalized.

Intravenous, Intramuscular, or Subcutaneous dosage Adults

1 mg IV, IM, or subcutaneously once daily, initially; resistant cases may require higher doses. Reduce dose to 0.4 mg IV, IM, or subcutaneously once daily when clinical symptoms have subsided and laboratory parameters have normalized.

Pregnant or Lactating Persons

1 mg IV, IM, or subcutaneously once daily, initially; resistant cases may require higher doses. Reduce dose to 0.8 mg IV, IM, or subcutaneously once daily when clinical symptoms have subsided and laboratory parameters have normalized.

Children and Adolescents 4 to 17 years

1 mg IV, IM, or subcutaneously once daily, initially; resistant cases may require higher doses. Reduce dose to 0.4 mg IV, IM, or subcutaneously once daily when clinical symptoms have subsided and laboratory parameters have normalized.

Children 1 to 3 years

1 mg IV, IM, or subcutaneously once daily, initially; resistant cases may require higher doses. Reduce dose to 0.1 to 0.3 mg IV, IM, or subcutaneously once daily when clinical symptoms have subsided and laboratory parameters have normalized.

Infants

1 mg IV, IM, or subcutaneously once daily, initially; resistant cases may require higher doses. Reduce dose to 0.1 mg IV, IM, or subcutaneously once daily when clinical symptoms have subsided and laboratory parameters have normalized.

For the treatment of folate deficiency megaloblastic anemia in persons with tropical sprue. Oral dosage Adults

5 mg PO once daily for 6 months. The FDA-approved dose is 1 mg PO once daily, initially; resistant cases may require higher doses. Reduce dose to 0.4 mg PO once daily when clinical symptoms have subsided and laboratory parameters have normalized.

Intravenous dosage Adults

5 mg IV, IM, or subcutaneously once daily for 6 months. The FDA-approved dose is 1 mg IV, IM, or subcutaneously once daily, initially; resistant cases may require higher doses. Reduce dose to 0.4 mg IV, IM, or subcutaneously once daily when clinical symptoms have subsided and laboratory parameters have normalized.

For the treatment of folate deficiency megaloblastic anemia in persons with alcohol use disorders. Oral dosage Adults

0.4 to 1 mg PO once daily for several days.

Intravenous dosage Adults

0.4 to 1 mg IV once daily for several days.  

For the treatment of folate deficiency megaloblastic anemia in malabsorptive states. Oral dosage Adults

5 mg PO once daily. May increase the dose up to 15 mg PO once daily for 4 months.

For the treatment of folate deficiency megaloblastic anemia in chronic hemolytic states or dialysis. Oral dosage Adults

5 mg PO once daily, initially. May increase the dose by 5 mg/day based on plasma homocysteine concentrations. Dose range: 5 mg PO once weekly to 15 mg PO once daily based on diet, plasma homocysteine concentrations, and/or rate of hemolysis. Max: 15 mg/day.

For nutritional supplementation. For nutritional supplementation in healthy persons based on recommended dietary allowances (RDA). Oral dosage Adults

0.4 mg/day PO.

Pregnant Persons

0.6 mg/day PO.

Lactating Persons

0.5 mg/day PO.

Adolescents 14 to 17 years

0.4 mg/day PO.

Children 9 to 13 years

0.3 mg/day PO.

Children 4 to 8 years

0.2 mg/day PO.

Children 1 to 3 years

0.15 mg/day PO.

Infants 7 to 11 months

80 mcg/day PO is the recommended Adequate Intake. No RDA has been established.

Infants 1 to 6 months

65 mcg/day PO is the recommended Adequate Intake. No RDA has been established.

Neonates

65 mcg/day PO is the recommended Adequate Intake. No RDA has been established.

For nutritional supplementation in persons with sickle cell disease. Oral dosage Adults

1 mg PO once daily. In the acute crisis, a dose of 5 mg/day has been used; however, 1 mg/day is stated to be more than adequate.

Children and Adolescents

1 mg PO once daily. In the acute crisis, a dose of 5 mg/day has been used; however, 1 mg/day is stated to be more than adequate.

For nutritional supplementation in persons with thalassemia. Oral dosage Adults

1 mg PO once daily.

Children and Adolescents

1 mg PO once daily.

For the adjunct treatment of primary homocystinuria. Oral dosage Adults, Adolescents and Children

Doses listed in references vary. Initially, 0.4—1 mg/day PO (end range 1—5 mg/day PO); adjust to clinical response.

For methotrexate toxicity prophylaxis† in patients receiving methotrexate for rheumatoid arthritis. Oral dosage Adults

Seventy-nine patients receiving methotrexate for rheumatoid arthritis were randomized to either placebo, folic acid 5 mg/week (administered as 1 mg PO once daily 5 times per week), or folic acid 27.5 mg/week (administered as 5.5 mg PO once daily 5 times per week). Both groups receiving folic acid demonstrated less methotrexate toxicity than the group receiving placebo with no loss of methotrexate efficacy.

For folate deficiency diagnosis†, to detect the presence of folate deficiency without concealing pernicious anemia in patients with megaloblastic anemia. Oral or Intramuscular dosage Adults, Adolescents and Children

0.1—0.2 mg PO or IM for 10 days while maintaining a diet low in folate and vitamin B12.

For neural tube defect prophylaxis† in persons of reproductive age who may become pregnant.
NOTE: Daily folic acid supplementation to prevent neural tube defects (NTDs) is recommended in all persons planning to or who could become pregnant.
For neural tube defect prophylaxis in those at high-risk for an NTD-affected pregnancy.
NOTE: Persons at increased risk of NTDs include those with a history of pregnancy complicated by fetal NTDs or those with seizure disorders.
Oral dosage Adults

4 mg/day PO initiated 3 months prior to conception and continuing until 12 weeks of gestational age has been recommended in ACOG guidelines.

Adolescents

4 mg/day PO initiated 3 months prior to conception and continuing until 12 weeks of gestational age has been recommended in ACOG guidelines.

For neural tube defect prophylaxis in those at average risk of neural tube defects.
NOTE: Average risk persons include those without a prior pregnancy with NTDs or who do not have an underlying condition that may increase risk for NTDs (e.g., taking anticonvulsant medications).
Oral dosage Adults

0.4 to 0.8 mg/day PO. To achieve benefit, persons planning to or who could become pregnant should start daily folic acid supplementation at least 1 month prior to anticipated conception and continue through the first 2 to 3 months of pregnancy.

Adolescents

0.4 to 0.8 mg/day PO. To achieve benefit, persons planning to or who could become pregnant should start daily folic acid supplementation at least 1 month prior to anticipated conception and continue through the first 2 to 3 months of pregnancy.

†Indicates off-label use

Dosing Considerations
Hepatic Impairment

No dosage adjustments are needed.

Renal Impairment

No dosage adjustments are needed.
 
Intermittent hemodialysis
No dosage adjustments are needed.

Drug Interactions

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) 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.
Amiloride; Hydrochlorothiazide, HCTZ: (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) 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) 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.
Azilsartan; Chlorthalidone: (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) 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%.
Bisoprolol; Hydrochlorothiazide, HCTZ: (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.
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.
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) 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.
Capecitabine: (Moderate) Monitor for an increase in capecitabine-related adverse reactions if coadministration with folic acid is necessary. Capecitabine is an orally administered prodrug of fluorouracil; leucovorin enhances the binding of fluorouracil to thymidylate synthase, increasing exposure to fluorouracil. Folic acid (vitamin B9) is converted to folinic acid in vivo; leucovorin is the calcium salt of folinic acid. Deaths from severe enterocolitis, diarrhea, and dehydration have been reported in elderly patients receiving weekly leucovorin and fluorouracil.
Captopril; Hydrochlorothiazide, HCTZ: (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.
Chloramphenicol: (Minor) Concurrent use of chloramphenicol with folic acid can antagonize the hematopoietic response to folic acid. Hematologic response should be monitored in patients requiring folic acid if chloramphenicol is administered concomitantly.
Chlorothiazide: (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) 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; Clonidine: (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) Chronic administration of cholestyramine may interfere with folic acid, vitamin B9 oral absorption. Patients receiving both drugs should take folic acid 1 hour before or 4 to 6 hours after a dose of cholestyramine.
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.
Clevidipine: (Minor) Monitor blood pressure during concurrent use of calcium and calcium-channel blockers. Concomitant use may reduce the response to calcium-channel blockers.
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.
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.
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.
Diethylstilbestrol, DES: (Minor) Estrogens can increase calcium absorption. Use caution in patients predisposed to hypercalcemia or nephrolithiasis.
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.
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) 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) 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.
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) 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: (Minor) Concurrent use of folic acid, vitamin B9 and phenytoin (and fosphenytoin) may result in decreased folic acid serum concentrations and decreased anticonvulsant effect. It is important to maintain adequate folic acid concentrations in epileptic patients taking enzyme-inducing anticonvulsants, and maintenance doses may require upward adjustment. However, in large amounts, folic acid may counteract the anticonvulsant effect of some agents, including phenytoin. Therefore, it has been recommended that oral folic acid supplementation not exceed 1 mg/day in epileptic patients taking anticonvulsants. If large doses are used, monitor phenytoin concentrations upon folic acid initiation, dose titration, and discontinuation and adjust the anticonvulsant dosage as appropriate. Prolonged administration of phenytoin reportedly has resulted in a folate deficiency in 27% to 91% of patients. Megaloblastic anemia occurs in fewer than 1% of patients receiving phenytoin. The proposed mechanisms of this phenomenon include an increase in folate catabolism, folate malabsorption, or use of folic acid secondary to enzyme induction by phenytoin. Some evidence suggests that the anticonvulsant effect of phenytoin is partially the result of a reduction in folic acid concentrations. Folic acid replacement has resulted in an increase in metabolism of phenytoin and a decrease in phenytoin concentration in some patients, apparently through increased metabolism and/or redistribution of phenytoin in the brain and CSF. A clinically significant increase in seizure activity has occurred with this drug combination in rare instances, especially when doses of 4 mg/day or more were utilized.
Hydrochlorothiazide, HCTZ: (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; Methyldopa: (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) 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: (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) 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.
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.
Lisinopril; Hydrochlorothiazide, HCTZ: (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) 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.
Methotrexate: (Moderate) Folic acid may compete with methotrexate for entry into cells. However, in some situations, folic acid supplementation may be used to decrease adverse reactions such as mouth sores in patients receiving methotrexate for arthritis and other non-malignant diseases. Folic acid, vitamin B9, is NOT effective for methotrexate rescue therapy since folic acid requires dihydrofolate reductase for bioactivation and methotrexate inhibits this enzyme. Therefore folic acid should not be used to prevent toxicity of moderate- to high-dose methotrexate therapy.
Methyclothiazide: (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.
Metolazone: (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) 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.
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) 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) 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.
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.
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.
Phenobarbital: (Minor) Concurrent use of folic acid, vitamin B9 and phenobarbital may result in decreased folic acid serum concentrations and decreased anticonvulsant effect. It is important to maintain adequate folic acid concentrations in epileptic patients taking enzyme-inducing anticonvulsants, and maintenance doses may require upward adjustment. However, in large amounts, folic acid may counteract the anticonvulsant effect of some agents, including phenobarbital. Therefore, it has been recommended that oral folic acid supplementation not exceed 1 mg/day in epileptic patients taking anticonvulsants. If large doses are used, monitor phenobarbital concentrations upon folic acid initiation, dose titration, and discontinuation. Adjust the anticonvulsant dosage as appropriate.
Phenobarbital; Hyoscyamine; Atropine; Scopolamine: (Minor) Concurrent use of folic acid, vitamin B9 and phenobarbital may result in decreased folic acid serum concentrations and decreased anticonvulsant effect. It is important to maintain adequate folic acid concentrations in epileptic patients taking enzyme-inducing anticonvulsants, and maintenance doses may require upward adjustment. However, in large amounts, folic acid may counteract the anticonvulsant effect of some agents, including phenobarbital. Therefore, it has been recommended that oral folic acid supplementation not exceed 1 mg/day in epileptic patients taking anticonvulsants. If large doses are used, monitor phenobarbital concentrations upon folic acid initiation, dose titration, and discontinuation. Adjust the anticonvulsant dosage as appropriate.
Phenytoin: (Minor) Concurrent use of folic acid, vitamin B9 and phenytoin may result in decreased folic acid serum concentrations and decreased anticonvulsant effect. It is important to maintain adequate folic acid concentrations in epileptic patients taking enzyme-inducing anticonvulsants, and maintenance doses may require upward adjustment. However, in large amounts, folic acid may counteract the anticonvulsant effect of some agents, including phenytoin. Therefore, it has been recommended that oral folic acid supplementation not exceed 1 mg/day in epileptic patients taking anticonvulsants. If large doses are used, monitor phenytoin concentrations upon folic acid initiation, dose titration, and discontinuation and adjust the anticonvulsant dosage as appropriate. Prolonged administration of phenytoin reportedly has resulted in a folate deficiency in 27% to 91% of patients. Megaloblastic anemia occurs in fewer than 1% of patients receiving phenytoin. The proposed mechanisms of this phenomenon include an increase in folate catabolism, folate malabsorption, or use of folic acid secondary to enzyme induction by phenytoin. Some evidence suggests that the anticonvulsant effect of phenytoin is partially the result of a reduction in folic acid concentrations. Folic acid replacement has resulted in an increase in metabolism of phenytoin and a decrease in phenytoin concentration in some patients, apparently through increased metabolism and/or redistribution of phenytoin in the brain and CSF. A clinically significant increase in seizure activity has occurred with this drug combination in rare instances, especially when doses of 4 mg/day or more were utilized.
Phosphorated Carbohydrate Solution: (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: (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: (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: (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.
Primidone: (Minor) Concurrent use of folic acid, vitamin B9 and phenobarbital and primidone may result in decreased folic acid serum concentrations and decreased anticonvulsant effect. It is important to maintain adequate folic acid concentrations in epileptic patients taking enzyme-inducing anticonvulsants, and maintenance doses may require upward adjustment. However, in large amounts, folic acid may counteract the anticonvulsant effect of some agents, including phenobarbital and primidone. Therefore, it has been recommended that oral folic acid supplementation not exceed 1 mg/day in epileptic patients taking anticonvulsants. If large doses are used, monitor phenobarbital concentrations upon folic acid initiation, dose titration, and discontinuation. Adjust the anticonvulsant dosage as appropriate.
Propranolol; Hydrochlorothiazide, HCTZ: (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.
Pyrimethamine: (Moderate) Pyrimethamine is a folate antagonist. Some evidence suggests that administration of folic acid to leukemia patients receiving pyrimethamine for Pneumocystis carinii resulted in exacerbation of leukemia symptoms. Folic acid, vitamin B9 reportedly interferes with the action of pyrimethamine in treating toxoplasmosis. Further study is needed to confirm these interactions.
Quinapril; Hydrochlorothiazide, HCTZ: (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.
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.
Segesterone Acetate; Ethinyl Estradiol: (Minor) Estrogens can increase calcium absorption. Use caution in patients predisposed to hypercalcemia or nephrolithiasis.
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.
Spironolactone; Hydrochlorothiazide, HCTZ: (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.
Sulfamethoxazole; Trimethoprim, SMX-TMP, Cotrimoxazole: (Minor) Folate antagonists, such as trimethoprim, especially when used in high doses or over a prolonged period, inhibit dihydrofolate reductase and thus may inhibit the action of folic acid, vitamin B9.
Sulfasalazine: (Minor) Sulfasalazine exhibits antifolate activity, and can inhibit the absorption and lower the plasma concentrations of folic acid, vitamin B9. Patients receiving sulfasalazine treatment may require folic acid supplementation.
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) 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.
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) 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.
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) 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.
Trimethoprim: (Minor) Folate antagonists, such as trimethoprim, especially when used in high doses or over a prolonged period, inhibit dihydrofolate reductase and thus may inhibit the action of folic acid, vitamin B9.
Valsartan; Hydrochlorothiazide, HCTZ: (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.
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.

How Supplied

Folic Acid (Vitamin B9) Intramuscular Inj Sol: 1mL, 5mg
Folic Acid (Vitamin B9) Intravenous Inj Sol: 1mL, 5mg
Folic Acid (Vitamin B9) Subcutaneous Inj Sol: 1mL, 5mg
Folic Acid (Vitamin B9)/Folicet/Q-TABS Oral Tab: 1mg

Maximum Dosage
Adults

1 mg/day PO/IV is FDA-approved maximum; however, doses as high as 5 mg/day PO/IV have been used off-label.

Geriatric

1 mg/day PO/IV is FDA-approved maximum; however, doses as high as 5 mg/day PO/IV have been used off-label.

Adolescents

1 mg/day PO/IV is FDA-approved maximum; however, doses as high as 5 mg/day PO/IV have been used off-label.

Children

1 mg/day PO/IV is FDA-approved maximum; however, doses as high as 5 mg/day PO/IV have been used off-label.

Infants

1 mg/day PO/IV.

Mechanism Of Action

Folic acid, a biochemically inactive compound, is the precursor for tetrahydrofolic acid and methyltetrahydrofolate. Tetrahydrofolic acid, methyltetrahydrofolate, and other folic acid congeners are essential for the maintenance of normal erythropoiesis and are also required cofactors for the synthesis of purine and thymidylate nucleic acids. They are also necessary for the interconversion of amino acids such as the metabolism of histidine to glutamic acid and the interconversion of serine and glycine. Folic acid congeners are transported across cells by receptor-mediated endocytosis where they function and are stored. Other processes involving folate coenzymes include generation and use of formate and methylation of transfer RNA. Impaired thymidylate synthesis, which leads to faulty DNA synthesis, is responsible for megaloblastic and macrocytic anemias.
 
An important role of folic acid is the formation of methionine from homocysteine using vitamin B12 as a cofactor. Adequate folic acid intakes can normalize high homocysteine levels via increased remethylation of homocysteine to methionine via 5-methyltetrahydrofolate-homocysteine methyltransferase (a.k.a.; methionine synthetase). Reduced folic acid intake is associated with hyperhomocysteinemia. Hyperhomocysteinemia is recognized as an independent risk factor for artherosclerosis of the coronary, cerebral, and peripheral vasculature. There is mounting evidence that elevated plasma homocysteine (and therefore decreased serum methionine) contributes to congenital neural tube defects. High serum homocysteine levels may also be important in the pathogenesis of colon cancer, diabetic retinopathy, and other diseases.

Pharmacokinetics

Folic acid is administered orally and parenterally. Folic acid congeners are extensively bound to plasma proteins and are distributed throughout the body including the CSF. They also appear in breast milk. After administration of small doses, reduction and methylation of folic acid to methyltetrahydrofolate occurs in the liver. Following large doses, folic acid may appear unchanged in the plasma. Active forms of folic acid are reabsorbed through enterohepatic recirculation. Folic acid is eliminated primarily renally as metabolites. When body stores become saturated, excess folic acid is excreted unchanged in the urine. 

Oral Route

Following oral administration, folic acid is rapidly absorbed from the small intestine. Because dietary folate is primarily in the polyglutamyl form, it must be converted to the monoglutamate form by intestinal conjugase enzymes prior to absorption. The monoglutamate form is then reduced and methylated to methyltetrahydrofolate by dihydrofolate reductase during transport across the intestinal mucosa. Absorption of dietary folic acid is impaired in the presence of malabsorption syndromes; however, the absorption of synthetic, commercially available folic acid is unaffected. The peak activity of this vitamin occurs within 1 hour.

Pregnancy And Lactation
Pregnancy

Appropriate maternal folic acid intake is essential to the fetus and no harms are associated with appropriate folic acid supplementation during pregnancy as recommended in expert guidelines. There is significant evidence that most fetal neural tube defects (NTDs) can be prevented if folic acid therapy is initiated before conception and continued during early pregnancy (the first 12 weeks of conception) in both persons with increased risk and those with no known increased risk for having an NTD-affected pregnancy. While not all NTDs are preventable with folic acid supplementation, a large percentage are.

Appropriate maternal folic acid intake is important during lactation, and no problems have been identified with supplementation to achieve adequate intake goals during breast-feeding. The American Academy of Pediatrics (AAP) considers folic acid supplementation compatible with breast-feeding.