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    Zinc Supplements

    DEA CLASS

    Rx, OTC

    DESCRIPTION

    Essential trace element for many biologic functions
    Zinc sulfate is the most common form of zinc used when a nutritional supplement is needed, including in parenteral nutrition
    Copper deficiency may occur with long-term use

    COMMON BRAND NAMES

    Galzin, Zincate

    HOW SUPPLIED

    Galzin Oral Cap: 25mg, 50mg
    Zinc Chloride/Zinc Sulfate Intravenous Inj Sol: 1mL, 1mg, 3mg, 5mL, 5mg, 25mg

    DOSAGE & INDICATIONS

    For nutritional supplementation.
    For the recommended dietary allowance (RDA) of oral zinc for nutritional supplementation in healthy individuals, expressed as elemental zinc.
    NOTE: RDAs were revised by the IOM Food and Nutrition Board in 2001.
    Oral dosage
    Adult and Adolescent pregnant females

    11—13 mg PO per day.

    Adult and Adolescent lactating females

    12—14 mg PO per day for 12 months.

    Adult and Adolescent males >= 14 years

    11 mg PO per day.

    Adult females >= 19 years

    8 mg PO per day.

    Adolescent females >= 14 years

    9 mg PO per day.

    Children 9—13 years

    8 mg PO per day.

    Children 4—8 years

    5 mg PO per day.

    Children 1—3 years

    3 mg PO per day.

    Infants 7—12 months

    3 mg PO per day.

    Infants birth to 6 months

    2 mg PO per day is the Adequate Intake (AI). No RDA is established.

    For nutritional supplementation to promote wound healing† in wound-care patients with low serum zinc concentrations (< 110 mcg/dl).
    Oral dosage
    Adults

    50 mg elemental zinc (e.g., 220 mg zinc sulfate) PO three times per day until wound healed.

    For nutritional supplementation of zinc in parenteral nutrition solutions (e.g., TPN) to prevent deficiency.
    Intravenous dosage (zinc chloride or zinc sulfate)
    Adults

    If stable metabolically, give 2.5—4 mg elemental zinc/day IV in TPN; if in a catabolic state, give 4.5—6 mg elemental zinc/day. For fluid loss from small bowel, give an additional 12 mg elemental zinc/liter TPN or give 17 mg elemental zinc per kg of stool or ileostomy output.

    Children

    50 mcg/kg/day IV in TPN. Maximum dose is 5 mg.

    Infants >= 3 months

    100 mcg/kg/day in TPN.

    Term infants < 3 months

    250 mcg/kg/day in TPN. Avoid use of preparations containing benzyl alcohol in neonates.

    Premature neonates

    400 mcg/kg/day in TPN. Avoid use of preparations containing benzyl alcohol in neonates.

    For the treatment of zinc deficiency.
    For the oral treatment of deficiency.
    Oral dosage
    Adults

    25—50 mg PO of elemental zinc per day.

    Infants and Children

    0.5—1 mg elemental zinc/kg/day PO in divided doses given 1—3 times per day; larger doses may be needed if impaired intestinal absorption or an excessive loss of zinc (e.g., excessive, prolonged diarrhea).

    For the intravenous treatment of deficiency.
    Intravenous dosage (zinc chloride or zinc sulfate)
    Adults

    2.5—4 mg of elemental zinc IV per day, added to TPN.

    Children <= 5 years and term infants

    100 mcg of elemental zinc/kg IV per day added to TPN.

    Premature neonates (weight <= 3 kg):

    300 mcg of elemental zinc/kg IV per day added to TPN. Avoid use of preparations containing benzyl alcohol in neonates.

    For the treatment of Wilson's disease.
    Although zinc is usually reserved for maintenance treatment, it has been used as first-line therapy, most commonly for asymptomatic or presymptomatic patients.
    Oral dosage (zinc acetate, zinc gluconate, zinc sulfate)

    NOTE: Zinc acetate is associated with the lowest incidence of GI adverse reactions, followed by zinc gluconate and zinc sulfate.

    Adults weighing 50 kg or more

    50 mg elemental zinc PO 3 times daily on an empty stomach. The minimum effective dose is 25 mg elemental zinc PO 3 times daily. This lower dose may be an acceptable maintenance dosage. Adequate maintenance dosage should target a 24-hour urinary copper excretion of 30 to 75 mcg (0.5 to 1.2 micromol/L); low 24-hour urinary copper concentrations (less than 30 mcg) suggest zinc overdosage. In addition, serum zinc concentrations and 24-hour urinary zinc excretion should be maintained above 125 mg/dL and 2 mg/day, respectively; lower concentrations generally indicate poor compliance to therapy.

    Adults weighing less than 50 kg

    25 mg elemental zinc PO 3 times daily on an empty stomach. May increase to 50 mg PO 3 times daily if needed. Adequate maintenance dosage should target a 24-hour urinary copper excretion of 30 to 75 mcg (0.5 to 1.2 micromol/L); low 24-hour urinary copper concentrations (less than 30 mcg) suggest zinc overdosage. In addition, serum zinc concentrations and 24-hour urinary zinc excretion should be maintained above 125 mg/dL and 2 mg/day, respectively; lower concentrations generally indicate poor compliance to therapy.

    Children and Adolescents 6 to 17 years weighing 50 kg or more

    50 mg elemental zinc PO 3 times daily on an empty stomach. The minimum effective dose is 25 mg elemental zinc PO three times per day. This lower dose may be an acceptable maintenance dosage. Adequate maintenance dosage should target a 24-hour urinary copper excretion of 30 to 75 mcg (0.5 to 1.2 micromol/L); low 24-hour urinary copper concentrations (less than 30 mcg) suggest zinc overdosage. In addition, serum zinc concentrations and 24-hour urinary zinc excretion should be maintained above 125 mg/dL and 2 mg/day, respectively; lower concentrations generally indicate poor compliance to therapy.

    Children and Adolescents 6 to 17 years weighing less than 50 kg

    25 mg elemental zinc PO 3 times daily on an empty stomach. May increase to 50 mg PO 3 times daily if needed. Adequate maintenance dosage should target a 24-hour urinary copper excretion of 30 to 75 mcg (0.5 to 1.2 micromol/L); low 24-hour urinary copper concentrations (less than 30 mcg) suggest zinc overdosage. In addition, serum zinc concentrations and 24-hour urinary zinc excretion should be maintained above 125 mg/dL and 2 mg/day, respectively; lower concentrations generally indicate poor compliance to therapy.

    Children 1 to 5 years

    25 mg elemental zinc PO twice daily on an empty stomach. Adequate maintenance dosage should target a 24-hour urinary copper excretion of 30 to 75 mcg (0.5 to 1.2 micromol/L); low 24-hour urinary copper concentrations (less than 30 mcg) suggest zinc overdosage. In addition, serum zinc concentrations and 24-hour urinary zinc excretion should be maintained above 125 mg/dL and 2 mg/day, respectively; lower concentrations generally indicate poor compliance to therapy.

    For the relief of symptoms associated with the common cold.
    Oral dosage (zinc gluconate lozenges; homeopathic product; e.g., Cold-Eeze lozenge)
    Adults

    Dissolve one 13.3 mg lozenge in mouth; do not chew. Repeat every 2 to 4 hours as needed until all symptoms subside. Max: 6 lozenges/day. For best results, begin treatment at start of symptoms (within 24 to 48 hours of onset). A meta-analysis has suggested that any benefit is modest, and that data are not sufficient to prove efficacy given the inherent limitations of the individual studies.

    Children and Adolescents 12 to 17 years

    Dissolve one 13.3 mg lozenge in mouth; do not chew. Repeat every 2 to 4 hours as needed until all symptoms subside. Max: 4 lozenges/day. For best results, begin treatment at start of symptoms (within 24 to 48 hours of onset).

    Oral dosage (chewable or orally-disintegrating tablets; homeopathic product; e.g., Zicam Cold Remedy RapidMelts)
    Adults

    1 tablet PO at the onset of symptoms; chew or dissolve as directed on product label; may repeat every 3 hours as needed until symptoms subside. Max: 6 tablets/day. A meta-analysis has suggested that any benefit is modest, and that data are not sufficient to prove efficacy given the inherent limitations of the individual studies.

    Children and Adolescents 12 to 17 years

    1 tablet PO at the onset of symptoms; chew or dissolve as directed on product label; may repeat every 3 hours as needed until symptoms subside. Max: 6 tablets/day.

    For zinc supplementation in persons with infectious diarrhea†, including cholera†.
    Oral dosage
    Infants and Children 6 months to 5 years

    20 mg/day elemental zinc PO for 10 to 14 days reduces the severity and duration of diarrhea in children who reside in countries with high prevalence of zinc deficiency or who have signs of malnutrition.

    Infants 1 to 5 months

    10 mg/day elemental zinc PO for 10 to 14 days reduces the severity and duration of diarrhea in children who reside in countries with high prevalence of zinc deficiency or who have signs of malnutrition.

    †Indicates off-label use

    MAXIMUM DOSAGE

    The following are recommended tolerable upper intake levels.

    Adults

    40 mg/day PO.

    Elderly

    40 mg/day PO.

    Adolescents

    >= 14 years: 34 mg/day PO.

    Children

     9—13 years: 23 mg/day PO.
     4—8 years: 12 mg/day PO.
     1—3 years: 7 mg/day PO.

    Infants

     7—12 months: 5 mg/day PO.
     birth to 6 months: 4 mg/day PO.

    DOSING CONSIDERATIONS

    Hepatic Impairment

    Specific guidelines for dosage adjustments in hepatic impairment are not available; it appears that no dosage adjustments are needed.

    Renal Impairment

    Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are needed.

    ADMINISTRATION

    Oral Administration

    Administer on an empty stomach, at least 1 hour before or after meals. If gastric irritation occurs, zinc supplements may be administered with food; however, the zinc will be less bioavailable.[64467]

    Injectable Administration

    For intravenous use ONLY after dilution into parenteral nutrition admixture; do NOT give by direct IV administration or intramuscular administration due to the acidic pH of the zinc injection solutions which can cause considerable tissue damage.
    Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit. A slight yellow color does not affect the quality and efficacy of the product.

    Intravenous Administration

    Zinc Sulfate injection
    Zinc sulfate injection must be diluted and used as an admixture in parenteral nutrition solutions; do not administer by direct IV infusion.
    Follow proper admixing sequence as related to parenteral nutrition.
    Storage: Use of zinc sulfate injection for admixing should be limited to up to 4 hours at room temperature after container has been penetrated; discard any remaining drug. After mixing in parenteral nutrition solutions, admixtures are stable for 24 hours under refrigeration; after removal from refrigeration, use solution promptly and complete the infusion within 24 hours. Discard any remaining admixture.
     
    Zinc Chloride Injection
    Zinc chloride injection must be diluted and used as an admixture in parenteral nutrition solutions; do not administer by direct IV infusion.
    Follow proper admixing sequence as related to parenteral nutrition.
    Storage: Contains no bacteriostat; use within 24 hours and discard any remaining drug.[58284] After mixing in parenteral nutrition solutions, admixtures are stable for 24 hours under refrigeration; after removal from refrigeration, use solution promptly and complete the infusion within 24 hours. Discard any remaining admixture.

    STORAGE

    Generic:
    - Store at room temperature (between 59 to 86 degrees F)
    Cold Remedy Melteez:
    - Store at controlled room temperature (between 68 and 77 degrees F)
    Galzin:
    - Store at room temperature (between 59 to 86 degrees F)
    Zincate :
    - Store at room temperature (between 59 to 86 degrees F)
    - Store in a dry place

    CONTRAINDICATIONS / PRECAUTIONS

    General Information

    Zinc products are contraindicated in patients with known hypersensitivity to zinc. Hypersensitivity reactions to zinc-containing insulin products, for example, have been identified in postmarketing case reports. Reported reactions included injection site induration, erythema, pruritus, papular rash, generalized urticaria, facial swelling, and dyspnea. Patients did not manifest symptoms after changing to zinc-free insulin or another product with a reduced amount of zinc. In some cases, allergy testing confirmed the allergy to the zinc component. If hypersensitivity reactions occur, discontinue the zinc product and initiate appropriate medical treatment.

    Hypocupremia

    Zinc supplementation can interfere with the absorption of copper, particularly with high doses and long-term use. Administration of zinc to patients with hypocupremia (copper deficiency) can further decrease serum copper levels.

    Premature neonates, renal failure, renal impairment

    Aluminum toxicity may occur with prolonged administration of zinc sulfate or chloride during parenteral nutrition in high-risk patients, including premature neonates and those patients with renal impairment or renal failure. Premature neonates are particularly at risk for aluminum toxicity because the kidneys are immature. Research indicates that patients with renal impairment, including preterm neonates, who receive parenteral aluminum at rates greater than 4 to 5 mcg/kg/day may accumulate aluminum at levels associated with CNS and bone toxicity. Tissue loading may occur at lower administration rates. Exposure to aluminum from zinc sulfate injection is not more than 0.6 mcg/kg/day. When prescribing zinc for use in parenteral nutrition containing other small volume parenteral products, the total daily patient exposure to aluminum from the admixture should be considered and maintained at no more than 5 mcg/kg/day.[57509]

    Intramuscular administration, thrombophlebitis, thrombosis

    Zinc sulfate and chloride injections have a low pH (are acidic) and must be diluted and used as an admixture in parenteral nutrition solutions; do not administer by direct IV injection or intramuscular administration due to the potential for considerable tissue irritation. In addition, consider the osmolarity of the final parenteral nutrition solution in determining peripheral versus central administration. Hypertonic solutions (osmolarity of 900 mOsm/L or greater) should be infused through a central catheter. Infusion of hypertonic nutrient solutions through a peripheral vein may result in vein irritation/damage, thrombophlebitis, and/or thrombosis. Remove the IV catheter as soon as possible if thrombophlebitis occurs.

    Pregnancy

    Appropriate administration and nutritional supplementation with zinc to meet nutritional requirements is not expected to cause major birth defects, miscarriage or adverse maternal or fetal outcomes during pregnancy. Animal reproduction studies have not been conducted. Deficiency of trace elements, including zinc, is associated with adverse pregnancy and fetal outcomes. During pregnancy there is an increased metabolic demand for trace elements, including zinc. Parenteral nutrition with zinc should be considered if a pregnant patient's nutritional requirements cannot be fulfilled by oral or enteral intake.[41825] [57509]

    Breast-feeding

    Maternal zinc supplementation during lactation appears to have no significant effect on zinc concentrations normally found in human milk. Use of zinc supplementation within the recommended daily dietary intake for lactating women is generally recognized as safe and is not expected to cause harm to a breastfed infant. There are no data available on the effects of zinc supplementation on milk production. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition.[27966] [41825] [57509]

    ADVERSE REACTIONS

    Severe

    sideroblastic anemia / Delayed / Incidence not known

    Moderate

    neutropenia / Delayed / Incidence not known
    leukopenia / Delayed / Incidence not known
    hypocupremia / Delayed / Incidence not known

    Mild

    nausea / Early / Incidence not known
    vomiting / Early / Incidence not known
    dyspepsia / Early / Incidence not known
    abdominal pain / Early / Incidence not known
    anosmia / Delayed / Incidence not known
    dysosmia / Delayed / Incidence not known

    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; 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.
    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; 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.
    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. (Major) Do not administer baloxavir with products that contain zinc. Polyvalent cations, such as zinc, 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.
    Bendroflumethiazide; Nadolol: (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. (Moderate) Administer oral zinc at least two hours before or four hours after taking oral cabotegravir. Zinc 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. (Moderate) Administer oral zinc at least two hours before or four hours after taking oral cabotegravir. Zinc 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 Carbonate; 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.
    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.
    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.
    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. Sporadic case reports have suggested that hypercalcemia may predispose persons to digoxin toxicity. If calcium is administered intravenously rapidly in a person receiving digoxin, serious arrhythmias may occur.
    Cephalexin: (Minor) Caution may be warranted with coadminstration of cephalexin and zinc salts as zinc may decrease the absorption of cephalexin. In a randomized, single-dose, four-way crossover study (n = 12), patients received cephalexin alone, in combination with zinc sulfate (250 mg), 3 hours after zinc sulfate, or 3 hours before zinc sulfate. When administered in combination with zinc, the cephalexin Cmax decreased from 18.07 +/- 4.27 mcg/ml to 12.46 +/- 2.73 mcg/ml (p < 0.05) and the AUC decreased from 41.97 +/- 6.04 mcg x h/ml to 30.47 +/- 3.52 mcg x h/ml (p < 0.05). When cephalexin was administered 3 hours after zinc, the Cmax and AUC were 16 +/- 4.06 mcg/ml (p < 0.05) and 34.37 +/- 1.58 mcg x h/mL (p < 0.05), respectively. When cephalexin was administered 3 hours before zinc, there were no significant differences in the cephalexin Cmax or AUC. One in vitro study suggested that zinc is a competitive inhibitor of the intestinal peptide transporter, PEPT1, which may inhibit the uptake of oral cephalosporins. An additional in vitro study suggested that trace elements may have an antagonistic effect on cephalosporins.
    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.
    Ciprofloxacin: (Major) Administer oral ciprofloxacin at least 2 hours before or 6 hours after oral products that contain zinc. 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 multivitamins that contain zinc. (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.
    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.
    Deferiprone: (Moderate) Concurrent use of deferiprone with food, mineral supplements, and antacids that contain polyvalent (trivalent) cations has not been studied. However, since deferiprone has the potential to bind polyvalent cations (e.g., iron, aluminum, and zinc), allow at least a 4-hour interval between deferiprone and other medications or dietary supplements containing these polyvalent cations. Such medications can include antacids, iron salts, aluminum hydroxide, dietary supplements containing polyvalent minerals, and zinc salts.
    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. (Major) Administer oral delafloxacin at least 2 hours before or 6 hours after oral products that contain zinc. Delafloxacin absorption may be reduced as quinolone antibiotics can chelate with divalent or trivalent cations. Examples of compounds that may interfere with quinolone bioavailability include multivitamins that contain zinc.
    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.
    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. (Major) Concomitant use of zinc supplements with calcium EDTA can decrease the effectiveness of both agents due to chelation. Zinc salts should not be administered until edetate calcium therapy is completed.
    Edetate Disodium, Disodium EDTA: (Major) Because edetate disodium chelates and lowers serum calcium, oral or parenteral calcium salts should not be administered concomitantly. (Major) Concomitant use of zinc supplements with calcium EDTA can decrease the effectiveness of both agents due to chelation. Zinc salts should not be administered until edetate calcium therapy is completed.
    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. (Major) Eltrombopag chelates polyvalent cations (e.g., zinc salts) in foods, 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 2 hours before or 4 hours after any oral products containing zinc salts.
    Elvitegravir: (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. (Moderate) Separate administration of elvitegravir and zinc 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 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. (Moderate) Separate administration of elvitegravir and zinc 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. (Moderate) Separate administration of elvitegravir and zinc 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.
    Enteral Feedings: (Minor) Absorption of zinc from enteral feedings may be impaired, despite the presence of zinc as a component of the enteral feeding formula; patients on chronic enteral feeding therapy may require additional zinc supplementation to ensure adequate nutritional intake.
    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 Cypionate; Medroxyprogesterone: (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: (Minor) Estrogens can increase calcium absorption. Use caution in patients predisposed to hypercalcemia or nephrolithiasis.
    Ethinyl Estradiol; Levonorgestrel; Folic Acid; Levomefolate: (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.
    Ferric Maltol: (Moderate) Orally administered zinc salts compete with iron supplements for absorption from the intestine. To minimize the interaction, separate oral iron and zinc doses by at least 2 hours. The oral receipt of 100 mg of iron as ferrous gluconate with 12 mg zinc in 11 patients with normal iron status and comparable total exchangeable zinc pools yielded a mean zinc absorption of 26.4% +/- 14.4% of the administered dose as compared with 44.5% +/- 22.5% of the dose given without concomitant iron. Concomitant use of iron 400 mg as ferrous gluconate yielded a mean zinc absorption of 22.9% +/- 6.4% of the zinc dose.
    Food: (Moderate) Breads, vegetables, fruits, eggs, and beverages appear to interfere with the oral absorption of Zinc. For optimal absorption, oral zinc salts should be separated from food and beverages, other than water, by at least 1 hour.
    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.
    Gemifloxacin: (Major) Administer oral products that contain zinc at least 3 hours before or 2 hours after gemifloxacin. Gemifloxacin absorption may be reduced as quinolone antibiotics can chelate with divalent or trivalent cations. Examples of compounds that may interfere with quinolone bioavailability include multivitamins that contain zinc.
    Hydralazine; 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: (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.
    Intrauterine Copper Contraceptive: (Major) Orally administered zinc salts compete with copper salts for absorption from the intestines. Since a large portion of administered zinc doses are excreted via biliary and pancreatic secretions, parenteral zinc therapy may also interfere with the oral absorption of copper salts.
    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.
    Iron Salts: (Moderate) Orally administered zinc salts compete with iron supplements for absorption from the intestine. To minimize the interaction, separate oral iron and zinc doses by at least 2 hours. The oral receipt of 100 mg of iron as ferrous gluconate with 12 mg zinc in 11 patients with normal iron status and comparable total exchangeable zinc pools yielded a mean zinc absorption of 26.4% +/- 14.4% of the administered dose as compared with 44.5% +/- 22.5% of the dose given without concomitant iron. Concomitant use of iron 400 mg as ferrous gluconate yielded a mean zinc absorption of 22.9% +/- 6.4% of the zinc dose.
    Iron: (Moderate) Orally administered zinc salts compete with iron supplements for absorption from the intestine. To minimize the interaction, separate oral iron and zinc doses by at least 2 hours. The oral receipt of 100 mg of iron as ferrous gluconate with 12 mg zinc in 11 patients with normal iron status and comparable total exchangeable zinc pools yielded a mean zinc absorption of 26.4% +/- 14.4% of the administered dose as compared with 44.5% +/- 22.5% of the dose given without concomitant iron. Concomitant use of iron 400 mg as ferrous gluconate yielded a mean zinc absorption of 22.9% +/- 6.4% of the zinc dose.
    Levofloxacin: (Major) Administer oral products that contain zinc 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 multivitamins that contain zinc. (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.
    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.
    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.
    Mestranol; Norethindrone: (Minor) Estrogens can increase calcium absorption. Use caution in patients predisposed to hypercalcemia or nephrolithiasis.
    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. (Major) Administer oral moxifloxacin at least 4 hours before or 8 hours after oral products that contain zinc. 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 multivitamins that contain zinc.
    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.
    Norethindrone Acetate; Ethinyl Estradiol; Ferrous fumarate: (Moderate) Orally administered zinc salts compete with iron supplements for absorption from the intestine. To minimize the interaction, separate oral iron and zinc doses by at least 2 hours. The oral receipt of 100 mg of iron as ferrous gluconate with 12 mg zinc in 11 patients with normal iron status and comparable total exchangeable zinc pools yielded a mean zinc absorption of 26.4% +/- 14.4% of the administered dose as compared with 44.5% +/- 22.5% of the dose given without concomitant iron. Concomitant use of iron 400 mg as ferrous gluconate yielded a mean zinc absorption of 22.9% +/- 6.4% of the zinc dose. (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: (Moderate) Orally administered zinc salts compete with iron supplements for absorption from the intestine. To minimize the interaction, separate oral iron and zinc doses by at least 2 hours. The oral receipt of 100 mg of iron as ferrous gluconate with 12 mg zinc in 11 patients with normal iron status and comparable total exchangeable zinc pools yielded a mean zinc absorption of 26.4% +/- 14.4% of the administered dose as compared with 44.5% +/- 22.5% of the dose given without concomitant iron. Concomitant use of iron 400 mg as ferrous gluconate yielded a mean zinc absorption of 22.9% +/- 6.4% of the zinc dose. (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: (Major) Administer oral products that contain zinc 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 multivitamins that contain zinc. (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.
    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.
    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. (Minor) It has been reported that high intakes of phosphates, such as are found in dietary supplements or food additives, can interfere with absorption of trace nutrients such as iron, copper, and zinc. The magnitude of the effect may be small, and the interactions require further study to judge clinical significance. The theorized mechanism is the formation of insoluble complexes within the gut. Until more data are available, it may be helpful to separate administration times of potassium phosphate; sodium phosphateby as much as possible from the oral administration of iron (e.g., iron salts or polysaccharide-iron complex), copper salts, or zinc salts to limit any potential interactions.
    Polysaccharide-Iron Complex: (Moderate) Orally administered zinc salts compete with iron supplements for absorption from the intestine. To minimize the interaction, separate oral iron and zinc doses by at least 2 hours. The oral receipt of 100 mg of iron as ferrous gluconate with 12 mg zinc in 11 patients with normal iron status and comparable total exchangeable zinc pools yielded a mean zinc absorption of 26.4% +/- 14.4% of the administered dose as compared with 44.5% +/- 22.5% of the dose given without concomitant iron. Concomitant use of iron 400 mg as ferrous gluconate yielded a mean zinc absorption of 22.9% +/- 6.4% of the zinc dose.
    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.
    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.
    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 Ferric Gluconate Complex; ferric pyrophosphate citrate: (Moderate) Orally administered zinc salts compete with iron supplements for absorption from the intestine. To minimize the interaction, separate oral iron and zinc doses by at least 2 hours. The oral receipt of 100 mg of iron as ferrous gluconate with 12 mg zinc in 11 patients with normal iron status and comparable total exchangeable zinc pools yielded a mean zinc absorption of 26.4% +/- 14.4% of the administered dose as compared with 44.5% +/- 22.5% of the dose given without concomitant iron. Concomitant use of iron 400 mg as ferrous gluconate yielded a mean zinc absorption of 22.9% +/- 6.4% of the zinc dose.
    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.
    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.
    Tetracyclines: (Major) Concurrent administration of oral zinc salts with oral tetracyclines can decrease the absorption of these antiinfectives and possibly interfere with their therapeutic response. This is a result of the formation of insoluble chelates between zinc and the antiinfective. Oral zinc supplements should be administered at least 6 hours before or 2 hours after administering 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.
    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.
    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.
    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.

    PREGNANCY AND LACTATION

    Pregnancy

    Appropriate administration and nutritional supplementation with zinc to meet nutritional requirements is not expected to cause major birth defects, miscarriage or adverse maternal or fetal outcomes during pregnancy. Animal reproduction studies have not been conducted. Deficiency of trace elements, including zinc, is associated with adverse pregnancy and fetal outcomes. During pregnancy there is an increased metabolic demand for trace elements, including zinc. Parenteral nutrition with zinc should be considered if a pregnant patient's nutritional requirements cannot be fulfilled by oral or enteral intake.[41825] [57509]

    Maternal zinc supplementation during lactation appears to have no significant effect on zinc concentrations normally found in human milk. Use of zinc supplementation within the recommended daily dietary intake for lactating women is generally recognized as safe and is not expected to cause harm to a breastfed infant. There are no data available on the effects of zinc supplementation on milk production. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition.[27966] [41825] [57509]

    MECHANISM OF ACTION

    Zinc is a component of many metalloenzymes in the human body. Serving as a cofactor, zinc is involved in such functions as synthesis or degradation of major metabolites (i.e., carbohydrates, lipids, proteins, nucleic acids), stabilization of protein and nucleic acid structure, transport processes, immune function, and expression of genetic information. Zinc is abundant in the nucleus of cells where it serves to stabilize RNA and DNA structure and is required for the activity of RNA polymerases important in cell division. Zinc is also present in the crystalline structure of bone, in bone enzymes, and at the zone of demarcation where it is thought to be important for adequate osteoblastic activity, the formation of bone enzymes (i.e., alkaline phosphatase), and calcification.[57509] [64468]
     
    Zinc deficiency is manifest in a variety of organ systems signifying the importance of the mineral for biological function and development. Clinical characterization of zinc deficiency includes growth retardation, hypogonadism and hypospermia, delayed sexual maturation, alopecia, impaired wound healing, skin lesions, immune deficiencies, behavioral disturbances, night blindness, and hypogeusia (impaired taste). Some biochemical markers of zinc deficiency include decreased plasma zinc, reduced alkaline phosphatase, low plasma testosterone, decreased retinal alcohol dehydrogenase, and decreased RNA polymerase activity in some tissues. Also, there is impaired T-lymphocyte function and decreased collagen synthesis. Zinc supplementation and adequate nutrition usually result in noticeable clinical improvement in zinc-deficient patients.[64468]
     
    Zinc blocks the intestinal absorption of copper from the diet and the reabsorption of endogenously secreted copper such as that from the saliva, gastric juice, and bile. Zinc induces the production of metallothionein in the enterocyte, a protein that binds copper thereby preventing its serosal transfer into the blood. Metallothioneins are believed to have a role in cellular antioxidant protection by scavenging free radicals. Metallothioneins bind copper with a much higher affinity than zinc; hence, the occurrence of copper deficiency with high dose zinc therapy. The bound copper is then lost in the stool following desquamation of the intestinal cells.

    PHARMACOKINETICS

    Zinc sulfate is administered orally or intravenously. Once in the systemic blood circulation, zinc is primarily bound to albumin (80%) and is transported to the liver where some is stored and the rest delivered to extrahepatic tissues. In the plasma, zinc is localized in erythrocytes and leukocytes. Plasma concentrations tend to correspond with dietary intake and physiologic factors (i.e., injury or inflammation) and drop by 50% in the acute phase response to injury probably due to the sequestering of zinc by the liver. Over 85% of total body zinc is found in skeletal muscles and bone. Other organs containing zinc include the liver, pancreas, kidney, skin, brain, heart, parts of the eye, and prostate gland. Zinc is primarily excreted via the gastrointestinal tract and eliminated in the bile. A small amount is excreted renally. Urinary excretion rates are higher in premature neonates compared to adults and decline to adult values at approximately 2 months of age. Endogenous zinc loss also occurs from hair, skin desquamation, and sweat.[57509]

    Oral Route

    Following oral administration, zinc is absorbed by diffusion and a carrier-mediated process regulated by metallothionein. The amount absorbed is controlled by the level of zinc in the diet and the presence of substances that interfere with zinc absorption. Zinc absorption is promoted by a diet rich in protein due to the formation of zinc-amino acid chelates which present zinc in a more absorbable form. High levels of zinc decrease the absorption of copper by displacing copper from metallothionein. Food and beverages have been shown to decrease the uptake of zinc, thereby decreasing the bioavailability of zinc.