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  • CLASSES

    Calcium with Other Drugs Combination Supplements
    Cough and Cold Preparations
    Zinc Supplements

    DEA CLASS

    OTC, Rx

    DESCRIPTION

    Essential trace element; zinc sulfate commonly used for nutritional supplementation or wound healing; oral zinc chloride is more nauseating; oral lozenges and intranasal zinc gluconate claimed to reduce cold symptoms, FDA recommends against use of nasal products due to the risk of permanent loss of smell; topical zinc oxide is an astringent, sunblock and protectant.

    COMMON BRAND NAMES

    Galzin, Zincate

    HOW SUPPLIED

    Galzin/Zinc/Zinc Sulfate/Zincate Oral Cap: 25mg, 50mg, 220mg
    Zinc Chloride/Zinc Sulfate Intravenous Inj Sol: 1mg, 1mL, 5mL, 25mg
    Zinc/Zinc Sulfate/Zinc Sulfate, Calcium/Zinc, Calcium Oral Tab: 50mg, 100mg, 220mg, 220-95mg, 50-16mg

    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.
    Oral dosage (zinc acetate)
    Adults

    50 mg elemental zinc PO three times per day 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.

    Adults <50 kg or pregnant or nursing females

    25 mg elemental zinc PO three times per day. May increase to 50 mg PO three times per day if needed.

    Children >= 10 yrs

    25 mg elemental zinc PO three times per day on an empty stomach.

    Children < 10 yrs

    Safety and efficacy have not been established.

    For the non-prescription treatment of Rhus dermatitis (e.g., poison ivy).
    Topical dosage (zinc acetate 2% lotions, e.g., Ivy-Dry and Super Ivy-Dry)
    Adults and Children

    Apply liberally as often as necessary. If condition worsens, or if symptoms persist for > 7 days, discontinue use. Do not use on large areas of blistered/broken skin or around the eyes.

    For the treatment of ocular inflammation.
    Ophthalmic dosage (0.217% zinc sulfate ophthalmic solution; NOTE - only available in combination with a topical vasoconstrictor [e.g., naphazoline, phenylephrine, or tetrahydrozoline])
    Adults

    Instill 2 drops of 0.217% solution into affected eye(s) 2—3 times per day.

    For the treatment of symptoms associated with the common cold†.
    Oral dosage (zinc gluconate, Cold-Eeze or zinc acetate lozenges)
    Adults

    Dissolve one 13.3 mg lozenge in mouth; do not chew. Repeat every 3—4 hours as needed. Maximum dose 6 lozenges/day. One study administered zinc or placebo within 24 hours of the onset of cold symptoms; the duration of many symptoms was significantly shorter in the zinc group. A separate study of zinc acetate lozenges produced similar results. However, a meta-analysis of all available studies 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 > 3 years

    Dissolve one 13.3 mg zinc lozenge in the mouth every 4 hours as needed. Do not chew. Maximum dosage 6 lozenges/day.

    Intranasal dosage (Zicam nasal gel spray)
    Adults, Adolescents, and Children >= 3 years

    The manufacturer recommends the following dosage; administer 1 spray to each nostril as directed every 2—4 hours until cold symptoms subside; after symptoms subside, continue use for an additional 48 hours. One multicenter study found zinc nasal gel (Zicam(TM)) effective in shortening cold symptom duration. Another study found no effect of a lower concentration zinc nasal spray (non-Zicam(TM) formulation) on the duration of common cold symptoms.

    †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.
     
    Intermittent hemodialysis
    Specific guidelines for dosage adjustments with intermittent hemodialysis are not available; it appears that no dosage adjustments are needed.

    ADMINISTRATION

    NOTE: 1 mg of elemental zinc is provided by the following: 2.8 mg zinc acetate, 2.09 mg zinc chloride, 7.14 mg zinc gluconate, and 4.4 mg zinc sulfate.
     

    Oral Administration

    Zinc is approximately 20% bioavailable after oral administration.
    Administer on an empty stomach, at least one hour before or two to three hours after meals. If stomach irritation occurs, zinc salts may be administered with food, however, the zinc will be less bioavailable.

    Oral Solid Formulations

    Zinc gluconate lozenges: Dissolve completely in the mouth, do not chew. To avoid minor upset, do not take on an empty stomach. Do not eat or drink citrus fruits or juices 30 minutes before and after dissolving the lozenge, as this will negate the effect of zinc. Otherwise drink plenty of fluids.

    Injectable Administration

    Parenteral zinc injections must be diluted prior to IV administration. Do not give undiluted zinc injections.
    Do not use injections containing benzyl alcohol in neonates.
    Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit.

    Intravenous Administration

    Intravenous infusion (zinc chloride or zinc sulfate):
    Dilute in a sufficient volume of a compatible IV infusion solution, such as an amino-acid and dextrose containing total parenteral nutritional formula (TPN), to allow administration over 8—24 hours.

    Topical Administration

    For topical dermatologic use only; do not take zinc topical formulations by mouth or get in the eyes.
    Apply liberally as often as necessary to affected area. Do not use on large areas of blistered/broken skin.

    Inhalation Administration
    Intranasal Inhalation Administration

    Have patient blow nose prior to administration.
    Prior to use of zinc nasal spray, the nasal pump must be primed by pumping several times into a clean tissue until the gel is dispensed.
    Instruct patient on proper administration technique (see Patient Information on Zicam package).
    For nasal use only. Take care to avoid accidental contact with eyes.
    After administration, wipe the tip of the bottle with a clean tissue. Replace the cap right after cleaning. Replace the safety clip.
    To avoid the spread of infection, do not use the container for more than one person.
    If the nasal pump is not used for >= 10 days, it must be reprimed.

    Ophthalmic Administration

    Zinc ophthalmic products are for ophthalmic use only.
    Instruct patient on the proper instillation technique (see Patient Information).
    Do not to touch the tip of the dropper to the eye, fingertips, or other surface.
    To avoid the spread of infection, do not use the container for more than one person.

    STORAGE

    Generic:
    - Store in a cool, dry place
    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 :
    - Avoid excessive heat (above 104 degrees F)
    - Store at room temperature (between 59 to 86 degrees F)
    - Store in a dry place

    CONTRAINDICATIONS / PRECAUTIONS

    Pregnancy

    Parenteral zinc salts are classified as pregnancy category C. No adequate and well-controlled trials in pregnant women have been performed with parenteral zinc. Exercise caution when using parenteral zinc supplementation during pregnancy. Adverse effects have not been reported with the normal daily intake of zinc within the recommended dietary daily intakes for a pregnant female. Galzin (oral zinc acetate) studies conducted in the US for Wilson's disease included 19 symptomatic and presymptomatic women who became pregnant and continued treatment; these women delivered 26 live birth babies. At the time of delivery, the duration of zinc acetate therapy had ranged from 0.7 to 13.7 years and all patients were using zinc acetate within the normally recommended dosage ranges. Measurement of urinary copper excretion indicated adequate control of copper levels in most patients before and during pregnancy. The results also indicated that during pregnancy, the mothers' health was protected by zinc acetate therapy, and no adverse effects on liver or neurological functions were reported. Limited pregnancy outcome data indicates an incidence of miscarriages consistent with those in the general population. In a separate double-blind study, 580 African-American pregnant women with low plasma zinc levels were randomized to receive daily doses of either zinc 25 mg or placebo until delivery. Higher infant birth weights and larger infant head circumferences were observed in newborns of women receiving zinc supplementation and with a body mass index (BMI) of less than 26 kg/m2.

    Breast-feeding

    Maternal zinc supplementation during lactation appears to have no significant effect on zinc concentrations normally found in human milk. Use of zinc salts within the recommended daily dietary intake for lactating women is generally recognized as safe. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. If a breast-feeding infant experiences an adverse effect related to a maternally administered drug, healthcare providers are encouraged to report the adverse effect to the FDA.

    Hypocupremia

    Zinc supplementation can interfere with the absorption of copper. Administration of zinc to patients with hypocupremia (copper deficiency) can further decrease serum copper levels.

    Neonates, premature neonates, renal failure, renal impairment

    Zinc Chloride injection contains aluminum which may reach toxic levels with prolonged administration in patients with renal impairment or renal failure. Premature neonates are at particular risk for aluminum toxicity following administration of aluminum-containing injectables since they have immature kidneys. Research indicates that patients with renal impairment, including neonates, who receive parenteral aluminum at rates greater than 4—5 mcg/kg/day may accumulate aluminum at levels associated with CNS and bone toxicity. Tissue loading may occur at lower administration rates.

    ADVERSE REACTIONS

    Severe

    sideroblastic anemia / Delayed / Incidence not known

    Moderate

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

    Mild

    nausea / Early / Incidence not known
    abdominal pain / Early / Incidence not known
    vomiting / Early / Incidence not known
    dyspepsia / 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 cation-containing antacids. The chemical structure of these antacids contain either magnesium or aluminum which can bind dolutegravir in the GI tract. Taking these drugs simultaneously may result in reduced bioavailability of dolutegravir.
    Aliskiren; Amlodipine; Hydrochlorothiazide, HCTZ: (Moderate) The simultaneous administration of thiazide diuretics and calcium salts or calcium carbonate may lead to hypercalcemia. Thiazides cause a decrease in renal tubular excretion of calcium as well as increase in distal tubular reabsorption. Moderate increases in serum calcium have been seen during the treatment with thiazides; if calcium salts are used concomitantly, careful monitoring of serum calcium in recommended.
    Aliskiren; Hydrochlorothiazide, HCTZ: (Moderate) The simultaneous administration of thiazide diuretics and calcium salts or calcium carbonate may lead to hypercalcemia. Thiazides cause a decrease in renal tubular excretion of calcium as well as increase in distal tubular reabsorption. Moderate increases in serum calcium have been seen during the treatment with thiazides; if calcium salts are used concomitantly, careful monitoring of serum calcium in recommended.
    Amiloride; Hydrochlorothiazide, HCTZ: (Moderate) The simultaneous administration of thiazide diuretics and calcium salts or calcium carbonate may lead to hypercalcemia. Thiazides cause a decrease in renal tubular excretion of calcium as well as increase in distal tubular reabsorption. Moderate increases in serum calcium have been seen during the treatment with thiazides; if calcium salts are used concomitantly, careful monitoring of serum calcium in recommended.
    Amlodipine; Hydrochlorothiazide, HCTZ; Olmesartan: (Moderate) The simultaneous administration of thiazide diuretics and calcium salts or calcium carbonate may lead to hypercalcemia. Thiazides cause a decrease in renal tubular excretion of calcium as well as increase in distal tubular reabsorption. Moderate increases in serum calcium have been seen during the treatment with thiazides; if calcium salts are used concomitantly, careful monitoring of serum calcium in recommended.
    Amlodipine; Hydrochlorothiazide, HCTZ; Valsartan: (Moderate) The simultaneous administration of thiazide diuretics and calcium salts or calcium carbonate may lead to hypercalcemia. Thiazides cause a decrease in renal tubular excretion of calcium as well as increase in distal tubular reabsorption. Moderate increases in serum calcium have been seen during the treatment with thiazides; if calcium salts are used concomitantly, careful monitoring of serum calcium in recommended.
    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) The simultaneous administration of thiazide diuretics and calcium salts or calcium carbonate may lead to hypercalcemia. Thiazides cause a decrease in renal tubular excretion of calcium as well as increase in distal tubular reabsorption. Moderate increases in serum calcium have been seen during the treatment with thiazides; if calcium salts are used concomitantly, careful monitoring of serum calcium in recommended. (Minor) Calcium antacids (e.g., calcium carbonate) and supplements (e.g., other oral calcium salts) have been reported to reduce the mean peak concentrations by 51% and the AUC of atenolol by 32%. In another study, antacids reduced the AUC of atenolol by 33%. Separate doses of atenolol and calcium-containing antacids or supplements by at least 2 hours to minimize this potential interaction,. However, most clinicians consider the interaction of atenolol with antacids to be of minor clinical significance, since clinical efficacy (heart rate and blood pressure parameters) appear to be unchanged under usual intermittent clinical use.
    Atracurium: (Moderate) Calcium salts may antagonize the effects of nondepolarizing neuromuscular blockers.
    Azelaic Acid; Copper; Folic Acid; Nicotinamide; Pyridoxine; Zinc: (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.
    Azilsartan; Chlorthalidone: (Moderate) The simultaneous administration of thiazide diuretics and calcium salts or calcium carbonate may lead to hypercalcemia. Thiazides cause a decrease in renal tubular excretion of calcium as well as increase in distal tubular reabsorption. Moderate increases in serum calcium have been seen during the treatment with thiazides; if calcium salts are used concomitantly, careful monitoring of serum calcium in recommended.
    Benazepril; Hydrochlorothiazide, HCTZ: (Moderate) The simultaneous administration of thiazide diuretics and calcium salts or calcium carbonate may lead to hypercalcemia. Thiazides cause a decrease in renal tubular excretion of calcium as well as increase in distal tubular reabsorption. Moderate increases in serum calcium have been seen during the treatment with thiazides; if calcium salts are used concomitantly, careful monitoring of serum calcium in recommended.
    Bendroflumethiazide; Nadolol: (Moderate) The simultaneous administration of thiazide diuretics and calcium salts or calcium carbonate may lead to hypercalcemia. Thiazides cause a decrease in renal tubular excretion of calcium as well as increase in distal tubular reabsorption. Moderate increases in serum calcium have been seen during the treatment with thiazides; if calcium salts are used concomitantly, careful monitoring of serum calcium in recommended.
    Beta-Carotene: (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.
    Betamethasone; 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).
    Bisoprolol; Hydrochlorothiazide, HCTZ: (Moderate) The simultaneous administration of thiazide diuretics and calcium salts or calcium carbonate may lead to hypercalcemia. Thiazides cause a decrease in renal tubular excretion of calcium as well as increase in distal tubular reabsorption. Moderate increases in serum calcium have been seen during the treatment with thiazides; if calcium salts are used concomitantly, careful monitoring of serum calcium in recommended.
    Bisphosphonates: (Moderate) Separating times of administration of the oral bisphosphonate from calcium-containing supplements and medications will maximize absorption and clinical benefit. Calcium will interfere with the absorption of the orally administered bisphosphonates alendronate, etidronate, ibandronate, risedronate, and tiludronate. At least 30 minutes should elapse after the oral administration of alendronate before taking any calcium containing product. At least 1 hour should elapse after the oral administration of ibandronate before taking any calcium containing product. At least 2 hours should elapse after the oral administration of etidronate, risedronate, or tiludronate before administering any calcium containing product.
    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).
    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.
    Candesartan; Hydrochlorothiazide, HCTZ: (Moderate) The simultaneous administration of thiazide diuretics and calcium salts or calcium carbonate may lead to hypercalcemia. Thiazides cause a decrease in renal tubular excretion of calcium as well as increase in distal tubular reabsorption. Moderate increases in serum calcium have been seen during the treatment with thiazides; if calcium salts are used concomitantly, careful monitoring of serum calcium in recommended.
    Captopril; Hydrochlorothiazide, HCTZ: (Moderate) The simultaneous administration of thiazide diuretics and calcium salts or calcium carbonate may lead to hypercalcemia. Thiazides cause a decrease in renal tubular excretion of calcium as well as increase in distal tubular reabsorption. Moderate increases in serum calcium have been seen during the treatment with thiazides; if calcium salts are used concomitantly, careful monitoring of serum calcium in recommended.
    Cardiac glycosides: (Major) Calcium salts augment the actions of digoxin. In addition, when calcium is administered via rapid intravenous injection, the risk of serious arrhythmias in digitalized patients is increased. It is recommended that serum calcium be monitored regularly in patients receiving digoxin.
    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) The simultaneous administration of thiazide diuretics and calcium salts or calcium carbonate may lead to hypercalcemia. Thiazides cause a decrease in renal tubular excretion of calcium as well as increase in distal tubular reabsorption. Moderate increases in serum calcium have been seen during the treatment with thiazides; if calcium salts are used concomitantly, careful monitoring of serum calcium in recommended.
    Chlorthalidone: (Moderate) The simultaneous administration of thiazide diuretics and calcium salts or calcium carbonate may lead to hypercalcemia. Thiazides cause a decrease in renal tubular excretion of calcium as well as increase in distal tubular reabsorption. Moderate increases in serum calcium have been seen during the treatment with thiazides; if calcium salts are used concomitantly, careful monitoring of serum calcium in recommended.
    Chlorthalidone; Clonidine: (Moderate) The simultaneous administration of thiazide diuretics and calcium salts or calcium carbonate may lead to hypercalcemia. Thiazides cause a decrease in renal tubular excretion of calcium as well as increase in distal tubular reabsorption. Moderate increases in serum calcium have been seen during the treatment with thiazides; if calcium salts are used concomitantly, careful monitoring of serum calcium in recommended.
    Ciprofloxacin: (Major) 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. (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.
    Cisatracurium: (Moderate) Calcium salts may antagonize the effects of nondepolarizing neuromuscular blockers.
    Cod Liver Oil: (Moderate) Concomitant cod liver oil and calcium supplementation should be undertaken with caution. The vitamin D contained within cod liver oil can increase serum calcium concentrations; the combination may result in hypercalcemia. Additionally, doses in excess of 1,500 to 2,000 mcg/day of vitamin A may lead to bone loss and can counteract the effects of supplementation with calcium salts. (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.
    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.
    Cyanocobalamin, Vitamin B12: (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.
    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.
    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 cation-containing antacids. The chemical structure of these antacids contain either magnesium or aluminum which can bind dolutegravir in the GI tract. Taking these drugs simultaneously may result in reduced bioavailability of dolutegravir.
    Doxacurium: (Moderate) Calcium salts may antagonize the neuromuscular blocking effects of doxacurium.
    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.
    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.
    Enalapril; Hydrochlorothiazide, HCTZ: (Moderate) The simultaneous administration of thiazide diuretics and calcium salts or calcium carbonate may lead to hypercalcemia. Thiazides cause a decrease in renal tubular excretion of calcium as well as increase in distal tubular reabsorption. Moderate increases in serum calcium have been seen during the treatment with thiazides; if calcium salts are used concomitantly, careful monitoring of serum calcium in recommended.
    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) The simultaneous administration of thiazide diuretics and calcium salts or calcium carbonate may lead to hypercalcemia. Thiazides cause a decrease in renal tubular excretion of calcium as well as increase in distal tubular reabsorption. Moderate increases in serum calcium have been seen during the treatment with thiazides; if calcium salts are used concomitantly, careful monitoring of serum calcium in recommended.
    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.
    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.
    Ethanol: (Minor) Chronic ethanol consumption can result in deficiency of several nutrients. These include zinc salts. Patients with chronic alcoholism should receive vitamin supplementation.
    Ethinyl Estradiol: (Minor) Estrogens can increase calcium absorption. Use caution in patients predisposed to hypercalcemia or nephrolithiasis.
    Ethinyl Estradiol; Desogestrel: (Minor) Estrogens can increase calcium absorption. Use caution in patients predisposed to hypercalcemia or nephrolithiasis.
    Ethinyl Estradiol; Ethynodiol Diacetate: (Minor) Estrogens can increase calcium absorption. Use caution in patients predisposed to hypercalcemia or nephrolithiasis.
    Ethinyl Estradiol; Etonogestrel: (Minor) Estrogens can increase calcium absorption. Use caution in patients predisposed to hypercalcemia or nephrolithiasis.
    Ethinyl Estradiol; Levonorgestrel: (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; Norethindrone Acetate; 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.
    Ethinyl Estradiol; Norethindrone: (Minor) Estrogens can increase calcium absorption. Use caution in patients predisposed to hypercalcemia or nephrolithiasis.
    Ethinyl Estradiol; Norethindrone; 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.
    Ethinyl Estradiol; Norgestimate: (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.
    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) The simultaneous administration of thiazide diuretics and calcium salts or calcium carbonate may lead to hypercalcemia. Thiazides cause a decrease in renal tubular excretion of calcium as well as increase in distal tubular reabsorption. Moderate increases in serum calcium have been seen during the treatment with thiazides; if calcium salts are used concomitantly, careful monitoring of serum calcium in recommended.
    Gallium: (Moderate) Concurrent administration products containing calcium salts may antagonize the effects of gallium nitrate.
    Gemifloxacin: (Major) Administer oral products that contain calcium at least 2 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 antacids and multivitamins that contain calcium. (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) The simultaneous administration of thiazide diuretics and calcium salts or calcium carbonate may lead to hypercalcemia. Thiazides cause a decrease in renal tubular excretion of calcium as well as increase in distal tubular reabsorption. Moderate increases in serum calcium have been seen during the treatment with thiazides; if calcium salts are used concomitantly, careful monitoring of serum calcium in recommended.
    Hydrochlorothiazide, HCTZ: (Moderate) The simultaneous administration of thiazide diuretics and calcium salts or calcium carbonate may lead to hypercalcemia. Thiazides cause a decrease in renal tubular excretion of calcium as well as increase in distal tubular reabsorption. Moderate increases in serum calcium have been seen during the treatment with thiazides; if calcium salts are used concomitantly, careful monitoring of serum calcium in recommended.
    Hydrochlorothiazide, HCTZ; Irbesartan: (Moderate) The simultaneous administration of thiazide diuretics and calcium salts or calcium carbonate may lead to hypercalcemia. Thiazides cause a decrease in renal tubular excretion of calcium as well as increase in distal tubular reabsorption. Moderate increases in serum calcium have been seen during the treatment with thiazides; if calcium salts are used concomitantly, careful monitoring of serum calcium in recommended.
    Hydrochlorothiazide, HCTZ; Lisinopril: (Moderate) The simultaneous administration of thiazide diuretics and calcium salts or calcium carbonate may lead to hypercalcemia. Thiazides cause a decrease in renal tubular excretion of calcium as well as increase in distal tubular reabsorption. Moderate increases in serum calcium have been seen during the treatment with thiazides; if calcium salts are used concomitantly, careful monitoring of serum calcium in recommended.
    Hydrochlorothiazide, HCTZ; Losartan: (Moderate) The simultaneous administration of thiazide diuretics and calcium salts or calcium carbonate may lead to hypercalcemia. Thiazides cause a decrease in renal tubular excretion of calcium as well as increase in distal tubular reabsorption. Moderate increases in serum calcium have been seen during the treatment with thiazides; if calcium salts are used concomitantly, careful monitoring of serum calcium in recommended.
    Hydrochlorothiazide, HCTZ; Methyldopa: (Moderate) The simultaneous administration of thiazide diuretics and calcium salts or calcium carbonate may lead to hypercalcemia. Thiazides cause a decrease in renal tubular excretion of calcium as well as increase in distal tubular reabsorption. Moderate increases in serum calcium have been seen during the treatment with thiazides; if calcium salts are used concomitantly, careful monitoring of serum calcium in recommended.
    Hydrochlorothiazide, HCTZ; Metoprolol: (Moderate) The simultaneous administration of thiazide diuretics and calcium salts or calcium carbonate may lead to hypercalcemia. Thiazides cause a decrease in renal tubular excretion of calcium as well as increase in distal tubular reabsorption. Moderate increases in serum calcium have been seen during the treatment with thiazides; if calcium salts are used concomitantly, careful monitoring of serum calcium in recommended.
    Hydrochlorothiazide, HCTZ; Moexipril: (Moderate) The simultaneous administration of thiazide diuretics and calcium salts or calcium carbonate may lead to hypercalcemia. Thiazides cause a decrease in renal tubular excretion of calcium as well as increase in distal tubular reabsorption. Moderate increases in serum calcium have been seen during the treatment with thiazides; if calcium salts are used concomitantly, careful monitoring of serum calcium in recommended.
    Hydrochlorothiazide, HCTZ; Olmesartan: (Moderate) The simultaneous administration of thiazide diuretics and calcium salts or calcium carbonate may lead to hypercalcemia. Thiazides cause a decrease in renal tubular excretion of calcium as well as increase in distal tubular reabsorption. Moderate increases in serum calcium have been seen during the treatment with thiazides; if calcium salts are used concomitantly, careful monitoring of serum calcium in recommended.
    Hydrochlorothiazide, HCTZ; Propranolol: (Moderate) The simultaneous administration of thiazide diuretics and calcium salts or calcium carbonate may lead to hypercalcemia. Thiazides cause a decrease in renal tubular excretion of calcium as well as increase in distal tubular reabsorption. Moderate increases in serum calcium have been seen during the treatment with thiazides; if calcium salts are used concomitantly, careful monitoring of serum calcium in recommended.
    Hydrochlorothiazide, HCTZ; Quinapril: (Moderate) The simultaneous administration of thiazide diuretics and calcium salts or calcium carbonate may lead to hypercalcemia. Thiazides cause a decrease in renal tubular excretion of calcium as well as increase in distal tubular reabsorption. Moderate increases in serum calcium have been seen during the treatment with thiazides; if calcium salts are used concomitantly, careful monitoring of serum calcium in recommended.
    Hydrochlorothiazide, HCTZ; Spironolactone: (Moderate) The simultaneous administration of thiazide diuretics and calcium salts or calcium carbonate may lead to hypercalcemia. Thiazides cause a decrease in renal tubular excretion of calcium as well as increase in distal tubular reabsorption. Moderate increases in serum calcium have been seen during the treatment with thiazides; if calcium salts are used concomitantly, careful monitoring of serum calcium in recommended.
    Hydrochlorothiazide, HCTZ; Telmisartan: (Moderate) The simultaneous administration of thiazide diuretics and calcium salts or calcium carbonate may lead to hypercalcemia. Thiazides cause a decrease in renal tubular excretion of calcium as well as increase in distal tubular reabsorption. Moderate increases in serum calcium have been seen during the treatment with thiazides; if calcium salts are used concomitantly, careful monitoring of serum calcium in recommended.
    Hydrochlorothiazide, HCTZ; Triamterene: (Moderate) The simultaneous administration of thiazide diuretics and calcium salts or calcium carbonate may lead to hypercalcemia. Thiazides cause a decrease in renal tubular excretion of calcium as well as increase in distal tubular reabsorption. Moderate increases in serum calcium have been seen during the treatment with thiazides; if calcium salts are used concomitantly, careful monitoring of serum calcium in recommended.
    Hydrochlorothiazide, HCTZ; Valsartan: (Moderate) The simultaneous administration of thiazide diuretics and calcium salts or calcium carbonate may lead to hypercalcemia. Thiazides cause a decrease in renal tubular excretion of calcium as well as increase in distal tubular reabsorption. Moderate increases in serum calcium have been seen during the treatment with thiazides; if calcium salts are used concomitantly, careful monitoring of serum calcium in recommended.
    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.
    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 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. (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.
    Mestranol; Norethindrone: (Minor) Estrogens can increase calcium absorption. Use caution in patients predisposed to hypercalcemia or nephrolithiasis.
    Methyclothiazide: (Moderate) The simultaneous administration of thiazide diuretics and calcium salts or calcium carbonate may lead to hypercalcemia. Thiazides cause a decrease in renal tubular excretion of calcium as well as increase in distal tubular reabsorption. Moderate increases in serum calcium have been seen during the treatment with thiazides; if calcium salts are used concomitantly, careful monitoring of serum calcium in recommended.
    Metolazone: (Moderate) The simultaneous administration of thiazide diuretics and calcium salts or calcium carbonate may lead to hypercalcemia. Thiazides cause a decrease in renal tubular excretion of calcium as well as increase in distal tubular reabsorption. Moderate increases in serum calcium have been seen during the treatment with thiazides; if calcium salts are used concomitantly, careful monitoring of serum calcium in recommended.
    Mivacurium: (Moderate) Calcium salts may antagonize the neuromuscular blocking effects of mivacurium.
    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.
    Norfloxacin: (Major) Administer oral products that contain calcium at least 2 hours before or 2 hours after norfloxacin. Norfloxacin 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 products that contain zinc at least 2 hours before or 2 hours after norfloxacin. Norfloxacin 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.
    Ofloxacin: (Major) 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. (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.
    Omeprazole; Sodium Bicarbonate: (Minor) Prolonged use of sodium bicarbonate along with calcium carbonate may result in milk-alkali syndrome.
    Pancuronium: (Moderate) Calcium salts usually reverse the effects of nondepolarizing neuromuscular blocking agents such as pancuronium.
    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 Salts: (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; 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.
    Rocuronium: (Moderate) Calcium salts may antagonize the effects of nondepolarizing neuromuscular blockers, such as rocuronium.
    Sodium Bicarbonate: (Minor) Prolonged use of sodium bicarbonate along with calcium carbonate may result in milk-alkali syndrome.
    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.
    Succinylcholine: (Moderate) Calcium salts may antagonize the effects of nondepolarizing neuromuscular blockers.
    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. (Major) 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) The simultaneous administration of thiazide diuretics and calcium salts or calcium carbonate may lead to hypercalcemia. Thiazides cause a decrease in renal tubular excretion of calcium as well as increase in distal tubular reabsorption. Moderate increases in serum calcium have been seen during the treatment with thiazides; if calcium salts are used concomitantly, careful monitoring of serum calcium in recommended.
    Thyroid hormones: (Major) 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. To avoid the interaction, thyroid hormones should be administered at least 4 hours before or after ingestion of oral calcium supplements.
    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.
    Tubocurarine: (Moderate) Calcium salts may antagonize the effects of nondepolarizing neuromuscular blockers.
    Vecuronium: (Moderate) Calcium salts may antagonize the effects of nondepolarizing neuromuscular 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) Dose adjustment of vitamin D analogs may be necessary during coadministration with calcium salts. Additionally, serum calcium concentrations should be monitored frequently. Monitor more frequently in patients with a history of hypercalcemia. Hypercalcemia may be exacerbated by coadministration of vitamin D analogs and high doses of calcium-containing salts.

    PREGNANCY AND LACTATION

    Pregnancy

    Parenteral zinc salts are classified as pregnancy category C. No adequate and well-controlled trials in pregnant women have been performed with parenteral zinc. Exercise caution when using parenteral zinc supplementation during pregnancy. Adverse effects have not been reported with the normal daily intake of zinc within the recommended dietary daily intakes for a pregnant female. Galzin (oral zinc acetate) studies conducted in the US for Wilson's disease included 19 symptomatic and presymptomatic women who became pregnant and continued treatment; these women delivered 26 live birth babies. At the time of delivery, the duration of zinc acetate therapy had ranged from 0.7 to 13.7 years and all patients were using zinc acetate within the normally recommended dosage ranges. Measurement of urinary copper excretion indicated adequate control of copper levels in most patients before and during pregnancy. The results also indicated that during pregnancy, the mothers' health was protected by zinc acetate therapy, and no adverse effects on liver or neurological functions were reported. Limited pregnancy outcome data indicates an incidence of miscarriages consistent with those in the general population. In a separate double-blind study, 580 African-American pregnant women with low plasma zinc levels were randomized to receive daily doses of either zinc 25 mg or placebo until delivery. Higher infant birth weights and larger infant head circumferences were observed in newborns of women receiving zinc supplementation and with a body mass index (BMI) of less than 26 kg/m2.

    Maternal zinc supplementation during lactation appears to have no significant effect on zinc concentrations normally found in human milk. Use of zinc salts within the recommended daily dietary intake for lactating women is generally recognized as safe. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. If a breast-feeding infant experiences an adverse effect related to a maternally administered drug, healthcare providers are encouraged to report the adverse effect to the FDA.

    MECHANISM OF ACTION

    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, formation of bone enzymes (i.e., alkaline phosphatase), and calcification.Topically administered zinc acts as an astringent and weak antiseptic. These actions are thought to be mediated by precipitation of proteins by zinc ions. Topical zinc salts include zinc chloride, zinc stearate, zinc oxide, zinc acetate, and zinc sulfate. In addition to its astringent and antiseptic effects, zinc sulfate administered as an ophthalmic solution also aids in the clearance of mucous from the outer surface of the eye and produces mild vasodilatation, however, it does not have any decongestant activity.To reduce the duration of symptoms of the common cold, oral lozenges of zinc gluconate have been beneficial. It is thought that zinc prevents rhinovirus particles from entering cells by combining with the carboxyl termini of rhinovirus coat proteins. This inhibits further virus reproduction. Zinc may also exert its antiviral effects, in part, by stabilizing and protecting cellular membranes. Cold symptom relief may be explained by an inhibitory effect of zinc ions on prostaglandin metabolism. There is still much debate on the mechanism and efficacy of zinc in treating the common cold.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 results in noticeable clinical improvement in zinc deficient patients.Non-enzymatic proteins called metallothioneins contain large amounts of zinc. The exact role of zinc in metallothionein function is not known, however, administration of zinc stimulates the production of metallothioneins. 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 use of zinc acetate in treating Wilson's disease and the occurrence of copper deficiency with high dose zinc therapy. In treating Wilson's disease, zinc acetate interferes with copper absorption/reabsorption from the gut by inducing the production of metallothionein in the enterocyte, thereby preventing the serosal transfer of copper into the blood. The protein-bound copper is then excreted in the stool following desquamation of intestinal cells.

    PHARMACOKINETICS

    Zinc supplementation may be administered orally or parenterally. Once in the systemic blood circulation, zinc is primarily bound to albumin 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. Tissue distribution of zinc is highest for the liver, pancreas, kidney, bone, and voluntary muscles. High concentrations also occur in parts of the eye, skin, hair, fingernails, toenails, prostate gland, and spermatozoa. Up to 25% of the daily loss is via biliary and pancreatic secretions.

    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.