vitamin A (OTC)

Brand and Other Names:Retinol, Aquasol A, more...retinyl acetate, retinyl palmitate
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Dosing & Uses

AdultPediatric

Dosage Forms & Strengths

capsule

  • 7,500 U
  • 8000 U
  • 10,000 U
  • 25,000 U

injectable solution

  • 50,000 U/mL

tablet

  • 10,000 U
  • 15,000 U

RDA

Described as retinol activity equivalent (RAE)

1 RAE = Retinol 1 mcg

Males: 900 mcg/day (3000 U/day)

Females

  • 700 mcg/day (2330 U/day)
  • >18 years pregnant: 750-770 mcg/day (2500-2600 U/day)
  • >18 years breastfeeding: 1300 mcg RAE (4330 U)

Upper Intake Levels

>18 years: 3000 mcg/day RAE (10,000 U)

Pregnancy: 3000 mcg/day RAE (10,000 U)

Lactation: 3000 mcg/day RAE (10,000 U)

Vitamin A Deficiency

Malabsorption or oral administration not feasible: 100,000 U/day IM for 3 days; then 50,000 U/day for 2 weeks; follow with oral therapy.

Oral therapy: Take oral therapeutic multivitamin containing 10,000-20,000 U/day vitamin A for 2 months

Deficiency prophylaxis: 10,000-50,000 U PO qDay

Xerophthalmia (Off-label)

Recommended dose except for females of reproductive age: 200,000 units PO qDay for 2 days; repeat dose again after 2 weeks

Females of reproductive age with night blindness or Bitot's spots: 5000-10,000 units/day; 10,000 units/day maximum or ≤25,000 units once weekly for ≥4 weeks

Bronchopulmonary Dysplasia (Orphan)

Orphan designation of vitamin A palmitate for prevention of bronchopulmonary dysplasia

Sponsors

  • Fox Pharma, Inc; 6097 Hidden Valley Drive; Doylestown, PA 18902
  • Advent Therapeutics, Inc; 6500 Old Carversville Road; Lumberville, PA 18933-9729

Dosage Forms & Strengths

capsule

  • 7,500 U
  • 8,000 U
  • 10,000 U
  • 25,000 U

injectable solution

  • 50,000 U/mL

tablet

  • 10,000 U
  • 15,000 U

RDA

0-6 months: 400 mcg/day RAE (1333 U/day)

6-12 months: 500 mcg/day RAE (1666 U/day)

1-3 years: 300 mcg/day RAE (1000 U/day)

3-8 years: 400 mcg/day RAE (1333 U/day)

8-13 years: 600 mcg/day RAE (2000 U/day)

13-18 years: 900 mcg/day RAE (3000 U/day)

Upper Intake Levels

0-3 years: 600/day mcg RAE (2000 U/day)

3-8 years: 900/day mcg RAE (3000 U/day)

8-13 years: 1700 mcg/day RAE (5667 U/day)

13-18 years: 2800 mcg/day RAE (9333 U/day)

13-18 years pregnant: 2800 mcg/day RAE (9333 U/day)

13-18 years breastfeeding: 2800 mcg/day RAE (9333 U/day)

Deficiency

Use IM route when oral administraiton is not possible or in malabsorption syndrome

Infants: 7500-15000 units/day for 10 days

1-8 years: 17,500-35,000 units/day for 10 days

>8 years

  • Malabsorption or oral administration not feasible: 100,000 U/day IM for 3 days; then 50,000 U/day for 2 weeks; follow with oral therapy.
  • Oral therapy: Take oral therapeutic multivitamin containing 10,000-20,000 U/day vitamin A for 2 months
  • Deficiency prophylaxis: 10,000-50,000 U PO qDay

Xerophthalmia

<6 months: 50,000 units qDay for 2 days; repeat once with single dose after 2 weeks

6-12 months: 100,000 units qDay for 2 days; repeat with single dose after 2 weeks

>1 year except females of reproductive age: 200,000 units qDay for 2 days; repeat with single dose after 2 weeks

Females of reproductive age with night blindness or Bitot's spots: 5000-10,000 units/day; 10,000 units/day maximum or ≤25,000 units once weekly for ≥4 weeks

Retinopathy of Prematurity (Orphan)

Retinol palmitate

Orphan designation for prevention of retinopathy of prematurity (ROP)

Sponsor

  • Orphanix GmbH; 41 Peter-Rosegger-Strabe; Ried im Innkreis; Austria
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Interactions

Interaction Checker

and vitamin A

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    Interactions Found

    Contraindicated

      Serious - Use Alternative

        Significant - Monitor Closely

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            Contraindicated (0)

              Serious - Use Alternative (2)

              • pexidartinib

                vitamin A and pexidartinib both increase Other (see comment). Avoid or Use Alternate Drug. Pexidartinib can cause hepatotoxicity. Avoid coadministration of pexidartinib with other products know to cause hepatoxicity.

              • pretomanid

                vitamin A, pretomanid. Either increases toxicity of the other by Other (see comment). Avoid or Use Alternate Drug. Comment: Pretomanid regimen associated with hepatotoxicity. Avoid alcohol and hepatotoxic agents, including herbal supplements and drugs other than bedaquiline and linezolid.

              Monitor Closely (6)

              • beta carotene

                vitamin A, beta carotene. Either increases levels of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Administration of beta-carotene with vitamin A usually is not necessary and should be avoided to prevent the development of hypervitaminosis A.

              • bexarotene

                bexarotene increases toxicity of vitamin A by pharmacodynamic synergism. Use Caution/Monitor. (Vitamin A) Additive retinoid effects. Avoid consuming vitamin-A containing supplements in amounts exceeding FDA recommended daily allowance.

              • dichlorphenamide

                dichlorphenamide, vitamin A. Either increases toxicity of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Both drugs can cause metabolic acidosis.

              • etretinate

                etretinate increases toxicity of vitamin A by pharmacodynamic synergism. Use Caution/Monitor. (Vitamin A) Additive retinoid effects.

              • isotretinoin

                isotretinoin increases toxicity of vitamin A by pharmacodynamic synergism. Use Caution/Monitor. (Vitamin A) Additive retinoid effects.

              • mipomersen

                mipomersen, vitamin A. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: Both drugs have potential to increase hepatic enzymes; monitor LFTs.

              Minor (45)

              • acitretin

                acitretin increases toxicity of vitamin A by pharmacodynamic synergism. Minor/Significance Unknown. (Vitamin A) Additive retinoid effects.

              • busulfan

                vitamin A, busulfan. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Antioxidants such as vitamin A enhance the efficacy, and reduce toxicity, of antineoplastic drugs.

              • capecitabine

                vitamin A, capecitabine. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Antioxidants such as vitamin A enhance the efficacy, and reduce toxicity, of antineoplastic drugs.

              • carboplatin

                vitamin A, carboplatin. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Antioxidants such as vitamin A enhance the efficacy, and reduce toxicity, of antineoplastic drugs.

              • carmustine

                vitamin A, carmustine. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Antioxidants such as vitamin A enhance the efficacy, and reduce toxicity, of antineoplastic drugs.

              • chitosan

                chitosan decreases levels of vitamin A by inhibition of GI absorption. Applies only to oral form of both agents. Minor/Significance Unknown.

              • chlorambucil

                vitamin A, chlorambucil. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Antioxidants such as vitamin A enhance the efficacy, and reduce toxicity, of antineoplastic drugs.

              • cholestyramine

                cholestyramine decreases levels of vitamin A by inhibition of GI absorption. Applies only to oral form of both agents. Minor/Significance Unknown. (Vitamin A).

              • cisplatin

                vitamin A, cisplatin. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Antioxidants such as vitamin A enhance the efficacy, and reduce toxicity, of antineoplastic drugs.

              • cladribine

                vitamin A, cladribine. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Antioxidants such as vitamin A enhance the efficacy, and reduce toxicity, of antineoplastic drugs.

              • colestipol

                colestipol decreases levels of vitamin A by inhibition of GI absorption. Applies only to oral form of both agents. Minor/Significance Unknown. (Vitamin A).

              • cytarabine

                vitamin A, cytarabine. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Antioxidants such as vitamin A enhance the efficacy, and reduce toxicity, of antineoplastic drugs.

              • dacarbazine

                vitamin A, dacarbazine. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Antioxidants such as vitamin A enhance the efficacy, and reduce toxicity, of antineoplastic drugs.

              • decitabine

                vitamin A, decitabine. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Antioxidants such as vitamin A enhance the efficacy, and reduce toxicity, of antineoplastic drugs.

              • docetaxel

                vitamin A, docetaxel. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Antioxidants such as vitamin A enhance the efficacy, and reduce toxicity, of antineoplastic drugs.

              • floxuridine

                vitamin A, floxuridine. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Antioxidants such as vitamin A enhance the efficacy, and reduce toxicity, of antineoplastic drugs.

              • fludarabine

                vitamin A, fludarabine. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Antioxidants such as vitamin A enhance the efficacy, and reduce toxicity, of antineoplastic drugs.

              • fluorouracil

                vitamin A, fluorouracil. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Antioxidants such as vitamin A enhance the efficacy, and reduce toxicity, of antineoplastic drugs.

              • gemcitabine

                vitamin A, gemcitabine. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Antioxidants such as vitamin A enhance the efficacy, and reduce toxicity, of antineoplastic drugs.

              • ifosfamide

                vitamin A, ifosfamide. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Antioxidants such as vitamin A enhance the efficacy, and reduce toxicity, of antineoplastic drugs.

              • irinotecan

                vitamin A, irinotecan. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Antioxidants such as vitamin A enhance the efficacy, and reduce toxicity, of antineoplastic drugs.

              • irinotecan liposomal

                vitamin A, irinotecan liposomal. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Antioxidants such as vitamin A enhance the efficacy, and reduce toxicity, of antineoplastic drugs.

              • lomustine

                vitamin A, lomustine. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Antioxidants such as vitamin A enhance the efficacy, and reduce toxicity, of antineoplastic drugs.

              • mechlorethamine

                vitamin A, mechlorethamine. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Antioxidants such as vitamin A enhance the efficacy, and reduce toxicity, of antineoplastic drugs.

              • melphalan

                vitamin A, melphalan. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Antioxidants such as vitamin A enhance the efficacy, and reduce toxicity, of antineoplastic drugs.

              • mercaptopurine

                vitamin A, mercaptopurine. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Antioxidants such as vitamin A enhance the efficacy, and reduce toxicity, of antineoplastic drugs.

              • mineral oil

                mineral oil decreases levels of vitamin A by inhibition of GI absorption. Applies only to oral form of both agents. Minor/Significance Unknown.

              • minocycline

                minocycline, vitamin A. Mechanism: unspecified interaction mechanism. Minor/Significance Unknown. Risk of benign intracranial hypertension.

              • nelarabine

                vitamin A, nelarabine. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Antioxidants such as vitamin A enhance the efficacy, and reduce toxicity, of antineoplastic drugs.

              • neomycin PO

                neomycin PO decreases levels of vitamin A by inhibition of GI absorption. Applies only to oral form of both agents. Minor/Significance Unknown. (Vitamin A).

              • orlistat

                orlistat decreases levels of vitamin A by inhibition of GI absorption. Applies only to oral form of both agents. Minor/Significance Unknown. Separate by 2 hours.

              • oxaliplatin

                vitamin A, oxaliplatin. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Antioxidants such as vitamin A enhance the efficacy, and reduce toxicity, of antineoplastic drugs.

              • paclitaxel

                vitamin A, paclitaxel. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Antioxidants such as vitamin A enhance the efficacy, and reduce toxicity, of antineoplastic drugs.

              • paclitaxel protein bound

                vitamin A, paclitaxel protein bound. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Antioxidants such as vitamin A enhance the efficacy, and reduce toxicity, of antineoplastic drugs.

              • pentostatin

                vitamin A, pentostatin. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Antioxidants such as vitamin A enhance the efficacy, and reduce toxicity, of antineoplastic drugs.

              • pralatrexate

                vitamin A, pralatrexate. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Antioxidants such as vitamin A enhance the efficacy, and reduce toxicity, of antineoplastic drugs.

              • streptozocin

                vitamin A, streptozocin. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Antioxidants such as vitamin A enhance the efficacy, and reduce toxicity, of antineoplastic drugs.

              • thioguanine

                vitamin A, thioguanine. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Antioxidants such as vitamin A enhance the efficacy, and reduce toxicity, of antineoplastic drugs.

              • thiotepa

                vitamin A, thiotepa. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Antioxidants such as vitamin A enhance the efficacy, and reduce toxicity, of antineoplastic drugs.

              • topotecan

                vitamin A, topotecan. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Antioxidants such as vitamin A enhance the efficacy, and reduce toxicity, of antineoplastic drugs.

              • treosulfan

                vitamin A, treosulfan. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Antioxidants such as vitamin A enhance the efficacy, and reduce toxicity, of antineoplastic drugs.

              • vinblastine

                vitamin A, vinblastine. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Antioxidants such as vitamin A enhance the efficacy, and reduce toxicity, of antineoplastic drugs.

              • vincristine

                vitamin A, vincristine. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Antioxidants such as vitamin A enhance the efficacy, and reduce toxicity, of antineoplastic drugs.

              • vincristine liposomal

                vitamin A, vincristine liposomal. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Antioxidants such as vitamin A enhance the efficacy, and reduce toxicity, of antineoplastic drugs.

              • vinorelbine

                vitamin A, vinorelbine. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Antioxidants such as vitamin A enhance the efficacy, and reduce toxicity, of antineoplastic drugs.

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              Adverse Effects

              Frequency Not Defined

              Anaphylaxsis & death after IV use

              Facial dermatitis

              Stratum corneum fragility

              Conjunctivities

              Sticky skin

              Granuloma-like lesions in acne

              Dry mucus

              Paranochia

              Corneal opacities

              Palmoplanar peeling

              Cheilitis

              Alopecia

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              Warnings

              Contraindications

              Hypersensitivity

              IV use

              Hypervitaminosis A

              Malabasorption syndrome (oral therapy)

              Pregnancy (dose >RDA)

              Cautions

              Use caution if dose >25,000 units/day (monitor closely)

              Evaluate additional vitamin deficiencies if diagnosis of vitamin deficiency occurs (single vitamin A deficiency rare)

              Caution in renal impairment (toxicity reported)

              Monitor prolonged administration over 25,000 units/day; take into account vitamin intake from other dietary and supplement sources

              Efficacy of large systemic doses of 100,000 to 300,000 units/day vitamin A for the treatment of acne not established

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              Pregnancy & Lactation

              Pregnancy Category: A (oral); C (doses exceeding RDA); X (>6,000 units/day administered parenterally)

              Lactation: Distributed into milk; safe at RDA levels

              Pregnancy Categories

              A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

              B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

              C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

              D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

              X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

              NA: Information not available.

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              Nutrition

              Sources: Liver, butter, eggs, green leafy vegetables, colorful fruits & vegetables (carrots, mango, pumpkin, sweet potatoes)

              Functions: Growth & development, maintenance of epithelial tissue

              Deficiency: Night blindness, dry eyes, susceptibility to infections, follicular hyperkeratosis

              Toxicity: hypervitaminosis A

              Acute: Nausea, fatigue, dizziness, dry skin, cerebral edema, increased ICP, skin loss, liver failure

              Chronic: Osteoporosis, hair loss, high cholesterol, coma, swelling of the optic eye, rash, mouth sores, liver failure

              Teratogenicity: fetal toxicity, birth defects (>10,000 units/day)

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              Pharmacology

              Mechanism of Action

              Vitamin A supplementation plays a role in embryonic development, visual adaptation to darkness, immune function, and maintenance of epithelial cells

              Pharmacokinetics

              Serum concentration: 300-700 ng/mL (adults); 200-500 ng/mL (infants)

              Peak plasma time: 4-5 hr (oil solution); 304 hr (water-miscible)

              Protein Bound: Retinol binding protein

              Distribution: Mainly stored in liver as retinyl palmitate

              Metabolism: hepatic glucuronidation, decarboxylation

              Metabolites: retinoic acid, retinal

              Excretion: Urine and feces (via bile)

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              Images

              BRAND FORM. UNIT PRICE PILL IMAGE
              vitamin A oral
              -
              10,000 unit capsule

              Copyright © 2010 First DataBank, Inc.

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              Patient Handout

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              Patient Education
              vitamin A oral

              VITAMIN A - ORAL

              COMMON BRAND NAME(S): Aquasol A

              USES: Vitamin A is used to prevent or treat low levels of the vitamin in people who do not get enough of it from their diets. Most people who eat a normal diet do not need extra vitamin A. However, some conditions (such as protein deficiency, diabetes, hyperthyroidism, liver/pancreas problems) can cause low levels of vitamin A. Vitamin A plays an important role in the body. It is needed for growth and bone development and to maintain the health of the skin and eyesight. Low levels of vitamin A may cause vision problems (such as night blindness) and permanent eye damage.

              HOW TO USE: Take this vitamin by mouth with or without food, usually once daily. Follow all directions on the product package, or take as directed by your doctor. If you have any questions, ask your doctor or pharmacist.If you are using the liquid form of this medication, carefully measure the dose using a special measuring device/spoon. Do not use a household spoon because you may not get the correct dose.Dosage is based on your age, medical condition, and response to treatment.Use this vitamin regularly to get the most benefit from it. To help you remember, take it at the same time each day. Do not increase your dose or use this vitamin more often than recommended. Your condition will not improve any faster, and your risk of side effects will increase.Tell your doctor if your condition persists or worsens. If you think you may have a serious medical problem, seek immediate medical attention.

              SIDE EFFECTS: This vitamin usually has no side effects when used in recommended doses. If you have any unusual effects, contact your doctor or pharmacist promptly.A very serious allergic reaction to this vitamin is rare. However, seek immediate medical attention if you notice any symptoms of a serious allergic reaction, including: rash, itching/swelling (especially of the face/tongue/throat), severe dizziness, trouble breathing.This is not a complete list of possible side effects. If you notice other effects not listed above, contact your doctor or pharmacist.In the US -Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088 or at www.fda.gov/medwatch.In Canada - Call your doctor for medical advice about side effects. You may report side effects to Health Canada at 1-866-234-2345.

              PRECAUTIONS: Before taking vitamin A, tell your doctor or pharmacist if you are allergic to it; or if you have any other allergies. This product may contain inactive ingredients (such as soy found in some brands),which can cause allergic reactions or other problems. Talk to your pharmacist for more details.During pregnancy, this vitamin has been found to be safe only when used in recommended doses. It must not be used in doses that are higher than recommended because doing so may harm an unborn baby. Consult your doctor for more details.This vitamin passes into breast milk and is considered safe during breast-feeding when used in recommended doses. Consult your doctor for more information.

              DRUG INTERACTIONS: The effects of some drugs can change if you take other drugs or herbal products at the same time. This can increase your risk for serious side effects or may cause your medications not to work correctly. These drug interactions are possible, but do not always occur. Your doctor or pharmacist can often prevent or manage interactions by changing how you use your medications or by close monitoring.To help your doctor and pharmacist give you the best care, be sure to tell your doctor and pharmacist about all the products you use (including prescription drugs, nonprescription drugs, and herbal products) before starting treatment with this product. While using this product, do not start, stop, or change the dosage of any other medicines you are using without your doctor's approval.Some products that may interact with this vitamin include: acitretin, alitretinoin, bexarotene, cholestyramine, isotretinoin, tretinoin, other products that contain vitamin A (such as multivitamins), warfarin.Avoid taking vitamin A at the same time as you take neomycin, orlistat, and mineral oil. If you take any of these medications, separate your doses from your dose of vitamin A by at least 2 hours.This document does not contain all possible drug interactions. Keep a list of all the products you use. Share this list with your doctor and pharmacist to lessen your risk for serious medication problems.

              OVERDOSE: If someone has overdosed and has serious symptoms such as passing out or trouble breathing, call 911. Otherwise, call a poison control center right away. US residents can call their local poison control center at 1-800-222-1222. Canada residents can call a provincial poison control center. Symptoms of overdose may include: severe headache, tiredness, dizziness, mental/mood changes (such as irritability, depression), vision changes (such as double vision, blurred vision), dry/peeling skin, bone/joint pain, loss of appetite, yellowing skin/eyes, dark urine, severe stomach/abdominal pain.

              NOTES: This product is not a substitute for a proper diet. It is best to get your vitamins from healthy foods. Vitamin A is commonly found in fruits (such as apricots, oranges, peaches), vegetables (such as carrots, sweet potatoes, spinach), dairy products, and eggs, among others. Consult your doctor, pharmacist, or nutritionist for more details.

              MISSED DOSE: If you miss a dose, take it as soon as you remember. If it is near the time of the next dose, skip the missed dose. Take your next dose at the regular time. Do not double the dose to catch up.

              STORAGE: Different brands of this vitamin have different storage needs. Check the product package for instructions on how to store your brand, or ask your pharmacist. Do not store in the bathroom. Keep all medicines away from children and pets.Do not flush medications down the toilet or pour them into a drain unless instructed to do so. Properly discard this product when it is expired or no longer needed. Consult your pharmacist or local waste disposal company for more details about how to safely discard your product.

              Information last revised May 2020. Copyright(c) 2021 First Databank, Inc.

              IMPORTANT: HOW TO USE THIS INFORMATION: This is a summary and does NOT have all possible information about this product. This information does not assure that this product is safe, effective, or appropriate for you. This information is not individual medical advice and does not substitute for the advice of your health care professional. Always ask your health care professional for complete information about this product and your specific health needs.

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              Medscape prescription drug monographs are based on FDA-approved labeling information, unless otherwise noted, combined with additional data derived from primary medical literature.