Drug class: Vitamin B Complex
ATC class: A11HA04
VA class: VT106
CAS number: 83-88-5

Introduction

Water-soluble, B complex vitamin.^{a b}

Uses for Riboflavin

Riboflavin Deficiency

Used to prevent and treat riboflavin deficiency (ariboflavinosis).^{a b}

Riboflavin deficiency may occur in patients with long-standing infections, liver disease, alcoholism, malignancy, cardiac disease, diabetes mellitus, and those taking probenecid.^a

Dietary Requirements

Adequate intake needed to prevent riboflavin deficiency (ariboflavinosis).^{101 b}

Adequate intake of riboflavin usually can be accomplished through consumption of foodstuffs, including milk, bread products, and fortified cereals.^{101 b}

Estimated Average Requirement (EAR) and Recommended Dietary Allowance (RDA) in adults based on a combination of criteria including erythrocyte glutathione reductase activity and urinary excretion of riboflavin.^{101 b}

Adequate intake (AI) established for infants ≤6 months of age based on riboflavin intake of infants fed principally human milk;^b AI for infants 7–12 months of age based on the AI for younger infants and data from adults.^b

EAR and RDA for children 1–18 years of age based on data in adults.^{101 b}

Urinalysis Marker

Used as a urine marker when mixed with various drugs to test for patient compliance with the therapeutic regimen of these drugs.^a

Migraine Headaches

Has been used for prophylaxis of migraine headache^{† [off-label]} to decrease the frequency and duration of attacks.¹⁰²

Riboflavin Dosage and Administration

General

• Correct poor dietary habits and consider a multivitamin preparation containing riboflavin in patients with vitamin deficiencies since poor dietary habits often result in concurrent deficiencies.^a

Administration

Administer orally.^{a e}

May be given by IM injection or IV infusion as a component of a multivitamin injection.^a A parenteral formulation containing riboflavin alone is not currently commercially available.^a

Oral Administration

Administer orally, preferably with food.^e

Dosage

Pediatric Patients

Riboflavin Deficiency (Ariboflavinosis)

Oral

Usually, 3–10 mg daily.^a

Dietary and Replacement Requirements

Oral

Infants <6 months of age: AI is 0.3 mg (0.04 mg/kg) daily.¹⁰¹

Infants 6–12 months of age: AI is 0.4 mg (0.04 mg/kg) daily.¹⁰¹

Children 1–3 years of age: RDA is 0.5 mg daily.¹⁰¹

Children 4–8 years of age: RDA is 0.6 mg daily.¹⁰¹

Children 9–13 years of age: RDA is 0.9 mg daily.¹⁰¹

Girls 14–19 years of age: RDA is 1 mg daily.¹⁰¹

Boys 14–19 years of age: RDA is 1.3 mg daily.¹⁰¹

Adults

Riboflavin Deficiency (Ariboflavinosis)

Oral

Usually, 5–30 mg daily given in divided doses.^a

Patients with normocytic, normochromic anemia: 10 mg daily usually increases reticulocyte count within a few days.^a

Dietary and Replacement Requirements

Oral

Women ≥19 years of age: RDA is 1.1 mg daily.¹⁰¹

Men ≥19 years of age: RDA is 1.3 mg daily.¹⁰¹

These RDAs will not meet the needs of individuals with severe malabsorption.^{101 b}

Migraine Headaches† [off-label]

Oral

400 mg daily; maximal benefit may occur after 3 months of prophylaxis therapy.¹⁰²

Special Populations

Pregnant women: RDA is 1.4 mg daily.¹⁰¹ Riboflavin intake exceeding this RDA may be needed by women who are pregnant with more than one fetus.^{101 b}

Lactating women: RDA is 1.6 mg daily.¹⁰¹ Riboflavin intake exceeding this RDA may be needed by mothers nursing more than one infant.^{101 b}

May require additional riboflavin intake in patients who are extremely physically active.^b

Renal Impairment

Patients undergoing hemodialysis or peritoneal dialysis may require additional riboflavin.^b

Cautions for Riboflavin

Contraindications

• Known hypersensitivity to riboflavin or any ingredient in the formulation.^c

Warnings/Precautions

Warnings

Concomitant Diseases

Increased riboflavin deficiency risk in patients with cancer, cardiac disease, or diabetes mellitus.^b

General Precautions

Fixed-Combination Preparations

Consider the cautions, precautions, and contraindications associated with other drug(s) and vitamins in fixed-combination preparations.^c

Specific Populations

Pregnancy

Category A.^d Category C (for dosages >RDA).^d (See Special Populations under Dosage and Administration.)

Lactation

Distributed into human milk.^{101 a d}

Common Adverse Effects

Usually nontoxic even in large doses.^{a b}

Drug Interactions

Specific Drugs and Laboratory Tests

Riboflavin Pharmacokinetics

Absorption

Bioavailability

Readily absorbed from the upper GI tract.^{a b} Rate of absorption is proportional to intake.^b

Onset

Therapeutic response in riboflavin-deficient patients may require several days for ocular and dermatologic manifestations of deficiency to improve.^a

Following oral administration in deficient patients with normocytic, normochromic anemia, an increase in reticulocyte count usually occurs within a few days.^a

Food

Food increases extent of absorption.^{a b}

Special Populations

Extent of absorption is decreased in patients with hepatitis, cirrhosis, or biliary obstruction.^a

Distribution

Extent

Widely distributed into most tissues, including GI mucosal cells, erythrocytes, and the liver as riboflavin 5-phosphate (flavin mononucleotide [FMN]) and flavin adenine dinucleotide (FAD).^{a b} Free riboflavin is present in the retina.^a

Stored in limited amounts in the liver, spleen, kidneys, and heart, mainly as FAD.^a

Crosses the placenta and is distributed into milk.¹⁰¹

Plasma Protein Binding

About 60% as FAD and FMN.^a

Elimination

Metabolism

Phosphorylated to FMN in GI mucosal cells, erythrocytes, and the liver; FMN is converted to FAD in the liver.^a

Elimination Route

Urine (about 9%) as unchanged drug; fate of the remainder of the dose not determined.^a

Half-life

Following oral or IM administration, about 66–84 minutes.^a

Special Populations

Removal by hemodialysis is slower than normal renal excretion.^a

In neonates, urinary excretion is slow; however, the cumulative amount excreted is similar to the amount excreted by older infants.^b

Stability

Storage

Oral

Tablets

Tight, light-resistant containers at 15–30°C.^a

Compatibility

Incompatible with alkaline solutions.^a

Actions

• An exogenous source of riboflavin is required for tissue respiration.^a

• Converts to coenzymes (FMN and FAD) involved in oxidation-reduction reactions of organic substrates and in intermediary metabolism.^{a b e}

• Flavocoenzymes are involved in the formation of some vitamins and their coenzymes, including niacin, vitamin B₆, and vitamin B₁₂.^{101 b}

• Indirectly involved in maintaining erythrocyte integrity.^a

Advice to Patients

• Importance of proper dietary habits, including taking appropriate AI or RDA of vitamin B₂.

• Inform patients that large doses of riboflavin can result in bright yellow urine.^a

• Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.^b

• Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs.^b

• Importance of informing patients of other important precautionary information. (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

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