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NIACINAMIDE
DRUGDEX® Evaluations
OVERVIEW
1) Class
a) This drug is a member of the following class(es):
Antiacne
Antihyperlipidemic
Nicotinic Acid (class)
Nutritive Agent
Vitamin B
2) Dosing Information
a) Adult
1) Pellagra
a) ORAL, 300-500 mg/day, divided into 2-3 doses
b) IM, 50-100 mg/day in 5 or more divided doses
c) IV, 25-100 mg every 2-3 hr, MAX 1g/day
b) Pediatric
1) Pellagra
a) ORAL, 100-300 mg/day, divided into 2-3 doses
3) Contraindications
a) active peptic ulcer disease
b) hypersensitivity to niacinamide products
c) liver disease
4) Serious Adverse Effects
a) Hepatotoxicity
5) Clinical Applications
a) FDA Approved Indications
1) Pellagra
DOSING INFORMATION
Drug Properties
A) Information on specific products and dosage forms can be obtained by referring to the
Tradename List (Product Index)
B) Synonyms
Niacinamide
Niacinamide Ascorbate
Nicotinamide
Nicotinamide Ascorbate
Nicotinic Acid Amide
Adult Dosage
Normal Dosage
Intramuscular route
1) If given intramuscularly, the recommended dose for the acute treatment of
pellagra is 50 to 100 milligrams daily, in 5 or more divided doses
[12]
.
Intravenous route
1) The preferred parenteral route of administration of niacinamide is intravenous.
For the acute treatment of PELLAGRA, the recommended intravenous dose is 25
to 100 milligrams every 2 to 3 hours (maximum dose = 1 gram daily). Oral
administration and a well-balanced diet should be initiated as soon as possible
[12]
.
2) When given intravenously, niacinamide should be given slowly, with
concentrations not exceeding 10 milligrams/milliliter. Alternatively, the dose may
be diluted in 500 milliliters of normal saline and administered at a rate of 2
milligrams/minute
[12]
.
Oral route
Bullous pemphigoid
a) Another small trial reported the successful treatment of BULLOUS
PEMPHIGOID (N=16) with a combination regimen of oral
OXYTETRACYCLINE (500 milligrams (mg) 4 times daily), oral niacinamide
(400 mg 3 times daily), and topical 0.5% clobetasol propionate cream.
Once lesions began to heal, the oral doses were tapered over several
weeks and clobetasol was replaced with a moisturizing emollient
(Hornshuh et al, 1997).
Commonly used doses for BULLOUS PEMPHIGOID include 1 gram to 2 grams a
day of TETRACYCLINE in combination with 1.2 grams to 2 grams a day of
NIACINAMIDE for a duration of a few weeks to years (mean, 7 months). Within 1
to 2 weeks improvement may be noticed, however, adjunctive topical steroids
may alleviate new lesions during the beginning of therapy. Up to 1 month of
treatment may be needed before response occurs
[18]
. When treating extensive bullous pemphigoid, tapering-off over 1 to 2 months,
may be necessary; a more rapid taper is possible if using topical steroids
[18]
.
The oral route is preferred for the treatment of PELLAGRA. Recommended oral
doses of niacinamide for the acute treatment of pellagra are 300 to 500 milligrams
orally daily in divided doses. In patients with less severe deficiency, 50 to 100
milligrams daily can be given
[12]
.
PERIPHERAL NEURITIS associated with thiamine deficiency does not respond
to niacinamide, and thiamine replacement is indicated in these patients.
Macrocytic anemia in pellagra patients may be related to folic acid deficiency;
however, most clinicians recommend small doses of all B complex vitamins, as
well as a well-balanced diet with adequate protein to provide tryptophan, as
adjunctive therapy of pellagra
[12]
[19]
.
For MAINTENANCE THERAPY, preparations containing Recommended Dietary
Allowances (RDA) of niacinamide, thiamine, riboflavin, and pyridoxine should be
administered daily
[12]
.
The Recommended Dietary Allowance (RDA) of niacinamide in adults is 13 to 19
milligrams/day. This amount exceeds the minimum requirement necessary to
prevent deficiency. Oral doses of 10 to 20 milligrams daily are recommended for
DIETARY SUPPLEMENTATION
[12]
. For individuals who consume few calories, such as the elderly, daily intake
should not fall below 13 milligrams
[19]
.
Larger amounts of niacinamide are needed during periods of increased
metabolism, including pregnancy, lactation, prolonged infection, hyperthyroidism,
and burns
[12]
.
Pediatric Dosage
Normal Dosage
Oral route
1) The oral route is preferred for the treatment of PELLAGRA. The recommended
dose of niacinamide for the acute treatment of pellagra in children, is 100 to 300
milligrams daily in divided doses
[12]
.
2) PERIPHERAL NEURITIS associated with thiamine deficiency does not
respond to niacinamide, and thiamine replacement is indicated in these patients.
Macrocytic anemia in pellagra patients may be related to folic acid deficiency;
however, most clinicians recommend small doses of all B complex vitamins, as
well as a well-balanced diet with adequate protein to provide tryptophan, as
adjunctive therapy of pellagra
[12]
[19]
.
3) The Recommended Dietary Allowance (RDA) of niacinamide in children is 9 to
16 milligrams/day. This amount exceeds the minimum requirement necessary to
prevent deficiency
[12]
.
4) Larger amounts of niacinamide are needed during periods of increased
metabolism, including prolonged infection, hyperthyroidism, and burns
[12]
.
5) The efficacy of niacinamide 250 milligrams/day orally in the treatment of
HARTNUP DISEASE was reported in a 12-year-old boy presenting with pellagra
and CEREBELLAR ATAXIA
[13]
.
PHARMACOKINETICS
Onset and Duration
A) Onset
1) Initial Response
a) Pellagra, oral: 24 hours
[41]
.
Drug Concentration Levels
A) Therapeutic Drug Concentration
1) Tumor radiosensitization, 700 nanomoles/milliliter
[42]
B) Time to Peak Concentration
1) Oral: 1 to 4 hours
[42]
C) Area Under the Curve
1) 20,000 nanomoles x hr/mL
[42]
ADME
Distribution
A) Distribution Sites
1) OTHER DISTRIBUTION SITES
a) Placenta
1) Concentrations in the fetus and newborn are higher than in the mother
[43]
[44]
.
b) Tissues
1) Niacinamide is rapidly distributed to all tissues
[41]
.
Metabolism
A) Metabolism Sites and Kinetics
1) Liver
a) NIACINAMIDE is formed in vivo from metabolism of NIACIN. NIACINAMIDE is further
metabolized in the liver
[45]
[41]
.
B) Metabolites
1) Nicotinamide adenine dinucleotide (NAD), active
[46]
.
2) Nicotinamide adenine dinucleotide phosphate (NADP), active
[46]
.
3) N-methylniacinamide
[45]
[41]
.
4) Nicotinuric acid, possibly active
[45]
.
a) Nicotinuric acid (detoxification metabolite of NIACIN) is present in large amounts
following oral administration of NIACIN
[47]
[45]
but has been absent in the urine following repeated doses of NIACINAMIDE
[45]
. Nicotinuric acid reportedly possesses lipid-lowering activity
[45]
.
Excretion
A) Kidney
1) NIACINAMIDE and its metabolites are excreted in urine. With physiologic doses, only
small amounts of unchanged NIACINAMIDE are recovered; however, unchanged
NIACINAMIDE is the major urinary component after large oral doses
[45]
[41]
.
Elimination Half-life
A) Parent Compound
1) Elimination half life: 10 hours
[42]
CAUTIONS
Contraindications
A) active peptic ulcer disease
B) hypersensitivity to niacinamide products
C) liver disease
Precautions
A) diabetes
B) gallbladder disease
C) gout
D) history of liver disease
E) history of peptic ulcer
F) pregnancy/lactation
Adverse Reactions
Dermatologic Effects
Flushing
1) Niacin produces peripheral vasodilation and flushing, an effect not generally
shared with niacinamide
[19]
[24]
[33]
[34]
. However, flushing has been observed rarely with niacinamide
[25]
[24]
suggesting the vitamin may not be totally devoid of vasodilating activity.
2) In one study employing oral niacinamide, in combination with topical 6aminonicotinamide for psoriasis, flushing was observed in 3 of 204 patients.
These 3 patients had received niacinamide in doses of 100 to 200 mg three times
daily; reduction of the dose by 50% resulted in lessening or disappearance of
flushing, enabling continuation of niacinamide therapy
[24]
.
Rash
1) In contrast to niacin, skin reactions such as rash, hives, and facial erythema
have been reported only rarely with niacinamide
[24]
[25]
[23]
. The acanthosis nigricans-like reactions observed with niacin have not been
reported with niacinamide.
2) No cutaneous reactions were reported in 315 adult schizophrenic patients
treated with niacinamide 3 to 12 g daily
[30]
. In another series, a severe skin rash was observed in only 1 of 982
schizophrenic patients receiving 3 to 6 g of niacinamide daily
[23]
.
Endocrine/Metabolic Effects
Hyperglycemia
1) In contrast to niacin, niacinamide has only rarely been associated with
diabetogenic effects
[27]
[28]
. Diabetes mellitus is not an absolute contraindication to the use of niacinamide;
however, blood glucose monitoring is advisable during therapy
[29]
.
2) Improvement in diabetic control (reduced insulin requirements) was reported in
an insulin-dependent diabetic following administration of niacinamide
[28]
.
3) In a series of 982 schizophrenic patients treated with high doses of
niacinamide (up to 6 g daily), no changes in carbohydrate metabolism were
observed
[23]
.
Gastrointestinal Effects
Diarrhea
1) Diarrhea has been reported during niacinamide therapy, particularly with large
doses
[24]
[25]
[23]
[30]
[26]
[22]
. The incidence of diarrhea is low, and possibly less than with high doses of niacin
[24]
[28]
.
Nausea
1) Nausea has been reported during niacinamide therapy, particularly with large
doses
[24]
[25]
[23]
[30]
[26]
[22]
. The incidence of nausea is low, and possibly less than with high doses of niacin
[24]
[28]
.
Vomiting
1) Vomiting has been reported during niacinamide therapy, particularly with large
doses
[24]
[25]
[23]
[30]
[26]
[22]
. However, the incidence of vomiting is low, and possibly less than with high
doses of niacin
[24]
[28]
.
2) A gastrointestinal flu-like syndrome with persistent vomiting has been reported
in some patients following administration of high doses (3 to 12 g daily) of
niacinamide for the ineffective treatment of schizophrenia . A similar syndrome
occurred with high dose niacin in this study. With both agents, flu-like
gastrointestinal symptoms were mainly seen with doses exceeding 8 g daily
[30]
.
Hepatic Effects
Hepatotoxicity
1) Incidence: rare
2) Elevations in liver function tests and liver damage (including obstructive
jaundice and parenchymal hepatic cell injury) have been reported with
administration of niacinamide in relatively large doses
[24]
[23]
[31]
.
3) The incidence of hepatotoxicity is probably very low. Only 1 of 6000
schizophrenic patients developed hepatic complications with high-dose
niacinamide or niacin in 1 series
[23]
. Although direct comparative studies are lacking, hepatotoxicity appears to occur
less frequently with niacinamide as compared to niacin
[24]
[32]
[23]
[28]
; this may be attributable to the lesser frequency of use of niacinamide. However,
liver function tests should be monitored during niacinamide therapy, particularly
with the use of higher doses.
4) Parenchymal-cell injury, portal fibrosis, and cholestasis were reported in a 35year-old male schizophrenic patient receiving niacinamide 9 g daily. Hepatotoxic
effects were reversible and reproducible upon rechallenge
[31]
.
Neurologic Effects
Dizziness
1) Dizziness has been observed occasionally during niacinamide therapy
[22]
.
Headache
1) Headache has occurred with administration of therapeutic or high doses of
niacinamide (300 mg to 6 g daily)
[23]
[24]
[25]
[26]
. However, the incidence of this adverse effect is low, even with large doses. In
one series of 262 patients treated with niacinamide 3 g daily for schizophrenia,
headache was observed in 4
[24]
. In a further report, employing the use of niacinamide 100 to 3000 mg daily (in
combination with topical 6-aminonicotinamide for psoriasis), headache was
reported in only 1 of 204 patients
[25]
.
Ophthalmic Effects
Blurred vision
1) Blurring of the vision has been described rarely with niacinamide
[24]
.
Teratogenicity/Effects in Pregnancy/Breastfeeding
A) Teratogenicity/Effects in Pregnancy
1) Thomson Pregnancy Rating: Fetal risk is minimal.
a) The weight of an adequate body of evidence suggests this drug poses minimal risk when
used in pregnant women or women of childbearing potential.
See Drug Consult reference:
PREGNANCY RISK CATEGORIES
2) Crosses Placenta: Yes
3) Clinical Management
a) Niacinamide is the amide metabolite of niacin. A number of prenatal vitamins contain
niacinamide, and such supplements are indicated for the improvement of nutritional status prior
to conception and throughout pregnancy
[37]
[38]
. Nutritional supplement doses of vitamins and minerals are generally considered safe during
pregnancy. Daily niacin requirements are increased during pregnancy to a dietary reference
intake of 18 nanograms dietary niacin equivalents, an amount 28% over nonreproducing adult
women
[39]
.
B) Breastfeeding
1) Thomson Lactation Rating: Infant risk cannot be ruled out.
a) Available evidence and/or expert consensus is inconclusive or is inadequate for determining
infant risk when used during breastfeeding. Weigh the potential benefits of drug treatment
against potential risks before prescribing this drug during breastfeeding.
2) Clinical Management
a) There is insufficient data in regards to nursing while on niacinamide and the potential for
adverse effects in the nursing infant from exposure to the drug are unknown. Until additional
data are available, caution should be exercised with the use of niacinamide in women who
breastfeed their infants.
3) Literature Reports
a) Niacinamide is probably excreted in breast milk, as is niacin
[40]
.
Drug Interactions
Drug-Drug Combinations
Carbamazepine
1) Interaction Effect: an increased risk of carbamazepine toxicity (ataxia,
nystagmus, diplopia, headache, vomiting, apnea, seizures, coma)
2) Summary: Two case reports describe a decrease in carbamazepine clearance
when niacinamide was added to therapy. The decrease seen in the
carbamazepine clearance correlated highly with increasing niacinamide doses
[36]
.
3) Severity: moderate
4) Onset: delayed
5) Substantiation: probable
6) Clinical Management: Monitor carbamazepine plasma levels in patients
receiving niacinamide concomitantly. Adjust carbamazepine doses accordingly.
7) Probable Mechanism: inhibition of cytochrome P450 enzymes by niacinamide
8) Literature Reports
a) Carbamazepine concentration increased in two epileptic patients after the
addition of niacinamide. Both patients were also receiving primidone therapy, and
niacinamide was added to decrease the conversion of primidone to phenobarbital.
Patient 1, a 23-month old male receiving carbamazepine 72.7 mg/kg/day, had a
carbamazepine clearance of 11.6 L/kg/day prior to niacinamide treatment, and the
carbamazepine clearance decreased to 2.16 L/kg/day by the time the niacinamide
dose had been titrated up to 178 mg/kg/day. In patient 2, a 10-year old male, the
carbamazepine clearance decreased from 8.0 L/kg/day before niacinamide
therapy to 3.37 L/kg/day when the niacinamide dose was 60 mg/kg/day. It was
suspected that niacinamide inhibited the cytochrome P450 metabolism of
carbamazepine
[35]
.
Intravenous Admixtures
Drugs
Cephaloridine
1) Incompatible
a) Cephaloridine (250 mg/L niacinamide 1 g/L in sterile distilled water
exhibited significant antibiotic activity reduction in 1 hour at 25 degrees C)
[71]
b) Niacinamide (1 g/L with cephaloridine 250 mg/L in sterile distilled water
exhibited significant antibiotic activity reduction in 1 hour at 25 degrees C)
[72]
Solutions
ALKALINE SOLUTIONS
1) Incompatible
a) Alkaline solutions reported to cause decomposition of nicotinamide;
conditions not specified
[73]
TOTAL PARENTERAL NUTRITION
1) Compatible
a) Nicotinamide as a component of a multivitamin solution with total
parenteral nutrition, no significant degradation of nicotinamide reported
when the admixture was stored for 96 hours at 2 to 8 degrees C in
darkness in ethylene vinyl acetate - EVA - containers; specific composition
of total parenteral solution described below
[74]
:
Intralipid(R) 20%
Vitalipid(R) N Adult
Soluvit(R) N (multivitamin solution)
Vamin(R) glucose
Glucose 30%
Addamel(R) electrolytes and trace
elements
Addiphos(R) phosphate solution
Addex(R) sodium chloride solution
Addex(R) magnesium solution
Potassium acetate (2.5 mM/mL)
Zinc Acetate (10 micromole/mL)
CLINICAL APPLICATIONS
Monitoring Parameters
500 mL
5 mL
one-half ampule
1000 mL
500 mL
5 mL
5 mL
23 mL
4.5 mL
37 mL
5 mL
A) Therapeutic
1) Physical Findings
a) In patients with pellagra, rapid resolution of symptoms of tongue swelling, oral infections,
gastrointestinal symptoms, delayed wound healing, and mental symptoms are indicative of a
therapeutic response to niacinamide.
B) Toxic
1) Laboratory Parameters
a) Liver function tests, blood glucose levels, and serum uric acid levels should be monitored
periodically during therapy.
Patient Instructions
A) Niacinamide (By mouth)
Niacinamide
Lowers cholesterol and triglyceride levels in your blood. This medicine is a vitamin (B3).
When This Medicine Should Not Be Used:
You should not use this medicine if you have had an allergic reaction to niacinamide (niacin).
You may not be able to use this medicine if you have severe liver disease, ulcers, or if you
have certain bleeding problems.
How to Use This Medicine:
Tablet, Capsule, Long Acting Tablet
Your doctor will tell you how much of this medicine to use and how often. Your dose may need
to be changed several times in order to find out what works best for you. Do not use more
medicine or use it more often than your doctor tells you to.Carefully follow your doctor's
instructions about any special diet or exercise program.
It is best to take this medicine after your last meal of the day.
Swallow the extended-release tablet whole. Do not crush, break, or chew it.
If a Dose is Missed:
If you miss a dose or forget to use your medicine, use it as soon as you can. If it is almost time
for your next dose, wait until then to use the medicine and skip the missed dose. Do not use
extra medicine to make up for a missed dose.
How to Store and Dispose of This Medicine:
Store the medicine in a closed container at room temperature, away from heat, moisture, and
direct light.
Ask your pharmacist, doctor, or health caregiver about the best way to dispose of any outdated
medicine or medicine no longer needed.
Keep all medicine away from children and never share your medicine with anyone.
Drugs and Foods to Avoid:
Ask your doctor or pharmacist before using any other medicine, including over-the-counter
medicines, vitamins, and herbal products.
Make sure your doctor knows if you are using another medicine to lower cholesterol such as
lovastatin, Lescol®, Lipitor®, Pravachol®, or Zocor®. Tell your doctor if you are using aspirin,
vitamin supplements, or a nitrate medicine such as nitroglycerin or isosorbide.
Make sure your doctor knows if you are also using medicine to lower blood pressure. Some
blood pressure medicines are atenolol, diltiazem, nifedipine, propranolol, verapamil, Cartia®,
Coreg®, Lotrel®, Norvasc®, Plendil®, Tiazac®, and Toprol®.
Make sure your doctor knows if you drink alcohol on a daily or regular basis.
Warnings While Using This Medicine:
Make sure your doctor knows if you are pregnant or breast feeding, or if you have diabetes. Tell
your doctor if you have angina (chest pain) or low blood pressure. Your doctor will need to
know if you have a history of liver or gallbladder disease, ulcers, gout, or jaundice (skin or eyes
turn yellow).
Follow your doctor's instructions carefully if you are switching to this medicine from another
form of niacinamide. The dose may be different if you switch from the regular tablet to the
extended-release tablet.
Your doctor will need to check your blood at regular visits while you are using this medicine. Be
sure to keep all appointments.
Make sure any doctor or dentist who treats you knows that you are using this medicine. This
medicine may affect the results of certain medical tests.
This medicine may cause a warmth or redness in your face, neck, arms, or upper chest. This is
called "flushing," and it usually improves after you have been taking niacinamide on a regular
basis for a few weeks. To help prevent flushing, do not drink alcohol or hot drinks when you
take this medicine, and do not take it on an empty stomach. You should also ask your doctor
about taking aspirin or an anti-inflammatory medicine (such as ibuprofen) before you use this
medicine.
Possible Side Effects While Using This Medicine:
Call your doctor right away if you notice any of these side effects:
Dark-colored urine or pale stools.
Fast, uneven, or pounding heartbeat.
Nausea, vomiting, loss of appetite, pain in your upper stomach.
Yellowing of your skin or the whites of your eyes.
If you notice these less serious side effects, talk with your doctor:
Headache.
Lightheadedness or fainting.
Mild diarrhea, vomiting, or upset stomach.
Muscle pain, tenderness, or weakness.
Vision changes.
If you notice other side effects that you think are caused by this medicine, tell your doctor.
B) Niacinamide (On the skin)
Niacinamide
Reduces dryness, redness, or irritation of your skin caused by acne or acne medicines.
When This Medicine Should Not Be Used:
You should not use this medicine if you have had an allergic reaction to niacinamide.
How to Use This Medicine:
Cream, Gel/Jelly
Your doctor will tell you how much of this medicine to use and how often. Do not use more
medicine or use it more often than your doctor tells you to.
This medicine is for use on the skin only. Do not get it in your eyes, nose, or mouth. Do not use
it on skin areas that have cuts or scrapes. If it does get on these areas, rinse it off right away.
Wash your hands with soap and water before and after using this medicine.
Before using this medicine, wash your face with a mild soap or a cleansing lotion as directed by
your doctor.
Apply a thin layer to the affected area. Rub it in gently.
You may apply cosmetics or other acne medicines over this medicine if desired.
This medicine does not treat acne. Keep using all other acne medicines as directed by your
doctor.
If a Dose is Missed:
If you miss a dose or forget to use your medicine, apply it as soon as you can. If it is almost
time for your next dose, wait until then to apply the medicine and skip the missed dose. Do not
apply extra medicine to make up for a missed dose.
How to Store and Dispose of This Medicine:
Store the medicine at room temperature, away from heat and direct light. Do not freeze.
Ask your pharmacist, doctor, or health caregiver about the best way to dispose of the used
medicine container and any leftover medicine after you have finished your treatment. You will
also need to throw away old medicine after the expiration date has passed.Keep all medicine
away from children and never share your medicine with anyone.
Drugs and Foods to Avoid:
Ask your doctor or pharmacist before using any other medicine, including over-the-counter
medicines, vitamins, and herbal products.
Warnings While Using This Medicine:
Make sure your doctor knows if you are pregnant or breast feeding.
Do not use this medicine for a skin problem that has not been checked by your doctor.
Your doctor will need to check your progress at regular visits while you are using this medicine.
Be sure to keep all appointments.
Possible Side Effects While Using This Medicine:
Call your doctor right away if you notice any of these side effects:
If you notice these less serious side effects, talk with your doctor:
Mild skin rash.
If you notice other side effects that you think are caused by this medicine, tell your doctor.
Place In Therapy
A) The only clear indication for niacinamide is the prevention and treatment of pellagra.
Niacinamide is preferable to niacin as it produces less flushing and may be associated with a
lower incidence of other adverse effects.
B) Megadoses of niacinamide have no place in the treatment of schizophrenia or other
psychiatric disorders. Although niacinamide may possess some degree of lipid-lowering
activity, it is not indicated in the treatment of hyperlipidemia.
C) Niacinamide has lessened the loss of insulin secretion in type I diabetes patients in some
studies but not others. Further well-controlled trials involving larger patient populations are
required to assess efficacy of the drug as a means of preserving beta-cell function in these
patients.
D) Although beneficial results have been observed with niacinamide therapy in some patients
with bullous pemphigoid and granuloma annular, more definitive studies are needed to
determine its place in therapy in these conditions.
Mechanism of Action / Pharmacology
A) MECHANISM OF ACTION
1) Niacinamide (nicotinamide) is the amide metabolite of niacin (nicotinic acid). Both
niacinamide and niacin are water-soluble, B complex vitamins
[41]
[48]
.
2) Niacinamide is formed in vivo from metabolism of niacin. Niacinamide is an essential
precursor of nicotinamide adenine dinucleotide (NAD) and nicotinamide adenine dinucleotide
phosphate (NADP), which are the physiologically active forms of niacin. Serving as coenzymes
for several dehydrogenases, NAD and NADP are functional groups of electron-transfer agents
active in cellular respiration, glycolysis, and lipid synthesis
[48]
[45]
[41]
.
3) As B complex vitamins, niacin and niacinamide have identical physiological effects
[41]
. However, these vitamins differ in some of their actions. Niacin produces peripheral
vasodilation and flushing, an effect not generally shared with niacinamide
[41]
[49]
[50]
[51]
; however, flushing has been observed with niacinamide in some studies
[52]
[49]
suggesting the vitamin may not be totally devoid of vasodilating activity. The overall incidence
and severity of adverse effects, including hepatotoxicity, gastrointestinal complaints, and
hyperuricemia, may be less with niacinamide as compared to niacin
[53]
[54]
[50]
[49]
[41]
.
4) Niacin can also reduce serum levels of very low-density lipoprotein (VLDL) and low-density
lipoprotein (LDL), while at the same time increasing high-density lipoprotein (HDL) levels, and
is used as an agent of choice in the treatment of hyperlipidemia
[45]
[48]
. In contrast, niacinamide has lacked this effect in most studies
[55]
[56]
[45]
, although some evidence of lipid-lowering activity has been observed with long-term
administration, possibly due to conversion of niacinamide to niacin
[57]
[45]
.
5) A deficiency of niacin results in pellagra. This condition can result from primary dietary
deficiency of niacin or most commonly from secondary niacin deficiency (ie, chronic
alcoholism). Either niacinamide or niacin can be used to treat pellagra
[48]
[41]
. The amino acid tryptophan is also a dietary source of niacin, provided by animal protein.
Tryptophan is converted to niacin and then niacinamide in vivo, and a deficiency of tryptophan
in the diet can result in pellagra
[41]
[58]
. Approximately 60 mg of dietary tryptophan is equivalent to 1 mg niacin
[48]
[41]
. Tryptophan has also been used successfully in the treatment of pellagra
[41]
.
Therapeutic Uses
Carcinoma of larynx; Adjunct
1) Overview
FDA Approval: Adult, no; Pediatric, no
Efficacy: Adult, Evidence is inconclusive
Recommendation: Adult, Class III
Strength of Evidence: Adult, Category B
See Drug Consult reference:
RECOMMENDATION AND EVIDENCE RATINGS
2) Summary:
Niacinamide decreases acute hypoxia in tumors, permitting increased effectiveness of
radiation treatment
3) Adult:
a) Combining carbogen breathing (95% oxygen, 5% carbon dioxide) and oral
nicotinamide with accelerated radiotherapy greatly increases tumor control and survival
in patients with CANCER OF THE LARYNX. Because the response of cells to radiation
is strongly dependent on the availability of oxygen, patients with histologically confirmed
squamous cell carcinomas of the larynx at stage III or IV were given carbogen to breathe
4 minutes before and throughout radiation treatment (to increase tissue partial pressure
of oxygen and thereby increase the diffusion distance of oxygen) and nicotinamide 1
hour before radiation treatment (to increase tumor perfusion). Because the probability of
tumor control decreases as overall time of radiation therapy increases, treatment time
was reduced by giving multiple fractions per day (accelerated radiotherapy). Sixty-two
patients were given a total of 64 Gray (Gy) to the primary tumor and 68 Gy to metastatic
nodes in 35 to 37 days. Doses of 2 Gy were given daily for 5 days per week until the last
week and a half, when 2 doses were given twice per day, separated by 6 hours. The
initial daily dose of nicotinamide was 6 grams (g), later reduced to 80 milligrams/kilogram
(mg/kg), with a maximum of 6 g, because of side effects. For those experiencing severe
side effects, the dose was reduced further to 60 mg/kg. Eleven patients received
accelerated radiation with carbogen only and 51 received accelerated radiation with
carbogen and nicotinamide. Ten patients (16%) were unable to breathe carbogen. A
third of the patients receiving nicotinamide discontinued drug intake because of sideeffects (mainly nausea and vomiting). All patients developed confluent mucositis, and
some required tube feeding. There was complete healing of the mucosa in all cases. At
6 weeks after treatment, there was complete regression of the primary tumor and the
nodal metastases in all cases (100% response rate). This response rate is much greater
than that reported with other treatments. Five patients had local recurrence at 5, 8, 14,
18, and 31 months, respectively. Of those, 2 had received carbogen only and 2 of those
receiving nicotinamide had discontinued nicotinamide after 8 and 25 days, respectively.
Local control rates were 92% at 2 years and 87% at 3 years. Survival was 85% at 2
years and 77% at 3 years
[10]
.
Diabetes mellitus
1) Overview
FDA Approval: Adult, no; Pediatric, no
Efficacy: Adult, Evidence is inconclusive; Pediatric, Evidence is inconclusive
Recommendation: Adult, Class III; Pediatric, Class III
Strength of Evidence: Adult, Category B; Pediatric, Category B
See Drug Consult reference:
RECOMMENDATION AND EVIDENCE RATINGS
2) Summary:
Clinical studies have reported conflicting results regarding the efficacy of NIACINAMIDE
in lessening the loss of insulin secretion in type I diabetic patients.
3) Adult:
a) Controlled studies have reported that oral administration of high doses of
NIACINAMIDE (3 grams daily) is effective in protecting residual beta-cell function and
inducing transient remissions in type I (insulin-dependent) diabetic patients
[1]
[2]
. In these studies, a significant reduction in INSULIN requirements and lower
glycosylated hemoglobin values and improved maintenance of C-peptide responses to
glucagon were observed in NIACINAMIDE treated patients as compared to controls.
b) Combination therapy with oral NIACINAMIDE 50 milligrams/kilogram/day and oral
CYCLOSPORINE did not significantly improve remission rates in 35 recently diagnosed
type I diabetic patients in an open study
[3]
. Further, NIACINAMIDE administration during dose reductions of CYCLOSPORINE was
unable to prevent resumption of the disease.
4) Pediatric:
a) In a double-blind study involving 35 children and adolescents with newly-diagnosed
type I diabetes, NIACINAMIDE in maximum doses of 1.5 grams daily did not preserve
insulin secretion
[4]
. During the 1-year study, values of glycosylated hemoglobin and mean insulin dosages
were similar for the NIACINAMIDE and placebo groups; fasting and glucagon-stimulated
C-peptide levels, which were similar at initiation of therapy, did not differ after 4 and 12
months, and no differences in remission rates were observed between the 2 groups.
Granuloma annulare
1) Overview
FDA Approval: Adult, no; Pediatric, no
Efficacy: Adult, Evidence is inconclusive
Recommendation: Adult, Class III
Strength of Evidence: Adult, Category C
See Drug Consult reference:
RECOMMENDATION AND EVIDENCE RATINGS
2) Summary:
Niacinamide has been used with varying success in treating granuloma annulare.
3) Adult:
a) Niacinamide 1500 milligrams/day for 6 months was successful in clearing multiple
lesions in a 63-year-old woman diagnosed with granuloma annulare. Previously, topical
steroids, erythromycin, and oral zinc had been ineffective. Lesions reappeared when the
dose of niacinamide was reduced to 900 milligrams daily for 3 months and resolved
within 2 months when the dose of 1500 milligrams was reinstituted
[5]
.
Hyperlipidemia
1) Overview
FDA Approval: Adult, no; Pediatric, no
Efficacy: Adult, Evidence is inconclusive
Recommendation: Adult, Class III
Strength of Evidence: Adult, Category C
See Drug Consult reference:
RECOMMENDATION AND EVIDENCE RATINGS
2) Summary:
NIACINAMIDE is not indicated for the treatment of hyperlipidemia; in contrast, NIACIN is
an effective lipid-lowering agent. NIACINAMIDE may have some lipid-lowering potential
in humans after long-term but not short-term use. These effects may be indirect,
attributable to metabolism of NIACINAMIDE back to NIACIN.
3) Adult:
a) In contrast to NIACIN, which effectively lowers serum cholesterol levels
[6]
, NIACINAMIDE administration in doses of 3 to 6 grams daily for up to 3 months has not
resulted in lipid-lowering effects in several studies
[6]
[7]
[8]
. However, oral NIACINAMIDE in a dose of 3 grams daily for approximately 4 months
was effective in reducing triglyceride levels in 1 patient with massive
hypertriglyceridemia
[9]
.
Necrobiosis lipoidica diabeticorum
1) Overview
FDA Approval: Adult, no; Pediatric, no
Efficacy: Adult, Evidence is inconclusive
Recommendation: Adult, Class IIb
Strength of Evidence: Adult, Category B
See Drug Consult reference:
RECOMMENDATION AND EVIDENCE RATINGS
2) Summary:
In a small, open study, some patients with necrobiosis lipoidica responded to
nicotinamide treatment.
3) Adult:
a) Clinical improvement was reported in 8 of 13 evaluable patients with necrobiosis
lipoidica following at least 1 month of oral therapy with NIACINAMIDE in an open study.
Patients most likely to respond were those with pain or soreness associated with
significant inflammatory change or ulceration
[11]
.
Pellagra
FDA Labeled Indication
1) Overview
FDA Approval: Adult, yes; Pediatric, yes
Efficacy: Adult, Effective; Pediatric, Effective
Recommendation: Adult, Class I; Pediatric, Class I
Strength of Evidence: Adult, Category B; Pediatric, Category B
See Drug Consult reference:
RECOMMENDATION AND EVIDENCE RATINGS
2) Summary:
NIACINAMIDE is effective in preventing NIACIN deficiency and treating PELLAGRA; it is
preferred over NIACIN due to its lesser propensity to cause flushing and other adverse
effects.
3) Adult:
a) The daily Recommended Dietary Allowance (RDA) of NIACIN (and NIACINAMIDE) in
adults is 13 to 19 milligrams. For treatment of pellagra, recommended doses in adults
are 300 to 500 milligrams orally daily in divided doses
[12]
.
4) Pediatric:
a) The daily Recommended Dietary Allowance (RDA) of niacin is 9 to 16 milligrams.
b) NIACINAMIDE 250 milligrams orally daily was effective in the treatment of HARTNUP
DISEASE in a 12-year-old boy presenting with pellagra and cerebellar ataxia. Skin
lesions disappeared following 2 months of therapy, with resolution of cerebellar signs
being observed after 4 months
[13]
.
c) NIACINAMIDE 400 milligrams orally daily was effective in the treatment of a pellagralike syndrome possibly related to VALPROIC ACID therapy (500 milligrams daily for 6
weeks) in a 10-year-old epileptic boy. Erythema and abdominal cramps resolved within
48 hours of initiation of therapy. The authors speculate that VALPROIC ACID may
interfere with NIACIN utilization in certain instances. However, nutritional deficiency
could not be ruled out in this case
[14]
.
Pemphigoid
1) Overview
FDA Approval: Adult, no; Pediatric, no
Efficacy: Adult, Evidence favors efficacy
Recommendation: Adult, Class IIb
Strength of Evidence: Adult, Category B
See Drug Consult reference:
RECOMMENDATION AND EVIDENCE RATINGS
2) Summary:
Oral niacinamide 1 to 2.5 grams daily in combination with oral tetracycline has produced
beneficial responses in some patients with BULLOUS PEMPHIGOID
Adding niacinamide to tetracycline treatment for CICATRICIAL PEMPHIGOID brought
clinical improvement in cases unresponsive to tetracyclines alone
3) Adult:
a) Treatment of CICATRICIAL PEMPHIGOID, an autoimmune blistering disease
manifested primarily in mucous membranes, with a combination of nicotinamide and
tetracyclines resulted in marked clinical improvement in the 6 of 8 patients who were
able to sustain full-dose treatment for 6 months. Patients had been taking tetracyclines
for at least 12 weeks without adequate symptomatic control. Nicotinamide treatment was
initiated at 500 milligrams (mg) daily and the dose increased by 500-mg increments at 2week intervals until symptomatic control or a dose of 3 grams per day was reached.
After the maximum dose was reached, patients were maintained on that regimen for 6
months. Two patients dropped out, one after 4 weeks because of dizziness and nausea
and the other after 12 weeks because of progression of disease. The other patients
showed clinical improvement during treatment and at 4 months after discontinuation of
treatment. None of the patients completing the study experienced adverse effects, and
no liver abnormalities were detected
[15]
.
b) Combined treatment of BULLOUS PEMPHIGOID with tetracycline, niacinamide, and
a topical corticosteroid was effective in 14 of 16 patients. Initially, patients received oral
oxytetracycline, 500 mg 4 times per day, oral niacinamide, 400 mg 3 times per day, and
0.5% clobetasol propionate cream once per day. Complete clearance of lesions
occurred in 13 patients within 4 weeks. Another took 5 months; 2 did not respond. After
clearance of lesions, the corticosteroid treatment was removed and the tetracycline was
stepped down 500 mg every 4 weeks to 250 mg 4 times/day and then reduced 250 mg
every 4 weeks. Then, if no new blisters appeared, niacinamide was reduced in steps of
600 mg every month. One responding patient arbitrarily discontinued treatment after 7
months and had a recurrence within 20 days that responded to the same regimen. Blood
levels of osteocalcin did not change with the topical corticosteroid treatment as they do
with oral administration of corticosteroids
[16]
.
c) Niacinamide monotherapy was sufficient to control BULLOUS PEMPHIGOID in a 58year-old woman. The bullae were localized to the left breast, which had been treated
with radiation and subsequent reconstruction after mastectomy. Initial treatment of the
bullous pemphigoid with fluocinonide 0.05% cream was marginally successful.
Subsequent treatment with tetracycline 500 milligrams (mg) twice daily and niacinamide
500 mg 3 times daily cleared lesions promptly. On 2 occasions, when her niacinamide
had run out and she continued the tetracycline, new eruptions occurred in the same
area, which responded immediately to resumption of niacinamide. She was then
maintained on niacinamide alone, 3 times daily, without disease activity (Honl & Elston,
1998).
Primary intracranial tumor; Adjunct
1) Overview
FDA Approval: Adult, no; Pediatric, no
Efficacy: Adult, Evidence is inconclusive
Recommendation: Adult, Class III
Strength of Evidence: Adult, Category B
See Drug Consult reference:
RECOMMENDATION AND EVIDENCE RATINGS
2) Summary:
Niacinamide did not increase survival time
Associated with increased toxicity
3) Adult:
a) High dose niacinamide (nicotinamide), given with or without carbogen (95% oxygen
and 5% carbon dioxide) breathing during accelerated radiotherapy of GLIOBLASTOMA
MULTIFORME, did not increase survival rate compared to carbogen alone during
accelerated radiotherapy; furthermore, niacinamide treatment was associated with more
frequent and more severe toxicity than was carbogen. Resistance of glioblastoma
multiforme to radiation therapy is thought to result from its fast proliferative nature and to
hypoxia of a large proportion of tumor cells, which makes them more aggressive and
more resistant to radiotherapy. Acceleration of the radiotherapy schedule is intended to
combat the fast proliferation rate; carbogen breathing and niacinamide treatment are
intended to reduce the unfavorable effects of hypoxia. Niacinamide, given at 85
milligrams per kilogram per day, did not appear to be beneficial and is not a feasible
treatment, owing to its toxicity
[17]
.
Comparative Efficacy / Evaluation With Other Therapies
Niacin
1) Efficacy
a) As B complex vitamins, niacin and niacinamide have identical physiological effects
[59]
. However, these vitamins differ in other effects. Niacin produces peripheral
vasodilatation and flushing, an effect not generally shared with niacinamide
[59]
[60]
[61]
[62]
; however, flushing has been observed with niacinamide in some studies
[63]
[60]
suggesting the vitamin may not be totally devoid of vasodilating activity. The overall
incidence and severity of adverse effects, including hepatotoxicity, gastrointestinal
complaints, and hyperuricemia, may be less with niacinamide as compared to niacin
[64]
[65]
[61]
[60]
[59]
.
b) Niacin can also reduce serum levels of very low-density lipoprotein (VLDL) and lowdensity lipoprotein (LDL), while at the same time increasing high-density lipoprotein
(HDL) levels, and is used as an agent of choice in the treatment of hyperlipidemia
[66]
[67]
. In contrast, niacinamide has lacked this effect in most studies
[68]
[69]
[66]
, although some evidence of lipid-lowering activity has been observed with long-term
administration, possibly due to conversion of niacinamide to niacin
[70]
[66]
.
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Last Modified: June 08, 2012
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