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<!--Pediatric Indications and Dosage-->
<!--FDA-Labeled Indications and Dosage (Pediatric)-->
|fdaLIADPed======Condition1=====
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<!--Off-Label Use and Dosage (Pediatric)-->
<!--Guideline-Supported Use (Pediatric)-->
|offLabelPedGuideSupport======Condition1=====
* Developed by:
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* Dosing Information
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There is limited information regarding <i>Off-Label Non–Guideline-Supported Use</i> of {{PAGENAME}} in pediatric patients.
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|contraindications=* Condition1
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|warnings=* Description
====Precautions====
* Description
<!--Adverse Reactions-->
<!--Clinical Trials Experience-->
|clinicalTrials=There is limited information regarding <i>Clinical Trial Experience</i> of {{PAGENAME}} in the drug label.
=====Body as a Whole=====
=====Cardiovascular=====
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=====Metabolic and Nutritional=====
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=====Neurologic=====
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=====Special Senses=====
=====Urogenital=====
=====Miscellaneous=====
<!--Postmarketing Experience-->
|postmarketing=There is limited information regarding <i>Postmarketing Experience</i> of {{PAGENAME}} in the drug label.
=====Body as a Whole=====
=====Cardiovascular=====
=====Digestive=====
=====Endocrine=====
=====Hematologic and Lymphatic=====
=====Metabolic and Nutritional=====
=====Musculoskeletal=====
=====Neurologic=====
=====Respiratory=====
=====Skin and Hypersensitivy Reactions=====
'''Retinol (Afaxin)''', the animal form of [[vitamin A]], is a fat-soluble vitamin important in [[visual system|vision]] and [[bone]] growth. It belongs to the family of chemical compounds known as [[retinoid]]s.
=====Special Senses=====
Retinol is ingested in a precursor form; animal sources ([[liver]] and [[Egg (food)|egg]]s) contain retinyl [[ester]]s, whereas [[plant]]s ([[carrot]]s, [[spinach]]) contain pro-vitamin A [[carotenoid]]s. Hydrolysis of retinyl esters results in retinol while pro-vitamin A carotenoids can be cleaved to produce [[retinal]]. Retinal, also known as retinaldehyde, can be reversibly reduced to produce retinol or it can be irreversibly oxidized to produce retinoic acid. The best described active retinoid metabolites are 11-''cis''-retinal and the all-trans and 9-cis-isomers of retinoic acid.
==Discovery==
In 1913, [[Elmer McCollum]], a [[biochemist]] at the [[University of Wisconsin-Madison]], and colleague [[Marguerite Davis]] identified a fat-soluble nutrient in [[butterfat]] and [[cod liver oil]]. Their work confirmed that of [[Thomas Osborne (biochemist)|Thomas Osborne]] and [[Lafayette Mendel]], at [[Yale University|Yale]], which suggested a fat-soluble nutrient in butterfat, also in 1913.<ref name=Semba>Semba RD. Vitamin A as "Anti-Infective" Therapy, 1920–1940. Journal of Nutrition. 1999;129:783-791. PMID 10203551. [http://www.nutrition.org/cgi/content/full/129/4/783 Full Text Available]</ref> Vitamin A was first synthesized in 1947 by two Dutch chemists, [[David Adriaan van Dorp]] and Jozef Ferdinand Arens.
==Chemical structure and function==
Many different geometric isomers of retinol, retinal and retinoic acid are possible as a result of either a ''[[trans]]'' or ''[[cis]]'' configuration of four of the five [[double bond]]s found in the [[polyene]] chain. The ''cis'' isomers are less stable and can readily convert to the all-''trans'' configuration (as seen in the structure of all-''trans''-retinol shown here). Nevertheless, some ''cis'' isomers are found naturally and carry out essential functions. For example, the 11-''cis''-retinal isomer is the [[chromophore]] of [[rhodopsin]], the [[vertebrate]] [[photoreceptor]] molecule. Rhodopsin is comprised of the 11-cis-retinal covalently linked via a [[Schiff base]] to the [[opsin]] protein (either rod opsin or blue, red or green cone opsins). The process of vision relies on the light-induced isomerisation of the chromophore from 11-''cis'' to all-''trans'' resulting in a change of the conformation and activation of the photoreceptor molecule. One of the earliest signs of vitamin A deficiency is night-blindness followed by decreased visual acuity.
[[George Wald]] won the [[1967]] [[Nobel Prize in Physiology or Medicine]] for his work with [[retina]] pigments (also called visual pigments), which led to the understanding of the role of vitamin A in vision.
=====Urogenital=====
Many of the non-visual functions of vitamin A are mediated by retinoic acid, which regulates gene expression by activating intracellular [[retinoic acid receptor]]s. The non-visual functions of vitamin A are essential in the immunological function, reproduction and embryonic development of vertebrates as evidenced by the impaired growth, susceptibility to infection and birth defects observed in populations receiving suboptimal vitamin A in their diet.
===Role in embryology===<!-- This section is linked from [[Postpartum depression]] -->
Retinoic acid via the retinoic acid receptor influences the process of cell differentiation, hence, the growth and development of embryos. During development there is a concentration gradient of retinoic acid along the anterior-posterior (head-tail) axis. Cells in the embryo respond differently to retinoic acid depending on the amount present. For example, in vertebrates the hindbrain transiently forms eight rhombomers and each rhombomere has a specific pattern of genes being expressed. If retinoic acid is not present the last four rhombomeres do not develop. Instead rhombomeres 1-4 grow to cover the same amount of space as all eight would normally occupy. Retinoic acid has its effects by turning on a differential pattern of Hox genes which encode different homeodomain transcription factors which in turn can turn on cell type specific genes. Deletion of the Hox-1 gene from rhombomere 4 makes the neurons growing in that region behave like neurons from rhombomere 2. The retina is also patterned by retinoic acid, with a concentration gradient that is high on the ventral side of the retina and low on the dorsal side.
===Stem cell biology===
=====Miscellaneous=====
Retinoic acid is an influential factor used in [[differentiation]] of stem cells to more committed fates, echoing retinoic acid's importance in natural embryonic developmental pathways. It is thought to initiate differentiation into a number of different cell lineages by unsequestering certain sequences in the genome.
It has numerous applications in a plethora of stem cell differentiation protocols; amongst these are the differentiation of human [[embryonic stem cell]]s to posterior foregut lineages and also to functional [[motor neuron]]s.
===Vision===
<!--Drug Interactions-->
{{Main|visual cycle}}
|drugInteractions=* Drug
Vitamin A is required in the production of [[rhodopsin]], the [[visual pigment]] used in low light levels. This is why eating foods rich in vitamin A is said to allow an individual to see in the dark.
:* Description
===Epithelial Cells===
<!--Use in Specific Populations-->
Vitamin A is essential for the correct functioning of [[epithelial cells]]. In Vitamin A deficiency, [[mucus-secreting cells]] are replaced by [[keratin]] producing cells, leading to [[xerosis]].
|useInPregnancyFDA=* '''Pregnancy Category'''
|useInPregnancyAUS=* '''Australian Drug Evaluation Committee (ADEC) Pregnancy Category'''
===Glycoprotein synthesis===
There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of {{PAGENAME}} in women who are pregnant.
[[Glycoprotein]] synthesis requires adequate Vitamin A status. In severe Vitamin A deficiency, lack of glycoproteins may lead to corneal ulcers or liquefaction.
|useInLaborDelivery=There is no FDA guidance on use of {{PAGENAME}} during labor and delivery.
|useInNursing=There is no FDA guidance on the use of {{PAGENAME}} with respect to nursing mothers.
|useInPed=There is no FDA guidance on the use of {{PAGENAME}} with respect to pediatric patients.
|useInGeri=There is no FDA guidance on the use of {{PAGENAME}} with respect to geriatric patients.
|useInGender=There is no FDA guidance on the use of {{PAGENAME}} with respect to specific gender populations.
|useInRace=There is no FDA guidance on the use of {{PAGENAME}} with respect to specific racial populations.
|useInRenalImpair=There is no FDA guidance on the use of {{PAGENAME}} in patients with renal impairment.
|useInHepaticImpair=There is no FDA guidance on the use of {{PAGENAME}} in patients with hepatic impairment.
|useInReproPotential=There is no FDA guidance on the use of {{PAGENAME}} in women of reproductive potentials and males.
|useInImmunocomp=There is no FDA guidance one the use of {{PAGENAME}} in patients who are immunocompromised.
===Immune System===
<!--Administration and Monitoring-->
Vitamin A is essential to maintain intact [[epithelial tissue]]s as a physical barrier to infection; it is also involved in maintaining a number of immune cell types from both the innate and acquired immune systems. These include the [[lymphocytes]] ([[B-cells]], [[T-cells]], and [[natural killer cells]]), as well as many myelocytes ([[neutrophils]], [[macrophages]], and myeloid [[dendritic cells]]).
|administration=* Oral
===Formation of red blood cells (Haematopoiesis)===
* Intravenous
Vitamin A may be needed for normal [[haematopoiesis]]; deficiency causes abnormalities in [[iron metabolism]].
|monitoring=There is limited information regarding <i>Monitoring</i> of {{PAGENAME}} in the drug label.
===Growth===
* Description
Vitamin A affects the production of [[Growth hormone|human growth hormone]].
==Clinical use==
<!--IV Compatibility-->
{{main|Tretinoin}}
|IVCompat=There is limited information regarding <i>IV Compatibility</i> of {{PAGENAME}} in the drug label.
All retinoid forms of vitamin A are used in cosmetic and medical applications applied to the skin. Retinoic acid, termed [[Tretinoin]] in clinical usage, is used in the treatment of [[Acne vulgaris|acne]] and [[keratosis pilaris]] in a topical cream. An isomer of tretinoin, [[isotretinoin]] is also used orally (under the trade names ''[[Accutane]]'' and ''Roaccutane''), generally for severe or recalcitrant acne.
In cosmetics, vitamin A derivatives are used as [[Anti-aging cream|anti-aging]] chemicals- vitamin A is absorbed through the skin and increases the rate of skin turnover, and gives an increase in [[collagen]] giving a more youthful appearance<ref>[http://archderm.ama-assn.org/cgi/content/abstract/143/5/606 Archives of Dermatology]</ref>
<!--Overdosage-->
|overdose====Acute Overdose===
Tretinoin, under the alternative name of '''all-trans retinoic acid''' (ATRA), is used as chemotherapy for [[acute promyelocytic leukemia]], a subtype of [[acute myelogenous leukemia]]. This is because cells of this subtype of leukemia are sensitive to agonists of the retinoic acid receptors (RARs).
====Signs and Symptoms====
==Units of measurement==
* Description
When referring to dietary allowances or [[nutrition]]al science, retinol is usually measured in [[international unit]]s (IU). IU refers to biological activity and therefore is unique to each individual compound, however 1 IU of retinol is equivalent to approximately 0.3 micrograms (300 nanograms).
This vitamin plays an essential role in vision, particularly night vision, normal bone and tooth development, reproduction, and the health of skin and mucous membranes (the mucus-secreting layer that lines body regions such as the respiratory tract). Vitamin A also acts in the body as an antioxidant, a protective chemical that may reduce the risk of certain cancers.
There are two sources of dietary vitamin A. Active forms, which are immediately available to the body are obtained from animal products. These are known as retinoids and include retinal and retinol. Precursors, also known as provitamins, which must be converted to active forms by the body, are obtained from fruits and vegetables containing yellow, orange and dark green pigments, known as carotenoids, the most well-known being beta-carotene. For this reason, amounts of vitamin A are measured in Retinal Equivalents (RE). One RE is equivalent to 0.001 mg of retinal, or 0.006 mg of beta-carotene, or 3.3 International Units of vitamin A.
* Description
In the intestine, vitamin A is protected from being chemically changed by vitamin E. Vitamin A is fat-soluble and can be stored in the body. Most of the vitamin A you eat is stored in the liver. When required by a particular part of the body, the liver releases some vitamin A, which is carried by the blood and delivered to the target cells and tissues.
===Chronic Overdose===
===Dietary intake===
There is limited information regarding <i>Chronic Overdose</i> of {{PAGENAME}} in the drug label.
The [[Dietary Reference Intake]] (DRI) Recommended Daily Amount (RDA) for Vitamin A for a 25-year old male is 900 micrograms/day, or 3000 IU.
The [[Food Standards Agency]] states that an average adult should not consume more than 1500 micrograms (5000 IU) per day, because this increases the chance of [[osteoporosis]].
<!--Pharmacology-->
During the absorption process in the [[intestine]]s, retinol is incorporated into [[chylomicron]]s as the ester form, and it is these particles that mediate transport to the [[liver]]. Liver cells ([[hepatocyte]]s) store vitamin A as the ester, and when retinol is needed in other tissues, it is de-esterifed and released into the blood as the alcohol. Retinol then attaches to a serum carrier, [[retinol binding protein]], for transport to target tissues. A binding protein inside cells, [[cellular retinoic acid binding protein]], serves to store and move retinoic acid [[intracellular]]ly. Carotenoid [[bioavailability]] ranges between 1/5 to 1/10 of retinol's. Carotenoids are better absorbed when ingested as part of a fatty meal. Also, the carotenoids in vegetables, especially those with tough cell walls (e.g. carrots), are better absorbed when these cell walls are broken up by cooking or mincing.
<!--Drug box 2-->
|drugBox=<!--Mechanism of Action-->
|mechAction=*
===Deficiency===
<!--Structure-->
:''see [[Vitamin A deficiency]] for details''
|structure=*
[[Image:Vitamin A deficiency.PNG|right|thumb|360px|Prevalence of vitamin A deficiency. Source: [[World Health Organization|WHO]]]]
Vitamin A deficiency is common in developing countries but rarely seen in developed countries. Approximately 250,000 to 500,000 malnourished children in the developing world go blind each year from a deficiency of vitamin A. [[Night blindness]] is one of the first signs of vitamin A deficiency. Vitamin A deficiency contributes to blindness by making the [[cornea]] very dry and damaging the [[retina]] and cornea.
===Retinoid overdose (toxicity)===<!-- This section is linked from [[Cod liver oil]] -->
: [[File:{{PAGENAME}}01.png|thumb|none|600px|This image is provided by the National Library of Medicine.]]
:''see [[Hypervitaminosis A]] for details''
The [[Dietary Reference Intake|Tolerable Upper Intake Level]] (UL) for vitamin A, for a 25-year old male, is 3,000 micrograms/day, or about 10,000 IU.
Too much vitamin A in retinoid form can be harmful or fatal, resulting in what is known as hypervitaminosis A. The body converts the dimerized form, [[carotene]], into vitamin A as it is needed, therefore high levels of carotene are not toxic compared to the ester (animal) forms. The livers of certain animals, especially those adapted to polar environments, often contain amounts of vitamin A that would be toxic to humans. Thus, vitamin A toxicity is typically reported in Arctic explorers and people taking large doses of synthetic vitamin A. The first documented death due to vitamin A poisoning was [[Xavier Mertz]], a [[Switzerland|Swiss]] scientist who died in January 1913 on an [[Antarctica|Antarctic]] expedition that had lost its food supplies and fell to eating its sled dogs. Mertz consumed lethal amounts of vitamin A by eating the dogs' livers.<ref>[http://www.studentbmj.com/back_issues/0502/life/158.html An account of Mertz's illness], retrieved 20 June 2007.</ref>
<!--Pharmacodynamics-->
|PD=There is limited information regarding <i>Pharmacodynamics</i> of {{PAGENAME}} in the drug label.
If eaten in one meal, 30 to 90 grams of [[polar bear]] liver is enough to kill a human being, or to make even sled dogs very ill. <ref>[http://prof_anil_aggrawal.tripod.com/poiso032.html A. Aggrawal, Death by Vitamin A]</ref>
<!--Pharmacokinetics-->
|PK=There is limited information regarding <i>Pharmacokinetics</i> of {{PAGENAME}} in the drug label.
Excess vitamin A has also been suspected to be a contributor to [[osteoporosis]]. This seems to happen at much lower doses than those required to induce acute intoxication. Only preformed vitamin A can cause these problems, because the conversion of carotenoids into vitamin A is downregulated when physiological requirements are met. An excessive uptake of carotenoids can, however, cause [[carotenosis]].
<!--Nonclinical Toxicology-->
|nonClinToxic=There is limited information regarding <i>Nonclinical Toxicology</i> of {{PAGENAME}} in the drug label.
The carotenoid [[beta carotene]] was interestingly associated with an increase in [[lung cancer]] when it was studied in a lung cancer prevention trial in male smokers. In non-smokers, the opposite effect has been noted.
<!--Clinical Studies-->
|clinicalStudies=There is limited information regarding <i>Clinical Studies</i> of {{PAGENAME}} in the drug label.
Excess preformed vitamin A during early pregnancy has also been associated with a significant increase in birth defects.<ref>Challem, Jack, [http://www.thenutritionreporter.com/A-vitamins.html Caution Urged With Vitamin A in Pregnancy: But Beta-Carotene is Safe], ''The Nutrition Reporter Newsletter'', 1995, retrieved 20 June 2007.</ref> These defects may be severe, even life-threatening. Even twice the daily recommended amount can cause severe birth defects.<ref>Stone, Brad. [http://www.fda.gov/bbs/topics/ANSWERS/ANS00689.html Vitamin A and Birth Defects], 6 October 1995, retrieved 20 June 2007.</ref> The FDA currently recommends that pregnant women get their Vitamin A from foods containing beta carotene and that they should ensure that they consume no more than 5,000 IU of preformed Vitamin A (if any) per day. Although Vitamin A is necessary for fetal development, most women carry stores of Vitamin A in their fat cells, so oversupplementation should be strictly avoided.
<!--How Supplied-->
|howSupplied=*
|packLabel=<!--Patient Counseling Information-->
|fdaPatientInfo=There is limited information regarding <i>Patient Counseling Information</i> of {{PAGENAME}} in the drug label.
A review of all randomized controlled trials in the scientific literature by the [[Cochrane Collaboration]] published in [[Journal of the American Medical Association|JAMA]] in 2007 found that vitamin A significantly ''increased'' mortality by 16% (Relative Risk 1.16, 95% confidence interval 1.10-1.24).<ref>Bjelakovic et al., [http://jama.ama-assn.org/cgi/content/abstract/297/8/842 Mortality in randomized trials of antioxidant supplements for primary and secondary prevention: Systematic review and meta-analysis], ''JAMA'', 297:842; February 28, 2007.</ref>
<!--Precautions with Alcohol-->
|alcohol=* Alcohol-{{PAGENAME}} interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.
===Sources===
<!--Brand Names-->
All [[Vitamin_A#Sources|sources of vitamin A]] can provide retinol, but retinoids are found naturally in some foods of animal origin. Each of the following contains at least 0.15 mg of retinoids per 1.75-7 oz. (50-200 g):
|brandNames=* ®<ref>{{Cite web | title = | url = }}</ref>
* [[Cod Liver Oil]]
* [[Butter]]
* [[Liver]] (beef, pork, chicken, turkey, fish)
* [[Egg (food)|Eggs]]
===Synthetic Sources===
<!--Look-Alike Drug Names-->
[[Chemical synthesis|Synthetic]] retinol is marketed under the following trade names: Acon, Afaxin, Agiolan, Alphalin, Anatola, Aoral, Apexol, Apostavit, Atav, Avibon, Avita, Avitol, Axerol, Dohyfral A, Epiteliol, Nio-A-Let, Prepalin, Testavol, Vaflol, Vi-Alpha, Vitpex, Vogan, and Vogan-Neu.
|lookAlike=* A® — B®<ref name="www.ismp.org">{{Cite web | last = | first = | title = http://www.ismp.org | url = http://www.ismp.org | publisher = | date = }}</ref>
===Night vision===
<!--Drug Shortage Status-->
Night blindness—the inability to see well in dim light—is associated with a deficiency of [[vitamin A]]. At first, the most light sensitive (containing more retinal) protein [[rhodopsin]] is influenced. Less pigmented by retinal [[iodopsin]]s (three forms/colors in humans), responsible for [[color vision]] and sensing relatively high light intensities (day vision), are less impaired at early stages of the [[vitamin A]] deficiency. All these protein-pigment complexes are located in the light-sensing cells in eye's [[retina]].
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<!--Pill Image-->
When stimulated by light, rhodopsin splits into a protein and a cofactor: opsin and all-''trans''-retinal (a form of vitamin A). The regeneration of active rhodopsin requires opsin and 11-''cis''-retinal. The regeneration of 11-''cis''-retinal occurs in vertebrates via a sequence of chemical transformations that constitute "the visual cycle" and which occurs primarily in the retinal pigmented epithelial cells.
Without adequate amounts of retinal, regeneration of rhodopsin is incomplete and night blindness occurs. Since carrots are a good source of beta-carotene, there is truth in the old belief that carrots help you see better in the dark.
*Retinyl palmitate ("vitamin A" or "pro-vitamin A")
==Genetically engineered vitamin A enriched rice==
Due to the high prevalence of vitamin A deficiency in [[developing country|developing countries]], there are efforts to produce [[genetically modified]] rice rich in beta carotene. The idea is that this would help poor people, who can not afford a varied diet containing sufficient natural sources of vitamin A, meet their dietary needs. The [[golden rice]] project is one such effort, and is already undergoing trials.
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Black Box Warning
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See full prescribing information for complete Boxed Warning.
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Overview
Retinol is a {{{drugClass}}} that is FDA approved for the {{{indicationType}}} of {{{indication}}}. There is a Black Box Warning for this drug as shown here. Common adverse reactions include .
Adult Indications and Dosage
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Off-Label Use and Dosage (Adult)
Guideline-Supported Use
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There is limited information regarding Off-Label Guideline-Supported Use of Retinol in adult patients.
Non–Guideline-Supported Use
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There is limited information regarding Off-Label Non–Guideline-Supported Use of Retinol in adult patients.
Pediatric Indications and Dosage
FDA-Labeled Indications and Dosage (Pediatric)
Condition1
Dosing Information
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There is limited information regarding FDA-Labeled Use of Retinol in pediatric patients.
Off-Label Use and Dosage (Pediatric)
Guideline-Supported Use
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Developed by:
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There is limited information regarding Off-Label Guideline-Supported Use of Retinol in pediatric patients.
Non–Guideline-Supported Use
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There is limited information regarding Off-Label Non–Guideline-Supported Use of Retinol in pediatric patients.
Contraindications
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See full prescribing information for complete Boxed Warning.
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Adverse Reactions
Clinical Trials Experience
There is limited information regarding Clinical Trial Experience of Retinol in the drug label.
Body as a Whole
Cardiovascular
Digestive
Endocrine
Hematologic and Lymphatic
Metabolic and Nutritional
Musculoskeletal
Neurologic
Respiratory
Skin and Hypersensitivy Reactions
Special Senses
Urogenital
Miscellaneous
Postmarketing Experience
There is limited information regarding Postmarketing Experience of Retinol in the drug label.
