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{{drugbox |
{{DrugProjectFormSinglePage
| IUPAC_name = (2''Z'',4''E'',6''E'',8''E'')-3,7-dimethyl-9-(2,6,6-trimethyl-1-<br>cyclohexenyl)nona-2,4,6,8-tetraenoic acid
|authorTag=<!--Overview-->
| image = Isotretinoin skeletal.svg
|aOrAn=a
| image2 = Isotretinoin3d.svg
|hasBlackBoxWarning=Yes
| width2 = 250px
|adverseReactions=<!--Black Box Warning-->
| CAS_number = 4759-48-2
|blackBoxWarningTitle=<span style="color:#FF0000;">ConditionName: </span>
| ATC_prefix = D10
|blackBoxWarningBody=<i><span style="color:#FF0000;">ConditionName: </span></i>
| ATC_suffix = AD04
 
| PubChem = 5282379
* Content
| DrugBank = APRD00140
 
| C = 20 |H = 28 |O = 2
<!--Adult Indications and Dosage-->
| molecular_weight = 300.44 g/mol
 
| bioavailability = Variable
<!--FDA-Labeled Indications and Dosage (Adult)-->
| metabolism = [[Liver|Hepatic]]
|fdaLIADAdult======Condition1=====
| protein_bound = 99.9%
 
| elimination_half-life = 10–20 hours
* Dosing Information
| excretion = [[Kidney|Renal]] and fecal
 
| licence_US = Isotretinoin
:* Dosage
| pregnancy_AU = X
 
| pregnancy_US = X
=====Condition2=====
| legal_AU = S4
 
| legal_UK = POM
* Dosing Information
| legal_US = Rx-only
 
| routes_of_administration = Oral, topical
:* Dosage
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{{SI}}
=====Condition3=====
{{CMG}}
 
* Dosing Information
 
:* Dosage
 
=====Condition4=====
 
* Dosing Information
 
:* Dosage
 
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* Developed by:
 
* Class of Recommendation:
 
* Strength of Evidence:
 
* Dosing Information
 
:* Dosage
 
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:* Dosage
 
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<!--Pediatric Indications and Dosage-->
 
<!--FDA-Labeled Indications and Dosage (Pediatric)-->
|fdaLIADPed======Condition1=====
 
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:* Dosage
 
=====Condition2=====
 
There is limited information regarding <i>FDA-Labeled Use</i> of {{PAGENAME}} in pediatric patients.
 
<!--Off-Label Use and Dosage (Pediatric)-->
 
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|offLabelPedGuideSupport======Condition1=====
 
* Developed by:
 
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* Strength of Evidence:
 
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:* Dosage
 
=====Condition2=====
 
There is limited information regarding <i>Off-Label Guideline-Supported Use</i> of {{PAGENAME}} in pediatric patients.
 
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:* Dosage
 
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|warnings=* Description
 
====Precautions====
 
* Description
 
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|clinicalTrials=There is limited information regarding <i>Clinical Trial Experience</i> of {{PAGENAME}} in the drug label.
 
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=====Body as a Whole=====
 
 
 
=====Cardiovascular=====
 
 
 
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=====Endocrine=====
 
 
 
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'''Isotretinoin''' ([[International Nonproprietary Name|INN]]) ({{pronEng|ˌaɪsoʊˈtrɛtɨnɔɪn}} or {{IPA|/ˌaɪsoʊtrɨˈtɪnoʊɨn/}}<ref>http://dictionary.reference.com/browse/isotretinoin</ref>) is a [[medication]] used for the treatment of severe [[Acne vulgaris|acne]]. It is sometimes used in prevention and treatment of certain skin cancers.  It is a [[retinoid]], meaning it derives from [[vitamin A]] and is found in small quantities naturally in the body. Oral isotretinoin is marketed under various trade names, most commonly  '''Accutane''' ([[Hoffman-La Roche|Roche]]), '''Amnesteem''' ([[Mylan Laboratories Inc.|Mylan]]), '''Claravis''' ([[Barr Pharmaceuticals|Barr]]), '''Decutan''' ([[Actavis]]), '''Isotane''' ([[Pacific Pharmaceuticals]]), '''Sotret''' ([[Ranbaxy Laboratories, Inc.|Ranbaxy]]), '''Oratane''' (Genepharm Australasia) or '''Roaccutane''' ([[Hoffman-La Roche|Roche]]); while topical isotretinoin is most commonly marketed under the trade names '''Isotrex''' or '''Isotrexin''' ([[Stiefel]]).
=====Urogenital=====


==History==
Prior to the development of isotretinoin, the mainstay treatment of moderate to severe or persistent acne was oral [[antibiotics]] such as the [[tetracycline antibiotics|tetracyclines]] and [[erythromycin]]. While these drugs have proven efficacy, they worked against only one contributing factor of acne – the ''[[Propionibacterium acnes]]'' bacteria. The antibiotics gradually became less effective over time as more resistant strains of the bacterium became prominent.


An early, effective treatment of acne was high doses of the fat-soluble vitamin A. At these dose levels (sometimes 500,000 [[International Unit|IU]] per day) effects such as reduced production of [[sebum]] and dry hair could be noticed . However the vitamin also had many other prominent side effects which inhibited its widespread use.


Increasingly higher dosages of isotretinoin will result in higher toxicity, resembling vitamin A toxicity (the higher the dosage, the more pronounced the side effects will be).  The "upper limit" for Vitamin A (Retinol) is 3 milligrams (10,000 IU).  This is the dosage at which the scientific community agrees there are no side effects for Vitamin A.  Isotretinoin is available in 2.5mg capsules (as well as 5mg, 10mg, 20mg, 40mg).  However, isotretinoin is more teratogenic (causes birth defects) than vitamin A at the same dosage.
=====Miscellaneous=====


The development of the [[retinoic acid]] derivative isotretinoin (13-''cis''-retinoic acid), and its release in [[1982]] by [[Hoffmann-La Roche]], was a great step forward in the treatment of acne. The synthetic compound provided better therapeutic benefit than vitamin A, while also producing fewer [[adverse effect]]s. In February 2002, Roche's patents for isotretinoin expired and there are now many other companies selling cheaper generic versions of the drug. 


Because of a 1984 study funded by Roche, high dosages of the drug became mainstream in treatment. Lower dosages were found to be effective in treatment by independent research (see dosage section of this article), but Roche's dosage recommendations still continue to be used.


Presently, isotretinoin continues to be used only after other acne treatments fail to produce results.  Treatment of acne begins with topical medications (e.g. [[benzoyl peroxide]], [[adapalene]], etc), followed by oral antibiotics (or a combination) and finally isotretinoin therapy.  This is because other treatments, while less effective than isotretinoin, are thought to be associated with fewer adverse effects and lower cost.  The higher cost is due to the higher dosages used.  Taking a toxic level of any substance requires medical supervision.  The cost of the medicine is also a factor (example: taking 5, 10, or even 20mg daily is far less expensive than taking 80mg daily).
<!--Drug Interactions-->
|drugInteractions=* Drug
:* Description


From the time of its introduction the drug was known to have [[teratogenic]] potential, and pregnancies with the drug were strongly discouraged. When they occurred, they were found to have approximately 30% rates of congenital malformation, versus a 3-5% baseline risk.<ref name="pmid17214828">{{cite journal |author=Bérard A, Azoulay L, Koren G, Blais L, Perreault S, Oraichi D |title=Isotretinoin, pregnancies, abortions and birth defects: a population-based perspective |journal=British journal of clinical pharmacology |volume=63 |issue=2 |pages=196-205 |year=2007 |pmid=17214828 |doi=10.1111/j.1365-2125.2006.02837.x}}</ref> Beginning in 1998, prescriptions of the drug came under scrutiny, as fewer than half of prescribers were testing for pregnancy, usually relying on less sensitive urine tests.<ref name="pmid9580798">{{cite journal |author=Holmes SC, Bankowska U, Mackie RM |title=The prescription of isotretinoin to women: is every precaution taken? |journal=Br. J. Dermatol. |volume=138 |issue=3 |pages=450-5 |year=1998 |pmid=9580798 |doi=}}</ref> On the grounds that pregnancies by women taking the drug had been underreported by the manufacturer between 1982 and 2000, and that once generic manufacturers entered the market risk management was no longer centralized, the FDA instituted restrictions on prescribing and dispensing the drug, first with the "System to Manage Accutane Related Teratogenicity" (SMART) in 2000, and subsequently the [[iPLEDGE]] program in 2006. A retrospective cohort study recently found that pregnancy rates were quite high during the period (1 per 30 women per year), but 84% of pregnancies were ended by induced [[abortion]].<ref name="pmid17214828"> </ref>
<!--Use in Specific Populations-->
|useInPregnancyFDA=* '''Pregnancy Category'''
|useInPregnancyAUS=* '''Australian Drug Evaluation Committee (ADEC) Pregnancy Category'''


In countries that do not restrict distribution of isotretinoin, pharmacists recommend 5mg or 10mg daily, since at lower dosages the adverse side effects are diminished. Isotretinoin in topical form is also prescribed.
There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of {{PAGENAME}} in women who are pregnant.
|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.


Isotretinoin is available over the internet from countries where it can be dispensed without a prescription.  It is an ongoing problem for governments where a prescription is required, as it is mailed illegally across borders.
<!--Administration and Monitoring-->
|administration=* Oral


==Pharmacodynamics==
* Intravenous
Isotretinoin noticeably reduces the production of [[sebum]] and shrinks the [[sebaceous glands]]. It stabilizes [[keratinization]] and prevents [[comedones]] from forming.  The exact [[mechanism of action]] is unknown, however it is known that like other [[retinoid]]s, Isotretinoin works by altering [[DNA transcription]].<ref>[http://redpoll.pharmacy.ualberta.ca/drugbank/cgi-bin/getCard.cgi?CARD=APRD00140.txt DrugBank database - Isotretinoin (APRD00140), 12 November 2006], [[University of Alberta]], accessed January 2007</ref> This effect decreases the size and output of sebaceous glands, makes the cells that are sloughed off into the sebaceous glands less sticky, and therefore less able to form comedones.
|monitoring=There is limited information regarding <i>Monitoring</i> of {{PAGENAME}} in the drug label.


==Pharmacokinetics==
* Description
Isotretinoin, when administered orally, is best absorbed when taken after a high fat meal, as it has a high level of [[lipophilicity]]. In a crossover study, it was found that the peak plasma concentration more than doubled when taken after a high fat meal versus a fasted condition. Isotretinoin is primarily (99.9%) bound to plasma proteins, mostly albumin. At least three metabolites have been detected in human plasma after oral administration of isotretinoin. These are 4-oxo-isotretinoin, retinoic acid and 4-oxo-retinoic acid. Isotretinoin also oxidises, irreversibly, to 4-oxo-isotretinoin. The metabolites of isotretinoin are excreted through both [[urine]] and [[feces]]. The mean [[elimination half-life]] is 21 hours, with a standard deviation from this mean of 8.2 hours.


==Clinical use==
<!--IV Compatibility-->
===Indications===
|IVCompat=There is limited information regarding <i>IV Compatibility</i> of {{PAGENAME}} in the drug label.
Isotretinoin is indicated for the treatment of severe cystic [[acne vulgaris]].<ref name="AMH2006">Rossi S, editor. [[Australian Medicines Handbook]] 2006. Adelaide: Australian Medicines Handbook; 2006. ISBN 0-9757919-2-3
</ref><ref name="Micromedex">Klasco RK, editor. Drugdex system, vol. 128. Greenwood Village (CO): Thomson Micromedex; 2006.</ref> It is also effective for [[hidradenitis suppurativa]] and some cases of severe [[acne rosacea]].<ref name="Micromedex" /> It can also be used to help treat [[Harlequin type ichthyosis|harlequin ichthyosis]], and is used in [[xeroderma pigmentosum]] cases to relieve [[keratose]]s.<br/>Although extremely rare, isotretinoin has been used as a treatment for Fibrodysplasia Ossificans Progressiva.


===Prescribing restrictions===
<!--Overdosage-->
In the United Kingdom, this drug may only be prescribed by, or under the supervision of, a consultant [[dermatologist]].<ref name="BNF47">Joint Formulary Committee. [[British National Formulary]]. 47th ed. London: British Medical Association and Royal Pharmaceutical Society of Great Britain. ISBN 0-85369-584-9</ref> A similar situation exists in most [[Australia]]n states – in [[New South Wales]] and [[Victoria (Australia)|Victoria]], for instance, the prescriber must be a [[Fellow]] of the Australasian College of Dermatologists (FACD).<ref>Pharmaceutical Services Branch. Guide to poisons and therapeutic goods legislation for medical practitioners and dentists. Sydney: NSW Department of Health; 2006.</ref> In [[New Zealand]], isotretinoin can be prescribed by any doctor but is subsidised only if prescribed by a skin specialist/[[dermatologist]]. As New Zealand General Practitioner visits are subsidised it is usually cheaper for the patient to buy their isotretinoin with a GP prescription than to pay to see a dermatologist.
|overdose====Acute Overdose===


Since [[1 March]] [[2006]], the dispensing of isotretinoin '''in the United States''' has been controlled by a [[Food and Drug Administration|FDA]]-mandated website called [[iPLEDGE]] – dermatologists are required to register their patients before prescribing and pharmacists are required to check the website before dispensing the drug. Doctors may not prescribe more than a 30-day supply. A new prescription may not be written for at least 30 days. Pharmacies are also under similar restriction.  There is also a 30-day window in which the medication must be picked up at the pharmacy. If the original prescription is lost, or pick-up window is missed, the patient must wait 30 days without any medication. Doctors and pharmacists must also verify written prescriptions in an online system before patients may fill the prescription.
====Signs and Symptoms====


In Mexico, this drug is of restricted use, and an official identification and patient signature is required by the pharmacies.
* Description


===Dosage===
====Management====
[[Image:Roaccutane.JPG|thumb|left|200px|10 mg capsule]]
The dose of isotretinoin a patient receives is dependent on their weight and the severity of the condition.  High dose treatments are administered between 0.5 mg/kg/day to 2 mg/kg/day (usually at 0.5 to 1 mg/kg/day<ref>United States Pharmacopeia Staff. Consumer Reports Complete Drug Reference. Yonkers, NY: Consumer Reports Books, 1995. Pg 998.</ref>, divided into two doses), for a total treatment of 4–6 months. A second course may be used two months following the cessation of the initial course if severe acne recurs. Efficacy appears to be related to the cumulative dose of isotretinoin taken, with a total cumulative dose of 120–150 mg/kg used as a guideline.<ref name="AMH2006" /><ref name="Micromedex" /> High dose treatments should only be used as a last resort due to adverse side effects.


Other studies show that lower dosage treatments are just as effective.<ref name="Amichai2006">{{cite journal | author = Amichai B, Shemer A, Grunwald M | title = Low-dose isotretinoin in the treatment of acne vulgaris | journal = J Am Acad Dermatol | volume = 54 | issue = 4 | pages = 644–6 | year = 2006 | id = PMID 16546586}} [http://dermatology.jwatch.org/cgi/content/full/2006/425/1 Summary of study results]</ref><ref name="Seukeran1998">{{cite journal | author = Seukeran D, Cunliffe W | title = Acne vulgaris in the elderly: the response to low-dose isotretinoin | journal = Br J Dermatol | volume = 139 | issue = 1 | pages = 99–101 | year = 1998 | id = PMID 9764156}}</ref>
* Description
In these experiments, subjects used 20mg/day, which is 0.25 mg/kg/day for an 80 kg (176 pounds) person.


More experiments and studies showing the success of low dosage treatments with diminished or non-existent side effects:<br/>
===Chronic Overdose===
http://www.uspharmacist.com/oldformat.asp?url=newlook/files/Feat/apr00iso.cfm&pub_id=8&article_id=508<br/>
http://archderm.ama-assn.org/cgi/content/abstract/130/3/319<br/>
http://www.blackwell-synergy.com/doi/abs/10.1111/j.1365-4362.1994.tb01500.x<br/>
http://www.blackwell-synergy.com/doi/abs/10.1111/j.1468-3083.1998.tb00763.x<br/>
http://content.karger.com/ProdukteDB/produkte.asp?Aktion=ShowFulltext&ProduktNr=223854&Ausgabe=227284&ArtikelNr=45270


===Preparations===
There is limited information regarding <i>Chronic Overdose</i> of {{PAGENAME}} in the drug label.
Isotretinoin is marketed under many brand names by various manufacturers. It is typically available as 5 mg, 10 mg, 20 mg, 30mg and (in the USA) 40 mg capsules. Some brands of oral isotretinoin include: ''Accure'' ([[Alphapharm]]), ''Accutane'' and ''Roaccutane'' ([[Hoffmann-La Roche|Roche]]), ''Aknenormin'' ([[Hermal]]), ''Amnesteem'' ([[Mylan]]), ''Ciscutan'' ([[Pelpharma]]), ''Claravis'' ([[Barr Pharmaceuticals|Barr]]), ''Clarus'' ([[Prepharm Canada|Prepharm]]), ''Isohexal'' ([[Hexal Australia]]), ''Isotane'' ([[Pacific Pharmaceuticals]]), ''Isotroin'' ([[Cipla]]), ''Oratane'' ([[Douglas Pharmaceuticals]]), and ''Sotret'' ([[Ranbaxy]]).


It is also available as a 0.05% [[topical]] preparation, marketed by [[Stiefel]] under the trade name ''Isotrex'' or ''Isotrexin'' (with [[erythromycin]])..
<!--Pharmacology-->


==Adverse effects==
<!--Drug box 2-->
Increasingly higher dosages will result in higher toxicity, resembling vitamin A toxicity.  [[Adverse drug reaction]]s associated with isotretinoin therapy include:<ref name="AMH2006" />
|drugBox=<!--Mechanism of Action-->
*Common: mild acne flare, dryness of skin, lips and mucous membranes, [[infection]] of the [[cuticles]], [[cheilitis]], itch, skin fragility, skin peeling, rash, flushing, [[photosensitivity]], [[nose bleed]]s, dry eyes, eye irritation, [[conjunctivitis]], reduced tolerance to [[contact lenses]], [[hyperlipidaemia]], raised [[liver enzyme]]s, headaches, hair thinning, [[myalgia]] and/or [[arthralgia]].
|mechAction=*  
*Infrequent: severe acne flare, raised blood [[glucose]] level, increased [[erythrocyte sedimentation rate]], fatigue.
*Rare: impaired [[night vision#biological night vision|night vision]], [[cataract]]s, [[optic neuritis]], [[menstrual cycle|menstrual]] disturbances, [[inflammatory bowel disease]], [[pancreatitis]], [[hepatitis]], [[cornea]]l opacities, [[papilloedema]], [[idiopathic intracranial hypertension]], [[skeleton|skeletal]] [[hyperostosis]], extraosseous [[calcification]], and it is believed that severe depression can occur, although there is no conclusive evidence for this.
The following adverse effects have been reported to persist, even after discontinuing therapy: [[alopecia]] (hair loss), arthralgias, decreased night vision, [[degenerative disc disease]], [[keloid]]s, bone disease. High dosages of isotretinoin have been reported to cause [[rosacea]] (a disease of severe facial skin redness and irritation).


[[Erectile dysfunction]] in the form of difficulty in maintaining [[erection]] was reported in several patients in a clinical study. The [[impotence]] may have been caused by the [[psychiatric]] side effects of isotretinoin.<ref>{{cite journal | author = Tirado Sánchez A | coauthors = León Dorantes G. | year = 2005 | month = Nov-Dec | title = [Erectile dysfunction during isotretinoin therapy] | journal = Actas urologicas españolas. | volume = 29 | issue = 10 | pages = 974-6 | pmid = 16447596 }}</ref>
<!--Structure-->
|structure=*


While [[vitamin E]] supplements have been advocated by some to reduce the toxicity of high-dose retinoids without reducing drug efficacy, test results have proven this to be false.<ref name="Kus2005">Kus S, Gün D, Demirçay Z, Sur H. Vitamin E does not reduce the side-effects of isotretinoin in the treatment of acne vulgaris. Int J Dermatol 2005;44(3):248-51. PMID 15807739</ref>
: [[File:{{PAGENAME}}01.png|thumb|none|600px|This image is provided by the National Library of Medicine.]]


Patients receiving isotretinoin therapy are not permitted to donate blood during and for at least one month after discontinuation of isotretinoin therapy due to reported birth defects to unborn children.
<!--Pharmacodynamics-->
|PD=There is limited information regarding <i>Pharmacodynamics</i> of {{PAGENAME}} in the drug label.


===Teratogenicity (Birth Defects)===<!-- This section is linked from [[Postpartum depression]] -->
<!--Pharmacokinetics-->
Isotretinoin is a [[teratogen]] and is highly likely to cause birth defects if taken during pregnancy. Isotretinoin is classified as [[Food and Drug Administration|FDA]] [[Pregnancy category (pharmaceutical)|Pregnancy Category]] X and [[Australian Drug Evaluation Committee|ADEC]] Category X, and use is contraindicated in pregnancy.<ref name="Micromedex" />
|PK=There is limited information regarding <i>Pharmacokinetics</i> of {{PAGENAME}} in the drug label.


The manufacturer recommends that pregnancy be excluded in female patients two weeks prior to commencement of isotretinoin, and that they should use effective contraception (sometimes two simultaneous forms are recommended) at least one month prior to commencement, during, and for at least one month following isotretinoin therapy.<ref name="RoaccutanePI">Roche Products Pty Ltd. Roaccutane (Australian Approved Product Information). Dee Why (NSW): Roche; 2005.</ref>
<!--Nonclinical Toxicology-->
|nonClinToxic=There is limited information regarding <i>Nonclinical Toxicology</i> of {{PAGENAME}} in the drug label.


In the [[United States|U.S.]] more than 2,000 women have become pregnant while taking the drug between 1982 and 2003, with most pregnancies ending in [[abortion]] or [[miscarriage]]. About 160 babies with birth defects were born. Consequently, the [[iPLEDGE]] program was introduced by the U.S. [[Food and Drug Administration]] on [[12 August]] [[2005]] in an attempt to ensure that female patients receiving isotretinoin do not become pregnant – as of [[1 March]] [[2006]], only prescribers registered and activated in iPLEDGE are able to prescribe isotretinoin, and only patients registered and qualified in iPLEDGE will be able to have isotretinoin dispensed.
<!--Clinical Studies-->
|clinicalStudies=There is limited information regarding <i>Clinical Studies</i> of {{PAGENAME}} in the drug label.


===Depression===
<!--How Supplied-->
Several studies have suggested a possible link between isotretinoin and [[clinical depression]].<ref name="ODonnell2003">O'Donnell J. Overview of existing research and information linking isotretinoin (accutane), depression, psychosis, and suicide. Am J Ther 2003;10(2):148-59. PMID 12629595</ref><ref name="Bremner2003">Bremner JD. Does isotretinoin cause depression and suicide? Psychopharmacol Bull 2003;37(1):64-78. PMID 14561949</ref> However, no conclusive evidence has been produced. Despite this, the argument that isotretinoin caused depression and suicide has won a few lawsuits, and is partially responsible for the strict control of the drug, especially in the United States. Various case reports of depression, suicidal ideation, suicide attempt, and suicide in patients treated with isotretinoin have been reported to the U.S. FDA Adverse Events Reporting System, with 431 cases reported between 1982 and May 2001 – of these 37 patients had committed suicide.<ref name="Wysowski2001">Wysowski DK, Pitts M, Beitz J. An analysis of reports of depression and suicide in patients treated with isotretinoin. J Am Acad Dermatol 2001;45(4):515-9. PMID 11568740</ref> While analyses have suggested an association between isotretinoin therapy and depression, no causal relationship has been established and further studies are required.<ref name="Ng2003">Ng CH, Schweitzer I. The association between depression and isotretinoin use in acne. Aust N Z J Psychiatry 2003;37(1):78-84. PMID 12534661</ref><ref name="Hull2003">Hull PR, D'Arcy C. Isotretinoin use and subsequent depression and suicide: presenting the evidence. Am J Clin Dermatol 2003;4(7):493-505. PMID 12814338</ref>
|howSupplied=*


Studies have shown that patients with acne, the population group eligible to receive isotretinoin therapy, have an increased risk of clinical depression compared with the general population.<ref name="Gupta1998">Gupta MA, Gupta AK. Depression and suicidal ideation in dermatology patients with acne, alopecia areata, atopic dermatitis and psoriasis. Br J Dermatol. 1998;139(5):846-50. PMID 9892952</ref><ref name="Niemeier1998">Niemeier V, Kupfer J, Demmelbauer-Ebner M, Stangier U, Effendy I, Gieler U. Coping with acne vulgaris. Evaluation of the chronic skin disorder questionnaire in patients with acne. Dermatology 1998;196(1):108-15. PMID 9557243</ref> Chee Hong describes Isotretinoin-related depression as "an [[Idiosyncratic drug reactions|idiosyncratic]] side-effect", claiming, often anxiety can bring on acne and depression, creating more anxiety.<ref>Chee Hong Ng, Isaac Schweitzer (2003)The association between depression and isotretinoin use in acne Australian and New Zealand Journal of Psychiatry 37 (1), 78–84. doi:10.1046/j.1440-1614.2003.01111.x</ref> Correspondingly, treatment of severe acne with isotretinoin has been shown to reduce anxiety and depression, for tests have shown acne to be a main depressant in most tested patients' lives.<ref name="Rubinow1987">Rubinow DR, Peck GL, Squillace KM, Gantt GG. Reduced anxiety and depression in cystic acne patients after successful treatment with oral isotretinoin. J Am Acad Dermatol 1987;17(1):25-32. PMID 2956296</ref><ref name="Chia2005">Chia CY, Lane W, Chibnall J, Allen A, Siegfried E. Isotretinoin therapy and mood changes in adolescents with moderate to severe acne: a cohort study. Arch Dermatol 2005;141(5):557-60. PMID 15897376</ref>
<!--Patient Counseling Information-->
|fdaPatientInfo=There is limited information regarding <i>Patient Counseling Information</i> of {{PAGENAME}} in the drug label.


One study utilising [[positron emission tomography]] (PET) showed functional brain imaging changes in patients treated with isotretinoin, however the clinical relevance of this finding is unclear.<ref name="Bremner2005">Bremner JD, Fani N, Ashraf A, Votaw JR, Brummer ME, Cummins T, et al. Functional brain imaging alterations in acne patients treated with isotretinoin. [[American Journal of Psychiatry|Am J Psychiatry]] 2005;162(5):983-91. PMID 15863802</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.


U.S. Representative [[Bart Stupak]] (D-MI) is known for his distrust of Accutane. He believes unadvertised psychological side effects from the drug drove his teenage son, Bartholomew Thomas "B.J" Stupak Jr., to commit suicide in [[2000]].
<!--Brand Names-->
|brandNames=* ®<ref>{{Cite web | title =  | url =  }}</ref>


==Drug interactions==
<!--Look-Alike Drug Names-->
The concurrent use of isotretinoin with [[tetracycline antibiotics]] or [[vitamin A]] supplementation is not recommended. Concurrent use of isotretinoin with tetracyclines significantly increases the risk of [[idiopathic intracranial hypertension]]. Concurrent intake of [[Vitamin A]] supplementation increases the risk of vitamin A toxicity.<ref name="Micromedex" />
|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>


Concurrent use of isotretinoin with [[methotrexate]] increases the risk of [[hepatotoxicity]] and may increase methotrexate levels. The combination is used with caution and close monitoring of adverse effects and [[liver function tests]].<ref name="AMH2006" />
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==See also==
*[[Tazarotene]]
*[[Hypervitaminosis A syndrome]]


==References==
{{Reflist|2}}


==External links==
<!--Label Display Image-->
* [http://www.roche.com Hoffmann-La Roche] (Makers of (Ro) accutane)
* [http://www.accutaneandacne.com Accutane Information]
* [http://www.fda.gov/cder/drug/infopage/accutane/default.htm FDA's Accutane Information Page]
* [http://www.fda.gov/cder/drug/infopage/accutane/accutanemedicationguide.pdf FDA distributed "Accutane Medication Guide"]
* [http://www.drugs.com/MTM/isotretinoin.html Drugs.com Isotretinoin Information]
* [http://dermatology.cdlib.org/95/letters/isotretinoin/danby.html Dermatology Vol 9: issue 5:  Night blindness, vitamin A deficiency, and isotretinoin psychotoxicity]
* {{DermNet|treatments/isotretinoin}}


{{Acne Agents}}




[[Category:Retinoids]]
[[Category:Teratogens]]
[[Category:Hematology]]


[[de:Isotretinoin]]
[[es:Isotretinoína]]
[[fa:ایزوترتینوین]]
[[fr:Isotrétinoïne]]
[[it:Isotretinoina]]
[[he:איזוטרטינואין]]
[[nl:Isotretinoïne]]
[[pt:Isotretinoína]]
[[sl:Izotretinoin]]


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Revision as of 14:29, 12 December 2014

Isotretinoin
Black Box Warning
Adult Indications & Dosage
Pediatric Indications & Dosage
Contraindications
Warnings & Precautions
Adverse Reactions
Drug Interactions
Use in Specific Populations
Administration & Monitoring
Overdosage
Pharmacology
Clinical Studies
How Supplied
Images
Patient Counseling Information
Precautions with Alcohol
Brand Names
Look-Alike Names

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1];

Disclaimer

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Black Box Warning

ConditionName:
See full prescribing information for complete Boxed Warning.
ConditionName:
  • Content

Overview

Isotretinoin 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

FDA-Labeled Indications and Dosage (Adult)

Condition1
  • Dosing Information
  • Dosage
Condition2
  • Dosing Information
  • Dosage
Condition3
  • Dosing Information
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Condition4
  • Dosing Information
  • Dosage

Off-Label Use and Dosage (Adult)

Guideline-Supported Use

Condition1
  • Developed by:
  • Class of Recommendation:
  • Strength of Evidence:
  • Dosing Information
  • Dosage
Condition2

There is limited information regarding Off-Label Guideline-Supported Use of Isotretinoin in adult patients.

Non–Guideline-Supported Use

Condition1
  • Dosing Information
  • Dosage
Condition2

There is limited information regarding Off-Label Non–Guideline-Supported Use of Isotretinoin in adult patients.

Pediatric Indications and Dosage

FDA-Labeled Indications and Dosage (Pediatric)

Condition1
  • Dosing Information
  • Dosage
Condition2

There is limited information regarding FDA-Labeled Use of Isotretinoin in pediatric patients.

Off-Label Use and Dosage (Pediatric)

Guideline-Supported Use

Condition1
  • Developed by:
  • Class of Recommendation:
  • Strength of Evidence:
  • Dosing Information
  • Dosage
Condition2

There is limited information regarding Off-Label Guideline-Supported Use of Isotretinoin in pediatric patients.

Non–Guideline-Supported Use

Condition1
  • Dosing Information
  • Dosage
Condition2

There is limited information regarding Off-Label Non–Guideline-Supported Use of Isotretinoin in pediatric patients.

Contraindications

  • Condition1

Warnings

ConditionName:
See full prescribing information for complete Boxed Warning.
ConditionName:
  • Content
  • Description

Precautions

  • Description

Adverse Reactions

Clinical Trials Experience

There is limited information regarding Clinical Trial Experience of Isotretinoin 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 Isotretinoin 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

Drug Interactions

  • Drug
  • Description

Use in Specific Populations

Pregnancy

Pregnancy Category (FDA):

  • Pregnancy Category


Pregnancy Category (AUS):

  • Australian Drug Evaluation Committee (ADEC) Pregnancy Category

There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Isotretinoin in women who are pregnant.

Labor and Delivery

There is no FDA guidance on use of Isotretinoin during labor and delivery.

Nursing Mothers

There is no FDA guidance on the use of Isotretinoin with respect to nursing mothers.

Pediatric Use

There is no FDA guidance on the use of Isotretinoin with respect to pediatric patients.

Geriatic Use

There is no FDA guidance on the use of Isotretinoin with respect to geriatric patients.

Gender

There is no FDA guidance on the use of Isotretinoin with respect to specific gender populations.

Race

There is no FDA guidance on the use of Isotretinoin with respect to specific racial populations.

Renal Impairment

There is no FDA guidance on the use of Isotretinoin in patients with renal impairment.

Hepatic Impairment

There is no FDA guidance on the use of Isotretinoin in patients with hepatic impairment.

Females of Reproductive Potential and Males

There is no FDA guidance on the use of Isotretinoin in women of reproductive potentials and males.

Immunocompromised Patients

There is no FDA guidance one the use of Isotretinoin in patients who are immunocompromised.

Administration and Monitoring

Administration

  • Oral
  • Intravenous

Monitoring

There is limited information regarding Monitoring of Isotretinoin in the drug label.

  • Description

IV Compatibility

There is limited information regarding IV Compatibility of Isotretinoin in the drug label.

Overdosage

Acute Overdose

Signs and Symptoms

  • Description

Management

  • Description

Chronic Overdose

There is limited information regarding Chronic Overdose of Isotretinoin in the drug label.

Pharmacology

There is limited information regarding Isotretinoin Pharmacology in the drug label.

Mechanism of Action

Structure

File:Isotretinoin01.png
This image is provided by the National Library of Medicine.

Pharmacodynamics

There is limited information regarding Pharmacodynamics of Isotretinoin in the drug label.

Pharmacokinetics

There is limited information regarding Pharmacokinetics of Isotretinoin in the drug label.

Nonclinical Toxicology

There is limited information regarding Nonclinical Toxicology of Isotretinoin in the drug label.

Clinical Studies

There is limited information regarding Clinical Studies of Isotretinoin in the drug label.

How Supplied

Storage

There is limited information regarding Isotretinoin Storage in the drug label.

Images

Drug Images

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Package and Label Display Panel

{{#ask: Label Page::Isotretinoin |?Label Name |format=template |template=DrugLabelImages |mainlabel=- |sort=Label Page }}

Patient Counseling Information

There is limited information regarding Patient Counseling Information of Isotretinoin in the drug label.

Precautions with Alcohol

  • Alcohol-Isotretinoin interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.

Brand Names

Look-Alike Drug Names

Drug Shortage Status

Price

References

The contents of this FDA label are provided by the National Library of Medicine.

  1. ↑ Empty citation (help)
  2. ↑ "http://www.ismp.org". External link in |title= (help)

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