Isotretinoin
Systematic (IUPAC) name
(2Z,4E,6E,8E)-3,7-dimethyl-9-(2,6,6-trimethyl-1- cyclohexenyl)nona-2,4,6,8-tetraenoic acid
Identifiers
CAS number	4759-48-2
ATC code	D10AD04
PubChem	5282379
DrugBank	APRD00140
Chemical data
Formula	C20H28O2
Mol. mass	300. IUPAC Nomenclature is a system of naming Chemical compounds and of describing the science of Chemistry in general CAS registry numbers are unique numerical identifiers for Chemical compounds Polymers biological sequences mixtures and Alloys They are also referred to The Anatomical Therapeutic Chemical Classification System is used for the classification of drugs It is controlled by the WHO Collaborating Centre for Drug A section of the Anatomical Therapeutic Chemical Classification System. PubChem is a Database of chemical Molecules The system is maintained by the National Center for Biotechnology Information (NCBI a component The DrugBank database available at the University of Alberta is a unique Bioinformatics and Cheminformatics resource that combines detailed drug (i A chemical formula is a way of expressing information about the Atoms that constitute a particular Chemical compound, and how the relationship between those atoms changes Carbon (kɑɹbən is a Chemical element with the symbol C and its Atomic number is 6 Hydrogen (ˈhaɪdrədʒən is the Chemical element with Atomic number 1 Oxygen (from the Greek roots ὀξύς (oxys (acid literally "sharp" from the taste of acids and -γενής (-genēs (producer literally begetteris the The molecular mass (abbreviated m of a substance, more commonly referred to as molecular weight and abbreviated as MW, is the Mass of one 44 g/mol
Pharmacokinetic data
Bioavailability	Variable
Protein binding	99. In Pharmacology, bioavailability is used to describe the fraction of an administered Dose of unchanged drug that reaches the Systemic circulation, one of A drug's efficiency may be affected by the degree to which it binds to the proteins within Blood plasma. 9%
Metabolism	Hepatic
Half life	10–20 hours
Excretion	Renal and fecal
Therapeutic considerations
Licence data	US
Pregnancy cat.	X(AU) X(US)
Legal status	Prescription Only (S4)(AU) POM(UK) ℞-only(US)
Routes	Oral, topical

Isotretinoin (INN) (pronounced /aɪsoʊtrɨˈtɪnoʊɨn/ or /ˌaɪsoʊtrɨˈtɪnoʊɨn/^[1]) is a medication used for the treatment of severe acne. Drug metabolism is the Metabolism of drugs, their Biochemical modification or degradation usually through specialized enzymatic systems The liver is a vital organ in the human body and is present in Vertebrates and some other animals The biological half-life of a substance is the time it takes for a substance (drug radioactive nuclide or other to lose half of its pharmacologic physiologic or radiologic activity Excretion is the process of eliminating waste products of Metabolism and other non-useful materials The kidneys are complicated organs that have numerous biological roles The regulation of therapeutic goods, that is drugs and therapeutic devices, varies by jurisdiction The pregnancy category of a pharmaceutical agent is an assessment of the risk of fetal injury due to the pharmaceutical if it is used as directed by the mother during For a topic outline on this subject see List of basic Australia topics. The United States of America —commonly referred to as the The regulation of therapeutic goods, that is drugs and therapeutic devices, varies by jurisdiction The Standard for the Uniform Scheduling of Drugs and Poisons, abbreviated SUSDP, is a document used in the regulation of drugs and poisons in Australia. For a topic outline on this subject see List of basic Australia topics. A prescription drug is a licensed medicine that is regulated by legislation to require a prescription before it can be obtained The United Kingdom of Great Britain and Northern Ireland, commonly known as the United Kingdom, the UK or Britain,is a Sovereign state located A prescription drug is a licensed medicine that is regulated by legislation to require a prescription before it can be obtained The United States of America —commonly referred to as the In Pharmacology and Toxicology, a route An International Nonproprietary Name ( INN; also known as rINN, for recommended International Nonproprietary Name or pINN for proposed Medication, also referred to as medicine, can be loosely defined as any substance intended for use in the diagnosis cure mitigation treatment or prevention of disease Acne vulgaris (commonly called acne) is a Skin disease caused by changes in the Pilosebaceous units (skin structures consisting of a Hair follicle It is sometimes used as a chemotherapy medication for prevention and treatment of certain skin cancers. In some cases, it is used to treat Harlequin type ichthyosis. Harlequin-type ichthyosis (also harlequin ichthyosis, ichthyosis congenita, Ichthyosis fetalis or keratosis It is a retinoid, meaning it derives from vitamin A and is found in small quantities naturally in the body. The retinoids are a class of Chemical compounds that are related chemically to Vitamin A. Vitamin A refers to a family of similarly shaped molecules the Retinoids. Oral isotretinoin is marketed under various trade names, most commonly Accutane (Roche), Amnesteem (Mylan), Claravis (Barr), Decutan (Actavis), Isotane (Pacific Pharmaceuticals), Sotret (Ranbaxy), Oratane (Genepharm Australasia) or Roaccutane (Roche); while topical isotretinoin is most commonly marketed under the trade names Isotrex or Isotrexin (Stiefel). F Hoffmann–La Roche Ltd is a Swiss global health-care company which operates world-wide under two divisions Pharmaceuticals and Diagnostics. Barr Pharmaceuticals Inc, ( is global specialty pharmaceutical company that operates in more than 30 countries worldwide and is engaged in the development manufacture and marketing Actavis is an international generic pharmaceutical company founded in 1956 as Pharmaco Ranbaxy Laboratories Limited is India's largest Pharmaceutical company F Hoffmann–La Roche Ltd is a Swiss global health-care company which operates world-wide under two divisions Pharmaceuticals and Diagnostics.

Contents 1 History 2 Pharmacodynamics 3 Pharmacokinetics 4 Clinical use 4.1 Indications 4.2 Prescribing restrictions 4.3 Dosage 4.4 Preparations 5 Adverse effects 5.1 Teratogenicity (Birth Defects) 5.2 Depression 5.3 Psychological effects 5.4 Crohn's Disease and Ulcerative colitis 6 Drug interactions 7 See also 8 References 9 External links

History

Prior to the development of isotretinoin, the mainstay treatment of moderate to severe or persistent acne was oral antibiotics such as the tetracyclines and erythromycin. In modern usage an antibiotic is a Chemotherapeutic agent with activity against Microorganisms such as Bacteria, fungi or Protozoa Tetracyclines are a group of Broad-spectrum antibiotics whose general usefulness has been reduced with the onset of bacterial resistance Erythromycin is a Macrolide Antibiotic that has an antimicrobial spectrum similar to or slightly wider than that of Penicillin, and is often used for people While these drugs have proven efficacy, they worked against only one contributing factor of acne – the Propionibacterium acnes bacteria. Propionibacterium acnes is a relatively slow growing typically Aerotolerant Anaerobic Gram positive Bacterium that is linked to the 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 IU per day) effects such as reduced production of sebum and dry hair could be noticed. In Pharmacology, the International Unit is a unit of measurement for the amount of a substance based on measured Biological activity or effect The sebaceous glands are Glands found in the Skin of Mammals Locations and morphology A branched type of Acinar gland, these 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.

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. Year 1982 ( MCMLXXXII) was a Common year starting on Friday (link displays the 1982 Gregorian calendar) F Hoffmann–La Roche Ltd is a Swiss global health-care company which operates world-wide under two divisions Pharmaceuticals and Diagnostics. The synthetic compound provided better therapeutic benefit than vitamin A, while also producing fewer adverse effects. In Medicine, an adverse effect is a harmful and undesired effect resulting from a medication or other intervention such as Chemotherapy or Surgery. 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.

Currently, 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. Benzoyl peroxide (ˈbɛnzɔɪl pəˈrɒksaɪd is a Chemical in the Organic peroxide family Adapalene is a topical Retinoid primarily used in the treatment of acne and is also used ( off-label) to treat Keratosis pilaris as 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 medical supervision required in taking a toxic dosage. 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).

From the time of its introduction the drug was known to have teratogenic potential, and pregnancies with the drug were strongly discouraged. Teratology stems from the Greek ( Genitive) meaning monster, or marvel and, meaning word, speech. When they occurred, they were found to have approximately 30% rates of congenital malformation, versus a 3-5% baseline risk. ^[2] 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. ^[3] 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. The iPLEDGE program is a mandatory distribution program in the United States for Isotretinoin (commonly sold under the trade names Accutane Amneesteen Claravis or 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. An ^[2]

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.

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.

Pharmacodynamics

Isotretinoin noticeably reduces the production of sebum and shrinks the sebaceous glands. The sebaceous glands are Glands found in the Skin of Mammals Locations and morphology A branched type of Acinar gland, these The sebaceous glands are Glands found in the Skin of Mammals Locations and morphology A branched type of Acinar gland, these It stabilizes keratinization and prevents comedones from forming. Keratins are a family of fibrous structural proteins; tough and insoluble they form the hard but nonmineralized structures found in Reptiles Birds A blackhead (medically known as an open comedo, plural comedones) is a yellowish or blackish bump or plug on the skin The exact mechanism of action is unknown, however it is known that like other retinoids, Isotretinoin works by altering DNA transcription. In Pharmacology, the term mechanism of action (MOA refers to the specific biochemical interaction through which a drug substance produces its pharmacological effect The retinoids are a class of Chemical compounds that are related chemically to Vitamin A. Transcription is the synthesis of RNA under the direction of DNA ^[4] 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.

Pharmacokinetics

Isotretinoin, when administered orally, is best absorbed when taken after a high fat meal, as it has a high level of lipophilicity. Lipophilicity, fat-liking, refers to the ability of a Chemical compound to dissolve in fats oils lipids and non-polar solvents such as Hexane or 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. Urine is a liquid waste product of the body secreted by the Kidneys by a process of filtration from Blood and Excreted through the Urethra. Feces, faeces, or fæces (see spelling differences) is a waste product from an animal's digestive tract expelled through the Anus The mean elimination half-life is 21 hours, with a standard deviation from this mean of 8. The biological half-life of a substance is the time it takes for a substance (drug radioactive nuclide or other to lose half of its pharmacologic physiologic or radiologic activity 2 hours.

Clinical use

Indications

Isotretinoin is indicated for the treatment of severe cystic acne vulgaris. Acne vulgaris (commonly called acne) is a Skin disease caused by changes in the Pilosebaceous units (skin structures consisting of a Hair follicle ^[5][6] It is also effective for hidradenitis suppurativa and some cases of severe acne rosacea. Hidradenitis suppurativa or HS is a Skin disease that affects areas bearing Apocrine sweat glands and Hair follicles such as the underarms groin Rosacea (rəʊˈzeɪʃə is a common but often misunderstood condition that is estimated to affect over 45 million people worldwide ^[6] It can also be used to help treat harlequin ichthyosis, and is used in xeroderma pigmentosum cases to relieve keratoses. Harlequin-type ichthyosis (also harlequin ichthyosis, ichthyosis congenita, Ichthyosis fetalis or keratosis Xeroderma pigmentosum, or XP is an Autosomal recessive Genetic disorder of DNA repair in which the ability to repair damage caused by Ultraviolet Keratosis is a growth of Keratin on the skin More specifically it can refer to Actinic keratosis (also known as Solar keratosis)
Although extremely rare, isotretinoin has been used as a treatment for Fibrodysplasia Ossificans Progressiva.

Prescribing restrictions

In the United Kingdom, this drug may only be prescribed by, or under the supervision of, a consultant dermatologist. Dermatology (from Greek grc δέρμα derma, "skin" and grc -λογία -logia) is a branch of Medicine dealing with ^[7] A similar situation exists in most Australian states – in New South Wales and Victoria, for instance, the prescriber must be a Fellow of the Australasian College of Dermatologists (FACD). For a topic outline on this subject see List of basic Australia topics. A fellow in the broadest sense is someone who is an equal or a comrade ^[8] In New Zealand, isotretinoin can be prescribed by any doctor but is subsidised only if prescribed by a skin specialist/dermatologist. New Zealand is an Island country in the south-western Pacific Ocean comprising two main landmasses (the North Island and the South Island Dermatology (from Greek grc δέρμα derma, "skin" and grc -λογία -logia) is a branch of Medicine dealing with 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.

Since 1 March 2006, the dispensing of isotretinoin in the United States has been controlled by a 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. Events 86 BC - Lucius Cornelius Sulla, at the head of a Roman Republic army enters in Athens, removing the Tyrant Year 2006 ( MMVI) was a Common year starting on Sunday of the Gregorian calendar. The iPLEDGE program is a mandatory distribution program in the United States for Isotretinoin (commonly sold under the trade names Accutane Amneesteen Claravis or The patient must visit the iPLEDGE website or call the hotline number in order to log in with his or her ID code to answer the iPLEDGE questionaire. The prescription may not be dispensed until all three parties have complied. A physician 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 7-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 re-qualify to have another prescription written. Doctors and pharmacists must also verify written prescriptions in an online system before patients may fill the prescription.

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

Dosage

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^[9], 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. ^[5][6] 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. ^[10][11] 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:
http://www.uspharmacist.com/oldformat.asp?url=newlook/files/Feat/apr00iso.cfm&pub_id=8&article_id=508
http://archderm.ama-assn.org/cgi/content/abstract/130/3/319
http://www.blackwell-synergy.com/doi/abs/10.1111/j.1365-4362.1994.tb01500.x
http://www.blackwell-synergy.com/doi/abs/10.1111/j.1468-3083.1998.tb00763.x
http://content.karger.com/ProdukteDB/produkte.asp?Aktion=ShowFulltext&ProduktNr=223854&Ausgabe=227284&ArtikelNr=45270

Preparations

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 (Roche), Aknenormin (Hermal), Amnesteem (Mylan), Ciscutan (Pelpharma), Claravis (Barr), Clarus (Prepharm), Isohexal (Hexal Australia), Isotane (Pacific Pharmaceuticals), Isotroin (Cipla), Oratane (Douglas Pharmaceuticals), and Sotret (Ranbaxy). Alphapharm is a generic drug manufacturing company based in Australia. F Hoffmann–La Roche Ltd is a Swiss global health-care company which operates world-wide under two divisions Pharmaceuticals and Diagnostics. Barr Pharmaceuticals Inc, ( is global specialty pharmaceutical company that operates in more than 30 countries worldwide and is engaged in the development manufacture and marketing Hexal Australia is a large pharmaceutical manufacturer formed in 1995 with Hexal AG Germany Cipla, originally founded as The Chemical Industrial & Pharmaceutical Laboratories is a prominent Indian Pharmaceutical company, best-known outside The following is a list of the 50 largest Pharmaceutical and Biotech companies ranked by healthcare revenue Ranbaxy Laboratories Limited is India's largest Pharmaceutical company

It is also available as a 0. 05% topical preparation, marketed by Stiefel under the trade name Isotrex or Isotrexin (with erythromycin). In Medicine, a topical Medication is applied to body surfaces such as the Skin or Mucous membranes for example the Vagina Erythromycin is a Macrolide Antibiotic that has an antimicrobial spectrum similar to or slightly wider than that of Penicillin, and is often used for people .

Adverse effects

Increasingly higher dosages will result in higher toxicity, resembling vitamin A toxicity. Adverse drug reactions associated with isotretinoin therapy include:^[5]

• 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 bleeds, dry eyes, eye irritation, conjunctivitis, reduced tolerance to contact lenses, hyperlipidaemia, raised liver enzymes, headaches, hair thinning, myalgia and/or arthralgia. An adverse drug reaction (abbreviated ADR) or adverse drug event (abbreviated ADE) is an expression that describes the unwanted negative consequences An infection is the detrimental Colonization of a host Organism by a foreign Species. In Biology, the term cuticle or cuticula is given to a variety of tough but flexible non-mineral outer coverings of an organism or part of an organism that Cheilitis is a medical condition involving Inflammation of the Lip. Photosensitivity is the amount to which an object reacts upon receiving Photons especially Visible light. Epistaxis (or a nosebleed in Plain English) is the relatively common occurrence of Hemorrhage from the Nose, usually noticed when the blood drains Conjunctivitis (commonly called " Pink Eye " or " Red Eye " in North America and " Madras eye " in India) is an inflammation A contact lens (also known simply as a contact) is a corrective, cosmetic, or therapeutic lens usually placed on the Cornea Hyperlipidemia, hyperlipoproteinemia or dyslipidemia is the presence of raised or abnormal levels of Lipids and/or Lipoproteins in the Liver function tests (LFTs or LFs which include liver enzymes, are groups of Clinical biochemistry laboratory blood assays designed to give information about the Myalgia means " Muscle Pain " and is a symptom of many diseases and disorders Arthralgia (from Greek arthro-, joint + -algos, pain literally means joint pain; it is a symptom of injury infection illnesses -- in particular
• Infrequent: severe acne flare, raised blood glucose level, increased erythrocyte sedimentation rate, fatigue. Glucose (Glc a Monosaccharide (or simple Sugar) also known as grape sugar, is an important Carbohydrate in Biology. The erythrocyte sedimentation rate (ESR also called a sedimentation rate, sed rate, or Biernacki Reaction, is the rate at which Red blood cells
• Rare: impaired night vision, cataracts, optic neuritis, menstrual disturbances, inflammatory bowel disease, pancreatitis, hepatitis, corneal opacities, papilloedema, idiopathic intracranial hypertension, skeletal hyperostosis, extraosseous calcification, psychosis, and it is believed that severe depression can occur, although there is no conclusive evidence for this. Night vision is the ability to see in a dark environment Whether by biological or technological means night vision is made possible by a combination of two approaches sufficient A cataract is a clouding that develops in the crystalline lens of the Eye or in its envelope varying in degree from slight to complete opacity Optic Neuritis is the Inflammation of the Optic nerve that may cause a complete or partial loss of vision The menstrual cycle is a recurring cycle of physiologic changes that occurs in reproductive-age Females Overt menstruation (where there is blood flow from the In Medicine, inflammatory bowel disease ( IBD) is a group of inflammatory conditions of the large intestine and Small intestine Pancreatitis is the Inflammation of the Pancreas. See also Acute pancreatitis and Chronic pancreatitis for more details Hepatitis (plural hepatitides) implies injury to the Liver characterized by the presence of Inflammatory cells in the tissue of The cornea is the transparent front part of the Eye that covers the iris, Pupil, and Anterior chamber. Papilledema (or papilloedema) is Optic disc swelling that is caused by increased Intracranial pressure. Idiopathic intracranial hypertension (IIH sometimes called benign intracranial hypertension (BIH or pseudotumor cerebri (PTC is a Neurological disorder In Biology, the skeleton is a strong and often a rigid framework that supports the body of an animal holding it upright and giving it shape and strength (Also skeletal Hyperostosis is an excessive growth of Bone. It may lead to Exostosis. Calcification is the process in which the mineral calcium builds up in soft tissue causing it to harden Psychosis (from the Greek ψυχή "psyche" for mind or soul and -οσις "-osis" for abnormal condition with adjective psychotic

The following adverse effects have been reported to persist, even after discontinuing therapy: alopecia (hair loss), arthralgias, decreased night vision, inflammatory bowel disease,degenerative disc disease, keloids, bone disease. Alopecia or hair loss is the medical description of the loss of hair from the head or body sometimes to the extent of Baldness. Degeneration of the Intervertebral disc, which is often called " degenerative disc disease " (DDD of the spine, is a condition that can be painful and can A keloid is a type of Hypertrophic scar with mainly type I and some type III collagen which results in an overgrowth of tissue at the site of a healed skin injury High dosages of isotretinoin have been reported to cause rosacea (a disease of severe facial skin redness and irritation). Rosacea (rəʊˈzeɪʃə is a common but often misunderstood condition that is estimated to affect over 45 million people worldwide

Erectile dysfunction in the form of difficulty in maintaining erection was reported in several patients in a clinical study. The erection of the Penis, Clitoris or a Nipple is its enlarged and firm state The impotence may have been caused by the psychiatric side effects of isotretinoin. Psychiatry is a medical specialty which exists to study, prevent, and treat Mental disorders in Humans Psychiatric ^[12] Despite this, sexual dysfunction is not acknowledged as a side-effect in the official literature accompanying the medication.

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 (though no indication of what form of vitamin E was used). See also Tocopherol, Tocotrienol Vitamin E is the collective name for a set of 8 related Tocopherols and Tocotrienols which are fat-soluble ^[13]

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.

Patients that get a tattoo while on this medication might get scarring on the tattoed area, and also rejection of the ink. A tattoo is a permanent marking made by inserting ink into the layers of Skin to change the pigment for decorative or other reasons

Teratogenicity (Birth Defects)

Isotretinoin is a teratogen and is highly likely to cause birth defects if taken during pregnancy. Teratology stems from the Greek ( Genitive) meaning monster, or marvel and, meaning word, speech. A few of the more common birth defects that this drug can cause are hearing and visual impairment, missing earlobes, facial dysmorphism, and mental retardation. Isotretinoin is classified as FDA Pregnancy Category X and ADEC Category X, and use is contraindicated in pregnancy. The pregnancy category of a pharmaceutical agent is an assessment of the risk of fetal injury due to the pharmaceutical if it is used as directed by the mother during The Australian Drug Evaluation Committee or ADEC, is a Committee that provides independent scientific advice to the Australian Government regarding therapeutic ^[6]

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. ^[14]

In the 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. The United States of America —commonly referred to as the An Miscarriage or spontaneous abortion is the natural or spontaneous end of a Pregnancy at a stage where the embryo or fetus is incapable of surviving generally defined About 160 babies with birth defects were born. Consequently, the iPLEDGE program was introduced by the U. The iPLEDGE program is a mandatory distribution program in the United States for Isotretinoin (commonly sold under the trade names Accutane Amneesteen Claravis or 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. Events 1099 - First Crusade: Battle of Ascalon - Crusaders under the command of Godfrey of Bouillon defeat Fatimid Year 2005 ( MMV) was a Common year starting on Saturday (link displays full calendar of the Gregorian calendar. Events 86 BC - Lucius Cornelius Sulla, at the head of a Roman Republic army enters in Athens, removing the Tyrant Year 2006 ( MMVI) was a Common year starting on Sunday of the Gregorian calendar.

Depression

Several studies have suggested a possible link between isotretinoin and clinical depression. Major depressive disorder, also known as major depression, unipolar depression, unipolar disorder, clinical depression, or simply depression ^[15][16] 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. ^[17] While analyses have suggested an association between isotretinoin therapy and depression, no causal relationship has been established and further studies are required. ^[18][19]

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. ^[20][21] Chee Hong describes Isotretinoin-related depression as "an idiosyncratic side-effect", claiming, often anxiety can bring on acne and depression, creating more anxiety. Idiosyncratic drug reactions, also known as type B reactions are drug reactions which occur rarely and unpredictably amongst the population ^[22] 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. ^[23][24]

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. Positron emission tomography ( PET) is a Nuclear medicine imaging technique which produces a three-dimensional image or map of functional processes in the ^[25]

U. S. Representative Bart Stupak (D-MI) is known for his distrust of Accutane. Bartholomew Thomas "Bart" Stupak (born February 29, 1952) American politician has been a Democrat in the United States House He believes unadvertised psychological side effects from the drug drove his teenage son, Bartholomew Thomas "B. J" Stupak Jr. , to commit suicide in 2000. 2000 ( MM) was a Leap year that started on Saturday of the Common Era, in accordance with the Gregorian calendar.

Psychological effects

In addition to possible anxiety, several studies have shown that male patients taking isotretinoin show increased sensitivity to testosterone, and related psychological effects such as unusual irritability, over-inflated self-confidence and increased sexual desire. It should be noted that none of these symptoms have been known to last more than one month after the end of the treatment. Am J Psychiatry 2007;122(5):996-67. The American Journal of Psychiatry (AJP is the official journal of the American Psychiatric Association (APA and the most widely read and cited Psychiatric PMID 16363402

Crohn's Disease and Ulcerative colitis

Several scientific studies have posited that Accutane is a probable cause of Crohn's Disease and Ulcerative colitis in some individuals. Crohn's disease is a Disease of the Digestive system which may affect any part of the Gastrointestinal tract from Mouth to Anus Ulcerative colitis ( Colitis ulcerosa, UC) is a form of Inflammatory bowel disease (IBD Three cases in the United States have gone to trial thus far, with all three resulting in multi-million dollar judgements against the makers of isotretinoin; there are an additional 425 cases pending. [1] [2] [3] [4] [5]

Drug interactions

The concurrent use of isotretinoin with tetracycline antibiotics or vitamin A supplementation is not recommended. Tetracyclines are a group of Broad-spectrum antibiotics whose general usefulness has been reduced with the onset of bacterial resistance Vitamin A refers to a family of similarly shaped molecules the Retinoids. Concurrent use of isotretinoin with tetracyclines significantly increases the risk of idiopathic intracranial hypertension. Idiopathic intracranial hypertension (IIH sometimes called benign intracranial hypertension (BIH or pseudotumor cerebri (PTC is a Neurological disorder Concurrent intake of Vitamin A supplementation increases the risk of vitamin A toxicity. Vitamin A refers to a family of similarly shaped molecules the Retinoids. ^[6]

Concurrent use of isotretinoin with methotrexate increases the risk of hepatotoxicity and may increase methotrexate levels. Drug metabolism in liver The human body identifies almost all drugs as foreign substances (i The combination is used with caution and close monitoring of adverse effects and liver function tests. Liver function tests (LFTs or LFs which include liver enzymes, are groups of Clinical biochemistry laboratory blood assays designed to give information about the ^[5]

See also

• Tazarotene
• Hypervitaminosis A syndrome

References

External links

• Hoffmann-La Roche (Makers of (Ro) accutane)
• Accutane Information
• FDA's Accutane Information Page
• FDA distributed "Accutane Medication Guide"
• Drugs.com Isotretinoin Information
• Dermatology Vol 9: issue 5: Night blindness, vitamin A deficiency, and isotretinoin psychotoxicity
• DermNet treatments/isotretinoin

• vitminA. The New Zealand Dermatological Society is a medical organization best known outside New Zealand for its "DermNet" website which provides photographs and descriptions org's Practical Guide to Accutane Side Effects

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