Amcinonide

Last updated
Amcinonide
Amcinonide.png
Amcinonide 3D.png
Clinical data
Trade names Cyclocort
AHFS/Drugs.com Micromedex Detailed Consumer Information
Routes of
administration 		Topical
ATC code
Legal status
Legal status
Pharmacokinetic data
Metabolism Hepatic
Excretion Urine and bile
Identifiers
  • 2-[(1S,2S,4R,8S,9S,11S,12R,13S)-12'-fluoro-11'-hydroxy-9',13'-dimethyl-16'-oxo-5',7'-dioxaspiro[cyclopentane-1,6'-pentacyclo[10.8.0.02,9.04,8.013,18]icosane]-14',17'-dien-8'-yl]-2-oxoethyl acetate
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard 100.051.724 OOjs UI icon edit-ltr-progressive.svg
Chemical and physical data
Formula C28H35FO7
Molar mass 502.579 g·mol−1
3D model (JSmol)
Density 1.33 g/cm3
Boiling point 635.9 °C (1,176.6 °F)
  • O=C(OCC(=O)[C@]45OC6(O[C@@H]5C[C@@H]2[C@@]4(C[C@H](O)[C@]3(F)[C@]/1(/C=C\C(=O)\C=C\1CC[C@@H]23)C)C)CCCC6)C
  • InChI=1S/C28H35FO7/c1-16(30)34-15-22(33)28-23(35-26(36-28)9-4-5-10-26)13-20-19-7-6-17-12-18(31)8-11-24(17,2)27(19,29)21(32)14-25(20,28)3/h8,11-12,19-21,23,32H,4-7,9-10,13-15H2,1-3H3/t19-,20-,21-,23+,24-,25-,27-,28+/m0/s1 Yes check.svgY
  • Key:ILKJAFIWWBXGDU-MOGDOJJUSA-N Yes check.svgY
 X mark.svgNYes check.svgY  (what is this?)    (verify)

Amcinonide (trade name Cyclocort) is a topical glucocorticoid used to treat itching, redness and swelling associated with several dermatologic conditions such as atopic dermatitis and allergic contact dermatitis. [1] [2] Amcinonide can also be classified as a multi-functional small molecule corticosteroid, which has been approved by the FDA and is currently marketed as an ointment, lotion, or cream. [3] It acts as both a transcription factor for responses to glucocorticoids and modulator for other transcription factors while also regulating phospholipase A2 activity. [4]

Contents

Medical Uses

Corticosteroids applied topically are used for the relief of the inflammatory and pruritic manifestations of corticosteroid-responsive dermatoses, particularly dermatitis, eczema, and psoriasis. [5] [6] Cyclocort's active ingredient is Amcinonide, with inactive ingredients including petrolatum, benzyl alcohol, sorbitol, butylated hydroxyanisole, propyl gallate, citric acid, glycerin, and/ or propylene glycol. The specific inactive ingredients used depend on the dosage form (ointment, area, or lotion) and help the product retain its chemical and physical integrity while increasing the shelf-life. [7] [8] [9]

Dermatitis, Psoriasis, & Eczema

0.1% Amcinonide cream or ointment is typically applied two to three times daily to treat dermatitis, psoriasis, and/ or eczema while the same strength lotion is usually only used twice daily. This information can be found on the FDA approved label or from the prescribing doctor or pharmacist. Occlusive dressings may be used to supplement Amcinonide treatment, particularly when treating psoriasis. [6]

Adverse Effects

Amcinonide exhibits side effects common among other corticosteroids. While these reactions are uncommon for most delivery vehicles, the use of occlusive dressings increases the likelihood of such effects. [5] These include burning, itching, skin dryness and irritation, acne/ pimples, skin atrophy, blistering, and/ or skin discoloration. [5] [10] While most side effects are mild, a medical professional should be contacted if severe rash, acne, skin deterioration, excessive hair growth, or abnormal weight gain occur. Following package insert instructions for a single topical dose, as detailed on the package insert, should not lead to any toxicities. [10]

Pharmacology

Cyclocort is a synthetic corticosteroid created to imitate natural glucocorticoids. In order to do so, amcinonide acts as an agonist to target glucocorticoid receptors. After interacting with the receptor, endocytosis occurs at which point the drug can bind to DNA within the cell. Gene expression is subsequently modified to produce anti-inflammatory mediators while preventing the formation of inflammatory agents thus reducing overall inflammation and immune system response. [11]

Mechanism of Action

The mechanism by which Amcinonide causes anti-inflammatory responses is unclear with current research focused on similar topical steroids that may possess the same mechanism. [12] This is thought to occur via the induction of lipocortin (phospholipase A2 inhibitor proteins). Ongoing research predicts that Amcinonide presents the release of arachidonic acid which, in turn, stops the synthesis of the inflammation mediators prostaglandins and leukotrienes. Phospholipase A2 normally causes membrane phospholipids to release arachidonic acid, therefore causing a cascade of reactions leading to inflammation of the skin. Due to Amcinonide's high affinity for the glucocorticoid receptor, a neuroactive ligand-receptor interaction occurs and the initial acid release is inhibited, thus helping to alleviate any itching/ burning symptoms. [13] [14]

Metabolism & Elimination

Amcinonide undergoes transdermal absorption with pharmacokinetic profiles similar to that of other corticosteroids administered systematically. Metabolism occurs mainly in the liver and its hepatic cells. The metabolized compound is predominately filtered through the kidneys and excreted in urine although a small amount is excreted in the bile. [13]

History

Amcinonide was first developed in the United Kingdom in the 1960s and 1970s before being patented by the American Cyanamid company. [15] Lederle Laboratories, most famous for the discovery of the antibacterial tetracycline drug class, began to manufacture of Amcinonide before being acquired by Cyanamid. In 1994, American Cyanamid and its Lederle Lab division was purchased by American Home Products (AHP) before eventually changing the company's name to Wyeth Pharmaceuticals in 2002. [16] Wyeth Pharma was eventually purchased by rival Pfizer in 2009 for $68 billion although the manufacture of Amcinonide has since been discontinued by the company. [17]

Research & Clinical Trials

Amcinonide is produced from the reaction of 16α,17α-Cyciopentylidenedioxy-9α-fluoro-11β,21-dihydroxy-1,4pregnadiene-3,20-dione and acetic anhydride in which 11.1g and 5.5mL, respectively, of each reactant are consumed to produce 7.0g of pure product. [15] Only 4.7% of patients in clinical trials reported experiencing side effects as a result of continued use of Amcinonide. Specifically, in one acceptability study conducted on a weekly basis, one-fifth of patients using both placebo and Cyclocort 0.1% lotion reported various discomforts at multiple interviews. [18] The outcomes of relevant trials are included below.

One of the initial clinical studies into Amcinonide, conducted by Woodford & Barry, 1979, compared topical applications Amcinonide to Triamcinolone Acetonide. Specifically, 0.1% strength preparations of each compound were tested against 0.025% Synalar Gel and 0.1% Betnovate Cream using a vasoconstrictor assay to determine bioavailability and anti-inflammatory effects. All formulations had similar bioavailability profiles with the peak of the curve coming approximately 12 hours after topical administration and covering with an occlusive dressing. Concluding, the study found Amcinonide cream to be the most effective with the highest bio-activity and area under the curve (pharmacokinetics). [19]

A French study by Binet et al., 1979, compared 0.1% Amcinonide ointment to equal strength Fluocinonide ointment, a similar corticosteroid already on the market. A double-blind comparative analysis was conducted to determine if Amcinonide was bioequivalent for the treatment of psoriasis and eczema. Each group contained both males and females of varying ages (mean = 54.8) and compared objective criteria (crust, scales, swelling, etc.) and subjective criteria (itching, burning, pain). It was found that treatment of dermatitis with Amcinonide achieved significant improvement over the one-week trial period, thus demonstrating adequate efficacy in treating psoriasis, eczema, and even parapsoriasis. [20]

Similar to the Woodford & Barry study in 1977, Woodford & Haigh, 1979 sought to determine the potency of 0.1% Amcinonide through the use of a vasoconstrictor assay. Three equal strength formulations of Amcinonide were prepared (cream, combination-ointment, combination-cream) were compared against similar corticosteroids already on the market in the United Kingdom (Betnovate, Metosyn, Synalar, Temetex, Dermovate, and Halciderm). It was found that 0.1% Amcinonide cream was significantly more bio-active than other 'potent' classified drugs and was subsequently assigned to the 'very potent' category, as established by the UK MIMS potency classification system. Amcinonide cream was also determined to be bioequivalent to other proprietary corticosteroids on the English market. [21]

In a study conducted by Fedler, Pilz, & Frosch, 1993, the long term usage of Amcinonide, along with other topical corticosteroids, was tested on women with a history of dermatitis who had otherwise been relatively healthy. It was found that corticosteroid usage may eventually cause erythematous reactions and spreading hives. The study concluded that contact allergies may be developed, in some cases, when using Amcinonide to treat chronic dermatitis. These findings should be considered when treating dermatological conditions with multiple corticosteroids, including Amcinonide. [22]

Commercialization

First introduced to the market in 1979 as 0.025% and 0.1% creams, Amcinonide has been available continuously since then, being prescribed for a variety of similar dermatological symptoms. [23] Lederle Laboratories first manufactured Amcinonide for distribution to countries in North America, Europe, and Asia. In 1979, marketed under the trade name of Cyclocort, Amcinonide was made available in the United States. Also produced by American Cyanamid, Amcinonide was then marketed to West Germany as Amcinonid beginning in 1981. Shortly thereafter in 1982, Lederle introduced the product to France and Japan as Visderm and Penticort, respectively. [15]

After acquiring production rights from American Home Products, Amcinonide is currently being produced in the United States by Taro Pharmaceuticals USA and Fougera, a subsidiary of Sandoz and Novartis. [24] [25] GlaxoSmithKline and Teva Canada also produce Amcinonide for international sales. While most products are manufactured at 0.1% strength ointment, cream, or lotion, it is important to note that none of the producers sell Amcinonide as an over-the-counter (OTC) medication but only as a prescription product. [25]

While the initial patents obtained by American Cyanamid company in the late 1970s/ early 1980s for ointment, cream, and lotion formulations have expired, new patents have been obtained for alternative transdermal delivery methods. [26] [27] More recently, however, the drug formulation itself has not been patented but ways to incorporate it into occlusive dressings such as a pressure sensitive adhesive layer as demonstrated by Senju USA, Inc. in 2012 - 2014. Specifically, these new dosage forms target diseases of the eyelid such as blepharitis, allergic conjunctivitis, vernal keratoconjunctivitis, and atopic keratoconjunctivitis. [28] [29] [30] This is significant as previous formulations of Amcinonide have not been used to treat ocular inflammations. Patents such as these are likely to continue to be published as research searches for low cost alternatives to new drugs to increase bioavailability and patient compliance.

Regulatory

Taro Pharmaceuticals obtained FDA approval to begin production of Amcinonide cream in 2002 after proving the product was bioequivalent to Cyclocort products already on the market. This was the first generic Amcinonide product to be sold in the United States, thus introducing a lower-priced alternative for patients with applicable dermatological ailments. [31] In 2003, Fougera Pharmaceutical became the main competitor to Taro after acquiring FDA approval for production of 0.1% Amcinonide cream. [32]

In 2009, Taro Pharmaceuticals was warned by the FDA that they were not meeting good manufacturing practices for their ointment and that their final product was non-sterile. Following additional FDA investigations, this was eventually resolved after two years, at which point the company regained good standing with FDA regulations. [33] [34]

Related Research Articles

Hydrocortisone Glucocorticoid and Mineralocorticoid hormone Cortisol supplied as a medication

Hydrocortisone is the name for the hormone cortisol when supplied as a medication. Uses include conditions such as adrenocortical insufficiency, adrenogenital syndrome, high blood calcium, thyroiditis, rheumatoid arthritis, dermatitis, asthma, and COPD. It is the treatment of choice for adrenocortical insufficiency. It can be given by mouth, topically, or by injection. Stopping treatment after long-term use should be done slowly.

Topical medication Medication applied to body surfaces

A topical medication is a medication that is applied to a particular place on or in the body. Most often topical administration means application to body surfaces such as the skin or mucous membranes to treat ailments via a large range of classes including creams, foams, gels, lotions, and ointments. Many topical medications are epicutaneous, meaning that they are applied directly to the skin. Topical medications may also be inhalational, such as asthma medications, or applied to the surface of tissues other than the skin, such as eye drops applied to the conjunctiva, or ear drops placed in the ear, or medications applied to the surface of a tooth. The word topical derives from Greek τοπικόςtopikos, "of a place".

Pimecrolimus

{{Drugbox | Verifiedfields = changed | Watchedfields = changed | verifiedrevid = 464206673 | IUPAC_name = (3S,4R,5S,8R,9E,12S,14S,15R,16S,18R,19R,26aS)-3-{(E)-2-[(1R,3R,4S)-4-chloro-3 -methoxycyclohexyl]-1-methylvinyl}-8-ethyl-5,6,8,11,12,13,14,15,16,17,18,19,24,25,26,26a-hexadecahydro-5,19-dihydroxy-14,16-dimethoxy-4,10,12,18-tetramethyl-15,19-epoxy-3H-pyrido[2,1-c][1,4]oxaazacyclotricosin-1,7,20,21(4H,23H)-tetrone | image = Pimecrolimus2DACS.svg | width = 200 | image2 = Pimecrolimus ball-and-stick.png | tradename = Elidel | Drugs.com = Monograph | pregnancy_AU = B3 | pregnancy_US = C | legal_US = Rx-only | routes_of_administration = topical | bioavailability = low systemic absorption | protein_bound = 74%–87% | metabolism = Hepatic CYP3A | elimination_half-life = | excretion = | CAS_number_Ref =   | CAS_number = 137071-32-0 | ATC_prefix = D11 | ATC_suffix = AH02 | PubChem = 16051947 | DrugBank_Ref =  

| DrugBank = DB00337
Clobetasol propionate

Clobetasol propionate is a corticosteroid used to treat skin conditions such as eczema, contact dermatitis, seborrheic dermatitis, and psoriasis. It is applied to the skin as a cream, ointment, or shampoo. Use should be short term and only if other weaker corticosteroids are not effective. Use is not recommended in rosacea or perioral dermatitis.

Triamcinolone Steroid medication

Triamcinolone is a glucocorticoid used to treat certain skin diseases, allergies, and rheumatic disorders among others. It is also used to prevent worsening of asthma and COPD. It can be taken in various ways including by mouth, injection into a muscle, and inhalation.

Betamethasone Steroid medication

Betamethasone is a steroid medication. It is used for a number of diseases including rheumatic disorders such as rheumatoid arthritis and systemic lupus erythematosus, skin diseases such as dermatitis and psoriasis, allergic conditions such as asthma and angioedema, preterm labor to speed the development of the baby's lungs, Crohn's disease, cancers such as leukemia, and along with fludrocortisone for adrenocortical insufficiency, among others. It can be taken by mouth, injected into a muscle, or applied to the skin topically in cream, lotion, or liquid forms.

Desonide

Desonide (INN) is a low-potency topical corticosteroid anti-inflammatory that has been available since the 1970s. It is primarily used to treat atopic dermatitis (eczema), seborrheic dermatitis, contact dermatitis and psoriasis in both adults and children. It has a fairly good safety profile and is available as a cream, ointment, lotion, and as a foam under the tradename Verdeso Foam. Other trade names for creams, lotions, and ointments include Tridesilon, DesOwen, Desonate. It is a group VI corticosteroid under US classification, the second least potent group.

Fluticasone propionate Medication

Fluticasone propionate, sold under the brand names Flovent and Flonase among others, is a steroid medication. When inhaled it is used for the long term management of asthma and COPD. In the nose it is used for hay fever and nasal polyps. It can also be used for mouth ulcers.

Betamethasone dipropionate

Betamethasone dipropionate is a glucocorticoid steroid with anti-inflammatory and immunosuppressive abilities. It is applied as a topical cream, ointment, lotion or gel (Diprolene) to treat itching and other minor skin conditions such as eczema. Minor side effects include dry skin and mild, temporary stinging when applied. Betamethasone dipropionate is a "super high potency" corticosteroid used to treat inflammatory skin conditions such as dermatitis, eczema and psoriasis. It is a synthetic analog of the adrenal corticosteroids. Although its exact mechanism of action is not known, it is effective when applied topically to cortico-responsive inflammatory dermatoses. It is available as a generic medication.

Betamethasone valerate

Betamethasone valerate is a synthetic glucocorticoid ester. It is the 17-valerate ester of betamethasone. Betamethasone valerate is often used to treat mild eczema with good efficacy and lower incidence of steroid induced adverse effects due to its lower potency compared to other glucocorticoids. Betamethasone-17-valerate is available in cream, ointment, lotion, and foam preparations for topical use.

Fluocinonide

Fluocinonide is a potent glucocorticoid used topically as an anti-inflammatory agent for the treatment of skin disorders such as eczema and seborrhoeic dermatitis. It relieves itching, redness, dryness, crusting, scaling, inflammation, and discomfort.

Calcipotriol

Calcipotriol, also known as calcipotriene, is a synthetic derivative of calcitriol, a form of vitamin D. It is used in the treatment of psoriasis. It is safe for long-term application in psoriatic skin conditions.

Alclometasone

Alclometasone is a synthetic corticosteroid for topical dermatologic use, possessing anti-inflammatory, antipruritic, and vasoconstrictive properties.

Lotion Skin treatment preparation

A lotion is a low-viscosity topical preparation intended for application to the skin. By contrast, creams and gels have higher viscosity, typically due to lower water content. Lotions are applied to external skin with bare hands, a brush, a clean cloth, or cotton wool.

Clocortolone

Clocortolone (Cloderm) is a topical steroid. It is used in the form of an ester, clocortolone pivalate, and applied as a cream. It is used for the treatment of dermatitis and is considered a medium-strength corticosteroid. It is unusual among steroids in that it contains a chlorine atom and a fluorine atom.

Diflorasone diacetate

Diflorasone diacetate is a topical steroid that comes in the form of a cream. It is manufactured by E. Fougera & Co. and is used as an anti-inflammatory and anti-itching agent, like other topical corticosteroids. It is prescribed for psoriasis and atopic dermatitis, among other conditions. With respect to potency, it is regarded as a Class I corticosteroid [of classes I – VII] in the United States.

Topical steroids are the topical forms of corticosteroids. Topical steroids are the most commonly prescribed topical medications for the treatment of rash, eczema, and dermatitis. Topical steroids have anti-inflammatory properties, and are classified based on their skin vasoconstrictive abilities. There are numerous topical steroid products. All the preparations in each class have the same anti-inflammatory properties, but essentially differ in base and price.

Calcipotriol/betamethasone dipropionate

Calcipotriol/betamethasone dipropionate, sold under the brand name Taclonex among others, is a fixed-dose combination medication of the synthetic vitamin D3 analog calcipotriol (also known as calcipotriene) and the synthetic corticosteroid betamethasone dipropionate for the treatment of plaque psoriasis. It is used in the form of ointment, topical suspension, gel, aerosol, and foam.

Topical glucocorticoids

Topical glucocorticoids are the topical forms of glucocorticoids. Topical glucocorticoids are used in the treatment of many skin conditions. They provide anti-inflammatory, antimitotic, and immune-system suppressing actions through various mechanisms.

Topical drug delivery system

Topical drug delivery system is a route of administration of drugs via the skin to provide topical therapeutic effects. As skin is one of the largest and most superficial organs in the human body, pharmacists utilise it to deliver various drugs. This system usually provides a local effect on certain positions of the body. In ancient times, people used herbs to put on wounds for relieving the inflammatory effect or as pain relievers. The use of topical drug delivery system is much broader now, from smoking cessation to beauty purposes. Nowadays, there are numerous dosage forms that can be used topically, including cream, ointment, lotion, patches, dusting powder and much more. There are many advantages for this drug delivery system - avoiding first pass metabolism which can increase its bioavailability, being convenient and easy to apply to a large area, being easy to terminate the medication and avoiding gastro-intestinal irritations. All these can increase the patient compliance. However, there are several disadvantages for this system - causing skin irritations and symptoms like rashes and itchiness may occur. Also, only small particles can pass through the skin, which limits the choice of drugs. Since skin is the main medium of topical drug delivery system, its conditions determine the rate of skin penetration leading to affecting the pharmacokinetics of the drug. The temperature, pH value and dryness of the skin need to be considered. There are some novel topical drugs in the market which can utilise the system as much as possible. 

References

  1. ↑ Drugs.com: Amcinonide topical
  2. ↑ Bickers DR (August 1984). "A comparative study of amcinonide and halcinonide in the treatment of eczematous dermatitis". Cutis. 34 (2): 190–4. PMID   6383735.
  3. ↑ DrugBank.ca: Amcinonide Pharmacoeconomics
  4. ↑ PubChem.gov:Amcinonide
  5. 1 2 3 Fougera.com: Amcinonide Ointment USP, 0.1% Archived 2015-11-21 at the Wayback Machine
  6. 1 2 Drugs.com:Amcinonide Dosage
  7. ↑ FDA.gov:Fougera Amcinonide Ointment Label
  8. ↑ FDA.gov:Fougera Amcinonide Cream Label
  9. ↑ FDA.gov:Taro Amcinonide Labels
  10. 1 2 Drugs.com: Amcinonide Topical
  11. ↑ NCIt.NCI.NIH.gov: Amcinonide
  12. ↑ DrugBank.ca: Amcinonide
  13. 1 2 DrugBank.ca:Amcinonide Pharmacology
  14. ↑ Genome.jp:Drug D01387
  15. 1 2 3 Pharmaceutical Manufacturing Encyclopedia: Amcinonide
  16. ↑ FundingUniverse.com: History of Wyeth
  17. ↑ NYtimes.com:Pfizer Agrees to Pay $68 Billion for Rival Drug Maker Wyeth
  18. ↑ DrugBank.ca:Cyclocort (Amcinonide) Archived 2016-03-04 at the Wayback Machine
  19. ↑ Woodford R, Barry BW, Frosch PJ (1977). "Activity and Bioavailability of Amcinonide and Triamcinolone Acetonide in Experimental and Proprietary Topical Preparations". Current Therapeutic Research. 21 (6): 877–886.
  20. ↑ Binet O, Brunetiere RA, Bruneau O, Bogaievsky Y (1979). "A Double-Blind Comparative Trial Between Amcinonide and Fluocinonide in Dermatology". Current Therapeutic Research. 25 (4): 500–507.
  21. ↑ Woodford R, Haigh JM (1979). "Bioavailability and Activity of 0.1% Amcinonide Preparations: Comparison with Proprietary Topical Corticosteroid Formulations of Differing Potencies". Current Therapeutic Research. 26 (3): 301–310.
  22. ↑ Fedler R, Pilz B, Frosch PJ (February 1993). "[Contact allergy to topical glucocorticoids]". Der Hautarzt; Zeitschrift für Dermatologie, Venerologie, und Verwandte Gebiete. 44 (2): 91–5. PMID   8449700.
  23. ↑ FDA.gov:Amcinonide Approval
  24. ↑ Sandoz.com:Fougera Acquisition Archived 2015-09-10 at the Wayback Machine
  25. 1 2 DrugBank.ca:Amcinonide Identification
  26. ↑ Google.com: Topical Ointment Patent
  27. ↑ Google.com: Topical Ointment Patent 2
  28. ↑ Google: Transdermal Drug Delivery System and Method Patent
  29. ↑ Google.com: Transdermal Drug Delivery System and Method Patent 2
  30. ↑ Google.com: Transdermal Drug Delivery System and Method Patent 3
  31. ↑ TheFreeLibrary.com:Taro Pharmaceuticals Receives FDA Approval for Amcinonide Cream USP, 0.1%
  32. ↑ FDA.gov:Amcinonide Approval
  33. ↑ PharmCast.com:FDA Warning Letter to Taro Archived 2011-06-17 at the Wayback Machine
  34. ↑ BusinessWire.com:Taro Resolves FDA Warning Letter
This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.