Flurandrenolide

0.6

0.6

Crystals from acetone + hexane

WHITE TO OFF-WHITE, FLUFFY CRYSTALLINE POWDER

Insoluble

FREELY SOL IN CHLOROFORM; SOL IN METHANOL; SPARINGLY SOL IN ALC; PRACTICALLY INSOL IN WATER & ETHER

5.78e-02 g/L

251

247-255 °C

251 °C

201.8 Ų [M-H]- [CCS Type: DT; Buffer gas: N2; Ionization: ESI-; Dataset: TOXCAST; Source Identifier: DTXSID2047434]；186.9 Ų [M+H]+ [CCS Type: DT; Buffer gas: N2; Ionization: ESI+; Dataset: TOXCAST; Source Identifier: DTXSID2047434]

199.91 Ų [M+H]+ [CCS Type: TW; Method: calibrated with polyalanine and drug standards]；224.66 Ų [M+Na]+ [CCS Type: TW; Method: calibrated with polyalanine and drug standards]；189.64 Ų [M+H-H2O]+ [CCS Type: TW; Method: calibrated with polyalanine and drug standards]

201.2 Ų [M+H]+ [CCS Type: TW; Method: calibrated with polyalanine and drug standards]

Warning

H319 (97.6%): Causes serious eye irritation [Warning Serious eye damage/eye irritation]

P264+P265, P280, P305+P351+P338, and P337+P317 (click each P-code to see the statement)

Aggregated GHS information provided per 41 reports by companies from 4 notifications to the ECHA C&L Inventory.；Information may vary between notifications depending on impurities, additives, and other factors. The percentage value in parenthesis indicates the notified classification ratio from companies that provide hazard codes. Only hazard codes with percentage values above 10% are shown. For more detailed information, please visit ECHA C&L website.

IMAP assessments - Pregn-4-ene-3,20-dione, 6-fluoro-11,21-dihydroxy-16,17-[(1-methylethylidene)bis(oxy)]-, (6.alpha.,11.beta.,16.alpha.)-: Environment tier I assessment；IMAP assessments - Pregn-4-ene-3,20-dione, 6-fluoro-11,21-dihydroxy-16,17-[(1-methylethylidene)bis(oxy)]-, (6.alpha.,11.beta.,16.alpha.)-: Human health tier I assessment

The Approved Drug Products with Therapeutic Equivalence Evaluations List identifies currently marketed prescription drug products, incl flurandrenolide approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act.

Flurandrenolide cream, lotion, and ointment should be protected from light and stored in tight containers at a temperature less than 40 °C, preferably between 15-30 °C; freezing should be avoided. Flurandrenolide tape should be stored at 15-30 °C.

SRP: At the time of review, criteria for land treatment or burial (sanitary landfill) disposal practices are subject to significant revision. Prior to implementing land disposal of waste residue (including waste sludge), consult with environmental regulatory agencies for guidance on acceptable disposal practices.

The effect of glucocorticoids on oral anticoagulant therapy is variable, and the efficacy of oral anticoagulants has been reported to be enhanced or diminished with concomitant glucocorticoid administration. Patients receiving glucocorticoids and oral anticoagulants concomitantly should be monitored (e.g., using coagulation indices) in order to maintain desired anticoagulant effect. /Corticosteroids/

Because corticosteroids inhibit antibody response, the drugs may cause a diminished response to toxoids and live or inactivated vaccines. In addition, corticosteroids may potentiate replication of some organisms contained in live, attenuated vaccines and supraphysiologic dosages of the drugs can aggravate neurologic reactions to some vaccines. Routine administration of vaccines or toxoids should generally be deferred until corticosteroid therapy is discontinued. Administration of live virus or live, attenuated vaccines, including smallpox vaccine, is contraindicated in patients receiving immunosuppressive dosages of glucocorticoids. In addition, if inactivated vaccines are administered to such patients, expected serum antibody response may not be obtained. The Public Health Service Advisory Committee on Immunization Practices (ACIP) and American Academy of Family Physicians (AAFP) state that administration of live virus vaccines usually is not contraindicated in patients receiving corticosteroid therapy as short-term (less than 2 weeks) treatment, in low to moderate dosages, as long-term alternate-day treatment with short-acting preparations, in maintenance physiologic dosages (replacement therapy), or if corticosteroids are administered topically, ophthalmically, intra-articularly, bursally, or into a tendon. If immunization is necessary in a patient receiving corticosteroid therapy, serologic testing may be needed to ensure adequate antibody response and additional doses of the vaccine or toxoid may be necessary. Immunization procedures may be undertaken in patients receiving nonimmunosuppressive doses of glucocorticoids or in patients receiving glucocorticoids as replacement therapy (e.g., Addison's disease). /Corticosteroids/

Potassium-depleting diuretics (e.g., thiazides, furosemide, ethacrynic acid) and other drugs that deplete potassium, such as amphotericin B, may enhance the potassium-wasting effect of glucocorticoids. Serum potassium should be closely monitored in patients receiving glucocorticoids and potassium-depleting drugs. /Corticosteroids/

Concomitant administration of ulcerogenic drugs such as indomethacin during corticosteroid therapy may increase the risk of GI ulceration. Aspirin should be used cautiously in conjunction with glucocorticoids in patients with hypoprothrombinemia. Although concomitant therapy with salicylates and corticosteroids does not appear to increase the incidence or severity of GI ulceration, the possibility of this effect should be considered. /Corticosteroids/

/SIGNS AND SYMPTOMS/ Glucocorticoids may cause fetal damage when administered to pregnant women. One retrospective study of 260 women who received pharmacologic dosages of glucocorticoids during pregnancy revealed 2 instances of cleft palate, 8 stillbirths, 1 spontaneous abortion, and 15 premature births. Another study reported 2 cases of cleft palate in 86 births. Occurrence of cleft palate in these studies is higher than in the general population but could have resulted from the underlying diseases as well as from the steroids. Other fetal abnormalities that have been reported following glucocorticoid administration in pregnant women include hydrocephalus and gastroschisis. Women should be instructed to inform their physicians if they become or wish to become pregnant while receiving glucocorticoids. If glucocorticoids must be used during pregnancy or if the patient becomes pregnant while taking one of these drugs, the potential risks should be carefully considered. /Corticosteroids/

/CASE REPORTS/ Intraocular pressure was elevated in both eyes and a glaucomatous field defect developed in one eye of an 18-year-old Caucasian man after prolonged topical use of flurandrenolide. Spontaneous remission occurred in one eye, the eye with least drug exposure, within a few weeks. The other eye continued to show evidence of elevated intraocular pressure and further field loss developed over 4 years after discontinuation of the steroid. The most serverly affected eye became myopic. This case strongly suggests that chronic application of flurandrenolide into the conjuctival sac can produce corticosteroid-induced glaucoma in susceptible individuals. Although both eyes were normal before exposure to the steroid and elevations of the same level developed in both eyes at the peak of the disease, the eye with the least drug exposure underwent complete and spontaneous remission whereas the eye exposed more frequently appeared to show irreversible changes in the aqueous humor outflow pathway with subsequent loss of visual field.

Glucocorticoids should be used with caution in patients with hypothyroidism or cirrhosis, because such patients often show exaggerated response to the drugs. Glucocorticoids should be used with caution in psychotic patients or patients with hypertension or congestive heart failure. /Corticosteroids/

Because an apparent association has been suggested between use of corticosteroids and left ventricular free-wall rupture after a recent myocardial infarction, corticosteroids should be used with extreme caution in these patients. /Corticosteroids/

Because glucocorticoids increase susceptibility to and mask symptoms of infection, the drugs should not be used, except in life-threatening situations, in patients with viral infections or bacterial infections not controlled by anti-infectives. Manufacturers state that glucocorticoid oral inhalation therapy should be used with caution, if at all, in patients with untreated systemic fungal, bacterial, viral, or parasitic infections. Patients whose susceptibility to infection is high, such as those receiving glucocorticoids as immunosuppressive therapy, are especially likely to develop secondary infections. Patients receiving glucocorticoids who are potentially immunosuppressed should be warned of the risk of exposure to certain infections (e.g., chickenpox, measles) and of the importance of obtaining medical advice if such exposure occurs. Since glucocorticoid therapy can reactivate tuberculosis, treatment of latent tuberculosis infection should be included in the regimen of patients with a history of active tuberculosis undergoing prolonged glucocorticoid therapy. If glucocorticoids are indicated in patients with latent tuberculosis or tuberculin reactivity, close observation is necessary. Use of glucocorticoids in patients with active tuberculosis should be restricted to those with fulminating or disseminated tuberculosis in which glucocorticoids are used in conjunction with appropriate antimycobacterial chemotherapy. Manufacturers state that glucocorticoid oral inhalation therapy should be used with caution, if at all, in patients with clinical or asymptomatic Mycobacterium tuberculosis infections of the respiratory tract. Since glucocorticoids can reactivate latent amebiasis, any patient who has been in the tropics or who has unexplained diarrhea should be evaluated for amebiasis to exclude these patients prior to initiating therapy. In the treatment of acute or disseminated tuberculosis, glucocorticoids should only be used as part of a total antituberculosis reg

Corticosteroids should be used with caution in patients with active or latent peptic ulcer, diverticulitis, nonspecific ulcerative colitis (if there is a probability of impending perforation, abscess, or other pyogenic infection), and in those with recent intestinal anastomoses. Manifestations of peritoneal irritation following GI perforation may be minimal or absent in patients receiving glucocorticoids. /Corticosteroids/

Glucocorticoids may cause fetal damage when administered to pregnant women. One retrospective study of 260 women who received pharmacologic dosages of glucocorticoids during pregnancy revealed 2 instances of cleft palate, 8 stillbirths, 1 spontaneous abortion, and 15 premature births. Another study reported 2 cases of cleft palate in 86 births. Occurrence of cleft palate in these studies is higher than in the general population but could have resulted from the underlying diseases as well as from the steroids. Other fetal abnormalities that have been reported following glucocorticoid administration in pregnant women include hydrocephalus and gastroschisis. Women should be instructed to inform their physicians if they become or wish to become pregnant while receiving glucocorticoids. If glucocorticoids must be used during pregnancy or if the patient becomes pregnant while taking one of these drugs, the potential risks should be carefully considered. /Corticosteroids/

While data specific to flurandrenolide were not located(SRC, 2007), the literature suggests that some pharmaceutically active compounds originating from human and veterinary therapy are not eliminated completely in municipal sewage treatment plants and are therefore discharged into receiving waters(1). Wastewater treatment processes often were not designed to remove them from the effluent(2). Selected organic waste compounds may be degrading to new and more persistent compounds that may be released instead of or in addition to the parent compound(2). Studies have indicated that several polar pharmaceutically active compounds can leach through soil(1).

/SRP:/ Immediate first aid: Ensure that adequate decontamination has been carried out. If patient is not breathing, start artificial respiration, preferably with a demand valve resuscitator, bag-valve-mask device, or pocket mask, as trained. Perform CPR if necessary. Immediately flush contaminated eyes with gently flowing water. Do not induce vomiting. If vomiting occurs, lean patient forward or place on the left side (head-down position, if possible) to maintain an open airway and prevent aspiration. Keep patient quiet and maintain normal body temperature. Obtain medical attention. /Poisons A and B/

/SRP:/ Basic treatment: Establish a patent airway (oropharyngeal or nasopharyngeal airway, if needed). Suction if necessary. Watch for signs of respiratory insufficiency and assist ventilations if needed. Administer oxygen by nonrebreather mask at 10 to 15 L/min. Monitor for pulmonary edema and treat if necessary ... . Monitor for shock and treat if necessary ... . Anticipate seizures and treat if necessary ... . For eye contamination, flush eyes immediately with water. Irrigate each eye continuously with 0.9% saline (NS) during transport ... . Do not use emetics. For ingestion, rinse mouth and administer 5 mL/kg up to 200 mL of water for dilution if the patient can swallow, has a strong gag reflex, and does not drool ... . Cover skin burns with dry sterile dressings after decontamination ... . /Poisons A and B/

/SRP:/ Advanced treatment: Consider orotracheal or nasotracheal intubation for airway control in the patient who is unconscious, has severe pulmonary edema, or is in severe respiratory distress. Positive-pressure ventilation techniques with a bag valve mask device may be beneficial. Consider drug therapy for pulmonary edema ... . Consider administering a beta agonist such as albuterol for severe bronchospasm ... . Monitor cardiac rhythm and treat arrhythmias as necessary ... . Start IV administration of D5W /SRP: "To keep open", minimal flow rate/. Use 0.9% saline (NS) or lactated Ringer's if signs of hypovolemia are present. For hypotension with signs of hypovolemia, administer fluid cautiously. Watch for signs of fluid overload ... . Treat seizures with diazepam or lorazepam ... . Use proparacaine hydrochloride to assist eye irrigation ... . /Poisons A and B/

◉ Summary of Use during Lactation；Flurandrenolide has not been studied during breastfeeding. Since only extensive application of the most potent corticosteroids may cause systemic effects in the mother, it is unlikely that short-term application of topical corticosteroids would pose a risk to the breastfed infant by passage into breastmilk. However, it would be prudent to use the least potent drug on the smallest area of skin possible. It is particularly important to ensure that the infant's skin does not come into direct contact with the areas of skin that have been treated. Only the lower potency corticosteroids should be used on the nipple or areola where the infant could directly ingest the drugs from the skin. Only water-miscible cream or gel products should be applied to the breast because ointments may expose the infant to high levels of mineral paraffins via licking. Any topical corticosteroid should be wiped off thoroughly prior to nursing if it is being applied to the breast or nipple area.；◉ Effects in Breastfed Infants；Topical application of a corticosteroid with relatively high mineralocorticoid activity (isofluprednone acetate) to the mother's nipples resulted in prolonged QT interval, cushingoid appearance, severe hypertension, decreased growth and electrolyte abnormalities in her 2-month-old breastfed infant. The mother had used the cream since birth for painful nipples.；◉ Effects on Lactation and Breastmilk；Relevant published information was not found as of the revision date.

The Approved Drug Products with Therapeutic Equivalence Evaluations List identifies currently marketed prescription drug products, incl flurandrenolide approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act.

D - Dermatologicals；D07 - Corticosteroids, dermatological preparations；D07A - Corticosteroids, plain；D07AC - Corticosteroids, potent (group iii)；D07AC07 - Fludroxycortide

QD - Dermatologicals；QD07 - Corticosteroids, dermatological preparations；QD07A - Corticosteroids, plain；QD07AC - Corticosteroids, potent (group iii)；QD07AC07 - Fludroxycortide

Flurandrenolide is a topical corticosteroid. It is normally applied to a plastic tape called Cordran. Cordran is primarily effective because of its anti-inflammatory, antipruritic, and vasoconstrictive actions. Flurandrenolide, which is slowly released from the Cordran tape, binds to the cytosolic glucocorticoid receptor. After binding the receptor the newly formed receptor-ligand complex translocates itself into the cell nucleus, where it binds to many glucocorticoid response elements (GRE) in the promoter region of the target genes. The DNA bound receptor then interacts with basic transcription factors, causing the increase in expression of specific target genes. The anti-inflammatory actions of corticosteroids are thought to involve lipocortins, phospholipase A2 inhibitory proteins which, through inhibition arachidonic acid, control the biosynthesis of prostaglandins and leukotrienes. Specifically glucocorticoids induce lipocortin-1 (annexin-1) synthesis, which then binds to cell membranes preventing the phospholipase A2 from coming into contact with its substrate arachidonic acid. This leads to diminished eicosanoid production. Cyclooxygenase (both COX-1 and COX-2) expression is also suppressed, potentiating the effect. In another words, the two main products in inflammation Prostaglandins and Leukotrienes are inhibited by the action of Glucocorticoids. Glucocorticoids also stimulate the lipocortin-1 escaping to the extracellular space, where it binds to the leukocyte membrane receptors and inhibits various inflammatory events: epithelial adhesion, emigration, chemotaxis, phagocytosis, respiratory burst and the release of various inflammatory mediators (lysosomal enzymes, cytokines, tissue plasminogen activator, chemokines etc.) from neutrophils, macrophages and mastocytes. Additionally the immune system is suppressed by corticosteroids due to a decrease in the function of the lymphatic system, a reduction in immunoglobulin and complement concentrations, the p

The mechanism of the anti-inflammatory effect of topical corticosteroids is not completely understood. Various laboratory methods, including vasoconstrictor assays, are used to compare and predict potencies and/or clinical efficacies of the topical corticosteroids. There is some evidence to suggest that a recognizable correlation exists between vasoconstrictor potency and therapeutic efficacy in man. Corticosteroids with antiinflammatory activity may stabilize cellular and lysosomal membranes. There is also the suggestion that the effect on the membranes of lysosomes prevents the release of proteolytic enzymes and, thus, plays a part in reducing inflammation. /Topical corticosteroids/

Glucocorticoids are capable of suppressing the inflammatory process through numerous pathways. They interact with specific intracellular receptor proteins in target tissues to alter the expression of corticosteroid-responsive genes. Glucocorticoid-specific receptors in the cell cytoplasm bind with steroid ligands to form hormone-receptor complexes that eventually translocate to the cell nucleus. There these complexes bind to specific DNA sequences and alter their expression. The complexes may induce the transcription of mRNA leading to synthesis of new proteins. Such proteins include lipocortin, a protein known to inhibit PLA2a and thereby block the synthesis of prostaglandins, leukotrienes, and PAF. Glucocorticoids also inhibit the production of other mediators including AA metabolites such as COX, cytokines, the interleukins, adhesion molecules, and enzymes such as collagenase. /Glucocorticoids/

Corticosteroids diffuse across cell membranes and complex with specific cytoplasmic receptors. These complexes then enter the cell nucleus, bind to DNA (chromatin), and stimulate transcription of messenger RNA (mRNA) and subsequent protein synthesis of various inhibitory enzymes responsible for the anti-inflammatory effects of topical corticosteroids. These anti-inflammatory effects include inhibition of early processes such as edema, fibrin deposition, capillary dilatation, movement of phagocttes into the area, and phagocytic activities. Later processes, such as capillary production, collagen deposition, and keloid formation also are inhibited by corticosteroids. The overall actions of topical corticosteroids are catabolic. /Corticosteroids (topical)/

Primarily hepatic

/Topical corticosteroids/ are metabolized primarily in the liver and then excreted in the kidneys. Some of the topical corticosteroids and their metabolites are also excreted into the bile. /Topical corticosteroids/

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FLURANDRENOLIDE

Established Pharmacologic Class [EPC] - Corticosteroid

Mechanisms of Action [MoA] - Corticosteroid Hormone Receptor Agonists

Flurandrenolide is a Corticosteroid. The mechanism of action of flurandrenolide is as a Corticosteroid Hormone Receptor Agonist.

FLURANDRENOLIDE

Substances that reduce or suppress INFLAMMATION.

A group of CORTICOSTEROIDS that affect carbohydrate metabolism (GLUCONEOGENESIS, liver glycogen deposition, elevation of BLOOD SUGAR), inhibit ADRENOCORTICOTROPIC HORMONE secretion, and possess pronounced anti-inflammatory activity. They also play a role in fat and protein metabolism, maintenance of arterial blood pressure, alteration of the connective tissue response to injury, reduction in the number of circulating lymphocytes, and functioning of the central nervous system.

Once absorbed through the skin, topical corticosteroids are handled through pharmacokinetic pathways similar to those of systemically administered corticosteroids

Topical corticosteroids can be absorbed from normal intact skin. They are metabolized primarily in the liver and then excreted in the kidneys. Some of the topical corticosteroids and their metabolites are also excreted into the bile.

Topical corticosteroids can be absorbed from normal intact skin. Inflammation and/or other disease processes in the skin increase percutaneous absorption. ... Once absorbed through the skin, topical corticosteroids are handled through pharmacokinetic pathways similar to systemically administered corticosteroids. Corticosteroids are bound to plasma proteins in varying degrees. They are metabolized primarily in the liver and then excreted in the kidneys. Some of the topical corticosteroids and their metabolites are also excreted into the bile. /Topical corticosteroids/

For relief of the inflammatory and pruritic manifestations of corticosteroid-responsive dermatoses, particularly dry, scaling localized lesions.

THERAP CAT: Glucocorticoid; antipsoriatic

MEDICATION

Prepn: Ringold et al, German patent 1,131,213 corresponds to US patent 3,126,375 (1962, 1964 both to Syntex).

FLURANDRENOLONE (6ALPHA-FLUORO-16ALPHA-HYDROXY-CORTISOL) IS CONDENSED WITH ACETONE BY TREATING ITS SOLN IN ACETONE WITH 70% PERCHLORIC ACID.