Paramethasone

392.46

392.46

200-169-2

VFC6ZX3584

DTXSID3023421

H - Systemic hormonal preparations, excl. sex hormones and insulins

94.8

1.68 (est)

Solid

1.32 g/cm3

228-241°C

573.5ºC at 760 mmHg

300.6ºC

1.589

1.45e-01 g/L

6.93X10-14 mm Hg at 25 deg C (est)

Henry's Law constant = 7.15X10-8 atm-cu m/mole at 25 °C (est)

Decomposes at 228-241 °C; sol in ethanol, acetone; slightly sol in water. Specific optical rotation: + 85 deg; max absorption (ethanol): 243 nm (log e= 4.16) /21-Acetate/|Hydroxyl radical reaction rate constant = 6.63X10-11 cu cm/molec-sec at 25 °C (est)

EXPOSURE TO LIGHT SHOULD BE AVOIDED /ACETATE/

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 Approved Drug Products with Therapeutic Equivalence Evaluations List identifies discontinued drug products, incl paramethasone acetate. /Paramethasone acetate/

Side effects include inhibition of bone formation, suppression of calcium absorption delayed wound healing, immune suppression, and hyperglycemia.

HYPERGLYCEMIC ACTION OF CORTISONE MAY OFFSET THE HYPOGLYCEMIC EFFECT OF CHLORPROPAMIDE...CONCURRENT ADMIN...MAY INCR LIKELIHOOD OF PPTN GASTRIC ULCER, BUT...NO CLINICAL REPORTS OF THIS...IN HUMANS. ...PARAMETHASONE /SHOULD INTERACT IN SIMILAR MANNER/.|SYSTEMIC EFFECTS OF ADMIN CORTICOSTEROIDS...MAY BE DIMINISHED BY LARGE DOSES OF BARBITURATES SUCH AS PHENOBARBITAL. ...PARAMETHASONE...MAY BE EXPECTED TO INTERACT...|PHENYTOIN...INCR METAB OF HYDROCORTISONE...& METHYLPREDNISOLONE IN HUMANS. ...LIKELY THAT...PARAMETHASONE...WOULD INTERACT SIMILARLY.|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/|For more Interactions (Complete) data for PARAMETHASONE (7 total), please visit the HSDB record page.

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 regimen. ... /Corticosteroids/|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/

80%

While data specific to paramethasone 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).

Corticosteroids may be distributed into milk ... . /Corticosteroids/

For the treatment of all conditions in which corticosteroid therapy is indicated except adrenal-deficiency states for which its lack of sodium-retaining properties makes it less suitable than hydrocortisone with supplementary fludrocortisone.

Anti-Inflammatory Agents, Steroidal; Glucocorticoids, Synthetic|PARAMETHASONE, A SYNTHETIC ANALOGUE OF HYDROCORTISONE, IS USEFUL IN TREATING INFLAMMATORY OR ALLERGIC CONDITIONS & OTHER DISEASES THAT RESPOND TO GLUCOCORTICOIDS. IN ANTI-INFLAMMATORY EFFECT, 2 MG PARAMETHASONE IS APPROX EQUIVALENT TO 20 MG HYDROCORTISONE.|IT IS 10 TIMES AS POTENT AS CORTISONE, BUT POTENCY DOES NOT CONFER ANY PARTICULAR ADVANTAGES. /PARAMETHASONE ACETATE/|VET: LIMITED, IN VETERINARY MEDICINE. INTRASYNOVIALLY, 10 MG OF SOL PHOSPHATE ESTER WAS ONLY EFFECTIVE FOR 1 DAY IN STIFLE JOINT OF DOGS.|For more Therapeutic Uses (Complete) data for PARAMETHASONE (6 total), please visit the HSDB record page.

UNDESIREABLE EFFECTS ARE SIMILAR TO THOSE OBSERVED WITH OTHER GLUCOCORTICOIDS. INCR APPETITE WITH WT GAIN OCCURS IN ABOUT 1/3 PT.|...LACKS THE SODIUM-RETAINING PROPERTIES OF HYDROCORTISONE, ALTHOUGH EDEMA & HYPERTENSION ARE OBSERVED INFREQUENTLY. THUS, PARAMETHASONE IS NOT RECOMMENDED FOR REPLACEMENT THERAPY IN ADRENOCORTICAL INSUFFICIENCY.|...ALMOST DEVOID OF MINERALOCORTICOID SIDE EFFECTS... CATABOLIC EFFECTS, SUCH AS PROTEIN DEPLETION & OSTEOPOROSIS, ARE ONLY MODERATE WITH LOW TO MODERATE DOSES OF THE DRUG. /PARAMETHASONE ACETATE/|The immunosuppressive effects of glucocorticoids may result in activation of latent infection or exacerbation of intercurrent infections, including those caused by Candida, Mycobacterium, Toxoplasma, Strongyloides, Pneumocystis, Cryptococcus, Nocardia, or Ameba. Glucocorticoids should be used with great care in patients with known or suspected Strongyloides (threadworm) infection. In such patients, glucocorticoid-induced immunosuppression may lead to Strongyloides hyperinfection and dissemination with widespread larval migration, often accompanied by severe enterocolitis and potentially fatal gram-negative septicemia. /Corticosteroids/|For more Drug Warnings (Complete) data for PARAMETHASONE (29 total), please visit the HSDB record page.

Paramethasone is a glucocorticoid with the general properties of corticosteroids. Glucocorticoids are a class of steroid hormones characterised by an ability to bind with the cortisol receptor and trigger a variety of important cardiovascular, metabolic, immunologic and homeostatic effects. Glucocorticoids are distinguished from mineralocorticoids and sex steroids by having different receptors, target cells, and effects. Technically, the term corticosteroid refers to both glucocorticoids and mineralocorticoids, but is often used as a synonym for glucocorticoid. Glucocorticoids suppress cell-mediated immunity. They act by inhibiting genes that code for the cytokines IL-1, IL-2, IL-3, IL-4, IL-5, IL-6, IL-8 and TNF-alpha, the most important of which is the IL-2. Reduced cytokine production limits T cell proliferation. Glucocorticoids also suppress humoral immunity, causing B cells to express lower amounts of IL-2 and IL-2 receptors. This diminishes both B cell clonal expansion and antibody synthesis. The diminished amounts of IL-2 also leads to fewer T lymphocyte cells being activated.

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. (See all compounds classified as Glucocorticoids.)|Substances that reduce or suppress INFLAMMATION. (See all compounds classified as Anti-Inflammatory Agents.)

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

Hepatic.

Glucocorticoids such as paramethasone can inhibit leukocyte infiltration at the site of inflammation, interfere with mediators of inflammatory response, and suppress humoral immune responses. The antiinflammatory actions of glucocorticoids are thought to involve phospholipase A2 inhibitory proteins, lipocortins, which control the biosynthesis of potent mediators of inflammation such as prostaglandins and leukotrienes. Paramethasone reduces inflammatory reaction by limiting the capillary dilatation and permeability of the vascular structures. These compounds restrict the accumulation of polymorphonuclear leukocytes and macrophages and reduce the release of vasoactive kinins. Recent research suggests that corticosteroids may inhibit the release of arachidonic acid from phospholipids, thereby reducing the formation of prostaglandins. Prednisolone is a glucocorticoid receptor agonist. On binding, the corticoreceptor-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 an increase or decrease in expression of specific target genes, including suppression of IL2 (interleukin 2) expression.|Because paramethasone acetate suppresses basal and midcycle LH surge and blocks estrogen synthesis in the female, its possible effect upon testicular physiology was evaluated in 13 healthy men by measuring the circulating levels of FSH, LH, prolactin, testosterone, dihydrotestosterone, androstenedione, estradiol and cortisol every 4 hr throughout the day, before (control) and after paramethasone acetate (6 mg/day/7 days). The total concentrations of each hormone, as well as the paramethasone acetate-induced suppressibility (measured as percent decrease in the mean 24 hr plasma level) were analyzed. paramethasone acetate suppressed neither the basal nor circadian rhythm of testosterone and had no effect on LH, FSH or prolactin output. Dihydrotestosterone, androstenedione, estradiol were significantly reduced and the basal concentrations and circadian variations of cortisol were abolished. Paramethasone acetate showed a dual control on the pituitary gonadal axis and while causing a maximal suppressed adrenocortical activity it had no interference in testosterone synthesis. /Paramethasone acetate/|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/

/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/

/OTHER TOXICITY INFORMATION/ To test the antiestrogenic action of paramethasone acetate (PA), a group of five postmenopausal women were treated in two ways. For phase I, PA + mestranol, 6 mg + 80 micrograms per day for 10 days, was administered. Ten days were allowed for withdrawal of medication. For phase II, mestranol, 80 micrograms per day for 10 days, free of the glucocorticoid was administered. Daily samples of cervical mucus, vaginal cells, and peripheral blood were obtained to analyze fernlike crystallization (%), cornified pyknotic nuclei cells (%), and concentrations of ethynyl-estradiol (EE-2, pg/ml) during both phases. The fernlike crystallization pattern had a mean value of 8 +/- 0.9% for phase I, while for phase II it was 85 +/- 8% (P less than 0.05). The percentage mean value of cornified pyknotic nuclei cells of phase I was 28 +/- 5% in comparison with 53 +/- 7% observed in phase II (P less than 0.05). EE-2 mean value concentrations for phase I were 85 +/- 90 pg/ml, while for phase II they were 724 +/- 418 pg/ml (P less than 0.05). These results demonstrate that 6 mg of PA is able to compete against the estrogenic action in the parameters of the study selected.|/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/

Paramethasone

HALDRONE (LILLY). ORAL: TABLETS 1 & 2 MG. STEMEX (SYNTEX). ORAL: TABLETS 2 MG.

Analyte: paramethasone acetate; matrix: chemical identification; procedure: infrared absorption spectrophotometry with comparison to standards /paramethasone acetate/|Analyte: paramethasone acetate; matrix: chemical identification; procedure: ultraviolet absorption spectrophotometry with comparison to standards /paramethasone acetate/|Analyte: paramethasone acetate; matrix: chemical identification; procedure: thin-layer chromatography with detection using short-wavelength ultraviolet light and comparison to standards /paramethasone acetate/|Analyte: paramethasone acetate; matrix: chemical purity; procedure: thin-layer chromatography with detection using ultraviolet light; ultraviolet absorption spectrophotometry at 242 nm with comparison to standards /paramethasone acetate/|For more Analytic Laboratory Methods (Complete) data for PARAMETHASONE (6 total), please visit the HSDB record page.

Analyte: paramethasone; matrix: blood (serum); procedure: reversed-phase high-performance liquid chromatography with ultraviolet detection at 245 nm; limit of detection: 1-10 ng/mL