Dydrogesterone

312.45

312.45

205-806-8

90I02KLE8K

92336

DTXSID1022974

Crystals from acetone + hexane|White to off-white...crystalline powder.

G03DB01|G - Genito urinary system and sex hormones

34.1

3.4

Solid

1.0697 (rough estimate)

169-170 °C

392.36°C (rough estimate)

172.2±25.7 °C

1.4900 (estimate)

Practically insoluble in water, soluble in acetone, sparingly soluble in ethanol (96 per cent).

Refrigerator

7.08X10-7 mm Hg at 25 deg C (est)

LD50 oral in rat: > 4600mg/kg

D25 -484.5° (chloroform)

Odorless

Henry's Law constant = 4.65X10-8 atm-cu m/mol at 25 °C (est)

Hydroxyl radical reaction rate constant = 1.94X10-10 cu cm/molec-sec at 25 °C (est)|Ozone radical reaction rate constant = 5.26X10-17 cu cm/molec-sec at 25 °C (est)

III

6.1

UN 3077 9 / PGIII

3

S26-S37/39

P260, P264, P270, P273, P314, P391, P501

H372

SRP: At the time of review, regulatory criteria for small quantity disposal are subject to significant revision, however, household quantities of waste pharmaceuticals may be managed as follows: Mix with wet cat litter or coffee grounds, double bag in plastic, discard in trash.|SRP: Expired or waste pharmaceuticals shall carefully take into consideration applicable DEA, EPA, and FDA regulations. It is not appropriate to dispose by flushing the pharmaceutical down the toilet or discarding to trash. If possible return the pharmaceutical to the manufacturer for proper disposal being careful to properly label and securely package the material. Alternatively, the waste pharmaceutical shall be labeled, securely packaged and transported by a state licensed medical waste contractor to dispose by burial in a licensed hazardous or toxic waste landfill or incinerator.

The Approved Drug Products with Therapeutic Equivalence Evaluations identifies discontinued drug products. Dydrogesterone is included on this list.

No serious or unexpected toxicity has been observed with dydrogesterone. In acute toxicity studies, the LD50 doses in rats exceeded 4,640mg/kg for the oral route.

Generally recognised risk factors for venous thrombo embolus (VTE) include a personal or family history, severe obesity (BMI>30 kg/sq m) and systemic lupus erythematosus (SLE). There is no consensus about the possible role of varicose veins in VTE.|Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.

NIOSH (NOES Survey 1981-1983) has statistically estimated that 191 workers (82 of these were female) were potentially exposed to dydrogesterone in the US(1).

Used to treat irregular duration of cycles and irregular occurrence and duration of periods caused by progesterone deficiency. Also used to prevent natural abortion in patients who have a history of habitual abortions.

Progestational Hormones, Synthetic|/Dydrogesterone is indicated as/ Hormone replacement therapy (HRT) for estrogen deficiency symptoms in peri and postmenopausal women. Prevention of osteoporosis in postmenopausal women at high risk of future fractures who are intolerant of, or contraindicated for, other medicinal products approved for the prevention of osteoporosis.|/EXPTL THER:/ The aim of the present study was to evaluate dydrogesterone for luteal-phase support in assisted reproductive technologies (ART) and to compare it with micronized vaginal progesterone. All patients underwent long-term downregulation with gonadotropin-releasing hormone agonists. In phase I, 498 patients were divided into three groups: long protocol and not at risk of ovarian hyperstimulation syndrome (OHSS) (group A); long protocol and at risk of OHSS (group B); and those in a donor oocyte program (group C). All patients received micronized progesterone 600 mg/day, vaginally. They were also randomized to dydrogesterone 20 mg/day (n = 218) or placebo (n = 280). The pregnancy rate was higher with dydrogesterone than with placebo in group A (33.0% vs. 23.6%), group B (36.8% vs. 28.1%) and group C (42.9% vs. 15.6%; p < 0.001). In phase II, 675 patients were divided into the same three groups (groups D, E and F) and were randomized to dydrogesterone 30 mg/day (n = 366) or micronized progesterone 600 mg/day (n = 309). The pregnancy rate was significantly higher with dydrogesterone than with progesterone in group D (39.1% vs. 26.7%; p < 0.01), group E (41.2% vs. 35.6%; p < 0.01) and group F (48.2% vs. 33.9%; p < 0.001). In conclusion, dydrogesterone is effective in luteal-phase support in ART.|Dydrogesterone has no inherent estrogenic activity and no androgenic effects. Priming with estrogen is necessary prior to use. Drug is claimed to be nonthermogenic and does not consistently inhibit ovulation.|Spectrum of progestin therapy has changed & expanded during last few yr. Drug-therapy of choice in endometriosis is medication of progestins for at least 6 months. If patient wants additional children the "more gentle" dydrogesterone should be considered.

There is no conclusive evidence for improvement of cognitive function. There is some evidence from the WHI trial of increased risk of probable dementia in women who start using continuous combined CEE and MPA after the age of 65. It is unknown whether the findings apply to younger post-menopausal women or other HRT products.|For the treatment of postmenopausal symptoms, HRT should only be initiated for symptoms that adversely affect quality of life. In all cases, a careful appraisal of the risks and benefits should be undertaken at least annually and HRT should only be continued as long as the benefit outweighs the risk.|Known, past or suspected breast cancer; Known or suspected estrogen-dependent malignant tumours (eg endometrial cancer); Undiagnosed genital bleeding; Untreated endometrial hyperplasia; Previous idiopathic or current venous thromboembolism (deep vein thrombosis, pulmonary embolism); Active or recent arterial thromboembolic disease (eg angina, myocardial infarction); Acute liver disease or a history of liver disease as long as liver function tests have failed to return to normal; Known hypersensitivity to the active substances or to any of the excipients; Porphyria.|Femoston is not indicated during pregnancy. If pregnancy occurs during medication with Femoston, treatment should be withdrawn immediately.|For more Drug Warnings (Complete) data for DYDROGESTERONE (26 total), please visit the HSDB record page.

Dydrogesterone is an orally active progestogen which acts directly on the uterus, producing a complete secretory endometrium in an estrogen-primed uterus. At therapeutic levels, dydrogesterone has no contraceptive effect as it does not inhibit or interfere with ovulation or the corpus luteum. Furthermore, dydrogesterone is non-androgenic, non-estrogenic, non-corticoid, non-anabolic and is not excreted as pregnanediol. Dydrogesterone helps to regulate the healthy growth and normal shedding of the uterus lining. Therefore, it may be useful in the treatment of menstrual disorders such as absent, irregular or painful menstrual periods, infertility, premenstrual syndrome and endometriosis.

Compounds that interact with PROGESTERONE RECEPTORS in target tissues to bring about the effects similar to those of PROGESTERONE. Primary actions of progestins, including natural and synthetic steroids, are on the UTERUS and the MAMMARY GLAND in preparation for and in maintenance of PREGNANCY. (See all compounds classified as Progestins.)

Rapidly absorbed in the gastrointestinal tract with a bioavailability of 28%.|After oral administration of labelled dydrogesterone, on average 63% of the dose is excreted into the urine. Within 72 hours, excretion is complete.|After oral administration of dydrogesterone, plasma concentrations of DHD are substantially higher as compared to the parent drug. The AUC and Cmax ratios of DHD to dydrogesterone are in the order of 40 and 25, respectively. Dydrogesterone is rapidly absorbed. The Tmax values of dydrogesterone and DHD vary between 0.5 and 2.5 hours.|The dihydrodydrogesterone Caverage is 13 ng/mL, the Cmin is 4.1 ng/mL and the Cmax is 63 ng/mL. The dydrogesterone Caverage is 0.38 ng/mL the Cmin is <0.1 ng/mL and the Cmax is 2.5 ng/mL.|Progestins are reportedly distributed into milk. The possible effects of progestins in milk on nursing infants have not been determined. /Progestins General Statement/

Metabolism is complete to a 20-dihydrodydrogesterone (DHD) metabolite.|In man, dydrogesterone is completely metabolised. The main metabolite of dydrogesterone is 20alpha-dihydrodydrogesterone (DHD) and is present in the urine predominantly as the glucuronic acid conjugate. A common feature of all metabolites characterized is the retention of the 4,6 diene-3-one configuration of the parent compound and the absence of 17alpha-hydroxylation. This explains the absence of estrogenic and androgenic activity.|Dydrogesterone is not excreted in urine as pregnanediol, like progesterone. Analysis of endogenous progesterone production based on pregnanediol excretion therefore remains possible.

Dydrogesterone: 5-7 hours, 20-dihydrodydrogesterone (DHD) metabolite: 14-17 hours|Mean terminal half lives of dydrogesterone and DHD vary between 5 to 7 and 14 to 17 hours, respectively.

Dydrogesterone is a progestogen that works by regulating the healthy growth and normal shedding of the womb lining by acting on progesterone receptors in the uterus.|Dydrogesterone is an orally-active progestagen. The addition of a progestagen greatly reduces the estrogen-induced risk of endometrial hyperplasia and cancer in non-hysterectomised women, by reducing the growth of the endometrium.|Progestins cannot be equated as group with progesterone because some are inherently estrogenic, some slightly androgenic, and some purely progestational; correspondingly, their ovulation-inhibiting potentialities may be mediated in somewhat different ways. /Progestins/|The 17-hydroxy or acetoxy compounds, on the other hand, elicit responses more nearly resembling those of progesterone. They have little or no estrogenic or androgenic activity and may produce catabolic and slight diuretic effects. The 19-nor derivatives are more effective in postponing the normal menstrual period. /Progestins/|Accumulating evidence indicates that the neuropeptide substance P (SP) is predominantly involved in neurogenic inflammation and pain perception via its high-affinity neurokinin 1 receptor (NK-1R). Intriguingly, decreased pain sensitivity is found to be associated with high plasma progesterone levels. We hypothesize that progesterone may attenuate nociception and associated inflammatory response via NK-1R-dependent pathways. To address our hypothesis, we incubated splenic lymphocytes from CBA/J female mice with different concentrations of the progesterone derivative dydrogesterone. Subsequently, the expressions of NK-1R and T helper (Th1)-type cytokines were analyzed by flow cytometry. Next, we subcutaneously injected CBA/J mice with 1.25 mg of dydrogesterone in 200-microl sesame oil; control mice were sham-injected. Tail flick test to detect the nociceptive threshold was performed in 30-min intervals upon injection. Lymphocytes were isolated from blood and uterus and analyzed for NK-1R surface expression. Immunohistochemical analyses were performed to investigate the uterine tissue distribution of NK-1R. Dydrogesterone induced a decrease in the percentage of NK-1R+ lymphocytes in vitro and in vivo. Additionally, an increase in Th2-type and a decrease in Th1-type cytokines could be detected in vitro after incubation with dydrogesterone. An increased tail flick latency following dydrogesterone injection supported the concept that decreased expression of the NK-1R on lymphocytes is associated with an increased pain threshold. Taken together, these results clearly reveal a pathway by which dydrogesterone or progesterone respectively modulates the cross talk of the nervous, endocrine and immune systems in inflammation and pain.|For more Mechanism of Action (Complete) data for DYDROGESTERONE (6 total), please visit the HSDB record page.

/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/

/HUMAN EXPOSURE STUDIES/ The aim of this study was to evaluate the impact of a three-month continuous administration of oral E2, alone, or combined with 2 different dosages of dydrogesterone, on the glucose tolerance and insulin sensitivity in postmenopausal women. In a prospective placebo-controlled study, 43 normal weight and normoinsulinemic women were randomized to receive either 2 mg of oral 17beta E2 daily (group A), or 2 mg E2 daily plus 5 mg daily oral dydrogesterone, from day 14 to 28, in a sequentially combined regimen (group B), or 2 mg of E2 and 10 mg dydrogesterone in the same sequentially combined regimen (group C) or placebo for 12 weeks. An OGTT and a euglycemic hyperinsulinemic clamp were performed before and after treatment. Serum glucose and insulin concentrations were measured both in fasting conditions and after OGTT. C-peptide pancreatic secretion was tested only in fasting conditions. Total body glucose utilization (M), for insulin sensitivity evaluation, was determined in each subject. Postmenopausal women treated with unopposed 17beta E2 (group A) showed a slight but statistically significant decrease of insulin sensitivity (p<0.05). A more marked deterioration of the same parameter was observed in the 2 groups treated with E2 plus dydrogesterone (group B and group C: p<0.01). Post hoc testing for the percent change from baseline indicated that group A significantly differed from group C (p<0.05) and all treated groups significantly differed from the placebo group (p<0.01). Finally, after treatment in group C, a significant reduction of insulin and an increase of glucose responses to OGTT (p<0.01) were observed. These results indicate that, in a short-term period, the use of 17beta E2 and overall 17beta E2 plus dydrogesterone, even with the reduction of insulin plasma levels, might cause a decrease in insulin sensitivity in normal weight and normoinsulinemic post-menopausal women.|/SIGNS AND SYMPTOMS/ Both estradiol and dydrogesterone are substances with low toxicity. Theoretically, symptoms such as nausea, vomiting, sleepiness and dizziness could occur in cases of overdosing. It is unlikely that any specific or symptomatic treatment will be necessary.|/CASE REPORTS/ In December, 1986, a 29 year old woman developed nephrosis due to systemic lupus erythematosus after taking oral contraceptives (OC) for 6.5 years. Hospitalized for 3 months, she received steroid treatment, which lowered albumin in urine. At the time of hospitalization, the following symptoms were noted. Edema on all her limbs, 4.5 g/dl of urine albumin per day, white blood cell count of 2600/mm, 640 time positive anti-nuclear antibodies, pseudo-positive response to syphilis via bentonite flocculation on particle (BFP). OC she had taken since 1980 were 0.5 mg of norgestrel day and 0/05 mg of ethinyl estradiol day. She had been routinely checked on her kidney function biannually and everything had been normal till then. For 2 months starting in December, 1987, at the patient's request, progesterone along (dydrogesterone 10 mg/day) was administered for contraception. No urine albumin was detected. It appears that autoimmune-type thyroid gland abnormality preceded systemic lupus erythematosus (SLE) which was triggered by the oral contraceptive use. Estrogen metabolism of SLE patients is characterized by estrogen active 16 alpha hydroxyestrone.|/CASE REPORTS/ Dydrogesterone, similar to women's natural progesterone, has been used in a wide range of gynecological conditions. /The authors/ describe a case of hepatitis and warm antibody hemolytic anemia due to dydrogesterone.|For more Human Toxicity Excerpts (Complete) data for DYDROGESTERONE (23 total), please visit the HSDB record page.

6 Dehydro 9 beta 10 alpha progesterone

Estradiol/dydrogesterone (Femoston) combination tablets: Round, biconvex, grey film-coated tablets|...MARKETED AS 5- & 10-MG TABLETS.

...Derivative of retroprogesterone... /PRC: purely progestational/

Determination of progesterone and synthetic progestins in pharmaceutical forms by differential pulse polarography had a precision of +/- 1% for 10-5 to 10-3 molar/L.|... Infra-red and ultra-violet absorption spectrophotometry with comparison to standards as methods for identifying dydrogesterone; ultra-violet absorption spectrophotometry and liquid chromatography are used to assay its purity. Dydrogesterone is identified in pharmaceutical preparations by infra-red and ultra-violet absorption spectrophotometry; ultra-violet absorption spectrophotometry and liquid chromatography are used to assay for dydrogesterone content.|Analyte: dydrogesterone; matrix: chemical identification; procedure: infrared absorption spectrophotometry with comparison to standards|Analyte: dydrogesterone; matrix: chemical identification; procedure: ultraviolet absorption spectrophotometry with comparison to standards|For more Analytic Laboratory Methods (Complete) data for DYDROGESTERONE (7 total), please visit the HSDB record page.

Human Drugs -> FDA Approved Drug Products with Therapeutic Equivalence Evaluations (Orange Book) -> Active Ingredients