Ethynodiol

300.43512

300.44

214-971-5

9E01C36A9S

DTXSID1023025

40.46000

3.28430

1.0597 (rough estimate)

149-152 °C

381.66°C (rough estimate)

201.9ºC

1.4800 (estimate)

In water, 9.93 mg/L at 25 deg C (est)

Store at 20 deg to 25 deg C (68 deg to 77 deg F)

2.43X10-9 mm Hg at 25 deg C (est)

Henry's Law constant = 1.04X10-7 atm-cu m/mol at 25 °C (est)

Hydroxyl radical reaction rate constant = 1.27X10-10 cu cm/molec-sec at 25 °C (est)

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.|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.

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

... Rifampicin treatment (7.5 mg/kg/day, orally) for 8 days decreased the half-life of total 14C in plasma following a single oral dose of 4-[14C]ethynodiol diacetate (0.15 mg/kg) from 44 +/- to 24 +/- 2 hr. Fecal elimination of total 14C was significantly increased to 29 +/- 5% of the dose following rifampicin treatment, but urinary excretion was unchanged. Rifampicin treatment increased the amount of polar metabolites and decreased the amount of norethisterone in the free and conjugated fractions of plasma and urine. The amounts of sulphate and non-hydrolysed conjugates in feces were increased after rifampicin treatment.|Reduced efficacy and increased incidence of breakthrough bleeding and menstrual irregularities have been associated with concomitant use of rifampin. A similar association, though less marked, has been suggested for barbiturates, phenylbutazone, phenytoin sodium, and possibly with griseofulvin, ampicillin, and tetracyclines.|Administration of troglitazone concomitantly with a combination oral contraceptive (estrogen and progestin) reduced the plasma concentrations of both hormones by approximately 30%. This could result in loss of contraceptive efficacy.

Oral contraceptives have been reported to produce harmful ocular effects in myopic women. In women who developed myopia at or near puberty and in whom myopia became stable in adulthood, the drugs have reportedly increased the refractive error 2- to 3-fold, usually after 6 months of use. In women who are myopic and have considerable astigmatism, oral contraceptives may produce marked changes in the astigmatic error, possibly leading to frank keratoconus. In addition, oral contraceptives may produce a rapid advancement of the ocular disorder in patients with a family history of marked myopic astigmatism or keratoconus. Contact lens wearers receiving estrogen-progestin contraceptives may have more difficulties with their contact lenses than do nonusers who wear contact lenses. Contact lens wearers who develop visual disturbances or changes in lens tolerance during estrogen-progestin contraceptive use should be assessed by an ophthalmologist; temporary or permanent cessation of contact lens wear should be considered. /Estrogen-Progestin Combination/|Mental depression may occur in women receiving oral contraceptives. In a few cases, mental depression has been severe and has led to suicidal behavior. Mental depression appears to occur most frequently in patients with a history of depression, including premenstrual depression; however, relief of premenstrual tension occurs in some women. Patients with a history of mental depression should be observed carefully and the estrogen-progestin contraceptive discontinued if severe depression recurs during use. /Estrogen-Progestin Combination/

Small amounts of oral contraceptive steroids have been identified in the milk of nursing mothers ...

Contraceptives, Oral, Synthetic|Ethynodiol diacetate and ethinyl estradiol tablets, USP are indicated for the prevention of pregnancy in women who elect to use oral contraceptives as a method of contraception. /Included in US product label/

Cigarette smoking increases the risk of serious cardiovascular side effects from oral contraceptive use. This risk increases with age and with heavy smoking (15 or more cigarettes per day) and is quite marked in women over 35 years of age. Women who use oral contraceptives should be strongly advised not to smoke.|Both the relative and attributable risks of cerebrovascular events (thrombotic and hemorrhagic strokes) have been reported to be increased with oral contraceptive use, although, in general, the risk was greatest among older (over 35 years), hypertensive women who also smoked. Hypertension was reported to be a risk factor for both users and nonusers, for both types of strokes, while smoking increased the risk for hemorrhagic strokes.|Because of changes in practice and, also, because of some limited new data that suggest that the risk of cardiovascular disease with the use of oral contraceptives may now be less than previously observed, the Fertility and Maternal Health Drugs Advisory Committee was asked to review the topic in 1989. The Committee concluded that, although cardiovascular disease risks may be increased with oral contraceptive use after age 40 in healthy nonsmoking women (even with the newer low-dose formulations), there are greater potential health risks associated with pregnancy in older women and with the alternative surgical and medical procedures that may be necessary if such women do not have access to effective and acceptable means of contraception.|Benign hepatic adenomas and other hepatic lesions have been associated with oral contraceptive use, although the incidence of such benign tumors is rare in the United States. Indirect calculations have estimated the attributable risk to be in the range of 3.3 cases per 100,000 for users, a risk that increases after 4 or more years of use. Rupture of benign, hepatic adenomas or other lesions may cause death through intra-abdominal hemorrhage. Therefore, such lesions should be considered in women presenting with abdominal pain and tenderness, abdominal mass, or shock. About one quarter of the cases presented because of abdominal masses; up to one half had signs and symptoms of acute intraperitoneal hemorrhage. Diagnosis may prove difficult. Studies from the U.S., Great Britain, and Italy have shown an increased risk of hepatocellular carcinoma in long-term (>8 years; relative risk of 7-20) oral contraceptive users. However, these cancers are rare in the United States, and the attributable risk (the excess incidence) of liver cancers in oral contraceptive users approaches less than 1 per 1,000,000 users.|For more Drug Warnings (Complete) data for Ethynodiol (41 total), please visit the HSDB record page.

Absorption, distribution, excretion and metabolism of SC-11800EE, a combined steroid preparation consisting of SC-11800(ethynodiol diacetate)as gestagen and ethinyl estradiol (EE)as estrogen in 20:1 (w:w), were studied with the use of 14C-SC-11800 and 3H-EE by radiometry in female rats and by the whole body autoradiography in female normal and pregnant mice. The gestagen orally given with EE was rapidly absorbed from digestive tracts and distributed in tissues in various levels. Gestagen levels in liver and kidney exceeded that in plasma. About 75% of dosed radioactivity was excreted in feces largely via bile and more than 20% in urine within 72 hr after administration. The gestagen was metabolized extensively to more polar products and their conjugates. The pharmacokinetic behavior of the gestagen given with EE did not alter after repeated administrations for 7 days, but was slightly different from that without EE, possibly due to the estrogen effect. The pharmacokinetic behavior of the estrogen was independent from the gestagen given simultaneously. The distribution of the gestagen given with EE revealed by the whole body autoradiography in normal mice were essentially consistent with the radiometric results in rats and that in the pregnant mice showed that the gestagen in fetus was virtually nil under the present conditions.|Bioavailability and pharmacokinetics of norethisterone (NE) were studied in 12 women, aged 21-37 years, after oral doses of ethynodiol diacetate (EDA). Plasma NE levels, measured by radioimmunoassay, were used to compare the bioavailability of EDA tablets (Ovulen 50; 1 mg EDA plus .05 mg ethinyl estradiol) with that of a standard oral solution of EDA. The 3 different batches of tablets studied showed different in vitro dissolution rates, 82.6%, 94.6%, and 99% at 3 hours. No marked differences were seen in the bioavailability of the tablet formulations, which were essentially bioequivalent to the solution. Peak plasma NE levels were reached within 4 hours of EDA administration in solution or tablets. Following the peak, NE plasma levels declined in 2 phases, with mean terminal elimination 1/2-lives of 4-6.9 hours. These results have shown that small variations in in vitro dissolution rates do not affect the bioavailability of NE from tablets containing EDA.|Small amounts of oral contraceptive steroids have been identified in the milk of nursing mothers ...

After oral administration, norethisterone acetate and ethynodiol diacetate are rapidly converted to norethisterone by esterases during hepatic first-pass metabolism.|On administration of a single oral dose of [4-(14)C]ethynodiol diacetate (0.15 mg/kg) to rhesus monkey, plasma concentration of total 14C peaked after about 4 hr. About 60% of the plasma radioactivity was present as glucuronide conjugates and no unchanged drug was detected. Some 67 +/- 6% (mean +/- S.D.) of the dose of 14C was excreted in 4 days, 50 +/- 6% in urine and 18 +/- 2% in feces. Most of the urinary excretion occurred within 24 hr of dosage. Glucuronide conjugates accounted for 60% of the urinary 14C, and 46% of the fecal 14C was free steroids. Norethisterone and its tetrahydro metabolites were identified in the free, glucuronide and sulphate fractions of plasma and urine. Keto-4,5-dihydronorethisterones and trihydroxy metabolites were identified in the conjugated fractions of urine, and a complex mixture of polar metabolites was detected in feces.|All of the 17beta-ethynyl progestins reviewed follow similar metabolic paths. For three of these, norethynodrel, ethynodiol diacetate and lynestrenol, a principal metabolite is norethindrone. Biotransformation to more polar metabolites and conjugation proceed rapidly for these three precursor drugs and norethindrone. ... The compounds appear to be readily absorbed, and they and their metabolites are excreted to a greater extent in the urine than in the feces.|... The ethynodiol diacetate was metabolized extensively to more polar products and their conjugates. ...|There is limited information on the metabolism of levonorgestrel, norethindrone and structurally related contraceptive steroids. Both levonorgestrel and norethindrone undergo extensive reduction of the alpha, beta-unsaturated ketone in ring A. Levonorgestrel also undergoes hydroxylation at carbons 2 and 16. The metabolites of both compounds circulate predominantly as sulfates. In urine, levonorgestrel metabolites are found primarily in the glucuronide form, whereas norethindrone metabolites are present in approximately equal amounts as sulfates and glucuronides. Of the progestogens structurally related to norethindrone, norethindrone acetate, ethynodiol diacetate, norethindrone enanthate, and perhaps lynestrenol, undergo rapid hydrolysis and are converted to the parent compound and its metabolites. There is no convincing evidence that norethynodrel is converted to norethindrone. Of the progestogens structurally related to levonorgestrel, it appears that neither desogestrel nor gestodene are transformed to the parent compound. However, there is evidence that norgestimate can be, at least partly, converted to levonorgestrel. ...

Combination oral contraceptives act primarily by suppression of gonadotropins. Although the primary mechanism of this action is inhibition of ovulation, other alterations in the genital tract, including changes in the cervical mucus (which increase the difficulty of sperm entry into the uterus) and the endometrium (which may reduce the likelihood of implantation) may also contribute to contraceptive effectiveness.|Progesterone increases urinary sodium excretion at least in part by competition for renal mineralocorticoid receptors. In contrast, synthetic progestagens do not increase sodium excretion or even cause a slight sodium retention. /Investigators/ therefore compared the ability of progesterone and 12 progesterone like compounds to displace [3H]aldosterone from binding at cytoplasmic mineralocorticoid receptors in rat kidney. All synthetic progesteronelike steroids were less active than progesterone in competing with [3H]aldosterone for the receptor binding: progesterone 100%, 11 beta-OH progesterone 50%, 17 alpha OH-progesterone 24% and 16 alpha-methyl-progesterone 3%. Derivates of 17 alpha OH-progesterone (medrogestone 5%, dydrogestone 4%, medroxy progesterone-acetate 2% and chlormadinone-acetate 0.5%) were more potent than 19-nor-testosterone derivates: ethisterone 1%, norethisterone less than 1%, norethindrone less than 1%, norethyl-nodrel less than 1%, and ethynodiol-diacetate less than 1%. The decreased affinity of synthetic progestins for mineralocorticoid receptors explains in part the lack of natriuretic activity of these compounds.

/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 effects of 5 mg/day ethyodiol diacetate (ED) and Enovid on carbohydrate metabolism were compared in 2 groups of 36 parous women at the end of 1-year of treatment. Blood glucose and plasma insulin levels in women taking ED did not differ markedly over pretreatment values at the end of 1-year. However, in women taking Enovid, a significant increase was observed in blood glucose levels in the fasting state (p less than .01) and at each intravenous glucose tolerance testing period (p less than .02). Also mean plasma insulin levels were significantly (ps less than .01 and less than .02) increased at all testing times, except 120 minutes.|/HUMAN EXPOSURE STUDIES/ Medical histories of 436 patients treated with Ovulen after childbirth or an abortion were examined in order to collect a sample of women who had taken the orals for 6-12 cycles. A group of 70 patients was thus formed. The following parameters were investigated: weight variation; blood pressure; nausea and vomiting; varicosities; variation in menstrual flow and length of period; breast-related side effects; jaundice; psychic alteration, i.e., nervousness, anxiety, or depression; changes in libido; headaches; skin changes; and pregnancy. Results are presented both in graph and table form. Weight change was found to tend more to loss than to gain. No statistically significant changes in blood pressure were observed. Nausea and associated symptoms tended to disappear after the 9th cycle. Edema was present in only 6% of all cycles. The most common side effect was varicosities, present in 25% of the sample, but in no instance did thrombosis occur nor was varicosity a cause for discontinuation in any case. Breast-related side effects were more common at the outset. No jaundice was observed. Psychic alterations were not common and were mostly insignificant and tended to occur more frequently at the outset. 12% of the sample had headaches from the beginning of treatment up until the 8th month, after which they began to disappear. Only 1 patient had chloasma and then only during the 1st 2 cycles. There was a marked tendency toward menorrhagia which was thought to be beneficial due to the prevalence of anemia in the group. Changes in libido were minimal and tended to disappear after the 8th cycle. None of the patients became pregnant.|/SIGNS AND SYMPTOMS/ Serious ill effects have not been reported following acute ingestion of large doses of oral contraceptives by young children. Overdosage may cause nausea, and withdrawal bleeding may occur in females.|/CASE REPORTS/ ... A 30-year-old nulligravida nulliparous woman presented with menometrorrhagia. She had had normal menses since age 11, she had smoked a pack of cigarettes a day for 15 years, and had been obese since age 15 (weighing 302 pounds). At age 26, she started taking a combination OC containing .1 mg ethynodiol diacetate and 35 mcg ethynyl estradiol (EE). 4 years later she gradually developed menorrhagia which improved upon changing the OC to .3 mg norgestrel and 30 mcg EE. Subsequently she developed early cycle metrorrhagia and was placed on .5 mg norgestrel and 50 mcg EE. She continued having early and midcycle breakthrough bleeding with clots. Physical examination and test results including a PAP smear were normal. She was taken to the emergency department because of continued bleeding. The uterus sounded to 14 cm. Curettings were consistent with grade 1-2, well-differentiated adenocarcinoma of the endometrium. 3 weeks later, she had total abdominal hysterectomy, bilateral salpingo-oophorectomy, and peritoneal biopsy for cytological examination. The pelvis and the abdomen were free of metastasis. Histological examination revealed a superficially invasive, well-differentiated adenocarcinoma consistent with stage IB, grade 1%. Ploidy analysis uncovered 12.5% tetraploid, with 0% aneuploid or hyperploid cells with 8.5% of the cells in S phase and 21% in the proliferative phase. Both estrogen and progesterone receptors were positive. The ploidy analysis and receptor status were consistent with the low-grade nature of the lesions. Postoperative radiation was not recommended, and the patient was well 6 months postoperatively.|For more Human Toxicity Excerpts (Complete) data for Ethynodiol (42 total), please visit the HSDB record page.

ethinodiol

Diacetate mixture with mestranol. Luteolas, Metrulen, Ovaras, Ovulen.|Diacetate mixture with ethinyl estradiol. Conova, Demulen, Miniluteolas.|Ethynodiol diacetate is available commercially alone or as a component of a combination tablet that contains ethynodiol diacetate plus ethinylestradiol or mestranol. /Ethynodiol diacetate/

... Infra-red and ultra-violet absorption spectrophotometry with comparison to standards ... /are/ methods for identifying ethynodiol diacetate; potentiometric titration with sodium hydroxide and liquid chromatography are used to assay its purity. Thin-layer chromatography is specified to identify ethynodiol diacetate in combination formulations; liquid chromatography is used to assay the quantity of ethynodiol diacetate in combination tablets. /Ethynodiol diacetate/