|Clomiphene Citrate Chemical Properties|
|Hazard Codes ||T|
|Risk Statements ||60-63|
|Safety Statements ||53-36/37-45|
|WGK Germany ||3|
|Clomiphene Citrate Usage And Synthesis|
|Anti-hormone drugs||Clomiphene citrate is a kind of anti-hormone drugs. It has strong anti-estrogenic effect and weak estrogenic effects, and is easily absorbed in the gastrointestinal tract, and can be slowly excreted through the liver into the bile duct; it is clinically useful in the treatment of women infertility with a certain level of estrogen but being anovulatory or less ovulatory and treatment of male infertility with luteal phase defect or few sperm; it can also used for testing ovarian function and probing the dysfunction of male hypothalamus (pituitary) gonadal axis. The mechanism of action is to competitively bind to the hypothalamus estrogen receptor binding site for taking effect. Estrogen is displaced out from these areas, then the hypothalamus will be aware of the apparent lack of circulating estrogen, leading to the release of gonadotropin hormone for stimulation of follicle stimulating hormone (FSH) and luteinizing hormone (LH) secretion with whom to trigge the normal menstrual cycle .
|Pharmacological effects||Clomiphene citrate is a kind of triphenylethylene derivatives with its structure being similar to estrogen and has a strong anti-estrogen but weak estrogenic activity. The ovulation induction mechanism of this product is to promote an increase in the secretion of pituitary gonadotropins; gonadotropin stimulates the follicle growth and maturation inside the ovary, further causing production and secretion of luteinizing hormone with a clinical pregnancy curing rate of 35% for patients suffering ovulation disorders. However, for patients with primary pituitary or ovarian dysfunction, such as primary amenorrhea, it is usually for applying this drug for treatment. In addition, anovulation caused by factors of other organs (such as thyroid, adrenal dysfunction) is not suitable for subjecting to this treatment. Clomiphene citrate has an effect of promoting the sperm production of men which is clinically used for the treatment azoospermia. The prerequisite for clinical application is a certain function in ovarian and a normal or a bit lower hormone levels. It is mainly used for: |
1. Ovulation induction: for the treatment of anovulatory or inadequate luteal malfunction; infertility women who hope for pregnancy. At the 3-5 days of menstrual bleeding or progesterone withdrawal bleeding, orally administrate 50 mg daily and continuously take for five days. Usually ovulation occurs at about 7 days after stopping drugs when having intercourse is easy to increase the pregnancy rate. If the dose can induce ovulation, the treatment can be repeated; if there is no ovulation, the daily dose can be increased to 100 ~ 150 mg with administration in twice upon an empty stomach for 5 consecutive days. At appropriate indications, most patients can ovulate in the first cycle of treatment, for patients of long-term amenorrhea; their endometrial is not sensitive enough which requires two to three cycles of treatment for induction menstruation. If ovulation still doesn’t occur after three cycles, people should be reconsidered whether the diagnosis is correct.
2. Functional uterine bleeding, secondary amenorrhea or severe oligomenorrhea, and polycystic ovary syndrome: for people who ha menstruation, they should begin to take drug at the 5th day of menstrual; People without menstruation may start at any day or at the 5th day of the in artificial cycle with 1/d 50 ~ 100mg.
3. Male with low sperm and infertility: 25mg /d/per time; consecutively take for 25 days as one treatment course. Repeat it after stopping for five days until the sperm count reach normal standards; this process normally takes 3 to 12 courses. Male patients with no sperm should not apply clomiphene citrate for therapy.
4. Senile vaginitis and non-specific vaginitis: apply one tablets of clomiphene citrate per day; place it with vaginal suppositories (each tablets contains clomiphene 0.1 mg and chloramphenicol 250 mg) into the vagina with a week being a course; It is reported that it has better efficiency than chlorhexidine suppository.
5. Treatment of the anus, vulva, scrotum itching and eczema, dermatitis, chilblains, scabies; can apply 10% clomiphene citrate cream for treating affected area with a rapid efficacy, a long duration and high safety.
Reference: Liu Xinmin editor Internal Medicine • Volume II. Beijing: Military Medical Science Press .2009 p. 1114-1115.
|Adverse reactions||Within the prescribed dose range, adverse reactions of clomiphene citrate is not obvious, it does not affect the efficacy of treatment with overdose and long-term medication causing a increased adverse reactions such as the suppression of spermatogenesis in treating male infertility. The main adverse reactions seen in: |
1 Vasomotor symptom: Some women may have hot flashes, sweating and other menopausal syndrome, which is related to the anti-estrogen effect of drugs; this can disappear after treatment, it can also be alleviated by increased administration of estrogen.
2. Abdominal symptoms: bloating, a sense of falling and ovulation pain; these symptoms are often associated with ovulation and ovarian enlargement; It is necessary to be subject to a medical examination to rule out the possibility of ovarian enlargement.
3. Ovarian enlargement and ovarian cysts: applying predetermined dose rarely cause enlarged ovaries; once ovarian enlargement occurs, discontinue treatment until restoring back into normal ovarian size; be sure the reduce the drug dose and duration in the next course of drug; once ovarian cysts appears, treatment should also be discontinued immediately in order to avoid ovarian hyperstimulation syndrome.
4. Visually impairment: a few people may get blurred vision, double vision, flashing lights, etc., The symptoms may be deteriorated under strong light; once visual disturbances occurs, treatment should be discontinued immediately, and patients should be subject to eye examinations at the same time.
5. Multiple pregnancies and teratogenic: it has been already demonstrated that clomiphene citrate can significantly increase the incidence of multiple births, so it is necessary to perform fetal reduction surgeries if necessary. Orally administration of clomiphene can cause an incidence of birth defects being about 2.5%.
6. Other adverse reactions are rare, mostly due to the long treatment causes, including nausea, vomiting, nervousness, fatigue, dizziness, headache, insomnia, breast swelling and pain, increased menstrual flow, atopic dermatitis, increased weight, polyuria, and mild alopecia which may disappear after treatment. This product is metabolized by the liver so that patients having a history of liver dysfunction should not take. Patients of ovarian cysts and other gynecological cancer should be disabled. Clomiphene citrate may also induce abortion and teratogenic so pregnant women, should be disabled.
The above information is edited by the chemicalbook of Dai Xiongfeng.
|Chemical Properties||It is white or white crystalline powder. Melting point 116.5-118 °C; it is slightly soluble in ethanol, chloroform, water, and insoluble in ether.
|Uses||1. The product is an anti-estrogen (fertility inducer) drug used for treating dysfunctional uterine bleeding, polycystic ovary, menstrual disorders and drug-induced amenorrhea and other gynecological diseases.|
2. It is a kind of hormone drugs for treating luteal insufficiency, anovulatory infertility, dysfunctional uterine bleeding.
|Production methods||4-hydroxy benzophenone and diethyl amino ethyl chloride hydrochloride is etherified first to give diethylamino benzophenone; via addition, hydrolysis, elimination, chlorination to make clomiphene [(911-45-5]), and finally converted to salt using a citrate to obtain the final products.
|Chemical Properties||Crystalline Solid|
|Usage||An unducer of ovulation. A gonad-stimulating principle|
|Usage||Synthetic estrogen agonist-antagonist. Gonad-stimulating principle.|
|Usage||A selective estrogen receptor modulator|
|Clomiphene Citrate Preparation Products And Raw materials|