Historical issue Indication and dosage Mode of action Adjuvant Pharmacokinetics Adverse reactions Precaution References
ChemicalBook > CAS DataBase List > Clomiphene Citrate

Clomiphene Citrate

Historical issue Indication and dosage Mode of action Adjuvant Pharmacokinetics Adverse reactions Precaution References
Product Name
Clomiphene Citrate
CAS No.
50-41-9
Chemical Name
Clomiphene Citrate
Synonyms
mer41;mrl41;fertyl;omifin;CLOMID;dyneric;genozym;clomivid;fertivet;nsc35770
CBNumber
CB0488051
Molecular Formula
C32H36ClNO8
Formula Weight
598.08
MOL File
50-41-9.mol
More
Less

Clomiphene Citrate Property

Melting point:
116.5-118°C
storage temp. 
2-8°C
solubility 
Slightly soluble in water, sparingly soluble in ethanol (96 per cent).
form 
neat
Water Solubility 
Slightly soluble in water, methanol, chloroform (slightly), and DMSO (10 mM). Insoluble in ether.
InChIKey
PYTMYKVIJXPNBD-OQKDUQJOSA-N
CAS DataBase Reference
50-41-9(CAS DataBase Reference)
IARC
3 (Vol. 21, Sup 7) 1987
EPA Substance Registry System
Clomiphene citrate (50-41-9)
More
Less

Safety

Hazard Codes 
T
Risk Statements 
60-63
Safety Statements 
53-36/37-45
WGK Germany 
3
RTECS 
YE0875000
HazardClass 
IRRITANT
HS Code 
2922190900
Toxicity
LD50 oral in rat: 5750mg/kg
More
Less

Hazard and Precautionary Statements (GHS)

Symbol(GHS)
Signal word
Warning
Hazard statements

H360May damage fertility or the unborn child

H361Suspected of damaging fertility or the unborn child

Precautionary statements

P201Obtain special instructions before use.

P202Do not handle until all safety precautions have been read and understood.

P280Wear protective gloves/protective clothing/eye protection/face protection.

P281Use personal protective equipment as required.

P308+P313IF exposed or concerned: Get medical advice/attention.

P405Store locked up.

More
Less

N-Bromosuccinimide Price

Sigma-Aldrich
Product number
C6272
Product name
Clomiphene citrate salt
Purity
analytical standard
Packaging
1g
Price
$71.4
Updated
2021/03/22
Sigma-Aldrich
Product number
1140000
Product name
Clomiphene citrate
Purity
United States Pharmacopeia (USP) Reference Standard
Packaging
500mg
Price
$366
Updated
2021/03/22
Alfa Aesar
Product number
J63663
Product name
Clomiphene citrate
Packaging
2g
Price
$72.1
Updated
2021/03/22
Alfa Aesar
Product number
J63663
Product name
Clomiphene citrate
Packaging
10g
Price
$134
Updated
2021/03/22
Cayman Chemical
Product number
16087
Product name
Clomiphene (citrate)
Purity
≥98%
Packaging
5g
Price
$94
Updated
2021/03/22
More
Less

Clomiphene Citrate Chemical Properties,Usage,Production

Historical issue

It has been stated that 40 to 50 percent of successfully treated women conceive[2].
Unfortunately, results in men have been ambiguous and somewhat less favorable. The reasons for discrepancy between studies, which range from the mid 1960s to the present, are many. Various dosages (1 to 400 mg. daily) and treatment intervals (3 to 24 months) have been used. Selection of candidates provides another source of inconsistency. Criteria for inclusion into trial and pre-trial evaluation have varied markedly. Wives were not always evaluated for infertility" Furthermore here have been no well-defined standards for what constitutes significant improvement in sperm quality. In addition to an already capricious situation, there have been only a few placebo-controlled trials to date[7, 8].

Indication and dosage

It is used mainly in female infertility due to anovulation (e.g. due to polycystic ovary syndrome) to induce ovulation. CC has also been employed for ovarian stimulation in ovulating women, mainly for idiopathic (unexplained) infertility and often combined with IUI. The rationale is presumably that CC overcomes a subtle defect in ovulatory function or increases the number of mature follicles so increasing the likelihood of pregnancy[9]. Here the success rate has been, understandably, notably less than in anovulatory women.
CC is given orally in a dose of 50–250 mg per day for 5 days from day 2, 3, 4 or 5 of spontaneous or induced bleeding, starting with the lowest dose and increasing the dose in increments of 50 mg/day per cycle until an ovulatory cycle is achieved. The starting day of treatment, whether on day 2 or through day 5 of the cycle, does not influence the results[10]. Although 50 mg/day is the recommended dose in the first cycle, a meta-analysis of 13 published reports[11] suggests that only 46% will respond to this dose with ovulation, a further 21% will respond to 100 mg and another 8% will ovulate with 150 mg/day. There is no apparent advantage of using a daily dose of 150 mg that seems to significantly increase neither the ovulation rate nor follicular recruitment[12]. Some practitioners often use a starting dose of 100 mg/day from day 4 or 5, only resorting to 50 mg/day in the case of exquisite sensitivity or persistent cyst formation. The advantage of starting with a 100 mg daily dose rather than 50 mg is that it will cut down the number of ‘superfluous’ cycles of treatment until ovulation is achieved and until those resistant to CC are identified. It is difficult to state what effect, if any, this course of action has on the multiple pregnancy rates.

Mode of action

Clomiphene contains an unequal mixture of two isomers as their citrate salts, enclomiphene and zuclomiphene. Zuclomiphene is much the more potent of the two for induction of ovulation, accounts for 38% of the total drug content of one tablet and has a much longer half-life than enclomiphene, being detectable in plasma 1 month following its administration. Rostami-Hodjegan et al[11] have suggested that wide variability in the metabolism of the zuclomiphene component contributes to variability in response to the drug.
CC is capable of inducing a discharge of FSH from the anterior pituitary and this is often enough to reset the cycle of events leading to ovulation into motion. The release of even small amounts of FSH into the system will often induce ovulation and pregnancy in a proportion of eu-estrogenic anovulatory women. This is achieved indirectly, through the action of CC, a non-steroidal compound closely resembling an estrogen, in blocking hypothalamic estrogen receptors, signalling a lack of circulating estrogen to the hypothalamus and inducing a change in the pattern of pulsatile release of GnRH. Clomifene has no apparent progestational, androgenic, or antrandrogenic effects and does not appear to interfere with pituitary-adrenal or pituitary-thyroid function.

Adjuvant

In order to improve the outcome of treatment with CC, several adjuvants to CC treatment have been suggested. A correctly timed ovulation-triggering dose of HCG (5000– 10000 IU) is only theoretically warranted when the reason for a non-ovulatory response is that the LH surge is delayed or absent despite the presence of a well developed follicle. Although the routine addition of HCG at mid-cycle seems to add little to the improvement of conception rates[13], we have found it very useful, if given when an ultrasonically demonstrated leading follicle attains a diameter of 19–24 mm, for the timing of intercourse or IUI. The addition of dexamethazone as an adjunct to CC therapy in a dose of 0.5 mg at bedtime is said to suppress adrenal androgen secretion and induce responsiveness to CC in previous non-responders, mostly hyperandrogenic women with PCOS and elevated concentrations of dehydroepiandrosterone sulphate (DHEAS)[14]. However, glucocorticoid steroid therapy often induces side effects including increased appetite and weight gain, and should probably be reserved for women who have congenital adrenal hyperplasia as a cause for their anovulation.

Pharmacokinetics

Based on early studies with 14 C-labeled clomifene, the drug was shown to be readily absorbed orally in humans. The drug was shown to be readily absorbed orally in humans and excreted principally in the feces. Mean urinary excretion was approximately 8% with fecal excretion of about 42%.

Adverse reactions

Unpleasant side effects of CC are few and far between, although some women will complain of hot flushes and some of nausea. CC is, however, usually very well tolerated. While mild ovarian enlargement is relatively common, in almost 40 years of practice, it has never seen a full-blown ovarian hyperstimulation syndrome (OHSS) as a result of CC treatment. Occasional cyst formation can be treated conservatively.
Some specific side effects (rare) include bloating, stomach or pelvic pain, blurred vision, sensitivity of eyes to light, nausea or vomiting, nervousness, restlessness, tiredness, trouble in sleeping and mental depression[15, 16]. Some side effects of clomiphene may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them.

Precaution

You should not take this drug if you have the following conditions: abnormal vaginal bleeding; an ovarian cyst that is not related to polycystic ovary syndrome; past or present liver disease; a tumor of your pituitary gland; an untreated or uncontrolled problem with your thyroid or adrenal gland; or if you are pregnant.
You should not take it if you are already pregnant. Talk to your doctor if you have concerns about the possible effects of this medicine on a new pregnancy. Clomiphene can pass into breast milk and may harm a nursing baby. This medication may slow breast milk production in some women. Tell your doctor if you are breast-feeding a baby. Using clomiphene for longer than 3 treatment cycles may increase your risk of developing an ovarian tumor. Ask your doctor about your specific risk. Fertility treatment may increase your chance of having multiple births (twins, triplets). These are high-risk pregnancies both for the mother and the babies. Talk to your doctor if you have concerns about this risk.

References

  1. Goodman, L. S., Gilman, A. G. and Gilman, A. Z.: The Pharmacological Basis of Therapeutics, 6th ed. New York: MacMillan Publishing Co., Inc., p. 1432, 1980.
  2. Goodman L. S., Gilman, A. G. and Gilman, A. Z.: The Pharmacological Basis of Therapeutics, 6th ed. New York: MacMillan Publishing Co., Inc., p. 1433, 1980
  3. Attia GR, Rainey WE and Carr BR (2001) Metformin directly inhibits androgen production in human thecal cells. Fertil Steril 76,517–524.
  4. Mansfield R, Galea R, Brincat M, Hole D and Mason H (2003) Metformin has direct effects on human ovarian steroidogenesis. Fertil Steril 79, 956–962.
  5. Mitwally MF and Casper RF (2001) Use of an aromatase inhibitor for induction of ovulation in patients with an inadequate response to clomiphene citrate. Fertil Steril 75,305–309.
  6. Lopez E, Gunby J, Daya S, Parrilla JJ, Abad L and Balasch J (2004) Ovulation induction in women with polycystic ovary syndrome: randomized trial of clomiphene citrate versus low-dose recombinant FSH as first line therapy. Reprod Biomed Online 9,382–390.
  7. Foss, G. L., Tindall, V. R. and Birkett, J. P.: The treatment of subfertile men with clomiphene citrate. J. Reprod. Fertil., 32: 167, 1973.
  8. Ronnberg, L.: The effect of clomiphene citrate on different sperm parameters and serum hormone levels in preselected infertile men: a controlled double-blind cross-over study. Int. J. Androl., 3: 479, 1980.
  9. Guzick DS, Sullivan MW, Adamson GD, Cedars MI, Falk RJ, Peterson EP and Steinkampf MP (1998) Efficacy of treatment for unexplained infertility. Fertil Steril 70,207–213.
  10. Wu CH and Winkel CA (1989) The effect of therapy initiation day on clomiphene citrate therapy. Fertil Steril 52,564–568.
  11. Rostami-Hodjegan A, Lennard MS, Tucker GT and Ledger WL (2004) Monitoring plasma concentrations to individualize treatment with clomiphene citrate. Fertil Steril 81,1187–1193
  12. Dickey RP, Taylor SN, Curole DN, Rye PH, Lu PY and Pyrzak R (1997) Relationship of clomiphene dose and patient weight to successful treatment. Hum Reprod 12,449–453
  13. Agarwal SK and Buyalos RP (1995) Corpus luteum function and pregnancy rates with clomiphene citrate therapy: comparison of human chorionic gonadotrophin-induced versus spontaneous ovulation. Hum Reprod 10, 328–331.
  14. Daly DC, Walters CA, Soto-Albors, Tohan N and Riddick DH (1984) A randomized study of dexamethasone in ovulation induction with clomiphene citrate. Fertil Steril 41,844–848.
  15. Mauss, J., Mohnfeld, G. and Biirsch, G.: Synthetic LH-releasing factor and clomiphene stimulation in oligospermic males with normal FSH excretion. J. Reprod. Fertil., 40: 171, 1974.
  16. Espinasse, J.: Utilisation du citrate de clomiphene isolement ou en association avec !es androgenes dans le traitement des hypofertilities masculines idiopathiques. A propos de 7 4 cas. PhD dissertation, University of Toulouse.

Chemical Properties

Crystalline Solid

Originator

Clomid,Lepetit,Italy,1966

Uses

An unducer of ovulation. A gonad-stimulating principle

Uses

Synthetic estrogen agonist-antagonist. Gonad-stimulating principle.

Uses

A selective estrogen receptor modulator

Uses

Clomiphene is a selective estrogen receptor modulator that impairs the activation of estrogen receptors (ERs) by 17β-estradiol. It potently binds both ERα and ERβ (Ki = 0.9 and 1.2 nM, respectively). Clomiphene enhances the release of gonadotropin-releasing hormone, stimulating the release of follicle-stimulating hormone and luteinizing hormone, culminating in ovulation.

Manufacturing Process

A mixture of 20 g of 1-[p-(β-diethylaminoethoxy)phenyl]-1,2-diphenylethanol in 200 cc of ethanol containing an excess of hydrogen chloride was refluxed 3 hours. The solvent and excess hydrogen chloride were removed under vacuum, and the residue was dissolved in a mixture of ethyl acetate and methylene chloride. 1-[p-(β-diethylaminoethoxy)phenyl]-1,2-diphenylethylene hydrochloride was obtained, melting at 148° to 157°C. This hydrochloride salt was treated with N-chlorosuccinimide in dry chloroform under reflux. The product then obtained was converted to the free base and treated with citric acid. The dihydrogen citrate salt of 1-[p-(β-diethylaminoethoxy)phenyl]-1,2- diphenylchloroethylene was obtained, melting at 116.5° to 118°C.
The intermediate 1-[p-(β-diethylaminoethoxy)phenyl]-1,2-diphenylethanol was obtained by treating 4-(β-diethylaminoethoxy)benzophenone with benzylmagnesium chloride. It melted at 95° to 96°C.

brand name

Clomid (Sanofi Aventis); Serophene (Serono).

Therapeutic Function

Antiestrogen

Clomiphene Citrate Preparation Products And Raw materials

Raw materials

Preparation Products

More
Less

Clomiphene Citrate Suppliers

Yueyang Tianqing Biological Technology Co., Ltd.
Tel
15173087635
Email
tq201818@163.com
Country
CHINA
ProdList
35
Advantage
58
Chongqing Xingcan Pharmaceutical Technology Co., Ltd.
Email
xingcanyaoye@sina.com;
Country
China
ProdList
2250
Advantage
58
Suzhou Unite pharmTech Co., Ltd ,
Tel
792-3901125- ;
Fax
0512-62575043
Email
sales@unite-pharm.com;tech@unite-pharm.com
Country
China
ProdList
139
Advantage
56
J & K SCIENTIFIC LTD.
Tel
010-82848833- ;010-82848833-
Fax
86-10-82849933
Email
jkinfo@jkchemical.com;market6@jkchemical.com
Country
China
ProdList
96815
Advantage
76
3B Pharmachem (Wuhan) International Co.,Ltd.
Tel
821-50328103-801
Fax
86-21-50328109
Email
3bsc@sina.com
Country
China
ProdList
15877
Advantage
69
Chembest Research Laboratories Limited
Tel
021-20908456-
Fax
021-58180499
Email
sales@BioChemBest.com
Country
China
ProdList
5948
Advantage
61
Beijing Ouhe Technology Co., Ltd
Tel
010-82967028-
Fax
+86-10-82967029
Email
2355560935@qq.com
Country
China
ProdList
12356
Advantage
60
Nanjing Chemlin Chemical Co., Ltd
Tel
Fax
+86-25-83453306
Email
info@chemlin.com.cn
Country
China
ProdList
19999
Advantage
64
Chemsky(shanghai)International Co.,Ltd.
Tel
021-50135380
Email
shchemsky@sina.com
Country
China
ProdList
32358
Advantage
50
Chengdu XiYa Chemical Technology Co., Ltd.
Tel
;
Fax
0539-6365991
Email
sale@xiyashiji.com;3007716753@qq.com
Country
China
ProdList
10578
Advantage
57
More
Less

View Lastest Price from Clomiphene Citrate manufacturers

WUHAN CIRCLE POWDER TECHNOLOGY CO.,LTD
Product
Clomifene Citrate
Price
US $0.00/KG
Min. Order
100g
Purity
98%+
Supply Ability
100kg
Release date
2020-09-29
Anhui Rencheng Technology Co., Ltd
Product
Clomiphene Citrate 50-41-9
Price
US $10.00-180.00/KG
Min. Order
0.5KG
Purity
>99%
Supply Ability
20tons
Release date
2020-12-29
Hebei Lingding Biological Technology Co., Ltd
Product
Clomiphene Citrate 50-41-9
Price
US $820.00/KG
Min. Order
1KG
Purity
99%
Supply Ability
9000kg/per week
Release date
2021-05-20

50-41-9, Clomiphene CitrateRelated Search:


  • {2-[4-(2-chloro-1,2-diphenylvinyl)phenoxy]ethyl}diethylamine 2-hydroxy-1,2,3-propanetricarboxylate (salt)
  • 2-(4-(2-Chloro-1,2-diphenylvinyl)phenoxy)-N,N-diethylethanaMine 2-hydroxypropane-1,2,3-tricarboxylate
  • CloMiphene Cit
  • 2-[4-(2-chloro-1,2-diphenylethenyl)phenoxy]-N,N-diethyl-ethanamine, 2-hydroxy-1,2,3-propanetricarboxylate (1:1)
  • Clometeu Citrate
  • Clomiphene,ClomifeneCltrate
  • 2-(p-(2-chloro-1,2-diphenylvinyl)phenoxy)-triethylamincitrate(1:1)
  • 2-(p-(2-chloro-1,2-diphenylvinyl)phenoxy)triethylaminecitrate(1:1)
  • 2-chloro-1-(p-(beta-diethylaminoethoxy)phenyl)-1,2-diphenylethylenecitrate(
  • chloramiphene
  • clomifenedihydrogencitrate
  • clomifeno
  • clomiphenedihydrogencitrate
  • clomiphene-r
  • clomiphine
  • clomivid
  • clostilbegyt
  • dyneric
  • fertivet
  • fertyl
  • genozym
  • ikaclomin
  • mer41
  • mrl41
  • nsc35770
  • omifin
  • racemicclomiphenecitrate
  • {2-[4-(2-Chloro-1,2-diphenylvinyl)phenoxy]ethyl}diethylamine(2-Hydroxypropane-1,2,3- tricarbox
  • SEROPHENE
  • PERGOTIME
  • CLOMPHID
  • CLOMID
  • CLOMIFENE CITRATE
  • CLOMIPHENE CITRATE
  • CLOMIPHENE CITRATE SALT
  • 2-[4-(2-CHLORO-1,2-DIPHENYLETHENYL)-PHENOXY]-N,N-DIETHYLETHANAMINE CITRATE SALT
  • 1-(p-(beta-diethylaminoethoxy)phenyl)-1,2-diphenyl-2-chloroethylenecitrate
  • CLOMEPHENE CITRATE
  • clomifen dihydrogen citrate
  • ClomipheneAcetate
  • Clomid, Clomphid, Pergotime, Serophene,
  • 2-(4-[2-Chloro-1,2-diphenylethenyl]phenoxy)-N,N-diethylethanamine citrate
  • {2-[4-(2-Chloro-1,2-diphenylvinyl)phenoxy]ethyl}di ethylamine 2-hydroxy-1,2,3-propanetricarboxylate (
  • CloMiphene Citrate (cis-trans Mixture)
  • Ethanamine, 2-4-(2-chloro-1,2-diphenylethenyl)phenoxy-N,N-diethyl-, 2-hydroxy-1,2,3-propanetricarboxylate (1:1)
  • usp1140000
  • CLOMIPHENECITRATE,USP
  • 2-[4-(2-Chloro-1,2-diphenylethenyl)-phenoxy]-N,N-diethyl-2-hydroxy-1,2,3-propanetricaboxylate ethanamine
  • Clomiphene Citrate (500 mg)
  • cloMifene citrate (CloMid )
  • CloMifene citrate (Serophene)
  • 2-[4-(2-Chloro-1,2-diphenylethenyl)phenoxy]-N,N-diethylethanaMine 2-Hydroxy-1,2,3-propanetricarboxylate
  • CloMifene Citrate API
  • (Z)-2-(4-(2-chloro-1,2-diphenylvinyl)phenoxy)-N,N-diethylethanaMine 2-hydroxypropane-1,2,3-tricarboxylate
  • CloMiphene Citrate(CloMid)
  • CloMifene Citrate Capsules
  • {2-[4-(2-Chloro-1,2-diphenylvinyl)phenoxy]ethyl}diethylamine (2-Hydroxypropane-1,2,3- tricarboxyl
  • Clomifene Citrate / Clomiphene Citrate