Enclomiphene

Enclomiphene is an Ovulation Stimulator belonging to the pharmacology class of Selective Estrogen Receptor Modulators.

Enclomiphene is not approved by the FDA and is used to treat infertility in females, particularly in women who are unable to become pregnant due to ovulation problems or polycystic ovary syndrome (PCOS).

Enclomiphene undergoes rapid absorption post-oral administration, binding to plasma proteins and distributing to target tissues. Hepatic metabolism, primarily via CYP3A4, yields metabolites like zuclomiphene. Elimination occurs mainly through faeces.

The common side effects of enclomiphene include nausea, vomiting, heavy bleeding at the initial stage, and weight gain.

Enclomiphene is available in tablet form.

The molecule is available in India, Japan, Germany, and China.

Enclomiphene is an Ovulation Stimulator belonging to the pharmacology class of Selective Estrogen Receptor Modulators.

Inhibiting negative feedback signals, clomiphene binds to estrogen receptors in the hypothalamus. The more physiologically active isomer of clomiphene is its primary form, in contrast to clomiphene. Luteinizing hormone and follicle-stimulating hormone output increases when gonadotropin-releasing hormone (GRH) is released by the hypothalamus as a result of inhibiting testosterone feedback. By encouraging spermatogenesis and raising testosterone production, elevated levels of these substances subsequently improve testicular function. To help men with testosterone insufficiency regain hormonal equilibrium, this mechanism presents clomiphene as a possible treatment for diseases like secondary hypogonadism.

Enclomiphene is available in Tablets.

Tablets: To be swallowed whole with water/liquid. Do not chew, crush or break it.

As the physician recommends, a single daily dose after meals.

• Enclomiphene can be used in the treatment of female infertility
• Treating male reproductive health issues, such as secondary hypogonadism.

• Enclomiphene helps in the treatment of female infertility, primarily in cases involving anovulation (lack of ovulation), ovulatory dysfunction, and polycystic ovary syndrome (PCOS). It promotes the healthy development of eggs within the ovaries and stimulates the release of mature eggs, which increases the chance of successful pregnancy.
• Treating male reproductive health issues like secondary hypogonadism. By stimulating the release of gonadotropins, it enhances testicular function, promoting spermatogenesis and increasing testosterone production. This hormonal balance restoration can positively impact affected individuals' fertility and overall reproductive health.

Enclomiphene is approved for use in the following clinical indications:

• Treatment of infertility in women: It is used for treating infertility in women who are not ovulating correctly and in patients desiring to become pregnant.
• Treating male reproductive health issues like secondary hypogonadism: Enclomiphene improves male reproductive health by enhancing testosterone and promoting spermatogenesis.

Tablets: 25mg, 50 mg

Tablets

Dose adjustment in adults

• Secondary hypogonadism: 12.5 mg to 25 mg per day, administered orally.
• Infertility in women: 50 mg daily for five days, beginning on the 3rd, 4th, or 5th day of the menstrual cycle.

Hypersensitivity to Enclomiphene citrate or any of its components.

Enclomiphene use may increase cardiovascular risk; evaluate individuals, especially those with heart disease or risk factors.

Assess thromboembolic risk, particularly in those with a history of thromboembolism, as Enclomiphene use is associated with such events.

Evaluate liver function before and during Enclomiphene treatment; discontinue if significant increases in liver enzymes are observed.

Exercise caution in patients prone to oedema, as Enclomiphene may cause fluid retention.

Regularly monitor individuals during Enclomiphene treatment for therapeutic efficacy and potential adverse effects, adjusting treatment as necessary.

There is no sufficient scientific evidence traceable regarding the use and safety of Enclomiphene in concurrent use with alcohol.

Enclomiphene is present in breast milk. Should be used with caution during breastfeeding

Not recommended for use during pregnancy

The adverse reactions related to Enclomiphene can be categorized as

Common Adverse effects: Nausea, headache, stomach pain, blurred vision, and hot flushes.

Less Common Adverse effects: Vomiting, weight gain, rapid heartbeat, and abdominal pain.

Rare Adverse effects: Heavy bleeding, cloudy lenses in the eye, and skin rash.

Drug Interactions: Enclomiphene may interact with drugs used in chemotherapy (such as Vinorelbine), pain relief medications for sex (such as Ospemifene), schistosomiasis medication (such as Oxamniquine), anxiety medications, hypertension, angina pectoris, and arrhythmias (such as Oxprenolol).

Drug-Food Interactions: Alcohol intake should be avoided entirely.

Drug-Disease Interactions: Eclomiphene may cause side effects in people who already have liver or kidney damage, atypical menstrual bleeding, hormone-driven malignancy, or an ovarian cyst.

The most common side effects of enclomiphene include nausea, vomiting, heavy bleeding, weight gain, stomach ache, bloating, hot flashes, blurred vision, headaches, rapid or irregular heartbeat, speech problems, skin rash or itching, feelings of sickness, cloudy lenses in the eye, abdominal pain, hair loss or thinning, increased levels of liver enzymes, and heightened feelings of anxiety or nervousness.

• Pregnancy and Lactation

There is no advantage to treating pregnant women with clomiphene; therefore, it is not recommended.

It's unclear if human milk contains clomiphene excretion. Giving clomiphene to a breastfeeding woman should be done with caution because a lot of medications are excreted in human milk. Therapy may help some individuals stop nursing.

• Paediatrics Use

As per the FDA, clomiphene in pediatric patients is not recommended.

Dose Adjustment in Kidney Impairment Patients:

It should be used with caution in those with pre-existing kidney disease. There are no specific dosage adjustments provided.

Dose Adjustment in Hepatic Impairment Patients:

It is probably unsafe to use in patients with liver disease and should be avoided.

Symptoms: Nausea, vomiting, abdominal pain, blurred vision, and hormonal imbalances.

Management: There is no specific antidote. Supportive measures may include monitoring vital signs, symptomatic treatment, and gastric lavage if ingestion is recent.

Pharmacodynamics:

In vivo, total testosterone (TT) levels increased in all treatment groups between the baseline and 16 weeks. At 16 weeks, FSH and LH levels went up in the clomiphene citrate group and down in the testosterone gel group. Throughout the treatment, clomiphene citrate kept the sperm concentration within the usual range, whereas the testosterone gel group's spermatogenesis significantly decreased.

Pharmacokinetics:

Absorption: Following oral administration, clomiphene is efficiently absorbed in the gastrointestinal tract, reaching peak plasma concentrations relatively quickly.

Distribution: Distribution involves the transport of clomiphene throughout the body, with a significant portion binding to plasma proteins.

Metabolism: Metabolism of clomiphene primarily occurs in the liver through cytochrome P450 enzymes, particularly CYP3A4. This metabolic process generates metabolites, including zuclomiphene, the less biologically active enantiomer. These metabolites may contribute to the overall pharmacological profile and clearance of clomiphene.

Excretion: Elimination involves the removal of the drug and its metabolites from the body. Enclomiphene is predominantly eliminated through faeces, with a smaller fraction excreted in urine.

• Rodriguez KM, Pastuszak AW, Lipshultz LI. Enclomiphene citrate for the treatment of secondary male hypogonadism. Expert Opin Pharmacother. 2016 Aug;17(11):1561-7. doi: 10.1080/14656566.2016.1204294. Epub 2016 Jul 4. PMID: 27337642; PMCID: PMC5009465.
• Hill S, Arutchelvam V, Quinton R. Enclomiphene, an estrogen receptor antagonist for the treatment of testosterone deficiency in men. IDrugs. 2009 Feb;12(2):109-19. PMID: 19204885.
• Earl JA, Kim ED. Enclomiphene citrate: A treatment that maintains fertility in men with secondary hypogonadism. Expert Rev Endocrinol Metab. 2019 May;14(3):157-165. doi: 10.1080/17446651.2019.1612239. Epub 2019 May 7. PMID: 31063005.
• Kaminetsky J, Werner M, Fontenot G, Wiehle RD. Oral enclomiphene citrate stimulates the endogenous production of testosterone and sperm counts in men with low testosterone: comparison with testosterone gel. J Sex Med. 2013 Jun;10(6):1628-35. doi: 10.1111/jsm.12116. Epub 2013 Mar 26. PMID: 23530575.

• https://www.fda.gov/media/159043/donload
• https://www.researchgate.net/profile
• https://cdn.caymanchem.com/cdn/insert/30965.pdf