Clomiphene citrate

Package leaflet (information for patients)

Tradename
Clomiphene citrate

Dosage form
Tablets 50 mg.

Description
Round, flat, beveled to the edge white tablets with an imprint in the form of the brand name "V" on one side.

Structure
Active ingredient: Clomiphene citrate 50 mg.
Excipients: microcrystalline cellulose 102, calcium stearate, aerosil ® 200 (hydrophilic pyrogenic silicon dioxide).

Pharmacotherapeutic group
Antiestrogen

Pharmacological properties
Pharmacokinetics:
After oral administration, it is well absorbed from the gastrointestinal tract. Clomiphene is metabolized in the liver. The half-life is 5-7 days. Within 5 days, 50% of the oral dose is excreted, mainly through the intestines (42%) and urine (8%). Clomiphene is found in feces for 6 weeks. The average% of the withdrawn dose on the 31st - 35th day after the administration of the drug labeled with the 14C isotope averaged 0.73%, and on the 42nd - 45th day - 0.45%. Stool and urine samples were taken from 6 subjects between days 14 and 53 of the study. The untreated parent / metabolite is slowly excreted during enterohepatic circulation. Long-term use of clomiphene may alter the rate of cholesterol synthesis. Long-term treatment with clomiphene in patients may increase serum cholesterol levels.
Clomiphene citrate is a racemic mixture of cis- (zuclomiphene) and trans- (enclomiphene) isomers. The cis isomer is more active, the content of which in the preparation is at least 30-50%. The half-life of zuclomiphene is longer than that of the trans isomer. Zuclomiphene is found in healthy volunteers one month after ingestion. This fact indicates the intestinal-hepatic recirculation of the drug, which has stereospecificity. Clomiphene can be detected early in pregnancy in women who have taken it to induce ovulation.
Pharmacodynamics:
Clomiphene citrate is a non-steroidal antiestrogenic drug. The mechanism of action is explained by the ability to specifically bind to estrogen receptors in the hypothalamus, inhibiting the binding of estradiol to receptors. According to the principle of positive feedback, the production of gonadotropin increases and, thus, ovulation is simulated.

Indications for use
Stimulation of ovulation in women with anovulatory cycle in order to achieve pregnancy. The tablets can only be used in patients with proven ovulatory cycle disorders. Before prescribing the drug, other causes of impaired fertility should be excluded or adequately treated.

Method of administration and dosage
The drug is used strictly according to the doctor's prescription!
1st course of treatment : the recommended dose is 50 mg (1 tablet) per day for 5 days. In the absence of recent uterine bleeding, treatment can be started any day. If it is planned to induce bleeding with a progestin, or in the presence of spontaneous cyclic bleeding, it is recommended to start treatment from the 5th day of the cycle. If ovulation occurs with a dose of 50 mg, then further increase in the dose in subsequent cycles has no advantage.
2nd course of treatment : this regimen should be used if the 1st course of treatment is ineffective. If ovulation does not occur after the 1st course of treatment, 100 mg of the drug should be prescribed daily (two tablets of 50 mg as a single daily dose) for 5 days, starting from the 5th day of the next cycle, that is, 30 days after the previous cycle... Do not exceed the dose or duration of treatment (more than 100 mg / day for 5 days). Most responsive patients respond to the first course of treatment. Three courses of treatment can usually be considered an adequate therapeutic measure. In the absence of ovulation bleeding, the diagnosis should be clarified. In patients without signs of ovulation, further treatment is not advisable.
Long-term treatment :
Not recommended
Special patient groups:
In patients with hypersensitivity to pituitary gonadotropin (for example, with polycystic ovary syndrome), special care should be taken and, if possible, the drug should be prescribed at lower doses and for a shorter period of time.

Side effects
– vasomotor hot flashes
– ovarian enlargement - headache
– nausea, vomiting, flatulence
– visual impairment (blurred spots or flashes in the form of spots, a feeling of vibrating light in the eyes
– so-called scintillating scotomas, afterimages)
– discomfort and soreness of the mammary glands
– acyclic uterine bleeding, menorrhagia
– depression
– dizziness
– vertigo (feeling of rotation)
– nervous tension, fatigue
Studies have shown that side reactions develop more often with prolonged use of the drug and when using higher doses. When using the drug in recommended doses, adverse reactions are insignificant and only in rare cases become an obstacle to treatment.
As the total dose is increased, the incidence of symptoms known as blurred vision, as well as the appearance of spots or flares (atrial scotoma), increases. The appearance of a sequential image (" after-image ") has also been reported. It is characteristic that the first appearance or intensification of these symptoms on the part of the organ of vision is mainly observed in bright light. There are reports of ophthalmologically confirmed scotomas, phosphenes, and deterioration in visual acuity.
In rare cases, cataracts and optic neuritis have been reported. These visual impairments are usually reversible, although there have been reports of prolonged visual impairment after the end of clomiphene treatment. In some cases, visual impairment can also be irreversible, especially when using clomiphene in high doses or when it is prescribed for a long period of time.

Contraindication
– increased sensitivity to active or auxiliary substance preparation
– disorders function liver or their presence in the history
– cyst Ovary (for excluding syndrome of polycystic ovaries)
– metrorrhagia unclear etiology
– hormone-dependent tumors
– endometriosis
– dysgenesis ovarian, menopause or any state, when which is not expected to answer to the treatment
– pregnancy
– children's and teenage age till 18 years

Overdose
Symptoms: hepatotoxicity and toxicity. During intoxication, sweating, nausea, and vomiting may occur. These symptoms can be eliminated by reducing the dose. Treatment: in case of signs of poisoning, induce vomiting or gastric lavage, prescribe activated charcoal and a laxative, and consult a doctor. Intoxication and hepatotoxicity are more likely in elderly patients and especially in young children (therapeutic overdose or accidental intoxication can be very dangerous for them).

Precautions
– Pregnancy: May cause virilization in female fetuses.
– Breastfeeding: It is not known how this drug is excreted in breast milk. In accordance with the adverse reactions that may occur in infants, it is necessary to decide whether to stop breastfeeding or stop taking the drug.
– Pediatrics: the use of the drug can have serious consequences, the benefits of them should be assessed before starting therapy.
long-term treatment with high doses of androgens.

Interaction with other medicinal products
There are no data on drug interactions for Clomiphene citrate.

Special instructions
It is recommended to regularly monitor liver function. Before starting treatment, a thorough gynecological examination of the patient is necessary. The use of the drug should be under the constant supervision of a gynecologist. Adequate endogenous estrogen levels (determined from vaginal smears, endometrial biopsies, urinary estrogen levels, or endometrial bleeding in response to progesterone) are required for ovulation in response to Clomiphene citrate treatment. Decreased estrogen levels - although clinically less favorable - do not preclude treatment efficacy. Treatment with Clomiphene citrate is not effective in primary pituitary failure or ovaries. Treatment with the drug does not replace special treatment for ovarian failure caused by other causes, for example, in diseases of the thyroid gland or adrenal glands. Hyperprolactinemia can also be treated with other methods. For infertility associated with low birth weight, Clomiphene citrate is not the first choice and does not affect the elevated FSH levels seen in early menopause.

Pregnancy and elbowing
This drug should not be used during pregnancy and lactation. During pregnancy, the drug can cause virilization in female fetuses. When breastfeeding, it is not known how this drug is excreted in breast milk. In accordance with the adverse reactions that may occur in infants, it is necessary to decide whether to stop breastfeeding or stop taking the drug.

Influence on the ability to drive vehicles and work with mechanisms
Does not affect.

Storage conditions
Store in a dry, dark place at a temperature not exceeding 25 ° C, out of the reach of children.

Shelf life
3 years. Do not use after the expiration date printed on the package.

Vacation conditions
By prescription.

Packaging
Clomiphene citrate 50 mg Tablets. There are 25 tablets in a blister. 4 blisters are packed in a cardboard box together with an enclosed leaflet.

Manufacturer's name, address
SC Vizega Pharmaceuticals SRL
1076 Dr. E Moses Road, Mumbai – 400 018, India