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What is Clomid? Clomid Description clomiphene citrate (Serophene)

What is Clomid?

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Clomid is the brand name for the fertility drug clomiphene citrate. Clomiphene citrate may also be sold under the brand name Serophene. Whether you’re taking the brand name Clomid, Serophene, or a generic version of clomiphene citrate, it’s all the same drug. (Think of Clomid in the same way that we use Kleenex® to refer to facial tissues.)

Clomid is the most well-known fertility drug, probably because it is the most commonly used. And with good reason. About 25% of female factor infertility involves a problem with ovulation, and clomiphene citrate, as a fertility drug, is easy to use (taken as a pill, not an injection), with not too many side effects, is pretty inexpensive compared to other fertility drugs, and is effective in stimulating ovulation 80% of the time.
Will Clomid Work For You?
Anovulation: Causes, Diagnosis, and Treatment

In this article, I’ll refer to clomiphene citrate by the brand name Clomid, just because that is how most people know the drug.
When is Clomid Used?

Clomid is used when there are problems with ovulation, but no problems with blocked fallopian tubes. (In that case, stimulating ovulation would be pointless –- the egg and sperm can’t meet if the tubes are blocked.) If a woman has irregular cycles, or anovulatory cycles (menstruation without ovulation), Clomid may be tried first.

Clomid is often used in the treatment of polycystic ovarian syndrome (PCOS) related infertility. It may also be used in cases of unexplained infertility, or when a couple prefers not to use the more expensive and invasive fertility treatments, like IVF.

Clomid may also be used during an IUI (intrauterine insemination) procedure, but it is rarely used during IVF treatment. With IVF, injectable ovulation meds are more frequently chosen.
All About Fertility Drugs
How is Clomid Taken?

You should follow the directions your doctor gives you, as every doctor has a slightly different protocol.

However, the most common dosage of Clomid is 50 mg, taken for five days, on days 3 through 7 of your cycle, or days 5 through 9 of your cycle. (With day one of your cycle being the first day of real menstrual bleeding, and not just spotting.) Ovulation and pregnancy rates have been shown to be similar whether the drug is started on day two, three, four, or five, so don’t feel concerned if your doctor tells you a different protocol to follow than your friend.
When Should You Have Sex While Taking Clomid?

If 50 mg doesn’t work, your doctor may increase the medication, according to their judgment, for a successive cycle. Or, they may give it another try at 50 mg. You might think that more is always better, but higher doses, especially at or above 150 mg, can actually make conception more difficult. (See below, under side effects.)
What are Clomid’s Common Side Effects?

Clomid’s side effects aren’t so bad, as far as fertility drugs are concerned. The most common side effects are hot flashes, breast tenderness, mood swings, and nausea. But once the medication is stopped, the side effects will leave, too.
Clomid Side Effects

The side effect you’re probably most familiar with is the risk of multiples. You have a 10% chance of having twins when taking Clomid, but triplets or multiples of more are rare, happening less than 1% of the time.
Will You Have Clomid Twins?
Should You Try To Have Twins?

One of the more annoying side effects to comprehend is that Clomid can decrease the quality of your cervical mucus (which sperm need to make their way to the egg), making conception more difficult. Clomid can also make the lining of your uterus thinner and less ideal for implantation. This is why “more” is not necessarily better when it comes to Clomid dosage and use.
How Successful Is Clomid?

Clomid will jumpstart ovulation in 80% of patients, and about 40% to 45% of women using Clomid will get pregnant within six cycles of use.

Using Clomid for more than six cycles is not generally recommended. If six cycles go by, and pregnancy is not achieved, other alternatives may be considered.

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Clomid (clomiphene citrate tablets USP) is an orally administered, nonsteroidal, ovulatory stimulant designated chemically as 2-[p-(2-chloro-1,2-diphenylvinyl)phenoxy] triethylamine citrate (1:1). It has the molecular formula of C26H28ClNO • C6H8O7 and a molecular weight of 598.09. It is represented structurally as:

Clomiphene citrate is a white to pale yellow, essentially odorless, crystalline powder. It is freely soluble in methanol; soluble in ethanol; slightly soluble in acetone, water, and chloroform; and insoluble in ether.

Clomid is a mixture of two geometric isomers [cis (zuclomiphene) and trans (enclomiphene)] containing between 30% and 50% of the cis-isomer.

Each white scored tablet contains 50 mg clomiphene citrate USP. The tablet also contains the following inactive ingredients: corn starch, lactose, magnesium stearate, pregelatinized cornstarch, and sucrose.
Clomid - Clinical Pharmacology
Action

Clomid is a drug of considerable pharmacologic potency. With careful selection and proper management of the patient, Clomid has been demonstrated to be a useful therapy for the anovulatory patient desiring pregnancy.

Clomiphene citrate is capable of interacting with estrogen-receptor-containing tissues, including the hypothalamus, pituitary, ovary, endometrium, vagina, and cervix. It may compete with estrogen for estrogen-receptor-binding sites and may delay replenishment of intracellular estrogen receptors. Clomiphene citrate initiates a series of endocrine events culminating in a preovulatory gonadotropin surge and subsequent follicular rupture. The first endocrine event in response to a course of clomiphene therapy is an increase in the release of pituitary gonadotropins. This initiates steroidogenesis and folliculogenesis, resulting in growth of the ovarian follicle and an increase in the circulating level of estradiol. Following ovulation, plasma progesterone and estradiol rise and fall as they would in a normal ovulatory cycle.

Available data suggest that both the estrogenic and antiestrogenic properties of clomiphene may participate in the initiation of ovulation. The two clomiphene isomers have been found to have mixed estrogenic and antiestrogenic effects, which may vary from one species to another. Some data suggest that zuclomiphene has greater estrogenic activity than enclomiphene.

Clomiphene citrate has no apparent progestational, androgenic, or antiandrogenic effects and does not appear to interfere with pituitary-adrenal or pituitary-thyroid function.

Although there is no evidence of a “carryover effect” of Clomid, spontaneous ovulatory menses have been noted in some patients after Clomid therapy.
Pharmacokinetics

Based on early studies with 14C-labeled clomiphene citrate, the drug was shown to be readily absorbed orally in humans and excreted principally in the feces. Cumulative urinary and fecal excretion of the 14C averaged about 50% of the oral dose and 37% of an intravenous dose after 5 days. Mean urinary excretion was approximately 8% with fecal excretion of about 42%.

Some 14C label was still present in the feces 6 weeks after administration. Subsequent single-dose studies in normal volunteers showed that zuclomiphene (cis) has a longer half-life than enclomiphene (trans). Detectable levels of zuclomiphene persisted for longer than a month in these subjects. This may be suggestive of stereo-specific enterohepatic recycling or sequestering of the zuclomiphene. Thus, it is possible that some active drug may remain in the body during early pregnancy in women who conceive in the menstrual cycle during Clomid therapy.

Clinical Studies

During clinical investigations, 7578 patients received Clomid, some of whom had impediments to ovulation other than ovulatory dysfunction (see INDICATIONS AND USAGE). In those clinical trials, successful therapy characterized by pregnancy occurred in approximately 30% of these patients.

There were a total of 2635 pregnancies reported during the clinical trial period. Of those pregnancies, information on outcome was only available for 2369 of the cases. Table 1 summarizes the outcome of these cases.

Of the reported pregnancies, the incidence of multiple pregnancies was 7.98%: 6.9% twin, 0.5% triplet, 0.3% quadruplet, and 0.1% quintuplet. Of the 165 twin pregnancies for which sufficient information was available, the ratio of monozygotic to dizygotic twins was about 1:5. Table 1 reports the survival rate of the live multiple births.

A sextuplet birth was reported after completion of original clinical studies; none of the sextuplets survived (each weighed less than 400 g), although each appeared grossly normal.
Table 1. Outcome of Reported Pregnancies in Clinical Trials (n = 2369)Outcome Total Number of Pregnancies Survival Rate
Pregnancy Wastage
Spontaneous Abortions 483*
Stillbirths 24
Live Births
Single Births 1697 98.16%†
Multiple Births 165 83.25%†
*
Includes 28 ectopic pregnancies, 4 hydatiform moles, and 1 fetus papyraceous.
†
Indicates percentage of surviving infants from these pregnancies.

The overall survival of infants from multiple pregnancies including spontaneous abortions, stillbirths, and neonatal deaths is 73%.
Indications and Usage for Clomid

Clomid is indicated for the treatment of ovulatory dysfunction in women desiring pregnancy. Impediments to achieving pregnancy must be excluded or adequately treated before beginning Clomid therapy. Those patients most likely to achieve success with clomiphene therapy include patients with polycystic ovary syndrome (see WARNINGS: Ovarian Hyperstimulation Syndrome), amenorrhea-galactorrhea syndrome, psychogenic amenorrhea, post-oral-contraceptive amenorrhea, and certain cases of secondary amenorrhea of undetermined etiology.

Properly timed coitus in relationship to ovulation is important. A basal body temperature graph or other appropriate tests may help the patient and her physician determine if ovulation occurred. Once ovulation has been established, each course of Clomid should be started on or about the 5th day of the cycle. Long-term cyclic therapy is not recommended beyond a total of about six cycles (including three ovulatory cycles). (See DOSAGE AND ADMINISTRATION and PRECAUTIONS.)

Clomid is indicated only in patients with demonstrated ovulatory dysfunction who meet the conditions described below (see CONTRAINDICATIONS):
Patients who are not pregnant.
Patients without ovarian cysts. Clomid should not be used in patients with ovarian enlargement except those with polycystic ovary syndrome. Pelvic examination is necessary prior to the first and each subsequent course of Clomid treatment.
Patients without abnormal vaginal bleeding. If abnormal vaginal bleeding is present, the patient should be carefully evaluated to ensure that neoplastic lesions are not present.
Patients with normal liver function.

In addition, patients selected for Clomid therapy should be evaluated in regard to the following:
Estrogen Levels. Patients should have adequate levels of endogenous estrogen (as estimated from vaginal smears, endometrial biopsy, assay of urinary estrogen, or from bleeding in response to progesterone). Reduced estrogen levels, while less favorable, do not preclude successful therapy.
Primary Pituitary or Ovarian Failure. Clomid therapy cannot be expected to substitute for specific treatment of other causes of ovulatory failure.
Endometriosis and Endometrial Carcinoma. The incidence of endometriosis and endometrial carcinoma increases with age as does the incidence of ovulatory disorders. Endometrial biopsy should always be performed prior to Clomid therapy in this population.
Other Impediments to Pregnancy. Impediments to pregnancy can include thyroid disorders, adrenal disorders, hyperprolactinemia, and male factor infertility.
Uterine Fibroids. Caution should be exercised when using Clomid in patients with uterine fibroids due to the potential for further enlargement of the fibroids.

There are no adequate or well-controlled studies that demonstrate the effectiveness of Clomid in the treatment of male infertility. In addition, testicular tumors and gynecomastia have been reported in males using clomiphene. The cause and effect relationship between reports of testicular tumors and the administration of Clomid is not known.

Although the medical literature suggests various methods, there is no universally accepted standard regimen for combined therapy (ie, Clomid in conjunction with other ovulation-inducing drugs). Similarly, there is no standard Clomid regimen for ovulation induction in in vitro fertilization programs to produce ova for fertilization and reintroduction. Therefore, Clomid is not recommended for these uses.
Contraindications
Hypersensitivity

Clomid is contraindicated in patients with a known hypersensitivity or allergy to clomiphene citrate or to any of its ingredients.
Pregnancy

Clomid should not be administered during pregnancy. Clomid may cause fetal harm in animals (see Animal Fetotoxicity). Although no causative evidence of a deleterious effect of Clomid therapy on the human fetus has been established, there have been reports of birth anomalies which, during clinical studies, occurred at an incidence within the range reported for the general population (see Fetal/Neonatal Anomalies and Mortality; ADVERSE REACTIONS).

To avoid inadvertent Clomid administration during early pregnancy, appropriate tests should be utilized during each treatment cycle to determine whether ovulation occurs. The patient should be evaluated carefully to exclude pregnancy, ovarian enlargement, or ovarian cyst formation between each treatment cycle. The next course of Clomid therapy should be delayed until these conditions have been excluded.
Fetal/Neonatal Anomalies and Mortality

The following fetal abnormalities have been reported subsequent to pregnancies following ovulation induction therapy with Clomid during clinical trials. Each of the following fetal abnormalities were reported at a rate of <1% (experiences are listed in order of decreasing frequency): Congenital heart lesions, Down syndrome, club foot, congenital gut lesions, hypospadias, microcephaly, harelip and cleft palate, congenital hip, hemangioma, undescended testicles, polydactyly, conjoined twins and teratomatous malformation, patent ductus arteriosus, amaurosis, arteriovenous fistula, inguinal hernia, umbilical hernia, syndactyly, pectus excavatum, myopathy, dermoid cyst of scalp, omphalocele, spina bifida occulta, ichthyosis, and persistent lingual frenulum. Neonatal death and fetal death/stillbirth in infants with birth defects have also been reported at a rate of <1%. The overall incidence of reported birth anomalies from pregnancies associated with maternal Clomid ingestion during clinical studies was within the range of that reported for the general population.

In addition, reports of birth anomalies have been received during postmarketing surveillance of Clomid (see ADVERSE REACTIONS).
Animal Fetotoxicity

Oral administration of clomiphene citrate to pregnant rats during organogenesis at doses of 1 to 2 mg/kg/day resulted in hydramnion and weak, edematous fetuses with wavy ribs and other temporary bone changes. Doses of 8 mg/kg/day or more also caused increased resorptions and dead fetuses, dystocia, and delayed parturition, and 40 mg/kg/day resulted in increased maternal mortality. Single doses of 50 mg/kg caused fetal cataracts, while 200 mg/kg caused cleft palate.

Following injection of clomiphene citrate 2 mg/kg to mice and rats during pregnancy, the offspring exhibited metaplastic changes of the reproductive tract. Newborn mice and rats injected during the first few days of life also developed metaplastic changes in uterine and vaginal mucosa, as well as premature vaginal opening and anovulatory ovaries. These findings are similar to the abnormal reproductive behavior and sterility described with other estrogens and antiestrogens.

In rabbits, some temporary bone alterations were seen in fetuses from dams given oral doses of 20 or 40 mg/kg/day during pregnancy, but not following 8 mg/kg/day. No permanent malformations were observed in those studies. Also, rhesus monkeys given oral doses of 1.5 to 4.5 mg/kg/day for various periods during pregnancy did not have any abnormal offspring.
Liver Disease

Clomid therapy is contraindicated in patients with liver disease or a history of liver dysfunction (see also INDICATIONS AND USAGE and ADVERSE REACTIONS).
Abnormal Uterine Bleeding

Clomid is contraindicated in patients with abnormal uterine bleeding of undetermined origin (see INDICATIONS AND USAGE).
Ovarian Cysts

Clomid is contraindicated in patients with ovarian cysts or enlargement not due to polycystic ovarian syndrome (see INDICATIONS AND USAGE and WARNINGS).
Other

Clomid is contraindicated in patients with uncontrolled thyroid or adrenal dysfunction or in the presence of an organic intracranial lesion such as pituitary tumor (see INDICATIONS AND USAGE).
Warnings
Visual Symptoms

Patients should be advised that blurring or other visual symptoms such as spots or flashes (scintillating scotomata) may occasionally occur during therapy with Clomid. These visual symptoms increase in incidence with increasing total dose or therapy duration and generally disappear within a few days or weeks after Clomid is discontinued. Patients should be warned that these visual symptoms may render such activities as driving a car or operating machinery more hazardous than usual, particularly under conditions of variable lighting.

These visual symptoms appear to be due to intensification and prolongation of afterimages. Symptoms often first appear or are accentuated with exposure to a brightly lit environment. While measured visual acuity usually has not been affected, a study patient taking 200 mg Clomid daily developed visual blurring on the 7th day of treatment, which progressed to severe diminution of visual acuity by the 10th day. No other abnormality was found, and the visual acuity returned to normal on the 3rd day after treatment was stopped.

Ophthalmologically definable scotomata and retinal cell function (electroretinographic) changes have also been reported. A patient treated during clinical studies developed phosphenes and scotomata during prolonged Clomid administration, which disappeared by the 32nd day after stopping therapy.

Postmarketing surveillance of adverse events has also revealed other visual signs and symptoms during Clomid therapy (see ADVERSE REACTIONS).

While the etiology of these visual symptoms is not yet understood, patients with any visual symptoms should discontinue treatment and have a complete ophthalmological evaluation carried out promptly.
Ovarian Hyperstimulation Syndrome

The ovarian hyperstimulation syndrome (OHSS) has been reported to occur in patients receiving clomiphene citrate therapy for ovulation induction. In some cases, OHSS occurred following cyclic use of clomiphene citrate therapy or when clomiphene citrate was used in combination with gonadotropins. Transient liver function test abnormalities suggestive of hepatic dysfunction, which may be accompanied by morphologic changes on liver biopsy, have been reported in association with ovarian hyperstimulation syndrome (OHSS).

OHSS is a medical event distinct from uncomplicated ovarian enlargement. The clinical signs of this syndrome in severe cases can include gross ovarian enlargement, gastrointestinal symptoms, ascites, dyspnea, oliguria, and pleural effusion. In addition, the following symptoms have been reported in association with this syndrome: pericardial effusion, anasarca, hydrothorax, acute abdomen, hypotension, renal failure, pulmonary edema, intraperitoneal and ovarian hemorrhage, deep venous thrombosis, torsion of the ovary, and acute respiratory distress. The early warning signs of OHSS are abdominal pain and distention, nausea, vomiting, diarrhea, and weight gain. Elevated urinary steroid levels, varying degrees of electrolyte imbalance, hypovolemia, hemoconcentration, and hypoproteinemia may occur. Death due to hypovolemic shock, hemoconcentration, or thromboembolism has occurred. Due to fragility of enlarged ovaries in severe cases, abdominal and pelvic examination should be performed very cautiously. If conception results, rapid progression to the severe form of the syndrome may occur.

To minimize the hazard associated with occasional abnormal ovarian enlargement associated with Clomid therapy, the lowest dose consistent with expected clinical results should be used. Maximal enlargement of the ovary, whether physiologic or abnormal, may not occur until several days after discontinuation of the recommended dose of Clomid. Some patients with polycystic ovary syndrome who are unusually sensitive to gonadotropin may have an exaggerated response to usual doses of Clomid. Therefore, patients with polycystic ovary syndrome should be started on the lowest recommended dose and shortest treatment duration for the first course of therapy (see DOSAGE AND ADMINISTRATION).

If enlargement of the ovary occurs, additional Clomid therapy should not be given until the ovaries have returned to pretreatment size, and the dosage or duration of the next course should be reduced. Ovarian enlargement and cyst formation associated with Clomid therapy usually regresses spontaneously within a few days or weeks after discontinuing treatment. The potential benefit of subsequent Clomid therapy in these cases should exceed the risk. Unless surgical indication for laparotomy exists, such cystic enlargement should always be managed conservatively.

A causal relationship between ovarian hyperstimulation and ovarian cancer has not been determined. However, because a correlation between ovarian cancer and nulliparity, infertility, and age has been suggested, if ovarian cysts do not regress spontaneously, a thorough evaluation should be performed to rule out the presence of ovarian neoplasia.
Precautions
General

Careful attention should be given to the selection of candidates for Clomid therapy. Pelvic examination is necessary prior to Clomid treatment and before each subsequent course (see CONTRAINDICATIONS and WARNINGS).
Information for Patients

The purpose and risks of Clomid therapy should be presented to the patient before starting treatment. It should be emphasized that the goal of Clomid therapy is ovulation for subsequent pregnancy. The physician should counsel the patient with special regard to the following potential risks:
Visual Symptoms

Advise that blurring or other visual symptoms occasionally may occur during or shortly after Clomid therapy. Warn that visual symptoms may render such activities as driving a car or operating machinery more hazardous than usual, particularly under conditions of variable lighting (see WARNINGS).

The patient should be instructed to inform the physician whenever any unusual visual symptoms occur. If the patient has any visual symptoms, treatment should be discontinued and complete ophthalmologic evaluation performed.
Abdominal/Pelvic Pain or Distention

Ovarian enlargement may occur during or shortly after therapy with Clomid. To minimize the risks associated with ovarian enlargement, the patient should be instructed to inform the physician of any abdominal or pelvic pain, weight gain, discomfort, or distention after taking Clomid (see WARNINGS).
Multiple Pregnancy

Inform the patient that there is an increased chance of multiple pregnancy, including bilateral tubal pregnancy and coexisting tubal and intrauterine pregnancy, when conception occurs in relation to Clomid therapy. The potential complications and hazards of multiple pregnancy should be explained.
Pregnancy Wastage and Birth Anomalies

The physician should explain the assumed risk of any pregnancy, whether ovulation is induced with the aid of Clomid or occurs naturally. The patient should be informed of the greater risks associated with certain characteristics or conditions of any pregnant woman, eg, age of female and male partner, history of spontaneous abortions, Rh genotype, abnormal menstrual history, infertility history, organic heart disease, diabetes, exposure to infectious agents such as rubella, familial history of birth anomaly, that may be pertinent to the patient for whom Clomid is being considered. Based upon the evaluation of the patient, genetic counseling may be indicated.

The overall incidence of reported birth anomalies from pregnancies associated with maternal Clomid ingestion during the investigational studies was within the range of that reported in published references for the general population. (See CONTRAINDICATIONS: Pregnancy.)

During clinical investigation, the experience from patients with known pregnancy outcome (Table 1) shows a spontaneous abortion rate of 20.4% and stillbirth rate of 1.0%. (See CLINICAL PHARMACOLOGY.)
Drug Interactions

Drug interactions with Clomid have not been documented.
Carcinogenesis, Mutagenesis, Impairment of Fertility

Long-term toxicity studies in animals have not been performed to evaluate the carcinogenic or mutagenic potential of clomiphene citrate.

Oral administration of Clomid to male rats at doses of 0.3 or 1 mg/kg/day caused decreased fertility, while higher doses caused temporary infertility. Oral doses of 0.1 mg/kg/day in female rats temporarily interrupted the normal cyclic vaginal smear pattern and prevented conception. Doses of 0.3 mg/kg/day slightly reduced the number of ovulated ova and corpora lutea, while 3 mg/kg/day inhibited ovulation.
Pregnancy

Pregnancy Category X. (See CONTRAINDICATIONS.)
Nursing Mothers

It is not known whether Clomid is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised if Clomid is administered to a nursing woman. In some patients, Clomid may reduce lactation.
Ovarian Cancer

Prolonged use of clomiphene citrate tablets USP may increase the risk of a borderline or invasive ovarian tumor (see ADVERSE REACTIONS).
Adverse Reactions
Clinical Trial Adverse Events

Clomid, at recommended dosages, is generally well tolerated. Adverse reactions usually have been mild and transient and most have disappeared promptly after treatment has been discontinued. Adverse experiences reported in patients treated with clomiphene citrate during clinical studies are shown in Table 2.
Table 2. Incidence of Adverse Events in Clinical Studies (Events Greater than 1%) (n = 8029*)Adverse Event %
Ovarian Enlargement 13.6
Vasomotor Flushes 10.4
Abdominal-Pelvic Discomfort/Distention/Bloating 5.5
Nausea and Vomiting 2.2
Breast Discomfort 2.1
Visual Symptoms 1.5
Blurred vision, lights, floaters, waves, unspecified visual complaints, photophobia, diplopia, scotomata, phosphenes
Headache 1.3
Abnormal Uterine Bleeding 1.3
Intermenstrual spotting, menorrhagia
*
Includes 498 patients whose reports may have been duplicated in the event totals and could not be distinguished as such. Also, excludes 47 patients who did not report symptom data.

The following adverse events have been reported in fewer than 1% of patients in clinical trials: Acute abdomen, appetite increase, constipation, dermatitis or rash, depression, diarrhea, dizziness, fatigue, hair loss/dry hair, increased urinary frequency/volume, insomnia, light-headedness, nervous tension, vaginal dryness, vertigo, weight gain/loss.

Patients on prolonged Clomid therapy may show elevated serum levels of desmosterol. This is most likely due to a direct interference with cholesterol synthesis. However, the serum sterols in patients receiving the recommended dose of Clomid are not significantly altered. Ovarian cancer has been infrequently reported in patients who have received fertility drugs. Infertility is a primary risk factor for ovarian cancer; however, epidemiology data suggest that prolonged use of clomiphene may increase the risk of a borderline or invasive ovarian tumor.
Postmarketing Adverse Events

The following adverse experiences were reported spontaneously with Clomid. The cause and effect relationship of the listed events to the administration of Clomid is not known.

Dermatologic: Acne, allergic reaction, erythema, erythema multiforme, erythema nodosum, hypertrichosis, pruritus

Central Nervous System: Migraine headache, paresthesia, seizure, stroke, syncope

Psychiatric: Anxiety, irritability, mood changes, psychosis

Visual Disorders: Abnormal accommodation, cataract, eye pain, macular edema, optic neuritis, photopsia, posterior vitreous detachment, retinal hemorrhage, retinal thrombosis, retinal vascular spasm, temporary loss of vision

Cardiovascular: Arrhythmia, chest pain, edema, hypertension, palpitation, phlebitis, pulmonary embolism, shortness of breath, tachycardia, thrombophlebitis

Musculoskeletal: Arthralgia, back pain, myalgia

Hepatic: Transaminases increased, hepatitis

Neoplasms: Liver (hepatic hemangiosarcoma, liver cell adenoma, hepatocellular carcinoma); breast (fibrocystic disease, breast carcinoma); endometrium (endometrial carcinoma); nervous system (astrocytoma, pituitary tumor, prolactinoma, neurofibromatosis, glioblastoma multiforme, brain abcess); ovary (luteoma of pregnancy, dermoid cyst of the ovary, ovarian carcinoma); trophoblastic (hydatiform mole, choriocarcinoma); miscellaneous (melanoma, myeloma, perianal cysts, renal cell carcinoma, Hodgkin’s lymphoma, tongue carcinoma, bladder carcinoma); and neoplasms of offspring (neuroectodermal tumor, thyroid tumor, hepatoblastoma, lymphocytic leukemia)

Genitourinary: Endometriosis, ovarian cyst (ovarian enlargement or cysts could, as such, be complicated by adnexal torsion), ovarian hemorrhage, tubal pregnancy, uterine hemorrhage

Body as a Whole: Fever, tinnitus, weakness

Other: Leukocytosis, thyroid disorder
Fetal/Neonatal Anomalies

The following fetal abnormalities have also been reported during postmarketing surveillance: delayed development; abnormal bone development including skeletal malformations of the skull, face, nasal passages, jaw, hand, limb (ectromelia including amelia, hemimelia, and phocomelia), foot, and joints; tissue malformations including imperforate anus, tracheoesophageal fistula, diaphragmatic hernia, renal agenesis and dysgenesis, and malformations of the eye and lens (cataract), ear, lung, heart (ventricular septal defect and tetralogy of Fallot), and genitalia; as well as dwarfism, deafness, mental retardation, chromosomal disorders, and neural tube defects (including anencephaly).
Drug Abuse and Dependence

Tolerance, abuse, or dependence with Clomid has not been reported.
Overdosage
Signs and Symptoms

Toxic effects accompanying acute overdosage of Clomid have not been reported. Signs and symptoms of overdosage as a result of the use of more than the recommended dose during Clomid therapy include nausea, vomiting, vasomotor flushes, visual blurring, spots or flashes, scotomata, ovarian enlargement with pelvic or abdominal pain. (See CONTRAINDICATIONS: Ovarian Cyst.)
Oral LD50

The acute oral LD50 of Clomid is 1700 mg/kg in mice and 5750 mg/kg in rats. The toxic dose in humans is not known.
Dialysis

It is not known if Clomid is dialyzable.
Treatment

In the event of overdose, appropriate supportive measures should be employed in addition to gastrointestinal decontamination.
Clomid Dosage and Administration
General Considerations

The workup and treatment of candidates for Clomid therapy should be supervised by physicians experienced in management of gynecologic or endocrine disorders. Patients should be chosen for therapy with Clomid only after careful diagnostic evaluation (see INDICATIONS AND USAGE). The plan of therapy should be outlined in advance. Impediments to achieving the goal of therapy must be excluded or adequately treated before beginning Clomid. The therapeutic objective should be balanced with potential risks and discussed with the patient and others involved in the achievement of a pregnancy.

Ovulation most often occurs from 5 to 10 days after a course of Clomid. Coitus should be timed to coincide with the expected time of ovulation. Appropriate tests to determine ovulation may be useful during this time.
Recommended Dosage

Treatment of the selected patient should begin with a low dose, 50 mg daily (1 tablet) for 5 days. The dose should be increased only in those patients who do not ovulate in response to cyclic 50 mg Clomid. A low dosage or duration of treatment course is particularly recommended if unusual sensitivity to pituitary gonadotropin is suspected, such as in patients with polycystic ovary syndrome (see WARNINGS; Ovarian Hyperstimulation Syndrome).

The patient should be evaluated carefully to exclude pregnancy, ovarian enlargement, or ovarian cyst formation between each treatment cycle.

If progestin-induced bleeding is planned, or if spontaneous uterine bleeding occurs prior to therapy, the regimen of 50 mg daily for 5 days should be started on or about the 5th day of the cycle. Therapy may be started at any time in the patient who has had no recent uterine bleeding. When ovulation occurs at this dosage, there is no advantage to increasing the dose in subsequent cycles of treatment.

If ovulation does not appear to occur after the first course of therapy, a second course of 100 mg daily (two 50 mg tablets given as a single daily dose) for 5 days should be given. This course may be started as early as 30 days after the previous one after precautions are taken to exclude the presence of pregnancy. Increasing the dosage or duration of therapy beyond 100 mg/day for 5 days is not recommended.

The majority of patients who are going to ovulate will do so after the first course of therapy. If ovulation does not occur after three courses of therapy, further treatment with Clomid is not recommended and the patient should be reevaluated. If three ovulatory responses occur, but pregnancy has not been achieved, further treatment is not recommended. If menses does not occur after an ovulatory response, the patient should be reevaluated. Long-term cyclic therapy is not recommended beyond a total of about six cycles.

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Klomifen citrate, clomid

Klomifen citrate, clomid

Pharmacological Effects
Antiestrogennoe. Links estrogen receptors in the hypothalamus and the ovaries. If ingestion is well absorbed from the ZHKT. Metabolized in the liver. Ekskretiruetsya with bile, subjected enterogepaticheskoy recycling. Because the body is displayed with the faeces. The half is 5-7 days. In small doses, increases the secretion of gonadotrophic hormones (prolactin, FSH and LH) stimulates ovulation. With a low content of endogenous estrogens in the body has a modest effect of estrogen, with a high level - antiestrogenny. By reducing the level of circulating estrogen, promotes secretion of gonadotropin. In high doses, inhibits secretion of gonadotropin. Gestagennoy and androgenic activity does not possess.

Indications for use
Anovulyatornoe infertility, dysfunctional uterine bleeding, amenorrhea (disgonadotropnaya form secondary postkontratseptivnaya) galaktoreya (on the background of pituitary tumor), polikistoz ovaries (Stein syndrome - Levental) Chiari syndrome - Frommelya, androgenic insufficiency oligospermiya to diagnose violations of pituitary gonadotrophic function .

Contraindications
Hypersensitivity, severe hepatic, renal failure, uterine bleeding unclear etiology, ovarian cyst, tumor or pituitary function insufficiency, pregnancy (including suspected it).

Side Effects
Headache, dizziness, depression, increased fatigue, anxiety, insomnia, visual impairment, nausea, vomiting, increase in cystic ovaries, dysmenorrhea, pollakiuriya, poliuriya, multiple pregnancy, the tides, the increase in body mass, lower abdominal pain in the chest, testicles ( men), hyperthermia, reversible hair loss, allergic skin reactions.

Interaction
Compatible with drugs gonadotrophic hormones.

Overdosage
Symptoms: nausea, vomiting, hot flushes, visual impairment, and pain in the abdomen. Treatment: symptomatic therapy.

Cautions
You can not assign without the liberation of the working people, professional activity which requires quick physical and mental reactions. If you raise ovarian cancer or cystic transformation treatment klomifenom be suspended until the normalization of the size of the ovaries. Therapy continues with the use of minimal doses or shorten the period of treatment. Against the background of treatment is recommended to monitor liver function.

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Viagra, Levitra, Cialis - win new segments of the market

“Viagra”, «Levitra» and «cialis» - three similar medicines for an impotence - win all new segments of the market. If earlier, in the first advertising campaign of “Viagra”, the elderly senator a Doul Bean now heroes of rollers of the man do not become more senior forty acted in film.

Experts in marketing any more do not suggest buyers to be treated for an impotence, and position the preparations as tablets for pleasure. «Levitra», for example, is painted in cheerful orange colour.
Who now buys “Viagra”

As newspaper The New York Times writes, the first people really sick of an impotence began to receive such medicines. Under the recipe of the doctor the sexual life managed to be adjusted suffering from a diabetes, neurologic infringements or by-effects of energizers.

However demand for “Viagra” has sharply increased in a consequence. First, doctors began to write out without superfluous questions recipes to all who asked. Secondly, there were numerous Internet drugstores which offered preparations from an impotence without the recipe and with delivery.

Accordingly, the circle of buyers has extended also. Healthy people who wished to make secure before disturbing appointment became “patients”.

The portrait of one of such consumers is described in New York Times. 41-year-old Chris London (Chris London) lives in New York and works as the lawyer. One of its business partners has declared once, that cannot normally work with the man if before it they did not have a sex. London has been at least discouraged by such statement, but has agreed to meet after work. According to the advice of the familiar doctor he has won the excitement by the “Viagra” silently swallowed in a bathroom.

Easier speaking, “Viagra”, «Levitra» and «cialis» all who wishes to be assured of the sexual possibilities irrespective of circumstances now buy. Manufacturers of medicines thus underline, that food intake or alcohol does not influence at all their efficiency.
What impotence?

The impotence (a erektilnaja dysfunction) is defined as repeated inability to support a erektsiju necessary for sexual intercourse.

This frustration young enough men suffer both elderly, and. In the first case the impotence reason are chronic diseases or traumas more often, and in the second the impotence is a psychological problem.

Contrary to opinion of many men, “Viagra” and its analogues operate exclusively on blood supply of a sexual member and have no psychotropic effects. That is, such preparations can improve a potentiality, but do not stimulate a libido. However, as doctors have found out, together with a normal erektsiej the desire of sex frequently comes.
Sex In The City

According to psychologists, the requirement for “Viagra” and its analogues first of all is at inhabitants of large cities. Sexual revolution has led to that even more often sexual contacts occur between unfamiliar people: the fellow workers who have got acquainted on a party or under the announcement on the Internet.

Thus in consciousness of the majority of people there is an image of the ideal man always ready to sex and the interested person this. Trying to correspond to such representation, men accept tablets secretly, as Chris London mentioned above. Entering into a bedroom with a flush on cheeks - a widespread by-effect of “Viagra” - they complain of a heat and closeness. And in the morning often hide as suffer from a headache.

As omechaet The New York Times, such tablets are drunk frequently also by men-gays. Both lovers do it secretly the friend-from to the friend, and then those by-effects together worry.

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Viagra - Sildenafil

Viagra

viagra (sildenafil)

Medicinal forms
Tablets covered with a cover 25мг, tablets covered with a cover 50мг, tablets covered with a cover 100mg

Manufacturers
Pfajzer (United States of America), Pfajzer of a PGM (France)

FarmGruppa
Agents stimulating a potency

The international nepatentovannoe the name
Sildenafil Citras

Structure
Active substance - a sildenafila Citras.

Pharmacological action
Improving erectile function. Selectively inhibits a cGMP-dependent of a fosfodiesterazu of type 5 (ФДЭ5), containing mainly in unstriated muscles of a cavernous body, and interferes with cGMP destruction. Rising of level of the last leads to depression of intracellular concentration of calcium and a relaxation of a gladkomyshechnyh of cells of a cavernous body with the subsequent raised filling of sine with blood against augmentation of an arterial blood flow in a sexual member and a prelum of taking out veins. Strengthens and enlarges duration of the erection which have resulted sex stimulation. Does not render influence on morphology, mobility and viability of spermatozoons, volume and viscosity of an ejaculate. Inhibits ФДЭ6 retinas (though and is more weak, than ФДЭ5, selectivity of action 10:1) and can cause disturbances of colour sight. Raises a antiagregantnyj and a dezagregatsionnyj effects of a oksida of nitrogen (II) and its donors, formation of thrombuses ex vivo blocks. Dilates both arterial, and venous vessels, depression causes a garden and a dAD, CARDIAC CONTRACTIONS RATE augmentation. Antidiuretic an effect has. Does not influence genesial function, has no teratogennyh, mutagen, a klastogennyh (studying of chromosomal abberatsy) and cancerogenic properties. At intake on an empty stomach quickly and practically it is completely soaked up. The maximum concentration in plasma is reached through 0,5-2 ch, absolute bioavailability - 41 % (is exposed to a presistemnomu to a metabolism), reception of fat nutrition reduces absorption degree on 11 %, the maximum concentration on 29 %. Substantially (96 %) contact fibers of plasma, a half-life period - 4 ch (2-8 ch). Collects in an organism: at application 3 times a day within 9 days, the cumulation makes 36 %. To 80 % of metabolites of a sildenafila it is deduced with excrements and 14 % - with urine.

Indications to application
Erection disturbances (organic, psychogenic, admixed), in т.ch. At sick of a diabetes, adiposity, after a radical prostatectomy or a spinal cord trauma.

Contraindications
Hypersensitivity, therapy by Sodium nitritums. Restrictions to application: Serious disturbances of function of a liver and kidneys, anatomic deformations of a sexual member, a multiple myeloma, acute leukoses, a sickemia, the raised predilection to bleedings, a hereditary pigmental retinitis, an exacerbation of a peptic ulcer of a stomach and a duodenum, serious forms of an arterial hypertonia and a hypotension, anamnestic indicatings on the infarct transferred in previous 6 months and a stroke menacing to a life of an arrhythmia, a heart failure, an astable stenocardia, age till 18 years.

Side effect
Headache, giddiness, vazodilatatsija (inflow), hypotension, asthenia, nose zalozhennost, dacryagogue, disturbance sveto - and colour perception, a sight sharpness, a dyspepsia, a diarrhoeia, a nausea, a abdominalgija, a ljumbalgija, an arthralgia, a mialgija, a hypertonus of muscles, a sleeplessness, a dyspnea, dermal rashes, predisposition to an infection of respiratory and urinary ways, a long painful erection (more than 4 ch).

Interaction
Strengthens the orthostatic hypotension caused by Nitroglycerinum, a antiagregantnye effects of Sodium nitroprussidum. Inhibitors CYР3А4 (Cimetidinum, a ketokonazol, a intrakonazol, erythromycin, etc.) raise concentration in plasma, inductors (etc.) - reduce rifampicin.

Overdosage
Symptoms: it is shown by sensation of fever, giddiness, a face reddening, a headache, disturbance of a sharpness of sight, the dyspeptic phenomena, BP depression. Treatment: symptomatic, the dialysis is noneffective.

Special indicatings
Before the beginning of reception for diagnostics of disturbances of an erection, definition of its possible reasons and a choice of adequate methods of treatment it is necessary to collect the full medical anamnesis and to spend careful urological and a obshcheklinicheskoe inspection, especially at patients with accompanying cardiovascular diseases at which the raised sex activity is undesirable (for example, serious forms of an ischemic heart disease and an idiopathic hypertensia). Appointment of high doses is not recommended to elderly patients. Frequent (more than 1 time a day) use in high doses enlarges risk of by-effects. Patients concern a category of the raised risk from an accompanying ischemic heart disease, since renewal of an active sexual life, in т.ch. The augmentation of number of sexual contacts, can negatively affect a current of the basic somatopathy or demand correction of medicamental therapy. The estimation of a parity advantage/risk is necessary at patients with a heart failure, a low OTSK. Care at appointment is required to men with an arterial hypertensia (a BP of 170/110 mm hg) and an arterial hypotension (a BP of 90/50 mm hg). With extra care prescribe the patient with the accompanying arterial hypertensia, receiving multicomponent hypotensive pharmacotherapy, it is cautious - at the diseases contributing to development of a priapism. It is not recommended to combine with other preparations used for treatment of erectile dysfunction.

Alprazolam - Xanax

Synonym: a Alprazolam.

Xanax pharmacological action. A derivative triazolo - benzodiazepine. The anksioliticheskoe an effect has. Reduces anxiety, feeling of alarm, pavor, a strain. Antidepressive activity is noted. Possesses central miorelaksirujushchej and moderate somnolent activity.

Xanax indications to application. Disturbing conditions and the neurosises accompanied by feeling of alarm, danger, anxiety, a strain, dream deterioration, irritability, and also somatic disturbances. Neurotic reaktivno - depressions. Neurotic depressions against somatopathies.

Xanax a way of application and a dose. The adult at anxiety and alarm conditions. The initial dose makes on 0,25 - 0,5 mg 3 times a day, an average maintenance dose 0,5 - 4 mg/sut in stages. At depression the initial dosage makes on 0,5 mg 3 times a day; if necessary gradually raise doses to 1-4 mg/days At treatment of the elderly or weakened patients it is necessary to use smaller doses: 0,25 mg 2 - 3 times/sut, if necessary gradual rising to 0,5-0,75 mg/days

Side effect. Often drowsiness and giddiness, it is less frequent sight disturbances, a headache, depression, nervousness, alarm, a tremor, memory and coordination disturbances; a nausea, vomiting, cases of an icterus, rising of activity of hepatic transaminases.

Changes of mass of a body, a delay or an incontience of urine, libido disturbance, an irregularity of a menstrual cycle.

Xanax contraindications. The Hypersensibility to benzodiazepine derivatives.

Caution. It is necessary to prescribe with care a preparation the patient with disturbances of functions of a liver and kidneys, acute respiratory insufficiency and at an acute attack of a glaucoma, to the patients, suffering psychomotor block. At preparation application it is necessary to refrain from driving of vehicles or work with mechanisms.

Interaction. Simultaneous application psychotropic, anticonvulsant, antihistaminics and ethyl alcohol strengthens overwhelming action of a preparation on a TSNS.

Xanax the release form. Tablets on 0,25; 0,5; 1,2 mg, in packing - 10, 20, 30, 50 and 100 pieces.

Xanax storage conditions. Usual.

Xanax a period of validity 2 years.