Clomid

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*)

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 reactions have been identified during post approval use of Clomid. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Body as a Whole: Fever, tinnitus, weakness

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

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

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

Fetal/Neonatal Anomalies

• Abnormal bone development: skeletal malformations of the skull, face, nasal passages, jaw, hand, limb (ectromelia including amelia, hemimelia, and phocomelia), foot (clubfoot), spine, and joints
• Cardiac abnormalities: septal heart defects, muscular ventricular septal defect, patent ductus arteriosus, tetralogy of Fallot, and coarctation of the aorta
• Chromosomal disorders: Downs syndrome
• Ear abnormalities and deafness
• Gastrointestinal tract abnormalities: cleft lip and palate, imperforate anus, tracheoesophageal fistula, diaphragmatic hernia, omphalocele
• Genitalia abnormalities: hypospadias, cloacal exstrophy
• Lung tissue malformations
• Malformations of the eye and lens (cataract)
• Neoplasms: neuroectodermal tumor, thyroid tumor, hepatoblastoma, lymphocytic leukemia
• Nervous system abnormalities: neural tube defects (anencephaly, meningomyelocele), microcephaly, and hydrocephalus
• Renal abnormalities: renal agenesis and renal dysgenesis
• Others: dwarfism, mental retardation

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

Hepatic: Transaminases increased, hepatitis

Musculoskeletal: Arthralgia, back pain, myalgia

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)

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 or prolonged loss of vision, possibly irreversible.

Other: Leukocytosis, thyroid disorder

Drug Abuse And Dependence

Tolerance, abuse, or dependence with CLOMID has not been reported.

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.)

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 is a prescription medication used to induce ovulation in women who do not produce eggs but wish to become pregnant.

This medication may be prescribed for other uses.  Ask your doctor or pharmacist for more information.

Serious side effects have been reported with Clomid including the following:

• Visual Symptoms. Blurring or other visual symptoms occasionally may occur during or shortly after Clomid therapy. Visual symptoms may make driving a car or operating machinery more hazardous than usual, particularly under conditions of variable lighting. Inform your doctor if any visual symptoms occur while using Clomid.
• Abdominal/Pelvic pain. Ovarian enlargement may occur during or shortly after therapy with Clomid. To minimize the risks with ovarian enlargement, inform your doctor of any abdominal or pelvic pain, weight gain, discomfort, or bloating after taking Clomid.
• Multiple Pregnancy. There is an increased chance of multiple pregnancy when taking Clomid.
• Ovarian Cancer. Long-term use of Clomid may increase the risk of ovarian cancer. Clomid should not be used for more than about six cycles. Talk to your doctor about the risks of taking this medication.

As mentioned, Clomid can cause visual disturbances and impair your ability to drive or operate heavy machinery. Do not drive or operate heavy machinery until you know how Clomid affects you.

Do not take Clomid if you:

• are allergic to Clomid or any of its ingredients
• are pregnant
• have liver disease
• have abnormal uterine bleeding
• have ovarian cysts
• have uncontrolled thyroid or adrenal dysfunction

Medications can interact with certain foods. In some cases, this may be harmful and your doctor may advise you to avoid certain foods. In the case of Clomid, there are no specific foods that you must exclude from your diet when receiving this medication.

Tell your doctor if you are pregnant.

The FDA categorizes medications based on safety for use during pregnancy. Five categories - A, B, C, D, and X, are used to classify the possible risks to an unborn baby when a medication is taken during pregnancy.

Clomid falls into category X. There are no situations where the benefits of the medication for the mother outweigh the risks of harm to the baby. These medicines should never be used by pregnant women.

Use caution when driving, operating machinery, or performing other hazardous activities. Clomiphene may cause blurred vision or other visual side effects during or shortly after therapy. Notify your doctor immediately if you develop any visual side effects and use caution when performing hazardous activities, especially under conditions of variable lighting.

Clomiphene is a nonsteroidal fertility medicine. It causes the pituitary gland to release hormones needed to stimulate ovulation (the release of an egg from the ovary).

Clomiphene is used to cause ovulation in women with certain medical conditions (such as polycystic ovary syndrome) that prevent naturally occurring ovulation.

Clomiphene may also be used for purposes not listed in this medication guide.

You should not use clomiphene if you are allergic to it, or if you have:

• 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.

To make sure clomiphene is safe for you, tell your doctor if you have:

• endometriosis or uterine fibroids.

Do not use clomiphene if you are already pregnant. Talk to your doctor if you have concerns about the possible effects of clomiphene on a new pregnancy.

Clomiphene can pass into breast milk and may harm a nursing baby. This medicine 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.

This medication may cause blurred vision. Be careful if you drive or do anything that requires you to be alert and able to see clearly.

In the U.S.

• Clomid
• Serophene

Available Dosage Forms:

• Tablet

Therapeutic Class: Female Reproductive Agent

Pharmacologic Class: Gonadotropin

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 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.

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 reactions have been identified during post approval use of Clomid. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Body as a Whole: Fever, tinnitus, weakness

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

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

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

Fetal/Neonatal Anomalies:

• Abnormal bone development: skeletal malformations of the skull, face, nasal passages, jaw, hand, limb (ectromelia including amelia, hemimelia, and phocomelia), foot (clubfoot), spine, and joints
• Cardiac abnormalities: septal heart defects, muscular ventricular septal defect, patent ductus arteriosus, tetralogy of Fallot, and coarctation of the aorta
• Chromosomal disorders: Downs syndrome
• Ear abnormalities and deafness
• Gastrointestinal tract abnormalities: cleft lip and palate, imperforate anus, tracheoesophageal fistula, diaphragmatic hernia, omphalocele
• Genitalia abnormalities: hypospadias, cloacal exstrophy
• Lung tissue malformations
• Malformations of the eye and lens (cataract)
• Neoplasms: neuroectodermal tumor, thyroid tumor, hepatoblastoma, lymphocytic leukemia
• Nervous system abnormalities: neural tube defects (anencephaly, meningomyelocele), microcephaly, and hydrocephalus
• Renal abnormalities: renal agenesis and renal dysgenesis
• Others: dwarfism, mental retardation

Gastrointestinal: Pancreatitis

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

Hepatic: Transaminases increased, hepatitis

Metabolism Disorders: Hypertriglyceridemia, in some cases with pancreatitis

Musculoskeletal: Arthralgia, back pain, myalgia

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)

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 or prolonged loss of vision, possibly irreversible.

Other: Leukocytosis, thyroid disorder

NDC 0068-0226-30

Clomid®

clomiphene citrate
tablets USP

50mg

30 Tablets

sanofi aventis

Get emergency medical help if you have any signs of an allergic reaction to Clomid: hives; difficult breathing; swelling of your face, lips, tongue, or throat.

Some women using this medicine develop a condition called ovarian hyperstimulation syndrome (OHSS), especially after the first treatment. OHSS can be a life threatening condition. Call your doctor right away if you have any of the following symptoms of OHSS:

• stomach pain, bloating;

• nausea, vomiting, diarrhea;

• rapid weight gain, especially in your face and midsection;

• little or no urinating; or

• pain when you breathe, rapid heart rate, feeling short of breath (especially when lying down).

Stop using Clomid and call your doctor at once if you have:

• pelvic pain or pressure, enlargement in your pelvic area;

• vision problems;

• seeing flashes of light or "floaters" in your vision;

• increased sensitivity of your eyes to light; or

• heavy vaginal bleeding.

Common Clomid side effects may include:

• flushing (warmth, redness, or tingly feeling);

• breast pain or tenderness;

• headache; or

• breakthrough bleeding or spotting.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.