Clomiphene

Pregnancy Category: X

Lactation: It is not known whether clomiphene is excreted in human milk. Use with caution in nursing women. In some patients, clomiphene may reduce lactation.

Pregnancy Categories

A:Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B:May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C:Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D:Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X:Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA:Information not available.

Clomiphene is part of the drug class:

• Ovulation stimulants, synthetic

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

Visual symptoms. Blurring or other visual symptoms may occur during or shortly after clomiphene 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 clomiphene.

Abdominal/pelvic pain. Ovarian enlargement may occur during or shortly after therapy with clomiphene. To minimize the risks associated with ovarian enlargement, inform your doctor of any abdominal or pelvic pain, weight gain, discomfort, and/or bloating after taking clomiphene.

Multiple pregnancies. There is an increased chance of multiple pregnancies when taking clomiphene.

Ovarian cancer. Long-term use of clomiphene may increase your risk of developing ovarian cancer. Clomiphene should not typically be used for more than six treatment cycles. Talk to your doctor about the risks of taking this medication.

Do not take clomiphene if you:

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

Clomiphene can cause blurred vision and/or dizziness. Do not drive or operate heavy machinery until you know how clomiphene affects you.

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.

Clomiphene 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 may increase the likelihood of multiple births. Multiple births may carry additional risk both for the mother and for the fetuses.

Do not use clomiphene if you are already pregnant.

You should not use clomiphene if you have: liver disease, abnormal vaginal bleeding, an uncontrolled adrenal gland or thyroid disorder, an ovarian cyst (unrelated to polycystic ovary syndrome), or if you are pregnant.

Usual Adult Dose for Ovulation Induction:

50 mg orally once a day for 5 days. Therapy should be initiated on or near the 5th day of the menstrual cycle, but may be started at any time in patients without recent uterine bleeding.

If ovulation occurs and pregnancy is not achieved, up to 2 additional courses of clomiphene 50 mg orally once a day for 5 days may be administered. Each subsequent course may be started as early as 30 days after the previous course and after pregnancy has been excluded.

Most patients ovulate following the first course of therapy. However, if the patient fails to ovulate, a second course of 100 mg/day for 5 days may be given as early as 30 days following the initial course. A third course of 100 mg/day for 5 days may be given after 30 days, if necessary.

Treatments beyond three cycles of clomiphene, dosages greater than 100 mg once a day, and/or course durations beyond 5 days are not recommended by the manufacturer. However, successful pregnancies and term deliveries have been reported in women receiving up to 200 mg/day for 5 days, or extended 10-day course of therapy, or consecutive cycles of treatment beyond the 3 recommended by the manufacturer.

Usual Adult Dose for Lactation Suppression:

50 to 100 mg orally once a day for 5 days. Generally, one course of therapy is sufficient.

Usual Adult Dose for Oligospermia:

25 to 100 mg orally once a day. Therapy is generally given over a period of several months.

Take clomiphene only as directed by your doctor. If you are to begin on Day 5, count the first day of your menstrual period as Day 1. Beginning on Day 5, take the correct dose every day for as many days as your doctor ordered. To help you to remember to take your dose of medicine, take it at the same time every day.

Dosing

The dose of clomiphene will be different for different patients. Follow your doctor's orders or the directions on the label. The following information includes only the average doses of clomiphene. If your dose is different, do not change it unless your doctor tells you to do so.

The amount of medicine that you take depends on the strength of the medicine. Also, the number of doses you take each day, the time allowed between doses, and the length of time you take the medicine depend on the medical problem for which you are using the medicine.

• For oral dosage form (tablets):
  • For treating infertility:
    • Adults—50 milligrams (mg) a day for five days of a menstrual cycle. The treatment is usually started on the fifth day of your menstrual period. If you do not have menstrual cycles, you can begin taking your medicine at any time. If you do not become pregnant after the first course, your doctor may increase your dose a little at a time up to 250 mg a day. Your treatment may be repeated until you do become pregnant or for up to four treatment cycles.

Missed Dose

If you miss a dose of clomiphene, take it as soon as possible. However, if it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not double doses.

If you do not remember until it is time for the next dose, take both doses together; then go back to your regular dosing schedule. If you miss more than one dose, check with your doctor.

Storage

Store the medicine in a closed container at room temperature, away from heat, moisture, and direct light. Keep from freezing.

Keep out of the reach of children.

Do not keep outdated medicine or medicine no longer needed.

Along with its needed effects, a medicine may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur:

• Bloating
• stomach or pelvic pain

Check with your doctor as soon as possible if any of the following side effects occur:

• Blurred vision
• decreased or double vision or other vision problems
• seeing flashes of light
• sensitivity of eyes to light
• yellow eyes or skin

Some side effects 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:

• Hot flashes

• Breast discomfort
• dizziness or lightheadedness
• headache
• heavy menstrual periods or bleeding between periods
• mental depression
• nausea or vomiting
• nervousness
• restlessness
• tiredness
• trouble in sleeping

Other side effects not listed may also occur in some patients. If you notice any other effects, check with your healthcare professional.

Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.

• If your symptoms or health problems do not get better or if they become worse, call your doctor.
• Do not share your drugs with others and do not take anyone else's drugs.
• Keep a list of all your drugs (prescription, natural products, vitamins, OTC) with you. Give this list to your doctor.
• Talk with the doctor before starting any new drug, including prescription or OTC, natural products, or vitamins.
• Some drugs may have another patient information leaflet. Check with your pharmacist. If you have any questions about this medicine, please talk with your doctor, nurse, pharmacist, or other health care provider.
• If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.

This information should not be used to decide whether or not to take clomiphene or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this medicine. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to clomiphene. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using this medicine.

Review Date: October 4, 2017

Tolerance, abuse, or dependence with Clomiphene citrate tablets USP has not been reported.

General Considerations

The workup and treatment of candidates for Clomiphene citrate tablets USP therapy should be supervised by physicians experienced in management of gynecologic or endocrine disorders. Patients should be chosen for therapy with Clomiphene citrate tablets USP 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 Clomiphene citrate tablets USP. 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 Clomiphene citrate tablets USP. 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 Clomiphene citrate tablets USP. 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 Clomiphene citrate tablets USP 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 6 cycles (see PRECAUTIONS).

Ovulation induction: Oral: Females: Note: Intercourse should be timed to coincide with the expected time of ovulation (usually 5 to 10 days after a clomiphene course).

Initial course: 50 mg once daily for 5 days. Begin on or about the fifth day of cycle if progestin-induced bleeding is scheduled or spontaneous uterine bleeding occurs prior to therapy. Therapy may be initiated at anytime in patients with no recent uterine bleeding.

Dose adjustment: Subsequent doses may be increased to 100 mg once daily for 5 days only if ovulation does not occur at the initial dose. Lower doses (12.5 to 25 mg daily) may be used in women sensitive to clomiphene or who consistently develop large ovarian cysts (ASRM 2013).

Repeat courses: If needed, the 5-day cycle may be repeated as early as 30 days after the previous one. Exclude the presence of pregnancy. The lowest effective dose should be used.

Maximum dose: 100 mg once daily for 5 days for up to 6 cycles. Discontinue if ovulation does not occur after 3 courses of treatment; or if 3 ovulatory responses occur but pregnancy is not achieved. Long-term therapy (>6 cycles) is not recommended. Re-evaluate if menses does not occur following ovulatory response. Doses have ranged from 50 to 250 mg daily, although doses >100 mg daily have not been shown to increase pregnancy rates (ASRM 2013). The maximum recommended dose in women with PCOS is 150 mg daily (ESHRE/ASRM 2008).

The total daily dose should be taken at one time to maximize effectiveness (Dickey, 1996).

>10%: Endocrine & metabolic: Ovary enlargement (14%)

1% to 10%:

Central nervous system: Headache (1%)

Endocrine & metabolic: Hot flash (10%)

Gastrointestinal: Abdominal distention (≤6%), abdominal distress (≤6%), bloating (≤6%), nausea (2%), vomiting (2%)

Genitourinary: Breast disease (discomfort: 2%), abnormal uterine bleeding (1%)

Ophthalmic: Visual disturbance (2%, includes blurred vision, diplopia, phosphene, photophobia, photopsia, scotomata, seeing visual waves, vitreous opacity)

<1% (Limited to important or life-threatening): Accommodation disturbance, acne vulgaris, alopecia, anxiety, arthralgia, back pain, cardiac arrhythmia, cataract, cerebrovascular accident, chest pain, constipation, depression, dermatitis, diarrhea, dizziness, dry hair, dyspnea, ectopic pregnancy, edema, endometriosis, erythema multiforme, erythema nodosum, eye pain, fatigue, fever, hepatitis, hypersensitivity reaction, hypertension, hypertrichosis, increased appetite, increased serum transaminases, increased urine output, insomnia, irritability, leukocytosis, macular edema, migraine, mood changes, myalgia, neoplasm, nervousness, optic neuritis, ovarian cyst, ovarian hemorrhage, palpitations, paresthesia, phlebitis, pruritus, psychosis, pulmonary embolism, retinal hemorrhage, retinal thrombosis, retinal vascular spasm, seizure, severe abdominal pain, skin rash, syncope, tachycardia, thrombophlebitis, thyroid disease, tinnitus, urinary frequency, urticaria, uterine hemorrhage, vaginal dryness, vertigo, vision loss (temporary/prolonged), vitreous detachment (posterior), weakness, weight gain, weight loss