Serophene

Serophene is a prescription medication used to induce ovulation in women who do not produce eggs but wish to become pregnant.  Serophene belongs to a group of drugs called ovulatory stimulants. These work similarly to estrogen, a female hormone that causes eggs to develop in the ovaries and be released.

This medication comes in tablet form and is usually taken once a day by mouth, with or without food, for 5 days.

Common side effects of Serophene include upset stomach, flushing, nausea and vomiting, and breast discomfort.

Serophene can also cause blurred vision or dizziness.  Do not drive or operate heavy machinery until you know how Serophene affects you.

• EMD Serono, Inc.

Serious side effects have been reported with Serophene. See the "Drug Precautions" section.

The most common side effects of Serophene include the following:

• upset stomach
• nausea
• vomiting
• flushing (feeling of warmth)
• headache
• breast discomfort

This is not a complete list of Serophene side effects. Ask your doctor or pharmacist for more information.

Tell your doctor if you have any side effect that bothers you or that does not go away.

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

Your doctor will perform medical tests to make sure you do not have conditions that would prevent you from safely using clomiphene.

Follow all directions on your prescription label. Your doctor may occasionally change your dose to make sure you get the best results. Do not take this medicine in larger or smaller amounts or for longer than recommended.

Clomiphene is usually taken for 5 days, starting on the 5th day of your menstrual period. Follow your doctor's instructions.

You will need to have a pelvic examination before each treatment cycle. You must remain under the care of a doctor while you are using clomiphene.

You will most likely ovulate within 5 to 10 days after you take clomiphene. To improve your chance of becoming pregnant, you should have sexual intercourse while you are ovulating.

Your doctor may have you take your temperature each morning and record your daily readings on a chart. This will help you determine when you can expect ovulation to occur.

In most cases, clomiphene should not be used for more than 3 treatment cycles.

If ovulation occurs but you do not get pregnant after 3 treatment cycles, your doctor may stop treatment and evaluate your infertility further.

Store at room temperature away from moisture, heat, and light.

In deciding to use a medicine, the risks of taking the medicine must be weighed against the good it will do. This is a decision you and your doctor will make. For this medicine, the following should be considered:

Allergies

Tell your doctor if you have ever had any unusual or allergic reaction to this medicine or any other medicines. Also tell your health care professional if you have any other types of allergies, such as to foods, dyes, preservatives, or animals. For non-prescription products, read the label or package ingredients carefully.

Pregnancy

Breast Feeding

There are no adequate studies in women for determining infant risk when using this medication during breastfeeding. Weigh the potential benefits against the potential risks before taking this medication while breastfeeding.

Interactions with Medicines

Although certain medicines should not be used together at all, in other cases two different medicines may be used together even if an interaction might occur. In these cases, your doctor may want to change the dose, or other precautions may be necessary. Tell your healthcare professional if you are taking any other prescription or nonprescription (over-the-counter [OTC]) medicine.

Interactions with Food/Tobacco/Alcohol

Certain medicines should not be used at or around the time of eating food or eating certain types of food since interactions may occur. Using alcohol or tobacco with certain medicines may also cause interactions to occur. Discuss with your healthcare professional the use of your medicine with food, alcohol, or tobacco.

Other Medical Problems

The presence of other medical problems may affect the use of this medicine. Make sure you tell your doctor if you have any other medical problems, especially:

• Unusually large ovary or
• Cyst on ovary—Clomiphene may cause the cyst to increase in size

• Endometriosis—Inducing ovulation (including using clomiphene) may worsen endometriosis because the body estrogen level is increased; estrogen can cause growth of endometriosis implants

• Fibroid tumors of the uterus—Clomiphene may cause fibroid tumors to increase in size

• Inflamed veins due to blood clots—Clomiphene may make condition worse

• Liver disease (or history of)—Clomiphene may make any liver disease worse

• Mental depression—Existing depression may become worse because of hormone changes caused by clomiphene

• Unusual vaginal bleeding—Some irregular vaginal bleeding is a sign that the lining of the uterus is growing too much or is a sign of cancer of the uterus lining; these problems must be ruled out before clomiphene is used because clomiphene can make these conditions worse

This section provides information on the proper use of a number of products that contain clomiphene. It may not be specific to Serophene. Please read with care.

Take this medicine 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 this medicine 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 this medicine. 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 this medicine, 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.

• It is used to help women get pregnant.
• It may be given to you for other reasons. Talk with the doctor.

All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:

• Hot flashes.

These are not all of the side effects that may occur. If you have questions about side effects, call your doctor. Call your doctor for medical advice about side effects.

You may report side effects to the FDA at 1-800-FDA-1088. You may also report side effects at http://www.fda.gov/medwatch.

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 clomiPHENE citrate.  These visual symptoms increase in incidence with increasing total dose or therapy duration and generally disappear within a few days or weeks after clomiPHENE citrate therapy is discontinued. However, prolonged visual disturbances have been reported after clomiPHENE citrate therapy has been discontinued and these disturbances may be irreversible. 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 clomiPHENE citrate 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 clomiPHENE citrate administration, which disappeared by the 32nd day after stopping therapy.

Postmarketing surveillance of adverse events has also revealed other visual signs and symptoms during clomiPHENE citrate 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. It may progress rapidly (within 24 hours to several days) to become a serious medical event. 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 clomiPHENE citrate 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 clomiPHENE citrate.  Some patients with polycystic ovary syndrome who are unusually sensitive to gonadotropin may have an exaggerated response to usual doses of clomiPHENE citrate.  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 clomiPHENE citrate 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 clomiPHENE citrate therapy usually regress spontaneously within a few days or weeks after discontinuing treatment.  The potential benefit of subsequent clomiPHENE citrate 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.

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