Menopur

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

This medicine is injected under the skin. You may be shown how to use injections at home. Do not self-inject this medicine if you do not understand how to give the injection and properly dispose of used needles and syringes.

Menotropins come in a powder medicine that must be mixed with a liquid (diluent) before using it. If you are using the injections at home, be sure you understand how to properly mix and store the medicine.

Read all patient information, medication guides, and instruction sheets provided to you. Ask your doctor or pharmacist if you have any questions.

Gently swirl the medicine after mixing. Do not shake the mixed medicine or it may foam. Prepare your dose only when you are ready to give an injection, do not save it for later use. Do not use if the mixture has changed colors or has particles in it. Call your pharmacist for new medicine.

You may need to use more than 1 vial of menotropins for your entire dose.

After giving the injection, throw away any portion of the mixed medicine that is not used right away. Do not save it for later use.

For the best results from your fertility treatments, follow your doctor's instructions very carefully.

Use a disposable needle and syringe only once. Follow any state or local laws about throwing away used needles and syringes. Use a puncture-proof "sharps" disposal container (ask your pharmacist where to get one and how to throw it away). Keep this container out of the reach of children and pets.

To be sure the medicine is effective, you will need frequent blood tests and ultrasound exams. You may also need to record your temperature on a daily chart.

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

You may also store the powder in a refrigerator. Do not freeze.

Infertility is often treated with a combination of drugs. Use all medications as directed by your doctor. Read the medication guide or patient instructions provided with each medication. Do not change your doses or medication schedule without your doctor's advice.

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222.

Call your doctor for instructions if you miss a dose of menotropins.

• Ferring Pharmaceuticals, Inc.

Serious side effects have been reported with Menopur. See the “Drug Precautions” section.

Common side effects of Menopur include the following:

• stomach cramps 
• stomach pain
• stomach fullness and bloating
• enlarged ovaries
• headache
• injection site swelling, heat, redness, and pain

This is not a complete list of Menopur 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.

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 Menopur, there are no specific foods that you must exclude from your diet when receiving this medication.

Tell your doctor if you are pregnant or plan to become 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.

Menopur 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.

You should not use this medicine if you have primary ovarian failure, abnormal vaginal bleeding, uncontrolled thyroid or adrenal gland disorders, an ovarian cyst, breast cancer, uterine or ovarian cancer, a tumor of your pituitary gland or hypothalamus, or infertility that is not caused by lack of ovulation.

Do not use menotropins if you are pregnant.

• Store powder at room temperature or in a refrigerator.
• Protect powder from light.
• Use right away after mixing.
• Keep all drugs in a safe place. Keep all drugs out of the reach of children and pets.
• Check with your pharmacist about how to throw out unused drugs.

The following serious adverse reactions are discussed elsewhere in the labeling:

• Abnormal Ovarian Enlargement [see Warnings and Precautions (5.1)]
• Ovarian Hyperstimulation Syndrome [see Warnings and Precautions (5.2)]
• Atelectasis, acute respiratory distress syndrome and exacerbation of asthma [see Warnings and Precautions (5.3)]
• Thromboembolic events [see Warnings and Precautions (5.3)]
• Ovarian Torsion [see Warnings and Precautions (5.4)]
• Multi-fetal Gestation and Birth [see Warnings and Precautions (5.5)]
• Congenital Malformations [see Warnings and Precautions (5.6)]
• Ectopic Pregnancy [see Warnings and Precautions (5.7)]
• Spontaneous Abortion [see Warnings and Precautions (5.8)]
• Ovarian Neoplasms [see Warnings and Precautions (5.9)]

Clinical Trial Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trial of another drug and may not reflect the rates observed in practice.

In two single cycle, open label, multinational, multicenter, comparative trials, a total of 434 normal ovulatory infertile women were randomized and received subcutaneously administered Menopur as part of an in vitro fertilization (IVF) cycle (both trials) or intracytoplasmic sperm injection (ICSI)] cycle (one of the two trials). All women received pituitary down-regulation with gonadotropin releasing hormone (GnRH) agonist before stimulation. Adverse Reactions occurring at an incidence of ≥ 2% in women receiving Menopur are shown in Table 1.

In addition, thrombophlebitis was reported in less than 1% of subjects.

In an open label, US, multicenter, comparative IVF and ICSI trial, Menopur and BRAVELLE were administered in the same syringe to 60 normal ovulatory infertile women. OHSS, post retrieval cramping and nausea and spontaneous abortion were the most common adverse reactions occurring at an incidence of ≥ 5% in women receiving the combination of Menopur and BRAVELLE.

In another open label, US multicenter, comparative trial for ovulation induction in anovulatory or oligovulatory infertile women, 76 subjects received subcutaneous or intramuscular injections of Menopur. The most common adverse reactions occurring at an incidence of ≥ 5% in women receiving Menopur were: headache; OHSS; injection site reaction, abdominal cramps, fullness and pain; and nausea.

Postmarketing Experience

The following adverse reactions have been reported during postmarketing use of gonadotropins. Because these reactions were reported voluntarily from a population of uncertain size, the frequency or a causal relationship to Menopur cannot be reliably determined.

Gastrointestinal disorders: abdominal pain, abdominal pain lower, abdominal distension, nausea, vomiting, abdominal discomfort

General disorders and administration site conditions: injection site reactions (most frequently reported injection site reaction was injection site pain), fatigue

Nervous system disorders: headache, dizziness

Reproductive system disorders: OHSS [see Warnings and Precautions (5.2)], pelvic pain, ovarian cyst, breast complaints (including breast pain, breast tenderness, breast discomfort, and breast swelling)

Skin and subcutaneous tissue disorders: acne, rash

Vascular disorders: hot flush

No drug/drug interaction studies in humans have been conducted for Menopur.

Pregnancy

Teratogenic effects

Pregnancy Category X [see Contraindications (4)].

Nursing Mothers

It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in the nursing infant from Menopur, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.

Pediatric Use

Safety and effectiveness in pediatric patients have not been established.

Renal and Hepatic Insufficiency

Safety, efficacy, and pharmacokinetics of Menopur in women with renal or hepatic insufficiency have not been established.

The efficacy of Menopur was established in one randomized, open-label, multicenter, multinational (in Europe and Israel), comparative clinical trial of women undergoing in vitro fertilization (IVF) or IVF plus intracytoplasmic injection (ICSI) to achieve pregnancy.

All women began ovarian stimulation as part of an IVF cycle following pituitary suppression with a GnRH agonist. A total of 373 patients were randomized to the Menopur arm. Randomization was stratified by insemination technique [conventional IVF vs. ICSI]. Efficacy was assessed based on the primary efficacy parameter of continuing pregnancy. The initial daily dose of Menopur was 225 International Units administered subcutaneously for five days. Thereafter, the dose was individualized according to each patient's response, up to a maximum of 450 IU/day for a total maximum duration of stimulation of 20 days. Treatment outcomes are summarized in Table 3.

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

• Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.
• Breast pain.
• Enlarged breasts.
• A fast heartbeat.
• Yellow skin or eyes.
• Fast breathing.
• Pale skin.
• Change in color of skin to a bluish color like on the lips, nail beds, fingers, or toes.
• Flu-like signs.
• Ovarian hyperstimulation syndrome (OHSS) is a very bad side effect that may happen in some women who use this drug. Call your doctor right away if you have very bad stomach pain or bloating; very upset stomach, throwing up, or loose stools (diarrhea); a big weight gain; shortness of breath; or change in how much urine is passed.
• Blood clots have happened with this drug. Sometimes, these blood clots have been deadly. Call your doctor right away if you have chest, arm, back, neck, or jaw pain or pressure; coughing up blood; numbness or weakness on 1 side of your body, trouble speaking or thinking, change in balance, or change in eyesight; shortness of breath; or swelling, warmth, or pain in the leg or arm.