Menopur® (menotropins injection) is a drug that should only be used by physicians who are thoroughly familiar with infertility problems. It is a potent gonadotropic substance capable of Ovarian Hyperstimulation Syndrome (OHSS) in women with or without pulmonary or vascular complications. Gonadotropin therapy requires a certain time commitment by physicians and supportive health professionals, and its use requires the availability of appropriate monitoring facilities (see PRECAUTIONS -Laboratory Tests).

Overstimulation of the Ovary During Menopur® (menotropins injection) Therapy

Ovarian Enlargement: Mild to moderate uncomplicated ovarian enlargement which may be accompanied by abdominal distension and/or abdominal pain occurs in approximately 5 to 10 % of women treated with menotropins and hCG, and generally regresses without treatment within two or three weeks. The lowest dose consistent with expectation of good results and careful monitoring of ovarian response can further minimize the risk of overstimulation.

If the ovaries are abnormally enlarged on the last day of Menopur® (menotropins injection) therapy, hCG should not be administered in this course of treatment; this will reduce the chances of development of the Ovarian Hyperstimulation Syndrome (OHSS).

OHSS: OHSS is a medical event distinct from uncomplicated ovarian enlargement. OHSS may progress rapidly to become a serious medical event. It is characterized by an apparent dramatic increase in vascular permeability which can result in a rapid accumulation of fluid in the peritoneal cavity, thorax, and potentially, the pericardium. The early warning signs of development of OHSS are severe pelvic pain, nausea, vomiting, and weight gain. The following symptomatology has been seen with cases of OHSS: abdominal pain, abdominal distension, gastrointestinal symptoms including nausea, vomiting and diarrhea, severe ovarian enlargement, weight gain, dyspnea, and oliguria. Clinical evaluation may reveal hypovolemia, hemoconcentration, electrolyte imbalances, ascites, hemoperitoneum, pleural effusions, hydrothorax, acute pulmonary distress, and thromboembolic events (See "Pulmonary and Vascular Complications"). 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 the OHSS.

In the IVF clinical study, 0399E, OHSS occurred in 7.2% of the 373 Menopur® (menotropins injection) treated women.

Cases of OHSS are more common, more severe and more protracted if pregnancy occurs. OHSS develops rapidly; therefore patients should be followed for at least two weeks after hCG administration. Most often, OHSS occurs after treatment has been discontinued and reaches its maximum at about seven to ten days following treatment. Usually, OHSS resolves spontaneously with the onset of menses. If there is evidence that OHSS may be developing prior to hCG administration (see PRECAUTIONS -Laboratory Tests), the hCG should be withheld. If severe OHSS occurs, treatment must be stopped and the patient should be hospitalized.

A physician experienced in the management of the syndrome, or who is experienced in the management of fluid and electrolyte imbalances, should be consulted.

Pulmonary and Vascular Complications

Serious pulmonary conditions (e.g. atelectasis, acute respiratory distress syndrome) have been reported. In addition, thromboembolic events both in association with, and separate from, the OHSS have been reported following menotropins therapy. Intravascular thrombosis and embolism, which may originate in venous or arterial vessels, can result in reduced blood flow to critical organs or the extremities. Sequelae of such events have included venous tbrombophlebitis, pulmonary embolism, pulmonary infarction, cerebral vascular occlusion (stroke), and arterial occlusion resulting in loss of limb. In rare cases, pulmonary complications and/or thromboembolic events have resulted in death.

Multiple Pregnancies

In the clinical trial multiple pregnancy as diagnosed by ultrasound occurred in 35.3% (n=30) of 85 total pregnancies.

The patient and her partner should be advised of the potential risk of multiple births before starting treatment.

General

Careful attention should be given to the diagnosis of infertility in the selection of candidates for Menopur® therapy (see "INDICATIONS AND USAGE - Selection of Patients").

Laboratory Tests

The combination of both estradiol levels and ultrasonography are useful for monitoring the growth and development of follicles, timing hCG administration, as well as minimizing the risk of the OHSS and multiple gestations.

The clinical confirmation of ovulation, is determined by:

1. A rise in basal body temperature;
2. Increase in serum progesterone; and
3. Menstruation following the shift in basal body temperature.

When used in conjunction with indices of progesterone production, sonographic visualization of the ovaries will assist in determining if ovulation has occurred. Sonographic evidence of ovulation may include the following:

1. Fluid in the cul-de-sac;
2. Ovarian stigmata; and
3. Collapsed follicle.

Because of the subjectivity of the various tests for the determination of follicular maturation and ovulation, it cannot be overemphasized that the physician should choose tests with which he/she is thoroughly familiar.

Carcinogenesis and Mutagenesis

Long-term toxicity studies in animals have not been performed to evaluate the carcinogenic potential of menotropins.

Pregnancy

Pregnancy Category X: See CONTRAINDICATIONS section.

Nursing Mothers

It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised if menotropins are administered to a nursing woman.

Pediatric Patients

Safety and effectiveness in pediatric patients have not been established.

Geriatric Patients

Safety and effectiveness in geriatric patients have not been established.

Last reviewed on RxList: 2/25/2009
This monograph has been modified to include the generic and brand name in many instances.