Metrodin

Metrodin® (urofollitropin for injection) is a preparation of gonadotropin extracted from the urine of postmenopausal women. Each ampule of Metrodin® (urofollitropin for injection) contains 75 or 150 IU of follicle-stimulating hormone (FSH) activity, in not more than 0.83 mg (75 IU) or 1.66 mg (150 IU) of extract, plus 10 mg lactose in a sterile, lyophilized form. Metrodin® (urofollitropin for injection) is administered by intramuscular injection.

Metrodin® (urofollitropin for injection) contains an acidic, water soluble glycoprotein biologically standardized for FSH gonadotropin activity in terms of the Second International Reference Preparation for Human Menopausal Gonadotropins established in September, 1964 by the Expert Committee on Biological Standards of the World Health Organization. Negligible amounts (less than 1 IU per 75 IU FSH) of luteinizing hormone (LH) activity are contained in Metrodin® (urofollitropin for injection) .

Therapeutic Class: Infertility.

Metrodin® (urofollitropin for injection) and hCG given in a sequential manner are indicated for the stimulation of follicular development and the induction of ovulation in patients with polycystic ovary syndrome, and infertility, who have failed to respond or conceive following adequate clomiphene citrate therapy.

Metrodin® (urofollitropin for injection) and hCG may also be used to stimulate the development of multiple follicles in ovulatory patients undergoing Assisted Reproductive Technologies (ART) such as in vitro fertilization.

Selection of Patients

1. Before treatment with Metrodin® (urofollitropin for injection) is instituted, a thorough gynecologic and endocrinologic evaluation must be performed. This should include an assessment of pelvic anatomy. Patients with tubal obstruction should receive Metrodin® (urofollitropin for injection) only if enrolled in an in vitro fertilization program.

2. Primary ovarian failure should be excluded by the determination of gonadotropin levels.

3. Careful examination should be made to rule out the presence of early pregnancy.

4. Patients in late reproductive life have a greater predisposition to endometrial carcinoma as well as a higher incidence of anovulatory disorders. A thorough diagnostic examination should always be performed before starting Metrodin® (urofollitropin for injection) therapy in such patients who demonstrate abnormal uterine bleeding or other signs of endometrial abnormalities.

5. Evaluation of the husbands fertility potential should be included in the workup.

The following adverse reactions reported during Metrodin® (urofollitropin for injection) therapy are listed in decreasing order of potential severity:

1. Pulmonary and vascular complications (see WARNINGS),

2. Ovarian Hyperstimulation Syndrome (see WARNINGS),

3. Adnexal torsion (as a complication of ovarian enlargement),

4. Mild to moderate ovarian enlargement,

5. Abdominal pain,

6. Sensitivity to Metrodin® (urofollitropin for injection) ,

(Febrile reactions which may be accompanied by chills, musculoskeletal aches, joint pains, malaise, headache, and fatigue have occurred after the administration of Metrodin® (urofollitropin for injection) . It is not clear whether or not these were pyrogenic responses or possible allergic reactions.)

7. Ovarian cysts,

8. Gastrointestinal symptoms (nausea, vomiting, diarrhea, abdominal cramps, bloating),

9. Pain, rash, swelling, and/or irritation at the site of injection,

10. Breast tenderness,

11. Headache,

12. Dermatological symptoms (dry skin, body rash, hair loss, hives),

13. Hemoperitoneum has been reported during menotropins therapy and, therefore, may also occur during Metrodin® (urofollitropin for injection) therapy.

14. There have been infrequent reports of ovarian neoplasms, both benign and malignant, in women who have undergone multiple drug regimens for ovulation induction; however, a causal relationship has not been established.

The following medical events have been reported subsequent to pregnancies resulting from Metrodin® (urofollitropin for injection) therapy:

1. Ectopic pregnancy

2. Congenital abnormalities

(Three incidents of chromosomal abnormalities and four birth defects have been reported following Metrodin® (urofollitropin for injection) -hCG or Metrodin® (urofollitropin for injection) , Pergonal® (menotropins for injection, USP) hCG therapy in clinical trials for stimulation prior to in vitro fertilization. The aborted pregnancies included one Trisomy 13, one Trisomy 18, and one fetus with multiple congenital anomalies (hydrocephaly, omphalocele, and meningocele). One meningocele, one external ear defect, one dislocated hip and ankle, and one dilated cardiomyopathy in presence of maternal Systemic Lupus Erythematosis were reported. None of these events was thought to be drug-related. The incidence does not exceed that found in the general population.)

Drug Abuse and Dependence

There have been no reports of abuse or dependence with Metrodin® (urofollitropin for injection) .

If severe OHSS occurs, treatment should be stopped and the patient should be hospitalized. A physician experienced in the management of this syndrome, or who is experienced in the management in fluid and electrolyte imbalances should be consulted.

Pulmonary and Vascular Complications: The following paragraph describes serious medical events reported following gonadotropin therapy.

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 Ovarian Hyperstimulation Syndrome have been reported. Intravascular thrombosis and embolism can result in reduced blood wflow to critical organs or the extremities. Sequelae of such events have included venous thrombophlebitis, 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 Births: Reports of multiple births have been associated with Metrodin® (urofollitropin for injection) -hCG treatment, including triplet and quintuplet gestations. In clinical studies with Metrodin® (urofollitropin for injection) , 81.4% of the pregnancies following ovulation induction therapy resulted in single births and 18.6% in multiple births. The risk of multiple births in patients undergoing ART procedures is related to the number of embryos replaced. The patient and her husband should be advised of the potential risk of multiple births before starting treatment.

Prior to the therapy with Metrodin® (urofollitropin for injection) patients should be informed of the duration of treatment and monitoring of their condition that will be required. Possible adverse reactions (see ADVERSE REACTIONS) and the risk of multiple births should also be discussed.