Follitropin alfa

4 CONTRAINDICATIONS GONAL-f is contraindicated in women and men who exhibit: Prior hypersensitivity to recombinant FSH products or one of their excipients. Reactions have included anaphylaxis [see Warning and Precautions ] High levels of FSH indicating primary gonadal failure The presence of uncontrolled non-gonadal endocrinopathies (for example, thyroid, adrenal, or pituitary disorders) Sex hormone dependent tumors of the reproductive tract and accessory organs Tumors of pituitary gland or hypothalamus GONAL-f is also contraindicated in women who exhibit: Abnormal uterine bleeding of undetermined origin Ovarian cyst or enlargement of undetermined origin GONAL-f is contraindicated in women and men who exhibit: Prior hypersensitivity to recombinant FSH products or one of their excipients High levels of FSH indicating primary gonadal failure Uncontrolled non-gonadal endocrinopathies Sex hormone dependent tumors of the reproductive tract and accessory organs Tumors of pituitary gland or hypothalamus GONAL-f is also contraindicated in women who exhibit: Abnormal uterine bleeding of undetermined origin Ovarian cyst or enlargement of undetermined origin 5 WARNINGS AND PRECAUTIONS Hypersensitivity Reactions and Anaphylaxis: If occurs, initiate appropriate therapy including supportive measures, and discontinue GONAL-f Ovarian Hyperstimulation Syndrome: If serious, stop gonadotropins, including hCG, and determine if the woman needs to be hospitalized.

OHSS is characterized by a 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. Abdominal pain, abdominal distension, gastrointestinal symptoms including nausea, vomiting and diarrhea, severe ovarian enlargement [see Warnings and Precautions ] , weight gain, dyspnea, and oliguria have been reported with OHSS.

Because the use of diuretics can accentuate the diminished intravascular volume, avoid diuretics except in the late phase of resolution as described below. The management of OHSS is divided into three phases as follows: Acute Phase : Management is directed at preventing hemoconcentration due to loss of intravascular volume to the third space and minimizing the risk of thromboembolic phenomena and kidney damage.

Peripheral and/or pulmonary edema may result if the kidneys are unable to excrete third space fluid as rapidly as it is mobilized. Diuretics may be indicated during the resolution phase, if necessary, to combat pulmonary edema. Do not remove ascitic, pleural, and pericardial fluid, unless there is the necessity to relieve symptoms such as pulmonary distress or cardiac tamponade.

Important Dosage and Administration Information Only physicians who are experienced in infertility treatment, should treat women with GONAL-f. GONAL-f is a gonadotropin product capable of causing in women, Ovarian Hyperstimulation Syndrome (OHSS) with or without pulmonary or vascular complications [see Warnings and Precautions (5.2 , 5.3) ] and multiple births [see Warnings and Precautions ] .

Gonadotropin therapy requires the availability of appropriate monitoring facilities [see Warnings and Precautions ] . Use the lowest effective dose of GONAL-f. Give careful attention to the diagnosis of infertility and the selection of candidates for GONAL-f therapy [see Dosage and Administration (2.3 , 2.4) ] .

Preparation of GONAL-f and Selection of Injection Site Store lyophilized multiple-dose vials refrigerated or at room temperature (2°-25°C /36°-77°F) and protected from light. Prior to administration, parenteral drug products should be inspected visually for particulate matter and discoloration, whenever solution and container permit.

Instruct women and men to use the accompanying syringes, calibrated in International Units FSH for administration. The 27-gauge injection syringe (see figure below) has unit dose markings from