Pregnyl Choriogonadotropin Alfa Kit — NDC 50090-7089-0 (Billing 50090-7089-00)

WARNINGS Use hCG in conjunction with gonadotropin therapy only if the physician is experienced with infertility problems and is familiar with the criteria for patient selection, contraindications, warnings, precautions, and adverse reactions described in the package insert for gonadotropins. Gonadotropin therapy, including hCG, requires a certain time commitment by physicians and supportive health professionals, and requires the availability of appropriate monitoring facilities (see PRECAUTIONS/Laboratory Tests ). Safe and effective induction of ovulation with use of PREGNYL requires monitoring of ovarian response with serum estradiol and transvaginal ultrasound on a regular basis.

Anaphylaxis Anaphylaxis has been reported with urinary-derived hCG products. Ovarian Hyperstimulation Syndrome (OHSS) Ovarian Hyperstimulation Syndrome (OHSS) is a medical event distinct from uncomplicated ovarian enlargement and may progress rapidly to become a serious medical event. 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 the 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, weight gain, dyspnea, and oliguria have been reported with OHSS. Clinical evaluation may reveal hypovolemia, hemoconcentration, electrolyte imbalances, ascites, hemoperitoneum, pleural effusions, hydrothorax, acute pulmonary distress, and thromboembolic reactions.

Transient liver function test abnormalities suggestive of hepatic dysfunction with or without morphologic changes on liver biopsy, have been reported in association with OHSS. OHSS occurs after gonadotropin treatment has been discontinued and it can develop rapidly, reaching its maximum 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, withhold hCG. Cases of OHSS are more common, more severe, and more protracted if pregnancy occurs; therefore, assess women for the development of OHSS for at least two weeks after hCG administration. Severe OHSS may be life-threatening.

Monitor women undergoing ovarian stimulation for early signs and symptoms of OHSS. Women with known risk factors for a high ovarian response may be especially prone to the development of OHSS during or following treatment with PREGNYL. Adherence to the recommended PREGNYL dose and treatment regimen and careful monitoring of ovarian response is important to reduce the risk of OHSS.

If serious OHSS occurs, stop gonadotropins, including hCG, and consider whether the woman should be hospitalized. Treatment is primarily symptomatic and overall consists of bed rest, fluid and electrolyte management, and analgesics (if needed). Because the use of diuretics can accentuate the diminished intravascular volume, avoid diuretics except in the late phase of resolution.

Initiate early consultation with a physician experienced in the management of OHSS and fluid and electrolyte imbalances. Pulmonary and Vascular Complications Serious pulmonary conditions (e.g., atelectasis, acute respiratory distress syndrome) have been reported in women treated with gonadotropins. In addition, thromboembolic reactions both in association with, and separate from OHSS have been reported following gonadotropin therapy.

Intravascular thrombosis, which may originate in venous or arterial vessels, can result in reduced blood flow to vital organs or the extremities. Women with generally recognized risk factors for thrombosis, such as a personal or family history, severe obesity, or thrombophilia, may have an increased risk of venous or arterial thromboembolic events, during or following treatment with gonadotropins. Sequelae o… [Excerpted — this section continues on DailyMed.]

ADVERSE REACTIONS For males and females Immune system disorders Hypersensitivity reactions, both localized and systemic in nature, including anaphylaxis have been reported. In rare cases, generalized rash or fever may occur (see CONTRAINDICATIONS and WARNINGS ). If a hypersensitivity reaction is suspected, discontinue PREGNYL and assess for other potential causes for the event.

Psychiatric disorders Irritability Restlessness Depression Nervous system disorders Headache General disorders and administration site conditions PREGNYL may cause reactions at the site of injection, such as bruising, pain, redness, swelling and itching. Occasionally, allergic reactions have been reported, mostly manifesting as pain and/or rash at the injection site (see CONTRAINDICATIONS and WARNINGS ). Edema Fatigue In the female: Vascular disorders In rare instances, thromboembolism has been associated with FSH/hCG therapy, usually associated with severe OHSS (see WARNINGS ).

Respiratory, thoracic and mediastinal disorders Hydrothorax, as a complication of severe OHSS (see WARNINGS ). Gastrointestinal disorders Abdominal pain and gastrointestinal symptoms such as nausea and diarrhea, related to mild OHSS. Ascites, as a complication of severe OHSS (see WARNINGS ).

Reproductive system and breast disorders Unwanted ovarian hyperstimulation, mild or severe Ovarian Hyperstimulation Syndrome (see WARNINGS ). Mild to moderate enlargement of ovaries and ovarian cysts related to mild OHSS. Large ovarian cysts (prone to rupture), usually associated with severe OHSS (see WARNINGS ).

Painful breasts Investigations Weight gain as a characteristic of severe OHSS (see WARNINGS ). In the male: Metabolism and nutrition disorders Water and sodium retention is occasionally seen after administration of high dosages; this is regarded as a result of excessive androgen production. Reproductive system and breast disorders HCG treatment may sporadically cause gynecomastia.

Precocious puberty

PRECAUTIONS General Induction of androgen secretion by hCG may cause fluid retention. Use hCG with caution in patients with cardiac or renal disease, hypertension, epilepsy, migraine, or asthma. Careful attention should be given to the diagnosis of infertility in candidates for hCG therapy (see INDICATIONS AND USAGE ).

Evaluate patients for uncontrolled non-gonadal endocrinopathies (e.g., thyroid, adrenal or pituitary disorders) and provide the appropriate specific treatment. Information for Patients Prior to therapy with hCG, patients should be informed of the duration of treatment and monitoring of their condition that will be required. The risks of Ovarian Hyperstimulation Syndrome and multiple births in women (see WARNINGS ) and other possible adverse reactions (see ADVERSE REACTIONS ) should also be discussed.

Laboratory Tests In most instances, treatment of women with FSH results only in follicular recruitment and development. In the absence of an endogenous LH surge, hCG is given when monitoring of the patient indicates that sufficient follicular development has occurred. This may be estimated by pelvic ultrasound alone or in combination with measurement of serum estradiol levels.

The combination of both pelvic ultrasound and serum estradiol measurement are useful for monitoring the development of follicles, for timing of the ovulatory trigger, as well as for detecting ovarian enlargement and minimizing the risk of the Ovarian Hyperstimulation Syndrome and multiple gestation. Confirm the number of growing follicles using ultrasonography because serum estrogens do not give an indication of the size or number of follicles. Human chorionic gonadotropins can crossreact in the radioimmunoassay of gonadotropins, especially luteinizing hormone.

Each individual laboratory should establish the degree of crossreactivity with their gonadotropin assay. Make the laboratory aware that the patient is on hCG, if gonadotropin levels are requested. The clinical confirmation of ovulation, with the exception of pregnancy, is obtained by direct and indirect indices of progesterone production as well as sonographic evidence of ovulation.

The indices most generally used are as follows: A rise in basal body temperature Increase in serum progesterone and Menstruation following a shift in basal body temperature Urinary or serum luteinizing hormone (LH) rise When used in conjunction with the 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: Fluid in the cul-de-sac Collapsed follicle Features consistent with corpus luteum formation (e.g., ovarian stigmata, secretory endometrium) Accurate interpretation of the indices of ovulation requires a physician who is experienced in the interpretation of these tests.

Sonographic evaluation of the early pregnancy is also important to rule out ectopic pregnancy. Carcinogenesis, Mutagenesis, Impairment of Fertility Long-term studies in animals have not been performed to evaluate the carcinogenic or mutagenic potential of chorionic gonadotropin. Pregnancy PREGNYL is not indicated in pregnancy.

PREGNYL may be used for luteal phase support, but is discontinued upon confirmation of pregnancy. There are no data on the use of hCG in pregnancy. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.

Pediatric Use Induction of androgen secretion by hCG may induce precocious puberty in pediatric patients treated for cryptorchidism. Discontinue therapy if signs of precocious puberty occur. Lactation 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 hCG is administered to a nursing woman. The developmental and health benefits of breastfeeding should be considered along with… [Excerpted — this section continues on DailyMed.]