Luveris

Follow your doctor's instructions about any restrictions on food, beverages, or activity.

Other drugs may interact with lutropin alfa, including prescription and over-the-counter medicines, vitamins, and herbal products. Tell each of your health care providers about all medicines you use now and any medicine you start or stop using.

Luveris is a prescription medication used to treat infertility in women. It is used with other fertility treatments to help promote the development of the follicle and helps with embryo implantation. 

It belongs to a group of drugs called gonadotropins. These work to help with infertility because it acts like a hormone that is critical in the development of the follicle and embryo implantation. 

This medication is available as an injection and is injected under the skin by a healthcare professional. 

Common side effects of Luveris include headache and stomach pain. 

Gonad-stimulating hormone; a biosynthetic (recombinant DNA origin) form of naturally occurring human LH.1

Contraindications

• Known hypersensitivity to lutropin alfa, other LH preparations, or any ingredient in the formulation.1 8

• Primary ovarian failure.1 8

• Uncontrolled thyroid or adrenal dysfunction.1 8

• Uncontrolled organic intracranial lesions (e.g., pituitary neoplasms).1 8

• Abnormal intrauterine bleeding of undetermined origin.1 8

• Ovarian cysts or enlargement of undetermined origin.1 8

• Sex-hormone-dependent neoplasms of the reproductive tract and accessory organs.1 8

• Known or suspected pregnancy.1 8

Warnings/Precautions

Warnings

Risk of mild to moderate uncomplicated ovarian enlargement; may be accompanied by abdominal distension and/or pain but generally regresses without treatment within 2–3 weeks.1 Careful monitoring of ovarian response recommended.1

If ovaries are abnormally enlarged (i.e., development of ≥3 follicles with a mean diameter of ≥15 mm) and/or if excessive estradiol production (>1100 pg/mL) occurs following the last dose of lutropin alfa and follitropin alfa, withhold hCG administration during the current course of therapy to minimize the risk of development of ovarian hyperstimulation syndrome (OHSS).1 (See Ovarian Hyperstimulation Syndrome under Cautions.)

Risk of potentially severe OHSS, characterized by an apparent dramatic increase in vascular permeability that may result in rapid accumulation of fluid in the peritoneal cavity, thorax, and potentially, the pericardium.1

OHSS may progress rapidly (within 24 hours to several days) and is initially manifested by severe pelvic pain, nausea, vomiting, and weight gain.1 Other symptoms include abdominal pain/distension, diarrhea, dyspnea, and oliguria.1 Hypovolemia, hemoconcentration, electrolyte imbalances, ascites, hemoperitoneum, pleural effusions, hydrothorax, acute pulmonary distress, and thromboembolic events may occur.1

Transient liver function test abnormalities, which may be accompanied by morphologic changes (as detected by liver biopsy) have been reported.1

OHSS occurs most often after completion of gonadotropin therapy; develops rapidly, reaching maximum severity after 7–10 days; and usually resolves spontaneously with the onset of menses.1 OHSS may be more severe and protracted if pregnancy occurs.1

Discontinue therapy with lutropin alfa and follitropin alfa if ovaries are abnormally enlarged or abdominal pain occurs; withhold hCG administration and advise patient to avoid sexual intercourse.1

If severe OHSS occurs, discontinue therapy, hospitalize patient, and consult a clinician experienced in the management of OHSS or fluid and electrolyte imbalances.1

Multiple ovulations resulting in multiple gestations reported.1 3 6 8

Potential for arterial thromboembolism exists.1

General Precautions

Administer only under the supervision of qualified clinicians experienced in fertility disorders and in interpretation of indices of ovulation.1

Monitor follicular development (e.g., using ovarian ultrasound, serum estradiol concentrations) in order to correctly identify follicular maturation, determine timing of hCG administration, detect ovarian enlargement, and minimize risks of OHSS and multiple gestation.1

Obtain clinical confirmation of ovulation from direct and indirect indices of progesterone production, including a rise in basal body temperature, increase in serum progesterone, and menstruation following a shift in basal body temperature.1 Sonographic evidence of ovulation includes findings of fluid in the cul-de-sac, ovarian stigmata, collapsed follicle, and a secretory endometrium.1

Specific Populations

Category X.1 (See Contraindications under Cautions.)

Not known whether lutropin alfa is distributed into milk.1 Use not recommended.1

Safety and efficacy not established.1 Not indicated for use in pediatric patients.1

Safety and efficacy not established.1 Not indicated for use in geriatric patients.1

Pharmacokinetics not evaluated.1

Pharmacokinetics not evaluated.1

Common Adverse Effects

Headache,1 2 3 nausea,1 2 3 ovarian hyperstimulation,1 3 breast pain,1 abdominal pain,1 ovarian cyst.1

Luveris® (lutropin alfa for injection) is contraindicated in women who exhibit:

1. Prior hypersensitivity to hLH preparations or one of their excipients.
2. Primary ovarian failure.
3. Uncontrolled thyroid or adrenal dysfunction.
4. An uncontrolled organic intracranial lesion such as a pituitary tumor.
5. Abnormal uterine bleeding of undetermined origin (see “Selection of Patients”).
6. Ovarian cyst or enlargement of undetermined origin (see “Selection of Patients”).
7. Sex hormone dependent tumors of the reproductive tract and accessory organs.
8. Pregnancy.

Gonadotropins, including Luveris® (lutropin alfa for injection), should only be used by physicians who are thoroughly familiar with infertility problems and their management. Like other gonadotropin products, Luveris® is a potent gonadotropic substance capable of contributing to the development of Ovarian Hyperstimulation Syndrome (OHSS) in women with or without pulmonary or vascular complications. The risks of gonadotropin treatment should be considered for women with risk factors of thromboembolic events such as prior medical or family history.  Gonadotropin therapy 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 use of Luveris® requires monitoring of ovarian response with serum estradiol and ovary ultrasound on a regular basis.

Overstimulation of the Ovary Following Gonadotropin Therapy:

Ovarian Enlargement:

Mild to moderate uncomplicated ovarian enlargement which may be accompanied by abdominal distension and/or abdominal pain may occur in patients treated with gonadotropins (such as Luveris®). These conditions generally regress without treatment within two or three weeks.  Careful monitoring of ovarian response can further minimize the risk of overstimulation.

If the ovaries are abnormally enlarged on the last day of therapy with Luveris® and Gonal-f®, hCG should not be administered in this course of therapy. This will reduce the risk of development of Ovarian Hyperstimulation Syndrome.

Ovarian Hyperstimulation Syndrome (OHSS):

OHSS is a medical event distinct from uncomplicated ovarian enlargement. Severe OHSS may progress rapidly (within 24 hours to several days) 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 that are suggestive of hepatic dysfunction have been reported in association with Ovarian Hyperstimulation Syndrome (OHSS).  These liver function test abnormalities may be accompanied by morphological changes on liver biopsy.

In hypogonadotropic hypogonadal women with profound LH and FSH deficiency from five clinical trials, four cases of OHSS were reported in 4 of 70 (5.7%) patients treated with 75 IU Luveris® and Gonal-f® and one case was reported in 1 of 31 (3.2%) patients treated with Gonal-f® alone.  Among women treated with any dose of Luveris® in these studies, five of 96 (5.2%) patients reported 6 cases of OHSS after treatment with Luveris® and Gonal-f®.

OHSS may be 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 severity at 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”), hCG must be withheld.

If severe OHSS occurs, treatment with gonadotropins must be stopped and the patient should be hospitalized.

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

Multiple Births: Patients should be advised of the potential risk of multiple births before starting treatment.

Pulmonary and Vascular Complications: As with other gonadotropin products, a potential for the occurrence of arterial thromboembolism exists.

General

Careful attention should be given to the diagnosis of infertility in candidates for Luveris® therapy. (See “INDICATIONS AND USAGE / Selection of Patients”).

Information for Patients

Prior to therapy with Luveris®, 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 (see “WARNINGS”) and other possible adverse reactions (see “Adverse Reactions”) should also be discussed.

Laboratory Tests

In most instances, treatment of women with LH and 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 ultrasound alone or in combination with measurement of serum estradiol levels.  The combination of both 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.  It is recommended that the number of growing follicles be confirmed using ultrasonography because serum estrogens do not give an indication of the size or number of follicles.

With the exception of confirmation of pregnancy, the clinical confirmation of ovulation is obtained by direct and indirect indices of progesterone production. The indices most generally used are as follows:

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

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:

1. Fluid in the cul-de-sac
2. Ovarian stigmata
3. Collapsed follicle
4. Secretory endometrium

Accurate interpretation of the indices of ovulation requires a physician who is experienced in the interpretation of these tests.

Carcinogenesis, Mutagenesis, Impairment of Fertility

Long-term studies to evaluate the carcinogenic potential of Luveris® in animals have not been performed. In vitro mutagenicity testing of Luveris® in bacteria and mammalian cell lines, chromosome aberration assay in human lymphocytes and in vivo mouse micronucleus have shown no indication of genetic defects. Impaired fertility has been reported in animals exposed to high doses of lutropin alfa; increased pre- and post-implantation losses were observed in female rats and rabbits given lutropin alfa at doses of 10 IU/kg/day and higher.

Pregnancy

Pregnancy Category X. When administered to rats during the late period of pregnancy, doses of 10 IU/kg/day and higher were also shown to affect the postnatal survival and growth of the newborns. There was no evidence of teratogenic effect in either rats or rabbits. See “CONTRAINDICATIONS” section. Luveris® is contraindicated in women who are pregnant and may cause fetal harm when administered to a pregnant woman. Reproductive toxicity studies performed in female rats and rabbits showed that lutropin alfa at doses of 10 IU/kg/day and greater caused an increase in pre- and post-implantation losses.

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 Luveris® is administered to a nursing woman.

Pediatric Use

Luveris® is not indicated in pediatric patients. Safety and effectiveness in pediatric patients have not been established.

Geriatric Use

Luveris® is not indicated in geriatric patients. Safety and effectiveness in geriatric patients have not been established.

Luveris® (lutropin alfa for injection) is supplied in a sterile, lyophilized single dose vial containing 82.5 IU Luveris® to deliver 75 IU Luveris®, after reconstitution with the diluent.

The following package combination is available:

- 1 vial Luveris® 75 IU and 1 vial 1 mL Sterile Water for Injection, USP, NDC 44087-1375-1

Storage: Vials may be stored refrigerated or at room temperature (2°-25° C / 36°-77° F). Protect from light.

Store in original package. Use immediately after reconstitution. Discard unused material.

Rx Only

Manufactured for: EMD Serono, Inc. Rockland, MA  02370 USA

For more information, call toll-free 1-866-538-7879.

April 2009

N5150101F

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