These highlights do not include all the information needed to use MENOPUR safely and effectively.  See full prescribing information for MENOPUR. MENOPUR (menotropins for injection, USP) Initial U.S. Approval: 1975

MENOPUR administered subcutaneously is indicated for the development of multiple follicles and pregnancy in the ovulatory patients participating in an ART program.

Assisted Reproductive Technologies

The recommended initial dose of MENOPUR for patients who have received a GnRH agonist for pituitary suppression is 225 IU. Based on clinical monitoring (including serum estradiol levels and vaginal ultrasound results) subsequent dosing should be adjusted according to individual patient response. Adjustments in dose should not be made more frequently than once every two days and should not exceed 150 IU per adjustment. The maximum daily dose of MENOPUR given should not exceed 450 IU and dosing beyond 20 days is not recommended.

Once adequate follicular development is evident, hCG should be administered to induce final follicular maturation in preparation for oocyte retrieva l. The administration of hCG must be withheld in cases where the ovaries are abnormally enlarged on the last day of therapy. This should reduce the chance of developing OHSS.

Dissolve the contents of one to six vials of MENOPUR in one mL of sterile saline and ADMINISTER SUBCUTANEOUSLY immediately. Any unused reconstituted material should be discarded.

Parenteral drug products should be visually inspected for particulate matter and discoloration prior to administration, whenever solution and container permit.

The lower abdomen (alternating sides) should be used for subcutaneous administration.

75 IU FSH and 75 IU of LH activity, supplied as lyophilized powder or pellet in sterile vials with diluent vials and Q-Cap® vial adapters.

MENOPUR is contraindicated in women who have:

.

MENOPUR 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 Warnings and Precautions (5.5)]

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 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 eva luation may reveal hypovolemia, hemoconcentration, electrolyte imbalances, ascites, hernoperitoneum, pleural effusions, hydrothorax, acute pulmonary distress, and thromboembolic events [see Warnings and Precautions (5.2)]. 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 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 Warnings and Precautions (5.5)], 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.

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 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.

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.

Careful attention should be given to the diagnosis of infertility in the selection of candidates for MENOPUR therapy [see Dosage and Administration (2.1)]

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:

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:

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.

Because clinical studies are conducted under widely varying conditions, adverse reaction rates observed in the clinical studies of a drug cannot be directly compared to rates in the clinical studies of another drug and may not reflect the rates observes in practice.The safety of MENOPUR was examined in 3 clinical studies that enrolled a total of 575 patients receiving MENOPUR in the IVF and OI studies. All adverse events (without regard to causality assessment) occurring at an incidence of >2% in women treated with MENOPUR are listed in Table 1

Table 1: Highly Purified Menotropin SC and IM in Female Patients Undergoing IVF and OI Adverse Events With Onset on or After GnRH Administration, COSTART Classification (for Incidence of 2% or Greater)

 * Includes IM and SC subjects from Protocols MFK/IVF/0399E and MENOPUR 2000-02.

** Includes IM and SC subjects from Protocol MENOPUR 2000-01

No drug/drug interaction studies have been conducted for MENOPUR in humans.

MENOPUR is not indicated in women who are pregnant. There are limited human data on the effects of menotropins when administered during pregnancy [see Contraindication (4)]

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.

Safety and effectiveness in pediatric patients have not been established.

Aside from possible ovarian hyperstimulation [see Warnings and Precautions (5.1) ], little is known concerning the consequences of acute overdosage with MENOPUR.

MENOPUR (menotropins for injection, USP) is a preparation of gonadotropins, extracted from the urine of postmenopausal women, which has undergone additional steps for purification. Each vial of MENOPUR contains 75 International Units (IU) of follicle-stimulating hormone (FSH) activity and 75 IU of luteinizing hormone (LH) activity, plus 21 mg lactose monohydrate and 0.005 mg Polysorbate 20 and Sodium Phosphate Buffer (Sodium Phosphate Dibasic, Heptahydrate and Phosphoric Acid) in a sterile, lyophilized form intended for reconstitution with sterile 0.9% Sodium Chloride Injection, USP. MENOPUR is administered by subcutaneous (SC) injection.

The biological activity of MENOPUR is determined using the USP bioassays for FSH (ovarian weight gain assay in female rats) and LH (seminal vesicle weight gain assay in male rats), modified to increase the accuracy and reproducibility of these assays. The FSH and LH activity assays are standardized using the Fourth International Standard for Urinary FSH and Urinary LH, November 2000, by the Expert Committee on Biological Standardization of the World Health Organization (WHO ECBS). Human Chorionic Gonadotropin (hCG) is detected in MENOPUR.

Both FSH and LH are glycoproteins that are acidic and water soluble.

MENOPUR, administered for 7 to 20 days, produces ovarian follicular growth and maturation in women who do not have primary ovarian failure. In order to produce final follicular maturation and ovulation in the absence of an endogenous LH surge, hCG must be administered following MENOPUR treatment, at a time when patient monitoring indicates sufficient follicular development has occurred.

Two open-label, randomized, controlled trials were conducted to assess the pharmacokinetics of MENOPUR. Study 2003-02 compared single doses of SC administration of the US and European (EU) formulations of MENOPUR in 57 healthy, pre-menopausal females who had undergone pituitary suppression. The study established that the two formulations are bioequivalent. Study 2000-03 assessed single and multiple doses of MENOPUR administered SC and IM in a 3 phase cross-over design in 33 healthy, pre-menopausal females who had undergone pituitary suppression. The primary pharmacokinetic endpoints were FSH AUC and C values. The results are summarized in Table 2.

Table 2: Mean (±SD) FSH Pharmacokinetic Parameters Following MENOPUR Administration (Study 2000-03)

Single dose C AUC and multiple dose C and AUC

Absorption

The SC route of administration trends toward greater bioavailability than the IM route for single and multiple doses of MENOPUR.

Distribution

Human tissue or organ distribution of FSH and LH has not been studied for MENOPUR.

Metabolism

Metabolism of FSH and LH has not been studied for MENOPUR in humans.

Elimination

The elimination half-lives for FSH in the multiple-dose phase were similar (11-13 hours) for MENOPUR SC and MENOPUR IM.

Special Populations

Pregnancy (Category X)

MENOPUR is not indicated in women who are pregnant. There are limited human data on the effects of menotropins when administered during pregnancy [see Contraindications (4)].

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 Use

MENOPUR has not been studied in the pediatric population.

Geriatric Use

MENOPUR has not been studied in the geriatric population.

Renal Impairment

The safety and efficacy of MENOPUR in renal insufficiency have not been studied.

Hepatic Impairment

The safety and efficacy of MENOPUR in hepatic insufficiency have not been studied.

Drug Interactions

No drug/drug interaction studies have been conducted for MENOPUR in humans. 

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

The efficacy and safety of MENOPUR have been established in one randomized, controlled clinical study, 0399E, of women undergoing in vitro fertilization (IVF) or IVF plus intracytoplasmic injection to achieve pregnancy. Study 0399E was a Phase 3, randomized, open-label, multicenter, multinational (in Europe and Israel), comparative clinical trial of ovulatory, infertile females undergoing ovarian stimulation to produce multiple follicles for IVF and embryo transfer (IVF/ET) after pituitary suppression with a GnRH agonist. A total of 373 patients were randomized to the MENOPUR arm. Randomization was stratified by insemination technique [conventional in-vitro fertilization (IVF) vs. intra-cytoplasmic sperm injection (ICSI)]. Efficacy was assessed based on the primary efficacy parameter of continuing pregnancy. The initial daily dose of MENOPUR was 225 IU SC for five days. Thereafter, the dose was individualized according to each patient's response, up to a maximum of 450 IU/day for a total maximum duration of stimulation of 20 days. Treatment outcomes are summarized in Table 3.

Table 3: Efficacy Outcomes for IVF Study 0399E (one cycle of treatment)

Continuing pregnancy was defined as ultrasound visualization of gestational sac with fetal heartbeat at ≥10 weeks after ET

Non-inferior to comparator recombinant human FSH based on a two-sided 95% confidence interval, intent-to-treat analysis

Secondary efficacy parameter. Study 0399E was not powered to demonstrate differences in this parameter

MENOPUR (menotropins for injection, USP) is supplied in sterile vials as a lyophilized, white to off-white powder or pellet.

Each vial of MENOPUR is accompanied by a vial of sterile diluent containing 2 mL of 0.9% Sodium Chloride Injection, USP:

75 IU FSH and 75 IU of LH activity, supplied as:

NDC 55566-7501-1 : Box of 5 vials + 5 vials diluent.

NDC 55566-7501-2 : Box of 5 vials + 5 vials diluent + 5 Q•Cap vial adapters.

Lyophilized powder may be stored refrigerated or at room temperature (3° to 25°C/37° to 77°F). Protect from light. Use immediately after reconstitution. Discard unused material.

To safely dispose of medical sharps, place used needles and syringes in a closeable, puncture-resistant container, such as a red biohazard sharps container.  Sharps containers should then be taken to a collection center for proper disposal. Ask your physician or pharmacist or reference our website for more information about safely disposing used sharps.

State Laws: In some states, it is illegal to throw away medical sharps in household garbage, recycling, and compost bins. Needles and other sharps must be placed in an approved sharps container and disposed of at an approved drop-off site.

More information and options for sharps disposal can be found at our website www.ferringusa.com/sharps .

See 17 for PATIENT COUNSELING INFORMATION

Prior to therapy with MENOPUR, patients should be informed of the duration of treatment and the monitoring of their condition that will be required.

Inform patients that they should seek immediate medical attention if they notice symptoms of ovarian enlargement (e.g., severe pelvic pain, chest pain, abdominal pain, nausea, vomiting, sudden weight gain, bloating, or trouble breathing).

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

Instruct patient on how to properly self administer MENOPUR and properly dispose of needles [see How Supplied/Storage and Handling (16.3)]

MANUFACTURED FOR:

 FERRING PHARMACEUTICALS INC.Parsippany, NJ 07054

6314-01 Rev 06/2008

Menopur® 75IU

(menotropins for injection USP)

75 IU FSH, 75 IU LH

FOR SUBCUTANEOUS INJECTION ONLY

DISCARD UNUSED PORTION

Rx only

Manufactured For:

Ferring Pharmaceuticals Inc., Parsippany, NJ 07054

By: DRAXIS Specialty Pharmaceuticals Inc,, Quebec, Canada

NDS 55566-7501-0

LOT/EXP.

225490 6245-02

 MENOPUR® 75 IU

(menotrophins for injection, USP)

75 IU FSH, 75 IU LH

FOR SUBCUTANEOUS INJECTION ONLY

DISCARD UNUSED PORTION

Rx only

Manufactured For:

Ferring Pharmaceuticals Inc., Parsippany, NJ 07054

By: Ferring GmbH, Kiel Germany
NDC 55566-7501-0

LOT/EXP.

6225-02

 MENOPUR® 75 IU

(menotrophins for injection, USP)

6309-01

Manufactured for:

Ferring Pharmaceuticals Inc., Parsippany, NJ 07054

By: Ferring GmbH, Kiel, Germany

Diluent manufactured for Ferring Pharmaceuticals Inc.

NDC 55566-7501-1

5 single-dose vials of Menotrophins for Injection, USP

5 single-dose vials of 0.9% Sodium Chloride Injection, USP, 2 mL

Reconstitute with 1 mL 0.9% Sodium Chloride Injection, USP

Administer SC immediately after reconstitution.

Discard unused portion.

Usual Dosage: See package insert for dosage and complete Prescribing Information.

Lyophilized powder may be stored refrigerated or at room temperature (3˚ to 25˚ C/ 37˚ to 77˚ F). Protect from light.

FOR SUBCUTANEOUS INJECTION ONLY

Menopur® 75 IU

(menotropins for injection, USP)

6310-01

Manufactured for:

Ferring Pharmaceuticals Inc., Parsippany, NJ 07054

By: DRAXIS Specialty Pharmaceuticals Inc., Quebec, Canada

Diluent manufactured for Ferring Pharmaceuticals Inc.

NDC 55566-7501-1

Menopur® 75 IU

(menotropins for injection, USP)

5 single-dose vials of Menotropins for Injection, USP

5 single-dose vials of 0.9% Sodium Chloride Injection, USP, 2 mL

Reconstitute with 1 mL 0.9% Sodium Chloride Injection, USP.Administer SC immediately after reconstitution.Discard unused portion.Usual Dosage: See package insert for dosage and complete Prescribing Information.Lyophilized powder may be stored refrigerated or at room temperature (3˚ to 25˚ C/ 37˚ to 77˚ F). Protect from light.

FOR SUBCUTENEOUS INJECTION ONLY 

NDC 55566-7501-2

Menopur® 75 IU

(menotrophins for injection, USP)

5 single-dose vials of Menotropins for Injection, USP

5 single-dose vials of 0.9% Sodium Chloride Injection, USP, 2 mL

5 Q•Cap™ Vial Adapters

FOR SUBCUTANEOUS INJECTION ONLY

Rx only

Reconstitute with 1 mL 0.9% Sodium Chloride Injection, USP.

Administer SC immediately after reconstitution.

Discard unused portion.

Usual Dosage:See package insert for dosage and complete Prescribing Information.

Lyophilized powdermay be stored refrigerated or at roomtemperature (3˚ to 25˚C/37˚ to 77˚F). Protect from light.

6311-02

Each single-dose vial of diluent contains:

2 mL 0.9% Sodium Chloride Injection, USP.

Contents: Each single-dose vial of sterile, lyophilized menotropins contains: 75 IU ofFSH; 75 IU LH; Lactose Monohydrate 21 mg; Polysorbate 20 0.005 mg; SodiumPhosphate buffer (Sodium Phosphate Dibasic and Phosphoric Acid).

Manufacturer

Ferring Pharmaceuticals Inc.

Active Ingredients

Source

• U.S. National Library of Medicine
• DailyMed
•  Last Updated: 2nd of March 2011