Menopur Information
Menopur (Follitropin alpha)
Menopur (Follitropin alpha) Indications And Usage
Menopur (Follitropin alpha) administered subcutaneously is indicated for the development of multiple follicles and pregnancy in the ovulatory patients participating in an ART program.
Menopur (Follitropin alpha) Dosage And Administration
Assisted Reproductive Technologies
The recommended initial dose of Menopur (Follitropin alpha) 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 (Follitropin alpha) 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 retrieval. 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 (Follitropin alpha) in one mL of sterile saline and 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.
Menopur (Follitropin alpha) Dosage Forms And Strengths
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 (Follitropin alpha) Contraindications
Menopur (Follitropin alpha) is contraindicated in women who have:
.
Menopur (Follitropin alpha) Warnings And Precautions
Menopur (Follitropin alpha) 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 [
]
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 (Follitropin alpha) 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 evaluation may reveal hypovolemia, hemoconcentration, electrolyte imbalances, ascites, hernoperitoneum, pleural effusions, hydrothorax, acute pulmonary distress, and thromboembolic events [ Warnings and Precautions ]. 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 (Follitropin alpha) 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 [
], 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.
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.
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.
Menopur (Follitropin alpha) Drug Interactions
No drug/drug interaction studies have been conducted for Menopur (Follitropin alpha) in humans.
Menopur (Follitropin alpha) Overdosage
Aside from possible ovarian hyperstimulation [
], little is known concerning the consequences of acute overdosage with Menopur (Follitropin alpha) .
Menopur (Follitropin alpha) Description
Menopur (Follitropin alpha) (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 (Follitropin alpha) 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 (Follitropin alpha) is administered by subcutaneous (SC) injection.
The biological activity of Menopur (Follitropin alpha) 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 (Follitropin alpha) .
Both FSH and LH are glycoproteins that are acidic and water soluble.
Menopur (Follitropin alpha) Clinical Pharmacology
Menopur (Follitropin alpha) , 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 (Follitropin alpha) treatment, at a time when patient monitoring indicates sufficient follicular development has occurred.
Menopur (Follitropin alpha) Clinical Studies
The efficacy and safety of Menopur (Follitropin alpha) 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 (Follitropin alpha) 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 (Follitropin alpha) 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.
Menopur (Follitropin alpha) How Supplied/storage And Handling
Menopur (Follitropin alpha) (menotropins for injection, USP) is supplied in sterile vials as a lyophilized, white to off-white powder or pellet.
Each vial of Menopur (Follitropin alpha) 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.
Menopur (Follitropin alpha) Patient Counseling Information
See for PATIENT COUNSELING INFORMATION
Instruct patient on how to properly self administer Menopur (Follitropin alpha) and properly dispose of needles [ ()]
MANUFACTURED FOR:
FERRING PHARMACEUTICALS INC.Parsippany, NJ 07054
6314-01 Rev 06/2008
Menopur (Follitropin alpha) Package Label - Draxis Vial Label
Menopur (Follitropin alpha) ® 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 (Follitropin alpha) Package Label - Kiel Vial Label
Menopur (Follitropin alpha) ® 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 (Follitropin alpha) Package Label - Kiel Carton
Menopur (Follitropin alpha) ® 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.
Menopur (Follitropin alpha) Package Label.- Draxis Carton
Menopur (Follitropin alpha) ® 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 (Follitropin alpha) ® 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.
Menopur (Follitropin alpha) Package Label - Outer Carton
NDC 55566-7501-2
Menopur (Follitropin alpha) ® 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
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.
