MENOPUR- menotropins 
Ferring Pharmaceuticals Inc.

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HIGHLIGHTS OF PRESCRIBING INFORMATION

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) for subcutaneous use.



Initial U.S. Approval: 1975

INDICATIONS AND USAGE

MENOPUR® (menotropins for injection) is a gonadotropin indicated for:

  • Development of multiple follicles and pregnancy in ovulatory women as part of an Assisted Reproductive Technology (ART) cycle (1)

DOSAGE AND ADMINISTRATION

  • Initial starting dose of the first cycle - 225 International Units per day, administered subcutaneously (2.2)
  • Dosage adjustments after 5 days and by no more than 150 International Units at each adjustment (2.2)
  • Do not administer doses greater than 450 International Units per day (2.2)
  • MENOPUR may be administered together with BRAVELLE® (urofollitropin for injection, purified). Only the total starting dose of 225 International Units (150 International Units of MENOPUR and 75 International Units of BRAVELLE or 75 International Units of MENOPUR and 150 International Units of BRAVELLE) was studied in a clinical trial. (2.2)

DOSAGE FORMS AND STRENGTHS

Lyophilized powder for injection: containing 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. (3)

CONTRAINDICATIONS

MENOPUR is contraindicated in women who exhibit:

  • Prior hypersensitivity to MENOPUR or menotropins products or one of their excipients (4)
  • High levels of FSH indicating primary ovarian failure (4)
  • Pregnancy (4)
  • Presence of uncontrolled non-gonadal endocrinopathies (4)
  • Sex hormone dependent tumors of the reproductive tract and accessory organ (4)
  • Tumors of pituitary gland or hypothalamus (4)
  • Abnormal uterine bleeding of undetermined origin (4)
  • Ovarian cyst or enlargement of undetermined origin, not due to polycystic ovary syndrome (4)

WARNINGS AND PRECAUTIONS

  • Abnormal Ovarian Enlargement (5.1)
  • Ovarian Hyperstimulation Syndrome (OHSS) (5.2)
  • Pulmonary and Vascular Complications (5.3)
  • Ovarian Torsion (5.4)
  • Multi-fetal Gestation and Birth (5.5)
  • Congenital Malformation (5.6)
  • Ectopic Pregnancy (5.7)
  • Spontaneous Abortion (5.8)
  • Ovarian Neoplasms (5.9)

ADVERSE REACTIONS

The most common adverse reactions (≥2%) in ART include: abdominal cramps; abdomen enlarged; abdominal pain; headache; injection site pain and reaction; injection site inflammation; OHSS (6.1)

To report SUSPECTED ADVERSE REACTIONS, contact Ferring Pharmaceuticals Inc. at 1-888-FERRING (1-888-337-7464) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

DRUG INTERACTIONS

No drug/drug interaction studies have been conducted for MENOPUR in humans. (7)

USE IN SPECIFIC POPULATIONS

  • Pregnancy Category X. Do not use MENOPUR in pregnant women. (4, 8.1)
  • Nursing Mothers: It is not known whether this drug is excreted in human milk. (8.3)
  • Pediatric Use: Safety and efficacy not established. (8.4)
  • Renal and Hepatic Insufficiency: Safety, efficacy, and pharmacokinetics of MENOPUR in women with renal or hepatic insufficiency have not been established. (8.6)

See 17 for PATIENT COUNSELING INFORMATION and FDA-approved patient labeling.

Revised: 5/2018

FULL PRESCRIBING INFORMATION: CONTENTS*

1 INDICATIONS AND USAGE

2 DOSAGE AND ADMINISTRATION

2.1 General Dosing Information

2.2 Recommended Dosing for Assisted Reproductive Technology

3 DOSAGE FORMS AND STRENGTHS

4 CONTRAINDICATIONS

5 WARNINGS AND PRECAUTIONS

5.1 Abnormal Ovarian Enlargement

5.2 Ovarian Hyperstimulation Syndrome (OHSS)

5.3 Pulmonary and Vascular Complications

5.4 Ovarian Torsion

5.5 Multi-fetal Gestation and Birth

5.6 Congenital Malformations

5.7 Ectopic Pregnancy

5.8 Spontaneous Abortion

5.9 Ovarian Neoplasms

5.10 Laboratory Tests

6 ADVERSE REACTIONS

6.1 Clinical Trial Experience

6.2 Postmarketing Experience

7 DRUG INTERACTIONS

8 USE IN SPECIFIC POPULATIONS

8.1 Pregnancy

8.3 Nursing Mothers

8.4 Pediatric Use

8.6 Renal and Hepatic Insufficiency

10 OVERDOSAGE

11 DESCRIPTION

12 CLINICAL PHARMACOLOGY

12.1 Mechanism of Action

12.3 Pharmacokinetics

13 NONCLINICAL TOXICOLOGY

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

14 CLINICAL STUDIES

16 HOW SUPPLIED/STORAGE AND HANDLING

16.1 How Supplied

16.2 Storage and Handling

17 PATIENT COUNSELING INFORMATION

17.1 Dosing and Use

17.2 Duration and Monitoring Required

17.3 Instructions Regarding a Missed Dose

17.4 Ovarian Hyperstimulation Syndrome

17.5 Multi-fetal Gestation and Birth

*
Sections or subsections omitted from the full prescribing information are not listed.

FULL PRESCRIBING INFORMATION

1 INDICATIONS AND USAGE

Development of Multiple Follicles and Pregnancy in Ovulatory Women as Part of an Assisted Reproductive Technology (ART) Cycle

Prior to initiation of treatment with MENOPUR® (menotropins for injection):

  • Perform a complete gynecologic and endocrinologic evaluation, and diagnose the cause of infertility
  • Exclude the possibility of pregnancy
  • Evaluate the fertility status of the male partner
  • Exclude a diagnosis of primary ovarian failure

2 DOSAGE AND ADMINISTRATION

2.1 General Dosing Information

  • Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.
  • Administer MENOPUR subcutaneously in the abdomen as described in Instructions for Use.
  • MENOPUR may be administered together with BRAVELLE® (urofollitropin for injection, purified).

2.2 Recommended Dosing for Assisted Reproductive Technology

The recommended dosing scheme for patients undergoing IVF follows a stepwise approach and is individualized for each woman. The recommended initial dose of MENOPUR for women who have received a GnRH agonist for pituitary suppression is 225 International Units. MENOPUR may be administered together with BRAVELLE and the total initial dose when the products are combined should not exceed 225 International Units (150 International Units of MENOPUR and 75 International Units of BRAVELLE or 75 International Units of MENOPUR and 150 International Units of BRAVELLE).

  • Beginning on cycle day 2 or 3, a starting dose of 225 International Units of MENOPUR is administered subcutaneously daily. Adjust the dose after 5 days based on the woman's ovarian response, as determined by ultrasound evaluation of follicular growth and serum estradiol levels.
  • Do not make additional dosage adjustments more frequently than every 2 days or by more than 150 International Units at each adjustment.
  • Continue treatment until adequate follicular development is evident, and then administer hCG.
    Withhold the administration of hCG in cases where the ovarian monitoring suggests an increased risk of OHSS on the last day of MENOPUR therapy [see Warnings and Precautions (5.1, 5.2, 5.10)].
  • Do not administer daily doses of MENOPUR or MENOPUR in combination with BRAVELLE that exceed 450 International Units.
  • Therapy should not exceed 20 days.

3 DOSAGE FORMS AND STRENGTHS

Lyophilized powder for Injection containing 75 International Units FSH and 75 International Units of LH activity, supplied as lyophilized powder or pellet in sterile vials with diluent vials and Q•Cap® vial adapters.

4 CONTRAINDICATIONS

MENOPUR is contraindicated in women who exhibit:

5 WARNINGS AND PRECAUTIONS

MENOPUR should only be used by physicians who are experienced in infertility treatment. MENOPUR contains gonadotropic substances 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 (5.5)]. Gonadotropin therapy requires the availability of appropriate monitoring facilities [see Warnings and Precautions (5.10)]. Use the lowest effective dose.

5.1 Abnormal Ovarian Enlargement

In order to minimize the hazards associated with abnormal ovarian enlargement that may occur with MENOPUR therapy, treatment should be individualized and the lowest effective dose should be used [see Dosage and Administration (2.2)]. Use of ultrasound monitoring of ovarian response and/or measurement of serum estradiol levels is important to minimize the risk of ovarian stimulation [see Warnings and Precautions (5.10)].

If the ovaries are abnormally enlarged on the last day of MENOPUR therapy, hCG should not be administered in order to reduce the chance of developing Ovarian Hyperstimulation Syndrome (OHSS) [see Warnings and Precautions (5.2)]. Prohibit intercourse in women with significant ovarian enlargement because of the danger of hemoperitoneum resulting from rupture of ovarian cysts [see Warnings and Precautions (5.2)].

5.2 Ovarian Hyperstimulation Syndrome (OHSS)

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 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 effusion, hydrothorax, acute pulmonary distress, and thromboembolic reactions [see Warnings and Precautions (5.3)]. 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 [see Warnings and Precautions (5.1)], the hCG must be withheld.

Cases of OHSS are more common, more severe, and more protracted if pregnancy occurs; therefore, women should be assessed for the development of OHSS for at least two weeks after hCG administration.

If serious OHSS occurs, gonadotropins, including hCG, should be stopped and consideration should be given as to whether the woman needs to be hospitalized. Treatment is primarily symptomatic and overall should consist of bed rest, fluid and electrolyte management, and analgesics (if needed). Because the use of diuretics can accentuate the diminished intravascular volume, diuretics should be avoided except in the late phase of resolution as described below. The management of OHSS may be divided into three phases as follows:

  • Acute Phase:
    Management should be directed at preventing hemoconcentration due to loss of intravascular volume to the third space and minimizing the risk of thromboembolic phenomena and kidney damage. Fluid intake and output, weight, hematocrit, serum and urinary electrolytes, urine specific gravity, BUN and creatinine, total proteins with albumin: globulin ratio, coagulation studies, electrocardiogram to monitor for hyperkalemia, and abdominal girth should be thoroughly assessed daily or more often based on the clinical need. Treatment, consisting of limited intravenous fluids, electrolytes, human serum albumin, is intended to normalize electrolytes while maintaining an acceptable but somewhat reduced intravascular volume. Full correction of the intravascular volume deficit may lead to an unacceptable increase in the amount of third space fluid accumulation.
  • Chronic Phase:
    After the acute phase is successfully managed as above, excessive fluid accumulation in the third space should be limited by instituting severe potassium, sodium, and fluid restriction.
  • Resolution Phase:
    As third space fluid returns to the intravascular compartment, a fall in hematocrit and increasing urinary output are observed in the absence of any increase in intake. 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.

OHSS increases the risk of injury to the ovary. Pelvic examination or intercourse may cause rupture of an ovarian cyst, which may result in hemoperitoneum, and should be avoided.

If bleeding occurs and requires surgical intervention, the clinical objective should be to control the bleeding and retain as much ovarian tissue as possible. A physician experienced in the management of this syndrome, or who is experienced in the management of fluid and electrolyte imbalances, should be consulted.

In the IVF clinical trial for MENOPUR, OHSS occurred in 7.2% of the 373 MENOPUR treated women.

5.3 Pulmonary and Vascular Complications

Serious pulmonary conditions (e.g. atelectasis, acute respiratory distress syndrome, and exacerbation of asthma) have been reported in women treated with gonadotropins. In addition, thromboembolic events both in association with, and separate from the Ovarian Hyperstimulation Syndrome (OHSS) have been reported in women treated with gonadotropins. Intravascular thrombosis and embolism, which may originate in venous or arterial vessels, can result in reduced blood flow to critical organs or the extremities. Women with generally recognized risk factors for thrombosis, such as 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 of such reactions have included venous thrombophlebitis, pulmonary embolism, pulmonary infarction, cerebral vascular occlusion (stroke), and arterial occlusion resulting in loss of limb and rarely in myocardial infarctions. In rare cases, pulmonary complications and/or thromboembolic reactions have resulted in death. In women with recognized risk factors, the benefits of ovulation induction and assisted reproductive technology need to be weighed against the risks. Pregnancy also carries an increased risk of thrombosis.

5.4 Ovarian Torsion

Ovarian torsion has been reported after treatment with gonadotropins. This may be related to OHSS, pregnancy, previous abdominal surgery, past history of ovarian torsion, previous or current ovarian cyst, and polycystic ovaries. Damage to the ovary due to reduced blood supply can be limited by early diagnosis and immediate detorsion.

5.5 Multi-fetal Gestation and Birth

Multi-fetal gestation and births have been reported with all gonadotropin therapy including therapy with MENOPUR.

In the IVF clinical trial of MENOPUR, multiple pregnancy as diagnosed by ultrasound occurred in 35.3% (n=30) of 85 total pregnancies.

Before beginning treatment with MENOPUR, advise the woman and her partner of the potential risk of multi-fetal gestation and birth.

5.6 Congenital Malformations

The incidence of congenital malformations after some ART [specifically in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI)] may be slightly higher than after spontaneous conception. This slightly higher incidence is thought to be related to differences in parental characteristics (e.g., maternal age, maternal and paternal genetic background, sperm characteristics) and to the higher incidence of multi-fetal gestations after IVF or ICSI. There are no indications that the use of gonadotropins during IVF or ICSI is associated with an increased risk of congenital malformations.

5.7 Ectopic Pregnancy

Since infertile women undergoing ART often have tubal abnormalities, the incidence of ectopic pregnancy may be increased. Early confirmation of intrauterine pregnancy should be determined by β-hCG testing and transvaginal ultrasound.

5.8 Spontaneous Abortion

The risk of spontaneous abortion (miscarriage) is increased with gonadotropin products. However, causality has not been established. The increased risk may be a factor of the underlying infertility.

5.9 Ovarian Neoplasms

There have been infrequent reports of ovarian neoplasms, both benign and malignant, in women who have had multiple drug therapy for controlled ovarian stimulation; however, a causal relationship has not been established.

5.10 Laboratory Tests

In most instances, treatment of women with MENOPUR will result only in follicular growth and maturation. In the absence of an endogenous LH surge, hCG is given when monitoring of the woman 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 follicular growth and maturation, timing of the ovulatory trigger, detecting ovarian enlargement and minimizing the risk of the OHSS and multiple gestation.

The clinical confirmation of ovulation is obtained by direct or indirect indices of progesterone production as well as sonographic evidence of ovulation.

Direct or indirect indices of progesterone production:

  • Urinary or serum luteinizing hormone (LH) rise
  • A rise in basal body temperature
  • Increase in serum progesterone
  • Menstruation following the shift in basal body temperature

Sonographic evidence of ovulation:

  • Collapsed follicle
  • Fluid in the cul-de-sac
  • Features consistent with corpus luteum formation
  • Secretory endometrium

6 ADVERSE REACTIONS

The following serious adverse reactions are discussed elsewhere in the labeling:

6.1 Clinical Trial Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trial of another drug and may not reflect the rates observed in practice.

In two single cycle, open label, multinational, multicenter, comparative trials, a total of 434 normal ovulatory infertile women were randomized and received subcutaneously administered MENOPUR as part of an in vitro fertilization (IVF) cycle (both trials) or intracytoplasmic sperm injection (ICSI) cycle (one of the two trials). All women received pituitary down-regulation with gonadotropin releasing hormone (GnRH) agonist before stimulation. Adverse Reactions occurring at an incidence of ≥ 2% in women receiving MENOPUR are shown in Table 1.

Table 1: MENOPUR Administered Subcutaneously in Women Undergoing IVF and ICSI. Adverse Reactions with Incidence of 2% or Greater Occurring on or After GnRH Administration.
IVF
n=434
Body System/Preferred TermN%
Body as a wholeAbdominal cramps133.0
Abdomen enlarged102.3
Abdominal pain296.7
Headache276.2
Injection site pain + reaction173.9
Injection site inflammation102.3
UrogenitalOvarian Hyperstimulation Syndrome (OHSS)276.2

In addition, thrombophlebitis was reported in less than 1% of subjects.

In an open label, US, multicenter, comparative IVF and ICSI trial, MENOPUR and BRAVELLE were administered in the same syringe to 60 normal ovulatory infertile women. OHSS, post retrieval cramping and nausea and spontaneous abortion were the most common adverse reactions occurring at an incidence of ≥ 5% in women receiving the combination of MENOPUR and BRAVELLE.

In another open label, US multicenter, comparative trial for ovulation induction in anovulatory or oligovulatory infertile women, 76 subjects received subcutaneous or intramuscular injections of MENOPUR. The most common adverse reactions occurring at an incidence of ≥ 5% in women receiving MENOPUR were: headache; OHSS; injection site reaction, abdominal cramps, fullness and pain; and nausea.

6.2 Postmarketing Experience

The following adverse reactions have been reported during postmarketing use of gonadotropins. Because these reactions were reported voluntarily from a population of uncertain size, the frequency or a causal relationship to MENOPUR cannot be reliably determined.

Gastrointestinal disorders: abdominal pain, abdominal pain lower, abdominal distension, nausea, vomiting, abdominal discomfort

General disorders and administration site conditions: injection site reactions (most frequently reported injection site reaction was injection site pain), fatigue

Nervous system disorders: headache, dizziness

Reproductive system disorders: OHSS [see Warnings and Precautions (5.2)], pelvic pain, ovarian cyst, breast complaints (including breast pain, breast tenderness, breast discomfort, and breast swelling)

Skin and subcutaneous tissue disorders: acne, rash

Vascular disorders: hot flush

7 DRUG INTERACTIONS

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

8 USE IN SPECIFIC POPULATIONS

8.1 Pregnancy

Teratogenic effects

Pregnancy Category X [see Contraindications (4)].

8.3 Nursing Mothers

It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in the nursing infant from MENOPUR, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.

8.4 Pediatric Use

Safety and effectiveness in pediatric patients have not been established.

8.6 Renal and Hepatic Insufficiency

Safety, efficacy, and pharmacokinetics of MENOPUR in women with renal or hepatic insufficiency have not been established.

10 OVERDOSAGE

Aside from possible OHSS [see Warnings and Precautions (5.2)] and multiple gestations [see Warnings and Precautions (5.5)], there is no additional information on the consequences of acute overdosage with MENOPUR.

11 DESCRIPTION

MENOPUR is a preparation of gonadotropins (FSH and LH activity), extracted from the urine of postmenopausal women, which has undergone additional steps for purification.

MENOPUR is a sterile, lyophilized powder intended for subcutaneous (SC) injection after reconstitution with sterile 0.9% Sodium Chloride Injection, USP. Each vial of MENOPUR contains 75 International Units of follicle-stimulating hormone (FSH) activity and 75 International Units 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).

The biological activity of MENOPUR is determined using the 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). Both FSH and LH are glycoproteins that are acidic and water-soluble. Human Chorionic Gonadotropin (hCG) is detected in MENOPUR.

MENOPUR has been mixed in vitro with BRAVELLE with no evidence of aggregation.

Therapeutic class: Infertility

12 CLINICAL PHARMACOLOGY

12.1 Mechanism of Action

MENOPUR, administered for 7 to 20 days, produces ovarian follicular growth and maturation in women who do not have primary ovarian failure. Treatment with MENOPUR in most instances results only in follicular growth and maturation. When sufficient follicular maturation has occurred, hCG must be given to induce ovulation.

12.3 Pharmacokinetics

Two open-label, randomized, controlled trials were conducted to assess the pharmacokinetics of MENOPUR. Study 2003-02 compared single doses of subcutaneous 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 subcutaneously and intramuscularly in a 3 phase crossover design in 33 healthy, pre-menopausal females who had undergone pituitary suppression. The primary pharmacokinetic endpoints were FSH AUC and Cmax values. The results are summarized in Table 2.

Table 2: FSH Pharmacokinetic Parameters [Mean (SD)] Following MENOPUR Administration (Study 2000-03)
PK ParametersSingle Dose
(225 IU)
Multiple Dose
(225 IU × 1 day then 150 IU × 6 days)
SubcutaneousIntramuscularSubcutaneousIntramuscular
*
Single dose C max, AUC 120 and multiple dose C maxss, AUC ss
Cmax* (mIU/mL)8.5 (2.5)7.8 (2.4)15.0 (3.6)12.5 (2.3)
Tmax (hr)17.9 (5.8)27.5 (25.4)8.0 (3.0)9.0 (7.0)
AUC†
(hr-mlU/mL)
726.2 (243.0)656.1 (233.7)622.7 (153.0)546.2 (91.2)

Absorption

The subcutaneous route of administration trends toward greater bioavailability than the intramuscular 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.

Excretion

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

13 NONCLINICAL TOXICOLOGY

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

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

14 CLINICAL STUDIES

The efficacy of MENOPUR was established in one randomized, open-label, multicenter, multinational (in Europe and Israel), comparative clinical trial of women undergoing in vitro fertilization (IVF) or IVF plus intracytoplasmic injection (ICSI) to achieve pregnancy.

All women began ovarian stimulation as part of an IVF cycle following pituitary suppression with a GnRH agonist. A total of 373 patients were randomized to the MENOPUR arm. Randomization was stratified by insemination technique [conventional IVF vs. ICSI]. Efficacy was assessed based on the primary efficacy parameter of continuing pregnancy. The initial daily dose of MENOPUR was 225 International Units administered subcutaneously 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 Outcome in IVF Study (one cycle of treatment)
ParameterSubcutaneously Administered MENOPUR
n=373
*
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 was not powered to demonstrate differences in this parameter
Continuing Pregnancy (%)*87 (23)
Clinical Pregnancy (%)98 (26)

16 HOW SUPPLIED/STORAGE AND HANDLING

16.1 How Supplied

MENOPUR (menotropins for injection) 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 for Injection, USP:

75 International Units FSH and 75 International Units of LH activity, supplied as

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

16.2 Storage and Handling

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

17 PATIENT COUNSELING INFORMATION

See FDA-approved patient labeling (Patient Information and Instructions for Use).

17.1 Dosing and Use

Instruct women on the correct usage and dosing of MENOPUR [see Dosage and Administration (2.2)]. Caution women not to change the dosage or the schedule of administration unless she is told to do so by her healthcare provider.

17.2 Duration and Monitoring Required

Prior to beginning therapy with MENOPUR, inform women about the time commitment and monitoring procedures necessary for treatment [see Dosage and Administration (2.2) and Warnings and Precautions (5.10)].

17.3 Instructions Regarding a Missed Dose

Inform the woman that if she misses or forgets to take a dose of MENOPUR, the next dose should not be doubled and she should call her healthcare provider for further dosing instructions.

17.4 Ovarian Hyperstimulation Syndrome

Inform women regarding the risks of OHSS [see Warnings and Precautions (5.2)] and OHSS-associated symptoms including lung and blood vessel problems [see Warnings and Precautions (5.3)] and ovarian torsion [see Warnings and Precautions (5.4)] with the use of MENOPUR.

17.5 Multi-fetal Gestation and Birth

Inform women regarding the risk of multi-fetal gestation and birth with the use of MENOPUR [see Warnings and Precautions (5.5)]

Vials of sterile diluent of 0.9% Sodium Chloride Injection, USP manufactured for Ferring Pharmaceuticals Inc.

MANUFACTURED FOR:
FERRING PHARMACEUTICALS INC.
PARSIPPANY, NJ 07054

8109000033
Rev: 05/2018

Patient Information

MENOPUR® (Men-oh-pyoor)
(menotropins for injection)
for subcutaneous use

Read this Patient Information before you start using MENOPUR® (menotropins for injection) and each time you get a refill. There may be new information. This information does not take the place of talking to your healthcare provider about your medical condition or your treatment.

What is MENOPUR?

MENOPUR is a prescription medicine that contains follicle stimulating hormone (FSH) and luteinizing hormone (LH). MENOPUR causes your ovaries to make multiple (more than 1) eggs as part of an Assisted Reproductive Technology (ART) cycle.

Who should not use MENOPUR?

Do not use MENOPUR if you:

What should I tell my healthcare provider before using MENOPUR?

Before you use MENOPUR, tell your healthcare provider if you:

Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.

Know the medicines you take. Keep a list of them to show your healthcare provider and pharmacist when you get a new medicine.

How should I use MENOPUR?

What are possible side effects of MENOPUR?

MENOPUR may cause serious side effects, including:

The most common side effects of MENOPUR include:

These are not all the possible side effects of MENOPUR. For more information, ask your healthcare provider or pharmacist.

Tell your healthcare provider if you have any side effect that bothers you or that does not go away.

How should I store MENOPUR?

Keep MENOPUR and all medicines out of the reach of children.

General Information about the safe and effective use of MENOPUR.

Medicines are sometimes prescribed for purposes other than those listed in a Patient Information leaflet. Do not use MENOPUR for a condition for which it was not prescribed. Do not give MENOPUR to other people, even if they have the same condition you have. It may harm them.

This Patient Information summarizes the most important information about MENOPUR. If you would like more information, talk with your healthcare provider. You can ask your healthcare provider or pharmacist for information about MENOPUR that is written for health professionals.

For more information go to www.menopur.com, or call 1-888-FERRING (1-888-337-7464).

What are the ingredients in MENOPUR?

Active ingredient: menotropins

Inactive ingredients: lactose monohydrate, polysorbate, sodium phosphate buffer (sodium phosphate dibasic, heptahydrate and phosphoric acid)

Instructions for Use

MENOPUR® (Men-oh-pyoor)

(menotropins for injection)

for subcutaneous use

Your healthcare provider should show you how to mix and inject MENOPUR® (menotropins for injection) or MENOPUR mixed with BRAVELLE® (urofollitropin for injection, purified) before you do it for the first time. Before using MENOPUR or MENOPUR mixed with BRAVELLE for the first time, read this Instructions for Use carefully. Keep this leaflet in a safe place and read it when you have questions.

Supplies you will need to give your injection of MENOPUR or MENOPUR mixed with BRAVELLE. See Figure A.

Figure A

Step 1. Preparing your MENOPUR or MENOPUR mixed with BRAVELLE.

Figure B
Figure C
Figure D
Figure E
Figure F
Figure G
Figure H
Figure I
Figure J
Figure K
Figure L
Figure M
Figure N

If your healthcare provider tells you to use more than 1 vial of MENOPUR or tells you to mix your MENOPUR with BRAVELLE in the same syringe:

Step 2. Removing the Q•Cap and adding your needle for injection.

Figure O
Figure P
Figure Q

Step 3. Prepare Injection site for MENOPUR or MENOPUR mixed with BRAVELLE.

Figure R
Figure S
Figure T
Figure U
Figure V

Step 4: Injection

Figure W
Figure X
Figure Y
Figure Z

Step 5. After your injection.

Figure AA

Step 6. Disposing of your used needles and syringes.

Do not dispose of your used sharps disposal container in your household trash unless your community guidelines permit this. Do not recycle your used sharps disposal container.

This Instructions for Use has been approved by the U.S. Food and Drug Administration.

MANUFACTURED FOR:
FERRING PHARMACEUTICALS INC.
PARSIPPANY, NJ 07054

8109000033
Rev: 05/2018

PRINCIPAL DISPLAY PANEL - Kit Carton

NDC 55566-7501-2

Menopur® 75 IU
(menotropins for injection)

5 single dose vials of Menotropins for Injection
5 single dose vials of 0.9% Sodium Chloride Injection, USP, 2 mL
5 Q•Cap® Vial Adapters

FOR SUBCUTANEOUS
INJECTION ONLY

Rx only

Q•Cap®
Vial Adapters
for Needle-Free
Reconstitution

For exclusive use with
Ferring reproductive health products

FERRING
PHARMACEUTICALS

PRINCIPAL DISPLAY PANEL - Kit Carton
MENOPUR 
menotropins kit
Product Information
Product TypeHUMAN PRESCRIPTION DRUGItem Code (Source)NDC:55566-7501
Packaging
#Item CodePackage DescriptionMarketing Start DateMarketing End Date
1NDC:55566-7501-21 in 1 CARTON10/29/2004
1NDC:55566-7501-11 in 1 CARTON
Quantity of Parts
Part #Package QuantityTotal Product Quantity
Part 15 VIAL, SINGLE-DOSE
Part 25 VIAL
Part 1 of 2
MENOPUR 
menotropins injection, powder, lyophilized, for solution
Product Information
Item Code (Source)NDC:55566-7502
Route of AdministrationSUBCUTANEOUS
Active Ingredient/Active Moiety
Ingredient NameBasis of StrengthStrength
FOLLITROPIN (UNII: 076WHW89TW) (FOLLITROPIN - UNII:076WHW89TW) FOLLITROPIN75 [iU]
LUTEINIZING HORMONE (UNII: 8XA4VN1LH4) (LUTEINIZING HORMONE - UNII:8XA4VN1LH4) LUTEINIZING HORMONE75 [iU]
Inactive Ingredients
Ingredient NameStrength
LACTOSE MONOHYDRATE (UNII: EWQ57Q8I5X) 21 mg
POLYSORBATE 20 (UNII: 7T1F30V5YH)  
SODIUM PHOSPHATE, DIBASIC, HEPTAHYDRATE (UNII: 70WT22SF4B)  
Product Characteristics
ColorwhiteScore    
ShapeSize
FlavorImprint Code
Contains    
Packaging
#Item CodePackage DescriptionMarketing Start DateMarketing End Date
1NDC:55566-7502-01 in 1 VIAL, SINGLE-DOSE; Type 1: Convenience Kit of Co-Package
Marketing Information
Marketing CategoryApplication Number or Monograph CitationMarketing Start DateMarketing End Date
BLABLA02166310/29/2004
Part 2 of 2
SODIUM CHLORIDE 
sodium chloride injection
Product Information
Route of AdministrationSUBCUTANEOUS
Active Ingredient/Active Moiety
Ingredient NameBasis of StrengthStrength
SODIUM CHLORIDE (UNII: 451W47IQ8X) (CHLORIDE ION - UNII:Q32ZN48698, SODIUM CATION - UNII:LYR4M0NH37) SODIUM CHLORIDE9 mg
Packaging
#Item CodePackage DescriptionMarketing Start DateMarketing End Date
11 in 1 VIAL; Type 1: Convenience Kit of Co-Package
Marketing Information
Marketing CategoryApplication Number or Monograph CitationMarketing Start DateMarketing End Date
BLABLA02166310/29/2004
Marketing Information
Marketing CategoryApplication Number or Monograph CitationMarketing Start DateMarketing End Date
BLABLA02166310/29/2004
Labeler - Ferring Pharmaceuticals Inc. (103722955)

Revised: 5/2021
Document Id: e5846836-f1fd-4569-82bf-dd62f310b595
Set id: 22c8db95-c3db-1770-8086-31356fbabe35
Version: 32
Effective Time: 20210504
 
Ferring Pharmaceuticals Inc.