DRUGS & SUPPLEMENTS

Pergonal

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Pergonal uses


1 INDICATIONS AND USAGE

Pergonal® (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)

Prior to initiation of treatment with Pergonal® (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

  • Initial starting dose of the first cycle - 225 International Units per day, administered subcutaneously
  • 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)
  • Pergonal may be administered together with BRAVELLE® (urofollitropin for injection, purified). Only the total starting dose of 225 International Units (150 International Units of Pergonal and 75 International Units of BRAVELLE or 75 International Units of Pergonal and 150 International Units of BRAVELLE) was studied in a clinical trial. (2.2)

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 Pergonal subcutaneously in the abdomen as described in Instructions for Use.
  • Pergonal 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 Pergonal for women who have received a GnRH agonist for pituitary suppression is 225 International Units. Pergonal 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 Pergonal and 75 International Units of BRAVELLE or 75 International Units of Pergonal and 150 International Units of BRAVELLE).

  • Beginning on cycle day 2 or 3, a starting dose of 225 International Units of Pergonal 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 Pergonal therapy [see Warnings and Precautions (5.1, 5.2, 5.10) ].

  • Do not administer daily doses of Pergonal or Pergonal in combination with BRAVELLE that exceed 450 International Units.
  • Therapy should not exceed 20 days.
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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.

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)

4 CONTRAINDICATIONS

Pergonal is contraindicated in women who exhibit:

  • Prior hypersensitivity to Pergonal or Pergonal products or one of their excipients
  • High levels of FSH indicating primary ovarian failure
  • Pregnancy

    Pergonal may cause fetal harm when administered to a pregnant woman . Pergonal is contraindicated in women who are pregnant. If this drug is used during pregnancy, or if the woman becomes pregnant while taking this drug, the woman should be apprised of the potential hazard to a fetus.

  • Presence of uncontrolled non-gonadal endocrinopathies (e.g., thyroid, adrenal, or pituitary disorders)
  • Sex hormone dependent tumors of the reproductive tract and accessory organs
  • Tumors of pituitary gland or hypothalamus
  • Abnormal uterine bleeding of undetermined origin
  • Ovarian cyst or enlargement of undetermined origin, not due to polycystic ovary syndrome

Pergonal is contraindicated in women who exhibit:

  • Prior hypersensitivity to Pergonal or Pergonal 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)
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5 WARNINGS AND PRECAUTIONS

Pergonal should only be used by physicians who are experienced in infertility treatment. Pergonal contains gonadotropic substances capable of causing in women, Ovarian Hyperstimulation Syndrome with or without pulmonary or vascular complications and multiple births . Gonadotropin therapy requires the availability of appropriate monitoring facilities . Use the lowest effective dose.

  • 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)

5.1 Abnormal Ovarian Enlargement

In order to minimize the hazards associated with abnormal ovarian enlargement that may occur with Pergonal therapy, treatment should be individualized and the lowest effective dose should be used . Use of ultrasound monitoring of ovarian response and/or measurement of serum estradiol levels is important to minimize the risk of ovarian stimulation .

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

5.2 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 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 . 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 , 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 Pergonal, OHSS occurred in 7.2% of the 373 Pergonal treated women.

5.3 Pulmonary and Vascular Complications

Serious pulmonary conditions 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 Pergonal.

In the IVF clinical trial of Pergonal, multiple pregnancy as diagnosed by ultrasound occurred in 35.3% of 85 total pregnancies.

Before beginning treatment with Pergonal, 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 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 Pergonal 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
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6 ADVERSE REACTIONS

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

  • Abnormal Ovarian Enlargement
  • Ovarian Hyperstimulation Syndrome
  • Atelectasis, acute respiratory distress syndrome and exacerbation of asthma
  • Thromboembolic events
  • Ovarian Torsion
  • Multi-fetal Gestation and Birth
  • Congenital Malformations
  • Ectopic Pregnancy
  • Spontaneous Abortion
  • Ovarian Neoplasms

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 .

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 Pergonal 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 Pergonal are shown in Table 1.

IVF

n=434

Body System/Preferred Term N %
Body as a whole Abdominal cramps 13 3.0
Abdomen enlarged 10 2.3
Abdominal pain 29 6.7
Headache 27 6.2
Injection site pain + reaction 17 3.9
Injection site inflammation 10 2.3
Urogenital Ovarian Hyperstimulation Syndrome (OHSS) 27 6.2

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

In an open label, US, multicenter, comparative IVF and ICSI trial, Pergonal 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 Pergonal 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 Pergonal. The most common adverse reactions occurring at an incidence of ≥ 5% in women receiving Pergonal 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 Pergonal 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 , 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

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7 DRUG INTERACTIONS

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

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

8 USE IN SPECIFIC POPULATIONS

  • Pregnancy Category X. Do not use Pergonal in pregnant women.
  • 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 Pergonal in women with renal or hepatic insufficiency have not been established. (8.6)

8.1 Pregnancy

Teratogenic effects

Pregnancy Category X .

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 Pergonal, 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 Pergonal in women with renal or hepatic insufficiency have not been established.

10 OVERDOSAGE

Aside from possible OHSS and multiple gestations , there is no additional information on the consequences of acute overdosage with Pergonal.

11 DESCRIPTION

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

Pergonal is a sterile, lyophilized powder intended for subcutaneous (SC) injection after reconstitution with sterile 0.9% Sodium Chloride Injection, USP. Each vial of Pergonal 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 Pergonal 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 Pergonal.

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

Therapeutic class: Infertility

12 CLINICAL PHARMACOLOGY

12.1 Mechanism of Action

Pergonal, administered for 7 to 20 days, produces ovarian follicular growth and maturation in women who do not have primary ovarian failure. Treatment with Pergonal 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 Pergonal. Study 2003-02 compared single doses of subcutaneous administration of the US and European (EU) formulations of Pergonal 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 Pergonal 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.

PK Parameters Single Dose

(225 IU)

Multiple Dose

(225 IU × 1 day then 150 IU × 6 days)

Subcutaneous Intramuscular Subcutaneous Intramuscular
Cmax Single dose Cmax, AUC120 and multiple dose Cmaxss, AUCss (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 Pergonal.

Distribution

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

Metabolism

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

Excretion

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

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 Pergonal.

14 CLINICAL STUDIES

The efficacy of Pergonal 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 Pergonal 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 Pergonal 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.

Parameter Subcutaneously Administered Pergonal
n=373
Continuing Pregnancy (%)Continuing pregnancy was defined as ultrasound visualization of gestational sac with fetal heartbeat at ≥10 weeks after ET 87 (23)Non-inferior to comparator recombinant human FSH based on a two-sided 95% confidence interval, intent-to-treat analysis
Clinical Pregnancy (%) 98 (26)Secondary efficacy parameter. Study was not powered to demonstrate differences in this parameter

16 HOW SUPPLIED/STORAGE AND HANDLING

16.1 How Supplied

Pergonal is supplied in sterile vials as a lyophilized, white to off-white powder or pellet.

Each vial of Pergonal 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

17.1 Dosing and Use

Instruct women on the correct usage and dosing of Pergonal . 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 Pergonal, inform women about the time commitment and monitoring procedures necessary for treatment .

17.3 Instructions Regarding a Missed Dose

Inform the woman that if she misses or forgets to take a dose of Pergonal, 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 and OHSS-associated symptoms including lung and blood vessel problems and ovarian torsion with the use of Pergonal.

17.5 Multi-fetal Gestation and Birth

Inform women regarding the risk of multi-fetal gestation and birth with the use of Pergonal

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

MANUFACTURED FOR:

FERRING PHARMACEUTICALS INC.

PARSIPPANY, NJ 07054

8109000029

Rev: 04/2017

Patient Information

Pergonal® (Men-oh-pyoor)

(menotropins for injection)

for subcutaneous use

Read this Patient Information before you start using Pergonal® (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 Pergonal?

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

Who should not use Pergonal?

Do not use Pergonal if you:

  • are allergic to Pergonal or any of the ingredients in Pergonal. See the end of this leaflet for a complete list of ingredients in Pergonal.
  • have ovaries that no longer make eggs (primary ovarian failure)
  • are pregnant or think you may be pregnant. If Pergonal is taken while you are pregnant, it may harm your baby.
  • have problems with your thyroid gland, adrenal gland, or pituitary gland that are not controlled by taking medicine.
  • have a tumor in your female organs, including your ovaries, breast, or uterus that may get worse with high levels of estrogen
  • have a tumor of your pituitary gland or hypothalamus
  • have abnormal bleeding from your uterus or vagina and the cause is not known
  • have ovarian cysts or enlarged ovaries, not due to a problem called polycystic ovary syndrome (PCOS)

What should I tell my healthcare provider before using Pergonal?

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

  • have been told by a healthcare provider that you are at an increased risk for blood clots (thrombosis)
  • have ever had a blood clot (thrombosis), or anyone in your family has ever had a blood clot
  • had twisting of your ovary (ovarian torsion)
  • had or have a cyst in your ovary
  • have any other medical conditions
  • are breast feeding or plan to breast feed. It is not known if Pergonal passes into your breast milk. You and your healthcare provider should decide if you will use Pergonal or breastfeed. You should not do both.

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 Pergonal?

  • Read the Instructions for Use at the end of this Patient Information about the right way to use Pergonal or Pergonal mixed with BRAVELLE® (urofollitropin for injection, purified).
  • Use Pergonal exactly as your healthcare provider tells you to use it.
  • Your healthcare provider will tell you how much Pergonal to use and when to use it.
  • Your healthcare provider may change your dose of Pergonal if needed.
  • If you miss a dose of Pergonal, call your healthcare provider right away. Do not double the amount of Pergonal you are using.
  • You may need more than 1 vial of Pergonal for your dose.
  • Pergonal may be mixed with BRAVELLE in the same syringe.

What are possible side effects of Pergonal?

Pergonal may cause serious side effects, including:

  • ovaries that are too large. Pergonal may cause your ovaries to be abnormally large. Symptoms of large ovaries include bloating or pain in your lower stomach (pelvic) area. If your ovaries become too large, your healthcare provider may tell you that you should not have intercourse (sex) so you do not rupture an ovarian cyst.
  • ovarian hyperstimulation syndrome (OHSS). Using Pergonal may cause OHSS. OHSS is a serious medical condition that can happen when your ovaries produce too many eggs (overstimulated). OHSS can cause fluid to suddenly build up in the area of your stomach, chest, heart, and cause blood clots to form. OHSS may also happen after you stop using Pergonal. Stop using Pergonal and call your healthcare provider or go to the nearest hospital emergency room right away if you have any of the following symptoms of OHSS:
    • severe pelvic or stomach pain
    • nausea
    • vomiting
    • sudden weight gain
    • swollen stomach
    • diarrhea
    • trouble breathing
    • decreased or no urine
  • lung problems. Pergonal may cause serious lung problems that can sometimes lead to death including fluid in the lungs, trouble breathing, and worsening of asthma.
  • blood clots. Pergonal may increase your chance of having blood clots in your blood vessels. Blood clots can cause:
    • blood vessel problems (thrombophlebitis)
    • stroke
    • loss of your arm or leg
    • blood clot in your lung (pulmonary embolus)
  • twisting (torsion) of your ovary. Pergonal may increase the chance of your ovary twisting, if you already have certain conditions such as OHSS, pregnancy, and previous abdominal surgery. Twisting of your ovary may lead to blood flow being cut off to your ovary.
  • pregnancy with and birth of multiple babies. Pergonal may increase your chance of having a pregnancy with more than 1 baby. Having a pregnancy and giving birth to more than 1 baby at a time increases the health risk for you and your babies. Your healthcare provider should talk to you about your chances of multiple births before you start using Pergonal.
  • birth defects. Babies born after ART may have an increased chance of birth defects. Your age, certain sperm problems, your genetic background, and that of your partner, and a pregnancy with more than 1 baby at a time may increase the chance that your baby may have birth defects.
  • ectopic pregnancy (pregnancy outside your womb). Pergonal may increase your chance of having a pregnancy that is abnormally outside of your womb. Your chance of having a pregnancy outside of your womb is increased if you also have fallopian tube problems.
  • miscarriage. Your chance of loss of an early pregnancy may be increased if you had difficulty becoming pregnant.
  • tumors of the ovary. If you have used medicines like Pergonal more than 1 time to get pregnant, you may have an increased chance of having tumors in your ovaries, including cancer.

The most common side effects of Pergonal include:

  • stomach cramps, fullness or pain
  • headache
  • injection site swelling, heat, redness and pain

These are not all the possible side effects of Pergonal. 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 Pergonal?

  • Before mixing, store Pergonal powder in the refrigerator or at room temperature between 37ºF to 77ºF (3ºC to 25ºC).
  • Protect Pergonal from light.
  • Pergonal should be used right after mixing.
  • Throw away any unused Pergonal.

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

General Information about the safe and effective use of Pergonal.

Medicines are sometimes prescribed for purposes other than those listed in a Patient Information leaflet. Do not use Pergonal for a condition for which it was not prescribed. Do not give Pergonal 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 Pergonal. If you would like more information, talk with your healthcare provider. You can ask your healthcare provider or pharmacist for information about Pergonal 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 Pergonal?

Active ingredient: Pergonal

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

Instructions for Use

Pergonal® (Men-oh-pyoor)

(menotropins for injection)

for subcutaneous use

Your healthcare provider should show you how to mix and inject Pergonal® (menotropins for injection) or Pergonal mixed with BRAVELLE® (urofollitropin for injection, purified) before you do it for the first time. Before using Pergonal or Pergonal 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 Pergonal or Pergonal mixed with BRAVELLE. See Figure A.

  • a clean, flat surface to work on, like a table
  • vials of Pergonal powder (and BRAVELLE powder if you are going to mix the 2 medicines)
  • 1 vial of 0.9% Sodium Chloride, USP used for mixing the medicine
  • alcohol pads
  • rubbing alcohol
  • gauze pads
  • 1 sterile syringe and 1 sterile needle with cap. Your healthcare provider should tell you which syringe and needle to use.
  • the Q-Cap® (vial adapter) that comes with your medicine
  • a sharps disposal container for throwing away your used needles and syringes. See " Disposing of your used needles and syringes " at the end of these instructions.

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

  • Wash your hands well with soap and water and dry them with a clean towel.
  • Place all the supplies you need on the clean surface you already prepared.
  • Check the vial(s) of Pergonal (and BRAVELLE if needed) to make sure there is powder or a pellet in the vial(s). If you do not see any powder in the vial(s) do not use the vial and call your pharmacist or healthcare provider.
  • Check the 0.9% Sodium Chloride, USP vial to make sure that the liquid is clear and does not contain any particles. If you see any particles in the liquid or the liquid is discolored, do not use the vial and call your pharmacist or healthcare provider.
  • Check the Q-Cap blister pack package to make sure it is intact. Do not use if the package is damaged.
  • Remove the plastic cap(s) from the vial(s) of Pergonal (and BRAVELLE if needed) and 0.9% Sodium Chloride, USP vial(s). See Figure B.
  • Wipe the tops of the vials with alcohol and allow them to dry. Do not touch the tops of the vials after you have wiped them. See Figure C.
  • Place the vial of 0.9% Sodium Chloride, USP on the table.
  • Open the Q-Cap blister pack by peeling back the lidding . Do not take the Q-Cap out of the blister pack at this time. Do not touch the spike or connector (luer) ends of the Q-Cap.
  • Hold the 0.9% Sodium Chloride, USP vial in 1 hand. With your other hand, hold the sides of the Q-Cap blister pack, turn the Q-Cap blister pack over, and place it on top of the vial. Push the Q-Cap straight down into the rubber stopper of the vial until the Q-Cap spike pierces the top of the vial and snaps into place. See Figure E.
    • Do not use the Q-Cap if it falls out of the blister pack. Throw it away and get a new one.
  • Remove the blister pack and throw it away in your household trash. Do not touch the connector end (luer) of the Q-Cap. See Figure F .
  • Take the syringe and pull down on the syringe plunger rod until you have withdrawn the amount of 0.9% Sodium Chloride, USP from the vial that your healthcare provider told you to use.
    • The usual amount of 0.9% Sodium Chloride, USP used to mix your Pergonal is 1 mL, but you should use the amount that your healthcare provider tells you to use. See Figure G.
    • Be very careful not to touch the syringe plunger during this step.
  • Place the tip of the syringe into the connector end (luer) of the Q-Cap then twist the syringe clockwise until it is tight. Be careful not to overtighten the syringe. See Figure H.
  • Slowly push down on the syringe plunger to push the air from the syringe into the vial. See Figure I.
  • Keeping the syringe and Q-Cap together, turn the vial upside down and pull down on the syringe plunger to withdraw the right amount of 0.9% Sodium Chloride, USP from the vial. Your healthcare provider should tell you the right amount of 0.9% Sodium Chloride, USP to use. See Figure J.
  • Separate the Q-Cap and syringe from the vial by pulling up on the syringe barrel. Do not pull the plunger to remove the Q-Cap. Throw away 0.9% Sodium Chloride, USP vial in your household trash. See Figure K.
  • Hold the vial of Pergonal powder in 1 hand. With your other hand, hold the sides of the syringe with the Q-Cap attached and place the tip of the Q-Cap over the top of the vial. Push the tip of the Q-Cap into the rubber stopper on the top of the vial until it stops and snaps into place. Be careful not to push down on the syringe plunger during this step. See Figure L. You may see the powder dissolve as the Q-Cap snaps into place, but continue with the steps listed below.
  • Slowly push down on the syringe plunger to push the 0.9% Sodium Chloride, USP into the vial with the Pergonal powder in it. The entire amount of the 0.9% Sodium Chloride, USP in the syringe should be added. Gently swirl the vial until the Pergonal powder is completely dissolved. Do not shake the vial as this will cause bubbles. See Figure M.
  • As soon as the powdered medicine has completely dissolved, push the plunger down to empty any remaining air from the syringe, then turn the vial upside down and slowly pull down on the plunger to withdraw all of the Pergonal into the syringe. See Figure N.
    • Be careful not to pull the plunger stopper all the way out of the syringe barrel.

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

  • Mix your first vial of Pergonal powder or BRAVELLE powder with 0.9% Sodium Chloride, USP. Do not inject your dose yet.
  • Use the liquid in the syringe you have just mixed to mix the next vial of Pergonal or BRAVELLE. See Figures K through M.
  • You can use the liquid in the syringe to mix up to 5 more vials of medicine.
  • Your healthcare provider will tell you how many vials of Pergonal and BRAVELLE to use.

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

  • When you have finished mixing the last vial needed for your injection and have withdrawn all the medicine into the syringe, remove the syringe from the Q-Cap by twisting the syringe counter-clockwise while holding the Q-Cap steady. See Figure O. Throw away the Q-Cap with the attached vial into your household trash.
  • You are now ready to attach the needle to the syringe for your injection.

    Your healthcare provider will tell you what needle you should use for your injection.

  • While holding the syringe with the syringe tip pointing up, place the needle on the top of the syringe. Gently push down on the needle and twist the needle onto the syringe in a clockwise direction until it is tight. See Figure P.
  • Do not remove the needle cap until you are ready for your injection. (See Step 4 )
    • Carefully set the syringe with the needle down on the table. See Figure Q.

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

  • Select a site to inject Pergonal or Pergonal mixed with BRAVELLE on your stomach area (abdomen).
    • Pick a site on your lower abdomen, 1-2 inches below the navel, alternating between left and right sides.
    • Each day, inject in a different site to help reduce soreness and skin problems. For example, on day 1, inject yourself on the right side of your abdomen. The next day, inject yourself on the left side of your abdomen. Changing your injection sites every day will help reduce soreness and skin problems. See Figure R.
  • Clean your injection site with an alcohol pad. Let the alcohol dry. See Figure S.
  • Carefully remove the needle cap from the syringe. See Figure T .
  • Hold the syringe with the needle pointing straight up. Pull down slightly on the plunger and tap the barrel of the syringe so that any air bubbles rise to the top. Slowly press the plunger up until all the air is out of the syringe and a small drop of liquid is seen at the tip of the needle. See Figure U.
  • Tap the syringe to remove the small drop of liquid at the tip of the needle. Do not let the needle touch anything to keep it sterile. See Figure V.
  • The medicine is now ready for you to inject. See Figure V .
Step 4: Injection

  • Hold the syringe in 1 hand. Use your other hand to gently pinch a fold of cleaned skin where you will insert your needle. Hold the skin between your thumb and index finger. See Figure W.
  • Hold your syringe at a right angle to your skin. Quickly insert the needle all the way into your skin fold. See Figure X.
  • Push down the plunger of the syringe with a steady motion. Keep pushing until all the fluid is injected into your skin. See Figure Y.
  • Let go of your skin fold and pull the needle straight out of your skin. See Figure Z.
Step 5. After your injection.

  • If there is any bleeding at your injection site, place a gauze pad over your injection site. Apply gentle pressure to stop the bleeding. Do not rub the site. See Figure AA.
  • If your injection site becomes sore or red, you may put ice on your injection site for 1 minute and then take it off for 3 minutes. If needed, you may repeat this 3 or 4 times.
Step 6. Disposing of your used needles and syringes.

  • Put your used needles and syringes in a FDA-cleared sharps disposal container right away after use. Do not throw away loose needles and syringes in your household trash.
  • If you do not have a FDA-cleared sharps disposal container, you may use a household container that:
    • is made of a heavy-duty plastic,
    • can be closed with a tight-fitting, puncture-resistant lid, without sharps being able to come out,
    • remains upright and stable during use,
    • is leak-resistant, and
    • is properly labeled to warn of hazardous waste inside the container.
  • When your sharps disposal container is almost full, you will need to follow your community guidelines for the right way to dispose of your sharps disposal container. There may be state or local laws about how you should throw away used needles and syringes. For more information about safe sharps disposal, and for specific information about sharps disposal in the state that you live in, go to the FDA's website at: http://www.fda.gov/safesharpsdisposal.

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.

Figure A 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 Figure O Figure P Figure Q Figure R Figure S Figure T Figure U Figure V Figure W Figure X Figure Y Figure Z Figure AA

MANUFACTURED FOR:

FERRING PHARMACEUTICALS INC.

PARSIPPANY, NJ 07054

8109000029

Rev: 04/2017

Pergonal pharmaceutical active ingredients containing related brand and generic drugs:

infoActive ingredient is the part of the drug or medicine which is biologically active. This portion of the drug is responsible for the main action of the drug which is intended to cure or reduce the symptom or disease. The other portions of the drug which are inactive are called excipients; there role is to act as vehicle or binder. In contrast to active ingredient, the inactive ingredient's role is not significant in the cure or treatment of the disease. There can be one or more active ingredients in a drug.


Pergonal available forms, composition, doses:

infoForm of the medicine is the form in which the medicine is marketed in the market, for example, a medicine X can be in the form of capsule or the form of chewable tablet or the form of tablet. Sometimes same medicine can be available as injection form. Each medicine cannot be in all forms but can be marketed in 1, 2, or 3 forms which the pharmaceutical company decided based on various background research results.
Composition is the list of ingredients which combinedly form a medicine. Both active ingredients and inactive ingredients form the composition. The active ingredient gives the desired therapeutic effect whereas the inactive ingredient helps in making the medicine stable.
Doses are various strengths of the medicine like 10mg, 20mg, 30mg and so on. Each medicine comes in various doses which is decided by the manufacturer, that is, pharmaceutical company. The dose is decided on the severity of the symptom or disease.


Pergonal destination | category:

infoDestination is defined as the organism to which the drug or medicine is targeted. For most of the drugs what we discuss, human is the drug destination.
Drug category can be defined as major classification of the drug. For example, an antihistaminic or an antipyretic or anti anginal or pain killer, anti-inflammatory or so.


Pergonal Anatomical Therapeutic Chemical codes:

infoA medicine is classified depending on the organ or system it acts [Anatomical], based on what result it gives on what disease, symptom [Therapeutical], based on chemical composition [Chemical]. It is called as ATC code. The code is based on Active ingredients of the medicine. A medicine can have different codes as sometimes it acts on different organs for different indications. Same way, different brands with same active ingredients and same indications can have same ATC code.


Pergonal pharmaceutical companies:

infoPharmaceutical companies are drug manufacturing companies that help in complete development of the drug from the background research to formation, clinical trials, release of the drug into the market and marketing of the drug.
Researchers are the persons who are responsible for the scientific research and is responsible for all the background clinical trials that resulted in the development of the drug.


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Frequently asked Questions

Can i drive or operate heavy machine after consuming Pergonal?

Depending on the reaction of the Pergonal after taken, if you are feeling dizziness, drowsiness or any weakness as a reaction on your body, Then consider Pergonal not safe to drive or operate heavy machine after consumption. Meaning that, do not drive or operate heavy duty machines after taking the capsule if the capsule has a strange reaction on your body like dizziness, drowsiness. As prescribed by a pharmacist, it is dangerous to take alcohol while taking medicines as it exposed patients to drowsiness and health risk. Please take note of such effect most especially when taking Primosa capsule. It's advisable to consult your doctor on time for a proper recommendation and medical consultations.

Is Pergonal addictive or habit forming?

Medicines are not designed with the mind of creating an addiction or abuse on the health of the users. Addictive Medicine is categorically called Controlled substances by the government. For instance, Schedule H or X in India and schedule II-V in the US are controlled substances.

Please consult the medicine instruction manual on how to use and ensure it is not a controlled substance.In conclusion, self medication is a killer to your health. Consult your doctor for a proper prescription, recommendation, and guidiance.

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Review

sDrugs.com conducted a study on Pergonal, and the result of the survey is set out below. It is noteworthy that the product of the survey is based on the perception and impressions of the visitors of the website as well as the views of Pergonal consumers. We, as a result of this, advice that you do not base your therapeutic or medical decisions on this result, but rather consult your certified medical experts for their recommendations.

Visitor reports

One visitor reported doses

What is the dose of Pergonal drug you are taking?
According to the survey conducted among sDrugs.com website users, the maximum number of people are using the following dose 6-10mg. Few medications come in only one or two doses. Few are specific for adult dose and child dose. The dose of the medicine given to the patient depends on the severity of the symptom/disease. There can be dose adjustments made by the doctor, based on the progression of the disease. Follow-up is important.
Visitors%
6-10mg1
100.0%

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The information was verified by Dr. Arunabha Ray, MD Pharmacology

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