DRUGS & SUPPLEMENTS
1 INDICATIONS AND USAGE
Pergonal® (menotropins for injection) is a gonadotropin indicated for:
Prior to initiation of treatment with Pergonal® (menotropins for injection):
2 DOSAGE AND ADMINISTRATION
2.1 General Dosing Information
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).
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)
Pergonal is contraindicated in women who exhibit:
Pergonal is contraindicated in women who exhibit:
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.
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:
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:
Sonographic evidence of ovulation:
6 ADVERSE REACTIONS
The following serious adverse reactions are discussed elsewhere in the labeling:
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.
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
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 .
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.
Aside from possible OHSS and multiple gestations , there is no additional information on the consequences of acute overdosage with Pergonal.
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.
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.
The subcutaneous route of administration trends toward greater bioavailability than the intramuscular route for single and multiple doses of Pergonal.
Human tissue or organ distribution of FSH and LH has not been studied for Pergonal.
Metabolism of FSH and LH has not been studied for Pergonal in humans.
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.
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.
FERRING PHARMACEUTICALS INC.
PARSIPPANY, NJ 07054
(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:
What should I tell my healthcare provider before using Pergonal?
Before you use Pergonal, 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 Pergonal?
What are possible side effects of Pergonal?
Pergonal may cause serious side effects, including:
The most common side effects of Pergonal include:
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?
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
(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.
Step 1. Preparing your Pergonal or Pergonal mixed with BRAVELLE.
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:
Step 2. Removing the Q-Cap and adding your needle for injection.
Step 3. Prepare Injection site for Pergonal or Pergonal mixed with BRAVELLE.
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
FERRING PHARMACEUTICALS INC.
PARSIPPANY, NJ 07054
Pergonal pharmaceutical active ingredients containing related brand and generic drugs:
Active 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:
Form 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:
Destination 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:
A 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:
Pharmaceutical 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.
Frequently asked QuestionsCan 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.
ReviewsDrugs.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.
One visitor reported dosesWhat 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.
The information was verified by Dr. Arunabha Ray, MD Pharmacology